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Object GRB 221009A is the brightest gamma-ray burst (GRB) detected in more than 50 yr of study. In this paper, we present observations in the X-ray and optical domains obtained by the GRANDMA Collaboration and the Insight Collaboration. We study the optical afterglow with empirical fitting using the GRANDMA+HXMT-LE data sets augmented with data from the literature up to 60 days. We then model numerically using a Bayesian approach, and we find that the GRB afterglow, extinguished by a large dust column, is most likely behind a combination of a large Milky Way dust column and moderate low-metallicity dust in the host galaxy. Using the GRANDMA+HXMT-LE+XRT data set, we find that the simplest model, where the observed afterglow is produced by synchrotron radiation at the forward external shock during the deceleration of a top-hat relativistic jet by a uniform medium, fits the multiwavelength observations only moderately well, with a tension between the observed temporal and spectral evolution. This tension is confirmed when using the augmented data set. We find that the consideration of a jet structure (Gaussian or power law), the inclusion of synchrotron self-Compton emission, or the presence of an underlying supernova do not improve the predictions. Placed in the global context of GRB optical afterglows, we find that the afterglow of GRB 221009A is luminous but not extraordinarily so, highlighting that some aspects of this GRB do not deviate from the global known sample despite its extreme energetics and the peculiar afterglow evolution.

ABSTRACT Human health is threatened by bacterial infections that are increasingly resistant to multiple drugs. A recently emerged strategy consists of disarming pathogenic bacteria by targeting and blocking their virulence factors. The type VI secretion system (T6SS) is a widespread secretion nanomachine encoded and employed by pathogenic strains to establish their virulence process during host invasion. Given the conservation of T6SS in several human bacterial pathogens, the discovery of an effective broad-spectrum T6SS virulence blocker represents an attractive target for development of antivirulence therapies. Here, we identified and validated a protein-protein interaction interface, TssK-TssG, as a key factor in the assembly of the T6SS baseplate (BP) complex in the pathogen enteroaggregative Escherichia coli (EAEC). In silico and biochemical studies revealed that the determinants of the interface are broadly conserved among pathogenic species, suggesting a role for this interface as a target for T6SS inhibition. Based on the high-resolution structure of the TssKFGE wedge complex, we rationally designed a biomimetic cyclic peptide (BCP) that blocks the assembly of the EAEC BP complex and inhibits the function of T6SS in bacterial cultures. Our BCP is the first compound completely designed from prior structural knowledge with anti-T6SS activity that can be used as a model to target human pathogens. IMPORTANCE New therapeutic options are urgently needed to fight drug-resistant and life-threatening infections. In contrast to antibiotics that inhibit the growth pathways of bacteria, the antivirulence strategy is a promising approach to disarm pathogens by interfering with bacterial virulence factors without exerting evolutionary pressure. The type VI secretion system (T6SS) is used by many pathogens, including members of the antibiotic-resistant ESKAPE bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), to establish their virulence during the invasion of the human host. Although the T6SS is undoubtedly involved in pathogenesis, strategies targeting this virulence factor are crucially lacking. Here, we used a combination of genetics, microbiology, biochemical, biophysics, and bioinformatics approaches to rationally design a biomimetic peptide that interferes with T6SS assembly and functioning. This study represents a novel proof of concept for an antivirulence strategy which aims to interfere with the assembly of the T6SS.

Bronchiolitis obliterans syndrome (BOS), the main manifestation of chronic lung allograft dysfunction, leads to poor long-term survival after lung transplantation. Identifying predictors of BOS is essential to prevent the progression of dysfunction before irreversible damage occurs. By using a large set of 107 samples from lung recipients, we performed microarray gene expression profiling of whole blood to identify early biomarkers of BOS, including samples from 49 patients with stable function for at least 3 years, 32 samples collected at least 6 months before BOS diagnosis (prediction group), and 26 samples at or after BOS diagnosis (diagnosis group). An independent set from 25 lung recipients was used for validation by quantitative PCR (13 stables, 11 in the prediction group, and 8 in the diagnosis group). We identified 50 transcripts differentially expressed between stable and BOS recipients. Three genes, namely POU class 2 associating factor 1 (POU2AF1), T-cell leukemia/lymphoma protein 1A (TCL1A), and B cell lymphocyte kinase, were validated as predictive biomarkers of BOS more than 6 months before diagnosis, with areas under the curve of 0.83, 0.77, and 0.78 respectively. These genes allow stratification based on BOS risk (log-rank test p

Objective: This study aimed to estimate the prevalence of traumatic brain injury (TBI) in a French prison population of young offenders and to study variables known to be associated with TBI. It also aimed to study whether TBI was associated with younger age at entry into prison; longer period of custody and re-offending. Participants: All young offenders (from 13 to 21) consecutively admitted to Fleury-Mérogis prison over a period of 3 months were included. Method: During the admission procedure, young offenders were interviewed by healthcare staff using a self-reported questionnaire. Comparisons between cases (TBI+) and controls (TBI−) were performed. Results: Three hundred thirty two young offenders were included. The prevalence of self-reported TBI was 24.5%. The first cause of TBI was violence-related outcomes (25%). No differences were found regarding the number of times in custody and the total time spent in prison during the preceding five years. Cases accumulated multiple health problems including mental health problems (16.3% vs. 4.9%; p = .002) and a regular use of cannabis (28.7% vs. 15.9%; p = .02). Conclusions: The results provide further evidence that specific measures need to be developed such as, first of all, screening for TBI and related impairments upon arrival in prison.

The ability to imitate complex sounds is rare, and among birds has been found only in parrots, songbirds, and hummingbirds. Parrots exhibit the most advanced vocal mimicry among non-human animals. A few studies have noted differences in connectivity, brain position and shape in the vocal learning systems of parrots relative to songbirds and hummingbirds. However, only one parrot species, the budgerigar, has been examined and no differences in the presence of song system structures were found with other avian vocal learners. Motivated by questions of whether there are important differences in the vocal systems of parrots relative to other vocal learners, we used specialized constitutive gene expression, singing-driven gene expression, and neural connectivity tracing experiments to further characterize the song system of budgerigars and/or other parrots. We found that the parrot brain uniquely contains a song system within a song system. The parrot "core" song system is similar to the song systems of songbirds and hummingbirds, whereas the "shell" song system is unique to parrots. The core with only rudimentary shell regions were found in the New Zealand kea, representing one of the only living species at a basal divergence with all other parrots, implying that parrots evolved vocal learning systems at least 29 million years ago. Relative size differences in the core and shell regions occur among species, which we suggest could be related to species differences in vocal and cognitive abilities.