GALNT2 as a novel modulator of adipogenesis and adipocyte insulin signaling

Background/objectives: A better understanding of adipose tissue biology is crucial to tackle insulin resistance and eventually coronary heart disease and diabetes, leading causes of morbidity and mortality worldwide. GALNT2, a GalNAc-transferase, positively modulates insulin signaling in human liver cells by down-regulating ENPP1, an insulin signaling inhibitor. GALNT2 expression is increased in adipose tissue of obese as compared to that of non-obese individuals. Whether this association is secondary to a GALNT2-insulin sensitizing effect exerted also in adipocytes is unknown. We then investigated in mouse 3T3-L1 adipocytes the GALNT2 effect on adipogenesis, insulin signaling and expression levels of both Enpp1 and 72 adipogenesis-related genes. Methods: Stable over-expressing GALNT2 and GFP preadipocytes (T 0 ) were generated. Adipogenesis was induced with (R+) or without (R−) rosiglitazone and investigated after 15 days (T 15 ). Lipid accumulation (by Oil Red-O staining) and intracellular triglycerides (by fluorimetric assay) were measured. Lipid droplets (LD) measures were analyzed at confocal microscope. Gene expression was assessed by RT-PCR and insulin-induced insulin receptor (IR), IRS1, JNK and AKT phosphorylation by Western blot. Results: Lipid accumulation, triglycerides and LD measures progressively increased from T 0 to T 15 R- and furthermore to T 15 R+. Such increases were significantly higher in GALNT2 than in GFP cells so that, as compared to T 15 R+GFP, T 15 R- GALNT2 cells showed similar (intracellular lipid and triglycerides accumulation) or even higher (LD measures, p < 0.01) values. In GALNT2 preadipocytes, insulin-induced IR, IRS1 and AKT activation was higher than that in GFP cells. GALNT2 effect was totally abolished during adipocyte maturation and completely reversed at late stage maturation. Such GALNT2 effect trajectory was paralleled by coordinated changes in the expression of Enpp1 and adipocyte-maturation key genes. Conclusions: GALNT2 is a novel modulator of adipogenesis and related cellular phenotypes, thus becoming a potential target for tackling the obesity epidemics and its devastating sequelae

Common germline variants within the CDKN2A/2B region affect risk of pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (PNETs) are heterogeneous neoplasms which represent only 2% of all pancreatic neoplasms by incidence, but 10% by prevalence. Genetic risk factors could have an important role in the disease aetiology, however only a small number of case control studies have been performed yet. To further our knowledge, we genotyped 13 SNPs belonging to the pleiotropic CDKN2A/B gene region in 320 PNET cases and 4436 controls, the largest study on the disease so far. We observed a statistically significant association between the homozygotes for the minor allele of the rs2518719 SNP and an increased risk of developing PNET (ORhom = 2.08, 95% CI 1.05-4.11, p = 0.035). This SNP is in linkage disequilibrium with another polymorphic variant associated with increased risk of several cancer types. In silico analysis suggested that the SNP could alter the sequence recognized by the Neuron-Restrictive Silencer Factor (NRSF), whose deregulation has been associated with the development of several tumors. The mechanistic link between the allele and the disease has not been completely clarified yet but the epidemiologic evidences that link the DNA region to increased cancer risk are convincing. In conclusion, our results suggest rs2518719 as a pleiotropic CDKN2A variant associated with the risk of developing PNETs

Common genetic variants associated with pancreatic adenocarcinoma may also modify risk of pancreatic neuroendocrine neoplasms (vol 39, pg 360, 2018)

Pancreatic neuroendocrine neoplasms (pNEN) account for less than 5% of all pancreatic neoplasms and genetic association studies on susceptibility to the disease are limited. We sought to identify possible overlap of genetic susceptibility loci between pancreatic ductal adenocarcinoma (PDAC) and pNEN; therefore, PDAC susceptibility variants (n=23) from Caucasian genome-wide association studies (GWAS) were genotyped in 369 pNEN cases and 3,277 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium to evaluate the odds associated with pNEN risk, disease onset and tumor characteristics. Main effect analyses showed four PDAC susceptibility variants – rs9854771, rs1561927, rs9543325 and rs10919791 to be associated with pNEN risk. Subsequently, only associations with rs9543325, rs10919791 and rs1561927 were noteworthy with false positive report probability (FPRP) tests. Stratified analyses considering age at onset (50 year threshold), showed rs2736098, rs16986825 and rs9854771 to be associated with risk of developing pNEN at a younger age. Stratified analyses also showed some SNPs to be associated with different degrees of tumor grade, metastatic potential and functionality. Our results identify known GWAS PDAC susceptibility loci, which may also be involved in sporadic pNEN etiology and suggest that some genetic mechanisms governing pathogenesis of these two entities may be similar, with few of these loci being more influential in younger cases or tumor subtypes

La funzione delle lettere alfabetiche nella glossa interlineare alla Regula Sancti Benedicti del manoscritto London, British Library, Cotton Tiberius A.III

I fogli 118r-163v del manoscritto London, Cotton Tiberius, A.III tramandano il testo latino della Regula Sancti Benedicti corredato da una glossa interlineare di natura composita che comprende le lettere dell’alfabeto, dalla a alla z. Si tratta di lettere finalizzate alla comprensione della sintassi del latino sia indicando l’ordine logico secondo cui disporre i singoli elementi di una frase, oppure l’ordine logico secondo cui disporre le frasi all’interno di periodi, sia evidenziando la funzione logica specifica di ciascun elemento. Il glossatore ha scelto la lettera a per indicare l’inizio di un nuovo periodo e per il verbo delle principali; la lettera b, invece, è la lettera del soggetto, strettamente connessa alla lettera del verbo; mentre le altre lettere hanno lo scopo di mettere in evidenza i diversi elementi che di volta in volta ricorrono nel periodo e le loro relazioni. La funzione delle lettere sintattiche e il risalto dato ai capitoli della RB dedicati alle lodi e ai salmi - i più ricchi di tali lettere - riconducono la glossa interlineare in esame a un centro monastico in cui il programma educativo e religioso di Æthelwold era conosciuto e messo in atto.MS London, Cotton Tiberius, A.III transmits the Benedictine Rule with a composite interlinear gloss in Old English, which includes the alphabetic letters from a to z. These letters help understand the Latin text showing both the logical order of phrases in a clause, or the logical order of the clauses in a sentence, and the logical function specific to each element. The glossator has chosen the letter a to mark the beginning of a sentence and for the verb of main clauses; while b is the letter of the subject, closely linked to the verb. The other letters underline the different elements that characterize the different clauses and their relationship. The function of the syntactic letters and the result given to the chapters of the Rule devoted to lauds and psalms – the richest in those letters – lead the interlinear gloss to a monastic centre acquainted with Æthelwold’s learning and religious plans

Risonanze III. La memoria dei testi dal medioevo a oggi

Il volume raccoglie saggi di studiosi di varie discipline sul testo e la sua eco nel tempo (e nello spazio). Il Leitmotiv è il tema della memoria del testo, delle sue riscritture e delle varie forme che assume nel corso della sua storia. Si indaga sul rapporto fra il testo e il pubblico, sia in senso diacronico (tradizione testuale, ricostruzione del testo, trasformazioni del testo che si adatta a un pubblico sempre diverso a seconda delle epoche), sia in senso sincronico (intertestualità, rapporto autore-pubblico, autoriscritture, forme di comunicazione, adattamenti musicali di un testo, passaggio dal testo letterario alle arti visive e, a volte, viceversa)

El siglo de Oro en escena

Del teatro de Sánchez de Badajoz (siglo xvi) al de Bances Candamo (finales del xvii), de las múltiples riquezas de la comedia lopesca a las excelencias del teatro calderoniano, de la prosa cervantina a la de un Mateo Alemán, del Pinciano al maestro Correas, y «trecientas cosas más»: los artículos reunidos en este libro componen un extenso panorama de los más recientes resultados de la investigación internacional sobre toda la literatura española del Siglo de Oro, ofrecidos al profesor Marc Vitse por sus más destacados discípulos, amigos y admiradores.À Marc,Odett