Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative genomics of microsporidian genomes reveals a minimal non-coding RNA set and new insights for transcription in minimal eukaryotic genomes

Abstract Microsporidia are ubiquitous intracellular pathogens whose opportunistic nature led to their increased recognition with the rise of the AIDS pandemic. As the RNA world was largely unexplored in this parasitic lineage, we developed a dedicated in silico methodology to carry out exhaustive identification of ncRNAs across the Encephalitozoon and Nosema genera. Thus, the previously missing U1 small nuclear RNA (snRNA) and small nucleolar RNAs (snoRNAs) targeting only the LSU rRNA were highlighted and were further validated using 5' and 3'RACE-PCR experiments. Overall, the 15 ncRNAs that were found shared between Encephalitozoon and Nosema spp. may represent the minimal core set required for parasitic life. Interestingly, the systematic presence of a CCC- or GGG-like motif in 5' of all ncRNA and mRNA gene transcripts regardless of the RNA polymerase involved suggests that the RNA polymerase machineries in microsporidia species could use common factors. Our data provide additional insights in accordance with the simplification processes observed in these reduce genomes and underline the usefulness of sequencing closely related species to help identify highly divergent ncRNAs in these parasites.
Role of ART in Imprinting Disorders

Abstract Assisted reproductive technologies (ART) offer revolutionary infertility treatments for millions of childless couples around the world. Currently, ART accounts for 1 to 3% of annual births in industrialized countries and continues to expand rapidly. Except for an increased incidence of premature births, these technologies are considered safe. However, new evidence published during the past decade has suggested an increased incidence of imprinting disorders in children conceived by ART. Specifically, an increased risk was reported for Beckwith-Wiedemann syndrome (BWS), Angelman syndrome (AS), Silver-Russell syndrome, and retinoblastoma. In contrast, some studies have found no association between ART and BWS, AS, Prader-Willi syndrome, transient neonatal diabetes mellitus, and retinoblastoma. The variability in ART protocols and the rarity of imprinting disorders complicate determining the causative relationship between ART and an increased incidence of imprinting disorders. Nevertheless, compelling experimental data from animal studies also suggest a link between increased imprinting disorders and ART. Further comprehensive, appropriately powered studies are needed to better address the magnitude of the risk for ART-associated imprinting disorders. Large longitudinal studies are particularly critical to evaluate long-term effects of ART not only during the perinatal period but also into adulthood. An important consideration is to determine if the implicated association between ART and imprinting disorders is actually related to the procedures or to infertility itself.
Gene Copy Number Aberrations Are Associated with Survival in Histologic Subgroups of Non-small Cell Lung Cancer

Introduction: Non-small cell lung cancer (NSCLC) is characterized by a multitude of genetic aberrations with unknown clinical impact. In this study, we aimed to identify gene copy number changes that correlate with clinical outcome in NSCLC. To maximize the chance to identify clinically relevant events, we applied a strategy involving two prognostically extreme patient groups. Methods: Short-term (<20 month; n = 53) and long-term survivors (>58 month; n = 47) were selected from a clinically well-characterized NSCLC patient cohort with available fresh frozen tumor specimens. The samples were analyzed using high-resolution single-nucleotide polymorphism array technology to assess gene copy number variations and array-based gene expression profiling. The molecular data were combined with information on clinical parameters. Results: Genetic aberrations were strongly associated with tumor histology. In adenocarcinoma (n = 50), gene copy number gains on chromosome 8q21-q24.3 (177 genes) were more frequent in long-term than in short-term survivors. In squamous cell carcinoma (n = 28), gains on chromosome 14q23.1-24.3 (133 genes) were associated with shorter survival, whereas losses in a neighboring region, 14q31.1-32.33 (110 genes), correlated with favorable outcome. In accordance with copy number gains and losses, messenger RNA expression levels of corresponding genes were increased or decreased, respectively. Conclusion: Comprehensive tumor profiling permits the integration of genomic, histologic, and clinical data. We identified gene copy number gains and losses, with corresponding changes in messenger RNA levels that were associated with prognosis in adenocarcinoma and squamous cell carcinoma of the lung.
Modelling the natural history of Huntington's disease progression

Background The lack of reliable biomarkers to track disease progression is a major problem in clinical research of chronic neurological disorders. Using Huntington's disease (HD) as an example, we describe a novel approach to model HD and show that the progression of a neurological disorder can be predicted for individual patients. Methods Starting with an initial cohort of 343 patients with HD that we have followed since 1995, we used data from 68 patients that satisfied our filtering criteria to model disease progression, based on the Unified Huntington’s Disease Rating Scale (UHDRS), a measure that is routinely used in HD clinics worldwide. Results Our model was validated by: (A) extrapolating our equation to model the age of disease onset, (B) testing it on a second patient data set by loosening our filtering criteria, (C) cross-validating with a repeated random subsampling approach and (D) holdout validating with the latest clinical assessment data from the same cohort of patients. With UHDRS scores from the past four clinical visits (over a minimum span of 2 years), our model predicts disease progression of individual patients over the next 2 years with an accuracy of 89–91%. We have also provided evidence that patients with similar baseline clinical profiles can exhibit very different trajectories of disease progression. Conclusions This new model therefore has important implications for HD research, most obviously in the development of potential disease-modifying therapies. We believe that a similar approach can also be adapted to model disease progression in other chronic neurological disorders.
Quantitation and biological activities of native tumour necrosis factor from LPS‐stimulated human monocytes

Human mononuclear cells (MNC) were stimulated in culture with LPS to produce tumour necrosis factor (TNF). The natural tumour necrosis factor (nTNF) was quantitated by ELISA and immunoblotting using rabbit antibodies to human recombinant TNF (rTNF) and the biotin‐avidin‐peroxidase system. Biologically active nTNF was determined by its cytotoxic activity for actinomycin‐D treated mouse fibroblasts and by its lethal effect in D‐galactosamine sensitized endotoxin‐resistant mice. Two different LPS preparations (Salmonella abortus equi and Pseudomonas aeruginosa) induced the formation of comparable amounts of nTNF. MNC from different donors, however, showed large variations in their ability to produce nTNF. The amount of nTNF induced in response to LPS could be enhanced by priming the MNC with interferon. The amounts of nTNF determined by ELISA generally correlated well with the activity of the nTNF in the two biological assays. On a weight basis, the lethal activity of nTNF in D‐galactosamine treated mice was very similar to that of human rTNF. Immunoblotting revealed a single band of nTNF with the same molecular weight (17 kD) as human rTNF. The lethality induced by nTNF was inhibited by rabbit anti‐human rTNF antibodies.
Proceedings of the 8th Annual Collaboration, Electronic messaging, Anti-Abuse and Spam Conference

The 8th Annual Collaboration, Electronic messaging, Anti-Abuse and Spam Conference (CEAS 2011) was held in the beautiful city of Perth, Western Australia. CEAS 2011 was organized by the Anti Spam Research Lab, which is part of the Digital Ecosystems & Business Intelligence Institute, Curtin University. It is the first time that the CEAS conference series was held outside of USA and the Anti Spam Research Lab was proud to host this successful event. This year CEAS 2011 received a total of 51 submissions from 12 countries. These submissions included papers from academia and industry. The program committee members along with the track chairs evaluated all the submissions and decided to accept 25 high quality papers. All submitted papers were strictly blind peer reviewed by the program committee members as well as experts from within the industry. All the accepted papers are indexed in ACM International Conference Proceedings Series (ICPS).
Effect of Lactulose on Bacterial Translocation and Intestinal Adaptation in a Rat Model of Short Bowel Syndrome

Background: It is frequently assumed that dietary nondigestible carbohydrates improve host resistance to intestinal infections by stimulating proliferation of the protective gut microflora. Therefore, the aim of this study was to define the effect of lactulose, a nondigestible carbohydrate, on bacterial translocation and intestinal adaptation in a rat model of short bowel syndrome (SBS). Materials and Methods: Male Sprague-Dawley rats were divided into 3 experimental groups. Sham rats underwent bowel transection, SBS rats underwent 75% small bowel resection, and SBS-LAC rats underwent bowel resection and were treated with oral lactulose given in drinking water at a dose of 1.5 g · kg−1 · day−1 from the 3rd to the 15th postoperative day. Bacterial translocation (to mesenteric lymph nodes, liver, and portal and peripheral blood) and parameters of intestinal adaptation were determined on day 15. Results: Treatment with lactulose did not change bacterial translocation, but decreased ileal mucosal weight (20%; P < 0.05), ileal mucosal DNA (2-fold decrease; P < 0.05) and protein (26%; P < 0.05), villus height in jejunum (21%; P < 0.05) and crypt depth in ileum (17%; P < 0.05), proliferation rates in jejunum (18%; P < 0.05) and ileum (15%; P < 0.05), and apoptotic index in jejunum (40%; P < 0.05) and ileum (36%; P < 0.05) compared with SBS animals. Bax expression was upregulated in SBS rats compared with control animals, but decreased following treatment with lactulose. Conclusions: In a rat model of SBS, oral lactulose does not improve bacterial translocation from the intestine, but inhibits intestinal adaptation.
THE INTERACTION OF SOLUBLE TIE2 WITH ANGIOPOIETINS AND PULMONARY VASCULAR PERMEABILITY IN SEPTIC AND NONSEPTIC CRITICALLY ILL PATIENTS

Circulating angiopoietin (Ang) 1 may inhibit and Ang-2 may enhance pulmonary vascular permeability in septic and nonseptic patients with or at risk for acute lung injury or acute respiratory distress syndrome. We hypothesized that the soluble form of the Ang-binding Tie2 receptor (sTie2), whose shedding may be induced by vascular endothelial growth factor (VEGF) levels, may bind circulating Angs and thereby inhibit their effects on pulmonary vascular permeability. In 24 septic and 40 nonseptic mechanically ventilated patients, sTie2, Ang-1, Ang-2, and VEGF plasma levels were measured together with the pulmonary leak index (PLI) for 67Gallium-labeled transferrin as a measure of pulmonary vascular permeability. Soluble Tie2 and VEGF levels correlated (r = 0.53, P = 0.001). Soluble Tie2 was higher in septic than in nonseptic patients (7.43 [6.57 - 8.40] vs. 5.03 [4.57 - 5.54] ng/mL; P < 0.001). Soluble Tie2 was associated with the PLI (standardized regression coefficient [&bgr;] = 0.26; P = 0.006) but lost its association with the PLI when the Angs were included in a multivariate model. Soluble Tie2 did not affect the association between Ang-1 or Ang-2 and the PLI (&bgr; = −0.39, P < 0.001; &bgr; = 0.52, P < 0.001, respectively), independently of underlying disease. Although limited to correlations and associations, the clinical data support in vivo shedding of sTie2 through VEGF signaling upon pulmonary vascular injury. However, this shedding may not prevent a direct role of Angs in pulmonary vascular permeability.
Contact with Thymic Epithelial Cells as a Prerequisite for Cytokine-Enhanced Human Immunodeficiency Virus Type 1 Replication in Thymocytes

ABSTRACT We report here that human immunodeficiency virus type 1 (HIV-1)-infected human thymocytes, in the absence of any exogenous stimulus but cocultivated with autologous thymic epithelial cells (TEC), obtained shortly (3 days) after thymus excision produce a high and sustained level of HIV-1 particles. The levels and kinetics of HIV-1 replication were similar for seven distinct viral strains irrespective of their phenotypes and genotypes. Contact of thymocytes with TEC is a critical requirement for optimal viral replication. Rather than an inductive signal resulting from the contact itself, soluble factors produced in the mixed culture are responsible for this effect. Specifically, the synergistic effects of tumor necrosis factor, interleukin-1 (IL-1), IL-6, and granulocyte-macrophage colony-stimulating factor may account by themselves for the high level of HIV-1 replication in thymocytes observed in mixed cultures. In conclusion, the microenvironment generated by TEC-thymocyte interaction might greatly favor optimal HIV-1 replication in the thymus.
Nurse-based management in patients with gestational diabetes.

OBJECTIVE To compare the rate of insulin treatment and perinatal outcome in women with gestational diabetes mellitus (GDM) under endocrinologist-based versus diabetes nurse-based metabolic management. RESEARCH DESIGN AND METHODS In a retrospective analysis, maternal characteristics, rate of insulin treatment, and perinatal outcome of patients with GDM delivering between 1 January 1995 and 30 June 1997 (n = 244) receiving endocrinologist-based care were compared with those delivering between 1 July 1997 and 31 December 1999 (n = 283) who received diabetes nurse-based care. The diabetes nurse's role was similar to that of an advanced practice nurse in the U.S. There were no changes in the metabolic goals and instruments or in obstetric and neonatal management. Quantitative data were compared with the Mann-Whitney U test and categorical data, with Fisher's exact test. RESULTS Maternal characteristics (age, BMI, family history of diabetes, prior glucose intolerance, gestational age, and blood glucose at diagnosis of GDM) did not differ between groups treated during the two periods. Rates of insulin treatment and perinatal outcome (hypertension, preterm delivery, cesarean section, low Apgar score, macrosomia, small- and large-for-gestational-age newborns, obstetric trauma, major malformations, hypoglycemia, hypocalcemia, polycythemia, jaundice, respiratory distress, and mortality) were also similar in both groups. CONCLUSIONS Comparison of periods of endocrinologist-based and diabetes nurse-based metabolic management of women with GDM showed no differences in the rate of insulin treatment and perinatal outcome. This supports a more active role of nurses in the management of women with GDM.
Macrophage Expression of Peroxisome Proliferator–Activated Receptor-&agr; Reduces Atherosclerosis in Low-Density Lipoprotein Receptor–Deficient Mice

Background— The peroxisome proliferator–activated receptor-&agr; (PPAR&agr;) plays important roles in lipid metabolism, inflammation, and atherosclerosis. PPAR&agr; ligands have been shown to reduce cardiovascular events in high-risk subjects. PPAR&agr; expression by arterial cells, including macrophages, may exert local antiatherogenic effects independent of plasma lipid changes. Methods and Results— To examine the contribution of PPAR&agr; expression by bone marrow–derived cells in atherosclerosis, male and female low-density lipoprotein receptor–deficient (LDLR−/−) mice were reconstituted with bone marrow from PPAR&agr;−/− or PPAR&agr;+/+ mice and challenged with a high-fat diet. Although serum lipids and lipoprotein profiles did not differ between the groups, the size of atherosclerotic lesions in the distal aorta of male and female PPAR&agr;−/−→LDLR−/− mice was significantly increased (44% and 46%, respectively) compared with controls. Male PPAR&agr;−/−→LDLR−/− mice also had larger (44%) atherosclerotic lesions in the proximal aorta than male PPAR&agr;+/+→LDLR−/− mice. Peritoneal macrophages from PPAR&agr;−/− mice had increased uptake of oxidized LDL and decreased cholesterol efflux. PPAR&agr;−/− macrophages had lower levels of scavenger receptor B type I and ABCA1 protein expression and an accelerated response of nuclear factor-&kgr;B–regulated inflammatory genes. A laser capture microdissection analysis verified suppressed scavenger receptor B type I and increased nuclear factor-&kgr;B gene expression levels in vivo in atherosclerotic lesions of PPAR&agr;−/−→LDLR−/− mice compared with the lesions of control PPAR&agr;+/+→LDLR−/− mice. Conclusions— These data demonstrate that PPAR&agr; expression by macrophages has antiatherogenic effects via modulation of cell cholesterol trafficking and inflammatory activity.
Pars Plana Vitrectomy and Internal Limiting Membrane Peeling in Epimacular Membranes: Correlation of Function and Morphology across the Macula

Purpose: To analyze the correlation between morphological and functional results 12 months after epiretinal membrane (ERM) surgery. Methods: 31 eyes from 31 consecutive patients with metamorphopsia and best corrected visual acuity (BCVA) below 20/32 underwent a transconjunctival 23- gauge vitrectomy with ERM and internal limiting membrane peeling. Preoperatively and 3, 6 and 12 months postoperatively, we assessed BCVA, microperimetry (MP-1) and spectral domain optical coherence tomography (SD-OCT). Photoreceptor inner and outer segment (IS/OS) was graded on SD-OCT images and correlated with microperimetry measurements in the fovea and parafoveal region. Results: The postoperative BCVA was significantly better in eyes with an intact IS/OS junction (p < 0.01). In addition, the mean defect depth was postoperatively decreased in the foveal and parafoveal area in eyes with an intact IS/OS junction. A correlation of SD-OCT IS/OS images and microperimetry in eyes with improvement in BCVA of at least 2 lines revealed a statistically significant result for the parafoveal quadrants (p < 0.011 for SD-OCT and p < 0.005 for microperimetry) but not for the foveal area alone. Conclusions: The IS/OS regeneration in the parafoveal quadrants contributes significantly to the recovery of BCVA following ERM surgery. Consequently, functional and morphological tests of the macular area should not be limited to the fovea but should be extended to the parafoveal region.
Combined Metabolomic Analysis of Plasma and Urine Reveals AHBA, Tryptophan and Serotonin Metabolism as Potential Risk Factors in Gestational Diabetes Mellitus (GDM)

Gestational diabetes mellitus during pregnancy has severe implications for the health of the mother and the fetus. Therefore, early prediction and an understanding of the physiology are an important part of prenatal care. Metabolite profiling is a long established method for the analysis and prediction of metabolic diseases. Here, we applied untargeted and targeted metabolomic protocols to analyze plasma and urine samples of pregnant women with and without GDM. Univariate and multivariate statistical analyses of metabolomic profiles revealed markers such as 2-hydroxybutanoic acid (AHBA), 3-hydroxybutanoic acid (BHBA), amino acids valine and alanine, the glucose-alanine-cycle, but also plant-derived compounds like sitosterin as different between control and GDM patients. PLS-DA and VIP analysis revealed tryptophan as a strong variable separating control and GDM. As tryptophan is biotransformed to serotonin we hypothesized whether serotonin metabolism might also be altered in GDM. To test this hypothesis we applied a method for the analysis of serotonin, metabolic intermediates and dopamine in urine by stable isotope dilution direct infusion electrospray ionization mass spectrometry (SID-MS). Indeed, serotonin and related metabolites differ significantly between control and GDM patients confirming the involvement of serotonin metabolism in GDM. Clustered correlation coefficient visualization of metabolite correlation networks revealed the different metabolic signatures between control and GDM patients. Eventually, the combination of selected blood plasma and urine sample metabolites improved the AUC prediction accuracy to 0.99. The detected GDM candidate biomarkers and the related systemic metabolic signatures are discussed in their pathophysiological context. Further studies with larger cohorts are necessary to underpin these observations.
Estimating users' intentions and behaviours of electronic bidding system

Electronic Bidding System (EBS) is one of the most important operational solutions of public administration, as well as the establishment of the conditions necessary for taking advantage of electronic administration. But few papers discussed the users' aesthesis in using Electronic Bidding System for the feedback control. Thus the main purpose of this paper is to investigate the current status and the factors of the users intentions and behaviors in using Electronic Bidding System. The judgment framework is Structural Equation Modeling (SEM) based on the Unified Theory of Acceptance and Use of Technology Model (UTAUT) to research the influence of the four factors, Performance Expectancy, Effort Expectancy, Social Influence, and Facilitating Conditions on the intentions and behaviors. A questionnaire survey is conducted to collect 192 valid samples for quantitative analysis. The sample number in Tainan Taiwan is 102 and the others are from Nanping Fujian. The results are shown as following. (1). Performance Expectancy and Social Influence have a significantly impact on the users' intentions and behaviors in using Electronic Bidding System, but not in Effort Expectancy. (2). Facilitating Conditions have a significantly impact on the users' behaviors in using Electronic Bidding System, but in use Intention. (3). The difference between samples from Tainan Taiwan and Nanping Fujian are significant in 5 of 9 factors.
Granulocyte chemotactic protein‐2 and related CXC chemokines: from gene regulation to receptor usage

Chemokines contribute to the inflammatory response by selective attraction of various leukocytic cell types. Human GCP‐2 was originally identified by amino acid sequence analysis as a CXC chemokine co‐produced with IL‐8 by osteosarcoma cells. Furthermore, the complete coding domain of human GCP‐2 was disclosed by means of RT‐PCR. Similarly, mouse GCP‐2 was isolated from fibroblastoid and epithelial cells and completely identified by sequence analysis. Human and mouse GCP‐2 share 61% identical amino acids. Both chemokines occur as multiple NH2‐terminally truncated forms. The shorter forms of mouse, but not those of human, GCP‐2 showed a higher neutrophil chemotactic potency and gelatinase B releasing capacity. Mouse GCP‐2 was a more potent neutrophil activator than human GCP‐2, natural mouse KC, and MIP‐2. Human GCP‐2 was not chemotactic for monocytes, lymphocytes, or eosinophils. Quantitative studies of mRNA expression in diploid fibroblasts revealed GCP‐2 induction by IL‐1β. Human GCP‐2 induced [Ca2+]i increase in neutrophils, which was reciprocally desensitized by IL‐8, GROα, and ENA‐78. Human GCP‐2 induced [Ca2+]i increases and chemotactic responses in both CXCR1‐ and CXCR2‐transfected cells. Finally, GCP‐2 provoked neutrophil accumulation and plasma extravasation in rabbit skin. In humans, GCP‐2 complements the activity of IL‐8 as neutrophil chemoattractant and activator but it constitutes a major neutrophil chemokine in the mouse. GCP‐2 induces neutrophil chemotaxis and activation but it might also contribute to detrimental tissue damage in sepsis, acute respiratory distress syndrome, acute hypersensitivity reactions, and autoimmune diseases. It might also influence the invasive capacity of GCP‐2‐secreting tumor cells. J. Leukoc. Biol.62: 563–569; 1997.