Extracellular matrix and vascular dynamics in the kidney of a murine model for Marfan syndrome

Fibrillin-1 is a pivotal structural component of the kidney’s glomerulus and peritubular tissue. Mutations in the fibrillin-1 gene result in Marfan syndrome (MFS), an autosomal dominant disease of the connective tissue. Although the kidney is not considered a classically affected organ in MFS, several case reports describe glomerular disease in patients. Therefore, this study aimed to characterize the kidney in the mgΔlpn-mouse model of MFS. Affected animals presented a significant reduction of glomerulus, glomerulus-capillary, and urinary space, and a significant reduction of fibrillin-1 and fibronectin in the glomerulus. Transmission electron microscopy and 3D-ultrastructure analysis revealed decreased amounts of microfibrils which also appeared fragmented in the MFS mice. Increased collagen fibers types I and III, MMP-9, and α-actin were also observed in affected animals, suggesting a tissue-remodeling process in the kidney. Video microscopy analysis showed an increase of microvessel distribution coupled with reduction of blood-flow velocity, while ultrasound flow analysis revealed significantly lower blood flow in the kidney artery and vein of the MFS mice. The structural and hemodynamic changes of the kidney indicate the presence of kidney remodeling and vascular resistance in this MFS model. Both processes are associated with hypertension which is expected to worsen the cardiovascular phenotype in MFS

Genomic history of coastal societies from eastern South America

Sambaqui (shellmound) societies are among the most intriguing archaeological phenomena in pre-colonial South America, extending from approximately 8,000 to 1,000 years before present (yr bp) across 3,000 km on the Atlantic coast. However, little is known about their connection to early Holocene hunter-gatherers, how this may have contributed to different historical pathways and the processes through which late Holocene ceramists came to rule the coast shortly before European contact. To contribute to our understanding of the population history of indigenous societies on the eastern coast of South America, we produced genome-wide data from 34 ancient individuals as early as 10,000 yr bp from four different regions in Brazil. Early Holocene hunter-gatherers were found to lack shared genetic drift among themselves and with later populations from eastern South America, suggesting that they derived from a common radiation and did not contribute substantially to later coastal groups. Our analyses show genetic heterogeneity among contemporaneous Sambaqui groups from the southeastern and southern Brazilian coast, contrary to the similarity expressed in the archaeological record. The complex history of intercultural contact between inland horticulturists and coastal populations becomes genetically evident during the final horizon of Sambaqui societies, from around 2,200 yr bp, corroborating evidence of cultural change

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Estimation of population genetic parameters in human isolates from Vale do Ribeira, São Paulo (quilombo populations)

A porção paulista do Vale do Ribeira concentra a maior quantidade de comunidades remanescentes de quilombos do estado de São Paulo, abrangendo uma área de cerca de 10% de seu território. Por meio das análises de marcadores moleculares, de frequências de casais com mesmo sobrenome e de dados genealógicos, procuramos obter parâmetros globais de caracterização das comunidades: sistema de cruzamentos e medidas de subestruturação populacional. Utilizamos dados genealógicos de cerca de 2000 indivíduos e moleculares de cerca de 1000 indivíduos das comunidades de Maria Rosa, Pilões, Galvão, São Pedro, Pedro Cubas, Ivaporanduva, Sapatu, André Lopes, Nhunguara, Abobral (margens esquerda e direita), Poça e Reginaldo. A estimativa média de F obtida pela análise de genealogias apresentou valor 0,00134, o qual, embora subestimado devido à falta de informações genealógicas, é cerca de 1,5 vezes mais elevado do que a estimativa apresentada para a população total brasileira e duas vezes maior que a obtida para o estado de São Paulo, comparando-se a valores apresentados em outros isolados da literatura. A partir das análises de locos genômicos obtivemos, para as comunidades separadamente, os valores médios de F relativos aos 239 locos de todas as comunidades, dentre os quais 12 (5%) mostraram-se estatisticamente diferentes de zero ao nível de P <= 0,05/n, frequência esperada de desvios ocorrendo ao acaso. Quando analisada de forma conjunta, a população apresentou quatro dos 30 locos (13,33%) com desvios significativos de pan-mixia, valor acima do esperado ao acaso, o que indica um excesso de homozigose no isolado total. Obtivemos o valor médio total de F pela ponderação dos F de cada um dos locos pelos recíprocos de suas variâncias, estas calculadas por meio de uma metodologia inédita proposta neste trabalho, a qual é aplicável a casos de marcadores contendo mais de dois alelos. O valor médio de F que obtivemos é comparável aos obtidos de outros isolados da literatura. Os valores do índice Fst obtidos em uma análise de subestruturação populacional tiveram valores modestos geralmente bem menores que 5%, indicando a presença de níveis de subestruturação muito modestos.Vale do Ribeira is a region located at the southern part of the state of São Paulo, corresponding to about 10% of its territory. Most of the quilombo remnants of the state are placed inside this region. Using both molecular markers and genealogical data analyses, we estimated population genetic parameters from the communities (breeding system and subestructure organization). Genealogical and molecular data (collected from 2000 and 1000 individuals respectively) were obtained from 13 quilombo communities: Maria Rosa, Pilões, Galvão, São Pedro, Pedro Cubas, Ivaporanduva, Sapatu, André Lopes, Nhunguara, Abobral (both left and right edges), Poça e Reginaldo. Genealogical analysis enabled us to obtain a mean F value of 0.00134, that represents an underestimate of the true value due to lack of reliable genealogical information. Even so, this value is almost 1.5 times higher than the value estimated for the total Brazilian population and almost twice as high than the same parameter estimated for the state of São Paulo. By means of genomic loci data analysis, we obtained mean nF/n value for the quilombo communities separately. Twelve (5%) out of a total of 239 loci from eight communities were in p2:2pq:q2 ratios, as expected by chance; and for the set of all quilombo communities, four (13.33%) out of 30 loci deviated significantly from Hardy-Weinberg ratios, indicating an excess of homozygosis. We also estimated the weighted mean value of F for the whole population by averaging the nF/n values obtained from each locus by the reciprocal of their corresponding variances. For calculating the variance of estimated nF/n values we developed a novel method that can be easily generalized to the case of any number of alleles segregating at an autosomal locus/ No significant levels of population subtructure were detected since the estimated Fst values among populations were in general quite modest. We present also, as attachment to this work, the listings of the main computer program codes we used in our calculations and a section on the evolution of the fixation index F under different systems of regular endogamy

Estudos sobre endocruzamento em um isolado quilombola do Estado de São Paulo

Endogamy levels are usually estimated using genealogical or molecular markers data. By means of both type of data from a traditional Brazilian tri-hybrid quilombo population aggregate (located at the Ribeira River Valley in the State of São Paulo), the aim of this work, using different methods, was to obtain reliable estimates of its average inbreeding coefficient, as well as to establish pertinent demographic inferences. The results we obtained are presented in three chapters. The first one, represented by the offprint of a published paper, deals with the estimation of the inbreeding coefficient using both a complete genealogical and comprehensive molecular information. F values were estimated for each community using all available pedigree information and averaging the inbreeding coefficients from all individuals represented in the genealogies. Molecular f values were estimated from the analysis of 30 highly heterogenous sets of molecular markers (14 biallelic SNPs and 16 multiallelic microsatellites), genotyped in different groups of individuals from the population. The second chapter (a research paper already published), presents a simplified method to estimate the variance of the inbreeding coefficient. The simple approximations we provided can be applied to a locus with any number of alleles, producing estimates fully validated by computer simulations. The last chapter is a manuscript yet to be published that deals with inbreeding and demographic inferences, obtained from the information of hundreds of thousands of biallelic SNP markers. A new manner to obtain estimates of Wright\'s fixation index f is presented, consisting in the use of the joint information of two sets of markers (one complete and another excluding markers in patent linkage disequilibrium). Quilombo demographic inferences were obtained by means of ROHs analyses, which were adapted to cope with a highly admixed population with a complex foundation historyOs níveis de endogamia de uma população são comumente estimados por meio do coeficiente de endocruzamento, que pode ser obtido de dados genealógicos (F) ou dados provenientes da análise de marcadores moleculares (f). O objetivo do trabalho foi obter estimativas confiáveis do coeficiente de endocruzamento populacional, bem como realizar inferências demográficas, usando dados de um agregado populacional quilombola miscigenado com ancestralidade complexa tri-híbrida, localizado no Vale do Rio Ribeira, na região sul do estado de São Paulo. No trabalho é apresentado em três capítulos. No primeiro (um trabalho já publicado), estimamos o coeficiente de endocruzamento usando dados genealógicos e moleculares. As estimativas genealógicas de F foram obtidas para cada comunidade por meio da média dos coeficientes individuais de todos os indivíduos representados nas genealogias da população. Os valores de f foram estimados por meio dos dados de 30 marcadores moleculares altamente heterogêneos (14 SNPs e 16 microssatélites), genotipados em diferentes grupos de indivíduos com diferentes finalidades. O segundo capítulo, representado por um trabalho também já publicado, apresenta um método simples para estimar a variância do coeficiente de endocruzamento f. As aproximações obtidas, validadas devidamente por simulações em computador, podem ser aplicadas a lóci multialélicos, produzindo estimativas que não diferem significativamente de outras aproximações complicadas descritas na literatura. O último capítulo (um manuscrito a ser submetido para publicação) apresenta inferências a respeito dos processos de endogamia e demografia no isolado quilombola, utilizando a informação de centenas de milhares de marcadores moleculares bialélicos. É apresentada uma nova maneira de se estimar o índice de fixação f de Wright, usando a informação combinada de dois conjuntos de marcadores (o conjunto completo de marcadores e um outro contendo apenas marcadores não ligados significativamente entre si). Também foram feitas inferências sobre a história demográfica do isolado por meio do estudo das regiões genômicas em homozigose (ROHs), uma contribuição inédita e importante do trabalho, adaptada à análise de um isolado populacional altamente miscigenado com contribuição tri-híbrida e uma história de fundação complex

Origin and age of the causative mutations in KLC2, IMPA1, MED25 and WNT7A unravelled through Brazilian admixed populations

Abstract The mutation age and local ancestry of chromosomal segments harbouring mutations associated with autosomal recessive (AR) disorders in Brazilian admixed populations remain unknown; additionally, inbreeding levels for these affected individuals continue to be estimated based on genealogical information. Here, we calculated inbreeding levels using a runs of homozygosity approach, mutation age and local ancestry to infer the origin of each chromosomal segments containing disorder-causing mutations in KLC2, IMPA1, MED25 and WNT7A. Genotyped data were generated from 18 patients affected by AR diseases and combined to the 1000 genome project (1KGP) and Simons genome diversity project (SGDP) databases to infer local ancestry. We found a major European contribution for mutated haplotypes with recent mutation age and inbreeding values found only in Native American and Middle East individuals. These results contribute to identifying the origin of and to understanding how these diseases are maintained and spread in Brazilian and world populations

Prevalência DO GENÓTIPO DE RISCO G1/G2 DO GENE DA APOLIPOPROTEÍNA L1 (APOL1) E ASSOCIAÇÃO COM DOENÇA RENAL CRÔNICA NÃO DIABÉTICA EM AUTODECLARADOS NEGROS NO SUL DO BRASIL

Introdução: A doença renal crônica (DRC) possui uma prevalência de 10% entre os brasileiros. A presença de dois alelos de risco chamados G1 e G2 do gene da Apo lipoproteína L1 ( APOL1 ), mais frequente em indivíduos associados de ascendência africana e foram à DRC. Objetivos: Determinar a prevalência dos alelos e genótipo de APOL1 em pacientes portadores de DRC em comparação com indivíduos afrodescendentes saudáveis. Métodos: Estudo caso controle, realizado nos ambulatórios de Nefrologia do hospital de Clínicas de Porto Alegre, na Santa Casa de Misericórdia de Porto Alegre; Clínicas de hemodiálise Grande Porto Alegre Litoral e Cidades de Pelotas e Osório. Resultados: Foram analisados 345 indivíduos, 175 casos e 170 controles. No total 7,9% são portadores dos alelos de risco (G1/G1, G1/G2, G2/G2) e 92,1% sem alelos de risco (G0). A frequência alélica foi estimada em 11% para G1, e 5% para G2. A análise multivariada, sexo, idade estimou OR = 4,717 (IC 95% 1,53 - 14,53, p = 0,007) para desenvolvimento de DRC em portador dos alelos de risco de APOL1 . O componente de ancestralidade africana se destacou em (49%), europeu (33%) e nativa americana (18%). Identificamos a presença dos alelos de risco, para o desenvolvimento da DRC nos portadores dos alelos G1 e G2. Conclusão: Estes dados corroboram a literatura, apontaram a necessidade de atenção à saúde e manejo na população negra brasileira. Este estudo foi aprovado pelo CEP do Hospital de Clínicas de Porto Alegre (CAAE: 36976820.5.0000.5327)