Lateral gene transfer acts as an evolutionary shortcut to efficient C4 biochemistry

The adaptation of proteins for novel functions often requires changes in their kinetics via amino acid replacement. This process can require multiple mutations, and therefore extended periods of selection. The transfer of genes among distinct species might speed up the process, by providing proteins already adapted for the novel function. However, this hypothesis remains untested in multicellular eukaryotes. The grass Alloteropsis is an ideal system to test this hypothesis due to its diversity of genes encoding phosphoenolpyruvate carboxylase (PEPC), an enzyme that catalyses one of the key reactions in the C4 pathway. Different accessions of Alloteropsis either use native isoforms relatively recently co-opted from other functions or isoforms that were laterally acquired from distantly related species that evolved the C4 trait much earlier. By comparing the enzyme kinetics we show that native isoforms with few amino acid replacements have substrate KM values similar to the non-C4 ancestral form, but exhibit marked increases in catalytic efficiency. The co-option of native isoforms was therefore followed by rapid catalytic improvements, which appear to rely on standing genetic variation observed within one species. Native C4 isoforms with more amino acid replacements exhibit additional changes in affinities, suggesting that the initial catalytic improvements are followed by gradual modifications. Finally, laterally acquired genes show both strong increases in catalytic efficiency and important changes in substrate handling. We conclude that the transfer of genes among distant species sharing the same physiological novelty creates an evolutionary shortcut toward more efficient enzymes, effectively accelerating evolution

High-resolution laser system for the S3-Low Energy Branch

In this paper we present the first high-resolution laser spectroscopy results obtained at the GISELE laser laboratory of the GANIL-SPIRAL2 facility, in preparation for the first experiments with the S$^3$-Low Energy Branch. Studies of neutron-deficient radioactive isotopes of erbium and tin represent the first physics cases to be studied at S$^3$. The measured isotope-shift and hyperfine structure data are presented for stable isotopes of these elements. The erbium isotopes were studied using the $4f^{12}6s^2$ $^3H_6 \rightarrow 4f^{12}(^3 H)6s6p$ $J = 5$ atomic transition (415 nm) and the tin isotopes were studied by the $5s^25p^2 (^3P_0) \rightarrow 5s^25p6s (^3P_1)$ atomic transition (286.4 nm), and are used as a benchmark of the laser setup. Additionally, the tin isotopes were studied by the $5s^25p6s (^3P_1) \rightarrow 5s^25p6p (^3P_2)$ atomic transition (811.6 nm), for which new isotope-shift data was obtained and the corresponding field-shift $F_{812}$ and mass-shift $M_{812}$ factors are presented

Smooth trends in fermium charge radii and the impact of shell effects.

The quantum-mechanical nuclear-shell structure determines the stability and limits of the existence of the heaviest nuclides with large proton numbers Z ≳ 100 (refs. 1-3). Shell effects also affect the sizes and shapes of atomic nuclei, as shown by laser spectroscopy studies in lighter nuclides4. However, experimental information on the charge radii and the nuclear moments of the heavy actinide elements, which link the heaviest naturally abundant nuclides with artificially produced superheavy elements, is sparse5. Here we present laser spectroscopy measurements along the fermium (Z = 100) isotopic chain and an extension of data in the nobelium isotopic chain (Z = 102) across a key region. Multiple production schemes and different advanced techniques were applied to determine the isotope shifts in atomic transitions, from which changes in the nuclear mean-square charge radii were extracted. A range of nuclear models based on energy density functionals reproduce well the observed smooth evolution of the nuclear size. Both the remarkable consistency of model prediction and the similarity of predictions for different isotopes suggest a transition to a regime in which shell effects have a diminished effect on the size compared with lighter nuclei

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Détermination des caractéristiques épidémiologiques et microbiologiques d’une cohorte prospective de patients en choc septique

Médecine. Anesthésie réanimatio

Early alterations of the neuronal network processing whisker‐related sensory signal during absence epileptogenesis

International audienceAbstract Objective Epileptogenesis is the particular process during which the epileptic network builds up progressively before the onset of the first seizures. Whether physiological functions are impacted by this development of epilepsy remains unclear. To explore this question, we used Genetic Absence Epilepsy Rats From Strasbourg (GAERS), in which spike‐and‐wave discharges are initiated in the whisker primary somatosensory cortex (wS1) and first occur during cortical maturation. We studied the development of both the epileptic and the physiological wS1 circuits during cortical maturation to understand the interactions between them and the consequences for the animals' behavior. Methods In sedated and immobilized rat pups, we recorded in vivo epileptic and whisker sensory evoked activities across the wS1 and thalamus using multicontact electrodes. We compared sensory evoked potentials based on current source density analysis. We then analyzed the multiunit activities evoked by whisker stimulation in GAERS and control rats. Finally, we evaluated behavioral performance dependent on the functionality of the wS1 cortex using the gap‐crossing task. Results We showed that the epileptic circuit changed during the epileptogenesis period in GAERS, by involving different cortical layers of wS1. Neuronal activities evoked by whisker stimulation were reduced in the wS1 cortex at P15 and P30 in GAERS but increased in the ventral posteromedial nucleus of the thalamus at P15 and in the posterior medial nucleus at P30, when compared to control rats. Finally, we observed lower performance in GAERS versus controls, at both P15 and P30, in a whisker‐mediated behavioral task. Significance Our data show that the functionality of wS1 cortex and thalamus is altered early during absence epileptogenesis in GAERS and then evolves before spike‐and‐wave discharges are fully expressed. They suggest that the development of the pathological circuit disturbs the physiological one and may be responsible for both the emergence of seizures and associated comorbidities

Combining Event History and Sequence Analysis to Study Vulnerability over the Life Course

AbstractThe life-course paradigm insists on the need to study trajectories and how they unfold over time. Two broad families of methodological strategies are generally used for this purpose. The first strategy focuses on the occurrence of events or transitions describing the dynamics of life trajectories. The second strategy emphasizes the holistic nature of trajectories or processes of categorical states by relying on sequence analysis. This chapter reviews recent methodological development combining these two approaches often presented as irreconcilable. “Competing Trajectory Analysis” aims to analyze jointly the occurrence of an event and the “trajectory” that immediately follows it. On the other hand, the “Sequence History Analysis” approach uses sequence analysis to better describe how an unfolding trajectory is linked with the occurrence of an upcoming event. The chapter proposes a theoretical presentation of these approaches discussing their respective strength and weaknesses for life-course research and more specifically the study of vulnerability over the life course. The added value of each approach is illustrated through a study of the relationship between divorce and professional trajectories using the retrospective data from the Swiss Household Panel.</jats:p