Brief Bursts Self-Inhibit and Correlate the Pyramidal Network

Inhibitory pathways are an essential component in the function of the neocortical microcircuitry. Despite the relatively small fraction of inhibitory neurons in the neocortex, these neurons are strongly activated due to their high connectivity rate and the intricate manner in which they interconnect with pyramidal cells (PCs). One prominent pathway is the frequency-dependent disynaptic inhibition (FDDI) formed between layer 5 PCs and mediated by Martinotti cells (MCs). Here, we show that simultaneous short bursts in four PCs are sufficient to exert FDDI in all neighboring PCs within the dimensions of a cortical column. This powerful inhibition is mediated by few interneurons, leading to strongly correlated membrane fluctuations and synchronous spiking between PCs simultaneously receiving FDDI. Somatic integration of such inhibition is independent and electrically isolated from monosynaptic excitation formed between the same PCs. FDDI is strongly shaped by I(h) in PC dendrites, which determines the effective integration time window for inhibitory and excitatory inputs. We propose a key disynaptic mechanism by which brief bursts generated by a few PCs can synchronize the activity in the pyramidal network.     

Ionotropic Receptors as a Driving Force behind Human Synapse Establishment

The origin of nervous systems is a main theme in biology and its mechanisms are largely underlied by synaptic neurotransmission. One problem to explain synapse establishment is that synaptic orthologs are present in multiple aneural organisms. We questioned how the interactions among these elements evolved and to what extent it relates to our understanding of the nervous systems complexity. We identified the human neurotransmission gene network based on genes present in GABAergic, glutamatergic, serotonergic, dopaminergic, and cholinergic systems. The network comprises 321 human genes, 83 of which act exclusively in the nervous system. We reconstructed the evolutionary scenario of synapse emergence by looking for synaptic orthologs in 476 eukaryotes. The Human–Cnidaria common ancestor displayed a massive emergence of neuroexclusive genes, mainly ionotropic receptors, which might have been crucial to the evolution of synapses. Very few synaptic genes had their origin after the Human–Cnidaria common ancestor. We also identified a higher abundance of synaptic proteins in vertebrates, which suggests an increase in the synaptic network complexity of those organisms.     

The Peculiar Facets of Nitric Oxide as a Cellular Messenger: From Disease-Associated Signaling to the Regulation of Brain Bioenergetics and Neurovascular Coupling

In this review, we address the regulatory and toxic role of ^·NO along several pathways, from the gut to the brain. Initially, we address the role on ^·NO in the regulation of mitochondrial respiration with emphasis on the possible contribution to Parkinson’s disease via mechanisms that involve its interaction with a major dopamine metabolite, DOPAC. In parallel with initial discoveries of the inhibition of mitochondrial respiration by ^·NO, it became clear the potential for toxic ^·NO-mediated mechanisms involving the production of more reactive species and the post-translational modification of mitochondrial proteins. Accordingly, we have proposed a novel mechanism potentially leading to dopaminergic cell death, providing evidence that NO synergistically interact with DOPAC in promoting cell death via mechanisms that involve GSH depletion. The modulatory role of NO will be then briefly discussed as a master regulator on brain energy metabolism. The energy metabolism in the brain is central to the understanding of brain function and disease. The core role of ^·NO in the regulation of brain metabolism and vascular responses is further substantiated by discussing its role as a mediator of neurovascular coupling, the increase in local microvessels blood flow in response to spatially restricted increase of neuronal activity. The many facets of NO as intracellular and intercellular messenger, conveying information associated with its spatial and temporal concentration dynamics, involve not only the discussion of its reactions and potential targets on a defined biological environment but also the regulation of its synthesis by the family of nitric oxide synthases. More recently, a novel pathway, out of control of NOS, has been the subject of a great deal of controversy, the nitrate:nitrite:NO pathway, adding new perspectives to ^·NO biology. Thus, finally, this novel pathway will be addressed in connection with nitrate consumption in the diet and the beneficial effects of protein nitration by reactive nitrogen species.

     

Biogeographical patterns and Rapoport's rule in southeastern Pacific benthic polychaetes of the Chilean coast

Recently three biogeographical units were identified along the Chilean coast (the Magellanic Province, an Intermediate Area, and the Peruvian Province), however few studies have focused on the factors and dynamic processes that formed these spatial units (e.g. Rapoport's rule and its causal mechanisms). In this study we used benthic polychaetes of the Chilean coast to evaluate patterns of latitudinal distribution and species richness, and the existence of the three main biogeographical provinces described for the Chilean coast. Additionally, we evaluated the latitudinal Rapoport effects and geometric constraint as a null hypothesis explaining the species richness distribution.
We found that benthic polychaete diversity increased towards southern latitudes. The cluster and ordination (non-metric MultiDimensional Scaling, nMDS) analyses of the distribution data, presented only two statistically significant (bootstrapping techniques) biogeographic provinces along the Chilean coast, with a break occurring between 41° and 42°S. While, our results did not support a latitudinal Rapoport effect, they did support the view that latitudinal Rapoport effects are a local phenomenon, occurring only for the Northeastern Pacific marine taxa. The relationship between latitudinal range extent and mean latitude indicated the existence of two hard boundaries at either extreme of the Chilean coast, limiting the geographical ranges of the species. However, geometric constraints tested using a Monte Carlo simulation approach showed a weak level of mid-domain effect on species richness. Finally, we propose that geometric constraint together with the geomorphology and historical characteristics of the Chilean coast explain the biogeographical patterns of benthic polychaete taxa in Chile.     

Semen cryopreservation in golden‐headed lion tamarin,Leontopithecus chrysomelas

Wild animal genetic resource banking (GRB) represents a valuable tool in conservation breeding programs, particularly in cases involving endangered species such as the golden‐headed lion tamarin (Leontopithecus chrysomelas). Thus, we aimed to assess a sperm freezing protocol for golden‐headed lion tamarins using two different exenders: BotuBOV® (BB) and Test Yolk Buffer® (TYB). Ejaculates were collected by penile vibrostimulation from animals housed at São Paulo Zoological Park Foundation, São Paulo, Brazil, and after immediate analysis, two aliquots were diluted in BB and TYB. Postthawing samples were evaluated for total and progressive motility, plasma membrane and acrosome integrities, mitochondrial activity, susceptibility to oxidative stress, and sperm–egg‐binding. No differences between BB and TYB were found for most seminal parameters, except for acrosome integrity and susceptibility to oxidative stress (in both cases BB showed higher values). However, in spite of these differences and regardless of the extender used, postthaw sperm motility and viability with the described protocol were encouraging (on average >50% and >80%, respectively), indicating that sperm cryopreservation may be a short‐term measure for the conservation of golden‐headed lion tamarins.     

Failure of testicular development associated with a rearrangement of 9p24.1 proximal to the SNF2 gene

In 46,XY individuals, testes are determined by the activity of the SRY gene (sex-determining region Y), located on the short arm of the Ychromosome. The other genetic components of the cascade that leads to testis formation are unknown and may be located on the Xchromosome or on the autosomes. Evidence for the existence of several loci associated with failure of male sexual development is indicated by reports of 46,XY gonadal dysgenesis associated with structural abnormalities of the Xchromosome or of autosomes (chromosomes9, 10, 11 and 17). In this report, we describe the investigation of a child presenting with multiple congenital abnormalities, mental retardation and partial testicular failure. The patient had a homogeneous de novo 46,XY,inv dup(9)(pter→p24.1::p21.1 →p23.3::p24.1→qter) chromosome complement. No deletion was found by either cytogenetic or molecular analysis. The SRY gene and DSS region showed no abnormalities. Southern blotting dosage analysis with 9p probes and fluorescent in situ hybridisation data indicated that the distal breakpoint of the duplicated fragment was located at 9p24.1, proximal to the SNF2 gene. We therefore suggest that a gene involved in normal testicular development and/or maintenance is present at this position on chromosome 9. Received: 20 January 1997 / Accepted: 5 November 1997     

Ocean Acidification and Increased Temperature Have Both Positive and Negative Effects on Early Ontogenetic Traits of a Rocky Shore Keystone Predator Species

The combined effect of ocean acidification and warming is expected to have significant effects on several traits of marine organisms. The gastropod Concholepas concholepas is a rocky shore keystone predator characteristic of the south-eastern Pacific coast of South America and an important natural resource exploited by small-scale artisanal fishermen along the coast of Chile and Peru. In this study, we used small juveniles of C. concholepas collected from the rocky intertidal habitats of southern Chile (39°S) to evaluate under laboratory conditions the potential consequences of projected near-future levels of ocean acidification and warming for important early ontogenetic traits. The individuals were exposed long-term (5.8 months) to contrasting pCO₂ (ca. 500 and 1400 μatm) and temperature (15 and 19°C) levels. After this period we compared body growth traits, dislodgement resistance, predator-escape response, self-righting and metabolic rates. With respect to these traits there was no evidence of a synergistic interaction between pCO₂ and temperature. Shell growth was negatively affected by high pCO₂ levels only at 15°C. High pCO₂ levels also had a negative effect on the predator-escape response. Conversely, dislodgement resistance and self-righting were positively affected by high pCO₂ levels at both temperatures. High tenacity and fast self-righting would reduce predation risk in nature and might compensate for the negative effects of high pCO₂ levels on other important defensive traits such as shell size and escape behaviour. We conclude that climate change might produce in C. concholepas positive and negative effects in physiology and behaviour. In fact, some of the behavioural responses might be a consequence of physiological effects, such as changes in chemosensory capacity (e.g. predator-escape response) or secretion of adhesive mucous (e.g. dislodgement resistance). Moreover, we conclude that positive behavioural responses may assist in the adaptation to negative physiological impacts, and that this may also be the case for other benthic organisms.     

Survival of Escherichia coli in the environment: fundamental and public health aspects

In this review, our current understanding of the species Escherichia coli and its persistence in the open environment is examined. E. coli consists of six different subgroups, which are separable by genomic analyses. Strains within each subgroup occupy various ecological niches, and can be broadly characterized by either commensalistic or different pathogenic behaviour. In relevant cases, genomic islands can be pinpointed that underpin the behaviour. Thus, genomic islands of, on the one hand, broad environmental significance, and, on the other hand, virulence, are highlighted in the context of E. coli survival in its niches. A focus is further placed on experimental studies on the survival of the different types of E. coli in soil, manure and water. Overall, the data suggest that E. coli can persist, for varying periods of time, in such terrestrial and aquatic habitats. In particular, the considerable persistence of the pathogenic E. coli O157:H7 is of importance, as its acid tolerance may be expected to confer a fitness asset in the more acidic environments. In this context, the extent to which E. coli interacts with its human/animal host and the organism''s survivability in natural environments are compared. In addition, the effect of the diversity and community structure of the indigenous microbiota on the fate of invading E. coli populations in the open environment is discussed. Such a relationship is of importance to our knowledge of both public and environmental health.     

Selecting high-dimensional mixed graphical models using minimal AIC or BIC forests

Background  

Chow and Liu showed that the maximum likelihood tree for multivariate discrete distributions may be found using a maximum weight spanning tree algorithm, for example Kruskal's algorithm. The efficiency of the algorithm makes it tractable for high-dimensional problems.