5,906 research outputs found
Versatile Roles of V-ATPases Accessory Subunit Ac45 in Osteoclast Formation and Function
Vacuolar-type H+-ATPases (V-ATPases) are macromolecular proton pumps that acidify intracellular cargos and deliver protons across the plasma membrane of a variety of specialized cells, including bone-resorbing osteoclasts. Extracellular acidification is crucial for osteoclastic bone resorption, a process that initiates the dissolution of mineralized bone matrix. While the importance of V-ATPases in osteoclastic resorptive function is well-defined, whether V-ATPases facilitate additional aspects of osteoclast function and/or formation remains largely obscure. Here we report that the V-ATPase accessory subunit Ac45 participates in both osteoclast formation and function. Using a siRNA-based approach, we show that targeted suppression of Ac45 impairs intracellular acidification and endocytosis, both are prerequisite for osteoclastic bone resorptive function in vitro. Interestingly, we find that knockdown of Ac45 also attenuates osteoclastogenesis owing to a reduced fusion capacity of osteoclastic precursor cells. Finally, in an effort to gain more detailed insights into the functional role of Ac45 in osteoclasts, we attempted to generate osteoclast-specific Ac45 conditional knockout mice using a Cathepsin K-Cre-LoxP system. Surprisingly, however, insertion of the neomycin cassette in the Ac45-FloxNeo mice resulted in marked disturbances in CNS development and ensuing embryonic lethality thus precluding functional assessment of Ac45 in osteoclasts and peripheral bone tissues. Based on these unexpected findings we propose that, in addition to its canonical function in V-ATPase-mediated acidification, Ac45 plays versatile roles during osteoclast formation and function
Self-rated health in middle-aged and elderly Chinese : distribution, determinants and associations with cardio-metabolic risk factors
Background: Self-rated health (SRH) has been demonstrated to be an accurate reflection of a person's health and a valid predictor of incident mortality and chronic morbidity. We aimed to evaluate the distribution and factors associated with SRH and its association with biomarkers of cardio-metabolic diseases among middle-aged and elderly Chinese.
Methods: Survey of 1,458 men and 1,831 women aged 50 to 70 years, conducted in one urban and two rural areas of Beijing and Shanghai in 2005. SRH status was measured and categorized as good (very good and good) vs. not good (fair, poor and very poor). Determinants of SRH and associations with biomarkers of cardio-metabolic diseases were evaluated using logistic regression.
Results: Thirty two percent of participants reported good SRH. Males and rural residents tended to report good SRH. After adjusting for potential confounders, residence, physical activity, employment status, sleep quality and presence of diabetes, cardiovascular disease, and depression were the main determinants of SRH. Those free from cardiovascular disease (OR 3.68; 95%CI 2.39; 5.66), rural residents (OR 1.89; 95% CI 1.47; 2.43), non-depressed participants (OR 2.50; 95% CI 1.67; 3.73) and those with good sleep quality (OR 2.95; 95% CI 2.22; 3.91) had almost twice or over the chance of reporting good SRH compared to their counterparts. There were significant associations -and trend- between SRH and levels of inflammatory markers, insulin levels and insulin resistance.
Conclusion: Only one third of middle-aged and elderly Chinese assessed their health status as good or very good. Although further longitudinal studies are required to confirm our findings, interventions targeting social inequalities, lifestyle patterns might not only contribute to prevent chronic morbidity but as well to improve populations' perceived health
Structure of hadron resonances with a nearby zero of the amplitude
We discuss the relation between the analytic structure of the scattering
amplitude and the origin of an eigenstate represented by a pole of the
amplitude.If the eigenstate is not dynamically generated by the interaction in
the channel of interest, the residue of the pole vanishes in the zero coupling
limit. Based on the topological nature of the phase of the scattering
amplitude, we show that the pole must encounter with the
Castillejo-Dalitz-Dyson (CDD) zero in this limit. It is concluded that the
dynamical component of the eigenstate is small if a CDD zero exists near the
eigenstate pole. We show that the line shape of the resonance is distorted from
the Breit-Wigner form as an observable consequence of the nearby CDD zero.
Finally, studying the positions of poles and CDD zeros of the KbarN-piSigma
amplitude, we discuss the origin of the eigenstates in the Lambda(1405) region.Comment: 7 pages, 3 figures, v2: published versio
Constraints on Spin-Independent Nucleus Scattering with sub-GeV Weakly Interacting Massive Particle Dark Matter from the CDEX-1B Experiment at the China Jin-Ping Laboratory
We report results on the searches of weakly interacting massive particles
(WIMPs) with sub-GeV masses () via WIMP-nucleus spin-independent
scattering with Migdal effect incorporated. Analysis on time-integrated (TI)
and annual modulation (AM) effects on CDEX-1B data are performed, with 737.1
kgday exposure and 160 eVee threshold for TI analysis, and 1107.5
kgday exposure and 250 eVee threshold for AM analysis. The sensitive
windows in are expanded by an order of magnitude to lower DM masses
with Migdal effect incorporated. New limits on at
90\% confidence level are derived as 1010
for TI analysis at 50180 MeV/, and
1010 for AM analysis at
75 MeV/3.0 GeV/.Comment: 5 pages, 4 figure
Limits on Light Weakly Interacting Massive Particles from the First 102.8 kg day Data of the CDEX-10 Experiment
We report the first results of a light weakly interacting massive particles
(WIMPs) search from the CDEX-10 experiment with a 10 kg germanium detector
array immersed in liquid nitrogen at the China Jinping Underground Laboratory
with a physics data size of 102.8 kg day. At an analysis threshold of 160 eVee,
improved limits of 8 and 3 cm at a
90\% confidence level on spin-independent and spin-dependent WIMP-nucleon cross
sections, respectively, at a WIMP mass () of 5 GeV/ are
achieved. The lower reach of is extended to 2 GeV/.Comment: 5 pages, 4 figure
Search for Light Weakly-Interacting-Massive-Particle Dark Matter by Annual Modulation Analysis with a Point-Contact Germanium Detector at the China Jinping Underground Laboratory
We present results on light weakly interacting massive particle (WIMP)
searches with annual modulation (AM) analysis on data from a 1-kg mass -type
point-contact germanium detector of the CDEX-1B experiment at the China Jinping
Underground Laboratory. Datasets with a total live time of 3.2 yr within a 4.2
yr span are analyzed with analysis threshold of 250 eVee. Limits on
WIMP-nucleus (-) spin-independent cross sections as function of WIMP
mass () at 90\% confidence level (C.L.) are derived using the dark
matter halo model. Within the context of the standard halo model, the 90\% C.L.
allowed regions implied by the DAMA/LIBRA and CoGeNT AM-based analysis are
excluded at 99.99\% and 98\% C.L., respectively. These results correspond to
the best sensitivity at 6 among WIMP AM
measurements to date.Comment: 5 pages, 4 figure
Dihydrolipoic Acid Induces Cytotoxicity in Mouse Blastocysts through Apoptosis Processes
α-Lipoic acid (LA) is a thiol with antioxidant properties that protects against oxidative stress-induced apoptosis. LA is absorbed from the diet, taken up by cells and tissues, and subsequently reduced to dihydrolipoic acid (DHLA). In view of the recent application of DHLA as a hydrophilic nanomaterial preparation, determination of its biosafety profile is essential. In the current study, we examined the cytotoxic effects of DHLA on mouse embryos at the blastocyst stage, subsequent embryonic attachment and outgrowth in vitro, in vivo implantation by embryo transfer, and early embryonic development in an animal model. Blastocysts treated with 50 μM DHLA exhibited significantly increased apoptosis and a corresponding decrease in total cell number. Notably, the implantation success rates of blastocysts pretreated with DHLA were lower than that of their control counterparts. Moreover, in vitro treatment with 50 μM DHLA was associated with increased resorption of post-implantation embryos and decreased fetal weight. Data obtained using an in vivo mouse model further disclosed that consumption of drinking water containing 100 μM DHLA led to decreased early embryo development, specifically, inhibition of development to the blastocyst stage. However, it appears that concentrations of DHLA lower than 50 μM do not exert a hazardous effect on embryonic development. Our results collectively indicate that in vitro and in vivo exposure to concentrations of DHLA higher than 50 μM DHLA induces apoptosis and retards early pre- and post-implantation development, and support the potential of DHLA to induce embryonic cytotoxicity
New measurement of via neutron capture on hydrogen at Daya Bay
This article reports an improved independent measurement of neutrino mixing
angle at the Daya Bay Reactor Neutrino Experiment. Electron
antineutrinos were identified by inverse -decays with the emitted
neutron captured by hydrogen, yielding a data-set with principally distinct
uncertainties from that with neutrons captured by gadolinium. With the final
two of eight antineutrino detectors installed, this study used 621 days of data
including the previously reported 217-day data set with six detectors. The
dominant statistical uncertainty was reduced by 49%. Intensive studies of the
cosmogenic muon-induced Li and fast neutron backgrounds and the
neutron-capture energy selection efficiency, resulted in a reduction of the
systematic uncertainty by 26%. The deficit in the detected number of
antineutrinos at the far detectors relative to the expected number based on the
near detectors yielded in the
three-neutrino-oscillation framework. The combination of this result with the
gadolinium-capture result is also reported.Comment: 26 pages, 23 figure
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