Inverse association of circulating SIRT1 and adiposity. A study on underweight, normal weight, and obese patients

Context: Sirtuins (SIRTs) are NAD+-dependent deacetylases, cellular sensors to detect energy availability, and modulate metabolic processes. SIRT1, the most studied family member, influences a number of tissues including adipose tissue. Expression and activity of SIRT1 reduce with weight gain and increase in conditions of starvation. Objective: To focus on SIRT1 plasma concentrations in different conditions of adiposity and to correlate SIRT1 with fat content and distribution, energy homeostasis and inflammation in under-weight, normal-weight, and obese individuals. Materials and Methods: 21 patients with anorexia nervosa, 26 normal-weight and 75 patients with obesity were evaluated. Body fat composition by dual-energy X-ray absorptiometry, ultrasound liver adiposity, echocardiographic epicardial fat thickness (EFT), inflammatory (ESR, CRP, and fibrinogen), and metabolic (FPG, insulin, LDL- and HDL-cholesterol, triglycerides) parameters, calculated basal metabolic rate (BMR) and plasma SIRT1 (ELISA) were measured. Results: SIRT1 was significantly higher in anorexic patients compared to normal-weight and obese patients (3.27 ± 2.98, 2.27 ± 1.13, and 1.36 ± 1.31 ng/ml, respectively). Linear regression models for each predictor variable adjusted for age and sex showed that SIRT1 concentration was inversely and significantly correlated with EFT, fat mass %, liver fat content, BMR, weight, BMI, WC, LDL-cholesterol, insulin, ESR. Stepwise multiple regression analysis revealed that age and EFT were the best independent correlates of SIRT1 (β = -0.026 ± 0.011, p = 0.025, and β = -0.516 ± 0.083, p < 0.001, respectively). Conclusions: Plasma SIRT1 shows a continuous pattern that inversely follows the whole spectrum of adiposity. SIRT1 significantly associates with EFT, a strong index of visceral fat phenotype, better than other indexes of adiposity studied here

Fracture-fill calcite as a record of microbial methanogenesis and fluid migration: a case study from the Devonian Antrim Shale, Michigan Basin

The Devonian Antrim Shale is an organic-rich, naturally fractured black shale in the Michigan Basin that serves as both a source and reservoir for natural gas. A well-developed network of major, through-going vertical fractures controls reservoir-scale permeability in the Antrim Shale. Many fractures are open, but some are partially sealed by calcite cements that retain isotopic evidence of widespread microbial methanogenesis. Fracture filling calcite displays an unusually broad spectrum of δ 13 C values (+34 to −41‰ PDB), suggesting that both aerobic and anaerobic bacterial processes were active in the reservoir. Calcites with high δ 13 C values (>+15‰) record cementation of fractures from dissolved inorganic carbon (DIC) generated during bacterial methanogenesis. Calcites with low δ 13 C values (<−32‰) are solely associated with outcrop samples and record methane oxidation during cement precipitation. Fracture-fill calcite with δ 13 C values between −10 and −30‰ can be attributed to variable organic matter oxidation pathways, methane oxidation, and carbonate rock buffering. Identification of 13 C-rich calcite provides unambiguous evidence of biogenic methane generation and may be used to identify gas deposits in other sedimentary basins. It is likely that repeated glacial advances and retreats exposed the Antrim Shale at the basin margin, enhanced meteoric recharge into the shallow part of the fractured reservoir, and initiated multiple episodes of bacterial methanogenesis and methanotrophic activity that were recorded in fracture-fill cements. The δ 18 O values in both formation waters and calcite cements increase with depth in the basin (−12 to −4‰ SMOW, and +21 to +27‰ PDB, respectively). Most fracture-fill cements from outcrop samples have δ 13 C values between −41 and −15‰ PDB. In contrast, most cement in cores have δ 13 C values between +15 and +34‰ PDB. Radiocarbon and 230 Th dating of fracture-fill calcite indicates that the calcite formed between 33 and 390 ka, well within the Pleistocene Epoch.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75720/1/j.1468-8123.2002.00036.x.pd

Heart rate variability and target organ damage in hypertensive patients

Background: We evaluated the association between linear standard Heart Rate Variability (HRV) measures and vascular, renal and cardiac target organ damage (TOD). Methods: A retrospective analysis was performed including 200 patients registered in the Regione Campania network (aged 62.4 ± 12, male 64%). HRV analysis was performed by 24-h holter ECG. Renal damage was assessed by estimated glomerular filtration rate (eGFR), vascular damage by carotid intima-media thickness (IMT), and cardiac damage by left ventricular mass index. Results: Significantly lower values of the ratio of low to high frequency power (LF/HF) were found in the patients with moderate or severe eGFR (p-value < 0.001). Similarly, depressed values of indexes of the overall autonomic modulation on heart were found in patients with plaque compared to those with a normal IMT (p-value <0.05). These associations remained significant after adjustment for other factors known to contribute to the development of target organ damage, such as age. Moreover, depressed LF/HF was found also in patients with left ventricular hypertrophy but this association was not significant after adjustment for other factors. Conclusions: Depressed HRV appeared to be associated with vascular and renal TOD, suggesting the involvement of autonomic imbalance in the TOD. However, as the mechanisms by which abnormal autonomic balance may lead to TOD, and, particularly, to renal organ damage are not clearly known, further prospective studies with longitudinal design are needed to determine the association between HRV and the development of TOD

Chemotherapy of Skull Base Chordoma Tailored on Responsiveness of Patient-Derived Tumor Cells to Rapamycin1,2

Skull base chordomas are challenging tumors due to their deep surgical location and resistance to conventional radiotherapy. Chemotherapy plays a marginal role in the treatment of chordoma resulting from lack of preclinical models due to the difficulty in establishing tumor cell lines and valuable in vivo models. Here, we established a cell line from a recurrent clival chordoma. Cells were cultured for more than 30 passages and the expression of the chordoma cell marker brachyury was monitored using both immunohistochemistry and Western blot. Sensitivity of chordoma cells to the inhibition of specific signaling pathways was assessed through testing of a commercially available small molecule kinase inhibitor library. In vivo tumorigenicity was evaluated by grafting chordoma cells onto immunocompromised mice and established tumor xenografts were treated with rapamycin. Rapamycin was administered to the donor patient and its efficacy was assessed on follow-up neuroimaging. Chordoma cells main- tained brachyury expression at late passages and generated xenografts closely mimicking the histology and phe- notype of the parental tumor. Rapamycin was identified as an inhibitor of chordoma cell proliferation. Molecular analyses on tumor cells showed activation of the mammalian target of rapamycin signaling pathway and mutation of KRAS gene. Rapamycin was also effective in reducing the growth of chordoma xenografts. On the basis of these results, our patient received rapamycin therapy with about six-fold reduction of the tumor growth rate upon 10-month follow-up neuroimaging. This is the first case of chordoma in whom chemotherapy was tailored on the basis of the sensitivity of patient-derived tumor cells

Analysis of end-to-end multi-domain management and orchestration frameworks for software defined infrastructures: An architectural survey

Over the last couple of years, industry operators' associations issued requirements towards an end-to-end management and orchestration plane for 5G networks. Consequently, standard organisations started their activities in this domain. This article provides an analysis and an architectural survey of these initiatives and of the main requirements, proposes descriptions for the key concepts of domain, resource and service slicing, end-to-end orchestration and a reference architecture for the end-to-end orchestration plane. Then, a set of currently available or under development domain orchestration frameworks are mapped to this reference architecture. These frameworks, meant to provide coordination and automated management of cloud and networking resources, network functions and services, fulfil multi-domain (i.e. multi-technology and multi-operator) orchestration requirements, thus enabling the realisation of an end-to-end orchestration plane. Finally, based on the analysis of existing single-domain and multi-domain orchestration components and requirements, this paper presents a functional architecture for the end-to-end management and orchestration plane, paving the way to its full realisation

Soft tissue non-Hodgkin lymphoma of shoulder in a HIV patient: a report of a case and review of the literature

The risk of developing lymphoma is greatly increased in HIV infection. Musculoskeletal manifestations of the human immunodeficiency virus (HIV) are common and are sometimes the initial presentation of the disease. Muscle, bone, and joints are involved by septic arthritis, myopathies and neoplasms. HIV-related neoplastic processes that affect the musculoskeletal system include Kaposi's sarcoma and non-Hodgkin's lymphoma, the latter being mainly localized at lower extremities, spine and skull

Prostacyclin reverses platelet stress fibre formation causing platelet aggregate instability

Prostacyclin (PGI2) modulates platelet activation to regulate haemostasis. Evidence has emerged to suggest that thrombi are dynamic structures with distinct areas of differing platelet activation. It was hypothesised that PGI2 could reverse platelet spreading by actin cytoskeletal modulation, leading to reduced capability of platelet aggregates to withstand a high shear environment. Our data demonstrates that post-flow of PGI2 over activated and spread platelets on fibrinogen, identified a significant reduction in platelet surface area under high shear. Exploration of the molecular mechanisms underpinning this effect revealed that PGI2 reversed stress fibre formation in adherent platelets, reduced platelet spreading, whilst simultaneously promoting actin nodule formation. The effects of PGI2 on stress fibres were mimicked by the adenylyl cyclase activator forskolin and prevented by inhibitors of protein kinase A (PKA). Stress fibre formation is a RhoA dependent process and we found that treatment of adherent platelets with PGI2 caused inhibitory phosphorylation of RhoA, reduced RhoA GTP-loading and reversal of myosin light chain phosphorylation. Phospho-RhoA was localised in actin nodules with PKA type II and a number of other phosphorylated PKA substrates. This study demonstrates that PGI2 can reverse key platelet functions after their initial activation and identifies a novel mechanism for controlling thrombosis

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO