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The state of the art in sentiment visualization

Visualization of sentiments and opinions extracted from or annotated in texts has become a prominent topic of research over the last decade. From basic pie and bar charts used to illustrate customer reviews to extensive visual analytics systems involving novel representations, sentiment visualization techniques have evolved to deal with complex multidimensional data sets, includingtemporal, relati

Neurophysiological recovery 5 years after carpal tunnel release in patients with diabetes

Introduction: The long-term results of neurophysiological recovery after carpal tunnel release in patients with diabetes have not been studied. Methods: Thirty-five patients with diabetes and carpal tunnel syndrome (CTS) were matched with 31 patients without diabetes who had idiopathic CTS, and 27 and 30 patients, respectively, participated in this follow-up study. Nerve conduction results at 5 ye

Risk factors for incident asthma and COPD in a cohort of young adults

Introduction: The aim of the study was to describe potential shared risk factors for incident asthma and COPD in a population-based, 9-year follow-up study. Methods: From a cohort of 1191 individuals, aged 20-44, who participated in baseline survey including spirometry, bronchial challenge, and skin prick test (SPT) 742 subjects (62%) were reexamined at follow-up in 2012-2014. Results: A total of

Identification of new disease mechanisms and treatments for type 2 diabetes based on genetic variants and gene expression networks

Improved understanding of the disease mechanisms underlying type 2 diabetes (T2D) is needed, and so are new treatments.A new T2D risk variant was recently identified in ADRA2A, which encodes the α2A-adrenergic receptor. The risk allele leads to receptor overexpression in β-cells that causes increased adrenergic signaling and impaired insulin secretion. We showed that the α2A-adrenergic receptor an

Towards the Molecular Foundations of Glutamatergic-targeted Antidepressants

BACKGROUND: Depression affects over 120 million individuals of all ages and is the leading cause of disability worldwide. The lack of objective diagnostic criteria, together with the heterogeneity of the depressive disorder itself, makes it challenging to develop effective therapies. The accumulation of preclinical data over the past 20 years derived from a multitude of models using many divergent

CK2 activity is required for the interaction of FGF14 with voltage-gated sodium channels and neuronal excitability

Recent data shows that fibroblast growth factor 14 (FGF14) binds to and controls the function of the voltage-gated sodium (Nav) channel with phenotypic outcomes on neuronal excitability. Mutations in the FGF14 gene in humans have been associated with brain disorders that are partially recapitulated in Fgf14(-/-) mice. Thus, signaling pathways that modulate the FGF14:Nav channel interaction may be

Inorganic Arsenic-Related Changes in the Stromal Tumor Microenvironment in a Prostate Cancer Cell-Conditioned Media Model

BACKGROUND: The tumor microenvironment plays an important role in the progression of cancer by mediating stromal-epithelial paracrine signaling, which can aberrantly modulate cellular proliferation and tumorigenesis. Exposure to environmental toxicants, such as inorganic arsenic (iAs), has also been implicated in the progression of prostate cancer.OBJECTIVE: The role of iAs exposure in stromal sig

Integrated Transcriptomic and Glycomic Profiling of Glioma Stem Cell Xenografts

Bone marrow-derived human mesenchymal stem cells (BM-hMSCs) have the innate ability to migrate or home toward and engraft in tumors such as glioblastoma (GBM). Because of this unique property of BM-hMSCs, we have explored their use for cell-mediated therapeutic delivery for the advancement of GBM treatment. Extravasation, the process by which blood-borne cells—such as BM-hMSCs—enter the tissue, is

ESI-MS/MS and MALDI-IMS Localization Reveal Alterations in Phosphatidic Acid, Diacylglycerol, and DHA in Glioma Stem Cell Xenografts

Glioblastoma (GBM) is the most common adult primary brain tumor. Despite aggressive multimodal therapy, the survival of patients with GBM remains dismal. However, recent evidence has demonstrated the promise of bone marrow-derived mesenchymal stem cells (BM-hMSCs) as a therapeutic delivery vehicle for anti-glioma agents due to their ability to migrate or home to human gliomas. While several studie

Quantitative proteomics reveals protein-protein interactions with fibroblast growth factor 12 as a component of the voltage-gated sodium channel 1.2 (nav1.2) macromolecular complex in Mammalian brain

Voltage-gated sodium channels (Nav1.1-Nav1.9) are responsible for the initiation and propagation of action potentials in neurons, controlling firing patterns, synaptic transmission and plasticity of the brain circuit. Yet, it is the protein-protein interactions of the macromolecular complex that exert diverse modulatory actions on the channel, dictating its ultimate functional outcome. Despite the

The Nav1.2 channel is regulated by GSK3

BACKGROUND: Phosphorylation plays an essential role in regulating voltage-gated sodium (Na(v)) channels and excitability. Yet, a surprisingly limited number of kinases have been identified as regulators of Na(v) channels. We posited that glycogen synthase kinase 3 (GSK3), a critical kinase found associated with numerous brain disorders, might directly regulate neuronal Na(v) channels.METHODS: We u

Data analysis techniques in phosphoproteomics

The interpretation of phosphoproteomics data sets is crucial for generating hypotheses that guide therapeutic solutions, yet not many techniques have been applied to this type of analysis. This paper intends to give an overview about the two main standard techniques that can be applied to the analysis of these large scale data sets. These are data-driven or exploratory techniques based on a statis

Role of the axonal initial segment in psychiatric disorders : function, dysfunction, and intervention

The progress of developing effective interventions against psychiatric disorders has been limited due to a lack of understanding of the underlying cellular and functional mechanisms. Recent research findings focused on exploring novel causes of psychiatric disorders have highlighted the importance of the axonal initial segment (AIS), a highly specialized neuronal structure critical for spike initi

A modified database search strategy leads to improved identification of in vitro brominated peptides spiked into a complex proteomic sample

Inflammation leads to activation of immune cells, resulting in production of hypobromous acid. Few investigations have been performed on protein bromination on a proteomic scale, even though bromination is a relatively abundant protein modification in endogenously brominated proteomes. Such studies have been hampered by the lack of an optimized database search strategy. In order to address this is

Integrative biological analysis for neuropsychopharmacology

Although advances in psychotherapy have been made in recent years, drug discovery for brain diseases such as schizophrenia and mood disorders has stagnated. The need for new biomarkers and validated therapeutic targets in the field of neuropsychopharmacology is widely unmet. The brain is the most complex part of human anatomy from the standpoint of number and types of cells, their interconnections

Identification of Cys255 in HIF-1α as a novel site for development of covalent inhibitors of HIF-1α/ARNT PasB domain protein-protein interaction

The heterodimer HIF-1α (hypoxia inducible factor)/HIF-β (also known as ARNT-aryl hydrocarbon nuclear translocator) is a key mediator of cellular response to hypoxia. The interaction between these monomer units can be modified by the action of small molecules in the binding interface between their C-terminal heterodimerization (PasB) domains. Taking advantage of the presence of several cysteine res

Discovery of a novel B-Raf fusion protein related to c-Met drug resistance

In recent years, there have been notable advances with the development of anticancer drugs including those targeting protein tyrosine kinases such as the c-Met receptor, which has been implicated in the development and progression of several cancers. However, despite such progress, drug resistance continues to be the single most important cause of cancer treatment failure, and understanding the me