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https://www.readbyqxmd.com/read/29228509/c-learning-a-new-classification-framework-to-estimate-optimal-dynamic-treatment-regimes
#1
Baqun Zhang, Min Zhang
A dynamic treatment regime is a sequence of decision rules, each corresponding to a decision point, that determine that next treatment based on each individual's own available characteristics and treatment history up to that point. We show that identifying the optimal dynamic treatment regime can be recast as a sequential optimization problem and propose a direct sequential optimization method to estimate the optimal treatment regimes. In particular, at each decision point, the optimization is equivalent to sequentially minimizing a weighted expected misclassification error...
December 11, 2017: Biometrics
https://www.readbyqxmd.com/read/29228465/ligand-induced-dimerization-of-a-truncated-parallel-myc-g-quadruplex
#2
Andrea Funke, Beatrice Karg, Jonathan Dickerhoff, Darko Balke, Sabine Müller, Klaus Weisz
Binding of an indoloquinoline derivative with an aminoalkyl side chain to a truncated sequence from the MYC promoter region was studied through isothermal titration calorimetry. The targeted MYC3 sequence lacks 3'-flanking nucleotides and forms a monomeric parallel quadruplex (G4) with a blunt-ended 3'-outer tetrad under the solution conditions employed. Analysis of ITC isotherms reveals multiple binding equilibria with the initial formation of a 1:2 ligand quadruplex complex. Evaluation of electrophoretic mobilities as well as NMR spectral data confirm a ligand-induced dimerization of MYC3 quadruplexes with the ligand sandwiched between the two 3'-outer tetrads...
December 11, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29228419/expression-and-clinical-significance-of-long-non-coding-rna-ghet1-in-pancreatic-cancer
#3
H-Y Zhou, H Zhu, X-Y Wu, X-D Chen, Z-G Qiao, X Ling, X-M Yao, J-H Tang
OBJECTIVE: To investigate the expression level and biological function of long non-coding RNA gastric carcinoma high expressed transcript 1 (lncRNA-GHET1) in pancreatic ductal adenocarcinoma (pancreatic cancer for short), to analyze the correlation between the expression of GHET1 and clinicopathological features and to explore the role and clinical significance of GHET1 in the development and progression of pancreatic cancer. PATIENTS AND METHODS: The relative expression of GHET1 in 5 human pancreatic cancer cell lines was detected by quantitative Real-time polymerase chain reaction (qRT-PCR)...
November 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29228394/the-psychiatric-risk-gene-transcription-factor-4-tcf4-regulates-neurodevelopmental-pathways-associated-with-schizophrenia-autism-and-intellectual-disability
#4
Marc P Forrest, Matthew J Hill, David H Kavanagh, Katherine E Tansey, Adrian J Waite, Derek J Blake
Background: Common genetic variants in and around the gene encoding transcription factor 4 (TCF4) are associated with an increased risk of schizophrenia. Conversely, rare damaging TCF4 mutations cause Pitt-Hopkins syndrome and have also been found in individuals with intellectual disability (ID) and autism spectrum disorder (ASD). Methods: Chromatin immunoprecipitation and next generation sequencing were used to identify the genomic targets of TCF4. These data were integrated with expression, epigenetic and disease gene sets using a range of computational tools...
December 8, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/29228389/high-resolution-melting-analysis-a-novel-approach-for-clade-differentiation-in-pythium-insidiosum-and-pythiosis
#5
Navaporn Worasilchai, Nitipong Permpalung, Ariya Chindamporn
Pythium insidiosum causes life-threatening human pythiosis. Based on phylogenetic analysis using internal transcribed spacer (ITS) region, mitochondrial cytochrome C oxidase II (COX2) gene, intergenic spacer (IGS) region and exo-1,3-β-glucanase gene (exo1), P. insidiosum is classified into clade ATH, BTH, and CTH related to geographic distribution. At present, polymerase chain reaction in any of these specific regions with DNA sequencing is the only technique to provide clade diagnosis. In this study, P. insidiosum-specific primers targeting COX2 gene were designed and used in real-time quantitative polymerase chain reaction (qPCR) with subsequent high-resolution melting (HRM) to provide rapid identification as well as clade classification for P...
December 8, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/29228377/genotyping-of-pneumocystis-jirovecii-in-colonized-patients-with-various-pulmonary-diseases
#6
Magdalena Sokulska, Marta Kicia, Maria Wesolowska, Pawel Piesiak, Aneta Kowal, Maria Luísa Lobo, Zaneta Kopacz, Andrzej B Hendrich, Olga Matos
Pneumocystis jirovecii is an opportunistic fungus causing Pneumocystis pneumonia primarily in immunosuppressed patients. However, immunocompetent individuals may become colonized and, as asymptomatic carriers, serve as reservoirs of the pathogen. Moreover, these asymptomatic carriers are at higher risk of developing pneumonia if favorable conditions occur. This study aimed to determine the prevalence of P. jirovecii in patients with various pulmonary diseases and to characterize the genetic diversity of organisms circulating in the studied population...
December 8, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/29228337/triplex-forming-oligonucleotides-a-third-strand-for-dna-nanotechnology
#7
Arun Richard Chandrasekaran, David A Rusling
DNA self-assembly has proved to be a useful bottom-up strategy for the construction of user-defined nanoscale objects, lattices and devices. The design of these structures has largely relied on exploiting simple base pairing rules and the formation of double-helical domains as secondary structural elements. However, other helical forms involving specific non-canonical base-base interactions have introduced a novel paradigm into the process of engineering with DNA. The most notable of these is a three-stranded complex generated by the binding of a third strand within the duplex major groove, generating a triple-helical ('triplex') structure...
December 8, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29228294/accurate-mapping-of-trna-reads
#8
Anne Hoffmann, Jörg Fallmann, Mario Mörl, Peter F Stadler, Fabian Amman
Motivation: Many repetitive DNA elements are transcribed at appreciable expression levels. Mapping the corresponding RNA sequencing reads back to a reference genome is notoriously difficult and error-prone task, however. This is in particular true if chemical modifications introduce systematic mismatches, while at the same time the genomic loci are only approximately identical, as in the case of tRNAs. Results: We therefore developed a dedicated mapping strategy to handle RNA-seq reads that map to tRNAs relying on a modified target genome in which known tRNA loci are masked and instead intronless tRNA precursor sequences are appended as artificial "chromosomes"...
December 8, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29228253/rare-potentially-pathogenic-variants-in-znf469-are-not-enriched-in-keratoconus-in-a-large-australian-cohort-of-european-descent
#9
Sionne E M Lucas, Tiger Zhou, Nicholas B Blackburn, Richard A Mills, Jonathan Ellis, Paul Leo, Emmanuelle Souzeau, Bronwyn Ridge, Jac C Charlesworth, Matthew A Brown, Richard Lindsay, Jamie E Craig, Kathryn P Burdon
Purpose: The Zinc Finger Protein 469 (ZNF469) gene has been proposed as a candidate gene for keratoconus due to the association of an upstream polymorphism (rs9938149) with the disease in two independent studies, and the role of the gene in the autosomal recessive disease Brittle Cornea Syndrome. Coding variants in ZNF469 have been assessed for association with keratoconus in several small studies, with conflicting results. We assessed rare, potentially pathogenic variants in ZNF469 for enrichment in keratoconus patients in a cohort larger than all previous studies combined...
December 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29228219/why-phenotype-robustness-promotes-phenotype-evolvability
#10
Xinzhu Wei, Jianzhi Zhang
Robustness and evolvability are fundamental characteristics of life whose relationship has intrigued generations of biologists. Studies of several genotype-phenotype maps (GPMs) such as the map between short DNA sequences and their bindings to transcription factors showed that phenotype robustness promotes phenotype evolvability, but the underlying reason is unclear. Here we show mathematically that the expected phenotype evolvability is a monotonically increasing function of the expected phenotype robustness in random GPMs...
December 8, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/29228193/deepsf-deep-convolutional-neural-network-for-mapping-protein-sequences-to-folds
#11
Jie Hou, Badri Adhikari, Jianlin Cheng
Motivation: Protein fold recognition is an important problem in structural bioinformatics. Almost all traditional fold recognition methods use sequence (homology) comparison to indirectly predict the fold of a target protein based on the fold of a template protein with known structure, which cannot explain the relationship between sequence and fold. Only a few methods had been developed to classify protein sequences into a small number of folds due to methodological limitations, which are not generally useful in practice...
December 8, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29228055/transcriptional-profiling-of-sugarcane-leaves-and-roots-under-progressive-osmotic-stress-reveals-a-regulated-coordination-of-gene-expression-in-a-spatiotemporal-manner
#12
Alejandro Pereira-Santana, Edyciel J Alvarado-Robledo, Jesus A Zamora-Briseño, Jorge T Ayala-Sumuano, Victor M Gonzalez-Mendoza, Francisco Espadas-Gil, Luis D Alcaraz, Enrique Castaño, Miguel A Keb-Llanes, Felipe Sanchez-Teyer, Luis Carlos Rodriguez-Zapata
Sugarcane is one of the most important crops worldwide and is a key plant for the global production of sucrose. Sugarcane cultivation is severely affected by drought stress and it is considered as the major limiting factor for their productivity. In recent years, this plant has been subjected to intensive research focused on improving its resilience against water scarcity; particularly the molecular mechanisms in response to drought stress have become an underlying issue for its improvement. To better understand water stress and the molecular mechanisms we performed a de novo transcriptomic assembly of sugarcane (var...
2017: PloS One
https://www.readbyqxmd.com/read/29228016/prevalence-and-molecular-profiling-of-epstein-barr-virus-ebv-among-healthy-blood-donors-from-different-nationalities-in-qatar
#13
Maria K Smatti, Hadi M Yassine, Raed AbuOdeh, Asmaa AlMarawani, Sara A Taleb, Asmaa A Althani, Gheyath K Nasrallah
BACKGROUND: The Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis. EBV is highly prevalent lymphotropic herpesvirus and has been linked to several malignancies. Transmission is generally by oral secretions, but can be through blood transfusions and organ transplantations. This study aimed to determine the seroprevalence, viremia rates, and circulating genotypes of EBV in healthy blood donors in Qatar. METHODS: Blood samples from 673 blood donors of different nationalities residing in Qatar (mainly Qatar, Egypt, Syria, Jordan, Pakistan, and India) were collected and tested for anti-EBV capsid (VCA; IgG & IgM), nuclear (EBNA; IgG), and early (EA-D; IgG) antigens...
2017: PloS One
https://www.readbyqxmd.com/read/29228005/rna-seq-reveals-transcriptome-changes-in-goats-following-myostatin-gene-knockout
#14
Lamei Wang, Bei Cai, Shiwei Zhou, Haijing Zhu, Lei Qu, Xiaolong Wang, Yulin Chen
Myostatin (MSTN) is a powerful negative regulator of skeletal muscle mass in mammalian species that is primarily expressed in skeletal muscles, and mutations of its encoding gene can result in the double-muscling trait. In this study, the CRISPR/Cas9 technique was used to edit MSTN in Shaanbei Cashmere goats and generate knockout animals. RNA sequencing was used to determine and compare the transcriptome profiles of the muscles from three wild-type (WT) goats, three fibroblast growth factor 5 (FGF5) knockout goats (FGF5+/- group) and three goats with disrupted expression of both the FGF5 and MSTN genes (FM+/- group)...
2017: PloS One
https://www.readbyqxmd.com/read/29227984/microrna-146b-5p-identified-in-porcine-liver-donation-model-is-associated-with-early-allograft-dysfunction-in-human-liver-transplantation
#15
Cheukfai Li, Qiang Zhao, Wei Zhang, Maogen Chen, Weiqiang Ju, Linwei Wu, Ming Han, Yi Ma, Xiaofeng Zhu, Dongping Wang, Zhiyong Guo, Xiaoshun He
BACKGROUND Poor transplant outcome was observed in donation after brain death followed by circulatory death (DBCD), since the donor organs suffered both cytokine storm of brain death and warm ischemia injury. MicroRNAs (miRNAs) have emerged as promising disease biomarkers, so we sought to establish a miRNA signature of porcine DBCD and verify the findings in human liver transplantation. MATERIAL AND METHODS MiRNA expression was determined with miRNA sequencing in 3 types of the porcine model of organ donation, including donation after brain death (DBD) group, donation after circulatory death (DCD) group, and DBCD group...
December 11, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29227978/osterix-decreases-the-chemosensitivity-of-breast-cancer-cells-by-upregulating-galnt14
#16
Jiahui Wu, Xiang Chen, Qianyi Bao, Rui Duan, Yucui Jin, Yifang Shui, Bing Yao, Xiangdong Lu, Yue Wang, Hongyan Cui, Lingyun Li, Hongyan Yuan, Changyan Ma
BACKGROUND/AIMS: Osterix (Osx), a key regulator of osteoblast differentiation and bone formation, has been recently reported to be associated with the progression of breast cancer. However, the precise roles of Osx in breast cancer remain unclear. METHODS: Drug sensitivity of the cancer cells was assessed using an 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Target genes were obtained by high-throughput Illumina sequencing and were confirmed in vitro and in vivo...
November 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29227833/vitamin-a-deficiency-in-mice-alters-host-and-gut-microbial-metabolism-leading-to-altered-energy-homeostasis
#17
Yuan Tian, Robert G Nichols, Jingwei Cai, Andrew D Patterson, Margherita T Cantorna
Vitamin A deficiency (A-) is a worldwide public health problem. To better understand how vitamin A status influences gut microbiota and host metabolism, we systematically analyzed urine, cecum, serum and liver samples from vitamin A sufficient (A+) and deficient (A-) mice using 1H NMR-based metabolomics, quantitative (q)PCR and 16S rRNA gene sequencing coupled with multivariate data analysis. The microbiota in the cecum of A- mice showed compositional as well as functional shifts compared to the microbiota from A+ mice...
November 5, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29227651/total-syntheses-of-scaparvins-b-c-and-d-enabled-by-a-key-c-h-functionalization
#18
Qinda Ye, Pei Qu, Scott A Snyder
The clerodane diterpene family possesses an impressive range of bioactivities and high synthetic challenge due to their unique amalgamation of rings, stereocenters, and oxygenation. Herein, we disclose the first total syntheses of three members, scaparvins B, C, and D, through a route fueled by several chemoselective and carefully orchestrated steps. One such operation is a tailored late-stage C-H functionalization converting a carboxylic acid into a lactone through the oxidation of a tertiary C-H bond under conditions that minimize epoxidation of an alkene...
December 11, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29227519/pediatric-poisoning-by-ingestion-developmental-overview-and-synopsis-of-national-trends
#19
Vincent R Lee, Michael Connolly, Diane P Calello
The American Association of Poison Control Centers' National Poison Data Surveillance System provides real-time toxico-surveillance and epidemiologic trends, and pediatric ingestions comprise most of those reports. The sequences in social and physical developmental milestones from young childhood to adolescence reveal the vulnerability of these age groups to a wide variety of potential poisonous ingestions. Most pediatric ingestions are exploratory. Some common agents associated with pediatric fatalities include disc batteries, laundry detergent "pods," opioid analgesics, acetaminophen, benzodiazepines, and amphetamines...
December 1, 2017: Pediatric Annals
https://www.readbyqxmd.com/read/29227476/the-molecular-landscape-of-pediatric-acute-myeloid-leukemia-reveals-recurrent-structural-alterations-and-age-specific-mutational-interactions
#20
Hamid Bolouri, Jason E Farrar, Timothy Triche, Rhonda E Ries, Emilia L Lim, Todd A Alonzo, Yussanne Ma, Richard Moore, Andrew J Mungall, Marco A Marra, Jinghui Zhang, Xiaotu Ma, Yu Liu, Yanling Liu, Jaime M Guidry Auvil, Tanja M Davidsen, Patee Gesuwan, Leandro C Hermida, Bodour Salhia, Stephen Capone, Giridharan Ramsingh, Christian Michel Zwaan, Sanne Noort, Stephen R Piccolo, E Anders Kolb, Alan S Gamis, Malcolm A Smith, Daniela S Gerhard, Soheil Meshinchi
We present the molecular landscape of pediatric acute myeloid leukemia (AML) and characterize nearly 1,000 participants in Children's Oncology Group (COG) AML trials. The COG-National Cancer Institute (NCI) TARGET AML initiative assessed cases by whole-genome, targeted DNA, mRNA and microRNA sequencing and CpG methylation profiling. Validated DNA variants corresponded to diverse, infrequent mutations, with fewer than 40 genes mutated in >2% of cases. In contrast, somatic structural variants, including new gene fusions and focal deletions of MBNL1, ZEB2 and ELF1, were disproportionately prevalent in young individuals as compared to adults...
December 11, 2017: Nature Medicine
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