Effects of balloon injury on neointimal hyperplasia in steptozotocin-induced diabetes and in hyperinsulinemic nondiabetic pancreatic islet-transplanted rats.

BACKGROUND: The mechanisms of increased neointimal hyperplasia after coronary interventions in diabetic patients are still unknown. METHODS AND RESULTS: Glucose and insulin effects on in vitro vascular smooth muscle cell (VSMC) proliferation and migration were assessed. The effect of balloon injury on neointimal hyperplasia was studied in streptozotocin-induced diabetic rats with or without adjunct insulin therapy. To study the effect of balloon injury in nondiabetic rats with hyperinsulinemia, pancreatic islets were transplanted under the kidney capsule in normal rats. Glucose did not increase VSMC proliferation and migration in vitro. In contrast, insulin induced a significant increase in VSMC proliferation and migration in cell cultures. Furthermore, in VSMC culture, insulin increased MAPK activation. A reduction in neointimal hyperplasia was consistently documented after vascular injury in hyperglycemic streptozotocin-induced diabetic rats. Insulin therapy significantly increased neointimal hyperplasia in these rats. This effect of hyperinsulinemia was totally abolished by transfection on the arterial wall of the N17H-ras-negative mutant gene. Finally, after experimental balloon angioplasty in hyperinsulinemic nondiabetic islet-transplanted rats, a significant increase in neointimal hyperplasia was observed. CONCLUSIONS: In rats with streptozotocin-induced diabetes, balloon injury was not associated with an increase in neointimal formation. Exogenous insulin administration in diabetic rats and islet transplantation in nondiabetic rats increased both blood insulin levels and neointimal hyperplasia after balloon injury. Hyperinsulinemia through activation of the ras/MAPK pathway, rather than hyperglycemia per se, seems to be of crucial importance in determining the exaggerated neointimal hyperplasia after balloon angioplasty in diabetic animals

Increasing pattern recognition accuracy for chemical sensing by evolutionary based drift compensation

Artificial olfaction systems, which mimic human olfaction by using arrays of gas chemical sensors combined with pattern recognition methods, represent a potentially low-cost tool in many areas of industry such as perfumery, food and drink production, clinical diagnosis, health and safety, environmental monitoring and process control. However, successful applications of these systems are still largely limited to specialized laboratories. Sensor drift, i.e., the lack of a sensor's stability over time, still limits real in dustrial setups. This paper presents and discusses an evolutionary based adaptive drift-correction method designed to work with state-of-the-art classification systems. The proposed approach exploits a cutting-edge evolutionary strategy to iteratively tweak the coefficients of a linear transformation which can transparently correct raw sensors' measures thus mitigating the negative effects of the drift. The method learns the optimal correction strategy without the use of models or other hypotheses on the behavior of the physical chemical sensors

A high resolution line survey of IRC+10216 with Herschel. First results: Detection of warm silicon dicarbide SiC2

We present the first results of a high-spectral-resolution survey of the carbon-rich evolved star IRC+10216 that was carried out with the HIFI spectrometer onboard Herschel. This survey covers all HIFI bands, with a spectral range from 488 to 1901GHz. In this letter we focus on the band-1b spectrum, in a spectral range 554.5-636.5GHz, where we identified 130 spectral features with intensities above 0.03 K and a signal-to-noise ratio >5. Detected lines arise from HCN, SiO, SiS, CS, CO, metal-bearing species and, surprisingly, silicon dicarbide (SiC2). We identified 55 SiC2 transitions involving energy levels between 300 and 900 K. By analysing these rotational lines, we conclude that SiC2 is produced in the inner dust formation zone, with an abundance of ~2x10^-7 relative to molecular hydrogen. These SiC2 lines have been observed for the first time in space and have been used to derive an SiC2 rotational temperature of ~204 K and a source-averaged column density of ~6.4x10^15 cm^-2. Furthermore, the high quality of the HIFI data set was used to improve the spectroscopic rotational constants of SiC2.Comment: A&A HIFI Special Issue, 201

Treatment with K6PC-5, a selective stimulator of SPHK1, ameliorates intestinal homeostasis in an animal model of Huntington's disease

Abstract Emerging evidence indicates that Huntington's disease (HD) may be described as multi-organ pathology. In this context, we and others have contributed to demonstrate that the disease is characterized by an impairment of the homeostasis of gastro-intestinal (GI) tract. Sphingolipids represent a class of molecules involved in the regulation and maintenance of different tissues and organs including GI system. In this study, we investigated whether the alteration of Sphingosine-1-phosphate (S1P) metabolism, previously described in human HD brains and animal models, is also detectable peripherally in R6/2 HD mice. Our findings indicate, for the first time, that sphingolipid metabolism is perturbed early in the disease in the intestinal tract of HD mice and, its modulation by K6PC-5, a selective activator of S1P synthesis, preserved intestinal integrity and homeostasis. These results further support the evidence that modulation of sphingolipid pathways may represent a potential therapeutic option in HD and suggest that it has also the potential to counteract the peripheral disturbances which may usually complicate the management of the disease and affect patient's quality of life

Phosphoproteomic Analysis of Platelets in Severe Obesity Uncovers Platelet Reactivity and Signaling Pathways Alterations

OBJECTIVE: Obesity is associated with a proinflammatory and prothrombotic state that supports atherosclerosis progression. The goal of this study was to gain insights into the phosphorylation events related to platelet reactivity in obesity and identify platelet biomarkers and altered activation pathways in this clinical condition. APPROACH AND RESULTS: We performed a comparative phosphoproteomic analysis of resting platelets from obese patients and their age- A nd gender-matched lean controls. The phosphoproteomic data were validated by mechanistic, functional, and biochemical assays. We identified 220 differentially regulated phosphopeptides, from at least 175 proteins; interestingly, all were up-regulated in obesity. Most of the altered phosphoproteins are involved in SFKs (Src-family kinases)-related signaling pathways, cytoskeleton reorganization, and vesicle transport, some of them validated by targeted mass spectrometry. To confirm platelet dysfunction, flow cytometry assays were performed in whole blood indicating higher surface levels of GP (glycoprotein) VI and CLEC (C-type lectin-like receptor) 2 in platelets from obese patients correlating positively with body mass index. Receiver operator characteristics curves analysis suggested a much higher sensitivity for GPVI to discriminate between obese and lean individuals. Indeed, we also found that obese platelets displayed more adhesion to collagen-coated plates. In line with the above data, soluble GPVI levels-indicative of higher GPVI signaling activation-were almost double in plasma from obese patients. CONCLUSIONS: Our results provide novel information on platelet phosphorylation changes related to obesity, revealing the impact of this chronic pathology on platelet reactivity and pointing towards the main signaling pathways dysregulatedThis work was supported by the Spanish Ministry of Science and Innovation (grants No. SAF2016-79662-R, and PID2019-108727RB-I00), co-funded by the European Regional Development Fund (ERDF). Financial support from the Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia (Centro Singular de investigación de Galicia accreditation 2019–2022, ED431G 2019/02; predoctoral grant 2018 Call) and the ERDF is also gratefully acknowledged. E.E. Gardiner and R.K. Andrews are supported by the National Health and Medical Research Council of Australia. The Proteomics Laboratory CSIC/UAB (Centro Superior de Investigaciones Científicas/Universidad Autónoma de Barcelona) is a member of Proteored, PRB3-ISCIII (Instituto de Salud Carlos III), and is supported by Grant PT17/0019/0008, funded by ISCIII and ERDF. L.A. Morán is supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 766118. S.P. Watson is supported by a BHF (British Heart Foundation) Chair (CH03/003)

238U(n, γ) reaction cross section measurement with C 6D6 detectors at the n-TOF CERN facility

This is an Open Access article distributed under the terms of the Creative Commons Attribution License 2.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly citedThe radiative capture cross section of 238U is very important for the developing of new reactor technologies and the safety of existing ones. Here the preliminary results of the 238U(n,γ) cross section measurement performed at n-TOF with C6D6 scintillation detectors are presented, paying particular attention to data reduction and background subtraction.Peer reviewe

The nucleosynthesis of heavy elements in Stars : The key isotope 25Mg

This is an Open Access article distributed under the terms of the Creative Commons Attribution License 2.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly citedWe have measured the radiative neutron-capture cross section and the total neutron-induced cross section of one of the most important isotopes for the s process, the 25Mg. The measurements have been carried out at the neutron time-of-flight facilities n-TOF at CERN (Switzerland) and GELINA installed at the EC-JRC-IRMM (Belgium). The cross sections as a function of neutron energy have been measured up to approximately 300 keV, covering the energy region of interest to the s process. The data analysis is ongoing and preliminary results show the potential relevance for the s process.Peer reviewe

Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

Atmospheric gas absorption knowledge in the submillimeter: Modeling, field measurements, and uncertainty quantification

Members of the atmospheric and astronomical science communities met to review the current state of the art of the submillimeter spectral region. Knowledge of gas spectroscopy is still questionable at these frequencies but is important to fully exploit upcoming meteorological satellite measurements