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

Mesoscopic Casimir forces from effects of discrete particle number in the quantum vacuum

Traditionally it is assumed that the Casimir vacuum pressure does not depend on the ultraviolet cut-off. There are, however, some arguments that the effect actually depends on the regularization procedure and thus on the trans-Planckian physics. We provide the condensed matter example where the Casimir forces do explicitly depend on the microscopic (correspondingly trans-Planckian) physics due to the mesoscopic finite-N effects, where N is the number of bare particles in condensed matter (or correspondingly the number of the elements comprising the quantum vacuum). The finite-N effects lead to mesoscopic fluctuations of the vacuum pressure. The amplitude of the mesoscopic flustuations of the Casimir force in a system with linear dimension L is larger by the factor N^{1/3}\sim L/a than the traditional value of the Casimir force given by effective theory, where a is the interatomic distance which plays the role of the Planck length.Comment: LaTeX file, 13 pages, no figures, submitted to JETP Letter

The Rotating Detector and Vacuum Fluctuations

In this work we compare the quantization of a massless scalar field in an inertial frame with the quantization in a rotating frame. We used the Trocheries-Takeno mapping to relate measurements in the inertial and the rotating frames. An exact solution of the Klein-Gordon equation in the rotating coordinate system is found and the Bogolubov transformation between the inertial and rotating modes is calculated, showing that the rotating observer defines a vacuum state different from the Minkowski one. We also obtain the response function of an Unruh-De Witt detector coupled with the scalar field travelling in a uniformly rotating world-line. The response function is obtained for two different situations: when the quantum field is prepared in the usual Minkowski vacuum state and when it is prepared in the Trocheries-Takeno vacuum state. We also consider the case of an inertial detector interacting with the field in the rotating vacuum.Comment: 15 pages, notations for the Green's functions are corrected only. to appear in Classical and Quantum Gravity (2000

Light-cone fluctuations and the renormalized stress tensor of a massless scalar field

We investigate the effects of light-cone fluctuations over the renormalized vacuum expectation value of the stress-energy tensor of a real massless minimally coupled scalar field defined in a ($d+1$)-dimensional flat space-time with topology ${\cal R}\times {\cal S}^d$. For modeling the influence of light-cone fluctuations over the quantum field, we consider a random Klein-Gordon equation. We study the case of centered Gaussian processes. After taking into account all the realizations of the random processes, we present the correction caused by random fluctuations. The averaged renormalized vacuum expectation value of the stress-energy associated with the scalar field is presented

Early melanoma invasivity correlates with gut fungal and bacterial profiles

7openInternationalItalian coauthor/editorBackground The microbiome is emerging as a crucial player of the immune checkpoint in cancer. Melanoma is a highly immunogenic tumour, and the composition of the gut microbiome has been correlated to prognosis and evolution of advanced melanoma and proposed as a biomarker for immune checkpoint therapy. Objectives We investigated the gut fungal and bacterial compositions in early-stage melanoma and correlated microbial profiles with histopathological features. Methods Sequencing of bacterial 16S rRNA and the fungal internal transcribed spacer region was performed on faecal samples of patients with stage I and II melanoma, and healthy controls. A meta-analysis with gut microbiota data from patients with metastatic melanoma was also carried out. Results We found a combination of gut fungal and bacterial profiles significantly discriminating patients with melanoma from controls. In patients with melanoma, we observed an abundance of Prevotella copri and yeasts belonging to the order Saccharomycetales. We found that the bacterial and fungal community correlated to melanoma invasiveness, whereas the specific fungal profile correlated to melanoma regression. Bacteroides was identified as general marker of immunogenicity, being shared by regressive and invasive melanoma. In addition, the bacterial communities in patients with stage I and II melanoma were different in structure and richer than those from patients with metastatic melanoma. Conclusions The composition of the gut microbiota in early-stage melanoma changes along the gradient from in situ to invasive (and metastatic) melanoma. Changes in the microbiota and mycobiota are correlated to the histological features of early-stage melanoma, and to the clinical course and response to immune therapies of advanced-stage melanoma, through direct or indirect immunomodulation.openVitali, F.; Colucci, R.; Di Paola, M.; Pindo, M.; De Filippo, C.; Moretti, S.; Cavalieri, D.Vitali, F.; Colucci, R.; Di Paola, M.; Pindo, M.; De Filippo, C.; Moretti, S.; Cavalieri, D

Finite dimensional corrections to mean field in a short-range p-spin glassy model

In this work we discuss a short range version of the $p$-spin model. The model is provided with a parameter that allows to control the crossover with the mean field behaviour. We detect a discrepancy between the perturbative approach and numerical simulation. We attribute it to non-perturbative effects due to the finite probability that each particular realization of the disorder allows for the formation of regions where the system is less frustrated and locally freezes at a higher temperature.Comment: 18 pages, 5 figures, submitted to Phys Rev