95 research outputs found
RETRACTED ARTICLE: Role of oxidative stress in Retinitis pigmentosa: new involved pathways by an RNA-Seq analysis
No full textWe, the Editor[s] and Publisher of Cell Cycle, have retracted the following article: Role of oxidative stress in Retinitis pigmentosa: new involved pathways by an RNA-Seq analysis Luigi Donato, Concetta Scimone, Giacomo Nicocia, Rosalia D’Angelo & Antonina Sidoti Pages 84-104 | https://doi.org/10.1080/15384101.2018.1558873 The above article has been retracted as a result of concerns regarding the use of raw data by one of the authors upon which the presented research has been based. After examination and approval from the author concerned, the consensus is that the data was used without consent, and that therefore the article must be retracted. We note that we received, peer-reviewed, accepted, and published the article in good faith based on the purported veracity of these representations and warranties. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.</p
Possible A2E Mutagenic Effects on RPE Mitochondrial DNA from Innovative RNA-Seq Bioinformatics Pipeline
No full textMitochondria are subject to continuous oxidative stress stimuli that, over time, can impair their genome and lead to several pathologies, like retinal degenerations. Our main purpose was the identification of mtDNA variants that might be induced by intense oxidative stress determined by N-retinylidene-N-retinylethanolamine (A2E), together with molecular pathways involving the genes carrying them, possibly linked to retinal degeneration. We performed a variant analysis comparison between transcriptome profiles of human retinal pigment epithelial (RPE) cells exposed to A2E and untreated ones, hypothesizing that it might act as a mutagenic compound towards mtDNA. To optimize analysis, we proposed an integrated approach that foresaw the complementary use of the most recent algorithms applied to mtDNA data, characterized by a mixed output coming from several tools and databases. An increased number of variants emerged following treatment. Variants mainly occurred within mtDNA coding sequences, corresponding with either the polypeptide-encoding genes or the RNA. Time-dependent impairments foresaw the involvement of all oxidative phosphorylation complexes, suggesting a serious damage to adenosine triphosphate (ATP) biosynthesis, that can result in cell death. The obtained results could be incorporated into clinical diagnostic settings, as they are hypothesized to modulate the phenotypic expression of mtDNA pathogenic variants, drastically improving the field of precision molecular medicine
Update on Novel CCM Gene Mutations in Patients with Cerebral Cavernous Malforzmations
No full textCerebral cavernous malformations (CCMs) are lesions affecting brain microvessels. The pathogenesis is not clearly understood. Conventional classification criterion is based on genetics, and thus, familial and sporadic forms can be distinguished; however, classification of sporadic cases with multiple lesions still remains uncertain. To date, three CCM causative genes have been identified: CCM1/KRIT1, CCM2/MGC4607 and CCM3/PDCD10. In our previous mutation screening, performed in a cohort of 95 Italian patients, with both sporadic and familial cases, we identified several mutations in CCM genes. This study represents further molecular screening in a cohort of 19 Italian patients enrolled by us in the few last years and classified into familial, sporadic and sporadic with multiple lesions cases. Direct sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis were performed to detect point mutations and large genomic rearrangements, respectively. Effects of detected mutations and single-nucleotide polymorphisms (SNPs) were evaluated by an in silico approach and by western blot analysis. A novel nonsense mutation in CCM1 and a novel missense mutation in CCM2 were detected; moreover, several CCM2 gene polymorphisms in sporadic CCM patients were reported. We believe that these data enrich the mutation spectrum of CCM genes, which is useful for genetic counselling to identify both familial and sporadic CCM cases, as early as possible
ON MACHINE LEARNING IN BIOMEDICINE
No full textMachine Learning (ML) is a field of Scientific Computing that emerged in the last decades to investigate complex phenomena based on huge amounts of observational data. In the context of Biomedicine, an increasing body of literature makes use of ML based approaches as an alternative to standard statistical
inference. Moreover, a number of studies are now focusing on adopting ML to disclose new results that
otherwise would have not been possible to achieve with classical inference. In this short review we outline fundamentals of ML, by further providing examples gathered from scientific literature to highlight the potentialities of ML for clinical purposes
Methylome analysis of endothelial cells suggests new insights on sporadic brain arteriovenous malformation
No full textArteriovenous malformation of the brain (bAVM) is a vascular phenotype related to brain defective angiogenesis. Involved vessels show impaired expression of vascular differentiation markers resulting in the arteriolar to venule direct shunt. In order to clarify aberrant gene expression occurring in bAVM, here we describe results obtained by methylome analysis performed on endothelial cells (ECs) isolated from bAVM specimens, compared to human cerebral microvascular ECs. Results were validated by quantitative methylation-specific PCR and quantitative realtime-PCR. Differential methylation events occur in genes already linked to bAVM onset, as RBPJ and KRAS. However, among differentially methylated genes, we identified EPHB1 and several other loci involved in EC adhesion as well as in EC/vascular smooth muscle cell (VSMC) crosstalk, suggesting that only endothelial dysfunction might not be sufficient to trigger the bAVM phenotype. Moreover, aberrant methylation pattern was reported for many lncRNA genes targeting transcription factors expressed during neurovascular development. Among these, the YBX1 that was recently shown to target the arteridin coding gene. Finally, in addition to the conventional CpG methylation, we further considered the role of impaired CHG methylation, mainly occurring in brain at embryo stage. We showed as differentially CHG methylated genes are clustered in pathways related to EC homeostasis, as well as to VSMC-EC crosstalk, suggesting as impairment of this interaction plays a prominent role in loss of vascular differentiation, in bAVM phenotype
Pirandello Pirandello Pirandello (Gleijeses, Dini, Scimone/Sframeli)
No full textRoberto Alonge’s contribution takes note of the fact that Pirandello’s dramaturgy constitutes a fixed point in the programmes of Italian theatres. Three Pirandello shows examined: Il piacere dell’onestà [The pleasure of honesty], Così è (se vi pare) [Thus is (if you like)] and Sei personaggi in cerca d’autore [Six characters in search of an author]. The pleasure of honesty is a good product, built on the acting skill of the first actor, Geppy Gleijeses. The second performance, directed by Filippo Dini, has the ambition to attempt new interpretative keys of a well-known text. For some traits Dini confesses his debt to the famous edition of Massimo Castri which, at the moment, remains the most convincing testimony of an original reading of the text, based on the hypothesis that the incest between father and daughter is the secret hidden in the depths of comedy. Finally the Six characters of Spiro Scimone and Francesco Sframeli, presented with the title Six, are a very interesting example of theatre adaptation. Pirandello’s famous comedy is trimmed, reduced to a performance of just over an hour, and in many places it also undergoes a rewriting operation, often personal but never random and free, because the two theatre actors from Messina are valuable artists.Il contributo di Roberto Alonge prende atto del fatto che la drammaturgia di Pirandello costituisce ormai un punto fisso dei cartelloni dei teatri italiani, ed esamina tre spettacoli pirandelliani: Il piacere dell’onestà, Così è (se vi pare) e Sei personaggi in cerca d’autore. Il primo è un buon prodotto, costruito sull’abilità consumata di un grandattore di vaglia, Geppy Gleijeses. Il secondo, diretto da Filippo Dini, ha l’ambizione di aprire nuove chiavi interpretative di un testo molto studiato. Per certi tratti Dini confessa il suo debito alla celebre messinscena di Massimo Castri che, per il momento, resta la più convincente testimonianza di una lettura originale del testo, fondata sull’ipotesi che l’incesto tra padre e figlia sia il segreto nascosto nello strato profondo della commedia. Per concludere, i Sei personaggi di Spiro Scimone e Francesco Sframeli, presentati con il titolo Sei, sono un esempio di adattamento drammaturgico molto interessante. La famosa commedia di Pirandello è sfoltita drasticamente, ridotta a una rappresentazione di poco più di un’ora, in molti punti sottoposta a un’operazione di riscrittura, spesso personale ma mai libera e gratuita, perché i due teatranti messinesi sono artisti di valore
POSSIBLE RELATED FUNCTIONS OF THE NON-HOMOLOGOUS CO-REGULATED GENE PAIR PDCD10 AND SERPINI1
No full textGene expression in mammalians is a very finely controlled mechanism, and bidirectional promoters can be
considered one of the most compelling examples of the accuracy of genic expression coordination. As
recently reported, a bidirectional promoter regulates the expression of the PDCD10(whose mutations
cause familial Cerebral Cavernous Malformations (CCMs) and SERPINI1 gene pair, even though they are
non-homologous genes. The aim of this study was to identify any potential common roles of these two coregulated
genes. An in-silico approach was used to identify functional correlations, using the BioGraph,
IPA® and Cytoscape tools and the KEGG pathway database. The results obtained show that PDCD10 and
SERPINI1 may co-regulate some cellular processes, particularly those related to focal adhesion
maintenance. All common pathways identified for PDCD10 and SERPINI1 are closely associated with the
pathogenic characteristics of CCMs; we thus hypothesize that genes involved in these networks may
contribute to the development of CCMs
SM_ Manuscript "Deciphering impact of single nucleotide polymorphisms on co-transcriptional modification in CCM gene mRNAs",C-00279-2022R1
No full textData obtained by in-silico analysis of epitranscriptome modifications occurring in CCM genes</p
Loss Given Default for residential real estate banks: Evidence from the Euro area
No full textLoss given default (LGD) for residential real estate loans is affected by real estate market trends due to the impact on the value of debtors’ main collateral. Banks specialized in real estate lending are expected to be better at selecting lending opportunities, properly evaluating real estate collaterals, and managing the recovery process. The recovery process is expected to differ for specialized lenders but there is no consensus about their differences from other market players. The paper examines LGD for a representative sample of European banks to underline the key differences related to real estate specialization. Results show that real estate banks, on average, perform a better recovery process. Moreover, real estate banks not fully specialized in real estate can better manage the real estate market cycle effect, reducing the pro-cyclicality of LGD
RETRACTED ARTICLE: Non-coding RNAome of RPE cells under oxidative stress suggests unknown regulative aspects of Retinitis pigmentosa etiopathogenesis
No full textAbstract 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
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