The RCSB Protein Data Bank: views of structural biology for basic and applied research and education.

The RCSB Protein Data Bank (RCSB PDB, http://www.rcsb.org) provides access to 3D structures of biological macromolecules and is one of the leading resources in biology and biomedicine worldwide. Our efforts over the past 2 years focused on enabling a deeper understanding of structural biology and providing new structural views of biology that support both basic and applied research and education. Herein, we describe recently introduced data annotations including integration with external biological resources, such as gene and drug databases, new visualization tools and improved support for the mobile web. We also describe access to data files, web services and open access software components to enable software developers to more effectively mine the PDB archive and related annotations. Our efforts are aimed at expanding the role of 3D structure in understanding biology and medicine

IL-36 Promotes Systemic IFN-I Responses in Severe Forms of Psoriasis

Psoriasis is an immune-mediated skin disorder associated with severe systemic comorbidities. Whereas IL-36 is a key disease driver, the pathogenic role of this cytokine has mainly been investigated in skin. Thus, its effects on systemic immunity and extracutaneous disease manifestations remain poorly understood. To address this issue, we investigated the consequences of excessive IL-36 activity in circulating immune cells. We initially focused our attention on generalized pustular psoriasis (GPP), a clinical variant associated with pervasive upregulation of IL-36 signaling. By undertaking blood and neutrophil RNA sequencing, we demonstrated that affected individuals display a prominent IFN-I signature, which correlates with abnormal IL-36 activity. We then validated the association between IL-36 deregulation and IFN-I over-expression in patients with severe psoriasis vulgaris (PV). We also found that the activation of IFN-I genes was associated with extracutaneous morbidity, in both GPP and PV. Finally, we undertook mechanistic experiments, demonstrating that IL-36 acts directly on plasmacytoid dendritic cells, where it potentiates toll-like receptor (TLR)-9 activation and IFN-α production. This effect was mediated by the upregulation of PLSCR1, a phospholipid scramblase mediating endosomal TLR-9 translocation. These findings identify an IL-36/ IFN-I axis contributing to extracutaneous inflammation in psoriasis.</p

Droplets I: Pressure-Dominated Sub-0.1 pc Coherent Structures in L1688 and B18

We present the observation and analysis of newly discovered coherent structures in the L1688 region of Ophiuchus and the B18 region of Taurus. Using data from the Green Bank Ammonia Survey (GAS), we identify regions of high density and near-constant, almost-thermal, velocity dispersion. Eighteen coherent structures are revealed, twelve in L1688 and six in B18, each of which shows a sharp "transition to coherence" in velocity dispersion around its periphery. The identification of these structures provides a chance to study the coherent structures in molecular clouds statistically. The identified coherent structures have a typical radius of 0.04 pc and a typical mass of 0.4 Msun, generally smaller than previously known coherent cores identified by Goodman et al. (1998), Caselli et al. (2002), and Pineda et al. (2010). We call these structures "droplets." We find that unlike previously known coherent cores, these structures are not virially bound by self-gravity and are instead predominantly confined by ambient pressure. The droplets have density profiles shallower than a critical Bonnor-Ebert sphere, and they have a velocity (VLSR) distribution consistent with the dense gas motions traced by NH3 emission. These results point to a potential formation mechanism through pressure compression and turbulent processes in the dense gas. We present a comparison with a magnetohydrodynamic simulation of a star-forming region, and we speculate on the relationship of droplets with larger, gravitationally bound coherent cores, as well as on the role that droplets and other coherent structures play in the star formation process.Comment: Accepted by ApJ in April, 201

Sarah: historiografkinja prošlosti i sadašnjosti žene francuskog poručnika

The article argues that Sarah, the title character of Fowles’ novel The French Lieutenant’s Woman (1969), resists the oppressive ideology of her time by writing her own historiography. In the process, not only does she emplot a tragic past for herself but she also insists on being identified as a depraved woman in the present. The analysis attempts to highlight the fact that Sarah, like a historiographer, selects the referents for her historiography—Mrs. Poulteney and Charles—and imposes her emplotment and prefiguration on her historiography of both her past and present. Employing Hayden White’s theories of postmodern historiography and Linda Hutcheon’s concept of historiographic metafiction, the paper illustrates ways in which Sarah historicizes her own past through tragic emplotment and metaphoric prefiguration of her narrative in order to convey her anarchist ideology, at the same time portraying herself as the “Woman” who has been abandoned by the French Lieutenant. Furthermore, by means of her historiography of the present, she imposes her liberal ideology through satiric emplotment of her fictional construct and ironic prefiguration of the referents of textualized oppression in society. She ironically puts Mrs. Poulteney and Charles in the situations in which their oppressive ideology is unraveled; in this way, she satirizes the codes of behavior of her present time.U članku se tvrdi da se Sarah, naslovni lik Fowlesova romana Ženska francuskog poručnika (1969), opire opresivnoj ideologiji svojega vremena pišući vlastitu historiografiju. Na taj način ona fabulira tragičnu prošlost za sebe i inzistira na tome da ju se percipira kao izopačenu ženu u sadašnjosti. Analiza pokušava istaknuti činjenicu da Sarah, poput povjesničara, odabire referente za svoju historiografiju – gđu Poulteney i Charlesa – i nameće svoju fabulaciju i prefiguraciju historiografije vlastite prošlosti i sadašnjosti. Koristeći se teorijom postmoderne historiografije Haydena Whitea i konceptom historiografske metafikcije Linde Hutcheon, rad prikazuje načine na koje Sarah historizira vlastitu prošlost kroz tragičnu fabulaciju i metaforičku prefiguraciju svoje pripovijesti kako bi istaknula svoju anarhističku ideologiju i istodobno sebe prikazala kao „žensku“ koju je napustio francuski poručnik. Nadalje, pomoću svoje historiografije sadašnjosti ona nameće svoju liberalnu ideologiju satiričkom fabulacijom svog fikcionalnog konstrukta i ironičnom prefiguracijom referenata tekstualiziranog društvenog ugnjetavanja. Na ironičan način, ona gospođu Poulteney i Charlesa stavlja u situacije u kojima se njihova represivna ideologija razotkriva; na taj način satirizira kodove ponašanja u svojoj sadašnjosti

The face of equipoise - delivering a structured education programme within a randomized controlled trial: qualitative study

Background: In trials of behavioural interventions, the individuals who deliver the intervention are in a position of key influence on the success of the trial. Their fidelity to the intervention is crucial. Yet little is understood about the experiences of this group of trial personnel. This study aimed to investigate the views and experiences of educators who delivered a structured education intervention to people with type 2 diabetes, which incorporated training in self-monitoring of either blood glucose (SMBG) or urine glucose (SMUG) as part of a randomized controlled trial (RCT). Methods: Educators’ views were explored through focus groups before and after training (N = 18) and approximately 1 year into the trial (N = 14), and semi-structured telephone interviews at approximately 2 years (N = 7). Analysis was based on the constant comparative method. Results: Educators held preferences regarding the intervention variants; thus, they were not in individual equipoise. Training raised awareness of preferences and their potential to impact on delivery. Educators were confident in their unbiased delivery, but acknowledged the challenges involved. Concealing their preferences was helped by a sense of professionalism, the patient-centred nature of the intervention, and concessions in the trial protocol (enabling participants to swap monitoring methods if needed). Commitment to unbiased delivery was explained through a desire for evidence-based knowledge in the contentious area of SMBG. Conclusions: The findings provide insight into a previously unexplored group of trial personnel - intervention deliverers in trials of behavioural interventions - which will be useful to those designing and running similar trials. Rather than individual equipoise, it is intervention deliverers’ awareness of personal preferences and their potential impact on the trial outcome that facilitates unbiased delivery. Further, awareness of community equipoise, the need for evidence, and relevance to the individual enhance commitment to the RCT

Weight, Diet, and Physical Activity-Related Beliefs and Practices Among Pregnant and Postpartum Latino Women: The Role of Social Support

Objectives : Eating and physical activity patterns may contribute to excessive pregnancy weight gain and postpartum retention that increase the risks of obesity and diabetes for both Latino mothers and their children. Social support is an important health determinant and may affect health-related beliefs and behaviors. The objective of this study was to investigate the influence of social support on weight, diet, and physical activity-related beliefs and behaviors among pregnant and postpartum Latinas. Methods : A community-based participatory project, Promoting Healthy Lifestyles among Women, was conducted in southwest Detroit to plan interventions aimed at reducing risks of obesity and type 2 diabetes. Qualitative analyses of in-depth semistructured interviews with dyads of 10 pregnant and postpartum Latinas, and 10 people who influenced them were conducted. Results : Husbands and some female relatives were primary sources of emotional, instrumental, and informational support for weight, diet, and physical activity-related beliefs and behaviors for Latina participants. Holistic health beliefs and the opinions of others consistently influenced Latinas' motivation and beliefs about the need to remain healthy and the links between behavior and health. Absence of mothers, other female relatives, and friends to provide childcare, companionship for exercise, and advice about food were prominent barriers that limited women's ability to maintain healthy practices during and after pregnancy. Conclusion : The findings support evidence that low-income, recently immigrated pregnant and postpartum Latinas could benefit from community-based, family-oriented interventions that provide social support necessary to promote and sustain healthy lifestyles.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45320/1/10995_2005_Article_25.pd

A Global Portrait of Counselling Psychologists’ Characteristics, Perspectives, and Professional Behaviors

Counselling psychologists in eight countries (Australia, Canada, New Zealand, South Africa, South Korea, Taiwan, the United Kingdom, and the United States) responded to survey questions that focused on their demographics as well as their professional identities, roles, settings and activities. As well, they were asked about satisfaction with the specialty and the extent to which they endorsed 10 core counselling psychology values. This article reports those results, focusing both on areas in which there were between-country similarities as well as on those for which there were differences. These data provide is a snapshot of counselling psychology globally and establish a foundation for the other articles in this special issue of the journal

Upregulation of the cell-cycle regulator RGC-32 in Epstein-Barr virus-immortalized cells

Epstein-Barr virus (EBV) is implicated in the pathogenesis of multiple human tumours of lymphoid and epithelial origin. The virus infects and immortalizes B cells establishing a persistent latent infection characterized by varying patterns of EBV latent gene expression (latency 0, I, II and III). The CDK1 activator, Response Gene to Complement-32 (RGC-32, C13ORF15), is overexpressed in colon, breast and ovarian cancer tissues and we have detected selective high-level RGC-32 protein expression in EBV-immortalized latency III cells. Significantly, we show that overexpression of RGC-32 in B cells is sufficient to disrupt G2 cell-cycle arrest consistent with activation of CDK1, implicating RGC-32 in the EBV transformation process. Surprisingly, RGC-32 mRNA is expressed at high levels in latency I Burkitt's lymphoma (BL) cells and in some EBV-negative BL cell-lines, although RGC-32 protein expression is not detectable. We show that RGC-32 mRNA expression is elevated in latency I cells due to transcriptional activation by high levels of the differentially expressed RUNX1c transcription factor. We found that proteosomal degradation or blocked cytoplasmic export of the RGC-32 message were not responsible for the lack of RGC-32 protein expression in latency I cells. Significantly, analysis of the ribosomal association of the RGC-32 mRNA in latency I and latency III cells revealed that RGC-32 transcripts were associated with multiple ribosomes in both cell-types implicating post-initiation translational repression mechanisms in the block to RGC-32 protein production in latency I cells. In summary, our results are the first to demonstrate RGC-32 protein upregulation in cells transformed by a human tumour virus and to identify post-initiation translational mechanisms as an expression control point for this key cell-cycle regulator

What Parents of Children Who Have Received Emergency Care Think about Deferring Consent in Randomised Trials of Emergency Treatments: Postal Survey

OBJECTIVE: To investigate parents' views about deferred consent to inform management of trial disclosure after a child's death. METHODS: A postal questionnaire survey was sent to members of the Meningitis Research Foundation UK charity, whose child had suffered from bacterial meningitis or meningococcal septicaemia within the previous 5 years. Main outcome measures were acceptability of deferred consent; timing of requesting consent; and the management of disclosure of the trial after a child's death. RESULTS: 220 families were sent questionnaires of whom 63 (29%) were bereaved. 68 families responded (31%), of whom 19 (28%) were bereaved. The majority (67%) was willing for their child to be involved in the trial without the trial being explained to them beforehand; 70% wanted to be informed about the trial as soon as their child's condition had stabilised. In the event of a child's death before the trial could be discussed the majority of bereaved parents (66% 12/18) anticipated wanting to be told about the trial at some time. This compared with 37% (18/49) of non-bereaved families (p = 0.06). Parents' free text responses indicated that the word 'trial' held strongly negative connotations. A few parents regarded gaps in the evidence base about emergency treatments as indicating staff lacked expertise to care for a critically ill child. Bereaved parents' free text responses indicated the importance of individualised management of disclosure about a trial following a child's death. DISCUSSION: Deferred consent is acceptable to the majority of respondents. Parents whose children had recovered differed in their views compared to bereaved parents. Most bereaved parents would want to be informed about the trial in the aftermath of a child's death, although a minority strongly opposed such disclosure. Distinction should be drawn between the views of bereaved and non-bereaved parents when considering the acceptability of different consent processes