bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different Requirements for Scavenger Receptor Class B Type I in Hepatitis C Virus Cell-Free versus Cell-to-Cell Transmission
Authors: Catanese Maria Teresa , Loureiro Joana , Jones Christopher T. , Dorner Marcus , von Hahn Thomas , Rice Charles M. 
Published: May 2013

ABSTRACT

Hepatitis C virus (HCV) is believed to initially infect the liver through the basolateral side of hepatocytes, where it engages attachment factors and the coreceptors CD81 and scavenger receptor class B type I (SR-BI). Active transport toward the apical side brings the virus in close proximity of additional entry factors, the tight junction molecules claudin-1 and occludin. HCV is also thought to propagate via cell-to-cell spread, which allows highly efficient virion delivery to neighboring cells. In this study, we compared an adapted HCV genome, clone 2, characterized by superior cell-to cell spread, to its parental genome, J6/JFH-1, with the goal of elucidating the molecular mechanisms of HCV cell-to-cell transmission. We show that CD81 levels on the donor cells influence the efficiency of cell-to-cell spread and CD81 transfer between neighboring cells correlates with the capacity of target cells to become infected. Spread of J6/JFH-1 was blocked by anti-SR-BI antibody or in cells knocked down for SR-BI, suggesting a direct role for this receptor in HCV cell-to-cell transmission. In contrast, clone 2 displayed a significantly reduced dependence on SR-BI for lateral spread. Mutations in E1 and E2 responsible for the enhanced cell-to-cell spread phenotype of clone 2 rendered cell-free virus more susceptible to antibody-mediated neutralization. Our results indicate that although HCV can lose SR-BI dependence for cell-to-cell spread, vulnerability to neutralizing antibodies may limit this evolutionary option
in vivo
. Combination therapies targeting both the HCV glycoproteins and SR-BI may therefore hold promise for effective control of HCV dissemination.
Full Conversion of the Hemagglutinin-Neuraminidase Specificity of the Parainfluenza Virus 5 Fusion Protein by Replacement of 21 Amino Acids in Its Head Region with Those of the Simian Virus 41 Fusion Protein
Authors: Tsurudome Masato , Nakahashi Mito , Matsushima Yoshiaki , Ito Morihiro , Nishio Machiko , Kawano Mitsuo , Komada Hiroshi , Nosaka Tetsuya 
Published: May 2013

ABSTRACT
For most parainfluenza viruses, a virus type-specific interaction between the hemagglutinin-neuraminidase (HN) and fusion (F) proteins is a prerequisite for mediating virus-cell fusion and cell-cell fusion. The molecular basis of this functional interaction is still obscure partly because it is unknown which region of the F protein is responsible for the physical interaction with the HN protein. Our previous cell-cell fusion assay using the chimeric F proteins of parainfluenza virus 5 (PIV5) and simian virus 41 (SV41) indicated that replacement of two domains in the head region of the PIV5 F protein with the SV41 F counterparts bestowed on the PIV5 F protein the ability to induce cell-cell fusion on coexpression with the SV41 HN protein while retaining its ability to induce fusion with the PIV5 HN protein. In the study presented here, we furthered the chimeric analysis of the F proteins of PIV5 and SV41, finding that the PIV5 F protein could be converted to an SV41 HN-specific chimeric F protein by replacing five domains in the head region with the SV41 F counterparts. The five SV41 F-protein-derived domains of this chimera were then divided into 16 segments; 9 out of 16 proved to be not involved in determining its specificity for the SV41 HN protein. Finally, mutational analyses of a chimeric F protein, which harbored seven SV41 F-protein-derived segments, revealed that replacement of at most 21 amino acids of the PIV5 F protein with the SV41 F-protein counterparts was enough to convert its HN protein specificity.
Provision of an out-of-hours emergency endoscopy service: the Leicester experience
Authors: Ramiah Rekha , Wurm Peter 
Published: May 2013

IntroductionThe British Society of Gastroenterology (BSG) Strategy document ‘Care of patients with Gastrointestinal (GI) disorders’ recommends that all acute hospitals should have arrangements for out-of-hours (OOH) endoscopy staffed with appropriately trained endoscopists. The UK national audit published in 2010 found that only 52% of hospitals across the UK had a formal consultant-led OOH endoscopy on-call rota. The University Hospitals of Leicester (UHL) established a consultant-led rota in 2006, which now provides 24/7 endoscopy cover. To define the workload of a newly established OOH service, we examined procedures performed since the introduction of an OOH service in 2006.MethodsThe audit period covered August–January (6 months) for each of five consecutive years. Data were gathered from formal endoscopy reports on Unisoft reporting tool and OOH record books. We examined indication for endoscopy, timing of procedure, findings at index endoscopy, intervention and immediate outcome.ResultsAcross the three UHL sites, data on 982 patients were analysed. Eighty-one percent of procedures performed were gastroscopies. 63% of the procedures were performed for GI bleed indications. Over the five years, there was an overall increase in the number of procedures performed where no pathology was found. Immediate outcomes postendoscopy were good, with over 90% being returned to their base ward.ConclusionsThe experience at UHL appears to show a trend towards an increasing number of procedures performed OOH, with fewer positive findings and less need for therapy. A likely contributing factor is the ongoing shortage of medical beds, requiring more routine work to be done OOH in order to expedite discharges. However, early specialist endoscopic input is likely to improve patient management. The impact of an OOH service on other services, however, needs to be carefully considered.
Essence of reusability in aspect-oriented systems
Authors: Chaudhary Ritika , Chatterjee Ram 
Published: May 2013

Programmers practicing software development have long realized that reusability is an important area of concern- it is an attribute of quality, which depicts the extent to which a module can be used again in different applications with slight modification.
Software professionals often adopt the Module-oriented Approach (MOA) and / or the Object-Oriented Approach (OOA) to develop reusable software. However, these approaches do not address crosscutting concerns (such as logging, security etc.), which are scattered throughout the code and which if poorly done adversely affect reusability and maintainability.
Readers may note that "reusability" is a quality attribute whose assessment remains quite underexplored. This paper discusses the importance of reusability as a quality attribute and its essence in Aspect-Oriented Systems.
This paper has been split into Introduction, Quality Parameters, Conclusion and Future Scope. In the Introduction, the focus is on how Aspect-Oriented Software development addresses the problem of crosscutting concerns. Quality parameters emphasize the concept of reusability within the domains of Object-Oriented Programming and Aspect-Oriented Programming and signify the importance of assessing reusability in Aspect-Oriented Systems. In the future, maintainability will be one of the factors to be considered for assessment of Aspect-Oriented Systems.
Forecasting the Future of Stroke in the United States
Authors: Ovbiagele Bruce , Goldstein Larry B. , Higashida Randall T. , Howard Virginia J. , Johnston S. Claiborne , Khavjou Olga A. , Lackland Daniel T. , Lichtman Judith H. , Mohl Stephanie , Sacco Ralph L. , Saver Jeffrey L. , Trogdon Justin G. 
Published: May 2013

Background and Purpose—
Stroke is a leading cause of disability, cognitive impairment, and death in the United States and accounts for 1.7% of national health expenditures. Because the population is aging and the risk of stroke more than doubles for each successive decade after the age of 55 years, these costs are anticipated to rise dramatically. The objective of this report was to project future annual costs of care for stroke from 2012 to 2030 and discuss potential cost reduction strategies.

Methods and Results—
The American Heart Association/American Stroke Association developed methodology to project the future costs of stroke-related care. Estimates excluded costs associated with other cardiovascular diseases (hypertension, coronary heart disease, and congestive heart failure). By 2030, 3.88% of the US population >18 years of age is projected to have had a stroke. Between 2012 and 2030, real (2010$) total direct annual stroke-related medical costs are expected to increase from $71.55 billion to $184.13 billion. Real indirect annual costs (attributable to lost productivity) are projected to rise from $33.65 billion to $56.54 billion over the same period. Overall, total annual costs of stroke are projected to increase to $240.67 billion by 2030, an increase of 129%.

Conclusions—
These projections suggest that the annual costs of stroke will increase substantially over the next 2 decades. Greater emphasis on implementing effective preventive, acute care, and rehabilitative services will have both medical and societal benefits. (Stroke. 2013;44:2361-2375.)
Deladenus prorsus n. sp. (Nematoda: Neotylenchidae) in dunnage wood from Malaysia intercepted in Ningbo, China
Authors: Yu Qing , Gu Jianfeng , Ye Weimin 
Published: May 2013

Deladenus prorsus n. sp., isolated from dunnage wood originating from Malaysia and intercepted in Ningbo port, P.R. China, is described and illustrated. The dunnage wood material appeared to have holes resembling the typical exit holes of wood-boring insects and have associated blue stain. The new species is characterised by the presence of both the mycophagous and infective forms (Deladenus consists of mycetophagous-only forms and those with known female dimorphism), the body length of 814 (670-1147) and 898 (812-979) μm for mycetophagous males and females, respectively, and 1129 (1114-1352) μm for the infective female, and by the very anterior position of the excretory pore which is situated at 30.7 (24.4-33.0), 30.6 (25.4-35.6) and 37.9 (27.3-39.7) μm for the mycetophagous males and females and infective females, respectively, and the distance that the excretory pore is located anterior to the hemizonid which is 82 (77-90), 74 (54-92) and 86 (64-106) μm for the mycetophagous males and females and infective females, respectively. The diagnostic value of the excretory pore and the hemizonid of the species of the genus are discussed. The ribosomal DNA ITS region was sequenced and analysed.
Predictive value of 1 month retinal nerve fiber layer thinning for deficits at 6 months after acute optic neuritis
Authors: Kupersmith Mark J , Anderson Susan , Kardon Randy 
Published: May 2013

Background: Retinal nerve fiber layer (RNFL) loss occurs with multiple sclerosis and after optic neuritis. Vision or RNFL changes at presentation of optic neuritis are not predictive of outcome, but vision loss at 1 month correlates with vision deficits at 6 months. We hypothesized that RFNL thinning at 1 month would predict RNFL loss at 6 months. Methods: We prospectively studied the RNFL by optical coherence tomography (OCT) and scanning laser polarimetry (SLP), and determined the threshold field mean deviation, in 25 subjects with acute optic neuritis over a 6-month period. RNFL values, including the amount of thinning at 1-month, were correlated with 6-month outcome. Results: Baseline visual performance and RNFL values were similar for eyes grouped by 1 month RNFL thinning. Eyes with 1 month RNFL thinning had greater and significant RNFL thinning at 6 months, for all quadrants by OCT and for the nasal and inferior quadrants by SLP. RNFL thinning by OCT and SLP at 1 month correlated with 6-month OCT ( r = 0.58; p = 0.006) and SLP ( r = 0.59; p = 0.002) RNFL thinning, respectively. Conclusion: Early RNFL loss at 1 month was predictive of the RNFL thinning at 6 months, which corroborated the importance of the 1-month time point for predicting the outcome of an optic neuritis attack.
WT1 regulates murine hematopoiesis via maintenance of VEGF isoform ratio
Authors: Cunningham Thomas J. , Palumbo Ilaria , Grosso Michela , Slater Nicholas , Miles Colin G. 
Published: May 2013

Key PointsWT1 mutations predict poor prognosis in AML; Wt1 mutant embryonic stem cells show reduced hematopoiesis, elevated apoptosis, and abnormal Vegf-a isoforms. Wt1 regulates Vegf-a splicing; exogenous Vegf-a restores hematopoiesis in Wt1 mutant ES cells, and this pathway may have therapeutic potential.
Association between a frequent variant of the FTO gene and anthropometric phenotypes in Brazilian children
Authors: da Silva Carmela Farias , Zandoná Marília Remuzzi , Vitolo Márcia Regina , Campagnolo Paula Dal Bó , Rotta Liane Nanci , Almeida Silvana , Mattevi Vanessa Suñé 
Published: May 2013

Abstract

Background
Our goal was to analyze the association of the fat mass and obesity- associated (FTO) gene rs9939609 variant (T/A) with the anthropometric and dietary intake phenotypes related to obesity in Brazilian children.

Methods
We analyzed the association of this single nucleotide polymorphism (SNP) with phenotypes related to the accumulation of body mass in a cohort of 348 children followed from the time of birth until 8 years old and then replicated the main findings in an independent schoolchildren sample (n = 615).

Results
At the age of 4, we observed a significant association between the A/A genotype and a higher mean BMI Z-score (P = 0.036). At the age of 8, the A/A individuals still presented with a higher BMI Z-score (P = 0.011) and with marginal differences in the volume of subcutaneous fat (P = 0.048). We replicated these findings in the schoolchildren sample, which showed that those with at least one copy of the A allele presented with a higher BMI Z-score (P = 0.029) and volume of subcutaneous fat (P = 0.016).

Conclusion
Our results indicate that this FTO variant is associated with increased body mass and subcutaneous fat in Brazilian children beginning at the age of 4.
Processing of meats and cardiovascular risk: time to focus on preservatives
Authors: Micha Renata , Michas Georgios , Lajous Martin , Mozaffarian Dariush 
Published: May 2013

Abstract
Dietary guidelines emphasize selecting lean (low-fat) meats to reduce saturated fat and cholesterol, but growing evidence suggests that health effects may relate to other ingredients, such as sodium, heme iron, or L-carnitine. Understanding how meats influence health, and on which nutrients this relationship depends, is essential to advise consumer choices, set guidelines, and inform food reformulations. A recent study published in BMC Medicine involving 448,568 participants in 10 European countries, provides important evidence in this regard. After multivariate adjustment, intake of unprocessed red meat was not significantly associated with total or cause-specific mortality; conversely, intake of processed meat was associated with a 30% higher rate of cardiovascular disease (CVD) (per 50 g/day, relative risk 1.30, 95% confidence interval 1.17 to 1.45) and also higher cancer mortality. These findings are consistent with our previous meta-analysis, based on smaller studies, showing strong associations of processed meats, but not unprocessed meats, with CVD. Preservatives are the notable difference; the calculated blood-pressure effects of sodium differences (around 400% higher in processed meats) explain most of the observed higher risk. Although unprocessed red meats seem to be relatively neutral for CVD, healthier choices are available, including fish, nuts, legumes, fruits, and vegetables. Public-health guidance should prioritize avoidance of processed meats, including the low-fat deli meats currently marketed as healthy choices, and the food industry should substantially reduce sodium and other preservatives in processed meats.
See related research article here http://www.biomedcentral.com/1741-7015/11/63.
Cidofovir selectivity is based on the different response of normal and cancer cells to DNA damage
Authors: De Schutter Tim , Andrei Graciela , Topalis Dimitri , Naesens Lieve , Snoeck Robert 
Published: May 2013

AbstractBackgroundCidofovir (CDV) proved efficacious in treatment of human papillomaviruses (HPVs) hyperplasias. Antiproliferative effects of CDV have been associated with apoptosis induction, S-phase accumulation, and increased levels of tumor suppressor proteins. However, the molecular mechanisms for the selectivity and antitumor activity of CDV against HPV-transformed cells remain unexplained.MethodsWe evaluated CDV drug metabolism and incorporation into cellular DNA, in addition to whole genome gene expression profiling by means of microarrays in two HPV+cervical carcinoma cells, HPV-immortalized keratinocytes, and normal keratinocytes.ResultsDetermination of the metabolism and drug incorporation of CDV into genomic DNA demonstrated a higher rate of drug incorporation in HPV+tumor cells and immortalized keratinocytes compared to normal keratinocytes. Gene expression profiling clearly showed distinct and specific drug effects in the cell types investigated. Although an effect on inflammatory response was seen in all cell types, different pathways were identified in normal keratinocytes compared to immortalized keratinocytes and HPV+tumor cells. Notably, Rho GTPase pathways, LXR/RXR pathways, and acute phase response signaling were exclusively activated in immortalized cells. CDV exposed normal keratinocytes displayed activated cell cycle regulation upon DNA damage signaling to allow DNA repair via homologous recombination, resulting in genomic stability and survival. Although CDV induced cell cycle arrest in HPV-immortalized cells, DNA repair was not activated in these cells. In contrast, HPV+cells lacked cell cycle regulation, leading to genomic instability and eventually apoptosis.ConclusionsTaken together, our data provide novel insights into the mechanism of action of CDV and its selectivity for HPV-transformed cells. The proposed mechanism suggests that this selectivity is based on the inability of HPV+cells to respond to DNA damage, rather than on a direct anti-HPV effect. Since cell cycle control is deregulated by the viral oncoproteins E6 and E7 in HPV+cells, these cells are more susceptible to DNA damage than normal keratinocytes. Our findings underline the therapeutic potential of CDV for HPV-associated malignancies as well as other neoplasias.
Amplification and overexpression of the egf receptor gene in primary human glioblastomas
Authors: Libermann Towia A. , Nusbaum Harris R. , Razon Nissim , Kris Richard , Lax Irit , Soreq Hermona , Whittle Nigel , Waterfield Michael D. , Ullrich Axel , Schlessinger Joseph 
Published: May 2013

ABSTRACT
The expression of epidermal growth factor (EGF) receptor in brain tumours of glial origin was studied at the protein, mRNA and genomic levels. Four out of 10 glioblastomas that overexpress EGF receptor also have gene amplification. The amplified genes appear to be rearranged, generating an aberrant mRNA in at least one of these tumours. Such receptor defects may be relevant to tumorigenesis of human glioblastomas.
Receptor-mediated endocytosis of transferrin and epidermal growth factor receptors: a comparison of constitutive and ligand-induced uptake
Authors: Hopkins C. R. , Miller K. , Beardmore J. M. 
Published: May 2013

ABSTRACT
The distribution of cell surface receptors for transferrin-iron and epidermal growth factor (EGF) on the surface of cultured epitheloid (A431) cells has been identified by immunocytochemical electron microscopy. The patterns of movement displayed by these two receptor populations as they transfer to their sites of internalization on the cell surface are different. The movement of recycling transferrin receptors over the surface is ligand-independent whereas EGF receptors are more stable residents and remain monodisperse until they bind ligand.
Prior to uptake transferrin receptors cluster, predominantly within existing clathrin-coated pits while the aggregates formed by EGF ligand-receptor complexes induce new membrane invaginations. These results are discussed in relation to receptor populations concerned with constitutive, high capacity uptake processes and receptors involved in signal transduction.
The Physics of Cell Motility
Authors: Oster George F. , Perelson Alan S. 
Published: May 2013

ABSTRACT
Cell locomotion begins with a protrusion from the leading periphery of the cell. What drives this extension? Here we present a model for the extension of cell protuberances that unifies certain aspects of this phenomenon, and is based on the hypothesis that osmotic pressure drives cell extensions. This pressure arises from membrane-associated reactions, which liberate osmotically active particles, and from the swelling of the actin network that underlies the membrane.
Nuclear transport in vitro
Authors: Finlay Deborah R. , Newmeyer Donald D. , Hartl Philippe M. , Horecka Joseph , Forbes Douglass J. 
Published: May 2013

ABSTRACT
In this paper, progress towards the goal of understanding communication between the nucleus and cytoplasm using an in vitro system is reviewed. To probe the mechanism of nuclear targeting, we developed an in vitro transport system and have begun to dissect the highly selective process of nuclear transport. The basic parameters of transport were defined using an easily isolated nuclear protein, nucleoplasmin. To study the interaction of nuclear targeting signals with the pore, an artificial nuclear transport substrate was constructed, which consists of human serum albumin coupled to the signal sequence of the SV40 T-antigen. A similar peptide-protein conjugate was made using a mutant signal sequence. These conjugates were fluorescently labeled and/or tagged with gold and tested for transport in the in vitro system. High levels of nuclear transport of the wild-type signal sequence-containing protein were observed, while no transport of the mutant signal sequence-containing protein was seen. Thus, the in vitro system correctly recognizes the single amino acid change between the wild-type and mutant signal sequences. We found that the observed nuclear transport was completely dependent on the presence of ATP.
Using the in vitro system we identified a specific inhibitor of nuclear transport, the lectin wheat germ agglutinin (WGA), which we find binds directly to the nuclear pore. Probing blots of nuclear proteins with 125I-WGA identified a family of nuclear pore glycoproteins, including one major glycoprotein of 62K (K = 103Mr) molecular weight. With the inhibitor and the in vitro assay, it has been possible to experimentally separate nuclear transport into two steps: (1) a step in which the signal sequence-bearing protein binds to the pore, followed by (2) a step in which the protein translocates through the pore. It is this second step which is the ATP-dependent step of transport, since pore binding but not translocation was seen to occur in the absence of ATP.