152 research outputs found

    Tachyon search speeds up retrieval of similar sequences by several orders of magnitude

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    Summary: The usage of current sequence search tools becomes increasingly slower as databases of protein sequences continue to grow exponentially. Tachyon, a new algorithm that identifies closely related protein sequences ~200 times faster than standard BLAST, circumvents this limitation with a reduced database and oligopeptide matching heuristic

    A CRISPR screen identifies a pathway required for paraquat-induced cell death

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    Paraquat, a herbicide linked to Parkinson's disease, generates reactive oxygen species (ROS), which causes cell death. Because the source of paraquat-induced ROS production remains unknown, we conducted a CRISPR-based positive-selection screen to identify metabolic genes essential for paraquat-induced cell death. Our screen uncovered three genes, POR (cytochrome P450 oxidoreductase), ATP7A (copper transporter), and SLC45A4 (sucrose transporter), required for paraquat-induced cell death. Furthermore, our results revealed POR as the source of paraquat-induced ROS production. Thus, our study highlights the use of functional genomic screens for uncovering redox biology

    Stillbirths: recall to action in high-income countries.

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    Variation in stillbirth rates across high-income countries and large equity gaps within high-income countries persist. If all high-income countries achieved stillbirth rates equal to the best performing countries, 19,439 late gestation (28 weeks or more) stillbirths could have been avoided in 2015. The proportion of unexplained stillbirths is high and can be addressed through improvements in data collection, investigation, and classification, and with a better understanding of causal pathways. Substandard care contributes to 20-30% of all stillbirths and the contribution is even higher for late gestation intrapartum stillbirths. National perinatal mortality audit programmes need to be implemented in all high-income countries. The need to reduce stigma and fatalism related to stillbirth and to improve bereavement care are also clear, persisting priorities for action. In high-income countries, a woman living under adverse socioeconomic circumstances has twice the risk of having a stillborn child when compared to her more advantaged counterparts. Programmes at community and country level need to improve health in disadvantaged families to address these inequities.Mater Research Institute – The University of Queensland provided infrastructure and funding for the research team to enable this work to be undertaken. The Canadian Research Chair in Psychosocial Family Health provided funding for revision of the translation of the French web-based survey of care providers.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/S0140-6736(15)01020-

    CT colonography with limited bowel preparation for the detection of colorectal neoplasia in an FOBT positive screening population

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    Item does not contain fulltextPURPOSE: Aim was to evaluate the accuracy of computed tomography colonography (CTC) for detection of colorectal neoplasia in a Fecal Occult Blood Test (FOBT) positive screening population. METHODS: In three different institutions, consecutive FOBT positives underwent CTC after laxative free iodine tagging bowel preparation followed by colonoscopy with segmental unblinding. Each CTC was read by two experienced observers. For CTC and for colonoscopy the per-polyp sensitivity and per-patient sensitivity and specificity were calculated for detection of carcinomas, advanced adenomas, and adenomas. RESULTS: In total 22 of 302 included FOBT positive participants had a carcinoma (7%) and 137 had an adenoma or carcinoma >/=10 mm (45%). CTC sensitivity for carcinoma was 95% with one rectal carcinoma as false negative finding. CTC sensitivity for advanced adenomas was 92% (95% CI: 88-96) vs. 96% (95% CI: 93-99) for colonoscopy (P = 0.26). For adenomas and carcinomas >/=10 mm the CTC per-polyp sensitivity was 93% (95% CI: 89-97) vs. 97% (95% CI: 94-99) for colonoscopy (P = 0.17). The per-patient sensitivity for the detection of adenomas and carcinomas >/=10 mm was 95% (95% CI: 91-99) for CTC vs. 99% (95% CI: 98-100) for colonoscopy (P = 0.07), while the per-patient specificity was 90% (95% CI: 86-95) and 96% (95% CI: 94-99), respectively (P < 0.001). CONCLUSION: CTC with limited bowel preparation performed in an FOBT positive screening population has high diagnostic accuracy for the detection of adenomas and carcinomas and a sensitivity similar to that of colonoscopy for relevant lesions.1 december 201

    Rare Exonic Minisatellite Alleles in MUC2 Influence Susceptibility to Gastric Carcinoma

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    BACKGROUND: Mucins are the major components of mucus and their genes share a common, centrally-located region of sequence that encodes tandem repeats. Mucins are well known genes with respect to their specific expression levels; however, their genomic levels are unclear because of complex genomic properties. In this study, we identified eight novel minisatellites from the entire MUC2 region and investigated how allelic variation in these minisatellites may affect susceptibility to gastrointestinal cancer. METHODOLOGY/PRINCIPLE FINDINGS: We analyzed genomic DNA from the blood of normal healthy individuals and multi-generational family groups. Six of the eight minisatellites exhibited polymorphism and were transmitted meiotically in seven families, following Mendelian inheritance. Furthermore, a case-control study was performed that compared genomic DNA from 457 cancer-free controls with DNA from individuals with gastric (455), colon (192) and rectal (271) cancers. A statistically significant association was identified between rare exonic MUC2-MS6 alleles and the occurrence of gastric cancer: odds ratio (OR), 2.56; 95% confidence interval (CI), 1.31-5.04; and p = 0.0047. We focused on an association between rare alleles and gastric cancer. Rare alleles were divided into short (40, 43 and 44) and long (47, 50 and 54), according to their TR (tandem repeats) lengths. Interestingly, short rare alleles were associated with gastric cancer (OR = 5.6, 95% CI: 1.93-16.42; p = 0.00036). Moreover, hypervariable MUC2 minisatellites were analyzed in matched blood and cancer tissue from 28 patients with gastric cancer and in 4 cases of MUC2-MS2, minisatellites were found to have undergone rearrangement. CONCLUSIONS/SIGNIFICANCE: Our observations suggest that the short rare MUC2-MS6 alleles could function as identifiers for risk of gastric cancer. Additionally, we suggest that minisatellite instability might be associated with MUC2 function in cancer cells

    KMT-2021-BLG-1547Lb: Giant microlensing planet detected through a signal deformed by source binarity

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    We investigate the previous microlensing data collected by the KMTNet survey in search of anomalous events for which no precise interpretations of the anomalies have been suggested. From this investigation, we find that the anomaly in the lensing light curve of the event KMT-2021-BLG-1547 is approximately described by a binary-lens (2L1S) model with a lens possessing a giant planet, but the model leaves unexplained residuals. We investigate the origin of the residuals by testing more sophisticated models that include either an extra lens component (3L1S model) or an extra source star (2L2S model) to the 2L1S configuration of the lens system. From these analyses, we find that the residuals from the 2L1S model originate from the existence of a faint companion to the source. The 2L2S solution substantially reduces the residuals and improves the model fit by Δχ2=67.1\Delta\chi^2=67.1 with respect to the 2L1S solution. The 3L1S solution also improves the fit, but its fit is worse than that of the 2L2S solution by Δχ2=24.7\Delta\chi^2=24.7. According to the 2L2S solution, the lens of the event is a planetary system with planet and host masses (Mp/MJ,Mh/M)=(1.470.77+0.64,0.720.38+0.32)(M_{\rm p}/M_{\rm J}, M_{\rm h}/M_\odot)=\left( 1.47^{+0.64}_{-0.77}, 0.72^{+0.32}_{-0.38}\right) lying at a distance \D_{\rm L} =5.07^{+0.98}_{-1.50}~kpc, and the source is a binary composed of a subgiant primary of a late G or an early K spectral type and a main-sequence companion of a K spectral type. The event demonstrates the need of sophisticated modeling for unexplained anomalies for the construction of a complete microlensing planet sample.Comment: 9 pages, 4 tables, 7 figure
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