The Biomphalaria glabrata DNA methylation machinery displays spatial tissue expression, is differentially active in distinct snail populations and is modulated by interactions with Schistosoma mansoni

BBSRC Grant (BB/K005448/1)Background The debilitating human disease schistosomiasis is caused by infection with schistosome parasites that maintain a complex lifecycle alternating between definitive (human) and intermediate (snail) hosts. While much is known about how the definitive host responds to schistosome infection, there is comparably less information available describing the snail?s response to infection. Methodology/Principle findings Here, using information recently revealed by sequencing of the Biomphalaria glabrata intermediate host genome, we provide evidence that the predicted core snail DNA methylation machinery components are associated with both intra-species reproduction processes and inter-species interactions. Firstly, methyl-CpG binding domain protein (Bgmbd2/3) and DNA methyltransferase 1 (Bgdnmt1) genes are transcriptionally enriched in gonadal compared to somatic tissues with 5-azacytidine (5-AzaC) treatment significantly inhibiting oviposition. Secondly, elevated levels of 5-methyl cytosine (5mC), DNA methyltransferase activity and 5mC binding in pigmented hybrid- compared to inbred (NMRI)- B. glabrata populations indicate a role for the snail?s DNA methylation machinery in maintaining hybrid vigour or heterosis. Thirdly, locus-specific detection of 5mC by bisulfite (BS)-PCR revealed 5mC within an exonic region of a housekeeping protein-coding gene (Bg14-3-3), supporting previous in silico predictions and whole genome BS-Seq analysis of this species? genome. Finally, we provide preliminary evidence for parasite-mediated host epigenetic reprogramming in the schistosome/snail system, as demonstrated by the increase in Bgdnmt1 and Bgmbd2/3 transcript abundance following Bge (B. glabrata embryonic cell line) exposure to parasite larval transformation products (LTP). Conclusions/Significance The presence of a functional DNA methylation machinery in B. glabrata as well as the modulation of these gene products in response to schistosome products, suggests a vital role for DNA methylation during snail development/oviposition and parasite interactions. Further deciphering the role of this epigenetic process during Biomphalaria/Schistosoma co-evolutionary biology may reveal key factors associated with disease transmission and, moreover, enable the discovery of novel lifecycle intervention strategiespublishersversionPeer reviewe

Improved Measurement of Electron Antineutrino Disappearance at Daya Bay

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Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Noise control for a dipole sound source using micro-perforated panel housing integrated with a Herschel–Quincke tube

202211 bckwAccepted ManuscriptRGCOthersThe Hong Kong Polytechnic UniversityPublishe

Relationship between UGT1A1*6/*28 polymorphisms and severe toxicities in Chinese patients with pancreatic or biliary tract cancer treated with irinotecan-containing regimens

Chen Yang,1 Ying Liu,1 Wen-qi Xi,1 Chen-fei Zhou,2 Jin-ling Jiang,1 Tao Ma,1 Zheng-bao Ye,1 Jun Zhang,1 Zheng-gang Zhu1,2 1Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China Purpose: The aim of this retrospective study was to investigate the relationship between UGT1A1 polymorphisms and toxicities in Chinese patients with pancreatic or biliary tract cancer receiving irinotecan-containing regimens as the second- or third-line chemotherapy.Patients and methods: A total of 36 patients with unresectable pancreatic cancer and 12 patients with unresectable biliary tract cancer were included. Approximately 33 patients were treated with FOLFIRI regimen, a chemotherapy regimen, where FOL stands for folinic acid, F for fluorouracil, and IRI for irinotecan (irinotecan 180 mg/m2 at day 1, CF 200 mg/m2 at day 1–2, 5-FU 400 mg/m2 at day 1–2, followed by continuous infusion of 5-FU 600 mg/m2 for 22 hours at day 1–2, every 2 weeks). The other 15 patients were treated with irinotecan monotherapy (180 mg/m2, every 2 weeks). UGT1A1*6/*28 polymorphisms were detected by direct sequencing.Results: The frequencies of GG, GA, AA genotypes for UGT1A1*6 were 70.8% (n=34), 25.0% (n=12), and 4.2% (n=2), respectively. And those of TA6/TA6, TA6/TA7, TA7/TA7 for UGT1A1*28 were 79.2% (n=38), 18.8% (n=9), and 2.0% (n=1), respectively. A total of 22 patients (45.8%) had grade III–IV neutropenia, and six patients (12.5%) experienced grade III–IV diarrhea. The incidence of grade III–IV neutropenia in patients with UGT1A1*6 GA or AA genotype was 71.4%, which was significantly higher than that with GG genotype (35.3%, P=0.022). No relationship was found between grade III–IV neutropenia and UGT1A1*28 polymorphism. The statistical analysis between grade III–IV diarrhea and UGT1A1*6/*28 polymorphisms was not conducted in view of the limited number of patients.Conclusion: In Chinese patients with pancreatic or biliary tract cancer administered irinotecan-containing regimens, those with UGT1A1*6 variant may have a high risk of severe neutropenia. Keywords: UGT1A1 polymorphism, irinotecan, pancreatic cancer, biliary tract cancer, neutropenia, diarrhe

Target detection of hyperspectral image based on spectral saliency

Target detection of hyperspectral image (HSI) is a research hotspot in the field of remote sensing. It is of particular importance in many domains, especially in military application. Unsupervised target detection is usually more difficult because there is no prior information about target. Traditional algorithms exploit spectral information, only. This study introduces the idea of saliency detection from the visual technique into HSI processing domain and proposes a novel approach named spectral saliency target detection (SSD). It establishes a novel salient model, which utilises both spatial saliency and spectral saliency. In the framework of SSD, it combines the model with spectral matching algorithm to make it perform well even in situations where the target is concealed and small. A HSI set comprised of eight different scenes with complex background is setup to evaluate the performance of the proposed algorithm. The final visible detection results demonstrate that the SSD algorithm outperforms the others. The receiver operation characteristic (ROC) curve and area under the ROC curve are applied to evaluate the results. The proposed algorithm shows superior and stable performance

Hyperspectral image classification based on joint spectrumof spatial space and spectral space

This paper presents a novel feature extraction model that incorporates local histogram in spatial space and pixel spectrum in spectral space, with the goal of hyperspectral image classification. We named this joint spectrum as 3D spectrum. Moreover, as a pre-processing step, an iterative procedure, which exploits spectral information in such a way that it considers corrupted bands existing in the data cube, is applied to original hyperspectral image. Further, Affine transform is applied to the bands chosen by the aforementioned procedure. The final feature is extracted by affine transform and 3D spectrum model, and as an input of widely used classifier of Support Vector Machine. As a post-processing step, multiple iterative results are fused in the level of probability. Our experimental results indicate that the proposed methodology leads to state-of-the-art classification results when combined with probabilistic classifiers for several widely used hyperspectral data sets, even when very only limited training samples are available