Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice

Hypersomnolence disorder (HD) is characterized by excessive sleep, which is a common sequela following stroke, infection or tumorigenesis. HD is traditionally thought to be associated with lesions of wake-promoting nuclei. However, lesions of a single wake-promoting nucleus, or even two simultaneously, did not exert serious HD. Therefore, the specific nucleus and neural circuitry for HD remain unknown. Here, we observed that the paraventricular nucleus of the hypothalamus (PVH) exhibited higher c-fos expression during the active period (23:00) than during the inactive period (11:00) in mice. Therefore, we speculated that the PVH, in which most neurons are glutamatergic, may represent one of the key arousal-controlling centers. By using vesicular glutamate transporter 2 (vglut2Cre) mice together with fiber photometry, multichannel electrophysiological recordings, and genetic approaches, we found that PVHvglut2 neurons were most active during wakefulness. Chemogenetic activation of PVHvglut2 neurons induced wakefulness for 9 h, and photostimulation of PVHvglut2→parabrachial complex/ventral lateral septum circuits immediately drove transitions from sleep to wakefulness. Moreover, lesioning or chemogenetic inhibition of PVHvglut2 neurons dramatically decreased wakefulness. These results indicate that the PVH is critical for arousal promotion and maintenance.

Electrophoretic method for the study of blood serum proteins in the diagnosis of latent active rheumatism

In case of rheumatic heart defects with circulatory disorders in the inactive period, according to the literature, there is a slight increase in P - and y-globulins, a2-globulins and fibrinogen remain within normal limits.

The Evolutionary Ecology of Dormancy in Nature and in Cancer

Dormancy is an inactive period of an organism’s life cycle that permits it to survive through phases of unfavorable conditions in highly variable environments. Dormancy is not binary. There is a continuum of dormancy phenotypes that represent some degree of reduced metabolic activity (hypometabolism), reduced feeding, and reduced reproduction or proliferation. Similarly, normal cells and cancer cells exhibit a range of states from quiescence to long-term dormancy that permit survival in adverse environmental conditions. In contrast to organismal dormancy, which entails a reduction in metabolism, dormancy in cells (both normal and cancer) is primarily characterized by lack of cell division. “Cancer dormancy” also describes a state characterized by growth stagnation, which could arise from cells that are not necessarily hypometabolic or non-proliferative. This inconsistent terminology leads to confusion and imprecision that impedes progress in interdisciplinary research between ecologists and cancer biologists. In this paper, we draw parallels and contrasts between dormancy in cancer and other ecosystems in nature, and discuss the potential for studies in cancer to provide novel insights into the evolutionary ecology of dormancy.

Abstract P219: Mice Exposed To Early Life Stress Have Impaired Autonomic Activity At Baseline And In Response To Acute Stress In Adulthood

Early life stress (ELS) is an independent risk factor for the development of cardiovascular disease in adulthood in both humans and rodent models. Maternal separation and early weaning (MSEW), a model of ELS, produces mice with an increased risk of cardiovascular dysfunction in adulthood, despite resting blood pressures (BP), heart rates (HR), and body weights comparable to normally reared controls. Autonomic regulation of HR and BP is an important component of the homeostatic response to stress but has not been investigated in MSEW mice. We hypothesized that exposure to MSEW impairs autonomic function at baseline and in response to an acute psychosocial stressor in adult male mice. C57Bl/6J litters were randomly assigned to MSEW or normally reared control conditions. MSEW litters were separated from dams for 4 h on postnatal days (PDs) 2-5, 8 h on PDs 6-16, and weaned at PD 17. Control litters were undisturbed until weaning at PD 21. At 9 weeks old, telemeters were implanted in MSEW (n=16) and control mice (n=12). During cage switch stress (CSS), mice were moved to a soiled, unfamiliar cage for 4 h. HR, systolic BP (SBP), diastolic BP (DBP), and activity (monitored by telemetry) were similar between control and MSEW mice at baseline and during CSS (p>0.05, 2-way ANOVA). Spectral analysis of HR, SBP, and DBP indicated that HR variability (HRV) total power was lower in MSEW mice during the 12 h inactive period compared to controls (18.9±1.1 ms 2 vs. 27.5±3.1 ms 2 ; p=0.0033, 2-way ANOVA) at baseline. HRV low frequency (LF) power was also lower during the 12 h inactive period in MSEW mice (4.2±0.4 ms 2 vs.6.6±0.9 ms 2 ; p=0.009). At baseline, 12 h and 24 h DBP variability LF/high frequency (HF) ratio, normalized LF, and normalized HF power were lower in the MSEW group (p<0.05, all comparisons). During the final 90 minutes of CSS, MSEW mice had lower HRV total, LF, and HF power compared to controls (p<0.05); although HR, SBP, DBP, and activity remained similar between groups. These data suggest that MSEW mice have impaired autonomic control of HR and DBP and lack the ability to robustly respond and recover from an acute stressor. Reduced responsiveness of the autonomic nervous system may contribute to the increased risk of cardiovascular disease development in adult mice exposed to MSEW.

Abstract MP17: Time Restricted Feeding Improves Cardiovascular Rhythms And Vascular Metabolism In Mice On A Chronic High Fat Diet

Irregular timing of food intake increases hypertension and cardiometabolic disease risk. A chronic high fat diet (HFD) also disrupts circadian rhythms. We hypothesized that active period time restricted feeding (TRF) during the last 2 weeks in mice on a chronic HFD will improve blood pressure rhythm, diurnal variation of circulating plasma factors, and vascular metabolism. Mice (male 8-week old, C57BL/6J) were fed a normal diet (ND; 10% fat) or HFD (45% fat) for 20 weeks ad libitum. For the final 2 weeks, half of the HFD mice were subjected to TRF. Mean arterial pressure (MAP), heart rate (HR), and locomotor activity were assessed by telemetry. TRF significantly increased the active-inactive period difference in MAP and HR in in mice fed a HFD (ΔMAP: ND: 16±0.7 mmHg, HFD: 15±0.8 mmHg, HFD+TRF: 18±0.9 mmHg, n=6-8, p=0.01; ΔHR: ND: 68±5.1 bpm, HFD: 69±6.5 bpm, HFD+TRF: 113±7.9 bpm, n=6-8, p<0.01). Diurnal changes in locomotor activity are not different between groups. At the end of the study, plasma was collected at 4 hour intervals over a 24 hour period (ZT0 at 7AM; ZT12 at 7PM). Circulating levels of liver-derived mediators β-hydroxybutyrate (βHB) and insulin-like growth factor-1 (IGF-1) showed significant differences due to diet but not TRF (βHB, ZT21: ND: 0.16±0.01 mM, HFD: 0.20±0.02 mM, HFD+TRF: 0.19±0.01 mM, n=5-6, p=0.02; IGF-1, ZT5: ND: 232±18 ng/mL, HFD: 292±34 ng/mL , HFD+TRF: 371±14 ng/mL, n=5-6, p<0.01). Plasma leptin was significantly higher in mice on HFD and reduced by TRF at ZT12 (ND: 5.3±1.3 ng/mL, HFD: 22.5±2.9 ng/mL, HFD+TRF: 10.3±3.5ng/mL, n=5-6, p<0.01) and ZT17 (ND: 6.7±1.1 ng/mL, HFD: 32.5±3.0 ng/mL, HFD+TRF: 25.0±1.3 ng/mL, n=5-6, p<0.01). Plasma adiponectin was unchanged between all groups. TRF in HFD mice increased NAD + , important for metabolism, in renal vessels at ZT17 (HFD: 0.10±0.02 pmol/μg; HFD+TRF: 0.19±0.03 pmol/μg; n=5, p=0.03). Aortic NAD + at ZT1 was not affected by TRF in HFD mice (HFD: 1.83±0.35 pmol/μg, HFD+TRF: 1.35±0.35 pmol/μg, n=4, p=0.37). Our results indicate that TRF in mice on HFD increases the active-inactive period difference in MAP and HR and alters plasma metabolites, suggesting the timing of food intake on a chronic HFD improves cardiovascular rhythms with increased renal vascular metabolism and reduced leptin levels.

ALMA observations of PSR B1259−63/LS 2883 in an inactive period: Variable circumstellar disk?

We report Atacama Large Millimeter/submillimeter Array (ALMA) observations of the gamma-ray binary system containing the pulsar PSR B1259−63 orbiting around a massive star LS 2883 in an inactive period between the 2017 and 2021 periastron passages. We detected radio continuum emission from the binary system at 97 GHz (Band 3) and 343 GHz (Band 7). Compared with our previous ALMA observations performed soon after the 2017 periastron passage, the fluxes have decreased by a factor of six at 97 GHz and of two at 343 GHz. The flux at 343 GHz is large relative to that at 97 GHz and appears to be thermal emission from the circumstellar disk around LS 2883. The decrease of the 343 GHz flux may indicate that the disk has expanded and become partially optically thin since the disk is no longer affected by pulsar winds. The flux at 97 GHz is consistent with that expected from the pulsed emission from the pulsar, which indicates that the unpulsed emission that had been produced through pulsar-disk or pulsar-stellar wind interaction has disappeared. The image of the system is consistent with a point source and shows no sign of ejecta.

Biológiai terápia szisztémás alkalmazása a szemészetben

We present herewith cases of non-infectious uveitis with biological treatment where the ocular complaints were the initial symptoms indicating a multi-organ autoimmune disease. The first case was a patient with panuveitis and Vogt–Koyanagi–Harada disease, the second case was also a panuveitic patient with sarcoidosis and the third case was a patient with intermediate uveitis and inflammatory bowel disease. In all cases, emerging new, biological therapy (adalimumab) was necessary to achieve permanent inactive period of uveitis and the autoimmune disease. Introducing systemic biological treatment (adalimumab) in ophthalmology is crucial in the therapy of immune-mediated, non-infectious uveitis in order to preserve visual acuity. Orv Hetil. 2019; 160(44): 1744–1750.