scholarly journals The Progenetix oncogenomic resource in 2021

2021 ◽  
Author(s):  
Qingyao Huang ◽  
Paula Carrio-Cordo ◽  
Bo Gao ◽  
Rahel Paloots ◽  
Michael Baudis
Keyword(s):  
Molecular Mechanisms ◽  
Meta Analysis ◽  
Fold Increase ◽  
Data Access ◽  
Data Availability ◽  
Data Repositories ◽  
Sample Number ◽  
Genome Variations ◽  
Disease Concepts ◽  
Somatic Genome

AbstractIn cancer, copy number aberrations (CNA) represent a type of nearly ubiquitous and frequently extensive structural genome variations. To disentangle the molecular mechanisms underlying tumorigenesis as well as identify and characterize molecular subtypes, the comparative and meta-analysis of large genomic variant collections can be of immense importance. Over the last decades, cancer genomic profiling projects have resulted in a large amount of somatic genome variation profiles, however segregated in a multitude of individual studies and datasets. The Progenetix project, initiated in 2001, curates individual cancer CNA profiles and associated metadata from published oncogenomic studies and data repositories with the aim to empower integrative analyses spanning all different cancer biologies.During the last few years, the fields of genomics and cancer research have seen significant advancement in terms of molecular genetics technology, disease concepts, data standard harmonization as well as data availability, in an increasingly structured and systematic manner. For the Progenetix resource, continuous data integration, curation and maintenance have resulted in the most comprehensive representation of cancer genome CNA profiling data with 138’663 (including 115’357 tumor) CNV profiles. In this article, we report a 4.5-fold increase in sample number since 2013, improvements in data quality, ontology representation with a CNV landscape summary over 51 distinctive NCIt cancer terms as well as updates in database schemas, and data access including new web front-end and programmatic data access. Database URL:progenetix.org

scholarly journals How Are We Doing? Data Access and Replication in Political Science

2016 ◽  
Vol 49 (02) ◽  
pp. 268-272 ◽  
Author(s):  
Ellen M. Key
Keyword(s):  
Political Science ◽  
Data Access ◽  
Data Availability ◽  
Data Repositories ◽  
Institutional Data ◽  
Technological Advances ◽  
Research Transparency ◽  
The Cost ◽  
The Impact ◽  
Mandatory Provision

ABSTRACTData access and research transparency (DA-RT) is a growing concern for the discipline. Technological advances have greatly reduced the cost of sharing data, enabling full replication archives consisting of data and code to be shared on individual websites, as well as journal archives and institutional data repositories. But how do we ensure that scholars take advantage of these resources to share their replication archives? Moreover, are the costs of research transparency borne by individuals or by journals? This article assesses the impact of journal replication policies on data availability and finds that articles published in journals with mandatory provision policies are 24 times more likely to have replication materials available than articles those with no requirements.

Web-based Tools for Drug Repurposing: Successful Examples of Collaborative Research

2020 ◽  
Vol 28 (1) ◽  
pp. 181-195
Author(s):  
Quentin Vanhaelen
Keyword(s):  
User Interfaces ◽  
Collaborative Research ◽  
Meta Analysis ◽  
A Priori ◽  
Drug Repurposing ◽  
Data Access ◽  
Estimation Methods ◽  
Large Set ◽  
Computational Tools ◽  
Web Based

: Computational approaches have been proven to be complementary tools of interest in identifying potential candidates for drug repurposing. However, although the methods developed so far offer interesting opportunities and could contribute to solving issues faced by the pharmaceutical sector, they also come with their constraints. Indeed, specific challenges ranging from data access, standardization and integration to the implementation of reliable and coherent validation methods must be addressed to allow systematic use at a larger scale. In this mini-review, we cover computational tools recently developed for addressing some of these challenges. This includes specific databases providing accessibility to a large set of curated data with standardized annotations, web-based tools integrating flexible user interfaces to perform fast computational repurposing experiments and standardized datasets specifically annotated and balanced for validating new computational drug repurposing methods. Interestingly, these new databases combined with the increasing number of information about the outcomes of drug repurposing studies can be used to perform a meta-analysis to identify key properties associated with successful drug repurposing cases. This information could further be used to design estimation methods to compute a priori assessment of the repurposing possibilities.

scholarly journals Neuron-specific activation of necroptosis signaling in multiple sclerosis cortical grey matter

2021 ◽  
Vol 141 (4) ◽  
pp. 585-604 ◽  
Author(s):  
Carmen Picon ◽  
Anusha Jayaraman ◽  
Rachel James ◽  
Catriona Beck ◽  
Patricia Gallego ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Signaling Pathway ◽  
Cortical Neurons ◽  
Grey Matter ◽  
Molecular Mechanisms ◽  
Fold Increase ◽  
Cell Types ◽  
Meningeal Inflammation ◽  
Cortical Grey Matter

AbstractSustained exposure to pro-inflammatory cytokines in the leptomeninges is thought to play a major role in the pathogenetic mechanisms leading to cortical pathology in multiple sclerosis (MS). Although the molecular mechanisms underlying neurodegeneration in the grey matter remain unclear, several lines of evidence suggest a prominent role for tumour necrosis factor (TNF). Using cortical grey matter tissue blocks from post-mortem brains from 28 secondary progressive MS subjects and ten non-neurological controls, we describe an increase in expression of multiple steps in the TNF/TNF receptor 1 signaling pathway leading to necroptosis, including the key proteins TNFR1, FADD, RIPK1, RIPK3 and MLKL. Activation of this pathway was indicated by the phosphorylation of RIPK3 and MLKL and the formation of protein oligomers characteristic of necrosomes. In contrast, caspase-8 dependent apoptotic signaling was decreased. Upregulation of necroptotic signaling occurred predominantly in macroneurons in cortical layers II–III, with little expression in other cell types. The presence of activated necroptotic proteins in neurons was increased in MS cases with prominent meningeal inflammation, with a 30-fold increase in phosphoMLKL+ neurons in layers I–III. The density of phosphoMLKL+ neurons correlated inversely with age at death, age at progression and disease duration. In vivo induction of chronically elevated TNF and INFγ levels in the CSF in a rat model via lentiviral transduction in the meninges, triggered inflammation and neurodegeneration in the underlying cortical grey matter that was associated with increased neuronal expression of TNFR1 and activated necroptotic signaling proteins. Exposure of cultured primary rat cortical neurons to TNF induced necroptosis when apoptosis was inhibited. Our data suggest that neurons in the MS cortex are dying via TNF/TNFR1 stimulated necroptosis rather than apoptosis, possibly initiated in part by chronic meningeal inflammation. Neuronal necroptosis represents a pathogenetic mechanism that is amenable to therapeutic intervention at several points in the signaling pathway.

scholarly journals Expression and potential molecular mechanisms of miR‑204‑5p in breast cancer, based on bioinformatics and a meta‑analysis of 2,306�cases

2018 ◽  
Author(s):  
Kai‑Teng Cai ◽  
An‑Gui Liu ◽  
Ze‑Feng Wang ◽  
Hang‑Wei Jiang ◽  
Jing‑Jing Zeng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Meta Analysis

A novel epithelial cell from neonatal rat lung: isolation and differentiated phenotype

1990 ◽  
Vol 259 (6) ◽  
pp. L415-L425 ◽  
Author(s):  
P. E. Roberts ◽  
D. M. Phillips ◽  
J. P. Mather
Keyword(s):  
Epithelial Cell ◽  
Molecular Mechanisms ◽  
Basal Medium ◽  
Fold Increase ◽  
Cell Types ◽  
Cell Number ◽  
Neonatal Rat ◽  
Rat Lung ◽  
Cell Type

A novel epithelial cell from normal neonatal rat lung has been isolated, established, and maintained for multiple passages in the absence of serum, without undergoing crisis or senescence. By careful manipulation of the nutrition/hormonal microenvironment, we have been able to select, from a heterogeneous population, a single epithelial cell type that can maintain highly differentiated features in vitro. This cell type has characteristics of bronchiolar epithelial cells. A clonal line, RL-65, has been selected and observed for greater than 2 yr in continuous culture. It has been characterized by ultrastructural, morphological, and biochemical criteria. The basal medium for this cell line is Ham's F12/Dulbecco's modified Eagle's (DME) medium plus insulin (1 micrograms/ml), human transferrin (10 micrograms/ml), ethanolamine (10(-4) M), phosphoethanolamine (10(-4) M), selenium (2.5 x 10(-8) M), hydrocortisone (2.5 x 10(-7) M), and forskolin (5 microM). The addition of 150 micrograms/ml of bovine pituitary extract to the defined basal medium stimulates a greater than 10-fold increase in cell number and a 50- to 100-fold increase in thymidine incorporation. The addition of retinoic acid results in further enhancement of cell growth and complete inhibition of keratinization. We have demonstrated a strategy that may be applicable to isolating other cell types from the lung and maintaining their differentiated characteristics for long-term culture in vitro. Such a culture system promises to be a useful model in which to study cellular events associated with differentiation and proliferation in the lung and to better understand the molecular mechanisms involved in these events.

scholarly journals Resource-Aware Cooperative Caching on Mobile Ad-hoc Peer to Peer Networks

2021 ◽  
Author(s):  
Hoda R.K. Nejad
Keyword(s):  
Ad Hoc Networks ◽  
Overlay Networks ◽  
Ad Hoc ◽  
Data Access ◽  
Peer To Peer ◽  
Data Availability ◽  
Cooperative Caching ◽  
P2p Systems ◽  
Hoc Networks ◽  
Resource Aware

With the emergence of wireless devices, service delivery for ad-hoc networks has started to attract a lot of attention recently. Ad-hoc networks provide an attractive solution for networking in the situations where network infrastructure or service subscription is not available. We believe that overlay networks, particularly peer-to-peer (P2P) systems, is a good abstraction for application design and deployment over ad-hoc networks. The principal benefit of this approach is that application states are only maintained by the nodes involved in the application execution and all other nodes only perform networking related functions. On the other hand, data access applications in Ad-hoc networks suffer from restricted resources. In this thesis, we explore how to use Cooperative Caching to improve data access efficiency in Ad-hoc network. We propose a Resource-Aware Cooperative Caching P2P system (RACC) for data access applications in Ad-hoc networks. The objective is to improve data availability by considering energy of each node, demand and supply of network. We evaluated and compared the performance of RACC with Simple Cache, CachePath and CacheData schemes. Our simulation results show that RACC improves the lay of query as well as energy usage of the network as compared to Simple Cache, CachePath and CacheData.

scholarly journals The Brazilian cohort of pulp and paper workers: the logistic of a cancer mortality study

1998 ◽  
Vol 14 (suppl 3) ◽  
pp. S117-S123 ◽  
Author(s):  
Anaclaudia Gastal Fassa ◽  
Luiz Augusto Facchini ◽  
Marinel Mór Dall'Agnol
Keyword(s):  
Data Access ◽  
Pulp And Paper ◽  
Data Accuracy ◽  
Data Availability ◽  
International Agency ◽  
Historical Cohort ◽  
Increased Risk ◽  
Risk Of Cancer ◽  
Access Data ◽  
Brazilian Cohort

The International Agency for Research on Cancer (IARC) proposed this international historical cohort study trying to solve the controversy about the increased risk of cancer in the workers of the Pulp and Paper Industry. One of the most important aspects presented by this study in Brazil was the strategies used to overcome the methodological challenges, such as: data access, data accuracy, data availability, multiple data sources, and the large follow-up period. Through multiple strategies it was possible to build a Brazilian cohort of 3,622 workers, to follow them with a 93 percent success rate and to identify in 99 percent of the cases the cause of death. This paper, has evaluated the data access, data accuracy and the effectiveness of the strategies used and the different sources of data.

scholarly journals Increased Inflammation in Atherosclerotic Lesions of DiabeticAkita-LDLr−/−Mice Compared to NondiabeticLDLr−/−Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Daniel Engelbertsen ◽  
Fong To ◽  
Pontus Dunér ◽  
Olga Kotova ◽  
Ingrid Söderberg ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Plasma Cholesterol ◽  
Microvascular Complications ◽  
Fold Increase ◽  
Inflammatory Cells ◽  
Glucose Levels ◽  
Atherosclerotic Lesions ◽  
Blood Glucose Levels ◽  
Plaque Inflammation

Background. Diabetes is associated with increased cardiovascular disease, but the underlying cellular and molecular mechanisms are poorly understood. One proposed mechanism is that diabetes aggravates atherosclerosis by enhancing plaque inflammation. TheAkitamouse has recently been adopted as a relevant model for microvascular complications of diabetes. Here we investigate the development of atherosclerosis and inflammation in vessels ofAkitamice onLDLr−/−background.Methods and Results.Akita-LDLr−/−andLDLr−/−mice were fed high-fat diet from 6 to 24 weeks of age. Blood glucose levels were higher in both male and femaleAkita-LDLr−/−mice (137% and 70%, resp.). MaleAkita-LDLr−/−mice had markedly increased plasma cholesterol and triglyceride levels, a three-fold increase in atherosclerosis, and enhanced accumulation of macrophages and T-cells in plaques. In contrast, femaleAkita-LDLr−/−mice demonstrated a modest 29% increase in plasma cholesterol and no significant increase in triglycerides, atherosclerosis, or inflammatory cells in lesions. MaleAkita-LDLr−/−mice had increased levels of plasma IL-1βcompared to nondiabetic mice, whereas no such difference was seen between female diabetic and nondiabetic mice.Conclusion.Akita-LDLr−/−mice display considerable gender differences in the development of diabetic atherosclerosis. In addition, the increased atherosclerosis in maleAkita-LDLr−/−mice is associated with an increase in inflammatory cells in lesions.

Abstract P215: β3-Adrenergic Receptor Mediated NOS Signaling in Cardiomyocytes

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Vabren L Watts ◽  
Xiaolin Niu ◽  
Karen L Miller ◽  
Lili A Barouch
Keyword(s):  
Molecular Mechanisms ◽  
Pressure Overload ◽  
Fold Increase ◽  
Left Ventricular ◽  
Neonatal Rat ◽  
Regulatory Site ◽  
Ventricular Cardiomyocytes ◽  
Unstimulated Control ◽  
Key Factor ◽  
Nos Isoforms

Beta3 -adrenergic receptors play a pivotal role in modulating cardiac function, though their precise role in the heart remains controversial. We have recently demonstrated alterations in Ca 2+ -dependent NOS isoforms and decreased NOS activity in left ventricular tissue of beta3 -/- mice after pressure overload. However, the exact manner in which beta3-AR signaling regulates these isoforms to stimulate NOS activity at the cardiomyocyte level is not well understood. In this study we used a specific beta3-AR agonist, BRL37344 (BRL), to assess the role of beta3-AR in eNOS and nNOS regulation in hypertrophied isolated neonatal rat ventricular cardiomyocytes (NRVM). To induce hypertrophy we pretreated cells with norepinephrine for 72 hours, which resulted in a 70% increase in cell size and a 25% increase in beta3-AR mRNA expression as compared with non-hypertrophied cells, analyzed by immunocytochemistry and real-time PCR. In hypertrophied cardiomyocytes, BRL administration lead to a time-dependent 5-fold increase in NOS activity, measured by the arginine-to-citrulline conversion assay. beta3-activation also caused a 1.5-fold increase in nNOS phosphorylation at positive regulatory site Ser1416, and dephosphorylation of negative regulatory site Ser847 as compared with unstimulated control. NOS activity and nNOS phosphorylation overlapped in time. In addition BRL induced phosphorylation eNOS-Ser114, which indicates eNOS deactivation. Pretreatment with pertussis toxin (PTX) suppressed BRL-induced nNOS-Ser1416 phosphorylation, nNOS-Ser847 dephosphorylation, and NOS activity, suggesting G i/o dependency. Taken together, our data suggest that BRL regulates NOS signaling in ventricular cardiomyocytes via phosphorylation regulation of nNOS. To our knowledge this is first study to demonstrate a role for nNOS phosphorylation as a key factor in beta3-AR signaling. These results contribute significantly to our understanding the negative inotropic properties of myocardial beta3-AR at cellular levels during cardiac sympathetic overstimulation, and will ultimately aid in drug discoveries that target the molecular mechanisms associated heart failure.

Abstract P280: CCL5 Causes Vascular Injury Via CCR5 And Nadph Oxidase 1- Derived Ros

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Shubhnita Singh ◽  
Ariane Bruder Nascimento ◽  
Anita Bargaje ◽  
Thiago Bruder Nascimento
Keyword(s):  
Vascular Injury ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Vascular Inflammation ◽  
Fold Increase ◽  
Cellular Migration ◽  
Vascular Growth ◽  
Aortic Smooth Muscle ◽  
The Family ◽  
Nadph Oxidase 1

Chemokine (C-Cmotif) ligand 5 (CCL5) and its receptor CCR5 belong to the family of chemokines and are expressed and active in the vasculature. NADPH oxidases (Noxs) are the major source of reactive oxygen species (ROS) in vascular cells, but whether the activation of these oxidases is CCL5/CCR5 sensitive and whether such interaction participates in the genesis of vascular disease is not fully known. We investigated whether CCL5/CCR5 leads to vascular injury by activating Nox1. Carotid ligation model (CL, for 2-weeks) was used to induce pathological vascular growth in 10-weeks old (C57BL6/J) mice. Rat aortic smooth muscle cells (RASMC) were treated with recombinant CCL5 (100ng/mL) to study the molecular mechanisms. CL induces neointima formation, which was associated with increase in IL1β, TNFα, CCR3, CCR5 (3-fold increase), CCL5, and Nox1 gene expression. No difference was observed for Nox2 and 4. Treatment with CCR5 blocker (maraviroc, 25mg/Kg/day i.p) partially inhibited CL-induced vascular injury (media/intima ratio, CL: 1.2 ± 0.2 vs CL + maraviroc: 0.7 ± 0.2) and Nox1 expression (Fold changes: CL: 2.1 ± 0.4 vs CL + maraviroc: 1.2 ± 0.4). In RASMC, CCL5 induced Nox1 expression, which was blunted by pre-treating cells with maraviroc (10uM). Also, it increases p47phox content in membrane fraction (index of Nox activation), and elevated ROS production, analyzed by L012. CCL5 also induced cell migration, measured by transwell assay (number of cells per spot, control: 21.3 ± 3.1 vs CCL5: 31.1 ± 2.4), proliferation, analyzed by Edu+ cells (% of cells per spot, control: 10.6 ± 4.3 vs CCL5: 22.8 ± 5.1), and inflammation (studied by IL1β and TNFα levels). Lastly, CCL5 elevated NF-κB translocation into the nucleus, indicating NF-κB activation. Strikingly, inhibition of Nox1 (GKT771, 10uM), blocked CCL5-induced vascular migration, proliferation, and inflammation, as well as NF-κB activation. We propose that CCL5 activates Nox1 in the vasculature leading to local injury characterized by vascular inflammation and cellular migration and proliferation, perhaps by activating NF-κB signaling. Herein, we place CCR5 signaling as possible therapeutic target to reduce the cardiovascular risk in inflammatory diseases associated with dysregulation of CCL5 and/or CCR5

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