Evolution récente du régime hydrologique de quelquesrivières de Roumanie Centrale. (Courte note)

L'étude de la stationnarité de séries de débits annuels et saisonniers de 15 rivières roumaines et du Danube à Orsova met en évidence l'existence d'une "phase hydrologique" sèche importante depuis 1983. L'écoulement hivernal a diminué de 50% depuis cette date et semble principalement responsable de cette sécheresse hydrologique. L'extension géographique de cette sécheresse est précisée en Roumanie Centrale. L'analyse des débits du Danube montre qu'une partie importante de son bassin versant est touché par le phénomène.A statistical study of annual and seasonal discharges series for 15 Romanian rivers and the Danube River at Orsova exhibits a very important dry hydrological period which began around 1983. The winter discharge decreased 50% during this period and seems to be the main cause of this hydrological drought. The spatial distribution of this drought is defined in Central Romania. The analysis of the Danube discharge series demonstrates that an important part of its watershed is in the same situation

phot1 inhibition of ABCB19 primes lateral auxin fluxes in the shoot apex required for phototropism

It is well accepted that lateral redistribution of the phytohormone auxin underlies the bending of plant organs towards light. In monocots, photoreception occurs at the shoot tip above the region of differential growth. Despite more than a century of research, it is still unresolved how light regulates auxin distribution and where this occurs in dicots. Here, we establish a system in Arabidopsis thaliana to study hypocotyl phototropism in the absence of developmental events associated with seedling photomorphogenesis. We show that auxin redistribution to the epidermal sites of action occurs at and above the hypocotyl apex, not at the elongation zone. Within this region, we identify the auxin efflux transporter ATP-BINDING CASSETTE B19 (ABCB19) as a substrate target for the photoreceptor kinase PHOTOTROPIN 1 (phot1). Heterologous expression and physiological analyses indicate that phosphorylation of ABCB19 by phot1 inhibits its efflux activity, thereby increasing auxin levels in and above the hypocotyl apex to halt vertical growth and prime lateral fluxes that are subsequently channeled to the elongation zone by PIN-FORMED 3 (PIN3). Together, these results provide new insights into the roles of ABCB19 and PIN3 in establishing phototropic curvatures and demonstrate that the proximity of light perception and differential phototropic growth is conserved in angiosperm

Switching the stereochemical outcome of 6-endo-trig cyclizations; Synthesis of 2,6-Cis-6-substituted 4-oxopipecolic acids

A base-mediated 6-endo-trig cyclization of readily accessible enone-derived α-amino acids has been developed for the direct synthesis of novel 2,6-cis-6- substituted-4-oxo-L-pipecolic acids. A range of aliphatic and aryl side chains were tolerated by this mild procedure to give the target compounds in good overall yields. Molecular modeling of the 6-endo-trig cyclization allowed some insight as to how these compounds were formed, with the enolate intermediate generated via an equilibrium process, followed by irreversible tautomerization/neutralization providing the driving force for product formation. Stereoselective reduction and deprotection of the resulting 2,6-cis-6-substituted 4-oxo-L-pipecolic acids to the corresponding 4-hydroxy-L-pipecolic acids was also performed

Promoting the use of Motor Function Measure (MFM) as outcome measure in patients with Duchenne Muscular Dystrophy (DMD) treated by corticosteroids

ObjectivesAssessing muscle function is a key step in measuring changes and evaluating the outcomes of therapeutic interventions in Duchenne Muscular Dystrophy (DMD). Regarding the large use of corticosteroids (CS) in this population to delay the loss of function, our goal was to monitor the evolution of motor function in patients with DMD treated by corticosteroids (CS) and to study the responsiveness of Motor Function Measure (MFM) in this population in order to provide an estimation of the number of subject needed for a clinical trial.MethodA total of 76 patients with DMD, aged 5.9 to 11.8 years, with at least 6 months of follow-up and 2 MFM were enrolled, 30 in the CS treated group (8±1.62 y) and 46 in the untreated group (7.91±1.50 y).ResultsThe relationship between MFM scores and age was studied in CS treated patients and untreated patients. The evolution of these scores was compared between groups, on a 6-, 12- and 24-month period by calculating slopes of change and standardized response mean. At 6, 12 and 24 months, significant differences in the mean score change were found, for all MFM scores, between CS treated patients and untreated patients. For D1 subscore specifically, at 6 months, the increase is significant in the treated group (11.3±14%/y; SRM 0.8) while a decrease is observed in the untreated group (–17.8±17.7%/y; SRM 1). At 12 and 24 months, D1 subscore stabilized for treated patients but declined significantly for untreated boys (–15.5±15.1%/y; SRM 1 at 12 mo and–18.8±7.1%/y; SRM 2.6 at 24 mo). 21 patients lost the ability to walk during the study: 6 in the CS treated group (25% at 24 months, mean age: 10.74±1.28 y) and 15 in the untreated group (64.71% at 24 months, mean age: 9.20±1.78 y).Discussion and conclusionPatients with DMD treated by CS present a different course of the disease described in this paper using the MFM. Based on these results, an estimation of the number of patients needed for clinical trial could be done

Collateral fattening in body composition autoregulation: its determinants and significance for obesity predisposition

Collateral fattening refers to the process whereby excess fat is deposited as a result of the body’s attempt to counter a deficit in lean mass through overeating. Its demonstration and significance to weight regulation and obesity can be traced to work on energy budget strategies in growing mammals and birds, and to men recovering from experimental starvation. The cardinal features of collateral fattening rests upon (i) the existence of a feedback system between lean tissue and appetite control, with lean tissue deficit driving hyperphagia, and (ii) upon the occurrence of a temporal desynchronization in the recovery of body composition, with complete recovery of fat mass preceeding that of lean mass. Under these conditions, persistent hyperphagia driven by the need to complete the recovery of lean tissue will result in the excess fat deposition (hence collateral fattening) and fat overshooting. After reviewing the main lines of evidence for the phenomenon of collateral fattening in body composition autoregulation, this article discusses the causes and determinants of the desynchronization in fat and lean tissue recovery leading to collateral fattening and fat overshooting, and points to their significance in the mechanisms by which dieting, developmental programming and sedentariness predispose to obesity

A new Late Agenian (MN2a, Early Miocene) fossil assemblage from Wallenried (Molasse Basin, Canton Fribourg, Switzerland)

Excavations of two fossiliferous layers in the Wallenried sand- and marl pit produced a very diversified vertebrate fauna. New material allows the reassessment of the taxonomic position of the ruminant taxa Andegameryx andegaviensis and endemic Friburgomeryx wallenriedensis. An emended diagnosis for the second species is provided and additional material of large and small mammals, as well as ectothermic vertebrates, is described. The recorded Lagomorpha show interesting morphological deviations from other Central European material, and probably represent a unique transitional assemblage with a co-occurrence of Titanomys, Lagopsis and Prolagus. Rodentia and Eulipotyphla belong to typical and well-known species of the Agenian of the Swiss Molasse Basin. Abundant small mammal teeth have allowed us to pinpoint the biostratigraphic age of Wallenried to late MN2a. The biostratigraphic age conforms to data derived from the charophyte assemblages and confirms the oldest occurrence of venomous snake fangs. The palaeoenvironmental context is quite complex. Sedimentary structures and fauna (fishes, frogs, salamanders, ostracods) are characteristic for a humid, lacustrine environment within a flood plain system

Effect of oral lactulose on clinical and immunohistochemical parameters in patients with inflammatory bowel disease: a pilot study

<p>Abstract</p> <p>Background</p> <p>The prebiotic potential of lactulose is well established and preclinical studies demonstrated a protective effect of lactulose in murine models of colitis. The aim of the present study was to investigate the clinical and histological efficacy of lactulose in patients with inflammatory bowel disease (IBD), for which probiotic therapy yielded promising results.</p> <p>Methods</p> <p>Patients were treated with standard medication alone or combined with 10 g lactulose daily as adjuvant therapy for 4 months. Clinical efficacy of treatment was assessed using clinical activity indices, a quality of life index (IBDQ), endoscopic scores, defecation frequency and monitoring corticosteroid medication. Orsomucoid, alpha1-antitrypsin and other laboratory parameters were determined. In addition, in some participants colonic biopsies were analyzed with haematoxylin-eosin staining or with antibodies against HLA-DR, CD68, IgA and CD3, and evaluated systematically. All measurements were performed both at enrolment and at the end of the trial.</p> <p>Results</p> <p>14 patients presenting ulcerative colitis (UC) and 17 patients presenting Crohn's disease (CD), most of them in a clinically active state, were enrolled in this pilot study. After 4 month no significant improvement of clinical activity index, endoscopic score or immunohistochemical parameters was observed in CD or UC patients receiving lactulose in comparison to the control group. However, significant improvement of quality of life was observed in UC patients receiving lactulose compared to the control group (p = 0.04).</p> <p>Conclusion</p> <p>The findings of the present pilot study indicate that oral lactulose has no beneficial effects in IBD patients in particular with regard to clinical activity, endoscopic score or immunohistochemical parameters. The importance of the beneficial effect of lactulose in UC patients regarding the quality of life needs further evaluation in larger controlled clinical trials.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN92101486</p

Clinicogenomic factors of biotherapy immunogenicity in autoimmune disease: A prospective multicohort study of the ABIRISK consortium

BACKGROUND: Biopharmaceutical products (BPs) are widely used to treat autoimmune diseases, but immunogenicity limits their efficacy for an important proportion of patients. Our knowledge of patient-related factors influencing the occurrence of antidrug antibodies (ADAs) is still limited. METHODS AND FINDINGS: The European consortium ABIRISK (Anti-Biopharmaceutical Immunization: prediction and analysis of clinical relevance to minimize the RISK) conducted a clinical and genomic multicohort prospective study of 560 patients with multiple sclerosis (MS, n = 147), rheumatoid arthritis (RA, n = 229), Crohn's disease (n = 148), or ulcerative colitis (n = 36) treated with 8 different biopharmaceuticals (etanercept, n = 84; infliximab, n = 101; adalimumab, n = 153; interferon [IFN]-beta-1a intramuscularly [IM], n = 38; IFN-beta-1a subcutaneously [SC], n = 68; IFN-beta-1b SC, n = 41; rituximab, n = 31; tocilizumab, n = 44) and followed during the first 12 months of therapy for time to ADA development. From the bioclinical data collected, we explored the relationships between patient-related factors and the occurrence of ADAs. Both baseline and time-dependent factors such as concomitant medications were analyzed using Cox proportional hazard regression models. Mean age and disease duration were 35.1 and 0.85 years, respectively, for MS; 54.2 and 3.17 years for RA; and 36.9 and 3.69 years for inflammatory bowel diseases (IBDs). In a multivariate Cox regression model including each of the clinical and genetic factors mentioned hereafter, among the clinical factors, immunosuppressants (adjusted hazard ratio [aHR] = 0.408 [95% confidence interval (CI) 0.253-0.657], p < 0.001) and antibiotics (aHR = 0.121 [0.0437-0.333], p < 0.0001) were independently negatively associated with time to ADA development, whereas infections during the study (aHR = 2.757 [1.616-4.704], p < 0.001) and tobacco smoking (aHR = 2.150 [1.319-3.503], p < 0.01) were positively associated. 351,824 Single-Nucleotide Polymorphisms (SNPs) and 38 imputed Human Leukocyte Antigen (HLA) alleles were analyzed through a genome-wide association study. We found that the HLA-DQA1*05 allele significantly increased the rate of immunogenicity (aHR = 3.9 [1.923-5.976], p < 0.0001 for the homozygotes). Among the 6 genetic variants selected at a 20% false discovery rate (FDR) threshold, the minor allele of rs10508884, which is situated in an intron of the CXCL12 gene, increased the rate of immunogenicity (aHR = 3.804 [2.139-6.764], p < 1 × 10-5 for patients homozygous for the minor allele) and was chosen for validation through a CXCL12 protein enzyme-linked immunosorbent assay (ELISA) on patient serum at baseline before therapy start. CXCL12 protein levels were higher for patients homozygous for the minor allele carrying higher ADA risk (mean: 2,693 pg/ml) than for the other genotypes (mean: 2,317 pg/ml; p = 0.014), and patients with CXCL12 levels above the median in serum were more prone to develop ADAs (aHR = 2.329 [1.106-4.90], p = 0.026). A limitation of the study is the lack of replication; therefore, other studies are required to confirm our findings. CONCLUSION: In our study, we found that immunosuppressants and antibiotics were associated with decreased risk of ADA development, whereas tobacco smoking and infections during the study were associated with increased risk. We found that the HLA-DQA1*05 allele was associated with an increased rate of immunogenicity. Moreover, our results suggest a relationship between CXCL12 production and ADA development independent of the disease, which is consistent with its known function in affinity maturation of antibodies and plasma cell survival. Our findings may help physicians in the management of patients receiving biotherapies

Tractability in Constraint Satisfaction Problems: A Survey

International audienceEven though the Constraint Satisfaction Problem (CSP) is NP-complete, many tractable classes of CSP instances have been identified. After discussing different forms and uses of tractability, we describe some landmark tractable classes and survey recent theoretical results. Although we concentrate on the classical CSP, we also cover its important extensions to infinite domains and optimisation, as well as #CSP and QCSP