Poly(ADP‐ribose) polymerase‐1 (PARP‐1) safeguards genomic integrity by limiting sister chromatid exchanges. Overstimulation of PARP‐1 by extensive DNA damage, however, can result in cell death, as prolonged PARP‐1 activation depletes NAD+, a substrate, and elevates nicotinamide, a product. The decline of NAD+ and the rise of nicotinamide may downregulate the activity of Sir2, the NAD+‐dependent deacetylases, because deacetylation by Sir2 is dependent on high concentration of NAD+ and inhibited by physiologic level of nicotinamide. The Sir2 deacetylase family has been implicated in (...) mediating gene silencing, longevity and genome stability. It is conceivable that poly(ADP‐ribosyl)ation by PARP‐1, which is induced by DNA damage, could modulate protein deacetylation by Sir2 via the NAD+/nicotinamide connection. The possible linkage of the two ancient pathways that mediate broad biological activities may spell profound evolutionary roles for the conserved PARP‐1 and Sir2 gene families in multicellular eukaryotes. BioEssays 25:808–814, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Vacuolar ATPases (V‐ATPases, V1Vo‐ATPases) are rotary motor proton pumps that acidify intracellular compartments, and, when localized to the plasma membrane, the extracellular space. V‐ATPase is regulated by a unique process referred to as reversible disassembly, wherein V1‐ATPase disengages from Vo proton channel in response to diverse environmental signals. Whereas the disassembly step of this process is ATP dependent, the (re)assembly step is not, but requires the action of a heterotrimeric chaperone referred to as the RAVE complex. Recently, an alternative pathway (...) of holoenzyme disassembly was discovered that involves binding of Oxidation Resistance 1 (Oxr1p), a poorly characterized protein implicated in oxidative stress response. Unlike conventional reversible disassembly, which depends on enzyme activity, Oxr1p induced dissociation can occur in absence of ATP. Yeast Oxr1p belongs to the family of TLDc domain containing proteins that are conserved from yeast to mammals, and have been implicated in V‐ATPase function in a variety of tissues. This brief perspective summarizes what we know about the molecular mechanisms governing both reversible (ATP dependent) and Oxr1p driven (ATP independent) V‐ATPase dissociation into autoinhibited V1 and Vo subcomplexes. (shrink)

Mitochondrial respiration is the predominant source of ATP. Excessive rates of electron transport cause a higher production of harmful reactive oxygen species (ROS). There are two regulatory mechanisms known. The first, according to Mitchel, is dependent on the mitochondrial membrane potential that drives ATP synthase for ATP production, and the second, the Kadenbach mechanism, is focussed on the binding of ATP to Cytochrome c Oxidase (CytOx) at high ATP/ADP ratios, which results in an allosteric conformational change to CytOx, causing (...) class='Hi'>inhibition. In times of stress, ATP‐dependent inhibition is switched off and the activity of CytOx is exclusively determined by the membrane potential, leading to an increase in ROS production. The second mechanism for respiratory control depends on the quantity of electron transfer to the Heme aa3 of CytOx. When ATP is bound to CytOx the enzyme is inhibited, and ROS formation is decreased, although the mitochondrial membrane potential is increased. (shrink)

A number of roles have been ascribed to poly(ADP‐ribose) polymerase* including involvement in DNA repair, cell proliferation, differentiation and transformation. Cloning of the gene has allowed the development of molecular biological approaches to elucidate the structure and the function(s) of this highly conserved enzyme. This article will review the recent results obtained in this field.

Inhibition, associated with self-efficacy, enables people to control thought and action and inhibit disturbing stimulus and impulsion and has certain evolutionary significance. This study analyzed the neural correlates of inhibition modulated by self-efficacy. Self-efficacy was assessed by using the survey adapted from the Motivated Strategies for Learning Questionnaire. Fifty college students divided into low and high self-efficacy groups participated in the experiments. Their ability to conduct inhibitory control was studied through Go/No-Go tasks. During the tasks, we recorded students’ (...) brain activity, focusing on N2 and P3 components in the event-related potential. Larger No-Go N2 amplitudes for the high self-efficacy group were found compared with the low self-efficacy group. Conflict detection as represented by N2 was modulated by self-efficacy, whereas conflict inhibition as represented by P3 was not modulated by self-efficacy. The highly self-efficacious students were more capable of detecting conflicts but not necessarily more capable of inhibiting action given that conflict was detected. Taken together, these findings offer neurophysiological evidence of the important regulatory role of self-efficacy in inhibitory control ability development. (shrink)

Recent studies suggest that instrumental hypnosis is a useful experimental tool to investigate emotional and language processing effects. However, the capacity of hypnotic suggestions to intervene during the response inhibition of emotional words remains elusive. This study investigated whether hypnotic suggestion can improve the inhibition of prepotent negative word responses in an emotional Hayling sentence completion task. High-suggestible participants performed a computerised emotional Hayling task. They were first asked to select the appropriate words ending highly predictable sentences among (...) two propositions (initiation part), and then to select the filler words that did not end the sentences correctly (inhibition part). Half of the expected final words had a negative emotional valence, while the other half was neutral. The task was performed in a control condition (without suggestion) and with a hypnotic suggestion to decrease emotional reactivity. The results revealed that hypnotic suggestion (compared to the control condition) hastened response times on negative final words in the inhibition part, showing that hypnotic suggestion can enhance cognitive control over prepotent negative word responses in a sentence completion task. We suggest that this modulation stems from a reduction in the emotional relevance of the final words caused by the hypnotic suggestion. (shrink)

Gain or omission/termination of loss produces approach; while loss or omission/termination of gain produces withdrawal. Control of approach/withdrawal motivation is distinct from valuation of gain/loss and does not entail learning – making “reward” and “punishment” ambiguous. Approach-withdrawal goal conflict engages a neurally distinct Behavioural Inhibition System, which controls “anxiety” but not “fear”.

This study focuses on latent inhibition, a mechanism behind selective attention, as the biological basis of creativity in schoolchildren. The main objective of this study is to know if low levels of attention positively affect the levels of creativity manifested in students between the ages of nine and 12. The design of this study is non-experimental with an explanatory-correlational cross-sectional quantitative approach. In order to achieve the objective suggested, several education centers located in Murcia were selected, in which 476 (...) students took part in a creativity test, an attention test, and another test about intelligence depending on the educational level. The results obtained showed that selective attention was negatively correlated with graphic creativity, understanding that behind it lies the latent inhibition, and that when certain levels of intelligence are present, this negative correlation increases. In this way, the simultaneous existence of creative and inattentive subjects is demonstrated. (shrink)

In 5 experiments, participants read text that was briefly replaced by a transient image for 33 ms at random intervals. A decrease in saccadic frequency, referred to as saccadic inhibition, occurred as early as 60 –70 ms following the onset of abrupt changes in visual input. It was demonstrated that the saccadic inhibition was influenced by the saliency of the visual event (Experiment 3) and was not produced in response to abrupt but irrelevant auditory stimuli (Experiment 1). Display (...) changes restricted to an area either inside or outside the perceptual span required for normal reading produced strong saccadic inhibition (Experiment 2). Finally, Experiments 4 and 5 demonstrated higher level cognitive or attentional modulation of the saccadic inhibition effect. (shrink)

Diauxie is at the origin of research that led Jacques Monod, François Jacob, and André Lwoff to win the Nobel Prize in Physiology or Medicine in 1965 for their description of the first genetic regulatory model. Diauxie is a term coined by Jacques Monod in 1941 in his doctoral dissertation that refers to microbial growth in two phases. In this article, we first examine Monod’s thesis to demonstrate how and why Monod interpreted diauxie as a phenomenon of enzyme inhibition (...) or suppression of adaptive enzymes. We also briefly investigate prior enzyme suppression studies, before Monod’s work, which indicate that he is the first person to observe diauxic growth. Second, we analyse Monod’s post-thesis publications throughout his scientific career, revealing that diauxic inhibition was a significant part of Monod’s scientific activities and greatly fascinated Monod until the end of his life. Paradoxically, Monod’s work and interest on diauxic inhibition are still neglected in historical recounts, focused mostly on Monod’s enzymatic adaptation studies. Indeed, we uncovered a statement by Monod’s colleague, Lwoff, who transformed a quotation from Monod by replacing the word phenomenon with enzymatic adaptation, which we believe has influenced historians. Finally, we offer hypotheses to explain why Lwoff altered Monod’s statement. (shrink)

Anamniote animals, such as fish and amphibians, are able to regenerate damaged CNS nerves following injury, but regeneration in the mammalian CNS tracts, such as the optic nerve, does not occur. However, severed adult mammalian retinal axons can regenerate into peripheral nerve segments grafted into the brain and this finding has emphasized the importance of the environment in explaining regenerative failure in the adult mammalian CNS. Following lesions, regenerating axons encounter the glial cells, oligodendrocytes and astro‐cytes, and their derivatives, respectively (...) myelin and the astrocytic scar. Experiments to investigate the influence of these components on axon growth in culture have revealed cell‐surface and extracellular matrix molecules that inhibit axon extension and growth cone motility. Structural and functional characterization of these ligands and their receptors is underway, and may solve the interesting neurobiological conundrum posed by the failure of mammalian CNS regeneration. Simultaneously, this might allow new possibilities for treatment of the severe clinical disabilities resulting from injury to the brain and spinal cord. (shrink)

The crux of the dispute on the mutual relations between attention and consciousness, and to which I have referred in this paper, lies in the question of what can be attended in spatial attention that obviously resonates with the phenomenological issue of intentionality. The discussion has been initiated by Christopher Mole. He began by calling for a commonsense psychology, according to which one is conscious of everything that one pays attention to, but one does not pay attention to all the (...) things that one is conscious of. In other words, attention is supposed to be a condition which is sufficient but not necessary for consciousness, i.e., consciousness is a necessary concomitant of attention, but attention is not a necessary concomitant of consciousness. Mole seeks to validate his stance with data from psychology labs. His view is, however, partly confronted, for instance, by Robert Kentridge, Lee de-Wit and Charles Heywood, who used their experimental research on a neurological condition called blindsight as evidence of a dissociation between attention and consciousness, i.e., that visual attention is not a sufficient precondition for visual awareness. In this meta-theoretical state of affairs, I would like to focus on the cognitive phenomenon most often referred to as Inhibition of Return and suggest that, following its micro dynamics from the perspective of micro-phenomenology, it can be used to actually showcase all of the options on both sides of the argument. One of my leading goals would be also to follow Mole’s attempt to link attention with agency but where we differ is that I wish to heuristically articulate the matter in terms of Merleau-Ponty’s phenomenological notion of embodied pre-reflective intentionality. (shrink)

In everyday parlance, "inhibition" suggests repression, tight control, the opposite of freedom. In medicine and psychotherapy the term is commonplace, its definition understood. Relating how inhibition—the word and the concept—became a bridge between society at large and the natural sciences of mind and brain, Smith constructs an engagingly original history of our view of ourselves. Not until the late nineteenth century did the term "inhibition" become common in English, connoting the dependency of reason and of civilization itself (...) on the repression of "the beast within." This usage followed a century of Enlightenment thought about human nature and the nature of the human mind. Smith traces theories of inhibitory control from the moralistic psychologies of the early nineteenth century to the famous twentieth-century schools of Sherrington, Pavlov, and Freud. He finds that the meanings of "inhibition" cross disciplinary boundaries and outline the growth of our belief in the self-regulated person. (shrink)