Increase in Tomato Locule Number Is Controlled by Two Single-Nucleotide Polymorphisms Located

In tomato (Solanum lycopersicum) fruit, the number of locules (cavities containing seeds that are derived from carpels) varies from two to up to 10 or more. Locule number affects fruit shape and size and is controlled by several quantitative trait loci(QTLs). The large majority of the phenotypic variation is explained by two of these QTLs, fasciated (fas) and locule number (lc), that interact epistatically with one another. FAS has been cloned, and mutations in the gene are described as key factors leading to the increase in fruit size in modern varieties. Here, we report the map-based cloning of lc. The lc QTL includes a 1,600-bp region that is located 1,080 bp from the 3# end of WUSCHEL, which encodes a homeodomain protein that regulates stem cell fate in plants. The molecular evolution of lc showed a reduction of diversity in cultivated accessions with the exception of two single-nucleotide polymorphisms. These two single-nucleotide polymorphisms were shown to be responsible for the increase in locule number. An evolutionary model of locule number is proposed herein, suggesting that the fas mutation appeared after the mutation in the lc locus to confer the extreme high-locule-number phenotype

CREWS - l'Ecritoire Analysis for the Implementation of a medical image database for mammography

International audienceIn this paper, we present our approach in order to implement a Medical Image Database (MIDB) for archiving mammograms and their related information in the Department of Radiology of the Necker Hospital (Paris). The aim of such a database is to help breast cancer screening in clinics, research and education. As implementation of such a MIDB requires the understanding of users' needs, we have analyzed requirements by using the Crews-l'Ecritoire (Cooperative REquirements With Scenarios) approach developed in our laboratory. This approach is based on the "Requirement Engineering" concept. It helps understanding users' needs using a semi-automatic analysis of textual scenarios, i.e. scenarios written in natural language. This approach mixes concepts of goals and of scenarios into the notion of "Requirement Chunk". Authored scenarios and goal discovery are guided by rules, which lead to a structured network of scenarios. Our analysis resulted in 58 Requirements Chunks gathering 72 authored scenarios and 300 goals which represent MIDB services requested by radiologists in the course of their daily practice

HIV-1 VPR impairs cell growth through the inactivation of two genetically distinct host cell proteins

International audiencen.

Protocol for a prospective multicenter longitudinal randomized controlled trial (CALIN) of sensory-tonic stimulation to foster parent child interactions and social cognition in very premature infants

IntroductionPremature birth is associated with long-term somatic and neurological disorders, including cognitive, social and behavioral impairments. Moreover, the mothers of infants born preterm exhibit a higher prevalence of anxiety and depressive symptoms after birth. Early rehabilitation, developmental care, and parenting support have already been shown to have a positive impact on neurological outcome. However, no randomized controlled study has so far assessed the effects on parenting and long-term neurological outcomes of proprioceptive stimulation to trigger positive brain plasticity in very preterm babies. The CALIN project will therefore investigate the impact of sensory-tonic stimulation (STS) of extremely preterm infants by their parents on child parent interactions, infants' morphological and functional brain development and subsequent cognition (including social cognition), and parents' anxiety and depressive symptoms in the postpartum period.Methods and analysisInfants born between 25 and 32 weeks of gestation will be randomly assigned to the “STS + Kangaroo care” or “Kangaroo care” group. The primary endpoint, child and parent interactions, will be rated at 12 months corrected age using the Coding Interactive Behavior system. Secondary endpoints include: 1/functional and anatomical brain maturation sequentially assessed during neonatal hospitalization using electroencephalogram (EEG), amplitude-integrated EEG (aEEG), cranial ultrasound and MRI performed at term-corrected age, 2/social and cognitive outcomes assessed at 15 months, 2, 4 and 6 years, and 3/parents' anxiety and depressive symptoms assessed at 7 ± 1 weeks after birth, using dedicated questionnaires.Ethics and disseminationThis study was approved by the French Ethics Committee for the Protection of Persons on 18 October 2021. It is registered with the French National Agency for the Safety of Medicines and Health Products (ANSM; no. 2020-A00382–37). The registry number on ClinicalTrials.gov is NCT04380051

Genome analysis of the necrotrophic fungal pathogens Sclerotinia sclerotiorum and Botrytis cinerea

Sclerotinia sclerotiorum and Botrytis cinerea are closely related necrotrophic plant pathogenic fungi notable for their wide host ranges and environmental persistence. These attributes have made these species models for understanding the complexity of necrotrophic, broad host-range pathogenicity. Despite their similarities, the two species differ in mating behaviour and the ability to produce asexual spores. We have sequenced the genomes of one strain of S. sclerotiorum and two strains of B. cinerea. The comparative analysis of these genomes relative to one another and to other sequenced fungal genomes is provided here. Their 38–39 Mb genomes include 11,860–14,270 predicted genes, which share 83% amino acid identity on average between the two species. We have mapped the S. sclerotiorum assembly to 16 chromosomes and found large-scale co-linearity with the B. cinerea genomes. Seven percent of the S. sclerotiorum genome comprises transposable elements compared t

5-oxoETE triggers nociception in constipation-predominant irritable bowel syndrome through MAS-related G protein-coupled receptor D.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is characterized by chronic abdominal pain concurrent with altered bowel habit. Polyunsaturated fatty acid (PUFA) metabolites are increased in abundance in IBS and are implicated in the alteration of sensation to mechanical stimuli, which is defined as visceral hypersensitivity. We sought to quantify PUFA metabolites in patients with IBS and evaluate their role in pain. Quantification of PUFA metabolites by mass spectrometry in colonic biopsies showed an increased abundance of 5-oxoeicosatetraenoic acid (5-oxoETE) only in biopsies taken from patients with IBS with predominant constipation (IBS-C). Local administration of 5-oxoETE to mice induced somatic and visceral hypersensitivity to mechanical stimuli without causing tissue inflammation. We found that 5-oxoETE directly acted on both human and mouse sensory neurons as shown by lumbar splanchnic nerve recordings and Ca2+ imaging of dorsal root ganglion (DRG) neurons. We showed that 5-oxoETE selectively stimulated nonpeptidergic, isolectin B4 (IB4)-positive DRG neurons through a phospholipase C (PLC)- and pertussis toxin-dependent mechanism, suggesting that the effect was mediated by a G protein-coupled receptor (GPCR). The MAS-related GPCR D (Mrgprd) was found in mouse colonic DRG afferents and was identified as being implicated in the noxious effects of 5-oxoETE. Together, these data suggest that 5-oxoETE, a potential biomarker of IBS-C, induces somatic and visceral hyperalgesia without inflammation in an Mrgprd-dependent manner. Thus, 5-oxoETE may play a pivotal role in the abdominal pain associated with IBS-C.BBSRC BB/R006210/1 to James R F Hockley and Ewan St John Smith Rosetrees 834 Postdoctoral Grant (A1296) awarded to James R F Hockley and Ewan St John Smit

SNX12 Role in Endosome Membrane Transport

In this paper, we investigated the role of sorting nexin 12 (SNX12) in the endocytic pathway. SNX12 is a member of the PX domain-containing sorting nexin family and shares high homology with SNX3, which plays a central role in the formation of intralumenal vesicles within multivesicular endosomes. We found that SNX12 is expressed at very low levels compared to SNX3. SNX12 is primarily associated with early endosomes and this endosomal localization depends on the binding to 3-phosphoinositides. We find that overexpression of SNX12 prevents the detachment (or maturation) of multivesicular endosomes from early endosomes. This in turn inhibits the degradative pathway from early to late endosomes/lysosomes, much like SNX3 overexpression, without affecting endocytosis, recycling and retrograde transport. In addition, while previous studies showed that Hrs knockdown prevents EGF receptor sorting into multivesicular endosomes, we find that overexpression of SNX12 restores the sorting process in an Hrs knockdown background. Altogether, our data show that despite lower expression level, SNX12 shares redundant functions with SNX3 in the biogenesis of multivesicular endosomes

Genomic Analysis of the Necrotrophic Fungal Pathogens Sclerotinia sclerotiorum and Botrytis cinerea

Sclerotinia sclerotiorum and Botrytis cinerea are closely related necrotrophic plant pathogenic fungi notable for their wide host ranges and environmental persistence. These attributes have made these species models for understanding the complexity of necrotrophic, broad host-range pathogenicity. Despite their similarities, the two species differ in mating behaviour and the ability to produce asexual spores. We have sequenced the genomes of one strain of S. sclerotiorum and two strains of B. cinerea. The comparative analysis of these genomes relative to one another and to other sequenced fungal genomes is provided here. Their 38–39 Mb genomes include 11,860–14,270 predicted genes, which share 83% amino acid identity on average between the two species. We have mapped the S. sclerotiorum assembly to 16 chromosomes and found large-scale co-linearity with the B. cinerea genomes. Seven percent of the S. sclerotiorum genome comprises transposable elements compared to <1% of B. cinerea. The arsenal of genes associated with necrotrophic processes is similar between the species, including genes involved in plant cell wall degradation and oxalic acid production. Analysis of secondary metabolism gene clusters revealed an expansion in number and diversity of B. cinerea–specific secondary metabolites relative to S. sclerotiorum. The potential diversity in secondary metabolism might be involved in adaptation to specific ecological niches. Comparative genome analysis revealed the basis of differing sexual mating compatibility systems between S. sclerotiorum and B. cinerea. The organization of the mating-type loci differs, and their structures provide evidence for the evolution of heterothallism from homothallism. These data shed light on the evolutionary and mechanistic bases of the genetically complex traits of necrotrophic pathogenicity and sexual mating. This resource should facilitate the functional studies designed to better understand what makes these fungi such successful and persistent pathogens of agronomic crops

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)