424 results match your criteria: "Institute of Genetics and Biophysics "Adriano Buzzati-Traverso"[Affiliation]"
Clin Epigenetics
May 2022
Department of Environmental Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), Università Degli Studi Della Campania "Luigi Vanvitelli", Caserta, Italy.
Background: Beckwith-Wiedemann syndrome (BWS) and Pseudohypoparathyroidism type 1B (PHP1B) are imprinting disorders (ID) caused by deregulation of the imprinted gene clusters located at 11p15.5 and 20q13.32, respectively.
View Article and Find Full Text PDFLife (Basel)
May 2022
IRCCS Neuromed, Località Camerelle, 86077 Pozzilli, Italy.
The mitochondrial uncoupling protein 2 (UCP2) acts as an anion transporter and as an antioxidant factor able to reduce the reactive oxygen species level. Based on its effects, UCP2 prevents the membrane lipids, proteins, and DNA damage while preserving normal cellular functions. Many variants have been identified within the human .
View Article and Find Full Text PDFFront Cell Dev Biol
April 2022
Institute of Genetics and Biophysics "Adriano Buzzati-Traverso", National Research Council, Naples, Italy.
Cancers (Basel)
April 2022
Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE), Tampere University, 33100 Tampere, Finland.
Despite remarkable efforts of computational and predictive pharmacology to improve therapeutic strategies for complex diseases, only in a few cases have the predictions been eventually employed in the clinics. One of the reasons behind this drawback is that current predictive approaches are based only on the integration of molecular perturbation of a certain disease with drug sensitivity signatures, neglecting intrinsic properties of the drugs. Here we integrate mechanistic and chemocentric approaches to drug repositioning by developing an innovative network pharmacology strategy.
View Article and Find Full Text PDFInt J Mol Sci
March 2022
Institute of Genetics and Biophysics "Adriano Buzzati-Traverso", National Research Council (CNR), 80131 Naples, Italy.
The X-linked gene encoding aristaless-related homeobox () is a bi-functional transcription factor capable of activating or repressing gene transcription, whose mutations have been found in a wide spectrum of neurodevelopmental disorders (NDDs); these include cortical malformations, paediatric epilepsy, intellectual disability (ID) and autism. In addition to point mutations, duplications of the locus have been detected in male patients with ID. These rearrangements include telencephalon ultraconserved enhancers, whose structural alterations can interfere with the control of expression in the developing brain.
View Article and Find Full Text PDFBiomolecules
March 2022
Institute of Biochemistry and Cell Biology, National Research Council of Italy, Via P. Castellino 111, 80131 Naples, Italy.
Cellular functions are regulated through the gene expression program by the transcription of new messenger RNAs (mRNAs), alternative RNA splicing, and protein synthesis. To this end, the post-translational modifications (PTMs) of proteins add another layer of complexity, creating a continuously fine-tuned regulatory network. ADP-ribosylation (ADPr) is an ancient reversible modification of cellular macromolecules, regulating a multitude of key functional processes as diverse as DNA damage repair (DDR), transcriptional regulation, intracellular transport, immune and stress responses, and cell survival.
View Article and Find Full Text PDFCancers (Basel)
March 2022
Institute of Genetics and Biophysics "Adriano Buzzati Traverso", Consiglio Nazionale dele Ricerche (CNR), 80131 Naples, Italy.
The genetic and epigenetic changes affecting transcription factors, coactivators, and chromatin modifiers are key determinants of the hallmarks of cancer. The acquired dependence on oncogenic transcriptional regulators, representing a major determinant of cancer cell vulnerability, points to transcription factors as ideal therapeutic targets. However, given the unavailability of catalytic activities or binding pockets for small-molecule inhibitors, transcription factors are generally regarded as undruggable proteins.
View Article and Find Full Text PDFRev Neurosci
October 2022
Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy.
In a million years, under the pressure of natural selection, hominins have acquired the abilities for vocal learning, music, and language. Music is a relevant human activity, highly effective in enhancing sociality, is a universal experience common to all known human cultures, although it varies in rhythmic and melodic complexity. It has been part of human life since the beginning of our history, or almost, and it strengthens the mother-baby relation even within the mother's womb.
View Article and Find Full Text PDFClin Epigenetics
March 2022
Department of Clinical Genetics, Kennedy Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Background: Imprinting disorders are a group of congenital diseases which are characterized by molecular alterations affecting differentially methylated regions (DMRs). To date, at least twelve imprinting disorders have been defined with overlapping but variable clinical features including growth and metabolic disturbances, cognitive dysfunction, abdominal wall defects and asymmetry. In general, a single specific DMR is affected in an individual with a given imprinting disorder, but there are a growing number of reports on individuals with so-called multilocus imprinting disturbances (MLID), where aberrant imprinting marks (most commonly loss of methylation) occur at multiple DMRs.
View Article and Find Full Text PDFBMC Mol Cell Biol
March 2022
Department of Medical-Surgical Sciences and Biotechnologies, University of Rome La Sapienza, Corso della Repubblica 79, 04100, Latina, Italy.
Background: The nucleolus is a subnuclear, non-membrane bound domain that is the hub of ribosome biogenesis and a critical regulator of cell homeostasis. Rapid growth and division of cells in tumors are correlated with intensive nucleolar metabolism as a response to oncogenic factors overexpression. Several members of the Epidermal Growth Factor Receptor (EGFR) family, have been identified in the nucleus and nucleolus of many cancer cells, but their function in these compartments remains unexplored.
View Article and Find Full Text PDFPharmaceuticals (Basel)
January 2022
Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy.
Autism spectrum disorders (ASD) are a group of heterogeneous neurodevelopmental conditions characterized by social deficits, repetitive stereotyped behaviors, and altered inflammatory responses. Accordingly, children with ASD show decreased plasma levels of lipoxin A4 (LXA4), a mediator involved in the resolution of inflammation, which is the endogenous ligand of the formyl peptide receptor 2 (FPR2). To investigate the role of FPR2 in ASDs, we have used a new ureidopropanamide derivative able to activate the receptor, named MR-39.
View Article and Find Full Text PDFInt J Mol Sci
January 2022
Institute of Genetics and Biophysics "Adriano Buzzati-Traverso", IGB-CNR, Via P. Castellino, 111, 80131 Naples, Italy.
De novo somatic mutations are well documented in diseases such as neoplasia but are rarely reported in rare diseases. Hovewer, severe genetic diseases that are not compatible with embryonic development are caused exclusively by deleterious mutations that could only be found as mosaic and not as inherited mutations. We will review here the paradigmatic case of Incontinentia Pigmenti, a rare X-linked dominant disease caused by deficiency of the NEMO (also called IKKgamma) protein, which plays a pivotal role in tissue homeostasis.
View Article and Find Full Text PDFACS Chem Neurosci
February 2022
Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, via Orabona 4, 70125 Bari, Italy.
During the last decade, the kinetics of drug-target interaction has received increasing attention as an important pharmacological parameter in the drug development process. Several studies have suggested that the lipophilicity of a molecule can play an important role. To date, this aspect has been studied for several G protein-coupled receptors (GPCRs) ligands but not for the 5-HT receptor (5-HTR), a GPCR proposed as a valid therapeutic target in neurodevelopmental and neuropsychiatric disorders associated with abnormal neuronal connectivity.
View Article and Find Full Text PDFHum Mol Genet
June 2022
Institute of Genetics and Biophysics ``Adriano Buzzati-Traverso'', National Research Council of Italy, 80131, Naples, Italy.
X-linked lissencephaly with abnormal genitalia (XLAG) and developmental epileptic encephalopathy-1 (DEE1) are caused by mutations in the Aristaless-related homeobox (ARX) gene, which encodes a transcription factor responsible for brain development. It has been unknown whether the phenotypically diverse XLAG and DEE1 phenotypes may converge on shared pathways. To address this question, a label-free quantitative proteomic approach was applied to the neonatal brain of Arx knockout (ArxKO/Y) and knock-in polyalanine (Arx(GCG)7/Y) mice that are respectively models for XLAG and DEE1.
View Article and Find Full Text PDFHortic Res
January 2022
Institute of Biosciences and Bioresources, National Research Council of Italy, Via Universita` 133, 80055 Portici, Italy.
In this study we investigated the transcriptome and epigenome dynamics of the tomato fruit during post-harvest in a landrace belonging to a group of tomatoes (Solanum lycopersicum L.) collectively known as "Piennolo del Vesuvio", all characterized by a long shelf-life. Expression of protein-coding genes and microRNAs as well as DNA methylation patterns and histone modifications were analysed in distinct post-harvest phases.
View Article and Find Full Text PDFCells
December 2021
Institute of Genetics and Biophysics ''Adriano Buzzati-Traverso'', CNR, Via P. Castellino 111, 80131 Naples, Italy.
Low-grade chronic inflammation and reduced differentiation capacity are hallmarks of hypertrophic adipose tissue (AT) and key contributors of insulin resistance. We identified PPARGΔ5 as a dominant-negative splicing isoform overexpressed in the AT of obese/diabetic patients able to impair adipocyte differentiation and PPARγ activity in hypertrophic adipocytes. Herein, we investigate the impact of macrophage-secreted pro-inflammatory factors on splicing, focusing on PPARGΔ5.
View Article and Find Full Text PDFEpigenomes
November 2020
Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso', CNR, 80131 Naples, Italy.
The epigenome refers to the entirety of DNA methylations, histone modifications, nucleosome occupancy, and coding and non-coding RNAs (and their modifications) in different cell types [...
View Article and Find Full Text PDFNature
December 2021
Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, MI, USA.
Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels, heart disease remains the leading cause of death worldwide. Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease.
View Article and Find Full Text PDFBiomedicines
October 2021
Institute of Genetics and Biophysics "Adriano Buzzati Traverso", National Research Council, 80131 Naples, Italy.
An insertion or deletion of a nucleotide (nt) in the penultimate or the last exon can result in a frameshift and premature termination codon (PTC), giving rise to an unstable protein variant, showing a dominant phenotype. We described two α-globin mutants created by the deletion of a nucleotide in the penultimate or the last exon of the α1-globin gene: the or α1 cod95 (-C), causing a frameshift resulting in a PTC at codon 102, and the or α1 cod109 (-C), causing a frameshift and formation of a PTC at codon 133. The carriers showed α-thalassemia alterations (mild microcytosis with normal Hb A2) and lacked hemoglobin variants.
View Article and Find Full Text PDFSci Rep
October 2021
Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lübeck, Via Luigi Galvani 31, 39100, Bozen/Bolzano, Italy.
Levodopa is the standard long-term dopamine replacement therapy to treat Parkinson's disease (PD) symptoms. With time, levodopa may induce debilitating dyskinesias (LID), the treatment of which represents a large clinically unmet need. However, time-to-LID onset varies between patients, reflecting a possible genetic component.
View Article and Find Full Text PDFFront Mol Neurosci
September 2021
Department of Chemistry and Biology, "Adolfo Zambelli", University of Salerno, Fisciano, Italy.
Objectives: mutant mice are a widely used model of 22q11.2 deletion syndrome (22q11.2DS) because they manifest a broad spectrum of physical and behavioral abnormalities that is similar to that found in 22q11.
View Article and Find Full Text PDFGenes (Basel)
July 2021
Institute of Genetics and Biophysics Adriano Buzzati-Traverso, CNR, 80131 Naples, Italy.
Dysregulation of transcriptional pathways is observed in multiple forms of neurodevelopmental disorders (NDDs), such as intellectual disability (ID), epilepsy and autism spectrum disorder (ASD). We previously demonstrated that the NDD genes encoding lysine-specific demethylase 5C () and its transcriptional regulators Aristaless related-homeobox (ARX), PHD Finger Protein 8 (PHF8) and Zinc Finger Protein 711 () are functionally connected. Here, we show their relation to each other with respect to the expression levels in human and mouse datasets and in vivo mouse analysis indicating that the coexpression of these syntenic X-chromosomal genes is temporally regulated in brain areas and cellular sub-types.
View Article and Find Full Text PDFMethods Mol Biol
January 2022
Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso', Consiglio Nazionale delle Ricerche (CNR), Naples, Italy.
The engagement of TNF on TNFR can result in cell survival or cell death depending on the different complex formation downstream this interaction. Here we describe reagents and assay procedures that can be used to study caspase-independent cell death (necroptosis) in cultured cells, in response to pharmacological interventions with NF-kappaB and death inhibitors. We provide protocol to detect death-specific proteins using immunoblot and to dissect necrosome complex by sequential co-immunoprecipitation of death-specific components during necroptosis.
View Article and Find Full Text PDFSci Rep
July 2021
Department of Environmental Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), Università degli Studi della Campania "Luigi Vanvitelli", 81100, Caserta, Italy.
ZFP57 is required to maintain the germline-marked differential methylation at imprinting control regions (ICRs) in mouse embryonic stem cells (ESCs). Although DNA methylation has a key role in genomic imprinting, several imprinted genes are controlled by different mechanisms, and a comprehensive study of the relationship between DMR methylation and imprinted gene expression is lacking. To address the latter issue, we differentiated wild-type and Zfp57 hybrid mouse ESCs into neural precursor cells (NPCs) and evaluated allelic expression of imprinted genes.
View Article and Find Full Text PDFMol Neurodegener
June 2021
IRCCS Istituto Neurologico Mediterraneo Neuromed, Pozzilli, Isernia, Italy.
Background: Parkinson's disease (PD) is a neurodegenerative movement disorder affecting 1-5% of the general population for which neither effective cure nor early diagnostic tools are available that could tackle the pathology in the early phase. Here we report a multi-stage procedure to identify candidate genes likely involved in the etiopathogenesis of PD.
Methods: The study includes a discovery stage based on the analysis of whole exome data from 26 dominant late onset PD families, a validation analysis performed on 1542 independent PD patients and 706 controls from different cohorts and the assessment of polygenic variants load in the Italian cohort (394 unrelated patients and 203 controls).