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1.
Food Chem ; 336: 127729, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32768914

RESUMO

The roles of lipid oxidation substrates and muscle microstructure in lipid oxidation were investigated in two muscle models (cod and pig). Added myoglobin (Mb) promoted lipid oxidation in washed cod muscle (WCM) but not in washed pig muscle (WPM). The differing microstructure of WCM e.g. more exposed fat cells or membrane of muscle cells compared to the "denseness" or "wrapped" structure of WPM, may have contributed to the better ability of Mb to facilitate lipid oxidation in the WCM. Added phospholipids with polyenoic indexes of 282 and 24 activated Mb as an oxidant similarly in WPM while added neutral lipids and added free fatty acids had little effect. It is suggested that muscle microstructure and accessibility of Mb to phospholipids play critical roles in relation to Mb-mediated lipid oxidation while the degree of unsaturation in the phospholipids was less important.


Assuntos
Gadiformes/metabolismo , Lipídeos/química , Músculos/metabolismo , Mioglobina/química , Animais , Cromatografia Gasosa , Peroxidação de Lipídeos , Lipídeos/análise , Suínos , alfa-Tocoferol/análise
2.
Nat Commun ; 11(1): 5010, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024114

RESUMO

PIX proteins are guanine nucleotide exchange factors (GEFs) that activate Rac and Cdc42, and are known to have numerous functions in various cell types. Here, we show that a PIX protein has an important function in muscle. From a genetic screen in C. elegans, we found that pix-1 is required for the assembly of integrin adhesion complexes (IACs) at borders between muscle cells, and is required for locomotion of the animal. A pix-1 null mutant has a reduced level of activated Rac in muscle. PIX-1 localizes to IACs at muscle cell boundaries, M-lines and dense bodies. Mutations in genes encoding proteins at known steps of the PIX signaling pathway show defects at muscle cell boundaries. A missense mutation in a highly conserved residue in the RacGEF domain results in normal levels of PIX-1 protein, but a reduced level of activated Rac in muscle, and abnormal IACs at muscle cell boundaries.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Transporte/metabolismo , Células Musculares/fisiologia , Músculos/citologia , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/genética , Proteínas de Transporte/química , Proteínas de Transporte/genética , Regulação da Expressão Gênica , Locomoção , Simulação de Dinâmica Molecular , Mutação , Domínios Proteicos , Fatores de Troca de Nucleotídeo Guanina Rho/química , Sarcômeros/fisiologia , Proteínas rac de Ligação ao GTP/metabolismo
4.
Nat Commun ; 11(1): 5432, 2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-33116134

RESUMO

Adeno-associated virus (AAV) forms the basis for several commercial gene therapy products and for countless gene transfer vectors derived from natural or synthetic viral isolates that are under intense preclinical evaluation. Here, we report a versatile pipeline that enables the direct side-by-side comparison of pre-selected AAV capsids in high-throughput and in the same animal, by combining DNA/RNA barcoding with multiplexed next-generation sequencing. For validation, we create three independent libraries comprising 183 different AAV variants including widely used benchmarks and screened them in all major tissues in adult mice. Thereby, we discover a peptide-displaying AAV9 mutant called AAVMYO that exhibits superior efficiency and specificity in the musculature including skeletal muscle, heart and diaphragm following peripheral delivery, and that holds great potential for muscle gene therapy. Our comprehensive methodology is compatible with any capsids, targets and species, and will thus facilitate and accelerate the stratification of optimal AAV vectors for human gene therapy.


Assuntos
Proteínas do Capsídeo/genética , Dependovirus/genética , Vetores Genéticos , Músculos/metabolismo , Músculos/virologia , Animais , Capsídeo , Código de Barras de DNA Taxonômico , Feminino , Biblioteca Gênica , Terapia Genética/métodos , Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Especificidade de Órgãos
5.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3220-3223, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018690

RESUMO

Localized muscle fatigue (LMF) decreases muscular strength, while affects the performance and potentially increases the risk of musculoskeletal disorders (MSD). An important mechanism in recovering from muscle fatigue is blood flow (BF). The BF response to muscle contraction and fatigue is highly dynamic and difficult to predict, as it depends on both metabolic demand and intramuscular pressure. The aim of this study was to measure both fatigue and BF during intermittent exertion of the first dorsal interosseous (FDI) muscle, in order to better characterize the relationship between BF and LMF during muscle contraction and rest. This study utilized Diffuse Correlation Spectroscopy (DCS) for BF measurement within the microvasculature of the FDI muscle. Exertion levels (EL) for intermittent fatiguing contraction were set to 20%, 30%, and 40% of an individual's maximum voluntary contraction (MVC). Our results showed that as an individual fatigued, relative BF rates increased, on average, by ~66% during exertion periods and ~330% during rest periods. Differences between exerting and resting BF increased over time for every EL (p<0.04), increasing by up to 11 times the baseline BF. At the same levels of muscle capacity (%MVC), resting BF was also found to increase with EL consistently. Our findings highlight BF dependence on both EL and history of muscle contraction. These results imply a variable recovery rate based on both the current state of contraction, (i.e., exertion vs. rest), and the muscle contraction history. The outcome of our study may facilitate the estimation of BF, thus, the muscle recovery rate, which can be implemented in the fatigue models to improve the prediction of muscle capacity to generate force/power.


Assuntos
Contração Isométrica , Músculos , Humanos , Microvasos , Contração Muscular , Fadiga Muscular
6.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 4839-4843, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019074

RESUMO

Control of human arm in reaching task is a result of complex neural interaction involving central nervous and musculoskeletal system, where, group of muscle activation are planned through synergistic and coordinated recruitment, often to reach an optimal strategy. Aim of this paper is to explore muscle synergy distribution on several reaching task of similar elbow trajectory but changing shoulder configuration. A musculoskeletal model of human arm comprising shoulder, elbow and wrist joint have been designed and is used to calculate muscle activation required to perform three specific reaching tasks. Muscle synergy have been computed on the simulated activation to find a relation between synergy and energy requirement with the change of rotation and elevation of shoulder and its effect on the motion path of the elbow joint. These findings may help to define optimal joint configuration for a planned range of motion during rehabilitation exercises and also in developing neural prosthesis and myoelectric interfaces for efficient arm motion control.


Assuntos
Articulação do Cotovelo , Ombro , Mãos , Humanos , Músculos , Punho
7.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1436-1439, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018260

RESUMO

Gastric motility disorders are associated with bioelectrical abnormalities in the stomach. Recently, gastric ablation has emerged as a potential therapy to correct gastric dysrhythmias. However, the tissue-level effects of gastric ablation have not yet been evaluated. In this study, radiofrequency ablation was performed in vivo in pigs (n=7) at temperature-control mode (55-80°C, 5-10 s per point). The tissue was excised from the ablation site and routine H&E staining protocol was performed. In order to assess tissue damage, we developed an automated technique using a fully convolutional neural network to segment healthy tissue and ablated lesion sites within the muscle and mucosa layers of the stomach. The tissue segmentation achieved an overall Dice score accuracy of 96.18 ± 1.0 %, and Jacquard score of 92.77 ± 1.9 %, after 5-fold cross validation. The ablation lesion was detected with an overall Dice score of 94.16 ± 0.2 %. This method can be used in combination with high-resolution electrical mapping to define the optimal ablation dose for gastric ablation.Clinical Relevance-This work presents an automated method to quantify the ablation lesion in the stomach, which can be applied to determine optimal energy doses for gastric ablation, to enable clinical translation of this promising emerging therapy.


Assuntos
Aprendizado Profundo , Redes Neurais de Computação , Animais , Músculos , Estômago/diagnóstico por imagem , Suínos , Vísceras
8.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2092-2095, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018418

RESUMO

Functional muscle imaging is essential for diagnostics of a multitude of musculoskeletal afflictions such as degenerative muscle diseases, muscle injuries, muscle atrophy, and neurological related issues such as spasticity. However, there is currently no solution, imaging or otherwise, capable of providing a map of active muscles over a large field of view in dynamic scenarios.In this work, we look at the feasibility of applying longitudinal sound speed measurements to the task of dynamic muscle imaging of contraction or activation. We perform the assessment using a deep learning network applied to prebeamformed ultrasound channel data for sound speed inversion.Preliminary results show that dynamic muscle contraction can be detected in the calf and that this contraction can be positively assigned to the operating muscles. Potential frame rates in the hundreds to thousands of frames per second are necessary to accomplish this.


Assuntos
Aprendizado Profundo , Músculos , Contração Muscular , Músculos/diagnóstico por imagem , Som , Ultrassonografia
9.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3981-3984, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018872

RESUMO

Remote monitoring of fluid status via calf bioimpedance measurements could improve the experience of patients with congestive heart failure and reduce readmission rates. Most measurements today use conventional Ag/AgCl electrodes and a short inter-electrode spacing, resulting in current flowing primarily near the electrodes, preventing deeper current penetration and in turn accurate volume estimation. Textile band electrodes may more evenly distribute current throughout the calf. In the present study, simulations were conducted to investigate the impact of inter-electrode spacing/placement and fat tissue on bioimpedance using both Ag/AgCl electrodes and textile band electrodes. Simulation results showed that increasing the inter-electrode spacing can improve current distribution in the tissue, but there are still errors that increase with fat thickness (14.3% error at 10 cm spacing down to 1.7% error at 20 cm spacing for a "nominal" fat thickness, vs. -0.3% and -0.5% error for band electrodes). Band electrodes most closely matched the expected resistance and seem the most suitable regardless of inter-electrode spacing.


Assuntos
Perna (Membro) , Músculos , Anisotropia , Impedância Elétrica , Eletrodos , Humanos
10.
PLoS One ; 15(9): e0239467, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32970731

RESUMO

Dystrophin plays a vital role in maintaining muscle health, yet low mRNA expression, lengthy transcription time and the limitations of traditional in-situ hybridization (ISH) methodologies mean that the dynamics of dystrophin transcription remain poorly understood. RNAscope is highly sensitive ISH method that can be multiplexed, allowing detection of individual transcript molecules at sub-cellular resolution, with different target mRNAs assigned to distinct fluorophores. We instead multiplex within a single transcript, using probes targeted to the 5' and 3' regions of muscle dystrophin mRNA. Our approach shows this method can reveal transcriptional dynamics in health and disease, resolving both nascent myonuclear transcripts and exported mature mRNAs in quantitative fashion (with the latter absent in dystrophic muscle, yet restored following therapeutic intervention). We show that even in healthy muscle, immature dystrophin mRNA predominates (60-80% of total), with the surprising implication that the half-life of a mature transcript is markedly shorter than the time invested in transcription: at the transcript level, supply may exceed demand. Our findings provide unique spatiotemporal insight into the behaviour of this long transcript (with implications for therapeutic approaches), and further suggest this modified multiplex ISH approach is well-suited to long genes, offering a highly tractable means to reveal complex transcriptional dynamics.


Assuntos
Distrofina/genética , Expressão Gênica/genética , Hibridização In Situ/métodos , Animais , Distrofina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase Multiplex/métodos , Músculos/metabolismo , RNA Mensageiro/genética , Transcrição Genética/genética
11.
Jpn J Clin Oncol ; 50(10): 1097-1107, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32895714

RESUMO

Radical cystectomy is the gold standard treatment for muscle invasive bladder cancer, but some patients have medically inoperable disease or refuse cystectomy to preserve their bladder function. Bladder preservation therapy with transurethral resection of the bladder tumor and concurrent chemoradiotherapy, known as trimodal treatment, is regarded to be a curative-intent alternative to radical cystectomy for patients with muscle invasive bladder cancer during the past decade. After the development of immune checkpoint inhibitors, a world-changing breakthrough occurred in the field of metastatic urothelial carcinoma and many clinical trials have been conducted against non-muscle invasive bladder cancer. Interestingly, preclinical and clinical studies against other malignancies have shown that immune checkpoint inhibitors interact with the radiation-induced immune reaction. As half of the patients with muscle invasive bladder cancer are elderly, and some have renal dysfunction, not only as comorbidity but also because of hydronephrosis caused by their tumors, immune checkpoint inhibitors are expected to become part of a new therapeutic approach for combination treatment with radiotherapy. Accordingly, clinical trials testing immune checkpoint inhibitors have been initiated to preserve bladder for muscle invasive bladder cancer patients using radiation and immune checkpoint inhibitors with/without chemotherapy. The objective of this review is to summarize the evidence of trimodal therapy for muscle invasive bladder cancer during the past decade and to discuss the future directions of bladder preservation therapy in immuno-oncology era.


Assuntos
Músculos/patologia , Tratamentos com Preservação do Órgão/tendências , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia , Humanos , Invasividade Neoplásica , Qualidade de Vida , Resultado do Tratamento
12.
J Vis Exp ; (162)2020 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-32865531

RESUMO

Ex vivo perfusion is an important physiological tool to study the function of isolated organs (e.g. liver, kidneys). At the same time, due to the small size of mouse organs, ex vivo perfusion of bone, bladder, skin, prostate, and reproductive organs is challenging or not feasible. Here, we report for the first time an in situ lower body perfusion circuit in mice that includes the above tissues, but bypasses the main clearance organs (kidney, liver, and spleen). The circuit is established by cannulating the abdominal aorta and inferior vena cava above the iliac artery and vein and cauterizing peripheral blood vessels. Perfusion is performed via a peristaltic pump with perfusate flow maintained for up to 2 h. In situ staining with fluorescent lectin and Hoechst solution confirmed that the microvasculature was successfully perfused. This mouse model can be a very useful tool for studying pathological processes as well as mechanisms of drug delivery, migration/metastasis of circulating tumor cells into/from the tumor, and interactions of immune system with perfused organs and tissues.


Assuntos
Perfusão/métodos , Animais , Feminino , Fêmur , , Membro Posterior , Masculino , Camundongos , Músculos , Próstata , Pele , Testículo , Bexiga Urinária
13.
Bull Environ Contam Toxicol ; 105(5): 750-757, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32970223

RESUMO

We summarized available data concerning contamination of the Czech part of the Elbe River by mercury and assessed the potential risks to humans connected with the consumption of contaminated fish. Total mercury concentrations were evaluated in dorsal muscle of chub (Squalius cephalus) and bream (Abramis brama) that were collected at 11 sampling sites in the period from 1991 to 2016. Significant differences among sites were found for both species. The highest contamination was observed near the non-ferrous Kovohute metal works at Celakovice and also downstream from the Spolana chemical plant at Neratovice. A significant decline in contamination with time (concentrations decreasing from 1.65 to 0.22 mg kg-1; p = 0.004) was revealed in chub downstream from the Spolana plant. Calculated hazard indices (HIs) were below 1, therefore, adverse health effects on the general Czech population connected with the consumption of fish from the Elbe River were not expected.


Assuntos
Monitoramento Ambiental/métodos , Mercúrio/análise , Rios/química , Poluentes Químicos da Água/análise , Animais , Cyprinidae/crescimento & desenvolvimento , República Tcheca , Contaminação de Alimentos/análise , Humanos , Músculos/química , Medição de Risco , Análise Espaço-Temporal
14.
Rev. am. med. respir ; 20(3): 215-224, sept. 2020. graf, tab
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1123025

RESUMO

Introducción: La debilidad adquirida en la unidad de cuidados intensivos (DAUCI) compromete tanto a los músculos de las extremidades como el diafragma, asociándose con variables de resultado negativas. El objetivo del estudio fue describir las características epidemiológicas e incidencia de DAUCI en adultos con requerimiento de ventilación mecánica invasiva (VMI) mayor a 72 horas en un Hospital General de Agudos de la Ciudad de Buenos Aires. Método: Estudio de cohorte retrospectivo. Se incluyeron pacientes adultos con requerimiento de VMI por más de 72 horas en la Unidad de Cuidados Intensivos (UCI). Las principales variables de interés registradas fueron: incidencia de DAUCI, días de VMI, estadía y mortalidad tanto en UCI como hospitalaria. Resultados: Se incluyeron 262 pacientes de los cuales 87 (33,21%) intercurrieron con debilidad. No se establecieron diferencias estadísticamente significativas entre los pacientes con y sin DAUCI para las variables edad, motivo de ingreso a VMI, número de antecedentes personales y mortalidad tanto en UCI como hospitalaria. En el presente estudio se establecieron como factores de riesgo independiente al sexo femenino (OR: 1,98; IC 95%: 1,02 ­3,81), delirio (OR 8,4; IC 95%: 4,38-16,11) y días de VMI (OR: 1,05; IC 95%: 1,02-1,08). Conclusiones: El presente estudio nos permitió conocer la incidencia y las características epidemiológicas de los pacientes que presentan DAUCI en una UCI del sistema público de salud de Argentina. Se observó que el sexo femenino, los días de VMI y el delirio en UCI fueron factores de riesgo independiente para DAUCI.


Assuntos
Humanos , Polineuropatias , Respiração Artificial , Fatores de Risco , Unidades de Terapia Intensiva , Músculos
15.
Rev. am. med. respir ; 20(3): 225-234, sept. 2020. graf, tab
Artigo em Inglês | LILACS, BINACIS | ID: biblio-1123028

RESUMO

Introduction: Intensive care unit-acquired weakness (ICUAW) affects the muscles of the limbs and diaphragm; and is associated with negative outcome variables. The purpose of this study was to describe the epidemiological characteristics and incidence of ICUAW in adults requiring invasive mechanical ventilation (IMV) for more than 72 hours in a General Hospital for Acute Diseases in the City of Buenos Aires. Method: Retrospective cohort study. We included adult patients requiring IMV for more than 72 hours in the Intensive Care Unit (ICU). The main recorded variables of interest were: incidence of ICUAW, days of IMV, length of stay and mortality both in the ICU and in the hospital. Results: 262 patients were included in the study; 87 of them (33.21%) developed weakness. No statistically significant differences were established between patients with and without ICUAW regarding the variables of age, reason for admission to IMV, medical history and mortality both in the ICU and the hospital. In this study, the variables established as independent risk factors were: female gender (OR: 1,98; 95% CI: 1.02-3.81), delirium (OR 8.4; 95% CI: 4.38-16.11) and days of IMV (OR: 1.05; 95% CI: 1.02-1.08). Conclusions: This study allowed us to know the incidence and epidemiological characteristics of patients with ICUAW in an ICU of the public health system of Argentina. It was observed that female gender, days of IMV and delirium at the ICU were independent risk factors for ICUAW.


Assuntos
Humanos , Polineuropatias , Respiração Artificial , Fatores de Risco , Unidades de Terapia Intensiva , Músculos
16.
PLoS One ; 15(9): e0236430, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32956357

RESUMO

Rhesus macaques represent an important species for translational and pre-clinical research studies across a multitude of disease and injury models, including aging. Ketamine anesthesia is used in humans and non-human primates but may be associated with adverse effects, including neuromuscular reactions. The effects of aging on ketamine adverse effects is not well characterized. Urodynamic recordings and electromyography (EMG) studies were performed in aged (>20 years old) and adult (3.9-14.9 years old) female rhesus macaques under an equal and light plane of sedation by constant rate infusion (CRI) of ketamine. A total of 4 of 41 adult subjects (9.7%) showed clinical signs of ketamine-induced abnormal neuromuscular reactivity, whereas a larger portion of 14 of 26 aged subjects showed similar ketamine-induced neuromuscular reactivity (53.8%; P< 0.001). The ketamine CRI rate was 19.8±0.9 mg/kg/h in adults and lower in aged subjects at 16.5±1.4 mg/kg/h (P<0.05). The ketamine CRI rate was negatively correlated with age (r = -0.30, P<0.05, n = 64). The incidence of ketamine reactivity or CRI rate was not different between aged pre-and post-menopausal females. EMG recordings during neuromuscular reactivity showed coordinated activation of multiple muscles, suggesting a central nervous system (CNS) mechanism for ketamine-associated neuromuscular reactivity. The incidence of ketamine-induced neuromuscular reactivity is age related but not affected by the estrous cycle in female rhesus macaques. A coordinated activation of multiple muscles, innervated by different peripheral nerves, suggests that ketamine-induced neuromuscular reactivity originates in the CNS.


Assuntos
Envelhecimento , Anestésicos Dissociativos/efeitos adversos , Ketamina/efeitos adversos , Macaca mulatta/fisiologia , Músculos/efeitos dos fármacos , Envelhecimento/efeitos dos fármacos , Animais , Eletromiografia , Feminino , Músculos/inervação , Músculos/fisiologia
17.
PLoS One ; 15(9): e0238123, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881944

RESUMO

An effective and pain-free killing method is required to achieve the goal of euthanasia, a "good death". Overdose of sodium pentobarbital (PB) by intraperitoneal (IP) injection is a widely accepted technique in laboratory rats, but questions remain regarding pain associated with administration. As PB rapidly causes sedation and loss of consciousness, most studies have relied on indirect evidence of pain. The objective of this study was to assess pain associated with IP PB using an appropriate vehicle control. Adult male and female Sprague Dawley (SD) and female Wistar rats (N = 84) were block randomised by sex and strain to receive one of three treatments: 1) 800 mg/kg PB (pH 11), 2) saline or 3) vehicle controls (pH 11 or 12.5). Behavior (Rat Grimace Scale (RGS), writhing, back arching) was evaluated at baseline, before loss of righting reflex (LORR, PB group), and at 80s, 151s and 10 min post-injection (PI; saline and vehicle control groups). In the PB group, mean time to LORR was 78 ± 7.9 seconds. In the vehicle control groups, RGS scores were increased at 151s PI (SD: p = 0.0002, 95%CI 0.73 to 0.20) from baseline, as was relative frequency of writhing (SD: p < 0.0001; Wistar; p = 0.0004). RGS scores remained elevated 10 mins PI (SD: p = 0.0005, 95%CI 0.71 to 0.18; Wistar: p = 0.0234, 95%CI 0.91 to 0.07) but the relative frequency of writhing did not (p > 0.999). The RGS scores and the relative frequency of writhing remained low in the PB and saline groups (p > 0.05). These results show that, vehicle controls for IP PB result in signs associated with pain, pain may not be experienced following IP PB when LORR occurs quickly, and that the effects of PB limit behavioral pain assessments.


Assuntos
Hipnóticos e Sedativos/administração & dosagem , Dor/tratamento farmacológico , Pentobarbital/administração & dosagem , Animais , Comportamento Animal , Feminino , Injeções Intraperitoneais , Fígado/patologia , Masculino , Músculos/patologia , Dor/patologia , Ratos , Ratos Sprague-Dawley , Ratos Wistar
18.
PLoS One ; 15(9): e0239143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32941478

RESUMO

Feed efficiency (FE) is a key trait in pig production, as improvement in FE has positive economic and environmental impact. FE is a complex phenotype and testing animals for FE is costly. Therefore, there has been a desire to find functionally relevant single nucleotide polymorphisms (SNPs) as biomarkers, to improve our biological understanding of FE as well as accuracy of genomic prediction for FE. We have performed a cis- and trans- eQTL (expression quantitative trait loci) analysis, in a population of Danbred Durocs (N = 11) and Danbred Landrace (N = 27) using both a linear and ANOVA model based on muscle tissue RNA-seq. We analyzed a total of 1425x19179 or 2.7x107 Gene-SNP combinations in eQTL detection models for FE. The 1425 genes were from RNA-Seq based differential gene expression analyses using 25880 genes related to FE and additionally combined with mitochondrial genes. The 19179 SNPs were from applying stringent quality control and linkage disequilibrium filtering on genotype data using a GGP Porcine HD 70k SNP array. We applied 1000 fold bootstrapping and enrichment analysis to further validate and analyze our detected eQTLs. We identified 13 eQTLs with FDR < 0.1, affecting several genes found in previous studies of commercial pig breeds. Examples include MYO19, CPT1B, ACSL1, IER5L, CPT1A, SUCLA2, CSRNP1, PARK7 and MFF. The bootstrapping results showed statistically significant enrichment (p-value<2.2x10-16) of eQTLs with p-value < 0.01 in both cis and trans-eQTLs. Enrichment analysis of top trans-eQTLs revealed high enrichment for gene categories and gene ontologies associated with genomic context and expression regulation. This included transcription factors (p-value = 1.0x10-13), DNA-binding (GO:0003677, p-value = 8.9x10-14), DNA-binding transcription factor activity (GO:0003700,) nucleus gene (GO:0005634, p-value<2.2x10-16), negative regulation of expression (GO:0010629, p-value<2.2x10-16). These results would be useful for future genome assisted breeding of pigs to improve FE, and in the improved understanding of the functional mechanism of trans eQTLs.


Assuntos
Cruzamento , Locos de Características Quantitativas , Sus scrofa/genética , Transcriptoma , Criação de Animais Domésticos , Animais , Dinamarca , Genes Mitocondriais , Masculino , Músculos/metabolismo , Polimorfismo de Nucleotídeo Único
19.
PLoS One ; 15(9): e0239358, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32970715

RESUMO

There is an extensive literature establishing, validating, and quantifying a wide range of responses of fishes to fasting. Our study complements this work by comparing fed and unfed treatments of hatchery-raised Delta Smelt (Hypomesus transpacificus)-an imperiled fish that is endemic to the San Francisco Estuary and its tributaries in California, USA-across a diverse suite of endpoints over a two-month time series. The experiment was conducted at 15.9°C, and individuals were sampled at 12 time points as starvation became increasingly severe. We found that hepatosomatic index and condition factor were relatively sensitive to starvation, becoming significantly depressed at Day 4 and 7, respectively. Histological analysis of liver showed elevated cytoplasmic inclusion bodies at Day 7, followed by increased glycogen depletion, single cell necrosis, and hydropic vacuolar degeneration at Day 14, 21, and 28, respectively. Of four antioxidants measured, glutathione decreased at Day 4, superoxide dismutase increased at Day 14, catalase increased at Day 56, and glutathione peroxidase was not affected by starvation. The net result was a ~2-fold increase in lipid peroxidation (malondialdehyde) in fasted fish that was highly inconsistent through time. RNA to DNA ratio and triglycerides in muscle were relatively insensitive to starvation, only consistently decreasing with fasting after mortality began increasing in the 'No Feeding' treatment, at Day 21. Together, these results suggest that Delta Smelt mobilize hepatic energy stores far more rapidly than lipids in muscle when subjected to fasting, leading to rapid atrophy of liver and the development of cytoplasmic inclusion bodies-possibly autophagosomes-in hepatocytes.


Assuntos
Osmeriformes/metabolismo , Inanição , Animais , Catalase/metabolismo , Glutationa/metabolismo , Glicogênio/metabolismo , Corpos de Inclusão/metabolismo , Fígado/metabolismo , Fígado/patologia , Malondialdeído/metabolismo , Músculos/metabolismo , Músculos/patologia , Necrose , Osmeriformes/crescimento & desenvolvimento , Superóxido Dismutase/metabolismo , Fatores de Tempo
20.
PLoS One ; 15(9): e0238208, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881928

RESUMO

INTRODUCTION: Peripheral nerve injury (PNI) often leads to significant functional loss in patients and poses a challenge to physicians since treatment options for improving functional outcomes are limited. Recent studies suggest that erythropoietin and glucocoticoids have beneficial effects as mediators of neuro-regenerative processes. We hypothesized that combination treatment with erythropoietin and glucocoticoids would have a synergistic effect on functional outcome after PNI. MATERIALS AND METHODS: Sciatic nerve crush injury was simulated in ten-week-old male C57BL/6 mice. The mice were divided into four groups according to the type of drugs administered (control, erythropoietin, dexamethasone, and erythropoietin with dexamethasone). Motor functional recovery was monitored by walking track analysis at serial time points up to 28 days after injury. Morphological analysis of the nerve was performed by immunofluorescent staining for neurofilament (NF) heavy chain and myelin protein zero (P0) in cross-sectional and whole-mount nerve preparations. Additionally, morphological analysis of the muscle was performed by Hematoxylin and eosin staining. RESULTS: Combination treatment with erythropoietin and dexamethasone significantly improved the sciatic functional index at 3, 7, 14, and 28 days after injury. Fluorescence microscopy of cross sectional nerve revealed that the combination treatment increased the ratio of P0/NF-expressing axons. Furthermore, confocal microscopy of the whole-mount nerve revealed that the combination treatment increased the fluorescence intensity of P0 expression. The cross-sectional area and minimum Feret's diameter of the muscle fibers were significantly larger in the mice which received combination treatment than those in the controls. CONCLUSION: Our results demonstrated that combination treatment with erythropoietin and dexamethasone accelerates functional recovery and reduces neurogenic muscle atrophy caused by PNI in mice, which may be attributed to the preservation of myelin and Schwann cell re-myelination. These findings may provide practical therapeutic options for patients with acute PNI.


Assuntos
Dexametasona/uso terapêutico , Eritropoetina/uso terapêutico , Músculos/metabolismo , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Nervo Isquiático/metabolismo , Doença Aguda , Animais , Axônios/metabolismo , Dexametasona/farmacologia , Modelos Animais de Doenças , Quimioterapia Combinada , Eritropoetina/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Músculos/patologia , Atrofia Muscular/patologia , Atrofia Muscular/prevenção & controle , Proteína P0 da Mielina/metabolismo , Traumatismos dos Nervos Periféricos/patologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Remielinização/efeitos dos fármacos , Células de Schwann/citologia , Células de Schwann/metabolismo , Nervo Isquiático/patologia
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