In mammals, erythropoietin (EPO), produced in the kidney, is essential for bone marrow erythropoiesis, and hypoxia induction of EPO production provides for the important erythropoietic response to ...ischemic stress, such as during blood loss and at high altitude. Erythropoietin acts by binding to its cell surface receptor which is expressed at the highest level on erythroid progenitor cells to promote cell survival, proliferation, and differentiation in production of mature red blood cells. In addition to bone marrow erythropoiesis, EPO causes multi-tissue responses associated with erythropoietin receptor (EPOR) expression in non-erythroid cells such neural cells, endothelial cells, and skeletal muscle myoblasts. Animal and cell models of ischemic stress have been useful in elucidating the potential benefit of EPO affecting maintenance and repair of several non-hematopoietic organs including brain, heart and skeletal muscle. Metabolic and glucose homeostasis are affected by endogenous EPO and erythropoietin administration affect, in part via EPOR expression in white adipose tissue. In diet-induced obese mice, EPO is protective for white adipose tissue inflammation and gives rise to a gender specific response in weight control associated with white fat mass accumulation. Erythropoietin regulation of fat mass is masked in female mice due to estrogen production. EPOR is also expressed in bone marrow stromal cells (BMSC) and EPO administration in mice results in reduced bone independent of the increase in hematocrit. Concomitant reduction in bone marrow adipocytes and bone morphogenic protein suggests that high EPO inhibits adipogenesis and osteogenesis. These multi-tissue responses underscore the pleiotropic potential of the EPO response and may contribute to various physiological manifestations accompanying anemia or ischemic response and pharmacological uses of EPO.
Erythropoietin (EPO) regulates erythropoiesis by binding to erythropoietin receptor (Epor) on erythroid progenitor cells. Epor is also expressed on bone forming osteoblasts and bone loss accompanies ...EPO‐stimulated erythropoiesis in mice. Mice with Epor restricted to erythroid tissue exhibit reduced bone and increased marrow adipocytes; in contrast, transgenic mice (Tg) with osteoblastic‐specific deletion of Epor exhibit reduced trabecular bone with age without change in marrow adipocytes. By 12 weeks, male Tg mice had 22.2% and female Tg mice had 29.6% reduced trabecular bone volume (BV) compared to controls. EPO administration (1200 U/kg) for 10 days reduced trabecular bone in control mice but not in Tg mice. There were no differences in numbers of osteoblasts, osteoclasts, and marrow adipocytes in Tg mice, suggesting independence of EPO signaling in mature osteoblasts, osteoclasts, and adipocytes. Female Tg mice had increased number of dying osteocytes and male Tg mice had a trend for more empty lacunae. Osteogenic cultures from Tg mice had reduced differentiation and mineralization with reduced Alpl and Runx2 transcripts. In conclusion, endogenous EPO‐Epor signaling in osteoblasts is important in bone remodeling, particularly trabecular bone and endogenous Epor expression in osteoblasts is required for bone loss accompanying EPO‐stimulated erythropoiesis.
Art engagement, which includes individual art activities and museum and gallery visits, potentially contributes to improving psychological well-being. However, there is insufficient evidence of its ...effects on the older population, and few reports are from Asia, including Japan. This study examined the association between art engagement and psychological well-being among older adults in Japan.
An observational cross-sectional study design was used.
Community-dwelling older adults aged ≥60 years were recruited from the visitors to public facilities (including community centres, sports centres and cultural centres) in Aichi, Japan, in 2022, and completed questionnaires. The psychological well-being assessment included five domains according to Seligman's PERMA framework: Positive emotion, Engagement, Relationship, Meaning and Accomplishment. Regarding art engagement, the frequencies of active art engagement (e.g. activities by individuals and participation in groups, such as music and painting) and receptive art engagement (e.g. visiting museums, galleries and the theatres) were assessed.
A total of 522 participants were included in the analysis (mean age = 74.1 years; 78.0% females). Results from the multivariable linear regression analysis, which adjusted for demographic and socio-economic factors, revealed that higher frequencies of active art engagement were significantly associated with higher scores in all five PERMA domain scores. Higher frequencies of receptive art engagement were significantly associated with higher levels of Positive emotion, Engagement and Meaning domain scores, but were only marginally associated with the Accomplishment domain and were not associated with the Relationships domain.
This study indicates that art engagement has the potential to enhance psychological well-being among older adults. National and local government strategies to increase accessibility to art and cultural activities for older adults are recommended.
The Hayabusa2 spacecraft investigated the C-type (carbonaceous) asteroid (162173) Ryugu. The mission performed two landing operations to collect samples of surface and subsurface material, the latter ...exposed by an artificial impact. We present images of the second touchdown site, finding that ejecta from the impact crater was present at the sample location. Surface pebbles at both landing sites show morphological variations ranging from rugged to smooth, similar to Ryugu's boulders, and shapes from quasi-spherical to flattened. The samples were returned to Earth on 6 December 2020. We describe the morphology of >5 grams of returned pebbles and sand. Their diverse color, shape, and structure are consistent with the observed materials of Ryugu; we conclude that they are a representative sample of the asteroid.
Many pufferfish of the family Tetraodontidae possess a potent neurotoxin, tetrodotoxin (TTX). In marine pufferfish species, toxicity is generally high in the liver and ovary, whereas in brackish ...water and freshwater species, toxicity is higher in the skin. In 1964, the toxin of the California newt was identified as TTX as well, and since then TTX has been detected in a variety of other organisms. TTX is produced primarily by marine bacteria, and pufferfish accumulate TTX via the food chain that begins with these bacteria. Consequently, pufferfish become non-toxic when they are fed TTX-free diets in an environment in which the invasion of TTX-bearing organisms is completely shut off. Although some researchers claim that the TTX of amphibians is endogenous, we believe that it also has an exogenous origin, i.e., from organisms consumed as food. TTX-bearing animals are equipped with a high tolerance to TTX, and thus retain or accumulate TTX possibly as a biologic defense substance. There have been many cases of human intoxication due to the ingestion of TTX-bearing pufferfish, mainly in Japan, China, and Taiwan, and several victims have died. Several cases of TTX intoxication due to the ingestion of small gastropods, including some lethal cases, were recently reported in China and Taiwan, revealing a serious public health issue.
We studied the effect of these quasiparticles on the temperature and microwave power dependence of the characteristics of superconducting thin-film resonator, assuming that there are a significant ...number of quasiparticles in the superconductor even at <inline-formula><tex-math notation="LaTeX">T \ll T_c</tex-math></inline-formula>. It is demonstrated that the temperature dependence of both the internal quality factor and resonance frequency are well described by that of the normal conductivity of quasiparticles including the contributions from Kondo effect, phonon, and electron-electron scatterings. It also found that the readout microwave power dependence of the internal quality factor is well explained by the change of quasiparticle density due to the energy re-distribution of quasiparticles under microwave field in the resonator.
We examined the association between living alone and mental health and the moderating effects of face-to-face and non–face-to-face social contacts, among community-dwelling older adults.
...Cross-sectional study.
This cross-sectional study recruited Japanese adults older than 60 years, who attended health check-ups held in a suburban town hall in July and August of 2018 and 2019. As mental health outcomes, depression was assessed using the Geriatric Depression Scale 15-items, loneliness was assessed using the University of California, Los Angeles Loneliness Scale 3-items, and happiness was self-rated on a 10-point scale. Face-to-face social contacts were evaluated by participants' frequency of meetings with relatives or friends, whereas non–face-to-face contacts were measured by the frequency of interactions via letter, telephone or e-mail. Multivariable linear regression analysis was conducted to examine the association between living alone with each mental health outcome and the effect modifications of having face-to-face and non–face-to-face social contacts.
Data from 300 older adults were analysed. The participants' mean age was 73.0 years, 51.3% were female, and 16.0% lived alone. Living alone was significantly associated with poorer mental health. Regarding loneliness and low happiness, having face-to-face and non–face-to-face contacts more than once a week alleviated the adverse association of living alone (loneliness: face-to-face contacts, P = 0.020; non–face-to-face contacts, P = 0.028; happiness: face-to-face contacts, P = 0.020; non–face-to-face contacts, P = 0.001).
Our findings suggest that non–face-to-face, as well as face-to-face social contacts have a moderating effect on the adverse association of living alone with loneliness and happiness.
Nitric oxide (NO) appears to play an important role in the regulation of thrombosis and hemostasis by inhibiting platelet function. The discovery of NO generation by reduction of nitrite (NO₂⁻) and ...nitrate (NO₃⁻) in mammals has led to increased attention to these anions with respect to potential beneficial effects in cardiovascular diseases. We have previously shown that nitrite anions at 0.1 µM inhibit aggregation and activation of human platelet preparations in vitro in the presence of red blood cells and this effect was enhanced by deoxygenation, an effect likely due to NO generation. In the present study, we hypothesized that nitrite and nitrate derived from the diet could also alter platelet function upon their conversion to NO in vivo. To manipulate the levels of nitrite and nitrate in mouse blood, we used antibiotics, NOS inhibitors, low nitrite/nitrate (NOx) diets, endothelial NOS knock-out mice and also supplementation with high levels of nitrite or nitrate in the drinking water. We found that all of these perturbations affected nitrite and nitrate levels but that the lowest whole blood values were obtained by dietary restriction. Platelet aggregation and ATP release were measured in whole blood and the results show an inverse correlation between nitrite/nitrate levels and platelet activity in aggregation and ATP release. Furthermore, we demonstrated that nitrite-supplemented group has a prolonged bleeding time compared with control or low NOx diet group. These results show that diet restriction contributes greatly to blood nitrite and nitrate levels and that platelet reactivity can be significantly affected by these manipulations. Our study suggests that endogenous levels of nitrite and nitrate may be used as a biomarker for predicting platelet function and that dietary manipulation may affect thrombotic processes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The reflectance spectra of the most abundant meteorites, ordinary chondrites, are different from those of the abundant S-type (mnemonic for siliceous) asteroids. This discrepancy has been thought to ...be due to space weathering, which is an alteration of the surfaces of airless bodies exposed to the space environment. Here we report evidence of space weathering on particles returned from the S-type asteroid 25143 Itokawa by the Hayabusa spacecraft. Surface modification was found in 5 out of 10 particles, which varies depending on mineral species. Sulfur-bearing Fe-rich nanoparticles exist in a thin (5 to 15 nanometers) surface layer on olivine, low-Ca pyroxene, and plagioclase, which is suggestive of vapor deposition. Sulfur-free Fe-rich nanoparticles exist deeper inside (<60 nanometers) ferromagnesian silicates. Their texture suggests formation by metamictization and in situ reduction of Fe2+.
Erythropoietin (EPO) receptor (EPOR) determines EPO response. High level EPOR on erythroid progenitor cells gives rise to EPO regulated production of red blood cells. Animal models provide evidence ...for EPO activity in non-hematopoietic tissue mediated by EPOR expression. Beyond erythropoiesis, EPO activity includes neuroprotection in brain ischemia and trauma, endothelial nitric oxide production and cardioprotection, skeletal muscle wound healing, and context dependent bone remodeling affecting bone repair or bone loss. This review highlights examples of EPO protective activity in select non-hematopoietic tissue with emphasis on metabolic response mediated by EPOR expression in fat and brain and sex-specific regulation of fat mass and inflammation associated with diet induced obesity. Endogenous EPO maintains glucose and insulin tolerance and protects against fat mass accumulation and inflammation. Accompanying the increase in erythropoiesis with EPO treatment is improved glucose tolerance and insulin response. During high fat diet feeding, EPO also decreases fat mass accumulation in male mice. The increased white adipose tissue inflammation and macrophage infiltration associated with diet induced obesity are also reduced with EPO treatment with a shift toward an anti-inflammatory state and decreased inflammatory cytokine production. In female mice the protective effect of estrogen against obesity supersedes EPO regulation of fat mass and inflammation, and requires estrogen receptor alpha activity. In brain, EPOR expression in the hypothalamus localizes to proopiomelanocortin neurons in the arcuate nucleus that promotes a lean phenotype. EPO stimulation of proopiomelanocortin neurons increases STAT3 signaling and production of proopiomelanocortin. Cerebral EPO contributes to metabolic response, and elevated brain EPO reduces fat mass and hypothalamus inflammation during diet induced obesity in male mice without affecting EPO stimulated erythropoiesis. Ovariectomy abrogates the sex-specific metabolic response of brain EPO. The sex-dimorphic EPO metabolic response associated with fat mass accumulation and inflammation during diet induced obesity provide evidence for crosstalk between estrogen and EPO in their anti-obesity potential in female mice mediated in part via tissue specific response in brain and white adipose tissue. Endogenous and exogenous EPO response in non-hematopoietic tissue demonstrated in animal models suggests additional activity by which EPO treatment may affect human health beyond increased erythropoiesis.
PDF
