Crystal structure of human IPS-1/MAVS/VISA/Cardif caspase activation recruitment domain

Background: IPS-1/MAVS/VISA/Cardif is an adaptor protein that plays a crucial role in the induction of interferons in response to viral infection. In the initial stage of the intracellular antiviral response two RNA helicases, retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-association gene 5 (MDA5), are independently able to bind viral RNA in the cytoplasm. The 62 kDa protein IPS-1/MAVS/VISA/Cardif contains an N-terminal caspase activation and recruitment (CARD) domain that associates with the CARD regions of RIG-I and MDA5, ultimately leading to the induction of type I interferons. As a first step towards understanding the molecular basis of this important adaptor protein we have undertaken structural studies of the IPS-1 MAVS/VISA/Cardif CARD region. Results: The crystal structure of human IPS-1/MAVS/VISA/Cardif CARD has been determined to 2.1 angstrom resolution. The protein was expressed and crystallized as a maltose-binding protein (MBP) fusion protein. The MBP and IPS-1 components each form a distinct domain within the structure. IPS-1/MAVS/VISA/Cardif CARD adopts a characteristic six-helix bundle with a Greek-key topology and, in common with a number of other known CARD structures, contains two major polar surfaces on opposite sides of the molecule. One face has a surface-exposed, disordered tryptophan residue that may explain the poor solubility of untagged expression constructs. Conclusion: The IPS-1/MAVS/VISA/Cardif CARD domain adopts the classic CARD fold with an asymmetric surface charge distribution that is typical of CARD domains involved in homotypic protein-protein interactions. The location of the two polar areas on IPS-1/MAVS/VISA/Cardif CARD suggest possible types of associations that this domain makes with the two CARD domains of MDA5 or RIG-I. The N-terminal CARD domains of RIG-I and MDA5 share greatest sequence similarity with IPS-1/MAVS/VISA/Cardif CARD and this has allowed modelling of their structures. These models show a very different charge profile for the equivalent surfaces compared to IPS-1/MAVS/VISA/Cardif CARD.Publisher PDFPeer reviewe

Short-Interval Cortical Inhibition and Intracortical Facilitation during Submaximal Voluntary Contractions Changes with Fatigue

This study determined whether short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) change during a sustained submaximal isometric contraction. On 2 days, 12 participants (6 men, 6 women) performed brief (7-s) elbow flexor contractions before and after a 10-min fatiguing contraction; all contractions were performed at the level of integrated electromyographic activity (EMG) which produced 25 % maximal unfatigued torque. During the brief 7-s and 10-min submaximal contractions, single (test) and paired (conditioning–test) transcranial magnetic stimuli were applied over the motor cortex (5 s apart) to elicit motor-evoked potentials (MEPs) in biceps brachii. SICI and ICF were elicited on separate days, with a conditioning–test interstimulus interval of 2.5 and 15 ms, respectively. On both days, integrated EMG remained constant while torque fell during the sustained contraction by ~51.5 % from control contractions, perceived effort increased threefold, and MVC declined by 21–22 %. For SICI, the conditioned MEP during control contractions (74.1 ± 2.5 % of unconditioned MEP) increased (less inhibition) during the sustained contraction (last 2.5 min: 86.0 ± 5.1 %; P \u3c 0.05). It remained elevated in recovery contractions at 2 min (82.0 ± 3.8 %; P \u3c 0.05) and returned toward control at 7-min recovery (76.3 ± 3.2 %). ICF during control contractions (conditioned MEP 129.7 ± 4.8 % of unconditioned MEP) decreased (less facilitation) during the sustained contraction (last 2.5 min: 107.6 ± 6.8 %; P \u3c 0.05) and recovered to 122.8 ± 4.3 % during contractions after 2 min of recovery. Both intracortical inhibitory and facilitatory circuits become less excitable with fatigue when assessed during voluntary activity, but their different time courses of recovery suggest different mechanisms for the fatigue-related changes of SICI and ICF

Filamentous cyanobacteria preserved in masses of fungal hyphae from the Triassic of Antarctica

This work is licensed under a Creative Commons Attribution 4.0 International License.Permineralized peat from the central Transantarctic Mountains of Antarctica has provided a wealth of information on plant and fungal diversity in Middle Triassic high-latitude forest paleoecosystems; however, there are no reports as yet of algae or cyanobacteria. The first record of a fossil filamentous cyanobacterium in this peat consists of wide, uniseriate trichomes composed of discoid cells up to 25 µm wide, and enveloped in a distinct sheath. Filament morphology, structurally preserved by permineralization and mineral replacement, corresponds to the fossil genus Palaeo-lyngbya, a predominantly Precambrian equivalent of the extant Lyngbya sensu lato (Oscillatoriaceae, Oscillatoriales). Specimens occur exclusively in masses of interwoven hyphae produced by the fungus Endochaetophora antarctica, suggesting that a special micro-environmental setting was required to preserve the filaments. Whether some form of symbiotic relationship existed between the fungus and cyanobacterium remains unknown

Chronicity and Mental Health Service Utilization for Anxiety, Mood, and Substance Use Disorders among Black Men in the United States; Ethnicity and Nativity Differences.

This study investigated ethnic and nativity differences in the chronicity and treatment of psychiatric disorders of African American and Caribbean Black men in the U.S. Data were analyzed from the National Survey of American Life, a population-based study which included 1859 self-identified Black men (1222 African American, 176 Caribbean Black men born within the U.S., and 461 Caribbean Black men born outside the U.S.). Lifetime and twelve-month prevalence of DSM-IV mood, anxiety, and substance use disorders (including Bipolar I and Dysthmia), disorder chronicity, and rate of mental health services use among those meeting criteria for a lifetime psychiatric disorder were examined. Logistic regression models were employed to determine ethnic differences in chronicity, and treatment utilization for disorders. While rates of DSM-IV disorders were generally low in this community sample of Black men, their disorders were chronic and remained untreated. Caribbean Black men born in the U.S. had higher prevalence of Post-Traumatic Stress Disorder, Major Depressive Disorder, and Alcohol Abuse Disorder compared with African American men. Foreign born Caribbean Black men experienced greater chronicity in Social Phobia and Generalized Anxiety Disorder compared to other Black Men. Utilization of mental health service was low for all groups of Black Men, but lowest for the foreign born Caribbean Black men. Results underscore the large unmet needs of both African American and Caribbean Black men in the United States. Results also highlight the role of ethnicity and nativity in mental disorder chronicity and mental health service utilization patterns of Black men

Crystal structure of human IPS-1/MAVS/VISA/Cardif caspase activation recruitment domain

<p>Abstract</p> <p>Background</p> <p>IPS-1/MAVS/VISA/Cardif is an adaptor protein that plays a crucial role in the induction of interferons in response to viral infection. In the initial stage of the intracellular antiviral response two RNA helicases, retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-association gene 5 (MDA5), are independently able to bind viral RNA in the cytoplasm. The 62 kDa protein IPS-1/MAVS/VISA/Cardif contains an N-terminal caspase activation and recruitment (CARD) domain that associates with the CARD regions of RIG-I and MDA5, ultimately leading to the induction of type I interferons. As a first step towards understanding the molecular basis of this important adaptor protein we have undertaken structural studies of the IPS-1 MAVS/VISA/Cardif CARD region.</p> <p>Results</p> <p>The crystal structure of human IPS-1/MAVS/VISA/Cardif CARD has been determined to 2.1Å resolution. The protein was expressed and crystallized as a maltose-binding protein (MBP) fusion protein. The MBP and IPS-1 components each form a distinct domain within the structure. IPS-1/MAVS/VISA/Cardif CARD adopts a characteristic six-helix bundle with a Greek-key topology and, in common with a number of other known CARD structures, contains two major polar surfaces on opposite sides of the molecule. One face has a surface-exposed, disordered tryptophan residue that may explain the poor solubility of untagged expression constructs.</p> <p>Conclusion</p> <p>The IPS-1/MAVS/VISA/Cardif CARD domain adopts the classic CARD fold with an asymmetric surface charge distribution that is typical of CARD domains involved in homotypic protein-protein interactions. The location of the two polar areas on IPS-1/MAVS/VISA/Cardif CARD suggest possible types of associations that this domain makes with the two CARD domains of MDA5 or RIG-I. The N-terminal CARD domains of RIG-I and MDA5 share greatest sequence similarity with IPS-1/MAVS/VISA/Cardif CARD and this has allowed modelling of their structures. These models show a very different charge profile for the equivalent surfaces compared to IPS-1/MAVS/VISA/Cardif CARD.</p

The clinical effectiveness of different parenting programmes for children with conduct problems : a systematic review of randomised controlled trials

Background Conduct problems are common, disabling and costly. The prognosis for children with conduct problems is poor, with outcomes in adulthood including criminal behaviour, alcoholism, drug abuse, domestic violence, child abuse and a range of psychiatric disorders. There has been a rapid expansion of group based parent-training programmes for the treatment of children with conduct problems in a number of countries over the past 10 years. Existing reviews of parent training have methodological limitations such as inclusion of non-randomised studies, the absence of investigation for heterogeneity prior to meta-analysis or failure to report confidence intervals. The objective of the current study was to systematically review randomised controlled trials of parenting programmes for the treatment of children with conduct problems. Methods Standard systematic review methods were followed including duplicate inclusion decisions, data extraction and quality assessment. Twenty electronic databases from the fields of medicine, psychology, social science and education were comprehensively searched for RCTs and systematic reviews to February 2006. Inclusion criteria were: randomised controlled trial; of structured, repeatable parenting programmes; for parents/carers of children up to the age of 18 with a conduct problem; and at least one measure of child behaviour. Meta-analysis and qualitative synthesis were used to summarise included studies. Results 57 RCTs were included. Studies were small with an average group size of 21. Meta-analyses using both parent (SMD -0.67; 95% CI: -0.91, -0.42) and independent (SMD -0.44; 95% CI: -0.66, -0.23) reports of outcome showed significant differences favouring the intervention group. There was insufficient evidence to determine the relative effectiveness of different approaches to delivering parenting programmes. Conclusion Parenting programmes are an effective treatment for children with conduct problems. The relative effectiveness of different parenting programmes requires further research

Are pregnancy outcomes associated with risk factor reporting in routinely collected perinatal data?

Relatório de estágio do mestrado em Ensino da Educação Física dos Ensinos Básico e Secundário, apresentado à Faculdade de Ciências do Desporto e Educação Física da Universidade de CoimbraApresentado como um documento reflexivo e figurativo das experiências e vivências tidas durante o ano de Estágio Pedagógico em Ensino da Educação Física nos Ensinos Básico e Secundário, este relatório final foi desenvolvido com base no contexto da Turma do 11º PS da Escola Secundária de Avelar Brotero, contendo, assim, todas as expetativas, conceções, aprendizagens, dificuldades, estratégias, soluções e etapas superadas. Estruturado em cinco capítulos – Enquadramento pessoal onde consta as expetativas iniciais relativas ao Estágio Pedagógico; contextualização da prática desenvolvida, onde caracterizamos o contexto; realização da prática profissional, da qual consta uma reflexão sobre todo o processo de planeamento, realização e avaliação; reflexões acerca do processo pedagógico, onde expomos opiniões edificantes dos desafios e dilemas na condução do processo de ensino-aprendizagem; e o aprofundamento do tema problema – foi evidenciado o caminho que fomos (re)construindo com identidade, partilha e reflexão, e a forma como encaramos o compromisso com as aprendizagens dos alunos. Fundamentado no paradigma construtivista, o desenvolvimento curricular foi neste relatório assumido como um processo que deverá centrar-se no aluno, aludindo ao conjunto de estratégias, métodos e procedimentos que permitem a concretização de um projeto de formação pessoal e social que a prática desportiva pode potenciar. Tendo em atenção os contextos e cenários de aprendizagem, os papéis e responsabilidades de quem ensina e de quem aprende, fomos delegando ao aluno autonomia, iniciativa, criatividade, capacidade de cooperação e entreajuda, capacidade de decidir, vontade de aprender e de praticar. O Modelo de Educação Desportiva, enquanto modelo de ensino, foi um marco neste processo, pelo que foi objeto de um estudo mais aprofundado. This document was presented as a reflective essay on the experiences lived during the year of Practicum in Teaching of Physical Education on learning stages of Elementary School and High School. This final report was based on the class of 11º PS of Avelar Brotero’s High School, and represents all the expectations, conceptions, learning skills, difficulties found in the process, strategies adopted, solutions found and overcome barriers. It was structured in five chapters: initial expectations relating to the Practicum; characterization of the context; professional practice, in which lies was a reflexion about all the process of planning, making and evaluation; problems and challenges occurred during the process of teaching and learning; and finally deep reflection about he main theme - was then noted the way in which we had been (re)building our study with identity, sharing and reflexion and the way we faced the commitment with the students own learning skills and paths. Under the influence of the constructivist paradigm, curriculum development was seen as a process that will focus on the student, alluding to the set of strategies, methods and procedures that allow the making of a project of personal and social development that the sports practice may enhance, delegating the student autonomy, responsibility, initiative, creativity, ability to cooperate and assist others, and ability to learn and share. The Sport Education Model while teaching model it was a milestone in this process, whereat it was object of further study

Investigating linkage rates among probabilistically linked birth and hospitalization records

BACKGROUND: With the increasing use of probabilistically linked administrative data in health research, it is important to understand whether systematic differences occur between the populations with linked and unlinked records. While probabilistic linkage involves combining records for individuals, population perinatal health research requires a combination of information from both the mother and her infant(s). The aims of this study were to (i) describe probabilistic linkage for perinatal records in New South Wales (NSW) Australia, (ii) determine linkage proportions for these perinatal records, and (iii) assess records with linked mother and infant hospital-birth record, and unlinked records for systematic differences. METHODS: This is a population-based study of probabilistically linked statutory birth and hospital records from New South Wales, Australia, 2001-2008. Linkage groups were created where the birth record had complete linkage with hospital admission records for both the mother and infant(s), partial linkage (the mother only or the infant(s) only) or neither. Unlinked hospital records for mothers and infants were also examined. Rates of linkage as a percentage of birth records and descriptive statistics for maternal and infant characteristics by linkage groups were determined. RESULTS: Complete linkage (mother hospital record – birth record – infant hospital record) was available for 95.9% of birth records, partial linkage for 3.6%, and 0.5% with no linked hospital records (unlinked). Among live born singletons (complete linkage = 96.5%) the mothers without linked infant records (1.6%) had slightly higher proportions of young, non-Australian born, socially disadvantaged women with adverse pregnancy outcomes. The unlinked birth records (0.4%) had slightly higher proportions of nulliparous, older, Australian born women giving birth in private hospitals by caesarean section. Stillbirths had the highest rate of unlinked records (3-4%). CONCLUSIONS: This study shows that probabilistic linkage of perinatal records can achieve high, representative levels of complete linkage. Records for mother’s that did not link to infant records and unlinked records had slightly different characteristics to fully linked records. However, these groups were small and unlikely to bias results and conclusions in a substantive way. Stillbirths present additional challenges to the linkage process due to lower rates of linkage for lower gestational ages, where most stillbirths occur