Environmental Perturbations Lift the Degeneracy of the Genetic Code to Regulate Protein Levels in Bacteria

The genetic code underlying protein synthesis is a canonical example of a degenerate biological system. Degeneracies in physical and biological systems can be lifted by external perturbations, thus allowing degenerate systems to exhibit a wide range of behaviors. Here we show that the degeneracy of the genetic code is lifted by environmental perturbations to regulate protein levels in living cells. By measuring protein synthesis rates from a synthetic reporter library in Escherichia coli, we find that environmental perturbations, such as reduction of cognate amino acid supply, lift the degeneracy of the genetic code by splitting codon families into a hierarchy of robust and sensitive synonymous codons. Rates of protein synthesis associated with robust codons are up to 100-fold higher than those associated with sensitive codons under these conditions. We find that the observed hierarchy between synonymous codons is not determined by usual rules associated with tRNA abundance and codon usage. Rather, competition among tRNA isoacceptors for aminoacylation underlies the robustness of protein synthesis. Remarkably, the hierarchy established using the synthetic library also explains the measured robustness of synthesis for endogenous proteins in E. coli. We further found that the same hierarchy is reflected in the fitness cost of synonymous mutations in amino acid biosynthesis genes and in the transcriptional control of σ-factor genes. Our study suggests that organisms can exploit degeneracy lifting as a general strategy to adapt protein synthesis to their environment.Molecular and Cellular Biolog

Entanglement entropy and multifractality at localization transitions

The von Neumann entanglement entropy is a useful measure to characterize a quantum phase transition. We investigate the non-analyticity of this entropy at disorder-dominated quantum phase transitions in non-interacting electronic systems. At these critical points, the von Neumann entropy is determined by the single particle wave function intensity which exhibits complex scale invariant fluctuations. We find that the concept of multifractality is naturally suited for studying von Neumann entropy of the critical wave functions. Our numerical simulations of the three dimensional Anderson localization transition and the integer quantum Hall plateau transition show that the entanglement at these transitions is well described using multifractal analysis.Comment: v3, 5 pages, published versio

Boundary criticality and multifractality at the 2D spin quantum Hall transition

Multifractal scaling of critical wave functions at a disorder-driven (Anderson) localization transition is modified near boundaries of a sample. Here this effect is studied for the example of the spin quantum Hall plateau transition using the supersymmetry technique for disorder averaging. Upon mapping of the spin quantum Hall transition to the classical percolation problem with reflecting boundaries, a number of multifractal exponents governing wave function scaling near a boundary are obtained exactly. Moreover, additional exact boundary scaling exponents of the localization problem are extracted, and the problem is analyzed in other geometries.Comment: v2, 17 pages, 10 figures, published versio

A serine sensor for multicellularity in a bacterium

We report the discovery of a simple environmental sensing mechanism for biofilm formation in the bacterium Bacillus subtilis that operates without the involvement of a dedicated RNA or protein. Certain serine codons, the four TCN codons, in the gene for the biofilm repressor SinR caused a lowering of SinR levels under biofilm-inducing conditions. Synonymous substitutions of these TCN codons with AGC or AGT impaired biofilm formation and gene expression. Conversely, switching AGC or AGT to TCN codons upregulated biofilm formation. Genome-wide ribosome profiling showed that ribosome density was higher at UCN codons than at AGC or AGU during biofilm formation. Serine starvation recapitulated the effect of biofilm-inducing conditions on ribosome occupancy and SinR production. As serine is one of the first amino acids to be exhausted at the end of exponential phase growth, reduced translation speed at serine codons may be exploited by other microbes in adapting to stationary phase. DOI: http://dx.doi.org/10.7554/eLife.01501.00

GlobULeS. IV. UVIT/AstroSat detection of extremely low mass white dwarf companions to blue straggler stars in NGC 362

We report the discovery of extremely low mass white dwarfs (ELM WDs) as a companion of blue straggler stars (BSSs) in the Galactic globular cluster NGC 362 using images from AstroSat's Ultra Violet Imaging Telescope (UVIT). Spectral energy distributions (SEDs) for 26 far-UV (FUV) bright member BSSs are created using data from the UVIT, the UltraViolet and Optical Telescope (UVOT), Gaia EDR3, and the 2.2 m ESO/MPI telescope. A single SED is fitted to 14 BSSs, whereas double-SED fits revealed ELM WDs as binary companions in 12 of the 26 BSSs studied. The effective temperature, radius, luminosity, and mass of the 12 ELM WDs are found to have a range of Teff = 9750−18,000 K, R = 0.1−0.4 R⊙, L = 0.4−3.3 L⊙, and M = 0.16−0.20 M⊙. These suggest that 12 BSSs are post-mass-transfer systems formed through the case A/B mass transfer pathway. To the best of our knowledge, this is the first finding of ELM WDs as companions to BSSs in globular clusters. This cluster is known to have a binary BSS sequence, and the 12 binary and 14 single BSSs (as classified by the SEDs) follow the mass transfer and collisional sequence of BSSs in the color–magnitude diagram. The cooling ages of nine of the ELM WDs are found to be younger than 500 Myr. Though the binary BSSs may have formed during the core collapse (∼200 Myr) or as part of the dynamical evolution of the cluster, they provide new insights on the dynamics of this cluster

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks