Timing of food intake has become a critical factor in determining overall cardiometabolic health. We hypothesized that timing of food intake entrains circadian rhythms of blood pressure (BP) and ...renal excretion in mice. Male C57BL/6J mice were fed ad libitum or reverse feeding (RF) where food was available at all times of day or only available during the 12-h lights-on period, respectively. Mice eating ad libitum had a significantly higher mean arterial pressure (MAP) during lights-off compared to lights-on (113 ± 2 mmHg vs 100 ± 2 mmHg, respectively;
< 0.0001); however, RF for 6 days inverted the diurnal rhythm of MAP (99 ± 3 vs 110 ± 3 mmHg, respectively;
< 0.0001). In contrast to MAP, diurnal rhythms of urine volume and sodium excretion remained intact after RF. Male
knockout mice (Bmal1KO) underwent the same feeding protocol. As previously reported, Bmal1KO mice did not exhibit a diurnal MAP rhythm during ad libitum feeding (95 ± 1 mmHg vs 92 ± 3 mmHg, lights-off vs lights-on;
> 0.05); however, RF induced a diurnal rhythm of MAP (79 ± 3 mmHg vs 95 ± 2 mmHg, lights-off vs lights-on phase;
< 0.01). Transgenic PERIOD2::LUCIFERASE knock-in mice were used to assess the rhythm of the clock protein PERIOD2 in ex vivo tissue cultures. The timing of the PER2::LUC rhythm in the renal cortex and suprachiasmatic nucleus was not affected by RF; however, RF induced significant phase shifts in the liver, renal inner medulla, and adrenal gland. In conclusion, the timing of food intake controls BP rhythms in mice independent of Bmal1, urine volume, or sodium excretion.
Early life stress (ELS) is associated with cardiovascular disease (CVD) risk in adulthood, but the underlying vascular mechanisms are poorly understood. Increased hemoglobin and heme have recently ...been implicated to mediate endothelial dysfunction in several vascular diseases. Chronic physiological stress is associated with alterations in the heme pathway that have been well‐described in the literature. However, very little is known about the heme pathway with exposure to ELS or chronic psychosocial stress. Utilizing a mouse model of ELS, maternal separation with early weaning (MSEW), we previously reported that MSEW induces endothelial dysfunction via increased superoxide production. We reasoned that heme dysregulation may be one of the culprits induced by MSEW and sustained throughout adulthood; thus, we hypothesized that MSEW induces heme dysfunction. We investigated whether circulating levels of heme, a circulating pro‐oxidant mediator, are increased by MSEW and examined the role of the heme metabolic pathway and heme homeostasis in this process. We found that circulating levels of heme are increased in mice exposed to MSEW and that plasma from MSEW mice stimulated higher superoxide production in cultured mouse aortic endothelial cells (MAECs) compared to plasma from normally reared mice. The heme scavenger hemopexin blunted this enhanced superoxide production. Splenic haptoglobin abundance was significantly lower and hemoglobin levels per red blood cell were significantly higher in MSEW versus control mice. These findings lead us to propose that ELS induces increased circulating heme through dysregulation of the haptoglobin‐hemoglobin system representing a mechanistic link between ELS and CVD risk in adulthood.
Early life stress (ELS) is associated with cardiovascular disease (CVD) risk in adulthood, but the underlying vascular mechanisms are poorly understood. Increased hemoglobin and heme have recently been implicated to mediate endothelial dysfunction in several vascular diseases. However, very little is known about the heme pathway with exposure to ELS or chronic psychosocial stress. We found that ELS induces increased circulating heme through dysregulation of the haptoglobin‐hemoglobin system representing a mechanistic link between ELS and CVD risk in adulthood.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The liver plays a central role that influences cardiovascular disease outcomes through regulation of glucose and lipid metabolism. It is recognized that the local liver molecular clock regulates some ...liver-derived metabolites. However, it is unknown whether the liver clock may impact cardiovascular function. Perivascular adipose tissue (PVAT) is a specialized type of adipose tissue surrounding blood vessels. Importantly, cross talk between the endothelium and PVAT via vasoactive factors is critical for vascular function. Therefore, we designed studies to test the hypothesis that cardiovascular function, including PVAT function, is impaired in mice with liver-specific circadian clock disruption.
is a core circadian clock gene, thus studies were undertaken in male hepatocyte-specific
knockout (HBK) mice and littermate controls (i.e., flox mice). HBK mice showed significantly elevated plasma levels of β-hydroxybutyrate, nonesterified fatty acids/free fatty acids, triglycerides, and insulin-like growth factor 1 compared with flox mice. Thoracic aorta PVAT in HBK mice had increased mRNA expression of several key regulatory and metabolic genes,
,
,
,
, and
, suggesting altered PVAT energy metabolism and thermogenesis. Sensitivity to acetylcholine-induced vasorelaxation was significantly decreased in the aortae of HBK mice with PVAT attached compared with aortae of HBK mice with PVAT removed, however, aortic vasorelaxation in flox mice showed no differences with or without attached PVAT. HBK mice had a significantly lower systolic blood pressure during the inactive period of the day. These new findings establish a novel role of the liver circadian clock in regulating PVAT metabolic gene expression and PVAT-mediated aortic vascular function.
Protein-energy malnutrition (PEM) is a treatable disease with high prevalence among hospitalized patients. It can cause significant increases in the duration of hospitalization and costs. PEM is ...especially important for health systems since malnourished patients present higher morbidity and mortality. The objective of the present study was to assess the evolution of nutritional status (NS) and the effect of malnutrition on clinical outcome of patients at a public university hospital of high complexity in Brazil. Patients hospitalized in internal medicine (n = 54), oncology (n = 43), and infectious diseases (n = 12) wards were included. NS was evaluated using subjective global assessment up to 48 h after admission, and thereafter at intervals of 4-6 days. On admission, patients (n = 109) were classified as well-nourished (n = 73), moderately malnourished or at risk of malnutrition (n = 28), and severely malnourished (n = 8). During hospitalization, malnutrition developed or worsened in 11 patients. Malnutrition was included in the clinical diagnosis of only 5/36 records (13.9% of the cases, P = 0.000). Nutritional therapy was administered to only 22/36 of the malnourished patients; however, unexpectedly, 6/73 well-nourished patients also received commercial enteral diets. Complications were diagnosed in 28/36 malnourished and 9/73 well-nourished patients (P = 0.000). Death occurred in 12/36 malnourished and 3/73 well-nourished patients (P = 0.001). A total of 24/36 malnourished patients were discharged regardless of NS. In summary, malnutrition remains a real problem, often unrecognized, unappreciated, and only sporadically treated, even though its effects can be detrimental to the clinical course and prognosis of patients. The amount of public and private funds unnecessarily dispersed because of hospital malnutrition is significant.
Renal interstitial fibrosis is characterized by the development of myofibroblasts, originating from resident renal and immigrating cells. Myofibroblast formation and extracellular matrix production ...during kidney damage are triggered by various factors. Among these, endothelins have been discussed as potential modulators of renal fibrosis. Utilizing mouse models of adenine nephropathy (AN) and unilateral ureter occlusion (UUO), this study aimed to investigate the contribution of endothelin signaling in stromal mesenchymal resident renal interstitial cells. We found in controls that adenine feeding and UUO caused marked upregulations of endothelin-1 (ET-1) gene expression in endothelial and in tubular cells and a strong upregulation of ET
A
-receptor (ET
A
-R) gene expression in interstitial and mesangial cells, while the gene expression of ET
B
-receptor (ET
B
-R) did not change. Conditional deletion of ET
A
-R and ET
B
-R gene expression in the FoxD1 stromal cell compartment which includes interstitial cells significantly reduced renal ET
A
-R gene expression and moderately lowered renal ET
B
-R gene expression. ET receptor (ET-R) deletion exerted no apparent effects on kidney development nor on kidney function. Adenine feeding and UUO led to similar increases in profibrotic and proinflammatory gene expression in control as well as in ET
A
flfl
ET
B
flfl
FoxD1
Cre+
mice (ET-Ko). In summary, our findings suggest that adenine feeding and UUO activate endothelin signaling in interstitial cells which is due to upregulated ET
A
-R expression and enhanced renal ET-1 production Our data also suggest that the activation of endothelin signaling in interstitial cells has less impact for the development of experimentally induced fibrosis.
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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
Considering that the economic valuation of ecosystem services is a useful approach to support the conservation of natural areas, we aimed to estimate the monetary value of the benefits provided by a ...protected area in southeast Brazil, the Serra do Cipó National Park. We calculated the visitor's willingness to pay to conserve the ecosystems of the protected area using the contingent valuation method. Located in a region under intense anthropogenic pressure, the Serra do Cipó National Park is mostly composed of rupestrian grassland ecosystems, in addition to other Cerrado physiognomies. We conducted a survey consisting of 514 interviews with visitors of the region and found that the mean willingness to pay was R$ 7.16 year-1, which corresponds to a total of approximately R$ 716,000.00 year-1. We detected that per capita income, the household size, the level of interest in environmental issues and the place of origin influenced the likelihood that individuals are willing to contribute to the conservation of the park, as well as the value of the stated willingness to pay. This study conveys the importance of conserving rupestrian grassland and other Cerrado physiognomies to decision makers and society.
A new germanium spectrometer especially suited for large sample measurements is described in detail. It is operated in the Gran Sasso underground laboratory under shielding rock of 3300 m water ...equivalent, which reduces the muon flux by six orders of magnitude. The integral background counting rate in the energy range from 50 to 2750 keV is about 0.15 min−1. The low peak count rates of mostly less than 1 count per day together with a relative efficiency of 102% and the high sample capacity makes this spectrometer one of the most sensitive worldwide. Some sample measurements for the solar neutrino experiment BOREXINO and the detector efficiency calibration by the Monte Carlo method are discussed as well.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The EUROMET project 428 examines efficiency transfer results for Ge gamma-ray spectrometers when the efficiency is known for a reference point source geometry. For this, different methods are used, ...such as Monte Carlo simulation or semi-empirical computation. The exercise compares the application of these methods to the same selected experimental cases to determine the usage limitations versus the requested accuracy. For carefully examining these results and trying to derive information for improving the computation codes, this study was limited to a few simple cases. The first part concerns the simplest case of geometry transfer, i.e., using point sources for 3 source-to-detector distances: 2, 5 and 20cm; the second part deals with transfer from point source geometry to cylindrical geometry with three different matrices. The general conclusion is that the deviations between the computed results and the measured efficiencies are within 10% mostly. The quality of the results is rather inhomogeneous and shows that these codes cannot be used directly for metrological purposes. However, most of them are operational for routine measurements when efficiency uncertainties of 5–10% can be sufficient.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
9.
The Borexino detector at the Laboratori Nazionali del Gran Sasso Back, H.; Balata, M.; de Bellefon, A. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
03/2009, Volume:
600, Issue:
3
Journal Article
Peer reviewed
Open access
Borexino, a large volume detector for low energy neutrino spectroscopy, is currently running underground at the Laboratori Nazionali del Gran Sasso, Italy. The main goal of the experiment is the ...real-time measurement of sub-MeV solar neutrinos, and particularly of the monoenergetic (862
keV)
7Be electron capture neutrinos, via neutrino–electron scattering in an ultra-pure liquid scintillator. This paper is mostly devoted to the description of the detector structure, the photomultipliers, the electronics, and the trigger and calibration systems. The real performance of the detector, which always meets, and sometimes exceeds, design expectations, is also shown. Some important aspects of the Borexino project, i.e. the fluid handling plants, the purification techniques and the filling procedures, are not covered in this paper and are, or will be, published elsewhere (see Introduction and Bibliography).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We report the direct measurement of the {sup 7}Be solar neutrino signal rate performed with the Borexino detector at the Laboratori Nazionali del Gran Sasso. The interaction rate of the 0.862 MeV ...{sup 7}Be neutrinos is 49{+-}3{sub stat}{+-}4{sub syst} counts/(day{center_dot}100 ton). The hypothesis of no oscillation for {sup 7}Be solar neutrinos is inconsistent with our measurement at the 4{sigma} C.L. Our result is the first direct measurement of the survival probability for solar {nu}{sub e} in the transition region between matter-enhanced and vacuum-driven oscillations. The measurement improves the experimental determination of the flux of {sup 7}Be, pp, and CNO solar {nu}{sub e}, and the limit on the effective neutrino magnetic moment using solar neutrinos.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
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