Information Theoretic Study of COVID-19 Genome.

In this paper, we analyse the genome sequence of COVID-19 on a information point of view, and we compare that with past and present genomes. We use the powerful tool of joint complexity in order to quantify the similarities measured between the various potential parent genomes. The tool has a computing complexity of several orders of magnitude below the classic Smith-Waterman algorithm and would allow it to be used on a larger scale.

The TR-icOS setup at the ESRF: time-resolved microsecond UV-Vis absorption spectroscopy on protein crystals.

The technique of time-resolved macromolecular crystallography (TR-MX) has recently been rejuvenated at synchrotrons, resulting in the design of dedicated beamlines. Using pump-probe schemes, this should make the mechanistic study of photoactive proteins and other suitable systems possible with time resolutions down to microseconds. In order to identify relevant time delays, time-resolved spectroscopic experiments directly performed on protein crystals are often desirable. To this end, an instrument has been built at the icOS Lab (in crystallo Optical Spectroscopy Laboratory) at the European Synchrotron Radiation Facility using reflective focusing objectives with a tuneable nanosecond laser as a pump and a microsecond xenon flash lamp as a probe, called the TR-icOS (time-resolved icOS) setup. Using this instrument, pump-probe spectra can rapidly be recorded from single crystals with time delays ranging from a few microseconds to seconds and beyond. This can be repeated at various laser pulse energies to track the potential presence of artefacts arising from two-photon absorption, which amounts to a power titration of a photoreaction. This approach has been applied to monitor the rise and decay of the M state in the photocycle of crystallized bacteriorhodopsin and showed that the photocycle is increasingly altered with laser pulses of peak fluence greater than 100 mJ cm-2, providing experimental laser and delay parameters for a successful TR-MX experiment.

How dieting might make some fatter: modeling weight cycling toward obesity from a perspective of body composition autoregulation.

The notion that dieting makes some people fatter has in the past decade gained considerable interest from both epidemiological predictions and biological plausibility. Several large-scale prospective studies have suggested that dieting to lose weight is associated with future weight gain and obesity, with such predictions being stronger and more consistent among dieters who are in the normal range of body weight rather than in those with obesity. Furthermore, the biological plausibility that dieting predisposes people who are lean (rather than those with overweight or obesity) to regain more body fat than what had been lost (referred to as fat overshooting) has recently gained support from a re-analysis of data on body composition during weight loss and subsequent weight recovery from the classic longitudinal Minnesota Starvation Experiment. These have revealed an inverse exponential relationship between the amount of fat overshot and initial adiposity, and have suggested that a temporal desynchronization in the recoveries of fat and lean tissues, in turn residing in differences in lean-fat partitioning during weight loss vs. during weight recovery (with fat recovery faster than lean tissue recovery) is a cardinal feature of fat overshooting. Within a conceptual framework that integrates the relationship between post-dieting fat overshooting with initial adiposity, the extent of weight loss and the differential lean-fat partitioning during weight loss vs. weight recovery, we describe here a mathematical model of weight cycling to predict the excess fat that could be gained through repeated dieting and multiple weight cycles from a standpoint of body composition autoregulation.

Prediction of regulatory long intergenic non-coding RNAs acting in trans through base-pairing interactions.

BACKGROUND: Long intergenic non-coding RNAs (lincRNAs) can act as regulators of expression of protein-coding genes. Trans-natural antisense transcripts (trans-NATs) are a type of lincRNAs that contain sequence complementary to mRNA from other loci. The regulatory potential of trans-NATs has been poorly studied in eukaryotes and no example of trans-NATs regulating gene expression in plants are reported. The goal of this study was to identify lincRNAs, and particularly trans-NATs, in Arabidopsis thaliana that have a potential to regulate expression of target genes in trans at the transcriptional or translational level. RESULTS: We identified 1001 lincRNAs using an RNAseq dataset from total polyA+ and polysome-associated RNA of seedlings grown under high and low phosphate, or shoots and roots treated with different phytohormones, of which 550 were differentially regulated. Approximately 30% of lincRNAs showed conservation amongst Brassicaceae and 25% harbored transposon element (TE) sequences. Gene co-expression network analysis highlighted a group of lincRNAs associated with the response of roots to low phosphate. A total of 129 trans-NATs were predicted, of which 88 were significantly differentially expressed under at least one pairwise comparison. Five trans-NATs showed a positive correlation between their expression and target mRNA steady-state levels, and three showed a negative correlation. Expression of four trans-NATs positively correlated with a change in target mRNA polysome association. The regulatory potential of these trans-NATs did not implicate miRNA mimics nor siRNAs. We also looked for lincRNAs that could regulate gene expression in trans by Watson-Crick DNA:RNA base pairing with target protein-encoding loci. We identified 100 and 81 with a positive or negative correlation, respectively, with steady-state level of their predicted target. The regulatory potential of one such candidate lincRNA harboring a SINE TE sequence was validated in a protoplast assay on three distinct genes containing homologous TE sequence in their promoters. Construction of networks highlighted other putative lincRNAs with multiple predicted target loci for which expression was positively correlated with target gene expression. CONCLUSIONS: This study identified lincRNAs in Arabidopsis with potential in regulating target gene expression in trans by both RNA:RNA and RNA:DNA base pairing and highlights lincRNAs harboring TE sequences in such activity.

Control of Cognate Sense mRNA Translation by cis-Natural Antisense RNAs.

Cis-Natural Antisense Transcripts (cis-NATs), which overlap protein coding genes and are transcribed from the opposite DNA strand, constitute an important group of noncoding RNAs. Whereas several examples of cis-NATs regulating the expression of their cognate sense gene are known, most cis-NATs function by altering the steady-state level or structure of mRNA via changes in transcription, mRNA stability, or splicing, and very few cases involve the regulation of sense mRNA translation. This study was designed to systematically search for cis-NATs influencing cognate sense mRNA translation in Arabidopsis (Arabidopsis thaliana). Establishment of a pipeline relying on sequencing of total polyA+ and polysomal RNA from Arabidopsis grown under various conditions (i.e. nutrient deprivation and phytohormone treatments) allowed the identification of 14 cis-NATs whose expression correlated either positively or negatively with cognate sense mRNA translation. With use of a combination of cis-NAT stable over-expression in transgenic plants and transient expression in protoplasts, the impact of cis-NAT expression on mRNA translation was confirmed for 4 out of 5 tested cis-NAT:sense mRNA pairs. These results expand the number of cis-NATs known to regulate cognate sense mRNA translation and provide a foundation for future studies of their mode of action. Moreover, this study highlights the role of this class of noncoding RNAs in translation regulation.

Standing economy: does the heterogeneity in the energy cost of posture maintenance reside in differential patterns of spontaneous weight-shifting?

PURPOSE: Due to sedentarity-associated disease risks, there is much interest in methods to increase low-intensity physical activity. In this context, it is widely assumed that altering posture allocation can modify energy expenditure (EE) to impact body-weight regulation and health. However, we have recently shown the existence of two distinct phenotypes pertaining to the energy cost of standing-with most individuals having no sustained increase in EE during steady-state standing relative to sitting comfortably. Here, we investigated whether these distinct phenotypes are related to the presence/absence of spontaneous "weight-shifting", i.e. the redistribution of body-weight from one foot to the other. METHODS: Using indirect calorimetry to measure EE in young adults during sitting and 10 min of steady-state standing, we examined: (i) heterogeneity in EE during standing (n = 36); (ii) EE and spontaneous weight-shifting patterns (n = 18); (iii) EE during spontaneous weight-shifting versus experimentally induced weight-shifting (n = 7), and; (iv) EE during spontaneous weight-shifting versus intermittent leg/body displacement (n = 6). RESULTS: Despite heterogeneity in EE response to steady-state standing, no differences were found in the amount or pattern of spontaneous weight-shifting between the two phenotypes. Whilst experimentally induced weight-shifting resulted in a mean EE increase of only 11% (range: 0-25%), intermittent leg/body displacement increased EE to >1.5 METs in all participants. CONCLUSIONS: Although the variability in spontaneous weight-shifting signatures between individuals does not appear to underlie heterogeneity in the energy cost of standing posture maintenance, these studies underscore the fact that leg/body displacement, rather than standing posture alone, is needed to increase EE above the currently defined sedentary threshold.

Nucleosome Stability Distinguishes Two Different Promoter Types at All Protein-Coding Genes in Yeast.

Previous studies indicate that eukaryotic promoters display a stereotypical chromatin landscape characterized by a well-positioned +1 nucleosome near the transcription start site and an upstream -1 nucleosome that together demarcate a nucleosome-free (or -depleted) region. Here we present evidence that there are two distinct types of promoters distinguished by the resistance of the -1 nucleosome to micrococcal nuclease digestion. These different architectures are characterized by two sequence motifs that are broadly deployed at one set of promoters where a nuclease-sensitive ("fragile") nucleosome forms, but concentrated in a narrower, nucleosome-free region at all other promoters. The RSC nucleosome remodeler acts through the motifs to establish stable +1 and -1 nucleosome positions, while binding of a small set of general regulatory (pioneer) factors at fragile nucleosome promoters plays a key role in their destabilization. We propose that the fragile nucleosome promoter architecture is adapted for regulation of highly expressed, growth-related genes.

Incidence, severity, mortality, and confounding factors for dissecting AAA detection in angiotensin II-infused mice: a meta-analysis.

AIMS: While angiotensin II-infused mice are the most popular model for preclinical aneurysm research, representative data on incidence, severity, and mortality of dissecting abdominal aortic aneurysms (AAAs) have never been established, and the influence of confounding factors is unknown. METHODS AND RESULTS: We performed a meta-analysis including 194 manuscripts representing 1679 saline-infused, 4729 non-treated angiotensin II-infused, and 4057 treated angiotensin II-infused mice. Incidence (60%) and mortality (20%) rates are reported overall as well as for grade I (22%), grade II (26%), grade III (29%), and grade IV (24%) aneurysms. Dissecting AAA incidence was significantly (P < 0.05) influenced by sex, age, genetic background, infusion time, and dose of angiotensin II. Mortality was influenced by sex, genetic background, and dose, but not by age or infusion time. Surprisingly, both incidence and mortality were significantly different (P < 0.05) when comparing angiotensin II-infused mice in descriptive studies (56% incidence and 19% mortality) with angiotensin II-infused mice that served as control animals in treatment studies designed to either enhance (35% incidence and 13% mortality) or reduce (73% incidence and 25% mortality) dissecting AAA formation. After stratification to account for confounding factors (selection bias), the observed effect was still present for incidence, but not for mortality. Possible underlying causes are detection bias (non-uniform definition for detection and quantification of dissecting AAA in mice) or publication bias (studies with negative results, related to incidence in the control group, not being published). CONCLUSIONS: Our data provide a new meta-analysis-based reference for incidence and mortality of dissecting AAA in angiotensin II-infused mice, and indicate that treatment studies using this mouse model should be interpreted with caution.

Two distinct promoter architectures centered on dynamic nucleosomes control ribosomal protein gene transcription.

In yeast, ribosome production is controlled transcriptionally by tight coregulation of the 138 ribosomal protein genes (RPGs). RPG promoters display limited sequence homology, and the molecular basis for their coregulation remains largely unknown. Here we identify two prevalent RPG promoter types, both characterized by upstream binding of the general transcription factor (TF) Rap1 followed by the RPG-specific Fhl1/Ifh1 pair, with one type also binding the HMG-B protein Hmo1. We show that the regulatory properties of the two promoter types are remarkably similar, suggesting that they are determined to a large extent by Rap1 and the Fhl1/Ifh1 pair. Rapid depletion experiments allowed us to define a hierarchy of TF binding in which Rap1 acts as a pioneer factor required for binding of all other TFs. We also uncovered unexpected features underlying recruitment of Fhl1, whose forkhead DNA-binding domain is not required for binding at most promoters, and Hmo1, whose binding is supported by repeated motifs. Finally, we describe unusually micrococcal nuclease (MNase)-sensitive nucleosomes at all RPG promoters, located between the canonical +1 and -1 nucleosomes, which coincide with sites of Fhl1/Ifh1 and Hmo1 binding. We speculate that these "fragile" nucleosomes play an important role in regulating RPG transcriptional output.

On the entropy of a hidden Markov process.

We study the entropy rate of a hidden Markov process (HMP) defined by observing the output of a binary symmetric channel whose input is a first-order binary Markov process. Despite the simplicity of the models involved, the characterization of this entropy is a long standing open problem. By presenting the probability of a sequence under the model as a product of random matrices, one can see that the entropy rate sought is equal to a top Lyapunov exponent of the product. This offers an explanation for the elusiveness of explicit expressions for the HMP entropy rate, as Lyapunov exponents are notoriously difficult to compute. Consequently, we focus on asymptotic estimates, and apply the same product of random matrices to derive an explicit expression for a Taylor approximation of the entropy rate with respect to the parameter of the binary symmetric channel. The accuracy of the approximation is validated against empirical simulation results. We also extend our results to higher-order Markov processes and to Rényi entropies of any order.