Regulation of the promoter region of the human adiponutrin/PNPLA3 gene by glucose and insulin

Previous biochemical, cardiovascular and behavioral work has given evidence for the existence of antagonistic galanin receptor-5-HT1A receptor interactions in the brain. In this study we investigated the existence of GalR1-5-HT1A receptor heteromers and their functional characteristics. In mammalian cells transfected with GFP2-tagged 5-HT1A receptor and YFP-tagged GalR1 receptor, a proximity-based fluorescence resonance energy transfer technique was used and it has been demonstrated that GalR1-5-HT1A receptors heteromerize. Furthermore, signaling by either the mitogen-activated protein kinase (MAPK) or adenylyl cyclase (AC) pathways by these heteromers indicates a trans-inhibition phenomenon through their interacting interface via allosteric mechanisms that block the development of an excessive activation of G_i/o and an exaggerated inhibition of AC or stimulation of MAPK activity. The presence of these heteromers in the discrete brain regions is postulated based on the existence of GalR-5-HT1A receptor-receptor interactions previously described in the brain and gives rise to explore possible novel therapeutic strategies for treatment of depression by targeting the GalR1-5-HT1A heteromers.     

The ESX-4 substrates,EsxU and EsxT,modulate Mycobacterium abscessus fitness

ESX type VII secretion systems are complex secretion machineries spanning across the mycobacterial membrane and play an important role in pathogenicity, nutrient uptake and conjugation. We previously reported the role of ESX-4 in modulating Mycobacterium abscessus intracellular survival. The loss of EccB4 was associated with limited secretion of two effector proteins belonging to the WXG-100 family, EsxU and EsxT, and encoded by the esx-4 locus. This prompted us to investigate the function of M. abscessus EsxU and EsxT in vitro and in vivo. Herein, we show that EsxU and EsxT are substrates of ESX-4 and form a stable 1:1 heterodimer that permeabilizes artificial membranes. While expression of esxU and esxT was up-regulated in M. abscessus-infected macrophages, their absence in an esxUT deletion mutant prevented phagosomal membrane disruption while maintaining M. abscessus in an unacidified phagosome. Unexpectedly, the esxUT deletion was associated with a hyper-virulent phenotype, characterised by increased bacterial loads and mortality in mouse and zebrafish infection models. Collectively, these results demonstrate that the presence of EsxU and EsxT dampens survival and persistence of M. abscessus during infection.     

Ten simple rules to host an inclusive conference

Conferences are spaces to meet and network within and across academic and technical fields, learn about new advances, and share our work. They can help define career paths and create long-lasting collaborations and opportunities. However, these opportunities are not equal for all. This article introduces 10 simple rules to host an inclusive conference based on the authors’ recent experience organizing the 2021 edition of the useR! statistical computing conference, which attracted a broad range of participants from academia, industry, government, and the nonprofit sector. Coming from different backgrounds, career stages, and even continents, we embraced the challenge of organizing a high-quality virtual conference in the context of the Coronavirus Disease 2019 (COVID-19) pandemic and making it a kind, inclusive, and accessible experience for as many people as possible. The rules result from our lessons learned before, during, and after the organization of the conference. They have been written mainly for potential organizers and selection committees of conferences and contain multiple practical tips to help a variety of events become more accessible and inclusive. We see this as a starting point for conversations and efforts towards building more inclusive conferences across the world. * Translated versions of the English abstract and the list of rules are available in 10 languages in S1 Text: Arabic, French, German, Italian, Japanese, Korean, Portuguese, Spanish, Tamil, and Thai.     

New data and collaborations at the Saccharomyces Genome Database: updated reference genome,alleles, and the Alliance of Genome Resources

Saccharomyces cerevisiae is used to provide fundamental understanding of eukaryotic genetics, gene product function, and cellular biological processes. Saccharomyces Genome Database (SGD) has been supporting the yeast research community since 1993, serving as its de facto hub. Over the years, SGD has maintained the genetic nomenclature, chromosome maps, and functional annotation, and developed various tools and methods for analysis and curation of a variety of emerging data types. More recently, SGD and six other model organism focused knowledgebases have come together to create the Alliance of Genome Resources to develop sustainable genome information resources that promote and support the use of various model organisms to understand the genetic and genomic bases of human biology and disease. Here we describe recent activities at SGD, including the latest reference genome annotation update, the development of a curation system for mutant alleles, and new pages addressing homology across model organisms as well as the use of yeast to study human disease.     

Hyperthermia in radiofrequency-exposed rhesus monkeys: a comparison of frequency and orientation effects

To compare the effects of exposure to a near-resonant frequency of microwaves at two orientations with a higher frequency exposure, five rhesus monkeys were exposed for 4 hr to 225 MHz, electric field oriented parallel to the long axis of the body (225 MHz-E), and to 225 MHz, magnetic field orientation (225 MHz-H), or to 1290 MHz, electric field orientation. On a separate occasion, the monkeys were exposed at night to 225 MHz-E. Exposures were conducted with the animal chair restrained in an anechoic chamber with rectal temperature continuously monitored. Blood samples were taken hourly during the 225-MHz-E exposures for cortisol analysis. The power densities used were 0, 1.2, 2.5, 5.0, 7.5, 10.0, and 15.0 mW/cm2 for 225 MHz-E (day), 0 and 5 mW/cm2 (225 MHz-E night and 225 MHz-H), and 0, 20, 28, and 38 mW/cm2 (1290 MHz). The monkeys were unable to tolerate exposure at power densities equal to or greater than 7.5 mW/cm2 (5.1 W/kg) at 225 MHz-E for longer than 90 min. The criterion for tolerance was that the rectal temperature would not exceed 41.5 degrees C. Average rectal temperature increases for day exposure to 225 MHz-E were 0.4 and 1.7 degrees C for 4-hr exposures to 2.5 and 5.0 mW/cm2 (1.7 and 3.4 W/kg). No changes in circulating cortisol levels occurred during any exposures to 5 mW/cm2 or less. Night exposures to 5 mW/cm2 (3.4 W/kg) at 225 MHz-E raised mean rectal temperature 2.1 degrees C. Exposure to 5 mW/cm2 (1.2 W/kg) at 225 MHz-H for 4 hr resulted in a 0.2 degree rise in mean rectal temperature. For 4 hr of 1290-MHz exposure to 20, 28, or 38 mW/cm2 (2.9, 4.0, and 5.4 W/kg), the mean body temperature increases were 0.4, 0.7, and 1.3 degrees C, respectively. The degree of hyperthermia caused by radiofrequency (rf) exposure was shown to be frequency and orientation dependent for equivalent power densities of exposure.     

Crystal structure of polyglycine I

An electron diffraction study has been made of oriented polyglycine I (the β modification of polyglycine) and of single crystals grown from solution. The unit cell is very similar to that postulated by Astbu?y (1949). It is monoclinic with parameters a = 9.54 Å, b(chainaxis) = 7.044 Å, c = 3.67 Å and β = 113°. Examination of the possible structures suggests that polyglycine I does not have the familiar antiparallel pleated sheet, but rather the closely related antiparallel rippled sheet structure first described by Pauling &; Corey (1953a).     

Structure of polyglycine I: a comparison of the antiparallel pleated and antiparallel rippled sheets

Packing energy calculations are made for two possible sheet structures of polyglycine I, i.e. the antiparallel pleated and rippled sheets. They indicate that the rippled sheet is the more stable structure and that its calculated lattice parameters are close to those experimentally determined. Furthermore, the results on the packing of pleated sheets of polyglycine improve understanding of the well-known model of silk fibroin structure of Marsh et al. (1955). They also suggest that the sheet structures of l-polypeptides with short side-chains should pack in monoclinic unit cells rather than the orthorhombic ones which are observed. A possible origin of this discrepancy is discussed.     

Reforestation and surface cooling in temperate zones: Mechanisms and implications

Land‐use/cover change (LUCC) is an important driver of environmental change, occurring at the same time as, and often interacting with, global climate change. Reforestation and deforestation have been critical aspects of LUCC over the past two centuries and are widely studied for their potential to perturb the global carbon cycle. More recently, there has been keen interest in understanding the extent to which reforestation affects terrestrial energy cycling and thus surface temperature directly by altering surface physical properties (e.g., albedo and emissivity) and land–atmosphere energy exchange. The impacts of reforestation on land surface temperature and their mechanisms are relatively well understood in tropical and boreal climates, but the effects of reforestation on warming and/or cooling in temperate zones are less certain. This study is designed to elucidate the biophysical mechanisms that link land cover and surface temperature in temperate ecosystems. To achieve this goal, we used data from six paired eddy‐covariance towers over co‐located forests and grasslands in the temperate eastern United States, where radiation components, latent and sensible heat fluxes, and meteorological conditions were measured. The results show that, at the annual time scale, the surface of the forests is 1–2°C cooler than grasslands, indicating a substantial cooling effect of reforestation. The enhanced latent and sensible heat fluxes of forests have an average cooling effect of ?2.5°C, which offsets the net warming effect (+1.5°C) of albedo warming (+2.3°C) and emissivity cooling effect (?0.8°C) associated with surface properties. Additional daytime cooling over forests is driven by local feedbacks to incoming radiation. We further show that the forest cooling effect is most pronounced when land surface temperature is higher, often exceeding ?5°C. Our results contribute important observational evidence that reforestation in the temperate zone offers opportunities for local climate mitigation and adaptation.     

Modelling optimal vaccination strategy for SARS-CoV-2 in the UK

The COVID-19 outbreak has highlighted our vulnerability to novel infections.Faced with this threat and no effective treatment, in line with many other countries, the UK adopted enforced social distancing (lockdown) to reduce transmission—successfully reducing the reproductive number R below one. However, given the large pool of susceptible individuals that remain, complete relaxation of controls is likely to generate a substantial further outbreak. Vaccination remains the only foreseeable means of both containing the infection and returning to normal interactions and behaviour. Here, we consider the optimal targeting of vaccination within the UK, with the aim of minimising future deaths or quality adjusted life year (QALY) losses. We show that, for a range of assumptions on the action and efficacy of the vaccine, targeting older age groups first is optimal and may be sufficient to stem the epidemic if the vaccine prevents transmission as well as disease.