Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 20
Filtrar
2.
Curr Biol ; 34(12): 2623-2632.e5, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38823383

RESUMO

The sense of taste is essential for survival, as it allows animals to distinguish between foods that are nutritious from those that are toxic. However, innate responses to different tastants can be modulated or even reversed under pathological conditions. Here, we examined whether and how the internal status of an animal impacts taste valence by using Drosophila models of hyperproliferation in the gut. In all three models where we expressed proliferation-inducing transgenes in intestinal stem cells (ISCs), hyperproliferation of ISCs caused a tumor-like phenotype in the gut. While tumor-bearing flies had no deficiency in overall food intake, strikingly, they exhibited an increased gustatory preference for aristolochic acid (ARI), which is a bitter and normally aversive plant-derived chemical. ARI had anti-tumor effects in all three of our gut hyperproliferation models. For other aversive chemicals we tested that are bitter but do not have anti-tumor effects, gut tumors did not affect avoidance behaviors. We demonstrated that bitter-sensing gustatory receptor neurons (GRNs) in tumor-bearing flies respond normally to ARI. Therefore, the internal pathology of gut hyperproliferation affects neural circuits that determine taste valence postsynaptic to GRNs rather than altering taste identity by GRNs. Overall, our data suggest that increased consumption of ARI may represent an attempt at self-medication. Finally, although ARI's potential use as a chemotherapeutic agent is limited by its known toxicity in the liver and kidney, our findings suggest that tumor-bearing flies might be a useful animal model to screen for novel anti-tumor drugs.


Assuntos
Drosophila melanogaster , Paladar , Animais , Paladar/fisiologia , Drosophila melanogaster/fisiologia , Drosophila melanogaster/efeitos dos fármacos , Ácidos Aristolóquicos , Neoplasias Intestinais/tratamento farmacológico , Neoplasias Intestinais/patologia
3.
J Health Polit Policy Law ; 48(4): 569-592, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36693180

RESUMO

On June 24, 2022, the US Supreme Court decided in Dobbs vs. Jackson Women's Health Organization (597 U.S. (2022)) to overturn the constitutional right to abortion, a seismic shift in abortion policy that makes the states key battlegrounds in fights over abortion and broader reproductive rights. This article focuses on the role of state supreme courts in setting state abortion policies. Using an original data set of state court decisions surrounding abortion from the past 20 years, the authors investigate how two overarching factors affect state supreme court decision-making on abortion. First, they track how states' political environments affect the decisions courts make about access to abortion. Second, the authors consider the scope of the abortion policy considered by the courts. The authors find that the partisan makeup of state legislatures does not influence the direction of state supreme courts' rulings on abortion issues, but it does affect the scope of abortion regulation being considered by the courts. Additionally, they find that elected judges tend to be more responsive to constituent preferences when ruling on abortion policies. Overall, these findings illustrate the multifaceted dynamics involved in state supreme courts' rulings on abortion.


Assuntos
Aborto Induzido , Decisões da Suprema Corte , Gravidez , Feminino , Humanos , Estados Unidos , Aborto Legal , Órgãos Governamentais , Políticas
4.
Ir Vet J ; 74(1): 27, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663462

RESUMO

BACKGROUND: Warmblood Fragile Foal Syndrome (WFFS) is an autosomal recessive disorder caused by a mutation in the procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) gene. Homozygosity for the mutation results in defective collagen synthesis which clinically manifests as the birth of non viable or still born foals with abnormally fragile skin. While the mutation has been identified in non Warmblood breeds including the Thoroughbred, to date all homozygous clinically affected cases reported in the scientific literature are Warmblood foals. The objective of this study was to investigate the carrier frequency of the mutation in the Thoroughbred and sport horse populations in Ireland. METHODS: A test was developed at the UCD School of Veterinary Medicine using real-time PCR to amplify the PLOD1 gene c.2032G > A variant. A subset of the samples was also submitted to an external laboratory with a licensed commercial WFFS genetic test. RESULTS: Warmblood Fragile Foal Syndrome genotyping was performed on hair samples from 469 horses representing 6 different breeds. Six of 303 (1.98%) sport horses tested and three of 109 (2.75%) Thoroughbreds tested were heterozygous for the WFFS polymorphism (N/WFFS). The WFFS polymorphism was not identified in the Standardbred, Cob, Connemara, or other pony breeds. CONCLUSIONS: The study identified a low frequency of the WFFS causative mutation in sport horses and Thoroughbreds in Ireland, highlighting the importance of WFFS genetic testing in order to identify phenotypically normal heterozygous carriers and to prevent the birth of nonviable foals.

5.
Front Vet Sci ; 8: 694774, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485428

RESUMO

Bovine viral diarrhoea (BVD) is an important endemic disease of cattle. In Ireland, an industry-led compulsory eradication programme began in January 2013. The main elements of this programme are the identification and elimination of persistently infected (PI) calves by testing all new-borns, the implementation of biosecurity to prevent re-introduction of disease and continuous surveillance. In 2016, a standardised framework was developed to investigate herds with positive results. This is delivered by trained private veterinary practitioners (PVP). The investigation's aims are 3-fold: firstly, to identify plausible sources of infection; secondly, to ensure that no virus-positive animals remain on farm by resolving the BVD status of all animals in the herd; and thirdly, agreeing up to three biosecurity measures with the herd owner to prevent the re-introduction of the virus. Each investigation follows a common approach comprising four steps based on information from the programme database and collected on-farm: firstly, identifying the time period when each virus-positive calf was exposed in utero (window of susceptibility, taken as 30-120 days of gestation); secondly, determining the location of the dam of each positive calf during this period; thirdly, to investigate potential sources of exposure, either within the herd or external to it; and finally, based on the findings, the PVP and herdowner agree to implement up to three biosecurity measures to minimise the risk of reintroduction. Between 2016 and 2020, 4,105 investigations were completed. The biosecurity recommendations issued more frequently related to the risks of introduction of virus associated with contact with neighbouring cattle at pasture, personnel (including the farmer), the purchase of cattle and vaccination. Although each investigation generates farm-specific outcomes and advice, the aggregated results also provide an insight into the most commonly identified transmission pathways for these herds which inform overall programme communications on biosecurity. The most widely identified plausible sources of infection over these years included retained BVD-positive animals, Trojan births, contact at boundaries and indirect contact through herd owner and other personnel in the absence of appropriate hygiene measures. While generated in the context of BVD herd investigations, the findings also provide an insight into biosecurity practises more generally on Irish farms.

6.
BMJ Open ; 10(8): e039856, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32759252

RESUMO

OBJECTIVES: Our objective was to review the literature on the inferred duration of the infectious period of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and provide an overview of the variation depending on the methodological approach. DESIGN: Rapid scoping review. Literature review with fixed search terms, up to 1 April 2020. Central tendency and variation of the parameter estimates for infectious period in (A) asymptomatic and (B) symptomatic cases from (1) virological studies (repeated testing), (2) tracing studies and (3) modelling studies were gathered. Narrative review of viral dynamics. INFORMATION SOURCES: Search strategies developed and the following searched: PubMed, Google Scholar, MedRxiv and BioRxiv. Additionally, the Health Information Quality Authority (Ireland) viral load synthesis was used, which screened literature from PubMed, Embase, ScienceDirect, NHS evidence, Cochrane, medRxiv and bioRxiv, and HRB open databases. RESULTS: There was substantial variation in the estimates, and how infectious period was inferred. One study provided approximate median infectious period for asymptomatic cases of 6.5-9.5 days. Median presymptomatic infectious period across studies varied over <1-4 days. Estimated mean time from symptom onset to two negative RT-PCR tests was 13.4 days (95% CI 10.9 to 15.8) but was shorter when studies included children or less severe cases. Estimated mean duration from symptom onset to hospital discharge or death (potential maximal infectious period) was 18.1 days (95% CI 15.1 to 21.0); time to discharge was on average 4 days shorter than time to death. Viral dynamic data and model infectious parameters were often shorter than repeated diagnostic data. CONCLUSIONS: There are limitations of inferring infectiousness from repeated diagnosis, viral loads and viral replication data alone and also potential patient recall bias relevant to estimating exposure and symptom onset times. Despite this, available data provide a preliminary evidence base to inform models of central tendency for key parameters and variation for exploring parameter space and sensitivity analysis.


Assuntos
Betacoronavirus , Doenças Transmissíveis/transmissão , Infecções por Coronavirus/transmissão , Pneumonia Viral/transmissão , Adulto , COVID-19 , Criança , Doenças Transmissíveis/complicações , Doenças Transmissíveis/mortalidade , Doenças Transmissíveis/virologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Saúde Global , Hospitalização , Humanos , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Reação em Cadeia da Polimerase , SARS-CoV-2 , Carga Viral
7.
Proc Natl Acad Sci U S A ; 117(19): 10357-10367, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32345720

RESUMO

Cystic fibrosis (CF) is a recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. The most common symptoms include progressive lung disease and chronic digestive conditions. CF is the first human genetic disease to benefit from having five different species of animal models. Despite the phenotypic differences among the animal models and human CF, these models have provided invaluable insight into understanding disease mechanisms at the organ-system level. Here, we identify a member of the ABCC4 family, CG5789, that has the structural and functional properties expected for encoding the Drosophila equivalent of human CFTR, and thus refer to it as Drosophila CFTR (Dmel\CFTR). We show that knockdown of Dmel\CFTR in the adult intestine disrupts osmotic homeostasis and displays CF-like phenotypes that lead to intestinal stem cell hyperplasia. We also show that expression of wild-type human CFTR, but not mutant variants of CFTR that prevent plasma membrane expression, rescues the mutant phenotypes of Dmel\CFTR Furthermore, we performed RNA sequencing (RNA-Seq)-based transcriptomic analysis using Dmel\CFTR fly intestine and identified a mucin gene, Muc68D, which is required for proper intestinal barrier protection. Altogether, our findings suggest that Drosophila can be a powerful model organism for studying CF pathophysiology.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Fibrose Cística/patologia , Modelos Animais de Doenças , Proteínas de Drosophila/metabolismo , Intestinos/patologia , Mutação , Células-Tronco/patologia , Animais , Fibrose Cística/genética , Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Proteínas de Drosophila/genética , Drosophila melanogaster , Sequenciamento de Nucleotídeos em Larga Escala , Homeostase , Humanos , Mucinas/genética , Mucinas/metabolismo , Fenótipo , Células-Tronco/metabolismo
8.
Mol Cell ; 77(6): 1251-1264.e9, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-32023484

RESUMO

Lipid droplets (LDs) store lipids for energy and are central to cellular lipid homeostasis. The mechanisms coordinating lipid storage in LDs with cellular metabolism are unclear but relevant to obesity-related diseases. Here we utilized genome-wide screening to identify genes that modulate lipid storage in macrophages, a cell type involved in metabolic diseases. Among ∼550 identified screen hits is MLX, a basic helix-loop-helix leucine-zipper transcription factor that regulates metabolic processes. We show that MLX and glucose-sensing family members MLXIP/MondoA and MLXIPL/ChREBP bind LDs via C-terminal amphipathic helices. When LDs accumulate in cells, these transcription factors bind to LDs, reducing their availability for transcriptional activity and attenuating the response to glucose. Conversely, the absence of LDs results in hyperactivation of MLX target genes. Our findings uncover a paradigm for a lipid storage response in which binding of MLX transcription factors to LD surfaces adjusts the expression of metabolic genes to lipid storage levels.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Regulação da Expressão Gênica , Glucose/metabolismo , Gotículas Lipídicas/metabolismo , Proteoma/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/antagonistas & inibidores , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Células Cultivadas , Testes Genéticos , Humanos , Macrófagos/citologia , Macrófagos/metabolismo , Ligação Proteica , Proteoma/análise , RNA Interferente Pequeno , Transcrição Gênica
9.
Bio Protoc ; 10(18): e3749, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-33659409

RESUMO

Most organs and tissues are composed of many types of cells. To characterize cellular state, various transcription profiling approaches are currently available, including whole-tissue bulk RNA sequencing, single cell RNA sequencing (scRNA-Seq), and cell type-specific RNA sequencing. What is missing in this repertoire is a simple, versatile method for bulk transcriptional profiling of cell types for which cell type-specific genetic markers or antibodies are not readily available. We therefore developed Probe-Seq, which uses hybridization of gene-specific probes to RNA markers for isolation of specific types of cells, to enable downstream FACS isolation and bulk RNA sequencing. We show that this method can enable isolation and profiling of specific cell types from mouse retina, frozen human retina, Drosophila midgut, and developing chick retina, suggesting that it is likely useful for most organisms.

10.
Elife ; 82019 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-31815670

RESUMO

Recent transcriptional profiling technologies are uncovering previously-undefined cell populations and molecular markers at an unprecedented pace. While single cell RNA (scRNA) sequencing is an attractive approach for unbiased transcriptional profiling of all cell types, a complementary method to isolate and sequence specific cell populations from heterogeneous tissue remains challenging. Here, we developed Probe-Seq, which allows deep transcriptional profiling of specific cell types isolated using RNA as the defining feature. Dissociated cells are labeled using fluorescent in situ hybridization (FISH) for RNA, and then isolated by fluorescent activated cell sorting (FACS). We used Probe-Seq to purify and profile specific cell types from mouse, human, and chick retinas, as well as from Drosophila midguts. Probe-Seq is compatible with frozen nuclei, making cell types within archival tissue immediately accessible. As it can be multiplexed, combinations of markers can be used to create specificity. Multiplexing also allows for the isolation of multiple cell types from one cell preparation. Probe-Seq should enable RNA profiling of specific cell types from any organism.


Assuntos
Citometria de Fluxo/métodos , Perfilação da Expressão Gênica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Animais , Galinhas , Drosophila , Humanos , Hibridização in Situ Fluorescente , Camundongos , Coloração e Rotulagem/métodos
11.
Mol Cell ; 75(2): 357-371.e7, 2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31227231

RESUMO

Carbohydrate response element binding protein (ChREBP) is a key transcriptional regulator of de novo lipogenesis (DNL) in response to carbohydrates and in hepatic steatosis. Mechanisms underlying nutrient modulation of ChREBP are under active investigation. Here we identify host cell factor 1 (HCF-1) as a previously unknown ChREBP-interacting protein that is enriched in liver biopsies of nonalcoholic steatohepatitis (NASH) patients. Biochemical and genetic studies show that HCF-1 is O-GlcNAcylated in response to glucose as a prerequisite for its binding to ChREBP and subsequent recruitment of OGT, ChREBP O-GlcNAcylation, and activation. The HCF-1:ChREBP complex resides at lipogenic gene promoters, where HCF-1 regulates H3K4 trimethylation to prime recruitment of the Jumonji C domain-containing histone demethylase PHF2 for epigenetic activation of these promoters. Overall, these findings define HCF-1's interaction with ChREBP as a previously unappreciated mechanism whereby glucose signals are both relayed to ChREBP and transmitted for epigenetic regulation of lipogenic genes.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Proteínas de Homeodomínio/genética , Fator C1 de Célula Hospedeira/genética , Lipogênese/genética , Hepatopatia Gordurosa não Alcoólica/genética , Animais , Carboidratos/genética , Epigênese Genética , Regulação da Expressão Gênica , Glucose/metabolismo , Hexosaminas/genética , Hexosaminas/metabolismo , Humanos , Fígado/metabolismo , Camundongos , Hepatopatia Gordurosa não Alcoólica/patologia , Regiões Promotoras Genéticas/genética , Mapas de Interação de Proteínas/genética
12.
Front Vet Sci ; 5: 261, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30406120

RESUMO

In recent years, there has been increasing recognition of the value of multiple data sources available to fulfill surveillance objectives, and the use of these has been applied to address many questions relating to animal health surveillance. In Ireland, we face a slightly different problem, namely, best use of an existing surveillance resource (serological samples collected over many years from cull cows at slaughter), which has been used to substantiate freedom from Brucella abortus following its successful eradication in 2009. In this study, we evaluate a sampling methodology to use this resource to substantiate freedom from bluetongue virus (BTV) infection. An examination of the degree to which cull cows were resident in the same herd throughout the midge biting season showed that, of 50,640 samples collected between 17 October and 23 December 2016, 80.2% were from animals resident in the same herd between 01 April 2016 and 2 months prior to their slaughter date, 74.1% for 1 month prior, 70.1% for 2 weeks prior, 66.4% for 1 week prior, and 56.4% up to 1 day prior to slaughter. An examination was made of the degree to which individual samples within the same 88-well frozen storage block came from geographically clustered herds, whether from a concentration of animals from the same herd in a single block, or from clustering around the slaughterhouse where the samples were taken. On the basis of these analyses, a sampling strategy was derived aimed at minimizing the number of storage blocks which needed to be thawed, whilst ensuring a large enough and representative sample, geographically stratified according to the bovine population of 51 squares, each 45 × 45 km, covering the entirety of Ireland. None of the 503 samples tested were positive for BTV, providing reassurance of national BTV freedom. More broadly, the study demonstrates the use of abattoir-based serological samples collected for one large scale surveillance programme in surveillance for other bovine infections.

13.
Cell Metab ; 19(2): 272-84, 2014 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-24506868

RESUMO

The homeostatic balance of hepatic glucose utilization, storage, and production is exquisitely controlled by hormonal signals and hepatic carbon metabolism during fed and fasted states. How the liver senses extracellular glucose to cue glucose utilization versus production is not fully understood. We show that the physiologic balance of hepatic glycolysis and gluconeogenesis is regulated by Bcl-2-associated agonist of cell death (BAD), a protein with roles in apoptosis and metabolism. BAD deficiency reprograms hepatic substrate and energy metabolism toward diminished glycolysis, excess fatty acid oxidation, and exaggerated glucose production that escapes suppression by insulin. Genetic and biochemical evidence suggests that BAD's suppression of gluconeogenesis is actuated by phosphorylation of its BCL-2 homology (BH)-3 domain and subsequent activation of glucokinase. The physiologic relevance of these findings is evident from the ability of a BAD phosphomimic variant to counteract unrestrained gluconeogenesis and improve glycemia in leptin-resistant and high-fat diet models of diabetes and insulin resistance.


Assuntos
Metabolismo Energético/fisiologia , Gluconeogênese/fisiologia , Fígado/metabolismo , Proteína de Morte Celular Associada a bcl/metabolismo , Animais , Metabolismo Energético/genética , Gluconeogênese/genética , Camundongos , Camundongos Mutantes , Fosforilação , Proteína de Morte Celular Associada a bcl/genética
14.
Anim Reprod Sci ; 141(1-2): 34-41, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23928154

RESUMO

Herd management record analysis facilitates accurate assessment of the current herd reproductive status; a crucial decision making tool to implement effective change. To determine the relative importance of cow and management factors on reproductive indices in moderate-yielding Irish seasonal-calving dairy herds, breeding records of 1173 cows were collected from 10 seasonal calving herds between 2007 and 2009. Backward-stepwise multivariable logistic regression analysis was utilised to determine the effect of cow factors including parity, calving timing, days post partum, heat detection accuracy and herd factors including herd size and heat detection efficiency on key reproductive indices. Mean farm six-week pregnancy and end of season not-in-calf rate were 46% (range 14-72%) and 22% (range 3-40%), respectively. Oestrous detection efficiency (P<0.001), timing of calving (P<0.001) relative to start of breeding, history of abnormal repeat intervals (P<0.001) and length of post partum interval (P<0.001) were each associated with lower six-week pregnancy rates. Timing of calving (P<0.001) and history of abnormal repeat intervals (P<0.001) were associated with higher not-in-calf rates. Herd size and cow parity were not associated (P>0.05) with either outcome when factors including existing calving pattern and heat detection accuracy and efficiency were accounted for. The existing spread in calving pattern, heat detection quality and length of voluntary waiting period were the most influential factors that reduced fertility performance in seasonal-calving herds.


Assuntos
Criação de Animais Domésticos/métodos , Bovinos/fisiologia , Parto/fisiologia , Reprodução/fisiologia , Estações do Ano , Animais , Bovinos/genética , Feminino , Irlanda , Modelos Logísticos , Modelos Biológicos , Análise Multivariada , Gravidez , Estudos Retrospectivos
15.
Proc Natl Acad Sci U S A ; 109(50): 20768-73, 2012 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-23184988

RESUMO

Contemporary high-throughput technologies permit the rapid identification of transcription factor (TF) target genes on a genome-wide scale, yet the functional significance of TFs requires knowledge of target gene expression patterns, cooperating TFs, and cis-regulatory element (CRE) structures. Here we investigated the myogenic regulatory network downstream of the Drosophila zinc finger TF Lame duck (Lmd) by combining both previously published and newly performed genomic data sets, including ChIP sequencing (ChIP-seq), genome-wide mRNA profiling, cell-specific expression patterns of putative transcriptional targets, analysis of histone mark signatures, studies of TF cooccupancy by additional mesodermal regulators, TF binding site determination using protein binding microarrays (PBMs), and machine learning of candidate CRE motif compositions. Our findings suggest that Lmd orchestrates an extensive myogenic regulatory network, a conclusion supported by the identification of Lmd-dependent genes, histone signatures of Lmd-bound genomic regions, and the relationship of these features to cell-specific gene expression patterns. The heterogeneous cooccupancy of Lmd-bound regions with additional mesodermal regulators revealed that different transcriptional inputs are used to mediate similar myogenic gene expression patterns. Machine learning further demonstrated diverse combinatorial motif patterns within tissue-specific Lmd-bound regions. PBM analysis established the complete spectrum of Lmd DNA binding specificities, and site-directed mutagenesis of Lmd and additional newly discovered motifs in known enhancers demonstrated the critical role of these TF binding sites in supporting full enhancer activity. Collectively, these findings provide insights into the transcriptional codes regulating muscle gene expression and offer a generalizable approach for similar studies in other systems.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/genética , Redes Reguladoras de Genes , Genoma de Inseto , Desenvolvimento Muscular/genética , Fatores de Regulação Miogênica/genética , Animais , Animais Geneticamente Modificados , Inteligência Artificial , Sequência de Bases , Sítios de Ligação/genética , DNA/genética , DNA/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citologia , Drosophila melanogaster/metabolismo , Elementos Facilitadores Genéticos , Regulação da Expressão Gênica no Desenvolvimento , Mesoderma/citologia , Mesoderma/crescimento & desenvolvimento , Mesoderma/metabolismo , Dados de Sequência Molecular , Mioblastos/citologia , Mioblastos/metabolismo , Fatores de Regulação Miogênica/metabolismo , Biologia de Sistemas , Transcriptoma
16.
Genes Dev ; 25(11): 1173-84, 2011 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-21632824

RESUMO

tRNAs, like other RNAs, are subject to quality control steps during and after biosynthesis. We previously described a rapid tRNA degradation (RTD) pathway in which the 5'-3' exonucleases Rat1 and Xrn1 degrade mature tRNA(Val(AAC)) in yeast mutants lacking m(7)G and m(5)C, and mature tRNA(Ser(CGA)) in mutants lacking Um and ac(4)C. To understand how the RTD pathway selects substrate tRNAs among different tRNAs lacking the same modifications, we used a genetic screen to examine tRNA(Ser(CGA)) variants. Our results suggest that RTD substrate recognition in vivo depends primarily on the stability of the acceptor and T-stems, and not the anti-codon stem, and does not necessarily depend on modifications, since fully modified tRNAs are subject to RTD if appropriately destabilized. We found that weaker predicted stability of the acceptor and T-stems of tRNAs is strongly correlated with RTD sensitivity, increased RNase T2 sensitivity of this region of the tRNA in vitro, and increased exposure of the 5' end to phosphatase. We also found that purified Xrn1 selectively degrades RTD substrate tRNAs in vitro under conditions in which nonsubstrates are immune. These results suggest that tRNAs have evolved not only for accurate translation, but for resistance to attack by RTD.


Assuntos
Estabilidade de RNA , RNA de Transferência/química , RNA de Transferência/metabolismo , Saccharomyces cerevisiae/metabolismo , Exorribonucleases/metabolismo , Mutação/genética , RNA de Transferência/genética , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
17.
Anim Reprod Sci ; 112(1-2): 66-82, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-18501537

RESUMO

The objectives were to determine the effects of (i) time during the first FSH increase of the estrous cycle (time-course study) and (ii) exogenous steroid treatment (steroid feedback study) on the relationship between circulating serum gonadotropins, and the proportions of pituitary cells immunoreactive for gonadotropins and steroid receptors during the estrous cycle in heifers. Pituitaries were collected from heifers (n=40) slaughtered at 13h (n=8), 30h (n=24) and 66h (n=8) after estrous onset, corresponding to before, during and after the first FSH increase of the estrous cycle. Heifers slaughtered during the FSH increase (at 30h) either received no treatment (n=8), or were treated (n=16) with estradiol benzoate and/or progesterone before slaughter. During the time-course study, the proportion of pituitary cells immunoreactive for FSH increased (P<0.05) during the first transient FSH increase reflecting serum concentrations. The proportion of pituitary cells immunoreactive for LH was unaltered, a reflection of serum LH concentrations. The proportion of estrogen receptors (ER)-alpha, but not ER-beta, was decreased (P<0.05) at 30h compared with at either 13 or 66h. During the steroid feedback study, exogenous progesterone with or without estradiol suppressed (P<0.05) the proportions of pituitary cells immunoreactive for gonadotropins, serum FSH concentrations and LH pulse frequency. Steroid treatment did not alter the proportion of pituitary cells positive for estrogen receptors (alpha and beta). While progesterone receptors (PR) were not detected in the anterior pituitary by immunohistochemistry during the early estrous cycle or in response to steroid treatment, quantitative real-time PCR revealed that mRNA for progesterone receptors was expressed at very low levels. The expression of pituitary PR mRNA was decreased (P<0.05) at 30 and 66h compared with 13h, and was suppressed (P<0.05) following steroid treatments. Alterations in pituitary steroid receptors are implicated in the differential regulation of gonadotropin secretion during the first transient FSH rise, but not in response to exogenous steroids. The time-course study and steroid feedback responses support the hypothesis that LH pulse frequency is tightly linked to regulation of GnRH pulse frequency. Serum FSH is regulated by its own synthesis, as reflected by pituitary FSH content and perhaps by alterations in pituitary sensitivity to circulating steroids by changes in steroid receptor content.


Assuntos
Bovinos , Hormônio Foliculoestimulante/sangue , Hormônios Esteroides Gonadais/administração & dosagem , Gonadotropinas Hipofisárias/análise , Hipófise/química , Receptores de Esteroides/análise , Animais , Estradiol/administração & dosagem , Estradiol/análogos & derivados , Receptor alfa de Estrogênio/análise , Receptor beta de Estrogênio/análise , Ciclo Estral/fisiologia , Retroalimentação Fisiológica , Feminino , Hormônio Foliculoestimulante/análise , Gonadotropinas Hipofisárias/sangue , Imuno-Histoquímica , Hormônio Luteinizante/análise , Hormônio Luteinizante/sangue , Progesterona/administração & dosagem , RNA Mensageiro/análise , Receptores de Progesterona/análise , Receptores de Progesterona/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
18.
Am J Reprod Immunol ; 60(5): 462-73, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19238751

RESUMO

PROBLEM: Pelvic inflammatory disease and metritis are important causes of infertility in humans and domestic animals. Uterine infection with Escherichia coli in cattle is associated with reduced ovarian follicle growth and decreased estradiol secretion. We hypothesized that this effect could be mediated by the bacterial lipopolysaccharide (LPS) or cytokines such as tumour necrosis factor alpha (TNFalpha). METHOD OF STUDY: In vitro, bovine ovarian theca and granulosa cells were treated with LPS or TNFalpha and steroid secretion measured. In vivo, the effect of LPS or TNFalpha intrauterine infusion was determined by ovarian ultrasonography and measurement of hormones in cattle. RESULTS: Lipopolysaccharide reduced granulosa cell estradiol secretion, whilst TNFalpha decreased theca and granulosa cell androstenedione and estradiol production, respectively. In vivo, fewer animals ovulated following intrauterine infusion with LPS or TNFalpha. CONCLUSION: Lipopolysaccharide and TNFalpha suppress ovarian cell function, supporting the concept that pelvic inflammatory disease and metritis are detrimental for bovine ovarian health.


Assuntos
Infecções por Escherichia coli/imunologia , Escherichia coli/imunologia , Folículo Ovariano/imunologia , Ovulação/imunologia , Doença Inflamatória Pélvica/imunologia , Fator de Necrose Tumoral alfa/imunologia , Androstenodiona/biossíntese , Androstenodiona/imunologia , Animais , Bovinos , Células Cultivadas , Estradiol/biossíntese , Estradiol/imunologia , Estrogênios/biossíntese , Estrogênios/imunologia , Feminino , Hormônio Foliculoestimulante/sangue , Lipopolissacarídeos/imunologia , Hormônio Luteinizante/sangue , Folículo Ovariano/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Doença Inflamatória Pélvica/etiologia , Fator de Necrose Tumoral alfa/farmacologia
19.
J Vet Med Educ ; 35(4): 631-6, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19228919

RESUMO

Problem-based learning (PBL) replicates life experiences to stimulate learning, the integration of knowledge, and lifelong learning skills, all of which are requirements for veterinary medical education. As the curricular content of veterinary schools expands to immense proportions following advances in medical knowledge and biotechnology, it becomes impracticable to ensure that all students at the beginning of their careers have such a wide knowledge base. Students who are faced with vast amounts of information to learn by rote, much of which may seem irrelevant to their prospective career, may become disillusioned with their chosen course, hence the temptation to convert to a PBL curriculum. The PBL strategy of teaching is becoming increasingly popular in veterinary faculties worldwide, encompassing both curriculum content and a process of learning. In PBL, clinical cases are carefully selected to provoke deep student learning by the acquisition of both basic scientific and clinical knowledge critical to the case; cultivate problem-solving abilities; and encourage the development of team-building, self-directed learning, communication, and self- and peer-assessment skills. Problem-solving skills, understanding of the basic sciences, and clinical performance are all improved by the PBL process. The aim of this paper is to review a decade of literature pertaining to the inclusion of PBL in veterinary and medical curricula.


Assuntos
Educação em Veterinária/métodos , Aprendizagem Baseada em Problemas , Atitude do Pessoal de Saúde , Docentes , Humanos , Resolução de Problemas , Avaliação de Programas e Projetos de Saúde , Faculdades de Medicina Veterinária , Pensamento
20.
Prim Dent Care ; 13(4): 130-4, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17236567

RESUMO

Following the publication of the National Service Framework for Older People, there have been developments across health and social care to facilitate holistic assessment of older people's needs, through what is called a 'single assessment process' or 'SAP'. In this paper, readers are introduced to the SAP. The process can be seen as a 'one-stop' approach to the assessment of vulnerable older people that facilitates cross-referral between the agencies involved and triggers access to dental care. The paper explores the benefits of this new way of working in support of older people and how it will provide an opportunity for innovative dental practitioners to integrate oral healthcare for people with complex health and social care needs into the SAP. In concludes that as local commissioning evolves, opportunities for practitioners to develop targeted services for this important patient group should be expanded to improve the uptake of healthcare and oral healthcare.


Assuntos
Assistência Odontológica para Idosos , Serviços de Saúde Bucal , Avaliação Geriátrica , Serviços de Saúde para Idosos/organização & administração , Avaliação das Necessidades/organização & administração , Atenção Primária à Saúde/organização & administração , Idoso , Idoso de 80 Anos ou mais , Humanos , Medicina Estatal/organização & administração , Reino Unido
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...