WHOLE TRANSCRIPTOME ANALAYSIS BY NEXT GENERATION SEQUENCING (NGS) IN AUTISM SPECTRUM DISORDERS (ASDs)

I disordini dello spettro autistico (ASDs) sono caratterizzati dalla compromissione dell\u2019interazione sociale e della comunicazione verbale e non verbale, e da comportamenti ripetitivi e stereotipati. L\u2019autismo \ue8 una delle pi\uf9 frequenti tra le malattie complesse ereditabili, tuttavia, solo pochi geni implicati nell\u2019eziologia sono stati identificati. Negli ultimi anni, in diversi studi, sono stati individuati polimorfismi a singolo nucleotide (SNP), anomalie cromosomiche e rare varianti genetiche associati al fenotipo autistico. Inoltre, in studi di ibridazione genomica comparativa (CGH), come fattori di rischio sono state individuate alcune variazioni del numero di copie (CNV). Altri studi hanno evidenziato che le cellule linfoblastoidi possono discriminare tra soggetti con ASD e campioni di controllo. Il presente studio \ue8 parte di un progetto Telethon, avviato nel 2009, che coinvolge diversi gruppi italiani di clinica e di ricerca. Questo progetto ha l\u2019obiettivo di analizzare le variazioni di espressione genica in 27 soggetti con ASD e 23 controlli sani. I probandi selezionati presentano CNV potenzialmente coinvolte nell'insorgenza dell'autismo. Il trascrittoma di 27 probandi e 23 controlli sani \ue8 stato analizzato attraverso la tecnica di sequenziamento di nuova generazione dell\u2019RNA (RNA sequencing). L\u2019analisi di arricchimento del gruppo di geni (GSEA) risultati differenzialmente espressi, compiuta sull\u2019intera coorte e su un sottogruppo con una delezione 22q13.3, ha rilevato che i principali pathway arricchiti appartengono ai disturbi autoimmuni e al pathway di presentazione dell'antigene. La sottoanalisi compiuta sui campioni con la delezione evidenzia il coinvolgimento di geni appartenenti al pathway di orientamento degli assoni, confermando che le linee cellulari linfoblastoidi possono presentare biomarcatori rilevanti per l'autismo. Inoltre, abbiamo dimostrato che tre geni \u201coutlier\u201d clusterizzano all'interno di una CNV sul cromosoma 16p13.1, suggerendo che questo \ue8 un potenziale candidato locus per autismo. Questo studio fornisce la prova che le varianti strutturali, potenzialmente causative di ASD, hanno un impatto funzionale attraverso alterazioni del trascrittoma e dimostra l'utilit\ue0 di integrare i dati di espressione genica con i dati genomici. Ulteriori analisi sui geni differenzialmente espressi e su CNVs, non selezionate in questo studio, contribuiranno a mettere in rilievo le basi genetiche e fisiopatologiche di ASD e ad evidenziare nuovi potenziali pathway coinvolti nei disordini dello spettro autistico.Autism Spectrum Disorders (ASDs) represent a group of childhood neurodevelopmental and neuropsychiatric disorders characterized by deficits in verbal communication, impairment of social interaction, and restricted and repetitive patterns of interests and behaviours. Evidences indicate that ASDs have strong genetic bases. Known chromosomal anomalies, rare genetic variants and single nucleotide polymorphisms (SNPs) have been related to ASD phenotypes in many studies. Furthermore Comparative Genomic Hybridization (CGH) studies have revealed copy number variations (CNVs) as risk factors. Recently, several studies have suggested that lymphoblastoid cells (LCLs) can discriminate between ASDs and control samples. This study is part of a Telethon project which has been started in 2009 and involves different Italian clinical and research groups; it aims to analyze gene expression variations in ASD subjects, characterized for CNVs potentially involved in the onset of autism. Transcriptome from LCLs of 27 ASD probands and 23 health controls have been analyzed through Next Generation Sequencing technology (RNA Sequencing). Gene set enrichment analysis (GSEA), on the total cohort and on a subgroup with a 22q13.3 deletion, revealed that autoimmune disorders and antigen processing and presentation pathways are the most enriched ones. Subgroup\u2019s GSEA highlights the involvement of axon guidance pathway, confirming that LCLs could exhibit biomarkers relevant to autism. Moreover, we demonstrate that three outlier genes cluster within a CNV on 16p13.1, suggesting that this is a potential candidate ASD region. This study provides evidence that potentially causative structural variants have a functional impact via transcriptome alterations in ASDs at a genome wide level and demonstrates the utility of integrating gene expression with mutation data. Further analysis of differentially expressed genes and CNVs not selected in this study will help understanding the genetic bases for ASD pathophysiology and unravelling potential new pathways involved in ASDs

Country rankings on the scientific production in endocrinology and diabetology

Diabetes represents a major global health problem. It was estimated that the global prevalence of diabetes in 2019 was approximately 9%, with the worrying projection to increase up to 11% by 2045 [1]. Importantly, it was also calculated that in 2016 worldwide nearly 1.6 million deaths were directly related to diabetes or high blood glucose [1]. In parallel, other important endocrinological diseases, such as obesity, thyroid diseases (i.e., hyperthyroidism, hypothyroidism, and cancer), polycystic ovary syndrome, and infertility, have a relevant clinical and socio-economic impact worldwide [2, 3]. These data strongly suggest that an additional uplift in research efforts is necessary in this area

Breastfeeding duration and reduced risk of NAFLD in midlife of parous women

the observational studies available so far and the result of our analysis reinforce the assertion that breastfeeding is relevant for the long-term health of the mother, with a protective effect on the risk of NAFLD

MAFLD and CKD: An Updated Narrative Review

Accumulating evidence now indicates that non-alcoholic fatty liver disease (NAFLD), which is the most common chronic liver disease observed in clinical practice worldwide, is independently associated with an increased risk of incident chronic kidney disease (CKD). Given that NAFLD is linked to insulin resistance, obesity and type 2 diabetes mellitus, an international panel of experts have recently proposed a name change from NAFLD to metabolic associated fatty liver disease (MAFLD). Since the diagnostic criteria for NAFLD and MAFLD are different, observational studies assessing the potential concordance (or even superiority) of MAFLD, compared with NAFLD, in detecting patients at increased risk of hepatic and extra-hepatic complications (including CKD) are required. Hence, in the last two years, some observational studies have investigated the potential relationship between MAFLD and CKD. The result is that, at present, evidence regarding the concordance or even superiority of MAFLD, compared with NAFLD, in detecting patients at higher risk of CKD is still preliminary, although some data indicate that MAFLD identifies patients with CKD as accurately as NAFLD. In this narrative review, we will discuss: (a) the epidemiological evidence assessing the association between NAFLD and risk of incident CKD, (b) the epidemiological data investigating the association between MAFLD and risk of CKD and (c) the biological mechanisms underlying the association between NAFLD/MAFLD and CKD

Glucose tolerance stages in Cystic Fibrosis are idenfied by a unique pattern of defects of Beta-cell function

To assess the order of severity of the defects of three direct determinants of glucose regulation, i.e., beta-cell function, insulin clearance and insulin sensitivity, in patients with CF categorized according their glucose tolerance status, including early elevation of mid-OGTT glucose values (>140 and < 200 mg/dL), named AGT140

In-lab characterization of HYPSOS, a novel stereo hyperspectral observing system: first results

HYPSOS (HYPerspectral Stereo Observing System, patented) is a novel remote sensing instrument able to extract the spectral information from the two channels of a pushbroom stereo camera; thus it simultaneously provides 4D information, spatial and spectral, of the observed features. HYPSOS has been designed to be a compact instrument, compatible with small satellite applications, to be suitable both for planetary exploration as well for terrestrial environmental monitoring. An instrument with such global capabilities, both in terms of scientific return and needed resources, is optimal for fully characterizing the observed surface of investigation. HYPSOS optical design couples a pair of folding mirrors to a modified three mirror anastigmat telescope for collecting the light beams from the optical paths of the two stereo channels; then, on the telescope focal plane, there is the entrance slit of an imaging spectrograph, which selects and disperses the light from the two stereo channels on a bidimensional detector. With this optical design, the two stereo channels share the large majority of the optical elements: this allowed to realize a very compact instrument, which needs much less resources than an equivalent system composed by a stereo camera and a spectrometer. To check HYPSOS actual performance, we realized an instrument prototype to be operated in a laboratory environment. The laboratory setup is representative of a possible flight configuration: the light diffused by a surface target is collimated on the HYPSOS channel entrance apertures, and the target is moved with respect to the instrument to reproduce the in- flight pushbroom acquisition mode. Here we describe HYPSOS and the ground support equipment used to characterize the instrument, and show the preliminary results of the instrument alignment activities

BC‐SIM‐TR‐026 STC ICO3 REPORT

The present document has been issued to describe the ICO#3 (Third Instrument Check Out Phase) Tests of STC, channel of the Spectrometers and Imagers for MPO BepiColombo Integrated Observatory SYStem (SIMBIO-SYS)

The dawn of a new era for nonalcoholic fatty liver disease?

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Letter to the Editor about PNPLA3 gene polymorphism in Brazilian patients with type 2 diabetes: A prognostic marker beyond liver disease?

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{PNPLA}3 gene and kidney disease

Chronic kidney disease (CKD) is a disease regularly seen in clinical practice. At present, CKD is described as a change of kidney structure and/or function and it is classified in relation to cause, values of glomerular filtration rate and albuminuria category. Seeing that CKD is closely linked to the development of end-stage renal disease and other comorbidities, the determination of additional independent predictors for CKD is clinically necessary. At present, there is evidence associating non-alcoholic fatty liver disease (NAFLD) with CKD, thereby suggesting that NAFLD patients may require intensive surveillance to reduce their risk of CKD. In 2008, genome-wide association studies documented an association between the variant rs738409 (C > G p.I148M) in the patatin-like phospholipase domain containing 3 (PNPLA3) gene (mainly implicated in the lipid regulation) and the entire spectrum of NAFLD (i.e., liver steatosis, non-alcoholic steatohepatitis, fibrosis, and hepatocellular carcinoma). In the last years, accumulating epidemiological evidence suggests the existence of a relationship between PNPLA3 rs738409 and risk of CKD, indicating that rs738409 may also contribute to the kidney injury. This is of particular scientific interest, as such association may explain, at least in part, the epidemiological association between liver and kidney disease. In this narrative review, we will discuss the accumulating evidence regarding the association between PNPLA3 rs738409 and risk of CKD, the putative biological mechanisms underpinning such relationship, and the possible future perspective