324 results match your criteria: "Institute of Genetics and Biophysics "Adriano Buzzati Traverso" CNR[Affiliation]"

Transcriptional regulation is a critical biological process that allows the cell or an organism to respond to a variety of intra- and extra-cellular signals, to define cell identity during development, to maintain it throughout its lifetime, and to coordinate cellular activity [...

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rearrangements as well as and mutations drive differential pathway activation in papillary thyroid carcinomas, leading to different tumor phenotypes and prognoses. Although The Cancer Genome Atlas Consortium has identified tumor subgroups based on protein-coding gene signatures, neither expression of long noncoding RNAs (lncRNA) nor their correlation with specific tumor-driving mutations and rearrangements have been systematically assessed. Here, we reanalyzed our RNA-sequencing data using a discovery approach to identify lncRNAs and define tumor subtype-specific signatures of annotated lncRNAs.

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Article Synopsis
  • The text refers to a correction made to a previously published article with the DOI: 10.1038/s42003-018-0226-0.
  • The correction is likely important for ensuring the accuracy and integrity of the research findings presented in the original article.
  • Readers are encouraged to check the corrected version for updated information that may affect the conclusions or interpretations of the study.
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Background And Purpose: Alzheimer's disease (AD) is a common neurodegenerative disease characterized by a neuroinflammatory state, and to date, there is no cure and its treatment represents a large unmet clinical need. The involvement of Th17 cells in the pathogenesis of AD-related neuroinflammation has been reported in several studies. However, the role of the cytokine, IL-17 has not been well addressed.

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Incontinentia pigmenti (Bloch-Sulzberger syndrome) is a rare neuroectodermal dysplasia. It is an X-linked dominant disorder caused by mutations in the IKBKG/NEMO gene on Xq28. Approximately 80% of patients have a deletion of exons 4 to 10.

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Genomic imprinting disorders: lessons on how genome, epigenome and environment interact.

Nat Rev Genet

April 2019

Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', Caserta; Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso' CNR, Napoli, Italy.

Genomic imprinting, the monoallelic and parent-of-origin-dependent expression of a subset of genes, is required for normal development, and its disruption leads to human disease. Imprinting defects can involve isolated or multilocus epigenetic changes that may have no evident genetic cause, or imprinting disruption can be traced back to alterations of cis-acting elements or trans-acting factors that control the establishment, maintenance and erasure of germline epigenetic imprints. Recent insights into the dynamics of the epigenome, including the effect of environmental factors, suggest that the developmental outcomes and heritability of imprinting disorders are influenced by interactions between the genome, the epigenome and the environment in germ cells and early embryos.

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Article Synopsis
  • Advances in next generation sequencing have made it easier to study genetics, but understanding genetic causes of eye diseases is still tough due to cost and limited access to human genetic data.
  • The International Mouse Phenotyping Consortium conducted a study evaluating 4,364 genes and found that 347 of them affect eye traits, with 75% being previously unknown in eye disease research.
  • This significant increase in known genes related to eye conditions could have future implications for understanding eye development and diseases in humans.
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DNA methylation plays important roles in gene expression regulation and chromatin structure. Its proper establishment and maintenance are essential for mammalian development and cellular differentiation. DNMT3B is the major DNA methyltransferase expressed and active during the early stage of embryonic development, including implantation.

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Peroxisome-proliferator-activated receptor γ (PPARγ) regulates glucose and lipid homeostasis, insulin signaling, and adipocyte differentiation. Here, we report the skipping of exon 5 as a legitimate splicing event generating PPARγΔ5, a previously unidentified naturally occurring truncated isoform of PPARγ, which lacks the entire ligand-binding domain. PPARγΔ5 is endogenously expressed in human adipose tissue and, during adipocyte differentiation, lacks ligand-dependent transactivation ability and acts as a dominant-negative isoform reducing PPARγ activity.

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The PR/SET domain gene family (PRDM) encodes 19 different transcription factors that share a subtype of the SET domain [Su(var)3-9, enhancer-of-zeste and trithorax] known as the PRDF1-RIZ (PR) homology domain. This domain, with its potential methyltransferase activity, is followed by a variable number of zinc-finger motifs, which likely mediate protein⁻protein, protein⁻RNA, or protein⁻DNA interactions. Intriguingly, almost all PRDM family members express different isoforms, which likely play opposite roles in oncogenesis.

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Elevated serum urate levels can cause gout, an excruciating disease with suboptimal treatment. Previous GWAS identified common variants with modest effects on serum urate. Here we report large-scale whole-exome sequencing association studies of serum urate and kidney function among ≤19,517 European ancestry and African-American individuals.

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OTX2 restricts entry to the mouse germline.

Nature

October 2018

MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh, EH16 4UU, Scotland.

The successful segregation of germ cells from somatic lineages is vital for sexual reproduction and species survival. In the mouse, primordial germ cells (PGCs), precursors of all germ cells, are induced from the post-implantation epiblast. Induction requires BMP4 signalling to prospective PGCs and the intrinsic action of PGC transcription factors.

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Establishment of stable iPS-derived human neural stem cell lines suitable for cell therapies.

Cell Death Dis

September 2018

Cellular Reprogramming Unit, IRCCS Casa Sollievo della Sofferenza, Viale dei Cappuccini, 71013, San Giovanni Rotondo, Foggia, Italy.

Establishing specific cell lineages from human induced pluripotent stem cells (hiPSCs) is vital for cell therapy approaches in regenerative medicine, particularly for neurodegenerative disorders. While neural precursors have been induced from hiPSCs, the establishment of hiPSC-derived human neural stem cells (hiNSCs), with characteristics that match foetal hNSCs and abide by cGMP standards, thus allowing clinical applications, has not been described. We generated hiNSCs by a virus-free technique, whose properties recapitulate those of the clinical-grade hNSCs successfully used in an Amyotrophic Lateral Sclerosis (ALS) phase I clinical trial.

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The Beckwith-Wiedemann syndrome is the most common genetic entity in overgrowth, with an approximate incidence of 1 in 10 00013 700births. Its broad clinical spectrum includes pre- and postnatal macrosomia, macroglossia, pinna abnormalities, abdominal wall defects, visceromegaly, and hyperinsulinemic hypoglycemia. This syndrome predisposes to childhood cancer and is caused by diverse genetic and/or epigenetic disorders that usually affect the regulation of genes imprinted on chromosome 11p15.

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Sphingosine 1-phosphate (S1P) has a role in many cellular processes. S1P is involved in cell growth and apoptosis, regulation of cell trafficking, production of cytokines and chemokines. The kinases SphK1 and SphK2 (SphKs) phosphorilate Sphingosine (Sph) to S1P and several phosphatases revert S1P to sphingosine, thus assuring a balanced pool that can be depleted by a Sphingosine lyase in hexadecenal compounds and aldehydes.

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The gene is haploinsufficient in 22q11.2 deletion syndrome (22q11.2DS), and genetic evidence from human patients and mouse models points to a major role of this gene in the pathogenesis of this syndrome.

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Novel spiroindoline HDAC inhibitors: Synthesis, molecular modelling and biological studies.

Eur J Med Chem

September 2018

European Research Centre for Drug Discovery and Development (NatSynDrugs) and Department of Biotechnology, Chemistry, and Pharmacy, Department of Excellence 2018-2022, University of Siena, via Aldo Moro 2, 53100, Siena, Italy.

This paper describes the rational development of a series of novel spiroindoline derivatives endowed with selective inhibitory activity on the HDAC6 isoform. A convenient multicomponent one-pot protocol was applied for the assembly of the desired N1-substituted spiroindoline core which allowed a straightforward analoging. Computational studies and in vitro determination of inhibitory potency for the developed compounds against HDAC6 and HDAC1 isoforms were flanked by cell-based studies on histone H3 and α-tubulin acetylation.

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Placental growth factor (PlGF) is a proangiogenic member of the vascular endothelial growth factor (VEGF) family playing a central role in pathological angiogenesis. PlGF-DE is a PlGF variant unable to bind vascular endothelial growth factor receptor 1 (VEGFR-1) but still able to generate heterodimer with VEGF-A. We have generated PlGF-DE knockin mice that are vital and fertile and show unaltered expression of Plgf, Vegf-a, Vegfr-1, and Vegfr-2 compared with wild-type mice.

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Human PRDM2: Structure, function and pathophysiology.

Biochim Biophys Acta Gene Regul Mech

June 2018

Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy. Electronic address:

PRDM2/RIZ is a member of a superfamily of histone/protein methyltransferases (PRDMs), which are characterized by the conserved N-terminal PR domain, with methyltransferase activity and zinc finger arrays at the C-terminus. Similar to other family members, two main protein types, known as RIZ1 and RIZ2, are produced from the PRDM2 locus differing by the presence or absence of the PR domain. The imbalance in their respective amounts may be an important cause of malignancy, with the PR-positive isoform commonly lost or downregulated and the PR-negative isoform always being present at higher levels in cancer cells.

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Folding mechanisms steer the amyloid fibril formation propensity of highly homologous proteins.

Chem Sci

April 2018

Department of Environmental, Biological and Pharmaceutical Sciences and Technologies , University of Campania "Luigi Vanvitelli", Via Vivaldi 43 , 81100 Caserta , Italy . Email:

Significant advances in the understanding of the molecular determinants of fibrillogenesis can be expected from comparative studies of the aggregation propensities of proteins with highly homologous structures but different folding pathways. Here, we fully characterize, by means of stopped-flow, T-jump, CD and DSC experiments, the unfolding mechanisms of three highly homologous proteins, zinc binding Ros87 and Ml1 and zinc-lacking Ml4. The results indicate that the three proteins significantly differ in terms of stability and (un)folding mechanisms.

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Article Synopsis
  • Giant Cell Tumour of Bone (GCT) is a kind of bone cancer that often comes back and usually appears in long bones, but very few cases happen in a part of the skull called the Clivus.
  • Researchers studied two rare cases of Clival GCT to see if they had the same genetic changes as GCTs found in long bones.
  • They found a specific mutation in the patients’ genes that confirms Clival GCT is similar to other GCTs, which could help doctors use known treatments for bone GCTs to treat these rare cases.
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Article Synopsis
  • The differentiation of dopaminergic neurons involves a crucial interaction between morphogens and transcription factors within a specific timeframe, with little known about microRNA's impact.
  • A microarray screening identified miR-34b/c as significantly upregulated during this differentiation, where it influences Wnt1 expression and promotes the transition of cells from the cycle, leading to increased dopaminergic neuron production.
  • Combining miR-34b/c with transcription factors ASCL1 and NURR1 effectively doubled the conversion of fibroblasts to dopaminergic neurons, which displayed dopamine synthesis and electrical activity similar to natural brain neurons, suggesting a promising avenue for improved neuronal generation in lab settings.
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Effect of nutrient deprivation on the expression and the epigenetic signature of sirtuin genes.

Nutr Metab Cardiovasc Dis

April 2018

Department of Sciences and Technologies, University of Sannio, Benevento, Italy. Electronic address:

Background And Aim: Over the last decades advances in understanding the molecular bases of the close relationship between nutrition, metabolism, and diseases have been impressive. However, there are always novel frontiers coming up and epigenetics is one of these. Sirtuins, are pivotal factors in the control of metabolic pathways according to nutrient availability.

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Successful long-term therapy with flecainide in a family with paramyotonia congenita.

J Neurol Neurosurg Psychiatry

November 2018

Department of Medicine, Surgery, Neurology, Metabolic and Aging Science, Reference Center for Neurological and Neuromuscular Rare Disease, Università degli Studi della Campania Luigi Vanvitelli, Napoli, Campania, Italy.

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Tissue-specific and mosaic imprinting defects underlie opposite congenital growth disorders in mice.

PLoS Genet

February 2018

Department of Environmental Technologies, Biological and Pharmaceutical Sciences, University of Campania, "Luigi Vanvitelli", Naples, Italy.

Differential DNA methylation defects of H19/IGF2 are associated with congenital growth disorders characterized by opposite clinical pictures. Due to structural differences between human and mouse, the mechanisms by which mutations of the H19/IGF2 Imprinting Control region (IC1) result in these diseases are undefined. To address this issue, we previously generated a mouse line carrying a humanized IC1 (hIC1) and now replaced the wildtype with a mutant IC1 identified in the overgrowth-associated Beckwith-Wiedemann syndrome.

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