Discrimination of three mutational events that result in a disruption of the R122 primary autolysis site of the human cationic trypsinogen (PRSS1) by denaturing high performance liquid chromatography

BACKGROUND: R122, the primary autolysis site of the human cationic trypsinogen (PRSS1), constitutes an important "self-destruct" or "fail-safe" defensive mechanism against premature trypsin activation within the pancreas. Disruption of this site by a missense mutation, R122H, was found to cause hereditary pancreatitis. In addition to a c.365G>A (CGC>CAC) single nucleotide substitution, a c.365~366GC>AT (CGC>CAT) gene conversion event in exon 3 of PRSS1 was also found to result in a R122H mutation. This imposes a serious concern on the genotyping of pancreatitis by a widely used polymerase chain reaction-restriction fragment length polymorphism assay, which could only detect the commonest c.365G>A variant. MATERIALS AND METHODS: DNA samples containing either the known c.365G>A or c.365~366GC>AT variant in exon 3 of PRSS1 were used as positive controls to establish a denaturing high performance liquid chromatography (DHPLC) assay. RESULTS: DHPLC could readily discriminate the two known different mutational events resulting in the R122H mutation. More importantly, under the same experimental conditions, it identified a further mutational event that also occurs in the R122 primary autolysis site but results in a different amino acid substitution: c.364C>T (CGC>TGC; R122C). CONCLUSIONS: A rapid, simple, and low-cost assay for detecting both the known and new mutations occuring in the R122 primary autolysis site of PRSS1 was established. In addition, the newly found R122C variant represents a likely pancreatitis-predisposing mutation

Association of circulating hsa-miRNAs with sarcopenia: the SarcoPhAge study.

peer reviewed[en] OBJECTIVE: To identify a microRNA signature associated to sarcopenia in community-dwelling older adults form the SarcoPhAge cohort. METHODS: In a screening phase by next generation sequencing (NGS), we compared the hsa-miRome expression of 18 subjects with sarcopenia (79.6 ± 6.8 years, 9 men) and 19 healthy subjects without sarcopenia (77.1 ± 6 years, 9 men) at baseline. Thereafter, we have selected eight candidate hsa-miRNAs according to the NGS results and after a critical assessment of previous literature. In a validation phase and by real-time qPCR, we then analyzed the expression levels of these 8 hsa-miRNAs at baseline selecting 92 healthy subjects (74.2 ± 10 years) and 92 subjects with sarcopenia (75.3 ± 6.8 years). For both steps, the groups were matched for age and sex. RESULTS: In the validation phase, serum has-miRNA-133a-3p and has-miRNA-200a-3p were significantly decreased in the group with sarcopenia vs controls [RQ: relative quantification; median (interquartile range)]: -0.16 (-1.26/+0.90) vs +0.34 (-0.73/+1.33) (p < 0.01) and -0.26 (-1.07/+0.68) vs +0.27 (-0.55/+1.10) (p < 0.01) respectively. Has-miRNA-744-5p was decreased and has-miRNA-151a-3p was increased in the group with sarcopenia vs controls, but this barely reached significance: +0.16 (-1.34/+0.79) vs +0.44 (-0.31/+1.00) (p = 0.050) and  +0.35 (-0.22/+0.90) vs  +0.03 (-0.68/+0.75) (p = 0.054). CONCLUSION: In subjects with sarcopenia, serum hsa-miRNA-133a-3p and hsa-miRNA-200a-3p expression were downregulated, consistent with their potential targets inhibiting muscle cells proliferation and differentiation

Introduction: building the history of language learning and teaching (HoLLT)

The papers presented in this issue are the result of a workshop held at the University of Nottingham in December 2012 as part of an Arts and Humanities Research Council research network Towards a History of Modern Foreign Language Teaching and Learning (2012–14) intended to stimulate historical research into language teaching and learning. This, the first workshop in the programme, focused on exchanging information on the history of language learning and teaching (HoLLT) across the different language traditions, for it had become clear to us that scholars working within their own language disciplines were often relatively unaware of work outside these. We hope that this special issue — with overview articles on the history of English, French, German, and Spanish as second/foreign languages — will help overcome that lack of awareness and facilitate further research collaboration. Charting the history of language teaching and learning will, in turn, make us all better informed in facing challenges and changes to policy and practice now and in the future. It is instructive in the current climate, for example, to realize that grave doubts were held about whether second foreign languages could survive alongside French in British schools in the early twentieth century (McLelland, forthcoming), or to look back at earlier attempts to establish foreign languages in primary schools (Bayley, 1989; Burstall et al., 1974; Hoy, 1977). As we write, language learning in England is undergoing yet more radical change. Language teaching for all children from the age of seven is being made compulsory in primary schools from 2014, while at Key Stage 3 (up to age 16), where a foreign language has not been compulsory since 2002, the most recent programme of study for England has virtually abandoned the recent focus on intercultural competence and now requires learners to ‘read great literature in the original language’,1 a radical change in emphasis compared to the previous half-century, which seems to reflect a very different view of what language learning is for. We seem to be little closer in 2014 than we were at the dawn of the twentieth century to answering with any certainty the questions that lie at the very foundations of language teaching: who should learn a foreign language, why learners learn, what they need to learn, and what we want to teach them — answers that we need before we can consider how we want to teach. The research programme begun under our research network is intended to help us to take ‘the long view’ on such questions

Description of manganese deposits collected by R/V "Jean Charcot" during its EQUAMARGE II expedition in the Equatorial Atlantic

During the Equamarge II cruise (February 4 to March 21, 1988), on board the R. V. "Jean Charcot", 12.500 kms of continuous geophysical profiling have been recorded along three sectors of the Equatorial Atlantic. Two segments ofthe West African transform margin have been intensively surveyed off Guinea and off Ivory Coast and Ghana. The active Romanche fracture zone has been surveyed in details on a distance of about 100 kms. These data (multibeam bathymetry, continuous seismic profiling, magnetism and gravity) have been supplemented by 16 geological stations (dredging and coring). This report gives a synthetic review of the onboard analysis and allows to better understand the geological structures of the three surveyed areas

Déterminations de l'enthalpie de formation du bisulsure de manganèse

Les mesures, par la méthode de Knudsen, des pressions de vapeur de soufre produite dans l'équilibre de dissociation de MnS2 synthétique ont été effectuées entre 440 eL 610 K. L'étude au spectromètre de masse de la composition de la vapeur a permis de déterminer l'intervalle de températures dans lequel la réaction de décomposition peut s'écrire :[math]Le calcul thermodynamique conduit aux résultats suivants : ΔH° = 14,8 ± 0,5 kcal/mol

Nouveaux modes d’obtention de MnSγ. Détermination de l’enthalpie de la réaction de transformation de MnSγ en MnSα par calorimétrie de réaction

Nous avons mis au point de nouveaux modes d’obtention de MnSγ. Tant par voie sèche que par voie humide, en modifiant les milieux réactionnels ordinairement utilisés, nous avons pu obtenir un produit d’une pureté satisfaisante et d’une bonne stabilité thermique. Il ne se transforme en MnSα que vers 420-430 °C, c’est-à-dire à une température bien supérieure à celle indiquée par la littérature. Nous observons un pic endothermique vers 420 °C à l’analyse thermique différentielle. Nous avons par ailleurs déterminé par calorimétrie de réaction dans l’acide chlorhydrique 6,2 M, son enthalpie de formation (— 45,3 kcal/mole) et sa chaleur de transformation en MnSα (+ 1,75 kcal/mole)