Riboswitch­mediated regulation of the Mycobacterium tuberculosis resuscitation promoting factor, rpfB

Mycobacterium tuberculosis, the causative agent of tuberculosis, results in over 1.5 million deaths every year. An estimated third of the world’s population may harbour a latent infection with risk of reactivation under permissive conditions. M. tuberculosis expresses a number of homologous resuscitation promoting factors (Rpfs) believed to facilitate resuscitation from dormancy. However, little is known about the regulation of Rpf expression. This study identifies a putative novel riboswitch in the 5’UTR of rpfB, which appears to be conserved in pathogenic mycobacteria, but not in non-pathogenic species. Northern blot analysis of M. tuberculosis RNA reveals short terminated transcripts and longer read-through transcripts suggesting transcription attenuation mediated by a transcriptional riboswitch. This has been further supported by 3’RACE, reporter gene assays and in vitro transcription. Findings indicate that rpfB is co-transcribed with the universally conserved rRNA methyltransferase ksgA, implicating the riboswitch in ksgA expression regulation, thereby linking resuscitation with ribosome maturation. Moreover, through translation start site mapping the RpfB start codon has been re-annotated and a ribosome binding site has been validated. This ribosome binding site is likely targeted by an rpfB antisense RNA produced from an antisense promoter that may also serve to regulate rpfB expression either by RNA polymerase clashing, sense antisense interaction, mRNA processing or all of the above. Expression of the rpfB locus has been investigated under multiple physiological stresses and throughout biofilm formation. Collectively, findings support the presence of a novel rpfB riboswitch transcriptional ‘on-switch’ capable of regulating expression through transcription attenuation. Understanding the stimuli and regulation of Rpf gene expression will improve understanding of their role in disease and resuscitation

Smart Charging of Electric Vehicles with Cloud-based Optimization and a Lightweight User Interface – A Real-World Application in the Energy Lab 2.0: Poster

Smart Charging (SC) of Electric Vehicles (EVs) integrates them into the power system to support grid stability by power management. Large-scale adoption of SC requires a high level of EV user acceptance. Therefore, it is imperative to make the underlying charging scheme tangible for the user. We propose a web app for the user to start, adjust and monitor the charging process via a User Interface (UI). We outline the integration of this web app into an Internet of Things (IoT) architecture to establish communication with the charging station. Two scenarios demonstrate the operation of the system. Future field studies on SC should involve the EV user due to individual preferences and responses to incentive schemes. Therefore, we propose the Smart Charging Wizard with a customizable UI and optimization module for future research and collaborative development

Synchronous and proportional deglacial changes in Atlantic meridional overturning and northeast Brazilian precipitation

Changes in heat transport associated with fluctuations in the strength of the Atlantic meridional overturning circulation (AMOC) are widely considered to affect the position of the Intertropical Convergence Zone (ITCZ), but the temporal immediacy of this teleconnection has to date not been resolved. Based on a high-resolution marine sediment sequence over the last deglaciation, we provide evidence for a synchronous and near-linear link between changes in the Atlantic interhemispheric sea surface temperature difference and continental precipitation over northeast Brazil. The tight coupling between AMOC strength, sea surface temperature difference, and precipitation changes over northeast Brazil unambiguously points to a rapid and proportional adjustment of the ITCZ location to past changes in the Atlantic meridional heat transport

Cell-wall synthesis and ribosome maturation are co-regulated by an RNA switch in Mycobacterium tuberculosis

The success of Mycobacterium tuberculosis relies on the ability to switch between active growth and non-replicating persistence, associated with latent TB infection. Resuscitation promoting factors (Rpfs) are essential for the transition between these states. Rpf expression is tightly regulated as these enzymes are able to degrade the cell wall, and hence potentially lethal to the bacterium itself. We have identified a regulatory element in the 5' untranslated region (UTR) of rpfB. We demonstrate that this element is a transcriptionally regulated RNA switch/riboswitch candidate, which appears to be restricted to pathogenic mycobacteria, suggesting a role in virulence. We have used translation start site mapping to re-annotate the RpfB start codon and identified and validated a ribosome binding site that is likely to be targeted by an rpfB antisense RNA. Finally, we show that rpfB is co-transcribed with ksgA and ispE downstream. ksgA encodes a universally conserved methyltransferase involved in ribosome maturation and ispE encodes an essential kinase involved in cell wall synthesis. This arrangement implies co-regulation of resuscitation, cell wall synthesis and ribosome maturation via the RNA switch

Malnutrition and Infection: Complex Mechanisms and Global Impacts

The authors discuss current concepts and controversies surrounding the complex influences of malnutrition on infection and immunity, and point to practical consequences of countermeasures in acute malnutrition

Genetic Landscape of the ACE2 Coronavirus Receptor

Background:SARS-CoV-2, the causal agent of COVID-19, enters human cells using the ACE2 (angiotensin-converting enzyme 2) protein as a receptor. ACE2 is thus key to the infection and treatment of the coronavirus. ACE2 is highly expressed in the heart and respiratory and gastrointestinal tracts, playing important regulatory roles in the cardiovascular and other biological systems. However, the genetic basis of the ACE2 protein levels is not well understood.Methods:We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28 000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics–based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data.Results:We identified 10 loci, including 8 novel, capturing 30% of the heritability of the protein. We detected that plasma ACE2 was genetically correlated with vascular diseases, severe COVID-19, and a wide range of human complex diseases and medications. An X-chromosome cis–protein quantitative trait loci–based mendelian randomization analysis suggested a causal effect of elevated ACE2 levels on COVID-19 severity (odds ratio, 1.63 [95% CI, 1.10–2.42]; P=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05–2.21]; P=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08–2.37]; P=0.02). Tissue- and cell type–specific transcriptomic and epigenomic analysis revealed that the ACE2 regulatory variants were enriched for DNA methylation sites in blood immune cells.Conclusions:Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor

Circulating Levels of Adiponectin, Leptin, Fetuin-A and Retinol-Binding Protein in Patients with Tuberculosis: Markers of Metabolism and Inflammation

BACKGROUND: Wasting is known as a prominent feature of tuberculosis (TB). To monitor the disease state, markers of metabolism and inflammation are potentially useful. We thus analyzed two major adipokines, adiponectin and leptin, and two other metabolic markers, fetuin-A and retinol-binding protein 4 (RBP4). METHODS: The plasma levels of these markers were measured using enzyme-linked immunosorbent assays in 84 apparently healthy individuals (=no-symptom group) and 46 patients with active pulmonary TB around the time of treatment, including at the midpoint evaluation (=active-disease group) and compared them with body mass index (BMI), C-reactive protein (CRP), chest radiographs and TB-antigen specific response by interferon-γ release assay (IGRA). RESULTS: In the no-symptom group, adiponectin and leptin showed negative and positive correlation with BMI respectively. In the active-disease group, at the time of diagnosis, leptin, fetuin-A and RBP4 levels were lower than in the no-symptom group [adjusted means 2.01 versus 4.50 ng/ml, P<0.0001; 185.58 versus 252.27 µg/ml, P<0.0001; 23.88 versus 43.79 µg/ml, P<0.0001, respectively]. High adiponectin and low leptin levels were associated with large infiltrates on chest radiographs even after adjustment for BMI and other covariates (P=0.0033 and P=0.0020). During treatment, adiponectin levels increased further and then decreased. Leptin levels remained low. Initial low levels of fetuin-A and RBP4 almost returned to the normal reference range in concert with reduced CRP. CONCLUSIONS: Our data and recent literature suggest that low fat store and underlying inflammation may regulate these metabolic markers in TB in a different way. Decreased leptin, increased adiponectin, or this ratio may be a promising marker for severity of the disease independent of BMI. We should further investigate pathological roles of the balance between these adipokines

Top-Down Control of Herbivory by Birds and Bats in the Canopy of Temperate Broad-Leaved Oaks (Quercus robur)

The intensive foraging of insectivorous birds and bats is well known to reduce the density of arboreal herbivorous arthropods but quantification of collateral leaf damage remains limited for temperate forest canopies

78Ni revealed as a doubly magic stronghold against nuclear deformation

Nuclear magic numbers correspond to fully occupied energy shells of protons or neutrons inside atomic nuclei. Doubly magic nuclei, with magic numbers for both protons and neutrons, are spherical and extremely rare across the nuclear landscape. Although the sequence of magic numbers is well established for stable nuclei, experimental evidence has revealed modifications for nuclei with a large asymmetry between proton and neutron numbers. Here we provide a spectroscopic study of the doubly magic nucleus 78 Ni, which contains fourteen neutrons more than the heaviest stable nickel isotope. We provide direct evidence of its doubly magic nature, which is also predicted by ab initio calculations based on chiral effective-field theory interactions and the quasi-particle random-phase approximation. Our results also indicate the breakdown of the neutron magic number 50 and proton magic number 28 beyond this stronghold, caused by a competing deformed structure. State-of-the-art phenomenological shell-model calculations reproduce this shape coexistence, predicting a rapid transition from spherical to deformed ground states, with 78 Ni as the turning point