bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chlamydia trachomatis Strains Show Specific Clustering for Men Who Have Sex with Men Compared to Heterosexual Populations in Sweden, the Netherlands, and the United States
Authors: Christerson Linus , Bom Reinier J. M. , Bruisten Sylvia M. , Yass Resha , Hardick Justin , Bratt Göran , Gaydos Charlotte A. , Morré Servaas A. , Herrmann Björn 
Published: August 2012

ABSTRACTHigh-resolution genotyping ofChlamydia trachomatisimproves the characterization of strains infecting different patient groups and sexual networks. In this study, multilocus sequence typing (MLST) andompAsequence determination were used for an analysis ofC. trachomatisstrains from 203 men who have sex with men (MSM) from Sweden, the Netherlands, and the United States. The results obtained were compared with data from 153 heterosexual women from Sweden and the Netherlands. The overlap in MLST/ompAprofiles between MSM from Sweden and the Netherlands was 68%, while the overlap between heterosexual populations from these countries was only 18%. The distribution of genotypes in MSM from the United States was less similar to that in MSM from the European countries, with 45% and 46% overlaps for MSM in Sweden and the Netherlands, respectively. Minimum-spanning-tree analysis of MLST/ompAsequence types identified two large clusters that contained almost exclusively samples from MSM and comprised 74% of all MSM samples. Three other clusters were predominated by samples from women but also contained MSM specimens. Of 19 detected variants of the MLST target CT144, three variants were highly associated with MSM. Our study supports the hypotheses of both tissue tropism as well as epidemiological network structures as explanations for the linkage between specific genetic variants and sexual orientation.
A Reliable and Reproducible Experimental Challenge Model for Peste des Petits Ruminants Virus
Authors: El Harrak Mehdi , Touil Nadia , Loutfi Chafiqua , Hammouchi Mustapha , Parida Satya , Sebbar Gizlane , Chaffai Nadia , Harif Bachir , Messoudi Nezha , Batten Carrie , Oura Chris A. L. 
Published: August 2012

ABSTRACT
Experimental challenge protocols that consistently reproduce clinical signs of peste des petits ruminants in Alpine goats infected with a tissue culture-passaged peste des petits ruminants virus are described. The protocols can be used to carry out quality-controlled vaccine efficacy and pathogenesis studies under experimental conditions.
The Assembly Domain of the Small Capsid Protein of Kaposi's Sarcoma-Associated Herpesvirus
Authors: Kreitler Dale , Capuano Christopher M. , Henson Brandon W. , Pryce Erin N. , Anacker Daniel , McCaffery J. Michael , Desai Prashant J. 
Published: August 2012

ABSTRACT
Self-assembly of Kaposi's sarcoma-associated herpesvirus capsids occurs when six proteins are coexpressed in insect cells using recombinant baculoviruses; however, if the small capsid protein (SCP) is omitted from the coinfection, assembly does not occur. Herein we delineate and identify precisely the assembly domain and the residues of SCP required for assembly. Hence, six residues, R14, D18, V25, R46, G66, and R70 in the assembly domain, when changed to alanine, completely abolish or reduce capsid assembly.
Susceptibility of Young Sheep to Oral Infection with Bovine Spongiform Encephalopathy Decreases Significantly after Weaning
Authors: Hunter Nora , Houston Fiona , Foster James , Goldmann Wilfred , Drummond Dawn , Parnham David , Kennedy Iain , Green Andrew , Stewart Paula , Chong Angela 
Published: August 2012

ABSTRACT

Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy (TSE) (or prion disease) that is readily transmissible to sheep by experimental infection and has the shortest incubation period in animals with the
ARQ
/
ARQ PRNP
genotype (at codons 136, 154, and 171). Because it is possible that sheep in the United Kingdom could have been infected with BSE by being fed contaminated meat and bone meal supplements at the same time as cattle, there is considerable interest in the responses of sheep to BSE inoculation. Epidemiological evidence suggests that very young individuals are more susceptible to TSE infection; however, this has never been properly tested in sheep. In the present study, low doses of BSE were fed to lambs of a range of ages (∼24 h, 2 to 3 weeks, 3 months, and 6 months) and adult sheep. The incidence of clinical BSE disease after inoculation was high in unweaned lambs (∼24 h and 2 to 3 weeks old) but much lower in older weaned animals The incubation period was also found to be influenced by the genotype at codon 141 of the
PRNP
gene, as lambs that were LF heterozygotes had a longer mean incubation period than those that were homozygotes of either type. The results suggest that sheep in the United Kingdom would have been at high risk of BSE infection only if neonatal animals had inadvertently ingested contaminated supplementary foodstuffs.
Complete Genomic Sequence of Goose-Origin Reovirus from China
Authors: Yun Tao , Ye Weicheng , Ni Zheng , Chen Liu , Yu Bin , Hua Jionggang , Zhang Yan , Zhang Cun 
Published: August 2012

ABSTRACT
We report the full-genome sequence of a goose-origin reovirus (GRV) strain 03G from Zhejiang Province, China. This is the first report of the complete genomic sequence (segments 1 to 10) of GRV. Phylogenetic analyses of the sequence suggest that GRV 03G represents a new species distinct from other established species within the avian reovirus (ARV) group of orthoreoviruses.
Human Cytomegalovirus pUL78 G Protein-Coupled Receptor Homologue Is Required for Timely Cell Entry in Epithelial Cells but Not Fibroblasts
Authors: O'Connor Christine M. , Shenk Thomas 
Published: August 2012

ABSTRACTHuman cytomegalovirus (HCMV) encodes four putative G protein-coupled receptors, including pUL78, whose rodent orthologues are known to be important for replication and spread in their hosts. To investigate the mechanism by which pUL78 contributes to viral replication and pathogenesis, we generated a derivative of the TB40/E clinical isolate of HCMV that is unable to express the receptor. Consistent with previous findings using laboratory strains of the virus, the mutant replicated normally in fibroblasts. Although laboratory strains are restricted to growth in fibroblasts, clinical isolates grow in many cell types, including epithelial and endothelial cells, in which the pUL78-deficient TB40/E derivative exhibited a growth defect. Infection with the mutant virus resulted in a significant decrease in viral RNA and protein expression. Although there was no difference in binding of the virus to the cell, we detected a delay in the entry and subsequent delivery of virion DNA and protein to the nuclei of epithelial cells following infection with the UL78 mutant virus. Taken together, our results demonstrate that pUL78 supports infection at a point after binding but before entry in epithelial cells, a cell type important forin vivoviral replication and spread.
Serial Analysis of the Gut and Respiratory Microbiome in Cystic Fibrosis in Infancy: Interaction between Intestinal and Respiratory Tracts and Impact of Nutritional Exposures
Authors: Madan J. C. , Koestler D. C. , Stanton B. A. , Davidson L. , Moulton L. A. , Housman M. L. , Moore J. H. , Guill M. F. , Morrison H. G. , Sogin M. L. , Hampton T. H. , Karagas M. R. , Palumbo P. E. , Foster J. A. , Hibberd P. L. , O’Toole G. A. 
Published: August 2012

ABSTRACT

Pulmonary damage caused by chronic colonization of the cystic fibrosis (CF) lung by microbial communities is the proximal cause of respiratory failure. While there has been an effort to document the microbiome of the CF lung in pediatric and adult patients, little is known regarding the developing microflora in infants. We examined the respiratory and intestinal microbiota development in infants with CF from birth to 21 months. Distinct genera dominated in the gut compared to those in the respiratory tract, yet some bacteria overlapped, demonstrating a core microbiota dominated by
Veillonella
and
Streptococcus
. Bacterial diversity increased significantly over time, with evidence of more rapidly acquired diversity in the respiratory tract. There was a high degree of concordance between the bacteria that were increasing or decreasing over time in both compartments; in particular, a significant proportion (14/16 genera) increasing in the gut were also increasing in the respiratory tract. For 7 genera, gut colonization presages their appearance in the respiratory tract. Clustering analysis of respiratory samples indicated profiles of bacteria associated with breast-feeding, and for gut samples, introduction of solid foods even after adjustment for the time at which the sample was collected. Furthermore, changes in diet also result in altered respiratory microflora, suggesting a link between nutrition and development of microbial communities in the respiratory tract. Our findings suggest that nutritional factors and gut colonization patterns are determinants of the microbial development of respiratory tract microbiota in infants with CF and present opportunities for early intervention in CF with altered dietary or probiotic strategies.

IMPORTANCE
While efforts have been focused on assessing the microbiome of pediatric and adult cystic fibrosis (CF) patients to understand how chronic colonization by these microbes contributes to pulmonary damage, little is known regarding the earliest development of respiratory and gut microflora in infants with CF. Our findings suggest that colonization of the respiratory tract by microbes is presaged by colonization of the gut and demonstrated a role of nutrition in development of the respiratory microflora. Thus, targeted dietary or probiotic strategies may be an effective means to change the course of the colonization of the CF lung and thereby improve patient outcomes.
Screening for abuse and mental health problems among illiterate runaway adolescents in an Indian metropolis
Authors: Bhat Deepti Pagare , Singh Meghachandra , Meena Gajendra Singh 
Published: August 2012

ObjectiveTo evaluate the prevalence of physical and sexual abuse, and their relation to mental health problems among the illiterate/semiliterate runaway adolescents in New Delhi, India.DesignCross sectional.SettingNew Delhi, India.PatientsRunaway adolescent boys (n=119) aged 11 to 18 years at an observation home.MethodsStudy subjects were screened for physical and sexual abuse using the Child Maltreatment History Self Report and Finkelhor's sexual abuse scale. Mental health problems were identified using the Achenbach's Youth Self-Report scale. As the participants were illiterate or semiliterate with Hindi being their primary language, the screening tools were appropriately translated, read out to them and their responses recorded.ResultsA total of 72 (62%) boys experienced domestic violence, 70 (59%) had engaged in substance abuse and 103 (87%) boys had been employed as child labourers. Physical abuse was reported by 86 (72%) and sexual abuse by 42 (35%). Mental health problems were recognised in 83 (70%) boys, which included internalising syndromes (59%) and externalising syndromes (34%). Multivariate analysis demonstrated that physical abuse was an independent predictor of internalising syndromes (OR: 3.3; 95% CI 1.2 to 9.1; p<0.01), while substance abuse and sexual abuse were independent predictors of externalising syndromes.ConclusionsOur study demonstrates that childhood abuse and mental health disorders are widely prevalent among the runaway adolescents evaluated at an observation home in New Delhi. Appropriate modification of the standardised self-report screening tools may allow the identification of mental health disorders in this vulnerable illiterate/semiliterate population.
The organisation and structure of inflammatory bowel disease services for children and young people in the UK in 2010: significant progress but still room for improvement
Authors: Fitzgerald Michael P , Mitton Sally G , Protheroe Aimee , Roughton Michael , Driscoll Richard , Arnott Ian D R , Russell Richard K 
Published: August 2012

BackgroundInflammatory bowel disease (IBD) is becoming more common in children. While treatment options remain limited the appropriate organisation and delivery of services are an integral part of good care.MethodsAll eligible UK paediatric sites were invited to submit data for organisation of paediatric IBD services as of 1 September 2010. Comparison, when relevant, was made with the previous paediatric audit (2008) and the concurrently running adult audit.Results24/25 (96%) of sites submitted data. The median number of patients managed and the median number of new IBD (ulcerative colitis and Crohn's disease only) cases per annum was 178 (IQR 136–281) and 32 (IQR 23–50), respectively. There was an increase in the IBD workforce including whole-time equivalent (WTE) IBD nurses (1.0 vs 1.5 WTE nurses, p=0.02). 1023 patients 16 years and younger were looked after in the 202 adult sites who submitted data; only 78/202 sites indicated they cared for 16-year-old and younger children; approximately half of these 78 sites had age-appropriate support facilities. Most paediatric sites have access to urgent endoscopy (83%), telephone advice (100%) and urgent clinic appointments (91%). Most sites did not have: shared care pathways with primary care (74%), annual reviews (71%), real time patient management systems (83%) and research network trial participation (78%).ConclusionsMany aspects of paediatric IBD care in the UK are good and have shown significant improvement over recent years. There are areas in need of further change and specific regional and national action plans should address identified deficiencies before any future audit of paediatric and adult IBD services.
RALBP1/RLIP76 Depletion in Mice Suppresses Tumor Growth by Inhibiting Tumor Neovascularization
Authors: Lee Seunghyung , Wurtzel Jeremy G. T. , Singhal Sharad S. , Awasthi Sanjay , Goldfinger Lawrence E. 
Published: August 2012

Abstract
RalBP1/RLIP76 is a widely expressed multifunctional protein that binds the Ral and R-Ras small GTPases. In the mouse, RLIP76 is nonessential but its depletion or blockade promotes tumorigenesis and heightens the sensitivity of normal and tumor cells to radiation and cytotoxic drugs. However, its pathobiologic functions, which support tumorigenesis, are not well understood. Here, we show that RLIP76 is required for angiogenesis and for efficient neovascularization of primary solid tumors. Tumor growth from implanted melanoma or carcinoma cells was blunted in RLIP76−/− mice. An X-ray microcomputed tomography-based method to model tumor vascular structures revealed defects in both the extent and form of tumor angiogenesis in RLIP76−/− mice. Specifically, tumor vascular volumes were diminished and vessels were fewer in number, shorter, and narrower in RLIP76−/− mice than in wild-type mice. Moreover, we found that angiogenesis was blunted in mutant mice in the absence of tumor cells, with endothelial cells isolated from these animals exhibiting defects in migration, proliferation, and cord formation in vitro. Taken together, our results establish that RLIP76 is required for efficient endothelial cell function and angiogenesis in solid tumors. Cancer Res; 72(20); 5165–73. ©2012 AACR.
Autologous Ectopic Grafting of Cryopreserved Testicular Tissue Preserves the Fertility of Prepubescent Monkeys That Receive Sterilizing Cytotoxic Therapy
Authors: Jahnukainen Kirsi , Ehmcke Jens , Nurmio Mirja , Schlatt Stefan 
Published: August 2012

Abstract
Boys faced with future sterility as a result of the need of a sterilizing cancer therapy might avoid this fate by engraftment of cryopreserved immature testicular tissue after therapy is completed. Efforts to address this important survivorship issue have been encouraged by reports of the long-term survival and proliferation of human spermatogonia after xenotransplant of cryopreserved immature testicular tissue into immunocompromised murine hosts. However, spermatogenic arrest at the pachytene spermatocyte stage that occurs in this situation has been associated with a failure in sperm production. In this study, we used a prepubescent simian model to address the possibility that testicular tissue engraftment is insufficiently supported in the model to allow suitable maturation of germ cells. Briefly, we carried out autologous orthotopic grafting of cryopreserved testicular tissue from four prepubescent monkeys and one pubescent rhesus monkey after testicular irradiation and castration of the host animal. Five months after implantation of scrotal grafts, we determined that 3% to 7% of the autografts could be recovered with spermatogenesis proceeding through spermatozoa formation in 13% to 17% of the seminiferous tubules formed in the grafts. In contrast, Sertoli cell-only tubules were detected in parallel xenografts transplanted into immunocompromised mice. Our results show that cryopreservation of testicular tissue from prepubescent primates can maintain the fully functional capacity of spermatogonia to produce sperm, but that host conditions are critical for spermatogenic maturation. Furthermore, our results establish an initial perspective on the quantity of cryopreserved material needed to ensure success in preserving fertility through testicular tissue grafts. Cancer Res; 72(20); 5174–8. ©2012 AACR.
A Retinoic Acid—Rich Tumor Microenvironment Provides Clonal Survival Cues for Tumor-Specific CD8+ T Cells
Authors: Guo Yanxia , Pino-Lagos Karina , Ahonen Cory A. , Bennett Kathy A. , Wang Jinshan , Napoli Joseph L. , Blomhoff Rune , Sockanathan Shanthini , Chandraratna Roshantha A. , Dmitrovsky Ethan , Turk Mary Jo , Noelle Randolph J. 
Published: August 2012

Abstract
While vitamin A has been implicated in host resistance to infectious disease, little is known about the role of vitamin A and its active metabolite, retinoic acid (RA) in host defenses against cancer. Here, we show that local RA production within the tumor microenvironment (TME) is increased up to 5-fold as compared with naïve surrounding tissue, with a commensurate increase in RA signaling to regionally infiltrating tumor-reactive T cells. Conditional disruption of RA signaling in CD8+ T cells using a dominant negative retinoic acid receptor α (dnRARα) established that RA signaling is required for tumor-specific CD8+ T-cell expansion/accumulation and protective antitumor immunity. In vivo analysis of antigen-specific CD8+ T-cell responses revealed that early T-cell expansion was RA-independent; however, late T-cell expansion and clonal accumulation was suppressed strongly in the absence of RA signaling. Our findings indicate that RA function is essential for the survival of tumor-reactive CD8+ T cells within the TME. Cancer Res; 72(20); 5230–9. ©2012 AACR.
Transition from Colitis to Cancer: High Wnt Activity Sustains the Tumor-Initiating Potential of Colon Cancer Stem Cell Precursors
Authors: Shenoy Anitha K. , Fisher Robert C. , Butterworth Elizabeth A. , Pi Liya , Chang Lung-Ji , Appelman Henry D. , Chang Myron , Scott Edward W. , Huang Emina H. 
Published: August 2012

Abstract
Ulcerative colitis (UC) increases the risk of colorectal cancer (CRC), but the mechanisms involved in colitis-to-cancer transition (CCT) are not well understood. CCT may involve a inflammation-dysplasia-carcinoma progression sequence compared with the better characterized adenoma-carcinoma progression sequence associated with sporadic CRC. One common thread may be activating mutations in components of the Wnt/β-catenin signaling pathway, which occur commonly as early events in sporadic CRC. To examine this hypothesis, we evaluated possible associations between Wnt/β-catenin signaling and CCT based on the cancer stem cell (CSC) model. Wnt/β-catenin immunostaining indicated that UC patients have a level of Wnt-pathway-active cells that is intermediate between normal colon and CRC. These UC cells exhibiting activation of the Wnt pathway constituted a major subpopulation (52% + 7.21) of the colonic epithelial cells positive for aldehyde dehydrogenase (ALDH), a putative marker of precursor colon CSC (pCCSC). We further fractionated this subpopulation of pCCSC using a Wnt pathway reporter assay. Over successive passages, pCCSCs with the highest Wnt activity exhibited higher clonogenic and tumorigenic potential than pCCSCs with the lowest Wnt activity, thereby establishing the key role of Wnt activity in driving CSC-like properties in these cells. Notably, 5/20 single cell injections of high-Wnt pCCSC resulted in tumor formation, suggesting a correlation with CCT. Attenuation of Wnt/β-catenin in high-Wnt pCCSC by shRNA-mediated downregulation or pharmacological inhibition significantly reduced tumor growth rates. Overall, the results of our study indicates (i) that early activation of Wnt/β-catenin signaling is critical for CCT and (ii) that high levels of Wnt/β-catenin signaling can further demarcate high-ALDH tumor-initiating cells in the nondysplastic epithelium of UC patients. As such, our findings offer plausible diagnostic markers and therapeutic target in the Wnt signaling pathway for early intervention in CCT. Cancer Res; 72(19); 5091–100. ©2012 AACR.
Profiles of Genomic Instability in High-Grade Serous Ovarian Cancer Predict Treatment Outcome
Authors: Wang Zhigang C. , Birkbak Nicolai Juul , Culhane Aedín C. , Drapkin Ronny , Fatima Aquila , Tian Ruiyang , Schwede Matthew , Alsop Kathryn , Daniels Kathryn E. , Piao Huiying , Liu Joyce , Etemadmoghadam Dariush , Miron Alexander , Salvesen Helga B. , Mitchell Gillian , DeFazio Anna , Quackenbush John , Berkowitz Ross S. , Iglehart J. Dirk , Bowtell David D.L. ,   for the Australian Ovarian Cancer Study Group, Matulonis Ursula A. 
Published: August 2012

Abstract
Purpose: High-grade serous cancer (HGSC) is the most common cancer of the ovary and is characterized by chromosomal instability. Defects in homologous recombination repair (HRR) are associated with genomic instability in HGSC, and are exploited by therapy targeting DNA repair. Defective HRR causes uniparental deletions and loss of heterozygosity (LOH). Our purpose is to profile LOH in HGSC and correlate our findings to clinical outcome, and compare HGSC and high-grade breast cancers.
Experimental Design: We examined LOH and copy number changes using single nucleotide polymorphism array data from three HGSC cohorts and compared results to a cohort of high-grade breast cancers. The LOH profiles in HGSC were matched to chemotherapy resistance and progression-free survival (PFS).
Results: LOH-based clustering divided HGSC into two clusters. The major group displayed extensive LOH and was further divided into two subgroups. The second group contained remarkably less LOH. BRCA1 promoter methylation was associated with the major group. LOH clusters were reproducible when validated in two independent HGSC datasets. LOH burden in the major cluster of HGSC was similar to triple-negative, and distinct from other high-grade breast cancers. Our analysis revealed an LOH cluster with lower treatment resistance and a significant correlation between LOH burden and PFS.
Conclusions: Separating HGSC by LOH-based clustering produces remarkably stable subgroups in three different cohorts. Patients in the various LOH clusters differed with respect to chemotherapy resistance, and the extent of LOH correlated with PFS. LOH burden may indicate vulnerability to treatment targeting DNA repair, such as PARP1 inhibitors. Clin Cancer Res; 18(20); 5806–15. ©2012 AACR.
The Promise of Patient-Derived Xenografts: The Best Laid Plans of Mice and Men
Authors: Kopetz Scott , Lemos Robert , Powis Garth 
Published: August 2012

Abstract
Compared with xenografts from previously established cell lines, patient-derived xenografts may more faithfully recapitulate the molecular diversity, cellular heterogeneity, and histology seen in patient tumors, although other limitations of murine models remain. The ability of these models to inform clinical development and answer mechanistic questions will determine their ultimate use. Clin Cancer Res; 18(19); 5160–2. ©2012 AACR.