Current concept on the pathogenesis of inflammatory bowel disease-crosstalk between genetic and microbial factors: Pathogenic bacteria and altered bacterial sensing or changes in mucosal integrity take "toll"?

The pathogenesis of inflammatory bowel disease (IBD) is only partially understood. Various environmental and host (e.g. genetic-, epithelial-, immune and non-immune) factors are involved. It is a multifactorial polygenic disease with probable genetic heterogeneity. Some genes are associated with IBD itself, while others increase the risk of ulcerative colitis (UC) or Crohn's disease (CD) or are associated with disease location and/or behaviour. This review addresses recent advances in the genetics of IBD. The article discusses the current information on the crosstalk between microbial and genetic factors (e.g. NOD2/CARD15, SLC22A46A5 and DLG5). The genetic data acquired in recent years help in understanding the pathogenesis of IBD and can identify a number of potential targets for therapeutic intervention. In the future, genetics may help more accurately diagnose and predict disease course in IBD

Variações multidecenais da precipitação na Colômbia e na Bacia do Prata e suas relações com os jatos de baixos níveis

The hypothesis investigated in this Thesis is that low frequency natural variations associated with the Atlantic Multidecadal Oscillation (AMO) can have a strong influence on the average behavior of precipitation and streamflow rates over the Colombian Biogeographic Choco (CBC) basins, and in extreme precipitation events over the La Plata Basin (LPB) driven by changes in low-level jets (LLJ) of South America. For this, spatial interpolations and cross-validation, trend and homogeneity tests, principal component analysis (PCA), extreme precipitation indices, and composite analysis were used. The main contributions of this research were: i) the interpolations allowed to examine the data and characteristics of annual and seasonal mean precipitation for the two study areas; through the cross-validation of multivariate geostatistical methods and deterministic methods, Cokriging was identified with the spherical (Gaussian) model as the best precipitation interpolator in the CBC region (in the LPB), using elevation as a secondary variable; ii) regarding the influence of the Atlantic Multidecadal Oscillation (AMO) on the variability of the Chocó Jet (CJ) and the Caribbean Low-Level Jet (CLLJ), there is an increase in the zonal wind in the center of the CJ during September-November (SON), reinforced after 1997, associated with negative sea surface temperature (SST) anomalies in the tropical Pacific Ocean and positive ones in the Caribbean Sea and Tropical North Atlantic (TNA), strengthen the CJ and weaken the CLLJ, enhanced the moisture transport to central and western Colombia, increasing the rainfall there. The results indicate that the combination of the cold phase of the PDO (CPDO) and the warm phase of the AMO (WAMO) defines a low-frequency medium state, which affects the interannual climate variability and can affect the CJ variability and the precipitation In Colombia; iii) the variations in the streamflow of the Atrato River Basin (ARB) during the 1965-2015 period, considering the cold (1965-1994) and warm (1995-2015) phases of the AMO, showed an increase after 1994. The warm tropical Atlantic during WAMO intensified the Walker circulation, causing an upward movement in the north and northwestern South America, which contributed to the positive rainfall anomalies and increased streamflow in the ARB; iv) the seasonal validation of the CHIRPS (Climate Hazards Group Infrared Precipitation with Stations) precipitation dataset for the LPB, through the PCA, indicated that the CHIRPS v.2 dataset captures the spatial patterns and variability at different time scales in the LPB; v) an increase in total wet-day precipitation (PRCPTOT) and number of heavy precipitation days (R10mm) in the southern LPB (S-LPB) during SON, and an increase in the consecutive dry days (CDD) in northern LPB (N-LPB) during June-August (JJA) were observed. An upward change in R10mm after 1999 is identified during SON in S-LPB, associated with: teleconnections with the positive Indian Ocean Dipole (IOD), drives an extratropical southern Rossby wave disturbance extending towards southeastern South America and configures a barotropic cyclone over the south of the continent, and favor the moisture transport from the northwestern and central Amazon to southern and western LPB; and increased moisture flow to LPB due to warming in the southwestern Atlantic. An important aspect discussed here is that the low-frequency background conditions are modulated by the Atlantic Multidecadal Oscillation (AMO). The results, as well as the proposed methods, are of interest for low-frequency climate monitoring and forecasting, for water resources management and hydrometeorological risk in two regions of particular environmental and economic importance in South America.A hipótese investigada nessa Tese é que variações naturais de baixa frequência, associadas à Oscilação Multidecenal do Atlântico (AMO) podem ter uma forte influência sobre o comportamento médio da precipitação e vazão sobre as bacias do Choco Biogeográfico Colombiano (CBC) e sobre os eventos extremos de precipitação sobre a Bacia do Prata (LPB) impulsionadas por mudanças nos jatos de baixos níveis (LLJs) na América do Sul. Para isso, foram utilizadas interpolações espaciais e validação cruzada, testes de tendência e homogeneidade, Análises de Componentes Principais (PCA), índices extremos de precipitação e análises de composições. As principais contribuições de esta investigação foram: i) as interpolações permitiram examinar os dados e características da precipitação média anual e sazonal para as duas áreas de estudo; através da validação cruzada de métodos geoestatísticos multivariados e determinísticos, Cokriging com o modelo esférico (Gaussiano) foi identificado como o melhor interpolador da precipitação na região do CBC (na LPB), usando a elevação como variável secundária; ii) sobre a influência da Oscilação Multidecenal do Atlântico (AMO) na variabilidade do Jato do Choco (CJ) e do Caribe (CLLJ), se observa o aumento do vento zonal no centro do CJ durante Setembro-Novembro (SON), reforçado após de 1997, associado as anomalias negativas da temperatura da superfície do mar (TSM) no Oceano Pacífico tropical e positivas no Mar do Caribe e no Atlântico Norte Tropical (TNA) que enfraquecem (intensificam) o CLLJ (CJ), aprimorando o transporte de umidade para a região central e oeste da Colômbia e aumentando as precipitações. Os resultados indicam que a combinação da fase fria da PDO (CPDO) e a quente da AMO (WAMO), definem um background de baixa frequência, o que afeta a variabilidade climática interanual, e podem influenciar o CJ e as precipitações na Colômbia; iii) variações da vazão na Bacia do Rio Atrato (ARB) durante o período de 1965-2015, considerando as fases fria (1965-1994) e quente (1995-2015) mostraram o aumentou após 1994. O Atlântico tropical quente durante a WAMO intensifica a circulação de Walker, causando movimento ascendente no norte e noroeste da América do Sul, o que contribuiu para as anomalias positivas de chuva e aumento da vazão na ARB; iv) a validação sazonal do conjunto de dados de precipitação de CHIRPS (Climate Hazards Group Infrared Precipitation with Stations) para a LPB, através de PCA, indicou que o conjunto de dados CHIRPS v.2 captura os padrões espaciais e a variabilidade em diferentes escalas de tempo na LPB; v) foram observadas tendências positivas na precipitação total em dias úmidos (PRCPTOT) e no número de dias de precipitação intensa (R10mm) na região sul da LPB (S-LPB) durante SON, e tendências positivas de dias secos consecutivos (CDD) no norte da LPB (N-LPB) durante Junho-Agosto (JJA). Uma mudança positiva no R10mm após de 1999 é identificada durante SON em S-LPB, associada com: teleconexões com o dipolo positivo do Oceano Indico (IOD), que gera uma perturbação extratropical de onda de Rossby no hemisfério sul que se estende em direção ao sudeste da América do Sul e configura um ciclone barotrópico sobre o sul do continente, favorecendo o transporte de umidade do noroeste e centro da Amazônia para o sul e oeste da LPB; e aumento do fluxo de umidade para a LPB devido ao aquecimento no Atlântico sudoeste. Um aspecto importante discutido aqui é que as condições do estado médio da baixa frequência são moduladas pela Oscilação Multidecenal do Atlântico (AMO). Os resultados, bem como os métodos propostos, são de interesse para o monitoramento e previsão climática de baixa frequência, a gestão dos recursos hídricos e o risco hidrometeorológico em duas regiões de especial interesses ambiental e econômico na América do Sul

Environmental sensing and response genes in cnidaria : the chemical defensome in the sea anemone Nematostella vectensis

Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Cell Biology and Toxicology 24 (2008): 483-502, doi:10.1007/s10565-008-9107-5.The starlet sea anemone Nematostella vectensis has been recently established as a new model system for the study of the evolution of developmental processes, as cnidaria occupy a key evolutionary position at the base of the bilateria. Cnidaria play important roles in estuarine and reef communities, but are exposed to many environmental stressors. Here I describe the genetic components of a ‘chemical defensome’ in the genome of N. vectensis, and review cnidarian molecular toxicology. Gene families that defend against chemical stressors and the transcription factors that regulate these genes have been termed a ‘chemical defensome,’ and include the cytochromes P450 and other oxidases, various conjugating enyzymes, the ATP-dependent efflux transporters, oxidative detoxification proteins, as well as various transcription factors. These genes account for about 1% (266/27200) of the predicted genes in the sea anemone genome, similar to the proportion observed in tunicates and humans, but lower than that observed in sea urchins. While there are comparable numbers of stress-response genes, the stress sensor genes appear to be reduced in N. vectensis relative to many model protostomes and deuterostomes. Cnidarian toxicology is understudied, especially given the important ecological roles of many cnidarian species. New genomic resources should stimulate the study of chemical stress sensing and response mechanisms in cnidaria, and allow us to further illuminate the evolution of chemical defense gene networks.WHOI Ocean Life Institute and NIH R01-ES01591

Padrões sazonais da variabilidade interanual da precipitação sobre a América do sul associadas às componentes enos e não-enos: impacto na vazão da bacia do Paraná

The anomalous seasonal patterns of interannual rainfall variability over South America (SA) and its impact on rivers in the Paraná basin associated with El Niño-Southern Oscillation (ENSO) and non-ENSO (residual) components were evaluated during the 1970-2013 period. Seasonal patterns were derived from the Empirical Orthogonal Functions (EOF) analyzes applied to the series of total and residual precipitation anomalies and are referred to here as total (TOT) and residual (RES) patterns, while the associated patterns to the ENSO mode were obtained through the linear correlations between the NINO index and the precipitation anomalies on SA. In relation to the EOF patterns, the winter and autumn seasons, the first mode is associated with variations occurring in the Tropical Atlantic while the component in ENOS is defined as secondary mode. Variations in the tropical Atlantic mainly affect precipitation in the region north and northeast of Brazil, while variations in the Southwest Atlantic are modulating the precipitation between central-east and southeast of SA. On the other hand, for the spring and summer seasons, the ENSO explains most of the variability of the dominant patterns. This relationship is mainly associated with precipitation in the north, northwest and south of SA. The dynamics of these relationships involve variations in Walker's circulation and in the Pacific/ North America (PNA) and Pacific/South America (PSA) teleconnections patterns. The results confirm that in years of ENSO precipitation signals are intensified in the southeast and north of the SA, but in the absence of ENSO, the extratropical teleconnections patterns weaken leading to the reduction of precipitation. The changes in the local SST of the South Atlantic mainly modulate the circulation near the east coast of the AS that generates a dipole between the center-east and southeast of Brazil. In addition, discharges from the Parana basin rivers responded to large-scale standards. In years of ENSO, flow rates are associated with the transport of South American Low Level Jets (SALLJ). On the other hand, the discharges associated to the non-ENSO component presented strong relations with transport from the South Atlantic. These results show the important role of local forcing for the precipitation on the east coast of the AS and for discharges of the rivers of an important basin of Brazil. In summary, the results presented in this study define the relative contribution of the components associated to ENOS and non-ENOS in the determination of the seasonal patterns of precipitation and discuss their impacts on the Paraná basinOs padrões sazonais anômalos da variabilidade interanual da precipitação sobre a América do Sul (AS) e seus impactos sobre a vazão dos rios na bacia do Paraná associada às componentes do El Niño-Oscilação Sul (ENOS) e não-ENOS (parte residual) foram avaliadas durante o período 1970-2013. Os padrões sazonais foram obtidos a partir das análises de Funções Ortogonais Empíricas (EOF, do inglês) aplicadas às séries de anomalias de precipitação total e residual e são referidos aqui como padrões totais (TOT) e residuais (RES), enquanto que os padrões associados ao modo ENOS foram obtidos através das correlações lineares entre o índice do NINO 3.4 e as anomalias de precipitação sobre a AS. Em relação aos campos da EOF, para as estações de inverno e outono, o primeiro modo está associado às variações que ocorrem no Atlântico Tropical enquanto que a componente do ENOS é definida como secundária. As variações no Atlântico Tropical afetam principalmente as precipitações na região norte, nordeste do Brasil enquanto que as variações no Atlântico Sudoeste modulam a precipitação entre o centro-leste e sudeste da AS. Por outro lado, para as estações da primavera e verão, o ENOS explica a maioria da variabilidade dos padrões dominantes. Essa relação está associada principalmente à precipitação no norte, noroeste e sul da AS. A dinâmica dessas relações envolve variações na circulação de Walker e no padrão de teleconexão Pacífico/América do Norte (PNA) e do Sul (PSA). Os resultados confirmam que em anos de ENOS os sinais da precipitação são intensificados no sudeste e norte da AS, porém, na ausência do ENOS, as teleconexões extratropicais se enfraquecem o que ocasiona a redução da precipitação. As variações na temperatura da superfície do mar (TSM) do Atlântico Sul modulam principalmente a circulação próxima à costa leste da AS o que gera um dipolo entre o centro-leste e sudeste do Brasil. Em consequência, as descargas dos rios da bacia do Paraná responderam aos padrões de grande escala. As vazões relacionadas à componente ENOS estão associadas ao transporte de Jatos de Baixos Níveis da América do Sul (JBNAS), por outro lado as descargas associadas à componente não-ENOS apresentaram fortes relações com transporte oriundo do Atlântico Sul. Esses resultados mostram o importante papel das forçantes locais para a precipitação na costa leste da AS e para descargas dos rios de uma importante bacia do Brasil. Em síntese, os resultados apresentados neste estudo definem a contribuição relativa das componentes associadas ao ENOS e não-ENOS na determinação dos padrões sazonais da precipitação e discutem seus impactos sobre a bacia do Paraná

Relationship between rainfall and streamflow in the La Plata Basin: annual cycles, interdecadal and multidecadal variability

The aim of this study is to understand the interaction between rainfall and streamflow variability in the La Plata basin (LPB) along a wide range of timescales. The LPB is divided in six sub-basins associated to the main rivers (Paraguay, Parana, Uruguay and Iguazu). The amplification of the streamflow response is addressed in order to evaluate to what extent river discharges variability can be explained by precipitation fluctuations. Mean annual cycles corresponding to 1931-2010 period and to each of the decades comprising it are analyzed. Streamflow interdecadal changes are observed in most of the gauging stations. In addition, an 11-year moving-average filter is applied to the normalized annual time series. Results exhibit a considerable higher percentage of explained variance in the streamflow filtered series, highlighting the predominance of medium and low frequencies variability present in these compared to those of precipitation. Consistently, river discharges show higher spectral density in the interdecadal/multidecadal frequencies compared to precipitation analysis. A simple statistical approach to advance in the understanding of the complex rainfall-streamflow physical relationship is addressed with promising results: streamflow spectrums are derived directly from the precipitation spectrum, transformed by a ´basin´ operator, characteristic of the basin itself. It is assumed that watersheds act on precipitation as spatio-temporal integrators operating as low-pass filters, like a moving average. Streamflow power spectrums are simulated assuming that the underlying process is an autoregressive moving average (ARMA). Considering as the only input the sub-basin areal-averaged precipitation timeseries, results show that simulated streamflow spectrums fits effectively the observations at the sub-basin scale.Fil: Gulizia, Carla. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias de la Atmósfera y los Océanos; Argentina. Instituto Franco-Argentino sobre Estudios del Clima y sus Impactos; ArgentinaFil: Camilloni, Ines Angela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias de la Atmósfera y los Océanos; Argentina. Instituto Franco-Argentino sobre Estudios del Clima y sus Impactos; Argentin

Phytocannabinoids as novel therapeutic agents in CNS disorders

The Cannabis sativa herb contains over 100 phytocannabinoid (pCB) compounds and has been used for thousands of years for both recreational and medicinal purposes. In the past two decades, characterisation of the body's endogenous cannabinoid (CB) (endocannabinoid, eCB) system (ECS) has highlighted activation of central CB1 receptors by the major pCB, Δ9-tetrahydrocannabinol (Δ9-THC) as the primary mediator of the psychoactive, hyperphagic and some of the potentially therapeutic properties of ingested cannabis. Whilst Δ9-THC is the most prevalent and widely studied pCB, it is also the predominant psychotropic component of cannabis, a property that likely limits its widespread therapeutic use as an isolated agent. In this regard, research focus has recently widened to include other pCBs including cannabidiol (CBD), cannabigerol (CBG), Δ9tetrahydrocannabivarin (Δ9-THCV) and cannabidivarin (CBDV), some of which show potential as therapeutic agents in preclinical models of CNS disease. Moreover, it is becoming evident that these non-Δ9-THC pCBs act at a wide range of pharmacological targets, not solely limited to CB receptors. Disorders that could be targeted include epilepsy, neurodegenerative diseases, affective disorders and the central modulation of feeding behaviour. Here, we review pCB effects in preclinical models of CNS disease and, where available, clinical trial data that support therapeutic effects. Such developments may soon yield the first non-Δ9-THC pCB-based medicines

Influência do el niño e da la niña na previsão intra-horária da irradiação solar global horizontal/ Influence of el niño and la niña on the intrahorary forecast of horizontal global solar irradiation

O presente trabalho consiste em avaliar a influência do el niño e da la niña na previsão da irradiação global horizontal da cidade de Fortaleza, Ceará, nos horizontes temporais de 2 min, 10 min e 30 min. essa influência foi inserida através do The Oceanic Niño Index, ONI. O banco de dados utilizados fazia referência aos anos de 2007 a 2019, com exceção dos anos 2009 e 2011. Foram utilizados modelos de aprendizagem de máquinas, florestas aleatórias - RF e rede neural artificial percéptron de múltiplas camadas - ANN, e um método de persistência, que serve de padrão mínimo de desempenho para avaliação dos métodos. A comparação de desempenho dos modelos foi feita, principalmente, pelo valor do nRMSE, que é a raiz do erro quadrático médio. Para a previsão foram considerados como preditores: temperatura e umidade do ar, velocidade e direção do vento, precipitação, irradiação do instante atual e de 5 instantes anteriores, data e hora da coleta do dado e o ONI. Os resultados apontam que as previsões realizadas com o preditor ONI apresentaram menor erro do que as sem essa variável, o que ressalta a importância desse preditor. Além disso, tanto os resultados do RF quanto do ANN apresentaram erros inferiores ao modelo de persistência, sendo o RF o método de melhor desempenho

Tree-ring oxygen isotopes record a decrease in Amazon dry season rainfall over the past 40 years

Extant climate observations suggest the dry season over large parts of the Amazon Basin has become longer and drier over recent decades. However, such possible intensification of the Amazon dry season and its underlying causes are still a matter of debate. Here we used oxygen isotope ratios in tree rings (δ18OTR) from six floodplain trees from the western Amazon to assess changes in past climate. Our analysis shows that δ18OTR of these trees is negatively related to inter-annual variability of precipitation during the dry season over large parts of the Amazon Basin, consistent with a Rayleigh rainout model. Furthermore δ18OTR increases by approximately 2‰ over the last four decades (~ 1970–2014) providing evidence of an Amazon drying trend independent from satellite and in situ rainfall observations. Using a Rayleigh rainout framework, we estimate basin-wide dry season rainfall to have decreased by up to 30%. The δ18OTR record further suggests such drying trend may not be unprecedented over the past 80 years. Analysis of δ18OTR with sea surface temperatures indicates a strong role of a warming Tropical North Atlantic Ocean in driving this long-term increase in δ18OTR and decrease in dry season rainfall

Climatic, Ecophysiological, and Phenological Controls on Plant Ecohydrological Strategies in Seasonally Dry Ecosystems

Large areas in the tropics and at mid-latitudes experience pronounced seasonality and inter-annual variability in rainfall and hence water availability. Despite the importance of these seasonally dry ecosystems (SDEs) for the global carbon cycling and in providing ecosystem services, a unifying ecohydrological framework to interpret the effects of climatic variability on SDEs is still lacking. A synthesis of existing data about plant functional adaptations in SDEs, covering some 400 species, shows that leaf phenological variations, rather than physiological traits, provide the dominant control on plant-water-carbon interactions. Motivated by this result, the combined implications of leaf phenology and climatic variability on plant water use strategies are here explored with a minimalist model of the coupled soil water and plant carbon balances. The analyses are extended to five locations with different hydroclimatic forcing, spanning seasonally dry tropical climates (without temperature seasonality) and Mediterranean climates (exhibiting out of phase seasonal patterns of rainfall and temperature). The most beneficial leaf phenology in terms of carbon uptake depends on the climatic regime: evergreen species are favoured by short dry seasons or access to persistent water stores, whereas high inter-annual variability of rainy season duration favours the coexistence of multiple drought-deciduous phenological strategies. We conclude that drought-deciduousness may provide a competitive advantage in face of predicted declines in rainfall totals, while reduced seasonality and access to deep water stores may favour evergreen species. This article has been contributed to by US Government employees and their work is in the public domain in the USA

Voltage-gated sodium channels (NaV) in GtoPdb v.2021.3

Sodium channels are voltage-gated sodium-selective ion channels present in the membrane of most excitable cells. Sodium channels comprise of one pore-forming α subunit, which may be associated with either one or two β subunits [177]. α-Subunits consist of four homologous domains (I-IV), each containing six transmembrane segments (S1-S6) and a pore-forming loop. The positively charged fourth transmembrane segment (S4) acts as a voltage sensor and is involved in channel gating. The crystal structure of the bacterial NavAb channel has revealed a number of novel structural features compared to earlier potassium channel structures including a short selectivity filter with ion selectivity determined by interactions with glutamate side chains [274]. Interestingly, the pore region is penetrated by fatty acyl chains that extend into the central cavity which may allow the entry of small, hydrophobic pore-blocking drugs [274]. Auxiliary β1, β2, β3 and β4 subunits consist of a large extracellular N-terminal domain, a single transmembrane segment and a shorter cytoplasmic domain.The nomenclature for sodium channels was proposed by Goldin et al., (2000) [144] and approved by the NC-IUPHAR Subcommittee on sodium channels (Catterall et al., 2005, [52])