Neutrino oscillation and expected event rate of supernova neutrinos in adiabatic explosion model

We study how the influence of the shock wave appears in neutrino oscillations and the neutrino spectrum using density profile of adiabatic explosion model of a core-collapse supernova which is calculated in an implicit Lagrangian code for general relativistic spherical hydrodynamics. We calculate expected event rates of neutrino detection at SK and SNO for various theta_{13} values and both normal and inverted hierarchies. The predicted event rates of bar{nu}_e and nu_e depend on the mixing angle theta_{13} for the inverted and normal hierarchies, respectively, and the influence of the shock appears for about 2 - 8 s when sin^2 2 theta_{13} is larger than 10^{-3}. These neutrino signals for the shock propagation is decreased by < 30 % for bar{nu}_e in inverted (SK) or by < 15 % for nu_e in normal hierarchy (SNO) compared with the case without shock. The obtained ratio of the total event for high-energy neutrinos (20 MeV < E_{nu} < 60 MeV) to low-energy neutrinos (5 MeV < E_{nu} < 20 MeV) is consistent with the previous studies in schematic semi-analytic or other hydrodynamic models of the shock propagation. The time dependence of the calculated ratio of the event rates of high-energy to low-energy neutrinos is a very useful observable which is sensitive to theta_{13} and hierarchies. Namely, time-dependent ratio shows clearer signal of the shock propagation that exhibits remarkable decrease by at most factor \sim 2 for bar{nu}_e in inverted (SK), whereas it exhibits smaller change by \sim 10 % for nu_e in normal hierarchy (SNO). Observing time-dependent high-energy to low-energy ratio of the neutrino events thus would provide a piece of very useful information to constrain theta_{13} and mass hierarchy, and eventually help understanding the propagation how the shock wave propagates inside the star.Comment: 19 pages, 9 figures, accepted for publication in Physical Review

A soluble endoplasmic reticulum factor as regenerative therapy for Wolfram syndrome

Endoplasmic reticulum (ER) stress-mediated cell death is an emerging target for human chronic disorders, including neurodegeneration and diabetes. However, there is currently no treatment for preventing ER stress-mediated cell death. Here, we show that mesencephalic astrocyte-derived neurotrophic factor (MANF), a neurotrophic factor secreted from ER stressed cells, prevents ER stress-mediated β cell death and enhances β cell proliferation in cell and mouse models of Wolfram syndrome, a prototype of ER disorders. Our results indicate that molecular pathways regulated by MANF are promising therapeutic targets for regenerative therapy of ER stress-related disorders, including diabetes, retinal degeneration, neurodegeneration, and Wolfram syndrome

In vitro feeding of all life stages of two-host Hyalomma excavatum and Hyalomma scupense and three-host Hyalomma dromedarii ticks

Ticks are blood-sucking ectoparasites and can transmit various pathogens of medical and veterinary relevance. The life cycle of ticks can be completed under laboratory conditions on experimental animals, but the artificial feeding of ticks has attracted increased interest as an alternative method. This study represents the first report on the successful in vitro feeding of all life stages of two-host tick species, Hyalomma scupense and Hyalomma excavatum, and the three-host tick Hyalomma dromedarii. The attachment and engorgement rates of adults were 84% (21/25) and 76% (19/25) for H. scupense females. For adult H. excavatum and H. dromedarii, 70% (21/30) and 34.4% (11/32) of the females attached and all attached females successfully fed to repletion. The oviposition rates of the artificially fed females were 36.4%, 57.1% and 63.1% for H. dromedarii, H. excavatum and H. scupense, respectively, with a reproductive efficiency index varying between 44.3 and 60.7%. For the larvae, the attachment and engorgement rates were 44.2% (313/708) and 42.8% (303/708) for H. dromedarii, 70.5% (129/183) and 56.8% (104/183) for H. excavatum and 92.6% (113/122) and 55.7% (68/122) for H. scupense. The attachment and engorgement rates for the nymphs were 90.2% (129/143) and 47.6% (68/143) for H. dromedarii, 66.7% (34/51) and 41.2% (21/51) for H. excavatum, and 44.1% (30/68) and 36.8% (25/68) for H. scupense. Molting rates of the immature stages varied between 71.3% (216/303) and 100% (68/68) for the larvae and between 61.9% (13/21) and 96% (24/25) for the nymphs. The successful in vitro feeding of all stages of the three Hyalomma species makes this method a valuable tool for tick research, with potential applications in studies on the pathogens transmitted by these tick species such as Theileria annulata

Neuroimaging evidence of deficient axon myelination in Wolfram syndrome

Wolfram syndrome is a rare autosomal recessive genetic disease characterized by insulin dependent diabetes and vision, hearing and brain abnormalities which generally emerge in childhood. Mutations in the WFS1 gene predispose cells to endoplasmic reticulum stress-mediated apoptosis and may induce myelin degradation in neuronal cell models. However, in vivo evidence of this phenomenon in humans is lacking. White matter microstructure and regional volumes were measured using magnetic resonance imaging in children and young adults with Wolfram syndrome (n = 21) and healthy and diabetic controls (n = 50). Wolfram patients had lower fractional anisotropy and higher radial diffusivity in major white matter tracts and lower volume in the basilar (ventral) pons, cerebellar white matter and visual cortex. Correlations were found between key brain findings and overall neurological symptoms. This pattern of findings suggests that reduction in myelin is a primary neuropathological feature of Wolfram syndrome. Endoplasmic reticulum stress-related dysfunction in Wolfram syndrome may interact with the development of myelin or promote degeneration of myelin during the progression of the disease. These measures may provide objective indices of Wolfram syndrome pathophysiology that will be useful in unraveling the underlying mechanisms and in testing the impact of treatments on the brain

Immunological profile in a family with nephrogenic diabetes insipidus with a novel 11 kb deletion in AVPR2 and ARHGAP4 genes

<p>Abstract</p> <p>Background</p> <p>Congenital nephrogenic diabetes insipidus (NDI) is characterised by an inability to concentrate urine despite normal or elevated plasma levels of the antidiuretic hormone arginine vasopressin. We report a Japanese extended family with NDI caused by an 11.2-kb deletion that includes the entire <it>AVPR2 </it>locus and approximately half of the <it>Rho GTPase-activating protein 4 </it>(<it>ARHGAP4</it>) locus. ARHGAP4 belongs to the RhoGAP family, Rho GTPases are critical regulators of many cellular activities, such as motility and proliferation which enhances intrinsic GTPase activity.</p> <p>ARHGAP4 is expressed at high levels in hematopoietic cells, and it has been reported that an NDI patient lacking <it>AVPR2 </it>and all of <it>ARHGAP4 </it>showed immunodeficiency characterised by a marked reduction in the number of circulating CD3+ cells and almost complete absence of CD8+ cells.</p> <p>Methods</p> <p>PCR and sequencing were performed to identify the deleted region in the Japanese NDI patients. Immunological profiles of the NDI patients were analysed by flow cytometry. We also investigated the gene expression profiles of peripheral blood mononuclear cells (PBMC) from NDI patients and healthy controls in microarray technique.</p> <p>Results</p> <p>We evaluated subjects (one child and two adults) with 11.2-kb deletion that includes the entire <it>AVPR2 </it>locus and approximately half of the <it>ARHGAP4</it>. Hematologic tests showed a reduction of CD4+ cells in one adult patient, a reduction in CD8+ cells in the paediatric patient, and a slight reduction in the serum IgG levels in the adult patients, but none of them showed susceptibility to infection. Gene expression profiling of PBMC lacking <it>ARHGAP4 </it>revealed that expression of RhoGAP family genes was not influenced greatly by the lack of <it>ARHGAP4</it>.</p> <p>Conclusion</p> <p>These results suggest that loss of <it>ARHGAP4 </it>expression is not compensated for by other family members. ARHGAP4 may play some role in lymphocyte differentiation but partial loss of <it>ARHGAP4 </it>does not result in clinical immunodeficiency.</p

Prospective study on the mismatch concept in acute stroke patients within the first 24 h after symptom onset - 1000Plus study

<p>Abstract</p> <p>Background</p> <p>The mismatch between diffusion weighted imaging (DWI) lesion and perfusion imaging (PI) deficit volumes has been used as a surrogate of ischemic penumbra. This pathophysiology-orientated patient selection criterion for acute stroke treatment may have the potential to replace a fixed time window. Two recent trials - DEFUSE and EPITHET - investigated the mismatch concept in a multicenter prospective approach. Both studies randomized highly selected patients (n = 74/n = 100) and therefore confirmation in a large consecutive cohort is desirable. We here present a single-center approach with a 3T MR tomograph next door to the stroke unit, serving as a bridge from the ER to the stroke unit to screen all TIA and stroke patients. Our primary hypothesis is that the prognostic value of the mismatch concept is depending on the vessel status. Primary endpoint of the study is infarct growth determined by imaging, secondary endpoints are neurological deficit on day 5-7 and functional outcome after 3 months.</p> <p>Methods and design</p> <p>1000Plus is a prospective, single centre observational study with 1200 patients to be recruited. All patients admitted to the ER with the clinical diagnosis of an acute cerebrovascular event within 24 hours after symptom onset are screened. Examinations are performed on day 1, 2 and 5-7 with neurological examination including National Institute of Health Stroke Scale (NIHSS) scoring and stroke MRI including T2*, DWI, TOF-MRA, FLAIR and PI. PI is conducted as dynamic susceptibility-enhanced contrast imaging with a fixed dosage of 5 ml 1 M Gadobutrol. For post-processing of PI, mean transit time (MTT) parametric images are determined by deconvolution of the arterial input function (AIF) which is automatically identified. Lesion volumes and mismatch are measured and calculated by using the perfusion mismatch analyzer (PMA) software from ASIST-Japan. Primary endpoint is the change of infarct size between baseline examination and day 5-7 follow up.</p> <p>Discussions</p> <p>The aim of this study is to describe the incidence of mismatch and the predictive value of PI for final lesion size and functional outcome depending on delay of imaging and vascular recanalization. It is crucial to standardize PI for future randomized clinical trials as for individual therapeutic decisions and we expect to contribute to this challenging task.</p> <p>Trial Registration</p> <p>clinicaltrials.gov NCT00715533</p

Prevention of Apoptosis by Mitochondrial Phosphatase PGAM5 in the Mushroom Body Is Crucial for Heat Shock Resistance in Drosophila melanogaster

The heat shock (HS) response is essential for survival of all organisms. Although the machinery of the HS response has been extensively investigated at the cellular level, it is poorly understood at the level of the organism. Here, we show the crucial role of the mushroom body (MB) in the HS response in Drosophila. Null mutants of the mitochondrial phosphatase Drosophila PGAM5 (dPGAM5) exhibited increased vulnerability to HS, which was reversed by MB-specific expression of the caspase inhibitor p35, and similar vulnerability was induced in wild-type flies by knockdown of MB dPGAM5. Elimination of the MB did not affect the HS response of wild-type flies, but did increase the resistance of dPGAM5-deficient flies to HS. Thus, the MB may possess an apoptosis-dependent toxic function, the suppression of which by dPGAM5 appears to be crucial for HS resistance