DJ-1 can inhibit microtubule associated protein 1 B formed aggregates

<p>Abstract</p> <p>Background</p> <p>Abnormal accumulation and aggregation of microtubule associated proteins (MAPs) plays an important role in the pathogenesis of neurodegenerative diseases. Loss-of-function mutation of DJ-1/Park7 can cause early onset of PD. DJ-1, a molecular chaperone, can inhibit α-synuclein aggregation. Currently, little is known whether or not loss of function of DJ-1 contributes to abnormal MAPs aggregation in neurodegenerative disorders such as PD.</p> <p>Results</p> <p>We presented evidence that DJ-1 could bind to microtubule associated protein1b Light Chain (MAP1b-LC). Overexpression of DJ-1 prevented MAP1b-LC aggregation in HEK293t and SH-SY5Y cells while DJ-1 knocking down (KD) enhanced MAP1b-LC aggregation in SH-SY5Y cells. The increase in insoluble MAP1b-LC was also observed in the DJ-1 null mice brain. Moreover, in the DJ-1 KD SH-SY5Y cells, overexpression of MAP1B-LC led to endoplasmic reticulum (ER) stress-induced apoptosis.</p> <p>Conclusion</p> <p>Our results suggest that DJ-1 acts as a molecular chaperone to inhibit MAP1B aggregation thus leading to neuronal apoptosis. Our study provides a novel insight into the mechanisms that underly the pathogenesis of Parkinson's disease (PD).</p

Surface skyrmions and dual topological Hall effect in antiferromagnetic topological insulator EuCd2_2As2_2

In this work, we synthesized single crystal of EuCd$_2$As$_2$, which exhibits A-type antiferromagnetic (AFM) order with in-plane spin orientation below $T_N$ = 9.5~K.Optical spectroscopy and transport measurements suggest its topological insulator (TI) nature with an insulating gap around 0.1eV. Remarkably, a dual topological Hall resistivity that exhibits same magnitude but opposite signs in the positive to negative and negative to positive magnetic field hysteresis branches emerges below 20~K. With magnetic force microscopy (MFM) images and numerical simulations, we attribute the dual topological Hall effect to the N\'{e}el-type skyrmions stabilized by the interactions between topological surface states and magnetism, and the sign reversal in different hysteresis branches indicates potential coexistence of skyrmions and antiskyrmions. Our work uncovers a unique two-dimensional (2D) magnetism on the surface of intrinsic AFM TI, providing a promising platform for novel topological quantum states and AFM spintronic applications.Comment: 7 pages, 3 figure

Lack of Association Between DJ-1 Gene Promoter Polymorphism and the Risk of Parkinson’s Disease

Low DJ-1 protein level caused by DJ-1 gene mutation leads to autosomal recessive Parkinson’s disease (PD) due to impaired antioxidative activity. In sporadic PD patients, although mutations were rarely found, lower DJ-1 protein level was also reported. Dysregulation of DJ-1 gene expression might contribute to low DJ-1 protein level. Since the promoter is the most important element to initiate gene expression, whether polymorphisms in the DJ-1 promoter result in the dysregulation of gene expression, thus leading to low protein level and causing PD, is worth exploring. The DJ-1 promoter region was sequenced in a Chinese cohort to evaluate possible links between DJ-1 promoter polymorphisms, PD risk and clinical phenotypes. Dual-luciferase reporter assay was conducted to evaluate the influence of promoter polymorphisms on DJ-1 transcriptional activity. Related information in an existing genome-wide association studies (GWAS) database were looked up, meta-analysis of the present study and other previous reports was conducted, and expression quantitative trait loci (eQTL) analysis was performed to further explore the association. Three single nucleotide polymorphisms (SNPs) (rs17523802, rs226249, and rs35675666) and one 18 bp deletion (rs200968609) were observed in our cohort. However, there was no significant association between the four detected genetic variations and the risk of PD either in allelic or genotype model, in single-point analysis or haplotype analysis. This was supported by the meta-analysis of this study and previous reports as well as that of GWAS database PDGene. Dual luciferase reporter assay suggested these promoter polymorphisms had no influence on DJ-1 transcriptive activity, which is consistent with the eQTL analysis results using the data from GTEx database. Thus, DJ-1 promoter polymorphisms may play little role in the dysregulation of DJ-1 expression and PD susceptibility in sporadic PD

The impact of different rose bengal formulations on corneal thickness and the efficacy of rose bengal/green light corneal cross-linking in the rabbit eye

PURPOSE:To examine central corneal thickness (CCT) changes during in vivo rose bengal-green light corneal cross-linking (RG-CXL) and compare the CXL efficacy of different rose bengal formulations. METHODS:After epithelium removal, the right eyes of rabbits were immersed in rose bengal solution prepared by different solvents (water, phosphate buffered saline, dextran, and hydroxypropyl methylcellulos [HPMC]) for 2 or 20 minutes, then the rose bengal distribution in the corneal stroma was analyzed by confocal fluorescence detection. During the RG-CXL process, the CCT was measured at seven time points. The left eyes served as the untreated control group. Corneal enzymatic resistance and corneal biomechanics were tested to compare the RG-CXL efficacy. RESULTS:The rose bengal infiltration depths were 120 and 200 µm for the 2- and 20-minute groups, respectively. CCT increased significantly after infiltration, then decreased significantly in the first 200 seconds of irradiation and decreased slowly for the next 400 seconds. The CCT of the 20-minute groups was significantly thicker than that of the 2-minute groups (P < .0001). All RG-CXL treatments improved the corneal enzymatic resistance and corneal biomechanics, with the effects being greater in the 20-minute groups. The inclusion of 1.1% HPMC in the rose bengal formulation helped to maintain CCT during irradiation while not affecting either the infiltration of rose bengal or the efficacy of RG-CXL. CONCLUSIONS:Within the range studied, RG-CXL efficacy increased with infiltration time. The incorporation of a 20-minute infiltration of 0.1% rose bengal-1.1% HPMC into the RG-CXL procedure may further improve the safety of the treatment and its prospects for clinical use

Single Endemic Genotype of Measles Virus Continuously Circulating in China for at Least 16 Years

The incidence of measles in China from 1991 to 2008 was reviewed, and the nucleotide sequences from 1507 measles viruses (MeV) isolated during 1993 to 2008 were phylogenetically analyzed. The results showed that measles epidemics peaked approximately every 3 to 5 years with the range of measles cases detected between 56,850 and 140,048 per year. The Chinese MeV strains represented three genotypes; 1501 H1, 1 H2 and 5 A. Genotype H1 was the predominant genotype throughout China continuously circulating for at least 16 years. Genotype H1 sequences could be divided into two distinct clusters, H1a and H1b. A 4.2% average nucleotide divergence was found between the H1a and H1b clusters, and the nucleotide sequence and predicted amino acid homologies of H1a viruses were 92.3%–100% and 84.7%–100%, H1b were 97.1%–100% and 95.3%–100%, respectively. Viruses from both clusters were distributed throughout China with no apparent geographic restriction and multiple co-circulating lineages were present in many provinces. Cluster H1a and H1b viruses were co-circulating during 1993 to 2005, while no H1b viruses were detected after 2005 and the transmission of that cluster has presumably been interrupted. Analysis of the nucleotide and predicted amino acid changes in the N proteins of H1a and H1b viruses showed no evidence of selective pressure. This study investigated the genotype and cluster distribution of MeV in China over a 16-year period to establish a genetic baseline before MeV elimination in Western Pacific Region (WPR). Continuous and extensive MeV surveillance and the ability to quickly identify imported cases of measles will become more critical as measles elimination goals are achieved in China in the near future. This is the first report that a single endemic genotype of measles virus has been found to be continuously circulating in one country for at least 16 years

Understanding the consequences of leisure sedentary behavior on periodontitis: A two-step, multivariate Mendelian randomization study

Background: The relationship between leisure sedentary behavior (LSB) and periodontitis risk remains unclear in terms of causality and the potential mediating effects of intermediate factors. Materials and methods: Using the aggregate data of several large-scale genetic association studies from participants of European descent, we conducted a univariate, two-step, and multivariate Mendelian random (MR) analysis to infer the overall effect of LSB on periodontitis, and quantified the intermediary proportion of intermediary traits such as smoking. Results: Our findings indicated that per 1-SD increase (1.87 h) in leisure screen time (LST), there was a 23 % increase in the risk of periodontitis. [odds ratios (95 % CI) = 1.23 (1.04–1.44), p = 0.013]. Smoking was found to partially mediate the overall causal effect of LST on periodontitis, with a mediation rate of 20.7 % (95 % CI: 4.9%–35.5 %). Multivariate MR analysis demonstrated that the causal effect of LST on periodontitis was weakened when adjusting for smoking, resulting in an odds ratio of 1.19 (95 % CI: 1.01–1.39, p = 0.049) for each 1 standard deviation increase in exposure. Conclusion: The study provides evidence of a potential causal relationship between LSB characterized by LST and periodontitis, thereby further supporting the notion that reducing LSB is beneficial for health. Furthermore, it confirms the role of smoking as a mediator in this process, suggesting that inhibiting smoking behavior among individuals with long-term LSB may serve as a strategy to mitigate the risk of periodontitis

Water-Use Strategies and Habitat Adaptation of Four Tree Species in Karstic Climax Forest in Maolan

The technique of stable hydrogen and oxygen isotope tracing has become an important means to study the mechanism of water movement due to its high sensitivity and traceability. In this study, four dominant tree species in the karst forest of Maolan, Guizhou Province, were selected, and their water-use strategies and the mechanism of maintenance of tree species diversity were investigated using the stable hydrogen and oxygen isotope tracing technique. The results show that: (1) The regional precipitation varied evidently with the alternation of seasons, i.e., the values of δD and δ18O in precipitation had a positive bias in spring and a negative bias in summer and autumn. The value of deuterium excess (d-excess) was between 11.67‰ and 31.02‰, with a mean value of 22.98‰. (2) The soil temperature (ST), soil water content (SWC) and precipitation, which have a significant positive correlation, imposed a joint impact on the dynamics of the soil evaporative fractionation. (3) The line-conditioned excess (LC-excess) varied seasonally in different water bodies, i.e., the relative evaporative fractionation of the rhizosphere soil of deciduous tree species was stronger than that of evergreen tree species, and the evaporative fractionation of hydrogen and oxygen isotopes in the leaf water of evergreen tree species was stronger than that of deciduous tree species in spring and summer. However, that of the latter was stronger than that of the former in autumn. (4) The soil water was the most important potential water source for dominant tree species in karst terrain (71%), followed by epikarstic water, which made up an effective supplement (29%). (5) Finally, trees of different life forms and species varied in capacity and proportion in terms of using the potential water sources in different seasons, i.e., deciduous tree species had a greater capacity for using water from potential sources and variable water-use strategies. This may be a major water-limiting mechanism that maintains photosynthesis in the leaves of evergreen tree species (leaves are evergreen and plants continue to grow via photosynthesis) and constrains photosynthesis in deciduous tree species (leaves fall and plants become dormant and stop growing). These results lead to the conclusion that the dominant tree species in karstic forests resist water stress and adjust water-use strategies towards each potential water source to adapt to the harsh karstic habitat through root plasticity and leaf defoliation

Amplified Hormonal Counterregulatory Responses to Hypoglycemia in Rats After Systemic Delivery of a SUR-1-Selective K+ Channel Opener?

OBJECTIVE— In glucose-sensing neurons, ATP-sensitive K+ channels (KATP channels) are thought to translate metabolic signals into an alteration in neuronal firing rates. Because these neurons express the Kir6.2/SUR-1 isoform of the KATP channel, we sought to examine the therapeutic potential of the SUR-1–selective potassium channel opener (KCO), NN414, to amplify counterregulatory response to hypoglycemia