Predicting the Proteins of Angomonas deanei, Strigomonas culicis and Their Respective Endosymbionts Reveals New Aspects of the Trypanosomatidae Family

Endosymbiont-bearing trypanosomatids have been considered excellent models for the study of cell evolution because the host protozoan co-evolves with an intracellular bacterium in a mutualistic relationship. Such protozoa inhabit a single invertebrate host during their entire life cycle and exhibit special characteristics that group them in a particular phylogenetic cluster of the Trypanosomatidae family, thus classified as monoxenics. in an effort to better understand such symbiotic association, we used DNA pyrosequencing and a reference-guided assembly to generate reads that predicted 16,960 and 12,162 open reading frames (ORFs) in two symbiont-bearing trypanosomatids, Angomonas deanei (previously named as Crithidia deanei) and Strigomonas culicis (first known as Blastocrithidia culicis), respectively. Identification of each ORF was based primarily on TriTrypDB using tblastn, and each ORF was confirmed by employing getorf from EMBOSS and Newbler 2.6 when necessary. the monoxenic organisms revealed conserved housekeeping functions when compared to other trypanosomatids, especially compared with Leishmania major. However, major differences were found in ORFs corresponding to the cytoskeleton, the kinetoplast, and the paraflagellar structure. the monoxenic organisms also contain a large number of genes for cytosolic calpain-like and surface gp63 metalloproteases and a reduced number of compartmentalized cysteine proteases in comparison to other TriTryp organisms, reflecting adaptations to the presence of the symbiont. the assembled bacterial endosymbiont sequences exhibit a high A+T content with a total of 787 and 769 ORFs for the Angomonas deanei and Strigomonas culicis endosymbionts, respectively, and indicate that these organisms hold a common ancestor related to the Alcaligenaceae family. Importantly, both symbionts contain enzymes that complement essential host cell biosynthetic pathways, such as those for amino acid, lipid and purine/pyrimidine metabolism. These findings increase our understanding of the intricate symbiotic relationship between the bacterium and the trypanosomatid host and provide clues to better understand eukaryotic cell evolution.Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)ERC AdG SISYPHEUniv Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Ultraestrutura Celular Hertha Meyer, BR-21941 Rio de Janeiro, BrazilUniv Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Metab Macromol Firmino Torres de Castro, BR-21941 Rio de Janeiro, BrazilLab Bioinformat, Lab Nacl Computacao Cient, Rio de Janeiro, BrazilINRIA Grenoble Rhone Alpes, BAMBOO Team, Villeurbanne, FranceUniv Lyon 1, CNRS, UMR5558, Lab Biometrie & Biol Evolut, F-69622 Villeurbanne, FranceUniv Estadual Campinas, Inst Biol, Dept Genet Evolucao & Bioagentes, São Paulo, BrazilUniv São Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Ciencias Farmaceut, São Paulo, BrazilLab Nacl Ciencia & Tecnol Bioetano, São Paulo, BrazilUniv Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Belo Horizonte, MG, BrazilUniv Fed Goias, Inst Ciencias Biol, Mol Biol Lab, Goiania, Go, BrazilFundacao Oswaldo Cruz, Inst Carlos Chagas, Lab Biol Mol Tripanossomatideos, Curitiba, Parana, BrazilFundacao Oswaldo Cruz, Inst Carlos Chagas, Lab Genom Func, Curitiba, Parana, BrazilUniv Estadual Campinas, Ctr Pluridisciplinar Pesquisas Quim Biol & Agr, São Paulo, BrazilUniv Fed Minas Gerais, Inst Ciencias Biol, Dept Parasitol, Belo Horizonte, MG, BrazilUniv Fed Santa Catarina, Dept Microbiol Imunol & Parasitol, Ctr Ciencias Biol, Lab Protozool & Bioinformat, Florianopolis, SC, BrazilUniv Fed Vicosa, Dept Bioquim & Biol Mol, Ctr Ciencias Biol & Saude, Vicosa, MG, BrazilInst Butantan, Lab Especial Ciclo Celular, São Paulo, BrazilUniv São Paulo, Dept Biol, Fac Filosofia Ciencias & Letras Ribeirao Preto, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilWeb of Scienc

The germline mutational landscape of BRCA1 and BRCA2 in Brazil

The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/availability of genetic testing. Aiming at the identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-six novel variants were reported from both genes, and BRCA2 showed higher mutational heterogeneity. Some recurrent mutations were reported exclusively in certain geographic regions, suggesting a founder effect. Our findings confirm that there is significant molecular heterogeneity in these genes among Brazilian carriers, while also suggesting that this heterogeneity precludes the use of screening protocols that include recurrent mutation testing only. This is the first study to show that profiles of recurrent mutations may be unique to different Brazilian regions. These data should be explored in larger regional cohorts to determine if screening with a panel of recurrent mutations would be effective.This work was supported in part by grants from Barretos Cancer Hospital (FINEP - CT-INFRA, 02/2010), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, 2013/24633-2 and 2103/23277-8), Fundação de Apoio à Pesquisa do Rio Grande do Norte (FAPERN), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Ministério da Saúde, the Breast Cancer Research Foundation (Avon grant #02-2013-044) and National Institute of Health/National Cancer Institute (grant #RC4 CA153828-01) for the Clinical Cancer Genomics Community Research Network. Support in part was provided by grants from Fundo de Incentivo a Pesquisa e Eventos (FIPE) from Hospital de Clínicas de Porto Alegre, by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, BioComputacional 3381/2013, Rede de Pesquisa em Genômica Populacional Humana), Secretaria da Saúde do Estado da Bahia (SESAB), Laboratório de Imunologia e Biologia Molecular (UFBA), INCT pra Controle do Câncer and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). RMR and PAP are recipients of CNPq Productivity Grants, and Bárbara Alemar received a grant from the same agencyinfo: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 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

Diretrizes Brasileiras de Medidas da Pressão Arterial Dentro e Fora do Consultório – 2023

Hypertension is one of the primary modifiable risk factors for morbidity and mortality worldwide, being a major risk factor for coronary artery disease, stroke, and kidney failure. Furthermore, it is highly prevalent, affecting more than one-third of the global population. Blood pressure measurement is a MANDATORY procedure in any medical care setting and is carried out by various healthcare professionals. However, it is still commonly performed without the necessary technical care. Since the diagnosis relies on blood pressure measurement, it is clear how important it is to handle the techniques, methods, and equipment used in its execution with care. It should be emphasized that once the diagnosis is made, all short-term, medium-term, and long-term investigations and treatments are based on the results of blood pressure measurement. Therefore, improper techniques and/or equipment can lead to incorrect diagnoses, either underestimating or overestimating values, resulting in inappropriate actions and significant health and economic losses for individuals and nations. Once the correct diagnosis is made, as knowledge of the importance of proper treatment advances, with the adoption of more detailed normal values and careful treatment objectives towards achieving stricter blood pressure goals, the importance of precision in blood pressure measurement is also reinforced. Blood pressure measurement (described below) is usually performed using the traditional method, the so-called casual or office measurement. Over time, alternatives have been added to it, through the use of semi-automatic or automatic devices by the patients themselves, in waiting rooms or outside the office, in their own homes, or in public spaces. A step further was taken with the use of semi-automatic devices equipped with memory that allow sequential measurements outside the office (ABPM; or HBPM) and other automatic devices that allow programmed measurements over longer periods (HBPM). Some aspects of blood pressure measurement can interfere with obtaining reliable results and, consequently, cause harm in decision-making. These include the importance of using average values, the variation in blood pressure during the day, and short-term variability. These aspects have encouraged the performance of a greater number of measurements in various situations, and different guidelines have advocated the use of equipment that promotes these actions. Devices that perform HBPM or ABPM, which, in addition to allowing greater precision, when used together, detect white coat hypertension (WCH), masked hypertension (MH), sleep blood pressure alterations, and resistant hypertension (RHT) (defined in Chapter 2 of this guideline), are gaining more and more importance. Taking these details into account, we must emphasize that information related to diagnosis, classification, and goal setting is still based on office blood pressure measurement, and for this reason, all attention must be given to the proper execution of this procedure.La hipertensión arterial (HTA) es uno de los principales factores de riesgo modificables para la morbilidad y mortalidad en todo el mundo, siendo uno de los mayores factores de riesgo para la enfermedad de las arterias coronarias, el accidente cerebrovascular (ACV) y la insuficiencia renal. Además, es altamente prevalente y afecta a más de un tercio de la población mundial. La medición de la presión arterial (PA) es un procedimiento OBLIGATORIO en cualquier atención médica o realizado por diferentes profesionales de la salud. Sin embargo, todavía se realiza comúnmente sin los cuidados técnicos necesarios. Dado que el diagnóstico se basa en la medición de la PA, es claro el cuidado que debe haber con las técnicas, los métodos y los equipos utilizados en su realización. Debemos enfatizar que una vez realizado el diagnóstico, todas las investigaciones y tratamientos a corto, mediano y largo plazo se basan en los resultados de la medición de la PA. Por lo tanto, las técnicas y/o equipos inadecuados pueden llevar a diagnósticos incorrectos, subestimando o sobreestimando valores y resultando en conductas inadecuadas y pérdidas significativas para la salud y la economía de las personas y las naciones. Una vez realizado el diagnóstico correcto, a medida que avanza el conocimiento sobre la importancia del tratamiento adecuado, con la adopción de valores de normalidad más detallados y objetivos de tratamiento más cuidadosos hacia metas de PA más estrictas, también se refuerza la importancia de la precisión en la medición de la PA. La medición de la PA (descrita a continuación) generalmente se realiza mediante el método tradicional, la llamada medición casual o de consultorio. Con el tiempo, se han agregado alternativas a través del uso de dispositivos semiautomáticos o automáticos por parte del propio paciente, en salas de espera o fuera del consultorio, en su propia residencia o en espacios públicos. Se dio un paso más con el uso de dispositivos semiautomáticos equipados con memoria que permiten mediciones secuenciales fuera del consultorio (AMPA; o MRPA) y otros automáticos que permiten mediciones programadas durante períodos más largos (MAPA). Algunos aspectos en la medición de la PA pueden interferir en la obtención de resultados confiables y, en consecuencia, causar daños en las decisiones a tomar. Estos incluyen la importancia de usar valores promedio, la variación de la PA durante el día y la variabilidad a corto plazo. Estos aspectos han alentado la realización de un mayor número de mediciones en diversas situaciones, y diferentes pautas han abogado por el uso de equipos que promuevan estas acciones. Los dispositivos que realizan MRPA o MAPA, que además de permitir una mayor precisión, cuando se usan juntos, detectan la hipertensión de bata blanca (HBB), la hipertensión enmascarada (HM), las alteraciones de la PA durante el sueño y la hipertensión resistente (HR) (definida en el Capítulo 2 de esta guía), están ganando cada vez más importancia. Teniendo en cuenta estos detalles, debemos enfatizar que la información relacionada con el diagnóstico, la clasificación y el establecimiento de objetivos todavía se basa en la medición de la presión arterial en el consultorio, y por esta razón, se debe prestar toda la atención a la ejecución adecuada de este procedimiento.A hipertensão arterial (HA) é um dos principais fatores de risco modificáveis para morbidade e mortalidade em todo o mundo, sendo um dos maiores fatores de risco para doença arterial coronária, acidente vascular cerebral (AVC) e insuficiência renal. Além disso, é altamente prevalente e atinge mais de um terço da população mundial. A medida da PA é procedimento OBRIGATÓRIO em qualquer atendimento médico ou realizado por diferentes profissionais de saúde. Contudo, ainda é comumente realizada sem os cuidados técnicos necessários. Como o diagnóstico se baseia na medida da PA, fica claro o cuidado que deve haver com as técnicas, os métodos e os equipamentos utilizados na sua realização. Deve-se reforçar que, feito o diagnóstico, toda a investigação e os tratamentos de curto, médio e longo prazos são feitos com base nos resultados da medida da PA. Assim, técnicas e/ou equipamentos inadequados podem levar a diagnósticos incorretos, tanto subestimando quanto superestimando valores e levando a condutas inadequadas e grandes prejuízos à saúde e à economia das pessoas e das nações. Uma vez feito o diagnóstico correto, na medida em que avança o conhecimento da importância do tratamento adequado, com a adoção de valores de normalidade mais detalhados e com objetivos de tratamento mais cuidadosos no sentido do alcance de metas de PA mais rigorosas, fica também reforçada a importância da precisão na medida da PA. A medida da PA (descrita a seguir) é habitualmente feita pelo método tradicional, a assim chamada medida casual ou de consultório. Ao longo do tempo, foram agregadas alternativas a ela, mediante o uso de equipamentos semiautomáticos ou automáticos pelo próprio paciente, nas salas de espera ou fora do consultório, em sua própria residência ou em espaços públicos. Um passo adiante foi dado com o uso de equipamentos semiautomáticos providos de memória que permitem medidas sequenciais fora do consultório (AMPA; ou MRPA) e outros automáticos que permitem medidas programadas por períodos mais prolongados (MAPA). Alguns aspectos na medida da PA podem interferir na obtenção de resultados fidedignos e, consequentemente, causar prejuízo nas condutas a serem tomadas. Entre eles, estão: a importância de serem utilizados valores médios, a variação da PA durante o dia e a variabilidade a curto prazo. Esses aspectos têm estimulado a realização de maior número de medidas em diversas situações, e as diferentes diretrizes têm preconizado o uso de equipamentos que favoreçam essas ações. Ganham cada vez mais espaço os equipamentos que realizam MRPA ou MAPA, que, além de permitirem maior precisão, se empregados em conjunto, detectam a HA do avental branco (HAB), HA mascarada (HM), alterações da PA no sono e HA resistente (HAR) (definidos no Capítulo 2 desta diretriz). Resguardados esses detalhes, devemos ressaltar que as informações relacionadas a diagnóstico, classificação e estabelecimento de metas ainda são baseadas na medida da PA de consultório e, por esse motivo, toda a atenção deve ser dada à realização desse procedimento