Genome evolution driven by host adaptations results in a more virulent and antimicrobial-resistant Streptococcus pneumoniae serotype 14

<p>Abstract</p> <p>Background</p> <p><it>Streptococcus pneumoniae </it>serotype 14 is one of the most common pneumococcal serotypes that cause invasive pneumococcal diseases worldwide. Serotype 14 often expresses resistance to a variety of antimicrobial agents, resulting in difficulties in treatment. To gain insight into the evolution of virulence and antimicrobial resistance traits in <it>S. pneumoniae </it>from the genome level, we sequenced the entire genome of a serotype 14 isolate (CGSP14), and carried out comprehensive comparison with other pneumococcal genomes. Multiple serotype 14 clinical isolates were also genotyped by multilocus sequence typing (MLST).</p> <p>Results</p> <p>Comparative genomic analysis revealed that the CGSP14 acquired a number of new genes by horizontal gene transfer (HGT), most of which were associated with virulence and antimicrobial resistance and clustered in mobile genetic elements. The most remarkable feature is the acquisition of two conjugative transposons and one resistance island encoding eight resistance genes. Results of MLST suggested that the major driving force for the genome evolution is the environmental drug pressure.</p> <p>Conclusion</p> <p>The genome sequence of <it>S. pneumoniae </it>serotype 14 shows a bacterium with rapid adaptations to its lifecycle in human community. These include a versatile genome content, with a wide range of mobile elements, and chromosomal rearrangement; the latter re-balanced the genome after events of HGT.</p

Annual Bands in Vertebrae Validated by Bomb Radiocarbon Assays Provide Estimates of Age and Growth of Whale Sharks

Publisher's version (útgefin grein)Conservation and management strategies for endangered and threatened species require accurate estimates of demographic parameters such as age and growth. The whale shark, Rhincodon typus, is the largest fish in the world and is highly valued in the eco-tourism sector. Despite conservation concerns and advances in our understanding of their life history, basic demographic parameters for growth, longevity and mortality are of questionable accuracy; previous growth studies could not agree whether the vertebral growth bands were formed annually or biannually. Here, we provide the first validation of the annual formation of growth bands within the vertebrae of the whale shark using bomb radiocarbon assays. Ages of up to 50 years were estimated from sectioned vertebrae of sharks collected in Taiwan and Pakistan. There was no cessation of the formation of growth bands in the vertebrae of older sharks and our study provides the oldest observed longevity for this species. Initial estimates of growth (k = 0.01–0.12) and natural mortality rates (M = 0.09–0.14) are consistent with those expected of long-lived sharks, which highlights their sensitivity to fishing pressure and conservation concerns.This work was supported by the Fisheries and Oceans Canada, US National Science Foundation Grant OCE-9985884, and the University of Iceland. Travel funding was provided by the Australian Institute of Marine Science.Peer Reviewe

Proteomic profiling reveals α1-antitrypsin, α1-microglobulin, and clusterin as preeclampsia-related serum proteins in pregnant women

AbstractObjectivePreeclampsia is a major cause of mortality in pregnant women but the underlying mechanism remains unclear to date. In this study, we attempted to identify candidate proteins that might be associated with preeclampsia in pregnant women by means of proteomics tools.Materials and methodsDifferentially expressed proteins in serum samples obtained from pregnant women with severe preeclampsia (n = 8) and control participants (n = 8) were identified using two-dimensional gel electrophoresis (2-DE) followed by peptide mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). Additional serum samples from 50 normal and 41 pregnant women with severe preeclampsia were analyzed by immunoassay for validation.ResultsTen protein spots were found to be upregulated significantly in women with severe preeclampsia. These protein spots had the peptide mass fingerprints matched to α1-antitrypsin, α1-microglobulin, clusterin, and haptoglobin. Immunoassays in an independent series of serum samples showed that serum α1-antitrypsin, α1-microglobulin, and clusterin levels of severe preeclampsia patients (n = 41) were significantly higher than those in the normal participants (n = 50; α1-antitrypsin 295.95 ± 50.94 mg/dL vs. 259.31 ± 33.90 mg/dL, p = 0.02; α1-microglobulin 0.029 ± 0.004 mg/mL vs. 0.020 ± 0.004 mg/mL, p < 0.0001; clusterin 77.6 ± 16.15 μg/dL vs. 67.6 ± 15.87 μg/dL, p < 0.05).ConclusionIdentification of these proteins by proteomics analysis enables further understanding of the pathophysiology of preeclampsia. Further studies are warranted to investigate the role of these biomarkers in prediction of this disease

Design and Synthesis of 2-(3-Benzo[ b ]thienyl)-6,7-methylenedioxyquinolin-4-one Analogues as Potent Antitumor Agents that Inhibit Tubulin Assembly

As part of our continuing investigation of azo-flavonoid derivatives as potential anticancer drug candidates, a series of 2-aryl-6,7-methylenedioxyquinolin-4-one analogs was designed and synthesized. The design combined structural features of 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one (CHM-1), a previously discovered compound with potent in vivo antitumor activity, and 2-arylquinolin-4-ones identified by CoMFA models. The newly synthesized analogs were evaluated for cytotoxicity against seven human cancer cell lines, and structure-activity relationship (SAR) correlations were established. Analogs 1, 37, and 39 showed potent cytotoxicity against different cancer cell lines. Compound 1 demonstrated selective cytotoxicity against Hep 3B (hepatoma) cells. Compound 37 was cytotoxic against HL-60 (leukemia), HCT-116 (colon cancer), Hep 3B (hepatoma), and SK-MEL-5 (melanoma) cells. Compound 39 exhibited broad cytotoxicity against all seven cancer cell lines, with IC50 values between 0.07–0.19 µM. Results from mechanism of action studies revealed that these new quinolone derivatives function as antitubulin agents

Twisting of the DNA-binding surface by a β-strand-bearing proline modulates DNA gyrase activity

DNA gyrase is the only topoisomerase capable of introducing (−) supercoils into relaxed DNA. The C-terminal domain of the gyrase A subunit (GyrA-CTD) and the presence of a gyrase-specific ‘GyrA-box’ motif within this domain are essential for this unique (−) supercoiling activity by allowing gyrase to wrap DNA around itself. Here we report the crystal structure of Xanthomonas campestris GyrA-CTD and provide the first view of a canonical GyrA-box motif. This structure resembles the GyrA-box-disordered Escherichia coli GyrA-CTD, both adopting a non-planar β-pinwheel fold composed of six seemingly spirally arranged β-sheet blades. Interestingly, structural analysis revealed that the non-planar architecture mainly stems from the tilted packing seen between blades 1 and 2, with the packing geometry likely being defined by a conserved and unusual β-strand-bearing proline. Consequently, the GyrA-box-containing blade 1 is placed at an angled spatial position relative to the other DNA-binding blades, and an abrupt bend is introduced into the otherwise flat DNA-binding surface. Mutagenesis studies support that the proline-induced structural twist contributes directly to gyrase’s (−) supercoiling activity. To our knowledge, this is the first demonstration that a β-strand-bearing proline may impact protein function. Potential relevance of β-strand-bearing proline to disease phenylketonuria is also noted

Comparison of single-incision mini-slings (Ajust) and standard transobturator midurethral slings (Align) in the management of female stress urinary incontinence: A 1-year follow-up

AbstractObjectiveTo investigate the effectiveness and safety of a new single-incision mini-sling (SIMS)—Ajust—compared with the standard transobturator midurethral sling (SMUS)—Align—for the treatment of female stress urinary incontinence (SUI).Materials and MethodsA retrospective cohort study was conducted between January 1, 2010 and August 31, 2012. Women with SUI who underwent either SMUS-Align or SIMS-Ajust were recruited. The primary outcomes included operation time, estimated operative blood loss, postoperative pain, and complications. The secondary outcomes included subjective and objective success, defined as an International Consultation on Incontinence Questionnaire (ICIQ) score of 0 or improvement as felt by the patient and a long-term complication, such as dyspareunia and mesh erosion after 6 months and 12 months of follow-up.ResultsA total of 136 patients were enrolled, including 76 receiving SMUS-Align and 60 receiving SIMS-Ajust. Baseline characteristics of the patients in both groups were similar, without a statistically significant difference. Primary outcomes between both groups were similar, except that women treated with SIMS-Ajust had statistically significantly shorter operation time (p = 0.003), less intent to treat (p < 0.05), and earlier postoperative discharge (p = 0.001) than women treated with SMUS-Align. Secondary outcomes were similar without a significant difference between the two groups (93% vs. 88% success rate in each group).ConclusionOur results showed that SIMS-Ajust was not inferior to SMUS-Align with respect to success rate, and might have a slight advantage in early discharge. A long-term follow-up or prospective study is needed to confirm the above findings

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe

An embedding technique to determine ττ backgrounds in proton-proton collision data

An embedding technique is presented to estimate standard model tau tau backgrounds from data with minimal simulation input. In the data, the muons are removed from reconstructed mu mu events and replaced with simulated tau leptons with the same kinematic properties. In this way, a set of hybrid events is obtained that does not rely on simulation except for the decay of the tau leptons. The challenges in describing the underlying event or the production of associated jets in the simulation are avoided. The technique described in this paper was developed for CMS. Its validation and the inherent uncertainties are also discussed. The demonstration of the performance of the technique is based on a sample of proton-proton collisions collected by CMS in 2017 at root s = 13 TeV corresponding to an integrated luminosity of 41.5 fb(-1).Peer reviewe