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The recent precise experimental determination of the monopole transition form factor from the ground state of ^{4}He to its 0_{2}^{+} resonance via electron scattering has reinvigorated discussions about the nature of this first excited state of the α particle. The 0_{2}^{+} state has been traditionally interpreted in the literature as the isoscalar monopole resonance (breathing mode) or, alternatively, as a particle-hole shell-model excitation. To better understand the nature of this state, which lies only â¼410 keV above the proton emission threshold, we employ the coupled-channel representation of the no-core Gamow shell model. By considering the [^{3}H+p], [^{3}He+n], and [^{2}H+^{2}H] reaction channels, we explain the excitation energy and monopole form factor of the 0_{2}^{+} state. We argue that the continuum coupling strongly impacts the nature of this state, which carries characteristics of the proton decay threshold.
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Muscle contraction is produced via the interaction of myofilaments and is regulated so that muscle performance matches demand. Myosin-binding protein C (MyBP-C) is a long and flexible protein that is tightly bound to the thick filament at its C-terminal end (MyBP-CC8C10), but may be loosely bound at its middle- and N-terminal end (MyBP-CC1C7) to myosin heads and/or the thin filament. MyBP-C is thought to control muscle contraction via the regulation of myosin motors, as mutations lead to debilitating disease. We use a combination of mechanics and small-angle X-ray diffraction to study the immediate and selective removal of the MyBP-CC1C7 domains of fast MyBP-C in permeabilized skeletal muscle. We show that cleavage leads to alterations in crossbridge kinetics and passive structural signatures of myofilaments that are indicative of a shift of myosin heads towards the ON state, highlighting the importance of MyBP-CC1C7 to myofilament force production and regulation.
Assuntos
Proteínas de Transporte , Sarcômeros , Sarcômeros/metabolismo , Proteínas de Transporte/metabolismo , Contração Muscular/fisiologia , Músculo Esquelético/metabolismo , Miosinas/metabolismoRESUMO
Cysteine, the rate-controlling amino acid in cellular glutathione synthesis is imported as cystine, by the cystine/glutamate antiporter, xCT, and subsequently reduced to cysteine. As glutathione redox is important in muscle regeneration in aging, we hypothesized that xCT exerts upstream control over skeletal muscle glutathione redox, metabolism and regeneration. Bioinformatic analyses of publicly available datasets revealed that expression levels of xCT and GSH-related genes are inversely correlated with myogenic differentiation genes. Muscle satellite cells (MuSCs) isolated from Slc7a11sut/sut mice, which harbour a mutation in the Slc7a11 gene encoding xCT, required media supplementation with 2-mercaptoethanol to support cell proliferation but not myotube differentiation, despite persistently lower GSH. Slc7a11sut/sut primary myotubes were larger compared to WT myotubes, and also exhibited higher glucose uptake and cellular oxidative capacities. Immunostaining of myogenic markers (Pax7, MyoD, and myogenin) in cardiotoxin-damaged tibialis anterior muscle fibres revealed greater MuSC activation and commitment to differentiation in Slc7a11sut/sut muscle compared to WT mice, culminating in larger myofiber cross-sectional areas at 21 days post-injury. Slc7a11sut/sut mice subjected to a 5-week exercise training protocol demonstrated enhanced insulin tolerance compared to WT mice, but blunted muscle mitochondrial biogenesis and respiration in response to exercise training. Our results demonstrate that the absence of xCT inhibits cell proliferation but promotes myotube differentiation by regulating cellular metabolism and glutathione redox. Altogether, these results support the notion that myogenesis is a redox-regulated process and may help inform novel therapeutic approaches for muscle wasting and dysfunction in aging and disease.
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Sistema y+ de Transporte de Aminoácidos , Diferenciação Celular , Metabolismo Energético , Glutationa , Músculo Esquelético , Oxirredução , Animais , Camundongos , Glutationa/metabolismo , Músculo Esquelético/metabolismo , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Desenvolvimento Muscular , Células Satélites de Músculo Esquelético/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Cistina/metabolismoRESUMO
In striated muscle, the sarcomeric protein myosin-binding protein-C (MyBP-C) is bound to the myosin thick filament and is predicted to stabilize myosin heads in a docked position against the thick filament, which limits crossbridge formation. Here, we use the homozygous Mybpc2 knockout (C2-/-) mouse line to remove the fast-isoform MyBP-C from fast skeletal muscle and then conduct mechanical functional studies in parallel with small-angle X-ray diffraction to evaluate the myofilament structure. We report that C2-/- fibers present deficits in force production and calcium sensitivity. Structurally, passive C2-/- fibers present altered sarcomere length-independent and -dependent regulation of myosin head conformations, with a shift of myosin heads towards actin. At shorter sarcomere lengths, the thin filament is axially extended in C2-/-, which we hypothesize is due to increased numbers of low-level crossbridges. These findings provide testable mechanisms to explain the etiology of debilitating diseases associated with MyBP-C.
Assuntos
Proteínas de Transporte , Camundongos Knockout , Animais , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Camundongos , Sarcômeros/metabolismo , Miofibrilas/metabolismo , Miofibrilas/genética , Músculo Esquelético/metabolismo , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/genética , Masculino , Miosinas/metabolismo , Miosinas/genéticaRESUMO
Hibernation is a period of metabolic suppression utilized by many small and large mammal species to survive during winter periods. As the underlying cellular and molecular mechanisms remain incompletely understood, our study aimed to determine whether skeletal muscle myosin and its metabolic efficiency undergo alterations during hibernation to optimize energy utilization. We isolated muscle fibers from small hibernators, Ictidomys tridecemlineatus and Eliomys quercinus and larger hibernators, Ursus arctos and Ursus americanus. We then conducted loaded Mant-ATP chase experiments alongside X-ray diffraction to measure resting myosin dynamics and its ATP demand. In parallel, we performed multiple proteomics analyses. Our results showed a preservation of myosin structure in U. arctos and U. americanus during hibernation, whilst in I. tridecemlineatus and E. quercinus, changes in myosin metabolic states during torpor unexpectedly led to higher levels in energy expenditure of type II, fast-twitch muscle fibers at ambient lab temperatures (20 °C). Upon repeating loaded Mant-ATP chase experiments at 8 °C (near the body temperature of torpid animals), we found that myosin ATP consumption in type II muscle fibers was reduced by 77-107% during torpor compared to active periods. Additionally, we observed Myh2 hyper-phosphorylation during torpor in I. tridecemilineatus, which was predicted to stabilize the myosin molecule. This may act as a potential molecular mechanism mitigating myosin-associated increases in skeletal muscle energy expenditure during periods of torpor in response to cold exposure. Altogether, we demonstrate that resting myosin is altered in hibernating mammals, contributing to significant changes to the ATP consumption of skeletal muscle. Additionally, we observe that it is further altered in response to cold exposure and highlight myosin as a potentially contributor to skeletal muscle non-shivering thermogenesis.
Many animals use hibernation as a tactic to survive harsh winters. During this dormant, inactive state, animals reduce or limit body processes, such as heart rate and body temperature, to minimise their energy use. To conserve energy during hibernation, animals can use different approaches. For example, garden dormice undergo periodic states of extremely low core temperatures (down to 48oC); whereas Eurasian brown bears see milder temperature drops (down to 2325oC). An important organ that changes during hibernation is skeletal muscle. Skeletal muscle typically uses large amounts of energy, making up around 50% of body mass. To survive, hibernating animals must change how their skeletal muscle uses energy. Traditionally, active myosin a protein found in muscles that helps muscles to contract was thought to be responsible for most of the energy use by skeletal muscle. But, more recently, resting myosin has also been found to use energy when muscles are relaxed. Lewis et al. studied myosin and skeletal muscle energy use changes during hibernation and whether they could impact the metabolism of hibernating animals. Lewis et al. assessed myosin changes in muscle samples from squirrels, dormice and bears during hibernation and during activity. Experiments showed changes in resting myosin in squirrels and dormice (whose temperature drops to 48oC during hibernation) but not in bears. Further analysis revealed that cooling samples from non-hibernating muscle to 48oC increased energy use in resting myosin, thereby generating heat. However, no increase in energy use was found after cooling hibernating muscle samples to 48oC. This suggest that resting myosin generates heat at cool temperatures a mechanism that is switched off in hibernating animals to allow them to cool their body temperature. These findings reveal key insights into how animals conserve energy during hibernation. In addition, the results show that myosin regulates energy use in skeletal muscles, which indicates myosin may be a potential drug target in metabolic diseases, such as obesity.
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Hibernação , Animais , Hibernação/fisiologia , Metabolismo Energético , Miosinas de Músculo Esquelético/metabolismo , Ursidae/metabolismo , Ursidae/fisiologia , Trifosfato de Adenosina/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Fibras Musculares Esqueléticas/metabolismo , ProteômicaRESUMO
We investigated the involvement of community members in response to the Ebola Virus Disease (EVD) epidemic in the North Kivu and Ituri provinces of the Democratic Republic of Congo. This cross-sectional study, conducted using mixed methods of data collection, included a uniformly structured questionnaire survey, which was administered to 800 randomly selected adults (aged ≥ 18 years). Further, we used qualitative tools of inquiry-focus group discussions (FGD) and in-depth interviews (IDI)-to guide the context of the information collected in the survey. Community leaders, religious leaders, and Ebola survivors were interviewed using the IDI guide, while young men (≤ 30 years), young women (≤30 years), adult community males (<30 years), and adult community females (<30 years) were in separate FGD sessions. The results revealed that the urban area was the most affected by the epidemic (79.2%) compared to 20.8% in rural areas. The χ2 calculated was 18.183 (P<0.001). Community members exhibited varying degrees of involvement in response to the EVD epidemic in the two provinces. Community members were mostly engaged in information dissemination. However, they believe they could have contributed more if they had been fully engaged. These findings were derived from the qualitative data. The study contributes to evidence on how community involvement could help response to public health events globally, hence this study provides valuable insights for future public health interventions and response.
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Perceptions and rumors about vaccinations can contribute to vaccine hesitancy. This study aimed to examine perceptions and rumors about the Ebola vaccine during the 10th Ebola Virus Disease outbreak in the Ituri and North Kivu provinces of the Democratic Republic of Congo. Eight hundred randomly selected respondents were surveyed with a uniform structured questionnaire. Further, we collected qualitative data through focus group discussions and using in-depth interview guides. Results revealed several misperceptions and rumors about the vaccine, which led to some level of vaccine hesitancy and refusal among the people. The acceptance rate of the vaccine was 67.3% (below the 80% threshold needed to create herd immunity in the population). More of the urban population (31.3%) than the rural population (10.4%) accepted the vaccine. Refusals were largely due to fear that the vaccine could activate other diseases in the body and could even kill. Some feared that it was a conspiracy of the government to reduce the population in the study area through forced fertility control and death, among other such concerns. In conclusion, these rumors increased mistrust, which challenged the efforts of the government and its partners to safeguard the health of the people.
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We reviewed the involvement of civil society organizations as well as other community level organizations and structures in the response to the Ebola Virus Disease (EVD) outbreak in the Democratic Republic of Congo. A total of 800 randomly selected adults were surveyed using a uniform set of structured questionnaires. An in-depth interview guide was employed to collect information from community members and religious leaders, while focus group discussions were held with community members. The results revealed some involvement of the different organizations in the communities in the response to the EVD outbreak. However, several challenges were encountered, namely security issues, poor awareness, and non-compliance to safety measures. The findings underscore that despite considerable experience over a long period with outbreaks in the DRC, people still need to be educated about the disease.
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We explored the perceptions and representations of diseases in the North Kivu and Ituri provinces of the Democratic Republic of Congo to identify perceived obstacles regarding responses to the country 's Ebola virus disease (EVD) outbreak using a mix-methods approach. We surveyed a representative sample including 800 adults aged 18 years and older, held in-depth interviews with 17 community leaders, and conducted 10 focus group discussions with community members (using same-sex interviewers/discussion leaders). The results revealed the existence of several health conditions among members of the two communities. Locals consider nearly 80 of these ailments as untreatable by orthodox medicines and methods, even when symptoms are similar to EVD. Creating awareness must be considered a critical goal of community education to further educate these populations about EVD and other health problems and their respective treatments.
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We explored issues around the integration of survivors in communities and the implications for the Ebola Virus Disease (EVD) response in the Democratic Republic of Congo (DRC). We conducted a survey with 800 randomly selected respondents using a structured questionnaire. Respondents were persons aged 18 years and above. Focus group discussions (FGDs) and in-depth interviews (IDIs) were employed to obtain contextual data on the issues. Community leaders, health workers, and response pillar leads engaged in IDIs, while community members were involved in FGDs. The results revealed that the survivors suffered stigmatization and, upon return to the communities, were avoided by the community members due to fear of contamination. Some thought that the survivors should be supported in adjusting to the community, while some recommended engaging the survivors in EVD response activities.
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O basquetebol é um esporte dinâmico com atletas que possuem características muito distintas quanto à estatura, massa corporal, funções e responsabilidade em quadra, que vivem uma busca por resultados e manutenção dos componentes físicos, somados a fatores estressantes da vida social e profissional, os quais podem leva-los a altos níveis de estresse e alterações no Perfi l de Estados de Humor (PEH) em situações de pré-jogo. Desta forma, o presente estudo tem por objetivo analisar os estados de humor pré-jogo em atletas de basquetebol entre competições e posições de jogo. Trata-se de uma pesquisa de caráter descritivo comparativo e transversal, os participantes foram atletas masculinos de basquetebol, divididos em dois grupos: 29 da competição um e 21 da competição dois, totalizando 50 atletas. Para a mensuração do humor foi utilizado a escala de humor de Brunel (BRUMS), que avalia por meio de 24 indicadores simples, que mede seis fatores: tensão, depressão, raiva, vigor, fadiga e confusão mental. A análise dos dados foi através do teste t independente e do teste Anova Oneway, com significância de 95% (p<0,05). A amostra apresentou média de idade de 19,8 ± 2,7 anos, estatura de 181,3 ± 8,5 cm e massa corporal de 78,7 ± 15,3 kg. Os resultados apontam que o PEH dos atletas de basquetebol, entre competições e entre as posições, apresentou um perfil iceberg, resultado considerado pela literatura favorável ao desempenho, não havendo diferenças significativas do PEH entre as posições e competições. Conclui-se que os atletas de basquetebol apresentam respostas semelhantes em relação ao estado emocional entre competições e posições....(AU)
Basketball is a dynamic sport with athletes who have very diff erent characteristics regarding height, body mass, functions and responsibility in court, who live a search for results and maintenance of the physical components, added to stress factors of the athlete's social and professional life, which can lead them to high levels of stress and changes in the Profi le of Mood States (PMS) in pre-game situations. In this way, the present study aims to analyze pre-game mood states in basketball athletes between competitions and game positions. It was a comparative and cross-sectional descriptive study, the participants were male, basketball athletes, divided into two groups: 29 from competition one and 21 from competition two, totaling 50 athletes. The Brunel Mood Scale (BRUMS) used to measure mood, using 24 simple indicators, measuring six factors: tension, depression, anger, force, fatigue and mental confusion. The data were analyzed using the independent t-test, with signifi cance of 95% (p <0.05). The sample had a mean age of 19.8 ± 2.7 years, height of 181.3 ± 8.5 cm and body mass of 78.7 ± 15.3 kg. The results show that the athletes' basketball score, between competitions and between positions, presented an iceberg profi le, result considered by the literature favorable to performance, with no signifi cant diff erences between the positions and competitions. We conclude that basketball athletes present similar responses regarding the emotional state between competitions and positions....(AU)
Assuntos
Humanos , Masculino , Adolescente , Adulto , Educação Física e Treinamento , Estresse Psicológico , Psicologia do EsporteRESUMO
Objetivo: O objetivo deste estudo foi avaliar a presença de DisfunçãoTemporomandibular (DTM) e envolvimento de fatores psicológicos e dor em uma população com Fibromialgia (FM). Materiais e métodos: A amostra foi composta por 50 mulheres tratadas no Ambulatório de Acupuntura e Dor do Hospital das Clínicas da Universidade Federal de Pernambuco (HC-UFPE) com diagnóstico de fibromialgia segundo os critérios do Colégio Americano de Reumatologia. Avaliaram-se a classificação e grau da DTM pelo índice Anamnésico Simplificado e fatores psicológicos envolvidosutilizando-se os Critérios Diagnósticos de Pesquisa em DTM (RDC/TMD): Eixo II. Para análise dos dados foram utilizados os testes estatísticos Qui-quadrado de Pearson e o teste Exato de Fisher. Os cálculos estatísticos foram realizados através do programa Statistical Package for the Social Sciences (SPSS) versão 15 Windows. Resultados: A presença de sinais e sintomas relacionados à DTM foi encontrada em 49 pacientes. A maioria (80,0%) relatou dor na face e com exceção de uma paciente todas tinham dor facial crônica. Depressão foi comprovada em 90,0% das participantes e o grau da DTM mostrou associação significativa (p < 0,05) com o grau da depressão. Conclusão: Há uma alta prevalência de DTMe depressão na população fibromiálgica. A DTM mostrou-se mais intensa nos indivíduos com maior severidade de depressão. Portanto, observa-se a real necessidade de uma abordagem cuidadosa e multidisciplinar aos pacientes com FM e este aspecto deve ser levado em consideração durante sua avaliação e tratamento.
Objective: The aim of this study was to evaluate the presence of Tempomandibular Disorder (TMD) and the involvement of psychological factors and pain in a population with fibromyalgia (FM). Materials and methods: The sample was composed of 50 women who were treated in the Acupuncture and Pain Facility of the Hospital das Clínicas of the Universidade Federal de Pernambuco (HC-UFPE) with diagnosis of fibromyalgia according to the criteria of the American College of Rheumatology (ACR). The TMD classification and degree were evaluated by the Simplified Anamnestic Index and involved psychological factors byusing the Research Diagnostic Criteria in TMD (RCD/TMD): Axis II. For data analysis, Pearson´s chi-squared and Fisher´s Exact Test statistical tests were used. The statistical calculi were fulfilled by means of the Statistical Package for the Social Sciences (SPSS) program version 15 Windows. Results: The presence of signs and symptoms related to TMD was found in 49 patients. The majority (80,0%) reported pain in the face and, with the exception of one patient, all had chronic facial pain. Depression was proved in 90,0% of the participants and the TMD degree showed significantassociation (p < 0,05) with the depression level. Conclusion: Thereis a high prevalence of TMD and depression in population with fibromyalgia. The TMD showed to be more intense in individuals with higher severity in depression. Therefore, the real need of a careful and multidisciplinary approach devoted to the patients with FM is observed and this aspect should be taken into consideration during its evaluation and treatment.