Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.Peer reviewe

Local Resistance in Early Medieval Chinese Historiography and the Problem of Religious Overinterpretation

Official Chinese historiography is a treasure trove of information on local resistance to the centralised empire in early medieval China (third to sixth century). Sinologists specialised in the study of Chinese religions commonly reconstruct the religious history of the era by interpreting some of these data. In the process, however, the primary purpose of the historiography of local resistance is often overlooked, and historical interpretation easily becomes ‘overinterpretation’—that is, ‘fabricating false intensity’ and ‘seeing intensity everywhere’, as French historian Paul Veyne proposed to define the term. Focusing on a cluster of historical anecdotes collected in the standard histories of the four centuries under consideration, this study discusses the supposedly ‘religious’ nature of some of the data they contain

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.</p

Consensus of discrete-time multi-agent systems with nonlinear local rules and time-varying delays,

Abstract-In a multi-agent system (MAS), the agents are often considered to be autonomous entities, such as robots or software programs, each under the influence of a local rule, representing its interaction with other agents. Over the past few years, most research in the study of discrete-time MAS&apos;s concentrates on linear local rules. However, local interactions between agents are more likely to be governed by nonlinear rules with time-varying delays. This paper investigates the consensus of discrete-time MAS&apos;s with nonlinear local rules and time-varying delays. Based on a representative model, we obtain some basic criteria for the consensus of such MAS&apos;s. These results cover several existing results as special cases. Moreover, the above criteria are applied to the consensus of the classical Vicsek model with time-varying delays. Simulation results are presented to validate the obtained criteria

Acute Exposure to Key Aquaculture Environmental Stressors Impaired the Aerobic Metabolism of Carassius auratus gibelio

Carassius auratus gibelio is an omnivore favored for its flavor and is commonly used as a benthic species in traditional pond polyculture. This study investigated the effects of common aquaculture stressors, such as high ammonia, high nitrite, high pH, and hypoxia on the aerobic metabolism of C. auratus gibelio. The results showed that the standard metabolic rate (SMR) was positively correlated with ammonia, nitrite, and pH, while the maximum metabolic rate (MMR) was negatively correlated with all four stressors. Thus, aerobic scope (AS) was reduced when C. auratus gibelio was exposed to high ammonia, high nitrite, high pH, and hypoxia. The peak of post-prandial O2 consumption was positively correlated with nitrite, pH, and the occurrence of the peak metabolic rate post-prandial was delayed in high ammonia, high nitrite, hypoxia, and high pH conditions. These findings indicated that, in experimental conditions, exposure to these environmental stressors can influence aerobic metabolism in C. auratus gibelio. With more energy required to maintain standard metabolic rates, less will be available for growth. While the C. auratus gibelio is one of the most hypoxia tolerance species, the reduction we observed in AS caused by stressors that commonly occur in ponds and in nature will likely affect growth in ponds and fitness in nature. These data have provided insight into the optimal, fitness-maximizing thresholds for these common stressors in this species of interest

Screening Effective Antifungal Substances from the Bark and Leaves of Zanthoxylum avicennae by the Bioactivity-Guided Isolation Method

To find good antifungal substances by the bioactivity-guided isolation method, we tracked down the effective antifungal substances in the bark and leaves of Zanthoxylum avicennae, and isolated three antifungal compounds 1, 2, and 3. The structures were identified as xanthyletin, luvangetin, and avicennin by 1H-NMR, 13C-NMR, and HRMS spectra. Particularly, compound 2 had several isomers, and the 1H-NMR spectra of 2 in different solvents showed a significant difference. To determine the stereo structure of 2, a single crystal was prepared and identified by X-ray diffraction as Luvangetin. Moreover, the difference of 1H-NMR data of 2 between in solvent dimethyl sulfoxide-d6 (DMSO-d6) and deuterated chloroform (CDCl3), and other reported isomers were discussed for the first time. The bioassay results indicated that the three compounds 1, 2, and 3 displayed low to high antifungal activities against tested phytopathogenic fungi. In particular, all compounds 1, 2, and 3 showed excellent antifungal activities against Pyricularia oryzae and Z. avicennae, with the values of half maximal effective concentration (EC50) ranging from 31 to 61 mg/L, and compound 3 was also identified as a more potent inhibitor against Fusaium graminearum (EC50 = 43.26 &plusmn; 1.76 mg/L) compared with fungicide PCA (phenazine-1-carboxylic acid) (EC50 = 52.34 &plusmn; 1.53 mg/L). The results revealed that compounds 1, 2, and 3 were the main antifungal substances of Z. avicennae, and can be used as lead compounds of a fungicide, which has good development value and prospect

A marine teleost, Opsanus beta, compensates acidosis in hypersaline water by H.sup.+ excretion or reduced HCO.sub.3.sup.- excretion rather than HCO.sub.3.sup.- uptake

Keywords: H.sup.+ excretion; H.sup.+-ATPase; Osmoregulation; Metabolic acidosis; Hypersaline water Increases in ambient salinity demand parallel increases in intestinal base secretion for maintenance of osmoregulatory status, which is likely the cause of a transient acidosis following transfer of euryhaline fish from freshwater to seawater. It was predicted that transfer of the marine Gulf toadfish (Opsanus beta) from seawater (35 ppt) to hypersaline (60 ppt) seawater (HSW) would lead to a transient acidosis that would be compensated by increases in branchial acid excretion to offset the acid--base disturbance. Toadfish exposed to HSW showed a significant decrease in blood pH and [HCO.sub.3.sup.-] but no increase in pCO.sub.2, followed by a full recovery after 48--96 h. A similar metabolic acidosis and recovery was found when fish were exposed to 60-ppt HCO.sub.3.sup.--free seawater (HEPES-buffered), which may suggest that compensation for intestinal base loss during hypersaline treatment is from gill H.sup.+ excretion rather than gill HCO.sub.3.sup.- uptake. However, we cannot rule out that reduced branchial HCO.sub.3.sup.- excretion contributed to an increase in net acid excretion. Since colchicine prevents full compensation, translocation of H.sup.+ and/or HCO.sub.3.sup.- transporters between cytosolic compartments and plasma membrane fractions might be involved in compensating for the hypersalinity-induced acidosis. Translocation of transporters rather than de novo synthesis may represent a faster and less energetically demanding response to rapidly fluctuating and high salinities encountered by toadfish in their natural environment. Author Affiliation: (1) Sino-US joint laboratory of Aquatic Animal Physiology, East China Sea Fisheries Research Institute, Chinese Academy of Fisheries Sciences, Shanghai, China (2) Department of Marine Biology and Ecology, Rosenstiel School of Marine and Atmospheric Science, University of Miami, Miami, FL, USA (3) Department of Biological Sciences, University of North Texas, Denton, TX, USA (4) Cardiovascular Sciences, School of Medical Sciences, The University of Manchester, Manchester, UK (a) [email protected] Article History: Registration Date: 09/30/2020 Received Date: 02/10/2020 Accepted Date: 09/29/2020 Online Date: 10/17/2020 Byline:Academi

Design, Synthesis, Phloem Mobility, and Bioactivities of a Series of Phenazine-1-Carboxylic Acid-Amino Acid Conjugates

Developing fungicides with phloem mobility that can be applied to leaves to control root or vascular pathogens has long been desirable. To achieve this goal, an efficient and economical strategy involves introducing an amino acid into the existing highly active parent pesticide molecule. Hence, 12 L-phenazine-1-carboxylic acid (PCA)-amino acid conjugates 4a&ndash;l were designed and synthesized via a simple synthetic route. In vitro bioassays results showed that all synthesized compounds 4a&ndash;l exhibited certain fungicidal activities against six tested fungi. Compound 4c exhibited relatively good fungicidal activity against Rhizoctonia solani, and the EC50 value was 0.084 &plusmn; 0.006 mmol/L. The phloem mobility experiments revealed that introducing an amino acid to PCA could effectively endow PCA with phloem mobility in R. communis L. Among them, nine conjugates were found in phloem sap, and L-PCA-Valine 4d exhibited the highest phloem mobility. Analysis results from the prediction of the Kleier model indicated that an active carrier-mediated mechanism may be involved in L-PCA-amino acid conjugates&mdash;a result that needs to be confirmed and complemented with further tests. The current research provides useful data for modifying non-phloem-mobile fungicidal molecules to phloem-mobile types

Design, synthesis and biological activity of hydroxybenzoic acid ester conjugates of phenazine-1-carboxylic acid

Abstract We prepared 16 novel hydroxybenzoic acid ester conjugates of phenazine-1-carboxylic acid (PCA) and investigated their biological activity. Most of the synthesized conjugates displayed some level of fungicidal activities in vitro against five phytopathogenic fungi. Nine conjugates 5b, 5c, 5d, 5e, 5h, 5i, 5m, 5n and 5o (EC50 between 3.2 μg/mL and 14.1 μg/mL) were more active than PCA (EC50 18.6 μg/mL) against Rhizoctonia solani. Especially conjugate 5c showed the higher fungicidal activity against Rhizoctonia solani which is 6.5-fold than PCA. And the results of the bioassay indicated that the fungicidal activity of conjugates was associated with their LogP, and the optimal LogP values of the more potent fungicidal activities within these conjugates ranged from 4.42 to 5.08. The systemic acquired resistance induced by PCA–SA ester conjugate 5c against rice sheath blight disease in rice seedlings was evaluated. The results revealed that PCA–SA ester conjugate 5c retained the resistance induction activity of SA against rice sheath blight