277,811 results match your criteria Bioinformatics Oxford England[Journal]


Learn to segment single cells with deep distance estimator and deep cell detector.

Comput Biol Med 2019 Apr 8;108:133-141. Epub 2019 Apr 8.

Department of Computational and System Biology, University of Pittsburgh, Pittsburgh, PA, 15260, USA; UPMC-Hillman Cancer Center, University of Pittsburgh, Pittsburgh, 15232, PA, USA. Electronic address:

Single cell segmentation is a critical and challenging step in cell imaging analysis. Traditional processing methods require time and labor to manually fine-tune parameters and lack parameter transferability between different situations. Recently, deep convolutional neural networks (CNN) treat segmentation as a pixel-wise classification problem and have become a general and efficient method for image segmentation. Read More

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http://dx.doi.org/10.1016/j.compbiomed.2019.04.006DOI Listing
April 2019
1 Read

Using a hybrid read-across method to evaluate chemical toxicity based on chemical structure and biological data.

Ecotoxicol Environ Saf 2019 Apr 17;178:178-187. Epub 2019 Apr 17.

Center for Computational and Integrative Biology, Rutgers University, Camden, NJ, USA; Department of Chemistry, Rutgers University, Camden, NJ, USA. Electronic address:

Read-across has become a primary approach to fill data gaps for chemical safety assessments. Chemical similarity based on structure, reactivity, and physic-chemical property information is a traditional approach applied for read-across toxicity studies. However, toxicity mechanisms are usually complicated in a biological system, so only using chemical similarity to perform the read-across for new compounds was not satisfactory for most toxicity endpoints, especially when the chemically similar compounds show dissimilar toxicities. Read More

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http://dx.doi.org/10.1016/j.ecoenv.2019.04.019DOI Listing

Cloning, expression, and purification of the recombinant pro-apoptotic dominant-negative survivin T34A-C84A protein in Escherichia coli.

Protein Expr Purif 2019 Apr 17. Epub 2019 Apr 17.

Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address:

Survivin is a well-known inhibitor-of-apoptosis proteins family member and a promising molecular target for anti-cancer treatment. However, it is widely accepted that survivin is only a "semi-druggable" target and development of survivin-specific small molecule inhibitors has shown to be difficult. In this study, we demonstrated that a histidine-tagged survivin T34A-C84A mutated protein (T34A-C84A-dNSur-His) can be produced using a bacterial recombinant protein expression system [E. Read More

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http://dx.doi.org/10.1016/j.pep.2019.04.003DOI Listing

Fan Therapy for the Treatment of Dyspnea in Adults: a Systematic Review.

J Pain Symptom Manage 2019 Apr 17. Epub 2019 Apr 17.

Department of Palliative, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. Electronic address:

Context: The use of a handheld or electric fan has been proposed as one component of the complex clinical interventions used in the relief of dyspnea; however, there is a lack of consensus regarding its efficacy.

Objectives: We performed a systematic review to determine the effectiveness of fan therapy for the treatment of dyspnea.

Methods: We searched the Medline, EMBASE, Web of Science, Scopus, CINAHL, PsycInfo, and Cochrane Library databases to identify all fan therapy studies published from January 1, 1946 to September 31, 2018. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S08853924193017
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http://dx.doi.org/10.1016/j.jpainsymman.2019.04.011DOI Listing
April 2019
1 Read

The effects of short-term and long-term environmental enrichment on locomotion, mood-like behavior, cognition and hippocampal gene expression.

Behav Brain Res 2019 Apr 17:111917. Epub 2019 Apr 17.

Psychiatric Neuroscience Lab, Discipline of Psychiatry, University of Adelaide, Adelaide, SA, Australia; Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Melbourne, VIC, Australia. Electronic address:

Background: Environmental enrichment (EE) has been shown to modulate behavior and hippocampal gene expression; however, the currently available literature does not explain the differential effects that may relate to the duration of EE.

Aim: To investigate the differential effects of short- and long-term EE on locomotion, anxiety-, depressive- and cognition-like behaviors, and hippocampal gene expression under physiological conditions.

Methods: We assigned either short-term or long-term intervention with respective controls to healthy C57BL/6 mice (n = 12-16/group). Read More

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http://dx.doi.org/10.1016/j.bbr.2019.111917DOI Listing

Targeting non-oncogene ROS pathway by alantolactone in B cell acute lymphoblastic leukemia cells.

Life Sci 2019 Apr 17. Epub 2019 Apr 17.

Department of Hematology, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China; Department of General Practice, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China. Electronic address:

Aims: Alantolactone (ALT) is active component of natural product Inula helenium with a lot of pharmacological effects, including anti-tumor effect. The present work aimed to explore the antitumor effect of ALT in B cell acute lymphoblastic leukemia (B-ALL).

Main Methods: B-ALL cells were treated with various concentrations of ALT, and then trypan blue assay, Annexin V/PI staining assay, PI staining assay, western blot analysis were employed to measure the effect of ALT on viability, apoptosis and cell cycle in B-ALL cells. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00243205193029
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http://dx.doi.org/10.1016/j.lfs.2019.04.034DOI Listing
April 2019
1 Read

Maternal Triacylglycerol Signature and Offspring Risk of Food Allergy.

J Allergy Clin Immunol 2019 Apr 17. Epub 2019 Apr 17.

Department of Population, Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, 21205, USA; Division of General Pediatrics & Adolescent Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Background: The prevalence of IgE-mediated food allergy (FA) is rising worldwide but the underlying mechanisms are poorly understood.

Objective: To examine the role of maternal lipidomic profiles in offspring risk of FA development; and to investigate the potential modification effects by timing of first solid food introduction.

Methods: This report included 1,068 mother-child dyads from the Boston Birth Cohort. Read More

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http://dx.doi.org/10.1016/j.jaci.2019.03.033DOI Listing

The Plant PTM Viewer, a central resource for exploring plant protein modifications.

Plant J 2019 Apr 20. Epub 2019 Apr 20.

Department of Biomolecular Medicine, Ghent University, 9000, Ghent, Belgium.

Posttranslational modifications (PTMs) of proteins are central in any kind of cellular signaling. Modern mass spectrometry technologies enable comprehensive identification and quantification of various PTMs. Given the increased numbers and types of mapped protein modifications, a database is necessary that simultaneously integrates and compares site-specific information for different PTMs, especially in plants for which the available PTM data are poorly catalogued. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1111/tpj.14345
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http://dx.doi.org/10.1111/tpj.14345DOI Listing
April 2019
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P300 Acetyltransferase is a Cytoplasm-to-Nucleus Shuttle for SMAD2/3 and TAZ Nuclear Transport in TGFβ-stimulated Hepatic Stellate Cells.

Hepatology 2019 Apr 20. Epub 2019 Apr 20.

Tumor Microenvironment and Metastasis, Hormel Institute, University of Minnesota, Austin, MN, USA.

Nuclear translocation of SMAD2/3, core transcription factors of TGFβ signaling, is critical for hepatic stellate cell (HSC) differentiation into metastasis-promoting myofibroblasts. SMAD2/3 have multiple coactivators, including WW domain-containing transcription regulator protein 1 (WWTR1 or TAZ) and p300 acetyltransferase. In the nucleus, TAZ binds to SMAD2/3 to prevent SMAD2/3 nuclear export. Read More

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http://dx.doi.org/10.1002/hep.30668DOI Listing

Energy costs of salt tolerance in crop plants.

New Phytol 2019 Apr 20. Epub 2019 Apr 20.

Australian Research Council (ARC) Centre of Excellence in Plant Energy Biology, School of Agriculture, Food and Wine, University of Adelaide, Glen Osmond, SA, 5064, Australia.

Agriculture is expanding into regions that are affected by salinity. This review considers energy costs of salinity tolerance in crop plants and provides a framework for a quantitative assessment of costs. Different sources of energy, and modifications of root system architecture that would maximise water versus ion uptake are addressed. Read More

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http://dx.doi.org/10.1111/nph.15864DOI Listing

The plant translatome surveyed by ribosome profiling.

Plant Cell Physiol 2019 Apr 20. Epub 2019 Apr 20.

RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama, Japan.

Although transcriptome changes have long been recognized as a mechanism to induce tentative substitution of expressed genes in diverse biological processes in plants, the regulation of translation-the final step of the central dogma of molecular biology-emerged as an alternative and prominent layer in defining the output of genes. Despite these demands, the genome-wide analysis of protein synthesis has posed technical challenges, resulting in the plant translatome being poorly understood. The development of ribosome profiling promises to address the hidden aspects of translation, and its application to plants is revolutionizing our knowledge of the translatome. Read More

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http://fdslive.oup.com/www.oup.com/pdf/production_in_progres
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http://dx.doi.org/10.1093/pcp/pcz059DOI Listing
April 2019
1 Read

BHap: a novel approach for bacterial haplotype reconstruction.

Bioinformatics 2019 Apr 20. Epub 2019 Apr 20.

Burnett School of Biomedical Science, College of Medicine, University of Central Florida, Orlando, FL, USA.

Motivation: The bacterial haplotype reconstruction is critical for selecting proper treatments for diseases caused by unknown haplotypes. Existing methods and tools do not work well on this task, because they are usually developed for viral instead of bacterial populations.

Results: In this study, we developed BHap, a novel algorithm based on fuzzy flow networks, for reconstructing bacterial haplotypes from next generation sequencing data. Read More

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https://academic.oup.com/bioinformatics/advance-article/doi/
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http://dx.doi.org/10.1093/bioinformatics/btz280DOI Listing
April 2019
1 Read

The EntOptLayout Cytoscape plug-in for the efficient visualization of major protein complexes in protein-protein interaction and signalling networks.

Bioinformatics 2019 Apr 20. Epub 2019 Apr 20.

Network Science Institute, Northeastern University, Boston MA, USA.

Motivation: Network visualizations of complex biological datasets usually result in 'hairball' images, which do not discriminate network modules.

Results: We present the EntOptLayout Cytoscape plug-in based on a recently developed network representation theory. The plug-in provides an efficient visualization of network modules, which represent major protein complexes in protein-protein interaction and signalling networks. Read More

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http://dx.doi.org/10.1093/bioinformatics/btz257DOI Listing

FuncTree2: an interactive radial tree for functional hierarchies and omics data visualization.

Bioinformatics 2019 Apr 20. Epub 2019 Apr 20.

Department of Life Science and Technology, Tokyo Institute of Technology, Tokyo, Japan.

Summary: Functional annotations and their hierarchical classification are widely used in omics workflows to build novel insight upon existing biological knowledge. Currently, a plethora of tools is available to explore omics datasets at the level of functional annotations, but there is a lack of feature rich and user-friendly tools that help scientists take advantage of their hierarchical classification for additional and often invaluable insights. Here we present FuncTree2, a user-friendly web application that turns hierarchical classifications into interactive and highly customizable radial trees, and enables researchers to visualize their data simultaneously on all its levels. Read More

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http://dx.doi.org/10.1093/bioinformatics/btz245DOI Listing

ORCA: A Comprehensive Bioinformatics Container Environment for Education and Research.

Bioinformatics 2019 Apr 20. Epub 2019 Apr 20.

Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada.

Summary: The ORCA bioinformatics environment is a Docker image that contains hundreds of bioinformatics tools and their dependencies. The ORCA image and accompanying server infrastructure provide a comprehensive bioinformatics environment for education and research. The ORCA environment on a server is implemented using Docker containers, but without requiring users to interact directly with Docker, suitable for novices who may not yet have familiarity with managing containers. Read More

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http://dx.doi.org/10.1093/bioinformatics/btz278DOI Listing

A framework for space-efficient variable-order Markov models.

Bioinformatics 2019 Apr 20. Epub 2019 Apr 20.

CAPA, DTISI, Centre de Recherche sur l'Information Scientifique et Technique, Algiers, Algeria.

Motivation: Markov models with contexts of variable length are widely used in bioinformatics for representing sets of sequences with similar biological properties. When models contain many long contexts, existing implementations are either unable to handle genome-scale training datasets within typical memory budgets, or they are optimized for specific model variants and are thus inflexible.

Results: We provide practical, versatile representations of variable-order Markov models and of interpolated Markov models, that support a large number of context-selection criteria, scoring functions, probability smoothing methods, and interpolations, and that take up to four times less space than previous implementations based on the suffix array, regardless of the number and length of contexts, and up to ten times less space than previous trie-based representations, or more, while matching the size of related, state-of-the-art data structures from Natural Language Processing. Read More

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https://academic.oup.com/bioinformatics/advance-article/doi/
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http://dx.doi.org/10.1093/bioinformatics/btz268DOI Listing
April 2019
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Empirical-likelihood-based criteria for model selection on marginal analysis of longitudinal data with dropout missingness.

Biometrics 2019 Apr 20. Epub 2019 Apr 20.

Division of Biostatistics and Bioinformatics, Department of Public Health Sciences Penn State College of Medicine, Hershey, PA, U.S.A.

Longitudinal data are common in clinical trials and observational studies, where missing outcomes due to dropouts are always encountered. Under such context with the assumption of missing at random, the weighted generalized estimating equations (WGEE) approach is widely adopted for marginal analysis. Model selection on marginal mean regression is a crucial aspect of data analysis, and identifying an appropriate correlation structure for model fitting may also be of interest and importance. Read More

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http://dx.doi.org/10.1111/biom.13060DOI Listing

Circular RNA MAT2B promotes glycolysis and malignancy of hepatocellular carcinoma via the miR-338-3p/PKM2 axis under hypoxic stress.

Hepatology 2019 Apr 20. Epub 2019 Apr 20.

School of Medicine, Southeast University, No.87, Dingjia Bridge, Nanjing, Jiangsu province, China.

Glucose metabolism reprogramming, which is a well-established characteristic of multiple cancers, demands a higher rate of glycolysis to meet the increasing demands for macromolecular synthesis and to maintain rapid proliferation in a hypoxic environment. However, the mechanism underlying this switch remains to be elucidated. In this study, we investigated the function of circular RNA MAT2B (circMAT2B) in hepatocellular carcinoma (HCC) glucose metabolism reprogramming and malignancy. Read More

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http://dx.doi.org/10.1002/hep.30671DOI Listing

A novel de novo PDGFRB variant in a child with severe cerebral malformations, intracerebral calcifications, and infantile myofibromatosis.

Am J Med Genet A 2019 Apr 19. Epub 2019 Apr 19.

Laboratory of embryology and genetics of malformations, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1163, Institut Imagine, Paris, France.

The spectrum of clinical consequences of variants in the Platelet derived growth factor receptor beta (PDGFRB) gene is wide. Missense variants leading to variable loss of signal transduction in vitro have been reported in the idiopathic basal ganglia calcification (IBGC) syndrome Type 4. In contrast, gain-of-function variants have been reported in infantile myofibromatosis, Penttinen syndrome, and Kosaki overgrowth syndrome. Read More

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http://dx.doi.org/10.1002/ajmg.a.61151DOI Listing

In silico markers: an evolutionary and statistical approach to select informative genes of human breast cancer subtypes.

Genes Genomics 2019 Apr 19. Epub 2019 Apr 19.

Department of Informatics, University of Evora, 7004-516, Evora, Portugal.

Background: Recent advancement in bioinformatics offers the ability to identify informative genes from high dimensional gene expression data. Selection of informative genes from these large datasets has emerged as an issue of major concern among researchers.

Objective: Gene functionality and regulatory mechanisms can be understood through the analysis of these gene expression data. Read More

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http://dx.doi.org/10.1007/s13258-019-00816-8DOI Listing

Potential role of lncRNA-TSIX, miR-548-a-3p, and SOGA1 mRNA in the diagnosis of hepatocellular carcinoma.

Mol Biol Rep 2019 Apr 19. Epub 2019 Apr 19.

Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, P.O. Box 11381, Egypt.

Recent trends are moving towards the use of the circulating transcriptome as a potential diagnostic and therapeutic tool for hepatocellular carcinoma (HCC). The aim of this study is to identify circulatory RNA based biomarker panel, in addition to their relationship to the outcome in HCC. First, utilizing bioinformatics tools, we selected an HCC-specific RNA-based biomarker panel that depended on the integration of suppressor of glucose autophagy-associated (SOGA1) gene expression with the chosen panel of epigenetic regulators of this gene [long non-coding RNA antisense for X-inactive-specific transcript (lncRNA-TSIX) and microRNA-548-a-3p (miR-548-a-3p)]. Read More

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http://link.springer.com/10.1007/s11033-019-04810-x
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http://dx.doi.org/10.1007/s11033-019-04810-xDOI Listing
April 2019
1 Read

Local-regional recurrence in women with small node-negative, HER2-positive breast cancer: results from a prospective multi-institutional study (the APT trial).

Breast Cancer Res Treat 2019 Apr 19. Epub 2019 Apr 19.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Purpose: Women with HER2-positive breast cancer treated prior to effective anti-HER2 therapy have higher rates of local-regional recurrence (LRR) than those with HER2-negative disease. Effective systemic therapy, however, has been shown to decrease LRR. This study examines LRR in women with HER2-positive breast cancer treated on a single-arm prospective multicenter trial of adjuvant trastuzumab (H) and paclitaxel (T). Read More

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http://dx.doi.org/10.1007/s10549-019-05238-4DOI Listing

Active site-induced evolutionary constraints follow fold polarity principles in soluble globular enzymes.

Mol Biol Evol 2019 Apr 19. Epub 2019 Apr 19.

Laboratory for Biomolecular Modeling, École Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, Lausanne, Switzerland.

A recent analysis of evolutionary rates in > 500 globular soluble enzymes revealed pervasive conservation gradients toward catalytic residues. By looking at amino acid preference profiles rather than evolutionary rates in the same dataset, we quantified the effects of active sites on site-specific constraints for physicochemical traits. We found that conservation gradients respond to constraints for polarity, hydrophobicity, flexibility, rigidity and structure in ways consistent with fold polarity principles; while sites far from active sites seem to experience no physicochemical constraint, rather being highly variable and favoring amino acids of low metabolic cost. Read More

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http://dx.doi.org/10.1093/molbev/msz096DOI Listing

Inference of ancient whole genome duplications and the evolution of the gene duplication and loss rate.

Mol Biol Evol 2019 Apr 19. Epub 2019 Apr 19.

Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium.

Gene tree - species tree reconciliation methods have been employed for studying ancient whole genome duplication (WGD) events across the eukaryotic tree of life. Most approaches have relied on using maximum likelihood trees and the maximum parsimony reconciliation thereof to count duplication events on specific branches of interest in a reference species tree. Such approaches do not account for uncertainty in the gene tree and reconciliation, or do so only heuristically. Read More

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http://dx.doi.org/10.1093/molbev/msz088DOI Listing

DamMet: ancient methylome mapping accounting for errors, true variants, and post-mortem DNA damage.

Gigascience 2019 Apr;8(4)

Lundbeck Foundation GeoGenetics Center, University of Copenhagen, Øster Voldgade 5-7, 1350K Copenhagen, Denmark.

Background: Recent computational advances in ancient DNA research have opened access to the detection of ancient DNA methylation footprints at the genome-wide scale. The most commonly used approach infers the methylation state of a given genomic region on the basis of the amount of nucleotide mis-incorporations observed at CpG dinucleotide sites. However, this approach overlooks a number of confounding factors, including the presence of sequencing errors and true variants. Read More

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http://dx.doi.org/10.1093/gigascience/giz025DOI Listing

Gene expression differences between matched pairs of ovarian cancer patient tumors and patient-derived xenografts.

Sci Rep 2019 Apr 19;9(1):6314. Epub 2019 Apr 19.

Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 55905, USA.

As patient derived xenograft (PDX) models are increasingly used for preclinical drug development, strategies to account for the nonhuman component of PDX RNA expression data are critical to its interpretation. A bioinformatics pipeline to separate donor tumor and mouse stroma transcriptome profiles was devised and tested. To examine the molecular fidelity of PDX versus donor tumors, we compared mRNA differences between paired PDX-donor tumors from nine ovarian cancer patients. Read More

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http://dx.doi.org/10.1038/s41598-019-42680-2DOI Listing

The effect of numerical aperture on quantitative use-wear studies and its implication on reproducibility.

Sci Rep 2019 Apr 19;9(1):6313. Epub 2019 Apr 19.

TraCEr, Laboratory for Traceology and Controlled Experiments at MONREPOS Archaeological Research Centre and Museum for Human Behavioural Evolution, RGZM, Schloss Monrepos, 56567, Neuwied, Germany.

Many archeologists are skeptical about the capabilities of use-wear analysis to infer on the function of archeological tools, mainly because the method is seen as subjective, not standardized and not reproducible. Quantitative methods in particular have been developed and applied to address these issues. However, the importance of equipment, acquisition and analysis settings remains underestimated. Read More

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http://dx.doi.org/10.1038/s41598-019-42713-wDOI Listing

Integrative Analysis of Long Noncoding RNA (lncRNA), microRNA (miRNA) and mRNA Expression and Construction of a Competing Endogenous RNA (ceRNA) Network in Metastatic Melanoma.

Med Sci Monit 2019 Apr 20;25:2896-2907. Epub 2019 Apr 20.

Department of Dermatology, The Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, Shandong, China (mainland).

Worldwide, metastatic melanoma of the skin has an aggressive course with high morbidity and mortality. Therefore, an increased understanding of the pathogenesis of metastatic melanoma has gained increasing attention, including the role of epigenetic modification and competing endogenous RNA (ceRNA). This study aimed to used bioinformatics data to undertake an integrative analysis of long noncoding RNA (lncRNA), microRNA (miRNA) and mRNA expression to construct a ceRNA network in metastatic melanoma. Read More

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http://dx.doi.org/10.12659/MSM.913881DOI Listing
April 2019
3 Reads

MAPK pathway and B cells overactivation in multiple sclerosis revealed by phosphoproteomics and genomic analysis.

Proc Natl Acad Sci U S A 2019 Apr 19. Epub 2019 Apr 19.

Center of Neuroimmunology, Institut d'Investigacions Biomèdiques August Pi Sunyer, Barcelona 08036, Spain;

Dysregulation of signaling pathways in multiple sclerosis (MS) can be analyzed by phosphoproteomics in peripheral blood mononuclear cells (PBMCs). We performed in vitro kinetic assays on PBMCs in 195 MS patients and 60 matched controls and quantified the phosphorylation of 17 kinases using xMAP assays. Phosphoprotein levels were tested for association with genetic susceptibility by typing 112 single-nucleotide polymorphisms (SNPs) associated with MS susceptibility. Read More

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http://dx.doi.org/10.1073/pnas.1818347116DOI Listing
April 2019
1 Read

Clonal haematopoiesis and risk of acute myeloid leukemia.

Haematologica 2019 Apr 19. Epub 2019 Apr 19.

Washington University School of Medicine;

Nearly all adults harbor acute myeloid leukemia-related clonal hematopoietic mutations at a variant allele fraction of ≥0.0001, yet relatively few develop hematologic malignancies. We conducted a nested analysis in the Nurses' Health Study and Health Professionals Follow-Up Study blood subcohorts, with up to 22 years of follow-up, to investigate associations of clonal mutations of ≥0. Read More

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http://dx.doi.org/10.3324/haematol.2018.215269DOI Listing
April 2019
2 Reads

A Clinical Applicable Gene Expression Classifier Reveals Intrinsic and Extrinsic Contributions to Consensus Molecular Subtypes in Primary and Metastatic Colon Cancer.

Clin Cancer Res 2019 Apr 19. Epub 2019 Apr 19.

Molecular Biology, Genentech Inc.

Purpose: Four consensus molecular subtypes (CMS1-4) of colorectal cancer (CRC) were identified in primary tumors and found to be associated with distinctive biological features and clinical outcomes. Given that distant metastasis largely accounts for CRC-related mortality, we examined the molecular and clinical attributes of CMS in metastatic CRC (mCRC).

Experimental Design: We developed a CRC-focused Nanostring based CMS classifier that is ideally suited to interrogate archival tissues. Read More

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http://dx.doi.org/10.1158/1078-0432.CCR-18-3032DOI Listing
April 2019
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Function and Evolution of Upstream ORFs in Eukaryotes.

Trends Biochem Sci 2019 Apr 16. Epub 2019 Apr 16.

State Key Laboratory of Protein and Plant Gene Research, Center for Bioinformatics, School of Life Sciences, Peking University, Beijing, 100871, China. Electronic address:

There is growing interest in the role of translational regulation in cellular homeostasis during organismal development. Translation initiation is the rate-limiting step in mRNA translation and is central to translational regulation. Upstream open reading frames (uORFs) are regulatory elements that are prevalent in eukaryotic mRNAs. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09680004193005
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http://dx.doi.org/10.1016/j.tibs.2019.03.002DOI Listing
April 2019
1 Read

Epigenome-wide Association Study of Attention-Deficit/Hyperactivity Disorder Symptoms in Adults.

Biol Psychiatry 2019 Mar 1. Epub 2019 Mar 1.

Department of Biological Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam.

Background: Previous studies have reported associations between attention-deficit/hyperactivity disorder symptoms and DNA methylation in children. We report the first epigenome-wide association study meta-analysis of adult attention-deficit/hyperactivity disorder symptoms, based on peripheral blood DNA methylation (Infinium HumanMethylation450K array) in three population-based adult cohorts.

Methods: An epigenome-wide association study was performed in the Netherlands Twin Register (N = 2258, mean age 37 years), Dunedin Multidisciplinary Health and Development Study (N = 800, age 38 years), and Environmental Risk Longitudinal Twin Study (N = 1631, age 18 years), and results were combined through meta-analysis (total sample size N = 4689). Read More

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http://dx.doi.org/10.1016/j.biopsych.2019.02.016DOI Listing

Quantitative Analysis of Nuclear Lamins Imaged by Super-Resolution Light Microscopy.

Cells 2019 Apr 18;8(4). Epub 2019 Apr 18.

Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

The nuclear lamina consists of a dense fibrous meshwork of nuclear lamins, Type V intermediate filaments, and is ~14 nm thick according to recent cryo-electron tomography studies. Recent advances in light microscopy have extended the resolution to a scale allowing for the fine structure of the lamina to be imaged in the context of the whole nucleus. We review quantitative approaches to analyze the imaging data of the nuclear lamina as acquired by structured illumination microscopy (SIM) and single molecule localization microscopy (SMLM), as well as the requisite cell preparation techniques. Read More

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https://www.mdpi.com/2073-4409/8/4/361
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http://dx.doi.org/10.3390/cells8040361DOI Listing
April 2019
1 Read

The widespread increase in inter-individual variability of gene expression in the human brain with age.

Aging (Albany NY) 2019 Apr 19. Epub 2019 Apr 19.

European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, CB10 1SD, UK.

Aging is broadly defined as a time-dependent progressive decline in the functional and physiological integrity of organisms. Previous studies and evolutionary theories of aging suggest that aging is not a programmed process but reflects dynamic stochastic events. In this study, we test whether transcriptional noise shows an increase with age, which would be expected from stochastic theories. Read More

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http://dx.doi.org/10.18632/aging.101912DOI Listing
April 2019
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Effect of glycolysis inhibition by miR-448 on glioma radiosensitivity.

J Neurosurg 2019 Apr 19:1-9. Epub 2019 Apr 19.

4Department of Neurosurgery, The Affiliated Hospital of Xiangnan University, Chenzhou, Hunan, People's Republic of China.

OBJECTIVEAlthough glucose metabolism reengineering is a typical feature of various tumors, including glioma, key regulators of glycolytic reprogramming are still poorly understood. The authors sought to investigate whether glycolysis inhibition by microRNA (miR)-448 increases radiosensitivity in glioma cells.METHODSThe authors used glioma tissue samples from glioma patients, cells from glioblastoma (GBM) cell lines and normal human astrocyte cells, and subcutaneous tumor-bearing U87 cells in mice to examine the effects of signaling regulation by miR-448 in the response of glioma tissues and cells to radiation treatment. Read More

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https://thejns.org/view/journals/j-neurosurg/aop/article-10.
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http://dx.doi.org/10.3171/2018.12.JNS181798DOI Listing
April 2019
1 Read

MicroRNA-181b-5p attenuates early postoperative cognitive dysfunction by suppressing hippocampal neuroinflammation in mice.

Cytokine 2019 Apr 16;120:41-53. Epub 2019 Apr 16.

Department of Anesthesiology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, Hubei, China. Electronic address:

Background: Postoperative cognitive dysfunction (POCD) is a common complication after surgery and its occurrence is associated with increased morbidity and mortality. However, the pathophysiology of this complication remains largely unknown. Efforts to identify causes of POCD have focused on the hippocampal neuroinflammation. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10434666193010
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http://dx.doi.org/10.1016/j.cyto.2019.04.005DOI Listing
April 2019
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Discoidin domain receptor 2: An emerging pharmacological drug target for prospective therapy against osteoarthritis.

Pharmacol Rep 2019 Jan 15;71(3):399-408. Epub 2019 Jan 15.

Department of Pharmaceutical Sciences, Drug Discovery Research Laboratorty, Assam University, Silchar, Assam, India. Electronic address:

Discoidin domain receptor2 (DDR2), a cell membrane tyrosine kinase on chondrocytes surface plays main role in cell-ECM interaction during the progressive degeneration of articular cartilage in osteoarthritis. The degraded component of ECM, type II collagen upon DDR2 binding provokes synthesis of matrix metalloproteinases (MMPs), responsible for severe destruction of joint tissues. DDR2 knockout has been investigated to decline the expression of MMP-1 and 13. Read More

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http://dx.doi.org/10.1016/j.pharep.2019.01.007DOI Listing
January 2019
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Suppression of miR-1197-3p attenuates HO-induced apoptosis of goat luteinized granulosa cells via targeting PPARGC1A.

Theriogenology 2019 Apr 11;132:72-82. Epub 2019 Apr 11.

Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address:

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A) acts as a powerful coactivator of many transcriptional factors that relate to granulosa cell (GC) apoptosis. In this study, the miRNAs mediating goat follicular atresia and luteinized granulosa cell (LGC) apoptosis induced by hydrogen peroxide (HO) via PPARGC1A were investigated. Our results showed that miR-1197-3p targeted PPARGC1A was predicted by bioinformatics algorithm and verified by luciferase reporter assay. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S0093691X193009
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http://dx.doi.org/10.1016/j.theriogenology.2019.04.008DOI Listing
April 2019
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Determinants of phthalate exposure and risk assessment in children from Poland.

Environ Int 2019 Apr 16;127:742-753. Epub 2019 Apr 16.

Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine (NIOM), Lodz, Poland.

Phthalates are a group of widely used chemicals and humans are exposed to them in their daily life. Some phthalates may affect the hormonal balance in both children and adults. The aim of this study was to assess the phthalate exposure and its determinants among children at age of 7 years from the Polish Mother and Child Cohort Study (REPRO_PL). Read More

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http://dx.doi.org/10.1016/j.envint.2019.04.011DOI Listing
April 2019
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Synthesis, biological activity and multiscale molecular modeling studies of bis-coumarins as selective carbonic anhydrase IX and XII inhibitors with effective cytotoxicity against hepatocellular carcinoma.

Bioorg Chem 2019 Mar 7;87:838-850. Epub 2019 Mar 7.

Sakarya University of Applied Sciences, Pamukova Vocational Highschool, Pamukova, Turkey.

A series of novel bis-coumarin derivatives containing triazole moiety as a linker between the alkyl chains was synthesized and their inhibitory activity against the human carbonic anhydrase (hCA) isoforms I, II, IX and XII were evaluated. In addition, cytotoxic effects of the synthesized compounds on renal adenocarcinoma (769P), hepatocellular carcinoma (HepG2) and breast adeno carcinoma (MDA-MB-231) cell lines were examined. While the hCA I and II isoforms were inhibited in the micromolar range, the tumor-associated isoform hCA IX and XII were inhibited in the high nanomolar range. Read More

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http://dx.doi.org/10.1016/j.bioorg.2019.03.003DOI Listing

Characterization, high production and antimicrobial activity of exopolysaccharides from Lactococcus lactis F-mou.

Microb Pathog 2019 Apr 16. Epub 2019 Apr 16.

Laboratory of Molecular Biology, Genomics and Bioinformatics, Faculty of Nature and Life Science, Hassiba Benbouali University, Chlef, Hay Essalam, 02000, Algeria.

A new exopolysaccharide (EPS) was produced by the Lactococcus lactis F-mou strain (LT898177.1) isolated from the Sahrawi camel milk in the Bir-Naam region, Algeria. The most influential production parameters were screened by the Plackett-Burman design for enhancing EPS yield utilizing the Mech-Degla juice as a low-cost raw material. Read More

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http://dx.doi.org/10.1016/j.micpath.2019.04.018DOI Listing
April 2019
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Identification of the anchoring protein SpoIIIJ for construction of the microbial cell surface display system in Bacillus spp.

Int J Biol Macromol 2019 Apr 16. Epub 2019 Apr 16.

Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China. Electronic address:

Microbial cell surface display technology is a powerful tool for displaying proteins on the surfaces of cells. However, few anchoring proteins can be employed for the display of target proteins on the cell surface of the environmentally benign Gram-positive bacterium Bacillus subtilis. In this study, bioinformatics tools were used to screen all of the encoded proteins of B. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S01418130193048
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http://dx.doi.org/10.1016/j.ijbiomac.2019.04.033DOI Listing
April 2019
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Polygenic Risk Scores Expand to Obesity.

Cell 2019 Apr;177(3):518-520

Scripps Research Translational Institute, La Jolla, CA 92037, USA; Department of Molecular Medicine, Scripps Research, La Jolla, CA 92037, USA. Electronic address:

Obesity is one of the most serious health challenges of our time. In this issue of Cell, Khera and co-authors demonstrate the striking ability of genetics, in the form of a polygenic risk score, to identify those individuals at high risk for obesity. This genetic risk expresses itself early as childhood obesity, reinforcing the notion that early prevention is essential to combatting the obesity epidemic. Read More

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http://dx.doi.org/10.1016/j.cell.2019.03.051DOI Listing
April 2019
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Evaluating DNA methylation age on the Illumina MethylationEPIC Bead Chip.

PLoS One 2019 19;14(4):e0207834. Epub 2019 Apr 19.

National Health and Environmental Effects Laboratory, US Environmental Protection Agency, Chapel Hill, NC, United States of America.

DNA methylation age (DNAm age) has become a widely utilized epigenetic biomarker for the aging process. The Horvath method for determining DNAm age is perhaps the most widely utilized and validated DNA methylation age assessment measure. Horvath DNAm age is calculated based on methylation measurements at 353 loci, present on Illumina's 450k and 27k DNA methylation microarrays. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0207834PLOS
April 2019
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Preclinical evaluation of EPHX2 inhibition as a novel treatment for inflammatory bowel disease.

PLoS One 2019 19;14(4):e0215033. Epub 2019 Apr 19.

Computational Biology, GlaxoSmithKline, Collegeville, Pennsylvania, United States of America.

Epoxyeicosatrienoic acids (EETs) are signaling lipids produced by cytochrome P450 epoxygenation of arachidonic acid, which are metabolized by EPHX2 (epoxide hydrolase 2, alias soluble epoxide hydrolase or sEH). EETs have pleiotropic effects, including anti-inflammatory activity. Using a Connectivity Map (CMAP) approach, we identified an inverse-correlation between an exemplar EPHX2 inhibitor (EPHX2i) compound response and an inflammatory bowel disease patient-derived signature. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215033PLOS
April 2019
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CancerInSilico: An R/Bioconductor package for combining mathematical and statistical modeling to simulate time course bulk and single cell gene expression data in cancer.

PLoS Comput Biol 2019 Apr 19;14(4):e1006935. Epub 2019 Apr 19.

Department of Oncology, Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD United States of America.

Bioinformatics techniques to analyze time course bulk and single cell omics data are advancing. The absence of a known ground truth of the dynamics of molecular changes challenges benchmarking their performance on real data. Realistic simulated time-course datasets are essential to assess the performance of time course bioinformatics algorithms. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006935DOI Listing

Challenges and promise at the interface of metaproteomics and genomics: an overview of recent progress in metaproteogenomic data analysis.

Expert Rev Proteomics 2019 Apr 19. Epub 2019 Apr 19.

b VIB - UGent Center for Medical Biotechnology , Ghent , Belgium.

Introduction: The study of microbial communities based on the combined analysis of genomic and proteomic data - called metaproteogenomics - has gained increased research attention in recent years. This relatively young field aims to elucidate the functional and taxonomic interplay of proteins in microbiomes and its implications on human health and the environment. Areas covered: This article reviews bioinformatics methods and software tools dedicated to the analysis of data from metaproteomics and metaproteogenomics experiments. Read More

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http://dx.doi.org/10.1080/14789450.2019.1609944DOI Listing

What's new on therapies for elevated lipoprotein(a).

Expert Rev Clin Pharmacol 2019 Apr 19. Epub 2019 Apr 19.

b School of Medicine, Faculty of Health and Medical Sciences , University of Western Australia , Perth Australia.

Introduction: The study of microbial communities based on the combined analysis of genomic and proteomic data - called metaproteogenomics - has gained increased research attention in recent years. This relatively young field aims to elucidate the functional and taxonomic interplay of proteins in microbiomes and its implications on human health and the environment. Areas covered: This article reviews bioinformatics methods and software tools dedicated to the analysis of data from metaproteomics and metaproteogenomics experiments. Read More

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http://dx.doi.org/10.1080/17512433.2019.1610391DOI Listing