History-Dependent Excitability as a Single-Cell Substrate of Transient Memory for Information Discrimination

Neurons react differently to incoming stimuli depending upon their previous history of stimulation. This property can be considered as a single-cell substrate for transient memory, or context-dependent information processing: depending upon the current context that the neuron “sees” through the subset of the network impinging on it in the immediate past, the same synaptic event can evoke a postsynaptic spike or just a subthreshold depolarization. We propose a formal definition of History-Dependent Excitability (HDE) as a measure of the propensity to firing in any moment in time, linking the subthreshold history-dependent dynamics with spike generation. This definition allows the quantitative assessment of the intrinsic memory for different single-neuron dynamics and input statistics. We illustrate the concept of HDE by considering two general dynamical mechanisms: the passive behavior of an Integrate and Fire (IF) neuron, and the inductive behavior of a Generalized Integrate and Fire (GIF) neuron with subthreshold damped oscillations. This framework allows us to characterize the sensitivity of different model neurons to the detailed temporal structure of incoming stimuli. While a neuron with intrinsic oscillations discriminates equally well between input trains with the same or different frequency, a passive neuron discriminates better between inputs with different frequencies. This suggests that passive neurons are better suited to rate-based computation, while neurons with subthreshold oscillations are advantageous in a temporal coding scheme. We also address the influence of intrinsic properties in single-cell processing as a function of input statistics, and show that intrinsic oscillations enhance discrimination sensitivity at high input rates. Finally, we discuss how the recognition of these cell-specific discrimination properties might further our understanding of neuronal network computations and their relationships to the distribution and functional connectivity of different neuronal types

Clock genes and their genomic distributions in three species of salmonid fishes: Associations with genes regulating sexual maturation and cell cycling

<p>Abstract</p> <p>Background</p> <p>Clock family genes encode transcription factors that regulate clock-controlled genes and thus regulate many physiological mechanisms/processes in a circadian fashion. Clock1 duplicates and copies of Clock3 and NPAS2-like genes were partially characterized (genomic sequencing) and mapped using family-based indels/SNPs in rainbow trout (RT)(<it>Oncorhynchus mykiss</it>), Arctic charr (AC)(<it>Salvelinus alpinus</it>), and Atlantic salmon (AS)(<it>Salmo salar</it>) mapping panels.</p> <p>Results</p> <p>Clock1 duplicates mapped to linkage groups RT-8/-24, AC-16/-13 and AS-2/-18. Clock3/NPAS2-like genes mapped to RT-9/-20, AC-20/-43, and AS-5. Most of these linkage group regions containing the Clock gene duplicates were derived from the most recent 4R whole genome duplication event specific to the salmonids. These linkage groups contain quantitative trait loci (QTL) for life history and growth traits (i.e., reproduction and cell cycling). Comparative synteny analyses with other model teleost species reveal a high degree of conservation for genes in these chromosomal regions suggesting that functionally related or co-regulated genes are clustered in syntenic blocks. For example, anti-müllerian hormone (amh), regulating sexual maturation, and ornithine decarboxylase antizymes (oaz1 and oaz2), regulating cell cycling, are contained within these syntenic blocks.</p> <p>Conclusions</p> <p>Synteny analyses indicate that regions homologous to major life-history QTL regions in salmonids contain many candidate genes that are likely to influence reproduction and cell cycling. The order of these genes is highly conserved across the vertebrate species examined, and as such, these genes may make up a functional cluster of genes that are likely co-regulated. CLOCK, as a transcription factor, is found within this block and therefore has the potential to cis-regulate the processes influenced by these genes. Additionally, clock-controlled genes (CCGs) are located in other life-history QTL regions within salmonids suggesting that at least in part, trans-regulation of these QTL regions may also occur via Clock expression.</p

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Mesoscopic segregation of excitation and inhibition in a brain network model

Neurons in the brain are known to operate under a careful balance of excitation and inhibition, which maintains neural microcircuits within the proper operational range. How this balance is played out at the mesoscopic level of neuronal populations is, however, less clear. In order to address this issue, here we use a coupled neural mass model to study computationally the dynamics of a network of cortical macrocolumns operating in a partially synchronized, irregular regime. The topology of the network is heterogeneous, with a few of the nodes acting as connector hubs while the rest are relatively poorly connected. Our results show that in this type of mesoscopic network excitation and inhibition spontaneously segregate, with some columns acting mainly in an excitatory manner while some others have predominantly an inhibitory effect on their neighbors. We characterize the conditions under which this segregation arises, and relate the character of the different columns with their topological role within the network. In particular, we show that the connector hubs are preferentially inhibitory, the more so the larger the node's connectivity. These results suggest a potential mesoscale organization of the excitation-inhibition balance in brain networks.This work was supported by the Ministerio de Economia y Competividad (Spain, project FIS2012-37655-C02- 01), and by the Generalitat de Catalunya (project 2009SGR1168). JGO acknowledges support from the ICREA Academia programme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Estudo de base populacional sobre as condições periodontais e determinantes socioeconômicos em adultos residentes no município de Guarulhos (SP), Brasil, 2006 Population based study on periodontal conditions and socioeconomic determinants in adults in the city of Guarulhos (SP), Brazil, 2006

OBJETIVO: Este estudo descreveu a prevalência de condições periodontais e sua associação com variáveis demográficas, socioeconômicas e comportamentais em adultos de 35 a 44 anos residentes no município de Guarulhos, São Paulo, 2006. MÉTODOS: Foi realizado estudo transversal de base populacional com delineamento amostral por conglomerados. Os inquéritos e os exames foram realizados nos domicílios sorteados. Para avaliação da condição periodontal foi utilizado o índice Community Periodontal Index (CPI). Os dados foram apurados pelo programas EPIINFO 6 e STATA 10. Para o modelo de associação empregou-se a razão de prevalências (RP), calculada por meio de análise de regressão de Poisson, com correção para delineamento de amostras complexas e ponderação pelo peso populacional. RESULTADOS: Foram examinadas 263 pessoas em 237 domicílios. No estudo multivariado, com modelo ajustado para amostras complexas e ponderação populacional, a prevalência de sangramento gengival e cálculo dentário esteve associada significativamente ao fato de ser homem (RP=1,12, p=0,04), fumante (RP=1,11, p=0,01), ter menos de oito anos de estudo (RP=1,14, p=0,01) e não visitar o cirurgião-dentista (CD) há mais de dois anos (RP=1,19, p=0,00). Para a presença de bolsa periodontal, houve associação com adultos que relataram o hábito de fumar (RP=1,71, p=0,02) e apresentavam mais de dois anos sem frequentar o CD (RP=1,97, p=0,03). CONCLUSÃO: Houve maior prevalência (62,7%) de indivíduos com sangramento gengival e cálculo dentário em relação à presença de bolsas periodontais rasas ou profundas (26,6%); as primeiras, reversíveis, têm possibilidades de resolução por meio de procedimentos de atenção básica em saúde bucal.<br>OBJECTIVE: This study described the prevalence of periodontal conditions and assessed its association with social, economical and behavioral variables in adults aged 35 to 44 years old, residents in the city of Guarulhos, State of Sao Paulo, 2006. METHODS: This study was a population based survey with cluster sampling. Data collecting and exams were done at houses drew at random. The Community Periodontal Index was used to assess the periodontal condition. Data analysis used EPIINFO 6 and STATA 10 softwares. The assessment of association used the prevalence ratio (PR), as calculated by Poisson regression models with complex sampling and weighted sample adjustments. RESULTS: The total number of people was 263 in 237 domiciles. In the multivariate model, the prevalence of gingival bleeding and dental calculus was significantly associated to being male (PR=1.12, p=0.04), smoking (PR=1.11, p=0.01), school level of less than eight years of study (PR=1.14, p=0.01), and who have not received dental care for more than two years (PR=1.19, p<0.01). As for the presence of periodontal pocket, associated factors were smoking (PR=1.71, p=0.02) and who have not received dental care for more than 2 years (PR=1.97, p=0.03). CONCLUSION: We observed a higher prevalence (62.7%) of individuals with gingival bleeding and dental calculus in relation to the presence of shallow or deep periodontal pockets (26,6%). As shallow pockets are reversible, their treatment may be resolute in programs of primary dental care