Activation of Human CD11b+ B1 B-Cells by Trypanosoma cruzi-Derived Proteins Is Associated With Protective Immune Response in Human Chagas Disease

B-cells mediate humoral adaptive immune response via the production of antibodies and cytokines, and by inducing T-cell activation. These functions can be attributed to distinct B-cell subpopulations. Infection with Trypanosoma cruzi, the causative agent of Chagas disease, induces a polyclonal B-cell activation and lytic antibody production, critical for controlling parasitemia. Individuals within the chronic phase of Chagas disease may remain in an asymptomatic form (indeterminate), or develop severe cardiomyopathy (cardiac form) that can lead to death. Currently, there is no effective vaccine to prevent Chagas disease, and no treatment to halt the development of the cardiomyopathy once it is installed. The pathology associated with cardiac Chagas disease is a result of an inflammatory reaction. Thus, discovering characteristics of the host's immune response that favor the maintenance of favorable heart function may unveil important immunotherapeutic targets. Given the importance of B cells in antibody production and parasite control, we investigated T. cruzi-derived antigenic fractions responsible for B-cell activation and whether frequencies and functional characteristics of B-cell subpopulations are associated with different clinical outcomes of human Chagas disease. We stimulated cells from indeterminate (I) and cardiac (C) Chagas patients, as well as non-infected individuals (NI), with T. cruzi-derived protein- (PRO), glycolipid- (GCL) and lipid (LIP)-enriched fractions and determined functional characteristics of B-cell subpopulations. Our results showed that the frequency of B-cells was similar amongst groups. PRO, but not GCL nor LIP, led to an increased frequency of B1 B-cells in I, but not C nor NI. Although stimulation with PRO induced higher TNF expression by B1 B-cells from C and I, as compared to NI, it induced expression of IL-10 in cells from I, but not C. Stimulation with PRO induced an increased frequency of the CD11b+ B1 B-cell subpopulation, which was associated with better cardiac function. Chagas patients displayed increased IgM production, and activation of gamma-delta T-cells, which have been associated with B1 B-cell function. Our data showed that PRO activates CD11b+ B1 B-cells, and that this activation is associated with a beneficial clinical status. These findings may have implications in designing new strategies focusing on B-cell activation to prevent Chagas disease cardiomyopathy

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

Activation of Human CD11b+ B1 B-Cells by Trypanosoma cruzi-Derived Proteins Is Associated With Protective Immune Response in Human Chagas Disease

Submitted by Nuzia Santos ([email protected]) on 2019-10-18T18:05:46Z No. of bitstreams: 1 Activation of Human CD11b+ B1 B-Cells.pdf: 1184928 bytes, checksum: 60dd296cf28c092dc46ba1ef0977c524 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2019-10-18T18:12:17Z (GMT) No. of bitstreams: 1 Activation of Human CD11b+ B1 B-Cells.pdf: 1184928 bytes, checksum: 60dd296cf28c092dc46ba1ef0977c524 (MD5)Made available in DSpace on 2019-10-18T18:12:17Z (GMT). No. of bitstreams: 1 Activation of Human CD11b+ B1 B-Cells.pdf: 1184928 bytes, checksum: 60dd296cf28c092dc46ba1ef0977c524 (MD5) Previous issue date: 2018Universidade Federal de Minas Gerais. Departamento de Morfologia Instituto de Ciências Biológicas. Laboratório de Interações Célula-Célula. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Pós-graduação em Parasitologia. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Departamento de Morfologia Instituto de Ciências Biológicas. Laboratório de Interações Célula-Célula. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Pós-graduação em Parasitologia. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Pós-graduação em Parasitologia. Belo Horizonte, MG, Brasil / Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Pós-graduação em Parasitologia. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Departamento de Morfologia Instituto de Ciências Biológicas. Laboratório de Interações Célula-Célula. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Departamento de Morfologia Instituto de Ciências Biológicas. Laboratório de Interações Célula-Célula. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Pós-graduação em Parasitologia. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Faculdade de Medicina. Departamento de Clínica Médica. Belo Horizonte, MG, Brasil.A. C. Camargo Centro de Câncer. Centro de Pesquisa Internacional. São Paulo, SP, Brasil / Instituto Nacional de Ciência e Tecnologia Doenças Tropicais. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Departamento de Morfologia Instituto de Ciências Biológicas. Laboratório de Interações Célula-Célula. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Pós-graduação em Parasitologia. Belo Horizonte, MG, Brasil / Instituto Nacional de Ciência e Tecnologia Doenças Tropicais. Belo Horizonte, MG, Brasil.B-cells mediate humoral adaptive immune response via the production of antibodies and cytokines, and by inducing T-cell activation. These functions can be attributed to distinct B-cell subpopulations. Infection with Trypanosoma cruzi, the causative agent of Chagas disease, induces a polyclonal B-cell activation and lytic antibody production, critical for controlling parasitemia. Individuals within the chronic phase of Chagas disease may remain in an asymptomatic form (indeterminate), or develop severe cardiomyopathy (cardiac form) that can lead to death. Currently, there is no effective vaccine to prevent Chagas disease, and no treatment to halt the development of the cardiomyopathy once it is installed. The pathology associated with cardiac Chagas disease is a result of an inflammatory reaction. Thus, discovering characteristics of the host's immune response that favor the maintenance of favorable heart function may unveil important immunotherapeutic targets. Given the importance of B cells in antibody production and parasite control, we investigated T. cruzi-derived antigenic fractions responsible for B-cell activation and whether frequencies and functional characteristics of B-cell subpopulations are associated with different clinical outcomes of human Chagas disease. We stimulated cells from indeterminate (I) and cardiac (C) Chagas patients, as well as non-infected individuals (NI), with T. cruzi-derived protein- (PRO), glycolipid- (GCL) and lipid (LIP)-enriched fractions and determined functional characteristics of B-cell subpopulations. Our results showed that the frequency of B-cells was similar amongst groups. PRO, but not GCL nor LIP, led to an increased frequency of B1 B-cells in I, but not C nor NI. Although stimulation with PRO induced higher TNF expression by B1 B-cells from C and I, as compared to NI, it induced expression of IL-10 in cells from I, but not C. Stimulation with PRO induced an increased frequency of the CD11b+ B1 B-cell subpopulation, which was associated with better cardiac function. Chagas patients displayed increased IgM production, and activation of gamma-delta T-cells, which have been associated with B1 B-cell function. Our data showed that PRO activates CD11b+ B1 B-cells, and that this activation is associated with a beneficial clinical status. These findings may have implications in designing new strategies focusing on B-cell activation to prevent Chagas disease cardiomyopathy

Rheumatic heart disease in the modern era: recent developments and current challenges

Abstract Rheumatic heart disease (RHD) remains a major cause of preventable death and disability in children and young adults. Despite significant advances in medical technology and increased understanding of disease mechanisms, RHD continues to be a serious public health problem throughout the world, especially in low- and middle-income countries. Echocardiographic screening has played a key role in improving the accuracy of diagnosing RHD and has highlighted the disease burden. Most affected patients present with severe valve disease and limited access to life-saving cardiac surgery or percutaneous valve intervention, contributing to increased mortality and other complications. Although understanding of disease pathogenesis has advanced in recent years, key questions remain to be addressed. Preventing or providing early treatment for streptococcal infections is the most important step in reducing the burden of this disease

LOW MUSCULARITY IMPACTS SURVIVAL IN PATIENTS WITH METASTATIC OR RECURRENT HEAD AND NECK CANCER

Introduction/Justification: The prognosis of patients with head and neck cancer (HNC) is determined by factors extrinsic and intrinsic to the patient and the disease, such as age, smoking, alcoholism, HPV infection, tumor staging, and performance status and facts involving low muscularity, which is an independent adverse prognostic factor in some types of cancer, such as HNC. However, the impact of muscularity in the scenario of metastatic or recurrent HNC (mHNC) patients has still been little explored, especially when evaluated at the level of the third cervical vertebra (C3). Objectives: To evaluate the impact of muscularity on the overall survival (OS) of patients with mHNC. Materials and Methods: Retrospective and analytical study carried out at the Hospital de Clínicas of the University of Campinas (HC-UNICAMP). Patients diagnosed with mHNC during the period from January 2010 to December 2018 were included. Demographic and clinical data were collected from information in the medical record. The computed tomography images were used to evaluate the area of muscle tissue at the C3 level (cm²), calculated with Software SliceOMatic V.5.0. Muscularity was calculated after converting the muscular cross-sectional area (CSA) at C3 to the CSA at L3. Fisher's exact test was applied to investigate the difference between groups, the Kaplan-Meier method was used to construct survival curves. The Cox Proportional Hazard Model was used to investigate the association of muscularity with OS. Model was adjusted for age (categorical) and ECOG (categorical). This study was approved by the Institutional Review Board (CAAE: 42743120.5.0000.5404). Results: The study population consisted of 101 adult and elderly patients of both sexes diagnosed with mHNC, 79 of which were classified as having normal muscularity (NM) and 22 with low muscularity (LM). The LM group had a higher proportion of individuals aged over 70 years and with a body mass index less than 18.5. They also had lower total adipose tissue area (mean; NM = 22,4 cm2; LM = 10,3 cm2; p = 0,019) and total adipose tissue index (mean; NM = 8,3 cm2/m2; LM = 3,7 cm2/m2; p = 0,018). The LM group had a significantly worse survival rate (HR = 1.73; 95% CI 1.02-2.92) when compared to the NM group. The median survival was 4.4 months for the LM group and 8.4 months for the NM group. The LM group also had lower adiposity (p = 0.018). Conclusion: Low muscularity impacts the mortality of patients with HNCm independent of age and ECOG

NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics

Xenarthrans—anteaters, sloths, and armadillos—have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, 10 anteaters, and 6 sloths. Our data set includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the southern United States, Mexico, and Caribbean countries at the northern portion of the Neotropics, to the austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n = 5,941), and Cyclopes sp. have the fewest (n = 240). The armadillo species with the most data is Dasypus novemcinctus (n = 11,588), and the fewest data are recorded for Calyptophractus retusus (n = 33). With regard to sloth species, Bradypus variegatus has the most records (n = 962), and Bradypus pygmaeus has the fewest (n = 12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other data sets of Neotropical Series that will become available very soon (i.e., Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans data set. Please cite this data paper when using its data in publications. We also request that researchers and teachers inform us of how they are using these data