bluuebunny/crossref_metadata_2025_split huggingface dataset:
Orthologous Gene Clusters and Taxon Signature Genes for Viruses of Prokaryotes
Authors: Kristensen David M. , Waller Alison S. , Yamada Takuji , Bork Peer , Mushegian Arcady R. , Koonin Eugene V. 
Published: December 2012

ABSTRACT
Viruses are the most abundant biological entities on earth and encompass a vast amount of genetic diversity. The recent rapid increase in the number of sequenced viral genomes has created unprecedented opportunities for gaining new insight into the structure and evolution of the virosphere. Here, we present an update of the phage orthologous groups (POGs), a collection of 4,542 clusters of orthologous genes from bacteriophages that now also includes viruses infecting archaea and encompasses more than 1,000 distinct virus genomes. Analysis of this expanded data set shows that the number of POGs keeps growing without saturation and that a substantial majority of the POGs remain specific to viruses, lacking homologues in prokaryotic cells, outside known proviruses. Thus, the great majority of virus genes apparently remains to be discovered. A complementary observation is that numerous viral genomes remain poorly, if at all, covered by POGs. The genome coverage by POGs is expected to increase as more genomes are sequenced. Taxon-specific, single-copy signature genes that are not observed in prokaryotic genomes outside detected proviruses were identified for two-thirds of the 57 taxa (those with genomes available from at least 3 distinct viruses), with half of these present in all members of the respective taxon. These signatures can be used to specifically identify the presence and quantify the abundance of viruses from particular taxa in metagenomic samples and thus gain new insights into the ecology and evolution of viruses in relation to their hosts.
Genotypic Prediction of HIV-1 CRF01-AE Tropism
Authors: Raymond Stéphanie , Delobel Pierre , Rogez Sylvie , Encinas Stéphanie , Bruel Patrick , Pasquier Christophe , Sandres-Sauné Karine , Marchou Bruno , Massip Patrice , Izopet Jacques 
Published: December 2012

ABSTRACT
HIV-1 subtype CRF01-AE predominates in south Asia and has spread throughout the world. The virus tropism must be determined before using CCR5 antagonists. Genotypic methods could be used, but the prediction algorithms may be inaccurate for non-B subtypes like CRF01-AE and the correlation with the phenotypic approach has not been assessed. We analyzed 61 CRF01-AE V3 clonal sequences of known phenotype from the GenBank database. The sensitivity of the Geno2pheno10 genotypic algorithm was 91%, but its specificity was poor (54%). In contrast, the combined 11/25 and net charge rule was highly specific (98%) but rather insensitive (64%). We thus identified subtype CRF01-AE determinants in the V3 region that are associated with CXCR4 use and developed a new simple rule for optimizing the genotypic prediction of CRF01-AE tropism. The concordance between the predicted CRF01-AE genotype and the phenotype was 95% for the clonal data set. We then validated this algorithm by analyzing the data from 44 patients infected with subtype CRF01-AE, whose tropism was determined using a recombinant phenotypic entry assay and V3-loop bulk sequencing. The CRF01-AE genotypic tool was 70% sensitive and 96% specific for predicting CXCR4 use, and the concordance between genotype and phenotype was 84%, approaching the concordance obtained for predicting the tropism of HIV-1 subtype B. Genotypic predictions that use a subtype CRF01-AE-specific algorithm appear to be preferable for characterizing coreceptor usage both in pathophysiological studies and for ensuring the appropriate use of CCR5 antagonists.
Multiple-Locus Variable-Number Tandem-Repeat Analysis of 201 Mycoplasma pneumoniae Isolates from Beijing, China, from 2008 to 2011
Authors: Zhao Fei , Liu Gang , Cao Bin , Wu Jiang , Gu Yixin , He Lihua , Meng Fanliang , Zhu Liang , Yin Yudong , Lv Min , Zhang Jianzhong 
Published: December 2012

ABSTRACT

A total of 201
Mycoplasma pneumoniae
clinical isolates from Beijing, China, isolated from 2008 to 2011, were clustered into 16 multiple-locus variable-number tandem-repeat analysis (MLVA) types, of which 6 new MLVA types have never been reported previously. Type 1 isolates based on p1 gene genotyping were mainly MLVA types E, J, P, U, and X. There was no correlation between macrolide-resistant
Mycoplasma pneumoniae
and their MLVA type.
Impaired Virion Secretion by Hepatitis B Virus Immune Escape Mutants and Its Rescue by Wild-Type Envelope Proteins or a Second-Site Mutation
Authors: Kwei Karen , Tang Xiaoli , Lok Anna S. , Sureau Camille , Garcia Tamako , Li Jisu , Wands Jack , Tong Shuping 
Published: December 2012

ABSTRACT
Hepatitis B virus immune escape mutants have been associated with vaccine failure and reinfection of grafted liver despite immune prophylaxis, but their biological properties remain largely unknown. Transfection of 20 such mutants in a human hepatoma cell line identified many with severe impairment in virion secretion, which can be rescued to various extents by coexpression of wild-type envelope proteins or introduction of a novel glycosylation site. Consistent with their role in maintaining intra- or intermolecular disulfide bonds, cysteine residues within the “a” determinant are critical for virion secretion.
Accounting for recent trends in the prevalence of diarrhoea in the Democratic Republic of Congo (DRC): results from consecutive cross-sectional surveys
Authors: Emina Jacques B O , Kandala Ngianga-Bakwin 
Published: December 2012

ObjectivesTo analyse trends in diarrhoea prevalence by maternal education, access to clean water and improved sanitation, household wealth index; to identify the sources of variation and assess contribution of changes in socioeconomic characteristics in the Democratic Republic of Congo (DRC).DesignConsecutive cross-sectional surveys.SettingDRC.ParticipantsThe databases contain information on 9748 children from the 2001 Multiple Indicators Cluster Survey and 7987 children from the 2007 Demographic and Health Survey.InterventionsN/A.Primary and secondary outcome measuresWhether the child had diarrhoea 14 days preceding the survey.ResultsThe overall prevalence of diarrhoea decreased by 26 percent (from 22.1% in 2001 to 16.4% in 2007). Findings from the three complementary statistical methods are consistent and confirm a significant decrease in diarrhoea regardless of socioeconomic characteristics. Changes in behaviour and/or in public health policy seem to be the likely main source of the change. There were no significant changes in diarrhoea prevalence associated with variation of the population structure. It is worth mentioning that the decrease in diarrhoea prevalence is in contrast to the generalised poor living conditions of the population. Therefore, it is difficult to ascertain whether the decline in diarrhoea prevalence was due to real improvement in public-health policy or to data quality issues.ConclusionsThe decline of diarrhoea prevalence in our study need to be further investigated by conducting district-based or provincial-based studies to validate findings from household surveys such as Demographic and Health Surveys and Multiple Indicators Cluster Survey taking into account the current context of the country: ongoing conflict, poor socioeconomic and poor health infrastructure. However, improvement in living conditions such as access to clean water and improved sanitation will contribute to accelerate the reduction of diarrhoea prevalence as well as reduction of child mortality.
Inhibition of Cholinergic Signaling Causes Apoptosis in Human Bronchioalveolar Carcinoma
Authors: Lau Jamie K. , Brown Kathleen C. , Thornhill Brent A. , Crabtree Clayton M. , Dom Aaron M. , Witte Theodore R. , Hardman W. Elaine , McNees Christopher A. , Stover Cody A. , Carpenter A. Betts , Luo Haitao , Chen Yi C. , Shiflett Brandon S. , Dasgupta Piyali 
Published: December 2012

Abstract
Recent case-controlled clinical studies show that bronchioalveolar carcinomas (BAC) are correlated with smoking. Nicotine, the addictive component of cigarettes, accelerates cell proliferation through nicotinic acetylcholine receptors (nAChR). In this study, we show that human BACs produce acetylcholine (ACh) and contain several cholinergic factors including acetylcholinesterase (AChE), choline acetyltransferase (ChAT), choline transporter 1 (CHT1, SLC5A7), vesicular acetylcholine transporter (VAChT, SLC18A3), and nACh receptors (AChRs, CHRNAs). Nicotine increased the production of ACh in human BACs, and ACh acts as a growth factor for these cells. Nicotine-induced ACh production was mediated by α7-, α3β2-, and β3-nAChRs, ChAT and VAChT pathways. We observed that nicotine upregulated ChAT and VAChT. Therefore, we conjectured that VAChT antagonists, such as vesamicol, may suppress the growth of human BACs. Vesamicol induced potent apoptosis of human BACs in cell culture and nude mice models. Vesamicol did not have any effect on EGF or insulin-like growth factor-II–induced growth of human BACs. siRNA-mediated attenuation of VAChT reversed the apoptotic activity of vesamicol. We also observed that vesamicol inhibited Akt phosphorylation during cell death and that overexpression of constitutively active Akt reversed the apoptotic activity of vesamicol. Taken together, our results suggested that disruption of nicotine-induced cholinergic signaling by agents such as vesamicol may have applications in BAC therapy. Cancer Res; 73(4); 1328–39. ©2012 AACR.
Twenty-fourth Annual Pezcoller Symposium: Molecular Basis for Resistance to Targeted Agents
Authors: Marais Richard , Sellers William , Livingston David , Mihich Enrico 
Published: December 2012

Abstract
The mechanisms of genetically determined mechanisms of resistance to several target drugs were discussed in breast cancer, melanoma, colorectal and prostate cancers, chronic myelogenous leukemia, small cell lung cancer, and medulloblastoma. In each case, heterogeneity of mechanisms was emphasized. In melanoma, therapeutic interference with the effects of BRAF mutations was repeatedly discussed. It was also reported that anti-CTLA4 antibodies provided the first treatment improving survival of patients with stage IV melanoma. Epithelial–mesenchymal transition (EMT) was introduced as a mechanism of resistance, particularly in lung and pancreatic cancer, where the role of microenvironment factors was also indicated. In colorectal and prostate cancers, the use of liquid biopsies, namely, measurements of tumor nucleic acid in blood, were indicated as a way to obtain whole-tumor assessment instead of the partial assessment obtainable with traditional biopsies. Knowledge of the mechanisms of drug action and resistance was stressed to be essential for the design of new agents and combination of agents aimed at increasing antitumor effectiveness and overcoming resistance. Cancer Res; 73(3); 1046–9. ©2012 AACR.
Cytokine Stimulation of Epithelial Cancer Cells: The Similar and Divergent Functions of IL-4 and IL-13
Authors: Hallett Miranda A. , Venmar Katherine T. , Fingleton Barbara 
Published: December 2012

AbstractThe Th2 cytokines interleukin (IL)-4 and -13 are acknowledged regulators of lymphocyte proliferation and activation. They have also been well studied in the regulation of various myeloid-derived populations in tumor biology. It has become clear, however, that both cytokines can have direct effects on epithelial tumor cells expressing appropriate receptors. Changes in tumor proliferation, survival, and metastatic capability have all been ascribed to IL-4 and/or IL-13 action. Here, we evaluate the evidence to support direct tumor-promoting roles of these cytokines. We also identify the questions that should be addressed before proceeding with therapeutic approaches based on neutralization of IL-4 or IL-13 pathways. Cancer Res; 72(24); 6338–43. ©2012 AACR.
High-Throughput Monitoring of Human Papillomavirus Type Distribution
Authors: Söderlund-Strand Anna , Dillner Joakim 
Published: December 2012

Abstract
Background: There is a need for a rapid and cost-effective evaluation of the effects of different human papillomavirus (HPV) vaccination strategies. Sexually active adolescents are a preferred target group for monitoring, as effects on HPV prevalence would be measurable shortly after implementation of vaccination programs.
Methods: The Swedish Chlamydia trachomatis testing program offers free Chlamydia trachomatis testing and reaches a majority of all adolescents in the population. We anonymized the 44,146 samples submitted for Chlamydia trachomatis testing in Southern Sweden during March to November 2008 and conducted HPV genotyping using PCR followed by mass spectrometry.
Results: The HPV positivity peaked at 54.4% [95% confidence interval (CI), 52.2–56.6] among 21-year-old women and at 15.0% (95% CI, 12.4–17.6) among 23-year-old men. The HPV positivity was 37.8% (95% CI, 37.3–38.3) for women and 11.2% (95% CI, 10.6–11.8) for men. The most prevalent types among women were HPV 16 (10.0%; 95% CI, 9.7–10.3) and HPV 51 (6.0%; 95% CI, 5.7–6.3) and, among men, HPV 16 (2.1%; 95% CI, 1.8–2.4) and HPV 6 and HPV 51 (1.7%; 95% CI, 1.5–1.9).
Conclusion: The high HPV prevalences seen in the Chlamydia trachomatis screening population enables monitoring of the HPV type distribution among sexually active adolescents at high precision.
Impact: Effectiveness of HPV vaccination programs in terms of reducing HPV infections has been difficult to measure because of logistic constraints. We describe a system for high-throughput monitoring of HPV type-specific prevalences using samples from the Chlamydia trachomatis screening program. Cancer Epidemiol Biomarkers Prev; 22(2); 242–50. ©2012 AACR.
In VitroSensitivity of CLL Cells to Fludarabine May Be Modulated by the Stimulation of Toll-like Receptors
Authors: Fonte Eleonora , Apollonio Benedetta , Scarfò Lydia , Ranghetti Pamela , Fazi Claudia , Ghia Paolo , Caligaris-Cappio Federico , Muzio Marta 
Published: December 2012

AbstractPurpose: The emerging role of Toll-like receptors (TLR) in the pathogenesis of chronic lymphocytic leukemia (CLL) led us to ask whether TLR stimulation may protect CLL cells from drug-induced apoptosis.Experimental Design: We cultured in vitro malignant B cells freshly isolated from 44 patients with CLLs in the presence or the absence of different concentrations of fludarabine before or after 24-hour TLR stimulation with specific ligands and evaluated cell viability, apoptosis, and molecular pathways involved.Results: Heterogeneity was observed among samples. In leukemic cells from patients bearing adverse prognostic factors, TLR stimulation caused a significant increase of protection to fludarabine treatment, whereas this did not occur in the cells from patients with good prognosis. To identify novel molecular mechanisms accounting for the dichotomy of response between the two groups of patients, we conducted an apoptosis gene expression profile on leukemic cells either unstimulated or stimulated with TLR9 ligand. Strikingly, TLR9 stimulation specifically upregulated the expression of lymphotoxin-α in cells where an increased protection to fludarabine treatment was observed. Also, the expression of miR-155-3p was significantly increased after stimulation of distinct TLR in cells where fludarabine treatment was less effective.Conclusions: These results suggest that at least in a proportion of patients, in vitro sensitivity to fludarabine may be modulated by the stimulation of TLR, likely mimicking microenvironmental signals occurring in vivo. Clin Cancer Res; 19(2); 367–79. ©2012 AACR.
The Perichondrium in Auricular Melanomas
Authors: Craig E. Stirling , Nagarajan Priyadharsini , Lee Esther S. , Lazova Rossitza , Terner Jordan , Narayan Deepak 
Published: December 2012

ObjectiveAuricular melanomas are now considered less aggressive than originally thought, but those located on the conchal bowl and posterior ear can create particular challenges for reconstruction. Given the paucity of cases, no standardized recommendations exist for tumor resection. In this study, we provide a pathologic basis in support of conservative tumor resection along the perichondrial plane.Study DesignCase series with review of pathology and medical records.SettingAcademic tertiary referral center.Subjects and MethodsWe retrospectively reviewed all ear melanomas from the archives of Yale Dermatopathology and Surgical Pathology laboratories between 1987 and 2009. Cases of melanoma in situ or malignant melanoma of the earlobe were excluded.ResultsFifty‐one cases were included in the study. Patients’ age ranged from 26 to 94 years, with a mean (SD) of 58.9 (17.5) years. The male to female ratio was of 5.4:1. Melanomas were distributed similarly between right and left ears, at 52% and 48%, respectively. The most common location was the helix (74.5%). The Breslow depth ranged from 0.19 to 11 mm, with a mean (SD) of 1.64 (1.6) mm. The lesion‐perichondrium distance ranged from 0 to 8.12 mm, with a mean (SD) of 1.11 (1.1) mm. Notably, the perichondrium was not invaded in any of the cases.ConclusionBased on the histopathologic characteristics of our cases, the perichondrium can be considered an effective barrier and therefore a biological plane for wide local resection in some cases of auricular melanomas, allowing surgeons to achieve negative margins without necessarily sacrificing underlying cartilage.
Wet-priming extracorporeal membrane oxygenation device maintains sterility for up to 35 days of follow-up
Authors: Naso F , Gandaglia A , Balboni P , Zanella F , Danesin R , Spina M , Gerosa G 
Published: December 2012

In emergency cases, rapid extracorporeal membrane oxygenation (ECMO) device initialization is able to drastically reduce the incidence of patient morbidity and/or mortality. Pre-assembled and ready-to-use ECMO circuits might save up to 30-60 critical minutes in patient management. Six ECMO circuits (Oxygenator D905 EOS with REVOLUTION™ pump and Sorin PTS) were assembled in the operating room in standard conditions and then placed at 37°C for 35 days in order to evaluate possible contamination and ingrowth of micro-organisms. Every 7 days after ECMO circuit assembly and wet-priming, samples of priming fluid were analyzed to verify the presence/absence of possible common contaminants ( Enterobacteriaceae, Staphylococcus aureus and fungi). Moreover, two supplementary circuits, used as positive controls, were deliberately inoculated with a known concentration of a Escherichia coli strain and prime samplings carried out at different time-points to determine bacterial growth rate. Sterility was maintained in the ECMO circuits for up to 35 days.
Effect of organomodified montmorillonite concentration on tensile and flow properties of low-density polyethylene–thermoplastic corn starch blends
Authors: Sabetzadeh Maryam , Bagheri Rouhollah , Masoomi Mahmood 
Published: December 2012

In this study, low-density polyethylene (LDPE)–thermoplastic corn starch blends containing various amounts of organomodified montmorillonite (OMMT, 0.5–3 part per hundred (phr) resins) were prepared using a twin screw extruder. A 3-wt% LDPE-grafted maleic anhydride was used as a compatibilizer. The tensile, flow and water absorption properties of all the samples were measured by means of standard methods. Intercalated structures were achieved in all the samples, based on the x-ray diffraction and transmission electron microscopic results. Increasing levels of clay also led to the higher gallery distance of silicate layers (i.e. 32.5–34.5 Å). Furthermore, increment in ultimate tensile strength (UTS) and Young’s modulus ( E) as well as decrement in elongation at break ( ∊b) were obtained with increase in clay loading. The sample containing 1 phr nanoparticles showed 20% and 63% increase in UTS and E when compared with the reference sample, respectively. However, ∊b of this sample decreased by 17%. In addition, the flow property measurements indicated that as shear rate and the clay content increased, the apparent viscosity of all the samples decreased and increased, respectively. Finally, the presence of OMMT led to decrease in the melt flow index (MFI) of the samples. The MFI values also decreased with increasing the OMMT concentration. It is believed that the samples prepared in this work may biodegrade after exposure to the environment.
Synthesis, characterization and thermal properties of polystyrene–poly(lactic acid)–polystyrene triblock copolymer via atom transfer radical polymerization
Authors: Shen Jun , Jiang Wei , Liu Ying , Wei Rong-qing , Zhong Yu , Li Lin-ling , Xue Gi , Liu Xiao-ning 
Published: December 2012

Polystyrene (PS)–poly(lactic acid) (PLA)–PS triblock copolymer is prepared with PLA and styrene (St) via atom transfer radical polymerization (ATRP). The structure and thermal properties of the copolymer are analyzed by infrared spectroscopy, gel permeation chromatography, nuclear magnetic resonance, thermogravimetry, differential scanning calorimetry and alcoholysis. The ATRP of St using bromine-terminated PLA as the initiator exhibits first-order kinetics and a low-molecular-weight distribution ( Mw/ Mn ≈ 1.5). The thermal stability of PLA is improved by copolymerization. Both the initial temperature of thermal decomposition and glass transition temperature are increased with an increasing length of PS block.
Aliskiren add-on therapy effectively reduces proteinuria in chronic kidney disease: An open-label prospective trial
Authors: Wu Men-Tai , Tung Shi-Cheng , Hsu Kao-Tai , Lee Chien-Te 
Published: December 2012

Introduction: The combination therapy of aliskiren and renin–angiotensin–aldosterone system (RAAS) blocker in chronic kidney disease (CKD) is controversial. Whether such dual blockade can effectively apply to patients with CKD irrespective of stage and amount of proteinuria remains uncertain. Methods: We added aliskiren at a dosage of 150 mg/day for six months in 103 Chinese CKD patients who had been treated with angiotensin converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) and still had significant proteinuria or uncontrolled hypertension. Blood pressure, serum creatinine, estimated glomerular filtration rate (eGFR), potassium, and spot urine protein-to-creatinine ratio (UPCR) were measured at three and six months after aliskiren add-on therapy and compared with baseline. Results: The combination of aliskiren and ACEi or ARB significantly reduced UPCR by 23% ( p=0.001) and mean arterial pressure by 7.9 ± 13.8 mmHg ( p<0.001) at six months. Twenty-five percent of subjects had a greater than 50% reduction in UPCR. No significant changes in eGFR and serum potassium level were noted at six months. Conclusions: Adding aliskiren on ACEi or ARB in CKD patients, both in diabetes and non-diabetes, has a favorable effect on reducing residual proteinuria and inadequately controlled blood pressure.
Murine anti–third-party central-memory CD8+ T cells promote hematopoietic chimerism under mild conditioning: lymph-node sequestration and deletion of anti-donor T cells
Authors: Ophir Eran , Or-Geva Noga , Gurevich Irina , Tal Orna , Eidelstein Yaki , Shezen Elias , Margalit Raanan , Lask Assaf , Shakhar Guy , Hagin David , Bachar-Lustig Esther , Reich-Zeliger Shlomit , Beilhack Andreas , Negrin Robert , Reisner Yair 
Published: December 2012

Key PointsA new approach to achieving immune tolerance and mixed chimerism with relevance for hematopoietic stem cell and organ transplantation. Anti–third-party central memory T cells support engraftment with nonablative conditioning by sequestering and deleting anti-donor T cells.