Morphological and Transcriptional Changes in Human Bone Marrow During Natural Plasmodium vivax Malaria Infections.

--- - Label: BACKGROUND NlmCategory: BACKGROUND content: The presence of Plasmodium vivax malaria parasites in the human bone marrow (BM) is still controversial. However, recent data from a clinical case and experimental infections in splenectomized nonhuman primates unequivocally demonstrated the presence of parasites in this tissue. - Label: METHODS NlmCategory: METHODS content: In the current study, we analyzed BM aspirates of 7 patients during the acute attack and 42 days after drug treatment. RNA extracted from CD71+ cell suspensions was used for sequencing and transcriptomic analysis. - Label: RESULTS NlmCategory: RESULTS content: We demonstrated the presence of parasites in all patients during acute infections. To provide further insights, we purified CD71+ BM cells and demonstrated dyserythropoiesis and inefficient erythropoiesis in all patients. In addition, RNA sequencing from 3 patients showed that genes related to erythroid maturation were down-regulated during acute infections, whereas immune response genes were up-regulated. - Label: CONCLUSIONS NlmCategory: CONCLUSIONS content: This study thus shows that during P. vivax infections, parasites are always present in the BM and that such infections induced dyserythropoiesis and ineffective erythropoiesis. Moreover, infections induce transcriptional changes associated with such altered erythropoietic response, thus highlighting the importance of this hidden niche during natural infections

Role of mitochondrial raft-like microdomains in the regulation of cell apoptosis

Lipid rafts are envisaged as lateral assemblies of specific lipids and proteins that dissociate and associate rapidly and form functional clusters in cell membranes. These structural platforms are not confined to the plasma membrane; indeed lipid microdomains are similarly formed at subcellular organelles, which include endoplasmic reticulum, Golgi and mitochondria, named raft-like microdomains. In addition, some components of raft-like microdomains are present within ER-mitochondria associated membranes. This review is focused on the role of mitochondrial raft-like microdomains in the regulation of cell apoptosis, since these microdomains may represent preferential sites where key reactions take place, regulating mitochondria hyperpolarization, fission-associated changes, megapore formation and release of apoptogenic factors. These structural platforms appear to modulate cytoplasmic pathways switching cell fate towards cell survival or death. Main insights on this issue derive from some pathological conditions in which alterations of microdomains structure or function can lead to severe alterations of cell activity and life span. In the light of the role played by raft-like microdomains to integrate apoptotic signals and in regulating mitochondrial dynamics, it is conceivable that these membrane structures may play a role in the mitochondrial alterations observed in some of the most common human neurodegenerative diseases, such as Amyotrophic lateral sclerosis, Huntington's chorea and prion-related diseases. These findings introduce an additional task for identifying new molecular target(s) of pharmacological agents in these pathologies

Primary resistance of HIV to antiretrovirals among individuals recently diagnosed at voluntary counselling and testing centres in the metropolitan region of Recife, Pernambuco

Determining the prevalence and type of antiretroviral (ARV) resistance among ARV-naïve individuals is important to assess the potential responses of these individuals to first-line regimens. The prevalence of primary resistance and the occurrence of recent infections among individuals with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) were identified among recently diagnosed patients at five sexually transmitted disease/AIDS testing and counselling centres in the metropolitan region of Recife (RMR), Pernambuco, Brazil, between 2007-2009. One-hundred and eight samples were analysed using the Calypte® BED assay. Males predominated (56%), as did patients aged 31-50 years. Twenty-three percent presented evidence of a recent HIV infection. The median CD4+ T lymphocyte count was 408 cells/mm³ and the median viral load was 3.683 copies/mL. The prevalence of primary resistance was 4.6% (confidence interval 95% = 1-8.2%) based on criteria that excluded common polymorphisms in accordance with the surveillance drug resistance mutation criteria. The prevalence of resistance to non-nucleoside reverse transcriptase, nucleoside/nucleotide reverse transcriptase and protease inhibitors were 3.8%, 1.5% and 0.8%, respectively. Fifty-seven percent of strains were from clade B, 37.7% were clade F and 3.1% were clade C; there were no statistically significant differences with respect to resistance between clades. Recent infection tended to be more common in men (p = 0.06) and in municipalities in the south of the RMR (Jaboatão dos Guararapes and Cabo de Santo Agostinho) (p = 0.046). The high prevalence of recent infection and the high prevalence of non-B strains in this poor Brazilian region merit further attention.Laboratório Central de Saúde Pública de Pernambuco Setor de VirologiaUniversidade Federal de Pernambuco Programa de Pós-Graduação em Medicina TropicalFiocruz Centro de Pesquisa Aggeu MagalhãesCentro de Testagem e Aconselhamento Herbert de SouzaUniversidade Federal de São Paulo (UNIFESP) Laboratório de RetrovirologiaUNIFESP, Laboratório de RetrovirologiaSciEL

How immunological profle drives clinical phenotype of primary Sjögren’s syndrome at diagnosis: analysis of 10,500 patients (Sjögren Big Data Project)

To evaluate the influence of the main immunological markers on the disease phenotype at diagnosis in a large international cohort of patients with primary Sjögren´s syndrome (SjS).METHODS:The Big Data Sjögren Project Consortium is an international, multicentre registry created in 2014. As a first step, baseline clinical information from leading centres on clinical research in SjS of the 5 continents was collected. The centres shared a harmonised data architecture and conducted cooperative online efforts in order to refine collected data under the coordination of a big data statistical team. Inclusion criteria were the fulfillment of the 2002 classification criteria. Immunological tests were carried out using standard commercial assays.RESULTS:By January 2018, the participant centres had included 10,500 valid patients from 22 countries. The cohort included 9,806 (93%) women and 694 (7%) men, with a mean age at diagnosis of primary SjS of 53 years, mainly White (78%) and included from European countries (71%). The frequency of positive immunological markers at diagnosis was 79.3% for ANA, 73.2% for anti-Ro, 48.6% for RF, 45.1% for anti- La, 13.4% for low C3 levels, 14.5% for low C4 levels and 7.3% for cryoglobulins. Positive autoantibodies (ANA, Ro, La) correlated with a positive result in salivary gland biopsy, while hypocomplementaemia and especially cryoglo-bulinaemia correlated with systemic activity (mean ESSDAI score of 17.7 for cryoglobulins, 11.3 for low C3 and 9.2 for low C4, in comparison with 3.8 for negative markers). The immunological markers with a great number of statistically-significant associations (p<0.001) in the organ-by-organ ESS- DAI evaluation were cryoglobulins (9 domains), low C3 (8 domains), anti-La (7 domains) and low C4 (6 domains).CONCLUSIONS:We confirm the strong influence of immunological markers on the phenotype of primary SjS at diagnosis in the largest multi-ethnic international cohort ever analysed, with a greater influence for cryoglobulinaemic-related markers in comparison with Ro/La autoantibodies and ANA. Immunological patterns play a central role in the phenotypic expression of the disease already at the time of diagnosis, and may guide physicians to design a specific personalised management during the follow-up of patients with primary SjS.Fil: Brito Zerón, Pilar. Hospital Sanitas CIMA; España. Universidad de Barcelona; EspañaFil: Acar Denizli, Nihan. Mimar Sinan Fine Arts University; TurquíaFil: Ng, Wan Fai. University of Newcastle; Reino UnidoFil: Zeher, Margit. University of Debrecen; HungríaFil: Rasmussen, Astrid. Oklahoma Medical Research Foundation; Estados UnidosFil: Mandl, Thomas. Lund University; SueciaFil: Seror, Raphaele. Université Paris Sud; FranciaFil: Xiaolin, Li. Anhui Provincial Hospital; ChinaFil: Baldini, Chiara. Università degli Studi di Pisa; ItaliaFil: Gottenberg, Jaques. Université de Strasbourg; Francia. Centre National de la Recherche Scientifique; FranciaFil: Danda, Debashish. Christian Medical College & Hospital; IndiaFil: Quartuccio, Luca. University Hospital “Santa María della Misericordia”; ItaliaFil: Priori, Roberta. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Hernandez Molina, Gabriela. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; MéxicoFil: Armagan, Berkan. Hacettepe University. Faculty of Medicine.Department of Internal Medicine; TurquíaFil: Kruize, Aike. University Medical Center Utrecht; Países BajosFil: Kwok, Seung Ki. The Catholic University of Korea; Corea del SurFil: Kvarnström, Marika. Karolinska University Hospital.Department of Medicine.Unit of Rheumatology. Karolinska Institutet ; SueciaFil: Praprotnik, Sonja. University Medical Centre; EsloveniaFil: Sene, Damien. Université Paris Diderot - Paris 7; FranciaFil: Bartoloni, Elena. Università di Perugia; ItaliaFil: Solans, R.. Hospital Vall d’Hebron; ItaliaFil: Rischmueller, M.. University of Western Australia; AustraliaFil: Suzuki, Y.. Kanazawa University Hospital; JapónFil: Isenberg, D. A.. University College London; Estados UnidosFil: Valim, V.. Federal University of Espírito Santo; BrasilFil: Wiland, P.. Wroclaw Medical Hospital; PoloniaFil: Nordmark, G.. Uppsala Universitet; SueciaFil: Fraile, G.. Hospital Ramón y Cajal; EspañaFil: Retamozo, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Hospital Privado Centro Medico de Córdoba; Argentina; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentin

Global transpiration data from sap flow measurements: the SAPFLUXNET database

Plant transpiration links physiological responses of vegetation to water supply and demand with hydrological, energy, and carbon budgets at the land?atmosphere interface. However, despite being the main land evaporative flux at the global scale, transpiration and its response to environmental drivers are currently not well constrained by observations. Here we introduce the first global compilation of whole-plant transpiration data from sap flow measurements (SAPFLUXNET, https://sapfluxnet.creaf.cat/, last access: 8 June 2021). We harmonized and quality-controlled individual datasets supplied by contributors worldwide in a semi-automatic data workflow implemented in the R programming language. Datasets include sub-daily time series of sap flow and hydrometeorological drivers for one or more growing seasons, as well as metadata on the stand characteristics, plant attributes, and technical details of the measurements. SAPFLUXNET contains 202 globally distributed datasets with sap flow time series for 2714 plants, mostly trees, of 174 species. SAPFLUXNET has a broad bioclimatic coverage, with woodland/shrubland and temperate forest biomes especially well represented (80 % of the datasets). The measurements cover a wide variety of stand structural characteristics and plant sizes. The datasets encompass the period between 1995 and 2018, with 50 % of the datasets being at least 3 years long. Accompanying radiation and vapour pressure deficit data are available for most of the datasets,while on-site soil water content is available for 56 % of the datasets. Many datasets contain data for species that make up 90 % or more of the total stand basal area, allowing the estimation of stand transpiration in diverse ecological settings. SAPFLUXNET adds to existing plant trait datasets, ecosystem flux networks, and remote sensing products to help increase our understanding of plant water use, plant responses to drought, and ecohydrological processes.Fil: Poyatos, Rafael. Universitat Autònoma de Barcelona; EspañaFil: Granda, Víctor. Universitat Autònoma de Barcelona; EspañaFil: Flo, Víctor. Universitat Autònoma de Barcelona; EspañaFil: Adams, Mark A.. Swinburne University of Technology; Australia. University of Sydney; AustraliaFil: Adorján, Balázs. University of Debrecen; HungríaFil: Aguadé, David. Universitat Autònoma de Barcelona; EspañaFil: Aidar, Marcos P. M.. Institute of Botany; BrasilFil: Allen, Scott. University of Nevada; Estados UnidosFil: Alvarado Barrientos, M. Susana. Instituto de Ecología A.C.; MéxicoFil: Anderson Teixeira, Kristina J.. Smithsonian Tropical Research Institute; PanamáFil: Aparecido, Luiza Maria. Arizona State University; Estados Unidos. Texas A&M University; Estados UnidosFil: Arain, M. Altaf. McMaster University; CanadáFil: Aranda, Ismael. National Institute for Agricultural and Food Research and Technology; EspañaFil: Asbjornsen, Heidi. University of New Hampshire; Estados UnidosFil: Robert Baxter. Durham University; Reino UnidoFil: Beamesderfer, Eric. McMaster University; Canadá. Northern Arizona University; Estados UnidosFil: Carter Berry, Z.. Chapman University; Estados UnidosFil: Berveiller, Daniel. Université Paris Saclay; Francia. Centre National de la Recherche Scientifique; FranciaFil: Blakely, Bethany. University of Illinois at Urbana-Champaign; Estados UnidosFil: Boggs, Johnny. United States Forest Service; Estados UnidosFil: Gil Bohrer. Ohio State University; Estados UnidosFil: Bolstad, Paul V.. University of Minnesota; Estados UnidosFil: Bonal, Damien. Université de Lorraine; FranciaFil: Bracho, Rosvel. University of Florida; Estados UnidosFil: Brito, Patricia. Universidad de La Laguna; EspañaFil: Brodeur, Jason. McMaster University; CanadáFil: Casanoves, Fernando. Centro Agronómico Tropical de Investigación y Enseñanza; Costa RicaFil: Chave, Jérôme. Université Paul Sabatier; FranciaFil: Chen, Hui. Xiamen University; ChinaFil: Peri, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Santa Cruz. Universidad Tecnológica Nacional. Facultad Regional Santa Cruz. Centro de Investigaciones y Transferencia de Santa Cruz. Universidad Nacional de la Patagonia Austral. Centro de Investigaciones y Transferencia de Santa Cruz; Argentin