A conceptual model of suicide in rural areas

Context: Suicide is an important public health issue among rural communities although there is no single pattern of suicide in rural areas. Despite this, there are common themes in much of the research evidence on suicide in rural areas. From the published research in the area, a conceptual model of rural suicide has been developed which can be used by clinical and public health services when considering possible routes of intervention.Issue: A conceptual model can be defined as 'a type of diagram which shows a set of relationships between factors that are believed to impact or lead to a target condition'. The model presented here uses the 'Cry of pain/ Entrapment' model of suicide risk to build a framework of factors which are associated with suicide in rural areas. Cross-setting factors associated with suicide rates include gender, poverty, mental illness, substance use, biological factors including apparent genetic risk, coping skills and media coverage of suicide. There are, however, other factors that appear to have particular importance in rural areas. These include rural stressors, such as isolation and political and social exclusion; factors affecting support, including social support, cultural norms on help-seeking, stigma associated with mental illness service availability; factors affecting the decision to self-harm, including modelling and cultural views on self-harm, and issues affecting the likelihood of self-harm resulting in death, including method availability, norms on methods of self-harm and treatment availability after harm occurs. Identifying which of these areas are the greatest local priorities helps to target activity.Lessons learned: This model provides a way of considering suicide in rural areas. Local staff can use it to consider which issues are most relevant to their area. It allows classification of existing interventions, and deciding which other areas of work might be of local value. For researchers and service planners, it provides a way of classifying interventions and describing projects

Making or Breaking Metal- Dependent Catalytic Activity: The Role of Stammers in Designed Three- Stranded Coiled Coils

While many life- critical reactions would be infeasibly slow without metal cofactors, a detailed understanding of how protein structure can influence catalytic activity remains elusive. Using de novo designed three- stranded coiled coils (TRI and Grand peptides formed using a heptad repeat approach), we examine how the insertion of a three residue discontinuity, known as a stammer insert, directly adjacent to a (His)3 metal binding site alters catalytic activity. The stammer, which locally alters the twist of the helix, significantly increases copper- catalyzed nitrite reductase activity (CuNiR). In contrast, the well- established zinc- catalyzed carbonic anhydrase activity (p- nitrophenyl acetate, pNPA) is effectively ablated. This study illustrates how the perturbation of the protein sequence using non- coordinating and non- acid base residues in the helical core can perturb metalloenzyme activity through the simple expedient of modifying the helical pitch adjacent to the catalytic center.The addition of a stammer discontinuity within a de novo designed three- stranded coiled coil containing a symmetric (His)3 metal binding site enhances copper nitrite reductase activity and ablates zinc esterase activity. These results suggest catalytic activity of designed α- helical systems can be modulated by inclusion of discontinuity insertions and deletions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163477/3/ange202008356_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163477/2/ange202008356-sup-0001-misc_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163477/1/ange202008356.pd

The microRNA-29 family in cartilage homeostasis and osteoarthritis

MicroRNAs have been shown to function in cartilage development and homeostasis, as well as in progression of osteoarthritis. The objective of the current study was to identify microRNAs involved in the onset or early progression of osteoarthritis and characterise their function in chondrocytes. MicroRNA expression in mouse knee joints post-DMM surgery was measured over 7 days. Expression of miR-29b-3p was increased at day 1 and regulated in the opposite direction to its potential targets. In a mouse model of cartilage injury and in end-stage human OA cartilage, the miR-29 family were also regulated. SOX9 repressed expression of miR-29a-3p and miR-29b-3p via the 29a/b1 promoter. TGFβ1 decreased expression of miR-29a, b and c (3p) in primary chondrocytes, whilst IL-1β increased (but LPS decreased) their expression. The miR-29 family negatively regulated Smad, NFκB and canonical WNT signalling pathways. Expression profiles revealed regulation of new WNT-related genes. Amongst these, FZD3, FZD5, DVL3, FRAT2, CK2A2 were validated as direct targets of the miR-29 family. These data identify the miR-29 family as microRNAs acting across development and progression of OA. They are regulated by factors which are important in OA and impact on relevant signalling pathways

Assessing the ability of rural agrarian areas to provide Cultural Ecosystem Services (CES): a Multi Scale Social Indicator Framework (MSIF)

Assessing the ways in which rural agrarian areas provide Cultural Ecosystem Services (CES) is proving difficult to achieve. This research has developed an innovative methodological approach named as Multi Scale Indicator Framework (MSIF) for capturing the CES embedded into the rural agrarian areas. This framework reconciles a literature review with a trans-disciplinary participatory workshop. Both of these sources reveal that societal preferences diverge upon judgemental criteria which in turn relate to different visual concepts that can be drawn from analysing attributes, elements, features and characteristics of rural areas. We contend that it is now possible to list a group of possible multi scale indicators for stewardship, diversity and aesthetics. These results might also be of use for improving any existing European indicators frameworks by also including CES. This research carries major implications for policy at different levels of governance, as it makes possible to target and monitor policy instruments to the physical rural settings so that cultural dimensions are adequately considered. There is still work to be developed on regional specific values and thresholds for each criteria and its indicator set. In practical terms, by developing the conceptual design within a common framework as described in this paper, a considerable step forward towards the inclusion of the cultural dimension in European wide assessments can be made

Novel inhibition of carbonic anhydrase isozymes I, II and III by carbamoyl phosphate

Carbamoyl phosphate has been shown to inhibit carbonic anhydrase (CA) isozymes CA I, CA II and CA III. This physiologically important molecule is the most potent, naturally occurring inhibitor of carbonic anhydrase yet found. It is also unique, among carbonic anhydrase inhibitors discovered hitherto, in that it inhibits the 3 isozymes with equal effect, despite their strikingly different properties. The results imply the participation of carbonic anhydrase in the regulation of substrate availability for the urea cycle.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24933/1/0000360.pd

Long-term Mortality in HIV-Positive Individuals Virally Suppressed for >3 Years With Incomplete CD4 Recovery

Virally suppressed HIV-positive individuals on combination antiretroviral therapy who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality. The increased mortality was seen across different patient groups and for all causes of deat

Precision measurements of A1N in the deep inelastic regime

We have performed precision measurements of the double-spin virtual-photon asymmetry A1A1 on the neutron in the deep inelastic scattering regime, using an open-geometry, large-acceptance spectrometer and a longitudinally and transversely polarized 3He target. Our data cover a wide kinematic range 0.277≤x≤0.5480.277≤x≤0.548 at an average Q2Q2 value of 3.078 (GeV/c)2, doubling the available high-precision neutron data in this x range. We have combined our results with world data on proton targets to make a leading-order extraction of the ratio of polarized-to-unpolarized parton distribution functions for up quarks and for down quarks in the same kinematic range. Our data are consistent with a previous observation of anA1n zero crossing near x=0.5x=0.5. We find no evidence of a transition to a positive slope in(Δd+Δd¯)/(d+d¯) up to x=0.548x=0.548

Comparative analyses imply that the enigmatic sigma factor 54 is a central controller of the bacterial exterior

Contains fulltext : 95738.pdf (publisher's version ) (Open Access)BACKGROUND: Sigma-54 is a central regulator in many pathogenic bacteria and has been linked to a multitude of cellular processes like nitrogen assimilation and important functional traits such as motility, virulence, and biofilm formation. Until now it has remained obscure whether these phenomena and the control by Sigma-54 share an underlying theme. RESULTS: We have uncovered the commonality by performing a range of comparative genome analyses. A) The presence of Sigma-54 and its associated activators was determined for all sequenced prokaryotes. We observed a phylum-dependent distribution that is suggestive of an evolutionary relationship between Sigma-54 and lipopolysaccharide and flagellar biosynthesis. B) All Sigma-54 activators were identified and annotated. The relation with phosphotransfer-mediated signaling (TCS and PTS) and the transport and assimilation of carboxylates and nitrogen containing metabolites was substantiated. C) The function annotations, that were represented within the genomic context of all genes encoding Sigma-54, its activators and its promoters, were analyzed for intra-phylum representation and inter-phylum conservation. Promoters were localized using a straightforward scoring strategy that was formulated to identify similar motifs. We found clear highly-represented and conserved genetic associations with genes that concern the transport and biosynthesis of the metabolic intermediates of exopolysaccharides, flagella, lipids, lipopolysaccharides, lipoproteins and peptidoglycan. CONCLUSION: Our analyses directly implicate Sigma-54 as a central player in the control over the processes that involve the physical interaction of an organism with its environment like in the colonization of a host (virulence) or the formation of biofilm

Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008

SCOPUS: ar.jinfo:eu-repo/semantics/publishe