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The evolutionary transition from uni- to multicellularity is associated with new properties resulting from collective cell behavior. The social amoeba Dictyostelium discoideum alternating between individual cells and multicellular forms of varying size provides a powerful biological system to characterize such emergent properties. Multicellular forms coined slugs have long been described as chemotactic towards cAMP, and also as phototactic. While chemotaxis is also well-documented at the single-cell level, which explains slug chemotaxis, we asked whether slug phototaxis is an emergent property of multicellularity. For this, we developed an automated microscopy setup to quantify and compare the migration trajectories of single cells and slugs moving in the dark or illuminated with lateral light. We find that single cells, either extracted from phototactic slugs or taken prior to multicellular aggregation, are not phototactic, implying that slug phototaxis results from interactions between cells that lack this property. Further, by analysing slugs composed of a varying number of cells, we find that phototaxis efficiency increases continuously with slug size. Cell-cell interactions combined with self-organization are thus key elements for this property to emerge.

\"This collection of 171 letters, most never before published, finally makes the fascinating Shaw/Murray correspondence available. With explanatory headnotes and footnotes by Charles A. Carpenter, Bernard Shaw and Gilbert Murray offers insight into an unusual literary and political friendship.\"-- Publisher description.

The human pathogen Streptococcus pyogenes secretes a short peptide (leaderless communication peptide, LCP) that mediates intercellular communication and controls bacterial virulence through interaction with its receptor, RopB. Here, we show that LCP and RopB homologues are present in other Firmicutes. We experimentally validate that LCPs with distinct peptide communication codes act as bacterial intercellular signals and regulate gene expression in Streptococcus salivarius , Streptococcus porcinus , Enterococcus malodoratus and Limosilactobacillus reuteri . Our results indicate that LCPs are more widespread than previously thought, and their characterization may uncover new signaling mechanisms and roles in coordinating diverse bacterial traits. The human pathogen Streptococcus pyogenes secretes a short peptide (LCP) that mediates intercellular communication and controls bacterial virulence. Here, the authors show that LCP homologues act as bacterial intercellular signals and regulate gene expression also in other bacteria.

كثيرا ما سأل بيتر إف. دراكر الأشخاص الذين عمل معهم سؤالا بسيطا : كيف تريدون أن يتذكركم الناس ؟. وفي معهد فرانسيس هيسبين للقيادة، وافقنا بالإجماع على مدى أهمية أن نلعب دورا في إلهام الجيل التالي من القادة. وفي عام 2009، اشترك معهد هيسبين مع جامعة بيتسبرج في إطلاق مشروع أكاديمية هيسبين العالمية للقيادة الطلابية والمشاركة المدنية، الذي استقطب 300 طالب موهوب من جميع القارات وعرض عليهم أعمال بيتر دراكر وفرانسيس هيسبين. إن الجيل الأصغر سنا في يومنا هذا-المعروف بجيل الألفية أو الجيل واي، المولود في الفترة ما بين عامي 1980 و 2000-ليس هو الجيل الأكبر بعد، ولكنه أكثر الأجيال تعلما وتنوعا ؛ فقد ضخم حجم التكنولوجيا وسهولة السفر حول العالم من أحلامهم بالعديد من الطرق. وجعلتهم حركة شبكات التواصل الاجتماعي والإعلام الرقمي، بدءا من القنوات المشفرة التقليدية ووصولا إلى مواقع ألفيس بوك وتويتر متواصلين مع بقية العالم بحيث يمكنهم ارتداء الماركات العالمية وكذلك التفاعل مع القضايا حول العالم بطرق استباقية جديدة. كما طوروا شبكات أصدقاء لم تتضمن الجيران أو رفقاءهم في صفوف الرياضة فقط بل تضمنت أصدقاء من أماكن نائية من العالم. ربما لم يلتقوا بهؤلاء الأصدقاء من قبل وجها لوجه، ولكن التواصل فيما بينهم كان له تأثير كبير على حيواتهم، كما نمى لديهم شعورا بالتعاطف العالمي، ولهذا أنا غالبا ما أشير إلى جيل الألفية بأنه الجيل العالمي الأول.

Azetidine-2-carboxylic acid (AZE) is a long-known plant metabolite. Recently, AZE synthases have been identified in bacterial natural product pathways involving non-ribosomal peptide synthetases. AZE synthases catalyse the intramolecular 4-exo-tet cyclisation of S -adenosylmethionine (SAM), yielding a highly strained heterocycle. Here, we combine structural and biochemical analyses with quantum mechanical calculations and mutagenesis studies to reveal catalytic insights into AZE synthases. The cyclisation of SAM is facilitated by an exceptional substrate conformation and supported by desolvation effects as well as cation-π interactions. In addition, we uncover related SAM lyases in diverse bacterial phyla, suggesting a wider prevalence of AZE-containing metabolites than previously expected. To explore the potential of AZE as a proline mimic in combinatorial biosynthesis, we introduce an AZE synthase into the pyrrolizixenamide pathway and thereby engineer analogues of azabicyclenes. Taken together, our findings provide a molecular framework to understand and exploit SAM-dependent cyclisation reactions. Azetidine-2-carboxylic acid synthases catalyse the formation of the proline analogue azetidine-2-carboxylic acid (AZE) in bacteria. In this work, the authors combine structural and biochemical analyses with quantum mechanical calculations and mutagenesis studies to obtain catalytic insights into AZE synthases.

Purpose: Some patients make a rational choice not to follow medical prescriptions; others fail to take their medications for reasons beyond their control, such as mere forgetfulness or a weak medication routine. The aim of this study was to elucidate the functioning of patient intentionality in medication adherence. Patients and Methods: This online study was conducted in metropolitan France in 2019. A cross-sectional survey of 50 questions was conducted with 3001 respondents diagnosed with diabetes, hypertension, and/or hypercholesterolemia identified from a panel of 54,000 people. These questions included a validated six-item questionnaire to detect nonadherence, two questions to detect intentional nonadherence by patients, and three questions on the effects of habit. Our questionnaire also included questions on the feelings of respondents regarding their doctor's attitude to their problems and needs, their trust in general practitioners (GP) and specialists, their sense of being involved in treatment decisions, and the influence of side effects and habits on patients' adherence. This study used the strategy of focusing on strictly adherent patients in the hope of finding ways to improve adherence. For this reason, we defined adherence as the absence of a positive response to the 6-item nonadherence screening questionnaire. Results: Of 3001 respondents, 1804 were diagnosed with hypertension, 1458 with hypercholesterolemia, and 774 with diabetes. Of the total number of patients, 72% were afflicted with one disease, 21% with two ailments, and 7% with three simultaneous illnesses. One-third (33%) of the patients did not tender a positive answer to the adherence questionnaire and were deemed adherent. 1) Thirty-two percent of the patients reported occasionally omitting their medication deliberately, and 84% said they had a reason for missing doses. These statements suggesting intentional nonadherence were negatively associated with adherence as identified via multivariate analysis (P = 0.0012 and P < 0.0001, for the first and second statement, respectively). 2) Univariate analyses revealed strong associations (P < 0.0001) between strict adherence on one hand and lack of intentional nonadherence, patient age, absence of drug side effects, taking drugs by habit, feeling involved in treatment decisions, getting information about treatment, and disease, and trust in doctors, on the other hand. 3) Specifically, univariate analysis of the absence of reported side effects revealed strong associations (P < 0.0001) with adequate information about medicines and diseases and trust in GP. These original data were consistent with the concept of the nocebo effect. 4) We observed a strong association between the absence of intentional nonadherence (statement of never deliberately missing medication) and respondent statements about generally sticking to the routine (P < 0.0001), ie, \"I take my medication because I am used to taking it.\" This important result suggests that patients are strictly adherent in two ways: the absence of intentional nonadherence and reliance on habit, which we term as \"unintentional adherence.\" 5) Finally, a multiple correspondence analysis illustrated all statistically significant relationships found in this study. Conclusion: We present a new global model of adherence in which patient adherence was improved both by reducing intentional nonadherence and by promoting the abovementioned unintentional adherence by habit. This model highlights the role of shared decision-making and the trust felt by patients in their doctors. These results could exert a major impact on medical practice and education by demonstrating the importance of physicians' attitudes, involving the patient in decisions (shared decision-making), offering information about medicines and diseases (patient education), understanding the problems of patients, and taking their needs into account (empathy). The development of these attitudes should be an important aspect of the medical curricula. Keywords: adherence; intentionality; intentional; unintentional, doctor-patient relationship, shared medical decision, trust, habit, side effects of drugs

Background Rapid referral of traumatic brain injury (TBI) patients requiring emergency neurosurgery to a specialized trauma center can significantly reduce morbidity and mortality. Currently, no model has been reported to predict the need for acute neurosurgery in severe to moderate TBI patients. This study aims to evaluate the performance of Machine Learning-based models to establish to predict the need for neurosurgery procedure within 24 h after moderate to severe TBI. Methods Retrospective multicenter cohort study using data from a national trauma registry (Traumabase®) from November 2011 to December 2020. Inclusion criteria correspond to patients over 18 years old with moderate or severe TBI (Glasgow coma score ≤ 12) during prehospital assessment. Patients who died within the first 24 h after hospital admission and secondary transfers were excluded. The population was divided into a train set (80% of patients) and a test set (20% of patients). Several approaches were used to define the best prognostic model (linear nearest neighbor or ensemble model). The Shapley Value was used to identify the most relevant pre-hospital variables for prediction. Results 2159 patients were included in the study. 914 patients (42%) required neurosurgical intervention within 24 h. The population was predominantly male (77%), young (median age 35 years [IQR 24–52]) with severe head injury (median GCS 6 [3–9]). Based on the evaluation of the predictive model on the test set, the logistic regression model had an AUC of 0.76. The best predictive model was obtained with the CatBoost technique (AUC 0.81). According to the Shapley values method, the most predictive variables in the CatBoost were a low initial Glasgow coma score, the regression of pupillary abnormality after osmotherapy, a high blood pressure and a low heart rate. Conclusion Machine learning-based models could predict the need for emergency neurosurgery within 24 h after moderate and severe head injury. Potential clinical benefits of such models as a decision-making tool deserve further assessment. The performance in real-life setting and the impact on clinical decision-making of the model requires workflow integration and prospective assessment.

IntroductionStatus epilepticus (SE) in adults is a serious neurological emergency that can lead to high morbidity and mortality rates. Although functional outcomes are often assessed using general scoring systems, limited data on health-related quality of life (HRQoL) in patients admitted to intensive care units (ICUs) are still limited. Furthermore, comprehensive evaluations of patient-reported physical, cognitive, mental health and psychological outcomes are lacking in this population. POSEIDON 2 aims to assess HRQoL and cognitive, physical and psychological impairments at 3 and 12 months after ICU discharge following SE and quantify caregiver burden.Methods and analysisPOSEIDON 2 is a prospective, multicentre, longitudinal study conducted in 19 French ICUs. The study combines data from the SE ICTAL Registry with data from patients who survived admission to the ICU for SE, who will be recruited for the study. The study also includes patient-reported outcome (PRO) data collected 3 (M3) and 12 (M12) months after discharge from the ICU using validated instruments. The Zarit scale will be used to measure the burden on caregivers at M3 and M12. The primary endpoint is the prevalence of overall HRQOL impairment at M3 and M12, as defined by dichotomous scores on the physical and mental components of the 36-Item Short Form Health Survey compared with those of the general population. Secondary endpoints include domain-specific impairments, such as cognitive function, dependence, mental health and patient experiences. The sample size has been calculated based on an estimated prevalence of 75% for HRQoL impairment, with a planned sample size of 140 patients.Ethics and disseminationThe POSEIDON 2 study protocol received ethical approval from the ethics committee ‘Comité de Protection des Personnes Ouest VI’ on 5 October 2023 (#2023-A01223-42). The study is conducted in accordance with the Declaration of Helsinki, Good Clinical Practice and the regulatory requirements of France. Written informed consent is obtained from participants, who are able to decline participation or withdraw from the study at any time. Findings will be disseminated through publication in peer-reviewed journals and presentations at scientific conferences.Trial registration numberNCT06100978.

The selection of predicted genes for interspecies communication within the CPR and DPANN genomes sheds some light onto the underlying mechanisms supporting their inferred symbiotic lifestyle. Also, considering the lack of core pathways such as the de novo synthesis of nucleotides or amino acids in the CPR and DPANN lineages, the persistence of these genes highlights how determinant social traits can be for the survival of some microorganisms. Finally, the considerable number of variants of QS proteins identified among the 69 CPR and DPANN phyla substantially expands our knowledge of prokaryotic communication across the tree of life and suggests that the multiplicity of “dialects” in the microbial world is probably larger than previously appreciated. The bacterial candidate phyla radiation (CPR) and the archaeal DPANN superphylum are two novel lineages that have substantially expanded the tree of life due to their large phylogenetic diversity. Because of their ultrasmall size, reduced genome, and lack of core biosynthetic capabilities, most CPR and DPANN members are predicted to be sustained through their interactions with other species. How the few characterized CPR and DPANN symbionts achieve these critical interactions is, however, poorly understood. Here, we conducted an in silico analysis on 2,597 CPR/DPANN genomes to test whether these ultrasmall microorganisms might encode homologs of reference proteins involved in the synthesis and/or the detection of 26 different types of communication molecules (quorum sensing [QS] signals), since QS signals are well-known mediators of intra- and interorganismic relationships. We report the discovery of 5,693 variants of QS proteins distributed across 63 CPR and 6 DPANN phyla and associated with 14 distinct types of communication molecules, most of which were characterized as interspecies QS signals. IMPORTANCE The selection of predicted genes for interspecies communication within the CPR and DPANN genomes sheds some light onto the underlying mechanisms supporting their inferred symbiotic lifestyle. Also, considering the lack of core pathways such as the de novo synthesis of nucleotides or amino acids in the CPR and DPANN lineages, the persistence of these genes highlights how determinant social traits can be for the survival of some microorganisms. Finally, the considerable number of variants of QS proteins identified among the 69 CPR and DPANN phyla substantially expands our knowledge of prokaryotic communication across the tree of life and suggests that the multiplicity of “dialects” in the microbial world is probably larger than previously appreciated.