The association between human endogenous retroviruses and multiple sclerosis: a systematic review and meta-analysis

Background: The interaction between genetic and environmental factors is crucial to multiple sclerosis (MS) pathogenesis. Human Endogenous Retroviruses (HERVs) are endogenous viral elements of the human genome whose expression is associated with MS. Objective: To perform a systematic review and meta-analysis and to assess qualitative and quantitative evidence on the expression of HERV families in MS patients. Methods: Medline, Embase and the Cochrane Library were searched for published studies on the association of HERVs and MS. Meta-analysis was performed on the HERV-W family. Odds Ratio (OR) and 95% confidence interval (CI) were calculated for association. Results: 43 reports were extracted (25 related to HERV-W, 13 to HERV-H, 9 to HERV-K, 5 to HRES-1 and 1 to HER-15 family). The analysis showed an association between expression of all HERV families and MS. For HERV-W, adequate data was available for meta-analysis. Results from meta-analyses of HERV-W were OR = 22.66 (95%CI 6.32 to 81.20) from 4 studies investigating MSRV/HERV-W(MS-associated retrovirus) envelope mRNA in peripheral blood mononuclear cells, OR = 44.11 (95%CI 12.95 to 150.30) from 6 studies of MSRV/ HERV-W polymerase mRNA in serum/plasma and OR = 6.00 (95%CI 3.35 to 10.74) from 4 studies of MSRV/HERV-W polymerase mRNA in CSF

Dynamic modeling of mean-reverting spreads for statistical arbitrage

Statistical arbitrage strategies, such as pairs trading and its generalizations, rely on the construction of mean-reverting spreads enjoying a certain degree of predictability. Gaussian linear state-space processes have recently been proposed as a model for such spreads under the assumption that the observed process is a noisy realization of some hidden states. Real-time estimation of the unobserved spread process can reveal temporary market inefficiencies which can then be exploited to generate excess returns. Building on previous work, we embrace the state-space framework for modeling spread processes and extend this methodology along three different directions. First, we introduce time-dependency in the model parameters, which allows for quick adaptation to changes in the data generating process. Second, we provide an on-line estimation algorithm that can be constantly run in real-time. Being computationally fast, the algorithm is particularly suitable for building aggressive trading strategies based on high-frequency data and may be used as a monitoring device for mean-reversion. Finally, our framework naturally provides informative uncertainty measures of all the estimated parameters. Experimental results based on Monte Carlo simulations and historical equity data are discussed, including a co-integration relationship involving two exchange-traded funds.Comment: 34 pages, 6 figures. Submitte

Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces

TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis and chemical cross-linking, the direct interactions between HIV-1 capsid protein (CA) assemblies and purified TRIM5αrh containing coiled-coil and SPRY domains (CC-SPRYrh). Concentration-dependent binding of CC-SPRYrh to CA assemblies was observed, while under equivalent conditions the human protein did not bind. Importantly, CC-SPRYrh, but not its human counterpart, disrupted CA tubes in a non-random fashion, releasing fragments of protofilaments consisting of CA hexamers without dissociation into monomers. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. The same disruption effect by TRIM5αrh on the inter-hexamer interfaces also occurred with purified intact HIV-1 cores. These results provide insights concerning how TRIM5α disrupts the virion core and demonstrate that structural damage of the viral capsid by TRIM5α is likely one of the important components of the mechanism of TRIM5α-mediated HIV-1 restriction. © 2011 Zhao et al

The view of teachers on bullying and implications for nursing

Objetivo: Compreender o bullying escolar, na perspectiva dos professores, e refletir sobre as possíveis ações da área da saúde em seu enfrentamento. Para tanto, tomaram- se por base as diretrizes do Programa Saúde na Escola, dos Ministérios da Saúde e da Educação. Método: Estudo de caso qualitativo, realizado com professores de uma escola pública de Minas Gerais. Foram utilizados grupos focais na coleta de dados e o material empírico foi decodificado a partir de técnica de análise temática de conteúdo, resultando em uma categoria analítica: concepções e experiências de professores diante do bullying. Resultados: Foram identificadas percepções pontuais sobre o fenômeno e utilização de recursos de intervenção pouco eficazes. No plano interpretativo, problematizaram-se as contribuições da saúde e da enfermagem no redimensionamento das intervenções e no processo de formação continuada dos professores. Conclusão: Os resultados apontam para a construção de práticas intersetoriais para o enfrentamento do bullying.To understand school bullying from the perspective of teachers and reflect about the possible actions of the health area when coping with it. The guidelines of the School Health Program of the Ministries of Health and Education were used to reach that purpose. Method: A qualitative study carried out with teachers of a public school in Minas Gerais. Focus groups were used to collect data and the empirical material was decoded from thematic analysis of content, resulting in an analytical category: conceptions and experiences of teachers on bullying. Results: Specific perceptions about the phenomenon and the use of ineffective intervention resources were identified. In the interpretive plan were problematized the health and nursing contributions with resizing the interventions and the continuing training process of teachers. Conclusion: The results point to the construction of intersectoral practices forcoping with bullying.Objetivo: Comprender el bullying escolar desde la perspectiva de los profesores, y reflexionar sobre las posibles acciones del área de salud en su enfrentamiento. Tomando como base los lineamientos del Programa de Salud Escolar, de los Ministerios de Salud y de Educación. Método: Estudio de caso cualitativo realizado con los profesores de una escuela pública en Minas Gerais. Para la recolección de datos se utilizaron grupos focales y el material empírico fue decodificado a partir de la técnica de análisis temático de contenido, dando lugar a una categoría analítica: concepciones y experiencias de los profesores sobre el acoso escolar. Resultados: Se identificaron percepciones específicas sobre el fenómeno y la utilización de recursos ineficaces de intervención. En el plano interpretativo, se problematizaron las contribuciones de la salud y de la enfermería en el redimensionamiento de las intervenciones y en el proceso de formación continua de los profesores. Conclusión: Los resultados apuntan a la construcción de prácticas intersectoriales para el enfrentamiento del bullying.CIEC - Centro de Investigação em Estudos da Criança, UM (UI 317 da FCT

From benzos to berries: treatment offered at an Aboriginal youth solvent abuse treatment centre relays the importance of culture.

First Nations and Inuit youth who abuse solvents are one of the most highly stigmatized substance-abusing groups in Canada. Drawing on a residential treatment response that is grounded in a culture-based model of resiliency, this article discusses the cultural implications for psychiatry's individualized approach to treating mental disorders. A systematic review of articles published in The Canadian Journal of Psychiatry during the past decade, augmented with a review of Canadian and international literature, revealed a gap in understanding and practice between Western psychiatric disorder-based and Aboriginal culture-based approaches to treatment and healing from substance abuse and mental disorders. Differing conceptualizations of mental health and substance abuse are discussed from Western psychiatric and Aboriginal worldviews, with a focus on connection to self, community, and political context. Applying an Aboriginal method of knowledge translation-storytelling-experiences from front-line workers in a youth solvent abuse treatment centre relay the difficulties with applying Western responses to Aboriginal healing. This lends to a discussion of how psychiatry can capitalize on the growing debate regarding the role of culture in the treatment of Aboriginal youth who abuse solvents. There is significant need for culturally competent psychiatric research specific to diagnosing and treating First Nations and Inuit youth who abuse substances, including solvents. Such understanding for front-line psychiatrists is necessary to improve practice. A health promotion perspective may be a valuable beginning point for attaining this understanding, as it situates psychiatry's approach to treating mental disorders within the etiology for Aboriginal Peoples

AglH, a thermophilic UDP‑<i>N</i>‑acetylglucosamine‑1‑phosphate:dolichyl phosphate GlcNAc‑1‑phosphotransferase initiating protein<i> N</i>‑glycosylation pathway in <i>Sulfolobus acidocaldarius</i>, is capable of complementing the eukaryal Alg7

AglH, a predicted UDP-GlcNAc-1-phosphate:dolichyl phosphate GlcNAc-1-phosphotransferase, is initiating the protein N-glycosylation pathway in the thermoacidophilic crenarchaeon Sulfolobus acidocaldarius. AglH successfully replaced the endogenous GlcNAc-1-phosphotransferase activity of Alg7 in a conditional lethal Saccharomyces cerevisiae strain, in which the first step of the eukaryal protein N-glycosylation process was repressed. This study is one of the few examples of cross-domain complementation demonstrating a conserved polyprenyl phosphate transferase reaction within the eukaryal and archaeal domain like it was demonstrated for Methanococcus voltae (Shams-Eldin et al. 2008). The topology prediction and the alignment of the AglH membrane protein with GlcNAc-1-phosphotransferases from the three domains of life show significant conservation of amino acids within the different proposed cytoplasmic loops. Alanine mutations of selected conserved amino acids in the putative cytoplasmic loops II (D(100)), IV (F(220)) and V (F(264)) demonstrated the importance of these amino acids for cross-domain AlgH activity in in vitro complementation assays in S. cerevisiae. Furthermore, antibiotic treatment interfering directly with the activity of dolichyl phosphate GlcNAc-1-phosphotransferases confirmed the essentiality of N-glycosylation for cell survival

Adaptive Evolution of Escherichia coli to an α-Peptide/β-Peptoid Peptidomimetic Induces Stable Resistance.

Antimicrobial peptides (AMPs) and synthetic analogues thereof target conserved structures of bacterial cell envelopes and hence, development of resistance has been considered an unlikely event. However, recently bacterial resistance to AMPs has been observed, and the aim of the present study was to determine whether bacterial resistance may also evolve against synthetic AMP analogues, e.g. α-peptide/β-peptoid peptidomimetics. E. coli ATCC 25922 was exposed to increasing concentrations of a peptidomimetic (10 lineages), polymyxin B (10 lineages), or MilliQ water (4 lineages) in a re-inoculation culturing setup covering approx. 500 generations. All 10 lineages exposed to the peptidomimetic adapted to 32 × MIC while this occurred for 8 out of 10 of the polymyxin B-exposed lineages. All lineages exposed to 32 × MIC of either the peptidomimetic or polymyxin B had a significantly increased MIC (16-32 ×) to the selection agent. Five transfers (≈ 35 generations) in unsupplemented media did not abolish resistance indicating that resistance was heritable. Single isolates from peptidomimetic-exposed lineage populations displayed MICs against the peptidomimetic from wild-type MIC to 32 × MIC revealing heterogeneous populations. Resistant isolates showed no cross-resistance against a panel of membrane-active AMPs. These isolates were highly susceptible to blood plasma antibacterial activity and were killed when plasma concentrations exceeded ≈ 30%. Notably, MIC of the peptidomimetic against resistant isolates returned to wild-type level upon addition of 25% plasma. Whole-genome sequencing of twenty isolates from four resistant lineages revealed mutations, in murein transglycosylase D (mltD) and outer-membrane proteins, which were conserved within and between lineages. However, no common resistance-conferring mutation was identified. We hypothesise that alterations in cell envelope structure result in peptidomimetic resistance, and that this may occur via several distinct mechanisms. Interestingly, this type of resistance result in a concomitant high susceptibility towards plasma, and therefore the present study does not infer additional concern for peptidomimetics as future therapeutics

A Reservoir of Drug-Resistant Pathogenic Bacteria in Asymptomatic Hosts

The population genetics of pathogenic bacteria has been intensively studied in order to understand the spread of disease and the evolution of virulence and drug resistance. However, much less attention has been paid to bacterial carriage populations, which inhabit hosts without producing disease. Since new virulent strains that cause disease can be recruited from the carriage population of bacteria, our understanding of infectious disease is seriously incomplete without knowledge on the population structure of pathogenic bacteria living in an asymptomatic host. We report the first extensive survey of the abundance and diversity of a human pathogen in asymptomatic animal hosts. We have found that asymptomatic swine from livestock productions frequently carry populations of Salmonella enterica with a broad range of drug-resistant strains and genetic diversity greatly exceeding that previously described. This study shows how agricultural practice and human intervention may lead and influence the evolution of a hidden reservoir of pathogens, with important implications for human health

Paradigms in multiple sclerosis: time for a change, time for a unifying concept

It has recently been suggested that, rather than being an autoimmune disease, multiple sclerosis (MS) is an example of a neurocristopathy, a pathological process resulting from a faulty development of the neural crest. Whilst several characteristics of the disease suggest a neurocristopathy, other aetiological factors require consideration, including hygiene-related factors that alter the immune responses to common pathogens resulting in an eclipse of immune reactivity that could protect against MS, the possible role of human endogenous retroviruses (HERVs) in pathogenesis and autoimmune phenomena, HLA polymorphism, vitamin D levels before and after birth and immune repair mechanisms. A postulated aetiological factor in MS, associated with altered vitamin D metabolism and abnormal HERV expression, is a long-lasting disturbed redox regulation in the biosynthesis of a melanoma-like melanin pigment. Although intensive further studies on melanin pigments in nerve tissue in MS are required, the known properties of a pathological form of such pigments in melanoma could explain a number of observations in MS, including the impact of light, UV-light, and vitamin D, and could explain the clinical manifestations of MS on the basis of an oscillating process of oxidative charge and discharge of the pigments and a threshold phenomenon with a change of the quasi-catalytic function of the pigment from destroying reactive oxygen radicals or species to transforming them to more harmful long-persisting highly reactive species. Taken together with the consequences of an adaptive process in partly demyelinated neurons, resulting in an increase in number of mitochondria, and the impact of stressful life events, these conditions are necessary and sufficient to explain the disease process of MS with its spatial (plaques) and temporal (attacks and remissions) characteristics. This suggested unifying concept of the pathogenesis of MS may open perspectives for prevention, diagnosis and therapy. In particular, prevention may be achieved by vaccinating against Epstein-Barr virus in early childhood