227 research outputs found
Generic features of Einstein-Aether black holes
We reconsider spherically symmetric black hole solutions in Einstein-Aether
theory with the condition that this theory has identical PPN parameters as
those for general relativity, which is the main difference from the previous
research. In contrast with previous study, we allow superluminal propagation of
a spin-0 Aether-gravity wave mode. As a result, we obtain black holes having a
spin-0 "horizon" inside an event horizon. We allow a singularity at a spin-0
"horizon" since it is concealed by the event horizon. If we allow such a
configuration, the kinetic term of the Aether field can be large enough for
black holes to be significantly different from Schwarzschild black holes with
respect to ADM mass, innermost stable circular orbit, Hawking temperature, and
so on. We also discuss whether or not the above features can be seen in more
generic vector-tensor theories.Comment: 9 pages, 9 figures, basic equations and their analytic arguments are
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Increased serum levels of macrophage migration inhibitory factor-related protein is a sensitive marker for acute coronary syndrome in patients with coronary artery disease
Exploring Hemodynamic Responses Using Mirror Visual Feedback With Electromyogram-Triggered Stimulation and Functional Near-Infrared Spectroscopy
In recent years, mirror visual feedback (MVF) therapy combined with electrical stimulation (ES) have been proposed for patients with hemiparesis. However, the neurophysiological effect remains unknown. We investigated the effects of MVF by itself and along with electromyogram-triggered ES (ETES) on hemodynamic responses using functional near-infrared spectroscopy (NIRS). Eighteen healthy subjects participated in this study. We measured changes in brain oxygenation using 48 NIRS channels. We investigated the effects of three main factors of visual feedback (observation of a mark, right hand, and hand movements via mirror) with or without ES on bilateral precentral gyrus (PrG), postcentral gyrus (PoG), supplementary motor area (SMA), supramarginal gyrus area (SMG), and angular gyrus (AG) to determine the contribution of each factor. The results showed that the left PoG was significantly more activated when performing mirrored tasks (MT) than when performing circle or Right-hand Tasks (RTs). In addition, the right PoG and right SMA in MT were significantly more activated than in MT + ES cases. Our findings suggested that observation of movements through the mirror caused activation of the postcentral gyrus rather than the PrG, and MVF along with ETES decreased cortical activation
Particle velocity in noncommutative space-time
We investigate a particle velocity in the -Minkowski space-time,
which is one of the realization of a noncommutative space-time. We emphasize
that arrival time analyses by high-energy -rays or neutrinos, which
have been considered as powerful tools to restrict the violation of Lorentz
invariance, are not effective to detect space-time noncommutativity. In
contrast with these examples, we point out a possibility that {\it low-energy
massive particles} play an important role to detect it.Comment: 16 pages, corrected some mistake
Angiotensin II alters the expression of duodenal iron transporters, hepatic hepcidin, and body iron distribution in mice
Purpose: Angiotensin II (ANG II) has been shown to affect iron metabolism through alteration of iron transporters, leading to increased cellular and tissue iron contents. Serum ferritin, a marker of body iron storage, is elevated in various cardiovascular diseases, including hypertension. However, the associated changes in iron absorption and the mechanism underlying increased iron content in a hypertensive state remain unclear.
Methods: C57BL6/J mice were treated with ANG II to generate a model of hypertension. Mice were divided into 3 groups: (1) control, (2) ANG II-treated, and (3) ANG II-treated and ANG II receptor blocker (ARB)-administered (ANG II-ARB) groups.
Results: Mice treated with ANG II showed increased serum ferritin levels compared to vehicle-treated control mice. In ANG II-treated mice, duodenal divalent metal transporter-1 (DMT1) and ferroportin (FPN) expression levels were increased and hepatic hepcidin mRNA expression and serum hepcidin concentration were reduced. The mRNA expression of bone morphogenetic protein 6 (BMP6) and CCAAT/enhancer binding protein alpha (C/EBPα), which are regulators of hepcidin, was also down-regulated in the livers of ANG II-treated mice. In terms of tissue iron content, macrophage iron content and renal iron content were increased by ANG II treatment, and these increases were associated with reduced expression of transferrin receptor 1 and FPN and increased expression of ferritin. These changes induced by ANG II treatment were ameliorated by administration of an ARB.
Conclusions: ANG II altered the expression of duodenal iron transporters and reduced hepcidin levels, contributing to the alteration of body iron distribution
Effect of Deferoxamine on Renal Fibrosis
Renal fibrosis plays an important role in the onset and progression of chronic kidney diseases (CKD). Although several mechanisms underlying renal fibrosis and candidate drugs for its treatment have been identified, the effect of iron chelator on renal fibrosis remains unclear. In the present study, we examined the effect of an iron chelator, deferoxamine (DFO), on renal fibrosis in mice with surgically induced unilateral ureter obstruction (UUO). Mice were divided into 4 groups: UUO with vehicle, UUO with DFO, sham with vehicle, and sham with DFO. One week after surgery, augmented renal tubulointerstitial fibrosis and the expression of collagen I, III, and IV increased in mice with UUO; these changes were suppressed by DFO treatment. Similarly, UUO-induced macrophage infiltration of renal interstitial tubules was reduced in UUO mice treated with DFO. UUO-induced expression of inflammatory cytokines and extracellular matrix proteins was abrogated by DFO treatment. DFO inhibited the activation of the transforming growth factor-β1 (TGF-β1)-Smad3 pathway in UUO mice. UUO-induced NADPH oxidase activity and p22phox expression were attenuated by DFO. In the kidneys of UUO mice, divalent metal transporter 1, ferroportin, and ferritin expression was higher and transferrin receptor expression was lower than in sham-operated mice. Increased renal iron content was observed in UUO mice, which was reduced by DFO treatment. These results suggest that iron reduction by DFO prevents renal tubulointerstitial fibrosis by regulating TGF-β-Smad signaling, oxidative stress, and inflammatory responses
Balancing risk-return decisions by manipulating the mesofrontal circuits in primates
リスクと報酬の意思決定バランスを光で調節 --精神神経疾患などの病態解明に期待--. 京都大学プレスリリース. 2024-01-05.Lighting the Circuits to Risky Decision-Making. 京都大学プレスリリース. 2024-01-05.Decision-making is always coupled with some level of risk, with more pathological forms of risk-taking decisions manifesting as gambling disorders. In macaque monkeys trained in a high risk–high return (HH) versus low risk–low return (LL) choice task, we found that the reversible pharmacological inactivation of ventral Brodmann area 6 (area 6V) impaired the risk dependency of decision-making. Selective optogenetic activation of the mesofrontal pathway from the ventral tegmental area (VTA) to the ventral aspect of 6V resulted in stronger preference for HH, whereas activation of the pathway from the VTA to the dorsal aspect of 6V led to LL preference. Finally, computational decoding captured the modulations of behavioral preference. Our results suggest that VTA inputs to area 6V determine the decision balance between HH and LL
Iron-induced atrophy via Akt-FOXO3-E3 Ubiquitin ligase pathway
Skeletal muscle wasting or sarcopenia is a critical health problem. Skeletal muscle atrophy is induced by an excess of iron, which is an essential trace metal for all living organisms. Excessive amounts of iron catalyze the formation of highly toxic hydroxyl radicals via the Fenton reaction. However, the molecular mechanism of iron-induced skeletal muscle atrophy has remained unclear. In this study, 8-weeks-old C57BL6/J mice were divided into 2 groups: vehicle-treated group and the iron-injected group (10 mg iron·day-1·mouse-1) during 2 weeks. Mice in the iron-injected group showed an increase in the iron content of the skeletal muscle and serum and ferritin levels in the muscle, along with reduced skeletal muscle mass. The skeletal muscle showed elevated mRNA expression of the muscle atrophy-related E3 ubiquitin ligases, atrogin-1 and muscle ring finger-1(MuRF1), on days 7 and 14 of iron treatment. Moreover, iron-treated mice showed reduced phosphorylation of Akt and forkhead box O3 (FOXO3a) in skeletal muscles. Inhibition of FOXO3a using siRNA in vitro in C2C12 myotube cells inhibited iron-induced upregulation of atrogin-1 and MuRF1 and reversed the reduction in myotube diameters. Iron-load caused oxidative stress, and an oxidative stress inhibitor abrogated iron-induced muscle atrophy by reactivating the Akt-FOXO3 pathway. Iron-induced skeletal muscle atrophy is suggested to involve the E3 ubiquitin ligase mediated by the reduction of Akt-FOXO3a signaling by oxidative stress
Deletion of H-ferritin in macrophages alleviates obesity and diabetes induced by high-fat diet in mice
Aims/hypothesis
Iron accumulation affects obesity and diabetes, both of which are ameliorated by iron reduction. Ferritin, an iron storage protein, plays a crucial role in iron metabolism. H-ferritin exerts its cytoprotective action by reducing toxicity via its ferroxidase activity. We investigated the role of macrophage H-ferritin in obesity and diabetes.
Methods
Conditional macrophage-specific H-ferritin knockout (LysM-Cre FthKO) mice were used and divided into 4 groups; Wild-type (WT) and LysM-Cre FthKO mice with normal diet (ND), and WT and LysM-Cre Fth-KO mice with high-fat diet (HFD).
Results
Iron concentration reduced, and mRNA expression of ferroportin increased in macrophages from LysM-Cre FthKO mice. HFD-induced obesity was lower in LysM-Cre FthKO mice than in WT mice at 12 weeks (body weight (g); KO 34.6 ± 5.6 vs. WT 40.1 ± 5.2). mRNA expression of inflammatory cytokines, infiltrated macrophages, and oxidative stress increased in the adipose tissue of WT mice with HFD, but was not elevated in LysM-Cre FthKO mice with HFD. However, WT mice with HFD had elevated iron concentration in adipose tissue and spleen, which was not observed in LysM-Cre FthKO mice with HFD (adipose (μmol Fe/g protein); KO 1496 ± 479 vs. WT 2316 ± 866, spleen (μmol Fe/g protein); KO 218 ± 54 vs. WT 334 ± 83). Moreover, HFD administration impaired both glucose tolerance and insulin sensitivity in WT mice, which was ameliorated in LysM-Cre FthKO mice. In addition, energy expenditure, mRNA expression of thermogenic genes, and body temperature were higher in KO mice with HFD than WT mice with HFD. In vitro experiments showed that iron content was reduced, and LPS-induced TNF-α mRNA upregulation was inhibited in a macrophage cell line transfected with Fth siRNA.
Conclusions/interpretation
Deletion of macrophage H-ferritin suppresses the inflammatory response by reducing intracellular iron levels, resulting in the prevention of HFD-induced obesity and diabetes. The findings from this study highlight macrophage iron levels as a potential therapeutic target for obesity and diabetes
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