Shifts of Gamma Phase across Primary Visual Cortical Sites Reflect Dynamic Stimulus-Modulated Information Transfer

Distributed neural processing likely entails the capability of networks to reconfigure dynamically the directionality and strength of their functional connections. Yet, the neural mechanisms that may allow such dynamic routing of the information flow are not yet fully understood. We investigated the role of gamma band (50–80 Hz) oscillations in transient modulations of communication among neural populations by using measures of direction-specific causal information transfer. We found that the local phase of gamma-band rhythmic activity exerted a stimulus-modulated and spatially-asymmetric directed effect on the firing rate of spatially separated populations within the primary visual cortex. The relationships between gamma phases at different sites (phase shifts) could be described as a stimulus-modulated gamma-band wave propagating along the spatial directions with the largest information transfer. We observed transient stimulus-related changes in the spatial configuration of phases (compatible with changes in direction of gamma wave propagation) accompanied by a relative increase of the amount of information flowing along the instantaneous direction of the gamma wave. These effects were specific to the gamma-band and suggest that the time-varying relationships between gamma phases at different locations mark, and possibly causally mediate, the dynamic reconfiguration of functional connections.     

Thermal specialization across large geographical scales predicts the resilience of mangrove crab populations to global warming

The broad prediction that ectotherms will be more vulnerable to climate change in the tropics than in temperate regions includes assumptions about centre/edge population effects that can only be tested by within‐species comparisons across wide latitudinal gradients. Here, we investigated the thermal vulnerability of two mangrove crab species, comparing populations at the centre (Kenya) and edge (South Africa) of their distributions. At the same time, we investigated the role of respiratory mode (water‐ versus air‐breathing) in determining the thermal tolerance in amphibious organisms. To do this, we compared the vulnerability to acute temperature fluctuations of two sympatric species with two different lifestyle adaptations: the free living Perisesarma guttatum and the burrowing Uca urvillei, both pivotal to the ecosystem functioning of mangroves. The results revealed the air‐breathing U. urvillei to be a thermal generalist with much higher thermal tolerances than P. guttatum. Importantly, however, we found that, while U. urvillei showed little difference between edge and centre populations, P. guttatum showed adaptation to local conditions. Equatorial populations had elevated tolerances to acute heat stress and mechanisms of partial thermoregulation, which make them less vulnerable to global warming than temperate conspecifics. The results reveal both the importance of respiratory mode to thermal tolerance and the unexpected potential for low latitude populations/species to endure a warming climate. The results also contribute to a conceptual model on the latitudinal thermal tolerance of these key species. This highlights the need for an integrated population‐level approach to predict the consequences of climate change.     

Synthesis,semipreparative HPLC separation,biological evaluation,and 3D-QSAR of hydrazothiazole derivatives as human monoamine oxidase B inhibitors

The present study reports on synthesis in high yields (70–99%), HPLC enantioseparation, inhibitory activity against human monoamino oxidases, and molecular modeling including 3D-QSAR studies, of a large series of (4-aryl-thiazol-2-yl)hydrazones (1–45). Most of the synthesized compounds proved to be potent and selective inhibitors of hMAO-B isoform in the micromolar or nanomolar range, thus demonstrating that hydrazothiazole could be considered a good pharmacophore to design new hMAO-B inhibitors. Due to the presence in some derivatives of a chiral center, we also performed a semipreparative chromatographic enantioseparation of these compounds obtained by a stereoconservative pattern. The separated enantiomers were submitted to in vitro biological evaluation to point out the stereorecognition of the active site of the enzyme towards these structures. Finally, a 3D-QSAR study was carried out using Comparative Molecular Field Analysis (CoMFA), aiming to deduce rational guidelines for the further structural modification of these lead compounds.     

Brief communication: A morphometric analysis of the neandertal upper second molar leuca I

The scarcity of Neandertal remains from Southern Europe hampers our understanding of Neandertal variability, and can bias interpretations about Neandertal geographic variation. To address this issue, it is often important to reassess human remains that, while discovered decades ago, remain relatively unknown to the scientific community. In this contribution, we provide a complete state‐of‐the‐art comparative morphometric analysis of Leuca I, an unworn left second upper molar (LM²) discovered in 1958 in Bambino's Cave (near Santa Maria di Leuca, Apulia, Italy) and attributed to Homo neanderthalensis. Our study includes comparisons of standard metric and nonmetric data, a 2D image analysis of the occlusal surface and measurements of both 2D and 3D enamel thickness and dental tissue proportions. Although Leuca I follows the Neandertal M²s trend in some morphometric aspects (i.e., small relative occlusal polygon area), in other cases it falls to the higher end (for 3D average enamel thickness) or even outside (for 3D‐relative enamel thickness) the Neandertal M² variability, thus increasing the known Neandertal range of variation. Am J Phys Anthropol 152:300–305, 2013. © 2013 Wiley Periodicals, Inc.     

Modulation of the immune response induced by gene electrotransfer of a hepatitis C virus DNA vaccine in nonhuman primates

Induction of multispecific, functional CD4+ and CD8+ T cells is the immunological hallmark of acute self-limiting hepatitis C virus (HCV) infection in humans. In the present study, we showed that gene electrotransfer (GET) of a novel candidate DNA vaccine encoding an optimized version of the nonstructural region of HCV (from NS3 to NS5B) induced substantially more potent, broad, and long-lasting CD4+ and CD8+ cellular immunity than naked DNA injection in mice and in rhesus macaques as measured by a combination of assays, including IFN-gamma ELISPOT, intracellular cytokine staining, and cytotoxic T cell assays. A protocol based on three injections of DNA with GET induced a substantially higher CD4+ T cell response than an adenovirus 6-based viral vector encoding the same Ag. To better evaluate the immunological potency and probability of success of this vaccine, we have immunized two chimpanzees and have compared vaccine-induced cell-mediated immunity to that measured in acute self-limiting infection in humans. GET of the candidate HCV vaccine led to vigorous, multispecific IFN-gamma+CD8+ and CD4+ T lymphocyte responses in chimpanzees, which were comparable to those measured in five individuals that cleared spontaneously HCV infection. These data support the hypothesis that T cell responses elicited by the present strategy could be beneficial in prophylactic vaccine approaches against HCV.     

Glutamate-induced calcium increase in myotubes depends on up-regulation of a sodium-dependent transporter

We report a study on the regulation by 2-chloro adenosine (2CA) of a glutamate (Glu) transporter in myogenic C2C12 cells. Long-term 2CA exposition significantly increased the V(max) of the Glu transporter. Moreover, 2CA-treated cells responded to Glu challenge by a rapid and transient increase in their intracellular calcium level. The above reported effects were totally abolished by treating C2C12 cells with the Na(+)-dependent Glu transporter inhibitors DL-threo-b-hydroxyaspartic acid and L-trans-pyrrolidine-2,4-dicarboxylic acid. We propose that the possible link between the Glu uptake increase and the Glu induction of calcium rise could be the depolarizing currents carried by Na(+) coupled with transporter activity.     

A laboratory study on the short-term zonal oscillations of the trochid Monodonta turbinata (Born) (Mollusca: Gastropoda)

Zonal oscillations of Monodonta turbinata (Born) were monitored with an actographic device which precluded clustering behaviour. Unfed snails maintained their cyclic pattern of behaviour for up to 8 days under a light-dark cycle which simulated the natural one. Under constant conditions of light or dark, however, the snails ceased migration and occupied a zonal position typical of day and night, respectively. Experiments in diffuse light and with light from below the floor of the experimental tank showed that the downward migration of M. turbinata in the daytime depends on positive geotaxis combined with negative phototaxis whilst the upward migration at night depends on a negative geotaxis. This mechanism is similar to that described in other littoral molluscs. There was no evidence of an endogenous control of rhythmic zonal activity.     

The complete amino acid sequences of cytosolic and mitochondrial aspartate aminotransferases from horse heart,and inferences on evolution of the isoenzymes

Summary We report here the complete amino acid sequences of the cytosolic and mitochondrial aspartate aminotransferases from horse heart. The two sequences can be aligned so that 48.1% of the amino acid residues are identical. The sequences have been compared with those of the cytosolic isoenzymes from pig and chicken, the mitochondrial isoenzymes from pig, chicken, rat, and human, and the enzyme fromEscherichia coli. The results suggest that the mammalian cytosolic and mitochondrial isoenzymes have evolved at equal and constant rates whereas the isoenzymes from chicken may have evolved somewhat more slowly. Based on the rate of evolution of the mammalian isoenzymes, the geneduplication event that gave rise to cytosolic and mitochondrial aspartate aminotransferases is estimated to have occurred at least 10⁹ years ago. The cytosolic and mitochondrial isoenzymes are equally related to the enzyme fromE. coli; the prokaryotic and eukaryotic enzymes diverged from one another at least 1.3×10⁹ years ago.     

Finding biological process modifications in cancer tissues by mining gene expression correlations

Background  

Through the use of DNA microarrays it is now possible to obtain quantitative measurements of the expression of thousands of genes from a biological sample. This technology yields a global view of gene expression that can be used in several ways. Functional insight into expression profiles is routinely obtained by using Gene Ontology terms associated to the cellular genes. In this paper, we deal with functional data mining from expression profiles, proposing a novel approach that studies the correlations between genes and their relations to Gene Ontology (GO). By using this "functional correlations comparison" we explore all possible pairs of genes identifying the affected biological processes by analyzing in a pair-wise manner gene expression patterns and linking correlated pairs with Gene Ontology terms.