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1.
Appl Environ Microbiol ; 90(7): e0039424, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38916291

RESUMO

Microbial communities perform various functions, many of which contribute to ecosystem-level nutrient cycling via decomposition. Factors influencing leaf detrital decomposition are well understood in terrestrial and aquatic ecosystems, but much less is known about arthropod detrital inputs. Here, we sought to infer how differences in arthropod detritus affect microbial-driven decomposition and community function in a carnivorous pitcher plant, Sarracenia purpurea. Using sterile mesh bags filled with different types of sterile arthropod prey, we assessed if prey type influenced the rate of decomposition in pitcher plants over 7 weeks. Additionally, we measured microbial community composition and function, including hydrolytic enzyme activity and carbon substrate use. When comparing decomposition rates, we found that ant and beetle prey with higher exoskeleton content lost less mass compared with fly prey. We observed the highest protease activity in the fly treatment, which had the lowest exoskeleton content. Additionally, we saw differences in the pH of the pitcher fluid, driven by the ant treatment which had the lowest pH. According to our results from 16S rRNA gene metabarcoding, prey treatments with the highest bacterial amplicon sequence variant (ASV) richness (ant and beetle) were associated with prey that lost a lower proportion of mass over the 7 weeks. Overall, arthropod detritus provides unique nutrient sources to decomposer communities, with different prey influencing microbial hydrolytic enzyme activity and composition. IMPORTANCE: Microbial communities play pivotal roles in nutrient cycling via decomposition and nutrient transformation; however, it is often unclear how different substrates influence microbial activity and community composition. Our study highlights how different types of insects influence decomposition and, in turn, microbial composition and function. We use the aquatic pools found in a carnivorous pitcher plant as small, discrete ecosystems that we can manipulate and study independently. We find that some insect prey (flies) breaks down faster than others (beetles or ants) likely because flies contain more things that are easy for microbes to eat and derive essential nutrients from. This is also reflected in higher enzyme activity in the microbes decomposing the flies. Our work bridges a knowledge gap about how different substrates affect microbial decomposition, contributing to the broader understanding of ecosystem function in a nutrient cycling context.


Assuntos
Formigas , Microbiota , Sarraceniaceae , Animais , Sarraceniaceae/microbiologia , Sarraceniaceae/metabolismo , Formigas/microbiologia , Artrópodes , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Bactérias/isolamento & purificação , Besouros/microbiologia , RNA Ribossômico 16S/genética , Ecossistema , Cadeia Alimentar
2.
Sci Rep ; 14(1): 12927, 2024 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839833

RESUMO

We aimed to characterize the cognitive profile of post-acute COVID-19 syndrome (PACS) patients with cognitive complaints, exploring the influence of biological and psychological factors. Participants with confirmed SARS-CoV-2 infection and cognitive complaints ≥ 8 weeks post-acute phase were included. A comprehensive neuropsychological battery (NPS) and health questionnaires were administered at inclusion and at 1, 3 and 6 months. Blood samples were collected at each visit, MRI scan at baseline and at 6 months, and, optionally, cerebrospinal fluid. Cognitive features were analyzed in relation to clinical, neuroimaging, and biochemical markers at inclusion and follow-up. Forty-nine participants, with a mean time from symptom onset of 10.4 months, showed attention-executive function (69%) and verbal memory (39%) impairment. Apathy (64%), moderate-severe anxiety (57%), and severe fatigue (35%) were prevalent. Visual memory (8%) correlated with total gray matter (GM) and subcortical GM volume. Neuronal damage and inflammation markers were within normal limits. Over time, cognitive test scores, depression, apathy, anxiety scores, MRI indexes, and fluid biomarkers remained stable, although fewer participants (50% vs. 75.5%; p = 0.012) exhibited abnormal cognitive evaluations at follow-up. Altered attention/executive and verbal memory, common in PACS, persisted in most subjects without association with structural abnormalities, elevated cytokines, or neuronal damage markers.


Assuntos
Biomarcadores , COVID-19 , Cognição , Imageamento por Ressonância Magnética , Neuroimagem , Testes Neuropsicológicos , Síndrome de COVID-19 Pós-Aguda , Humanos , Masculino , COVID-19/psicologia , COVID-19/diagnóstico por imagem , COVID-19/complicações , Feminino , Biomarcadores/sangue , Pessoa de Meia-Idade , Neuroimagem/métodos , Adulto , Imageamento por Ressonância Magnética/métodos , SARS-CoV-2/isolamento & purificação , Idoso , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/sangue , Ansiedade
3.
Environ Microbiol ; 26(5): e16631, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38757479

RESUMO

Peatlands, one of the oldest ecosystems, globally store significant amounts of carbon and freshwater. However, they are under severe threat from human activities, leading to changes in water, nutrient and temperature regimes in these delicate systems. Such shifts can trigger a substantial carbon flux into the atmosphere and diminish the water-holding capacity of peatlands. Microbes associated with moss in peatlands play a crucial role in providing these ecosystem services, which are at risk due to global change. Therefore, understanding the factors influencing microbial composition and function is vital. Our study focused on five peatlands along an altitudinal gradient in Switzerland, where we sampled moss on hummocks containing Sarracenia purpurea. Structural equation modelling revealed that habitat condition was the primary predictor of community structure and directly influenced other environmental variables. Interestingly, the microbial composition was not linked to the local moss species identity. Instead, microbial communities varied significantly between sites due to differences in acidity levels and nitrogen availability. This finding was also mirrored in a co-occurrence network analysis, which displayed a distinct distribution of indicator species for acidity and nitrogen availability. Therefore, peatland conservation should take into account the critical habitat characteristics of moss-associated microbial communities.


Assuntos
Bactérias , Briófitas , Ecossistema , Microbiota , Suíça , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Briófitas/microbiologia , Solo/química , Microbiologia do Solo , Nitrogênio/metabolismo , Nitrogênio/análise , Áreas Alagadas , Biodiversidade
4.
Diabetes ; 73(3): 412-425, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38015721

RESUMO

Glucagon is generally defined as a counterregulatory hormone with a primary role to raise blood glucose concentrations by increasing endogenous glucose production (EGP) in response to hypoglycemia. However, glucagon has long been known to stimulate insulin release, and recent preclinical findings have supported a paracrine action of glucagon directly on islet ß-cells that augments their secretion. In mice, the insulinotropic effect of glucagon is glucose dependent and not present during basal euglycemia. To test the hypothesis that the relative effects of glucagon on hepatic and islet function also vary with blood glucose, a group of healthy subjects received glucagon (100 ng/kg) during fasting glycemia or experimental hyperglycemia (∼150 mg/dL) on 2 separate days. During fasting euglycemia, administration of glucagon caused blood glucose to rise due to increased EGP, with a delayed increase of insulin secretion. When given during experimental hyperglycemia, glucagon caused a rapid, threefold increase in insulin secretion, as well as a more gradual increase in EGP. Under both conditions, insulin clearance was decreased in response to glucagon infusion. The insulinotropic action of glucagon, which is proportional to the degree of blood glucose elevation, suggests distinct physiologic roles in the fasting and prandial states.


Assuntos
Glucagon , Hiperglicemia , Humanos , Camundongos , Animais , Glucagon/metabolismo , Insulina/metabolismo , Glicemia , Secreção de Insulina , Glucose/farmacologia , Insulina Regular Humana
5.
Equine Vet J ; 55(1): 33-41, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35298851

RESUMO

BACKGROUND: Plantar osteochondral fragments (POF) are common but their effect on joint health of young Standardbreds in race training is largely unknown. OBJECTIVES: Evaluate the inflammatory effects of POF in metatarsophalangeal joints of young Standardbreds as a step towards developing evidence-based recommendations for surgical removal. STUDY DESIGN: Cohort study. METHODS: Forty-nine Standardbred horses (age 11-33 months) presented for surgical removal of POF from 56 metatarsophalangeal joints. Synovial tissue collected at arthroscopy was subjected to histopathology. IL-1ß, TNF-α, and PGE-2 were measured in synovial fluid using ELISA. Digital arthroscopy images were scored for inflammation. Racing performance data were retrieved from a public database. RESULTS: Median time in race training prior to surgery was 8 weeks (IQR 4-12; range 0-40). There was minimal evidence of synovial inflammation as assessed by histopathology (median total score 2/20, IQR 0-2, range 0-5) or arthroscopy (median average total score 2.67/15, IQR 1.79-4, range 0-8.83). IL-1ß was not detected in any sample. TNF-α (median 0 pg/mL, IQR 0-0) and PGE-2 (median 56.6 pg/mL, IRQ 40.5-99.8) were measured at low levels. Weeks in training prior to surgery was associated with the number of starts in the season after surgery (incidence rate ratio 1.02, 95% CI 1.00, 1.04, P = .03). MAIN LIMITATIONS: Small sample size from a single breed with a relatively short training time prior to surgery. CONCLUSIONS: There was minimal evidence of synovial inflammation in the metatarsophalangeal joints in this population of young Standardbred horses with POF. It is possible that POF may result in a different inflammatory response than other fragments because they are generally well-embedded in situ. These findings suggest that, in Standardbreds, race training can commence several weeks prior to surgical removal of POF with minimal detrimental effects on joint health, although further investigation of long-term effects of POF on joint health is warranted.


INTRODUCTION/CONTEXTE: Les fragments plantaires ostéochondraux (POF) sont communs mais leur effet au niveau sur la santé articulaire chez les jeunes Standardbreds en entraînement de course demeure inconnu. OBJECTIFS: Évaluer les effets inflammatoires des POF des articulations métatarsophalangiennes chez les jeunes Standardbreds dans le but d'ajouter à l'évidence disponible concernant les recommandations pour leur retrait chirurgical. TYPE D'ÉTUDE: Étude de cohorte descriptive clinique. MÉTHODES: Quarante-neuf chevaux Standardbreds (âgés 11-33 mois) ont été présentés pour retrait chirurgical de POF en provenance de 56 articulations métatarsophalangiennes. Un échantillon de membrane synoviale recueilli au moment de l'arthroscopie a été soumis en histopathologie. IL-1ß, TNF-α, and PGE-2 ont été mesurés dans le liquide synovial par ELISA. Les images digitales d'arthroscopie ont été évaluées pour la présence d'inflammation. Les données de performance en course ont été retrouvées via une base de données publique. RÉSULTATS: Le temps médian de retour à l'entraînement suivant la procédure chirurgicale était de 8 semaines (IQR 4-12; étendu 0-40). Peu d'inflammation synoviale a été détectée en histopathologie (score médian total 2/20, IQR 0-2, étendu 0-5) ou arthroscopie (score médian total 2.67/15, IQR 1.79-4, étendu 0-8.83). IL-1ß a été détectée dans aucun échantillon. TNF-α (médiane 0 pg/mL, IQR 0-0) et PGE-2 (médiane 56.6 pg/mL, IQR 40.5-99.8) ont été détectés en faible quantité. Le nombre de semaines à l'entraînement avant la procédure chirurgicale était associé au nombre de départs pour la saison suivant la chirurgie (IRR 1.02, P = 0.03). LIMITES PRINCIPALES: Petite taille d'échantillon provenant d'une seule race de chevaux ayant une période d'entraînement relativement courte avant la procédure chirurgicale. CONCLUSIONS: Il y a peu d'évidence d'inflammation synoviale dans les articulations métatarsophalangiennes chez cette population de jeunes chevaux Standardbreds ayant des POF. Il est possible que les POF entraînent une réponse inflammatoire différente des autres fragments puisqu'ils sont généralement bien attachés dans l'articulation. Ces résultats suggèrent que chez les Standardbreds, l'entraînement de course puisse commencer plusieurs semaines avant le retrait chirurgical des POF en ayant des effets délétères minimaux pour la santé articulaire. Ceci dit, davantage de recherche est nécessaire pour établir les effets à long-terme de ces POF sur la santé articulaire.


Assuntos
Doenças dos Cavalos , Cavalos , Animais , Doenças dos Cavalos/patologia , Estudos de Coortes , Fator de Necrose Tumoral alfa , Artroscopia/veterinária , Artroscopia/efeitos adversos , Inflamação/veterinária , Prostaglandinas E
6.
Vet Surg ; 51(7): 1106-1110, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35815735

RESUMO

OBJECTIVE: To assess the effect of repeated freezing and thawing on the suture pull-out strength in arytenoid and cricoid cartilages subjected to the laryngoplasty (LP) procedure. STUDY DESIGN: Ex vivo experimental study. SAMPLE POPULATION: Ten grossly normal equine cadaveric larynges. METHODS: Bilateral LP constructs were created using a standard LP technique. One hemilarynx was randomly allocated to the single freeze and thaw group and the other allocated to the repeated freeze and thaw (3 complete cycles) group. The suture ends of each LP construct were attached to a load frame and subjected to monotonic loading until construct failure. Mean load (N) and displacement (mm) at LP construct failure were compared between groups. RESULTS: All LP constructs failed by suture pull through the arytenoid cartilage. The mean load at failure was similar between groups (118.9 ± 25.5 N in the single freeze and thaw group and 113.4 ± 20.5 N in the repeated freeze and thaw group, P = .62). The mean displacement at failure was similar between groups (54.4 ± 15.1 mm in the single freeze and thaw group and 54.4 ± 15.4 mm in the repeated freeze and thaw group, P = .99). CONCLUSION: Repeated freezing and thawing did not affect the suture pullout strength of the arytenoid and cricoid cartilages. CLINICAL SIGNIFICANCE: Laryngeal specimens that have been subjected to repeated freezing and thawing can be utilized in the experimental evaluation of LP procedures because there is no alteration of the suture pull-out strength of the relevant cartilages.


Assuntos
Congelamento , Laringoplastia , Suturas , Animais , Cartilagem Aritenoide/cirurgia , Cadáver , Cartilagem Cricoide/cirurgia , Cavalos/cirurgia , Laringoplastia/métodos , Laringoplastia/veterinária , Suturas/veterinária
7.
J Clin Endocrinol Metab ; 107(9): 2500-2510, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-35775723

RESUMO

CONTEXT: Glucagon-like peptide 1 (GLP-1), an insulinotropic peptide released into the circulation from intestinal enteroendocrine cells, is considered a hormonal mediator of insulin secretion. However, the physiological actions of circulating GLP-1 have been questioned because of the short half-life of the active peptide. Moreover, there is mounting evidence for localized, intra-islet mediation of GLP-1 receptor (GLP-1r) signaling including a role for islet dipeptidyl-peptidase 4 (DPP4). OBJECTIVE: To determine whether GLP-1r signaling contributes to insulin secretion in the absence of enteral stimulation and increased plasma levels, and whether this is affected by DPP4. METHODS: Single-site study conducted at an academic medical center of 20 nondiabetic subjects and 13 subjects with type 2 diabetes. This was a crossover study in which subjects received either a DPP4 inhibitor (DPP4i; sitagliptin) or placebo on 2 separate days. On each day they received a bolus of intravenous (IV) arginine during sequential 60-minute infusions of the GLP-1r blocker exendin[9-39] (Ex-9) and saline. The main outcome measures were arginine-stimulated secretion of C-Peptide (C-PArg) and insulin (InsArg). RESULTS: Plasma GLP-1 remained at fasting levels throughout the experiments and IV arginine stimulated both α- and ß-cell secretion in all subjects. Ex-9 infusion reduced C-PArg in both the diabetic and nondiabetic groups by ~14% (P < .03 for both groups). Sitagliptin lowered baseline glycemia but did not affect the primary measures of insulin secretion. However, a significant interaction between sitagliptin and Ex-9 suggested more GLP-1r activation with DPP4i treatment in subjects with diabetes. CONCLUSION: GLP-1r activation contributes to ß-cell secretion in diabetic and nondiabetic people during α-cell activation, but in the absence of increased circulating GLP-1. These results are compatible with regulation of ß-cells by paracrine signals from α-cells. This process may be affected by DPP4 inhibition.


Assuntos
Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Arginina/uso terapêutico , Estudos Cross-Over , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dipeptidil Peptidase 4/metabolismo , Jejum , Peptídeo 1 Semelhante ao Glucagon , Humanos , Insulina/metabolismo , Secreção de Insulina , Fosfato de Sitagliptina/farmacologia , Fosfato de Sitagliptina/uso terapêutico
9.
mSystems ; 6(4): e0053021, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34427534

RESUMO

Microbiomes play essential roles in the health and function of animal and plant hosts and drive nutrient cycling across ecosystems. Integrating novel trait-based approaches with ecological theory can facilitate the prediction of microbial functional traits important for ecosystem functioning and health. In particular, the yield-acquisition-stress (Y-A-S) framework considers dominant microbial life history strategies across gradients of resource availability and stress. However, microbiomes are dynamic, and spatial and temporal shifts in taxonomic and trait composition can affect ecosystem functions. We posit that extending the Y-A-S framework to microbiomes during succession and across biogeographic gradients can lead to generalizable rules for how microbiomes and their functions respond to resources and stress across space, time, and diverse ecosystems. We demonstrate the potential of this framework by applying it to the microbiomes hosted by the carnivorous pitcher plant Sarracenia purpurea, which have clear successional trajectories and are distributed across a broad climatic gradient.

10.
J Vet Diagn Invest ; 33(5): 979-983, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34247559

RESUMO

An 8-y-old jenny was presented because of anorexia and mild depression. The jenny had weaned her colt 10 d before the admission. Upon arrival at the University of Illinois Veterinary Teaching Hospital, the heart rate was elevated, and the right udder was painful and swollen on palpation. Milk stripping of the affected side revealed purulent content; the contralateral udder had normal-appearing milk. Cytology of mammary gland secretions from the affected side revealed a large number of hypersegmented reactive neutrophils with phagocytized bacteria. Complete blood count, serum chemistry, and fibrinogen were within normal limits. A diagnosis of clinical mastitis was made, and the jenny was started on a 5-d course of broad-spectrum antibiotics, a non-steroidal anti-inflammatory, hydrotherapy, and milk stripping. Clinical signs reduced over time, and the cure was attained by 96 h post-admission. Aerobic culture and subsequent MALDI-TOF MS analysis identified a bacterium of the Streptococcus genus but not the species. Whole-genome analysis was performed, and 16S rDNA sequencing and analysis determined that our isolate 20-37394 clustered with 2 other Streptococcus strains (27284-01 and 28462). Single-nucleotide variations and phylogenetic tree analysis revealed that Streptococcus 20-37394 had 96.8% and 94.9% identities to Streptococcus strains 27284-01 and 28462, respectively; therefore, the bacteria isolated in our case was deemed as a new Streptococcus species.


Assuntos
Mastite , Infecções Estreptocócicas , Streptococcus , Animais , Equidae , Feminino , Cavalos , Hospitais Veterinários , Hospitais de Ensino , Masculino , Glândulas Mamárias Animais , Mastite/veterinária , Leite , Filogenia , Gravidez , Infecções Estreptocócicas/veterinária , Streptococcus/isolamento & purificação
11.
Vet Surg ; 50(7): 1409-1417, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34309058

RESUMO

OBJECTIVE: To evaluate the airway mechanics of modified toggle LP constructs in an airflow chamber model and compare these to the airway mechanics of standard LP constructs. STUDY DESIGN: Ex-vivo experimental study. SAMPLE POPULATION: Fifty-one equine cadaveric larynges. METHODS: Bilateral LP constructs were performed using a modified toggle (n = 23) or a standard (n = 21) LP technique. Constructs were tested in an airflow model before and after cyclic loading which was designed to mimic postoperative swallowing. The cross-sectional area (CSA), peak translaryngeal airflow (L/s), and impedance (cmH2 0/L/s) were determined and compared between LP constructs before and after cycling. RESULTS: The mean CSA of the rima glottidis of the modified toggle LP constructs was 15.2 ± 2.6 cm2 before and 14.7 ± 2.6 cm2 after cyclic loading, and the mean CSA of the rima glottidis of the standard LP constructs was 16.4 ± 2.9 cm2 before and 15.7 ± 2.8 cm2 after cyclic loading. The modified toggle LP constructs had similar peak translaryngeal impedance before and after cyclic loading (p = .13); however, the standard LP constructs had higher peak translaryngeal impedance after cyclic loading (p = .02). CONCLUSION: The modified toggle and standard LP constructs had comparable airway mechanics in an ex-vivo model. CLINICAL SIGNIFICANCE: Further investigation is warranted to determine the extent to which the modified toggle LP technique restores normal airway function in horses with RLN.


Assuntos
Laringoplastia , Laringe , Animais , Glote , Cavalos , Laringoplastia/veterinária , Vácuo
12.
Nat Commun ; 12(1): 2353, 2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33883555

RESUMO

One key hypothesis explaining the fate of exotic species introductions posits that the establishment of a self-sustaining population in the invaded range can only succeed within conditions matching the native climatic niche. Yet, this hypothesis remains untested for individual release events. Using a dataset of 979 introductions of 173 mammal species worldwide, we show that climate-matching to the realized native climatic niche, measured by a new Niche Margin Index (NMI), is a stronger predictor of establishment success than most previously tested life-history attributes and historical factors. Contrary to traditional climatic suitability metrics derived from species distribution models, NMI is based on niche margins and provides a measure of how distant a site is inside or, importantly, outside the niche. Besides many applications in research in ecology and evolution, NMI as a measure of native climatic niche-matching in risk assessments could improve efforts to prevent invasions and avoid costly eradications.


Assuntos
Clima , Espécies Introduzidas , Mamíferos , Modelos Biológicos , Animais , Teorema de Bayes , Bases de Dados Factuais , Ecossistema , Dinâmica Populacional
13.
Cell Metab ; 33(4): 804-817.e5, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33321098

RESUMO

Metabolic fuels regulate insulin secretion by generating second messengers that drive insulin granule exocytosis, but the biochemical pathways involved are incompletely understood. Here we demonstrate that stimulation of rat insulinoma cells or primary rat islets with glucose or glutamine + 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (Gln + BCH) induces reductive, "counter-clockwise" tricarboxylic acid (TCA) cycle flux of glutamine to citrate. Molecular or pharmacologic suppression of isocitrate dehydrogenase-2 (IDH2), which catalyzes reductive carboxylation of 2-ketoglutarate to isocitrate, results in impairment of glucose- and Gln + BCH-stimulated reductive TCA cycle flux, lowering of NADPH levels, and inhibition of insulin secretion. Pharmacologic suppression of IDH2 also inhibits insulin secretion in living mice. Reductive TCA cycle flux has been proposed as a mechanism for generation of biomass in cancer cells. Here we demonstrate that reductive TCA cycle flux also produces stimulus-secretion coupling factors that regulate insulin secretion, including in non-dividing cells.


Assuntos
Ciclo do Ácido Cítrico/fisiologia , Glucose/farmacologia , Glutamina/farmacologia , Secreção de Insulina/efeitos dos fármacos , Animais , Células Cultivadas , Glucose/metabolismo , Glutamina/metabolismo , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/metabolismo , Isocitrato Desidrogenase/antagonistas & inibidores , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Lipogênese/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxirredução , Compostos de Fenilureia/farmacologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Wistar , Sulfonamidas/farmacologia , Sumoilação/efeitos dos fármacos
14.
J Biol Chem ; 295(33): 11529-11541, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32554468

RESUMO

The insulinotropic actions of glucagon-like peptide 1 receptor (GLP-1R) in ß-cells have made it a useful target to manage type 2 diabetes. Metabolic stress reduces ß-cell sensitivity to GLP-1, yet the underlying mechanisms are unknown. We hypothesized that Glp1r expression is heterogeneous among ß-cells and that metabolic stress decreases the number of GLP-1R-positive ß-cells. Here, analyses of publicly available single-cell RNA-Seq sequencing (scRNASeq) data from mouse and human ß-cells indicated that significant populations of ß-cells do not express the Glp1r gene, supporting heterogeneous GLP-1R expression. To check these results, we used complementary approaches employing FACS coupled with quantitative RT-PCR, a validated GLP-1R antibody, and flow cytometry to quantify GLP-1R promoter activity, gene expression, and protein expression in mouse α-, ß-, and δ-cells. Experiments with Glp1r reporter mice and a validated GLP-1R antibody indicated that >90% of the ß-cells are GLP-1R positive, contradicting the findings with the scRNASeq data. α-cells did not express Glp1r mRNA and δ-cells expressed Glp1r mRNA but not protein. We also examined the expression patterns of GLP-1R in mouse models of metabolic stress. Multiparous female mice had significantly decreased ß-cell Glp1r expression, but no reduction in GLP-1R protein levels or GLP-1R-mediated insulin secretion. These findings suggest caution in interpreting the results of scRNASeq for low-abundance transcripts such as the incretin receptors and indicate that GLP-1R is widely expressed in ß-cells, absent in α-cells, and expressed at the mRNA, but not protein, level in δ-cells.


Assuntos
Receptor do Peptídeo Semelhante ao Glucagon 1/genética , Células Secretoras de Insulina/metabolismo , Animais , Células Cultivadas , Expressão Gênica , Receptor do Peptídeo Semelhante ao Glucagon 1/análise , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Análise de Célula Única
15.
Sci Rep ; 9(1): 18286, 2019 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-31797904

RESUMO

Dispersal is key for maintaining biodiversity at local- and regional scales in metacommunities. However, little is known about the combined effects of dispersal and climate change on biodiversity. Theory predicts that alpha-diversity is maximized at intermediate dispersal rates, resulting in a hump-shaped diversity-dispersal relationship. This relationship is predicted to flatten when competition increases. We anticipate that this same flattening will occur with increased temperature because, in the rising part of the temperature performance curve, interspecific competition is predicted to increase. We explored this question using aquatic communities of Sarracenia purpurea from early- and late-successional stages, in which we simulated four levels of dispersal and four temperature scenarios. With increased dispersal, the hump shape was observed consistently in late successional communities, but only in higher temperature treatments in early succession. Increased temperature did not flatten the hump-shape relationship, but decreased the level of alpha- and gamma-diversity. Interestingly, higher temperatures negatively impacted small-bodied species. These metacommunity-level extinctions likely relaxed interspecific competition, which could explain the absence of flattening of the diversity-dispersal relationship. Our findings suggest that climate change will cause extinctions both at local- and global- scales and emphasize the importance of intermediate levels of dispersal as an insurance for local diversity.


Assuntos
Biodiversidade , Microbiota , Sarraceniaceae/microbiologia , Mudança Climática , Dinâmica Populacional , Temperatura
16.
Diabetes ; 68(9): 1795-1805, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31201280

RESUMO

Exogenous ghrelin reduces glucose-stimulated insulin secretion and endogenous ghrelin protects against hypoglycemia during starvation. Islet ε-cells produce ghrelin and δ-cells express growth hormone secretagogue receptor (GHSR), suggesting the possibility of a paracrine mechanism for islet ghrelin to reach high local concentrations and affect insulin secretion. GHSR has high constitutive activity and may act independently of ghrelin. The objective in this study was to determine whether an intraislet ghrelin-GHSR axis modulates insulin secretion and glucose metabolism using mouse models lacking ghrelin (Ghrl-/- ) or GHSR (Ghsr-/- ). Ghsr-/- and Ghsr+/+ mice had comparable islet ghrelin concentrations. Exogenous ghrelin decreased insulin secretion in perifused isolated islets in a GHSR-dependent manner. Islets isolated from Ghrl-/- or Ghsr-/- mice did not differ from controls in glucose-, alanine-, or GLP-1-stimulated insulin secretion during perifusion. Consistent with this finding, Ghrl-/- and Ghsr-/- male mice studied after either 6 or 16 h of fasting had blood glucose concentrations comparable with those of controls following intraperitoneal glucose, or insulin tolerance tests, or after mixed nutrient meals. Collectively, our data provide strong evidence against a paracrine ghrelin-GHSR axis mediating insulin secretion or glucose tolerance in lean, chow-fed adult mice.


Assuntos
Glicemia/metabolismo , Grelina/metabolismo , Secreção de Insulina/fisiologia , Ilhotas Pancreáticas/metabolismo , Receptores de Grelina/metabolismo , Transdução de Sinais/fisiologia , Animais , Feminino , Grelina/sangue , Grelina/genética , Insulina/metabolismo , Masculino , Camundongos , Camundongos Knockout , Receptores de Grelina/genética
17.
Vet Surg ; 48(4): 473-480, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30883829

RESUMO

OBJECTIVE: To report our experience with partial arytenoidectomy in sedated standing horses. STUDY DESIGN: Retrospective study. ANIMALS: Fourteen client-owned adult horses. METHODS: The medical records (2013-2017) of horses treated with unilateral partial arytenoidectomy while standing and sedated were reviewed. Demographics, endoscopic findings, previous treatments, and outcome after surgery were investigated and recorded. RESULTS: Thirteen horses had unilateral left-sided recurrent laryngeal neuropathy (RLN) and 1 horse had bilateral RLN. Five horses had a previous failed prosthetic laryngoplasty. Left-sided partial arytenoidectomy without mucosal closure was successfully completed in all horses under sedation and local anesthesia. Report of long-term outcome was obtained via telephone conversations for 12 horses, of which 9 also had an endoscopic reevaluation performed; 3 horses had granulomas at the surgical site, of which 2 eventually required a permanent tracheostomy. Nine horses returned to athletic use without respiratory noise, 2 horses returned to athletic use with noise during exercise that was reduced compared with preoperative levels, and 1 horse continued to be used as a broodmare. CONCLUSION: Partial arytenoidectomy in standing horses was achieved with adequate sedation and local anesthesia. CLINICAL SIGNIFICANCE: Partial arytenoidectomy on standing sedated horses could be considered as an alternative to eliminate the risks associated with general anesthesia.


Assuntos
Cartilagem Aritenoide/cirurgia , Doenças dos Cavalos/cirurgia , Laringoplastia/veterinária , Anestesia Geral , Animais , Endoscopia , Feminino , Cavalos , Laringectomia/veterinária , Laringoplastia/métodos , Laringe/cirurgia , Masculino , Estudos Retrospectivos
18.
J Neuroendocrinol ; 31(7): e12705, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30849212

RESUMO

Ghrelin and its receptor, the growth hormone secretagogue receptor 1a (GHSR1a), are implicated in the regulation of glucose metabolism via direct actions in the pancreatic islet, as well as peripheral insulin-sensitive tissues and the brain. Although many studies have explored the role of ghrelin in glucose tolerance and insulin secretion, a complete mechanistic understanding remains to be clarified. This review highlights the local expression and function of ghrelin and GHSR1a in pancreatic islets and how this axis may modulate insulin secretion from pancreatic ß-cells. Additionally, we discuss the effect of ghrelin on in vivo glucose metabolism in rodents and humans, as well as the metabolic circumstances under which the action of ghrelin may predominate.


Assuntos
Grelina/metabolismo , Glucose/metabolismo , Insulina/metabolismo , Receptores de Grelina/metabolismo , Animais , Encéfalo/metabolismo , Metabolismo Energético , Humanos , Secreção de Insulina , Ilhotas Pancreáticas/metabolismo
19.
Am Nat ; 193(2): 227-239, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30720361

RESUMO

Gaining knowledge of how ecosystems provide essential services to humans is of primary importance, especially with the current threat of climate change. Yet little is known about how increased temperature will impact the biodiversity-ecosystem functioning (BEF) relationship. We tackled this subject theoretically and experimentally. We developed a BEF theory based on mechanistic population dynamic models, which allows the inclusion of the effect of temperature. Using experimentally established relationships between attack rate and temperature, the model predicts that temperature increase will intensify competition, and consequently the BEF relationship will flatten or even become negative. We conducted a laboratory experiment with natural microbial microcosms, and the results were in agreement with the model predictions. The experimental results also revealed that an increase in both temperature average and variation had a more intense effect than an increase in temperature average alone. Our results indicate that under climate change, high diversity may not guarantee high ecosystem functioning.


Assuntos
Mudança Climática , Ecossistema , Modelos Biológicos , Sarraceniaceae , Temperatura
20.
Endocrinology ; 159(12): 4023-4032, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30380031

RESUMO

The ghrelin-producing ε cell represents the fifth endocrine cell type in human pancreatic islets. The abundance of ε cells in adult pancreas is extremely low, which has hampered the investigation on the molecular pathways regulating the development and the function of this cell type. In this study, we explored the molecular features defining the function of pancreatic ε cells isolated from adult nondiabetic donors using single-cell RNA sequencing technology. We focus on transcription factors, cell surface receptors, and genes involved in metabolic pathways that contribute to regulation of cellular function. Furthermore, the genes that separate ε cells from the other islet endocrine cell types are presented. This study expands prior knowledge about the genes important for ε cell functioning during development and provides a resource to interrogate the transcriptome of this rare human islet cell type.


Assuntos
Grelina/metabolismo , Pâncreas/citologia , Pâncreas/metabolismo , Transcriptoma , Adulto , Contagem de Células , Separação Celular , Células Cultivadas , Perfilação da Expressão Gênica , Humanos , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/metabolismo , Análise em Microsséries , Transdução de Sinais/genética
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