Structural insight into SUMO chain recognition and manipulation by the ubiquitin ligase RNF4

The small ubiquitin-like modifier (SUMO) can form polymeric chains that are important signals in cellular processes such as meiosis, genome maintenance and stress response. The SUMO-targeted ubiquitin ligase RNF4 engages with SUMO chains on linked substrates and catalyses their ubiquitination, which targets substrates for proteasomal degradation. Here we use a segmental labelling approach combined with solution nuclear magnetic resonance (NMR) spectroscopy and biochemical characterization to reveal how RNF4 manipulates the conformation of the SUMO chain, thereby facilitating optimal delivery of the distal SUMO domain for ubiquitin transfer

Healthcare in schizophrenia: effectiveness and progress of a redesigned care network

<p>Abstract</p> <p>Background</p> <p>The aim of this study was designed to investigate the care-effectiveness of different healthcare models for schizophrenic patients and the impact of it on caregivers.</p> <p>Methods</p> <p>Sample cases were randomly selected from southern Taiwan, 257 patients in redesigned care network, including a general hospital, a chronic ward, 10 outpatient clinics, and multialternative community programs, was compared to 247 patients in other traditional healthcare provider that were utilized as the control group. The quality of life (QOL) questionnaire and the Chinese health questionnaire (CHQ) were used.</p> <p>Results</p> <p>The controls had longer duration of illness (<it>p </it>= 0.001) and were older (<it>p </it>= 0.004). The average resource utilization in the study group (US$2737/year, per case) was higher than the control group (US$ 2041) (<it>t </it>= 7.91, <it>p </it>< 0.001). For the study group, the average length of stay was shorter, but the admission rate was higher. The QOL of the patients in the study group was better than that of the controls (<it>p </it>= 0.01). The family burden of the study group was lower (<it>p </it>= 0.035) and the score of general health questionnaire higher (<it>p </it>= 0.019).</p> <p>Conclusion</p> <p>We found that patients in the redesigned care network had a better QOL, lower family burden, decreased days of hospital stay, higher medical resource utilization and less frequent admission to a hospital, and the caregivers had better mental health. Although the costs were higher, the continued care network was more helpful in providing comprehensive mental illness services.</p

Will the community nurse continue to function during H1N1 influenza pandemic: a cross-sectional study of Hong Kong community nurses?

<p>Abstract</p> <p>Background</p> <p>Healthcare workers have been identified as one of the high risk groups for being infected with influenza during influenza pandemic. Potential levels of absenteeism among healthcare workers in hospital settings are high. However, there was no study to explore the attitudes of healthcare workers in community setting towards the preparedness to the novel H1N1 influenza pandemic. The aim of this study was to explore the willingness of community nurses in Hong Kong to work during H1N1 influenza pandemic.</p> <p>Methods</p> <p>A cross-sectional survey was conducted among all 401 community nurses employed by the Hospital Authority in Hong Kong when the WHO pandemic alert level was 6.</p> <p>Results</p> <p>The response rate of this study was 66.6%. 76.9% participants reported being "not willing" (33.3%) or "not sure" (43.6%) to take care of patients during H1N1 influenza pandemic. The self-reported reasons for being unwilling to report to duty during H1N1 influenza pandemic were psychological stress (55.0%) and fear of being infected H1N1 influenza (29.2%). The reported unwillingness to report to duty was marginally significantly associated with the request for further training of using infection control clinical guideline (OR: 0.057; CI: 0.25-1.02). Those who reported unwillingness or not being sure about taking care of the patients during H1N1 influenza pandemic were more depressed (p < 0.001) and found work more emotionally stressful (p < 0.001).</p> <p>Conclusions</p> <p>Interventions to provide infection control training and address community nurses' psychological needs might increase their willingness to provide care to patients in the community during H1N1 influenza pandemic. This would help to ensure an effective and appropriate health system response during the H1N1 influenza pandemic.</p

Academic Impact of a Public Electronic Health Database: Bibliometric Analysis of Studies Using the General Practice Research Database

BACKGROUND: Studies that use electronic health databases as research material are getting popular but the influence of a single electronic health database had not been well investigated yet. The United Kingdom's General Practice Research Database (GPRD) is one of the few electronic health databases publicly available to academic researchers. This study analyzed studies that used GPRD to demonstrate the scientific production and academic impact by a single public health database. METHODOLOGY AND FINDINGS: A total of 749 studies published between 1995 and 2009 with 'General Practice Research Database' as their topics, defined as GPRD studies, were extracted from Web of Science. By the end of 2009, the GPRD had attracted 1251 authors from 22 countries and been used extensively in 749 studies published in 193 journals across 58 study fields. Each GPRD study was cited 2.7 times by successive studies. Moreover, the total number of GPRD studies increased rapidly, and it is expected to reach 1500 by 2015, twice the number accumulated till the end of 2009. Since 17 of the most prolific authors (1.4% of all authors) contributed nearly half (47.9%) of GPRD studies, success in conducting GPRD studies may accumulate. The GPRD was used mainly in, but not limited to, the three study fields of "Pharmacology and Pharmacy", "General and Internal Medicine", and "Public, Environmental and Occupational Health". The UK and United States were the two most active regions of GPRD studies. One-third of GRPD studies were internationally co-authored. CONCLUSIONS: A public electronic health database such as the GPRD will promote scientific production in many ways. Data owners of electronic health databases at a national level should consider how to reduce access barriers and to make data more available for research

Haplotype-based quantitative trait mapping using a clustering algorithm

BACKGROUND: With the availability of large-scale, high-density single-nucleotide polymorphism (SNP) markers, substantial effort has been made in identifying disease-causing genes using linkage disequilibrium (LD) mapping by haplotype analysis of unrelated individuals. In addition to complex diseases, many continuously distributed quantitative traits are of primary clinical and health significance. However the development of association mapping methods using unrelated individuals for quantitative traits has received relatively less attention. RESULTS: We recently developed an association mapping method for complex diseases by mining the sharing of haplotype segments (i.e., phased genotype pairs) in affected individuals that are rarely present in normal individuals. In this paper, we extend our previous work to address the problem of quantitative trait mapping from unrelated individuals. The method is non-parametric in nature, and statistical significance can be obtained by a permutation test. It can also be incorporated into the one-way ANCOVA (analysis of covariance) framework so that other factors and covariates can be easily incorporated. The effectiveness of the approach is demonstrated by extensive experimental studies using both simulated and real data sets. The results show that our haplotype-based approach is more robust than two statistical methods based on single markers: a single SNP association test (SSA) and the Mann-Whitney U-test (MWU). The algorithm has been incorporated into our existing software package called HapMiner, which is available from our website at . CONCLUSION: For QTL (quantitative trait loci) fine mapping, to identify QTNs (quantitative trait nucleotides) with realistic effects (the contribution of each QTN less than 10% of total variance of the trait), large samples sizes (≥ 500) are needed for all the methods. The overall performance of HapMiner is better than that of the other two methods. Its effectiveness further depends on other factors such as recombination rates and the density of typed SNPs. Haplotype-based methods might provide higher power than methods based on a single SNP when using tag SNPs selected from a small number of samples or some other sources (such as HapMap data). Rank-based statistics usually have much lower power, as shown in our study

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO