What is the function of the claustrum?

The claustrum is a thin, irregular, sheet-like neuronal structure hidden beneath the inner surface of the neocortex in the general region of the insula. Its function is enigmatic. Its anatomy is quite remarkable in that it receives input from almost all regions of cortex and projects back to almost all regions of cortex. We here briefly summarize what is known about the claustrum, speculate on its possible relationship to the processes that give rise to integrated conscious percepts, propose mechanisms that enable information to travel widely within the claustrum and discuss experiments to address these questions.     

What is the function of protein carboxyl methylation?

The following functions of protein carboxyl methylation seem to be reasonably well established: Multiple, stoichiometric methylation of chemotactic receptors in bacteria at glutamyl residues serves as one (but not the only) adaptation mechanism of the transduction chain to constant background levels of chemotactic stimuli. Stoichiometric methylation of hormones and hormone carrier proteins plays a role in hormone storage and secretion by the pituitary gland. Substoichiometric methylation at D-aspartyl residues is involved in a repair mechanism of aged proteins. Stoichiometric methylation of calmodulin modulates the sensitivity of calmodulin-dependent processes to calcium. Research of the past 3 years has indicated that in order to demonstrate an involvement of methylation in the coupling of surface receptors to intracellular events three new criteria have to be met: (a) the cell should possess a protein carboxyl methylase with relatively narrow substrate specificity; (b) methylation should take place at L-amino acid residues; (c) the methyl accepting proteins should be methylated in a stoichiometric fashion.     

What is the function of MSP-I on the malaria merozoite?

In the absence o f any clear enzymatic activity, attempts to define the role of merozoite surface protein-I have focused mainly on analysis of its structure, on its interaction with the immune system and on binding assays. But how does our knowledge of the structure o f this protein contribute to functional studies? Are there data to suggest a role in the evasion of effective host immune responses? Binding studies have used the intact protein or various fragments and peptides, but do such approaches provide a reliable indicator of function? In this article, Tony Holder and Mike Blackman review these areas.     

What is the role of PACAP in gonadotrope function?

Strong evidence in favor of a direct action of hypothalamic PACAP at the pituitary to modulate gonadotrope function has been acquired mainly by in vitro studies using cultured pituitary cells or gonadotrope cell lines. In particular, PACAP has been shown to cooperate with GnRH, the primary regulator of gonadotropes, to regulate/modulate gonadotropin subunit gene expression, gonadotropin release as well as gonadotrope responsiveness. These effects of PACAP appear to be due essentially to its high potent stimulatory action on the cAMP/protein kinase pathway. Ensuing mechanisms include signaling cross-talk and/or enhanced gene expression within gonadotropes. PACAP may also indirectly operate on these cells through paracrine mechanisms. While PACAP has long been viewed as a hypophysiotropic factor, a locally produced PACAP has also been described. Interestingly, both appear similarly up-regulated at proestrus of the reproductive cycle in female rats. Further in vivo investigation is now necessary to ascertain the physiological relevance of the observed pituitary PACAP effects and especially to evaluate the respective contribution of hypothalamic and pituitary PACAP in the dynamic control of gonadotrope function.     

What is the function of neuronal AP‐3?

Neurotransmission requires the proper organization and rapid recycling of synaptic vesicles. Rapid retrieval has been suggested to occur either by kiss-and-stay or kiss-and-run mechanisms, whereas classical recycling is mediated by clathrin-dependent endocytosis. Molecular coats are key components in the selection of cargos, AP-2 (adaptor protein 2) playing a prominent role in synaptic vesicle endocytosis. Another coat protein, AP-3, has been implicated in synaptic vesicle biogenesis and in the generation of secretory and lysosomal-related organelles. In the present review, we will particularly focus on the recent data concerning the recycling of synaptic vesicles and the function of AP-3 and the v-SNARE (vesicular soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) TI-VAMP (tetanus neurotoxin-insensitive vesicle-associated membrane protein) in these processes. We propose that AP-3 plays an important regulatory role in neurons which contributes to the basal and stimulated exocytosis of synaptic vesicles.     

What is the function of nitrogen catabolite repression in Saccharomyces cerevisiae?

In contrast to the previously held notion that nitrogen catabolite repression is primarily responsible for the ability of yeast cells to use good nitrogen sources in preference to poor ones, we demonstrate that this ability is probably the result of other control mechanisms, such as metabolite compartmentation. We suggest that nitrogen repression is functionally a long-term adaptation to changes in the nutritional environment of yeast cells.     

What is the ultimate goal in neural regulation of cardiovascular function?

We used the following multiple-choice question after a series of lectures in cardiovascular physiology in the first year of an undergraduate medical curriculum (n = 66) to assess whether students had understood the neural regulation of cardiovascular function. In health, neural cardiovascular mechanisms are geared toward maintaining A) cardiac output, B) total peripheral resistance (TPR), C) arterial blood pressure (BP), D) tissue blood flow. The same question was administered to 275 graduates preparing for postgraduate exams (but not following the same series of lectures as the undergraduates). In both groups, we found a large proportion of incorrect answers (70% in undergraduates and 85% in graduates) and sorted this out by offering a step-by-step explanation and two examples and found it successful: 1) What happens to BP and heart rate (HR) when a person loses 500 ml of blood ( approximately 10% of blood volume) in one minute? 2) What happens to your BP and HR as you get out of bed after a night's sleep? Flow = perfusion pressure/resistance to flow; cardiac output = BP/TPR; BP = cardiac output x TPR = [stroke volume (SV) x HR] x TPR. In both examples, BP decreases and is rapidly brought into the normal range by the arterial baroreflex mechanism. TBF is regulated chiefly by varying local vascular resistance (autoregulation). In summary, the ultimate goal of all neural cardiovascular reflex mechanisms is to maintain arterial BP within a range in which tissues can regulate their own blood flows. Cardiovascular control during exercise was used as an example to emphasize these facts. A discussion of this kind triggered interest in the minds of students and graduates, helping them get rid of a major misconception in about 20-40 minutes.     

What, if anything, is the adaptive function of countershading?

Countershading, the gradation of colour from dark on the dorsum to light on the ventrum, is generally considered to have the effect of making organisms difficult to detect. The mechanism that facilitates this form of crypsis is often considered to be concealment of shadows cast on the body of the animal. We review the current empirical evidence for the cryptic function of countershading and for the mechanism underlying it. We argue that there is no conclusive evidence that countershading per se provides any selective advantage in terrestrial or aerial environments. However, the highly refined adaptations of some marine organisms to match the different background light conditions against which they are set when viewed from different aspects strongly suggest an adaptive advantage to countershading in these environments. In none of the cases discussed in this review was the conventional explanation of self-shadow concealment a more plausible explanation for countershading than the alternative explanation that the dorsum and ventrum experience different selection pressures (often associated with background matching).     

What is the function of receptor and membrane endocytosis at the postsynaptic neuron?

This paper explores the implications of certain new developments in cell biology upon neuroscience. Until recently it was thought that neurotransmitters and neuromodulators had only one function, which was to stimulate their specific receptors at the cell surface. From here on, all activity was supposed to be effected by postsynaptic cascades. The discovery that membrane components, particularly G-protein-linked receptors, are not static but are subject to a massive and complex process of continual endocytosis, processing in the endosome system and recycling back to the external membrane, raises the question of its functional significance. In addition, it has been found that many neuromodulators such as polypeptides have their main locus of action inside the postsynaptic neuron. This review covers the role of the endocytic mechanism on receptor desensitization and resensitization, synaptic reorganization and plasticity synaptic scaling and the possible repair of oxidative damage. The possible involvement of this system in Alzheimer's disease is discussed.     

What is the value of oncology medicines?

Coverage with evidence development (CED), rather than quality-adjusted-life-year (QALY) thresholds, offers the best way forward in balancing evidence-based policy for new oncology products with the needs of developers, payers, physicians and patients.     

What is the extent of prokaryotic diversity?

The extent of microbial diversity is an intrinsically fascinating subject of profound practical importance. The term 'diversity' may allude to the number of taxa or species richness as well as their relative abundance. There is uncertainty about both, primarily because sample sizes are too small. Non-parametric diversity estimators make gross underestimates if used with small sample sizes on unevenly distributed communities. One can make richness estimates over many scales using small samples by assuming a species/taxa-abundance distribution. However, no one knows what the underlying taxa-abundance distributions are for bacterial communities. Latterly, diversity has been estimated by fitting data from gene clone libraries and extrapolating from this to taxa-abundance curves to estimate richness. However, since sample sizes are small, we cannot be sure that such samples are representative of the community from which they were drawn. It is however possible to formulate, and calibrate, models that predict the diversity of local communities and of samples drawn from that local community. The calibration of such models suggests that migration rates are small and decrease as the community gets larger. The preliminary predictions of the model are qualitatively consistent with the patterns seen in clone libraries in 'real life'. The validation of this model is also confounded by small sample sizes. However, if such models were properly validated, they could form invaluable tools for the prediction of microbial diversity and a basis for the systematic exploration of microbial diversity on the planet.