Original Article

Objective: Glucagon is well known to regulate blood glucose but may be equally important for amino acid metabolism. Plasma levels of amino acids are regulated by glucagon-dependent mechanism(s), while amino acids stimulate glucagon secretion from alpha cells, completing the recently described liver-alpha cell axis. The mechanisms underlying the cycle and the possible impact of hepatic steatosis are unclear. Methods: We assessed amino acid clearance in vivo in mice treated with a glucagon receptor antagonist (GRA), transgenic mice with 95% reduction in alpha cells, and mice with hepatic steatosis. In addition, we evaluated urea formation in primary hepatocytes from ob/ob mice and humans, and we studied acute metabolic effects of glucagon in perfused rat livers. We also performed RNA sequencing on livers from glucagon receptor knock-out mice and mice with hepatic steatosis. Finally, we measured individual plasma amino acids and glucagon in healthy controls and in two independent cohorts of patients with biopsy-verified non-alcoholic fatty liver disease (NAFLD). Results: Amino acid clearance was reduced in mice treated with GRA and mice lacking endogenous glucagon (loss of alpha cells) concomitantly with reduced production of urea. Glucagon administration markedly changed the secretion of rat liver metabolites and within minutes increased urea formation in mice, in perfused rat liver, and in primary human hepatocytes. Transcriptomic analyses revealed that three genes responsible for amino acid catabolism (Cps1, Slc7a2, and Slc38a2) were downregulated both in mice with hepatic steatosis and in mice with deletion of the glucagon receptor. Cultured ob/ob hepatocytes produced less urea upon stimulation with mixed amino acids, and amino acid clearance was lower in mice with hepatic steatosis. Glucagon-induced ureagenesis was impaired in perfused rat livers with hepatic steatosis. Patients with NAFLD had hyperglucagonemia and increased levels of glucagonotropic amino acids, including alanine in particular. Both glucagon and alanine levels were reduced after diet-induced reduction in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR, a marker of hepatic steatosis). Conclusions: Glucagon regulates amino acid metabolism both non-transcriptionally and transcriptionally. Hepatic steatosis may impair glucagon-dependent enhancement of amino acid catabolism. (C) 2020 The Author(s). Published by Elsevier GmbH

The geography of recent genetic ancestry across Europe

The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (the POPRES dataset) to conduct one of the first surveys of recent genealogical ancestry over the past three thousand years at a continental scale. We detected 1.9 million shared genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 10-50 genetic common ancestors from the last 1500 years, and upwards of 500 genetic ancestors from the previous 1000 years. These numbers drop off exponentially with geographic distance, but since genetic ancestry is rare, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1000 years. There is substantial regional variation in the number of shared genetic ancestors: especially high numbers of common ancestors between many eastern populations likely date to the Slavic and/or Hunnic expansions, while much lower levels of common ancestry in the Italian and Iberian peninsulas may indicate weaker demographic effects of Germanic expansions into these areas and/or more stably structured populations. Recent shared ancestry in modern Europeans is ubiquitous, and clearly shows the impact of both small-scale migration and large historical events. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world.Comment: Full size figures available from http://www.eve.ucdavis.edu/~plralph/research.html; or html version at http://ralphlab.usc.edu/ibd/ibd-paper/ibd-writeup.xhtm

Automating the Communication of Cybersecurity Knowledge: Multi-Case Study

Cybersecurity is essential for the protection of companies against cyber threats. Traditionally, cybersecurity experts assess and improve a company's capabilities. However, many small and medium-sized businesses (SMBs) consider such services not to be affordable. We explore an alternative do-it-yourself (DIY) approach to bringing cybersecurity to SMBs. Our method and tool, CYSEC, implements the Self-Determination Theory (SDT) to guide and motivate SMBs to adopt good cybersecurity practices. CYSEC uses assessment questions and recommendations to communicate cybersecurity knowledge to the end-user SMBs and encourage self-motivated change. In this paper, the operationalisation of SDT in CYSEC is presented and the results of a multi-case study shown that offer insight into how SMBs adopted cybersecurity practices with CYSEC. Effective automated cybersecurity communication depended on the SMB's hands-on skills, tools adaptedness, and the users' willingness to documenting confidential information. The SMBs wanted to learn in simple, incremental steps, allowing them to understand what they do. An SMB's motivation to improve security depended on the fitness of assessment questions and recommendations with the SMB's business model and IT infrastructure. The results of this study indicate that automated counselling can help many SMBs in security adoption. The final publication is available at Springer via https://link.springer.com/chapter/10.1007%2F978-3-030-59291-2_8Comment: 14 pages, 1 figure, 13th World Conference on Information Security Educatio

First 10 Months of TGF Observations by ASIM

The Atmosphere‐Space Interactions Monitor (ASIM) was launched to the International Space Station on 2 April 2018. The ASIM payload consists of two main instruments, the Modular X‐ray and Gamma‐ray Sensor (MXGS) for imaging and spectral analysis of Terrestrial Gamma‐ray Flashes (TGFs) and the Modular Multi‐spectral Imaging Array for detection, imaging, and spectral analysis of Transient Luminous Events and lightning. ASIM is the first space mission designed for simultaneous observations of Transient Luminous Events, TGFs, and optical lightning. During the first 10 months of operation (2 June 2018 to 1 April 2019) the MXGS has observed 217 TGFs. In this paper we report several unprecedented measurements and new scientific results obtained by ASIM during this period: (1) simultaneous TGF observations by Fermi Gamma‐ray Burst Monitor and ASIM MXGS revealing the very good detection capability of ASIM MXGS and showing substructures in the TGF, (2) TGFs and Elves produced during the same lightning flash and even simultaneously have been observed, (3) first imaging of TGFs giving a unique source location, (4) strong statistical support for TGFs being produced during the upward propagation of a leader just before a large current pulse heats up the channel and emits a strong optical pulse, and (5) the t 50 duration of TGFs observed from space is shorter than previously reported.publishedVersio

RNA interference in Lepidoptera: an overview of successful and unsuccessful studies and implications for experimental design

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