bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homology-based annotation of non-coding RNAs in the genomes of Schistosoma mansoni and Schistosoma japonicum
Authors: Copeland Claudia S , Marz Manja , Rose Dominic , Hertel Jana , Brindley Paul J , Santana Clara Bermudez , Kehr Stephanie , Attolini Camille Stephan-Otto , Stadler Peter F 
Published: October 2009

AbstractBackgroundSchistosomes are trematode parasites of the phylum Platyhelminthes. They are considered the most important of the human helminth parasites in terms of morbidity and mortality. Draft genome sequences are now available forSchistosoma mansoniandSchistosoma japonicum. Non-coding RNA (ncRNA) plays a crucial role in gene expression regulation, cellular function and defense, homeostasis, and pathogenesis. The genome-wide annotation of ncRNAs is a non-trivial task unless well-annotated genomes of closely related species are already available.ResultsA homology search for structured ncRNA in the genome ofS. mansoniresulted in 23 types of ncRNAs with conserved primary and secondary structure. Among these, we identified rRNA, snRNA, SL RNA, SRP, tRNAs and RNase P, and also possibly MRP and 7SK RNAs. In addition, we confirmed five miRNAs that have recently been reported inS. japonicumand found two additional homologs of known miRNAs. The tRNA complement ofS. mansoniis comparable to that of the free-living planarianSchmidtea mediterranea, although for some amino acids differences of more than a factor of two are observed: Leu, Ser, and His are overrepresented, while Cys, Meth, and Ile are underrepresented inS. mansoni. On the other hand, the number of tRNAs in the genome ofS. japonicumis reduced by more than a factor of four. Both schistosomes have a complete set of minor spliceosomal snRNAs. Several ncRNAs that are expected to exist in theS. mansonigenome were not found, among them the telomerase RNA, vault RNAs, and Y RNAs.ConclusionThe ncRNA sequences and structures presented here represent the most complete dataset of ncRNA from any lophotrochozoan reported so far. This data set provides an important reference for further analysis of the genomes of schistosomes and indeed eukaryotic genomes at large.
Modulation of pathogen-induced CCL20 secretion from HT-29 human intestinal epithelial cells by commensal bacteria
Authors: Sibartie Shomik , O'Hara Ann M , Ryan Jude , Fanning Áine , O'Mahony Jim , O'Neill Shaun , Sheil Barbara , O'Mahony Liam , Shanahan Fergus 
Published: October 2009

Abstract

Background
Human intestinal epithelial cells (IECs) secrete the chemokine CCL20 in response to infection by various enteropathogenic bacteria or exposure to bacterial flagellin. CCL20 recruits immature dendritic cells and lymphocytes to target sites. Here we investigated IEC responses to various pathogenic and commensal bacteria as well as the modulatory effects of commensal bacteria on pathogen-induced CCL20 secretion. HT-29 human IECs were incubated with commensal bacteria (Bifidobacterium infantis or Lactobacillus salivarius), or with Salmonella typhimurium, its flagellin, Clostridium difficile, Mycobacterium paratuberculosis, or Mycobacterium smegmatis for varying times. In some studies, HT-29 cells were pre-treated with a commensal strain for 2 hr prior to infection or flagellin stimulation. CCL20 and interleukin (IL)-8 secretion and nuclear factor (NF)-κB activation were measured using enzyme-linked immunosorbent assays.

Results
Compared to untreated cells, S. typhimurium, C. difficile, M. paratuberculosis, and flagellin activated NF-κB and stimulated significant secretion of CCL20 and IL-8 by HT-29 cells. Conversely, B. infantis, L. salivarius or M. smegmatis did not activate NF-κB or augment CCL20 or IL-8 production. Treatment with B. infantis, but not L. salivarius, dose-dependently inhibited the baseline secretion of CCL20. In cells pre-treated with B. infantis, C. difficile-, S. typhimurium-, and flagellin-induced CCL20 were significantly attenuated. B. infantis did not limit M. Paratuberculosis- induced CCL20 secretion.

Conclusion
This study is the first to demonstrate that a commensal strain can attenuate CCL20 secretion in HT-29 IECs. Collectively, the data indicate that M. paratuberculosis may mediate mucosal damage and that B. infantis can exert immunomodulatory effects on IECs that mediate host responses to flagellin and flagellated enteric pathogens.
Relevance of MRI in prediction of malignancy of musculoskeletal system-A prospective evaluation
Authors: Daniel Alex , Ullah Ekram , Wahab Shagufta , Kumar Vasantha 
Published: October 2009

Abstract

Background
The purpose of this study is to evaluate the role of MRI in musculoskeletal tumours, especially, in prediction of malignancy & to compare whether the diagnosis made on MRI correlates with the cytological/histopathological diagnosis.

Methods
50 consecutive patients presenting in the Outpatient and Inpatient department of the Department of Orthopaedics or Casualty of Jawaharlal Nehru Medical College and Hospital, AMU, Aligarh, India were included in this study. They were subjected to MR examination on 1.5 Tesla superconducting system (MAGNETOM Avanto, Siemens). After localizer sequences, T1W and STIR images were obtained in longitudinal planes followed by T2W and post contrast T1W images in axial planes. Additional sequences were taken when required. Various imaging characteristics of tumours were evaluated statistically and their respective sensitivity and specificity in prediction of malignancy were obtained.

Results
Features associated with benign diagnosis in a large percentage of cases, are size less than 8 cm, sharp margination, homogeneous T2 signal, absence of oedema, necrosis, calcification and fluid-fluid levels. Similarly, malignant tumours are commonly associated with presence of irregular margins, inhomogeneous signal intensity, oedema, necrosis, haemorrhage, fascial penetration, bone changes and neurovascular involvement. A correct histological diagnosis is reached on the basis of imaging studies alone in 65% to 75% of cases. The sensitivity for a MRI diagnosis of malignant tumour was 95% and specificity was 84%.

Conclusion
Differentiation of malignant from benign lesions of musculoskeletal system is best made by a combination of clinical and imaging parameters rather than by any single MR characteristic. When a lesion has a non-specific MR imaging appearance, it is useful to formulate a suitably ordered differential diagnosis based on tumour prevalence, patient age, and anatomic location. A systematic approach markedly improves diagnostic results.
Characterization of unknown genetic modifications using high throughput sequencing and computational subtraction
Authors: Tengs Torstein , Zhang Haibo , Holst-Jensen Arne , Bohlin Jon , Butenko Melinka A , Kristoffersen Anja Bråthen , Sorteberg Hilde-Gunn Opsahl , Berdal Knut G 
Published: October 2009

Abstract

Background
When generating a genetically modified organism (GMO), the primary goal is to give a target organism one or several novel traits by using biotechnology techniques. A GMO will differ from its parental strain in that its pool of transcripts will be altered. Currently, there are no methods that are reliably able to determine if an organism has been genetically altered if the nature of the modification is unknown.

Results
We show that the concept of computational subtraction can be used to identify transgenic cDNA sequences from genetically modified plants. Our datasets include 454-type sequences from a transgenic line of Arabidopsis thaliana and published EST datasets from commercially relevant species (rice and papaya).

Conclusion
We believe that computational subtraction represents a powerful new strategy for determining if an organism has been genetically modified as well as to define the nature of the modification. Fewer assumptions have to be made compared to methods currently in use and this is an advantage particularly when working with unknown GMOs.
Identification of glucocorticoid-induced leucine zipper as a key regulator of tumor cell proliferation in epithelial ovarian cancer
Authors: Redjimi Nassima , Gaudin Françoise , Touboul Cyril , Emilie Dominique , Pallardy Marc , Biola-Vidamment Armelle , Fernandez Hervé , Prévot Sophie , Balabanian Karl , Machelon Véronique 
Published: October 2009

Abstract

Background
Little is known about the molecules that contribute to tumor progression of epithelial ovarian cancer (EOC), currently a leading cause of mortality from gynecological malignancies. Glucocorticoid-Induced Leucine Zipper (GILZ), an intracellular protein widely expressed in immune tissues, has been reported in epithelial tissues and controls some of key signaling pathways involved in tumorigenesis. However, there has been no report on GILZ in EOC up to now. The objectives of the current study were to examine the expression of GILZ in EOC and its effect on tumor cell proliferation.

Results
GILZ expression was measured by immunohistochemical staining in tissue sections from 3 normal ovaries, 7 benign EOC and 50 invasive EOC. GILZ was not detected on the surface epithelium of normal ovaries and benign tumors. In contrast, it was expressed in the cytoplasm of tumor cells in 80% EOC specimens. GILZ immunostaining scores correlated positively to the proliferation marker Ki-67 (Spearman test in univariate analysis, P < 0.00001, r = 0.56). They were also higher in tumor cells containing large amounts of phosphorylated protein kinase B (p-AKT) (unpaired t test, P < 0.0001). To assess the effect of GILZ on proliferation and AKT activation, we used the BG-1 cell line derived from ovarian tumor cells as a cellular model. GILZ expression was either enhanced by stable transfection or decreased by the use of small interfering (si) RNA targeting GILZ. We found that GILZ increased cell proliferation, phospho-AKT cellular content and AKT kinase activity. Further, GILZ upregulated cyclin D1 and phosphorylated retinoblastoma (p-Rb), downregulated cyclin-dependent kinase inhibitor p21, and promoted the entry into S phase of cell cycle.

Conclusion
The present study is the first to identify GILZ as a molecule produced by ovarian cancer cells that promotes cell cycle progression and proliferation. Our findings clearly indicate that GILZ activates AKT, a crucial signaling molecule in tumorigenesis. GILZ thus appears as a potential key molecule in EOC.
Papular xanthomas and erosive arthritis in a 3 year old girl, is this a new MRH variant?
Authors: Matiz Catalina , Ferguson Polly J , Zaenglein Andrea , Groh Brandt , Bingham Catherine April 
Published: October 2009

AbstractXanthomatous skin lesions and arthritis in children are not a common association. We present the case of a 3 year old girl who presented with xanthomatous lesions in the periungual region of both hands, around the nares and on her forehead, associated with significant arthritis that was clinically compatible with multicentric reticulohistiocytosis. However, pathology of the xanthomatous lesions was more suggestive of papular xanthoma, a disease that is not associated with arthritis. Based on her presentation and the negative lipid workup, she was treated for presumed multicentric reticulohistiocytosis. Multiple treatment strategies were utilized, with improvement on a combination of infliximab, methotrexate, and prednisone. We review the different diagnoses that should be considered in children with xanthomas and arthritis as well as the different pharmacologic therapies used in children with multicentric reticulohistiocytosis.
Consanguinity and reproductive health among Arabs
Authors: Tadmouri Ghazi O , Nair Pratibha , Obeid Tasneem , Al Ali Mahmoud T , Al Khaja Najib , Hamamy Hanan A 
Published: October 2009

AbstractConsanguineous marriages have been practiced since the early existence of modern humans. Until now consanguinity is widely practiced in several global communities with variable rates depending on religion, culture, and geography. Arab populations have a long tradition of consanguinity due to socio-cultural factors. Many Arab countries display some of the highest rates of consanguineous marriages in the world, and specifically first cousin marriages which may reach 25-30% of all marriages. In some countries like Qatar, Yemen, and UAE, consanguinity rates are increasing in the current generation. Research among Arabs and worldwide has indicated that consanguinity could have an effect on some reproductive health parameters such as postnatal mortality and rates of congenital malformations. The association of consanguinity with other reproductive health parameters, such as fertility and fetal wastage, is controversial. The main impact of consanguinity, however, is an increase in the rate of homozygotes for autosomal recessive genetic disorders. Worldwide, known dominant disorders are more numerous than known recessive disorders. However, data on genetic disorders in Arab populations as extracted from the Catalogue of Transmission Genetics in Arabs (CTGA) database indicate a relative abundance of recessive disorders in the region that is clearly associated with the practice of consanguinity.
Blood feeding by the Rocky Mountain spotted fever vector, Dermacentor andersoni, induces interleukin-4 expression by cognate antigen responding CD4+ T cells
Authors: Boppana Venkata D , Thangamani Saravanan , Alarcon-Chaidez Francisco J , Adler Adam J , Wikel Stephen K 
Published: October 2009

AbstractBackgroundTick modulation of host defenses facilitates both blood feeding and pathogen transmission. Several tick species deviate host T cell responses toward a Th2 cytokine profile. The majority of studies of modulation of T cell cytokine expression by ticks were performed with lymphocytes from infested mice stimulated in vitro with polyclonal T cell activators. Those reports did not examine tick modulation of antigen specific responses. We report use of a transgenic T cell receptor (TCR) adoptive transfer model reactive with influenza hemagglutinin peptide (110-120) to examine CD4+ T cell intracellular cytokine responses during infestation with the metastriate tick,Dermacentor andersoni, or exposure to salivary gland extracts.ResultsInfestation with pathogen-freeD. andersoninymphs or administration of an intradermal injection of female or male tick salivary gland extract induced significant increases of IL-4 transcripts in skin and draining lymph nodes of BALB/c mice as measured by quantitative real-time RT-PCR. Furthermore, IL-10 transcripts were significantly increased in skin while IL-2 and IFN-γ transcripts were not significantly changed by tick feeding or intradermal injection of salivary gland proteins, suggesting a superimposed Th2 response. Infestation induced TCR transgenic CD4+ T cells to divide more frequently as measured by CFSE dilution, but more notably these CD4+ T cells also gained the capacity to express IL-4. Intracellular levels of IL-4 were significantly increased. A second infestation administered 14 days after a primary exposure to ticks resulted in partially reduced CFSE dilution with no change in IL-4 expression when compared to one exposure to ticks. Intradermal inoculation of salivary gland extracts from both male and female ticks also induced IL-4 expression.ConclusionThis is the first report of the influence of a metastriate tick on the cytokine profile of antigen specific CD4+ T cells. Blood feeding byD. andersonipathogen-free nymphs or intradermal injection of salivary gland extracts programs influenza hemagglutinin influenza peptide specific TCR transgenic CD4+ T cells to express IL-4.
Urinary estrogen metabolites and prostate cancer: a case-control study and meta-analysis
Authors: Barba Maddalena , Yang Li , Schünemann Holger J , Sperati Francesca , Grioni Sara , Stranges Saverio , Westerlind Kim C , Blandino Giovanni , Gallucci Michele , Lauria Rossella , Malorni Luca , Muti Paola 
Published: October 2009

Abstract

Objective
To investigate prostate cancer (Pca) risk in relation to estrogen metabolism, expressed as urinary 2-hydroxyestrone (2-OHE1), 16α-hydroxyestrone (16α-OHE1) and 2-OHE1 to 16α-OHE1 ratio.

Methods
We conducted a case-control study within the Western New York Health Cohort Study (WNYHCS) from 1996 to 2001. From January 2003 through September 2004, we completed the re-call and follow-up of 1092 cohort participants. Cases (n = 26) and controls (n = 110) were matched on age, race and recruitment period according to a 1:4 ratio. We used the unconditional logistic regression to compute crude and adjusted odds ratios (OR) and 95% confident interval (CI) of Pca in relation to 2-OHE1, 16αOHE1 and 2-OHE1 to 16α-OHE1 by tertiles of urine concentrations (stored in a biorepository for an average of 4 years). We identified age, race, education and body mass index as covariates. We also conducted a systematic review of the literature which revealed no additional studies, but we pooled the results from this study with those from a previously conducted case-control study using the DerSimonian-Laird random effects method.

Results
We observed a non-significant risk reduction in the highest tertile of 2-OHE1 (OR 0.72, 95% CI 0.25-2.10). Conversely, the odds in the highest tertile of 16α-OHE1 showed a non-significant risk increase (OR 1.76 95% CI 0.62-4.98). There was a suggestion of reduced Pca risk for men in the highest tertile of 2-OHE1 to 16α-OHE1 ratio (OR 0.56, 95% CI 0.19-1.68). The pooled estimates confirmed the association between an increased Pca risk and higher urinary levels of 16α-OHE1 (third vs. first tertile: OR 1.82, 95% CI 1.09-3.05) and the protective effect of a higher 2-OHE 1 to 16α-OHE1 ratio (third vs. first tertile: OR 0.53, 95% CI 0.31-0.90).

Conclusion
Our study and the pooled results provide evidence for a differential role of the estrogen hydroxylation pathway in Pca development and encourage further study.
Outcome of Different Nevirapine Administration Strategies in Preventin g Mother‐to‐Child Transmission (PMTCT) Programs in Tanzania and Uganda
Authors: Karcher Heiko , Kunz Andrea , Poggensee Gabriele , Mbezi Paulina , Mugenyi Kizito , Harms Gundel 
Published: October 2009

ObjectivePrevention‐of‐mother‐to‐child transmission (PMTCT) interventions based on single‐dose nevirapine (NVP) are widely implemented in Africa, but strategies differ regarding how and when to administer the drug to women and infants. The aim of this study was to analyze the outcome of different strategies with regard to NVP intake in pregnant women and their infants in Tanzania and Uganda.MethodsIn an observational study carried out between March 2002 and December 2004, we compared a directly observed NVP administration strategy in Tanzania (supervised NVP intake for women and infants at a health unit) and a semi‐observed administration strategy (self‐administered NVP for women at home and supervised intake for infants at a health unit) in Uganda.ResultsThe proportions of HIV‐positive women accepting receipt of NVP from the health units were similar in the 2 countries (42.4% in Tanzania vs 45.6% in Uganda; P = .06). NVP intake in infants was significantly higher in Tanzania than in Uganda (43.7% vs 24.1%; P < .001). In a multivariate analysis, maternal age above 25 years, secondary education, Catholic faith, and having undergone PMTCT counseling at a hospital were independently associated with infant NVP intake.ConclusionIn our settings, the directly observed administration strategy resulted in a higher NVP intake in infants. The semi‐observed strategy, which implies that, after home delivery, the infant has to be presented to a health unit for NVP administration, was less successful.
Genomic and Nongenomic Cross Talk between the Gonadotropin-Releasing Hormone Receptor and Glucocorticoid Receptor Signaling Pathways
Authors: Kotitschke Andrea , Sadie-Van Gijsen Hanél , Avenant Chanel , Fernandes Sandra , Hapgood Janet P. 
Published: October 2009

AbstractThe GnRH receptor (GnRHR), a member of the G protein-coupled receptor family, is a central regulator of reproductive function in all vertebrates. The peptide hormone GnRH exerts its effects via binding to the GnRHR in pituitary gonadotropes. We investigated the mechanisms of regulation of transcription of the mGnRHR gene in the mouse pituitary gonadotrope LβT2 cell line by GnRH and dexamethasone (dex). Reporter assays with transfected mGnRHR promoter show that both dex and GnRH increase transcription of the mGnRHR gene via an activating protein-1 (AP-1) site. Real-time PCR confirmed this on the endogenous mGnRHR gene, and small interfering RNA experiments revealed a requirement for the glucocorticoid receptor (GR) for both the dex and GnRH response. Chromatin immunoprecipitation (ChIP) and immunofluorescence assays provide evidence that both GnRH and dex up-regulate the GnRHR gene via nuclear translocation and interaction of the GR with the AP-1 region on the mGnRHR promoter. We show that GnRH activates the unliganded GR by rapid phosphorylation of the GR at Ser-234 in a GnRHR-dependent fashion to transactivate a GRE reporter gene in LβT2 and COS-1 cells. Using kinase inhibitors, we established a direct link between GnRH-induced protein kinase C and MAPK activation, leading to unliganded GR phosphorylation at Ser-234 and transactivation of the glucocorticoid response element. Furthermore, we show that GnRH and dex synergistically activate the endogenous GnRHR promoter in LβT2 cells, via a mechanism involving steroid receptor coactivator-1 recruitment to the GnRHR AP-1 region. Our results suggest a novel mechanism of rapid nongenomic cross talk between the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes via GnRHR-dependent phosphorylation and activation of the unliganded GR in response to GnRH.
COLD-PCR–Enhanced High-Resolution Melting Enables Rapid and Selective Identification of Low-Level Unknown Mutations
Authors: Milbury Coren A , Li Jin , Makrigiorgos G Mike 
Published: October 2009

Abstract
Background: Analysis of clinical samples often necessitates identification of low-level somatic mutations within wild-type DNA; however, the selectivity and sensitivity of the methods are often limiting. COLD-PCR (coamplification at lower denaturation temperature–PCR) is a new form of PCR that enriches mutation-containing amplicons to concentrations sufficient for direct sequencing; nevertheless, sequencing itself remains an expensive mutation-screening approach. Conversely, high-resolution melting (HRM) is a rapid, inexpensive scanning method, but it cannot specifically identify the detected mutation. To enable enrichment, quick scanning, and identification of low-level unknown mutations, we combined COLD-PCR with HRM mutation scanning, followed by sequencing of positive samples.
Methods: Mutation-containing cell-line DNA serially diluted into wild-type DNA and DNA samples from human lung adenocarcinomas containing low-level mutations were amplified via COLD-PCR and via conventional PCR for TP53 (tumor protein p53) exons 6–8, and the 2 approaches were compared. HRM analysis was used to screen amplicons for mutations; mutation-positive amplicons were sequenced.
Results: Dilution experiments indicated an approximate 6- to 20-fold improvement in selectivity with COLD-PCR/HRM. Conventional PCR/HRM exhibited mutation-detection limits of approximately 2% to 10%, whereas COLD-PCR/HRM exhibited limits from approximately 0.1% to 1% mutant-to-wild-type ratio. After HRM analysis of lung adenocarcinoma samples, we detected 7 mutations by both PCR methods in exon 7; however, in exon 8 we detected 9 mutations in COLD-PCR amplicons, compared with only 6 mutations in conventional-PCR amplicons. Furthermore, 94% of the HRM-detected mutations were successfully sequenced with COLD-PCR amplicons, compared with 50% with conventional-PCR amplicons.
Conclusions: COLD-PCR/HRM improves the mutation-scanning capabilities of HRM and combines high selectivity, convenience, and low cost with the ability to sequence unknown low-level mutations in clinical samples.