We analyze the behavior of axion dark matter before it falls into a galactic gravitational potential well. The axions thermalize sufficiently fast by gravitational self-interactions that almost all ...go to their lowest-energy state consistent with the total angular momentum acquired from tidal torquing. That state is a state of rigid rotation on the turnaround sphere. It predicts the occurrence and detailed properties of the caustic rings of dark matter for which observational evidence had been found earlier. We show that the vortices in the axion Bose-Einstein condensate (BEC) are attractive, unlike those in superfluid super(4)He and dilute gases. We expect that a large fraction of the vortices in the axion BEC join into a single big vortex along the rotation axis of the galaxy. The resulting enhancement of caustic rings explains the typical size of the rises in the Milky Way rotation curve attributed to caustic rings. We show that baryons and ordinary cold dark matter particles are entrained by the axion BEC and acquire the same velocity distribution. The resulting baryonic angular momentum distribution gives a good qualitative fit to the distributions observed in dwarf galaxies. We give estimates of the minimum fraction of dark matter that is composed of axions.
In this work the radiolytic stability of a TODGA based solvent has been investigated in alpha radiolysis measured by solvent extraction distribution ratios. Solutions of TODGA in alkane diluents have ...been subjected to
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Cm α-irradiation in the presence of nitric acid (0.5 M) and analysed using radiometric techniques to determine their rates of radiolytic degradation. It was shown that alpha radiolysis, similarly to external gamma irradiation, produces an exponential decrease of the free TODGA concentration of the organic solvent as the solvent is degraded with increasing absorbed alpha dose. The degradation constant, obtained from the exponential decrease, indicates that the free TODGA concentration is halved with every 1.0 MGy deposited to the solvent from internal alpha decay. This result could be useful information when dealing with high activity actinide solutions in TODGA based solvent extraction systems.
Highlights ► We evaluated astrocyte activation and inflammation involvement in human epilepsy samples. ► High GFAP is associated with increased AQP4, CX43, m-calpain, and L-type Ca2+ channels. ► ...Kir4.1, dystrophin, and α-syntrophin are decreased in human epilepsy. ► Inflammatory markers and glutamate receptors/subunits are also increased. ► Astrocyte-related inflammation may be a significant target for new epilepsy therapy.
Highlights • Estrogen receptor agonists upregulated estrogen receptors in VSC4.1 cells. • Estrogen receptor agonists enhanced expression of specific neuroprotective miRs. • miR-7-1 most effectively ...enhanced neuroprotective functions of estrogen (EST). • Combination of miR-7-1 and EST most significantly decreased Bax:Bcl-2 ratio. • miR-7-1 powered EST for inhibition of apoptosis and preservation of functionality.
A short, easy-to-use health status questionnaire is needed in the multidimensional assessment of chronic obstructive pulmonary disease (COPD) in routine practice. The performance of the eight-item ...COPD assessment test (CAT) was analysed in 1,817 patients from primary care in seven European countries. The CAT has a scoring range of 0-40 (high score representing poor health status). Mean CAT scores indicated significant health status impairment that was related to severity of airway obstruction, but within each Global Initiative for Obstructive Lung Disease stage (I to IV) there was a wide range of scores (I: 16.2 ± 8.8; II: 16.3 ± 7.9; III: 19.3 ± 8.2; and IV: 22.3 ± 8.7; I versus II, p = 0.88; II versus III, p<0.0001; III versus IV, p = 0.0001). CAT scores showed relatively little variability across countries (within ± 12% of the mean across all countries). Scores were significantly better in patients who were stable (17.2 ± 8.3) versus those suffering an exacerbation (21.3 ± 8.4) (p<0.0001); and in patients with no (17.3 ± 8.1) or one or two (16.6 ± 8.2) versus three or more (19.7 ± 8.5) comorbidities (p<0.0001 for both). The CAT distinguished between classes of other impairment measures and was strongly correlated with the St George's Respiratory Questionnaire (r = 0.8, p<0.0001). The CAT is a simple and easy-to-use questionnaire that distinguishes between patients of different degrees of COPD severity and appears to behave the same way across countries.
Abstract Exposure to environmental toxins increases the risk of neurodegenerative diseases including Parkinson’s disease (PD). Rotenone is a neurotoxin that has been used to induce experimental ...Parkinsonism in rats. We used the rotenone model of experimental Parkinsonism to explore a novel aspect of extra-nigral degeneration, the neurodegeneration of spinal cord (SC), in PD. Rotenone administration to male Lewis rats caused significant neuronal cell death in cervical and lumbar SC as compared with control animals. Dying neurons were motoneurons as identified by double immunofluorescent labeling for terminal deoxynucleotidyl transferase, recombinant–mediated dUTP nick-end labeling-positive (TUNEL+ ) cells and choline acetyltransferase (ChAT)-immunoreactivity. Neuronal death was accompanied by abundant astrogliosis and microgliosis as evidenced from glial fibrillary acidic protein (GFAP)-immunoreactivity and OX-42-immunoreactivity, respectively, implicating an inflammatory component during neurodegeneration in SC. However, the integrity of the white matter in SC was not affected by rotenone administration as evidenced from the non co-localization of any TUNEL+ cells with GFAP-immunoreactivity and myelin basic protein (MBP)-immunoreactivity, the selective markers for astrocytes and oligodendrocytes, respectively. Increased activities of 76 kD active m-calpain and 17/19 kD active caspase-3 further demonstrated involvement of these enzymes in cell death in SC. The finding of ChAT+ cell death also suggested degeneration of SC motoneurons in rotenone-induced experimental Parkinsonism. Thus, this is the first report of its kind in which the selective vulnerability of a putative parkinsonian target outside of nigrostriatal system has been tested using an environmental toxin to understand the pathophysiology of PD. Moreover, rotenone-induced degeneration of SC motoneuron in this model of experimental Parkinsonism progressed with upregulation of calpain and caspase-3.
Summary Pan-European data on health-related quality of life (HRQL) in chronic obstructive pulmonary disease (COPD) are lacking. This cross-sectional epidemiological study evaluated health status in ...1817 COPD patients from an ‘all-comers’ primary care population in seven European countries (87% stable disease; 13% with current exacerbation) using: St George’s Respiratory Questionnaire-COPD specific (SGRQ-C), the short form health survey (SF-12) and the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue scale. Mean total score for SGRQ was 44.7 ± 19.4 showing marked impairment of HRQL. Scores differed little between countries (range 39.2–50.1). Impairment was associated with the severity of airway obstruction, but within each GOLD stage the variation (SD) was wide Stage I: 38.5 ± 19.3 ( n = 223); Stage II: 40.4 ± 18.1 ( n = 868); Stage III: 50.2 ± 18.6 ( n = 551); Stage IV: 58.6 ± 17.7 ( n = 144). Patients suffering an exacerbation had a worse SGRQ score (54.9 ± 19.3) than those with stable disease (43.3 ± 19.0). The presence of ≥3 co-morbidities (CM) was also associated with a significantly worse score (49.9 ± 19.1) vs. 1–2 CM (42.1 ± 19.1) or no CM (42.3 ± 18.6). Findings with the SF-12 and FACIT-F results were consistent with those from the SGRQ-C. This large observational primary care study shows that health status is significantly impaired in COPD patients of all severities, even in those with mild airway obstruction. Within each GOLD stage of severity there is considerable heterogeneity in HRQL impairment among patients. (Study number: 111749).
Abstract Parkinson's disease (PD), characterized by selective midbrain nigrostriatal dopaminergic degeneration, is consistently associated with moderate systemic mitochondrial dysfunction. Downstream ...degeneration of spinal cord has also been suggested in PD, although the mechanisms have not been much investigated. In the present study, two mitochondrial toxicants, 1-methyl-4-phenylpyridinium ion (MPP+ ) and rotenone were tested in ventral spinal cord (VSC 4.1) motoneuronal cells. Cell death was assessed by morphological and biochemical means to discern a lower apoptosis-inducing concentration and lethal concentration of 50% cell death (LC50 ), which were subsequently compared in further cytoprotection experiments. Mitochondrial toxicants dose-dependently induced increase in intracellular free Ca2+ level, which was conducive for increased expression and activities of Ca2+ -activated neutral protease calpain and downstream caspase-3. Thus, mitochondrial damage triggered apoptotic mechanisms in spinal cord motoneurons. Inhibition of calpain by calpeptin significantly attenuated damaging effects of MPP+ and rotenone on motoneurons, especially at low apoptosis-inducing concentrations of toxicants and partly at their LC50 , as demonstrated by absence of DNA ladder formation and decrease in terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells. Cytoprotection by calpeptin was observed with marked decreases in Bax: Bcl-2 ratio and activities of calpain and caspase-3, which affirmed the role of mitochondrial dysfunction and involvement of intrinsic pathway in mediation of apoptosis. These findings strongly suggested that parkinsonian toxicants MPP+ and rotenone at low doses induced cascade of cell-damaging effects in spinal cord motoneurons, thus, highlighting the possibility of induction of apoptotic mechanisms in these cells, when subjected to mitochondrial stress. Cytoprotection rendered by calpeptin further validated the involvement of calpain in apoptosis and suggested calpain inhibition as a potential neuroprotective strategy.
Glioblastoma is the most malignant and prevalent brain tumor that still remains incurable. Recent studies reported anti-cancer effect of the broccoli-derived compound sulforaphane. We explored the ...mechanisms of sulforaphane-mediated apoptosis in human glioblastoma T98G and U87MG cells. Wright staining and ApopTag assay confirmed apoptosis in glioblastoma cells treated with sulforaphane. Increase in intracellular free Ca
2+ was detected by fura-2 assay, suggesting activation of Ca
2+-dependent pathways for apoptosis. Western blotting was used to detect changes in expression of Bax and Bcl-2 proteins resulting in increased Bax:Bcl-2 ratio that indicated a commitment of glioblastoma cells to apoptosis. Upregulation of calpain, a Ca
2+-dependent cysteine protease, activated caspase-12 that in turn caused activation of caspase-9. With the increased Bax:Bcl-2 ratio, cytochrome c was released from mitochondria to cytosol for sequential activation of caspase-9 and caspase-3. Increased calpain and caspase-3 activities generated 145 kD spectrin breakdown product and 120 kD spectrin breakdown product, respectively. Activation of caspase-3 also cleaved the inhibitor-of-caspase-activated-DNase. Accumulation of apoptosis-inducing-factor in cytosol suggested caspase-independent pathway of apoptosis as well. Two of the inhibitor-of-apoptosis proteins were downregulated because of an increase in ‘second mitochondrial activator of caspases/Direct inhibitor-of-apoptosis protein binding protein with low pI.’ Decrease in nuclear factor kappa B and increase in inhibitor of nuclear factor kappa B alpha expression favored the process of apoptosis. Collectively, our results indicated activation of multiple molecular mechanisms for apoptosis in glioblastoma cells following treatment with sulforaphane.
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