bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association of CD81 with tetraspanin-enriched microdomains is not essential for Hepatitis C virus entry
Authors: Rocha-Perugini Vera , Lavie Muriel , Delgrange David , Canton Jonathan , Pillez André , Potel Julie , Lecoeur Cécile , Rubinstein Eric , Dubuisson Jean , Wychowski Czeslaw , Cocquerel Laurence 
Published: May 2009

Abstract

Background
Three percent of the world's population is chronically infected with hepatitis C virus (HCV) and thus at risk of developing liver cancer. Although precise mechanisms regulating HCV entry into hepatic cells are still unknown, several cell surface proteins have been identified as entry factors for this virus. Among these molecules, the tetraspanin CD81 is essential for HCV entry. Interestingly, CD81 is also required for Plasmodium infection. A major characteristic of tetraspanins is their ability to interact with each other and other transmembrane proteins to build tetraspanin-enriched microdomains (TEM).

Results
In our study, we describe a human hepatoma Huh-7 cell clone (Huh-7w7) which has lost CD81 expression and can be infected by HCV when human CD81 (hCD81) or mouse CD81 (mCD81) is ectopically expressed. We took advantage of these permissive cells expressing mCD81 and the previously described MT81/MT81w mAbs to analyze the role of TEM-associated CD81 in HCV infection. Importantly, MT81w antibody, which only recognizes TEM-associated mCD81, did not strongly affect HCV infection. Furthermore, cholesterol depletion, which inhibits HCV infection and reduces total cell surface expression of CD81, did not affect TEM-associated CD81 levels. In addition, sphingomyelinase treatment, which also reduces HCV infection and cell surface expression of total CD81, raised TEM-associated CD81 levels.

Conclusion
In contrast to Plasmodium infection, our data show that association of CD81 with TEM is not essential for the early steps of HCV life cycle, indicating that these two pathogens, while using the same molecules, invade their host by different mechanisms.
Cemented versus non-cemented hemiarthroplasty of the hip as a treatment for a displaced femoral neck fracture: design of a randomised controlled trial
Authors: Vochteloo Anne JH , Niesten DieuDonné , Riedijk Roeland , Rijnberg Willard J , Bolder Stefan BT , Koëter Sander , Hei Keetie Kremers-van de , Gosens Taco , Pilot Peter 
Published: May 2009

Abstract

Background
A discussion is ongoing whether displaced femoral neck fractures in elderly patients should be treated with a non-cemented or a cemented hemiarthroplasty. A recent Cochrane analysis stresses the importance of further research into the relative merits of these techniques. We hypothesise that non-cemented hemiarthroplasty will result in at least the same technical-functional outcome and complication rate, with a shorter operation time.

Methods and design
A randomised controlled multicentre trial will be performed.
The study population consists of 200 patients of 70 years and older. Patients with a displaced femoral neck fracture will be allocated randomly to have a cemented or a non-cemented hemiarthroplasty. Data will be collected preoperatively, immediately postoperatively, and 6 weeks, 3 months and 1 year postoperatively.
The main outcome measures of this study are technical-functional results of the hemiarthroplasty, duration of surgery, complications, and mid-thigh pain. Secondary outcome measures are living conditions at final follow up, self-reported health-related quality of life, and radiological evaluation of the hemiarthroplasty.

Conclusion
A recent Cochrane analysis did not find arguments in favour of either non-cemented or cemented hemiarthroplasty. The forthcoming trial will compare treatment for a displaced femoral neck fracture by cemented versus non-cemented hemiarthroplasty. Our results will be published as soon as they become available.

Trial Registration
Trial Registration Number NTR1508
Analysis of proteins with the 'hot dog' fold: Prediction of function and identification of catalytic residues of hypothetical proteins
Authors: Pidugu Lakshmi S , Maity Koustav , Ramaswamy Karthikeyan , Surolia Namita , Suguna Kaza 
Published: May 2009

Abstract

Background
The hot dog fold has been found in more than sixty proteins since the first report of its existence about a decade ago. The fold appears to have a strong association with fatty acid biosynthesis, its regulation and metabolism, as the proteins with this fold are predominantly coenzyme A-binding enzymes with a variety of substrates located at their active sites.

Results
We have analyzed the structural features and sequences of proteins having the hot dog fold. This study reveals that though the basic architecture of the fold is well conserved in these proteins, significant differences exist in their sequence, nature of substrate and oligomerization. Segments with certain conserved sequence motifs seem to play crucial structural and functional roles in various classes of these proteins.

Conclusion
The analysis led to predictions regarding the functional classification and identification of possible catalytic residues of a number of hot dog fold-containing hypothetical proteins whose structures were determined in high throughput structural genomics projects.
Modeling of solvent-dependent conformational transitions in Burkholderia cepacia lipase
Authors: Trodler Peter , Schmid Rolf D , Pleiss Jürgen 
Published: May 2009

Abstract

Background
The characteristic of most lipases is the interfacial activation at a lipid interface or in non-polar solvents. Interfacial activation is linked to a large conformational change of a lid, from a closed to an open conformation which makes the active site accessible for substrates. While for many lipases crystal structures of the closed and open conformation have been determined, the pathway of the conformational transition and possible bottlenecks are unknown. Therefore, molecular dynamics simulations of a closed homology model and an open crystal structure of Burkholderia cepacia lipase in water and toluene were performed to investigate the influence of solvents on structure, dynamics, and the conformational transition of the lid.

Results
The conformational transition of B. cepacia lipase was dependent on the solvent. In simulations of closed B. cepacia lipase in water no conformational transition was observed, while in three independent simulations of the closed lipase in toluene the lid gradually opened during the first 10–15 ns. The pathway of conformational transition was accessible and a barrier was identified, where a helix prevented the lid from opening to the completely open conformation. The open structure in toluene was stabilized by the formation of hydrogen bonds.
In simulations of open lipase in water, the lid closed slowly during 30 ns nearly reaching its position in the closed crystal structure, while a further lid opening compared to the crystal structure was observed in toluene. While the helical structure of the lid was intact during opening in toluene, it partially unfolded upon closing in water. The closing of the lid in water was also observed, when with eight intermediate structures between the closed and the open conformation as derived from the simulations in toluene were taken as starting structures. A hydrophobic β-hairpin was moving away from the lid in all simulations in water, which was not observed in simulations in toluene. The conformational transition of the lid was not correlated to the motions of the β-hairpin structure.

Conclusion
Conformational transitions between the experimentally observed closed and open conformation of the lid were observed by multiple molecular dynamics simulations of B. cepacia lipase. Transitions in both directions occurred without applying restraints or external forces. The opening and closing were driven by the solvent and independent of a bound substrate molecule.
QDs versus Alexa: reality of promising tools for immunocytochemistry
Authors: Montón Helena , Nogués Carme , Rossinyol Emma , Castell Onofre , Roldán Mònica 
Published: May 2009

Abstract

Background
The unique photonic properties of the recently developed fluorescent semiconductor nanocrystals (QDs) have made them a potential tool in biological research. However, QDs are not yet a part of routine laboratory techniques. Double and triple immunocytochemistries were performed in HeLa cell cultures with commercial CdSe QDs conjugated to antibodies. The optical characteristics, due to which QDs can be used as immunolabels, were evaluated in terms of emission spectra, photostability and specificity.

Results
QDs were used as secondary and tertiary antibodies to detect β-tubulin (microtubule network), GM130 (Golgi complex) and EEA1 (endosomal system). The data obtained were compared to homologous Alexa Fluor 594 organic dyes. It was found that QDs are excellent fluorochromes with higher intensity, narrower bandwidth values and higher photostability than Alexa dyes in an immunocytochemical process. In terms of specificity, QDs showed high specificity against GM130 and EEA1 primary antibodies, but poor specificity against β-tubulin. Alexa dyes showed good specificity for all the targets tested.

Conclusion
This study demonstrates the great potential of QDs, as they are shown to have superior properties to Alexa dyes. Although their specificity still needs to be improved in some cases, QDs conjugated to antibodies can be used instead of organic molecules in routine immunocytochemistry.
Progesterone receptor does not improve the performance and test effectiveness of the conventional 3-marker panel, consisting of estrogen receptor, vimentin and carcinoembryonic antigen in distinguishing between primary endocervical and endometrial adenocarcinomas in a tissue microarray extension study
Authors: Liao Chiung-Ling , Lee Ming-Yung , Tyan Yeu-Sheng , Kok Lai-Fong , Wu Tina S , Koo Chiew-Loon , Wang Po-Hui , Chao Kuan-Chong , Han Chih-Ping 
Published: May 2009

Abstract

Objective
Endocervical adenocarcinomas (ECA) and endometrial adenocarcinomas (EMA) are uterine malignancies that have differing biological behaviors. The choice of an appropriate therapeutic plan rests on the tumor's site of origin. In this study, we propose to evaluate whether PR adds value to the performance and test effectiveness of the conventional 3-marker (ER/Vim/CEA) panel in distinguishing between primary ECA and EMA.

Methods
A tissue microarray was constructed using paraffin-embedded, formalin-fixed tissues from 38 hysterectomy specimens, including 14 ECA and 24 EMA. Tissue microarray (TMA) sections were immunostained with 4 antibodies, using the avidin-biotin complex (ABC) method for antigen visualization. The staining intensity and extent of the immunohistochemical (IHC) reactions were appraised using a semi-quantitative scoring system.

Results
The three markers (ER, Vim and CEA) and their respective panel expressions showed statistically significant (p < 0.05) frequency differences between ECA and EMA tumors. Although the additional ancillary PR-marker also revealed a significant frequency difference (p < 0.05) between ECA and EMA tumors, it did not demonstrate any supplementary benefit to the 3-marker panel.

Conclusion
According to our data, when histomorphological and clinical doubt exists as to the primary site of origin, we recommend that the conventional 3-marker (ER/Vim/CEA) panel is easier, sufficient and appropriate to use in distinguishing between primary ECA and EMA. Although the 4-marker panel containing PR also reveals statistically significant results, the PR-marker offers no supplemental benefit to the pre-existing 3-marker (ER/Vim/CEA) panel in the diagnostic distinction between ECA and EMA.
Varicella vaccination in Europe – taking the practical approach
Authors: Bonanni Paolo , Breuer Judith , Gershon Anne , Gershon Michael , Hryniewicz Waleria , Papaevangelou Vana , Rentier Bernard , Rümke Hans , Sadzot-Delvaux Catherine , Senterre Jacques , Weil-Olivier Catherine , Wutzler Peter 
Published: May 2009

Abstract
Varicella is a common viral disease affecting almost the entire birth cohort. Although usually self-limiting, some cases of varicella can be serious, with 2 to 6% of cases attending a general practice resulting in complications. The hospitalisation rate for varicella in Europe ranges from 1.3 to 4.5 per 100,000 population/year and up to 10.1% of hospitalised patients report permanent or possible permanent sequelae (for example, scarring or ataxia). However, in many countries the epidemiology of varicella remains largely unknown or incomplete.
In countries where routine childhood vaccination against varicella has been implemented, it has had a positive effect on disease prevention and control. Furthermore, mathematical models indicate that this intervention strategy may provide economic benefits for the individual and society. Despite this evidence and recommendations for varicella vaccination by official bodies such as the World Health Organization, and scientific experts in the field, the majority of European countries (with the exception of Germany and Greece) have delayed decisions on implementation of routine childhood varicella vaccination, choosing instead to vaccinate high-risk groups or not to vaccinate at all.
In this paper, members of the Working Against Varicella in Europe group consider the practicalities of introducing routine childhood varicella vaccination in Europe, discussing the benefits and challenges of different vaccination options (vaccination vs. no vaccination, routine vaccination of infants vs. vaccination of susceptible adolescents or adults, two doses vs. one dose of varicella vaccine, monovalent varicella vaccines vs. tetravalent measles, mumps, rubella and varicella vaccines, as well as the optimal interval between two doses of measles, mumps, rubella and varicella vaccines).
Assessment of the epidemiology of varicella in Europe and evidence for the effectiveness of varicella vaccination provides support for routine childhood programmes in Europe. Although European countries are faced with challenges or uncertainties that may have delayed implementation of a childhood vaccination programme, many of these concerns remain hypothetical and with new opportunities offered by combined measles, mumps, rubella and varicella vaccines, reassessment may be timely.
ApoE isoform-dependent changes in hippocampal synaptic function
Authors: Korwek Kimberly M , Trotter Justin H , LaDu Mary Jo , Sullivan Patrick M , Weeber Edwin J 
Published: May 2009

Abstract
The lipoprotein receptor system in the hippocampus is intimately involved in the modulation of synaptic transmission and plasticity. The association of specific apoE isoform expression with human neurodegenerative disorders has focused attention on the role of these apoE isoforms in lipoprotein receptor-dependent synaptic modulation. In the present study, we used the apoE2, apoE3 and apoE4 targeted replacement (TR) mice along with recombinant human apoE isoforms to determine the role of apoE isoforms in hippocampus area CA1 synaptic function. While synaptic transmission is unaffected by apoE isoform, long-term potentiation (LTP) is significantly enhanced in apoE4 TR mice versus apoE2 TR mice. ApoE isoform-dependent differences in LTP induction require NMDA-receptor function, and apoE isoform expression alters activation of both ERK and JNK signal transduction. Acute application of specific apoE isoforms also alters LTP induction while decreasing NMDA-receptor mediated field potentials. Furthermore, acute apoE isoform application does not have the same effects on ERK and JNK activation. These findings demonstrate specific, isoform-dependent effects of human apoE isoforms on adult hippocampus synaptic plasticity and highlight mechanistic differences between chronic apoE isoform expression and acute apoE isoform exposure.
Expressions of IGFBP-5, cFLIP in cervical intraepithelial neoplasia, cervical carcinoma and their clinical significances: a molecular pathology
Authors: Hou Xue-Jing , Zhang You-Zhong , Liu Xin , Meng Li-Hua , Qiao Yun-Bo 
Published: May 2009

Abstract

Background
Insulin-like growth factor binding protein (IGFBPs) have been as potential tumor suppressors in the occurrence and development of tumors. Cellular Fas-associated death domain-like interleukin-1β-converting enzyme (FLICE)-like inhibitory protein (cFLIP) contains a death effect domain (DED), which blocks death receptor pathway and inhibits apoptosis.

Methods
We collected normal cervical tissues from 28 subjects, CIN samples from 37 patients, and cervical cancer tissues from 40 patients. In these samples, we then measured the expression levels of IGFBP-5 and cFLIP via RT-PCR and immunohistochemistry, and we detected the presence of high-risk HPV by Hybrid capture II assays in cervical secretions provided by the subjects.

Results
significant differences in the expression of IGFBP-5 protein among the normal, CIN, and CC tissues (P < 0.05). The highest expression of IGFBP-5 protein was found in CIN stage II and III tissues, whereas the expression of IGFBP-5 in CC samples was decreased relative to controls. The expression level was affected by factors such as clinical stage, pathological differentiation, and lymph node metastasis. Relative to the controls, IGFBP-5 mRNA content was higher in the CC group and lower in the CIN group (P < 0.05). No expression of cFLIP protein or mRNA was detected in normal cervical tissues. However, the degree of pathological changes correlated with increasing expression of cFLIP protein and mRNA, and significant differences were therefore detected between groups (P < 0.05). The HPV infection rates in the CIN and CC groups were much higher than in the normal group (P < 0.05).

Conclusion
IGFBP-5 expression is up-regulated in response to progression of CIN and down-regulated in invasive cervical carcinoma. Detection of IGFBP-5 and cFLIP expression levels, may prove particularly useful for diagnosing and differentiating CIN and CC.
Regulation of catabolic gene expression in normal and degenerate human intervertebral disc cells: implications for the pathogenesis of intervertebral disc degeneration
Authors: Millward-Sadler S Jane , Costello Patrick W , Freemont Anthony J , Hoyland Judith A 
Published: May 2009

Abstract
Introduction
The aim of this study was to compare the effects of tumour necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1β) on protease and catabolic cytokine and receptor gene expression in normal and degenerate human nucleus pulposus cells in alginate culture.

Methods
Cells isolated from normal and degenerate nucleus pulposus regions of human intervertebral discs were cultured in alginate pellets and stimulated by the addition of 10 ng/mL TNF-α or IL-1β for 48 hours prior to RNA extraction. Quantitative real-time polymerase chain reaction was used to assess the effect of TNF-α or IL-β stimulation on the expression of matrix metalloproteinase (MMP)-3, -9 and -13, TNF-α, TNF receptor 1 (TNF-R1), TNF receptor 2 (TNF-R2), IL-1α, IL-1β, IL-1 receptor 1 (IL-1R1) and IL-1 receptor antagonist (IL-1Ra).

Results
MMP-3 and MMP-9 gene expressions were upregulated to a greater level by IL-1β than TNF-α. MMP-13 was upregulated by each cytokine to a similar extent. TNF-α and TNF-R2 expressions were upregulated by both TNF-α and IL-β, whereas TNF-R1 expression was not significantly affected by either cytokine. IL-1β and IL-1Ra expressions were significantly upregulated by TNF-α, whereas IL-1α and IL-1R1 were unchanged.

Conclusions
TNF-α does not induce MMP expression to the same degree as stimulation by IL-1β, but it does act to upregulate IL-1β expression as well as TNF-α and TNF-R2. The net result of this would be an increased inflammatory environment and accelerated degradation of the matrix. These results support the hypothesis that, while TNF-α may be an important initiating factor in matrix degeneration, IL-1β plays a greater role in established pathological degradation.
Patient information leaflets on psychotropic drugs: opinions and use by psychiatrists
Authors: Vaitheswaran Sridhar , MacManus Angela , Hamilton Ross 
Published: May 2009

Aims and MethodTo assess circumstances and frequency of use, opinions and suggestions for improvement from psychiatrists in a teaching hospital on UK Psychiatric Pharmacy Group patient information leaflets for psychotropic drugs. We also sought information from psychiatrists regarding use of alternate sources of information provision for their patients on psychotropic drugs. A questionnaire was designed, piloted and distributed.ResultsSixty-one psychiatrists were approached, of whom 49 (80%) responded. the most common indications for use were when initiating a new treatment and when information is sought by the individual or their carers. the most common reason for not using these leaflets was lack of awareness of their existence. Although 33 (67%) responders were of the opinion that these leaflets were useful for patients, only a small proportion was using them frequently.Clinical ImplicationsOur study suggested increasing awareness among psychiatrists to encourage the use of patient information leaflets. Various other themes to improve their use also emerged including easy accessibility to the patient information leaflets, modification in the content and structure, and recording the provision of patient information leaflets in the case records.
The trouble with NHS psychiatry in England
Authors: John-Smith Paul St , McQueen Daniel , Michael Albert , Ikkos George , Denman Chess , Maier Michael , Tobiansky Robert , Pathmanandam Hemachandran , Davies Teifon , Babu V. Sunil , Thachil Omana , Iqbal Furhan , Rao Ranga 
Published: May 2009

SummaryIn ‘Wake-up call for British psychiatry’ Craddock et al explained how recent attempts to improve psychosocial care for people with mental illness focus on non-specific psychosocial support. This has been at the expense of proper diagnostic assessment and prescription of treatment by psychiatrists aimed at treatment of specific disorders and recovery. They describe a creeping devaluation of psychiatry which is caricatured as narrow, biological, reductionist, oppressive, discriminatory and stigmatising. Some trusts have implemented ‘New Ways of Working for Psychiatrists’ in a way that undermines the central importance of psychiatrists in mental healthcare. Consequently, patients may be treated in secondary care without ever being seen by a psychiatrist. We consider a number of different changes that have interacted in unforeseen ways, with unintended adverse consequences for psychiatric services in England. We aim to continue the debate here.
The ‘Count Me In’ psychiatric in-patient census for 2007 and the elderly: evidence of improvement or cause for concern?
Authors: Shah Ajit 
Published: May 2009

SummaryThe recently published Count Me In 2007 census specifically reported age-standardised admission rates for individuals aged over 65 years from different Black and minority ethnic groups. the standardised admission ratio was higher in the White Irish, other White, White and Black Caribbean, other Asian, Black Caribbean, Black African and other Black ethnic groups; and lower in the White British and Chinese ethnic groups. As this census was undertaken on a single day for all psychiatric in-patients, it measured bed occupancy rather than admission rates and so it was actually referring to standardised bed occupancy ratios. Bed occupancy is a function of admission rates and length of stay. This editorial critically explores factors (including those related to institutional racism) that may affect both admission rates and length of stay, and ultimately bed occupancy, of Black and minority ethnic elders.