Evidence for the involvement of ASIC3 in sensory mechanotransduction in proprioceptors

This work was supported in Taipei by Institute of Biomedical Sciences, Academia Sinica and grants from the Ministry of Science and Technology, Taiwan (NSC100-2321-B-001-018, NSC102-2321-B-001-056, NSC102-2320-B-001-021-MY3, and MOST104-2325-B- 001-011) and in Aberdeen, by the Institute of Medical Sciences, University of Aberdeen, UK. We thank Dr David J. Anderson and Dr Yoshihiro Yoshihara for providing plasmids containing cDNA of eGFP-f and WGA, respectively. Dr John N. Wood, Dr Bai-Chuang Shyu and Dr Yu-Ting Yan for providing transgenic lines including Nav1.8-Cre, Parvalbumin-Cre, ROSA-Gt26 reporter and CAG-STOPfloxed-GFP reporter mice. Also we thank Dr Silvia Arber for offering Parvalbumin-Cre-specific genotyping primer sequence, Dr Philip LeDuc for critical reading of the manuscript, and the Transgenic Core Facility of Academia Sinica for the help on the generation of the 2 Asic3 mutant mice, as well as Dr Sin-Jhong Cheng of NPAS for technique support on electrophysiology

Using resilience to predict the effects of disturbance

Acknowledgements This work was funded by the Office of Naval Research (N00014-13-1-0696). We thank C Asher for her comments on an earlier version of this manuscript.

Limits to sustained energy intake XXIV : impact of suckling behaviour on the body temperatures of lactating female mice

We would like to thank the animal house staff and all members of the Energetics group for their invaluable help at various stages throughout the project. This work was supported by Natural Environment Research Council grant (NERC, NE/C004159/1). YG was supported by a scholarship from the rotary foundation. LV was supported by a Rubicon grant from the Netherlands Scientific Organisation (NWO).

A neuroendocrine role for chemerin in hypothalamic remodelling and photoperiodic control of energy balance

We thank Donna Wallace and the animal house staff for their help with the animal studies. We thank Pat Bain for help in preparing the figures. This work was supported by the Biotechnology and Biological Science Research Council (BBSRC) grant number BB/K001043/1 (G.H., A.W.R., P.N.S., P.J.Mc. and P.J.M.) and the Scottish Government (A.W.R., L.M.T., C.D.M. and P.J.M.).

Hsf1 and Hsp90 orchestrate temperature-dependent global transcriptional remodelling and chromatin architecture in Candida albicans

We thank Karim Gharbi and Urmi Trivedi for their assistance with RNA sequencing, carried out in the GenePool genomics facility (University of Edinburgh). We also thank Susan Fairley and Eduardo De Paiva Alves (Centre for Genome Enabled Biology and Medicine, University of Aberdeen) for help with the initial bioinformatics analysis. We thank Aaron Mitchell for kindly providing the ALS3 mutant, Julian Naglik for the gift of TR146 cells, and Jon Richardson for technical assistance. We thank the Genomics and Bioinformatics core of the Faculty of Health Sciences for Next Generation Sequencing and Bioinformatics support, the Information and Communication Technology Office at the University of Macau for providing access to a High Performance Computer and Jacky Chan and William Pang for their expert support on the High Performance Computer. Finally, we thank Amanda Veri for generating CaLC2928. M.D.L. is supported by a Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust 096072), R.A.F. by a Wellcome Trust-Massachusetts Institute of Technology (MIT) Postdoctoral Fellowship, L.E.C. by a Canada Research Chair in Microbial Genomics and Infectious Disease and by Canadian Institutes of Health Research Grants MOP-119520 and MOP-86452, A.J. P.B. was supported by the UK Biotechnology and Biological Sciences Research Council (BB/F00513X/1) and by the European Research Council (ERC-2009-AdG-249793-STRIFE), KHW is supported by the Science and Technology Development Fund of Macau S.A.R (FDCT) (085/2014/A2) and the Research and Development Administrative Office of the University of Macau (SRG2014-00003-FHS) and R.T.W. by the Burroughs Wellcome fund and NIH R15AO094406. Data availability RNA-sequencing data sets are available at ArrayExpress (www.ebi.ac.uk) under accession code E-MTAB-4075. ChIP-seq data sets are available at the NCBI SRA database (http://www.ncbi.nlm.nih.gov) under accession code SRP071687. The authors declare that all other data supporting the findings of this study are available within the article and its supplementary information files, or from the corresponding author upon request.

Violence is Rare in Autism : When It Does Occur, Is It Sometimes Extreme?

Peer reviewed

Are pharmacological randomised controlled clinical trials relevant to real-life asthma populations? : A protocol for an UNLOCK study from the IPCRG

Funding The IPCRG provided funding for this research project as an UNLOCK Group study for which the funding was obtained through an unrestricted grant by Novartis AG, Basel, Switzerland. Novartis has no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. This study will include data from the Optimum Patient Care Research Database and is undertaken in collaboration with Optimum Patient Care and the Respiratory Effectiveness Group.

Lymphocytes selected in allogeneic thymic epithelium mediate dominant tolerance toward tissue grafts of the thymic epithelium haplotype.

Athymic mice grafted at birth with allogeneic thymic epithelium (TE) from day 10 embryos before hematopoietic cell colonization reconstitute normal numbers of T cells and exhibit full life-long tolerance to skin grafts of the TE haplotype. Intravenous transfers of splenic cells, from these animals to adult syngeneic athymic recipients, reconstitute T-cell compartments and the ability to reject third-party skin grafts. The transfer of specific tolerance to skin grafts of the TE donor strain, however, is not observed in all reconstituted recipients, and the fraction of nontolerant recipients increases with decreasing numbers of cells transferred. Furthermore, transfers of high numbers of total or CD4+ T cells from TE chimeras to T-cell receptor-anti-H-Y antigen transgenic immunocompetent syngeneic hosts specifically hinder the rejection of skin grafts of the TE haplotype that normally occurs in such recipients. These observations demonstrate (i) that mice tolerized by allogeneic TE and bearing healthy skin grafts harbor peripheral immunocompetent T cells capable of rejecting this very same graft; and (ii) that TE selects for regulatory T cells that can inhibit effector activities of graft-reactive cells.

Orchestration of gene expression across the seasons : Hypothalamic gene expression in natural photoperiod throughout the year in the Siberian hamster

Funding for work in the laboratory of PB was supported by Scottish Government Rural and Environment Science and Analytical Services Division, BBSRC (grant BB/M001504/1), British Society for Neuroendocrinology (research visit grant to IP). Work in the laboratory of SS was supported by a grant from the DFG (Ste 331/8-1). We thank Siegried Hilken, Marianne Brüning, Dr. Esther Lipokatic-Takacs and Dr. Frank Scherbarth at UVMH for technical assistance. We thank Graham Horgan of Bioinformatics, Statistics Scotland for assistance with some of statistical tests.

O monitoramento domiciliar das condições crônicas e a tomada de decisão por idosos diabéticos e hipertensos

Introdução: A prevalência de doenças crônicas, sobretudo na população idosa, nos coloca diante da necessidade de modelos longitudinais de cuidado. Atualmente os sujeitos estão sendo cada vez mais responsabilizados pelo gerenciamento de sua saúde através do uso de dispositivos de monitoramento, tais como o glicosímetro e o aferidor de pressão arterial. Esta nova realidade culmina na tomada de decisão no próprio domicílio. Objetivos: Identificar a tomada de decisão de idosos no monitoramento domiciliar das condições crônicas; identificar se as variáveis: sexo, escolaridade e renda influenciam a tomada de decisão; identificar a percepção dos idosos quanto às ações de cuidado no domicílio; identificar as dificuldades e estratégias no manuseio dos dispositivos de monitoramento. Materiais e métodos: Estudo quantitativo, exploratório e transversal. Casuística: 150 sujeitos com 60 anos de idade ou mais, sem comprometimento cognitivo, sem depressão e que façam uso do glicosímetro e/ou do aferidor de pressão arterial no domicílio. Instrumentos para seleção dos participantes: (1) Mini Exame do Estado Mental; (2) Escala de Depressão Geriátrica e (3) Escala de Atividades Instrumentais de Vida Diária de Lawton e Brody; Coleta de dados: realizada na cidade de Ribeirão Preto - SP entre setembro de 2014 e outubro de 2015. Instrumentos: (1) Questionário Socioeconômico; (2) Questionário sobre a tomada de decisão no monitoramento da saúde no domicílio (3) Classificação do uso de dispositivos eletrônicos voltados aos cuidados à saúde. Análise dos dados: Realizada estatística descritiva e quantificações absolutas e percentuais para identificar a relação entre tomada de decisão de acordo com o sexo, escolaridade e renda. Resultados: Participaram 150 idosos, sendo 117 mulheres e 33 homens, com média de idade de 72 anos. Destes, 113 são hipertensos e 62 são diabéticos. Quanto à tomada de decisão imediata, tanto os que fazem uso do aferidor de pressão arterial (n=128) quanto do glicosímetro (n=62) referem em sua maioria procurar ajuda médica, seguida da administração do medicamento prescrito e opções alternativas de tratamento. Em médio prazo destaca-se a procura por ajuda profissional para a maioria dos idosos em ambos os grupos. Foi notada pequena diferença na tomada de decisão com relação ao sexo. Quanto à escolaridade, os idosos com mais anos de estudos tendem a procurar mais pelo serviço de saúde se comparado aos idosos de menor escolaridade. A renda não mostrou influencia entre os usuários do glicosímetro. Já entre os usuários do aferidor de pressão arterial, idosos de maior renda tendem a procurar mais pelo serviço de saúde. A maioria dos participantes se refere ao monitoramento domiciliar da saúde de maneira positiva, principalmente pela praticidade em não sair de casa, obtenção rápida de resultados e possibilidade de controle contínuo da doença. As principais dificuldades no manuseio do glicosímetro estão relacionadas ao uso da lanceta e fita reagente, seguida da checagem dos resultados armazenados. Já as dificuldades no uso do aferidor de pressão arterial estão relacionadas a conferir o resultado após cada medida e ao posicionamento correto do corpo durante o monitoramento. Em ambos os grupos as estratégias utilizadas são pedir o auxílio de terceiros e tentativa e erro. Conclusão: Os idosos tem se mostrado favoráveis às ações de monitoramento domiciliar da saúde. De maneira geral, de imediato decidem por ações dentro do próprio domicílio para o controle dos sintomas e isto reforça a necessidade do investimento em informação de qualidade e educação em saúde para que o gerenciamento domiciliar possa vir a ser uma vertente do cuidado integral no tratamento das condições crônicas.

O papel do terceiro facilitador na conciliação de conflitos previdenciários

A conciliação judicial de conflitos previdenciários envolve, em geral, uma proposta de acordo baseada na renúncia pelo indivíduo de parte dos valores do benefício em atraso em um processo no qual a decisão contrária ao entendimento do Instituto Nacional do Segurado Social (INSS) é muito provável. Como regra, há um notório desequilíbrio de poder envolvendo, de um lado, um litigante ocasional (indivíduo) e, de outro, um litigante habitual (INSS). O presente trabalho pretende discutir qual o papel do terceiro facilitador nesse contexto, de modo a legitimar a prática existente e avançar para uma mudança de paradigma. Para tanto, parte-se da tese de que a conciliação deve ser adequada ao conflito que se pretende tratar, cabendo ao terceiro facilitador atuar de acordo com as peculiaridades desse conflito. Desse modo, propõe-se que, para o tratamento do conflito previdenciário, o conceito de conciliador deve ser entendido em termos amplos, abrangendo não apenas o conciliador leigo, mas também o juiz conciliador e o Judiciário como conciliador interinstitucional. Embora cada uma dessas atuações possua características próprias, sustenta-se que o ponto em comum é o respeito a um devido processo legal mínimo que possibilite a existência de uma base adequada de poder e que permita, assim, a tomada de uma decisão informada pelas partes. Dessa forma, a flexibilidade instrumental própria da conciliação não impediria o estabelecimento de parâmetros mínimos da atuação do conciliador. Por isso, tendo como limite a tomada de uma decisão informada, o conciliador atuaria por meio de estratégias variadas, aproximando-se e distanciando-se das partes, com maior ou menor interferência, de acordo com as características do caso apresentado. Conclui-se que, com a atuação conjunta e coordenada das diversas espécies de conciliador é possível aprimorar qualitativamente a conciliação de conflitos previdenciários.

China's Strategic Choices towards North Korea and Iran

This study tests two hypotheses. First, China cooperates with the United States only when it is able to obtain material rewards. Second, without material incentives from the United States, China straddles between the United States on one hand and Iran and North Korea on the other. My findings show that neither Structural Realism, which holds anti-hegemonism alliance, nor Constructivism, which holds positive assimilation of the nuclear nonproliferation norm explains Chinese international behavior comprehensively. My balance of interest model explains Chinese foreign policy on the noncompliant states better. The cases cover the Sino-North Korean and Sino-Iranian diplomatic histories from 1990 to 2013 vis-à-vis the United States. The study is both a within-case comparison—that is, changes of China’s stance across time—and a cross-case comparison in China’s position regarding Iran and North Korea. My comparisons contribute to theoretical and empirical analyses in international relations literature. Theoretically, the research creates different options for the third party between the two antagonistic actors. China will have seven different types of reaction: balancing, bandwagoning, mediating, and abetting that foster strategic clarity versus hiding, delaying, and straddling which are symptomatic of strategic ambiguity. I argue that there is a gradation between pure balancing and pure supporting. Empirically, the test results show that Chinese leaders have tried to find a balance between its material interests and international reputation by engaging in straddling and delaying inconsistently. There are two major findings. First, China’s foreign policy has been reactive. Whereas prior to 2006, balancing against the U.S. had been a dominant strategy, since 2006, China has shown strategic ambiguity. Second, Chinese leaders believe that the preservation of stability in the region outweighs denuclearization of the noncompliant states, because it is in China’s interest to maintain a manageable tension between the U.S. and the noncompliant states. The balance of interest model suggests that the best way to understand China’s preferences is to consider them as products of rough calculation of risks and rewards on both the U.S. and the noncompliant states.

Cómo reacciona el personal de hotel cuando observa un trato (in)justo hacia los huéspedes

Este artículo sugiere que el personal de hotel ante un trato (in)justo del hotel hacia los clientes atribuye tal trato a la responsabilidad del hotel y, dependiendo que éste sea justo o injusto, aumentaría o disminuiría sus conductas orientadas al cliente (COBs). Los datos fueron recogidos mediante cuestionarios pasados a 204 empleados de ocho hoteles de lujo en las Islas Canarias (España). Para examinar las hipótesis se utilizaron modelos de ecuaciones estructurales (SEM). No así en el caso de percepciones de justicia distributiva, los resultados muestran que cuanta más justicia procedimental e interpersonal hacia los huéspedes perciban los empleados, más se implican en conductas orientadas al cliente (COBs). Los hallazgos sugieren la necesidad de prevenir episodios de maltrato a los huéspedes por parte del hotel, haciendo especial hincapié en aquellos que son visibles para los empleados, para promover así conductas orientadas al cliente (COBs). Hasta donde nosotros sabemos, este es el primer estudio empírico en donde la justicia organizativa (distributiva, procedimental e interpersonal) dirigida hacia los clientes y las conductas orientadas al cliente (COBs) de los empleados son examinadas conjuntamente en un mismo modelo.

Human iPSC derived disease model of MERTK-associated retinitis pigmentosa

Retinitis pigmentosa (RP) represents a genetically heterogeneous group of retinal dystrophies affecting mainly the rod photoreceptors and in some instances also the retinal pigment epithelium (RPE) cells of the retina. Clinical symptoms and disease progression leading to moderate to severe loss of vision are well established and despite significant progress in the identification of causative genes, the disease pathology remains unclear. Lack of this understanding has so far hindered development of effective therapies. Here we report successful generation of human induced pluripotent stem cells (iPSC) from skin fibroblasts of a patient harboring a novel Ser331Cysfs*5 mutation in the MERTK gene. The patient was diagnosed with an early onset and severe form of autosomal recessive RP (arRP). Upon differentiation of these iPSC towards RPE, patient-specific RPE cells exhibited defective phagocytosis, a characteristic phenotype of MERTK deficiency observed in human patients and animal models. Thus we have created a faithful cellular model of arRP incorporating the human genetic background which will allow us to investigate in detail the disease mechanism, explore screening of a variety of therapeutic compounds/reagents and design either combined cell and gene- based therapies or independent approaches.

Low doses of ivermectin cause sensory and locomotor disorders in dung beetles

Ivermectin is a veterinary pharmaceutical generally used to control the ecto- and endoparasites of livestock, but its use has resulted in adverse effects on coprophilous insects, causing population decline and biodiversity loss. There is currently no information regarding the direct effects of ivermectin on dung beetle physiology and behaviour. Here, based on electroantennography and spontaneous muscle force tests, we show sub-lethal disorders caused by ivermectin in sensory and locomotor systems of Scarabaeus cicatricosus, a key dung beetle species in Mediterranean ecosystems. Our findings show that ivermectin decreases the olfactory and locomotor capacity of dung beetles, preventing them from performing basic biological activities. These effects are observed at concentrations lower than those usually measured in the dung of treated livestock. Taking into account that ivermectin acts on both glutamate-gated and GABA-gated chloride ion channels of nerve and muscle cells, we predict that ivermectin’s effects at the physiological level could influence many members of the dung pat community. The results indicate that the decline of dung beetle populations could be related to the harmful effects of chemical contamination in the dung.