Modulation of cAMP levels by highâ fat diet and curcumin and regulatory effects on CD36/FAT scavenger receptor/fatty acids transporter gene expression

Curcumin, a polyphenol from turmeric (Curcuma longa), reduces inflammation, atherosclerosis, and obesity in several animal studies. In Ldlrâ /â mice fed a highâ fat diet (HFD), curcumin reduces plasma lipid levels, therefore contributing to a lower accumulation of lipids and to reduced expression of fatty acid transport proteins (CD36/FAT, FABP4/aP2) in peritoneal macrophages. In this study, we analyzed the molecular mechanisms by which curcumin (500, 1000, 1500 mg/kg diet, for 4 months) may influence plasma and tissue lipid levels in Ldlrâ /â mice fed an HFD. In liver, HFD significantly suppressed cAMP levels, and curcumin restored almost normal levels. Similar trends were observed in adipose tissues, but not in brain, skeletal muscle, spleen, and kidney. Treatment with curcumin increased phosphorylation of CREB in liver, what may play a role in regulatory effects of curcumin in lipid homeostasis. In cell lines, curcumin increased the level of cAMP, activated the transcription factor CREB and the human CD36 promoter via a sequence containing a consensus CREB response element. Regulatory effects of HFD and Cur on gene expression were observed in liver, less in skeletal muscle and not in brain. Since the cAMP/protein kinase A (PKA)/CREB pathway plays an important role in lipid homeostasis, energy expenditure, and thermogenesis by increasing lipolysis and fatty acid βâ oxidation, an increase in cAMP levels induced by curcumin may contribute to its hypolipidemic and antiâ atherosclerotic effects. © 2016 BioFactors, 43(1):42â 53, 2017Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136289/1/biof1307_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136289/2/biof1307.pd

WRF Sensitivity Analysis in Wind and Temperature Fields Simulation for the Northern Sahara and the Mediterranean Basin

Different configurations for the Weather Research and Forecasting (WRF) model were evaluated to improve wind and temperature fields predictions in the Northern Sahara and the Mediterranean basin. Eight setups, associated with different combinations of the surface layer physical parameters, the land surface model, and the grid nudging parameters, were considered. Numerical simulations covered the entire month of November 2017. Model results were compared with surface data from meteorological stations. The introduction of the grid nudging parameters leads to a general improvement of the modeled 10 m wind speed and 2 m temperature. In particular, nudging of wind speed parameter inside the planetary boundary layer (PBL) provides the most remarkable differences. In contrast, the nudging of temperature and relative humidity parameters inside the PBL may be switched off to reduce computational time and data storage. Furthermore, it was shown that the prediction of the 10 m wind speed and 2 m temperature is quite sensitive to the choice of the surface layer scheme and the land surface model. This paper provides useful suggestions to improve the setup of the WRF model in the Northern Sahara and the Mediterranean basin. These results are also relevant for topics related with the emission of mineral dust and sea spray within the Mediterranean region

Automated digital image quantification of histological staining for the analysis of the trilineage differentiation potential of mesenchymal stem cells

BACKGROUND Multipotent mesenchymal stem cells (MSCs) have the potential to repair and regenerate damaged tissues and are considered as attractive candidates for the development of cell-based regenerative therapies. Currently, there are more than 200 clinical trials involving the use of MSCs for a wide variety of indications. However, variations in their isolation, expansion, and particularly characterization have made the interpretation of study outcomes or the rigorous assessment of therapeutic efficacy difficult. An unbiased characterization of MSCs is of major importance and essential to guaranty that only the most suitable cells will be used. The development of standardized and reproducible assays to predict MSC potency is therefore mandatory. The currently used quantification methodologies for the determination of the trilineage potential of MSCs are usually based on absorbance measurements which are imprecise and prone to errors. We therefore aimed at developing a methodology first offering a standardized way to objectively quantify the trilineage potential of MSC preparations and second allowing to discriminate functional differences between clonally expanded cell populations. METHOD MSCs originating from several patients were differentiated into osteoblasts, adipocytes, and chondroblasts for 14, 17, and 21 days. Differentiated cells were then stained with the classical dyes: Alizarin Red S for osteoblasts, Oil Red O for adipocytes, and Alcian Blue 8GX for chondroblasts. Quantification of differentiation was then performed with our newly developed digital image analysis (DIA) tool followed by the classical absorbance measurement. The results from the two techniques were then compared. RESULT Quantification based on DIA allowed highly standardized and objective dye quantification with superior sensitivity compared to absorbance measurements. Furthermore, small differences between MSC lines in the differentiation potential were highlighted using DIA whereas no difference was detected using absorbance quantification. CONCLUSION Our approach represents a novel method that simplifies the laboratory procedures not only for the quantification of histological dyes and the degree of differentiation of MSCs, but also due to its color independence, it can be easily adapted for the quantification of a wide range of staining procedures in histology. The method is easily applicable since it is based on open source software and standard light microscopy

Magnetic and morphological characterization of Nd2Fe14B magnets with different quality grades at low temperature 5-300 K

An increasing number of cryogenic devices may benefit from the use of Nd2Fe14B permanent magnets. However, it is necessary to precisely know their behavior because magnetization varies significantly due to Spin Reorientation Transition. In this work, magnetic and morphological characterization of Nd2Fe14B commercial polycrystalline magnets with different quality grades from 5 to 300 K is provided. A set of magnets ranging from N35 to N52 quality have been analyzed. Mean grain dimension as well as material composition elements are provided. Higher quality magnets show smaller mean grain dimensions. Regarding cryogenic temperatures, the well know spin transition effect appears in all the magnets as expected, however, the transition temperature occurs at different temperatures in a range from 112 to 120 K which is lower than those obtained for single crystal samples. Moreover, the relative variation of the remanence from 300 to 5 K is lower than 4% while the maximum expected variation is in average 11%. As extra information, the same analyzes are provided for additional quality grades N40M, N40S, N40SH and N40UH.The research leading to these results has received funding from the European Community's Seventh Framework Programme ([FP7/2007-2013]) under grant agreement n° 263014

Performance of Magnetic-Superconductor Non-Contact Harmonic Drive for Cryogenic Space Applications

Harmonic drives are profusely used in aerospace mainly because of their compactness and large reduction ratio. However, their use in cryogenic environments is still a challenge. Lubrication and fatigue are non-trivial issues under these conditions. The objective of the Magnetic-Superconductor Cryogenic Non-contact Harmonic Drive (MAGDRIVE) project, funded by the EU Space FP7, is to design, build, and test a new concept of MAGDRIVE. Non-contact interactions among magnets, soft magnetic materials, and superconductors are efficiently used to provide a high reduction ratio gear that smoothly and naturally operates at cryogenic environments. The limiting elements of conventional harmonic drives (teeth, flexspline, and ball bearings) are substituted by contactless mechanical components (magnetic gear and superconducting magnetic bearings). The absence of contact between moving parts prevents wear, lubricants are no longer required, and the operational lifetime is greatly increased. This is the first mechanical reducer in mechanical engineering history without any contact between moving parts. In this paper, the test results of a −1:20 inverse reduction ratio MAGDRIVE prototype are reported. In these tests, successful operation at 40 K and 10−3 Pa was demonstrated for more than 1.5 million input cycles. A maximum torque of 3 N·m and an efficiency of 80% were demonstrated. The maximum tested input speed was 3000 rpm, six times the previous existing record for harmonic drives at cryogenic temperature

Early diagnosis, disease stage and prognosis in wild‐type transthyretin amyloid cardiomyopathy: The DIAMOND study

Aims: Disease staging and prognostic scoring in wild-type transthyretin-related cardiac amyloidosis (ATTRwt-CA) can be captured by two systems (NAC and Columbia scores). However, uncertainty remains as epidemiology of the disease is evolving rapidly. We evaluated features associated with staging systems across ATTRwt-CA patients from different diagnostic pathways, and their association with prognosis. Methods: We performed an analysis on DIAMOND patients with available data to evaluate NAC and Columbia score. DIAMOND was a retrospective study from 17 Italian referral centres for CA, enrolling 1281 patients diagnosed between 2016 and 2021, and aimed at describing characteristics of pathways leading to ATTRwt-CA diagnosis. Of the original cohort, 811 patients were included in this analysis. Each patient had NAC and Columbia score calculated. Patients were grouped according to NAC and Columbia scoring classes. We described characteristics of patients according to staging classes and diagnostic pathways at diagnosis. Prevalence of early diagnoses, defined as NAC Ia, NYHA class I, no use of diuretics, no history of heart failure (HF) hospitalizations nor of atrial fibrillation prior to diagnosis, was investigated. Finally, prognostic variables were tested alone and grouped as NAC or Columbia scores in Cox univariate and multivariate regression analyses. Prognosis was investigated as all-cause mortality, in the whole population and dividing patients in HF versus other diagnostic pathways. Results: Only 1% of the study population had an early ATTRwt-CA diagnosis. Distribution of prognostic variables and of NAC and Columbia classes was heterogeneous across diagnostic pathways. The prevalence of NAC III and Columbia III was higher in the HF diagnostic pathway, but all NAC and Columbia classes were present in all pathways. Both NAC and Columbia scores were associated with all-cause mortality at univariate Cox regression analysis in the whole population, in patients from the HF diagnostic pathway and in those from other pathways. At multivariate analysis, Columbia score remained significantly associated with the outcome, together with age at diagnosis, left ventricular ejection fraction and maximal wall thickness. Conclusions: In this contemporary nationwide cohort, an ATTRwt-CA early diagnosis was very rare. Disease staging with NAC and Columbia scoring systems determined classes of patients with heterogeneous features. Both scores were significantly associated with mortality, but other variables also had prognostic significance

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| < 0.03 at 95% confidence level. [Figure not available: see fulltext.

An embedding technique to determine ττ backgrounds in proton-proton collision data

An embedding technique is presented to estimate standard model tau tau backgrounds from data with minimal simulation input. In the data, the muons are removed from reconstructed mu mu events and replaced with simulated tau leptons with the same kinematic properties. In this way, a set of hybrid events is obtained that does not rely on simulation except for the decay of the tau leptons. The challenges in describing the underlying event or the production of associated jets in the simulation are avoided. The technique described in this paper was developed for CMS. Its validation and the inherent uncertainties are also discussed. The demonstration of the performance of the technique is based on a sample of proton-proton collisions collected by CMS in 2017 at root s = 13 TeV corresponding to an integrated luminosity of 41.5 fb(-1).Peer reviewe