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1.
Nature ; 625(7996): 728-734, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38200314

RESUMO

Trees structure the Earth's most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations1-6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth's 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories7, we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world's most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees.


Assuntos
Florestas , Árvores , Clima Tropical , Biodiversidade , Árvores/anatomia & histologia , Árvores/classificação , Árvores/crescimento & desenvolvimento , África , Sudeste Asiático
2.
Nature ; 624(7990): 92-101, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37957399

RESUMO

Forests are a substantial terrestrial carbon sink, but anthropogenic changes in land use and climate have considerably reduced the scale of this system1. Remote-sensing estimates to quantify carbon losses from global forests2-5 are characterized by considerable uncertainty and we lack a comprehensive ground-sourced evaluation to benchmark these estimates. Here we combine several ground-sourced6 and satellite-derived approaches2,7,8 to evaluate the scale of the global forest carbon potential outside agricultural and urban lands. Despite regional variation, the predictions demonstrated remarkable consistency at a global scale, with only a 12% difference between the ground-sourced and satellite-derived estimates. At present, global forest carbon storage is markedly under the natural potential, with a total deficit of 226 Gt (model range = 151-363 Gt) in areas with low human footprint. Most (61%, 139 Gt C) of this potential is in areas with existing forests, in which ecosystem protection can allow forests to recover to maturity. The remaining 39% (87 Gt C) of potential lies in regions in which forests have been removed or fragmented. Although forests cannot be a substitute for emissions reductions, our results support the idea2,3,9 that the conservation, restoration and sustainable management of diverse forests offer valuable contributions to meeting global climate and biodiversity targets.


Assuntos
Sequestro de Carbono , Carbono , Conservação dos Recursos Naturais , Florestas , Biodiversidade , Carbono/análise , Carbono/metabolismo , Conservação dos Recursos Naturais/estatística & dados numéricos , Conservação dos Recursos Naturais/tendências , Atividades Humanas , Recuperação e Remediação Ambiental/tendências , Desenvolvimento Sustentável/tendências , Aquecimento Global/prevenção & controle
3.
Nature ; 621(7980): 773-781, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37612513

RESUMO

Determining the drivers of non-native plant invasions is critical for managing native ecosystems and limiting the spread of invasive species1,2. Tree invasions in particular have been relatively overlooked, even though they have the potential to transform ecosystems and economies3,4. Here, leveraging global tree databases5-7, we explore how the phylogenetic and functional diversity of native tree communities, human pressure and the environment influence the establishment of non-native tree species and the subsequent invasion severity. We find that anthropogenic factors are key to predicting whether a location is invaded, but that invasion severity is underpinned by native diversity, with higher diversity predicting lower invasion severity. Temperature and precipitation emerge as strong predictors of invasion strategy, with non-native species invading successfully when they are similar to the native community in cold or dry extremes. Yet, despite the influence of these ecological forces in determining invasion strategy, we find evidence that these patterns can be obscured by human activity, with lower ecological signal in areas with higher proximity to shipping ports. Our global perspective of non-native tree invasion highlights that human drivers influence non-native tree presence, and that native phylogenetic and functional diversity have a critical role in the establishment and spread of subsequent invasions.


Assuntos
Biodiversidade , Meio Ambiente , Espécies Introduzidas , Árvores , Bases de Dados Factuais , Atividades Humanas , Espécies Introduzidas/estatística & dados numéricos , Espécies Introduzidas/tendências , Filogenia , Chuva , Temperatura , Árvores/classificação , Árvores/fisiologia
4.
Proc Natl Acad Sci U S A ; 119(6)2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35101981

RESUMO

One of the most fundamental questions in ecology is how many species inhabit the Earth. However, due to massive logistical and financial challenges and taxonomic difficulties connected to the species concept definition, the global numbers of species, including those of important and well-studied life forms such as trees, still remain largely unknown. Here, based on global ground-sourced data, we estimate the total tree species richness at global, continental, and biome levels. Our results indicate that there are ∼73,000 tree species globally, among which ∼9,000 tree species are yet to be discovered. Roughly 40% of undiscovered tree species are in South America. Moreover, almost one-third of all tree species to be discovered may be rare, with very low populations and limited spatial distribution (likely in remote tropical lowlands and mountains). These findings highlight the vulnerability of global forest biodiversity to anthropogenic changes in land use and climate, which disproportionately threaten rare species and thus, global tree richness.


Assuntos
Conservação dos Recursos Naturais , Florestas , Árvores/classificação , Planeta Terra , Árvores/crescimento & desenvolvimento
5.
BMC Genomics ; 25(1): 623, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902640

RESUMO

BACKGROUND: The genotype-by-environment interaction (GxE) in beef cattle can be investigated using reaction norm models to assess environmental sensitivity and, combined with genome-wide association studies (GWAS), to map genomic regions related to animal adaptation. Including genetic markers from whole-genome sequencing in reaction norm (RN) models allows us to identify high-resolution candidate genes across environmental gradients through GWAS. Hence, we performed a GWAS via the RN approach using whole-genome sequencing data, focusing on mapping candidate genes associated with the expression of reproductive and growth traits in Nellore cattle. For this purpose, we used phenotypic data for age at first calving (AFC), scrotal circumference (SC), post-weaning weight gain (PWG), and yearling weight (YW). A total of 20,000 males and 7,159 females genotyped with 770k were imputed to the whole sequence (29 M). After quality control and linkage disequilibrium (LD) pruning, there remained ∼ 2.41 M SNPs for SC, PWG, and YW and ∼ 5.06 M SNPs for AFC. RESULTS: Significant SNPs were identified on Bos taurus autosomes (BTA) 10, 11, 14, 18, 19, 20, 21, 24, 25 and 27 for AFC and on BTA 4, 5 and 8 for SC. For growth traits, significant SNP markers were identified on BTA 3, 5 and 20 for YW and PWG. A total of 56 positional candidate genes were identified for AFC, 9 for SC, 3 for PWG, and 24 for YW. The significant SNPs detected for the reaction norm coefficients in Nellore cattle were found to be associated with growth, adaptative, and reproductive traits. These candidate genes are involved in biological mechanisms related to lipid metabolism, immune response, mitogen-activated protein kinase (MAPK) signaling pathway, and energy and phosphate metabolism. CONCLUSIONS: GWAS results highlighted differences in the physiological processes linked to lipid metabolism, immune response, MAPK signaling pathway, and energy and phosphate metabolism, providing insights into how different environmental conditions interact with specific genes affecting animal adaptation, productivity, and reproductive performance. The shared genomic regions between the intercept and slope are directly implicated in the regulation of growth and reproductive traits in Nellore cattle raised under different environmental conditions.


Assuntos
Interação Gene-Ambiente , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Reprodução , Sequenciamento Completo do Genoma , Animais , Bovinos/genética , Bovinos/crescimento & desenvolvimento , Reprodução/genética , Feminino , Masculino , Genótipo , Fenótipo , Locos de Características Quantitativas , Desequilíbrio de Ligação
6.
N Engl J Med ; 384(7): 619-629, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33232588

RESUMO

BACKGROUND: Convalescent plasma is frequently administered to patients with Covid-19 and has been reported, largely on the basis of observational data, to improve clinical outcomes. Minimal data are available from adequately powered randomized, controlled trials. METHODS: We randomly assigned hospitalized adult patients with severe Covid-19 pneumonia in a 2:1 ratio to receive convalescent plasma or placebo. The primary outcome was the patient's clinical status 30 days after the intervention, as measured on a six-point ordinal scale ranging from total recovery to death. RESULTS: A total of 228 patients were assigned to receive convalescent plasma and 105 to receive placebo. The median time from the onset of symptoms to enrollment in the trial was 8 days (interquartile range, 5 to 10), and hypoxemia was the most frequent severity criterion for enrollment. The infused convalescent plasma had a median titer of 1:3200 of total SARS-CoV-2 antibodies (interquartile range, 1:800 to 1:3200). No patients were lost to follow-up. At day 30 day, no significant difference was noted between the convalescent plasma group and the placebo group in the distribution of clinical outcomes according to the ordinal scale (odds ratio, 0.83; 95% confidence interval [CI], 0.52 to 1.35; P = 0.46). Overall mortality was 10.96% in the convalescent plasma group and 11.43% in the placebo group, for a risk difference of -0.46 percentage points (95% CI, -7.8 to 6.8). Total SARS-CoV-2 antibody titers tended to be higher in the convalescent plasma group at day 2 after the intervention. Adverse events and serious adverse events were similar in the two groups. CONCLUSIONS: No significant differences were observed in clinical status or overall mortality between patients treated with convalescent plasma and those who received placebo. (PlasmAr ClinicalTrials.gov number, NCT04383535.).


Assuntos
Anticorpos Neutralizantes/sangue , COVID-19/terapia , Imunoglobulina G/sangue , Pneumonia Viral/terapia , SARS-CoV-2/imunologia , Idoso , Idoso de 80 Anos ou mais , Transfusão de Componentes Sanguíneos , COVID-19/complicações , COVID-19/mortalidade , Progressão da Doença , Método Duplo-Cego , Feminino , Hospitalização , Humanos , Imunização Passiva , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/etiologia , Pneumonia Viral/mortalidade , Índice de Gravidade de Doença , Soroterapia para COVID-19
7.
New Phytol ; 242(2): 700-716, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38382573

RESUMO

Orchids constitute one of the most spectacular radiations of flowering plants. However, their origin, spread across the globe, and hotspots of speciation remain uncertain due to the lack of an up-to-date phylogeographic analysis. We present a new Orchidaceae phylogeny based on combined high-throughput and Sanger sequencing data, covering all five subfamilies, 17/22 tribes, 40/49 subtribes, 285/736 genera, and c. 7% (1921) of the 29 524 accepted species, and use it to infer geographic range evolution, diversity, and speciation patterns by adding curated geographical distributions from the World Checklist of Vascular Plants. The orchids' most recent common ancestor is inferred to have lived in Late Cretaceous Laurasia. The modern range of Apostasioideae, which comprises two genera with 16 species from India to northern Australia, is interpreted as relictual, similar to that of numerous other groups that went extinct at higher latitudes following the global climate cooling during the Oligocene. Despite their ancient origin, modern orchid species diversity mainly originated over the last 5 Ma, with the highest speciation rates in Panama and Costa Rica. These results alter our understanding of the geographic origin of orchids, previously proposed as Australian, and pinpoint Central America as a region of recent, explosive speciation.


Assuntos
Clima , Orchidaceae , Austrália , Filogenia , Filogeografia , Orchidaceae/genética
8.
Gastric Cancer ; 27(3): 548-557, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38436762

RESUMO

BACKGROUND: PET-CT-based patient metabolic profiling is a novel concept to incorporate patient-specific metabolism into gastric cancer care. METHODS: Staging PET-CTs, demographics, and clinicopathologic variables of gastric cancer patients were obtained from a prospectively maintained institutional database. PET-CT avidity was measured in tumor, liver, spleen, four paired muscles, and two paired fat areas in each patient. The liver to rectus femoris (LRF) ratio was defined as the ratio of SUVmean of liver to the average SUVmean of the bilateral rectus femoris muscles. Kaplan-Meier and Cox-proportional hazards models were used to identify the impact of LRF ratio on OS. RESULTS: Two hundred and one patients with distal gastroesophageal (48%) or gastric (52%) adenocarcinoma were included. Median age was 65 years, and 146 (73%) were male. On univariate analysis, rectus femoris PET-CT avidity and LRF ratio were significantly associated with overall survival (p < 0.05). LRF ratio was significantly higher in males, early-stage cancer, patients with an ECOG 0 or 1 performance status, patients with albumin > 3.5 mg/dL, and those with moderately differentiated tumor histology. In multivariable regression, gastric cancer stage, albumin, and LRF ratio were significant independent predictors of overall survival (LRF ratio HR = 0.73 (0.56-0.96); p = 0.024). Survival curves showed that the prognostic impact of LRF was associated with metastatic gastric cancer (p = 0.009). CONCLUSIONS: Elevated LRF ratio, a patient-specific PET-CT-based metabolic parameter, was independently associated with an improvement in OS in patients with metastatic gastric cancer. With prospective validation, LRF ratio may be a useful, host-specific metabolic parameter for prognostication in gastric cancer.


Assuntos
Fluordesoxiglucose F18 , Neoplasias Gástricas , Humanos , Masculino , Idoso , Feminino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Gástricas/patologia , Prognóstico , Músculos/patologia , Fígado , Metaboloma , Albuminas , Estudos Retrospectivos , Compostos Radiofarmacêuticos
9.
Brain ; 2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37633260

RESUMO

Huntington's disease (HD) results from expansion of a polyglutamine tract (polyQ) in mutant huntingtin (mHTT) protein, but mechanisms underlying polyQ expansion-mediated toxic gain-of-mHTT function remain elusive. Here, deletion and antibody-based experiments revealed that a proline-rich domain (PRD) adjacent to the polyQ tract is necessary for mutant huntingtin (mHTT) to inhibit fast axonal transport and promote axonal pathology in cultured mammalian neurons. Further, polypeptides corresponding to subregions of the PRD sufficed to elicit the toxic effect on fast axonal transport, which was mediated by JNK kinases and involved PRD binding to one or more SH3-domain containing proteins. Collectively, these data suggested a mechanism whereby polyQ tract expansion in mHTT promotes aberrant PRD exposure and interactions of this domain with SH3 domain-containing proteins including some involved in activation of JNK kinases. In support, biochemical and immunohistochemical experiments linked aberrant PRD exposure to increased JNK activation in striatal tissues of the zQ175 mouse model and from post-mortem HD patients. Collectively, these findings support a critical role of PRD on mHTT toxicity, suggesting a novel framework for the potential development of therapies aimed to halt or reduce axonal pathology in HD.

11.
BMC Public Health ; 24(1): 429, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341528

RESUMO

BACKGROUND: Chronic malnutrition is a condition associated with negative impacts on physical and cognitive development. It is multi-causal and can start very early in life, already in utero, thus it is especially challenging to find appropriate interventions to tackle it. The government of Angola is implementing a standard of care program with potential to prevent it, and the provision of cash transfers and the supplementation with small quantity lipid-based nutrients (SQ-LNS) are also promising interventions. We aimed to evaluate the impact of the standard of care program alone and of the standard of care plus a cash transfer intervention in the lineal growth of children less than 2 years old and compare it to the effectiveness of a nutrition supplementation plus standard of care program in Southern Angola. METHODS/DESIGN: The three-arm parallel cluster randomised controlled trial is set in four communes of Huila and Cunene provinces. Clusters are villages or neighbourhoods with a population around 1075 people. A total of twelve clusters were selected per arm and forty pregnant women are expected to be recruited in each cluster. Pregnant women receive the standard of care alone, or the standard of care plus unconditional cash transfer or plus nutritional supplementation during the first 1000 days, from pregnancy to the child reaching 24 months. The primary outcome is the prevalence of stunting measured as height-for-age Z-score (HAZ) < -2 in children below 2 years. Impact will be assessed at 3, 6, 12, 18 and 24 months of children's age. Secondary outcomes include mortality, morbidity, caring, hygiene and nutrition behaviours and practices, and women and children's dietary diversity. Quantitative data are also collected on women's empowerment, household food security, expenditure and relevant clinical and social events at baseline, endline and intermediate time points. DISCUSSION: The results will provide valuable information on the impact of the standard of care intervention alone as well as combined with an unconditional cash transfer intervention compared to a nutrition supplementation plus standard of care intervention, carried out during the first 1000 days, in the children´s growth up to 2 years and related outcomes in Southern Angola. TRIAL REGISTRATION: Clinical Trials NCT05571280. Registered 7 October 2022.


Assuntos
Desnutrição , Padrão de Cuidado , Criança , Humanos , Feminino , Gravidez , Lactente , Pré-Escolar , Angola , Estado Nutricional , Suplementos Nutricionais , Desnutrição/prevenção & controle , Desnutrição/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
J Craniofac Surg ; 35(4): 1125-1128, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38656374

RESUMO

For many surgical procedures, enhanced recovery after surgery (ERAS) protocols have improved patient outcomes, particularly postoperative nausea and vomiting. The purpose of this study was to evaluate postoperative nausea following orthognathic surgery after the implementation of an ERAS protocol. This retrospective cohort study included patients between 12 and 35 years old who underwent orthognathic surgery at Boston Children's Hospital from April 2018 to December 2022. Patients with syndromes or a hospital stay greater than 48 hours were excluded from the study. The primary predictor was enrollment in our institutional ERAS protocol. The main outcome variable was postoperative nausea. Intraoperative and postoperative covariates were compared between groups using unpaired t tests and chi squared analysis. Univariate and multivariate regression models with 95% confidence intervals were performed to identify predictors for nausea. A P value<0.05 was considered significant. There were 128 patients (68 non-ERAS, 60 ERAS) included in this study (51.6% female, mean age 19.02±3.25 years). The ERAS group received less intraoperative fluid (937.0±462.3 versus 1583.6±847.6 mL, P ≤0.001) and experienced less postoperative nausea (38.3% versus 63.2%, P =0.005). Enhanced recovery after surgery status ( P =0.005) was a predictor for less postoperative nausea, whereas bilateral sagittal split osteotomy ( P =0.045) and length of stay ( P =0.007) were positive predictors for postoperative nausea in multivariate logistic regression analysis. Implementing an ERAS protocol for orthognathic surgery reduces postoperative nausea. Level of Evidence: Level III-therapeutic.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Procedimentos Cirúrgicos Ortognáticos , Náusea e Vômito Pós-Operatórios , Humanos , Feminino , Masculino , Náusea e Vômito Pós-Operatórios/prevenção & controle , Estudos Retrospectivos , Adolescente , Adulto , Adulto Jovem , Criança , Antieméticos/uso terapêutico , Protocolos Clínicos
13.
Environ Geochem Health ; 46(3): 87, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38367090

RESUMO

The ecotoxic effect of Zn species arising from the weathering of the marmatite-like sphalerite ((Fe, Zn)S) in Allium cepa systems was herein evaluated in calcareous soils and connected with its sulfide oxidation mechanism to determine the chemical speciation responsible of this outcome. Mineralogical analyses (X-ray diffraction patterns, Raman spectroscopy, scanning electron microscopy and atomic force microscopy), chemical study of leachates (total Fe, Zn, Cd, oxidation-reduction potential, pH, sulfates and total alkalinity) and electrochemical assessments (chronoamperometry, chronopotentiometry, cyclic voltammetry, and electrochemical impedance spectroscopy) were carried out using (Fe, Zn)S samples to elucidate interfacial mechanisms simulating calcareous soil conditions. Results indicate the formation of polysulfides (Sn2-), elemental sulfur (S0), siderite (FeCO3)-like, hematite (Fe2O3)-like with sorbed CO32- species, gunningite (ZnSO4·H2O)-like phase and smithsonite (ZnCO3)-like compounds in altered surface under calcareous conditions. However, the generation of gunningite (ZnSO4·H2O)-like phase was predominant bulk-solution system. Quantification of damage rates ranges from 75 to 90% of bulb cells under non-carbonated conditions after 15-30 days, while 50-75% of damage level is determined under neutral-alkaline carbonated conditions. Damage ratios are 70.08 and 30.26 at the highest level, respectively. These findings revealed lower ecotoxic damage due to ZnCO3-like precipitation, indicating the effect of carbonates on Zn compounds during vegetable up-taking (exposure). Other environmental suggestions of the (Fe, Zn)S weathering and ecotoxic effects under calcareous soil conditions are discussed.


Assuntos
Cebolas , Poluentes do Solo , Compostos de Zinco , Solo/química , Sulfetos/química , Tempo (Meteorologia) , Poluentes do Solo/análise
14.
Evol Dev ; 25(2): 153-169, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36373204

RESUMO

Developing organisms are often exposed to fluctuating environments that destabilize tissue-scale processes and induce abnormal phenotypes. This might be common in species that lay eggs in the external environment and with little parental care, such as many reptiles. In turtles, morphological development has provided striking examples of abnormal phenotypic patterns, though the influence of the environment remains unclear. To this end, we compared fluctuating asymmetry, as a proxy for developmental instability, in turtle hatchlings incubated in controlled laboratory and unstable natural conditions. Wild and laboratory hatchlings featured similar proportions of supernumerary scales (scutes) on the dorsal shell (carapace). Such abnormal scutes likely elevated shape asymmetry, which was highest in natural nests. Moreover, we tested the hypothesis that hot and dry environments cause abnormal scute formation by subjecting eggs to a range of hydric and thermal laboratory incubation regimes. Shape asymmetry was similar in hatchlings incubated at five constant temperatures (26-30°C). A hot (30°C) and severely Dry substrate yielded smaller hatchlings but scutes were not overtly affected. Our study suggests that changing nest environments contribute to fluctuating asymmetry in egg-laying reptiles, while clarifying the conditions at which turtle shell development remains buffered from the external environment.


Assuntos
Tartarugas , Animais , Embrião não Mamífero , Exoesqueleto , Temperatura
15.
Diabetes Obes Metab ; 25(11): 3268-3278, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37493025

RESUMO

AIM: To investigate the use of synthetic preimplantation factor (sPIF) as a potential therapeutic tool for improving glucose-stimulated insulin secretion (GSIS), glucose tolerance and insulin sensitivity in the setting of diabetes. MATERIALS AND METHODS: We used a preclinical murine model of type 2 diabetes (T2D) induced by high-fat diet (HFD) feeding for 12 weeks. Saline or sPIF (1 mg/kg/day) was administered to mice by subcutaneously implanted osmotic mini-pumps for 25 days. Glucose tolerance, circulating insulin and C-peptide levels, and GSIS were assessed. In addition, ß-cells (Min-6) were used to test the effects of sPIF on GSIS and insulin-degrading enzyme (IDE) activity in vitro. The effect of sPIF on GSIS was also tested in human islets. RESULTS: GSIS was enhanced 2-fold by sPIF in human islets ex vivo. Furthermore, continuous administration of sPIF to HFD mice increased circulating levels of insulin and improved glucose tolerance, independently of hepatic insulin clearance. Of note, islets isolated from mice treated with sPIF exhibited restored ß-cell function. Finally, genetic (shRNA-IDE) or pharmacological (6bK) inactivation of IDE in Min-6 abolished sPIF-mediated effects on GSIS, showing that both the protein and its protease activity are required for its action. CONCLUSIONS: We conclude that sPIF is a promising secretagogue for the treatment of T2D.


Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Insulisina , Ilhotas Pancreáticas , Camundongos , Humanos , Animais , Secreção de Insulina , Insulisina/metabolismo , Insulisina/farmacologia , Camundongos Obesos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ilhotas Pancreáticas/metabolismo
16.
Int J Ment Health ; 52(3): 260-284, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38013979

RESUMO

We evaluate the effectiveness of psychological interventions for depression in people with NCDs in South Asia and explore the individual, organizational, and policy-level barriers and facilitators for the implementation and scaling up of these interventions. Eight databases (and local web pages) were searched in May 2022. We conducted random effects models to evaluate the pooled effect of psychological interventions on depression in people with NCDs. We extracted the individual, organizational, and policy level barriers and facilitators. We found five randomized control trials, nine qualitative studies, and 35 policy documents that fitted the inclusion criteria. The pooled standardized mean difference in depression comparing psychological interventions with usual care was -2.31 (95% CI, -4.16 to -0.45; p = .015, I2 = 96.0%). We found barriers and facilitators to intervention delivery, mental health appears in the policy agenda in Bangladesh and Pakistan. However, there is a lack of policies relating to training in mental health for NCD health providers and a lack of integration of mental health care with NCD care. All of the psychological interventions reported to be effective in treating depression in this population. There are important delivery and policy barriers to the implementation and scaling up of psychological interventions for people with NCDs.

17.
J Neurosci ; 41(45): 9431-9451, 2021 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-34607969

RESUMO

Pathologic tau modifications are characteristic of Alzheimer's disease and related dementias, but mechanisms of tau toxicity continue to be debated. Inherited mutations in tau cause early onset frontotemporal lobar dementias (FTLD-tau) and are commonly used to model mechanisms of tau toxicity in tauopathies. Previous work in the isolated squid axoplasm model demonstrated that several pathogenic forms of tau inhibit axonal transport through a mechanism involving activation of protein phosphatase 1 (PP1). Here, we determined that P301L and R5L FTLD mutant tau proteins elicit a toxic effect on axonal transport as monomeric proteins. We evaluated interactions of wild-type or mutant tau with specific PP1 isoforms (α, ß, and γ) to examine how the interaction contributes to this toxic effect using primary rat hippocampal neurons from both sexes. Pull-down and bioluminescence resonance energy transfer experiments revealed selective interactions of wild-type tau with PP1α and PP1γ isoforms, but not PP1ß, which were significantly increased by the P301L tau mutation. The results from proximity ligation assays confirmed the interaction in primary hippocampal neurons. Moreover, expression of FTLD-linked mutant tau in these neurons enhanced levels of active PP1, also increasing the pausing frequency of fluorescently labeled vesicles in both anterograde and retrograde directions. Knockdown of PP1γ, but not PP1α, rescued the cargo-pausing effects of P301L and R5L tau, a result replicated by deleting a phosphatase-activating domain in the amino terminus of P301L tau. These findings support a model of tau toxicity involving aberrant activation of a specific PP1γ-dependent pathway that disrupts axonal transport in neurons.SIGNIFICANCE STATEMENT Tau pathology is closely associated with neurodegeneration in Alzheimer's disease and other tauopathies, but the toxic mechanisms remain a debated topic. We previously proposed that pathologic tau forms induce dysfunction and degeneration through aberrant activation of a PP1-dependent pathway that disrupts axonal transport. Here, we show that tau directly interacts with specific PP1 isoforms, increasing levels of active PP1. Pathogenic tau mutations enhance this interaction, further increasing active PP1 levels and impairing axonal transport in isolated squid axoplasm and primary hippocampal neurons. Mutant-tau-mediated impairment of axonal transport was mediated by PP1γ and a phosphatase-activating domain located at the amino terminus of tau. This work has important implications for understanding and potentially mitigating tau-mediated neurotoxicity in tauopathies.


Assuntos
Transporte Axonal/efeitos dos fármacos , Demência Frontotemporal , Neurônios/metabolismo , Proteína Fosfatase 1/metabolismo , Proteínas tau/farmacologia , Animais , Células Cultivadas , Decapodiformes , Feminino , Hipocampo , Humanos , Masculino , Mutação , Neurônios/efeitos dos fármacos , Ratos , Proteínas tau/genética
18.
BMC Genomics ; 23(1): 424, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35672696

RESUMO

BACKGROUND: Feed efficiency (FE) related traits play a key role in the economy and sustainability of beef cattle production systems. The accurate knowledge of the physiologic background for FE-related traits can help the development of more efficient selection strategies for them. Hence, multi-trait weighted GWAS (MTwGWAS) and meta-analyze were used to find genomic regions associated with average daily gain (ADG), dry matter intake (DMI), feed conversion ratio (FCR), feed efficiency (FE), and residual feed intake (RFI). The FE-related traits and genomic information belong to two breeding programs that perform the FE test at different ages: post-weaning (1,024 animals IZ population) and post-yearling (918 animals for the QLT population). RESULTS: The meta-analyze MTwGWAS identified 14 genomic regions (-log10(p -value) > 5) regions mapped on BTA 1, 2, 3, 4, 7, 8, 11, 14, 15, 18, 21, and 29. These regions explained a large proportion of the total genetic variance for FE-related traits across-population ranging from 20% (FCR) to 36% (DMI) in the IZ population and from 22% (RFI) to 28% (ADG) in the QLT population. Relevant candidate genes within these regions (LIPE, LPL, IGF1R, IGF1, IGFBP5, IGF2, INS, INSR, LEPR, LEPROT, POMC, NPY, AGRP, TGFB1, GHSR, JAK1, LYN, MOS, PLAG1, CHCD7, LCAT, and PLA2G15) highlighted that the physiological mechanisms related to neuropeptides and the metabolic signals controlling the body's energy balance are responsible for leading to greater feed efficiency. Integrated meta-analysis results and functional pathway enrichment analysis highlighted the major effect of biological functions linked to energy, lipid metabolism, and hormone signaling that mediates the effects of peptide signals in the hypothalamus and whole-body energy homeostasis affecting the genetic control of FE-related traits in Nellore cattle. CONCLUSIONS: Genes and pathways associated with common signals for feed efficiency-related traits provide better knowledge about regions with biological relevance in physiological mechanisms associated with differences in energy metabolism and hypothalamus signaling. These pleiotropic regions would support the selection for feed efficiency-related traits, incorporating and pondering causal variations assigning prior weights in genomic selection approaches.


Assuntos
Ingestão de Alimentos , Estudo de Associação Genômica Ampla , Ração Animal/análise , Animais , Bovinos/genética , Ingestão de Alimentos/genética , Metabolismo Energético/genética , Genômica , Fenótipo
19.
J Virol ; 95(11)2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33658338

RESUMO

Infections of Kashmir bee virus (KBV) are lethal for honeybees and have been associated with colony collapse disorder. KBV and closely related viruses contribute to the ongoing decline in the number of honeybee colonies in North America, Europe, Australia, and other parts of the world. Despite the economic and ecological impact of KBV, its structure and infection process remain unknown. Here we present the structure of the virion of KBV determined to a resolution of 2.8 Å. We show that the exposure of KBV to acidic pH induces a reduction in inter-pentamer contacts within capsids and the reorganization of its RNA genome from a uniform distribution to regions of high and low density. Capsids of KBV crack into pieces at acidic pH, resulting in the formation of open particles lacking pentamers of capsid proteins. The large openings of capsids enable the rapid release of genomes and thus limit the probability of their degradation by RNases. The opening of capsids may be a shared mechanism for the genome release of viruses from the family Dicistroviridae ImportanceThe western honeybee (Apis mellifera) is indispensable for maintaining agricultural productivity as well as the abundance and diversity of wild flowering plants. However, bees suffer from environmental pollution, parasites, and pathogens, including viruses. Outbreaks of virus infections cause the deaths of individual honeybees as well as collapses of whole colonies. Kashmir bee virus has been associated with colony collapse disorder in the US, and no cure of the disease is currently available. Here we report the structure of an infectious particle of Kashmir bee virus and show how its protein capsid opens to release the genome. Our structural characterization of the infection process determined that therapeutic compounds stabilizing contacts between pentamers of capsid proteins could prevent the genome release of the virus.

20.
J Exp Zool B Mol Dev Evol ; 338(8): 447-459, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35604321

RESUMO

Studies of domesticated animals have greatly contributed to our understanding of avian embryology. Foundational questions in developmental biology were motivated by Aristotle's observations of chicken embryos. By the 19th century, the chicken embryo was at the center stage of developmental biology, but how closely does this model species mirror the ample taxonomic diversity that characterizes the avian tree of life? Here, we provide a brief overview of the taxonomic breadth of comparative embryological studies in birds. We particularly focused on staging tables and papers that attempted to document the timing of developmental transformations. We show that most of the current knowledge of avian embryology is based on Galliformes (chicken and quail) and Anseriformes (duck and goose). Nonetheless, data are available for some ecologically diverse avian subclades, including Struthioniformes (e.g., ostrich, emu) and Sphenisciformes (penguins). Thus far, there has only been a handful of descriptive embryological studies in the most speciose subclade of Aves, that is, the songbirds (Passeriniformes). Furthermore, we found that temporal variances for developmental events are generally uniform across a consensus chronological sequence for birds. Based on the available data, developmental trajectories for chicken and other model species appear to be highly similar. We discuss future avenues of research in comparative avian embryology in light of the currently available wealth of data on domesticated species and beyond.


Assuntos
Galinhas , Domesticação , Animais , Embrião de Galinha , Gansos
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