Cathepsins and Parkinson’s disease: insights from Mendelian randomization analyses

BackgroundParkinson’s disease (PD), the second most prevalent neurodegenerative condition, has a multifaceted etiology. Cathepsin-cysteine proteases situated within lysosomes participate in a range of physiological and pathological processes, including the degradation of harmful proteins. Prior research has pointed towards a potential link between cathepsins and PD; however, the precise causal relationship between the cathepsin family and PD remains unclear.MethodsThis study employed univariate and multivariate Mendelian randomization (MR) analyses to explore the causal relationship between the nine cathepsins and Parkinson’s disease (PD) risk. For the primary analysis, genome-wide association study (GWAS) summary statistics for the plasma levels of the nine cathepsins and PD was obtained from the INTERVAL study and the International Parkinson’s Disease Genomics Consortium. GWAS for PD replication analysis were obtained from the FinnGen consortium, and a meta-analysis was performed for the primary and replication analyses to evaluate the association between genetically predicted cathepsin plasma levels and PD risk. After identifying significant MR estimates, genetic co-localization analyses were conducted to determine whether shared or distinct causal variants influenced both cathepsins and PD.ResultsElevated cathepsin B levels were associated with a decreased risk of PD in univariate MR analysis (odds ratio [OR] = 0.890, 95% confidence interval [CI]: 0.831–0.954, pFDR = 0.009). However, there was no indication that PD affected cathepsin B levels (OR = 0.965, 95% CI: 0.858–1.087, p = 0.852). In addition, after adjusting for the remaining cathepsins, cathepsin B levels independently and significantly contributed to the reduced risk of PD in multivariate MR analysis (OR = 0.887, 95% CI: 0.823–0.957, p = 0.002). The results of the replication MR analysis with the FinnGen GWAS for PD (OR = 0.921, 95% CI: 0.860–0.987, p = 0.020) and meta-analysis (OR = 0.905, 95% CI: 0.862–0.951, p < 0.001) were consistent with those of the primary analysis. Colocalization analysis did not provide any evidence of a shared causal variant between cathepsins and PD (PP.H4.abf = 0.005).ConclusionThis genetic investigation supports the hypothesis that cathepsin B exerts a protective effect against PD. The quantification of cathepsin B levels could potentially serve as a predictive biomarker for susceptibility to PD, providing new insights into the pathomechanisms of the disease and possible interventions

Exploration of the impact of demographic changes on life insurance consumption: empirical analysis based on Shanghai Cooperation Organization

Based on the panel data of eight member states of Shanghai Cooperation Organization (SCO) from 1996 to 2019, this study explores the impact of demographic changes on life insurance consumption in SCO member countries under the framework of static panel model and dynamic panel model. And the study analyzes the heterogeneity of religious division and different aging degrees. The empirical results show that both old-age dependency ratio and teenager dependency ratio have positive impacts on life insurance consumption in the SCO countries. Besides, the current consumption of ordinary life insurance significantly stimulates the future consumption of ordinary life insurance. Furthermore, demographic changes have heterogeneous impacts on life insurance consumption in terms of different religions and different degrees of aging. Our findings provide managerial implications for insurance companies that carry out life insurance business in SCO member states. Insurance companies should consider the policyholders’ life insurance consumption in accordance with demographic changes of both old-age dependency ratio and teenager dependency ratio, and also take differentiated life insurance sales strategies according to different degrees of aging and whether the residents believe in Islam

PHOTOMETRIC OBSERVATION OF 3024 HAINAN, 3920 AUBIGNAN, AND 5951 ALICEMONET

Three minor planets were measured photometrically between 2012 September 4 and 21 using the SARA (Southeastern Association for Research in Astronomy) South telescope, located in Cerro Tololo Inter-American Observatory. The following synodic periods were found: 3024 Hainan, P = 11.785 ± 0.005 h; 3920 Aubignan, P = 4.4762 ± 0.0005 h; and 5951 Alicemonet, P = 3.8871 ± 0.0005 h

Prevalent Exon-Intron Structural Changes in the APETALA1/FRUITFULL, SEPALLATA, AGAMOUS-LIKE6, and FLOWERING LOCUS C MADS-Box Gene Subfamilies Provide New Insights into Their Evolution

AP1/FUL, SEP, AGL6, and FLC subfamily genes play important roles in flower development. The phylogenetic relationships among them, however, have been controversial, which impedes our understanding of the origin and functional divergence of these genes. One possible reason for the controversy may be the problems caused by changes in the exon-intron structure of genes, which, according to recent studies, may generate non-homologous sites and hamper the homology-based sequence alignment. In this study, we first performed exon-by-exon alignments of these and three outgroup subfamilies (SOC1, AG, and STK). Phylogenetic trees reconstructed based on these matrices show improved resolution and better congruence with species phylogeny. In the context of these phylogenies, we traced evolutionary changes of exon-intron structures in each subfamily. We found that structural changes have occurred frequently following gene duplication and speciation events. Notably, exons 7 and 8 (if present) suffered more structural changes than others. With the knowledge of exon-intron structural changes, we generated more reasonable alignments containing all the focal subfamilies. The resulting trees showed that the SEP subfamily is sister to the monophyletic group formed by AP1/FUL and FLC subfamily genes and that the AGL6 subfamily forms a sister group to the three abovementioned subfamilies. Based on this topology, we inferred the evolutionary history of exon-intron structural changes among different subfamilies. Particularly, we found that the eighth exon originated before the divergence of AP1/FUL, FLC, SEP, and AGL6 subfamilies and degenerated in the ancestral FLC-like gene. These results provide new insights into the origin and evolution of the AP1/FUL, FLC, SEP, and AGL6 subfamilies

Protective effect of grifolin against brain injury in an acute cerebral ischemia rat model

Purpose: To evaluate the protective effects of grifolin against brain injury in an acute cerebral ischemia rat model.Methods: Rats were assigned to five groups: control, negative control, and grifolin (50, 100, and 200 mg/kg, p.o.) treated groups, which received the drug for 2 weeks. All the animals were sacrificed at the end of the protocol, and tissue homogenates were prepared from isolated brain tissue. Glutathione peroxidase (GPX), superoxide dismutase (SOD), malondialdehyde (MDA), and nitric oxide (NO), as oxidative stress indicators, were determined for the tissue homogenates of the ischemic rats. Inflammatory mediators (cytokines and nuclear factor kappa B p65, NF κB), DNA damage, and ATP and caspase 3 levels in the tissue homogenates were also assessed.Results: Treatment with grifolin increased SOD and GPX significantly and decreased MDA and NO levels in tissue homogenates of the cerebral ischemic rats compared with those in the negative control group (p < 0.05). Treatment with grifolin also attenuated the altered levels of inflammatory mediators (cytokines and NF-κB), caspase 3, and ATP levels in the tissue homogenate of cerebral ischemic rats (p < 0.05). The results of comet assay on the tissue homogenate suggest that treatment with grifolin reduced or prevented damage.Conclusions: The results show that treatment with grifolin protects against neuronal damage in acute cerebral ischemic rats via its anti-inflammatory and anti-oxidant properties.Keywords: Neuroprotection, Cerebral ischemia, Brain injury, DNA, Grifolin, Anti oxidan

PHOTOMETRIC OBSERVATIONS OF 782 MONTEFIORE, 3842 HARLANSMITH, 5542 MOFFATT, 6720 GIFU, AND (19979) 1989 VJ

Five solar system minor planets were measured photometrically between 2012 October and December using the SARA (Southeastern Association for Research in Astronomy) telescopes located in Kitt Peak National Observatory in USA and Cerro Tololo Inter-American Observatory in Chile. The following synodic periods were found: 782 Montefiore P = 4.0728 ± 0.0006 h; 3842 Harlansmith, P = 2.7938 ± 0.0005 h; 5542 Moffatt P = 5.187 ± 0.001 h; 6720 Gifu, P = 4.231 ± 0.001 h; and (19979) 1989 VJ, P = 7.568 ± 0.005 h

Diurnal humidity cycle driven selective ion transport across clustered polycation membrane

The ability to manipulate the flux of ions across membranes is a key aspect of diverse sectors including water desalination, blood ion monitoring, purification, electrochemical energy conversion and storage. Here we illustrate the potential of using daily changes in environmental humidity as a continuous driving force for generating selective ion flux. Specifically, self-assembled membranes featuring channels composed of polycation clusters are sandwiched between two layers of ionic liquids. One ionic liquid layer is kept isolated from the ambient air, whereas the other is exposed directly to the environment. When in contact with ambient air, the device showcases its capacity to spontaneously produce ion current, with promising power density. This result stems from the moisture content difference of ionic liquid layers across the membrane caused by the ongoing process of moisture absorption/desorption, which instigates selective transmembrane ion flux. Cation flux across the polycation clusters is greatly inhibited because of intensified charge repulsion. However, anions transport across polycation clusters is amplified. Our research underscores the potential of daily cycling humidity as a reliable energy source to trigger ion current and convert it into electrical current

Metal-Enriched Outflows in the Ultra-Luminous infrared Quasar Q1321+058

Quasar outflows may play important role in the evolution of its host galaxy and central black hole. In this paper, we present a detailed study of multiple outflows in the obscured ultra-luminous infrared quasar Q1321+058. The outflows reveal themselves in the complex optical and UV emission line spectrum, with a broad component blueshifted by 1650 km/s and a narrow component by 360 km/s, respectively.The higher velocity component shows ever strong N III] and strong Si III], in addition to strong [O III]5007 and [Ne III]3869 emission lines, suggesting an overabundance of N and Si relative to C. The abundance pattern is consistent a fast chemical enriching process associated with a recent starburst. The outflow extends to several tens to hundred parsecs from the quasar, and covers only a very small sky. We find that the outflow with line emitting gas is energetically insufficient to remove the ISM of the host galaxy. The velocity range and the column density suggest that the outflow might be part of the low ionization broad absorption line region as seen in a small class of quasars. The optical and UV continuum is starlight-dominated and can be modelled with a young-aged (1 Myr) plus an intermediate-aged (~0.5-1 Gyr) stellar populations, suggesting a fast building of the stellar mass in the host galaxy, consistent with the starburst-type metal abundances inferred from the high velocity outflow spectrum. The broad band spectral energy distribution shows that it is an obscured quasar with its bulk emission in the middle infrared. The star formation rate, independently estimated from UV, far-infrared, and emission line luminosity, is much lower than that is required for the co-evolution of the black hole and its host spheroid.Comment: 31 pages, accepted to Ap