Nitric oxide binds to the proximal heme coordination site of the ferrocytochrome c/cardiolipin complex: formation mechanism and dynamics.

Mammalian mitochondrial cytochrome c interacts with cardiolipin to form a complex (cyt. c/CL) important in apoptosis. Here we show that this interaction leads to structural changes in ferrocytochrome c that leads to an open coordinate site on the central iron, resulting from the dissociation of the intrinsic methionine residue, where NO can rapidly bind (k = 1.2 x 10(7) m(-1) s(-1)). Accompanying NO binding, the proximal histidine dissociates leaving the heme pentacoordinate, in contrast to the hexacoordinate nitrosyl adducts of native ferrocytochrome c or of the protein in which the coordinating methionine is removed by chemical modification or mutation. We present the results of stopped-flow and photolysis experiments that show that following initial NO binding to the heme, there ensues an unusually complex set of kinetic steps. The spectral changes associated with these kinetic transitions, together with their dependence on NO concentration, have been determined and lead us to conclude that NO binding to cyt. c/CL takes place via an overall scheme comparable to that described for cytochrome c' and guanylate cyclase, the final product being one in which NO resides on the proximal side of the heme. In addition, novel features not observed before in other heme proteins forming pentacoordinate nitrosyl species, include a high yield of NO escape after dissociation, rapid (<1 ms) dissociation of proximal histidine upon NO binding and its very fast binding (60 ps) after NO dissociation, and the formation of a hexacoordinate intermediate. These features all point at a remarkable mobility of the proximal heme environment induced by cardiolipin

Characterization of nuclear polyadenylated RNA-binding proteins in Saccharomyces cerevisiae.

To study the functions of heterogeneous nuclear ribonucleoproteins (hnRNPs), we have characterized nuclear polyadenylated RNA-binding (Nab) proteins from Saccharomyces cerevisiae. Nab1p, Nab2p, and Nab3p were isolated by a method which uses UV light to cross-link proteins directly bound to poly(A)+ RNA in vivo. We have previously characterized Nab2p, and demonstrated that it is structurally related to human hnRNPs. Here we report that Nab1p is identical to the Np13p/Nop3p protein recently implicated in both nucleocytoplasmic protein shuttling and pre-rRNA processing, and characterize a new nuclear polyadenylated RNA-binding protein, Nab3p. The intranuclear distributions of the Nab proteins were analyzed by three-dimensional immunofluorescence optical microscopy. All three Nab proteins are predominantly localized within the nucleoplasm in a pattern similar to the distribution of hnRNPs in human cells. The NAB3 gene is essential for cell viability and encodes an acidic ribonucleoprotein. Loss of Nab3p by growth of a GAL::nab3 mutant strain in glucose results in a decrease in the amount of mature ACT1, CYH2, and TPI1 mRNAs, a concomitant accumulation of unspliced ACT1 pre-mRNA, and an increase in the ratio of unspliced CYH2 pre-mRNA to mRNA. These results suggest that the Nab proteins may be required for packaging pre-mRNAs into ribonucleoprotein structures amenable to efficient nuclear RNA processing

Analysis of direct and indirect genetic effects in fighting sea anemones

Abstract Theoretical models of animal contests such as the Hawk-Dove game predict that variation in fighting behavior will persist due to mixed evolutionarily stable strategies (ESS) under certain conditions. However, the genetic basis for this variation is poorly understood and a mixed ESS for fighting can be interpreted in more than one way. Specifically, we do not know whether variation in aggression within a population arises from among-individual differences in fixed strategy (determined by an individual’s genotype—direct genetic effects [DGEs]), or from within-individual variation in strategy across contests. Furthermore, as suggested by developments of the original Hawk-Dove model, within-individual variation in strategy may be dependent on the phenotype and thus genotype of the opponent (indirect genetic effects—IGEs). Here we test for the effect of DGEs and IGEs during fights in the beadlet sea anemone Actinia equina. By exploiting the unusual reproductive system of sea anemones, combined with new molecular data, we investigate the role of both additive (DGE + IGE) and non-additive (DGE × IGE) genetic effects on fighting parameters, the latter of which have been hypothesized but never tested for explicitly. We find evidence for heritable variation in fighting ability and that fight duration increases with relatedness. Fighting success is influenced additively by DGEs and IGEs but we found no evidence for non-additive IGEs. These results indicate that variation in fighting behavior is driven by additive indirect genetic effects (DGE + IGE), and support a core assumption of contest theory that strategies are fixed by DGEs.</jats:p

Cell biology:Collagen secretion explained

Cells package proteins into vesicles for secretion to the extracellular milieu. A study shows that an enzyme modifies the packaging machinery to encapsulate unusually large proteins such as collagen

Human kin detection

Natural selection has favored the evolution of behaviors that benefit not only one's genes, but also their copies in genetically related individuals. These behaviors include optimal outbreeding (choosing a mate that is neither too closely related, nor too distant), nepotism (helping kin), and spite (hurting non-kin at a personal cost), and all require some form of kin detection or kin recognition. Yet, kinship cannot be assessed directly; human kin detection relies on heuristic cues that take into account individuals' context (whether they were reared by our mother, or grew up in our home, or were given birth by our spouse), appearance (whether they smell or look like us), and ability to arouse certain feelings (whether we feel emotionally close to them). The uncertainties of kin detection, along with its dependence on social information, create ample opportunities for the evolution of deception and self-deception. For example, babies carry no unequivocal stamp of their biological father, but across cultures they are passionately claimed to resemble their mother's spouse; to the same effect, neutral' observers are greatly influenced by belief in relatedness when judging resemblance between strangers. Still, paternity uncertainty profoundly shapes human relationships, reducing not only the investment contributed by paternal versus maternal kin, but also prosocial behavior between individuals who are related through one or more males rather than females alone. Because of its relevance to racial discrimination and political preferences, the evolutionary pressure to prefer kin to non-kin has a manifold influence on society at large

Women's experience of colposcopy: a qualitative investigation.

BACKGROUND: The last comprehensive investigation of women's experience of the colposcopy service in the UK was conducted in the 1980's. It highlighted women's anxiety and lack of information, resulting in recommendations for improvements. Since then the colposcopy service has changed substantially. It is therefore time to re-visit women's experience of this service and reflect upon the success of service changes in improving experience and reducing anxiety. The aim of this study was to investigate women's experience of being referred for, and attending, colposcopy appointments, and identify potential service improvements. METHODS: Qualitative in-depth interviews were conducted with 18 women newly referred for colposcopy in the West Midlands, UK. The interviews were designed to elicit the experience of colposcopy from the patients' perspective. RESULTS: The eight emerging themes were categorised as three overarching concepts, which were: feelings of emotional reaction, choices being accommodated and time delays. Women felt very apprehensive before their appointment, but when attending, appreciated being consulted about their preferences. Delays in referral and feeling 'rushed' by staff impacted negatively on women's experience. CONCLUSIONS: Service changes in information provision and increased respect for dignity seem to have improved the experience that women have of colposcopy, however, this does not appear to have translated into decreased anxiety. Women still have strong emotional reactions to being referred for, and attending, colposcopy appointments. Staff taking time to explain the diagnosis fully, and discuss their preferences about aspects of their consultation can alleviate their anxiety

The impact of COVID‐19 in Dravet syndrome: A UK survey

OBJECTIVES: To understand the risks, impact and outcome of COVID-19 in people affected by Dravet Syndrome (DS). MATERIALS AND METHODS: An anonymous cross-sectional online survey was conducted between June 17 and July 13, 2020, addressed to families of people with DS. RESULTS: A total of 116 responses were collected, from families of children (n = 86; 74%) and adults (30; 26%) with DS. The majority (106; 91%) were shielded at the family home during lockdown. Symptoms compatible with COVID-19 were reported in 22 (19%) individuals. Only four individuals with symptoms had a PCR swab test, none of which was positive. Only one symptomatic person had antibody testing (but not swab testing), which was positive. One person had repeatedly positive swab tests whilst in hospital for renal failure, but had no typical symptoms of COVID-19. In 50% of people with DS who developed possible or probable COVID-19 symptoms, seizure worsening was reported, in terms of increased seizure frequency or duration or both. Medical attention was required in 9/22 (41%), all of whom were children. CONCLUSIONS: In this cohort of people with DS, we observed an infection rate, determined by compatible symptoms, of 19%, with no deaths and benign outcome in most cases despite the underlying complex epilepsy although children often required medical attention. Early adoption of preventative measures, including testing of symptomatic individuals, regular surveillance for people living in residential care facilities, and shielding of individuals with comorbidities increasing the risk of severe outcome, may limit the impact of COVID-19

Short-scale turbulent fluctuations driven by the electron-temperature gradient in the national spherical torus experiment

Measurements with coherent scattering of electromagnetic waves in plasmas of the National Spherical Torus Experiment indicate the existence of turbulent fluctuations in the range of wave numbers k(perpendicular to)rho(e)=0.1-0.4, corresponding to a turbulence scale length nearly equal to the collisionless skin depth. Experimental observations and agreement with numerical results from a linear gyrokinetic stability code support the conjecture that the observed turbulence is driven by the electron-temperature gradient.X1155sciescopu

Multidisciplinary Views on Applying Explicit and Implicit Motor Learning in Practice: An International Survey.

Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tBACKGROUND: A variety of options and techniques for causing implicit and explicit motor learning have been described in the literature. The aim of the current paper was to provide clearer guidance for practitioners on how to apply motor learning in practice by exploring experts' opinions and experiences, using the distinction between implicit and explicit motor learning as a conceptual departure point. METHODS: A survey was designed to collect and aggregate informed opinions and experiences from 40 international respondents who had demonstrable expertise related to motor learning in practice and/or research. The survey was administered through an online survey tool and addressed potential options and learning strategies for applying implicit and explicit motor learning. Responses were analysed in terms of consensus (≥ 70%) and trends (≥ 50%). A summary figure was developed to illustrate a taxonomy of the different learning strategies and options indicated by the experts in the survey. RESULTS: Answers of experts were widely distributed. No consensus was found regarding the application of implicit and explicit motor learning. Some trends were identified: Explicit motor learning can be promoted by using instructions and various types of feedback, but when promoting implicit motor learning, instructions and feedback should be restricted. Further, for implicit motor learning, an external focus of attention should be considered, as well as practicing the entire skill. Experts agreed on three factors that influence motor learning choices: the learner's abilities, the type of task, and the stage of motor learning (94.5%; n = 34/36). Most experts agreed with the summary figure (64.7%; n = 22/34). CONCLUSION: The results provide an overview of possible ways to cause implicit or explicit motor learning, signposting examples from practice and factors that influence day-to-day motor learning decisions.Stichting Innovatie Alliantie (Innovation Alliance Foundation)RAAK-internationa

Using a Delphi technique to seek consensus regarding definitions, descriptions and classification of terms related to implicit and explicit forms of motor learning.

Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tBACKGROUND: Motor learning is central to domains such as sports and rehabilitation; however, often terminologies are insufficiently uniform to allow effective sharing of experience or translation of knowledge. A study using a Delphi technique was conducted to ascertain level of agreement between experts from different motor learning domains (i.e., therapists, coaches, researchers) with respect to definitions and descriptions of a fundamental conceptual distinction within motor learning, namely implicit and explicit motor learning. METHODS: A Delphi technique was embedded in multiple rounds of a survey designed to collect and aggregate informed opinions of 49 international respondents with expertise related to motor learning. The survey was administered via an online survey program and accompanied by feedback after each round. Consensus was considered to be reached if ≥70% of the experts agreed on a topic. RESULTS: Consensus was reached with respect to definitions of implicit and explicit motor learning, and seven common primary intervention strategies were identified in the context of implicit and explicit motor learning. Consensus was not reached with respect to whether the strategies promote implicit or explicit forms of learning. DISCUSSION: The definitions and descriptions agreed upon may aid translation and transfer of knowledge between domains in the field of motor learning. Empirical and clinical research is required to confirm the accuracy of the definitions and to explore the feasibility of the strategies that were identified in research, everyday practice and education.Stichting Alliantie Innovatie (Innovation Alliance Foundation)RAAK-internationa