Accumulation of neurotransmitters in the lumen of synaptic vesicles (SVs) relies on the activity of the vacuolar‐type H+‐ATPase. This pump drives protons into the lumen, generating a proton electrochemical gradient (ΔμH+) across the membrane. Recent work has demonstrated that the balance between the chemical (ΔpH) and electrical (ΔΨ) components of ΔμH+ is regulated differently by some distinct vesicle types. As different neurotransmitter transporters use ΔpH and ΔΨ with different relative efficiencies, regulation of this gradient balance has the potential to (...) influence neurotransmitter uptake. Nevertheless, the underlying mechanisms responsible for this regulation remain poorly understood. In this review, we provide an overview of current neurotransmitter uptake models, with a particular emphasis on the distinct roles of the electrical and chemical gradients and current hypotheses for regulatory mechanisms. -/- . (shrink)

The initial relationships between organisms leading to endosymbiosis and the first eukaryote are currently a topic of hot debate. Here, I present a theory that offers a gradual scenario in which the origins of phagocytosis and mitochondria are intertwined in such a way that the evolution of one would not be possible without the other. In this scenario, the premitochondrial bacterial symbiont became initially associated with a protophagocytic host on the basis of cooperation to kill prey with symbiont‐produced toxins and (...) reactive oxygen species (ROS). Subsequently, the cooperation was focused on the digestion stage, through the acidification of the protophagocytic cavities via exportation of protons produced by the aerobic respiration of the symbiont. The host gained an improved phagocytic capacity and the symbiont received organic compounds from prey. As the host gradually lost its membrane energetics to develop lysosomal digestion, respiration was centralized in the premitochondrial symbiont for energy production for the consortium. (shrink)

Despite thermodynamic, bioenergetic and phylogenetic failings, the 81‐year‐old concept of primordial soup remains central to mainstream thinking on the origin of life. But soup is homogeneous in pH and redox potential, and so has no capacity for energy coupling by chemiosmosis. Thermodynamic constraints make chemiosmosis strictly necessary for carbon and energy metabolism in all free‐living chemotrophs, and presumably the first free‐living cells too. Proton gradients form naturally at alkaline hydrothermal vents and are viewed as central to the origin (...) of life. Here we consider how the earliest cells might have harnessed a geochemically created proton‐motive force and then learned to make their own, a transition that was necessary for their escape from the vents. Synthesis of ATP by chemiosmosis today involves generation of an ion gradient by means of vectorial electron transfer from a donor to an acceptor. We argue that the first donor was hydrogen and the first acceptor CO2. (shrink)

Despite thermodynamic, bioenergetic and phylogenetic failings, the 81‐year‐old concept of primordial soup remains central to mainstream thinking on the origin of life. But soup is homogeneous in pH and redox potential, and so has no capacity for energy coupling by chemiosmosis. Thermodynamic constraints make chemiosmosis strictly necessary for carbon and energy metabolism in all free‐living chemotrophs, and presumably the first free‐living cells too. Proton gradients form naturally at alkaline hydrothermal vents and are viewed as central to the origin (...) of life. Here we consider how the earliest cells might have harnessed a geochemically created proton‐motive force and then learned to make their own, a transition that was necessary for their escape from the vents. Synthesis of ATP by chemiosmosis today involves generation of an ion gradient by means of vectorial electron transfer from a donor to an acceptor. We argue that the first donor was hydrogen and the first acceptor CO2. (shrink)

Protons are the most common coupling ions in bacterial energy conversions. However, while many organisms, such as the alkaliphilic Bacilli, employ H+‐bioenergetics for electron transport phosphorylation, they use Na+ as the coupling ion for transport and flagellar movement. The Na+ gradient required for these bioenergetic functions is established by the secondary Na+/H+ antiporter. In contrast, Vibrio alginolyticus and methanogenic bacteria have primary pumps for both H+ and Na+. They use the proton gradient for ATP synthesis while other, less energy‐consuming (...) membrane reactions are powered by the Na+ gradient. In a third mode, some anaerobic bacteria possess decarboxylases acting as primary Na+ pumps. For instance, in Klebsiella pneumoniae, the Na+ gradient established by oxaloacetate decarboxylase is used for the uptake of the growth substrate citrate, and Propionigenium modestum consumes the energy of the Na+ gradient formed by methylmalonyl‐CoA decarboxylase directly for ATP synthesis. (shrink)

Myxobacteria are social organisms that usually remain together even though they are not chemically attached to each other. They cooperatively feed and form aggregates and fruiting bodies. Their mode of movement, the forces and mechanisms that allow movement, the factors that keep them together, and the processes leading to the structures composed of many cells are only now beginning to be understood. Possibilities that may be key to their abilities are three models proposed elsewhere for different aspects of their biology. (...) One hypothesis attempts to explain mound and fruiting body formation by assuming that the cells move in circular patterns around the major cell mass. The second explains gliding motility on the existence of shunts that periodically short out the proton gradient across the cell membrane, causing expansion and contraction of portions of the cell. The third model proposes that occasionally cells arise that move unidirectional instead of back and forth. These few cells may lead the majority of cells in new directions. BioEssays 20:1030–1038, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

Attempts to solve the puzzling problem of oxidative phosphorylation led to four very different hypotheses each of which suggested a different view of the ATP synthase, the phosphorylating enzyme. During the 1960s and 1970s evidence began to accumulate which rendered Peter Mitchell’s chemiosmotic hypothesis, the novel part of which was the proton translocating ATP synthase (ATPase), a plausible explanation. The conformational hypothesis of Paul Boyer implied an enzyme where ATP synthesis was driven by the energy of conformational changes in (...) the respiratory proteins. This was finally abandoned as an explanation of the overall process. Nevertheless the conformational understanding of the enzyme became an acceptable proposal during the early 1970s and eventually led Boyer to a view of the enzyme that incorporated both hypotheses. The correspondence between Mitchell and Boyer, both Nobel laureates, exposes their different approaches to both this enzyme and to the hypotheses of oxidative phosphorylation and illuminates a key step in the development of bioenergetics. In particular Boyer was suspicious of proton gradients, because he could not envisage a chemical mechanism for the synthesis of ATP, while Mitchell distrusted conformational arguments because he believed the proton must act vectorially at the active site of the enzyme. This resulted in two different views of the mechanisms operating in this enzyme. Ultimately while Boyer was able to marry the two approaches, Mitchell retained his insistence on the role of the proton at the active site and was thus unable to give significance to Boyer’s conformational ideas. The underlying issues in this debate are discussed particularly with reference to the differing styles of Boyer and Mitchell and the influence of molecular biology, especially the development of protein technology. (shrink)

Origin of life on earth transpired once and from then on, it emerges as an endless eternal process. Matter and energy are constants of the cosmos and the hypothesis is that the origin of life is a moment when these constants intertwined or interacted. Energy from the cosmos interacted with inorganic matter to support matter with retention of this riveted energy, as energy to be circulated within the primitive channelized structures to conserve energy by the materialization of the proton (...) homeostasis mechanisms developed from the obtainable inorganic matter. The driver for these processes as we now confirm, exists in the quantum world and through quantum phenomenal processes could have combined these constants to create the magic of life. Primitive earth was a chemical reactive system that triggered a macromolecular evolution by means of open thermodynamic systems, driven by cyclic gradients of temperature, electromagnetic radiation and chemical potentials which sustained life and proto-consciousness in the first life forms driven by the quantum processes. The origin of life is always an intriguing topic but the purpose for finding the cause should never be inclined towards obliterating it; for if that is the case, the further we seek, the farther it will go. (shrink)

BackgroundWhile genomic data sharing can facilitate important health research and discovery benefits, these must be balanced against potential privacy risks and harms to individuals. Understanding public attitudes and perspectives on data sharing is important given these potential risks and to inform genomic research and policy that aligns with public preferences and needs.MethodsA cross sectional online survey measured attitudes towards genomic data sharing among members of the general public in an Eastern Canadian province.ResultsResults showed a moderate comfort level with sharing genomic (...) data, usually into restricted scientific databases with controlled access. Much lower comfort levels were observed for sharing data into open or publicly accessible databases. While respondents largely approved of sharing genomic data for health research permitted by a research ethics board, many general public members were concerned with who would have access to their data, with higher rates of approval for access from clinical or academic actors, but much more limited approval of access from commercial entities or governments. Prior knowledge about sequencing and about research ethics boards were both related to data sharing attitudes.ConclusionsWith evolving regulations and guidelines for genomics research and data sharing, it is important to consider the perspectives of participants most impacted by these changes. Participant information materials and informed consent documents must be explicit about the safeguards in place to protect genomic data and the policies governing the sharing of data. Increased public awareness of the role of research ethics boards and of the need for genomic data sharing more broadly is also needed. (shrink)

The concept of wild food does not play a significant role in contemporary nutritional science and it is seldom regarded as a salient feature within standard dietary guidelines. The knowledge systems of wild edible taxa are indeed at risk of disappearing. However, recent scholarship in ethnobotany, field biology, and philosophy demonstrated the crucial role of wild foods for food biodiversity and food security. The knowledge of how to use and consume wild foods is not only a means to deliver high-end (...) culinary offerings, but also a way to foster alternative models of consumption. Our aim in this paper is to provide a conceptual framework for wild foods, which can account for diversified wild food ontologies. In the first section of the paper, we survey the main conception of wild foods provided in the literature, what we call the Nature View. We argue that this view falls short of capturing characteristics that are core to a sound account of wilderness in a culinary sense. In the second part of the paper, we provide the foundation for an improved model of wild food, which can countenance multiple dimensions and degrees connoting wilderness in the culinary world. In the third part of the paper we argue that thanks to a more nuanced ontological analysis, the gradient framework can serve ethnobiologists, philosophers, scientists, and policymakers to represent and negotiate theoretical conflicts on the nature of wild food. (shrink)

The two parameters of leaf dimension namely, length and width, show inverse correlation with the third parameter, the thickness. A thermal diffusion model is proposed which explains the inverse relationship between these and envisages that while leaf length and width are directly influenced by the microclimate the thickness is affected by the microclimate through endoclimate and energy balance in the leaves. The significance of the model is discussed in the light of its importance in assessing the survival range of plant (...) species along the altitudinal gradient. (shrink)

In Gradient Acceptability and Linguistic Theory, Elaine J. Francis examines a challenging problem at the intersection of theoretical linguistics and the psychology of language: the problem of interpreting gradient judgments of sentence acceptability in relation to theories of grammatical knowledge. This problem is important because acceptability judgments constitute the primary source of data on which such theories have been built, despite being susceptible to various extra-grammatical factors. Through a review of experimental and corpus-based research on a variety of syntactic phenomena (...) and an in-depth examination of two case studies, Francis argues for two main positions. The first is that converging evidence from online comprehension tasks, elicited production tasks, and corpora of naturally-occurring discourse can help determine the sources of variation in acceptability judgments and narrow down the range of plausible theoretical interpretations. The second is that the interpretation of judgment data depends crucially on one's theoretical commitments and assumptions, especially with respect to the nature of the syntax-semantics interface and the choice of either a categorical or a gradient notion of grammaticality. The theoretical frameworks considered in this book include derivational theories (e.g. Minimalism, Principles and Parameters), constraint-based theories (e.g. Sign-based Construction Grammar, Simpler Syntax), competition-based theories (e.g. Stochastic Optimality Theory, Decathlon Model), and usage-based approaches. While showing that acceptability judgment data are typically compatible with the assumptions of various theoretical frameworks, Francis argues that some gradient phenomena are best captured within frameworks that permit soft constraints-non-categorical grammatical constraints that encode the conventional preferences of language users. (shrink)

Ductin is the highest conserved membrane protein yet found in eukaryotes. It is multifunctional, being the subunit c or proteolipid component of the vacuolar H+‐ATPase and at the same time the protein component of a form of gap junction in metazoan animals. Analysis of its structure shows it to be a tandem repeat of two 8‐kDa domains derived from the subunit c of the F0 proton pore from the F1F0 ATPase. Each domain contains two transmembrane α‐helices, which together may (...) form a four‐helix bundle. In both the V‐ATPase and gap junction channel, ductin is probably arranged as a hexamer of subunits forming a central channel of gap junction‐like proportions. The two functions appear to be seggregated by ductin having two orientations in the bilayer. Ductin is also the major component of the mediatophore, a protein complex which may aid in the release of neurotransmitters across the pre‐synaptic membrane. It is also a target for a class of poorly understood viral polypeptides. These polypeptides are small and highly hydrophobic and some have oncogenic activity. Ductin thus appears to be at the crossroads of a number of biological processes. (shrink)

Every year our sun should be losing about 10 20 protons (about a milligram's worth) in this way. This is not much of a loss, but it is irreversible, and it adds up. In 10..

It is proposed in this paper that enzymes, by virtue of a number of correctly positioned sites of interaction with substrates, can force the compression of hydrogen bonds, increasing the probability of proton transfer by quantum mechanical tunneling. By such a catalytic mechanism a rate enhancement of many orders of magnitude may be obtained with a very low energy input requirement. The mechanism would, however, require a highly structured catalyst.Pertinent aspects of hydrogen bond theory and of tunneling theory are (...) briefly reviewed. (shrink)

Recent decades have witnessed the rapid evolution of robotic applications and their expansion into a variety of spheres with remarkable achievements. This article researches a crucial technique of robot manipulators referred to as visual servoing, which relies on the visual feedback to respond to the external information. In this regard, the visual servoing issue is tactfully transformed into a quadratic programming problem with equality and inequality constraints. Differing from the traditional methods, a gradient-based recurrent neural network for solving the visual (...) servoing issue is newly proposed in this article in the light of the gradient descent method. Then, the stability proof is presented in theory with the pixel error convergent exponentially to zero. Specifically speaking, the proposed method is able to impel the manipulator to approach the desired static point while maintaining physical constraints considered. After that, the feasibility and superiority of the proposed GRNN are verified by simulative experiments. Significantly, the proposed visual servo method can be leveraged to medical robots and rehabilitation robots to further assist doctors in treating patients remotely. (shrink)

For the safe and economical construction of embankment dams, the mechanical behaviour of the rockfill materials used in the dam’s shell must be analyzed. The characterization of rockfill materials with specified shear strength is difficult and expensive due to the presence of particles greater than 500 mm in diameter. This work investigates the feasibility of using an extreme gradient boosting computing paradigm to estimate the shear strength of rockfill materials. To train and validate the proposed XGBoost model, a total of (...) 165 databases obtained from the literature are chosen. The XGBoost model was compared against support vector machine, adaptive boosting, random forest, and K-nearest neighbor models described in the literature. XGBoost beats SVM, RF, AdaBoost, and KNN models in terms of performance evaluation metrics such as coefficient of determination, Nash–Sutcliffe coefficient, and error in the root mean square ratio to the standard deviation of the measured data. The results demonstrated that the XGBoost model has the highest prediction performance with, followed by the SVM model with, RF, the AdaBoost model with and the KNN model with. A sensitivity analysis has been conducted to ascertain the impact of each investigated input parameter. This study demonstrates that the established XGBoost model for estimating the shear strength of rockfill materials is reliable. (shrink)

Mental representations have continuous as well as discrete, combinatorial properties. For example, while predominantly discrete, phonological representations also vary continuously; this is reflected by gradient effects in instrumental studies of speech production. Can an integrated theoretical framework address both aspects of structure? The framework we introduce here, Gradient Symbol Processing, characterizes the emergence of grammatical macrostructure from the Parallel Distributed Processing microstructure (McClelland, Rumelhart, & The PDP Research Group, 1986) of language processing. The mental representations that emerge, Distributed Symbol Systems, (...) have both combinatorial and gradient structure. They are processed through Subsymbolic Optimization–Quantization, in which an optimization process favoring representations that satisfy well-formedness constraints operates in parallel with a distributed quantization process favoring discrete symbolic structures. We apply a particular instantiation of this framework, λ-Diffusion Theory, to phonological production. Simulations of the resulting model suggest that Gradient Symbol Processing offers a way to unify accounts of grammatical competence with both discrete and continuous patterns in language performance. (shrink)

A novel photon-based proton model is developed. A proton’s ground state is assumed to be coherent to the degree that all of its mass-energy precipitates into a single uncharged spherical structure. A quantum vortex, initiated by the strong force, but sustained in the proton’s ground state by the circular Unruh effect and a spherical Rindler horizon, is proposed to confine the proton’s mass-energy in its ground state. A direct connection between the circular Unruh effect, the zitterbewegung (...) effect, spin, and general relativity is proposed. Such a structure acts as an uncharged zitterbewegung fermion, and may explain neutrino mass. A ground-state proton’s central zitterbewegung fermion is assumed to be surrounded by a halo of charge shells of both signs. Virtual photon standing waves are assumed to synchronize the inner shell with the central zitterbewegung fermion. The charge shells are proposed to be associated with isospin and proton g-factor. There are only two model inputs—proton mass and quantized electronic charge—and just one adjustable parameter. The adjustable parameter, reduced only by about 0.4% from an initial estimate, provides the proton’s experimentally determined magnetic moment to arbitrary precision. The resulting modeled proton charge radius agrees very well with the 2018 CODATA value. Magnetic moment and charge radius are calculated algebraically in a manner easily understood by undergraduate physics students. This proposed ground-state proton model could be considered a low-energy approximation to a full quantum chromodynamical proton model. (shrink)

Gap genes stand at the top of the zygotic segmentation hierarchy in Drosophila. Their expression domains are set up by a combination of maternal regulatory signals and interactions among themselves. In addition, these regulatory pathways are partially redundantly specified by the maternal and zygotic genomes, or by multiple zygotic gene products. The gap genes code for transcription factors which exert their function by foming short‐range morphogenetic gradients; differential concentrations of these transcription factors can either act as activators or as (...) repressors for the expression domains of neighbouring genes. It is possible to view the gap genes as a system of genes that subdivides the embryo by forming an activation‐repression cascade proceeding from anterior towards posterior. (shrink)