Lutetium(III) cyclo­tetra­phosphate

Single crystals of the title compound, tetra­lutetium(III) tris­(cyclo­tetra­phosphate), Lu4(P4O12)3, were obtained by solid-state reaction. The cubic structure is isotypic with its AlIII and ScIII analogues and is built up from four-membered (P4O12)4− phosphate ring anions ( symmetry), isolated from each other and further linked through isolated LuO6 octa­hedra (.3. symmetry) via corner sharing. Each LuO6 octa­hedron is linked to six (P4O12)4− rings, while each (P4O12)4− ring is linked to eight LuO6 octa­hedra

Genetic regulation of RNA splicing in human pancreatic islets

Background Non-coding genetic variants that influence gene transcription in pancreatic islets play a major role in the susceptibility to type 2 diabetes (T2D), and likely also contribute to type 1 diabetes (T1D) risk. For many loci, however, the mechanisms through which non-coding variants influence diabetes susceptibility are unknown. Results We examine splicing QTLs (sQTLs) in pancreatic islets from 399 human donors and observe that common genetic variation has a widespread influence on the splicing of genes with established roles in islet biology and diabetes. In parallel, we profile expression QTLs (eQTLs) and use transcriptome-wide association as well as genetic co-localization studies to assign islet sQTLs or eQTLs to T2D and T1D susceptibility signals, many of which lack candidate effector genes. This analysis reveals biologically plausible mechanisms, including the association of T2D with an sQTL that creates a nonsense isoform in ERO1B, a regulator of ER-stress and proinsulin biosynthesis. The expanded list of T2D risk effector genes reveals overrepresented pathways, including regulators of G-protein-mediated cAMP production. The analysis of sQTLs also reveals candidate effector genes for T1D susceptibility such as DCLRE1B, a senescence regulator, and lncRNA MEG3. Conclusions These data expose widespread effects of common genetic variants on RNA splicing in pancreatic islets. The results support a role for splicing variation in diabetes susceptibility, and offer a new set of genetic targets with potential therapeutic benefit.This research was supported by Ministerio de Ciencia e Innovación (BFU2014-54284-R, RTI2018-095666-B-I00), Medical Research Council (MR/L02036X/1), a Wellcome Trust Senior Investigator Award (WT101033), European Research Council Advanced Grant (789055), EU Horizon 2020 TDSystems (667191), ESPACE (874710), and Marie Sklodowska-Curie (643062, ZENCODE). S.B.G was supported by a Juan de la Cierva postdoctoral fellowship (MINECO; FJCI-2017-32090). M.C.A was supported by a Boehringer Ingelheim Fonds PhD fellowship. Work in CRG was supported by the CERCA Programme, Generalitat de Catalunya, Centro de Excelencia Severo Ochoa (CEX2020-001049), and support of the Spanish Ministry of Science and Innovation to the EMBL partnership. Work in Imperial College was supported by NIHR Imperial Biomedical Research Centre. M.I. was supported by a European Research Council consolidator award (101002275). D.J.M.C. and J.A.T. were supported by JDRF grants 9-2011-253, 5-SRA-2015-130-A-N, 4- SRA-2017-473-A-N, and Wellcome grants 091157/Z/10/Z and 107212/Z/15/Z, to the Diabetes and Inflammation Laboratory, Oxford, as well as the Oxford Biomedical Research Computing (BMRC) facility, a joint development between the Wellcome Centre for Human Genetics and the Big Data Institute supported by Health Data Research UK and NIHR Oxford Biomedical Research Centre, and Wellcome Trust Core Award grant 203141/Z/16/Z. D.M.J.C analysis with the UK Biobank Resource was conducted under Application 31295. A.L.G. is a Wellcome Senior Fellow in Basic Biomedical Science and was supported by the Wellcome Trust (095101, 200837, 106130, 203141), the NIDDK (U01DK105535 and UM1 DK126185), and the Oxford NIHR Biomedical Research Centre.Peer Reviewed"Article signat per 20 autors/es: Goutham Atla, Silvia Bonàs-Guarch, Mirabai Cuenca-Ardura, Anthony Beucher, Daniel J. M. Crouch, Javier Garcia-Hurtado, Ignasi Moran, the T2DSystems Consortium, Manuel Irimia, Rashmi B. Prasad, Anna L. Gloyn, Lorella Marselli, Mara Suleiman, Thierry Berney, Eelco J. P. de Koning, Julie Kerr-Conte, Francois Pattou, John A. Todd, Lorenzo Piemonti & Jorge Ferrer"Postprint (published version

Aluminium cyclo­hexa­phosphate

Single crystals of the title compound, Al2P6O18, were obtained by solid-state reaction. The monoclinic structure is isotypic with its CrIII, GaIII and RuIII analogues and is built up of six-membered phosphate ring anions, P6O18 6−, isolated from each other and further linked by isolated AlO6 octa­hedra by sharing corners. Each AlO6 octa­hedron is linked to four P6O18 6− rings. More accurately, two rings are linked through bidentate diphosphate groups attached in the cis-positions to the AlO6 octa­hedron. The other two rings are linked to the two remaining corners, also in cis-positions of the AlO6 octa­hedron

Semi-automatic algorithm for construction of the left ventricular area variation curve over a complete cardiac cycle

<p>Abstract</p> <p>Background</p> <p>Two-dimensional echocardiography (2D-echo) allows the evaluation of cardiac structures and their movements. A wide range of clinical diagnoses are based on the performance of the left ventricle. The evaluation of myocardial function is typically performed by manual segmentation of the ventricular cavity in a series of dynamic images. This process is laborious and operator dependent. The automatic segmentation of the left ventricle in 4-chamber long-axis images during diastole is troublesome, because of the opening of the mitral valve.</p> <p>Methods</p> <p>This work presents a method for segmentation of the left ventricle in dynamic 2D-echo 4-chamber long-axis images over the complete cardiac cycle. The proposed algorithm is based on classic image processing techniques, including time-averaging and wavelet-based denoising, edge enhancement filtering, morphological operations, homotopy modification, and watershed segmentation. The proposed method is semi-automatic, requiring a single user intervention for identification of the position of the mitral valve in the first temporal frame of the video sequence. Image segmentation is performed on a set of dynamic 2D-echo images collected from an examination covering two consecutive cardiac cycles.</p> <p>Results</p> <p>The proposed method is demonstrated and evaluated on twelve healthy volunteers. The results are quantitatively evaluated using four different metrics, in a comparison with contours manually segmented by a specialist, and with four alternative methods from the literature. The method's intra- and inter-operator variabilities are also evaluated.</p> <p>Conclusions</p> <p>The proposed method allows the automatic construction of the area variation curve of the left ventricle corresponding to a complete cardiac cycle. This may potentially be used for the identification of several clinical parameters, including the area variation fraction. This parameter could potentially be used for evaluating the global systolic function of the left ventricle.</p

Dietary Proteins as Determinants of Metabolic and Physiologic Functions of the Gastrointestinal Tract

Dietary proteins elicit a wide range of nutritional and biological functions. Beyond their nutritional role as the source of amino acids for protein synthesis, they are instrumental in the regulation of food intake, glucose and lipid metabolism, blood pressure, bone metabolism and immune function. The interaction of dietary proteins and their products of digestion with the regulatory functions of the gastrointestinal (GI) tract plays a dominant role in determining the physiological properties of proteins. The site of interaction is widespread, from the oral cavity to the colon. The characteristics of proteins that influence their interaction with the GI tract in a source-dependent manner include their physico-chemical properties, their amino acid composition and sequence, their bioactive peptides, their digestion kinetics and also the non-protein bioactive components conjugated with them. Within the GI tract, these products affect several regulatory functions by interacting with receptors releasing hormones, affecting stomach emptying and GI transport and absorption, transmitting neural signals to the brain, and modifying the microflora. This review discusses the interaction of dietary proteins during digestion and absorption with the physiological and metabolic functions of the GI tract, and illustrates the importance of this interaction in the regulation of amino acid, glucose, lipid metabolism, and food intake

Is the heat on for plant mitochondria?

International audienc

Devenir respiratoire à l’âge scolaire de la dysplasie bronchopulmonaire [Respiratory outcome of bronchopulmonary dysplasia in school-age children]

National audienceBackground - Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of infancy. The influence of its initial severity on long-term respiratory outcome remains uncertain. Objectives - The purpose of this study was to examine the impact of "new BPD" on respiratory morbidity as well as respiratory function at rest and during exercise in school-age children. Methods - The 93 preterm newborns (<33 weeks gestation) presenting with BPD between 1997 and 2004 at the Rennes University Hospital had been proposed for a specific follow-up program. The children included in this cohort and presenting without severe handicap or motor deficit were eligible for this observational retrospective study. Their standardized clinical evaluation and the results of the pulmonary function tests and cardiopulmonary exercise tests performed between the ages of 7 and 14 years were studied. BPD was considered to be moderate when respiratory or oxygen support continued at 36 weeks gestation with an FiO2 less than 30% and severe when FiO2 was greater than 30%. Results - Among the 36 children assessed, the initial severity of the BPD was mild in 12 cases, moderate in 12 cases, and severe in 12 cases. The mean age at the time of the pulmonary function test (PFT) was 9.9 (±1.9) years, 19 children (53%) had respiratory symptoms during the year before the test, and six (17%) underwent long-term treatment. The PFT was abnormal for 32 children (89%): 23 showed airway obstruction, 16 hyperinflation, three increases in bronchial reactivity, and two restrictions. The residual volume/total lung capacity ratio was the only parameter related to the severity of BPD (P<0.05). The cardiopulmonary exercise test was given to 35 children: 15 of them had normal exercise ability but with a limited ventilatory reserve. Conclusions - Half of the children included in this "new-BPD" follow-up cohort had clinical respiratory morbidity and most of the children followed presented with persistent alterations in pulmonary function tests at school age, which were not associated with significant alterations in the maximum aerobic performance

Efficient Diagnosis of Vulvovaginal Candidiasis by Use of a New Rapid Immunochromatography Test▿

The clinical symptoms of vulvovaginal candidiasis (VVC) are nonspecific, and misdiagnosis is common, leading to a delay in the initiation of antifungal treatment. We evaluated a new immunochromatography test (ICT), the CandiVagi assay (SR2B, Avrille, France), for the rapid diagnosis of VVC. This test, which employs an immunoglobulin M antibody directed against the β-1,2-mannopyranosyl epitopes found in the yeast cell wall, was compared with direct microscopic examination and culture of vaginal swabs. Two-hundred five women were investigated, including 130 women with symptomatic vaginitis and 75 asymptomatic controls. Two vaginal swabs were obtained from each woman: one was used to prepare a wet mount and Gram-stained preparations for direct microscopic examination and was also cultured on Sabouraud dextrose agar for the isolation of Candida spp., and the second swab was used for ICT. The sensitivities of microscopic examination, culture, and ICT for the diagnosis of VVC were 61%, 100%, and 96.6%, respectively, while the specificities of the three methods were 100%, 82%, and 98.6%, respectively. ICT had a negative predictive value of 98.6%, a positive predictive value of 96.6%, and an efficiency of 98%. ICT provided a rapid result and a better compromise between sensitivity and specificity than conventional microscopy and culture for the diagnosis of VVC. This easy-to-perform diagnostic test will be useful to practitioners treating women with symptoms of vaginitis

Experimental Evidence for Seed Metabolic Allometry in Barrel Medic (Medicago truncatula Gaertn.)

International audienceSeed size is often considered to be an important trait for seed quality, i.e., vigour and germination performance. It is believed that seed size reflects the quantity of reserve material and thus the C and N sources available for post-germinative processes. However, mechanisms linking seed size and quality are poorly documented. In particular, specific metabolic changes when seed size varies are not well-known. To gain insight into this aspect, we examined seed size and composition across different accessions of barrel medic (Medicago truncatula Gaertn.) from the genetic core collection. We conducted multi-elemental analyses and isotope measurements, as well as exact mass GC–MS metabolomics. There was a systematic increase in N content (+0.17% N mg−1) and a decrease in H content (–0.14% H mg−1) with seed size, reflecting lower lipid and higher S-poor protein quantity. There was also a decrease in 2H natural abundance (δ2H), due to the lower prevalence of 2H-enriched lipid hydrogen atoms that underwent isotopic exchange with water during seed development. Metabolomics showed that seed size correlates with free amino acid and hexoses content, and anticorrelates with amino acid degradation products, disaccharides, malic acid and free fatty acids. All accessions followed the same trend, with insignificant differences in metabolic properties between them. Our results show that there is no general, proportional increase in metabolite pools with seed size. Seed size appears to be determined by metabolic balance (between sugar and amino acid degradation vs. utilisation for storage), which is in turn likely determined by phloem source metabolite delivery during seed development