Microglia in the aging brain: relevance to neurodegeneration

Microglia cells are the brain counterpart of macrophages and function as the first defense in the brain. Although they are neuroprotective in the young brain, microglia cells may be primed to react abnormally to stimuli in the aged brain and to become neurotoxic and destructive during neurodegeneration. Aging-induced immune senescence occurs in the brain as age-associated microglia senescence, which renders microglia to function abnormally and may eventually promote neurodegeneration. Microglia senescence is manifested by both morphological changes and alterations in immunophenotypic expression and inflammatory profile. These changes are likely caused by microinvironmental factors, but intrinsic factors cannot yet be completely excluded. Microglia senescence appears to underlie the switching of microglia from neuroprotective in the young brain to neurotoxic in the aged brain. The hypothesis of microglia senescence during aging offers a novel perspective on their roles in aging-related neurodegeneration. In Parkinson's disease and Alzheimer's disease, over-activation of microglia may play an active role in the pathogenesis because microglia senescence primes them to be neurotoxic during the development of the diseases

Experimental Trapped-ion Quantum Simulation of the Kibble-Zurek dynamics in momentum space

The Kibble-Zurek mechanism is the paradigm to account for the nonadiabatic dynamics of a system across a continuous phase transition. Its study in the quantum regime is hindered by the requisite of ground state cooling. We report the experimental quantum simulation of critical dynamics in the transverse-field Ising model by a set of Landau-Zener crossings in pseudo-momentum space, that can be probed with high accuracy using a single trapped ion. We test the Kibble-Zurek mechanism in the quantum regime in the momentum space and find the measured scaling of excitations is in accordance with the theoretical prediction.Comment: 10 pages, 3 figures Published in Scientific Reports, http://www.nature.com/articles/srep3338

The unidirectional valve patch provides no benefits to early and long-term survival in patients with ventricular septal defect and severe pulmonary artery hypertension

ObjectiveOur aim was to test whether a unidirectional valve patch would provide benefit to early and long-term survival for patients with ventricular septal defect and severe pulmonary artery hypertension.MethodsEight hundred seventy-six cases of ventricular septal defect with severe pulmonary artery hypertension were closed with or without a unidirectional valve patch and were classified as the unidirectional valve patch (UVP) group (n = 195) and nonvalve patch (NVP) group (n = 681), respectively. Propensity scores of inclusion into the UVP group were used to match 138 pairs between the 2 groups. Kaplan–Meier survival curves were constructed to compare early and long-term survival.ResultsFor the 138 propensity-matched pairs, there were 7 and 9 early deaths (in-hospital deaths) in the UVP and NVP groups, respectively. The difference in early mortality between the 2 groups did not reach statistical significance (χ2 = 0.265, P = .6064). With a mean of 9.2 ± 4.92 years' and 2511 patient-years' follow-up, there were 6 late deaths in the UVP group and 7 late deaths in the NVP group. The difference in actuarial survival at 5, 10, 15, and 18 years between the 2 groups was not significant (log-rank test, χ2 = 0.565, P = .331). The difference in the late mortality between the groups with or without a patent patch at the time of discharge did not reach statistical significance (χ2 = 1.140, P = .2856). There was no difference between the 2 groups in the 6-minute walk distance assessed at the last follow-up (525.9 ± 88.0 meters for the UVP group and 536.5 ± 95.8 meters for the NVP group, F = 1.550, P = .214).ConclusionA unidirectional valve patch provides no benefits to early and long-term survival when it is used to deal with ventricular septal defect and severe pulmonary artery hypertension

Expression quantitative trait locus studies in the era of single-cell omics

Genome-wide association studies have revealed that the regulation of gene expression bridges genetic variants and complex phenotypes. Profiling of the bulk transcriptome coupled with linkage analysis (expression quantitative trait locus (eQTL) mapping) has advanced our understanding of the relationship between genetic variants and gene regulation in the context of complex phenotypes. However, bulk transcriptomics has inherited limitations as the regulation of gene expression tends to be cell-type-specific. The advent of single-cell RNA-seq technology now enables the identification of the cell-type-specific regulation of gene expression through a single-cell eQTL (sc-eQTL). In this review, we first provide an overview of sc-eQTL studies, including data processing and the mapping procedure of the sc-eQTL. We then discuss the benefits and limitations of sc-eQTL analyses. Finally, we present an overview of the current and future applications of sc-eQTL discoveries

2-(1-Methyl­ethoxy)-5-nitro­phenyl N-methyl­carbamate

In the title compound, C11H14N2O5, the nitro group is approximately coplanar with the benzene ring, making a dihedral angle of 4.26 (17)°. The dihedral angle between the methyl­carbamate group and the benzene ring is 72.47 (6)°. There is a strong inter­molecular N—H⋯O hydrogen bond between the N and O atoms from adjacent methyl­carbamate groups, forming a one-dimensional network along the a axis

Berberine Inhibits HIV Protease Inhibitor-Induced Inflammatory Response by Modulating ER Stress Signaling Pathways in Murine Macrophages

Background HIV protease inhibitor (PI)-induced inflammatory response plays an important role in HIV PI-associated dyslipidemia and cardiovascular complications. This study examined the effect of berberine, a traditional herb medicine, on HIV PI-induced inflammatory response and further investigated the underlying cellular/molecular mechanisms in macrophages. Methodology and Principal Findings Cultured mouse J774A.1 macrophages and primary mouse macrophages were used in this study. The expression of TNF-α and IL-6 were detected by real-time RT-PCR and ELISA. Activations of ER stress and ERK signaling pathways were determined by Western blot analysis. Immunofluorescent staining was used to determine the intracellular localization of RNA binding protein HuR. RNA-pull down assay was used to determine the association of HuR with endogenous TNF-α and IL-6. Berberine significantly inhibited HIV PI-induced TNF-α and IL-6 expression by modulating ER stress signaling pathways and subsequent ERK activation, in turn preventing the accumulation of the RNA binding protein HuR in cytosol and inhibiting the binding of HuR to the 3′-UTRs of TNF-α and IL-6 in macrophages. Conclusions and Significance Inhibition of ER stress represents a key mechanism by which berberine prevents HIV PI-induced inflammatory response. Our findings provide a new insight into the molecular mechanisms of berberine and show the potential application of berberine as a complimentary therapeutic agent for HIV infection