glycosidic linkages. For the CAD C/D modified plants, only γCellulose and βLignin are observed; due to analogous enthalpy values, those modes have the same molecular origin as in the non-modified plant. So, the βLignin mode is associated with the molecular mobility of the lignin-OH groups. The CAD C/D genemutation changes the chemical structure of lignin, which promotes hydrogen bonds in the network and inhibits molecular mobility of glucosidic rings. It is also interesting to note that the DML6 genemutation induces a higher cooperativity of this βCellulose relaxation than in wild vegetal composites. In fact, this mutation promotes molecular mobility of glycosidic rings thanks to β1–4 glycosidic linkages.
Considering the clinical studies, recent evidences point to a possible role of network dysfunction to cause the very early visual impairments observed in DS patients (arguing for the channelopathy theory). Indeed, the study proposed by Ricci et al. 2015 comprises five DS cases, that are visually impaired early in life, but only one patient carries the SCN1A genemutation. However, it is difficult to conclude on one patient diagnosis. Also, a similar progressive neurocognitive decline was observed in two children with DS, carrying de novo SCN1A truncations and different epileptic phenotype severity (Riva et al., 2009). Passamonti et al. 2015 shows a family with inherited transmission where all the members have visual problems, even one patient who carries the mutation, but never had seizures. However, this patient was tested at 74 years of age, and the visual problems could be a consequence of normal aging (Passamonti et al., 2015). No study thus far evaluated visual problems before the appearance of the first febrile/afebrile seizure. Therefore, it is possible that the visual impairment is the first behavioral consequence of seizures. Interestingly, however, visual deterioration has rarely been reported following a GTC event (Subash et al., 2010). In animal models, the visual-spatial memory is affected following neo-natal seizures in normal brains (Holmes et al., 1998; Neill et al., 1996). Also attention importantly influences visual perception (Sundberg et al., 2012) and attention deficits (associated with PFC dysfunction) are present in DS children at the onset.
Our results are consistent with previous reports that suggested that MEN1 genemutation is a rare event in pituitary adenomas. Indeed, Zhuang et al. using single strand conformational polymorphism analysis found only 2 missense mutations among 4 pituitary adenomas with LOH for MEN1 in a sample of 39 sporadic tumours (9). Prezant et al. using dideoxy fingerprinting analysis (which is more sensitive) studied 45 sporadic tumours but failed to reveal any mutations in the coding sequence of MEN1 (10). Recently, in a sample of 31 sporadic tumours, Tanaka et al. detected only 1 nonsense mutation in a GH/PRL adenoma with LOH in 11q13 (11).
of cellulose. We analysed the evolution of these modes with increasing moisture content and we observed, accordingly with Mont`es et al [ 19 – 21 ], that the β relaxation mode was not always detectable by dynamic dielectric spectroscopy. Contrarily, by TSC, the latter mode can be followed for each state of hydration. Moreover, a study of poplar cell wall by dielectric techniques shows the contribution of cellulose and lignin in the chain dynamics of vegetal composites [ 22 ]. Consequently, molecular mobility can become a tool for identifying mutation and lignin structure elucidation. TSC is a promising route to identify genemutation in Arabidopsis
Известен также аналог патента - способ секвенирования экзонов и промоторной области гена COL4A5 [Martin Р. и др. High mutation detection rate in the COL4A5 collagen gene in suspected Alport syndrome using PCR and direct DNA sequencing // J. Am. Soc. Nephrol. JASN. - 1998. - №12 (9). - C. 2291-2301] методом Сэнгера. Авторами данного способа вариант нуклеотидной последовательности COL4A5 c. 1871G>A, p. (Gly624Asp) был
firstname.lastname@example.org ; email@example.com
Abstract The peel color of fruit is an important commercial trait in cucumber, but the underlying molecular basis is largely unknown. A mutant showing light green exocarp was discovered from ethyl methane sulfonate (EMS) mutagenized cucumber line 406 with dark green exocarp. Genetic analysis showed the mutant phenotype is conferred by a single recessive gene, here designated as lgp (light green peel). By re-sequencing of bulked segregants, we identiﬁed the candidate gene Csa7G051430 encoding ACCUMULATION AND REPLICATION OF CHLOROPLASTS 5 (ARC5) that plays a vital role in chloroplast division in Arabidopsis. A single nucleotide polymorphism (SNP) causing amino acid alteration in the conserved GTPase domain of Csa7G051430 showed co-segregation with the altered phenotype. Furthermore, the transient RNA interference of this gene resulted in reduced number and enlarged size of chloroplasts, which
To explore the role of NAD + salvage pathway in the development
of DCM, we studied a mouse model that displays an Lmna muta- tion changing the histidine in position 222 into a proline ( 18 ). The male mice develop a progressive contractile dysfunction ( Supplementary Material, Table 1 ), cardiac remodeling and die by 32–34 weeks of age ( 18 ). Lmna p.H222P corresponds to a human disease-causing mutation associated with DCM ( 19 ). Given that a consequence of altered NAD + salvage pathways would lead
allele mutations in the patient, siblings and parents.
Figure 2 De novo individual acylcarnitine synthesis by whole blood samples from the mild MCADD patient, a healthy control and a adult carrier (top panels), and from patients with classical MCADD (bottom panels). De novo acylcarnitine synthesis rates generated from deuterated palmitate in the presence of added L-carnitine by whole blood samples and derived C8/C4 acylcarnitine production rates have been determined in patient (compound heterozygous for c.985A>G and c.145C>G ACADM mutations) and a adult healthy volunteer and is compared to the same exploration performed in a adult carrier for the c.985A>G ACADM mutation (see top panels). The series of bottom panels report results of these measurements in individual patients with the classical form of MCADD and with proven homozygocy for the c.985A>G ACADM genemutation. Formations of individual [D5]-acylcarnitines in whole blood samples are relative median rates expressed as percentages of median control values (framed profiles). The ratio between the rates of production of the major C8-acylcarnitine and the C4-acylcarnitine is expressed as relative median units, i.e. as the number of fold (and not the number of percents of) median control values. Values of C8 acylcarnitine production rates in disrupted histograms are given at the top of these histograms, and values for C8/C4 acylcarnitine ratios are given below each ratio histogram. The 5 th to 95 th percentile range for relative median production rate values is given in back position of each framed series of acylcarnitine production rates. The 5 th to 95 th percentile range for relative median C8/C4 acylcarnitine ratios is represented by
In monogenic diseases, the presence of several sequence variations in the same allele may complicate our understanding of genotype-phenotype relationships. We described new alterations identified in a cystic fibrosis patient harboring a 48C>G promoter sequence variation associated in cis of a 3532AC>GTA mutation and in trans with the F508del mutation . Functional analyses including in vitro experiments confirmed the deleterious effect of the 3532GTA frameshift mutation through the creation of a premature termination codon. The analyses also revealed that the 48G promoter variant has a negative effect on both transcription and mRNA level, thus demonstrating the importance of analyzing all mutations or sequence variations with potential impact on cystic fibrosis transmembrane conductance regulator (CFTR) processing, even when the two known disease-causing mutations have already been detected. Our results emphasize the need to perform, wherever possible, functional studies that may greatly assist the interpretation of the disease-causing potential of rare mutation-associated sequence variations.
In order to make somatic mutation profiles more amenable to statistical analysis, several studies have used gene networks as prior knowledge [19, 20]. Considering genes in the context of networks instead of analysing them independently allows sharing mutation information among neighbouring genes and identifying disruptions at the level of pathways or protein complexes instead of single genes. A popular method to leverage this prior knowledge consists in using a diffusion process on the gene network. This technique first appeared for the analysis of gene expression and GWAS data [21–25], and has more recently been used for mutation profiles [26–30]. Diffusion processes allow smoothing binary vectors of somatic gene mutations into dense vectors where the mutation status of a gene is increased when it is close to mutated genes in the network. This approach led to state-of-the-art methods for the discovery of driver pathways or complexes  and for the stratification of patients into clinically relevant subtypes  using whole-exome mutation profiles. In this work we propose NetNorM, a new method to enhance mutation data with gene networks. NetNorM transforms a patient’s binary mutation profile by either removing mutations or creating “proxy” mutations based on the gene network topology, until all patients reach a consensus number of mutations. The resulting mutation matrix is binary like the initial one, nonetheless we estab- lish that it encodes new information relative to genes’ local neighbourhood mutational burden and patient mutation rates. Compared to diffusion-based methods, NetNorM exhibits two main advan- tages. First, while diffusion-based methods transform a very sparse binary mutation matrix into a dense matrix, NetNorM allows integrating somatic mutations with gene networks while keeping the mutation matrix binary and sparse. This feature allows a better interpretability of the data by humans and preserves it from unwanted noise. Second, current methods for whole exome analysis do not account for the varying background mutation rates of tumours, which can hamper statistical analysis. NetNorM fills this gap by normalising mutation profiles.
matched control population. Clot retraction was severely impaired in both recalcified PRP and whole blood. Thrombus retraction was virtually absent 20 min and up to 4 hours upon recalcification and remained strongly inhibited even 4 hours after addition of 1 U/ml thrombin, as compared to PRP from a healthy donor. Genetic analysis revealed a previously unidentified mutation in exon 18 of the ITGA2B gene. The missense mutation (c.1722A>C) led to the substitution of the Asp591 to an Ala residue of the IIb subunit. Intriguingly, our patient was homozygous for the mutation although no notion of consanguinity appeared in her family history.
J. Fungi 2020, 6, 195 8 of 14
in one of the five screened strains, the same one that showed an MIC for terbinafine of 4 mg/L (Figure 4 for illustration). The patient was a 25 year old man, he presented itchy lesions all over the inguinal region and the trunk that spread for several weeks. Some lesions were squamous, with some being annular on the trunk. The patient also presented squamous lesions on the occiput. The patient had no animals and did not mention any travel in India. His sister was also affected by a dermatophyte infection. He received oral terbinafine (250 mg/day) for 3 weeks, associated with sulconazole nitrate (10 mg/mL) and ketoconazole shampoo. The patient never came back to the consultation, so we do not know if the lesions were healed. The other four strains of T. mentagrophytes shared a wild-type profile regarding SQLE gene.
The same mutation was also be identified in 5 as- ymptomatic relatives. This suggests a low penetrance of the mutation, as already described in most sporadic cases (16,17). Noteworthy, modifier genes have been proposed to influence the penetrance of AIP muta- tions in familial and also in sporadic settings (23). In this patient we studied some proliferative markers that are used to define prognosis in several oncologic con- ditions. The AIP immunostaining was weakly positive in tumor tissue, in accordance with previous reports in non-truncating mutations. However AIP immunos- taining does not appear to have any prognostic value in prolactinomas (18,26).
Df(3R)110 (82C4-82F3). To check whether some of these point mutants affect the 5-HT 2Dro
receptor gene, we refined further the mapping using Df(3R)HTRI (82C4-82D5) that deletes 5-
HT 2Dro and the Df(3R)HTR6 (82D2-82D5) that leaves the gene intact (figure 1A) (Colas et al.,
1999b). L(3)82CDb C1644 , l(3)82CDc C931 , l(3)82CDd C142 and l(3)82CDd C360 were lethal with
4) RQ4: Comparison to Dependency Analysis: As men- tioned in Section II-C, dependency analysis is used by proof engineers to analyze their verification projects, and may high- light some unused definitions similar to those we labeled DanglingDef. To enable comparing mutation proving with dependency analysis, we used the Coq dpdgraph plugin  to obtain, for each project, (1) a dependency graph of all definitions and lemmas, and (2) a list of the names of all definitions. We also extended dpdgraph to produce a tool dubbed defusage that counts edges to definitions in graphs. As a simple baseline, we used grep to record the number of matches for each definition in each project’s .v files. The first three columns in Table VII show the project name and number of definitions that had exactly one and more than one match, respectively, with grep. These can be compared to those in the last column, which show the total number of definitions. As a more robust alternative, we used defusage on the dependency graph of each project, with three thresholds in terms of number of incoming edges: 0 (unused), 5, and 10. Columns four to six in Table VII show the number of definitions at or below each threshold for all projects.
with IBD represent only a fraction of the genetic risk . Many susceptibility genes still remain to be discovered. Gene identifica- tion in humans is hampered by several factors including variable penetrance, low relative risk associated to a single disease allele, epistasis, genetic heterogeneity of human populations and variability of environmental factors . Thus, animal models of IBD, which develop under stable and controlled laboratory conditions, represent a very useful tool to study the pathogenesis of IBD by identifying the genes involved and deciphering their mechanisms of action. We propose that Themis, due to its role on CD4 T cell functions and immune system homeostasis, should now be considered as a candidate gene for IBD susceptibility, as well as for other immune mediated diseases where a dysfunction of Treg is documented or suspected. The rat model we describe will probably help to understand how Themis directs Treg function, which is indeed an important issue given the pivotal role of Treg in maintaining immunological tolerance.
Environnement et géomatique : des métiers en mutation 4
EchoGéo, 27 | 2014
le risque majeur d’inondation. La cartographie s’appuie depuis lors sur l’utilisation de la géomatique qui peut intégrer les données géoréférencées et permettre de gérer les éléments du PPR non seulement dans sa phase d’élaboration mais aussi dans sa phase d’exploitation notamment comme document réglementaire d’urbanisme, en particulier dans les Plans locaux d’urbanisme (PLU). Ce document présente l’avantage de pouvoir rapidement évoluer grâce à l’utilisation de bases de données intégrées à un système d’information géographique ; il devient interactif quand il intègre d’autres contraintes réglementaires, comme des Servitudes d’utilité publique localisées dans les périmètres du PPR. La loi de 2003, dite loi Bachelot est venue renforcer cette réglementation. En particulier, elle institue, pour les risques technologiques, les secteurs susceptibles de faire l’objet de compensations financières dans le cas de décisions d’expropriation ou de délaissement.
L’étude constitutionnelle des gènes BRCA1 chez des patients à haut risque de prédisposition génétique a permis de mettre en évidence un très grand nombre de mutations différentes affectant ces gènes. En France, la base de données développée par Institut Curie, (Paris) et INSERM UMR-S910, (Marseille), (Caputo, 2012), regroupe aujourd’hui près de 4000 mutations différentes (1675 pour BRCA1 et 2196 pour BRCA2). Il a été rapporté quelques mutations récurrentes sur ces gènes liés à des effets fondateurs (par exemple, la mutation c.3481_3491del11 de BRCA1 décrites dans de nombreuses familles originaires de l’est de la France), (Ferla, R. et al. 2007), mais la grande majorité d’entre elles sont des mutations dites « privées ».
trouver dans l’hétérogène et l’allogène les conditions de leur transformation. À cette hybridation d’abord spontanée répond une entreprise d’hybridation volontaire, de la part d’acteurs qui se saisissent en toute conscience de ce paradigme montant qu’est l’hybride pour contester à leur tour les modèles hérités, les fi- lières d’homogénéisation, les catégories d’espaces instituées par et pour l’action. La transgression des rationalités et des normes animent ces acteurs qui emboîtent le pas de la transformation en cours des espèces d’espaces, pour que la mutation l’emporte plus vite sur la crise. L’hybridation est désormais un des paradigmes forts de l’aménagement, même si les vieux modèles résistent.
16 ABSTRACTS OF THE 27TH MEETING OF THE BELGIAN ENDOCRINE SOCIETY A compound heterozygous mutation in the luteinizing hormone/chorionic
gonadotrophin receptor gene leading to Leydig cell hypoplasia type 1
Iulia Potoraca, Ashutosh Trehanb, Julie Fudvoyec, Kamila Szymanskad, Albert Thirye, Ilpo Huhtaniemib,f, F. Daly Adriana, Albert Beckersa, Anne-Simone Parentc and Adolfo Rivero- Müllerb,d,g