Genome-wide detection of hybrid genes with multiple components in human

<p>Abstract</p> <p>Background</p> <p>Previous studies showed that gene hybrid is one of the principal processes for generating new genes. Although some gene hybrid events have been reported to be inter- or intra-species, there lacks a well-organized method for large scale detection of the events with multiple components. Hence in this study, we focus on building up an efficient method for exploring all candidates of gene hybrid events in human genome and provide useful results for further study.</p> <p>Findings</p> <p>We have developed a method designated Triad Comparison Algorithm (TCA) to detect all potential <it>N</it>-hybrid events (i.e., an <it>N</it>-hybrid gene and its <it>N </it>non-overlapping component regions derived from <it>N </it>different genes) in human genome. The results reveal that there are many convoluted <it>N</it>-hybrid events with multiple components (<it>N </it>> 2) and that the most complicated <it>N</it>-hybrid genes detected in human by TCA are composed of six component regions. Interestingly, our results show that most of the hybrid events belong to the 3-hybrid category. Furthermore, we observe that a single gene might participate in different events. Twelve genes were found to have dual identities contained in different <it>N</it>-hybrid events (i.e., they were identified as hybrid genes as well as component genes). This points out that to a certain extent the gene hybrid mechanism has generated new genes during the course of human genome evolutionary history.</p> <p>Conclusion</p> <p>An efficient method, TCA, is developed for exploring all candidates of hybrid genes in the human genome and provides useful results for the evolutionary analysis. The advantage of TCA is its power of detecting any kinds of hybrid events in any species with a large genome size.</p

Nosocomial methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in Taiwan: Mortality analyses and the impact of vancomycin, MIC = 2 mg/L, by the broth microdilution method

<p>Abstract</p> <p>Background</p> <p>Previous studies regarding the prognosis of patients infected with MRSA isolates characterized by a high minimum inhibitory concentration (MIC) for vancomycin have generally used a commercial Etest. Little research has been conducted on determining the vancomycin susceptibility of MRSA using a reference microdilution. Additionally, there is discordance between the MIC result from an Etest and the value determined using the reference microdilution method.</p> <p>Methods</p> <p>Using a reference microdilution method, we determined the MIC of vancomycin for isolates from 123 consecutive patients with nosocomial MRSA bacteremia. The clinical features and outcome for these patients were recorded and the MRSA isolates were genotyped.</p> <p>Results</p> <p>Among the 123 non-duplicated isolates, 21.1% had a MIC = 2 mg/L, 76.4% had a MIC = 1 mg/L and 2.4% had MIC = 0.5 mg/L. Patients with MRSA bacteremia in the ICU or those who had been hospitalized for a long time were more likely to be infected with strains of high vancomycin MIC MRSA (MIC = 2 mg/L; <it>p </it>< 0.05). Cox regression analysis demonstrated that the high MIC group had a significantly higher 30-day mortality than the low MIC group (HR: 2.39; 95% CI: 1.20-4.79; <it>p </it>= 0.014). Multivariate analyses indicated that the presence of high MIC isolates, pneumonia, post-cardiothoracic surgery and a high Charlson comorbidity index were all independent predictors of a 30-day mortality. Genotyping of these high vancomycin MIC isolates demonstrated that SCC<it>mec </it>III, <it>spa </it>type037, was the predominant strain (> 80%). The rates of resistance to trimethoprim/sulfamethoxazole, gentamicin, levofloxacin, rifampin and tetracycline were also higher in the high MIC group than in the isolates belonging to low MIC group (<it>p </it>< 0.05).</p> <p>Conclusions</p> <p>In a high vancomycin MIC group in Taiwan, SCC<it>mec </it>III, <it>spa </it>type t037, was the predominant strain of MRSA identified. Patients with MRSA bacteremia in the ICU or who had prolonged hospitalization were more likely to be infected with <it>S. aureus </it>strains with high vancomycin MICs. The mortality rate was higher among patients infected with these strains compared to patients infected with low MIC strains.</p

Improving Conversational Passage Re-ranking with View Ensemble

This paper presents ConvRerank, a conversational passage re-ranker that employs a newly developed pseudo-labeling approach. Our proposed view-ensemble method enhances the quality of pseudo-labeled data, thus improving the fine-tuning of ConvRerank. Our experimental evaluation on benchmark datasets shows that combining ConvRerank with a conversational dense retriever in a cascaded manner achieves a good balance between effectiveness and efficiency. Compared to baseline methods, our cascaded pipeline demonstrates lower latency and higher top-ranking effectiveness. Furthermore, the in-depth analysis confirms the potential of our approach to improving the effectiveness of conversational search.Comment: SIGIR 202

Resolution of secondary pulmonary alveolar proteinosis following treatment of rhinocerebral aspergillosis

SummaryPulmonary alveolar proteinosis can be secondary to inhaled dust exposure, malignancy, and chronic pulmonary infections. However, pulmonary alveolar proteinosis secondary to extrapulmonary aspergillosis has never been reported. We report herein a case of pulmonary alveolar proteinosis secondary to invasive rhinocerebral aspergillosis. Neither immune modulators nor whole lung lavage was applied during the treatment course. The severe respiratory distress subsided, hypoxia resolved, and radiological infiltrates improved following the successful treatment of invasive rhinocerebral aspergillosis alone

Interannual Variation of Springtime Biomass Burning in Indochina: Regional Differences, Associated atmospheric dynamical changes, and downwind impacts

During March and April, widespread burning occurs across farmlands in Indochina in preparation for planting at the monsoon onset. The resultant aerosols impact the air quality downwind. In this study, we investigate the climatic aspect of the interannual variation of springtime biomass burning in Indochina and its correlation with air quality at Mt. Lulin in Taiwan using long-term (2005–2015) satellite and global reanalysis data. Based on empirical orthogonal function (EOF) analysis, we find that the biomass burning activities vary with two geographical regions: northern Indochina (the primary EOF mode) and southern Indochina (the secondary EOF mode). We determine that the variation of biomass burning over northern Indochina is significantly related with the change in aerosol concentrations at Mt. Lulin. This occurs following the change in the so-called India-Burma Trough in the lower and middle troposphere. When the India-Burma Trough is intensified, a stronger northwesterly wind (to the west of the trough) transports the dryer air from higher latitude into northern Indochina, and this promotes local biomass burning activities. The increase in upward motion to the east of the intensified India-Burma Trough lifts the aerosols, which are transported toward Taiwan by the increased low-level westerly jet. Further diagnoses revealed the connection between the India-Burma Trough and the South Asian jet\u27s wave train pattern as well as the previous winter\u27s El Niño–Southern Oscillation phase. This information highlights the role of the India-Burma Trough in modulating northern Indochina biomass burning and possibly predicting aerosol transport to East Asia on the interannual time scale

The Hot and Clumpy Molecular Cocoon Surrounding the Ultracompact HII Region G5.89-0.39

We present observations of CH3CN (12-11) emission at a resolution of 2" toward the shell-like ultracompact HII region G5.89-0.39 with the Submillimeter Array. The integrated CH3CN emission reveals dense and hot molecular cocoon in the periphery of the HII region G5.89-0.39, with a CH3CN deficient region roughly centered at G5.89-0.39. By analyzing the CH3CN emission using population diagram analysis, we find, for the first time, a decreasing temperature structure from 150 to 40 K with the projected distance from Feldt's star, which is thought to be responsible for powering the HII region. Our results further indicate that the majority of the heating energy in the observed dense gas is supplied by the Feldt's star. From the derived CH3CN column density profile, we conclude that the dense gas is not uniformly-distributed but centrally-concentrated, with a power-law exponent of 5.5 for r < 8000 AU, and 2.0 for 8000 AU < r < 20000 AU, where r is the distance to Feldt's star. The estimated large power index of 5.5 can be attributed to an enhancement of CH3CN abundance in the close vicinity of Feldt's star.Comment: accepted for publication in The Astrophysical Journal Letter

TCF1 and LEF1 Control Treg Competitive Survival and Tfr Development to Prevent Autoimmune Diseases.

CD4+ Foxp3+ T regulatory (Treg) cells are key players in preventing lethal autoimmunity. Tregs undertake differentiation processes and acquire diverse functional properties. However, how Treg's differentiation and functional specification are regulated remains incompletely understood. Here, we report that gradient expression of TCF1 and LEF1 distinguishes Tregs into three distinct subpopulations, particularly highlighting a subset of activated Treg (aTreg) cells. Treg-specific ablation of TCF1 and LEF1 renders the mice susceptible to systemic autoimmunity. TCF1 and LEF1 are dispensable for Treg's suppressive capacity but essential for maintaining a normal aTreg pool and promoting Treg's competitive survival. As a consequence, the development of T follicular regulatory (Tfr) cells, which are a subset of aTreg, is abolished in TCF1/LEF1-conditional knockout mice, leading to unrestrained T follicular helper (Tfh) and germinal center B cell responses. Thus, TCF1 and LEF1 act redundantly to control the maintenance and functional specification of Treg subsets to prevent autoimmunity

Impact of first-line protease inhibitors on predicted resistance to tipranavir in HIV-1-infected patients with virological failure

<p>Abstract</p> <p>Background</p> <p>Tipranavir (TPV) is a recently approved nonpeptidic protease inhibitor (PI) of HIV-1 and has been indicated for those infected with PIs-resistant HIV-1. However, in clinical practice, whether the HIV-1 from the patients with virological failure to the regimens containing first-line PIs remains susceptible to TPV/r may be questionable.</p> <p>Methods</p> <p>To assess the resistance levels to TPV of HIV-1 from patients with treatment failure to first-line PIs, patients who experienced virological failure were tested for genotypic resistance of HIV-1 since August 2006 in National Taiwan University Hospital. Patients were enrolled for this analysis if their failed regimens contained > 12 weeks of atazanavir or lopinavir/ritonavir (defined as ATV group and LPV/r group, respectively), but were excluded if they experienced both or other PIs. The levels of genotypic resistance to TPV/r were determined by TPV mutation score.</p> <p>Results</p> <p>Till May 2008, 21 subjects in ATV group and 20 subjects in LPV/r group were enrolled. The TPV mutation scores in subjects in LPV/r group were significantly higher than these in ATV group (median, 3 vs 1, P = 0.007). 95.2% subjects in ATV group and only 45% subjects in LPV/r group had an estimated maximal virological response to TPV/r (P < 0.001). The resistance levels to TPV/r correlated with the duration of exposure to first-line PIs, whether in ATV or LPV/r group.</p> <p>Conclusion</p> <p>Cross-resistance from first-line PIs may impede the effectiveness of TPV/r-containing salvage therapy. TPV/r should be used cautiously for patients with virological failure to LPV/r especially long duration of exposure.</p