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

COVID-19 and SARS: differences and similarities

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Effects of systemic glucocorticosteroids on peripheral neutrophil functions in asthmatic subjects: an ex vivo study

In 21 asthmatic subjects, several functions of isolated peripheral neutrophils (chemokinesis and chemotaxis toward 10% E. coli; superoxide anion generation after PMA; leukotriene B4 (LTB4) release from whole blood and isolated neutrophtls, before and after different stimuli) were evaluated during an acute exacerbation of asthma, and after 14 – 54 days of treatment with systemic glucocorticosteroids (GCS). During acute exacerbation, superoxide anion generation was higher in asthmatics than in eleven normal subjects (39.2 ± 14.1 vs. 25.2 ± 7.3 nmol, p < 0.05); there was a significant correlation between FEV1 (% of predicted) and neutrophil chemotaxis (r = −0.52, p = 0.04). After treatment, there was no significant change in all neutrophil functions, except for a decrease in neutrophil chemotaxis in subjects who showed an FEV1 increase > 20% after GCS treatment (from 131 ± 18 to 117 ± 21 μm, p = 0.005). Chemokinesis sicantly decreased in all subjects, and the changes significantly correlated with an arbitrary score of the total administered dose of GCS (r = 0.57, p < 0.05). These data suggest that neutrophil activation plays a minor role in asthma, and that treatment with GCS is not able to modify most functions of peripheral neutrophils in asthmatic subjects; chemotaxis seems to be related only to the severity of the asthma and it could reflect the improvement of the disease

High-velocity collimated outflows in planetary nebulae: NGC 6337, He 2-186, and K 4-47

We have obtained narrow-band images and high-resolution spectra of the planetary nebulae NGC 6337, He 2-186, and K 4-47, with the aim of investigating the relation between their main morphological components and several low-ionization features present in these nebulae. The data suggest that NGC 6337 is a bipolar PN seen almost pole on, with polar velocities higher than 200 km/s. The bright inner ring of the nebula is interpreted to be the "equatorial" density enhancement. It contains a number of low-ionization knots and outward tails that we ascribe to dynamical instabilities leading to fragmentation of the ring or transient density enhancements due to the interaction of the ionization front with previous density fluctuations in the ISM. The lobes show a pronounced point-symmetric morphology and two peculiar low-ionization filaments whose nature remains unclear. The most notable characteristic of He 2-186 is the presence of two high-velocity (higher than 135 km/s) knots from which an S-shaped lane of emission departs toward the central star. K 4-47 is composed of a compact core and two high-velocity, low-ionization blobs. We interpret the substantial broadening of line emission from the blobs as a signature of bow shocks, and using the modeling of Hartigan, Raymond, & Hartman (1987), we derive a shock velocity of 150 km/s and a mild inclination of the outflow on the plane of the sky. We discuss possible scenarios for the formation of these nebulae and their low-ionization features. In particular, the morphology of K 4-47 hardly fits into any of the usually adopted mass-loss geometries for single AGB stars. Finally, we discuss the possibility that point-symmetric morphologies in the lobes of NGC 6337 and the knots of He 2-186 are the result of precessing outflows from the central stars.Comment: 16 pages plus 7 figures, ApJ accepted. Also available at http://www.iac.es/publicaciones/preprints.htm

Gender may be related to the side of the motor syndrome and cognition in idiopathic Parkinson's disease.

Abstract Background and Sex and cognitive profile may be related to the laterality of motor symptoms in idiopathic Parkinson's disease. Introduction Parkinson's disease (PD) is well recognised as an inherently asymmetric disease with unilateral onset of motor symptoms. The laterality of motor symptoms may be linked to sex, clinical and demographic variables, and neuropsychological disorders. However, the available data are inconsistent. This study aimed to explore the potential association between the laterality of motor symptoms and clinical and demographic variables and deficits in specific cognitive domains. Material and methods We retrospectively recruited 97 participants with idiopathic PD without dementia; 60 presented motor symptoms on the left side and 37 on the right side. Both groups were comparable in terms of age, age at disease onset, disease duration, and severity of the neurological deficits according to the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr scale. Results Participants with left-side motor symptoms scored lower on the Schwab and England Activities of Daily Living scale. Our sample included more men than women (67% vs. 33%). Both sexes were not equally represented in the 2 groups: there were significantly more men than women in the group of patients with left-side motor symptoms (77% vs. 23%), whereas the percentages of men and women in the group of patients with right-side motor symptoms were similar (51% vs. 49%). Both groups performed similarly in all neuropsychological tasks, but women, independently of laterality, performed better than men in the naming task. Conclusion We found a clear prevalence of men in the group of patients with left-side motor symptoms; this group also scored lower on the Schwab and England Scale. Female sex was predictive of better performance in the naming task. Sex should always be considered in disorders that cause asymmetric involvement of the brain, such as PD

Ongoing spread of colistin-resistant Klebsiella pneumoniae in different wards of an acute general hospital, Italy, June to December 2011

We describe polyclonal spread of colistin-resistant Klebsiella pneumoniae in an acute general hospital in Italy. Between June and December 2011, 58 colistin-resistant K. pneumoniae isolates were recovered from 28 patients admitted to different wards, but mainly in the intensive care units. All isolates were tested for drug susceptibility and the presence of beta-lactamase (bla) genes. Clonality was investigated by repetitive extragenic palindromic (rep)-PCR and multilocus sequence typing (MLST). Fifty-two isolates had minimum inhibitory concentrations (MICs) for colistin of 6-128 mg/L, carried bla(KPC3) and were attributed to sequence type ST258. The remaining six isolates were susceptible to carbapenems, exhibited MICs for colistin of 3-32 mg/L, and belonged to two different types, ST15 and ST273. Rep-PCR included all isolates in three clusters, one containing all ST258 KPC-3-producing isolates and two containing ST15 and ST273 isolates.Cross-transmission containment measures and intensification of staff and environmental hygiene could not stop the outbreak. Selective pressure and horizontal transmission probably contributed to emergence and spread of three different strains of colistin-resistant K. pneumoniae in the hospital. Strict implementation of the above measures and a wider awareness of the antimicrobial resistance threat are crucial to preserve the last therapeutic options of the multidrug-resistant Gram-negative infection

Evaluation of performance of VDSR super resolution on real and synthetic images

This paper presents an evaluation of the suitability of the Very Deep Super Resolution (VDSR) architecture, to increase the spatial resolution of lower quality images. For this aim, two sets of tests are performed. The former being on real life images to determine the networks ability to improve low resolution images. The second test is performed on images of a resolution chart, and therefore synthetic. This is to analyse the frequency response of the network. For each test, three metrics are used to assess image quality. These are the Peak Signal to Noise Ratio (PSNR), Structural Similarity Index (SSIM) and Modulation Transfer Function (MTF). Experimental results show that the VDSR network is able to increase the quality of the images within the first test in all three metrics, therefore showing that the network is suitable for super resolution. The second test provides more information on the limitations of the network when given a high contrast image, and the resulting ringing effects it can create. Therefore results in PSNR/SSIM values are not improved over the low resolution images, however they have a higher MTF curve as well as more visually sharp images

Digital sculpting for historical representation: Neville tomb case study

Despite digital 3-D polygon modelling applications providing a common and powerful tool-set for archaeological, architectural and historical visualisation over recent years, the relatively recent developments in high-resolution sculpting software allow for the possibility to create digital outcomes with a degree of surface fidelity not previously obtainable from the more widely used poly-modelling software packages. Such digital sculpting applications are more commonly applied within the video games and TV/motion picture industries, the intention of this paper is to show how such tools and methodologies together with existing scanned data and some historical knowledge can remediate and re-imagine lost sculptural form. The intended research will focus on an examination and partial re-construction of the tomb of Sir John Neville, 3rd Baron Raby located at Durham Cathedral, County Durham UK

The impact of histopathology and NAB2-STAT6 fusion subtype in classification and grading of meningeal solitary fibrous tumor/hemangiopericytoma.

Meningeal solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) is a rare tumor with propensity for recurrence and metastasis. Although multiple classification schemes have been proposed, optimal risk stratification remains unclear, and the prognostic impact of fusion status is uncertain. We compared the 2016 WHO CNS tumor grading scheme (CNS-G), a three-tier system based on histopathologic phenotype and mitotic count, to the 2013 WHO soft-tissue counterpart (ST-G), a two-tier system based on mitotic count alone, in a cohort of 133 patients [59 female, 74 male; mean age 54&nbsp;years (range 20-87)] with meningeal SFT/HPC. Tumors were pathologically confirmed through review of the first tumor resection (n = 97), local recurrence (n = 35), or distant metastasis (n = 1). A STAT6 immunostain showed nuclear expression in 132 cases. NAB2-STAT6 fusion was detected in 99 of 111 successfully tested tumors (89%) including the single STAT6 immunonegative tumor. Tumors were classified by CNS-G as grade 1 (n = 43), 2 (n = 41), or 3 (n = 49), and by ST-G as SFT (n = 84) or malignant SFT (n = 49). Necrosis was present in 16 cases (12%). On follow-up, 42 patients had at least one subsequent recurrence or metastasis (7 metastasis only, 33 recurrence only, 2 patients had both). Twenty-nine patients died. On univariate analysis, necrosis (p = 0.002), CNS-G (p = 0.01), and ST-G (p = 0.004) were associated with recurrence-free (RFS) but not overall survival (OS). NAB2-STAT6 fusion type was not significantly associated with RFS or OS, but was associated with phenotype. A modified ST-G incorporating necrosis showed higher correlation with RFS (p = 0.0006) and remained significant (p = 0.02) when considering only the primary tumors. From our data, mitotic rate and necrosis appear to stratify this family of tumors most accurately and could be incorporated in a future grading scheme

Optical properties and charge-transfer excitations in edge-functionalized all-graphene nanojunctions

We investigate the optical properties of edge-functionalized graphene nanosystems, focusing on the formation of junctions and charge transfer excitons. We consider a class of graphene structures which combine the main electronic features of graphene with the wide tunability of large polycyclic aromatic hydrocarbons. By investigating prototypical ribbon-like systems, we show that, upon convenient choice of functional groups, low energy excitations with remarkable charge transfer character and large oscillator strength are obtained. These properties can be further modulated through an appropriate width variation, thus spanning a wide range in the low-energy region of the UV-Vis spectra. Our results are relevant in view of designing all-graphene optoelectronic nanodevices, which take advantage of the versatility of molecular functionalization, together with the stability and the electronic properties of graphene nanostructures.Comment: J. Phys. Chem. Lett. (2011), in pres