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The effect of centrally administered norepinephrine (NE) into the lateral ventricle on choline acetylase activity (ChAc), endogenous levels of NE, dopamine (DA) and serotonin (5HT) was studied in different regions of the rat brain. In normal rats, the highest activity of choline acetylase was found in the cerebral cortex, followed by the brain stem, the diencephalon, the hypothalamus and least in the cerebellum. Chronic administration of NE significantly increased the choline acetylase activity in all regions studied, whereas both the acute and the in vitro studies showed no significant change except in the brain stem. Serotonin level was increased in the cerebellum, but decreased in the diencephalon and the brain stem. There was no significant alteration in the level of NE in all areas studied except in the hypothalamus where there was an increase in the mean concentration. Tissue level of DA showed a significant increase in the cerebral cortex and the hypothalamus. Behaviourally, there was a significant increase in food intake on the first day of treatment with no significant change in water intake. The data suggests that NE may be involved in the regulation of acetylcholine synthesis. The significance of interaction between different monoamines and acetylcholine may be important in the study of drug tolerance phenomena. [ABSTRACT FROM AUTHOR]

In genomic-scale data sets, loci are closely packed within chromosomes and hence provide correlated information. Averaging across loci as if they were independent creates pseudoreplication, which reduces the effective degrees of freedom (df') compared to the nominal degrees of freedom, df. This issue has been known for some time, but consequences have not been systematically quantified across the entire genome. Here, we measured pseudoreplication (quantified by the ratio df'/df) for a common metric of genetic differentiation (F ST ) and a common measure of linkage disequilibrium between pairs of loci (r 2 ). Based on data simulated using models (SLiM and msprime) that allow efficient forward-in-time and coalescent simulations while precisely controlling population pedigrees, we estimated df' and df'/df by measuring the rate of decline in the variance of mean F ST and mean r 2 as more loci were used. For both indices, df' increases with N e and genome size, as expected. However, even for large N e and large genomes, df' for mean r 2 plateaus after a few thousand loci, and a variance components analysis indicates that the limiting factor is uncertainty associated with sampling individuals rather than genes. Pseudoreplication is less extreme for F ST , but df'/df ≤0.01 can occur in data sets using tens of thousands of loci. Commonly-used block-jackknife methods consistently overestimated var (F ST ), producing very conservative confidence intervals. Predicting df' based on our modelling results as a function of N e , L, S, and genome size provides a robust way to quantify precision associated with genomic-scale data sets., (© 2021 John Wiley & Sons Ltd. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Harmine is a β-carboline alkaloid isolated from Banisteria caapi and Peganum harmala L with various pharmacological activities, including antioxidant, anti-inflammatory, antitumor, anti-depressant, and anti-leishmanial capabilities. Nevertheless, the pharmacological effect of harmine on cardiomyocytes and heart muscle has not been reported. Here we found a protective effect of harmine on cardiac hypertrophy in spontaneously hypertensive rats in vivo. Further, harmine could inhibit the phenotypes of norepinephrine-induced hypertrophy in human embryonic stem cell-derived cardiomyocytes in vitro. It reduced the enlarged cell surface area, reversed the increased calcium handling and contractility, and downregulated expression of hypertrophy-related genes in norepinephrine-induced hypertrophy of human cardiomyocytes derived from embryonic stem cells. We further showed that one of the potential underlying mechanism by which harmine alleviates cardiac hypertrophy relied on inhibition of NF-κB phosphorylation and the stimulated inflammatory cytokines in pathological ventricular remodeling. Our data suggest that harmine is a promising therapeutic agent for cardiac hypertrophy independent of blood pressure modulation and could be a promising addition of current medications for cardiac hypertrophy., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Linkage disequilibrium (LD) across the genome provides information to identify the genes and variations related to quantitative traits in genome-wide association studies (GWAS) and for the implementation of genomic selection (GS). LD can also be used to evaluate genetic diversity and population structure and reveal genomic regions affected by selection. LD structure and Ne were assessed in a set of 83 water buffaloes, comprising Azeri (AZI), Khuzestani (KHU), and Mazandarani (MAZ) breeds from Iran, Kundi (KUN) and Nili-Ravi (NIL) from Pakistan, Anatolian (ANA) buffalo from Turkey, and buffalo from Egypt (EGY). The values of corrected r 2 (defined as the correlation between two loci) of adjacent SNPs for three pooled Iranian breeds (IRI), ANA, EGY, and two pooled Pakistani breeds (PAK) populations were 0.24, 0.28, 0.27, and 0.22, respectively. The corrected r values for adjacent SNPs in unrelated samples indicated that the Affymetrix Axiom 90 K SNP genomic array was suitable for GWAS and GS in these populations. The persistency of LD phase (PLDP) between populations was assessed, and results showed that PLPD values between the populations were more than 0.9 for distances of less than 100 Kb. The Ne in the recent generations has declined to the extent that breeding plans are urgently required to ensure that these buffalo populations are not at risk of being lost. We found that results are affected by sample size, which could be partially corrected for; however, additional data should be obtained to be confident of the results.2 between SNPs decreased with increasing physical distance from 100 Kb to 1 Mb. The LD values for IRI, ANA, EGY, and PAK populations were 0.16, 0.23, 0.24, and 0.21 for less than 100Kb, respectively, which reduced rapidly to 0.018, 0.042, 0.059, and 0.024, for a distance of 1 Mb. In all the populations, the decay rate was low for distances greater than 2Mb, up to the longest studied distance (15 Mb). The r 2 values for adjacent SNPs in unrelated samples indicated that the Affymetrix Axiom 90 K SNP genomic array was suitable for GWAS and GS in these populations. The persistency of LD phase (PLDP) between populations was assessed, and results showed that PLPD values between the populations were more than 0.9 for distances of less than 100 Kb. The Ne in the recent generations has declined to the extent that breeding plans are urgently required to ensure that these buffalo populations are not at risk of being lost. We found that results are affected by sample size, which could be partially corrected for; however, additional data should be obtained to be confident of the results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rahimmadar, Ghaffari, Mokhber and Williams.)