Attitudes et intentions du locuteur dans la traduction française du texte bouddhique Dhammapada : Marqueurs linguistiques et rôles de la modalité

Dans le présent travail, nous cherchons à repérer les attitudes et intentions du locuteur dans la traduction française du texte bouddhique Dhammapada. Nous identifions d’une part les marqueurs des attitudes du locuteur sur ses propos, autrement dit de la modalité, et d’autre part les rôles de ces marqueurs. Pour ce faire, nous nous basons sur la typologie de Le Querler (2004), qui a une approche sémantique et syntaxique dans l’étude de la modalité. Nous effectuons dans ce travail une analyse qualitative de la modalité. Notre corpus, le Dhammapada, est un recueil de versets qui rassemble les enseignements du Bouddha. Il est question d’un des textes les plus anciens et influents de la littérature canonique bouddhique. Les marqueurs morphologiques, lexicaux et syntaxiques indiquent des attitudes par rapport à des faits, comme des implications, un degré de certitude ou un conseil. Les implications renvoient aux modalités implicatives et les autres respectivement aux modalités épistémiques et aux modalités intersubjectives. En plus de cela, les marqueurs lexicaux peuvent présenter une attitude qui est associée à une connotation positive ou négative. Les marqueurs morphologiques sont représentés essentiellement par des tiroirs verbaux, les marqueurs lexicaux par des classes de mots et les marqueurs syntaxiques par des constructions propositionnelles ou par des signes de ponctuation. Par ailleurs, différentes modalités peuvent être combinées entre elles pour exprimer une attitude du locuteur. Les modalités épistémiques associées aux modalités implicatives indiquent une implication certaine ou incertaine. Ces deux types de modalités peuvent être combinées aux modalités appréciatives. Les implications comportent alors une connotation positive ou négative. Ces connotations sont exprimées de plusieurs façons différentes. Le contexte et les autres expressions des versets peuvent apporter une connotation nouvelle ou opposée, qui est positive ou négative, à un fait. Dans le Dhammapada, l’attitude du locuteur ou autrement dit la modalité est marquée explicitement pour appuyer l’opinion de l’auteur sur ces propos, sur le bien et sur les attitudes ou comportements bénéfiques à adopter. En indiquant ce qui est bien ou mal, on veut montrer qu’il vaut mieux suivre ce qui est bien. On oriente ainsi la lecture des versets du Dhammapada

FBXO32, encoding a member of the SCF complex, is mutated in dilated cardiomyopathy

Ubiquitination defect in cells expressing mutant FBXO32. a Co-immunopricipitation analysis. HEK293 cells were transfected with the indicated plasmids and immunoblot analysis was performed from total cell lysates using a specific anti-ubiquitin antibody. FBXO32 expression is shown as well as GAPDH. The blot is representative of three independent experiments. b Immunoblot analysis of the ubiquitination in cardiomyocytes. Cells were transfected with the Flag-FBXO32-WT or Flag-FBXO32-Mutant and whole cell extracts were analyzed by immunoblotting using the indicated antibodies. (TIF 1928 kb

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1.

With resistance to most antimalarials increasing, it is imperative that new drugs are developed. We previously identified an aryl acetamide compound, MMV006833 (M-833), that inhibited the ring-stage development of newly invaded merozoites. Here, we select parasites resistant to M-833 and identify mutations in the START lipid transfer protein (PF3D7_0104200, PfSTART1). Introducing PfSTART1 mutations into wildtype parasites reproduces resistance to M-833 as well as to more potent analogues. PfSTART1 binding to the analogues is validated using organic solvent-based Proteome Integral Solubility Alteration (Solvent PISA) assays. Imaging of invading merozoites shows the inhibitors prevent the development of ring-stage parasites potentially by inhibiting the expansion of the encasing parasitophorous vacuole membrane. The PfSTART1-targeting compounds also block transmission to mosquitoes and with multiple stages of the parasite's lifecycle being affected, PfSTART1 represents a drug target with a new mechanism of action

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

An electrochemical flow analysis system for putrescine using immobilized putrescine oxidase and horseradish peroxidase

An electrochemical flow analysis system was optimized together with immobilized putrescine oxidase and horseradish peroxidase for putrescine measurement. Four coupling agents, suberic acid bis(N-hydroxysuccinimide ester), gamma-maleimidobutyric N-hydroxysuccinimide ester, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and glutaraldehyde, were used for immobilizing the two enzymes on porous aminopropyl glass beads to form a bienzymic detection column. Although the glutaraldehyde crosslinking procedure offered the highest response, the immobilized bienzyme system was responsive to putrescine, spermidine (123% of the putrescine response at 250 muM) and cadaverine (98% of the putrescine response). In contrast, the enzymes immobilized on the glass beads using suberic acid bis(N-hydroxysuccinimide ester) offered significantly better selectivity towards putrescine at the same concentration. For comparison, cadaverine and spermidine only provoked a response of 4.7% and 27.5% of the putrescine signal. The response to cadaverine and spermidine was further suppressed by lowering the detection pH from 8 to 7. At 250 muM, the response obtained for cadaverine and spermidine was only 1.5% and 3.9%, respectively, of the signal obtained for putrescine. A linear response to putrescine was obtained from 5 to 75 muM (0.629 muAs muM-1, R2 = 0.997) with a detection limit of 5 muM (S/N = 3). The amperometric response retained 75% of its initial value after 600 repeated injections. The immobilized PUO/HRP (putrescine oxidase/horseradish peroxidase) was successfully demonstrated for measuring putrescine in fish extracts as an indicator of fish spoilage.NRC publication: Ye

An electrochemical flow analysis system for putrescine using immobilized putrescine oxidase and horseradish peroxidase

An electrochemical flow analysis system was optimized together with immobilized putrescine oxidase and horseradish peroxidase for putrescine measurement. Four coupling agents, suberic acid bis(N-hydroxysuccinimide ester), gamma-maleimidobutyric N-hydroxysuccinimide ester, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and glutaraldehyde, were used for immobilizing the two enzymes on porous aminopropyl glass beads to form a bienzymic detection column. Although the glutaraldehyde crosslinking procedure offered the highest response, the immobilized bienzyme system was responsive to putrescine, spermidine (123% of the putrescine response at 250 muM) and cadaverine (98% of the putrescine response). In contrast, the enzymes immobilized on the glass beads using suberic acid bis(N-hydroxysuccinimide ester) offered significantly better selectivity towards putrescine at the same concentration. For comparison, cadaverine and spermidine only provoked a response of 4.7% and 27.5% of the putrescine signal. The response to cadaverine and spermidine was further suppressed by lowering the detection pH from 8 to 7. At 250 muM, the response obtained for cadaverine and spermidine was only 1.5% and 3.9%, respectively, of the signal obtained for putrescine. A linear response to putrescine was obtained from 5 to 75 muM (0.629 muAs muM-1, R2 = 0.997) with a detection limit of 5 muM (S/N = 3). The amperometric response retained 75% of its initial value after 600 repeated injections. The immobilized PUO/HRP (putrescine oxidase/horseradish peroxidase) was successfully demonstrated for measuring putrescine in fish extracts as an indicator of fish spoilage.NRC publication: Ye

A pilot study of procoagulant platelet extracellular vesicles and P-selectin increase during induction treatment in acute lymphoblastic leukaemia paediatric patients: two new biomarkers of thrombogenic risk?

International audienceIn paediatric acute lymphoblastic leukaemia (ALL), focus has shifted towards preventing treatment-related complications, including venous thromboembolism, the cause of significant mortality and morbidity. To better understand thrombogenic mechanisms during induction treatment, we studied the number, origin and procoagulant activity of extracellular vesicles (EVs) and P-selectin level throughout the induction course in 24 paediatric patients. EVs were mainly of platelet origin. We observed a significant increase in EV number, in platelet EV number and P-selectin level throughout the induction course. There was a correlation between higher EV and platelet EV number, P-selectin level, higher platelet count and leucocyte count. We also observed a correlation between higher EV procoagulant activity and higher platelet count and leucocyte count and higher P-selectin level. Older age and T phenotype were associated with a higher EV procoagulant activity. Platelet EV generation may play a role in thrombogenic complications in ALL patients and could serve as a biomarker to identify patients with a high risk of thrombosis. As a marker of platelet activation, P-selectin may be another relevant marker with the advantage of being easier to analyse in clinical practice