Resting metabolic rate (RMR) adaptation occurs during obesity and is hypothesized to contribute to failed weight management. Angiotensin II (Ang-II) type 1 (AT1A) receptors in Agouti-related peptide ...(AgRP) neurons contribute to the integrative control of RMR, and deletion of AT1A from AgRP neurons causes RMR adaptation. Extracellular patch-clamp recordings identify distinct cellular responses of individual AgRP neurons from lean mice to Ang-II: no response, inhibition via AT1A and Gαi, or stimulation via Ang-II type 2 (AT2) receptors and Gαq. Following diet-induced obesity, a subset of Ang-II/AT1A-inhibited AgRP neurons undergo a spontaneous G-protein “signal switch,” whereby AT1A stop inhibiting the cell via Gαi and instead begin stimulating the cell via Gαq. DREADD-mediated activation of Gαi, but not Gαq, in AT1A-expressing AgRP cells stimulates RMR in lean and obese mice. Thus, loss of AT1A-Gαi coupling within the AT1A-expressing AgRP neuron subtype represents a molecular mechanism contributing to RMR adaptation.
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•Three AgRP neuron subtypes are dissociated via electrochemical responses to Ang-II•The Type 1 AgRP neuron subtype in lean mice is inhibited via AT1A and a Gαi cascade•Obesity induces a spontaneous AT1A-Gαi to -Gαq signal switch in Type 1 AgRP neurons•The loss of AT1A-Gαi coupling in Type 1 AgRP neurons contributes to RMR adaptation
Balapattabi et al. discovered that a specific subtype of Agouti-related peptide (AgRP) neuron in the hypothalamic arcuate nucleus is inhibited by the angiotensin II type 1 receptor (AT1R). Obesity causes AT1R within this AgRP subtype to switch from inhibitory Gαi to stimulatory Gαq signaling, resulting in dysfunctional control of resting metabolism.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A common preclinical model of hypertension characterized by low circulating renin is the "deoxycorticosterone acetate (DOCA)-salt" model, which influences blood pressure and metabolism through ...mechanisms involving the angiotensin II type 1 receptor (AT
R) in the brain. More specifically, AT
R within Agouti-related peptide (AgRP) neurons of the arcuate nucleus of the hypothalamus (ARC) has been implicated in selected effects of DOCA-salt. In addition, microglia have been implicated in the cerebrovascular effects of DOCA-salt and angiotensin II. To characterize DOCA-salt effects upon the transcriptomes of individual cell types within the ARC, we used single-nucleus RNA sequencing (snRNAseq) to examine this region from male C57BL/6J mice that underwent sham or DOCA-salt treatment. Thirty-two unique primary cell type clusters were identified. Sub-clustering of neuropeptide-related clusters resulted in identification of three distinct AgRP subclusters. DOCA-salt treatment caused subtype-specific changes in gene expression patterns associated with AT
R and G protein signaling, neurotransmitter uptake, synapse functions, and hormone secretion. In addition, two primary cell type clusters were identified as resting versus activated microglia, and multiple distinct subtypes of activated microglia were suggested by sub-cluster analysis. While DOCA-salt had no overall effect on total microglial density within the ARC, DOCA-salt appeared to cause a redistribution of the relative abundance of activated microglia subtypes. These data provide novel insights into cell-specific molecular changes occurring within the ARC during DOCA-salt treatment, and prompt increased investigation of the physiological and pathophysiological significance of distinct subtypes of neuronal and glial cell types.
Sleep and metabolic function Morselli, Lisa L.; Guyon, Aurore; Spiegel, Karine
Pflügers Archiv,
01/2012, Volume:
463, Issue:
1
Journal Article
Peer reviewed
Open access
Evidence for the role of sleep on metabolic and endocrine function has been reported more than four decades ago. In the past 30 years, the prevalence of obesity and diabetes has greatly increased in ...industrialized countries, and self-imposed sleep curtailment, now very common, is starting to be recognized as a contributing factor, alongside with increased caloric intake and decreased physical activity. Furthermore, obstructive sleep apnea, a chronic condition characterized by recurrent upper airway obstruction leading to intermittent hypoxemia and sleep fragmentation, has also become highly prevalent as a consequence of the epidemic of obesity and has been shown to contribute, in a vicious circle, to the metabolic disturbances observed in obese patients. In this article, we summarize the current data supporting the role of sleep in the regulation of glucose homeostasis and the hormones involved in the regulation of appetite. We also review the results of the epidemiologic and laboratory studies that investigated the impact of sleep duration and quality on the risk of developing diabetes and obesity, as well as the mechanisms underlying this increased risk. Finally, we discuss how obstructive sleep apnea affects glucose metabolism and the beneficial impact of its treatment, the continuous positive airway pressure. In conclusion, the data available in the literature highlight the importance of getting enough good sleep for metabolic health.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
The identification of an emission line is unambiguous when multiple spectral features are clearly visible in the same spectrum. However, in many cases, only one line is detected, making it ...difficult to correctly determine the redshift. We developed a freely available unsupervised machine-learning algorithm based on unbiased topology (UMLAUT) that can be used in a very wide variety of contexts, including the identification of single emission lines. To this purpose, the algorithm combines different sources of information, such as the apparent magnitude, size and color of the emitting source, and the equivalent width and wavelength of the detected line. In each specific case, the algorithm automatically identifies the most relevant ones (i.e., those able to minimize the dispersion associated with the output parameter). The outputs can be easily integrated into different algorithms, allowing us to combine supervised and unsupervised techniques and increasing the overall accuracy. We tested our software on WISP (WFC3 IR Spectroscopic Parallel) survey data. WISP represents one of the closest existing analogs to the near-IR spectroscopic surveys that are going to be performed by the future Euclid and Roman missions. These missions will investigate the large-scale structure of the universe by surveying a large portion of the extragalactic sky in near-IR slitless spectroscopy, detecting a relevant fraction of single emission lines. In our tests, UMLAUT correctly identifies real lines in 83.2% of the cases. The accuracy is slightly higher (84.4%) when combining our unsupervised approach with a supervised approach we previously developed.
Future surveys focusing on understanding the nature of dark energy (e.g., Euclid and WFIRST) will cover large fractions of the extragalactic sky in near-IR slitless spectroscopy. These surveys will ...detect a large number of galaxies that will have only one emission line in the covered spectral range. In order to maximize the scientific return of these missions, it is imperative that single emission lines are correctly identified. Using a supervised machine-learning approach, we classified a sample of single emission lines extracted from the WFC3 IR Spectroscopic Parallel survey, one of the closest existing analogs to future slitless surveys. Our automatic software integrates a spectral energy distribution (SED)-fitting strategy with additional independent sources of information. We calibrated it and tested it on a "gold" sample of securely identified objects with multiple lines detected. The algorithm correctly classifies real emission lines with an accuracy of 82.6%, whereas the accuracy of the SED-fitting technique alone is low (∼50%) due to the limited amount of photometric data available (≤6 bands). While not specifically designed for the Euclid and WFIRST surveys, the algorithm represents an important precursor of similar algorithms to be used in these future missions.
Radio Pharmaceutical Therapy (RPT) comes forth as a promising technique to treat a wide range of tumors while ensuring low collateral damage to nearby healthy tissues. This kind of cancer therapy ...exploits the radiation following the decay of a specific radionuclide to deliver a lethal dose to tumor tissues. In the framework of the ISOLPHARM project of INFN, 111Ag was recently proposed as a promising core of a therapeutic radiopharmaceutical. In this paper, the production of 111Ag via neutron activation of 110Pd-enriched samples inside a TRIGA Mark II nuclear research reactor is studied. The radioisotope production is modeled using two different Monte Carlo codes (MCNPX and PHITS) and a stand-alone inventory calculation code FISPACT-II, with different cross section data libraries. The whole process is simulated starting from an MCNP6-based reactor model producing the neutron spectrum and flux in the selected irradiation facility. Moreover, a cost-effective, robust and easy-to-use spectroscopic system, based on a Lanthanum Bromo-Chloride (LBC) inorganic scintillator, is designed and characterized, with the aim of using it, in the future, for the quality control of the ISOLPHARM irradiated targets at the SPES facility of the Legnaro National Laboratories of INFN. natPd and 110Pd-enriched samples are irradiated in the reactor main irradiation facility and spectroscopically characterized using the LBC-based setup and a multiple-fit analysis procedure. Experimental results are compared with theoretical predictions of the developed models, showing that inaccuracies in the available cross section libraries prevent an accurate reproduction of the generated radioisotope activities. Nevertheless, models are normalized to our experimental data allowing for a reliable planning of the 111Ag production in a TRIGA Mark II reactor.
•111Ag proposed in ISOLPHARM-INFN project as a promising core of radiopharmaceutical.•Temporary 111Ag production via neutron activation inside a TRIGA Mark II reactor.•Spectroscopic characterization of the production with a dedicated LBC-based setup.•Monte Carlo model and benchmark with experimental data to plan the 111Ag production.•Future 111Ag production with high-specific activity at the Italian SPES-ISOL facility.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The effect of leaching rain on the corrosion behaviour of bronze UNSC83600 was investigated as to the influence of alloying elements (Cu, Sn, Zn, Pb) through dropping tests simulating a severe runoff ...condition with a solution reproducing natural acid rain. Corrosion was followed with time monitoring both samples and leaching solutions (up to 30 days) by SEM, EDS, Raman spectroscopy, XRD, AAS. The bronze patina behaves as a porous layer enriched in stable tin compounds allowing uniform dissolution of Cu, Zn and partly of Pb. Laboratory results are in good agreement with field studies of outdoor bronzes in unsheltered condition.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Accelerator-based techniques with electromagnetic mass separation are considered among the most innovative and promising strategies to produce non-conventional radionuclides for nuclear medicine. ...Such approach was successfully used at CERN, where the dedicated MEDICIS facility was built, and at TRIUMF, where the ISAC radioactive beam facility was used to produce unconventional α-emitters. In such framework, the Legnaro National Laboratories of the Italian Institute of Nuclear Physics (INFN-LNL) proposed the ISOLPHARM project (ISOL technique for radioPHARMaceuticals), which will exploit radionuclides producible with the SPES (Selective Production of Exotic Species) ISOL (Isotope Separation On-Line) facility to develop novel radiopharmaceuticals. The ISOL technique utilizes the irradiation with a primary beam of particles/nuclei of a production target where radionuclides are produced. A radioactive ion beam is subsequently extracted from the production target unit, and transported up to an analyzing magnet, where non-isobaric contaminants are filtered out. The so-obtained purified radioactive beam is dumped onto an implantation substrate, referred as collection target. Then, the desired nuclides can be chemically harvested from the collected isobars, and the isotopically pure atom collection can be employed to radiolabel high specific activity radiopharmaceuticals. Metallic deposition targets in the form of coated metal foils were mostly used at TRIUMF and CERN. At ISOLPHARM, a different approach is under investigation which foresees the use of soluble cold-pressed collection targets, possibly facilitating the chemical purification process of the collected radionuclides. In this study, the production and characterization of some of the ISOLPHARM collection targets is presented, in particular, soluble salts (NaCl and NaNO3) and organic materials widely used for pharmaceutical tablets production are considered. All such materials proved to be potentially suitable as collection targets, since solid samples were easily produced and resulted compatible with the vacuum conditions required for the ion implantation process. Furthermore, some of the selected substrates were used for proof-of-concept deposition tests with stable silver, to prove their suitability as ISOLPHARM deposition substrates for silver-111, a promising candidate for radiotherapy. Such tests highlighted possible scenarios useful for the development of new alternative materials, as the use of insoluble organic targets.
•ISOL based techniques for the production of medical radionuclides require the use of an implantation target.•Generally, implantation targets are metallic foil, ISOLPHARM at INFN-LNL proposes saline or organic substrates.•NaCl, NaNO3, cellulosic and dextrates substrates were produced by direct compression.•All samples were characterized in terms of density, mechanical strength, disaggregation and vacuum compatibility.•Implantation depth calculations and tests with the deposition of Ag + ions were performed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We investigate a sample of 152 dusty sources at 1.5 < z < 2.5 to understand the connection of enhanced star formation rate (SFR) and black hole accretion rate. The sources are Herschel-selected, ...having stellar masses M* > 1010 M and SFR (∼100-1000 M yr−1) elevated (>4×) above the star-forming "main sequence," classifying them as starbursts (SBs). Through a multiwavelength fitting approach (including a dusty torus component), we divided the sample into active SBs (dominated by an active galactic nucleus (AGN) emission, SBs-AGN, ∼23% of the sample) and purely star-forming SBs (SBs-SFR). We visually inspected their Hubble Space Telescope/ultraviolet (UV) rest frame maps: SBs-SFR are generally irregular and composite systems; ∼50% of SBs-AGN are instead dominated by regular compact morphologies. We then found archival Atacama Large Millimeter/submillimeter Array continuum counterparts for 33 galaxies (12 SBs-AGN and 21 SBs-SFR). For these sources we computed dust masses, and, with standard assumptions, we also guessed total molecular gas masses. SBs turn into gas-rich systems (fgas = Mgas/(Mgas + M*) 20%-70%), and the gas fractions of the two SB classes are very similar (fgas = 43% 4% and fgas = 42% 2%). Our results show that SBs are consistent with a mixture of: (1) highly star-forming merging systems (dominating the SBs-SFR) and (2) primordial galaxies, rapidly growing their M* together with their black hole (mainly the more compact SBs-AGN). Feedback effects have not yet reduced their fgas. Indeed, SBs at z = 2, with relatively low bolometric AGN luminosities in the range 1044 < Lbol(AGN) < 1046 erg s−1 (compared to bright optical and X-ray quasars), are still relatively far from the epoch when the AGN feedback will quench the SFR in the host and will substantially depress the gas fractions.
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