Non-targeted metabolomics in sport and exercise science

Metabolomics incorporates the study of metabolites that are produced and released through physiological processes at both the systemic and cellular level. Biological compounds at the metabolite level are of paramount interest in the sport and exercise sciences, although research in this field has rarely been referred to with the global ‘omics terminology. Commonly studied metabolites in exercise science are notably within cellular pathways for ATP production such as glycolysis (e.g. pyruvate and lactate), β-oxidation of free fatty acids (e.g. palmitate) and ketone bodies (e.g. β-hydroxybutyrate). Non-targeted metabolomic technologies are able to simultaneously analyse the large numbers of metabolites present in human biological samples such as plasma, urine and saliva. These analytical technologies predominately employ nuclear magnetic resonance spectroscopy and chromatography coupled to mass spectrometry. Performing experiments based on non-targeted methods allows for systemic metabolite changes to be analysed and compared to a particular physiological state (e.g. pre/post-exercise) and provides an opportunity to prospect for metabolite signatures that offer beneficial information for translation into an exercise science context, for both elite performance and public health monitoring. This narrative review provides an introduction to non-targeted metabolomic technologies and discusses current and potential applications in sport and exercise science

Vitamin D during pregnancy: why observational studies suggest deficiency and interventional studies show no improvement in clinical outcomes? A narrative review

International audienc

Differential regulation of myeloid leukemias by the bone marrow microenvironment

Like their normal hematopoietic stem cell counterparts, leukemia stem cells (LSC) in chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML) are presumed to reside in specific niches in the bone marrow microenvironment (BMM)1, and may be the cause of relapse following chemotherapy.2 Targeting the niche is a novel strategy to eliminate persistent and drug-resistant LSC. CD443,4 and IL-65 have been implicated previously in the LSC niche. Transforming growth factor (TGF)-β1 is released during bone remodeling6 and plays a role in maintenance of CML LSCs7, but a role for TGF-β1 from the BMM has not been defined. Here, we show that alteration of the BMM by osteoblastic cell-specific activation of the parathyroid hormone (PTH) receptor8,9 attenuates BCR-ABL1-induced CML-like myeloproliferative neoplasia (MPN)10 but enhances MLL-AF9-induced AML11 in mouse transplantation models, possibly through opposing effects of increased TGF-β1 on the respective LSC. PTH treatment caused a 15-fold decrease in LSCs in wildtype mice with CML-like MPN, and reduced engraftment of immune deficient mice with primary human CML cells. These results demonstrate that LSC niches in chronic and acute myeloid leukemias are distinct, and suggest that modulation of the BMM by PTH may be a feasible strategy to reduce LSC, a prerequisite for the cure of CML

The role of peer physical activity champions in the workplace: a qualitative study

Aims: Peer health champions are suggested as an important component of multilevel workplace interventions to promote healthy behaviours such as physical activity. There is accumulating quantitative evidence of their effectiveness but as yet little exploration of why and how champions influence the behaviour of their peers. The current study explores the role of peer physical activity champions (PPACs) in influencing colleagues’ physical activity behaviour from the perspectives of both champions and colleagues. Methods: Seven months after the introduction of a workplace physical activity programme in 17 small and medium sized enterprices (SMEs) two focus groups were held with PPACs and four with programme participants. Focus groups were semi-structured and topics covered included: the influence of PPACs and other colleagues on their physical activity, characteristics of an effective PPAC and feelings about the PPAC role. Data were analysed using inductive thematic analysis. Results: Three overarching themes emerged: how PPACs encourage physical activity; valuable PPAC characteristics; and sustaining motivation for the PPAC role. Both direct encouragement from PPACs and facilitation of wider physical activity supportive social networks within the workplace encouraged behaviour change. Physical activity behaviour change is a delicate subject and it was important that PPACs provided enthusiastic and persistent encouragement without seeming judgemental. Being a physical activity role model was also a valuable characteristic. The PPACs found it satisfying to see positive changes in their colleagues who had become more active. However, colleagues often did not engage in suggested activities and PPACs required resilience to maintain personal motivation for the role despite this. Conclusions: The results indicate that it is feasible to incorporate PPACs into SME based physical activity interventions. Given the importance that participants attached to feeling part of a group of individuals with a common aim of increasing their physical activity, it is recommended that PPAC training includes suggestions for facilitating social connections between colleagues. Sensitivity is required when initiating and engaging in conversations with colleagues about increasing their physical activity and therefore brief motivational interviewing training may be helpful for PPACs. Programmes should ensure PPACs themselves are provided with social support, especially from others in the same role, to help sustain motivation for their role. These findings will be useful to health-promotion professionals developing workplace health programmes. Future research should explore the processes by which peer health champions facilitate changes in a range of health behaviours to identify common and behaviour specific recommendations

A monolithic single-chip point-of-care platform for metabolomic prostate cancer detection

There is a global unmet need for rapid and cost-effective prognostic and diagnostic tools that can be used at the bedside or in the doctor's office to reduce the impact of serious disease. Many cancers are diagnosed late, leading to costly treatment and reduced life expectancy. With prostate cancer, the absence of a reliable test has inhibited the adoption of screening programs. We report a microelectronic point-of-care metabolite biomarker measurement platform and use it for prostate cancer detection. The platform, using an array of photodetectors configured to operate with targeted, multiplexed, colorimetric assays confined in monolithically integrated passive microfluidic channels, completes a combined assay of 4 metabolites in a drop of human plasma in under 2 min. A preliminary clinical study using L-amino acids, glutamate, choline, and sarcosine was used to train a cross-validated random forest algorithm. The system demonstrated sensitivity to prostate cancer of 94% with a specificity of 70% and an area under the curve of 0.78. The technology can implement many similar assay panels and hence has the potential to revolutionize low-cost, rapid, point-of-care testing

Political Parties and Interest Organizations at the Crossroads: Perspectives on the Transformation of Political Organizations

This article reviews the case for considering the study of parties and interest organizations together, under the umbrella of “political organizations.” While both literatures are rather disconnected at the moment, we believe that they share many commonalities. A common narrative involves the apparent transformation of parties and interest organizations, as both organizations are continuously adapting to changing environments. In this review, we integrate both literatures and assess arguments for organizational convergence vis-à-vis claims of continuing diversity. Building upon recent work that takes a more joined-up approach, we advance a common research agenda that demonstrates the value and feasibility of studying these organizations in tandem.The politics and administration of institutional chang

Cryptic splicing events in the iron transporter ABCB7 and other key target genes in SF3B1-mutant myelodysplastic syndromes.

The splicing factor SF3B1 is the most frequently mutated gene in myelodysplastic syndromes (MDS), and is strongly associated with the presence of ring sideroblasts (RS). We have performed a systematic analysis of cryptic splicing abnormalities from RNA sequencing data on hematopoietic stem cells (HSCs) of SF3B1-mutant MDS cases with RS. Aberrant splicing events in many downstream target genes were identified and cryptic 3' splice site usage was a frequent event in SF3B1-mutant MDS. The iron transporter ABCB7 is a well-recognized candidate gene showing marked downregulation in MDS with RS. Our analysis unveiled aberrant ABCB7 splicing, due to usage of an alternative 3' splice site in MDS patient samples, giving rise to a premature termination codon in the ABCB7 mRNA. Treatment of cultured SF3B1-mutant MDS erythroblasts and a CRISPR/Cas9-generated SF3B1-mutant cell line with the nonsense-mediated decay (NMD) inhibitor cycloheximide showed that the aberrantly spliced ABCB7 transcript is targeted by NMD. We describe cryptic splicing events in the HSCs of SF3B1-mutant MDS, and our data support a model in which NMD-induced downregulation of the iron exporter ABCB7 mRNA transcript resulting from aberrant splicing caused by mutant SF3B1 underlies the increased mitochondrial iron accumulation found in MDS patients with RS