Characterizing and explaining the impact of disease-associated mutations in proteins without known structures or structural homologs

Mutations in human proteins lead to diseases. The structure of these proteins can help understand the mechanism of such diseases and develop therapeutics against them. With improved deep learning techniques, such as RoseTTAFold and AlphaFold, we can predict the structure of proteins even in the absence of structural homologs. We modeled and extracted the domains from 553 disease-associated human proteins without known protein structures or close homologs in the Protein Databank. We noticed that the model quality was higher and the Root mean square deviation (RMSD) lower between AlphaFold and RoseTTAFold models for domains that could be assigned to CATH families as compared to those which could only be assigned to Pfam families of unknown structure or could not be assigned to either. We predicted ligand-binding sites, protein–protein interfaces and conserved residues in these predicted structures. We then explored whether the disease-associated missense mutations were in the proximity of these predicted functional sites, whether they destabilized the protein structure based on ddG calculations or whether they were predicted to be pathogenic. We could explain 80% of these disease-associated mutations based on proximity to functional sites, structural destabilization or pathogenicity. When compared to polymorphisms, a larger percentage of disease-associated missense mutations were buried, closer to predicted functional sites, predicted as destabilizing and pathogenic. Usage of models from the two state-of-the-art techniques provide better confidence in our predictions, and we explain 93 additional mutations based on RoseTTAFold models which could not be explained based solely on AlphaFold models

SISTEMAS DE CULTIVOS NO DESENVOLVIMENTO RADICULAR DA SOJA

One of the characteristics most important in the development ofa culture is the study of the system to root, that ally the different forms ofhandling of the ground, will be able to reflect aspects important of itsperformance. That an experiment with different system of culture in thesoybean was carried through. The treatments had been: conventional system(SC), direct sowing during 5 years (DS5) and direct sowing during 10 years(DS10). Opened 2 trenches for each system and collected the samples of thesoil the culture in full flowering. Each trench had 100 cm of length in theline, enclosing of 10 and 12 plants, with 80 cm of width until reaching toanother line of plantation, consequently eliminating plantation line, withpurpose to inside facilitate to the work of the trench and depth of 60 cm. Theroots had been evaluated by the System Integrated for Analysis of Root deOverture of the Soil. To the long one of the profile of the ground 10 cm andevaluated had been collected samples to each: text of water, density of theground and porosity. The results had allowed to conclude that in theconventional system the roots, in its majority, had been superficial and thatin the system direct plantation, independent of the time, did not havedifferences in the distribution of the roots to the long one of the profile ofthe ground. The density of the ground in the superficial layer was lesser inthe conventional system. The conventional system presented the biggestmacroporosity and small microporosity, being that in the direct independentplantation of the time of this practical it had greater microporosity and lesservalues of macroporosity.Uma das características mais importantes no desenvolvimento deuma cultura é o estudo do sistema radicular, que aliado as formas de manejodo solo, poderá refletir aspectos importantes de seu desempenho. Assim, foirealizado um experimento com alguns sistemas de cultivo na cultura da soja.Os tratamentos foram: sistema convencional (SC), plantio direto durantecinco anos (PD5) e plantio direto durante 10 anos (PD10). Foram abertasduas trincheiras para cada sistema e coletadas amostras de solo com a culturaem pleno florescimento. Cada trincheira tinha 100 cm de comprimentona linha, abrangendo de 10-12 plantas, com 80 cm de largura até alcançar aoutra linha de semeadura, conseqüentemente eliminando linha de semeadura,com finalidade de facilitar o trabalho dentro da trincheira e profundidadede 60 cm. As raízes foram avaliadas pelo Sistema Integrado para Análisede Raízes de Cobertura do Solo (SIARCS). Ao longo do perfil do solo foramcoletadas amostras a cada 10 cm e avaliado: teor de água, densidade do soloe porosidade. Os resultados permitiram concluir que no sistema convencionalas raízes, na sua maioria, foram superficiais e que no sistema plantiodireto, independente do tempo, não houve diferenças na distribuição dasraízes ao longo do perfil do solo. A densidade do solo na camada superficialfoi menor no sistema convencional. O sistema convencional apresentou maiormacroporosidade e menor microporosidade, sendo que no plantio direto, independente do tempo dessa prática, a microporosidade foi maior e menor amacroporosidade

Matéria seca, carbono e nitrogênio de raízes de soja e milho em plantio direto e convencional

The objective of this work was to examine whether soil tillage systems affect the distribution and accumulation of dry matter (DM), carbon (C) and nitrogen (N) of root systems of soybean (Glycine max) and corn (Zea mays) in a clayey Typic Haplorthox. Volumetric rings were used for root sampling down to 1 m depth. The distribution in depth and accumulation of DM, C and N of soybean and corn roots were not affected by soil tillage systems. Root length density was 0.7–1.4 cm cm-3 for soybean and 1.2–1.6 cm cm-3 for corn in the 0–0.10 m layer and decreased in the other layers. Root DM input was 1.94–2.01 Mg ha-1 in soybean and 2.50–3.79 Mg ha-1 in corn. For soybean, C and N root inputs were 0.61–0.63 Mg ha-1 and 36.9–38.2 kg ha-1, respectively. For corn, C and N root inputs were 0.72–1.10 Mg ha-1 and 18.78–28.48 kg ha-1, respectively. Independently of the tillage system, 80% of the roots were concentrated in the upper surface layer 0.43 to 0.54 m deep for soybean and in the upper surface layer 0.40 to 0.46 m deep for corn.O objetivo deste trabalho foi verificar se o sistema de preparo do solo afeta a distribuição e o acúmulo de matéria seca (MS), carbono (C) e nitrogênio (N) das raízes de soja (Glycine max) e milho (Zea mays), em um Latossolo Vermelho distroférrico muito argiloso. A amostragem das raízes até 1 m de profundidade foi feita com anéis volumétricos. A distribuição em profundidade e o acúmulo de MS, C e N das raízes não foram influenciados pelo preparo do solo. A densidade de comprimento de raízes na camada de 0–0,10 m foi de 0,7 a 1,4 cm cm-3 em soja, e de 1,2 a 1,6 cm cm-3 em milho, e decresceu nas demais camadas. O acúmulo de MS das raízes foi de 1,94 a 2,01 Mg ha-1 em soja, e de 2,50 a 3,79 Mg ha-1 em milho. Houve acúmulo de 0,61 a 0,63 Mg ha-1 de C e de 36,9 a 38,2 kg ha-1 de N em soja, e de 0,72 a 1,10 Mg ha-1 de C e de 18,78 a 28,48 kg ha-1 de N em milho. Independentemente do sistema de preparo do solo, 80% das raízes situam-se entre 0,43 e 0,54 m de profundidade em soja, e entre 0,40 e 0,46 m em milho

The Helicobacter pylori Genome Project : insights into H. pylori population structure from analysis of a worldwide collection of complete genomes

Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics

Sistema radicular e desenvolvimento de plantas cítricas provenientes de viveiro telado e aberto Root system and development of citrus plants originated from open and protected nursery systems

O trabalho teve como objetivo avaliar o sistema radicular e o desenvolvimento vegetativo de plantas cítricas, provenientes de mudas produzidas em sistema de viveiro aberto e de telado. A avaliação das raízes foi realizada pela escavação de seis trincheiras para obtenção de imagens digitais das raízes que foram avaliadas pelo programa SIARCS 3.0. Para avaliação do desenvolvimento vegetativo, foram selecionadas 20 plantas. O delineamento estatístico utilizado foi o inteiramente casualizado, e os dados obtidos foram analisados pelo teste t de Student. As plantas provenientes de mudas de viveiro aberto foram superiores às plantas de telado na distância efetiva do sistema radicular, na entrelinha de plantio e no total geral de raízes. O diâmetro e o volume da copa foram superiores para as plantas provenientes de mudas de viveiro aberto em relação às plantas de telado.This research had as objective to evaluate the root system and development of citrus plants, originated from open and protected nursery systems. The roots were evaluated by the trench profile method with six replications for each nursery system, applying the SIARCS 3.0 software to determine root amount and distribution. Twenty plants were selected to evaluate vegetative development. A randomized design and the test t of Student were used for statistical analysis. The plants originated from open nursery system were superior to those from screen house regarding the root effective distance in the inter-rows and total amount of roots. The diameter and volume of the canopy were superior for plants originated from open nursery system

TEMPO DE CULTIVO DA SEMEADURA DIRETA SOB ATRIBUTOS FÍSICOS DO SOLO E DISTRIBUIÇÃO DO SISTEMA RADICULAR DA SOJA

O objetivo do trabalho foi comparar a influência do tempo de cultivo de semeadura direta conduzida por um, cinco e dez anos, sobre atributos físicos do solo e a distribuição do sistema radicular da soja. Foram abertas duas trincheiras para cada manejo do solo, avaliando-se dois perfis por trincheira, transversais às linhas de plantio, contemplando duas plantas de soja. O delineamento experimental utilizado foi o inteiramente casualizado, com os três períodos de sistemas de manejo do solo e seis profundidades (0,0-0,1 ; 0,1-0,2; 0,2-0,3; 0,3-0,4; 0,4-0,5 e 0,5-0,6 m). Os dados foram submetidos à análise de variância e ao teste de Tukey a 5% de probabilidade. A macroporosidade e porosidade total do solo foram maiores no sistema de semeadura direta com um ano de condução em relação à semeadura direta de cinco e dez anos apenas nas profundidades abaixo de 0,3 m, devido ao cultivo de mandioca um ano antes da implantação deste sistema. A densidade e microporosidade do solo foram superiores na semeadura direta com cinco anos e após dez anos igualou-se a semeadura direta com um ano. O sistema radicular da soja é mais bem distribuído no perfil do solo no sistema de semeadura direta conduzido por cinco e dez anos em relação ao sistema de semeadura direta conduzido por um ano

Differences in the genome, methylome, and transcriptome do not differentiate isolates of Streptococcus equi subsp. equi from horses with acute clinical signs from isolates of inapparent carriers

Streptococcus equi subsp. equi (SEE) is a host-restricted bacterium that causes the common infectious upper respiratory disease known as strangles in horses. Perpetuation of SEE infection appears attributable to inapparent carrier horses because it neither persists long-term in the environment nor infects other host mammals or vectors, and infection results in short-lived immunity. Whether pathogen factors enable SEE to remain in horses without causing clinical signs remains poorly understood. Thus, our objective was to use next-generation sequencing technologies to characterize the genome, methylome, and transcriptome of isolates of SEE from horses with acute clinical strangles and inapparent carrier horses-including isolates recovered from individual horses sampled repeatedly-to assess pathogen-associated changes that might reflect specific adaptions of SEE to the host that contribute to inapparent carriage. The accessory genome elements and methylome of SEE isolates from Sweden and Pennsylvania revealed no significant or consistent differences between acute clinical and inapparent carrier isolates of SEE. RNA sequencing of SEE isolates from Pennsylvania demonstrated no genes that were differentially expressed between acute clinical and inapparent carrier isolates of SEE. The absence of specific, consistent changes in the accessory genomes, methylomes, and transcriptomes of acute clinical and inapparent carrier isolates of SEE indicates that adaptations of SEE to the host are unlikely to explain the carrier state of SEE. Efforts to understand the carrier state of SEE should instead focus on host factors