CCR5Δ32 Polymorphism Associated with a Slower Rate Disease Progression in a Cohort of RR-MS Sicilian Patients

Multiple sclerosis (MS) disease is carried through inflammatory and degenerative stages. Based on clinical feaures, it can be subdivided into three groups: relapsing-remitting MS, secondary progressive MS, and primary progressive MS. Multiple sclerosis has a multifactorial etiology with an interplay of genetic predisposition, environmental factors, and autoimmune inflammatory mechanism in which play a key role CC-chemokines and its receptors. In this paper, we studied the frequency of CCR5 gene Δ32 allele in a cohort of Sicilian RR-MS patients comparing with general Sicilian population. Also, we evaluate the association between this commonly polymorphism and disability development and age of disease onset in the same cohort. Our results show that presence of CCR5Δ32 is significantly associated with expanded disability status scale score (EDSS) but not with age of disease onset

Stargardt Phenotype Associated With Two ELOVL4 Promoter Variants and ELOVL4 Downregulation: New Possible Perspective to Etiopathogenesis?

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Is chlorophyll-athe best surrogate for organic matter enrichment in submicron primary marine aerosol?

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Web Health Application for ADHD Monitoring (WHAAM): Context-Driven Framework

The Framework (FW) summarizes the experiences and vision of the WHAAM project partners, providing the basis for the development of the WHAAM app and online services. There are many approaches to the treatment of ADHD, with excellent resources available. This FW is a working tool based on partners' experiences, inspiring subsequent project activities. It is divided into three parts: part A explores general issues related to ADHD, focusing on key life contexts such as school, family, and social relationships. Each context is explored in terms of assessment, intervention and support. Part B delves into the relationship between ICT use and ADHD treatment. Finally, Part C briefly explains the main features of the WHAAM app, including functionality and interfaces. The WHAAM project considers the app and online service accessible via PC and mobile devices as a significant advancement in monitoring process management

Further Data on a 9.1-kb Insertion-Deletion Polymorphism: Survey of Mediterranean Populations

We report the distribution of a previously described 9.1-kb insertion- deletion polymorphism located on chromosome 22. We analyzed 1,844 individuals sampled from 26 Mediterranean populations in mainland Italy, Sicily, Sardinia, Tunisia, Libya, Morocco, Egypt, Greece, and Albania. The 9.1 kb allele is the prevalent allele in the North African (range, 0.53– 0.56), Greek (0.51), and Albanian (0.66) populations, whereas the 9.1 kb allele is most frequent in a mainland Italian town (0.55) and in all Sicilian and Sardinian towns and villages thus far tested, with marked fluctuation ranges of 0.53–0.78 and 0.56–0.80, respectively. In tests for Hardy- Weinberg equilibrium the genotype frequencies observed in Athens and in four of the nine towns in Sicily (but in none of the towns in Sardinia) departed highly significantly from the expected values. Identical results were found in the same towns for a second insertion-deletion polymorphism located on chromosome 22q13 at a distance compatible with a low incidence of recombination. The data, which are in good agreement with the different histories of the two islands (Sardinia and Sicily), are consistent with a westeast differentiation in Sicily and support the evidence for ancient gene flow from the Iberian peninsula to Sardinia

RETRACTED ARTICLE: Non-coding RNAome of RPE cells under oxidative stress suggests unknown regulative aspects of Retinitis pigmentosa etiopathogenesis

Abstract The discovery of thousands of non-coding RNAs has revolutionized molecular biology, being implicated in several biological processes and diseases. To clarify oxidative stress role on Retinitis pigmentosa, a very heterogeneous and inherited ocular disorder group characterized by progressive retinal degeneration, we realized a comparative transcriptome analysis of human retinal pigment epithelium cells, comparing two groups, one treated with oxLDL and one untreated, in four time points (1 h, 2 h, 4 h, 6 h). Data analysis foresaw a complex pipeline, starting from CLC Genomics Workbench, STAR and TopHat2/TopHat-Fusion alignment comparisons, followed by transcriptomes assembly and expression quantification. We then filtered out non-coding RNAs and continued the computational analysis roadmap with specific tools and databases for long non-coding RNAs (FEELnc), circular RNAs (CIRCexplorer, UROBORUS, CIRI, KNIFE, CircInteractome) and piwi-interacting RNAs (piRNABank, piRNA Cluster, piRBase, PILFER). Finally, all detected non-coding RNAs underwent pathway analysis by Cytoscape software. Eight-hundred and fifty-four non-coding RNAs, between long non-coding RNAs and PIWI-interacting, were differentially expressed throughout all considered time points, in treated and untreated samples. These non-coding RNAs target host genes involved in several biochemical pathways are related to compromised response to oxidative stress, visual functions, synaptic impairment of retinal neurotransmission, impairment of the interphotoreceptor matrix and blood – retina barrier, all leading to retinal cell death. These data suggest that non-coding RNAs could play a relevant role in Retinitis pigmentosa etiopathogenesis

A novel RLBP1 gene geographical area-related mutation present in a young patient with retinitis punctata albescens

Abstract Background Autosomal recessive forms of retinitis punctata albescens (RPA) have been described. RPA is characterized by progressive retinal degeneration due to alteration in visual cycle and consequent deposit of photopigments in retinal pigment epithelium. Five loci have been linked to RPA onset. Among these, the retinaldehyde-binding protein 1 gene, RLBP1, is the most frequently involved and several founder mutations were reported. We report results of a genetic molecular investigation performed on a large Sicilian family in which appears a young woman with RPA. Results The proband is in homozygous condition for a novel RLBP1 single-pair deletion, and her healthy parents, both heterozygous, are not consanguineous. Thenovelc.398delC (p.P133Qfs*258) involves the exon 6 and leads to a premature stop codon, resulting in a truncated protein entirely missing of CRAL-TRIO lipid-binding domain. Pedigree analysis showed other non-consanguineous relatives heterozygous for the same mutation in the family. Extension of mutation research in the native town of the proband revealed its presence also in healthy subjects, in a heterozygous condition. Conclusions A novel RLBP1 truncating mutation was detected in a young girl affected by RPA. Although her parents are not consanguineous, the mutation was observed in a homozygous condition. Being them native of the same small Sicilian town of Fiumedinisi, the hypothesis of a geographical area-related mutation was assessed and confirmed

Oxidative Stress and the Neurovascular Unit

The neurovascular unit (NVU) is a relatively recent concept that clearly describes the relationship between brain cells and their blood vessels. The components of the NVU, comprising different types of cells, are so interrelated and associated with each other that they are considered as a single functioning unit. For this reason, even slight disturbances in the NVU could severely affect brain homeostasis and health. In this review, we aim to describe the current state of knowledge concerning the role of oxidative stress on the neurovascular unit and the role of a single cell type in the NVU crosstalk

Discovery of GLO1 New Related Genes and Pathways by RNA-Seq on A2E-Stressed Retinal Epithelial Cells Could Improve Knowledge on Retinitis Pigmentosa

Endogenous antioxidants protect cells from reactive oxygen species (ROS)-related deleterious effects, and an imbalance in the oxidant/antioxidant systems generates oxidative stress. Glyoxalase 1 (GLO1) is a ubiquitous cellular enzyme involved in detoxification of methylglyoxal (MG), a cytotoxic byproduct of glycolysis whose excess can produce oxidative stress. In retinitis pigmentosa, one of the most diffuse cause of blindness, oxidative damage leads to photoreceptor death. To clarify the role of GLO1 in retinitis pigmentosa onset and progression, we treated human retinal pigment epithelium cells by the oxidant agent A2E. Transcriptome profiles between treated and untreated cells were performed by RNA-Seq, considering two time points (3 and 6 h), after the basal one. The exposure to A2E highlighted significant expression differences and splicing events in 370 GLO1 first-neighbor genes, and 23 of them emerged from pathway clustered analysis as main candidates to be associated with retinitis pigmentosa. Such a hypothesis was corroborated by the involvement of previously analyzed genes in specific cellular activities related to oxidative stress, such as glyoxylate and dicarboxylate metabolism, glycolysis, axo-dendritic transport, lipoprotein activity and metabolism, SUMOylation and retrograde transport at the trans-Golgi network. Our findings could be the starting point to explore unclear molecular mechanisms involved in retinitis pigmentosa etiopathogenesis

Adaptive Modelling of Mutated FMO3 Enzyme Could Unveil Unexplored Scenarios Linking Variant Haplotypes to TMAU Phenotypes

Background: Trimethylaminuria (TMAU) is a rare genetic disease characterized by the accumulation of trimethylamine (TMA) and its subsequent excretion trough main body fluids, determining the characteristic fish odour in affected patients. We realized an experimental study to investigate the role of several coding variants in the causative gene FMO3, that were only considered as polymorphic or benign, even if the available literature on them did not functionally explain their ineffectiveness on the encoded enzyme. Methods: Mutational analysis of 26 TMAU patients was realized by Sanger sequencing. Detected variants were, subsequently, deeply statistically and in silico characterized to determine their possible effects on the enzyme activity. To achieve this goal, a docking prediction for TMA/FMO3 and an unbinding pathway study were performed. Finally, a TMAO/TMA urine quantification by 1H-NMR spectroscopy was performed to support modelling results. Results: The FMO3 screening of all patients highlighted the presence of 17 variants distributed in 26 different haplotypes. Both non-sense and missense considered variants might impair the enzymatic kinetics of FMO3, probably reducing the interaction time between the protein catalytic site and TMA, or losing the wild-type binding site. Conclusions: Even if further functional assays will confirm our predictive results, considering the possible role of FMO3 variants with still uncertain effects, might be a relevant step towards the detection of novel scenarios in TMAU etiopathogenesis