IMMUNOLOGICAL ASPECTS OF CROHN'S DISEASE: A REGULATORY FUNCTION OF TIM-3/GALECTIN-9 IN LYTH1.

Crohn's disease (CD) is a type of inflammatory bowel disease (IBD) and its etiology is multifactorial and involves a combination of genetic environmental factors. The interaction of these factors causes an imbalance of the microbiota, leading to the activation of several immunological and inflammatory mechanism. From an immunological point of view, there seems to be an involvement of the TIM-3/GALECTIN-9 pathway and of the autoregulation of lyTh1. These studies show that in patients with CD the autoregulation of lyth1 is lost due to a reduced concentration of galectin-9 and a reduced TIM-3 expression in LyTh1. This could be one of the reason for the state of perpetual activation of lyTh1, resulting in the chronic inflammation process

Floquet-Markov description of the parametrically driven, dissipative harmonic quantum oscillator

Using the parametrically driven harmonic oscillator as a working example, we study two different Markovian approaches to the quantum dynamics of a periodically driven system with dissipation. In the simpler approach, the driving enters the master equation for the reduced density operator only in the Hamiltonian term. An improved master equation is achieved by treating the entire driven system within the Floquet formalism and coupling it to the reservoir as a whole. The different ensuing evolution equations are compared in various representations, particularly as Fokker-Planck equations for the Wigner function. On all levels of approximation, these evolution equations retain the periodicity of the driving, so that their solutions have Floquet form and represent eigenfunctions of a non-unitary propagator over a single period of the driving. We discuss asymptotic states in the long-time limit as well as the conservative and the high-temperature limits. Numerical results obtained within the different Markov approximations are compared with the exact path-integral solution. The application of the improved Floquet-Markov scheme becomes increasingly important when considering stronger driving and lower temperatures.Comment: 29 pages, 7 figure

Iterative algorithm versus analytic solutions of the parametrically driven dissipative quantum harmonic oscillator

We consider the Brownian motion of a quantum mechanical particle in a one-dimensional parabolic potential with periodically modulated curvature under the influence of a thermal heat bath. Analytic expressions for the time-dependent position and momentum variances are compared with results of an iterative algorithm, the so-called quasiadiabatic propagator path integral algorithm (QUAPI). We obtain good agreement over an extended range of parameters for this spatially continuous quantum system. These findings indicate the reliability of the algorithm also in cases for which analytic results may not be available a priori.Comment: 15 pages including 11 figures, one reference added, minor typos correcte

RNA-seq discovery, functional characterization, and comparison of sesquiterpene synthases from Solanum lycopersicum and Solanum habrochaites trichomes

Solanum lycopersicum and Solanum habrochaites (f. typicum) accession PI127826 emit a variety of sesquiterpenes. To identify terpene synthases involved in the production of these volatile sesquiterpenes, we used massive parallel pyrosequencing (RNA-seq) to obtain the transcriptome of the stem trichomes from these plants. This approach resulted initially in the discovery of six sesquiterpene synthase cDNAs from S. lycopersicum and five from S. habrochaites. Searches of other databases and the S. lycopersicum genome resulted in the discovery of two additional sesquiterpene synthases expressed in trichomes. The sesquiterpene synthases from S. lycopersicum and S. habrochaites have high levels of protein identity. Several of them appeared to encode for non-functional proteins. Functional recombinant proteins produced germacrenes, β-caryophyllene/α-humulene, viridiflorene and valencene from (E,E)-farnesyl diphosphate. However, the activities of these enzymes do not completely explain the differences in sesquiterpene production between the two tomato plants. RT-qPCR confirmed high levels of expression of most of the S. lycopersicum sesquiterpene synthases in stem trichomes. In addition, one sesquiterpene synthase was induced by jasmonic acid, while another appeared to be slightly repressed by the treatment. Our data provide a foundation to study the evolution of terpene synthases in cultivated and wild tomato

Genetic selection for bovine chromosome 18 haplotypes associated with divergent somatic cell score affects postpartum reproductive and metabolic performance

The susceptibility of animals to periparturient diseases has a great effect on the economic efficiency of dairy industries, on the frequency of antibiotic treatment, and on animal welfare. The use of selection for breeding cows with reduced susceptibility to diseases offers a sustainable tool to improve dairy cattle farming. Several studies have focused on the association of distinct bovine chromosome 18 genotypes or haplotypes with performance traits. The aim of this study was to test whether selection of Holstein Friesian heifers via SNP genotyping for alternative paternal chromosome 18 haplotypes associated with favorable (Q) or unfavorable (q) somatic cell scores influences postpartum reproductive and metabolic diseases. Thirty-six heifers (18 Q and 18 q) were monitored from 3 wk before calving until necropsy on d 39 (± 4 d) after calving. Health status and rectal temperature were measured daily, and body condition score and body weight were assessed once per week. Blood samples were drawn twice weekly, and levels of insulin, nonesterified fatty acids, insulin-like growth factor-I, growth hormone, and β-hydroxybutyrate were measured. Comparisons between the groups were performed using Fisher's exact test, chi-squared test, and the GLIMMIX procedure in SAS. Results showed that Q-heifers had reduced incidence of metritis compared with q-heifers and were less likely to develop fever. Serum concentrations of β-hydroxybutyrate were lower and insulin-like growth factor-I plasma concentrations were higher in Q- compared with q-heifers. However, the body condition score and withers height were comparable between haplotypes, but weight loss tended to be lower in Q-heifers compared with q-heifers. No differences between the groups were detected concerning retained fetal membranes, uterine involution, or onset of cyclicity. In conclusion, selection of chromosome 18 haplotypes associated with a reduced somatic cell score resulted in a decreased incidence of postpartum reproductive and metabolic diseases in this study. The presented data add to the existing knowledge aimed at avoiding negative consequences of genetic selection strategies in dairy cattle farming. The underlying causal mechanisms modulated by haplotypes in the targeted genomic region and immune competence necessitate further investigation

Sex differences in the association between plasma copeptin and incident type 2 diabetes: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study

AIMS/HYPOTHESIS: Vasopressin plays a role in osmoregulation, glucose homeostasis and inflammation. Therefore, plasma copeptin, the stable C-terminal portion of the precursor of vasopressin, has strong potential as a biomarker for the cardiometabolic syndrome and diabetes. Previous results were contradictory, which may be explained by differences between men and women in responsiveness of the vasopressin system. The aim of this study was to evaluate the usefulness of copeptin for prediction of future type 2 diabetes in men and women separately. METHODS: From the Prevention of Renal and Vascular Endstage Disease (PREVEND) study, 4,063 women and 3,909 men without diabetes at baseline were included. A total of 208 women and 288 men developed diabetes during a median follow-up of 7.7 years. RESULTS: In multivariable-adjusted models, we observed a stronger association of copeptin with risk of future diabetes in women (OR 1.49 [95% CI 1.24, 1.79]) than in men (OR 1.01 [95% CI 0.85, 1.19]) (p (interaction) < 0.01). The addition of copeptin to the Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) clinical model improved the discriminative value (C-statistic,+0.007, p = 0.02) and reclassification (integrated discrimination improvement [IDI] = 0.004, p < 0.01) in women. However, we observed no improvement in men. The additive value of copeptin in women was maintained when other independent predictors, such as glucose, high sensitivity C-reactive protein (hs-CRP) and 24 h urinary albumin excretion (UAE), were included in the model. CONCLUSIONS/INTERPRETATION: The association of plasma copeptin with the risk of developing diabetes was stronger in women than in men. Plasma copeptin alone, and along with existing biomarkers (glucose, hs-CRP and UAE), significantly improved the risk prediction for diabetes in women

Consumer\u27s Guide to Regulatory Impact Analysis: Ten Tips for Being an Informed Policymaker

Regulatory impact analyses (RIAs) weigh the benefits of regulations against the burdens they impose and are invaluable tools for informing decision makers.We offer 10 tips for nonspecialist policymakers and interested stakeholders who will be reading RIAs as consumers. Core problem: Determine whether the RIA identifies the core problem (compelling public need) the regulation is intended to address. Alternatives: Look for an objective, policy-neutral evaluation of the relative merits of reasonable alternatives. Baseline: Check whether the RIA presents a reasonable “counterfactual” against which benefits and costs are measured. Increments: Evaluate whether totals and averages obscure relevant distinctions and trade-offs. Uncertainty: Recognize that all estimates involve uncertainty, and ask what effect key assumptions, data, and models have on those estimates. Transparency: Look for transparency and objectivity of analytical inputs. Benefits: Examine how projected benefits relate to stated objectives. Costs: Understand what costs are included. Distribution: Consider how benefits and costs are distributed. Symmetrical treatment: Ensure that benefits and costs are presented symmetrically

Consumer\u27s Guide to Regulatory Impact Analysis: Ten Tips for Being an Informed Policymaker

Regulatory impact analyses (RIAs) weigh the benefits of regulations against the burdens they impose and are invaluable tools for informing decision makers.We offer 10 tips for nonspecialist policymakers and interested stakeholders who will be reading RIAs as consumers. Core problem: Determine whether the RIA identifies the core problem (compelling public need) the regulation is intended to address. Alternatives: Look for an objective, policy-neutral evaluation of the relative merits of reasonable alternatives. Baseline: Check whether the RIA presents a reasonable “counterfactual” against which benefits and costs are measured. Increments: Evaluate whether totals and averages obscure relevant distinctions and trade-offs. Uncertainty: Recognize that all estimates involve uncertainty, and ask what effect key assumptions, data, and models have on those estimates. Transparency: Look for transparency and objectivity of analytical inputs. Benefits: Examine how projected benefits relate to stated objectives. Costs: Understand what costs are included. Distribution: Consider how benefits and costs are distributed. Symmetrical treatment: Ensure that benefits and costs are presented symmetrically

Risk factors for oral mucositis in paediatric oncology patients receiving alkylant chemotherapy

BACKGROUND: We describe the risk indicators for oral mucositis (OM) in paediatric oncology patients hospitalised in the Institut Gustave Roussy (Villejuif-Paris) and treated with alkylant chemotherapy with autologous peripheral blood progenitor cells. METHODS: The sample was selected using PIGAS software. Three groups of subjects received different chemotherapy regimens: A. Melphalan, B. Busulfan and C. other alkylant protocols. The degree of mucositis was recorded by CTC version 2.0 (Common Toxicity Criteria). Descriptive statistics were performed. The association between mucositis and risk indicator variables was tested using a χ(2 )test. The association between case status and covariates was tested using unconditional logistic regression analysis. RESULTS: Of the 337 children enrolled, 241 showed mucositis (group 1) and 96 did not show mucositis (group 2) during alkylant chemotherapy. There was a higher prevalence of male patients in both groups. The three different chemotherapy regimen groups are correlated with the appearance of oral mucositis (χ(2 )= 22.42, p < 0.01). Weight loss was higher in group 1 (χ(2 )= 6.31, p = 0.01). The duration of aplasia was lower in the Busulfan protocol (7.5 days) than in the Melphalan group (9.3 days) or the other regimens (8.6 days). The use of Bufulfan(® )was directly associated with case status (presence of oral mucositis): odds ratio [OR] = 2.1 and confidence interval [95%CI] = 1.3–3.0. Also, occurrences of germinal tumours and secondary bacterial infections were directly linked with case status: [OR] = 1.4 and 1.8, confidence interval [95%CI] = 1.2 – 1.7 and 1.1 – 2.5, respectively. CONCLUSION: The presence of OM was associated with the three different chemotherapy regimens considered; in particularly patients treated with Busulfan had the highest prevalence