Microglia are highly dynamic immune cells of the CNS and their dynamism is proposed to be regulated by neuronal activities. However, the mechanisms underlying neuronal regulation of microglial ...dynamism have not been determined. Here, we found an increased number of microglial primary processes in the hippocampus during KA-induced seizure activity. Consistently, global glutamate induced robust microglial process extension toward neurons in both brain slices and in the intact brain in vivo. The mechanism of the glutamate-induced microglial process extension involves the activation of neuronal NMDA receptors, calcium influx, subsequent ATP release, and microglial response through P2Y12 receptors. Seizure-induced increases in microglial process numbers were also dependent on NMDA receptor activation. Finally, we found that P2Y12 KO mice exhibited reduced seizure-induced increases in microglial process numbers and worsened KA-induced seizure behaviors. Our results elucidate the molecular mechanisms underlying microglia-neuron communication that may be potentially neuroprotective in the epileptic brain.
Summary Background Dengue is the most common arbovirus infection globally, but its burden is poorly quantified. We estimated dengue mortality, incidence, and burden for the Global Burden of Disease ...Study 2013. Methods We modelled mortality from vital registration, verbal autopsy, and surveillance data using the Cause of Death Ensemble Modelling tool. We modelled incidence from officially reported cases, and adjusted our raw estimates for under-reporting based on published estimates of expansion factors. In total, we had 1780 country-years of mortality data from 130 countries, 1636 country-years of dengue case reports from 76 countries, and expansion factor estimates for 14 countries. Findings We estimated an average of 9221 dengue deaths per year between 1990 and 2013, increasing from a low of 8277 (95% uncertainty estimate 5353–10 649) in 1992, to a peak of 11 302 (6790–13 722) in 2010. This yielded a total of 576 900 (330 000–701 200) years of life lost to premature mortality attributable to dengue in 2013. The incidence of dengue increased greatly between 1990 and 2013, with the number of cases more than doubling every decade, from 8·3 million (3·3 million–17·2 million) apparent cases in 1990, to 58·4 million (23·6 million–121·9 million) apparent cases in 2013. When accounting for disability from moderate and severe acute dengue, and post-dengue chronic fatigue, 566 000 (186 000–1 415 000) years lived with disability were attributable to dengue in 2013. Considering fatal and non-fatal outcomes together, dengue was responsible for 1·14 million (0·73 million–1·98 million) disability-adjusted life-years in 2013. Interpretation Although lower than other estimates, our results offer more evidence that the true symptomatic incidence of dengue probably falls within the commonly cited range of 50 million to 100 million cases per year. Our mortality estimates are lower than those presented elsewhere and should be considered in light of the totality of evidence suggesting that dengue mortality might, in fact, be substantially higher. Funding Bill & Melinda Gates Foundation.
We combine Dark Energy Survey Year 1 clustering and weak lensing data with baryon acoustic oscillations and Big Bang nucleosynthesis experiments to constrain the Hubble constant. Assuming a flat ΛCDM ...model with minimal neutrino mass (∑m_ν = 0.06 eV), we find |$H_0=67.4^{+1.1}_{-1.2}\ \rm {km\,\rm s^{-1}\,\rm Mpc^{-1}}$| (68 per cent CL). This result is completely independent of Hubble constant measurements based on the distance ladder, cosmic microwave background anisotropies (both temperature and polarization), and strong lensing constraints. There are now five data sets that: (a) have no shared observational systematics; and (b) each constrains the Hubble constant with fractional uncertainty at the few-per cent level. We compare these five independent estimates, and find that, as a set, the differences between them are significant at the 2.5σ level (χ^2/dof = 24/11, probability to exceed = 1.1 per cent). Having set the threshold for consistency at 3σ, we combine all five data sets to arrive at |$H_0=69.3^{+0.4}_{-0.6}\ \rm {km\,\mathrm{ s}^{-1}\,\mathrm{ Mpc}^{-1}}$|.
Preparedness for a possible influenza pandemic caused by highly pathogenic avian influenza A subtype H5N1 has become a global priority. The spread of the virus to Europe and continued human infection ...in Southeast Asia have heightened pandemic concern. It remains unknown from where the pandemic strain may emerge; current attention is directed at Vietnam, Thailand, and, more recently, Indonesia and China. Here, we report that genetically and antigenically distinct sublineages of H5N1 virus have become established in poultry in different geographical regions of Southeast Asia, indicating the long-term endemicity of the virus, and the isolation of H5N1 virus from apparently healthy migratory birds in southern China. Our data show that H5N1 influenza virus, has continued to spread from its established source in southern China to other regions through transport of poultry and bird migration. The identification of regionally distinct sublineages contributes to the understanding of the mechanism for the perpetuation and spread of H5N1, providing information that is directly relevant to control of the source of infection in poultry. It points to the necessity of surveillance that is geographically broader than previously supposed and that includes H5N1 viruses of greater genetic and antigenic diversity.
Dapsone is an important medication for the treatment of leprosy, but a life-threatening drug hypersensitivity syndrome develops in some patients. In this report from China, an
HLA-B
locus is ...identified as a strong genetic risk factor for the syndrome.
Dapsone (4-4′-sulfonyldianiline), which was first synthesized in 1908,
1
is both an antibiotic and an antiinflammatory agent. Dapsone alone or in combination with other drugs has been used for the prevention and treatment of infectious diseases (e.g., leprosy, malaria, and actinomycetoma, as well as
Pneumocystis jirovecii
pneumonia in persons with human immunodeficiency virus HIV infection) and chronic inflammatory diseases characterized by the infiltration of neutrophils or eosinophils (e.g., dermatitis herpetiformis, linear IgA dermatosis, subcorneal pustular dermatosis, and erythema elevatum diutinum).
2
,
3
About 0.5 to 3.6% of persons treated with dapsone have a drug hypersensitivity syndrome,
3
–
5
which was first described by . . .
A kind of integrated process of extreme high-speed laser cladding (EHLC) and laser remelting (LR) was firstly proposed to comprehensively improve surface quality and internal interlayer bonding ...strength of pure EHLCed coatings. The influence mechanism of integrated process on microstructure and corrosion resistance was carefully studied. The integrated process effectively optimized the surface roughness (reduced >60%), and eliminated interlayer defects, especially for the multi-layer coating. Results indicated that both of the coatings manufactured by EHLC and EHLC-LR comprised dominant ultrafine grains. However, electrochemical measurements showed that the EHLC-LRed coating possessed better corrosion resistance and lower corrosion rate compared to EHLCed counterpart. It was proposed that this behavior was due to a high density of ultra-fine grains with numerous grain boundaries uniformly distributed on the coating surface forming a more stable oxide film.
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•Fe-based coatings were firstly prepared by an integrated process of EHLC and LR.•Defect of EHLCed Fe-based coatings could be eliminated via layer-by-layer LR.•EHLC-LRed coatings possessed much more uniform and finer microstructure.•Coatings manufactured by EHLC-LR exhibited superior corrosion behavior.
This paper presents an investigation of wave propagation through granite after different high-temperature treatments by using a pendulum impact setup. Propagation coefficients (attenuation ...coefficient and wavenumber) were successfully introduced to describe the attenuation of longitudinal waves through granite after high-temperature treatment. The attenuation rate of the longitudinal wave through the granite after different high-temperature treatments was obtained. In addition, the effects of temperature, amplitude and wavelength of longitudinal waves on the propagation coefficient and attenuation rate were discussed. The experimental results show that the propagation coefficient and the attenuation rate increase with increasing temperature. The attenuation rate decreases with increasing wavelength, while the propagation coefficient is not influenced by the wavelength. Meanwhile, the propagation coefficient and the attenuation rate are not influenced by the amplitude of the longitudinal wave.
A lung-inspired approach is employed to overcome reactant homogeneity issues in polymer electrolyte fuel cells. The fractal geometry of the lung is used as the model to design flow-fields of ...different branching generations, resulting in uniform reactant distribution across the electrodes and minimum entropy production of the whole system. 3D printed, lung-inspired flow field based PEFCs with N = 4 generations outperform the conventional serpentine flow field designs at 50% and 75% RH, exhibiting a ∼20% and ∼30% increase in performance (at current densities higher than 0.8 A cm −2 ) and maximum power density, respectively. In terms of pressure drop, fractal flow-fields with N = 3 and 4 generations demonstrate ∼75% and ∼50% lower values than conventional serpentine flow-field design for all RH tested, reducing the power requirements for pressurization and recirculation of the reactants. The positive effect of uniform reactant distribution is pronounced under extended current-hold measurements, where lung-inspired flow field based PEFCs with N = 4 generations exhibit the lowest voltage decay (∼5 mV h −1 ). The enhanced fuel cell performance and low pressure drop values of fractal flow field design are preserved at large scale (25 cm 2 ), in which the excessive pressure drop of a large-scale serpentine flow field renders its use prohibitive.
The aortic valve exhibits complex three-dimensional (3D) anatomy and heterogeneity essential for the long-term efficient biomechanical function. These are, however, challenging to mimic in de novo ...engineered living tissue valve strategies. We present a novel simultaneous 3D printing/photocrosslinking technique for rapidly engineering complex, heterogeneous aortic valve scaffolds. Native anatomic and axisymmetric aortic valve geometries (root wall and tri-leaflets) with 12-22 mm inner diameters (ID) were 3D printed with poly-ethylene glycol-diacrylate (PEG-DA) hydrogels (700 or 8000 MW) supplemented with alginate. 3D printing geometric accuracy was quantified and compared using Micro-CT. Porcine aortic valve interstitial cells (PAVIC) seeded scaffolds were cultured for up to 21 days. Results showed that blended PEG-DA scaffolds could achieve over tenfold range in elastic modulus (5.3±0.9 to 74.6±1.5 kPa). 3D printing times for valve conduits with mechanically contrasting hydrogels were optimized to 14 to 45 min, increasing linearly with conduit diameter. Larger printed valves had greater shape fidelity (93.3±2.6, 85.1±2.0 and 73.3±5.2% for 22, 17 and 12 mm ID porcine valves; 89.1±4.0, 84.1±5.6 and 66.6±5.2% for simplified valves). PAVIC seeded scaffolds maintained near 100% viability over 21 days. These results demonstrate that 3D hydrogel printing with controlled photocrosslinking can rapidly fabricate anatomical heterogeneous valve conduits that support cell engraftment.
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