FOOT STRIKE PATTERN trends in sub-elite half marathon runners

The purpose of this study was to examine the changes in foot strike patterns throughout a sub elite half-marathon and examine the relationship between foot strike pattern and race performance. Race participants were filmed at mile 2, 5.5 and 12.5. Video was analysed to determine if participants used a forefoot, mid-foot strike or rear foot strike pattern at each camera. Furthermore participants were broken down in performance groups of 50 based off of time taken to reach each camera. At mile 5.5 and 12.5 significant difference in foot strike pattern (

Expression patterns of Neil3 during embryonic brain development and neoplasia

<p>Abstract</p> <p>Background</p> <p>The base excision repair pathway is responsible for repairing small DNA base lesions caused by endogenous and exogenous damaging agents. Repair is initiated by DNA glycosylases that recognize and remove the lesions. NEIL3 is one of 11 mammalian DNA glycosylases identified to date and it was discovered on the basis of sequence homology to the <it>E. coli </it>Fpg and Nei glycosylases. Difficulties in purifying the protein have limited its biochemical characterization and in contrast to the other glycosylases, its function remains unclear.</p> <p>Results</p> <p>In this study we describe the expression pattern of <it>Neil3 </it>during mouse embryonic development with special focus on brain development. We have also looked at the expression of <it>NEIL3 </it>in several normal and tumor tissues. Quantitative real-time PCR and <it>in situ </it>hybridization revealed that <it>Neil3 </it>was highly expressed at embryonic days 12–13, when neurogenesis starts. The expression decreased during development and in the adult brain,<it>Neil3 </it>could not be detected in any of the brain areas examined by quantitative real-time PCR. During embryogenesis and in newborn mice specific expression was observed in areas known to harbour neural stem and progenitor cells such as the subventricular zone and the dentate gyrus. Finally, <it>NEIL3 </it>expression was higher in tumors compared to normal tissues, except for testis and pancreas.</p> <p>Conclusion</p> <p>Our findings indicate that mammalian NEIL3 is specifically expressed in brain areas where neurogenesis takes place during development and that its expression is tightly regulated both temporally and spatially. In addition, <it>NEIL3 </it>seems to be upregulated in tumor tissues compared to normal tissues. Altogether, mammalian <it>NEIL3 </it>seems to be highly expressed in cells with high proliferative potential.</p

Responsive and Equitable Health Systems-Partnership on Non-Communicable Diseases (RESPOND) study: a mixed-methods, longitudinal, observational study on treatment seeking for hypertension in Malaysia and the Philippines.

INTRODUCTION: Hypertension is a leading contributor to the global burden of disease. While safe and effective treatment exists, blood pressure control is poor in many countries, often reflecting barriers at the levels of health systems and services as well as at the broader level of patients' sociocultural contexts. This study examines how these interact to facilitate or hinder hypertension control, taking into account characteristics of service provision components and social contexts. METHODS AND ANALYSIS: The study, set in Malaysia and the Philippines, builds on two systematic reviews of barriers to effective hypertension management. People with hypertension (pre-existing and newly diagnosed) will be identified in poor households in 24-30 communities per country. Quantitative and qualitative methods will be used to examine their experiences of and pathways into seeking and obtaining care. These include two waves of household surveys of 20-25 participants per community 12-18 months apart, microcosting exercises to assess the cost of illness (including costs due to health seeking activities and inability to work (5 per community)), preliminary and follow-up in-depth interviews and digital diaries with hypertensive adults over the course of a year (40 per country, employing an innovative mobile phone technology), focus group discussions with study participants and structured assessments of health facilities (including formal and informal providers). ETHICS AND DISSEMINATION: Ethical approval has been granted by the Observational Research Ethics Committee at the London School of Hygiene and Tropical Medicine and the Research Ethics Boards at the Universiti Putra Malaysia and the University of the Philippines Manila. The project team will disseminate findings and engage with a wide range of stakeholders to promote uptake and impact. Alongside publications in high-impact journals, dissemination activities include a comprehensive stakeholder analysis, engagement with traditional and social media and 'digital stories' coproduced with research participants

C/EBP beta-LIP induces cancer-type metabolic reprogramming by regulating the let-7/LIN28B circuit in mice

The transcription factors LAP1, LAP2 and LIP are derived from the Cebpb-mRNA through the use of alternative start codons. High LIP expression has been associated with human cancer and increased cancer incidence in mice. However, how LIP contributes to cellular transformation is poorly understood. Here we present that LIP induces aerobic glycolysis and mitochondrial respiration reminiscent of cancer metabolism. We show that LIP-induced metabolic programming is dependent on the RNA-binding protein LIN28B, a translational regulator of glycolytic and mitochondrial enzymes with known oncogenic function. LIP activates LIN28B through repression of the let-7 microRNA family that targets the Lin28b-mRNA. Transgenic mice overexpressing LIP have reduced levels of let-7 and increased LIN28B expression, which is associated with metabolic reprogramming as shown in primary bone marrow cells, and with hyperplasia in the skin. This study establishes LIP as an inducer of cancer-type metabolic reprogramming and as a regulator of the let-7/LIN28B regulatory circuit

Rapid, ultra low coverage copy number profiling of cell-free DNA as a precision oncology screening strategy.

Current cell-free DNA (cfDNA) next generation sequencing (NGS) precision oncology workflows are typically limited to targeted and/or disease-specific applications. In advanced cancer, disease burden and cfDNA tumor content are often elevated, yielding unique precision oncology opportunities. We sought to demonstrate the utility of a pan-cancer, rapid, inexpensive, whole genome NGS of cfDNA approach (PRINCe) as a precision oncology screening strategy via ultra-low coverage (~0.01x) tumor content determination through genome-wide copy number alteration (CNA) profiling. We applied PRINCe to a retrospective cohort of 124 cfDNA samples from 100 patients with advanced cancers, including 76 men with metastatic castration-resistant prostate cancer (mCRPC), enabling cfDNA tumor content approximation and actionable focal CNA detection, while facilitating concordance analyses between cfDNA and tissue-based NGS profiles and assessment of cfDNA alteration associations with mCRPC treatment outcomes. Therapeutically relevant focal CNAs were present in 42 (34%) cfDNA samples, including 36 of 93 (39%) mCRPC patient samples harboring AR amplification. PRINCe identified pre-treatment cfDNA CNA profiles facilitating disease monitoring. Combining PRINCe with routine targeted NGS of cfDNA enabled mutation and CNA assessment with coverages tuned to cfDNA tumor content. In mCRPC, genome-wide PRINCe cfDNA and matched tissue CNA profiles showed high concordance (median Pearson correlation = 0.87), and PRINCe detectable AR amplifications predicted reduced time on therapy, independent of therapy type (Kaplan-Meier log-rank test, chi-square = 24.9, p &lt; 0.0001). Our screening approach enables robust, broadly applicable cfDNA-based precision oncology for patients with advanced cancer through scalable identification of therapeutically relevant CNAs and pre-/post-treatment genomic profiles, enabling cfDNA- or tissue-based precision oncology workflow optimization

Frizzled-3a and slit2 genetically interact to modulate midline axon crossing in the telencephalon

The anterior commissure forms the first axon connections between the two sides of the embryonic telencephalon. We investigated the role of the transmembrane receptor Frizzled-3a in the development of this commissure using zebrafish as an experimental model. Knock down of Frizzled-3a resulted in complete loss of the anterior commissure. This defect was accompanied by a loss of the glial bridge, expansion of the slit2 expression domain and perturbation of the midline telencephalic-diencephalic boundary. Blocking Slit2 activity following knock down of Frizzled-3a effectively rescued the anterior commissure defect which suggested that Frizzled-3a was indirectly controlling the growth of axons across the rostral midline. We have shown here that Frizzled-3a is essential for normal development of the commissural plate and that loss-of-function causes Slit2-dependent defects in axon midline crossing in the embryonic vertebrate forebrain. These data supports a model whereby Wnt signaling through Frizzled-3a attenuates expression of Slit2 in the rostral midline of the forebrain. The absence of Slit2 facilitates the formation of a midline bridge of glial cells which is used as a substrate for commissural axons. In the absence of this platform of glia, commissural axons fail to cross the rostral midline of the forebrain. Crown copyright (C) 2012 Published by Elsevier Ireland Ltd. All rights reserved

A threatened ecological community: Research advances and priorities for Banksia woodlands

The rapid expansion of urban areas worldwide is leading to native habitat loss and ecosystem fragmentation and degradation. Although the study of urbanisation\u27s impact on biodiversity is gaining increasing interest globally, there is still a disconnect between research recommendations and urbanisation strategies. Expansion of the Perth metropolitan area on the Swan Coastal Plain in south-western Australia, one of the world\u27s thirty-six biodiversity hotspots, continues to affect the Banksia Woodlands (BWs) ecosystem, a federally listed Threatened Ecological Community (TEC). Here, we utilise the framework of a 1989 review of the state of knowledge of BWs ecology and conservation to examine scientific advances made in understanding the composition, processes and functions of BWs and BWs\u27 species over the last 30 years. We highlight key advances in our understanding of the ecological function and role of mechanisms in BWs that are critical to the management of this ecosystem. The most encouraging change since 1989 is the integration of research between historically disparate ecological disciplines. We outline remaining ecological knowledge gaps and identify key research priorities to improve conservation efforts for this TEC. We promote a holistic consideration of BWs with our review providing a comprehensive document that researchers, planners and managers may reference. To effectively conserve ecosystems threatened by urban expansion, a range of stakeholders must be involved in the development and implementation of best practices to conserve and maintain both biodiversity and human wellbeing

Virological and serological surveillance for type A influenza in the black-legged kittiwake (Rissa tridactyla)

<p>Abstract</p> <p>Background</p> <p>The epidemiology of avian influenza viruses (AIVs) in gulls is only partially known. The role of the world's most numerous gull species, the black-legged kittiwake (<it>Rissa tridactyla</it>), as a potential AIV reservoir species has been unclear. The prevalence of AIV and humoral response against AIV were therefore studied in a colony of apparently healthy black-legged kittiwakes breeding in a nesting cliff in the South West Barents Region of Norway (70°22' N, 31°10' E), in 2008 and 2009.</p> <p>Results</p> <p>AIVs were detected from the oropharynx and cloaca in low amounts, with prevalences of 15% and 5%, in 2008 and 2009, respectively. Direct, partial sequencing of the hemagglutinin (HA) gene revealed that the H4 subtype was present. In 2009, antibodies to influenza A virus were detected in sera from 57 of 80 adult birds. In contrast, none of the three-week-old chicks (n = 18) tested seropositive. Hemagglutination inhibition (HI) assays demonstrated that the adult kittiwakes primarily had antibodies specific to the gull-associated H13 and H16 subtypes, with antibodies to H16 being most common.</p> <p>Conclusions</p> <p>These results support that the highly pelagic black-legged kittiwake is a reservoir of AIV. The serological findings suggest that H16 might be the main AIV subtype in the black-legged kittiwake. Further studies are needed to understand the ecology of AIV in the black-legged kittiwake and in gulls in general.</p