Influência de Fatores Ambientais em Diferentes Escalas Espaciais Sobre a Distribuição de Simulídeos (diptera; Nematocera) em Córregos Tropicais

Os simulídeos são insetos com ampla distribuição geográfica que cujos imaturos necessitam de ambientes lóticos para sobreviverem. Suas larvas vivem presas a diversos substratos como folhas, galhos, rochas submersas onde se alimentam de detritos e fitoplâncton, os quais são filtrados através de seus leques cefálicos. São conhecidos vulgarmente como piuns ou borrachudos, sendo que no Brasil são conhecidas 88 espécies. Os insetos adultos possuem hábito hematófago, sendo que algumas espécies têm preferência por sangue humano. O objetivo desse trabalho foi analisar quais os fatores são responsáveis pela distribuição espacial das espécies de simulídeos em córregos tropicais do estado do Espírito Santo, verificar se riqueza e a distribuição de espécies nas regiões de planícies e nas regiões de planalto são diferenciadas, bem como prover uma lista atualizada das espécies registradas para o estado. Foram realizadas 93 incursões em rios do Espírito Santo e as coletas foram realizadas por meio da catação manual e utilização de rede D. Os exemplares foram acondicionados em frascos contendo álcool 92.6% e posteriormente identificados ao nível de espécie em laboratório. Vinte e nove espécies de simulídeos foram coletadas, sendo 12 novos registros para o Estado e um também para a região Sudeste: Simulium scutistriatum, S. dinellii, S. exiguum, S. minusculum, S. distinctum, S. oyapockense s.l., S. rappae, S. botulibranchium, S. ochraceum, S. clavibranchium, Lutzsimulium hirticosta, S. lobatoi, S. pertinax, S. jujuyense, S. rubrithorax, S. travassosi, S. subnigrum, S. spinibranchium, S. anamariae, S. hirtipupa, S. lutzianum, S. nigrimanun, S. incrustatum, S. inaequale, S. subpallidum, S. perflavum, S. brachycladum, S. guianense e S. limbatum. A análise de correspondência destendenciada (DCA) apontou a formação de dois agrupamentos estatísticamente significantes. A variável altitude explica inversamente a riqueza, a abundância e a composição, já a largura explica a composição do eixo 1. Para a análise por espécies foi verificado que algumas respondem à velocidade (S. hirtipupa e S. pertinax), outras ao substrato (S. dinelli, S. hirtipupa, S. guianense e S. subpallidum), enquanto outras à altitude (S. dinelli, S.guianense e S. subpallidum)

Identification of two novel mutations in CDHR1 in consanguineous Spanish families with autosomal recessive retinal dystrophy.

Inherited retinal dystrophies present extensive phenotypic and genetic heterogeneity, posing a challenge for patients' molecular and clinical diagnoses. In this study, we wanted to clinically characterize and investigate the molecular etiology of an atypical form of autosomal recessive retinal dystrophy in two consanguineous Spanish families. Affected members of the respective families exhibited an array of clinical features including reduced visual acuity, photophobia, defective color vision, reduced or absent ERG responses, macular atrophy and pigmentary deposits in the peripheral retina. Genetic investigation included autozygosity mapping coupled with exome sequencing in the first family, whereas autozygome-guided candidate gene screening was performed by means of Sanger DNA sequencing in the second family. Our approach revealed nucleotide changes in CDHR1; a homozygous missense variant (c.1720C > G, p.P574A) and a homozygous single base transition (c.1485 + 2T > C) affecting the canonical 5' splice site of intron 13, respectively. Both changes co-segregated with the disease and were absent among cohorts of unrelated control individuals. To date, only five mutations in CDHR1 have been identified, all resulting in premature stop codons leading to mRNA nonsense mediated decay. Our work reports two previously unidentified homozygous mutations in CDHR1 further expanding the mutational spectrum of this gene

Opinion dynamics: models, extensions and external effects

Recently, social phenomena have received a lot of attention not only from social scientists, but also from physicists, mathematicians and computer scientists, in the emerging interdisciplinary field of complex system science. Opinion dynamics is one of the processes studied, since opinions are the drivers of human behaviour, and play a crucial role in many global challenges that our complex world and societies are facing: global financial crises, global pandemics, growth of cities, urbanisation and migration patterns, and last but not least important, climate change and environmental sustainability and protection. Opinion formation is a complex process affected by the interplay of different elements, including the individual predisposition, the influence of positive and negative peer interaction (social networks playing a crucial role in this respect), the information each individual is exposed to, and many others. Several models inspired from those in use in physics have been developed to encompass many of these elements, and to allow for the identification of the mechanisms involved in the opinion formation process and the understanding of their role, with the practical aim of simulating opinion formation and spreading under various conditions. These modelling schemes range from binary simple models such as the voter model, to multi-dimensional continuous approaches. Here, we provide a review of recent methods, focusing on models employing both peer interaction and external information, and emphasising the role that less studied mechanisms, such as disagreement, has in driving the opinion dynamics. [...]Comment: 42 pages, 6 figure

A global phylogenomic analysis of the shiitake genus Lentinula

Lentinula is a broadly distributed group of fungi that contains the cultivated shiitake mushroom, L. edodes. We sequenced 24 genomes representing eight described species and several unnamed lineages of Lentinula from 15 countries on four continents. Lentinula comprises four major clades that arose in the Oligocene, three in the Americas and one in Asia–Australasia. To expand sampling of shiitake mushrooms, we assembled 60 genomes of L. edodes from China that were previously published as raw Illumina reads and added them to our dataset. Lentinula edodes sensu lato (s. lat.) contains three lineages that may warrant recognition as species, one including a single isolate from Nepal that is the sister group to the rest of L. edodes s. lat., a second with 20 cultivars and 12 wild isolates from China, Japan, Korea, and the Russian Far East, and a third with 28 wild isolates from China, Thailand, and Vietnam. Two additional lineages in China have arisen by hybridization among the second and third groups. Genes encoding cysteine sulfoxide lyase (lecsl) and γ-glutamyl transpeptidase (leggt), which are implicated in biosynthesis of the organosulfur flavor compound lenthionine, have diversified in Lentinula. Paralogs of both genes that are unique to Lentinula (lecsl 3 and leggt 5b) are coordinately up-regulated in fruiting bodies of L. edodes. The pangenome of L. edodes s. lat. contains 20,308 groups of orthologous genes, but only 6,438 orthogroups (32%) are shared among all strains, whereas 3,444 orthogroups (17%) are found only in wild populations, which should be targeted for conservation

Ensemble approach to predict specificity determinants: benchmarking and validation

<p>Abstract</p> <p>Background</p> <p>It is extremely important and challenging to identify the sites that are responsible for functional specification or diversification in protein families. In this study, a rigorous comparative benchmarking protocol was employed to provide a reliable evaluation of methods which predict the specificity determining sites. Subsequently, three best performing methods were applied to identify new potential specificity determining sites through ensemble approach and common agreement of their prediction results.</p> <p>Results</p> <p>It was shown that the analysis of structural characteristics of predicted specificity determining sites might provide the means to validate their prediction accuracy. For example, we found that for smaller distances it holds true that the more reliable the prediction method is, the closer predicted specificity determining sites are to each other and to the ligand.</p> <p>Conclusion</p> <p>We observed certain similarities of structural features between predicted and actual subsites which might point to their functional relevance. We speculate that majority of the identified potential specificity determining sites might be indirectly involved in specific interactions and could be ideal target for mutagenesis experiments.</p

Combining specificity determining and conserved residues improves functional site prediction

<p>Abstract</p> <p>Background</p> <p>Predicting the location of functionally important sites from protein sequence and/or structure is a long-standing problem in computational biology. Most current approaches make use of sequence conservation, assuming that amino acid residues conserved within a protein family are most likely to be functionally important. Most often these approaches do not consider many residues that act to define specific sub-functions within a family, or they make no distinction between residues important for function and those more relevant for maintaining structure (e.g. in the hydrophobic core). Many protein families bind and/or act on a variety of ligands, meaning that conserved residues often only bind a common ligand sub-structure or perform general catalytic activities.</p> <p>Results</p> <p>Here we present a novel method for functional site prediction based on identification of conserved positions, as well as those responsible for determining ligand specificity. We define Specificity-Determining Positions (SDPs), as those occupied by conserved residues within sub-groups of proteins in a family having a common specificity, but differ between groups, and are thus likely to account for specific recognition events. We benchmark the approach on enzyme families of known 3D structure with bound substrates, and find that in nearly all families residues predicted by SDPsite are in contact with the bound substrate, and that the addition of SDPs significantly improves functional site prediction accuracy. We apply SDPsite to various families of proteins containing known three-dimensional structures, but lacking clear functional annotations, and discusse several illustrative examples.</p> <p>Conclusion</p> <p>The results suggest a better means to predict functional details for the thousands of protein structures determined prior to a clear understanding of molecular function.</p

Training Signaling Pathway Maps to Biochemical Data with Constrained Fuzzy Logic: Quantitative Analysis of Liver Cell Responses to Inflammatory Stimuli

Predictive understanding of cell signaling network operation based on general prior knowledge but consistent with empirical data in a specific environmental context is a current challenge in computational biology. Recent work has demonstrated that Boolean logic can be used to create context-specific network models by training proteomic pathway maps to dedicated biochemical data; however, the Boolean formalism is restricted to characterizing protein species as either fully active or inactive. To advance beyond this limitation, we propose a novel form of fuzzy logic sufficiently flexible to model quantitative data but also sufficiently simple to efficiently construct models by training pathway maps on dedicated experimental measurements. Our new approach, termed constrained fuzzy logic (cFL), converts a prior knowledge network (obtained from literature or interactome databases) into a computable model that describes graded values of protein activation across multiple pathways. We train a cFL-converted network to experimental data describing hepatocytic protein activation by inflammatory cytokines and demonstrate the application of the resultant trained models for three important purposes: (a) generating experimentally testable biological hypotheses concerning pathway crosstalk, (b) establishing capability for quantitative prediction of protein activity, and (c) prediction and understanding of the cytokine release phenotypic response. Our methodology systematically and quantitatively trains a protein pathway map summarizing curated literature to context-specific biochemical data. This process generates a computable model yielding successful prediction of new test data and offering biological insight into complex datasets that are difficult to fully analyze by intuition alone.National Institutes of Health (U.S.) (NIH grant P50-GM68762)National Institutes of Health (U.S.) (Grant U54-CA112967)United States. Dept. of Defense (Institute for Collaborative Biotechnologies

Fibroblast growth factor signalling controls nervous system patterning and pigment cell formation in Ciona intestinalis

During the development of the central nervous system (CNS), combinations of transcription factors and signalling molecules orchestrate patterning, specification and differentiation of neural cell types. In vertebrates, three types of melanin-containing pigment cells, exert a variety of functional roles including visual perception. Here we analysed the mechanisms underlying pigment cell specification within the CNS of a simple chordate, the ascidian Ciona intestinalis. Ciona tadpole larvae exhibit a basic chordate body plan characterized by a small number of neural cells. We employed lineage-specific transcription profiling to characterize the expression of genes downstream of fibroblast growth factor signalling, which govern pigment cell formation. We demonstrate that FGF signalling sequentially imposes a pigment cell identity at the expense of anterior neural fates. We identify FGF-dependent and pigment cell-specific factors, including the small GTPase, Rab32/38 and demonstrated its requirement for the pigmentation of larval sensory organs

1,3-Butadiene: Biomarkers and application to risk assessment

1,3-Butadiene (BD) is a known rodent and human carcinogen that is metabolized mainly by P450 2E1 to three epoxides, 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane (DEB) and 1,2-epoxy-3,4-butanediol (EB-diol). The individual epoxides vary up to 200-fold in their mutagenic potency, with DEB being the most mutagenic metabolite. It is important to understand the internal formation of the individual epoxides to assign the relative risk for each metabolite and to understand the molecular mechanisms responsible for major species differences in carcinogenicity. We have conducted extensive exposure-biomarker studies on mice, rats and humans. Using low exposures that range from current occupational levels to human exposures from tobacco smoke has provided evidence that mice are very different from humans, with mice forming ~200 times more DEB than humans at exposures of 0.1–1.5 ppm BD. While no gender differences have been noted in mice and rats for globin adducts or N-7 guanine adducts, female rats and mice had 2–3-fold higher Hprt mutations and DNA-DNA cross-links, suggesting a gender difference in DNA repair. Numerous molecular epidemiology studies have evaluated globin adducts and Hprt mutations, SCEs and chromosomal abnormalities. None of the blinded studies have shown evidence of human genotoxicity at current occupational exposures and studies of globin adducts have shown similar or lower formation of adducts in females than males. If one calculates the EB dose-equivalents for the three species, mice clearly differ from rats and humans, being ~44 and 174 times greater than rats and humans, respectively. These data provide a scientific basis for improved risk assessment of BD