Astrocytic expression of Parkinson's disease-related A53T α-synuclein causes neurodegeneration in mice

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease (PD) is the most common movement disorder. While neuronal deposition of α-synuclein serves as a pathological hallmark of PD and Dementia with Lewy Bodies, α-synuclein-positive protein aggregates are also present in astrocytes. The pathological consequence of astrocytic accumulation of α-synuclein, however, is unclear.</p> <p>Results</p> <p>Here we show that PD-related A53T mutant α-synuclein, when selectively expressed in astrocytes, induced rapidly progressed paralysis in mice. Increasing accumulation of α-synuclein aggregates was found in presymptomatic and symptomatic mouse brains and correlated with the expansion of reactive astrogliosis. The normal function of astrocytes was compromised as evidenced by cerebral microhemorrhage and down-regulation of astrocytic glutamate transporters, which also led to increased inflammatory responses and microglial activation. Interestingly, the activation of microglia was mainly detected in the midbrain, brainstem and spinal cord, where a significant loss of dopaminergic and motor neurons was observed. Consistent with the activation of microglia, the expression level of cyclooxygenase 1 (COX-1) was significantly up-regulated in the brain of symptomatic mice and in cultured microglia treated with conditioned medium derived from astrocytes over-expressing A53T α-synuclein. Consequently, the suppression of COX-1 activities extended the survival of mutant mice, suggesting that excess inflammatory responses elicited by reactive astrocytes may contribute to the degeneration of neurons.</p> <p>Conclusions</p> <p>Our findings demonstrate a critical involvement of astrocytic α-synuclein in initiating the non-cell autonomous killing of neurons, suggesting the viability of reactive astrocytes and microglia as potential therapeutic targets for PD and other neurodegenerative diseases.</p

Sub-channel analysis for LBE cooled fuel assembly with grid type spacers of China initiative accelerator driven system

The present study focuses on the thermal hydraulic characteristics of fuel assemblies in the China Initiative Accelerator Driven subcritical System (CiADS), which utilizes grid-type spacers to support lead bismuth eutectic (LBE) cooled fast reactors. While the structural design and mechanical analysis of CiADS triangular fuel assemblies with grid-type spacers have been preliminarily investigated, there is a pressing need to study the thermal hydraulic behavior of liquid LBE within these fuel assemblies. This analysis is crucial for assessing the safety and economy of the CiADS subcritical reactor. The sub-channel analysis code, based on the lumped parameter method, plays a vital role in rapidly evaluating the safety features of LBE-cooled fast reactor fuel assemblies. To comprehensively evaluate the thermal hydraulic performance of fuel assemblies with grid-type spacers in the CiADS LBE cooling system, the flow pressure drop model, turbulent mixing model, and convective heat transfer model for the fuel assembly structure with grid-type spacers were incorporated into the existing CiADS sub-channel analysis code. This enhanced code has been successfully employed in the thermal hydraulic analysis of fuel assemblies utilizing wire-type spacers in the CiADS system. To verify the validity and accuracy of the modified CiADS sub-channel analysis code in calculating triangular fuel assemblies with grid-type spacers, the code was first utilized to replicate a 19-rods flow heat transfer experiment with grid-type spacers cooling liquid LBE. A comparison between the simulation and experimental results confirms that the CiADS sub-channel analysis code can predict the coolant temperature and fuel rod surface temperature in fuel assemblies with grid-type spacers. Subsequently, the structure and thermal hydraulic design of the latest CiADS fuel assembly with grid-type spacers were reviewed. Finally, taking into account the aforementioned enhancements to the CiADS sub-channel analysis code, a comprehensive thermo-hydraulic calculation of the CiADS fuel assembly with grid-type spacers was conducted. The results demonstrate that the coolant outlet temperature, maximum cladding temperature, and maximum fuel pellet temperature all fall within the design parameters of CiADS. Furthermore, the impact of the number of rods in different rod bundles (91, 61, 37, and 7 rods) on thermal hydraulic performance was analyzed. The findings indicate that, while ensuring calculation accuracy and efficiency, the results obtained from the 37-rod bundle can effectively reflect the thermal hydraulic behavior of the reactor core

In C andida albicans hyphae, Sec2p is physically associated with SEC2 mRNA on secretory vesicles

andida albicans hyphae grow in a highly polarized fashion from their tips. This polarized growth requires the continuous delivery of secretory vesicles to the tip region. Vesicle delivery depends on Sec2p, the Guanine Exchange Factor (GEF) for the Rab GTPase Sec4p. GTP bound Sec4p is required for the transit of secretory vesicles from the trans-Golgi to sites of polarized growth. We previously showed that phosphorylation of Sec2p at residue S584 was necessary for Sec2p to support hyphal, but not yeast growth. Here we show that on secretory vesicles SEC2 mRNA is physically associated with Sec2p. Moreover, we show that the phosphorylation of S584 allows SEC2 mRNA to dissociate from Sec2p and we speculate that this is necessary for Sec2p function and/or translation. During hyphal extension, the growing tip may be separated from the nucleus by up to 15 μm. Transport of SEC2 mRNA on secretory vesicles to the tip localizes SEC2 translation to tip allowing a sufficient accumulation of this key protein at the site of polarized growth

Search for the decay J/ψ→γ+invisibleJ/\psi\to\gamma + \rm {invisible}

We search for $J/\psi$ radiative decays into a weakly interacting neutral particle, namely an invisible particle, using the $J/\psi$ produced through the process $\psi(3686)\to\pi^+\pi^-J/\psi$ in a data sample of $(448.1\pm2.9)\times 10^6$ $\psi(3686)$ decays collected by the BESIII detector at BEPCII. No significant signal is observed. Using a modified frequentist method, upper limits on the branching fractions are set under different assumptions of invisible particle masses up to 1.2 $\mathrm{\ Ge\kern -0.1em V}/c^2$. The upper limit corresponding to an invisible particle with zero mass is 7.0$\times 10^{-7}$ at the 90\% confidence level

Measurement of proton electromagnetic form factors in e+e−→ppˉe^+e^- \to p\bar{p} in the energy region 2.00-3.08 GeV

The process of $e^+e^- \rightarrow p\bar{p}$ is studied at 22 center-of-mass energy points ($\sqrt{s}$) from 2.00 to 3.08 GeV, exploiting 688.5~pb$^{-1}$ of data collected with the BESIII detector operating at the BEPCII collider. The Born cross section~($\sigma_{p\bar{p}}$) of $e^+e^- \rightarrow p\bar{p}$ is measured with the energy-scan technique and it is found to be consistent with previously published data, but with much improved accuracy. In addition, the electromagnetic form-factor ratio ($|G_{E}/G_{M}|$) and the value of the effective ($|G_{\rm{eff}}|$), electric ($|G_E|$) and magnetic ($|G_M|$) form factors are measured by studying the helicity angle of the proton at 16 center-of-mass energy points. $|G_{E}/G_{M}|$ and $|G_M|$ are determined with high accuracy, providing uncertainties comparable to data in the space-like region, and $|G_E|$ is measured for the first time. We reach unprecedented accuracy, and precision results in the time-like region provide information to improve our understanding of the proton inner structure and to test theoretical models which depend on non-perturbative Quantum Chromodynamics

First observations of hc→h_c \to hadrons

Based on $(4.48 \pm 0.03) \times 10^{8}$ $\psi(3686)$ events collected with the BESIII detector, five $h_c$ hadronic decays are searched for via process $\psi(3686) \to \pi^0 h_c$. Three of them, $h_c \to p \bar{p} \pi^+ \pi^-$, $\pi^+ \pi^- \pi^0$, and $2(\pi^+ \pi^-) \pi^0$ are observed for the first time, with statistical significances of 7.4$\sigma$, $4.9\sigma$, and 9.1$\sigma$, and branching fractions of $(2.89\pm0.32\pm0.55)\times10^{-3}$, $(1.60\pm0.40\pm0.32)\times10^{-3}$, and $(7.44\pm0.94\pm1.56)\times10^{-3}$, respectively, where the first uncertainties are statistical and the second systematic. No significant signal is observed for the other two decay modes, and the corresponding upper limits of the branching fractions are determined to be $B(h_c \to 3(\pi^+ \pi^-) \pi^0)<8.7\times10^{-3}$ and $B(h_c \to K^+ K^- \pi^+ \pi^-)<5.8\times10^{-4}$ at 90% confidence level.Comment: 17 pages, 16 figure

Precise Measurements of Branching Fractions for Ds+D_s^+ Meson Decays to Two Pseudoscalar Mesons

We measure the branching fractions for seven $D_{s}^{+}$ two-body decays to pseudo-scalar mesons, by analyzing data collected at $\sqrt{s}=4.178\sim4.226$ GeV with the BESIII detector at the BEPCII collider. The branching fractions are determined to be $\mathcal{B}(D_s^+\to K^+\eta^{\prime})=(2.68\pm0.17\pm0.17\pm0.08)\times10^{-3}$, $\mathcal{B}(D_s^+\to\eta^{\prime}\pi^+)=(37.8\pm0.4\pm2.1\pm1.2)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+\eta)=(1.62\pm0.10\pm0.03\pm0.05)\times10^{-3}$, $\mathcal{B}(D_s^+\to\eta\pi^+)=(17.41\pm0.18\pm0.27\pm0.54)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+K_S^0)=(15.02\pm0.10\pm0.27\pm0.47)\times10^{-3}$, $\mathcal{B}(D_s^+\to K_S^0\pi^+)=(1.109\pm0.034\pm0.023\pm0.035)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+\pi^0)=(0.748\pm0.049\pm0.018\pm0.023)\times10^{-3}$, where the first uncertainties are statistical, the second are systematic, and the third are from external input branching fraction of the normalization mode $D_s^+\to K^+K^-\pi^+$. Precision of our measurements is significantly improved compared with that of the current world average values

Measurements of Weak Decay Asymmetries of Λc+→pKS0\Lambda_c^+\to pK_S^0, Λπ+\Lambda\pi^+, Σ+π0\Sigma^+\pi^0, and Σ0π+\Sigma^0\pi^+

Using $e^+e^-\to\Lambda_c^+\bar\Lambda_c^-$ production from a 567 pb$^{-1}$ data sample collected by BESIII at 4.6 GeV, a full angular analysis is carried out simultaneously on the four decay modes of $\Lambda_c^+\to pK_S^0$, $\Lambda \pi^+$, $\Sigma^+\pi^0$, and $\Sigma^0\pi^+$. For the first time, the $\Lambda_c^+$ transverse polarization is studied in unpolarized $e^+e^-$ collisions, where a non-zero effect is observed with a statistical significance of 2.1$\sigma$. The decay asymmetry parameters of the $\Lambda_c^+$ weak hadronic decays into $pK_S^0$, $\Lambda\pi^+$, $\Sigma^+\pi^0$ and $\Sigma^0\pi^+$ are measured to be $0.18\pm0.43(\rm{stat})\pm0.14(\rm{syst})$, $-0.80\pm0.11(\rm{stat})\pm0.02(\rm{syst})$, $-0.57\pm0.10(\rm{stat})\pm0.07(\rm{syst})$, and $-0.73\pm0.17(\rm{stat})\pm0.07(\rm{syst})$, respectively. In comparison with previous results, the measurements for the $\Lambda\pi^+$ and $\Sigma^+\pi^0$ modes are consistent but with improved precision, while the parameters for the $pK_S^0$ and $\Sigma^0\pi^+$ modes are measured for the first time

Toward Sustainable and Comprehensive Control of Schistosomiasis in China: Lessons from Sichuan

Triggered by a fascinating publication in the New England Journal of Medicine detailing China's new multi-pronged strategy to control and eventually interrupt the transmission of Schistosoma japonicum, this PLoS Neglected Tropical Diseases Debate critically examines the generalizability and financial costs of the studies presented from the marshlands of the lake region. Edmund Seto from the University of California and colleagues emphasize that the epidemiology and control of schistosomiasis varies according to the social-ecological context. They conjecture that the successful intervention packages piloted in the lake region is not fully fit for the hilly and mountainous environments in Sichuan and Yunnan provinces, and hence call for more flexible, setting-specific, and less expensive control strategies. In response, Xiao-Nong Zhou from the National Institute of Parasitic Diseases at the Chinese Center of Disease Control and Prevention and colleagues explain the steps from designing pilot studies to the articulation and implementation of a new national control strategy through a careful process of scaling-up and adaptations. Finally, the two opponents converge. The need for integrated, intersectoral, and setting-specific control measures is stressed, supported by rigorous surveillance and continuous research. Experiences and lessons from China are important for shaping the schistosomiasis elimination agenda