Predictors of Segmented School Day Physical Activity and Sedentary Time in Children from A Northwest England Low-income Community

Background: Schools have been identified as important settings for health promotion through physical activity participation, particularly as children are insufficiently active for health. The aim of this study was to investigate the child and school-level influences on children′s physical activity levels and sedentary time during school hours in a sample of children from a low-income community; Methods: One hundred and eighty-six children (110 boys) aged 9–10 years wore accelerometers for 7 days, with 169 meeting the inclusion criteria of 16 h∙day−1 for a minimum of three week days. Multilevel prediction models were constructed to identify significant predictors of sedentary time, light, and moderate to vigorous physical activity during school hour segments. Child-level predictors(sex, weight status, maturity offset, cardiorespiratory fitness, physical activity self-efficacy, physical activity enjoyment) and school-level predictors (number on roll, playground area, provision score) were entered into the models; Results: Maturity offset, fitness, weight status, waist circumference-to-height ratio, sedentary time, moderate to vigorous physical activity, number of children on roll and playground area significantly predicted physical activity and sedentary time; Conclusions: Research should move towards considering context-specific physical activity and its correlates to better inform intervention strategies

Amyloid-Like Aggregates of the Yeast Prion Protein Ure2 Enter Vertebrate Cells by Specific Endocytotic Pathways and Induce Apoptosis

BACKGROUND: A number of amyloid diseases involve deposition of extracellular protein aggregates, which are implicated in mechanisms of cell damage and death. However, the mechanisms involved remain poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Here we use the yeast prion protein Ure2 as a generic model to investigate how amyloid-like protein aggregates can enter mammalian cells and convey cytotoxicity. The effect of three different states of Ure2 protein (native dimer, protofibrils and mature fibrils) was tested on four mammalian cell lines (SH-SY5Y, MES23.5, HEK-293 and HeLa) when added extracellularly to the medium. Immunofluorescence using a polyclonal antibody against Ure2 showed that all three protein states could enter the four cell lines. In each case, protofibrils significantly inhibited the growth of the cells in a dose-dependent manner, fibrils showed less toxicity than protofibrils, while the native state had no effect on cell growth. This suggests that the structural differences between the three protein states lead to their different effects upon cells. Protofibrils of Ure2 increased membrane conductivity, altered calcium homeostasis, and ultimately induced apoptosis. The use of standard inhibitors suggested uptake into mammalian cells might occur via receptor-mediated endocytosis. In order to investigate this further, we used the chicken DT40 B cell line DKOR, which allows conditional expression of clathrin. Uptake into the DKOR cell-line was reduced when clathrin expression was repressed suggesting similarities between the mechanism of PrP uptake and the mechanism observed here for Ure2. CONCLUSIONS/SIGNIFICANCE: The results provide insight into the mechanisms by which amyloid aggregates may cause pathological effects in prion and amyloid diseases

Elevated Plasma Von Willebrand Factor and Propeptide Levels in Malawian Children with Malaria

In children with malaria plasma VWF and propeptide levels are markedly elevated in both cerebral and mild paediatric malaria, with levels matching disease severity, and these normalize upon recovery. High levels of both markers also occur in retinopathy-negative 'cerebral malaria' cases, many of whom are thought to be suffering from diseases other than malaria, indicating that further studies of these markers will be required to determine their sensitivity and specificity

Bonobo personality traits are heritable and associated with vasopressin receptor gene 1a variation

Despite being closely related, bonobos and chimpanzees show remarkable behavioral differences, the proximate origins of which remain unknown. This study examined the link between behavioral variation and variation in the vasopressin 1a receptor gene (Avpr1a) in bonobos. Chimpanzees are polymorphic for a ~360 bp deletion (DupB), which includes a microsatellite (RS3) in the 5′ promoter region of Avpr1a. In chimpanzees, the DupB deletion has been linked to lower sociability, lower social sensitivity, and higher anxiety. Chimpanzees and bonobos differ on these traits, leading some to believe that the absence of the DupB deletion in bonobos may be partly responsible for these differences, and to the prediction that similar associations between Avpr1a genotypes and personality traits should be present in bonobos. We identified bonobo personality dimensions using behavioral measures (Sociability(B), Boldness(B), Openness(B), Activity(B)) and trait ratings (Assertiveness(R), Conscientiousness(R), Openness(R), Agreeableness(R), Attentiveness(R), Extraversion(R)). In the present study we found that all 10 dimensions have nonzero heritabilities, indicating there is a genetic basis to personality, and that bonobos homozygous for shorter RS3 alleles were lower in Attentiveness(R) and higher in Openness(B). These results suggest that variations in Avpr1a genotypes explain both within and between species differences in personality traits of bonobos and chimpanzees

Reoccurring patterns in hierarchical protein materials and music: The power of analogies

Complex hierarchical structures composed of simple nanoscale building blocks form the basis of most biological materials. Here we demonstrate how analogies between seemingly different fields enable the understanding of general principles by which functional properties in hierarchical systems emerge, similar to an analogy learning process. Specifically, natural hierarchical materials like spider silk exhibit properties comparable to classical music in terms of their hierarchical structure and function. As a comparative tool here we apply hierarchical ontology logs (olog) that follow a rigorous mathematical formulation based on category theory to provide an insightful system representation by expressing knowledge in a conceptual map. We explain the process of analogy creation, draw connections at several levels of hierarchy and identify similar patterns that govern the structure of the hierarchical systems silk and music and discuss the impact of the derived analogy for nanotechnology.Comment: 13 pages, 3 figure

The Role of Intrinsically Unstructured Proteins in Neurodegenerative Diseases

The number and importance of intrinsically disordered proteins (IUP), known to be involved in various human disorders, are growing rapidly. To test for the generalized implications of intrinsic disorders in proteins involved in Neurodegenerative diseases, disorder prediction tools have been applied to three datasets comprising of proteins involved in Huntington Disease (HD), Parkinson's disease (PD), Alzheimer's disease (AD). Results show, in general, proteins in disease datasets possess significantly enhanced intrinsic unstructuredness. Most of these disordered proteins in the disease datasets are found to be involved in neuronal activities, signal transduction, apoptosis, intracellular traffic, cell differentiation etc. Also these proteins are found to have more number of interactors and hence as the proportion of disorderedness (i.e., the length of the unfolded stretch) increased, the size of the interaction network simultaneously increased. All these observations reflect that, “Moonlighting” i.e. the contextual acquisition of different structural conformations (transient), eventually may allow these disordered proteins to act as network “hubs” and thus they may have crucial influences in the pathogenecity of neurodegenerative diseases

Cytotoxic drug sensitivity of Epstein-Barr virus transformed lymphoblastoid B-cells

BACKGROUND: Epstein-Barr virus (EBV) is the causative agent of immunosuppression associated lymphoproliferations such as post-transplant lymphoproliferative disorder (PTLD), AIDS related immunoblastic lymphomas (ARL) and immunoblastic lymphomas in X-linked lymphoproliferative syndrome (XLP). The reported overall mortality for PTLD often exceeds 50%. Reducing the immunosuppression in recipients of solid organ transplants (SOT) or using highly active antiretroviral therapy in AIDS patients leads to complete remission in 23–50% of the PTLD/ARL cases but will not suffice for recipients of bone marrow grafts. An additional therapeutic alternative is the treatment with anti-CD20 antibodies (Rituximab) or EBV-specific cytotoxic T-cells. Chemotherapy is used for the non-responding cases only as the second or third line of treatment. The most frequently used chemotherapy regimens originate from the non-Hodgkin lymphoma protocols and there are no cytotoxic drugs that have been specifically selected against EBV induced lymphoproliferative disorders. METHODS: As lymphoblastoid cell lines (LCLs) are well established in vitro models for PTLD, we have assessed 17 LCLs for cytotoxic drug sensitivity. After three days of incubation, live and dead cells were differentially stained using fluorescent dyes. The precise numbers of live and dead cells were determined using a custom designed automated laser confocal fluorescent microscope. RESULTS: Independently of their origin, LCLs showed very similar drug sensitivity patterns against 29 frequently used cytostatic drugs. LCLs were highly sensitive for vincristine, methotrexate, epirubicin and paclitaxel. CONCLUSION: Our data shows that the inclusion of epirubicin and paclitaxel into chemotherapy protocols against PTLD may be justified

MTF-1-Mediated Repression of the Zinc Transporter Zip10 Is Alleviated by Zinc Restriction

The regulation of cellular zinc uptake is a key process in the overall mechanism governing mammalian zinc homeostasis and how zinc participates in cellular functions. We analyzed the zinc transporters of the Zip family in both the brain and liver of zinc-deficient animals and found a large, significant increase in Zip10 expression. Additionally, Zip10 expression decreased in response to zinc repletion. Moreover, isolated mouse hepatocytes, AML12 hepatocytes, and Neuro 2A cells also respond differentially to zinc availability in vitro. Measurement of Zip10 hnRNA and actinomycin D inhibition studies indicate that Zip10 was transcriptionally regulated by zinc deficiency. Through luciferase promoter constructs and ChIP analysis, binding of MTF-1 to a metal response element located 17 bp downstream of the transcription start site was shown to be necessary for zinc-induced repression of Zip10. Furthermore, zinc-activated MTF-1 causes down-regulation of Zip10 transcription by physically blocking Pol II movement through the gene. Lastly, ZIP10 is localized to the plasma membrane of hepatocytes and neuro 2A cells. Collectively, these results reveal a novel repressive role for MTF-1 in the regulation of the Zip10 zinc transporter expression by pausing Pol II transcription. ZIP10 may have roles in control of zinc homeostasis in specific sites particularly those of the brain and liver. Within that context ZIP10 may act as an important survival mechanism during periods of zinc inadequacy

SiteSeek: Post-translational modification analysis using adaptive locality-effective kernel methods and new profiles

<p>Abstract</p> <p>Background</p> <p>Post-translational modifications have a substantial influence on the structure and functions of protein. Post-translational phosphorylation is one of the most common modification that occur in intracellular proteins. Accurate prediction of protein phosphorylation sites is of great importance for the understanding of diverse cellular signalling processes in both the human body and in animals. In this study, we propose a new machine learning based protein phosphorylation site predictor, SiteSeek. SiteSeek is trained using a novel compact evolutionary and hydrophobicity profile to detect possible protein phosphorylation sites for a target sequence. The newly proposed method proves to be more accurate and exhibits a much stable predictive performance than currently existing phosphorylation site predictors.</p> <p>Results</p> <p>The performance of the proposed model was compared to nine existing different machine learning models and four widely known phosphorylation site predictors with the newly proposed PS-Benchmark_1 dataset to contrast their accuracy, sensitivity, specificity and correlation coefficient. SiteSeek showed better predictive performance with 86.6% accuracy, 83.8% sensitivity, 92.5% specificity and 0.77 correlation-coefficient on the four main kinase families (CDK, CK2, PKA, and PKC).</p> <p>Conclusion</p> <p>Our newly proposed methods used in SiteSeek were shown to be useful for the identification of protein phosphorylation sites as it performed much better than widely known predictors on the newly built PS-Benchmark_1 dataset.</p

HelmCoP: An Online Resource for Helminth Functional Genomics and Drug and Vaccine Targets Prioritization

A vast majority of the burden from neglected tropical diseases result from helminth infections (nematodes and platyhelminthes). Parasitic helminthes infect over 2 billion, exerting a high collective burden that rivals high-mortality conditions such as AIDS or malaria, and cause devastation to crops and livestock. The challenges to improve control of parasitic helminth infections are multi-fold and no single category of approaches will meet them all. New information such as helminth genomics, functional genomics and proteomics coupled with innovative bioinformatic approaches provide fundamental molecular information about these parasites, accelerating both basic research as well as development of effective diagnostics, vaccines and new drugs. To facilitate such studies we have developed an online resource, HelmCoP (Helminth Control and Prevention), built by integrating functional, structural and comparative genomic data from plant, animal and human helminthes, to enable researchers to develop strategies for drug, vaccine and pesticide prioritization, while also providing a useful comparative genomics platform. HelmCoP encompasses genomic data from several hosts, including model organisms, along with a comprehensive suite of structural and functional annotations, to assist in comparative analyses and to study host-parasite interactions. The HelmCoP interface, with a sophisticated query engine as a backbone, allows users to search for multi-factorial combinations of properties and serves readily accessible information that will assist in the identification of various genes of interest. HelmCoP is publicly available at: http://www.nematode.net/helmcop.html