The outer membrane (OM) is an essential barrier that guards Gram‐negative bacteria from diverse environmental insults. Besides functioning as a chemical gatekeeper, the OM also contributes towards the strength and stiffness of cells and allows them to sustain mechanical stress. Largely influenced by studies of Escherichia coli, the OM is viewed as a rigid barrier where OM proteins and lipopolysaccharides display restricted mobility. Here the discussion is extended to other bacterial species, with a focus on Myxococcus xanthus. In (...) contrast to the rigid OM paradigm, myxobacteria possess a relatively fluid OM. It is concluded that the fluidity of the OM varies across environmental species, which is likely linked to their evolution and adaptation to specific ecological niches. Importantly, a fluid OM can endow bacteria with distinct functions for cell‐cell and cell‐environment interactions. (shrink)

Inactivation of the Ca2+ extrusion mode of the retinal rod Na- Ca + K exchanger is suggested to be the mechanism that prevents lowering of cytosolic free Ca2+ to < 1 nM when rod cells are saturated for a prolonged time under bright light conditions. Under these conditions, Ca2+ fluxes across disk membranes can contribute significantly to Ca2+ homeostasis in rods.

Damage repair is a fundamental requirement of all life as organisms find themselves in challenging and fluctuating environments. In particular, damage to the barrier between an organism and its environment (e.g. skin, plasma membrane, bacterial cell envelope) is frequent because these organs/organelles directly interact with the external world. Here, we discuss the general strategies that bacteria use to cope with damage to their cell envelope and their repair limits. We then describe a novel damage‐coping mechanism used by multicellular myxobacteria. (...) We propose that cell‐cell transfer of membrane material within a population serves as a wound‐healing strategy and provide evidence for its utility. We suggest that – similar to how tissues in eukaryotes have evolved cooperative methods of damage repair – so too have some bacteria that live a multicellular lifestyle. (shrink)

Mitochondrial function and biogenesis depend on the transport of a large variety of proteins, ions, and metabolites across the two surrounding membranes. While several specific transporters are present in the inner membrane, transport processes across the outer membrane are less understood. Recent studies reveal that the number of outer membrane channels and their transport mechanisms are more diverse than originally thought. Four protein‐conducting channels promote transport of distinct sets of precursor proteins across and into the (...) outer membrane. The voltage‐dependent anion channel (VDAC) forms the major channel for small hydrophilic molecules. In addition, three channels with yet unknown substrate specificity exist in the outer membrane. In this review, we outline the emerging functional diversity, selectivity, and regulation of mitochondrial outer membrane channels. The presence of several channel‐forming proteins challenges the traditional view that the outer membrane forms an unspecific size‐exclusion filter for the flux of small hydrophilic molecules. (shrink)

Outer membrane proteins (OMPs) maintain the viability of Gram‐negative bacteria by functioning as receptors, transporters, ion channels, lipases, and porins. Folding and assembly of OMPs involves synchronized action of chaperones and multi‐protein machineries which escort the highly hydrophobic polypeptides to their target outer membrane in a folding competent state. Previous studies have identified proteins and their involvement along the OMP biogenesis pathway. Yet, the mechanisms of action and the intriguing ability of all these molecular machines to (...) work without the typical cellular energy source of ATP, but solely based on thermodynamic principles, are still not well understood. Here, we highlight how different single‐molecule studies can shed additional light on the mechanisms and kinetics of OMP biogenesis. (shrink)

Ion channels mediate ion flux across biological membranes and regulate important organellar and cellular tasks. A recent study revealed the presence of four new proteins, the MIM complex (composed by Mim1 and Mim2), Ayr1, OMC7, and OMC8, that are able to form ion‐conducting channels in the outer mitochondria membrane (OMM). These findings strongly indicate that the OMM is endowed with many solute‐specific channels, in addition to porins and known channels mediating protein import into mitochondria. These solute‐specific channels provide (...) essential pathways for the controlled transport of ions and metabolites and may thus add a further layer of specificity to the regulation of mitochondrial function at the organelle‐cytosol and/or inter‐organellar interface. Future studies will be required to fully understand the way(s) of regulation of these new channels and to integrate them into signaling pathways within the cells. (shrink)

The Gram-negative outer membrane is a potent permeability barrier against antibiotics, limiting clinical options amid mounting rates of resistance. The Lol transport pathway delivers lipoproteins to the OM. All the OM assembly machines require one or more OM lipoprotein to function, making the Lol pathway central for all aspects of OM biogenesis. The Lol pathways of many medically important species clearly deviate from the Escherichia coli paradigm, perhaps with implications for efforts to develop novel antibiotics. Moreover, recent work (...) reveals the existence of an undiscovered alternate route for bringing lipoproteins to the OM. Here, lipoprotein transport mechanisms, and the quality control systems that underpin them, is re-examined in context of their diversity. All essential outer membrane assembly machines require lipoproteins to function. Hence, the transport mechanisms supplying these lipoproteins are critical for maintaining the integrity of the outer membrane barrier against antibiotics. Lipoprotein transport strategies of diverse Gram-negative bacteria will be reviewed in the context of recent discoveries. (shrink)

Most mitochondrial proteins are synthesized in the cytosol as preproteins with a cleavable presequence and are delivered to the import receptors on the mitochondria by cytoplasmic import factors. The proteins are then imported to the intramitochondrial compartments by the import systems of the outer and inner membranes, TOM and TIM. Mitochondrial outer membrane proteins are synthesized without a cleavable presequence and most of them contain hydrophobic transmembrane domains, which, in conjunction with the flanking segments, function as the (...) mitochondria import signals. Some of the proteins are inserted into the outer membrane by the TOM machinery; the import signal probably arrests further translocation and is released from the translocation channel to the lipid bilayer. The other proteins are inserted into the membrane by a novel pathway independent of the TOM machinery. This article reviews recent developments in the biogenesis of mitochondrial outer membrane proteins. BioEssays 22:364–371, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

Sometimes I think: I'm flying. And why am I flying? Because of the dress. The flesh, I think, is multiplying itself. Here are the children, I think, going away from me and coming to me. If all is one, I think, why this split?My body of thought is likewise made of a womb of wombs. Whatever it begets begets its own body [in this sense I may be said to be multiparous].I am beautiful like a snip of ivory. My face (...) is like the negative of another woman's face. Whatever she does I do moving backward.I spread a hundred fingers up against the wind and the wind dries the lacquer. At these parties I have no given name. I may be called Flora and I may be called Rosamund. The images of color that I set up in space redeem me.In the morning. After the dreams. I see the white body stitched in bed. My corporal body. The veins that store the precious fluid. What I think have they hauled up there from the deep?I get up as in the miracle that Our Teacher Rabbi Loew worked upon a lump of clay and turn on the stove.Sometimes the light bounces off of forks and knives into the eyes. The light of the fork into the eye of the fork and the light of the knife into the eye of the knife.What am I what am I I am thinking flattening out knives and forks on those wooden headstones they call a table?The bread is the showbread and the butter is the clot of my blood. What are they looking for in these blue thighs?The kitchen windows [as in the ancient Icelandic language] are the wind's eye. This is the house and these are the children's table-napkins.... Now. When everything is in place. I am waterboiling. Water pours out of the mouth of the tap into the mouth of the kettle and I am thinking about these hairs that I have. About the hundreds of thousands of fine threads that rise at night in utter silence from the skin. The walls close in on me but my head. As in the Book of Creation. Extracts from nothingness black streams.Through the drinking glasses I see a great field of ice. A white antelope eating a fish.... What am I with a round shoulder and milk muttering prices of chemicals. The cash registers cut the boundaries of my skin.In supermarkets with thousands of tins of canned peas ought to ambulate people covered with hair. Let them block one another's cart like they once did in the hippodromes of Byzantium.Let them speak—with those colorful rags that they tie around their necks—into mouthpieces of telephones. Let their voices run crisscross like stifled crow calls between wires inside the earth. Why have they enclosed me—I, who can cover entire fields like Bermuda grass—within the confines of an electric bell?At 7:20. As if down the ladder of angels painted by Raphael. The child descends the wooden staircase. His toes are depressed precisely according to the divine image of grief. Each toe and its mirror reflection in the other foot.The forest creatures on the pajama fabric with their mouths gaping open as in the sudden vision seen by our primogenitor when they spread the coat of many colors before him and said: Surely he has been torn to pieces.... When the child turned inside me and stood in the placental fluid with his head to the ground, the two of us were the complete converse figure. One head toward the outer boundary, the other head toward the middle point.It was unnatural how the head emerged. Why did it pierce the membrane in which it was enfolded and discharge the water?Windows previously shut were torn apart. Lids of cookware dropped to the floor. This rupture [Michael. Michael.] gave birth to unreason.The child [in my imaginations he is chasing gadflies] is sitting at the table waiting for his cornflakes. He is eating them flake by flake and inside every flake are little crystals of sugar.This game [being able to hold shreds of sugar inside tiny dents] fills his heart.... The light that radiates in every thing is the light of late autumn. I play with it the age-old game. Ask for its name and it replies.The kitchenware too bear their names [just as they bear the form].... I can write an inner play about The Non-Intervention of Time in Kitchenware. Time will get the leading role.In Act One it will set out [like Ulysses] on a journey. The kitchenware will stay put, each ware in its respective place, within daily life.In Acts Two and Three time will travel so far that one or two wares should drop out of place.Act Four will be called Fatal Incidence and Act Five, The Return of Time.... I shout [an inner shout] Dolores Dolores as if I had a friend whose name were like that.How do you do Dolores [I say in my heart] and exchange recipes for dresses with her.Then Dolores sets out in both directions at once. The direction of the great bird in the sky and the direction of Nachlat Binyamin St.... I can see [by means of two mirrors] my silk dressing gown.The silk dressing gown enfolds me and prepares me for verbal exchange. It enables me to communicate information. If it slides down I kneel down until it slides up [and then I kneel down].... When I think of recollection I wonder how the image of myself gets duplicated.The bathtub gets duplicated and the light above the bathtub. Time sends a facsimile of itself.In the black margins outside the sheet of paper hides my mother. Come out come out she is calling to me like you would to a snail.At that time were created the archetypes of things.The complete washbasin. The complete mirror. Next to every sound was inscribed the right clef.Every movement was a perfectum mobile: I jump and by force of this jump I jump again.... Through the window I see the crow called Salpeter.Good morning Old Salpeter. Did you get your black robe back from the dry cleaner?Sometimes you see me obliquely from the right and sometimes obliquely from the left. What am I? A very strange female crow?I adore your rich language. This single word of yours that has in it all the verb stems.... What is so logical about the sky? The window frame.The window frame is like the twelve apostles. Three in each lintel and in their midst [behind the nebula] is sitting the child Michael.The motion of a doll turned over and the motion of the trains sent by him flying in the air are the divine edict. Get'p get'p he tells me all of you and go'ver there.... See Dolores how simple everything is: There is the kitchen. There is the child. There is the wooden staircase.Whom are we to thank for this grace. The colors are so right Dolores and the shapes precise. Every thing I spell out is cut with utmost perfection for the space allotted to it and for the sequence of time.... My biography may easily be canceled.First cancel the alienation. Then cancel the kneeling in the dark. The joy of the assigned date. The bridal veil and the porcelainware.If a medical ground is required I can say I have edema.... I like the words earth quake.Sometimes I think the earth is quaking and the words are not and sometimes the words are quaking and the earth is not.The great catfish know the earth is about to quake and the Chinese who paint the words with a fine paintbrush six lines for the earth and fifteen for this quake set guards to watch the great catfish who knows what is about to take place.... As if after a very severe accident I have to practice life anew.My physiotherapist tells me: Now a slight movement with the right hand. Now a shake of the head.I learn to press handles. To turn sharply in this or that direction.Lately when they ask me anything I pretend that the reply answers the question.Look Dolores how I refute the theory about the formation of species:I take a bubble of soap from the sink and elevate it to the sun.... There is a thing Dolores and it is infinitely good and I shall not tell you what it is.You can hear it in the first hours of the night when darkness is gaping. It has the property of withdrawing into a point tiny as a tittle.Or you can search for it in places where there appears to be something and there is not. (shrink)

Don't tell terrible stories—everyone here has enough of their own. Everyone here has a whole bloody sack of terrible stories, and at the bottom of the sack is a hammer the narrator uses to pound you on the skull the instant you dare not believe your ears. Or to pound you when you do believe. Not long ago I saw a tomboyish girl on Khreshchatyk Street demand money of an elderly woman, threatening to bite her and infect her with syphilis. (...) Don't stroll through Volodymyr Hill Park, don't stroll around the botanical garden, and especially don't stroll on Kontraktova Square. Don't stroll anywhere. Don't go to the pavilion with the Golgotha panorama near St. Alexander's Church. Not even the twelve-meter-tall crucified Christ will save you. Don't go outside when it's dark and people turn into shadows a shade darker than dark. Also don't go where you can be seen from far away. Not to imply that people used to be like a bunch of lilies, but now they stink like a cellar of cabbage.The city, which earlier might have had some fun, is now going crazy. It's like a fish in warm water: it doesn't react to anything, swims slowly like it doesn't care if it swallows a hook or not. The excitement and exaltation pass into oppression, just as our necks have sunk into our shoulders, our shoulders into our lumbars, our lumbars into our nether regions. The holiday turns into a funeral, the parades into explosions, depression into mania. Winter passes into summer, people turn into beasts, the hours into ages, and the ages into hours. It's worth simply walking around the city to see a soldier from an unknown army taking a piss near the opera. Farther on is a row of identical old widows selling ball gowns and candelabra. Then there are the aristocrats and manufacturers who throw so much at the prostitutes that they'll soon be richer than their wives.I returned late through the Kyryliv Wood, not heeding all the warnings that I myself have given here. It really is dangerous—the place is famous for it. There's a madhouse nearby, caves where criminals and the sick can hide out. Also, once upon a time, as they say in fairy tales, the great dragon Zmei Gorynich lived here beside the Puchai River. The stench in these places drives away the most committed misanthropes and even one type of philanthrope—that is, perverts. It sounds dumb, but the stench is cleansing. I don't know where it comes from. After the operating theaters and the rooms with amputees, the stench no longer repelled or attracted me; it just was. And this was a great place to think. As I walked, I considered an incident with our patient.The patient, a respectable individual whose name carries too much weight for me to state it directly, one day began to assault people. He nearly strangled a merchant who he believed asked too much for a beaver coat. He likewise wanted to kill his business partner when he didn't say hello loudly enough. But the worst was, he lost all shame of his own nakedness. At first it was the police who took care of it. When our future patient slipped off his pants and undergarments, he was taken to Kyrylivska, which has had means for dealing with such cases dating back to the day when unhinged Cossacks and composers from Kyiv Mohyla Academy were taken there.During the examination we determined that the patient was experiencing a severe breakdown. His wife added that lately, more than once, he had allowed himself strong words in front of the children and often suffered from ennui. Furthermore, she said, the patient had been undergoing treatment for “the French disease” for some years—which was, obviously, where we needed to start.“Syphilis!” Skorsky spat out the matchstick he was chewing on. He was a specialist on the psychological aspects of diseases related to the venereal. “Tertiary syphilis! When poorly treated, over time ‘the French disease’ can destroy the central nervous system. Hence the patient's chicanery. Such theater!”Skorsky and I had not spoken since the incident at Bilinsky's. Meanwhile, something significant had happened to him. The most boring person on earth, Skorsky had simply caught fire. He said hello and kibitzed. I even heard the doctor got drunk alone in his office, then wandered through the forest. Could he be using narcotic substances?“Cocaine!” was the doctor's second proclamation. It was his favorite treatment for the psychological complications of syphilis. Skorsky himself never took what he called “the universal drug”—good for alcoholism and toothaches, neuroses and morphine dependency—though he had read in an article by a respectable Viennese physician, who used cocaine as a panacea, that it was not addictive. That doctor subsequently recanted, but Skorsky paid no attention. He believed the retraction was made under pressure from pharmacologists who had no incentive to cease production of the medications that cocaine might supplant. Their representatives either paid or threatened the Viennese to repent.As the patient was escorted to his room, he assaulted the orderly, Alevtyna. They tried pulling him off her, but, though he released his fingers from her neck, he buried his teeth in her leg. The poor orderly, who had not until then been attacked by a psychotic, nearly died of fear. Later, panic set in over Skorsky's diagnosis. He told her about the consequences of syphilis: grotesque patterns on one's face due to infection of the skin, mucous membranes, cartilage, and bones. He went on about the devastation to the central nervous system, which they had just observed in real life: “The face starts to look like lace some mangy dogs fought over before rolling in the mud.”Alevtyna, who had not yet regained her faculty of speech, straightened up. Ignoring the slavering male orderlies, she bared her leg to get a better look at the wound. She then ran down the hall and out into the garden, where she fell on the ground to rip up grass and small bunches of daisies. Alevtyna ate them along with the soil in their roots.“Minor hysteria. She needs fifteen milligrams of cocaine.”Skorsky took a snuff box out of his pocket and scooped up some white powder with a toothpick made from a goose feather. He gave the order to close Alevtyna's mouth and one of her nostrils, forcing her to snort the medication.We fretted over her so long that evening fell. I decided to walk down, along the ravine, behind the church.It was unlikely there were any large beasts there, but something was rustling. The pits and mounds, ravines, paths, graves of witches whose living sisters flew in the treetops from time to time, the whispers of the forest spirits, the spirits of the nutcases who died in the hospital, the spirits of the monks from the St. Cyril Monastery, Zmei Gorynich and the bogatyrs who wanted to defeat him. The city would be calmer without this forest. I saw the gaps between the trees and went off in the direction of the tram tracks.As I was coming out of the forest, there was a patch of Amanita muscaria that had been trampled into porridge. A bit farther on, the body of Professor Bilinsky lay killed in the blackberry bushes. The way he was lying it looked as though he had not struggled before death. I quickly examined his body but saw nothing out of the ordinary. There were no wounds, no dirt under the fingernails. Animals had not yet smelled the carrion, but swarms of various insects covered him. Oh, why did I have to find the putrid body?The best thing would be to take the tram to his house to inform his relatives. The doors closed, and I noticed my own calm. This death had not evoked any emotions in me other than a feeling of responsibility, the need to tell the family. But also—some alarm at the thought of who the murderer could be. I knew that it was murder.“Your nose is bleeding.” A woman as round as an onion, carrying two baskets full of strawberries, offered me an ironed and starched handkerchief.“Have I dirtied my shirt?”“No, it's as neat as a pin. It's just your nose that's dirty. Wipe it now before you spray blood on my strawberries.”“No one will see the red on red.”“Ah, but it's salty!”“You know why it's not sweet? We'd drink it like syrup.”“Those with Christ in their heart do not talk that way.”“Are your strawberries expensive?”“Why? What?”“I'm checking to see if you have God in your heart.”“Child, if you knew how I have to work for this berry! I have to weed it a hundred times. In a week, the quitch grass grows as high as a horse. And I water it with water I carry from the stream, it kills my arms... ”“How much are the berries?”“They're not for sale. Anyway, soon money won't mean a thing. Soon all money, all these papers made from the skins of sinners on their satanic presses will be annulled. What matters is how we treat each other.”“So if I try your strawberries for free, my ‘thank you’ will be enough?”“Hands off!” she said and thwacked my fingers.I heard loud laughter behind me—same laughter as from the café near the Continental. There was no one sitting near Alina. (This is what fate looks like, remember.) Without asking, I sat next to her, away from the old lady.“Excuse me, but the night before last didn't you, yes, didn't you intrude on my privacy?” She started right away.“I saw it a little differently. Who was that young man with the mustache who paid me for you?”“Are you checking to see if you can flirt?”The tram stopped. People got on and off.“Are you coming back from the hospital?” she asked. “Don't be shocked. My uncle works there. He's told me all about you.”“An uncle by the name of Skorsky?”(Remember: this is what fate looks like.)“Yes. Skorsky's been strange recently—says things that make me wonder if he hasn't lost his mind. Have you noticed anything?”“I don't know.”“You know perfectly well.”“Where are you going?” I tried to change the subject.“I have to send something to my theater friends in Odesa. By the way, they'll be putting on Oedipus Rex soon in Kyiv—in Ukrainian.”“Greek tragedy in Ukrainian! That's a first.”“Exactly. The troupe is rehearsing now in Odesa. The theater where they will perform this fall is being remodeled.”“Wait. Now I remember where I've seen you before—it was at a performance! Vynnychenko's Black Panther and White Bear, at the Bergonier on Fundukleivska.“The same director is doing the Oedipus. He's my friend.”“He's your friend in what sense?”“Again with that tired subject. By the way, I've been thinking about you.”“And I about you.”“That's good. I was thinking not about you, to be precise, but about that elevator you invited me on.”“Who was that man with you?”“Like a broken record! Even if he had been my fiancé, I'm not bought or inherited. I'm not a brooch or a hundred acres of land, and I'm not a house in Kaniv!... Who was with you when you saw Black Panther?“Ah, so.”“Answer!”“That was my mother. She looks very young. She is coming to Kyiv the day after tomorrow. I can introduce you.”“Oh, this is my stop.”I looked out the window and realized that I had long since passed the stop for Bilinsky's.“Can we see each other again?”“We can. But you have only one chance.”Alina the anarchist wrote something on a scrap of paper and handed it to me.Morning, not morning but a thick porridge (I hate porridge). Dew, thick spit, crushed fruits, urine, all on the sparkling cobblestones. The sun, just barely having made its appearance, is already scorching. The human masses scurry and grumble like poorly digested food inside a stomach.I walked diagonally across St. Sofia's Square, then along the perimeter, then one edge, then again diagonally across. I went underground. The basement café of the Continental Hotel was practically empty. I again asked the server to bring the cloth with the embroidered portrait, but I couldn't remember the musician's last name, only that it ended with -sky. The server said that -sky was currently in the southern cities of Yalta and Odesa. I added that Kurbas, the director, Alina's friend, was also in Odesa, rehearsing Oedipus Rex, and that he'd previously put on Black Panther.I was bored, so I walked along Khreshchatyk and then headed down, calling to mind all the Kyiv churches of Podil: there's Birth of Christ, St. Nicholas on the Shore, Intercession, Pyrohoshcha, Holy Presentation, St. Dymytrii Rostovsky, St. Illia's. And also the Epiphany Brotherhood Monastery, Ascension Convent, and St. Katherine's, all these whipped-cream churches on the waffles of our streets. A few of them reminded me of themselves by appearing suddenly out of nowhere.The smells on Kontraktova Plaza where commerce buzzed were like multicolored light bulbs turning on one after another. Here you could catch the aroma of Balabukha jam, which blended with the next smell, English shoe polish at the Raiskys’ shop. Then the crunchy-smelling cabbage from old women standing in a row like herons and spitting out the shells of sunflower seeds. Farther on, the stench of a good-sized rat that crawled under Mrs. Shevchuk's shop where she sells broadcloth. Oh, she can't scream: no, she'll quietly dig that rat out herself so as to not scare off her clients.I bought a paper and two pairs of underwear. I asked two laughing young chambermaids who were secretly puffing in a grape-filled yard for a smoke. I wandered around Podil until evening when I came across a sawmill near the Dnipro that surprisingly smelled pleasantly of mazut fuel oil. The weather was dry, yet in the middle of the road was an enormous puddle, a deep dark black. A forty-year-old woman in a pale pink dress stood near it. The theatricality of it all provoked me to pose her a question,“Ma'am, what should I do?”But she paid me no attention. I shouted,“What should I do?”“What to do, what to do?” she said in Polish. “Jump in the water and swim so far away that you cannot return.”I quickly crossed a section of the forest. The wind brought a mixture of unpleasant air, like a stinky handkerchief held under one's nose. Passing the trees, I saw light in the spaces between them and exited at the hospital.Outside the windows, two orderlies lay in chairs with their heads thrown back. Two others—fools—ran around the yard in different directions, peering out at... something. The lights on the first floor of the hospital were on, and the staff milled about.“You're just in time!” said Ivan, a tall, young orderly.“For what?”“Your patient ran away! We went into his room and he wasn't there.”“What patient?”“The one who bit Alevtyna,” said Danylo, the other orderly, short and middle-aged.“That's Skorsky's patient, not mine.”I had no intention of helping them. This was all history—like my family, Kyiv, and my previous life. I had no intention of thinking about it. I wanted to go to my office, pack up my field surgery kit, and get out. So what? Their psychotic syphilitic ran away—it happened.Of course, that patient could have something to do with Bilinsky's murder. But that was no longer my problem.“What a strange coincidence!” the doctor on duty said. “Comrade doctor, the other one responsible for this patient was just here.”“And where is he now?”“He took off toward the church to look for the patient.”“Didn't the patient escape earlier?”“Don't know.”“How do you not know? You had better call the police, moron, before he kills someone. And get those sleeping orderlies to look for him.”“They can't... ”“Why not? Should I go wake them?”“They're on morphine.”“And you, I can see, have lost your mind. Go, catch your psycho! If it turns out that he killed Bilinsky—and on your watch—you can't imagine what's in store for you.”I adjusted my homburg and set off in the direction of St. Cyril's, that unwelcoming monolithic cube. I glanced around—what if our escaped syphilitic were to jump out of the bushes and bite or strangle me. I looked around because I wasn't sure of my actions, wasn't sure of my choices. Tripping over a clump of clover, I reached the open doors of the church. I couldn't stop myself from going in.The walls and ceiling were covered with frescoes. There was what used to be an angel rolling up the sky on the southern column of the narthex. But also graffiti: people scratched their names on it so as not to be forgotten—their idea of eternity. Prince Volodymyr the Great compared this activity to the desecration of graves. The vandals paid a fine and were beaten with canes. During the raids of Batu Khan, the church was deserted and cracks appeared all over it. Wild martens and feral dogs sought shelter here; insects swarmed under the ceiling with its red mosaics. Birches grew in its midst. Water seeped in the cracks, the water became ice, the ice widened the cracks, more water seeped in the cracks, becoming more ice that further widened the cracks, the wall split and nearly fell over, and then the wall fell over. Yet the angel is still rolling up the sky... When I reached the exit, I heard a rustling behind me. I turned after I stepped outside: in the depths of the church, like a stick in a pot of tar, stood a man with a large bag thrown over his shoulder and a revolver pointed right at me.“Is that you, Doctor?“Don't move!”“What's... Skorsky, what's with you?”“Don't move, I say!”“What are you doing here?”And finally I understood... Skorsky was himself the psycho! (Really, I had known for a while.)“You are the murderer! I knew it! But—why?”“Shut up.”“It was you. You! The stolen cigarettes, the strange behavior, Bilinsky. If I shout, everybody will come running. They've already called the police!”There was heavy breathing behind me. And then a gun rang out.The city is overgrown with new buildings. They encircle everything that was once on the periphery. Kyiv has become an old lady that can no longer restrain herself in the face of pastries. The city climbs farther. It steps over the swamps, turns the old rivers into a series of lakes; the other bodies of water it drives into canals. The grain that falls from the wild wheat is black. When the sun heats it, the grain melts and trickles into the earth. St. Cyril's stands indestructible. No one spackles the small cracks in its walls with either expensive putty or glues, nor with cheap cement and whitewash. One day a small fox appears in the doorway. It runs inside and along the floor of simple gray tiles. The gods watch from the walls, watch and fall into ruin. The fox runs to the iconostasis. Before it is a time-darkened Virgin Mother and Child in oil on sheets of zinc. The fox runs the metal steps that wind up to the second floor. The fox runs past all the vaults, naves, all the frescoes. A buckthorn seed flies in through a broken window. It will be the first. Soon the buckthorn will grow everywhere. A dumb hare will make its nest in the buckthorn bushes and nightingales will settle in the upper branches to sing until the end of the world. The fox runs between the thick rays that penetrate the windows. It catches one of the rays, squints its eyes, and warms itself in the sun.The shot rang out, but I did not fall. I looked around—and on the church threshold was our syphilis patient bearing a rod. His head lay on the rocks by the doorway.“If only he'd been at the stage of nose deformity! Just imagine: a hole instead of a nose plus a hole from the bullet—like an extra pair of eyes!” Skorsky laughed at the corpse.“We need to call the orderlies.”“They heard the shot. They'll run here on their own. You see, Professor Bilinsky believed it would take two or three years to wrap up this patient's case,” Skorsky told me. “But I took care of it much faster!”“Excuse me, but I'm going crazy in this city. I thought that you were Bilinsky's murderer.”“Just so. Why not? I am Bilinsky's murderer.”“Don't tease. You've changed a lot recently, so... ”“Yes, I've started killing people. You might term such a change significant.”“You have the right to irony.”“I am not being ironic.”“Let's call it sarcasm.”“It's the honest-to-God truth.”“And yes, you have the right to mock me.”“Well then, let's be done. To the horses!”“What horses?”“Alina's waiting!”Alina, her uncle Skorsky, a few others I didn't know, and I rode like the wind that ripped off my homburg and carried it back to Kyiv.“There's a fresco in the choir loft at St. Cyril's where Vrubel painted himself and patients from the hospital as the apostles. When I came across it by accident, I really believed they were saints,” Alina said.“I've never been up there. I've only seen the church from below.”“Remember the way back so you can see it sometime.”“The Puchai River used to flow here. You shouldn't trust the landscape,” Skorsky said, reaching for something, perhaps his bag, just when we left the darkness of the trees and saw the endless steppe ahead of us.We rode all night without stopping. Though no one was chasing us. Though we had nowhere to be. We rode like beasts released from a cage. The promises of the horizon turned what we'd left behind into a cage fit for those from whom freedom had been severed, like an anomaly, at birth.The pre-morning sky looked at first like a sack of turnips—filled with something heavy. But with each verst, the sky became lighter. When it was finally light enough to see clearly, we arrived at a knoll at the foot of a stone wall that from a distance had appeared to be a gigantic piece of halva. The exterior ruins of the castle gave no hint of how it was when all was fine here, when people defended themselves successfully from the nomads’ raids. From far off, the wreckage looked like a natural agglomeration of stones—a rocky elevation, no more: a cluster of cliffs. It would rain a few hundred more times, a few hundred more winds from a few hundred directions would blow on this heap, and it would collapse as though nothing had ever been here.A few stalks of wheat grew from one of the rocks. Someone had probably cast a handful of grain here for some birds that forgot to eat it.“Who could this castle belong to?” I asked Skorsky.“I reckon the Swan Princess,” the doctor rejoined, hoping to sound knowledgeable.From behind one of the piles of gray sandstone emerged a young man in a black reptilian coat and a white papakha as lush, bright, and out of place as a dahlia. His name was Artem. The heat was melting our brains, but he was dressed like that, in rooster fashion, which was popular among the otamans. Artem helped Alina dismount her horse and tried to kiss her on the lips, but she offered him a cheek instead.Had she been racing to see this clown?We entered the yard—the ruins had fashioned an internal space that was more or less protected, at least from strangers’ eyes. It turned out that there were even places where it was possible to hide from the rain, and from there the ruins didn't look half bad.In the center of the court was a table, and on it a wooden bucket with pink gladiolas. How romantic! It all looked like it came from outer space. Where on earth, in the middle of the steppe, far from any village or town, did this table, this simple table, come from? And the gladiolas? The steppe hadn't been plowed in so long that any cultivars would have gone wild, degenerated, dried up completely.A campfire crackled nearby—a little preview of what we would soon do to the houses, villages, and cities. Artem the otaman brought over a cezve from the fire and poured the first portion into a small, copper cup for Alina. He also got out a porcelain cup with images of rosy cherubim—but how...?“Who else would like coffee?”Only Skorsky and I responded. The question excited me, even distracted me from the thought of the kiss I had recently witnessed and the Kyiv I had recently left.“It's obvious who the professors here are; cultured people drink coffee. Are you both doctors?”“Uh-huh.”“For wolves of the steppe, like us, doctors are gold, even more precious than gold. Actually, a Hippocrates like you should eat more, because those in your profession will soon be worth your weight in gold. Work on your figures, both of you.”“Who will take pity on the horses that have to carry us?”“We'll find the horses. And very large doctors can be transported on machine-gun carts. We'll need to seat the otamans near you. Only a fool would shoot at a doctor.”“I think we'll find quite enough fools here.”“With your beard, Doctor, you look like Tsar Nicholas II. But even so you won't be shot. You might even be canonized!”“We've only just arrived and you're going on about executions,” Skorsky grumbled and checked to make sure that he still had his bag.“Apologies, apologies, pardonnez-moi. But you are not merely a doctor. A venereologist! Skorsky, you're a specialist! A venereologist is the most important person in wartime. The most valuable! You are the botanists of war. You can't imagine what varieties of flowers grow here, and these beds have long awaited a proper gardener. Or even just a man with a scythe!”“Bite your tongue,” Alina said. “I don't need to listen to this.”“Yes, yes, of course. Excuse me, my r—. ” He almost said “rose.”We rested all day. We went down to a surprisingly close river overgrown with lilies. We rowed the boats left by fishermen. I talked to Skorsky. He took his bag everywhere, refusing even to swim so he wouldn't have to part with it. I asked him what he had in it, but he said it wasn't my damned business.Alina rowed with the otaman to the middle of the river. They were having a loud discussion. She was waving her hands. The current carried their boat downstream slowly and smoothly. What a nuisance, that current!I tried to meet with Alina one-on-one, but she was avoiding me. In the morning I was confused, by lunch I was sad, and after lunch I got angry.In the evening, I lay on the hot grass and drank another cup (I have no idea where they got such good coffee), which had no effect at all on my sleep. I watched the Perseids. Every year, the Earth passes through the tail of Comet Swift-Tuttle. People can see the meteor shower and make a wish. I wished. I counted forty-seven falling stars. All forty-seven of my wishes were for the same thing.Around the campfire, they were sitting, talking. I saw how he tickled her face with a piece of grass and she brushed him off in annoyance. Then they were screaming at each other. Later they again spoke kindly, after which they again quarreled. My joy grew after each tiny mistake that Artem made. I wanted him to show the worst he was capable of.They were screaming at each other, but all I could hear was beautiful opera singing. The stars fell to the sound of their screaming. The stars blessed my joy.Then this happened: Alina kicked the fire, scattered burnt kindling, and burned some of the grass. Artem grabbed her by the arm, but she broke away from him and ran off to the horses.“Go then! I guarantee you'll get to Katerynoslav and return with your tail between your legs.”“I'm going to Huliai-Pole! To Father Makhno!”I jumped up and ran after her.“Where do you think you're going?” Artem shouted.Really—where was I going? I was going after her: to Huliai-Pole, to Katerynoslav, to Rome, to Washington, to Istanbul, to Montevideo... “Go to sleep,” he said. “Come morning, this coquette will be here, right as rain. We've already been through this show. Tomorrow she'll be right here next to my boot!”... No, she won't.In some sort of shape we entered some town. There were some buildings that were some colors, some trees, some streets, some roads, and some signs. Posts, flustered birds’ nests, echoes, colors, shapes—each of some kind. A wedding procession was coming toward us. If you want to make orange, you need to add yellow to red, and then bam—it's black. If you want to salt the soup, shake in a little, and then bam—two handfuls. You want to say a kind word, and then bam—a punch in the face. I was rocked around like a watermelon on a boat and threw up my breakfast straight into the horse's fluffy mane. Sanko found this hilarious, but I said I'd pulverize him. So Sanko sped ahead.No one knew anything about Alina. The daytime sky was like a poorly washed bowl. The sun was a squashed, rotten apricot. The night sky looked like the sole of a boot to me. The moon was a dirty cheap copper coin that had gotten stuck to the sole. Everything seemed spoiled to me, irrelevant, unnecessary. Without her, this journey was a waste of time.“You'd better stay away from everyone,” Artem said. “You'll infect us with your pining, and pining is worse than the clap.”The wedding procession was before us. The young couple, still utter children, walked so calmly it was as if they didn't see us. As if we were made of a light breeze—our bodies, clothes, our horses and their iron shoes—of the lightest gasses. As if we were visible only to ourselves and the coal-black dog that barked, panting and gasping.The wedding was headed straight for us. We were in the middle of the road, and so were they. We approached each other slowly, a wave going toward a wave. Some ten meters before their indifferent faces, I noticed the color of the bride's eyes. And the coral-colored tulips that fell on the road before her. Round goose eggs on meaty stems, the flowers were falling and falling before her. The bride's eyes were almond shaped.“Hey there,” Artem shouted at me. “Wake up!”I came to and saw the whole village, everyone there, not realizing my group had turned left onto a side street away from the procession. The tulips disappeared—where'd they get tulips in the fall? I was sitting alone on my horse in the middle of the road, and the entire wedding procession came to a stop. I moved to the side, and the throng marched on, cutting off our escape route. We rode a few more meters and came across the synagogue.“You know what, you're right,” said the otaman.“Who is?”“Oleksii is the only one here who's right.”“About what?”Artem turned his horse and raced back. Everyone stood still while he ran his horse into the crowd and began firing his revolver. People scattered in all directions. Artem trotted, cackling like an imbecile. The horse kicked an old guy in the mouth. The man fell, spitting out his gold teeth. We rode up to the commotion and formed ranks, but none of us wanted to join the otaman.The bride stopped in the middle of the street. On both sides were buildings and trees, as well as dust, sky, and sun. She stood still, beautiful, as if nothing had happened. Then she adjusted her garland and walked calmly on.“Well, should we get some sugar now?” Artem laughed, looking at the bride, and off he went toward the sugar factory.It was then I noticed that all of the houses had shutters—fuchsia, blue, ocher—and that all the shutters were closed.We flew toward the dirty building, whistling and shouting. If there had been aesthetes among the otamans, they would certainly have razed the abomination in this field after seizing it. They would have spread soil on top and sown buckwheat. Long live buckwheat!, that wonderful crop. Like hunting dogs hot on the trail, we raced to our defenseless victim, with the baying of hundreds of hounds behind us. The field shook beneath us. We became an artist's canvas, evolving from Realism to Romanticism, Romanticism to Expressionism, Expressionism to Suprematism. If we had been painted in black and white, we would have been splotches (until the ink ran, annihilating all remaining patches of white).Two men stood near the gate—unarmed and undressed, in nothing but their undershirts and boots. Our fervor, our kinship with the elements, our entirety, were all for naught.“Jesus Christ! What bores!” Artem exclaimed. “How boring you are!”“Maybe boring for us, but fireworks for them,” Sanko said, dismounting his horse.“The fear of death engenders creativity,” our otaman—a distinguished philosopher of the early twentieth century, that demonic breed—prophesied.He went on, “Excuse me, but with all due respect, we are not going to search you. Just show us right away where the money is. Why are there so few of you? Don't say there's not much money. I want piles and piles of money! If you don't show it to us, we'll print our own on your skin. Believe me, we will.”We entered the factory grounds. There were no workers, only an enormous mountain of sugar beets that looked like a pile of coal from a distance and a pile of dead rats from up close.“So, did you have a good year?” Artem asked a man in an undershirt.“Not really—too dry.”“Nah, that's fine. You wouldn't have been able to gather most of the harvest this year anyway. There's a fire burning across all of Ukraine, all of Russia. The whole world!”While Artem tossed thoughts like well-chewed sunflower seeds into the crowd, the two men quietly stepped aside and then ran fast ahead to the factory's main hall. The gigantic door slammed shut. The gate was locked behind us! The windows were smashed! The factory roared from inside like a cumbersome machine starting up. Bullets whirred through every window.“Bastards! It's a trap! Quick, after me!”Still on horseback, Artem bounded over to a vast window, low to the ground, and smashed it mercilessly. He broke the frame and jumped inside on his horse. I and a few others followed. We broke into their lair, threw open the doors, and let the other warriors inside.Iron vats of hot sugar were steaming, pipes were clattering; machinery groaned.“Parasites!” Artem gritted his teeth. “I'll get you. I'll get you red sons of bitches. Painted whores!”At the word “painted,” his horse fell to the ground. Lying prone, Artem continued fighting, but the red soldiers wouldn't let him stand. Fighting nearby, I rode over to assist but did not know where to aim. Artem got up, ran forward, and brought his sword down on the head of the closest soldier, all the way to the middle of his skull, to the bridge of his nose. It was like butchering a pig. Artem thrust the sword into the buttock of another who was fleeing and cut off his leg at the bend in the knee.“I'll cut off every last one of your asses! Cut off your asses!” Artem bellowed.A half hour later, the dead were lying, the captured sitting, and the victors doing anything they pleased.“Skorsky, are there a lot of casualties?” I asked the doctor, whose hour it was. I hoped not, because I was too tired to help him.“Just a few. The dead are already dead, and the wounded are not ours.”Though Skorsky rarely asked my help, and though I'd become an ordinary soldier, the doctor in me was still present in the most unpleasant attribute—knowledge. Others saw an eviscerated man, pieces of dusty flesh smeared with clay, soil, sand, and straw. I saw a perfectly formed kidney hanging perfectly from the rest of its body like a child's mitten from its coat. You could try this death on for size. Wear it like a sanbenito of the Inquisition.Artem counted the money and then lay on the floor alongside the gigantic sugar mountain in the middle of the room. From time to time, the crystals rustled as they fell.“I didn't think you'd be such a fighter!” the otaman said without turning toward me. “I thought you'd be healing us. You'd keep to the rear and we'd hide you like a girl. But here you are, in the vanguard, like a lion!”“I got excited,” I told him, choosing not to react to the “girl” part.“’Cause Alina said there was no sense counting on you to fight.”“Really?”“Does that sting?”“Why would it? I'm a doctor—not everyone is. It requires a brain. Unlike waving a sword.”“Yeah, yeah. I gave her gladiolas. We were lying in the boat near that castle, doing all manner of things, and she told me all about you. How you met.”“You were lying in that boat talking about me?”“It was the day before you left Kyiv. You agreed to go with the anarchists so quickly!”“Were you surprised? Doctors make fast decisions.”“But you probably had great prospects. Your parents are rich, right?”“And who are your parents?”“Probably all your relatives fled abroad—bourgeois. Why did you stay?”“What the hell's your point?”“Alina, by the way, died a while ago. Probably.”“Don't jinx her.”“Listen here,” he said, staring at the ceiling. “And listen good. If you have designs on her—dead or alive—it's best you castrate yourself now.”“After you.”“If I want to kill somebody, you know, I just do it.”At last he looked at me. I was lying on the floor nearby and looking in his direction, sweaty and relaxed, my appearance complemented by my disdain for his opinion, his authority, his stupid hat. His everything.Artem raised his arm above his head, stuck a finger in the sugar mountain, and licked it. We both got up. Had I anticipated this turn of events, I would have readied a gift for him. Artem held his revolver. Under my hand I found a knife the workers used for gathering beets: it was a deliberately sharpened arc they sank into the swollen brassicas. I jumped up and quickly stepped around the sugar mountain.Artem's bullet hit a pane and broke the glass.“Not man enough for hand-to-hand?”The otaman shot again.“You should've challenged me to a duel, you romantic!”Encrusted with white crystals, I charged Artem from the sugar mountain. We fell in, and the sugar stuck in our hair, mustaches, nostrils, armpits.The gang ran in to get us apart, then backed off because it had nothing to do with them. By now the sugar mountain had burst its banks. Of the once perfect pyramid, a deformed mound remained.Wounded, Artem fell on the sugar mound, turning the white red.I stood before the gang sugar-coated and holding a bloody hook. The old otaman was drawing his last breath. Blood trickled from the corner of Artem's mouth and streamed from the left side of his breast.“What's the commotion?” Old Roman had just come in.“Be quiet,” the boys told him. And a good thing they did.“You killed him? You killed the otaman!”“Shut your mouth,” the boys told him.“You... ”I slugged Roman's stinky herring mouth. How did that son of a bitch find pickled herring in a sugar factory? My fist was now bigger and stronger than ever before, a steel anvil that could split nails and shatter memorial plaques. The unfortunate man's jaw twisted like an upper millstone that had gone off track from the lower.“Let's get out of here and go to Makhno's camp,” I gave my first order.We galloped so fast the grass burned beneath us. The birds and bugs had no time to fly out of the way; hooves trampled the burrows of rodents who didn't dare crawl out of their holes for a long time after. We raced like no one had ever raced before.The steppe, that sly fox, pretended to be an innocent fool. The steppe said, “I'm like Adam: I don't even know my own name.” But its grass harbored the tracks of thousands of armies and the heels of Herodotus, the crunch of Trypillia vessels, and the smell of Scythian hemp, Roman coins, clay figures of wolf people, the chevrons of Denikin's army, glass from the Chekists’ ruby stars, traces of uranium from flying saucers. I threatened it: “Steppe, show me your layers, or I will burn you, plow you under, flood you.” But it just replied: “I'm like Adam: I don't yet know my name.”I lost geography as if it were a silver coin. It fell out of my pocket and rolled through the feather grass that blanketed the steppe in white foam. The open space ahead was so endless that the whole world might as well have been steppe. If people ended up here from somewhere else, they would conclude they were on another planet. The coin fell and became an argentum, became one with the ring on the hand of the princess who had one green eye and one blue, with the twisted candlestick at the monastery on the other side of the steppe, with melted ingots. It broke down into simpler elements, simpler and simpler yet. The horse carried me spreading the seeds of northern plants to the south, just as southern riders had once brought flowers and weeds to the north. And then I turned back. Just as I had no geography, I had no time. Every night I fell asleep with the thought that the next day I would again race. Through all spacelessness, all timelessness. I exchanged one horse for another, got on a train, on a boat, traversed forty versts on foot—in rain that brought the river up to the road, in heat that overturned cattle. The earth I walked on became mine. Mine was the water in the lakes and springs, clean water, dirty water, enlightened water, contaminated with oil, stinking of algae, of fish that died in wells, stinking of the memory of atrocities, water as clean as broken bread. The water did not become Alina.I was doing this for her: I got the basturma out from under my saddle, sodden with the horse's sweat, sliced the throat of a rich man whose daughter I had danced with at a ball, climbed into a vat of beet juice and took a sugar bath, carried out the expropriation of the savings banks, wiped the sweat from my face with my shirt—and the cloth turned red; I didn't know from what. If it was someone else's blood, I didn't care; if it was my own, even less.We mostly came across Reds. We scraped them up like old red paint on a door in order to repaint the boards black. Black looked better. Red is tasteless, but black has style. Healthy men died before us of myocardial rupture like bunnies found in the nest. The ones whose hearts were sewn of steel wire envied the deceased. Seizing estates, banks, distilleries, and prisons reminded us of gathering in the harvest. If you're too lazy to pick an apple, you can shake the tree; some of the fruit gets bruised when it falls. We seized buildings like we were shaking apple trees. No one picked the fruits, we just shook: shook under the beds, under the tables, behind the curtains. No, there was no picking. We just shook until the red juice spurted from the apples.Near the Khorol River with Father Makhno and me in charge, we captured sixteen machine guns and four cannons, as well as five hundred prisoners who immediately came over to our side. The villagers voluntarily gave us bread and cheese, chickens and kvas. People joined us. The front of the machine-gun cart said “You can't run,” and “You won't catch us” at the back. We took factory after factory. Millions of karbovantsi, thousands of poods of sugar, weapons. We smashed the telephone exchanges and captured the telegraphs. We made alliances with some and then with others. Lenin, Wrangel, Frunze, the Germans, Chinese, Australians, Kaiser Wilhelm II, Cleopatra, Maria Theresa Walburga Amalia Christina. We ran the steppe. There were a hundred thousand of us. There were three hundred thousand of them. There were three hundred thousand of us. There were a million of them. There were two million of them. We were all of humanity. We were so many that we were none.The nobles’ estates were long ago forsaken. In the people's deepest trunks lay silks and guipure laces that were once perhaps used only to cover a table. Five steps from the barn in the direction of the pear tree, some silver candlesticks are buried; there's a plaster figure of an angel in the chicken coop, covered with shit and feathers.I was reluctant to be going to my home, but I didn't see any way out. Fate intended me to be a different being from the one I was before.Here my grandfathers and great-grandfathers were born. Here the ones who caused my grandfathers and great-grandfathers to flee had stopped. When we were still far off I noticed that someone was in the house. It was our men—Skorsky had brought them here, about twenty in all. I asked Sanko, whom I had walked with side by side more than once, where the doctor was now. All the men answered that he was around somewhere, but I didn't see him that evening.In 1918, the spirit of my great-grandfather Stepan, along with my mother and uncle, had gotten into a britzka and scrambled off to Paris, to Napoleon, against whom my great-grandfather had fought with the Cossacks, to whom the Russians promised to return self-rule. Following him in the cart went the soul of Grandpa Oleh, who lost a finger when he cut down the old linden near the house; his second finger was blown off by a cannonball near Balaklava, and later his entire hand was cut off by some Turk. Next went the spirit of my father, also Stepan, who did not take part in any war but died of measles at the age of forty. They all got the hell out of here. First, they went to Kyiv, led by my mother, Tamara Makarivna, in order to collect Uncle's family and me, their son. And their son, it turns out, has now come back to rob his own home (I didn't drive my war buddies away, did I?). It's a shame that I didn't know where the bathtub was, or whatever they bathed me in when I was small. It would have been good to walk through the ranks of anarchists with that basin and tell them all to spit into it.Remembering every room, I carried Alina upstairs to my mother's bedchamber. There was no longer furniture or pictures, only bare walls. The bed and mattress remained, but that was enough. Mother hated noise, so she set up her room far away from the running in the halls and the creaks on the stairs. I adjusted the mattress; in a gap, looking like a stalk of wheat, there lay a gold bracelet that she lost in the haste and that the thieves could not find in the mayhem. I tucked it into my pocket.The place could still be saved. It was strong, built under the leadership of my grandfather, who knew how to do it right. He built a sawmill, a gristmill, a dress factory (today it's probably been ransacked, maybe even by our own men).Alina had a complete, displaced break in her right fibula. We needed water first. I went downstairs—the guys were dragging out the piano like an old cow to the slaughter.“What are you doing with that?”“Taking it out.”“Why?”“What's it to you? We want to have fun.”“Can you play?”“We're not your bourgeois lily-handed bitches.”They couldn't play, but they were famous at destruction. “Noise is the music of the new time,” one of the smarter among them might have said. “But noise is the opposite of music. Just as a rose is the opposite of your ugly mugs,” I'd have responded if there was anyone to say it to. I could also have said that this was a Bosendorfer grand piano, that it was very valuable—but do the guys not deserve such a luxury?“Why are you so boring? We're relaxing.”“Then let me play a little first.”“Go ahead, but fast. One-two.”So I played. As before. My fingers ran up and down the black and white keys, which weren't simply keys of these, the simplest, colors. These were the keys that remembered my fingers specifically—achieved by that slovenly German Katerina, our governess. She knew a bundle of languages, could play the piano, and was interested in the latest scientific discoveries. But she had not an ounce of sympathy for anyone who couldn't master anything on the first try. More than once she hit my pinkie against the black key that remembered every one of its four thousand touches. She would pound it on the key and shout, “Si bémol! Si bémol,” and later bang my fingers and translate, “B flach! B flach!”I played. I could not expose myself, so the only thing I could do was believe in miracles. What if these coarse men saw value in this bit of furniture so unintelligible to them? And what if they didn't destroy it, this emblem of my childhood, my land, my air, which I could protect in no other way? My air. My water.“Shchedryk, shchedryk, shchedrivochka,” one of them who recognized the tune began to sing along.“Look at you.” They did not expect music from me, who had until recently been drinking blood like water.They said, “Again, again!”A group of curious men gathered around me. They were ordinary farmers, thieves, and recidivists, peasants and workers, everyone except for Skorsky. They needed this music as they needed baths. The music cleansed them from the inside, perhaps. They had not heard anything besides the whistle of a bullet, the neighing of a horse, or the knocking of a chisel and the whirring of a saw, amputating limbs, for a long time.But it could not go on long. I did not close the piano lid, just stood and went to fetch water for Alina, leaving the unfinished song for later. The well was to the north—that is, at the “Head.” My father once promised to give me a compass if I could learn to identify the ends of the earth by means of the sun. And to make it easier to remember, I gave each one of them a name: the east where the day begins was “Right” (my right hand), the west “Left,” the north “Head,” and the south “Feet.” Back when I could still do whatever I wanted all day long, I would wake in the morning and say: I'm going to the Feet. The mound was at the Feet, Left had the river, Right had the forest. It was only to the Head that I rarely went, because a village was located there. When the villagers saw me, they would speak in whispers and avoid the master's son.... I wiped her brow and her burning, sunken cheeks. I lay down next to her to feel the heat of her skin.When the fire in Alina calmed slightly, I went out into our orchard. My father had once been given a gift from Japan—a tulip tree that blossomed with yellow-green flowers. It had to have grown in the time that I was away. It would have been fatal had it been cut down. I again took the stairs down into the drawing room and came across nobody—they had all disappeared in search of food or were hidden away in their burrows. In the middle of the hall, like an opened rib cage, was the piano, irreparably shattered.B Flach! B Flach!Translation © Ali Kinsella 2022. (shrink)

The human immune system can directly lyse invading micro‐organisms and aberrant host cells by generating pores in the cell envelope, called membrane attack complexes (MACs). Recent studies using single‐particle cryoelectron microscopy have revealed that the MAC is an asymmetric, flexible pore and have provided a structural basis on how the MAC ruptures single lipid membranes. Despite these insights, it remains unclear how the MAC ruptures the composite cell envelope of Gram‐negative bacteria. Recent functional studies on Gram‐negative bacteria elucidate that (...) local assembly of MAC pores by surface‐bound C5 convertase enzymes is essential to stably insert these pores into the bacterial outer membrane (OM). These convertase‐generated MAC pores can subsequently efficiently damage the bacterial inner membrane (IM), which is essential for bacterial killing. This review summarizes these recent insights of MAC assembly and discusses how MAC pores kill Gram‐negative bacteria. Furthermore, this review elaborates on how MAC‐dependent OM damage could lead to IM destabilization, which is currently not well understood. A better understanding on how MAC pores kill bacteria could facilitate the future development of novel strategies to treat infections with Gram‐negative bacteria. (shrink)

The hemolysin toxin (HlyA) is secreted across both the cytoplasmic and outer membranes of pathogenic Escherichia coli and forms membrane pores in cells of the host immune system, causing cell dysfunction and death. The processes underlying the interaction of HlyA with the bacterial and mammalian cell membranes are remarkable. Secretion of HlyA occurs without a periplasmic intermediate and is directed by an uncleaved C‐terminal targetting signal and the HlyB and HlyD translocator proteins, the former being a member of (...) a transporter superfamily central to import and export of a wide range of substrates by prokaryotic and eukaryotic cells. The separate process by which HlyA is targetted to mammalian cell membranes is dependent upon fatty acylation of a non‐toxic precursor, proHlyA. This is achieved by a novel mechanism directed by the activator protein HlyC, which binds to an internal proHlyA recognition sequence and provides specificity for the transfer of fatty acid from cellular acyl carrier protein. (shrink)

Mammalian outer hair cells generate mechanical forces at acoustic frequencies and can thus amplify the sound stimulus within the inner ear. The mechanism of force generation depends upon the plasma membrane potential but not upon either calcium or ATP. Forces are generated in the lateral cortex along the full length of the cell. The cortex includes a two‐dimensional cytoskeletal lattice composed of circumferential filaments 6–7 nm thick that are cross‐linked by filaments 3–4 nm thick and 40–60 nm long. (...) The two filament types may, respectively, be actin and some form of spectrin. The lattice reinforces the cylindrical shape of the cell and permits limited changes in length. Beneath it lie the lateral cisternae, a regular system of multi‐layered membranes. Force–generation may depend upon voltage‐dependent shape changes in proteins that lie either in the plasma membrane or in the cytoskeletal lattice. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Buddhist-Christian Studies 22 (2002) 31-46 [Access article in PDF] Remedying Globalization and Consumerism: Joining the Inner and Outer Journeys in "Perfect Balance" Judith Simmer-Brown Naropa University One hundred forty years ago, Abraham Lincoln wrote in a prophetic voice: I see in the near future a crisis approaching that unnerves me and causes me to tremble for the safety of my country.... Corporations have been enthroned and an era (...) of corruption in high places will follow, and the money power of the country will endeavor to prolong its reign by working upon the prejudices of the people until all wealth is aggregated in a few hands and the Republic is destroyed. 1As the global economy has grown and the economic gap between the poor nations and the rich nations has become enormous, we are realizing Lincoln's nightmare.Globalization has effects more devastating than Lincoln could have imagined. What do we mean by globalization? The president of Nabisco once defined it as "a world of homogeneous consumption." 2 It is a world in which everyone, no matter what latitude or longitude, eats the same food, wears the same clothing, and derives pleasure from the same entertainment. It is the world of McDonald's, Holiday Inn, James Bond movies, Nike shoes, and Coca-Cola. Noam Chomsky, in a lecture at Boston College, described globalization as the "new face of capitalism." 3 It is a network of power centered in corporate interests and financial institutions that controls the flow of capital in order to promote the financial interests of those in power to the detriment of all others. The strategies of globalization have to do with centralizing all power in financial interest, reducing all value to money, and subsuming governments to the interests of the corporations. According to Chomsky, the strategies employed by the transnational network are designed to consolidate this control:Buy the executive branch of the states involved;Own the legislative branch through lobbyists, campaign contributions, and term extensions, or whatever else may work; [End Page 31]Set the conditions in which policy is determined, asserting the power of global capital;Control the doctrine and information systems, especially to invent new needs in order to bolster a culture of fashionable consumption. 4The players in this transnational network reside in the wealthy countries of the world, especially the governments of the G8, and most especially the United States. The global dominance of the International Monetary Fund and the World Trade Organization is funded by U.S. dollars funneled to them by the network. Yet this capital is not really exchange of cash; instead, it is speculation. Chomsky commented: In the last twenty-five years, there has been a huge explosion of financial institutions and financial capital, most of it speculative, with little actual capital in the economy. The flow of capital is $1.5 trillion per day, very little of it productive. Ninety-five percent of it is destructive and speculative. The return time on investments is very rapid; eighty percent has a return time of a week, and often it is less than a day. This daily flow of capital in international markets is twice the total foreign exchange of all states together. This concentrated power is interlinked, determining states' decisions. 5States are no longer autonomous agents; transnational economic interests have taken precedence over national sovereignty, regional power, and military concerns.The impact on developing countries and rural economies is devastating. The global monoculture is eradicating cultural diversity, replacing locally adapted forms of production with industrial systems divorced from natural cycles. Agriculture has become centrally managed and chemically dependent, delivering a narrower range of transportable foods to the international market. This, of course, robs the vitality of local communities and moves a greater proportion of villagers into urban life, creating megalopolises. Because everyone becomes dependent upon the same resources, "globalization creates efficiency for corporations, but it also creates artificial scarcity for consumers, thus heightening competitive pressures.... Globalization means the undermining of the livelihoods and cultural identities of the majority of the world's peoples." 6... (shrink)

Recently, a review regarding the mechanics and evolution of mitochondrial fission appeared in Nature. Surprisingly, it stated authoritatively that the mitochondrial outer membrane, in contrast with the inner membrane of bacterial descent, was acquired from the host, presumably during uptake. However, it has been known for quite some time that this membrane was also derived from the Gram‐negative, alpha‐proteobacterium related precursor of present‐day mitochondria. The zombie idea of the host membrane still surrounding the endosymbiont is (...) not only wrong, but more importantly, might hamper the proper conception of possible scenarios of eukaryogenesis. Why? Because it steers the imagination not only with regard to possible uptake mechanisms, but also regarding what went on before. Here I critically discuss both the evidence for the continuity of the bacterial outer membrane, the reasons for the persistence of the erroneous host membrane hypothesis and the wider implications of these misconceptions for the ideas regarding events occurring during the first steps towards the evolution of the eukaryotes and later major eukaryotic differentiations. I will also highlight some of the latest insights regarding different instances of endosymbiont evolution. (shrink)

Multidrug-resistant Acinetobacter baumannii is recognized to be among the most difficult antimicrobial-resistant gram negative bacilli to control and treat. One of the major challenges that the pathogenic bacteria face in their host is the scarcity of freely available iron. To survive under such conditions, bacteria express new proteins on their outer membrane and also secrete iron chelators called siderophores. Antibodies directed against these proteins associated with iron uptake exert a bacteriostatic or bactericidal effect against A. baumanii in vitro, (...) by blocking siderophore mediated iron uptake pathways. Attempts should be made to discover peptides that could mimic protein epitopes and possess the same immunogenicity as the whole protein. Subsequently, theoretical methods for epitope prediction have been developed leading to synthesis of such peptides that are important for development of immunodiagnostic tests and vaccines. The present study was designed to in silico resolving the major obstacles in the control or in prevention of the diseases caused by A. baumannii. We exploited bioinformatic tools to better understand and characterize the Baumannii acinetobactin utilization structure of A. baumannii and select appropriate regions as effective B cell epitopes. In conclusion, amino acids 26–191 of cork domain and 321–635 of part of the barrel domain including L4–L9, were selected as vaccine candidates. These two regions contain functional exposed amino acids with higher score of B cell epitopes properties. Majority of amino acids are hydrophilic, flexible, accessible, and favorable for B cells from secondary structure point of view. (shrink)

Neisseria gonorrhoeae, the bacterium that causes the sexually transmitted disease gonorrhea, demonstrates extensive antigenic heterogeneity in its surface components. The organism has the capacity to switch on and off the synthesis of different versions of components such as pili, outer membrane proteins, and lipopolysaccharide. Recent studies have shown that the gonococcus uses novel and complex mechanisms, of types not described previously, to store different versions of genetic information for surface proteins, and to regulate expression of those genes.

The pathogenic, Gram‐negative bacteria, Neisseria gon‐orrhoeae, Neisseria meningitidis and Haemophilus influenzae, secrete immunoglobulin A1 proteases into their extracellular surroundings. An extraordinary feature in the secretory pathway of these putative virulence factors is a self‐directed outer membrane transport step allowing the proteins to be secreted autonomously, even from foreign Gram‐negative host cells like Escherichia coli. Here we summarize recent achievements in the understanding of IgA protease outer membrane translocation.

This chapter contains sections titled: Phenomenological Reflections on Cycling Extended Embodiment – Cycling Thoughts Campagnolo Ti Amo (I Love You) A Multiple Bombardment of the Senses Settling of Accounts – In the Long Run It Is Impossible to Cheat Cycle Speech A Trembling Experience A Descent – Living Up to Its Reputation A Collective Shiver Notes.

Secretory proteins and membranes move in transfer vesicles from the rough endoplasmic reticulum through the transitional region to the outer saccule of the Golgi complex. In both arthropod and vertebrate cells, the GC beads are a characteristic structural component of the transitional region. The beads are particles about half the size of ribosomes arranged equidistantly from one another and the smooth face of the ER. In an active GC, the beads are in rings through which the ER membrane (...) emerges to form transfer vesicles. The beads may be part of the energy‐dependent step required for the movement of proteins along the secretory pathway, since they lose their ring arrangement under conditions that lower cellular ATP. The beads are organizers for Golgi complexes in the sense that they are the first recognizable components of new GCs as they arise from ER. Arthropod GC beads, but not those of vertebrates, can be visualized through their reaction with bismuth in vivo and in fixed tissue. Useful paradigms for traffic between the ER and the GC need to combine structural and biochemical information. Insect fat body, with its readily resolvable bismuth‐stained beads and easily fractionated cell components may have particular value for this problem. (shrink)

Rapid polymerization and depolymerization of actin filaments in response to extracellular stimuli is required for normal cell motility and development. Profilin is one of the most important actin‐binding proteins; it regulates actin polymerization and interacts with many cytoskeletal proteins that link actin to extracellular membrane. The molecular mechanism of profilin has been extensively considered and debated in the literature for over two decades. Here we discuss several accepted hypotheses regarding the mechanism of profilin function as well as new recently (...) emerged possibilities. Thermal noise is routine in molecular world and unsurprisingly, nature has found a way to utilize it. An increasing amount of theoretical and experimental research suggests that fluctuation‐based processes play important roles in many cell events. Here we show how a fluctuation‐based process of exchange diffusion is involved in the regulation of actin polymerization. (shrink)

PLATO’S Protagoras is composed of three distinct frames. The outer frame consists in Socrates’ brief discussion with an unnamed companion. The remainder of the Protagoras is willingly narrated by Socrates to the companion, from memory of course, and apparently right after the main action. The inner frame consists in Socrates’ dialogue with Hippocrates. Roused before dawn by the impetuous young man, Socrates leads Hippocrates to reflect on the wisdom of his enthusiastic desire to study with Protagoras. This is a (...) classic and successful little example of Socratic dialogue. He then takes Hippocrates to meet Protagoras; the bulk of the dialogue—call it the innermost frame—consists in Socrates’ exchanges with Protagoras. Hippocrates does not utter a word in this part of the dialogue, though it is initiated at his request and seems undertaken by Socrates for his benefit. (shrink)

We highlight the various domains of the flavivirus virulence factor NS1 and speculate on potential implications of the NS1 3D structure in understanding its role in flavivirus pathogenesis. Flavivirus non‐structural protein 1 (NS1) is a virulence factor with dual functions in genome replication and immune evasion. Crystal structures of NS1, combined with reconstructions from electron microscopy (EM), provide insight into the architecture of dimeric NS1 on cell membranes and the assembly of a secreted hexameric NS1‐lipid complex found in patient sera. (...) Three structural domains of NS1 likely have distinct roles in membrane association, replication complex assembly, and immune system avoidance. A conserved hydrophobic inner face is sequestered either on the membrane or in the interior of the secreted hexamer and contains regions implicated in viral replication. The exposed variable outer face is presented to cellular and secreted components of the immune system in infected patients and contains candidate regions for immune system modulation. We anticipate that knowledge of the distinct NS1 domains and assembly will lead to advances in elucidating virus‐host interactions mediated through NS1 and in dissecting the role of NS1 in viral genome replication. (shrink)

Reasons are given for suggesting that individuation of the human embryo does not begin until the primitive streak forms at about the fourteenth day after conception; this view, though contested by many, is held by very many committed Christians of all denominations. In the conceptus or pre-embryo, after the formation of a blastocyst at about four-five days after fertilisation, biopsy of a single cell from the outer layer of cells (which later can form the membranes and placenta) can be (...) used to determine the sex of the conceptus and will ultimately be used to detect the presence of an abnormal gene such as that for Duchenne-type muscular dystrophy, without detriment to development of the basal cell mass from which the embryo forms. The potential benefits in the prevention of inherited disease are profound. (shrink)

The retinal pigment epithelium (RPE) is a specialized epithelium at the back of the eye that carries out a variety of functions essential for visual health. Recent studies have advanced our molecular understanding of one of the major functions of the RPE; phagocytosis of spent photoreceptor outer segments (POS). Notably, a mechanical link, formed between apical integrins bound to extracellular POS and the intracellular actomyosin cytoskeleton, is proposed to drive the internalization of POS. The process may involve a “nibbling” (...) action, as an initial step, to sever outer segment tips. These insights have led us to hypothesize an “integrin adhesome‐like” network, atypically assembled at apical membrane RPE‐POS contacts. I propose that this hypothetical network orchestrates the complex membrane remodeling events required for particle internalization. Therefore, its analysis and characterization will likely lead to a more comprehensive understanding of the molecular mechanisms that control POS phagocytosis. (shrink)

What kind of symbiosis between archaeon and bacterium gave rise to their eventual merger at the origin of the eukaryotes? I hypothesize that conditions favouring bacterial uptake were based on exchange of intermediate carbohydrate metabolites required by recurring changes in availability and use of the two different terminal electron chain acceptors, the bacterial one being oxygen. Oxygen won, and definitive loss of the archaeal membrane potential allowed permanent establishment of the bacterial partner as the proto‐mitochondrion, further metabolic integration (...) and highly efficient ATP production. This represents initial symbiogenesis, when crucial eukaryotic traits arose in response to the archaeon‐bacterium merger. The attendant generation of internal reactive oxygen species (ROS) gave rise to a myriad of further eukaryotic adaptations, such as extreme mitochondrial genome reduction, nuclei, peroxisomes and meiotic sex. Eukaryotic origins could have started with shuffling intermediate metabolites as is still essential today. (shrink)

Apoptosis is a physiological mechanism for the removal of unwanted or damaged cells. Apoptotic cells are rarely seen in living tissues, however, because of their rapid and efficient removal by phagocytosis. Phagocytotic cells such as macrophages or dendritic cells recognize apoptotic cells by specific changes of cell surface markers, which usually are not present on normal cells. One such event is the exposure of phosphatidylserine, which moves from the plasma membrane inner leaflet to the outer leaflet in preapoptotic (...) cells. An unresolved problem, however, was the nature of the phosphatidylserine receptor on the phagocytotic cells. In a recent issue of Nature, Fadok et al.(1) have reported the cloning of a phosphatidylserine receptor using an antibody raised against activated macrophages. Antibody treatment of these macrophages blocks this capacity to engulf. BioEssays 22:878–881, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

Transport of macromolecules from the nucleus to the cytoplasm is essential for nearly all cellular and developmental events, and when mis‐regulated, is associated with diseases, tumor formation/growth, and cancer progression. Nuclear Envelope (NE)‐budding is a newly appreciated nuclear export pathway for large macromolecular machineries, including those assembled to allow co‐regulation of functionally related components, that bypasses canonical nuclear export through nuclear pores. In this pathway, large macromolecular complexes are enveloped by the inner nuclear membrane, transverse the perinuclear space, and (...) then exit through the outer nuclear membrane to release its contents into the cytoplasm. NE‐budding is a conserved process and shares many features with nuclear egress mechanisms used by herpesviruses. Despite its biological importance and clinical relevance, little is yet known about the regulatory and structural machineries that allow NE‐budding to occur in any system. Here we summarize what is currently known or proposed for this intriguing nuclear export process. (shrink)

Apoptosis proteins have a central role in the development and homeostasis of an organism. These proteins are very important for understanding the mechanism of programmed cell death, and their function is related to their types. According to the classification scheme by Zhou and Doctor (2003), the apoptosis proteins are categorized into the following four types: (1) cytoplasmic protein; (2) plasma membrane-bound protein; (3) mitochondrial inner and outer proteins; (4) other proteins. A powerful learning machine, the Support Vector Machine, (...) is applied for predicting the type of a given apoptosis protein by incorporating the sqrt-amino acid composition effect. High success rates were obtained by the re-substitute test (98/98 = 100 %) and the jackknife test (89/98 = 90.8%). (shrink)

Recoverin is a Ca2+-binding protein found primarily in vertebrate photoreceptors. The proposed physiological function of recoverin is based on the finding that recoverin inhibits light-stimulated phosphorylation of rhodopsin. Recoverin interacts with rod outer segment membranes in a Ca2+-dependent manner. This interaction requires N-terminal acylation of recoverin. Four types of fatty acids have been detected on the N-terminus of recoverin, but the functional significance of this heterogeneous acylation is not yet clear.

The first and rate‐limiting step of steroidogenesis is the transfer of cholesterol from the outer mitochondrial membrane to the inner membrane where it is converted to pregnenolone by cytochrome P450 side‐chain cleavage (P450scc). This reaction is modulated in the gonads and adrenals by the steroidogenic acute regulatory protein (StAR), however, the mechanism used by StAR is not understood. The outer and inner mitochondrial membranes are joined at contact sites that are thought to be held in place (...) by protein complexes that bridge the two membranes. While it is generally accepted that proteins are imported into the mitochondrion via contact sites, it is not clear whether cholesterol takes the same conduit to the inner membrane. Strategies to combat diseases caused by interrupted cholesterol transfer will rely on a full understanding of the steroidogenic mechanism. The challenge for the future is to determine whether StAR relies on the molecular architecture that spans the mitochondrial intermembrane space to deliver its cargo. BioEssays 25:252–258, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

The recent development of RNA replicating protocells and capsules that enclose complex biosynthetic cascade reactions are encouraging signs that we are gradually getting better at mastering the complexity of biological systems. The road to truly cellular compartments is still very long, but concrete progress is being made. Compartmentalization is a crucial natural methodology to enable control over biological processes occurring within the living cell. In fact, compartmentalization has been considered by some theories to be instrumental in the creation of life. (...) With the advancement of chemical biology, artificial compartments that can mimic the cell as a whole, or that can be regarded as cell organelles, have recently received much attention. The membrane between the inner and outer environment of the compartment has to meet specific requirements, such as semi‐permeability, to allow communication and molecular transport over the border. The membrane can either be built from natural constituents or from synthetic polymers, introducing robustness to the capsule. (shrink)

The closing chapters of Aristotle’s Nicomachean Ethics x are regularly described as “puzzling,” “extremely abrupt,” “awkward,” or “surprising” to readers. Whereas the previous nine books described—sometimes in lavish detail—the multifold ethical virtues of an embodied person situated within communities of family, friends, and fellow-citizens, NE x 6-8 extol the rarified, god-like and solitary existence of a sophos or sage (1179a32). The ethical virtues that take up approximately the first half of the Ethics describe moral exempla who experience fear fighting for (...) their communities, are sensitive to the esteem and recognition of others, and feel love for a desire to live together with a wide variety of kinds of friends. Such good people take pleasure in prudently expending sums to improve their communities—communities in which they exchange goods and participate in ruling and being ruled in a cooperative fashion. The exemplum of x 7-8, by contrast, is a person whose activity consists almost entirely in exercising his or her mind (nous)—a part of one’s soul that Aristotle explicitly notes is disconnected from human emotions and that can be exercised, insofar as one as wise, in a wholly solitary fashion (1178a15-16, a19-20; 1177a33-34). Although Aristotle’s claim that a “life in accord with the mind” is best and most pleasant (1178a6-7) may jar the intuitions of many people—he himself endorses Anaxagoras’ claim that the happy person will appear as “someone who is absurd” (atopos, 1179a15) to most people—it is false to claim that his conclusions in NE x 6-8 are unexpected or unanticipated, or that the text is in any way discontinuous with what precedes it. The Nicomachean Ethics exhibits aspects of ring-composition both within the work as a whole and within book 10. In NE i 5 Aristotle introduces his rendition of a trope that he inherits (most immediately) from Plato, viz. that the problem of the good can be considered like a contest between three different kinds of life—the life of enjoyment (apolaustikos), the life of politics (politikos), and the life of contemplation (theôrêtikos). NE x 6-8 returns to that contest, rendering a verdict about which life takes first, second, and third place. As the opening lines of NE x 6 note, that verdict presupposes central claims articulated between the first and last books of the Ethics, specifically about the nature of the virtues, the nature of friendship, and the nature of pleasure. NE i 5 and x 6-8 thus serve as “bookends” which encase arguments and proposition located between them. Book 10 exhibits a similar ring-composition. NE x opens with methodological reflection on the gap between the theoretical positions that thinkers articulate and the way they live their lives (especially in the case of scolds who simultaneously criticize pleasure on a scientific level but seek it on a practical level [1172a33-b8]). Chapter 8 concludes with an explicit reiteration of the methodological point, a reiteration that underscores how Aristotle’s treatment of the contest of lives incorporates central aspects of the discussion of pleasure in NE x 1-5. Aristotle’s reiteration of the problem of a gap between theory and practice also draws attention to the centrality of his treatment of pleasure in his adjudication of the three lives. Although the life of pleasure takes a distant third in the contest of lives, the contemplative life wins the contest in part because it itself is the most pleasant form of life. The central philosophical problem looming behind Aristotle’s treatment of the contest of lives concerns the relationship between the notion of activity (energeia) and the notion of a way of life (bios). In the last four decades, much of the scholarship on NE x 6-8 has sought to address the question of what activities a certain way of life includes or excludes. “Monistic” or “dominant” end interpretations of the best life have viewed it as including only contemplative activities whereas “inclusivist” end interpretations of the best life have viewed it as including non-contemplative activities. Although this chapter largely side-steps this debate—partially because there are ample recent first-rate introductory treatments of the debate, partially because I have addressed the question elsewhere in my own writing —I argue that focusing solely on the contest between the two best ways of life overshadows the way that Aristotle incorporates insights from the third way of life into the best way of life. Although the notion of a contest among different kinds of lives presupposes that the lives are mutually exclusive, Aristotle has no problem saying that the contemplative life trumps the life of pleasure because the contemplative life is more pleasant. I proceed in two parts. In the first part I examine what I will call the “outer” ring of the Ethics, namely the relationship between the contest of lives proposed in NE i 5 and its overall resolution in x 6-8. I show how i 5 and x 6 establish the framework for the contest, how x 7 adjudicates that contest in large part by relying upon premises articulated in the interim between books 1 and 10, and how x 6 and x 8 determine the second and third place positions in the contest. In the second part I focus on what I will call the “inner” ring of NE x. More than half of NE x struggles with the nature of pleasure, its role in a happy life, and the methodological problems of examining pleasure within a practical science. I show how x 1 and x 8 are “bookends” that underscore the methodological problem of examining pleasure and how the contest of lives draws upon the proximate conclusions concerning the nature of pleasure in NE x 1-5. (shrink)

Susan Haack has always maintained that her unquestionably important foundherentist theory of epistemic justification is not a foundationalism. In a 1997 "Synthese" exchange, Laurence BonJour questioned her right to this claim, and she dug in and defended it. What was at stake is of timeless importance to epistemology: it goes directly to the question, "What is foundationalism?" I inquire with greater care than either Haack or BonJour took in 1997, and I find decisively in favor of the view that (...) foundherentism is a foundationalism. In the process, I explore the outer limits of foundationalism: I examine just how far a foundationalism can go in allowing the relevance of coherence to epistemic justification. (shrink)

The Möbius transformation (MT) was analyzed as a coordinate transformation in the Minkowski form. The transformation function contains three separate light cones. The Weyl spheres were interpreted as basic constituents of local light cones. These cones are related to the denominators of the MT and its inverse, and their apexes define an axis with the top of the global light cone as the centerpoint. That axis represents the local part of the world-line of a moving frame of reference. On the (...) world-line, the scale factor of the MT is proportional to the ratio of the radii of the initial Weyl sphere and the equivalent transformed one. The projection centers, defining the transformation of the world-line, were determined graphically. There are two types of such MT's. Inner transformations have their projetion centers on the axes of the frame at rest, outer transformations on the axes of the “observed” moving frame. The signature of x 0 2 −r2 is conserved during inner transformations. All possible directions of the world-line of an inertial frame form a timelike “mass cone” around the time axis of the frame at rest. The mass cone and the related spacelike “phase cone” may be seen as projections of a lightlike central motion on the surface of a Weyl sphere. Conformal transformations leave both the mass cone and the phase cone invariant: the MT locally, and the Lorentz transformation globally. The moving frame of any lightlike particle rotates by π/2 radians, thus exchanging the time axis with one of the space axes. The measurable mass of such a particle is considered to be zero because only the central plane of the particle is space-oriented. The real mass is invariant. To test this hypothesis, the two γ-quanta produced by the electron pair annihilation should be led to a recollision, for recreating the initial electron-position pair. (shrink)

Context: Radical constructivism claims that we have no final truth criteria for establishing one ontology over another. This leaves us with the question of how we can come to know anything in a viable manner. According to von Glasersfeld, radical constructivism is a theory of knowledge rather than a philosophy of the world in itself because we do not have access to a human-independent world. He considers knowledge as the ordering of experience to cope with situations in a satisfactory way. (...) Problem: Von Foerster and Krippendorff show that the central goal of a constructivist theory of knowing must be to find a way of putting the knower into a known that is constructed so as to keep the knower, as well as the knowing process, viable in practice. Method: The conceptual and philosophical analysis of present theories and their necessary prerequisites suggests that such foundation for viable knowing can be built on the analysis of what the ontological prerequisites are for establishing viable observing, cognition, communication and observer-communicators, and communication media and vehicles. Results: The moment an observer chooses to accept his/her own embodied conscious presence in this world as well as language, he/she must accept other humans as partly independently existing conversation partners; if knowledge and knowing has to make sense, he/she must also accept as prerequisites for our observation and conversation a pre-linguistic reality from which our bodies come and which our conversation is often about. Furthermore, we can no longer claim that there is a reality that we do not know anything about: From being here in conversation, we know that the world can produce more or less stable embodied consciousnesses that can exchange and construct conceptual meanings through embodied conversations and actions that last over time and exist in space-time and mind, and are correlated to our embodied practices. We can also see that our communication works through signs for all living systems as well as in human language, understood as a structured and progressively developed system of communication. The prerequisite for this social semiotic production of meaning is the fourfold “semiotic star of cybersemiotics,” which includes at least four different worlds: our bodies, the combination of society, culture and language, our consciousness, and also an outer nature. Implications: The semiotic star in cybersemiotics claims that the internal subjective, the intersubjective linguistic, our living bodies, and nature are irreducible and equally necessary as epistemological prerequisites for knowing. The viable reality of any of them cannot be denied without self-refuting paradoxes. There is an obvious connectedness between the four worlds, which Peirce called “synechism.” It also points to Peirce’s conclusion that logic and rationality are part of the process of semiosis, and that meaning in the form of semiosis is a fundamental aspect of reality, not just a construction in our heads. Erratum: The paper erroneously refers to “pleroma.” The correct term is “plemora.” . (shrink)

Recently it has become clear that trafficking of integrins to late endosomes is key to the regulation of integrin expression and function during cell migration. Here we discuss the molecular machinery that dictates whether integrins are sorted to recycling endosomes or are targeted to late endosomes and lysosomes. Integrins and other receptors that are sorted to late endosomes are not necessarily degraded and, under certain circumstances, can be spared destruction and returned to the cell surface to drive cell migration and (...) invasion. We will discuss how the exchange of adhesion receptors and other key regulators of cell migration between late endosomes/lysosomes and the plasma membrane can promote dynamic turnover of adhesions during cell migration. (shrink)

This article summarizes the study of anion exchange mechanisms in bacteria. Along with defining at least two different families of anion exchange, an examination of such carrier‐mediated antiport reactions has led to techniques that considerably broaden the scope of biochemical methods for examining membrane proteins. Such advances have been exploited to show that anion exchange itself forms the mechanistic base of an entirely new kind of proton pump, one which may shed light on a variety of (...) bacterial events, including methanogenesis. Perhaps most important, the study of exchange provided the final link in a chain of evidence pointing to a structural [rhythm] that seems to characterize membrane carriers. These three issues ‐ a biochemical tool, a new proton pump, and a common structural rhythm ‐ are briefly examined in the context of their origins in the analysis of bacterial anion exchange. (shrink)

Fundamental questions arise in every age, questions such as those concerning the individual in society, social order, labor and exchange, meaning and ethics, and spiritual life and values. In addressing these questions Ervin Laszlo emphasizes insight and understanding, the mutability and flexibility of knowledge, cultural diversity and organizational interdependence, and harmony in nature. General Systems Theory and a theory of general evolution provide the framework for his thinking. He asks that as human beings we assume responsibility for creative, reasoned, (...) ethically sound decisions in dealing with the inner and outer limits of humanity. (shrink)

In this essay, I offer an interpretation of Abelard's Historia Calamitatum and letters exchanged with Heloise, arguing that both are informed by the attempt to look below the surfaces of language, self, and action to a reality beneath and to achieve authenticity, by which I mean coherence between surface and depth. This reading shows an emerging sense of self and self-knowledge based on the relationship between external act and internal intention. While using traditional medieval narrative forms, I argue, Abelard gives (...) his story a modern-sounding autobiographical twist: that its moral is about matching outer to inner self. While the project is never complete, the search itself becomes an identity; Abelard achieves authenticity in his rejection of all the models of it that were available to him. This is not done to unmask a self without place or parallel but to make the case for a new way of life in a new community for the inner self who is truly seeking God. Thus, like Augustine before and Rousseau after him, Abelard writes about his own life with a philosophical aim: to display the nature of what it is to be human and to make claims about how human life ought to be lived. (shrink)

An economically viable and environmental friendly method of generating hydrogen for fuel cells is by the reaction of certain metals with steam, called metalsteam reforming (MSR). This technique does not generate any toxic by-products nor contributes to the undesirable greenhouse effect. From the standpoint of favorable thermodynamics, total environmental benignity, and attractive economics, iron appears to be the metal of choice for such a process. An inexpensive source of iron for the MSR is the steel industry's mill-scale waste via hydrogen (...) and carbothermic reduction, both of which are energy-intensive processes. These have been eliminated by a novel, solution-based room temperature technique producing nanoscale iron, thus obviating the sintering of iron or iron oxide and deactivation during the cyclic operation of MSR. Some preliminary results are presented of an investigation aimed at converting the mill-scale waste into nanoscale iron, which was subsequently used in generating hydrogen for proton exchange membrane fuel cells. (shrink)

Sophists’ apologia. -/- Sophists were the first paid teachers ever. These ancient Greek enlighteners taught wisdom. Protagoras, Antiphon, Prodicus, Hippias, Lykophron are most famous ones. Sophists views and concerns made a unified encyclopedic system aimed at teaching common wisdom, virtue, management and public speaking. Of the contemporary “enlighters”, Deil Carnegy’s educational work seems to be the most similar to sophism. Sophists were the first intellectuals – their trade was to sell knowledge. They introduced a new type of teacher-student relationship – (...) the mutually beneficial communication on equal terms. They taught pupils how to think independently and how to persuade others, which was inseparably connected with the rise of democracy in the most advanced Greek polices. Sophists were the first to proclaim that all people are naturally equal. They put forward the idea of natural rights and social contract, working out the fundamentals of the present-day law. In addition, they developed the basics of philology, psychology, logic, and gave a scientific explanation to the origins of religions. They embodied definite positive ideals of their epoch. Sophistry flourished in the second half of the Vth through he first third of the IVth centuries B. C. The period coincides with the heyday of the entire Greek history – the so called Greek Miracle epoch. Sophists expressed some present-day concepts of Ancient Greek ideology and mentality, characteristic of its Golden Age times. The Ancient Athens of the times of Periclus were similar to the Florence of Renaissance as to the type of social structure. That is why (?) the art of eloquence (public speaking) was highly respected in Florence. The two cities had a lot of features of the present-day capitalist society, which was due to their role as the main centres of industry of their “worlds-economies”. During the subsequent Hellenic period, the Old Order was restored, based on the feudal rent recipients’ rule. The degradation of society resulted in the decline of sophistry. Sophistry represents the highest point in the evolution of Greek philosophy. It is also the most prominent school as to the novelty of its ideas. That was owing to the common propensity for innovation typical of Periclus’ Golden Age, which in its turn resulted from the establishment of the individualistic and rationalistic thinking similar to present-day mentality. Among other aspects, close attention was paid to ethnic issues; some humanistic ideas such as Master and Servant ethics and Enlightment as the primary condition of man’s freedom, received scientific grounding. The genre of philosophical dialogue was developed, as well as the rationalistic scientific gnoceology, aimed at consistently opposing any religion. Dialectics, the most outstanding achievement of the Antiquity, was also worked out by the sophists. Zeno of Helleas was one of the sophists. Democrites’ ideas were, too, quite close to dialectics. Socrates’ contemporaries regarded him ironically, as shown, for example, in the Aristophanes’ comedy “Clouds”. Nevertheless, this scholar can still be referred to as a sophist, although of somewhat weird personality. Socrates’ popularity, which came later, should be attributed to the fact that he was the first philosopher ever to have been sentenced and executed by law, rather than to any valuable scientific contributions. Sophistry as such, rather than Socrates, marks the line between pre-Socratic and post- Socratic schools. Plato, with the exception of his latest works, is considered to belong to the same philosophical school. Specifically, there are valid reasons to believe that he was paid fees by his disciples. In Plato’s Dialogues, all points of view will be proven and then disproved, so that an integral philosophical system is hard to observe. Plato’s “Idealism” is but one of the many possible theories. His ideal philosophy is a high-minded argument of wise men. As late as towards the end of his life, Plato betrayed the ideals of sophistry, turning into the world’s first proponent of totalitarianism. Sophistry is Greek classical literature. Later on, philosophy, as well as the entire Greek civilization, started to fall into decline. Over 500 subsequent years, Hellenistic-Roman scholars never came up with anything novel. The entire process of antique philosophical evolution can be subdivided into the following six stages: Phoenician (IX–VIIth centuries B. C.), archaic (VIth – the first half of IVth century B. C., classic (the epoch of sophistry: the second half of the Vth through the first decades of the IIIrd centuries B. C.), late antique (middle of the IIIrd – first decades of the VI th centuries B.C.) The fact that early in the VIth century B. C. sophistry was rejected in Athens, has a lot to do with the consequences of their defeat in Peloponnesian war, a social catastrophe. Ever since, the prevalent part of the criticism of sophistry is a criticism of sophists’ immoral ways of life and personalities, rather than the essentials of their philosophy. For instance, Aristotle’s criticism primarily concerns their pragmatism and tendency to make a profit out of teaching. However, Aristotle himself taught his disciples along similar lines, showing them how to “be able to prove both opposites”. It was Aristotle who summed up sophists’ century-long elaborations. The traditional modern interpretation of sophists as shown in Plato’s dialogues appears to be groundless. The truth of the matter is that Plato regards sophists as more serious philosophers than Socrates was. It becomes especially clear in the dialogue titled “Protagoras”, which shows the latter as gaining an undoubted victory over Socrates. Generally speaking, Plato’s works never regard sophists as weak or worthless opponents. A common opinion as to the essence of sophists’, in particular, Protagoras’s philosophy, has hitherto not been worked out. Many researchers renounce the very existence of any specific philosophical position in sophistry. The term “relativism” itself now has a bad name. However, it should be borne in mind that Protagoras doctrine emerged as a result of an attempt to get out of the ontological dead-end to which the entire Greek natural philosophy had come. To this purpose, he employed Anaxagoras’s idea about everything comprising everything, whereupon he built his physical-ontological theory, and Zeno of Helleas’s concept that all objects are such and different at the same time in the same respect. According to Protagoras’s philosophy, every object does not only seem, but is different from every other object, including human beings. Therefore, every person is his or her own measure of all other entities. The objective reality is the Ego’s relations with the outer world. Every object’s essence is defined through its interaction with ourselves. Nothing remains stagnant – every existence already contains non-existence, and vice-versa. However, the relativity of being is not to be regarded as absolute. That means, that relatively stable and therefore relatively cognizable entities do exist, among them the words we say. Doubt is not considered absolute by relativists either, which differentiates them from skeptics and agnostics. They dare to believe. Uncertainty is Godly – here, Protagoras becomes very close to the concept of apathetic theology. Gorgius shared Protagoras’s views and tried to prove them applying the same method as Zeno applied when upholding Parmenidis’s philosophy. He argued that if one accepts the opposite point of view and agrees that nothing can exist and not exist at the same time, one is bound to come to an the absurd conclusion that nothing is cognizable and nothing exists. To prove that there is a universal contradiction within the Existence itself, Protagoras and his followers in their turn put forward a number of special logical arguments, called rules of contraries, or sophisms. The most well-known of them is the Euathle’s sophism, which proves that an object can be such and different at the same time in the same respect. Generally speaking, all relationships of any entity are extraneous. The idea that all entities, including concepts, exist and do not exist at the same time, was also accepted by Plato. It should be stressed, that Plato’s philosophy as a whole is relativists’ greatest achievement. In his dispute against relativism, Aristotle put forward the main concepts of his ontology: the existence falls into the existence in possibility and the existence in reality, or substance and accidence – the ever changing “sublunary” world and the stable world of divine heavenly bodies. This division made his system self-contradictory to the point of absurd. Aristotle quite realized, that the direct disproof of relativism is hardly possible, which fact makes his criticism a mere tautology. It is very indicative in this respect that materialists, idealists and even skeptical agnostics applied the same arguments do disprove relativism. That demonstrates that the inner contradiction between any forms of “absolutism” and relativism is the most fundamental philosophical problem. Relativist ideas were repeatedly renewed throughout history, provided the social conditions were favourable. In variations, the concepts were advanced by Tzuan Tsi and ancient Chinese sophists, apostle Paul, Nicolas of Cusa, Galileo, Rene Descartes, G. Berkley, D. Hume, Ch. S. Pierce, E. Mach, A. Bogdanov, F. de Saussure, N. Bore, P. Feuerabend, U. Quain and others. However, no consistent relativist ontological system was developed after Protagoras. Meanwhile, a valid relativist theory could provide a clue to a fuller and more adequate general physical concept of the world, and to a deeper understanding of quantum mechanics. -/- Relativism as an ontological system of beliefs. -/- The relativist principle of relativity of all that exists is fundamental for the entire system of philosophy. Absolutely everything exists, but, at the same time, no existence is absolute. Anything is possible, but those entities only exist for us with which we interact this way or another, i. e., reality is interaction, “I interact – hence, I exist”. However, an overly close relationship between entities leads to non-existence – in other words, there is a certain existential optimum. For all of us, information, or perceptible heterogeneities, is real. Each of us is the center of a definite system of interactions with the world. If God is an endless Possibility, then the World is but the man’s dialogue with God. However, the ties that bind us with the world are of some definite kind, which predetermines our reality. The principle of relativity constrains itself, as any relativity is relative. On the one hand, that calls forth the Evil – caused by our own weakness. On the other hand, it makes our world relatively stable and cognizable. Generally speaking, the world is what we are. Everybody has an own Universe, but since people are fairly similar, our universes can be regarded as one Universe with common laws and regulations. It is possible for us to change the degree of objects’ existence in relation to ourselves and one another. It is equally important, though, to remain ourselves (keep following our “warrior’s path”). Since everything exists and no existence is absolute, the process of cognition should involve a criticism of everything but never a complete rebuttal of anything. The criterion of verity for any theory then is in its capacity to build itself upon a bigger number of diverse statements than in any other theory. Theoretically, all philosophies should ideally be complementary. The question of what in fact happened is meaningless unless we specify the “we”, the “where” and the “when”. The past can only exist as part of the present. When we change, our past undergoes corresponding qualitative objective changes, all of which are irreversible. The contemporary physics regards all objects of the Universe as existing for one another, which results in absurd conclusions. In fact, only what we interact with, exists. The so called “speed of light in vacuum” c is the maximum speed of direct interaction and direct exchange of signals. Specifically, at the oncoming speed c with a significant blue parallax the gamma-quantum is unable to interact with the matter. When this speed is reached, the gravitational mass of objects in relation to one another becomes equal to zero (imaginary), whereas their inertial mass equals infinity. Further acceleration will bring us into an entirely different Universe. That means that the Universe is an open system, which fact destroys all present-day cosmological models. Anything is possible in this world. Our reality is magic. Every bit of space contains a potentially limitless number of bits of other, however virtual, universes, as well as an infinite number of particles, which are still virtual for us (as postulated by quantum mechanics). In other words, there exists an infinity of different realities. With all the above in mind, the different levels of entities’ existence, in particular, of Life and Reason, should be taken into consideration. For example, to which extent a live system exists in relation to the inanimate forms of being is very indefinite, as what life is has to be determined by living creatures. An even greater compass of levels of existence can be brought about through interaction – that is the core idea of Godel’s theorem. As a result, the range of forms of existence tends towards infinity – the evolution of matter through super-intelligence will bring us up to God’s heights. A more generalized mathematical model of the physical world, including a universal operator of the co-existence of objects, can be developed based on the above considerations. The bonds between objects become weaker owing to 1) a high speed, 2) acceleration, 3) rotation, 4) strong gravity, 5) strong fields of other kinds, 6) the difference of levels of existence , 7) phase shifts. Yet, there always is an existential optimum. Such mathematical model is to operate certain non-transitive algebras. Relativist ontology assumes that the notion of “temperature” is relative, thus making it possible to ignore the Second Law of Thermodynamics. In its turn, that will allow for phase shifts. A perpetual motion machine of the second type will become a reality. Rotation could presumably be used to increase inertial and decrease gravitational mass, slowing down the time. An experimental research could shed light on the mentioned effects. (shrink)

In order to make an attempt at grouping the various aspects of brain functional imaging (fMRI, MRS, EEG-MEG, ...) within a coherent frame, we implemented a model consisting of a system of differential equations, that includes: (1) sodium membrane transport, (2) Na/K ATPase, (3) neuronal energy metabolism (i.e. glycolysis, buffering effect of phosphocreatine, and mitochondrial respiration), (4) blood-brain barrier exchanges and (5) brain hemodynamics, all the processes which are involved in the activation of brain areas. We assumed that the (...) correlation between brain activation and metabolism could be due to either changes in the concentrations of ATP and ADP following activation of Na/K ATPase that result from the changes in ion concentrations, or the involvement, in different phases of metabolism, of a second messenger such as calcium. In this article, we show how this type of model enables interpretation of MRS and fMRI published data that were obtained during prolonged stimulations. (shrink)

Stimulation of mitogenesis by the epidermal growth factor (EGF) operates through a pathway involving the receptor, the small G‐protein Ras and protein kinases of the MAP kinase cascade. It is proposed that two of the critical steps of that pathway utilize localization of components to the plasma membrane where Ras is located: recruitment of the nucleotide exchange protein Sos to the phosphorylated EGF receptor via a complex with the SH2/SH3‐containing protein Grb2 and recruitment of the protein kinase Raf (...) to activated Ras. Moreover, it is then proposed that Raf associates with the cytoskeleton at the membrane as it is being activated. Other signaling elements, including class I receptor kinases, nonreceptor tyrosine kinases and tyrosine phosphatases, are known to function at specific cellular sites. These observations have led us to propose that localization of signaling components, and particularly sites at membrane‐microfilament interfaces, play critical roles in cellular regulation. (shrink)

Neopoetics is a matrix for dynamic perceptual convergences between material and immaterial systems. The deep foundational ground for Neopoetics is the Poetics of Aristotle and its relation to the ancient Greek theatre as a practical systemic ideology for the mythic Greek drama. As Aristotle’s Poetics posits six basic components for the construction of drama (plot, character, thought, diction, song and spectacle) the neopoetic system has six constituent aspects: expanded embodiment, experiential metaphor, matrix architecture, perceptual resonance, the rheomode and neopoetic mythos. (...) Expanded embodiment describes an expansion of the corporeal body into fluid, dematerialized dimensions of experience, expression and exchange. Experiential metaphor is a sensate interface between the expanded body and the dematerialized field that contextualizes it in a neopoetic framework. It is what Roy Ascott terms an interspace: ‘found between the virtual and actual, where reality is renegotiated and the new consciousness is embodied’. The next three neopoetic aspects describe the language structures through which a new mythos is articulated. Matrix architecture is a framework for activation and alignment of the senses. It is a multisensory perceptual membrane that ignites the prism of the expanded body’s sensorium within the fluid interface of experiential metaphor. Matrix architecture articulates both a new sensorium and its interface with an integrated material/immaterial perceptual field. Perceptual resonance is the cathartic awakening of ‘the space between the senses’, evoked by the alignment of perceptual dimensions through matrix architecture. From this prismatic aperture emerges the mythic, transformative rheomode – the experiential language of the quantum wave. The rheomode is an expression of language. The term was coined by the quantum physicist David Bohm as an experiment in pursuit of a linguistic dimension of the wave. Yet in a neopoetic context, the rheomode becomes an evolutionary system. As Roy Ascott states,Language is not merely a device for communicating ideas about the world but rather a tool for bringing the world into existence. Art is a form of world building, of mind construction, of self-creation, whether through digital programming, genetic code, articulation of the body, imaging, simulation, or visual construction. Art is the search for new language, new metaphors, new ways of constructing reality, and for the means of redefining ourselves.Neopoetics mythos unfurls through the rheomode. It is an expression of an emerging ecology, an experiential awakening of the wave within the particle. Neopoetic myths are fluid evolutionary pulsations. They are transformation in the liquid convergences between material and immaterial dimensions. They are streams of lava birthing bedrock for an emerging paradigm. (shrink)

As McDowell makes clear in ‘On Pippin’s Postscript’ and in many other works, the interpretive question at issue in this exchange—how to understand the relation between Kant and Hegel, especially as that concerns Kant’s central ‘Deduction’ argument in the Critique of Pure Reason1—brings into the foreground an even larger problem on which all the others depend: the right way to understand at the highest level of generality the relation between active or spontaneous thought and our receptive and corporeal sensibility (...) and bodily embodiment. From Mind and World on, McDowell has indicated that this is in fact a problem so inclusive as to be common to theoretical and practical philosophy; that the issue of how thought informs our sensibility is at bottom the same (raises the same logical or conceptual issue) as the issue of how thought could be said to inform, to be active ‘in’, bodily action; that we can be in the grip of the same bad, misleading picture in accounting for executing an intention as in accounting for acquiring perceptual knowledge.2 I agree with, and follow his lead in, setting the basic framework for the particular issues in just this way. With matters so set out, there are two main areas of disagreement: (i) how to state the role of concepts and especially conceptual activity in the sensible uptake of the world and (ii) what to make of Hegel’s claim for a speculative ‘identity’ between inner and outer in action, or how to state the role of intentions ‘in’ bodily activity. In both cases, McDowell thinks I go too far; too far in terms of what is philosophically correct, and too far in attributing those positions to Hegel. It is the former topic that is in play in this exchange, although elements of the latter arise as well. There is first an issue lingering from the first exchange in Reading McDowell. (shrink)

Intermediate filaments, which form the structural framework of both the cytoskeleton and the nuclear lamina in most eukaryotic cells, have been found to be highly dynamic structures. A continuous exchange of subunit proteins at the filament surface and a stabilisation of soluble subunits by chaperone‐type proteins may modulate filament structure and plasticity. Recent studies on the cell cycle‐dependent interaction of intermediate filaments with associated proteins, and a detailed analysis of intermediate filament phosphorylation in defined subcellular locations at various stages (...) of mitosis, have brought new insights into the molecular mechanisms involved in the mitotic reorganisation of intermediate filaments. Some of these studies have allowed new speculations about the possible cellular functions of cytoplasmic intermediate filaments, and increased our understanding of the specific functions of the lamins and the lamina‐associated membrane proteins in the post‐mitotic reassembly of the nucleus. (shrink)

Stomata, the most influential components in gas exchange with the atmosphere, represent a revealing system for studying cell fate determination. Studies in Arabidopsis thaliana have demonstrated that many of the components, functioning in a signaling cascade, guide numerous cell fate transitions that occur during stomatal development. The signaling cascade is initiated at the cell surface through the activation of the membrane receptors TOO MANY MOUTHS (TMM) and/or ERECTA (ER) family members by the secretory peptide EPIDERMAL PATTERNING FACTOR1 (EPF1) (...) and/or a substrate processed proteolytically by the subtilase STOMATAL DENSITY AND DISTRIBUTION1 (SDD1) and transduced through cytoplasmic MAP kinases (YODA (YDA), MKK4/MKK5, and MPK3/MPK6) towards the nucleus. In the nucleus, these MAP kinases regulate the activity of the basic helix‐loop‐helix (bHLH) proteins SPEECHLESS (SPCH), MUTE, and FAMA, which act in concert with the bHLH‐Leu zipper protein SCREAM (SCRM) (and/or its closely related paralog, SCREAM2). This article reviews current insights into the role of this signaling cascade during stomatal development. (shrink)