A Molecular Phylogeny And New Infrageneric Classification Of Mucuna Adans. (leguminosae-papilionoideae) Including Insights From Morphology And Hypotheses About Biogeography

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Premise of research. The genus Mucuna has a pantropical distribution and comprises approximately 105 species, many of which show great economic value for forage, ornament, and medicine. To date, phylogenetic relationships within Mucuna have not been investigated using molecular data. The aim of this study was to build a phylogenetic framework for Mucuna to address questions about its monophyly, infrageneric relationships, divergence times, and biogeography. Methodology. We sequenced plastid (trnL-F) and nuclear ribosomal (internal transcribed spacer) regions and applied Bayesian and maximum likelihood analyses. An ancestral area reconstruction coupled with a divergence time analysis was used to investigate the historical biogeography of the genus. Pivotal results. Our results show that Mucuna is a monophyletic genus and that subgenus Stizolobium is a monophyletic group within it. We present here the analyses and results that support the need to recircumscribe subgenus Mucuna and to segregate a small group of species with large fruits into a newly proposed subgenus (to be described formally elsewhere after additional investigations). Conclusions. On the basis of ancestral area reconstruction and divergence time analyses, we conclude that the genus Mucuna originated and first diversified in the Paleotropics around 29.2 Ma and achieved a pantropical distribution through multiple long-distance dispersal events, which were facilitated by the occurrence of seeds adapted to oceanic dispersal.17717689Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Science without Borders Program [245590/2012-9]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Shirley A. Graham Fellowship, Missouri Botanical GardenBiologia Vegetal postgraduate program at Universidade Estadual de Campinas (UNICAMP), BrazilRoyal Botanic Gardens, KewMissouri Botanical GardenCentro de Biologia Molecular e Engenharia Genetica (CBMEG) Laboratory, BrazilEnvironment Research and Technology Development Fund of the Ministry of the Environment, Japan [S-9]Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Thermal, mechanical and chemical analysis of poly(vinyl alcohol) multifilament and braided yarns

Poly(vinyl alcohol) (PVA) in multifilament and braided yarns (BY) forms presents great potential for the design of numerous applications. However, such solutions fail to accomplish their requirements if the chemical and thermomechanical behaviour is not sufficiently known. Hence, a comprehensive characterisation of PVA multifilament and three BY architectures (6, 8, and 10 yarns) was performed involving the application of several techniques to evaluate the morphological, chem- ical, thermal, and mechanical features of those structures. Scanning electron microscopy (SEM) was used to reveal structural and morphological information. Differential thermal analysis (DTA) pointed out the glass transition temperature of PVA at 76 °C and the corresponding crystalline melt- ing point at 210 °C. PVA BY exhibited higher tensile strength under monotonic quasi-static loading in comparison to their multifilament forms. Creep tests demonstrated that 6BY structures present the most deformable behaviour, while 8BY structures are the least deformable. Relaxation tests showed that 8BY architecture presents a more expressive variation of tensile stress, while 10BY of- fered the least. Dynamic mechanical analysis (DMA) revealed storage and loss moduli curves with similar transition peaks for the tested structures, except for the 10BY. Storage modulus is always four to six times higher than the loss modulus.This work was funded by European Regional Development funds (FEDER) through the Competitiveness and Internationalization Operational Program (POCI)—COMPETE andby Na-tional Funds through Portuguese Fundação para a Ciência e Tecnologia (FCT) under the project UID/EMS/50022/2020, UID/EEA/04436/2019 andUID/ CTM/00264/2019. Andrea Zille acknowledges financial support of the FCT through the project PTDC/CTM-TEX/28295/2017,and Nuno Dourado acknowledges financial support of the FCT through the project PTDC/EME-SIS/28225/2017. M.F.S.M. de Moura acknowledges the ‘Laboratório Associado de Energia, Transportes e Aeronáutica’ (LAETA) for the financial support

Bone mineral density in juvenile systemic lupus erythematosus

We evaluated spine bone mineral density (BMD) in Brazilian children with juvenile systemic lupus erythematosus (JSLE) in order to detect potential predictors of reduction in bone mass. A cross-sectional study of BMD at the lumbar spine level (L2-L4) was conducted on 16 female JSLE patients aged 6-17 years. Thirty-two age-matched healthy girls were used as control. BMD at the lumbar spine was measured by dual-energy X-ray absorptiometry. Weight, height and pubertal Tanner stage were determined in patients and controls. Disease duration, mean daily steroid doses, mean cumulative steroid doses and JSLE activity measured by the systemic lupus erythematosus disease activity index (SLEDAI) were determined for all JSLE patients based on their medical charts. All parameters were used as potential determinant factors for bone loss. Lumbar BMD tended to be lower in the JSLE patients, however, this difference was not statistically significant (P = 0.10). No significant correlation was observed in JSLE girls between BMD and age, height, Tanner stage, disease duration, corticosteroid use or disease activity. We found a weak correlation between BMD and weight (r = 0.672). In the JSLE group we found no significant parameters to correlate with reduced bone mass. Disease activity and mean cumulative steroid doses were not related to BMD values. We did not observe reduced bone mass in female JSLE.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PediatriaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MedicinaUNIFESP, EPM, Depto. de PediatriaUNIFESP, EPM, Depto. de MedicinaSciEL

Velhas tardes de domingo (Notas sobre Domingão do Faustão e Programa Silvio Santos)

Nas tardes de domingo,as duas maiores redes de televisão brasileiras apresentam programas de auditório: a Rede Globo de Televisão transmite Domingão do Faustão e o Sistema Brasileiro de Televisão veicula o Programa Silvio Santos. Este estudo traça um breve histórico desses dois programas, descreve rapidamente suas estruturas, e, a partir daí, delineia hipóteses sobre possíveis funções desses produtos televisivos junto aos espectadores.

A dysflagellar mutant of Leishmania (Viannia) braziliensis isolated from a cutaneous leishmaniasis patient

<p>Abstract</p> <p>Background</p> <p>Parasites of the <it>Leishmania </it>genus alternate between the flagellated extracellular promastigote stage and intracellular amastigotes. Here we report the characterization of a <it>Leishmania </it>isolate, obtained from a cutaneous leishmaniasis patient, which presents peculiar morphological features.</p> <p>Methods</p> <p>The parasite was cultured <it>in vitro </it>and characterized morphologically using optical and electron microscopy. Identification was performed based on monoclonal antibodies and internal ribosomal spacer typing. <it>In vitro </it>macrophage cultures, murine experimental models and sand fly infections were used to evaluate infectivity <it>in vitro </it>and <it>in vivo</it>.</p> <p>Results</p> <p>The isolate was identified as <it>Leishmania </it>(<it>Viannia</it>) <it>braziliensis</it>. In the atypical promastigotes grown in culture, a short flagellum surrounded or interrupted by a protuberance of disorganized material was observed. A normal axoneme was present close to the basal body but without elongation much further outside the flagellar pocket. A disorganized swelling at the precocious end of the axoneme coincided with the lack of a paraflagellar rod structure. The isolate was able to infect macrophages <it>in vitro</it>, induce lesions in BALB/c mice and infect <it>Lutzomyia longipalpis</it>.</p> <p>Conclusions</p> <p>Notwithstanding the lack of an extracellular flagellum, this isolate infects macrophages <it>in vitro </it>and produces lesions when inoculated into mice. Moreover, it is able to colonize phlebotomine sand flies. Considering the importance attributed to the flagellum in the successful infection and survival of <it>Leishmania </it>in the insect midgut and in the invasion of macrophages, these findings may bring new light into the infectious mechanisms of <it>L</it>. (<it>V</it>.) <it>braziliensis</it>.</p

Microglia/Astrocytes–Glioblastoma Crosstalk: Crucial Molecular Mechanisms and Microenvironmental Factors

In recent years, the functions of glial cells, namely, astrocytes and microglia, have gained prominence in several diseases of the central nervous system, especially in glioblastoma (GB), the most malignant primary brain tumor that leads to poor clinical outcomes. Studies showed that microglial cells or astrocytes play a critical role in promoting GB growth. Based on the recent findings, the complex network of the interaction between microglial/astrocytes cells and GB may constitute a potential therapeutic target to overcome tumor malignancy. In the present review, we summarize the most important mechanisms and functions of the molecular factors involved in the microglia or astrocytes–GB interactions, which is particularly the alterations that occur in the cell’s extracellular matrix and the cytoskeleton. We overview the cytokines, chemokines, neurotrophic, morphogenic, metabolic factors, and non-coding RNAs actions crucial to these interactions. We have also discussed the most recent studies regarding the mechanisms of transportation and communication between microglial/astrocytes – GB cells, namely through the ABC transporters or by extracellular vesicles. Lastly, we highlight the therapeutic challenges and improvements regarding the crosstalk between these glial cells and GB

Natural Splice Variant of MHC Class I Cytoplasmic Tail Enhances Dendritic Cell-Induced CD8+ T-Cell Responses and Boosts Anti-Tumor Immunity

Dendritic cell (DC)-mediated presentation of MHC class I (MHC-I)/peptide complexes is a crucial first step in the priming of CTL responses, and the cytoplasmic tail of MHC-I plays an important role in modulating this process. Several species express a splice variant of the MHC-I tail that deletes exon 7-encoding amino acids (Δ7), including a conserved serine phosphorylation site. Previously, it has been shown that Δ7 MHC-I molecules demonstrate extended DC surface half-lives, and that mice expressing Δ7-Kb generate significantly augmented CTL responses to viral challenge. Herein, we show that Δ7-Db-expressing DCs stimulated significantly more proliferation and much higher cytokine secretion by melanoma antigen-specific (Pmel-1) T cells. Moreover, in combination with adoptive Pmel-1 T-cell transfer, Δ7-Db DCs were superior to WT-Db DCs at stimulating anti-tumor responses against established B16 melanoma tumors, significantly extending mouse survival. Human DCs engineered to express Δ7-HLA-A*0201 showed similarly enhanced CTL stimulatory capacity. Further studies demonstrated impaired lateral membrane movement and clustering of human Δ7-MHC-I/peptide complexes, resulting in significantly increased bioavailability of MHC-I/peptide complexes for specific CD8+ T cells. Collectively, these data suggest that targeting exon 7-encoded MHC-I cytoplasmic determinants in DC vaccines has the potential to increase CD8+ T-cell stimulatory capacity and substantially improve their clinical efficacy

Genetically predicted telomere length and Alzheimer’s disease endophenotypes: a Mendelian randomization study

Telomere length (TL) is associated with biological aging, consequently influencing the risk of age-related diseases such as Alzheimer's disease (AD). We aimed to evaluate the potential causal role of TL in AD endophenotypes (i.e., cognitive performance, N = 2233; brain age and AD-related signatures, N = 1134; and cerebrospinal fluid biomarkers (CSF) of AD and neurodegeneration, N = 304) through a Mendelian randomization (MR) analysis. Our analysis was conducted in the context of the ALFA (ALzheimer and FAmilies) study, a population of cognitively healthy individuals at risk of AD. A total of 20 single nucleotide polymorphisms associated with TL were used to determine the effect of TL on AD endophenotypes. Analyses were adjusted by age, sex, and years of education. Stratified analyses by APOE-epsilon 4 status and polygenic risk score of AD were conducted. MR analysis revealed significant associations between genetically predicted longer TL and lower levels of CSF A beta and higher levels of CSF NfL only in APOE-epsilon 4 non-carriers. Moreover, inheriting longer TL was associated with greater cortical thickness in age and AD-related brain signatures and lower levels of CSF p-tau among individuals at a high genetic predisposition to AD. Further observational analyses are warranted to better understand these associations

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens