bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome scale prediction of substrate specificity for acyl adenylate superfamily of enzymes based on active site residue profiles
Authors: Khurana Pankaj , Gokhale Rajesh S , Mohanty Debasisa 
Published: January 2010

Abstract

Background
Enzymes belonging to acyl:CoA synthetase (ACS) superfamily activate wide variety of substrates and play major role in increasing the structural and functional diversity of various secondary metabolites in microbes and plants. However, due to the large sequence divergence within the superfamily, it is difficult to predict their substrate preference by annotation transfer from the closest homolog. Therefore, a large number of ACS sequences present in public databases lack any functional annotation at the level of substrate specificity. Recently, several examples have been reported where the enzymes showing high sequence similarity to luciferases or coumarate:CoA ligases have been surprisingly found to activate fatty acyl substrates in experimental studies. In this work, we have investigated the relationship between the substrate specificity of ACS and their sequence/structural features, and developed a novel computational protocol for in silico assignment of substrate preference.

Results
We have used a knowledge-based approach which involves compilation of substrate specificity information for various experimentally characterized ACS and derivation of profile HMMs for each subfamily. These HMM profiles can accurately differentiate probable cognate substrates from non-cognate possibilities with high specificity (Sp) and sensitivity (Sn) (Sn = 0.91-1.0, Sp = 0.96-1.0) values. Using homologous crystal structures, we identified a limited number of contact residues crucial for substrate recognition i.e. specificity determining residues (SDRs). Patterns of SDRs from different subfamilies have been used to derive predictive rules for correlating them to substrate preference. The power of the SDR approach has been demonstrated by correct prediction of substrates for enzymes which show apparently anomalous substrate preference. Furthermore, molecular modeling of the substrates in the active site has been carried out to understand the structural basis of substrate selection. A web based prediction tool http://www.nii.res.in/pred_acs_substr.html has been developed for automated functional classification of ACS enzymes.

Conclusions
We have developed a novel computational protocol for predicting substrate preference for ACS superfamily of enzymes using a limited number of SDRs. Using this approach substrate preference can be assigned to a large number of ACS enzymes present in various genomes. It can potentially help in rational design of novel proteins with altered substrate specificities.
Longitudinal survey of Staphylococcus aureus in cystic fibrosis patients using a multiple-locus variable-number of tandem-repeats analysis method
Authors: Vu-Thien Hoang , Hormigos Katia , Corbineau Gaëlle , Fauroux Brigitte , Corvol Harriet , Moissenet Didier , Vergnaud Gilles , Pourcel Christine 
Published: January 2010

Abstract

Background

Staphylococcus aureus infection in patients with cystic fibrosis (CF) is frequent and may be due to colonization by a few pathogenic lineages. Systematic genotyping of all isolates, methicillin-susceptible S. aureus (MSSA) as well as methicillin-resistant S. aureus (MRSA) is necessary to identify such lineages and follow their evolution in patients. Multiple-locus variable-number tandem repeat analysis (MLVA/VNTR) was used to survey S. aureus clinical isolates in a French paediatric CF centre.

Results
During a 30 months period, 108 patients, aged 2 to 21 years, regularly followed up at the centre, provided sputum for culture. From 79 patients, a total of 278 isolates were genotyped by MLVA, resolving into 110 genotypes and 19 clonal complexes (CC) composed of similar or closely related isolates. 71% of the strains were distributed into four main CCs, in term of number of isolates and number of genotypes. Spa (Staphylococcus protein A) typing was performed on representative samples, showing an excellent concordance with MLVA. In 17 patients, strains from two to four different CCs were recovered over time. On six occasions, S. aureus isolates with the same genotype were shared by 2 different patients and they belonged to one of the four main clusters. Methicillin-resistance was observed in 60% of the isolates, 90% of which belonged to the main clonal complexes CC8, CC45 and CC5. In 5 patients, methicillin-resistance of S. aureus isolates was not associated with the mecA gene: for four patients, it was due to overproduction of β-lactamase, leading to BOR-SA (borderline S. aureus) isolates, while a strain showing probably a new modified penicillin-binding capacity (MOD-SA) was observed from one patient.

Conclusion
Systematic genotyping of S. aureus isolates recovered from sputum of CF children allows a thorough analysis of the strains responsible for sporadic as well as chronic colonization and the follow up of their evolution over time. We show here that more than 70% of these strains belong to 4 major CCs. MSSA as well as MRSA, BOR-SA and MOD-SA isolates can persist over several years, despite antibiotic treatments.
Patterns of smoking and its association with psychosocial work conditions among blue-collar and service employees of hospitality venues in Shenyang, PR China
Authors: Li Xun , Liang Huiying , Li Xuelian , Guan Peng , Yin Zhihua , Zhou Baosen 
Published: January 2010

Abstract

Background
To characterize the smoking patterns of hospitality employees in blue-collar and service occupations, and to examine its relations with psychosocial work conditions.

Methods
The Shenyang Hospitality Industry Employees Survey-a face-to-face cross-sectional study of representative hospitality industry employees-was conducted between March and July 2008. A total of 4,213 workers were selected using stratified random cluster sampling designs, and final analyses were performed on 2,508 blue-collar and service subjects. Multilevel-logistic regression models were used to estimate the contribution of psychosocial work conditions to smoking status.

Results
Blue-collar and service employees smoked at a rate 1.4 times that of the general population (49.4% vs. 35.8%), more particularly for females (12.9% vs. 3.08%). Strain jobs had significantly higher odds ratio of daily smoking (OR 2.09, 95%CI: 1.28-3.41) compared to the relaxed category. The passive jobs (OR 2.01, 95%CI 1.27 to 3.17), highest job demands (OR 1.72, 95%CI: 1.13-2.61), and lowest job control (OR 2.56, 95%CI: 1.57-4.16) were also associated with a significantly higher daily smoking ratio. The negative relationship between job stability and smoking behavior was slightly stronger among daily than occasional smokers. However, neither job strain nor any of its components was found to be significantly associated with occasional smoking.

Conclusions
Smoking in hospitality blue-collar and service employees is certainly a major occupational health problem in Shenyang. This evidence also suggests an association between psychosocial-work conditions and smoking status, and implies that more intervention studies where changes in work environment are carried out in combination with health promotion interventions should be performed.
Crystal structure of the signaling helix coiled-coil domain of the β1 subunit of the soluble guanylyl cyclase
Authors: Ma Xiaolei , Beuve Annie , van den Akker Focco 
Published: January 2010

AbstractBackgroundThe soluble guanylyl cyclase (sGC) is a heterodimeric enzyme that, upon activation by nitric oxide, stimulates the production of the second messenger cGMP. Each sGC subunit harbor four domains three of which are used for heterodimerization: H-NOXA/H-NOBA domain, coiled-coil domain (CC), and catalytic guanylyl cyclase domain. The CC domain has previously been postulated to be part of a larger CC family termed the signaling helix (S-helix) family. Homodimers of sGC have also been observed but are not functionally active yet are likely transient awaiting their intended heterodimeric partner.ResultsTo investigate the structure of the CC S-helix region, we crystallized and determined the structure of the CC domain of the sGCβ1 subunit comprising residues 348-409. The crystal structure was refined to 2.15 Å resolution.ConclusionsThe CC structure of sGCβ1 revealed a tetrameric arrangement comprised of a dimer of CC dimers. Each monomer is comprised of a long a-helix, a turn near residue P399, and a short second a-helix. The CC structure also offers insights as to how sGC homodimers are not as stable as (functionally) active heterodimers via a possible role for inter-helix salt-bridge formation. The structure also yielded insights into the residues involved in dimerization. In addition, the CC region is also known to harbor a number of congenital and man-made mutations in both membrane and soluble guanylyl cyclases and those function-affecting mutations have been mapped onto the CC structure. This mutant analysis indicated an importance for not only certain dimerization residue positions, but also an important role for other faces of the CC dimer which might perhaps interact with adjacent domains. Our results also extend beyond guanylyl cyclases as the CC structure is, to our knowledge, the first S-helix structure and serves as a model for all S-helix containing family members.
Reconstructing the ups and downs of primate brain evolution: implications for adaptive hypotheses and Homo floresiensis
Authors: Montgomery Stephen H , Capellini Isabella , Barton Robert A , Mundy Nicholas I 
Published: January 2010

AbstractBackgroundBrain size is a key adaptive trait. It is often assumed that increasing brain size was a general evolutionary trend in primates, yet recent fossil discoveries have documented brain size decreases in some lineages, raising the question of how general a trend there was for brains to increase in mass over evolutionary time. We present the first systematic phylogenetic analysis designed to answer this question.ResultsWe performed ancestral state reconstructions of three traits (absolute brain mass, absolute body mass, relative brain mass) using 37 extant and 23 extinct primate species and three approaches to ancestral state reconstruction: parsimony, maximum likelihood and Bayesian Markov-chain Monte Carlo. Both absolute and relative brain mass generally increased over evolutionary time, but body mass did not. Nevertheless both absolute and relative brain mass decreased along several branches. Applying these results to the contentious case ofHomo floresiensis, we find a number of scenarios under which the proposed evolution ofHomo floresiensis'small brain appears to be consistent with patterns observed along other lineages, dependent on body mass and phylogenetic position.ConclusionsOur results confirm that brain expansion began early in primate evolution and show that increases occurred in all major clades. Only in terms of an increase in absolute mass does the human lineage appear particularly striking, with both the rate of proportional change in mass and relative brain size having episodes of greater expansion elsewhere on the primate phylogeny. However, decreases in brain mass also occurred along branches in all major clades, and we conclude that, while selection has acted to enlarge primate brains, in some lineages this trend has been reversed. Further analyses of the phylogenetic position ofHomo floresiensisand better body mass estimates are required to confirm the plausibility of the evolution of its small brain mass. We find that for our dataset the Bayesian analysis for ancestral state reconstruction is least affected by inclusion of fossil data suggesting that this approach might be preferable for future studies on other taxa with a poor fossil record.
Vpu-dependent block to incorporation of GaLV Env into lentiviral vectors
Authors: Christodoulopoulos Ilias , Droniou-Bonzom Magali E , Oldenburg Jill E , Cannon Paula M 
Published: January 2010

Abstract

Background
The gibbon ape leukemia virus (GaLV) Env protein mediates entry into a wide range of human cells and is frequently used to pseudotype retroviral vectors. However, an incompatibility exists between GaLV Env and lentiviral vectors that results in decreased steady-state levels of the mature GaLV Env in cells and prevents its incorporation into lentiviral vector particles.

Results
We identified the HIV-1 Vpu protein as the major cause of the depletion in GaLV Env levels that occurs when lentiviral vector components are present. This activity of Vpu targeted the mature (cleaved) form of the GaLV Env that exists within or beyond the trans-Golgi. The activity required two conserved phospho-serines in the cytoplasmic tail of Vpu that are known to recruit β TrCP, a substrate adaptor for an SCF E3 ubiquitin ligase complex, and could be blocked by mutation of lysine 618 in the GaLV Env tail. Moreover, the Vpu-mediated decrease of GaLV Env levels was inhibited by the lysosomal inhibitor, bafilomycin A1. Interestingly, this activity of Vpu was only observed in the presence of other lentiviral vector components.

Conclusions
Similar to the mechanism whereby Vpu targets BST-2/tetherin for degradation, these findings implicate β-TrCP-mediated ubiquitination and the endo-lysosomal pathway in the degradation of the GaLV Env by lentiviral vector components. Possibly, the cytoplasmic tail of the GaLV Env contains features that mimic bona fide targets of Vpu, important to HIV-1 replication. Furthermore, the lack of effect of Vpu on GaLV Env in the absence of other HIV-1 proteins, suggests that a more complex interaction may exist between Vpu and its target proteins, with the additional involvement of one or more component(s) of the HIV-1 replication machinery.
Prompt improvement of a pressure ulcer by the administration of high viscosity semi-solid nutrition via a nasogastric tube in a man with tuberculosis: a case report
Authors: Nakayama Tamaki , Hayashi Seiji , Okishio Kyoichi , Tomishiro Tomoko , Hosogai Kaori , Ootsu Yuki , Morioka Yasushi , Hatsuda Kazuyoshi , Naito Eriko , Sakatani Mitsunori 
Published: January 2010

Abstract

Introduction
Semi-solid nutrition with high viscosity has the advantage of reducing gastroesophageal reflux and diarrhea and shortens the duration of administration compared with liquid nutrition. This is the first report describing the administration of semi-solid nutrition with high viscosity via a nasogastric tube, which achieved a remarkable improvement in the patient's nutritional state.

Case presentation
A 67-year-old man (mongoloid race, Japanese) with tuberculosis, a pressure ulcer and malnutrition was admitted to our hospital. He also had right hemiplegia, dysphagia and aphasia as sequelae of a cerebral hemorrhage. Before his admission, he had been treated at another hospital with 600 kcal/day of liquid nutrition via a nasogastric tube, which was insufficient and induced severe malnutrition. After he was admitted to our hospital, we increased the quantity of his liquid nutrition without success because of complications, specifically diarrhea and gastroesophageal reflux. As it was difficult to confirm whether or not he would accept gastrostomy feeding, we administered semi-solid nutrition with high viscosity (20,000 mPa x s) via a large-bore nasogastric tube (18 French). Soon after he was started on semi-solid nutrition, his pressure ulcer and malnutrition improved without diarrhea or complications accompanying the large-bore nasogastric tube.

Conclusion
When patients have problems with liquid nutrition, such as diarrhea or gastroesophageal reflux, semi-solid nutrition via a nasogastric tube is a useful method of achieving improvements in nutritional state in a short period of time.
The use of a blood conservation device to reduce red blood cell transfusion requirements: a before and after study
Authors: Mukhopadhyay Amartya , Yip Hwee S , Prabhuswamy Dimple , Chan Yiong H , Phua Jason , Lim Tow K , Leong Patricia 
Published: January 2010

Abstract
Introduction
Anaemia and the associated need for packed red blood cell (PRBC) transfusions are common in patients admitted to the intensive care unit (ICU). Among many causes, blood losses from repeated diagnostic tests are contributory.

Methods
This is a before and after study in a medical ICU of a university hospital. We used a closed blood conservation device (Venous Arterial blood Management Protection, VAMP, Edwards Lifesciences, Irvine, CA, USA) to decrease PRBC transfusion requirements. We included all adult (≥18 years) patients admitted to the ICU with indwelling arterial catheters, who were expected to stay more than 24 hours and were not admitted for active gastrointestinal or any other bleeding. We collected data for six months without VAMP (control group) immediately followed by nine months (active group) with VAMP. A restrictive transfusion strategy in which clinicians were strongly discouraged from any routine transfusions when haemoglobin (Hb) levels were above 7.5 g/dL was adopted during both periods.

Results
Eighty (mean age 61.6 years, 49 male) and 170 patients (mean age 60.5 years, 101 male) were included in the control and active groups respectively. The groups were comparable for age, gender, Acute Physiology and Chronic Health Evaluation (APACHE) II score, need for renal replacement therapy, length of stay, and Hb levels on discharge and at transfusion. The control group had higher Hb levels on admission (12.4 ± 2.5 vs. 11.58 ± 2.8 gm/dL, P = 0.02). Use of a blood conservation device was significantly associated with decreased requirements for PRBC transfusion (control group 0.131 unit vs. active group 0.068 unit PRBC/patient/day, P = 0.02) on multiple linear regression analysis. The control group also had a greater decline in Hb levels (2.13 ± 2.32 vs. 1.44 ± 2.08 gm/dL, P = 0.02) at discharge.

Conclusions
The use of a blood conservation device is associated with 1) reduced PRBC transfusion requirements and 2) a smaller decrease in Hb levels in the ICU.
IL-21 enhances NK cell functions and survival in healthy and HIV-infected patients with minimal stimulation of viral replication
Authors: Iannello Alexandre , Boulassel Mohamed-Rachid , Samarani Suzanne , Tremblay Cécile , Toma Emil , Routy Jean-Pierre , Ahmad Ali 
Published: January 2010

Abstract
IL-21 enhances NK cell functions and survival in healthy and HIV-infected patients with inhibition of viral replication.
IL-21 plays an important role in regulating immune response and controlling chronic viral infections. Recently, we reported its decreased serum concentrations and their immunological consequences in HIV-infected persons. In this study, we have investigated how exogenous IL-21 enhances NK cell responses in these persons. We show that the cytokine receptors are expressed equally on all NK cell subsets defined by expression of CD16 and CD56; the cytokine activates STAT-3, MAPK, and Akt to enhance NK cell functions; the STAT-3 activation plays a key role in constitutive and IL-21-mediated enhancement of NK cell functions; the cytokine increases expression of antiapoptotic proteins Bcl-2 and Bcl-XL and enhances viability of NK cells but has no effect on their proliferation; the cytokine enhances HIV-specific ADCC, secretory, and cytotoxic functions, as well as viability of NK cells from HIV-infected persons; it exerts its biological effects on NK cells with minimal stimulation of HIV-1 replication; and the cytokine-activated NK cells inhibit viral replication in cocultured, HIV-infected, autologous CD4+ T cells in a perforin- and LFA-1-dependent manner. These data suggest that IL-21 may serve as a valuable therapeutic tool for enhancing NK cell responses and inhibiting viral replication in HIV-infected patients.
Polypharmacy and high-dose antipsychotic regimes in the community
Authors: Tungaraza Tongeji E. , Gupta Seema , Jones Jane , Poole Rob , Slegg Gary 
Published: January 2010

Aims and methodTo determine the pattern of psychotropic prescribing in a group of people with psychosis who were living in the community under community mental health team (CMHT) care. Case-note entries over the previous 12 months were examined.ResultsOnly a third of individuals were on one psychotropic medication. Atypical antipsychotics were prescribed to 80.6%. Polypharmacy was common. A third of people were taking three or more psychotropic drugs and 13.7% were on high-dose regimes, mostly involving two atypical antipsychotics.Clinical implicationsThe use of atypicals has not eliminated polypharmacy or high-dose antipsychotic regimes. Clinicians need to be aware of this long-standing problem.
Characteristics of people with severe mental illness who obtain employment
Authors: Butler G. , Howard L. , Choi S. , Thornicroft G. 
Published: January 2010

Aims and methodWe explored sociodemographic and clinical factors associated with obtaining employment for people with severe mental illness. Standardised validated interviews and questionnaires were administered to participants who had been recruited into a randomised controlled trial of supported employment.ResultsOlder age and diagnosis of schizophrenia were found to be independent predictors of unemployment in the previous year. Other factors of unemployment such as ethnicity and educational level were not associated with obtaining employment.Clinical implicationsOlder people and those with a diagnosis of schizophrenia may need additional targeted help in obtaining employment if they are to be helped to meet their vocational aims. Further research is needed to determine how this can be done most effectively.
Electroconvulsive therapy: medical students' attitudes and knowledge
Authors: Kinnair Daniel , Dawson Sheila , Perera Roshan 
Published: January 2010

Aims and methodWith increasing numbers of students and falling numbers of individuals receiving electroconvulsive therapy (ECT) it has been difficult to timetable all students to witness ECT, and it has been suggested that this experience may be dispensed with. However, we wondered how the experience of witnessing ECT might enhance students' knowledge and, just as importantly, challenge negative perceptions of ECT. We surveyed students' attitudes and knowledge at the beginning and the end of their 8-week attachment in psychiatry.ResultsThere appears to be a clear benefit in terms of knowledge and positive attitudinal change for students who both witness ECT and receive a lecture on the subject.Clinical implicationsDirect observation of ECT can challenge and affect attitudes in ways a lecture may not. Any changes to the provision of ECT teaching for medical students, including replacing witnessing ECT, needs to be carefully developed and assessed.
Preparing for practice: a higher education perspective. Commentary on … A clinical librarian pilot project in psychiatry
Authors: Spoor Pat , Neilly Liz 
Published: January 2010

SummaryResearch suggests that contact time between clinical team and clinical librarian can have a direct and positive impact on patient care through encouraging a more rigorous approach to information retrieval and appraisal of the evidence base. This commentary focuses on the findings of a specific clinical librarian pilot project in a mental health trust. It discusses how clinicians could be better supported to develop improved information literacy skills through initiatives in higher education and what impact this might have on the model of clinical librarianship proposed by the project.