scholarly journals Enhancing the interoperability of glycan data flow between ChEBI, PubChem, and GlyGen.

2021 ◽  
Author(s):  
Rahi Navelkar ◽  
Gareth Owen ◽  
Venkatesh Mutherkrishnan ◽  
Paul Thiessen ◽  
Evan Bolton ◽  
...  
Keyword(s):  
Experimental Evidence ◽  
Critical Role ◽  
Direct Result ◽  
Keen Interest ◽  
Biological Source ◽  
Pubchem Database ◽  
Structural Ambiguity ◽  
Bioinformatics Databases ◽  
Health And Disease ◽  
Archival Database

Glycans have a critical role in health and disease. As a direct result, there is keen interest to identify and increase glycan data in bioinformatics databases like ChEBI and PubChem, and in connecting them to biomedical resources at the EMBL-EBI and NCBI. GlyTouCan is a comprehensive archival database that contains over 118,000 glycans, obtained primarily through batch upload from glycan repositories, submissions from glycoprotein databases, and individual laboratories. In many instances, the glycan structures deposited in GlyTouCan may not be fully defined or have supporting experimental evidence or biological source content. Databases like ChEBI and PubChem were designed to accommodate complete atomistic structures with well-defined chemical linkages. As a result, they cannot easily accommodate the structural ambiguity inherent in many glycan database representations. Consequently, there is a need to organize glycan data coherently to improve the connectivity across the major NCBI, EMBL-EBI, and glycoscience databases. This paper outlines a workflow developed in collaboration between GlyGen, ChEBI, and PubChem to improve the visibility and connectivity of glycan data across these resources. GlyGen hosts a subset of glycans (~29,000) from the GlyTouCan database and has submitted valuable glycan annotations to the PubChem database and registered or mapped over 10,500 (including ambiguously defined) glycans into the ChEBI database. The integrated glycans were prioritized based on links to PubChem and connectivity to glycoprotein data. The pipeline provides a blueprint for how glycan data can be harmonized between different resources. The current PubChem, ChEBI, and GlyTouCan mappings can be downloaded from GlyGen(https://data.glygen.org).

The Laryngeal Epithelium in Reflux

2011 ◽  
Vol 21 (3) ◽  
pp. 112-117 ◽  
Author(s):  
Elizabeth Erickson-Levendoski ◽  
Mahalakshmi Sivasankar
Keyword(s):  
Laryngopharyngeal Reflux ◽  
Critical Role ◽  
Structure And Function ◽  
Laryngeal Disease ◽  
Health And Disease ◽  
And Function ◽  
The Impact

The epithelium plays a critical role in the maintenance of laryngeal health. This is evident in that laryngeal disease may result when the integrity of the epithelium is compromised by insults such as laryngopharyngeal reflux. In this article, we will review the structure and function of the laryngeal epithelium and summarize the impact of laryngopharyngeal reflux on the epithelium. Research investigating the ramifications of reflux on the epithelium has improved our understanding of laryngeal disease associated with laryngopharyngeal reflux. It further highlights the need for continued research on the laryngeal epithelium in health and disease.

TESTING GOAL-DRIVEN CAPTURE BY THREAT

2019 ◽  
Author(s):  
Chris Robert Harrison Brown
Keyword(s):  
Experimental Evidence ◽  
Attentional Capture ◽  
Critical Role ◽  
Experimental Manipulation ◽  
Contingent Capture ◽  
Top Down ◽  
Affective Stimuli ◽  
Clinical Disorders ◽  
Positive Stimuli

Attention has long been characterised within prominent models as reflecting a competition between goal-driven and stimulus-driven processes. It remains unclear, however, how involuntary attentional capture by affective stimuli, such as threat-laden content, fits into such models. While such effects were traditionally held to reflect stimulus-driven processes, recent research has increasingly implicated a critical role of goal-driven processes. Here we test an alternative goal-driven account of involuntary attentional capture by threat, using an experimental manipulation of goal-driven attention. To this end we combined the classic ‘contingent capture’ and ‘emotion-induced blink’ (EIB) paradigms in an RSVP task with both positive or threatening target search goals. Across six experiments, positive and threat distractors were presented in peripheral, parafoveal, and central locations. Across all distractor locations, we found that involuntary attentional capture by irrelevant threatening distractors could be induced via the adoption of a search goal for a threatening category; adopting a goal for a positive category conversely led to capture only by positive stimuli. Our findings provide direct experimental evidence for a causal role of voluntary goals in involuntary capture by irrelevant threat stimuli, and hence demonstrate the plausibility of a top-down account of this phenomenon. We discuss the implications of these findings in relation to current cognitive models of attention and clinical disorders.

scholarly journals O-GlcNAcylation protein disruption by Thiamet G promotes changes on the GBM U87-MG cells secretome molecular signature

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Maria Cecilia Oliveira-Nunes ◽  
Glaucia Julião ◽  
Aline Menezes ◽  
Fernanda Mariath ◽  
John A. Hanover ◽  
...  
Keyword(s):  
Experimental Evidence ◽  
Critical Role ◽  
Molecular Signature ◽  
Label Free ◽  
Intercellular Signaling ◽  
Tumor Aggressiveness ◽  
Signaling Axis ◽  
Literature Evidence ◽  
Therapeutic Tools

AbstractGlioblastoma (GBM) is a grade IV glioma highly aggressive and refractory to the therapeutic approaches currently in use. O-GlcNAcylation plays a key role for tumor aggressiveness and progression in different types of cancer; however, experimental evidence of its involvement in GBM are still lacking. Here, we show that O-GlcNAcylation plays a critical role in maintaining the composition of the GBM secretome, whereas inhibition of OGA activity disrupts the intercellular signaling via microvesicles. Using a label-free quantitative proteomics methodology, we identified 51 proteins in the GBM secretome whose abundance was significantly altered by activity inhibition of O-GlcNAcase (iOGA). Among these proteins, we observed that proteins related to proteasome activity and to regulation of immune response in the tumor microenvironment were consistently downregulated in GBM cells upon iOGA. While the proteins IGFBP3, IL-6 and HSPA5 were downregulated in GBM iOGA cells, the protein SQSTM1/p62 was exclusively found in GBM cells under iOGA. These findings were in line with literature evidence on the role of p62/IL-6 signaling axis in suppressing tumor aggressiveness and our experimental evidence showing a decrease in radioresistance potential of these cells. Taken together, our findings provide evidence that OGA activity may regulate the p62 and IL-6 abundance in the GBM secretome. We propose that the assessment of tumor status from the main proteins present in its secretome may contribute to the advancement of diagnostic, prognostic and even therapeutic tools to approach this relevant malignancy.

scholarly journals Reactive Oxygen Species: Beyond Their Reactive Behavior

2021 ◽  
Vol 46 (1) ◽  
pp. 77-87
Author(s):  
Arnaud Tauffenberger ◽  
Pierre J. Magistretti
Keyword(s):  
Reactive Oxygen Species ◽  
Second Messengers ◽  
Critical Role ◽  
Complex Function ◽  
Reactive Oxygen ◽  
High Reactivity ◽  
Oxygen Species ◽  
Health And Disease ◽  
Cellular Dysfunction ◽  
The Brain

AbstractCellular homeostasis plays a critical role in how an organism will develop and age. Disruption of this fragile equilibrium is often associated with health degradation and ultimately, death. Reactive oxygen species (ROS) have been closely associated with health decline and neurological disorders, such as Alzheimer’s disease or Parkinson’s disease. ROS were first identified as by-products of the cellular activity, mainly mitochondrial respiration, and their high reactivity is linked to a disruption of macromolecules such as proteins, lipids and DNA. More recent research suggests more complex function of ROS, reaching far beyond the cellular dysfunction. ROS are active actors in most of the signaling cascades involved in cell development, proliferation and survival, constituting important second messengers. In the brain, their impact on neurons and astrocytes has been associated with synaptic plasticity and neuron survival. This review provides an overview of ROS function in cell signaling in the context of aging and degeneration in the brain and guarding the fragile balance between health and disease.

scholarly journals Creatine in Health and Disease

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 447
Author(s):  
Richard B. Kreider ◽  
Jeffery R. Stout
Keyword(s):  
Scientific Evidence ◽  
Critical Role ◽  
Creatine Supplementation ◽  
Cellular Metabolism ◽  
Medical Evidence ◽  
Therapeutic Benefits ◽  
Nutritional Strategy ◽  
Severity Of Injury ◽  
Health And Disease

Although creatine has been mostly studied as an ergogenic aid for exercise, training, and sport, several health and potential therapeutic benefits have been reported. This is because creatine plays a critical role in cellular metabolism, particularly during metabolically stressed states, and limitations in the ability to transport and/or store creatine can impair metabolism. Moreover, increasing availability of creatine in tissue may enhance cellular metabolism and thereby lessen the severity of injury and/or disease conditions, particularly when oxygen availability is compromised. This systematic review assesses the peer-reviewed scientific and medical evidence related to creatine’s role in promoting general health as we age and how creatine supplementation has been used as a nutritional strategy to help individuals recover from injury and/or manage chronic disease. Additionally, it provides reasonable conclusions about the role of creatine on health and disease based on current scientific evidence. Based on this analysis, it can be concluded that creatine supplementation has several health and therapeutic benefits throughout the lifespan.

scholarly journals CIRFESS: An interactive resource for querying the set of theoretically detectable peptides for cell surface and extracellular enrichment proteomic studies

2020 ◽  
Author(s):  
Matthew Waas ◽  
Jack Littrell ◽  
Rebekah L. Gundry
Keyword(s):  
Cell Surface ◽  
Critical Role ◽  
Affinity Reagents ◽  
Extracellular Proteome ◽  
Online Resource ◽  
Health And Disease ◽  
Limited Mass ◽  
Multiple Prediction ◽  
Surface Proteome ◽  
Cell Surface Proteome

AbstractCell surface transmembrane, extracellular, and secreted proteins are high value targets for immunophenotyping, drug development, and studies related to intercellular communication in health and disease. As the number of specific and validated affinity reagents that target this subproteome are limited, mass spectrometry (MS)-based approaches will continue to play a critical role in enabling discovery and quantitation of these molecules. Given the technical considerations that make MS-based cell surface proteome studies uniquely challenging, it can be difficult to select an appropriate experimental approach. To this end, we have integrated multiple prediction strategies and annotations into a single online resource, Compiled Interactive Resource for Extracellular and Surface Studies (CIRFESS). CIRFESS enables rapid interrogation of the human proteome to reveal the cell surface proteome theoretically detectable by current approaches and highlights where current prediction strategies provide concordant and discordant information. We applied CIRFESS to identify the percentage of various subsets of the proteome which are expected to be captured by targeted enrichment strategies, including two established methods and one that is possible but not yet demonstrated. These results will inform the selection of available proteomic strategies and development of new strategies to enhance coverage of the cell surface and extracellular proteome. CIRFESS is available at www.cellsurfer.net/cirfess.

scholarly journals Microbial trend analysis for common dynamic trend, group comparison and classification in longitudinal microbiome study

2020 ◽  
Author(s):  
Chan Wang ◽  
Jiyuan Hu ◽  
Martin J. Blaser ◽  
Huilin Li
Keyword(s):  
Trend Analysis ◽  
Critical Role ◽  
Human Microbiome ◽  
Real Data ◽  
Microbial Dynamics ◽  
Individual Subject ◽  
Microbial Profiling ◽  
Health And Disease ◽  
Microbiome Data

AbstractMotivationThe human microbiome is inherently dynamic and its dynamic nature plays a critical role in maintaining health and driving disease. With an increasing number of longitudinal microbiome studies, scientists are eager to learn the comprehensive characterization of microbial dynamics and their implications to the health and disease-related phenotypes. However, due to the challenging structure of longitudinal microbiome data, few analytic methods are available to characterize the microbial dynamics over time.ResultsWe propose a microbial trend analysis (MTA) framework for the high-dimensional and phylogenetically-based longitudinal microbiome data. In particular, MTA can perform three tasks: 1) capture the common microbial dynamic trends for a group of subjects on the community level and identify the dominant taxa; 2) examine whether or not the microbial overall dynamic trends are significantly different in groups; 3) classify an individual subject based on its longitudinal microbial profiling. Our extensive simulations demonstrate that the proposed MTA framework is robust and powerful in hypothesis testing, taxon identification, and subject classification. Our real data analyses further illustrate the utility of MTA through a longitudinal study in mice.ConclusionsThe proposed MTA framework is an attractive and effective tool in investigating dynamic microbial pattern from longitudinal microbiome studies.

scholarly journals Developmental Exposure to Endocrine Disrupting Chemicals and Its Impact on Cardio-Metabolic-Renal Health

2021 ◽  
Vol 3 ◽  
Author(s):  
Radha Dutt Singh ◽  
Kavita Koshta ◽  
Ratnakar Tiwari ◽  
Hafizurrahman Khan ◽  
Vineeta Sharma ◽  
...  
Keyword(s):  
Experimental Evidence ◽  
Energy Homeostasis ◽  
Endocrine Disrupting Chemicals ◽  
Developmental Exposure ◽  
Adverse Health Outcomes ◽  
Early Life Exposure ◽  
Endocrine Disrupting ◽  
Similar Mode ◽  
Health And Disease ◽  
Hormone System

Developmental origin of health and disease postulates that the footprints of early life exposure are followed as an endowment of risk for adult diseases. Epidemiological and experimental evidence suggest that an adverse fetal environment can affect the health of offspring throughout their lifetime. Exposure to endocrine disrupting chemicals (EDCs) during fetal development can affect the hormone system homeostasis, resulting in a broad spectrum of adverse health outcomes. In the present review, we have described the effect of prenatal EDCs exposure on cardio-metabolic-renal health, using the available epidemiological and experimental evidence. We also discuss the potential mechanisms of their action, which include epigenetic changes, hormonal imprinting, loss of energy homeostasis, and metabolic perturbations. The effect of prenatal EDCs exposure on cardio-metabolic-renal health, which is a complex condition of an altered biological landscape, can be further examined in the case of other environmental stressors with a similar mode of action.

scholarly journals Revealing the Bacterial Butyrate Synthesis Pathways by Analyzing (Meta)genomic Data

mBio ◽  
2014 ◽  
Vol 5 (2) ◽  
Author(s):  
Marius Vital ◽  
Adina Chuang Howe ◽  
James M. Tiedje
Keyword(s):  
Gut Microbiota ◽  
Critical Role ◽  
Human Microbiome ◽  
Genomic Analysis ◽  
16S Rrna Gene Sequencing ◽  
Emerging Diseases ◽  
Rrna Gene ◽  
Data Set ◽  
Genome Database ◽  
Health And Disease

ABSTRACTButyrate-producing bacteria have recently gained attention, since they are important for a healthy colon and when altered contribute to emerging diseases, such as ulcerative colitis and type II diabetes. This guild is polyphyletic and cannot be accurately detected by 16S rRNA gene sequencing. Consequently, approaches targeting the terminal genes of the main butyrate-producing pathway have been developed. However, since additional pathways exist and alternative, newly recognized enzymes catalyzing the terminal reaction have been described, previous investigations are often incomplete. We undertook a broad analysis of butyrate-producing pathways and individual genes by screening 3,184 sequenced bacterial genomes from the Integrated Microbial Genome database. Genomes of 225 bacteria with a potential to produce butyrate were identified, including many previously unknown candidates. The majority of candidates belong to distinct families within theFirmicutes, but members of nine other phyla, especially fromActinobacteria,Bacteroidetes,Fusobacteria,Proteobacteria,Spirochaetes, andThermotogae, were also identified as potential butyrate producers. The established gene catalogue (3,055 entries) was used to screen for butyrate synthesis pathways in 15 metagenomes derived from stool samples of healthy individuals provided by the HMP (Human Microbiome Project) consortium. A high percentage of total genomes exhibited a butyrate-producing pathway (mean, 19.1%; range, 3.2% to 39.4%), where the acetyl-coenzyme A (CoA) pathway was the most prevalent (mean, 79.7% of all pathways), followed by the lysine pathway (mean, 11.2%). Diversity analysis for the acetyl-CoA pathway showed that the same few firmicute groups associated with severalLachnospiraceaeandRuminococcaceaewere dominating in most individuals, whereas the other pathways were associated primarily withBacteroidetes.IMPORTANCEMicrobiome research has revealed new, important roles of our gut microbiota for maintaining health, but an understanding of effects of specific microbial functions on the host is in its infancy, partly because in-depth functional microbial analyses are rare and publicly available databases are often incomplete/misannotated. In this study, we focused on production of butyrate, the main energy source for colonocytes, which plays a critical role in health and disease. We have provided a complete database of genes from major known butyrate-producing pathways, using in-depth genomic analysis of publicly available genomes, filling an important gap to accurately assess the butyrate-producing potential of complex microbial communities from “-omics”-derived data. Furthermore, a reference data set containing the abundance and diversity of butyrate synthesis pathways from the healthy gut microbiota was established through a metagenomics-based assessment. This study will help in understanding the role of butyrate producers in health and disease and may assist the development of treatments for functional dysbiosis.

scholarly journals A Mechano-Activated Cell Reporter System as a Proxy for Flow-Dependent Endothelial Atheroprotection

2018 ◽  
Vol 23 (8) ◽  
pp. 869-876
Author(s):  
Bendix R. Slegtenhorst ◽  
Oscar R. Fajardo Ramirez ◽  
Yuzhi Zhang ◽  
Zahra Dhanerawala ◽  
Stefan G. Tullius ◽  
...  
Keyword(s):  
Vascular Endothelium ◽  
Critical Role ◽  
Green Fluorescence Protein ◽  
Dependent Manner ◽  
Reporter System ◽  
Health And Disease ◽  
Fluorescence Protein ◽  
Biomechanical Stimuli ◽  
Dose Dependent

The vascular endothelium plays a critical role in the health and disease of the cardiovascular system. Importantly, biomechanical stimuli generated by blood flow and sensed by the endothelium constitute important local inputs that are translated into transcriptional programs and functional endothelial phenotypes. Pulsatile, laminar flow, characteristic of regions in the vasculature that are resistant to atherosclerosis, evokes an atheroprotective endothelial phenotype. This atheroprotective phenotype is integrated by the transcription factor Kruppel-like factor-2 (KLF2), and therefore the expression of KLF2 can be used as a proxy for endothelial atheroprotection. Here, we report the generation and characterization of a cellular KLF2 reporter system, based on green fluorescence protein (GFP) expression driven by the human KLF2 promoter. This reporter is induced selectively by an atheroprotective shear stress waveform in human endothelial cells, is regulated by endogenous signaling events, and is activated by the pharmacological inducer of KLF2, simvastatin, in a dose-dependent manner. This reporter system can now be used to probe KLF2 signaling and for the discovery of a novel chemical-biological space capable of acting as the “pharmacomimetics of atheroprotective flow” on the vascular endothelium.

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