In vitro-generated Tc17 cells present a memory phenotype and serve as a reservoir of Tc1 cells in vivo

Indexación: Scopus.Memory CD8+ T cells are ideal candidates for cancer immunotherapy because they can mediate long-term protection against tumors. However, the therapeutic potential of different in vitro-generated CD8+ T cell effector subsets to persist and become memory cells has not been fully characterized. Type 1 CD8+ T (Tc1) cells produce interferon-γ and are endowed with high cytotoxic capacity, whereas IL-17-producing CD8+ T (Tc17) cells are less cytotoxic but display enhanced self-renewal capacity. We sought to evaluate the functional properties of in vitro-generated Tc17 cells and elucidate their potential to become long lasting memory cells. Our results show that in vitro-generated Tc17 cells display a greater in vivo persistence and expansion in response to secondary antigen stimulation compared to Tc1 cells. When transferred into recipient mice, Tc17 cells persist in secondary lymphoid organs, present a recirculation behavior consistent with central memory T cells, and can shift to a Tc1 phenotype. Accordingly, Tc17 cells are endowed with a higher mitochondrial spare respiratory capacity than Tc1 cells and express higher levels of memory-related molecules than Tc1 cells. Together, these results demonstrate that in vitro-generated Tc17 cells acquire a central memory program and provide a lasting reservoir of Tc1 cells in vivo, thus supporting the use of Tc17 lymphocytes in the design of novel and more effective therapies.https://www.frontiersin.org/articles/10.3389/fimmu.2018.00209/ful

Forest fire history in Amazonia inferred from intensive soil charcoal sampling and radiocarbon dating

This study was supported by funding from the UK Natural Environment Research Council (NERC, NE/N011570/1 and NE/R017980/1) and a radiocarbon dating allocation (allocation 2122.0818) from the NERC-funded NEIF Radiocarbon Laboratory.Fire has a historical role in tropical forests related to past climate and ancient land use spanning the Holocene; however, it is unclear from charcoal records how fire varied at different spatiotemporal scales and what sampling strategies are required to determine fire history and their effects. We evaluated fire variation in structurally intact, terra-firme Amazon forests, by intensive soil charcoal sampling from three replicate soil pits in sites in Guyana and northern and southern Peru. We used radiocarbon (14C) measurement to assess (1) locally, how the timing of fires represented in our sample varied across the surface of forest plots and with soil depth, (2) basin-wide, how the age of fires varies across climate and environmental gradients, and (3) how many samples are appropriate when applying the 14C approach to assess the date of last fire. Considering all 14C dates (n = 33), the most recent fires occurred at a similar time at each of the three sites (median ages: 728–851 cal years BP), indicating that in terms of fire disturbance at least, these forests could be considered old-growth. The number of unique fire events ranged from 1 to 4 per pit and from 4 to 6 per site. Based upon our sampling strategy, the N-Peru site—with the highest annual precipitation—had the most fire events. Median fire return intervals varied from 455 to 2,950 cal years BP among sites. Based on available dates, at least three samples (1 from the top of each of 3 pits) are required for the sampling to have a reasonable likelihood of capturing the most recent fire for forests with no history of a recent fire. The maximum fire return interval for two sites was shorter than the time since the last fire, suggesting that over the past ∼800 years these forests have undergone a longer fire-free period than the past 2,000–3,500 years. Our analysis from terra-firme forest soils helps to improve understanding of changes in fire regime, information necessary to evaluate post-fire legacies on modern vegetation and soil and to calibrate models to predict forest response to fire under climate change.Publisher PDFPeer reviewe

Desempenho e características das carcaças de novilhos superprecoces em pastos hibernais submetidos a intensidades de pastejo

O objetivo deste trabalho foi avaliar os efeitos de intensidades de pastejo na terminação de novilhos superprecoces, em pastagens de inverno em sucessão à soja. Foram avaliadas diferentes alturas de pré-pastejo de pastos mistos de azevém e aveia: 10, 20, 30 e 40 cm. Empregou-se o delineamento de blocos ao acaso, com três repetições. Foram utilizados machos mestiços de raças de corte, inteiros, com idade de 10 meses e peso médio inicial de 192±12 kg. As seguintes variáveis foram avaliadas: massa e oferta de forragem, altura do pasto, taxa de acúmulo diário e acúmulo total de forragem, ganho de peso médio diário (GMD), carga animal e ganho de peso vivo por unidade de área (GPA), além de características qualitativas de carcaça. Os novilhos foram abatidos aos 14 meses de idade. O GMD ajustou-se a um modelo de regressão quadrático e teve o ponto de máximo desempenho entre 20 e 25 cm de altura de pré-pastejo, enquanto o GPA ajustou-se a um modelo linear negativo. A qualidade da carcaça dos novilhos foi satisfatória, quando os pastos foram manejados em alturas superiores a 10 cm. É possível produzir carcaças de novilhos superprecoces, na fase de pastagem de sistemas integrados de produção, durante o inverno, em sucessão à soja. O manejo de pastos mistos de azevém e aveia, em alturas entre 20 e 25 cm, otimiza o desempenho animal individual e por área

Genetic divergence between two phenotypically distinct bottlenose dolphin ecotypes suggests separate evolutionary trajectories

Due to their worldwide distribution and occupancy of different types of environments, bottlenose dolphins display considerable morphological variation. Despite limited understanding about the taxonomic identity of such forms and connectivity among them at global scale, coastal (or inshore) and offshore (or oceanic) ecotypes have been widely recognized in several ocean regions. In the Southwest Atlantic Ocean (SWA), however, there are scarce records of bottlenose dolphins differing in external morphology according to habitat preferences that resemble the coastal‐offshore pattern observed elsewhere. The main aim of this study was to analyze the genetic variability, and test for population structure between coastal (n = 127) and offshore (n = 45) bottlenose dolphins sampled in the SWA to assess whether their external morphological distinction is consistent with genetic differentiation. We used a combination of mtDNA control region sequences and microsatellite genotypes to infer population structure and levels of genetic diversity. Our results from both molecular marker types were congruent and revealed strong levels of structuring (microsatellites FST = 0.385, p < .001; mtDNA FST = 0.183, p < .001; ΦST = 0.385, p < .001) and much lower genetic diversity in the coastal than the offshore ecotype, supporting patterns found in previous studies elsewhere. Despite the opportunity for gene flow in potential “contact zones”, we found minimal current and historical connectivity between ecotypes, suggesting they are following discrete evolutionary trajectories. Based on our molecular findings, which seem to be consistent with morphological differentiations recently described for bottlenose dolphins in our study area, we recommend recognizing the offshore bottlenose dolphin ecotype as an additional Evolutionarily Significant Unit (ESU) in the SWA. Implications of these results for the conservation of bottlenose dolphins in SWA are also discussed

Full-Exon Pyrosequencing Screening of BRCA Germline Mutations in Mexican Women with Inherited Breast and Ovarian Cancer

Hereditary breast cancer comprises 10% of all breast cancers. The most prevalent genes causing this pathology are BRCA1 and BRCA2 (breast cancer early onset 1 and 2), which also predispose to other cancers. Despite the outstanding relevance of genetic screening of BRCA deleterious variants in patients with a history of familial cancer, this practice is not common in Latin American public institutions. In this work we assessed mutations in the entire exonic and splice-site regions of BRCA in 39 patients with breast and ovarian cancer and with familial history of breast cancer or with clinical features suggestive for BRCA mutations by massive parallel pyrosequencing. First we evaluated the method with controls and found 41–485 reads per sequence in BRCA pathogenic mutations. Negative controls did not show deleterious variants, confirming the suitability of the approach. In patients diagnosed with cancer we found 4 novel deleterious mutations (c.2805_2808delAGAT and c.3124_3133delAGCAATATTA in BRCA1; c.2639_2640delTG and c.5114_5117delTAAA in BRCA2). The prevalence of BRCA mutations in these patients was 10.2%. Moreover, we discovered 16 variants with unknown clinical significance (11 in exons and 5 in introns); 4 were predicted as possibly pathogenic by in silico analyses, and 3 have not been described previously. This study illustrates how massive pyrosequencing technology can be applied to screen for BRCA mutations in the whole exonic and splice regions in patients with suspected BRCA-related cancers. This is the first effort to analyse the mutational status of BRCA genes on a Mexican-mestizo population by means of pyrosequencing

IV Foro Internacional de Ganadería Sustentable: conectividad ecosistémica y articulación territorial hacia la Agenda 2030

En este espacio plural de análisis y reflexiones, buscamos articular conceptos y posibilidades para los territorios de montaña del centro de México, dando importancia a medios de vida vinculados a la ganadería y su interacción ecosistémica, fundamentado en innovaciones, casos de éxito e iniciativas emblemáticas nacionales e internacionales. La socialización de experiencias es uno de los pilares para transitar hacia la sostenibilidad de los sistemas productivos ganaderos: compartir logros e iniciativas, crear sinergias e identificar vulnerabilidades desde distintos enfoques.GIZ, Agencia de Cooperación Aleman

Geographic patterns of tree dispersal modes in Amazonia and their ecological correlates

Aim: To investigate the geographic patterns and ecological correlates in the geographic distribution of the most common tree dispersal modes in Amazonia (endozoochory, synzoochory, anemochory and hydrochory). We examined if the proportional abundance of these dispersal modes could be explained by the availability of dispersal agents (disperser-availability hypothesis) and/or the availability of resources for constructing zoochorous fruits (resource-availability hypothesis). Time period: Tree-inventory plots established between 1934 and 2019. Major taxa studied: Trees with a diameter at breast height (DBH) ≥ 9.55 cm. Location: Amazonia, here defined as the lowland rain forests of the Amazon River basin and the Guiana Shield. Methods: We assigned dispersal modes to a total of 5433 species and morphospecies within 1877 tree-inventory plots across terra-firme, seasonally flooded, and permanently flooded forests. We investigated geographic patterns in the proportional abundance of dispersal modes. We performed an abundance-weighted mean pairwise distance (MPD) test and fit generalized linear models (GLMs) to explain the geographic distribution of dispersal modes. Results: Anemochory was significantly, positively associated with mean annual wind speed, and hydrochory was significantly higher in flooded forests. Dispersal modes did not consistently show significant associations with the availability of resources for constructing zoochorous fruits. A lower dissimilarity in dispersal modes, resulting from a higher dominance of endozoochory, occurred in terra-firme forests (excluding podzols) compared to flooded forests. Main conclusions: The disperser-availability hypothesis was well supported for abiotic dispersal modes (anemochory and hydrochory). The availability of resources for constructing zoochorous fruits seems an unlikely explanation for the distribution of dispersal modes in Amazonia. The association between frugivores and the proportional abundance of zoochory requires further research, as tree recruitment not only depends on dispersal vectors but also on conditions that favour or limit seedling recruitment across forest types

Comportamento de células do sistema imune frente ao desafio com Salmonella Enteritidis em aves tratadas e não tratadas com ácidos orgânicos

A Salmonelose é uma importante zoonose, considerada a principal causa de infecções bacterianas, sendo associada ao consumo de produtos avícolas. Como alternativa de controle, ácidos orgânicos têm sido amplamente usados. No entanto, pouco se conhece sobre o estado imunológico de aves de produção, e uma avaliação deste status é necessária para proteger frente a enfermidades e para garantir à aplicação segura de agentes terapêuticos ou imunização profilática. Este trabalho teve como objetivo verificar o comportamento do sistema imunológico das aves previamente infectadas com Salmonella Enteritidis (SE) tratadas com um composto de ácidos orgânicos em diferentes concentrações administrado via água e ração comparando com as aves infectadas e não tratadas. Foram inoculados 120 frangos de corte com 1mL de SE, via oral, na concentração de 1,0 x 108 UFC/mL, no 1º e 2º dia de idade, divididos em seis tratamentos com duas repetições, utilizando 200, 400, 500 e 1000ppm do ácido orgânico. Aos 35 dias de vida das aves, foram coletados, de todos os grupos, alíquotas de sangue de 3mL em tubo contendo EDTA para a avaliação das células imunes através de citometria de fluxo. Foram analisadas as porcentagens circulantes de células CD4+, CD8β+, MHC I+, MHC II+, TCRVβ1+, TCRVβ2+ e CD28+. Para análise microbiológica foram coletadas tonsilas cecais destas aves. Observou-se com esse estudo que os ácidos orgânicos nas dosagens 1000ppm na água e 500ppm na ração durante, dois e sete dias respectivamente antes do abate, foram eficazes na redução da infecção por SE em frangos de corte, comprovadas pelo método microbiológico e demonstradas através do comportamento das células do sistema imune. No presente estudo as aves infectadas apresentaram uma proporção menor de células T auxiliares circulantes quando comparadas às aves infectadas, mas tratadas com o AO ou com o grupo não infectado. A mesma tendência pode ser observada para as células CD28+, TCRVβ1+ e MHC IIbright+, e, com menor resolução, para CD8β+

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality