Is the Hypoglycemic Action of Vanadium Compounds Related to the Suppression of Feeding?

Vanadium compounds exhibit effective hypoglycemic activity in both type I and type II diabetes mellitus. However, there was one argument that the hypoglycemic action of vanadium compounds could be attributable to the suppression of feeding—one common toxic aspect of vanadium compounds. To clarify this question, we investigated in this work the effect of a vanadyl complex, BSOV (bis((5-hydroxy-4-oxo-4H-pyran-2-yl)methyl-2-hydroxy-benzoatato) oxovanadium (IV)), on diabetic obese (db/db) mice at a low dose (0.05 mmol/kg/day) when BSOV did not inhibit feeding. The experimental results showed that this dose of BSOV effectively normalized the blood glucose level in diabetic mice without affecting the body weight growth. Western blotting assays on the white adipose tissue of db/db mice further indicated that BSOV treatment significantly improved expression of peroxisome proliferator-activated receptor γ (PPARγ) and activated AMP-activated protein kinase (AMPK). In addition, vanadium treatment caused a significant suppression of phosphorylation of c-Jun N-terminal protein kinase (JNK), which plays a key role in insulin-resistance in type II diabetes. This is the first evidence that the mechanism of insulin enhancement action involves interaction of vanadium compounds with JNK. Overall, the present work indicated that vanadium compounds exhibit antidiabetic effects irrelevant to food intake suppression but by modulating the signal transductions of diabetes and other metabolic disorders.     

Neuronal variability: noise or part of the signal?

Sensory, motor and cortical neurons fire impulses or spikes at a regular, but slowly declining, rate in response to a constant current stimulus. Yet, the intervals between spikes often vary randomly during behaviour. Is this variation an unavoidable effect of generating spikes by sensory or synaptic processes ('neural noise') or is it an important part of the 'signal' that is transmitted to other neurons? Here, we mainly discuss this question in relation to sensory and motor processes, as the signals are best identified in such systems, although we also touch on central processes.     

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.     

Nuclear Recruitment of Neuronal Nitric-oxide Synthase by α-Syntrophin Is Crucial for the Induction of Mitochondrial Biogenesis

Neuronal nitric-oxide synthase (nNOS) has various splicing variants and different subcellular localizations. nNOS can be found also in the nucleus; however, its exact role in this compartment is still not completely defined. In this report, we demonstrate that the PDZ domain allows the recruitment of nNOS to nuclei, thus favoring local NO production, nuclear protein S-nitrosylation, and induction of mitochondrial biogenesis. In particular, overexpression of PDZ-containing nNOS (nNOSα) increases S-nitrosylated CREB with consequent augmented binding on cAMP response element consensus sequence on peroxisome proliferator-activated receptor γ co-activator (PGC)-1α promoter. The resulting PGC-1α induction is accompanied by the expression of mitochondrial genes (e.g., TFAM, MtCO1) and increased mitochondrial mass. Importantly, full active nNOS lacking PDZ domain (nNOSβ) does not localize in nuclei and fails in inducing the expression of PGC-1α. Moreover, we substantiate that the mitochondrial biogenesis normally accompanying myogenesis is associated with nuclear translocation of nNOS. We demonstrate that α-Syntrophin, which resides in nuclei of myocytes, functions as the upstream mediator of nuclear nNOS translocation and nNOS-dependent mitochondrial biogenesis. Overall, our results indicate that altered nNOS splicing and nuclear localization could be contributing factors in human muscular diseases associated with mitochondrial impairment.     

Is the post-disturbance composition of a plant population determined by selection for outcrossed seedlings or by the composition of the seedbank?

Seedbanks are expected to buffer populations against disturbances, such as fire, thatcould alter the genetic composition of smaller, ephemeral adult populations. However,seedling genotypes may be influenced by the spatially heterogeneous nature of both theseedbank and the disturbance (for example, germination may vary with local disturbance)and also by selection acting on germination and post-germination performance. We usedmicrosatellite-DNA surveys of seedlings emerging from the soil-stored seedbanks ofGrevillea macleayana after wildfire to compare diversity and spatial structurein seedlings and adults, and through resampling of the seedling data set, to determinewhether the resultant adult population reflected the effects of selection or randomseedling mortality. The large post-fire seedling cohorts captured the full allelicdiversity of the pre-fire adult population. However, we found a mismatch in the genotypicstructure of adults and seedlings. Seedlings displayed larger heterozygous deficits thanadults; however, over the ensuing 11 years, seedling heterozygosity eventually matchedvalues for the pre-fire adults. Increasing heterozygosity among adults has generally beenattributed to heterosis and/or reduction in Wahlund effects via self-thinning.Resampling of early post-fire seedlings to generate samples of equivalent size tosurvivors at 11 years showed that increases in heterozygosity must be driven by selectionfavouring outcrossed seed. This finding is important in an evolutionary context but alsohas implications for the restoration of natural or managed populations where a seedbank isa viable source of recruits.     

Is flight architecture determined by physical constraints or by natural selection?: the case of the midge Chironomus plumosus

Males of the midge Chironomus plumosus fly solely to mate. They maintain station for long periods in moving air. Females patrol in search of males and, after receiving a spermatophore, fly to oviposition sites. The requirements of flight in males and females are therefore fundamentally different. Females are larger than males, on average, so these differences could stem from scaling rules governing the geometry of space. The same explanation might apply to flight differences within the sexes and even to peculiarities of flight architecture in C. plumosus compared to other flying animals. In other words, might flight design be accounted for entirely by mechanical constraints without recourse to natural selection?
To test this hypothesis, the power output of C. plumosu was measured as size-specific muscle mass. Contrary to expectation, little evidence was found of scaling effects in this measure of power. Despite its being among the smallest of animals to fly, C. plumosus turns out to have the largest mass of flight muscle, relative to body size, yet found among animals. Differences both between C. plumosus and other species and within C. plumosus are, in general, more readily accounted for by the requirements of the mating system within the viscous universe encountered by small flying animals. We conclude that it is natural selection rather than mechanical constraint that is the primary influence determining the architecture of flight in this small animal.     

Is sociality driven by the costs of dispersal or the benefits of philopatry? A role for kin-discrimination mechanisms

The role of ecological constraints in promoting sociality is currently much debated. Using a direct-fitness approach, we show this role to depend on the kin-discrimination mechanisms underlying social interactions. Altruism cannot evolve under spatially based discrimination, unless ecological constraints prevent complete dispersal. Increasing constraints enhances both the proportion of philopatric (and thereby altruistic) individuals and the level of altruistic investments conceded in pairwise interactions. Familiarity-based discrimination, by contrast, allows philopatry and altruism to evolve at significant levels even in the absence of ecological constraints. Increasing constraints further enhances the proportion of philopatric (and thereby altruistic) individuals but not the level of altruism conceded. Ecological constraints are thus more likely to affect social evolution in species in which restricted cognitive abilities, large group size, and/or limited period of associative learning force investments to be made on the basis of spatial cues.     

A Decade Later,How Much of Rwanda's Musculoskeletal Impairment Is Caused by the War in 1994 and by Related Violence?

Background

In 1994 there was a horrific genocide in Rwanda following years of tension, resulting in the murder of at least 800,000 people. Although many people were injured in addition to those killed, no attempt has been made to assess the lasting burden of physical injuries related to these events. The aim of this study was to estimate the current burden of musculoskeletal impairment (MSI) attributable to the 1994 war and related violence.

Methodology/Principal Findings

A national cross-sectional survey of MSI was conducted in Rwanda. 105 clusters of 80 people were selected through probability proportionate to size sampling. Households within clusters were selected through compact segment sampling. Enumerated people answered a seven-question screening test to assess whether they might have an MSI. Those who were classed as potential cases in the screening test were examined and interviewed by a physiotherapist, using a standard protocol that recorded the site, nature, cause, and severity of the MSI. People with MSI due to trauma were asked whether this trauma occurred during the 1990–1994 war or during the episodes that preceded or followed this war. Out of 8,368 people enumerated, 6,757 were available for screening and examination (80.8%). 352 people were diagnosed with an MSI (prevalence = 5.2%, 95% CI = 4.5–5.9%). 106 cases of MSI (30.6%) were classified as resulting from trauma, based on self-report and the physiotherapist''s assessment. Of these, 14 people (13.2%) reported that their trauma-related MSI occurred during the 1990–1994 war, and a further 7 (6.6%) that their trauma-related MSI occurred during the violent episodes that preceded and followed the war, giving an overall prevalence of trauma-related MSI related to the 1990–1994 war of 0.3% (95% CI = 0.2–0.4%).

Conclusions/Significance

A decade on, the overall prevalence of MSI was relatively high in Rwanda but few cases appeared to be the result of the 1994 war or related violence.     

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.     

Is the purple color of bacteriorhodopsin maintained by lipid-protein interactions?

When bacteriorhodopsin is delipidated and purified in detergents, its purple chromophore can be reversibly titrated to a red one. The pK_a of this equilibrium depends on the nature of the detergent in which bacteriorhodopsin is dispersed. In the absence of solvating amphiphiles, lipid-free detergent-free bacteriorhodopsin is red (λ_max = 480 nm) at pH higher than 3.5.     

Congenital Myasthenic Syndrome Type 19 Is Caused by Mutations in COL13A1, Encoding the Atypical Non-fibrillar Collagen Type XIII α1 Chain

The neuromuscular junction (NMJ) consists of a tripartite synapse with a presynaptic nerve terminal, Schwann cells that ensheathe the terminal bouton, and a highly specialized postsynaptic membrane. Synaptic structural integrity is crucial for efficient signal transmission. Congenital myasthenic syndromes (CMSs) are a heterogeneous group of inherited disorders that result from impaired neuromuscular transmission, caused by mutations in genes encoding proteins that are involved in synaptic transmission and in forming and maintaining the structural integrity of NMJs. To identify further causes of CMSs, we performed whole-exome sequencing (WES) in families without an identified mutation in known CMS-associated genes. In two families affected by a previously undefined CMS, we identified homozygous loss-of-function mutations in COL13A1, which encodes the alpha chain of an atypical non-fibrillar collagen with a single transmembrane domain. COL13A1 localized to the human muscle motor endplate. Using CRISPR-Cas9 genome editing, modeling of the COL13A1 c.1171delG (p.Leu392Sfs^∗71) frameshift mutation in the C2C12 cell line reduced acetylcholine receptor (AChR) clustering during myotube differentiation. This highlights the crucial role of collagen XIII in the formation and maintenance of the NMJ. Our results therefore delineate a myasthenic disorder that is caused by loss-of-function mutations in COL13A1, encoding a protein involved in organization of the NMJ, and emphasize the importance of appropriate symptomatic treatment for these individuals.