Miracle-dz/UniFAR-FTUs huggingface dataset:
Systemic administration of TLR3 agonist induces IL‐7 expression and IL‐7‐dependent CXCR3 ligand production in the lung

In this study, we tested the hypothesis that systemic administration of TLR3 agonist poly I:C can enhance T cell infiltration of lung through up‐regulating IL‐7 expression. poly I:C, a synthetic analog of viral dsRNA and a TLR3 agonist, is studied extensively as vaccine adjuvant as a result of its pleotropic immune‐stimulatory effects. Here, we show that systemic poly I:C administration induces substantial IL‐7 production in the lung in a type 1 IFN‐ and IFN‐γ‐dependent fashion. Blockade of the IL‐7Rα signal with a neutralizing antibody abrogated poly I:C‐induced MCP‐1 up‐regulation, macrophage recruitment, and CXCR3 ligand expression in the lung. Conversely, administration of IL‐7 enhances these events, and it does so by enhancing T cell IFN‐γ production. We also show that the initial up‐regulation of CXCR3 ligands and infiltration of T cells in the lung are mediated by poly I:C‐induced IFN‐γ from NK cells; however, the sustained and optimal CXCR3 ligand expression and T cell infiltration require poly I:C‐induced IL‐7 and T cell‐derived IFN‐γ. In a model of multiorgan inflammation elicited by adoptive transfer of immune cells into RAG1−/− mice, we show that poly I:C enhances IL‐7 production in the lung and promotes expression of CXCR3 ligands and recruitment of IFN‐γ+ T cells in an IL‐7‐dependent fashion. Collectively, these results strongly support our hypothesis and delineate a new mechanism by which poly I:C boosts the T cell immune response in the lung by inducing local IL‐7 production, which in turn, enhances T cell‐derived IFN‐γ to promote macrophage recruitment, CXCR3 ligand expression, and T cell infiltration.
Determining the electrophoretic mobility and translational diffusion coefficients of DNA molecules in free solution

The free solution mobility of DNA molecules of different molecular weights, the sequence dependence of the mobility, and the diffusion coefficients of small single‐ and double‐stranded DNA (ss‐ and dsDNA) molecules can be measured accurately by capillary zone electrophoresis, using coated capillaries to minimize the electroosmotic flow (EOF) of the solvent. Very small differences in mobility between various analytes can be quantified if a mobility marker is used to correct for small differences in EOF between successive experiments. Using mobility markers, the molecular weight at which the free solution mobility of dsDNA becomes independent of molecular weight is found to be ∼ 170 bp in 40 mM Tris‐acetate‐EDTA buffer. A DNA fragment containing 170 bp has a contour length of ∼ 58 nm, close to the persistence length of DNA under these buffer conditions. Hence, the approach of the free solution mobility of DNA to a plateau value may be associated with the transition from a rod‐like to a coil‐like conformation in solution. Markers have also been used to determine that the free solution mobilities of ss‐ and dsDNA oligomers are sequence‐dependent. Double‐stranded 20‐bp oligomers containing runs of three or more adenine residues in a row (A‐tracts) migrate somewhat more slowly than 20‐mers without A‐tracts, suggesting that somewhat larger numbers of counterions are condensed in the ion atmospheres of A‐tract DNAs, decreasing their net effective charge. Single‐stranded 20‐mers with symmetric sequences migrate ∼ 1% faster than their double‐stranded counterparts, and faster than single‐stranded 20‐mers containing A5‐ or T5‐tracts. Interestingly, the average mobility of two complementary single‐stranded 20‐mers is equal to the mobility of the double‐stranded oligomer formed upon annealing. Finally, the stopped migration method has been used to measure the diffusion coefficients of single‐ and double‐stranded oligomers. The diffusion coefficients of ssDNA oligomers containing 20 nucleotides are ∼ 50% larger than those of double‐stranded DNA oligomers of the same size, reflecting the greater flexibility of ssDNA molecules. The methods used to carry out these experiments are also described in detail.
Aberrant Expression of the Long Non-coding RNA GHRLOS and Its Prognostic Significance in Patients with Colorectal Cancer

Long non-coding RNAs (lncRNAs), which have emerged as important regulatory RNA molecules that have been implicated in carcinogenesis and cancer progression, may also serve as novel potential biomarkers for cancer diagnosis and prognosis. Our previous analysis has identified the lncRNA GHRLOS, the ghrelin antisense strand non-coding RNA gene, as one of the hub genes in the co-expression network of differentially expressed lncRNAs/mRNAs in colorectal cancer (CRC). Here, we further evaluate the expression of GHRLOS in CRC and explore its clinical significance. The expression of GHRLOS in 366 pairs of CRC and adjacent non-cancerous tissues was detected by quantitative RT-PCR assays. The results showed that the expression level of GHRLOS was significantly lower in CRC tissues than in matched non-cancerous tissues (P < 0.001). Decreased GHRLOS expression was observed in 54.4% (199/366) of cases, and was significantly correlated with the occurrence of lymph node metastasis (P = 0.033) and distant metastasis (P = 0.005). A Kaplan-Meier analysis demonstrated that decreased GHRLOS expression contributed to poor disease-free survival (log-rank test, P < 0.001) and overall survival (log-rank test, P < 0.001). Moreover, a multivariate Cox regression analysis revealed the decreased expression of GHRLOS as an independent prognostic marker of poor outcomes [disease-free survival: hazard ratio (HR) = 2.02, 95% confidence interval (CI) = 1.42-3.88; overall survival: HR = 1.96, 95% CI = 1.34-2.86] in CRC patients. In conclusion, our data suggest that the lncRNA GHRLOS might serve as a candidate biomarker of tumor metastasis and a prognostic indicator in CRC.
Maturation cleavage of the murine leukemia virus Env precursor separates the transmembrane subunits to prime it for receptor triggering

The Env protein of murine leukemia virus matures by two cleavage events. First, cellular furin separates the receptor binding surface (SU) subunit from the fusion-active transmembrane (TM) subunit and then, in the newly assembled particle, the viral protease removes a 16-residue peptide, the R-peptide from the endodomain of the TM. Both cleavage events are required to prime the Env for receptor-triggered activation. Cryoelectron microscopy (cryo-EM) analyses have shown that the mature Env forms an open cage-like structure composed of three SU–TM complexes, where the TM subunits formed separated Env legs. Here we have studied the structure of the R-peptide precursor Env by cryo-EM. TM cleavage in Moloney murine leukemia virus was inhibited by amprenavir, and the Envs were solubilized in Triton X-100 and isolated by sedimentation in a sucrose gradient. We found that the legs of the R-peptide Env were held together by trimeric interactions at the very bottom of the Env. This suggested that the R-peptide ties the TM legs together and that this prevents the activation of the TM for fusion. The model was supported by further cryo-EM studies using an R-peptide Env mutant that was fusion-competent despite an uncleaved R-peptide. The Env legs of this mutant were found to be separated, like in the mature Env. This shows that it is the TM leg separation, normally caused by R-peptide cleavage, that primes the Env for receptor triggering.
Unified Theoretical Expressions for the Average Error Rate of Selection Diversity with Arbitrary Coded and Uncoded Modulation in Slow Rayleigh Fading and Their Application to Analytical, Semi-Analytical and Simulation Performance Evaluation

A unified theory for selection combining diversity in Rayleigh fading channels is derived. It is shown that the performance of arbitrary systems used with selection combining diversity can be expressed in terms of only the performance of the system on a single branch Rayleigh fading channel. The results are valid for coded and uncoded transmission as well as for balanced (equal power) diversity branches and unbalanced (unequal power) diversity branches. The unified theory encompasses both general noise and general interference.
Effects of Concentrated Ambient Particles on Heart Rate, Blood Pressure, and Cardiac Contractility in Spontaneously Hypertensive Rats During a Dust Storm Event

Epidemiological studies have suggested that cardiovascular mortality and morbidity increased during Asian dust events. The findings were still inconclusive though. We have shown an increased pulmonary toxicity in diseased animals during a dust storm event. However, the toxicity nature of dust storm particles remains unclear. It is our objective in this study to further investigate the cardiovascular effects of concentrated PM2.5 on spontaneously hypertensive rats during the same dust storm event. Four spontaneously hypertensive rats were implanted with radiotelemetry transmitters at the age of 10 wk. Baseline heart rate, mean blood pressure, and cardiac contractility (measured as QA interval, QAI) data were collected 4 wk before. Exposure group received concentrated ambient particles inhalation for 6 h during a dust storm event, while the control group received room air inhalation at the same time. Self-control data were collected 4 wk after the event during the same clock hours while there was no dust storm. Gravimetric analysis showed a particle mass concentration of 315.55 μg/m3 during the 6 h of exposure. A linear mixed-effects model revealed sigmoid increases in heart rate (to a maximum of 93.8 ± 18.8 bpm) and mean blood pressure (to a maximum of 14.8 ± 5.4 mm Hg), and a sigmoid decrease of QAI (to a maximum of − 3.5 ± 1.5 ms) during the exposure after an initial incubation period. We conclude that concentrated dust storm particles, which are different from products of automobile combustion process, may cause adverse cardiovascular effects on diseased animals.
Characterization of the Major Secreted Zinc Metalloprotease- Dependent Glycerophospholipid:Cholesterol Acyltransferase, PlaC, of Legionella pneumophila

ABSTRACT Legionella pneumophila, an intracellular pathogen causing a severe pneumonia, possesses distinct lipolytic activities which have not been completely assigned to specific enzymes so far. We cloned and characterized a gene, plaC, encoding a protein with high homology to PlaA, the major secreted lysophospholipase A of L. pneumophila and to other hydrolytic enzymes belonging to the GDSL family. Here we show that L. pneumophila plaC mutants possessed reduced phospholipase A and lysophospholipase A activities and lacked glycerophospholipid:cholesterol acyltransferase activity in their culture supernatants. The mutants' reduced phospholipase A and acyltransferase activities were complemented by reintroduction of an intact copy of plaC. Additionally, plaC conferred increased lysophospholipase A and glycerophospholipid:cholesterol acytransferase activities to recombinant Escherichia coli. Furthermore, PlaC was shown to be another candidate exported by the L. pneumophila type II secretion system and was activated by a factor present in the bacterial culture supernatant dependent on the zinc metalloprotease. Finally, the role of plaC in intracellular infection of Acanthamoeba castellanii and U937 macrophages with L. pneumophila was assessed, and plaC was found to be dispensable. Thus, L. pneumophila possesses another secreted lipolytic enzyme, a protein with acyltransferase, phospholipase A, and lysophospholipase A activities. This enzyme is distinguished from the previously characterized phospholipases A and lysophospholipases A by its capacity not only to cleave fatty acids from lipids but to transfer them to cholesterol. Cholesterol is an important compound of eukaryotic membranes, and an acyltransferase might be a tool for host cell modification to fit the needs of the bacterium.
Salmonella Serovars and Antimicrobial Resistance Profiles in Beef Cattle, Slaughterhouse Personnel and Slaughterhouse Environment in Ethiopia

The present study was undertaken to determine the occurrence, distribution and antimicrobial resistance profiles of Salmonella serovars in slaughter beef cattle, slaughterhouse environment and personnel engaged in flaying and evisceration during slaughtering process. A total of 800 samples (each sample type, n = 100) consisting of swabs from hides, slaughterhouse personnel hands at flaying and evisceration, rumen and caecal contents, mesenteric lymph nodes, carcasses and holding pens were collected. Of the total 100 beef cattle examined, 14% were Salmonella positive in caecal content and/or mesenteric lymph nodes. Of the various samples analysed, Salmonella was detected in 31% of hides, 19% of rumen contents, 8% of mesenteric lymph nodes, 6% of caecal contents, 2% of carcass swabs, 9% of palm swabs taken from the hands of personnel in the slaughterhouse during flaying (7%) and evisceration (2%), and in 12% of holding pen swabs. The Salmonella isolates (n = 87) belonged to eight different serovars of which S. Anatum (n = 54) and S. Newport (19) were the major serovars and both serovars were detected in all sample sources except in carcass swabs. Eighteen of the 87 (20.7%) Salmonella serovars consisting of Newport (n = 14), Anatum (n = 3) and Eastbourne (n = 1) were resistant to one or more antimicrobials. Among the antimicrobial resistant Salmonella serovars, S. Newport was multidrug resistant (15.6%) and exhibited resistance to streptomycin, sulphisoxazole and tetracycline.
Alterations of p16 and Prognosis in Biliary Tract Cancers from a Population-Based Study in China

Purpose: Biliary tract cancer is an uncommon malignancy with a poor survival rate. We evaluated p16 gene alteration as a prognostic marker for this disease. Experimental Design: We studied p16 gene alterations by sequencing, methylation, and loss of heterozygosity of chromosome 9p in 118 biliary tract carcinomas, including 68 gallbladder cancers, 33 extrahepatic bile duct cancers, and 17 ampullary cancers. Survival was evaluated in 57 patients with gallbladder carcinomas, 27 with bile duct carcinomas, and 16 with ampullary carcinomas with and without somatic p16 alterations detected by two different methods. Results: p16 gene alterations including silent mutations were present in 61.8% gallbladder cancers, 54.5% bile duct cancers, and 70.6% ampullary cancers. p16 gene nonsilent mutations, p16 methylation, and loss of chromosome 9p21-22 that targets p14, p15, and p16 genes were present in 13 of 53 (24.5%), 8 of 54 (14.8%), and 32 of 44 (72.7%) gallbladder tumors; 5 of 25 (20.0%), 5 of 31 (16.1%), and 12 of 21 (57.1%) bile duct tumors; and 3 of 13 (23.1%), 6 of 15 (40.0%), and 8 of 16 (50.0%) ampullary tumors, respectively. The mean survival of patients with gallbladder cancers without p16 alterations was 21.5 ± 14.8 months compared with 12.1 ± 11.4 months for patients with p16 alterations (P = 0.02). Conclusions: Alteration of p16 gene alone or in combination with alterations of other tumor suppressor genes on chromosome 9p is a prognostic indicator in gallbladder carcinoma, with more favorable survival rates associated with carcinomas lacking p16 gene alterations.
Les Cétiosaures (Dinosaura, sauropoda) et les sauropodes du Jurassique moyen : revision systématique, nouvelles découvertes et implications phylogénétiques

Les Cetiosauridae et plus generalement les sauropodes du Jurassique moyen demeurent l’un des groupes les plus enigmatiques de ces dinosaures herbivores. La revision des sauropodes du Jurassique moyen (Bothriospondylus madagascariensis et Lapparentosaurus madagascariensis de Madagascar, ? Cetiosaurus mogrebiensis du Maroc, Chebsaurus algeriensis d’Algerie et un nouveau specimen du Calvados, France) constitue une source considerable d’informations pour mieux comprendre l'anatomie et l'evolution des sauropodes de cette epoque. Les analyses phylogenetiques suggerent que les Cetiosauridae sont paraphyletiques et associes a une importante multifurcation. Cette irresolution s’expliquerait par de nombreuses donnees manquantes mais aussi par l’incongruence des caracteres qui concerne ces sauropodes. Cette incongruence pourrait etre le resultat d’une radiation evolutive qui aurait suivie l’extinction due a la crise du Pliensbachien-Toarcien et/ou qui serait le reflet du demantelement de la Pangee.
Antihypertensive use, prescription patterns, and cost of medications in a Teaching Hospital in Lagos, Nigeria.

INTRODUCTION Hypertension has been reported as the strongest modifiable risk factor for cardiovascular morbidity and mortality. AIMS The aim of the study was to identify the most prescribed antihypertensive drugs, its patterns, comorbidities, cost of medications, and laboratory investigations. SETTINGS AND DESIGN This study was a cross-sectional, descriptive study of hypertensive patients conducted at the Lagos State University Teaching Hospital, Ikeja. SUBJECTS AND METHODS A total of 200 case notes were retrieved from the medical records unit over a period of 8 weeks. Information on antihypertensive prescriptions and comorbidities was retrieved. The average cost of medications and laboratory investigations was calculated. Statistical Analysis Tool Used: SPSS software version 16. RESULTS The mean age of the patients was 58.44 ± 12.65 years. Of the 200 patients, 5 (2.5%) were on monotherapy and 195 (97.5%) were on combination therapy. One hundred and twenty (60%) patients had comorbidities which included congestive heart failure 55 (27.5%), diabetes mellitus 22 (11%), hyperlipidemia 15 (7.5%), and cardiovascular disease 13 (6.5%). The various classes of antihypertensive drugs prescribed were diuretics 128 (64.0%), beta-blockers 126 (63.0%), calcium channel blockers 106 (53.0%), angiotensin-converting enzymes inhibitors 103 (51.5%), angiotensin receptor blockers 33 (16.5%), alpha blockers 9 (4.5%), and fixed drug combinations 2 (1.0%). The average cost per month of the antihypertensive medications was ₦ 2045 (US$10.2). CONCLUSIONS Antihypertensive prescription pattern was in accordance with the seventh report of Joint National Committee on Prevention, Detection, Evaluation, and Treatment of high blood pressure. Community-based insurance scheme should be encouraged and effective implementation of integrated noncommunicable diseases screening into the primary health care services would be helpful.
Deletion-Robust Submodular Maximization at Scale

Can we efficiently extract useful information from a large user-generated dataset while protecting the privacy of the users and/or ensuring fairness in representation. We cast this problem as an instance of a deletion-robust submodular maximization where part of the data may be deleted due to privacy concerns or fairness criteria. We propose the first memory-efficient centralized, streaming, and distributed methods with constant-factor approximation guarantees against any number of adversarial deletions. We extensively evaluate the performance of our algorithms against prior state-of-the-art on real-world applications, including (i) Uber-pick up locations with location privacy constraints; (ii) feature selection with fairness constraints for income prediction and crime rate prediction; and (iii) robust to deletion summarization of census data, consisting of 2,458,285 feature vectors.
Lack of Association of OPRM1 and ABCB1 Single‐Nucleotide Polymorphisms to Oxycodone Response in Postoperative Pain

Purpose: The aim of the study was to search for an association between the single‐nucleotide polymorphisms A118G in OPRM1 and C3435T and G2677T/A in ABCB1 and the analgesic effect of intravenous oxycodone in postoperative pain. Methods: There were 268 patients with postoperative pain after, primarily, thyroidectomy. At given times during the first 24 hours postoperatively, their pain was rated at rest and during activity according to a numeric rating scale (0 = no pain, 10 = worst possible pain) and calculated as pain time area under the curve0–24 hours. A negative answer in a final questionnaire and/or the use of rescue medication categorized a patient as a nonresponder. Results: For OPRM1, there was no difference found between the wild type and the variant allele in the percentages of nonresponders (118AA = 16.4% vs 118AG/118GG = 17.0%, P = 1.0) or in the pain ratings. For ABCB1, no difference was found between the wild type and the variant alleles for single‐nucleotide polymorphism tested as percentages of nonresponders (3435CC = 17.5% vs 3435CT/3435TT = 15.8%, P = .85; 2677GG = 17.8% vs 2677GT/2677TT = 15.8%, P = .74) or pain ratings. Conclusion: No association was found between the tested single‐nucleotide polymorphisms in OPRM1 and ABCB1 and changes in the analgesic effect of oxycodone.
Health care use and patients' perceptions on quality of care in systemic sclerosis.

OBJECTIVES To assess health care utilisation in Dutch patients with systemic sclerosis (SSc) and its associated factors. To evaluate patients' perspectives on quality of care and its association with health care use. METHODS In a cross-sectional design, 198 Dutch patients with SSc completed an anonymous survey concerning health care utilisation, quality of care (CQ Index), and quality of life (SF-36). RESULTS In the last 12 months, 95% of the patients had contact with at least one medical specialist and two-thirds contacted at least one health professional (HP). The median numbers of visits to medical specialists and HPs were 7 and 7.5, respectively. Having a partner and reduced physical health status (SF-36 role-physical) were significantly associated with more visits to medical specialists and HPs. The median numbers of disciplines contacted since the onset of SSc and in the last 12 months were 8 and 4, respectively. Patients with less fatigue (SF-36 vitality) and more pain (SF-36 bodily pain) contacted more disciplines. A higher number of disciplines involved in the care was significantly associated with less satisfaction with the coordination of care (r=-0.14, p=0.03). CONCLUSIONS Health care utilisation in Dutch patients with SSc is substantial, as is reflected in the high number of visits and the number of disciplines. Patients' rating of care coordination was lower if more disciplines were involved in their care.
Expression and Immunohistochemical Detection of Leptin‐Like Peptide in the Gastrointestinal Tract of the South American Sea Lion (Otaria flavescens) and the Bottlenose Dolphin (Tursiops truncatus)

This study provides an immunohistochemical approach to the expression of leptin in the gastrointestinal tract of the monogastric South American sea lion (Otaria flavescens), and the poligastric bottlenose dolphin (Tursiops truncatus). The specific organization of the gastrointestinal tract is examined in relation to the neuroendocrine regulation of the gut exerted by leptin. In the South American sea lion some leptin‐like‐immunoreactive (ir) cells, and endocrine type cells, were found in the pit of gastric mucosal folds and in the epithelium of duodenum as well as numerous neurons were detected in the submucosal and myenteric plexuses of the stomach. In the bottlenose dolphin, many leptin‐like‐ir cells, and exocrine type cells, were identified in the mucosal layer of the main stomach as well as several neurons and nervous fibers were detected in nervous plexuses of main stomach, pyloric stomach, proximal, and middle intestine. Our data suggest that the distribution of leptin‐like peptides is similar in the two species, notwithstanding the different anatomical organization of the gastrointestinal apparatus of South American sea lion and bottlenose dolphin. These findings “suggest” the presence of a basal plan in the regulation of food intake, body weight, energy balance and of the gastrointestinal functions in general also in marine mammals with different and specific feeding habits. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.