Cooperative insulation of regulatory domains by CTCF-dependent physical insulation and promoter competition.

The specificity of gene expression during development requires the insulation of regulatory domains to avoid inappropriate enhancer-gene interactions. In vertebrates, this insulator function is mostly attributed to clusters of CTCF sites located at topologically associating domain (TAD) boundaries. However, TAD boundaries allow some physical crosstalk across regulatory domains, which is at odds with the specific and precise expression of developmental genes.

Untangling the mess of CGRP levels as a migraine biomarker: an in-depth literature review and analysis of our experimental experience.

Background: Calcitonin gene-related peptide (CGRP) is the most promising candidate to become the first migraine biomarker. However, literature shows clashing results and suggests a methodological source for such discrepancies. We aimed to investigate some of these methodological factors to evaluate the actual role of CGRP as biomarker.

Inhibition of pro-inflammatory signaling in human primary macrophages by enhancing arginase-2 via target site blockers.

The modulation of macrophage phenotype from a pro-inflammatory to an anti-inflammatory state holds therapeutic potential in the treatment of inflammatory disease. We have previously shown that arginase-2 (Arg2), a mitochondrial enzyme, is a key regulator of the macrophage anti-inflammatory response. Here, we investigate the therapeutic potential of Arg2 enhancement via target site blockers (TSBs) in human macrophages.

miRNA Signature in CSF From Patients With Primary Progressive Multiple Sclerosis.

Background And Objectives: Primary progressive multiple sclerosis (PPMS) displays a highly variable disease progression with a characteristic accumulation of disability, what makes difficult its diagnosis and efficient treatment. The identification of microRNAs (miRNAs)-based signature for the early detection in biological fluids could reveal promising biomarkers to provide new insights into defining MS clinical subtypes and potential therapeutic strategies. The objective of this cross-sectional study was to describe PPMS miRNA profiles in CSF and serum samples compared with other neurologic disease individuals (OND) and relapsing-remitting MS (RRMS).

Assessing the presence of oligoclonal IgM bands as a prognostic biomarker of cognitive decline in the early stages of multiple sclerosis.

Background: An association has been found between the presence of lipid-specific oligoclonal IgM bands (LS-OCMB) in cerebrospinal fluid and a more severe clinical multiple sclerosis course.

Objective: To investigate lipid-specific oligoclonal IgM bands as a prognostic biomarker of cognitive impairment in the early stages of multiple sclerosis.

Methods: Forty-four patients underwent neuropsychological assessment at baseline and 4 years.

Description of a CSF-Enriched miRNA Panel for the Study of Neurological Diseases.

Background: The study of circulating miRNAs in CSF has gained tremendous attention during the last years, as these molecules might be promising candidates to be used as biomarkers and provide new insights into the disease pathology of neurological disorders.

Objective: The main aim of this study was to describe an OpenArray panel of CSF-enriched miRNAs to offer a suitable tool to identify and characterize new molecular signatures in different neurological diseases.

Methods: Two hundred and fifteen human miRNAs were selected to be included in the panel, and their expression and abundance in CSF samples were analyzed.

Orphan CpG islands amplify poised enhancer regulatory activity and determine target gene responsiveness.

CpG islands (CGIs) represent a widespread feature of vertebrate genomes, being associated with ~70% of all gene promoters. CGIs control transcription initiation by conferring nearby promoters with unique chromatin properties. In addition, there are thousands of distal or orphan CGIs (oCGIs) whose functional relevance is barely known.

Radiologically isolated syndrome: targeting miRNAs as prognostic biomarkers.

Some clinical and biological characteristics have been described as prognostic factors for clinical conversion into clinically definite multiple sclerosis in radiologically isolated syndrome (RIS) population. The aim of this study was to assess signatures of circulating miRNAs in those patients according to their conversion status after 5 years of follow-up. OpenArray plates assessing 216 miRNA candidates were run in 15 RIS patients, and their relative abundances were analyzed.

Analysis of miRNA signatures in CSF identifies upregulation of miR-21 and miR-146a/b in patients with multiple sclerosis and active lesions.

Background: MicroRNAs (miRNAs) have been reported as deregulated in active brain lesions derived from patients with multiple sclerosis (MS). In there, these post-transcriptional regulators may elicit very important effects but proper identification of miRNA candidates as potential biomarkers and/or therapeutic targets is scarcely available.

Objective: The aim of the study was to detect the presence of a set of candidate miRNAs in cell-free cerebrospinal fluid (CSF) and to determine their association with gadolinium-enhancing (Gd+) lesions in order to assess their value as biomarkers of MS activity.

BRCA1 haploinsufficiency cell-autonomously activates RANKL expression and generates denosumab-responsive breast cancer-initiating cells.

Denosumab, a monoclonal antibody to the receptor activator of nuclear factor-κB ligand (RANKL), might be a novel preventative therapy for BRCA1-mutation carriers at high risk of developing breast cancer. Beyond its well-recognized bone-targeted activity impeding osteoclastogenesis, denosumab has been proposed to interfere with the cross-talk between RANKL-producing sensor cells and cancer-initiating RANK+ responder cells that reside within premalignant tissues of BRCA1-mutation carriers. We herein tested the alternative but not mutually exclusive hypothesis that BRCA1 deficiency might cell-autonomously activate RANKL expression to generate cellular states with cancer stem cell (CSC)-like properties.