Serum Amyloid A induces toll-like receptor 2-dependent inflammatory cytokine expression and atrophy in C2C12 skeletal muscle myotubes

Background Skeletal muscle wasting is an important comorbidity of Chronic Obstructive Pulmonary Disease (COPD) and is strongly correlated with morbidity and mortality. Patients who experience frequent acute exacerbations of COPD (AECOPD) have more severe muscle wasting and reduced recovery of muscle mass and function after each exacerbation. Serum levels of the pro-inflammatory acute phase protein Serum Amyloid A (SAA) can rise more than 1000-fold in AECOPD and are predictively correlated with exacerbation severity. The direct effects of SAA on skeletal muscle are poorly understood. Here we have examined SAA effects on pro-inflammatory cachectic cytokine expression (IL-6 and TNFα) and atrophy in C2C12 myotubes. Results SAA increased IL-6 (31-fold) and TNFα (6.5-fold) mRNA levels compared to control untreated cells after 3h of SAA treatment, and increased secreted IL-6 protein at 24h. OxPAPC, a dual TLR2 and TLR4 inhibitor, reduced the response to SAA by approximately 84% compared to SAA alone, and the TLR2 neutralising antibody T2.5 abolished SAA-induced expression of IL-6, indicating that SAA signalling in C2C12 myotubes is primarily via TLR2. SAA also reduced myotube width by 10-13% and induced a 2.5-fold increase in the expression of the muscle atrophy gene Atrogin-1, suggesting direct effects of SAA on muscle wasting. Blocking of TLR2 inhibited the SAA-induced decrease in myotube width and Atrogin-1 gene expression, indicating that SAA induces atrophy through TLR2. Conclusions These data demonstrate that SAA stimulates a robust pro-inflammatory response in skeletal muscle myotubes via the TLR2-dependent release of IL-6 and TNFα. Furthermore, the observed atrophy effects indicate that SAA could also be directly contributing to the wasting and poor recovery of muscle mass. Therapeutic strategies targeting this SAA-TLR2 axis may therefore ameliorate muscle wasting in AECOPD and a range of other inflammatory conditions associated with loss of m

Management of Reseeded Range and its Place in Ranch Operation

This material was digitized as part of a cooperative project between the Society for Range Management and the University of Arizona Libraries.The Journal of Range Management archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform August 202

Geochemical stratigraphy and correlation within Large Igneous Provinces : the final preserved stages of the Faroe Islands Basalt Group

Acknowledgements The authors would like to thank Andrew Kerr for editorial handling of the manuscript. Lotte Larsen and Bob Gooday are kindly thanked for detailed and constructive reviews of the original submission which substantially improved the manuscript.Peer reviewedPostprin

Mechanical stimulation of 3D bio-engineered skeletal muscle

Skeletal muscle is a highly plastic tissue, responding to exercise and mechanical loading. In vitro culture systems have been used to replicate this mechanical stimulus in order to study cellular and molecular adaptations. Previous research using such models has often lacked bio-mimicity, with respect to the in vitro culture, the mechanical loading, or both. This has lead to contradictory findings with regards to a variety of molecular outputs. Cell culture matrix and environment (2D or 3D), the type of mechanical loading (uni-axial or multi-axial) and the extent, speed and duration of stretching, are all likely to affect the adaptive responses of the cells and their maturation into functional muscle models. It is therefore necessary to develop a model which has greater physiological relevance if such models are to be used to further understand in vivo physiology

Emplacement of inflated Pāhoehoe flows in the Naude’s Nek Pass, Lesotho remnant, Karoo continental flood basalt province: use of flow-lobe tumuli in understanding flood basalt emplacement

Physical volcanological features are presented for a 710-m-thick section, of the Naude’s Nek Pass, within the lower part of the Lesotho remnant of the Karoo Large Igneous Province. The section consists of inflated pāhoehoe lava with thin, impersistent sedimentary interbeds towards the base. There are seven discreet packages of compound and hummocky pāhoehoe lobes containing flow-lobe tumuli, making up approximately 50% of the section. Approximately 45% of the sequence consists of 14 sheet lobes, between 10 and 52-m-thick. The majority of the sheet lobes are in two packages indicating prolonged periods of lava supply capable of producing thick sheet lobes. The other sheet lobes are as individual lobes or pairs, within compound flows, suggesting brief increases in lava supply rate. We suggest, contrary to current belief, that there is no evidence that compound flows are proximal to source and sheet lobes (simple flows) are distal to source and we propose that the presence of flow-lobe tumuli in compound flows could be an indicator that a flow is distal to source. We use detailed, previously published, studies of the Thakurvadi Formation (Deccan Traps) as an example. We show that the length of a lobe and therefore the sections that are ‘medial or distal to source’ are specific to each individual lobe and are dependent on the lava supply of each eruptive event, and as such flow lobe tumuli can be used as an indicator of relative distance from source

Use of an in vitro muscle model to investigate cellular and molecular aspects of exercise physiology: Answering the key questions

Research within exercise physiology has traditionally focused upon measurements of gross physiological function of skeletal muscle. However, in order to develop a greater understanding of the exact mechanisms that contribute to skeletal muscle in response to exercise, the cellular and molecular determinants need to be investigated. There is a growing body of in vivo research utilising methods of molecular biology, which has led to the establishment of proposed genes and proteins involved in the adaptation of skeletal muscle to exercise stimuli. In vivo exercise testing poses problems with regards to experimental control; accounting for inter-individual differences and methods relating to tissue sampling are common flaws of such research. In vitro models of skeletal muscle for investigating adaptation to exercise are in their infancy and generally lack biomimicity. It is therefore necessary to develop a model which has greater physiological relevance with respect to exercise, which encompasses the nature of the investigations currently underway in our laboratory

Serum amyloid A primes microglia for ATP-dependent interleukin-1\u3b2 release

Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves production of acute-phase proteins, including serum amyloid A (SAA). Interleukin-1\u3b2 (IL-1\u3b2), a master regulator of neuroinflammation produced by activated inflammatory cells of the myeloid lineage, in particular microglia, plays a key role in the pathogenesis of acute and chronic diseases of the peripheral nervous system and CNS. IL-1\u3b2 release is promoted by ATP acting at the purinergic P2X7 receptor (P2X7R) in cells primed with toll-like receptor (TLR) ligands

Reintroducing face-to-face support alongside remote support to form a hybrid stop smoking service in England: a formative mixed methods evaluation

Background During the COVID-19 pandemic, United Kingdom (UK) stop smoking services had to shift to remote delivery models due to social distancing regulations, later reintroducing face-to-face provision. The “Living Well Smokefree” service in North Yorkshire County Council adopted a hybrid model offering face-to-face, remote, or a mix of both. This evaluation aimed to assess the hybrid approach’s strengths and weaknesses and explore potential improvements. Methods Conducted from September 2022 to February 2023, the evaluation consisted of three components. First, qualitative interviews involved 11 staff and 16 service users, analysed thematically. Second, quantitative data from the QuitManager system that monitored the numbers and proportions of individuals selecting and successfully completing a 4-week quit via each service option. Third, face-to-face service expenses data was used to estimate the value for money of additional face-to-face provision. The qualitative findings were used to give context to the quantitative data via an “expansion” approach and complementary analysis. Results Overall, a hybrid model was seen to provide convenience and flexible options for support. In the evaluation, 733 individuals accessed the service, with 91.3% selecting remote support, 6.1% face-to-face, and 2.6% mixed provision. Remote support was valued by service users and staff for promoting openness, privacy, and reducing stigma, and was noted as removing access barriers and improving service availability. However, the absence of carbon monoxide monitoring in remote support raised accountability concerns. The trade-off in “quantity vs. quality” of quits was debated, as remote support reached more users but produced fewer carbon monoxide-validated quits. Primarily offering remote support could lead to substantial workloads, as staff often extend their roles to include social/mental health support, which was sometimes emotionally challenging. Offering service users a choice of support options was considered more important than the “cost-per-quit”. Improved dissemination of information to support service users in understanding their options for support was suggested. Conclusions The hybrid approach allows smoking cessation services to evaluate which groups benefit from remote, face-to-face, or mixed options and allocate resources accordingly. Providing choice, flexible provision, non-judgmental support, and clear information about available options could improve engagement and match support to individual needs, enhancing outcomes

The Prevalence of Sexually Transmitted Infections in Papua New Guinea: A Systematic Review and Meta-Analysis

Patellofemoral osteoarthritis (PF OA) is more prevalent than previously thought and contributes to patient's suffering from knee OA. Synthesis of prevalence data can provide estimates of the burden of PF OA

NP3 Exploratory Study 8:Report from the project New Purposes, New Practices, New Pedagogies (NP3)

New Purposes – New Practices – New Pedagogy (NP3) is a collaboration between The Open University, Lancaster University and Manchester Metropolitan University, led by Professor Peter Twining. NP3 is finding out about how children's digital practices influence teaching and learning. NP3 aims to find out about how children use digital devices outside school and what influence (if any) these practices have on what pupils and teachers do inside primary schools. The focus is on pedagogy across the curriculum (rather than the teaching of computing). Our Research Questions (RQs) for these exploratory studies are: RQ1 What are the digital practices that pupils bring to their learning in school? RQ2 Across subject domains what do teachers’ intended and enacted pedagogic practices indicate about their awareness of and the value accorded to pupils’ digital competencies, and how do pupils’ experience these pedagogic practices? RQ3 What institutional circumstances and practices enable or undermine how pupils’ digital competencies and practices are recognised (RQ1) and integrated into teachers’ practice (RQ2)? This brief report provides a snapshot of the digital practices evident in one of the 10 Exploratory Studies that we conducted between October 2015 and March 2016, with a summary of emerging findings from this Exploratory Study. For further details about NP3 go to http://www.np3.org.uk