A Novel fry1 Allele Reveals the Existence of a Mutant Phenotype Unrelated to 5′->3′ Exoribonuclease (XRN) Activities in Arabidopsis thaliana Roots

BACKGROUND Mutations in the FRY1/SAL1 Arabidopsis locus are highly pleiotropic, affecting drought tolerance, leaf shape and root growth. FRY1 encodes a nucleotide phosphatase that in vitro has inositol polyphosphate 1-phosphatase and 3',(2'),5'-bisphosphate nucleotide phosphatase activities. It is not clear which activity mediates each of the diverse biological functions of FRY1 in planta. PRINCIPAL FINDINGS A fry1 mutant was identified in a genetic screen for Arabidopsis mutants deregulated in the expression of Pi High affinity Transporter 1;4 (PHT1;4). Histological analysis revealed that, in roots, FRY1 expression was restricted to the stele and meristems. The fry1 mutant displayed an altered root architecture phenotype and an increased drought tolerance. All of the phenotypes analyzed were complemented with the AHL gene encoding a protein that converts 3'-polyadenosine 5'-phosphate (PAP) into AMP and Pi. PAP is known to inhibit exoribonucleases (XRN) in vitro. Accordingly, an xrn triple mutant with mutations in all three XRNs shared the fry1 drought tolerance and root architecture phenotypes. Interestingly these two traits were also complemented by grafting, revealing that drought tolerance was primarily conferred by the rosette and that the root architecture can be complemented by long-distance regulation derived from leaves. By contrast, PHT1 expression was not altered in xrn mutants or in grafting experiments. Thus, PHT1 up-regulation probably resulted from a local depletion of Pi in the fry1 stele. This hypothesis is supported by the identification of other genes modulated by Pi deficiency in the stele, which are found induced in a fry1 background. CONCLUSIONS/SIGNIFICANCE Our results indicate that the 3',(2'),5'-bisphosphate nucleotide phosphatase activity of FRY1 is involved in long-distance as well as local regulatory activities in roots. The local up-regulation of PHT1 genes transcription in roots likely results from local depletion of Pi and is independent of the XRNs.This work was supported by an ANR-GENOPLANT grant (RIBOROOT-ANR06 GPLA 011) and the CEA agency. Array hybridizations have been partly supported by RNG (Réseau National des Génopoles, Evry, France). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study

A Novel fry1 Allele Reveals the Existence of a Mutant Phenotype Unrelated to 5′->3′ Exoribonuclease (XRN) Activities in Arabidopsis thaliana Roots

International audienceBackgroundMutations in the FRY1/SAL1 Arabidopsis locus are highly pleiotropic, affecting drought tolerance, leaf shape and root growth. FRY1 encodes a nucleotide phosphatase that in vitro has inositol polyphosphate 1-phosphatase and 3′,(2′),5′-bisphosphate nucleotide phosphatase activities. It is not clear which activity mediates each of the diverse biological functions of FRY1 in planta.Principal FindingsA fry1 mutant was identified in a genetic screen for Arabidopsis mutants deregulated in the expression of Pi High affinity Transporter 1;4 (PHT1;4). Histological analysis revealed that, in roots, FRY1 expression was restricted to the stele and meristems. The fry1 mutant displayed an altered root architecture phenotype and an increased drought tolerance. All of the phenotypes analyzed were complemented with the AHL gene encoding a protein that converts 3′-polyadenosine 5′-phosphate (PAP) into AMP and Pi. PAP is known to inhibit exoribonucleases (XRN) in vitro. Accordingly, an xrn triple mutant with mutations in all three XRNs shared the fry1 drought tolerance and root architecture phenotypes. Interestingly these two traits were also complemented by grafting, revealing that drought tolerance was primarily conferred by the rosette and that the root architecture can be complemented by long-distance regulation derived from leaves. By contrast, PHT1 expression was not altered in xrn mutants or in grafting experiments. Thus, PHT1 up-regulation probably resulted from a local depletion of Pi in the fry1 stele. This hypothesis is supported by the identification of other genes modulated by Pi deficiency in the stele, which are found induced in a fry1 background.Conclusions/SignificanceOur results indicate that the 3′,(2′),5′-bisphosphate nucleotide phosphatase activity of FRY1 is involved in long-distance as well as local regulatory activities in roots. The local up-regulation of PHT1 genes transcription in roots likely results from local depletion of Pi and is independent of the XRNs.

Corrélation entre la dynamique de la population de Myodes glareolus et la prévalence de l'hantavirus Puumala

Zoonotic diseases have always been a major concern on the global economy and public health. To limit at best of their expansion, many programs are launched to prevent, monitor and fight against these diseases. Edenext program's mission is to study some hantaviruses, which cause hemorrhagic fever with renal syndrome to humans. To understand the persistence and the circulation of infectious agents, one must initially know the role and the functioning of animal reservoirs. We were interested in Puumala hantavirus and its host, the bank vole Myodes' glareolus. Our hypothesis was that the local prevalence of Puumala hantavirus (PUUV) is related to the population dynamics of voles. We tested this hypothesis by relying on some genetic parameters, the allelique richness (A) and the genetic divergence (FST) that are used as surrogates for inferring the population dynamics of voles. Thus, low A values and high FST values indicate that populations are small sized and isolated with others, whereas high A values and low FST values are indicative of large populations well connected with others. The study area is located in Belgian Flanders. This region is characterized by a low prevalence of hantaviruses and highly fragmented landscape, which consists of isolated groves and edge networks. We studied 375 voles caught in Fall 2004 in 15 localities. Genetic composition was measured with 19 microsatellite loci. We found that despite a low overall prevalence, it was higher or lower depending on the characteristics of the landscape. Indeed, we found that PUUV prevalence, although low in general, was highly correlated with allelic richness, with high prevalence in large populations (A values high) and low prevalence in small and isolated populations (A values small). Comparison with other works shows that this observation can be generalized to other geographic regions (Finland and France) and other types of landscapes (large boreal and temperate forests) characterized by high prevalence of Puumala hantavirus. Our work opens up new avenues of understanding of the factors limiting the geographic distribution of this virus in Western Europe.!Les zoonoses représentent un problème majeur depuis toujours sur l’économie mondiale et la santé publique. Pour limiter au mieux leur expansion, de nombreux programmes de recherche sont lancés en vue de prévenir, surveiller et lutter contre ces maladies. Le programme Edenext a pour mission d’étudier certains hantavirus qui provoquent des fièvres hémorragiques à syndrome rénal chez l’homme. Pour comprendre la persistance et la circulation des agents infectieux, il faut dans un premier temps connaître le rôle et le fonctionnement des animaux réservoirs. Nous nous sommes intéressés à l’hantavirus Puumala et à son hôte, le campagnol roussâtre Myodes'glareolus.'Notre hypothèse était que la dynamique des populations du campagnol détermine la prévalence de l’hantavirus. Nous avons testé cette hypothèse en nous appuyant sur des paramètres génétiques, la richesse allélique (A) et de l’isolement génétique (FST), qui donnent une mesure indirecte de la dynamique des populations des campagnols. Ainsi, lorsque A est faible et FST élevé, cela sous entend que la population est de petite taille et isolée (peu ou pas de liaison avec les autres populations). Dans le cas contraire (A fort et FST faible) c’est une population de grande taille et avec une grande connectivité avec d’autres populations. La zone d’étude se situe dans la Flandre belge. Cette région est caractérisée par une faible prévalence à l’hantavirus et par un paysage forestier fragmenté, composé de bosquets et de réseaux de haies assez isolés. Au total nous avons travaillé sur 375 animaux capturés à l’Automne 2004 dans 15 sites d’étude. La diversité génétique a été mesurée à l’aide de 19 marqueurs microsatellites. L’étude a révélé que la prévalence, bien que faible en général, était très corrélée aux paramètres génétiques, en particulier à la diversité génétique (A) : prévalence élevée dans les grandes populations bien connectées aux autres (A élevé) et faible dans les petites populations isolées (A faible). La comparaison avec d’autres travaux révèle que cette observation peut être généralisée à d’autres régions géographiques (Finlande et France) et dans d’autre type de paysages (grands massifs forestiers boréals et tempérés) caractérisés par de fortes prévalences d’hantavirus Puumala, Ce travail ouvre des voies de compréhension sur les facteurs qui limitent la distribution géographique de ce virus en Europe de l’Ouest

Glucose-galactose transporter DEFICIENCY: a diagnosis based on clinical observations.

Dehydration and major diarrhea in young infants is mainly linked to infectious diseases. However in case leading to denutrition and growth retardation, metabolic causes or malabsorption should be evocated. We report here the case of a few days old infant admitted for early recurrence of liquid stools and vomiting. XX is born at term (3450 grams, 51 cm) after an uneventful pregnancy. Consanguinity has been reported in the family. He was breastfed but presented rapidly liquid stools and vomiting. At 10 days old he was first admitted for dehydration, loss of weight below his birth weight (2900 grams) and severe hypernatremia. Semi elementary diet led to some improvement but he was readmitted at the age of one month for similar even worse symptoms including abdominal distension and explosive stools. Complementary investigations have excluded infection, parasitosis, malformation and immune deficits. Different diet formulas were tried with no significant benefit what led to the placement of parenteral nutrition thanks to which weight was gained. Hypothesis of peculiar carbohydrate malabsorption was made and the following tests have been carried out: -Clinitest: presence of reducing substances in the stools. -Lactose Breath test: between 15 and 90 ppm H2 with a peak value at 90 ppm H2 after 90 minutes. -Duodenal biopsy: normal histology; normal activity of lactase, maltase, saccharase-isomaltase. Considering the normality of these enzyme activities, hypothesis of “Na-dependant glucose-galactose transporter” deficit was put forward. This was confirmed according to the results of HGPO and glucose breath test. Search for SGTL1 gene mutation is still in progress. In conclusion despite of the huge progresses made at molecular biology level, clinical observation remain essential to the diagnosis of malabsorption. Precise reporting of the used milk formula and comparative analysis of their composition can orient the diagnosis and help to select the most accurate molecular test. Here, analyses exclude every enzyme activity deficiencies. Carbohydrate malabsorption from first days of live can be linked to a glucose-galactose transporter deficiency due to a SGLT1 mutation (chr 22). This autosomal recessive disorder has only been reported 200 times until now

Corrélation phénotype-génotype chez les enfants atteints de neurofibromatose de type 1

AbstractNeurofibromatosis type 1 (NF1) is a common autosomal dominant disorder with an incidence of ∼1 in 4,000 live births. Neurofibromin, the gene product, is ubiquitously expressed at high levels in the nervous system and functions as a tumor suppressor. Haploinsufficiency of neurofibromin through mutation leads to an increased risk of developing benign and malignant tumors in affected individuals. Although NF1 has complete penetrance, it displays considerable inter- and intrafamilial variability in phenotypic expression which poses disease prediction and management problems. Some NF1 genotype–phenotype correlations have been described. To evaluate the genetic component of variable expressivity in NF1, we examined the phenotypic correlations between affected relatives in 52 NF1 patients from 45 families.</jats:p

À propos de deux cas de méningococcémie. Revue de la littérature sur la méningococcémie chronique

Introduction : Neisseria meningitidis est une bactérie commensale responsable d’infections invasives rares graves, potentiellement mortelles. Dans certains cas, elle est à l’origine de formes atypiques de septicémies aiguës, subaiguës ou chroniques qui, bien que souvent d’évolution plus lente, font encourir les mêmes risques aux patients. Observation : Le patient 1 présentait une fièvre récurrente, des polyarthralgies et une éruption maculaire généralisée. Le patient 2 présentait une fièvre modérée depuis 10 jours, des douleurs cervicales postérieures et une éruption maculaire. Les hémocultures des deux patients ont permis de confirmer la présence d’un méningocoque du groupe B. L’amplification génique (PCR) sur le liquide céphalorachidien (LCR) du patient 2 était également positive pour le même germe, alors que la culture était stérile. L’évolution sous antibiothérapie a été favorable. Discussion : La méningococcémie chronique se caractérise par une triade clinique, comprenant une fièvre prolongée, des arthralgies et une éruption. L’évolution est favorable sans séquelles si la prise en charge est adéquate. La PCR sur LCR, les hémocultures et la culture du LCR se révèlent des outils complémentaires pour confirmer le diagnostic. Conclusion : L’infection à méningocoque peut se manifester de façons très différentes. Le diagnostic de méningococcémie chronique doit être évoqué devant une triade associant fièvre prolongée, éruption et arthralgies, et le germe activement recherché par des techniques comme la PCR, surtout quand la culture du LCR est stérile.[Two case reports of meningococcemia. Review of the literature on chronic meningococcemia]. INTRODUCTION: Neisseria meningitidis is a Gram-negative bacteria that can be highly pathogenic in humans and responsible for life-threatening and acute diseases. In a few cases, it can lead to an atypical form of sepsis-acute, subacute, or chronic-which, even if progression is slower, may carry the same risks for patients as conventional acute forms. CASES: Case 1 presented with recurrent fever, polyarthralgia, and generalized macular rash. Case 2 had fever for the previous 10days with neck pain and macular rash. Blood cultures were positive for group B meningococcus in both cases. Polymerase chain reaction (PCR) analysis for the same pathogen was also positive in the cerebrospinal fluid (CSF) of Case 2. Following intravenous antibiotic treatment, the progression was favorable in both cases. DISCUSSION: Chronic meningococcemia is characterized by a triad of clinical features, including a fever lasting for at least 1week, arthralgia, and a cutaneous rash. This condition evolves positively without any sequelae if treated properly. PCR and blood culture are two complimentary tools that support the diagnosis. CONCLUSION: Meningococcal infection can manifest in a variety of ways. Chronic meningococcemia diagnosis should be considered in a triad of prolonged fever, rash, and arthralgia. Better access to state-of-the-art techniques such as PCR is recommended in the future so as to provide optimal care of patients suffering from this condition

Décrochage de la courbe de périmètre crânien et si l’origine n'était pas neurologique

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