Caenorhabditis elegans as a model system for studying drug induced mitochondrial toxicity

Today HIV-1 infection is recognized as a chronic disease with obligatory lifelong treatment to keep viral titers below detectable levels. The continuous intake of antiretroviral drugs however, leads to severe and even life-threatening side effects, supposedly by the deleterious impact of nucleoside-analogue type compounds on the functioning of the mitochondrial DNA polymerase. For detailed investigation of the yet partially understood underlying mechanisms, the availability of a versatile model system is crucial. We therefore set out to develop the use of Caenorhabditis elegansto study drug induced mitochondrial toxicity. Using a combination of molecular-biological and functional assays, combined with a quantitative analysis of mitochondrial network morphology, we conclude that anti-retroviral drugs with similar working mechanisms can be classified into distinct groups based on their effects on mitochondrial morphology and biochemistry. Additionally we show that mitochondrial toxicity of antiretroviral drugs cannot be exclusively attributed to interference with the mitochondrial DNA polymerase

On the non-existence of an R-labeling

We present a family of Eulerian posets which does not have any R-labeling. The result uses a structure theorem for R-labelings of the butterfly poset.Comment: 6 pages, 1 figure. To appear in the journal Orde

On the Thermodynamic Geometry and Critical Phenomena of AdS Black Holes

In this paper, we study various aspects of the equilibrium thermodynamic state space geometry of AdS black holes. We first examine the Reissner-Nordstrom-AdS (RN-AdS) and the Kerr-AdS black holes. In this context, the state space scalar curvature of these black holes is analysed in various regions of their thermodynamic parameter space. This provides important new insights into the structure and significance of the scalar curvature. We further investigate critical phenomena, and the behaviour of the scalar curvature near criticality, for KN-AdS black holes in two mixed ensembles, introduced and elucidated in our earlier work arXiv:1002.2538 [hep-th]. The critical exponents are identical to those in the RN-AdS and Kerr-AdS cases in the canonical ensemble. This suggests an universality in the scaling behaviour near critical points of AdS black holes. Our results further highlight qualitative differences in the thermodynamic state space geometry for electric charge and angular momentum fluctuations of these.Comment: 1 + 37 Pages, LaTeX, includes 31 figures. A figure and a clarification added

Thermodynamics of phase transition in higher dimensional AdS black holes

We investigate the thermodynamics of phase transition for $(n+1)$ dimensional Reissner Nordstrom (RN)-AdS black holes using a grand canonical ensemble. This phase transition is characterized by a discontinuity in specific heat. The phase transition occurs from a lower mass black hole with negative specific heat to a higher mass black hole with positive specific heat. By exploring Ehrenfest's scheme we show that this is a second order phase transition. Explicit expressions for the critical temperature and critical mass are derived. In appropriate limits the results for $(n+1)$ dimensional Schwarzschild AdS black holes are obtained.Comment: LaTex, 11 pages, 5 figures, To appear in JHE

Zinc intake, status and indices of cognitive function in adults and children: a systematic review and meta-analysis

In developing countries, deficiencies of micronutrients are thought to have a major impact on child development; however, a consensus on the specific relationship between dietary zinc intake and cognitive function remains elusive. The aim of this systematic review was to examine the relationship between zinc intake, status and indices of cognitive function in children and adults. A systematic literature search was conducted using EMBASE, MEDLINE and Cochrane Library databases from inception to March 2014. Included studies were those that supplied zinc as supplements or measured dietary zinc intake. A meta-analysis of the extracted data was performed where sufficient data were available. Of all of the potentially relevant papers, 18 studies met the inclusion criteria, 12 of which were randomised controlled trials (RCTs; 11 in children and 1 in adults) and 6 were observational studies (2 in children and 4 in adults). Nine of the 18 studies reported a positive association between zinc intake or status with one or more measure of cognitive function. Meta-analysis of data from the adult’s studies was not possible because of limited number of studies. A meta-analysis of data from the six RCTs conducted in children revealed that there was no significant overall effect of zinc intake on any indices of cognitive function: intelligence, standard mean difference of <0.001 (95% confidence interval (CI) –0.12, 0.13) P=0.95; executive function, standard mean difference of 0.08 (95% CI, –0.06, 022) P=0.26; and motor skills standard mean difference of 0.11 (95% CI –0.17, 0.39) P=0.43. Heterogeneity in the study designs was a major limitation, hence only a small number (n=6) of studies could be included in the meta-analyses. Meta-analysis failed to show a significant effect of zinc supplementation on cognitive functioning in children though, taken as a whole, there were some small indicators of improvement on aspects of executive function and motor development following supplementation but high-quality RCTs are necessary to investigate this further

An Investigation into the Determining Factors of Zoo Visitor Attendances in UK Zoos

The debate as to which animals are most beneficial to keep in zoos in terms of financial and conservative value is readily disputed; however, demographic factors have also been shown to relate to visitor numbers on an international level. The main aims of this research were: (1) To observe the distribution and location of zoos across the UK, (2) to develop a way of calculating zoo popularity in terms of the species kept within a collection and (3) to investigate the factors related to visitor numbers regarding admission costs, popularity of the collection in terms of the species kept and local demographic factors. Zoo visitor numbers were positively correlated with generated popularity ratings for zoos based on the species kept within a collection and admission prices (Pearson correlation: n = 34, r = 0.268, P = 0.126 and n = 34, r = −0.430, P = 0.011). Animal collections are aggregated around large cities and tourist regions, particularly coastal areas. No relationship between demographic variables and visitor numbers was found (Pearson correlation: n = 34, r = 0.268, P = 0.126), which suggests that the popularity of a zoo's collection relative to the types and numbers of species kept is more indicative of a collection's visitor numbers than its surrounding demographic figures. Zoos should incorporate generating high popularity scores as part of their collection planning strategies, to ensure that they thrive in the future, not only as tourist attractions but also as major conservation organizations

Impact of the introduction of pneumococcal conjugate vaccine on immunization coverage among infants

Background The introduction of pneumococcal conjugate vaccine (PCV) to the U.S. recommended childhood immunization schedule in the year 2000 added three injections to the number of vaccinations a child is expected to receive during the first year of life. Surveys have suggested that the addition of PCV has led some immunization providers to move other routine childhood vaccinations to later ages, which could increase the possibility of missing these vaccines. The purpose of this study was to evaluate whether introduction of PCV affected immunization coverage for recommended childhood vaccinations among 13-month olds in four large provider groups. Methods In this retrospective cohort study, we analyzed computerized data on vaccinations for 33,319 children in four large provider groups before and after the introduction of PCV. The primary outcome was whether the child was up to date for all non-PCV recommended vaccinations at 13 months of age. Logistic regression was used to evaluate the association between PCV introduction and the primary outcome. The secondary outcome was the number of days spent underimmunized by 13 months. The association between PCV introduction and the secondary outcome was evaluated using a two-part modelling approach using logistic and negative binomial regression. Results Overall, 93% of children were up-to-date at 13 months, and 70% received all non-PCV vaccinations without any delay. Among the entire study population, immunization coverage was maintained or slightly increased from the pre-PCV to post-PCV periods. After multivariate adjustment, children born after PCV entered routine use were less likely to be up-to-date at 13 months in one provider group (Group C: OR = 0.5; 95% CI: 0.3 – 0.8) and were less likely to have received all vaccine doses without any delay in two Groups (Group B: OR = 0.4, 95% CI: 0.3 – 0.6; Group C: OR = 0.5, 95% CI: 0.4 – 0.7). This represented 3% fewer children in Group C who were up-to-date and 14% (Group C) to 16% (Group B) fewer children who spent no time underimmunized at 13 months after PCV entered routine use compared to the pre-PCV baseline. Some disruptions in immunization delivery were also observed concurrent with temporary recommendations to suspend the birth dose of hepatitis B vaccine, preceding the introduction of PCV. Conclusion These findings suggest that the introduction of PCV did not harm overall immunization coverage rates in populations with good access to primary care. However, we did observe some disruptions in the timely delivery of other vaccines coincident with the introduction of PCV and the suspension of the birth dose of hepatitis B vaccine. This study highlights the need for continued vigilance in coming years as the U.S. introduces new childhood vaccines and policies that may change the timing of existing vaccines

Does owning a pet protect older people against loneliness?

This article has been made available through the Brunel Open Access Publishing Fund.Pet ownership is thought to make a positive contribution to health, health behaviours and the general well-being of older people. More specifically pet ownership is often proposed as a solution to the problem of loneliness in later life and specific 'pet based' interventions have been developed to combat loneliness. However the evidence to support this relationship is slim and it is assumed that pet ownership is a protection against loneliness rather than a response to loneliness. The aim of this paper is to examine the association between pet ownership and loneliness by exploring if pet ownership is a response to, or protection against, loneliness using Waves 0-5 from the English Longitudinal Study of Ageing (ELSA)

Attentional modulations of the early and later stages of the neural processing of visual completion

The brain effortlessly recognizes objects even when the visual information belonging to an object is widely separated, as well demonstrated by the Kanizsa-type illusory contours (ICs), in which a contour is perceived despite the fragments of the contour being separated by gaps. Such large-range visual completion has long been thought to be preattentive, whereas its dependence on top-down influences remains unclear. Here, we report separate modulations by spatial attention and task relevance on the neural activities in response to the ICs. IC-sensitive event-related potentials that were localized to the lateral occipital cortex were modulated by spatial attention at an early processing stage (130–166 ms after stimulus onset) and modulated by task relevance at a later processing stage (234–290 ms). These results not only demonstrate top-down attentional influences on the neural processing of ICs but also elucidate the characteristics of the attentional modulations that occur in different phases of IC processing

Gremlin-1 Induces BMP-Independent Tumor Cell Proliferation, Migration, and Invasion

Gremlin-1, a bone morphogenetic protein (BMP) antagonist, is overexpressed in various cancerous tissues but its role in carcinogenesis has not been established. Here, we report that gremlin-1 binds various cancer cell lines and this interaction is inhibited by our newly developed gremlin-1 antibody, GRE1. Gremlin-1 binding to cancer cells was unaffected by the presence of BMP-2, BMP-4, and BMP-7. In addition, the binding was independent of vascular endothelial growth factor receptor-2 (VEGFR2) expression on the cell surface. Addition of gremlin-1 to A549 cells induced a fibroblast-like morphology and decreased E-cadherin expression. In a scratch wound healing assay, A549 cells incubated with gremlin-1 or transfected with gremlin-1 showed increased migration, which was inhibited in the presence of the GRE1 antibody. Gremlin-1 transfected A549 cells also exhibited increased invasiveness as well as an increased growth rate. These effects were also inhibited by the addition of the GRE1 antibody. In conclusion, this study demonstrates that gremlin-1 directly interacts with cancer cells in a BMP- and VEGFR2-independent manner and can induce cell migration, invasion, and proliferation