Is the K permeability of the resting membrane controlled by the excitable K channel?

To test whether or not the potassium permeability of the resting membrane is controlled by the excitable K channels (delayed rectifier), we examined changes in the Na and K permeability ratio, PNa/PK, of the squid axon before and after the excitable K channels were blocked. The blockage of the K channels was accomplished by three independent methods: internal application of tetraethylammonium, internal application of 4-aminopyridine plus Cs, and prolong internal perfusion of NaF solution. The permeability ratio was determined using two different methods: the conventional electrophysiological method and a new method based on the measurements of the hyperpolarizing effect of Na removal. We found that blocking the K channels did not cause a proportional decrease in the K permeability of the resting membrane, suggesting that the semipermeable property of the resting membrane is not determined by the excitable K channels.     

Is renal erythropoietin secretion consequence of local hypoxia coupled with local suppression of angiogenesis?

The kidney is a major source of systemic erythropoietin, despite itself showing little angiogenesis. Based on paper by Schumacher VA et-al. [J Am Soc Nephrol 2007;18:719-29] that renal synthesis of an inhibitory VEGF variant (VEGF165b) blocks local angiogenesis, we hypothesise that the chronic hypoxia in the renal medulla, due to limited perfusion through vasa recta stimulates continuous renal erythropoietin secretion.     

Is the mechanical activity of epithelial cells controlled by deformations or forces?

The traction forces developed by cells depend strongly on the substrate rigidity. In this letter, we characterize quantitatively this effect on MDCK epithelial cells by using a microfabricated force sensor consisting in a high-density array of soft pillars whose stiffness can be tailored by changing their height and radius to obtain a rigidity range from 2 nN/microm up to 130 nN/microm. We find that the forces exerted by the cells are proportional to the spring constant of the pillars meaning that, on average, the cells deform the pillars by the same amount whatever their rigidity. The relevant parameter may thus be a deformation rather than a force. These dynamic observations are correlated with the reinforcement of focal adhesions that increases with the substrate rigidity.     

Is Atlantic salmon production limited by number of territories?

Thirty Atlantic salmon Salmo salar parr (mean 135 mm total length, L _T) in the River Alta, Norway, were radio‐tagged and tracked during a 11–13 day period. The parr stayed within defined home ranges with a 95% probability of localization within an average area of 1286 m²(241–3484 m²). On average, each parr had overlapping home ranges with 7·7 other parr, and the overlap between pairs of fish covered on average 24% of their home range areas. Mean length of the river stretch used was 90 m (22–383 m). On average, during 38%(16–77%) of the tracking surveys, the fish had moved >10 m since the previous survey. Mean total distance moved during the whole study was 402 m (208–862 m). The Atlantic salmon were most often recorded in riffles, but 27% of the parr alternated between riffles and pools. The extensive movements, flexible habitat utilization and relatively large home ranges, together with the fact that all the parr had home ranges partly overlapping with other radio‐tagged parr, indicate a flexible and variable behaviour and, thereby, a more complex social structure than a rigid defence of a fixed territory. Thus, Atlantic salmon production seems not to be limited by the highest potential number of territories for large parr in a given area.     

Is neurotensin in the brain involved in thermoregulation of the monkey?

Cannulae for intracerebroventricular (ICV) infusion were implanted stereotaxically in monkeys (Macaca fasicularis) maintained post-operatively in a primate restraint chair. During each experiment, a series of physiological measures was recorded simultaneously on a polygraph which included colonic temperature, vasomotor tone, heart rate, respiratory rate, and basal metabolism as reflected by O₂ uptake. The ICV infusion in a volume of 0.5 ml of neurotensin (NT) in doses ranging from 3–150 μg produced neither a statistically significant nor consistent change in body temperature or vasomotor response. Although the highest dose of 450 μg NT infused ICV caused an immediate bradycardia and a concomitant decline in metabolic and respiratory rates, an average decline in core temperature of 0.6°C and the accompanying cutaneous vasodilation often had a latency as long as 1.0 hr. In contrast to the typical hypothermia in this species following an ICV infusion of catecholamines, implicated in the central pathways underlying thermoregulation, NT failed to elicit a coordinated set of physiological responses for heat dissipation in the monkey. Therefore, it is unlikely that this tridecapeptide plays a role in the central mechanisms mediating the control of body temperature of this primate species.     

Is the solitary dark neuron a manifestation of postmortem trauma to the brain inadequately fixed by perfusion?

Summary Dark neurons, classified as solitary because of their sparse occurrence, were discerned in the transitional zones between gray and white matter in various species of laboratory animals fixed by perfusion. These neurons, histologically indistinguishable from dark neurons in immersion fixed material, tended to develop when the saline perfusion was delayed or slow, the amount of the Bouin fixative was excessive, or the autopsy was performed shortly after the perfusion. Under these conditions, the white matter manifested a softer consistency and a paler color than the gray matter. These observations suggest that, as the consequence of regional differences in intensity and speed of fixation, distortion during extraction of the brain may activate a stress force in the transitional zones where incompletely fixed neurons become affected and acquire an abnormal affinity for aniline dyes and silver.     

Is adult stem cell aging driven by conflicting modes of chromatin remodeling?

Epigenetic control of gene expression by chromatin remodeling is critical for adult stem cell function. A decline in stem cell function is observed during aging, which is accompanied by changes in the chromatin structure that are currently unexplained. Here, we hypothesize that these epigenetic changes originate from the limited cellular capability to inherit epigenetic information. We suggest that spontaneous loss of histone modification, due to fluctuations over short time scales, gives rise to long-term changes in DNA methylation and, accordingly, in gene expression. These changes are assumed to impair stem cell function and, thus, to contribute to aging. We discuss cell replication as a major source of fluctuations in histone modification patterns. Gene silencing by our proposed mechanism can be interpreted as a manifestation of the conflict between the stem cell plasticity required for tissue regeneration and the permanent silencing of potentially deleterious genomic sequences.     

Can the grey mould disease of the grape-vine be controlled by yeast?

Botrytis cinerea has been found to be highly pathogenic to 'Chardonnay' and 'Pinot noir' cultivars of the grape-vine producing the characteristic grey mould symptoms within 7 days of inoculation to the vitro-plants. The yeast Pichia anomala (strain FY-102), isolated from apple skin, was found to be antagonistic to B. cinerea as it completely inhibited the appearance of the grey mould symptoms when grown together. The yeast was responsible for morphological changes such as coagulation and leakage of the cytoplasm of B. cinerea. The pathogen, when applied together with P. anomala, failed to bring about the grey mould symptoms on the grape-vine, suggesting that the yeast could control the expression of this disease. An account of the interaction between B. cinerea and P. anomala, as well as the sequences of the complete ITS region of the ribosomal DNA of the yeast are described here.     

Is the identification of antibodies against the nervous tissue an indicator of brain injury?

Using a modification of the ELISA method, auto-antibodies against the own nervous tissue have been identified in the serum of laboratory rats. The prevalence of the IgM class of antibodies suggests their physiological significance. Antibody levels are higher in females than in males. Brain hypoxic injury brings about a shift in the spectrum of antibodies towards the IgG class. It may thus serve as an indicator of brain impairment caused by a lack of oxygen.     

Is aldosterone synthesized within the rat brain?

Very small amounts of adrenocorticosteroids are synthesized by brain tissue in vitro. While there is evidence suggesting that the synthesis of aldosterone in the brain may have a role in the hypertension of the Dahl salt-sensitive rat, the de novo synthesis of aldosterone or corticosterone within the brain of a living animal has not been demonstrated. We have used sensitive ELISAs to measure aldosterone and corticosterone in the plasma and whole brains of intact rats receiving a normal-, low-, or high-salt diet to alter adrenal aldosterone production and of adrenalectomized rats provided sodium replacement, some of which received aldosterone, corticosterone, or DOC replacement. The results of several experiments were consistent. In intact rats, the brain concentration of aldosterone and corticosterone reflected that in the plasma. However, whereas aldosterone and corticosterone were undetectable or barely undetectable in the plasma of adrenalectomized animals, as was the corticosterone in their brains, aldosterone was consistently found in the brains of adrenalectomized rats, ranging from a mean of 6.6-41 pg/g, depending on the experiment. Provision of DOC as substrate for the endogenous aldosterone synthase and 11beta-hydroxylase did not significantly increase brain aldosterone or corticosterone content. It is postulated that the small amounts of aldosterone synthesized in the brain could provide a local ligand for autocrine or paracrine activation of the mineralocorticoid receptor.     

Is invasion efficiency in malaria controlled by pre-invasion events?

The invasion efficiency of Plasmodium falciparum merozoites was found to decrease with increasing red blood cell density, a finding relevant to protection strategies against falciparum malaria. The mechanism of this 'density effect' remained unexplained. Searching for possible explanations, we studied selected video recordings of the dynamic events during merozoite invasion and identified a pre-invasion stage as a crucial mediator of invasion efficiency. We suggest that the role of the pre-invasion stage is to induce the apical alignment of the merozoite, and propose a working hypothesis on its mechanism, with a crucial role for elevated intracellular Ca2+.     

Is the development of orientation selectivity instructed by activity?

Is the development of orientation selectivity in visual cortex instructed by the patterns of neural activity of input neurons? We review evidence as to the role of activity, review models of activity-instructed development, and discuss how these models can be tested. The models can explain the normal development of simple cells with binocularly matched orientation preferences, the effects of monocular deprivation and reverse suture on the orientation map, and the development of a full intracortical circuit sufficient to explain mature response properties including the contrast-invariance of orientation tuning. Existing experiments are consistent with the models, in that (a) selective blockade of ON-center ganglion cells, which will degrade or eliminate the information predicted to drive development of orientation selectivity, in fact prevents development of orientation selectivity; and (b) the spontaneous activities of inputs serving the two eyes are correlated in the lateral geniculate nucleus at appropriate developmental times, as was predicted to be required to achieve binocular matching of preferred orientations. However, definitive tests remain to be done to firmly establish the instructive rather than simply permissive role of activity and determine whether the retinotopically and center type-specific patterns of activity predicted by the models actually exist. We conclude by critically examining alternative scenarios for the development of orientation selectivity and maps, including the idea that maps are genetically prespecified.     

Is the parasitization capacity of Trichogramma cordubensis influenced by the age of the females?

We investigated the parasitization capacity of Trichogramma cordubensis Vargas & Cabello (Hymenoptera: Trichogrammatidae) females aged 24 h, 48 h, 72 h, 96 h, 120 h, and 144 h, using Ephestia kuehniella Zeller (Lepidoptera: Pyralidae) eggs as hosts. Wasps were held without hosts during the period of ageing, therefore being increasingly time-limited with respect to parasitization as they got older. The total number of parasitized hosts decreased as the age of the parasitoid increased. However, the proportion of lifetime parasitism carried out on the first day increased with wasp age, up to 120-h old females. These results show that the parasitization capacity of ageing T. cordubensis females changes as they become time-limited. The consequences of such changes for biological control programs are discussed.     

Phase transitions in nuclei and chromatin. Is nuclear volume controlled by the chromatin or by the nuclear matrix?

Changes in the volume of rat liver nuclei have been monitored as a function of modifications in ionic environment (from 0 to 20 mM), temperature (from 4 to 37 degrees C), and pH (from 1 to 8). An abrupt reduction of nuclear volume occurred with increasing ion concentration, this contraction being more pronounced with bivalent (either Ca2+ or Mg2+) than with monovalent (either Na+ or K+) cations. The lowering of pH produced a similar effect. Parallel changes in chromatin structure took place at the same time as phase-like transitions. Atomic absorption spectroscopy allowed determination of free and nuclei-bound ions, pointing to the presence of a sizeable number of free binding sites for chromatin-DNA even within intact nuclei. DNA-phosphate sites appear to be neutralized by ions strictly according to the size of the electric charge and polyelectrolyte theory. Partial digestion (by micrococcal nuclease) or simple breaks (by chemical carcinogens) of the chromatin-DNA fiber caused respectively elimination or reduction of the abrupt volume changes in the intact nuclei. The apparent role of chromatin structure versus nuclear matrix in determining the shape and volume of intact nuclei is briefly discussed.     

Can the stereochemical outcome of glycosylation reactions be controlled by the conformational preferences of the glycosyl donor?

Previous static and dynamical density functional theory studies of the 2,6-di-O-acetyl-3,4-O-isopropylidene-D-galactopyranosyl cations and their methanol adducts has led to an hypothesis that these cations exist in two families of conformers characterized as (2)S(O) and B(2,5), respectively. These families differ by ring inversion, each with its own reactivity. New calculations on the 2,6-di-O-acetyl-3,4-di-O-methyl-D-galactopyranosyl cation confirmed these trends. Removing the isopropylidene group allows more flexibility, but two families of conformers can be discerned with the monocyclic oxocarbenium ions in the E(3) conformation and the bicyclic dioxolenium ions in the (4)H(5) conformation. Attack on the beta-face of these monocyclic cations is favored by hydrogen bonding and the anomeric effect. The experimentally observed high beta-stereoselectivity of mannopyranosyl donors and high alpha-stereoselectivity of glucopyranosyl donors with the 4,6-O-benzylidene protecting groups can be rationalized assuming that the trans-fused 1,3-dioxane ring allows population of only one family of conformers. The combination of hydrogen bonding and conformational changes of the pyranose ring in response to the C-5[bond]O-5[bond]C-1[bond]C-2 torsion angle changes are identified as key factors in stereoselectivity. Based on these observations a strategy to design face discriminated glycosyl donors that exist predominantly in only one family of conformers is proposed.     

What are the sources of hydrogen peroxide production by heart mitochondria?

Coupled rat heart mitochondria produce externally hydrogen peroxide at the rates which correspond to about 0.8 and 0.3% of the total oxygen consumption at State 4 with succinate and glutamate plus malate as the respiratory substrates, respectively. Stimulation of the respiratory activities by ADP (State 4–State 3 transition) decreases the succinate- and glutamate plus malate-supported H₂O₂ production 8- and 1.3-times, respectively. NH₄⁺ strongly stimulates hydrogen peroxide formation with either substrate without any effect on State 4 and/or State 3 respiration. Rotenone-treated, alamethicin-permeabilized mitochondria catalyze NADH-supported H₂O₂ production at a rate about 10-fold higher than that seen in intact mitochondria under optimal (State 4 succinate-supported respiration in the presence of ammonium chloride) conditions. NADH-supported hydrogen peroxide production by the rotenone-treated mitochondria devoid of a permeability barrier for H₂O₂ diffusion by alamethicin treatment are only partially (～ 50%) sensitive to the Complex I NADH binding site-specific inhibitor, NADH-OH. The residual activity is strongly (～ 6-fold) stimulated by ammonium chloride. NAD⁺ inhibits both Complex I-mediated and ammonium-stimulated H₂O₂ production. In the absence of stimulatory ammonium about half of the total NADH-supported hydrogen peroxide production is catalyzed by Complex I. In the presence of ammonium about 90% of the total hydrogen peroxide production is catalyzed by matrix located, ammonium-dependent enzyme(s).