Signal processing properties of fast spiking interneurons

Fast spiking interneurons receive excitatory synaptic inputs from pyramidal cells and a relevant problem is to understand how these cells readout this information. Here this topic is investigated theoretically by using a biophysical modeling of a pair of coupled fast spiking interneuron models. The model predicts, in agreement with the experimental findings, that these cells are capable of transmitting pre-synaptic signals with high temporal precision and transferring high frequency inputs while preserving their relative timing. Moreover, it is shown that a pair of fast spiking interneurons, coupled through both inhibitory and electrical synapses, behaves as a coincidence detector. Lastly, to understand the mechanisms underlying these phenomena, a theoretical analysis is carried out by using a simpler modeling approach.     

Capture myopathy in little bustards after trapping and marking

Four little bustards (Tetrax tetrax) (one adult and three juvenile males), captured with leg nooses and fitted with a backpack radiotag, died after capture. The first bird was found after 16 days with its left foot caught in the harness and died after 1 day. The other birds showed symptoms of capture myopathy after release, such as the difficulty or inability to fly and/or walk. They died after 5, 6, and 8 days, respectively. At necropsy, muscles affected in all cases were those from the legs, and these were diffusely pale and dull, with a soft friable texture. Microscopically these muscles had multiple foci of myofiber fragmentation, loss of striation, and necrosis; a mononuclear cell infiltrate was observed in muscle from two birds. These findings suggest the little bustard is susceptible to capture myopathy and that caution should be exercised during its capture and handling.     

Mutant analysis of the Shal (Kv4) voltage-gated fast transient K+ channel in Caenorhabditis elegans

Shal (Kv4) alpha-subunits are the most conserved among the family of voltage-gated potassium channels. Previous work has shown that the Shal potassium channel subfamily underlies the predominant fast transient outward current in Drosophila neurons (Tsunoda, S., and Salkoff, L. (1995) J. Neurosci. 15, 1741-1754) and the fast transient outward current in mouse heart muscle (Guo, W., Jung, W. E., Marionneau, C., Aimond, F., Xu, H., Yamada, K. A., Schwarz, T. L., Demolombe, S., and Nerbonne, J. M. (2005) Circ. Res. 97, 1342-1350). We show that Shal channels also play a role as the predominant transient outward current in Caenorhabditis elegans muscle. Green fluorescent protein promoter experiments also revealed SHL-1 expression in a subset of neurons as well as in C. elegans body wall muscle and in male-specific diagonal muscles. The shl-1 (ok1168) null mutant removed all fast transient outward current from muscle cells. SHL-1 currents strongly resembled Shal currents in other species except that they were active in a more depolarized voltage range. We also determined that the remaining delayed-rectifier current in cultured myocytes was carried by the Shaker ortholog SHK-1. In shl-1 (ok1168) mutants there was a significant compensatory increase in the SHK-1 current. Male shl-1 (ok1168) animals exhibited reduced mating efficiency resulting from an apparent difficulty in locating the hermaphrodite vulva. SHL-1 channels are apparently important in fine-tuning complex behaviors, such as mating, that play a crucial role in the survival and propagation of the species.     

Sclerosing variant of PEComa: report of a case and review of the literature

Tumours of perivascular epithelioid cells (PEComas) are a heterogeneous group of uncommon mesenchymal neoplasms which exhibit a peculiar immunohistochemical co-expression of muscle and melanocytic markers. PEComas occur at various visceral and soft tissue sites, generally with a benign clinical course. Nevertheless, there has been evidence of cases having an unfavourable outcome, thus prompting investigation of pathological criteria for malignancy. A sclerosing variant of PEComa, more frequently encountered in the retroperitoneum of middle-aged women, has been reported. Prognosis has generally been regarded as favourable and complete surgical excision appears to be adequate treatment. To the best of our knowledge, only two cases of sclerosing PEComa displayed high-grade malignant morphology and were associated with adverse outcome. An additional case of retroperitoneal sclerosing PEComa with a two-year follow-up and indolent behaviour is herein described. Light and electron microscopy were performed, along with immunohistochemical analysis. Further studies are needed to clarify the histogenesis and to predict the biological behaviour of this uncommon entity.     

Inter-individual variability and conspecific densities: consequences for population regulation and range expansion

The presence of conspecifics can strongly modulate the quality of a breeding site. Both positive and negative effects of conspecifics can act on the same individuals, with the final balance between its costs and benefits depending on individual characteristics. A particular case of inter-individual variation found in many avian species is chromatic variability. Among birds, plumage coloration can co-vary with morphology, physiology and behavior as well as with age. These relationships suggest that cost-benefit balances of conspecific presence may be different for individuals with different colorations. We investigated whether inter-individual variability affects population regulation and expansion processes by analyzing potential differences in density-dependent productivity and settlement patterns in relation to plumage coloration in a population of a long-lived avian species recently undergoing a notable increase in numbers and distribution range. Our results show strong variation in the effect of density on productivity of breeding pairs depending on plumage coloration of their members. Productivity of dark birds decreased along the breeding density gradient while that of lighter breeders remained unchanged with conspecific density. In a similar way, our results showed an uneven occupation of localities by individuals with different plumage coloration in relation to local densities, with the breeding of lighter harriers more aggregated than that of dark-brown ones. At a population scale, darker birds had higher probability of colonization of the most isolated, empty sites. Explanations for species range expansion and population regulation usually make the inferred assumption that species traits are similar among individuals. However, in most species, there could be individual variation in niche requirements or dispersal propensities among individuals with different traits. Our results contribute to the growing appreciation that the individual traits, but not the average trait at the level of species, are important during population regulation and expansion processes.     

On the mechanism of Candida spp. photoinactivation by hypericin

The photoprocesses involved in hypericin photoinactivation of three different Candida species (C. albicans, C. parapsilosis and C. krusei) have been examined. Production of singlet oxygen from the triplet state and of superoxide from both the triplet state and the semiquinone radical anion are demonstrated. Hydrogen peroxide is formed downstream of these early events. The outcome of the photodynamic treatments is dictated by the intracellular distribution of hypericin, which is different in the three species and affects the ability of hypericin to produce the different reactive oxygen species and trigger cell-death pathways. The results are in line with the previously-observed different susceptibilities of the three Candida species to hypericin photodynamic treatments.     

Socio-geography of human mobility: a study using longitudinal mobile phone data

A relationship between people's mobility and their social networks is presented based on an analysis of calling and mobility traces for one year of anonymized call detail records of over one million mobile phone users in Portugal. We find that about 80% of places visited are within just 20 km of their nearest (geographical) social ties' locations. This figure rises to 90% at a 'geo-social radius' of 45 km. In terms of their travel scope, people are geographically closer to their weak ties than strong ties. Specifically, they are 15% more likely to be at some distance away from their weak ties than strong ties. The likelihood of being at some distance from social ties increases with the population density, and the rates of increase are higher for shorter geo-social radii. In addition, we find that area population density is indicative of geo-social radius where denser areas imply shorter radii. For example, in urban areas such as Lisbon and Porto, the geo-social radius is approximately 7 km and this increases to approximately 15 km for less densely populated areas such as Parades and Santa Maria da Feira.     

Synergistic activity and mode of action of flavonoids isolated from smaller galangal and amoxicillin combinations against amoxicillin-resistant Escherichia coli

Aim: The smaller galangal is extracted, purified and identified the bioactive compounds. The purpose of this research was to investigate whether these isolated compounds have antibacterial and synergistic activity against amoxicillin‐resistant Escherichia coli (AREC) when used singly and in combination with amoxicillin. The primarily mode of action is also studied. Method and Results: The galangin, kaempferide and kaempferide‐3‐O‐β‐d ‐glucoside were isolated. The minimum inhibitory concentrations(MIC) of amoxicillin and these flavonoids against AREC were between 500 and >1000 μg ml^?1. Synergistic activity was observed on combining amoxicillin with these flavonoids. The combinations of amoxicillin and these flavonoids exhibited a synergistic effect, reducing AREC cell numbers. Electron microscopy showed that these combinations damaged the ultrastructure of AREC cells. The results indicated that these combinations altered outer membrane permeability but not affecting cytoplasmic membrane. Enzyme assays showed that these flavonoids had an inhibitory activity against penicillinase. Conclusion: These results indicated that these flavonoids have the potential to reverse bacterial resistance to amoxicillin in AREC and may operate via three mechanisms: inhibition of peptidoglycan and ribosome synthesis, alteration of outer membrane permeability, and interaction with β‐lactamases. Significance and Impact of the Study: These findings offer the potential to develop a new generation of phytopharmaceuticals to treat AREC.     

Functional Characterization of a Newly Identified Group B Streptococcus Pullulanase Eliciting Antibodies Able to Prevent Alpha-Glucans Degradation

Streptococcal pullulanases have been recently proposed as key components of the metabolic machinery involved in bacterial adaptation to host niches. By sequence analysis of the Group B Streptococcus (GBS) genome we found a novel putative surface exposed protein with pullulanase activity. We named such a protein SAP. The sap gene is highly conserved among GBS strains and homologous genes, such as PulA and SpuA, have been described in other pathogenic streptococci. The SAP protein contains two N-terminal carbohydrate-binding motifs, followed by a catalytic domain and a C-terminal LPXTG cell wall-anchoring domain. In vitro analysis revealed that the recombinant form of SAP is able to degrade α-glucan polysaccharides, such as pullulan, glycogen and starch. Moreover, NMR analysis showed that SAP acts as a type I pullulanase. Studies performed on whole bacteria indicated that the presence of α-glucan polysaccharides in culture medium up-regulated the expression of SAP on bacterial surface as confirmed by FACS analysis and confocal imaging. Deletion of the sap gene resulted in a reduced capacity of bacteria to grow in medium containing pullulan or glycogen, but not glucose or maltose, confirming the pivotal role of SAP in GBS metabolism of α-glucans. As reported for other streptococcal pullulanases, we found specific anti-SAP antibodies in human sera from healthy volunteers. Investigation of the functional role of anti-SAP antibodies revealed that incubation of GBS in the presence of sera from animals immunized with SAP reduced the capacity of the bacterium to degrade pullulan. Of interest, anti-SAP sera, although to a lower extent, also inhibited Group A Streptococcus pullulanase activity. These data open new perspectives on the possibility to use SAP as a potential vaccine component inducing functional cross-reacting antibodies interfering with streptococcal infections.