The role of TH17 cells in a model of rheumatoid arthritis

Introduction: While many studies on rheumatoid arthritis have focused on the active phase of the disease, the events that lead to the development of autoimmunity remain poorly defined. We have developed a model of breach of self tolerance, where a Th1 response to irrelevant antigen (OVA) results in arthropathy associated with spontaneous induction of autoreactive T and B cell responses, which allows the investigation of the immnologival events that lead to the development of autoreactivity. Employing this model the role of Th17 cells, a a subset of IL-17 producing CD4+ T important in autoimmunity, was investigated in the development of autoimmunity. In addition, the relative ability of Th1 and Th17 polarised populations in supporting B cell responses was analysed. Finally, in this thesis the role of sterile damage regulation in the development of autoimmunity was assesed, by investigating the role of Siglec-G, a molecule involved in DAMP-signalling regulation, in this process. Results: Transfer of OVA specific Th17 cells induced similar levels of inflammation as Th1 cells, and could induce a breach of self tolerance as demonstrated by CII specific T and B cell responses. While the CII specific T cells in the Th1 recipients produced IFNγ and not IL-17, surprisingly the CII T cell responses in the Th17 recipients were predominantly IFNγ producers. Whereas the transferred OVA specific Th1 population retained its phenotype, the transferred Th17 population displayed significantly reduced IL-17 production. However, cells polarised under Th17 conditions expanded in a higher degree and persisted for longer time in response to immunisation. This resulted in a higher ability of Th17 polarised population in supporting B cell responses. Finally in this thesis, preliminaty data for a role of Siglec-G in the development of autoimmunity were presented, as Siglec-G deficient mice were protected from the development of autoreactive B cell responses. Conclusion: The results of this thesis suggest that the developing autoimmuniy in both Th1 and Th17 models is mediated by Th1 cells. These studies highlight the plasticity of transferred cell populations in vivo, and support the use of blocking and fate-mapping studies to definitively address how auto-reactive responses develop

Adaptation of leaves of Vitis vinifera L. to seasonal drought as affected by leaf age

Thermoluminescence (TL) glow curves were recorded from leaves of eight Vitis varieties grown in South-West India, viz. Thompson Seedless, Sonaka, Anab-E-Shahi, Kishmish Chami, Tas-A-Ganesh, Black Monuka, Bangalore Purple and American Dogridge belonging to the Vitis vinifera, V. labrusca and V. champini species. The TL peaks were analysed, using a computer-assisted model based on the general order kinetics theory, to determine thermodynamical parameters such as activation energy, entropy, frequency factor and free energy. It was observed that all six V. vinifera samples showed an entirely different TL pattern consisting of only one prominent and highly narrow peak at around -5 °C (peak II). The prominance oft this peak attributed to S2/S3 Qa· recombination suggests a modification at the plastoquinone electron acceptor sites. On the other band, the remaining two varieties Bangalore Purple and American Dogridge showed broader TL spectra consisting of a higher number of peaks. This basic difference is attributed to the difference in species of the selected varieties. Moreover, the TL recorded from Bangalore Purple resembled the standard TL spectra of spinach. The study undertaken in this paper may be relevant in grape breeding programs

Comparison of the effects of salmeterol and ipratropium bromide on exercise performance and breathlessness in patients with stable chronic obstructive pulmonary disease

AbstractTo compare the effects of salmeterol, an adrenergic drug, and ipratropium bromide, an anticholinergic drug, on breathlessness and gas exchange during exercise in patients with chronic obstructive lung disease (COPD), we performed a progressive treadmill exercise test on 15 patients on 3 days (24 h apart), after inhalation placebo, ipratropium bromide (120 μg) or salmeterol (50 μg) in a randomized fashion. Dyspnoea during exercise was evaluated from the regression slope between Borg scale (BS) scores and distance walked each minute on the treadmill. The regression was expressed as the distance walked at BS score 5, the threshold load of dyspnoea (TLD) and breakpoint load of dyspnoea. During and after the exercise, oxygen saturation was monitored by pulse oxymeter and we measured the lower SaO2 during exercise and the recovery time of SaO2 after exercise.In comparison to placebo inhalation we found the same small but significant improvement in airflow limitation after salmeterol or ipratropium inhalation, also the distance walked on treadmill increased after bronchodilators. After bronchodilators the magnitude of oxyhaemoglobin desaturation with exercise was similar to that observed after placebo but the duration of the recovery from sustained SaO2 desaturation after exercise was shorter to the same extent as after ipratropium or salmeterol. Dyspnoeic sensation, when assessed by the TLD and by the distance walked at BS score 5, was decreased after salmeterol and after ipratropium bromide to a similar extent.We conclude that the salmeterol, when given in conventional doses, produces significant improvement in the airway obstruction in the recovery of postexercise HbO2 desaturation and in dyspnoeic sensation in patients with COPD, effects which were similar to those observed after inhalation of the anticholinergic agent ipratropium bromide

Erratum

Adaptation of leaves of Vitis vinifera L to seasonal drought as affected by leaf ageVitis 36 (1), 1114 (1997

Midday measurements of leaf water potential and stomatal conductance are highly correlated with daily water use of Thompson Seedless grapevines

A study was conducted to determine the relationship between midday measurements of vine water status and daily water use of grapevines measured with a weighing lysimeter. Water applications to the vines were terminated on August 24th for 9 days and again on September 14th for 22 days. Daily water use of the vines in the lysimeter (ETLYS) was approximately 40 L vine−1 (5.3 mm) prior to turning the pump off, and it decreased to 22.3 L vine−1 by September 2nd. Pre-dawn leaf water potential (ΨPD) and midday Ψl on August 24th were −0.075 and −0.76 MPa, respectively, with midday Ψl decreasing to −1.28 MPa on September 2nd. Leaf g s decreased from ~500 to ~200 mmol m−2 s−1 during the two dry-down periods. Midday measurements of g s and Ψl were significantly correlated with one another (r = 0.96) and both with ETLYS/ETo (r = ~0.9). The decreases in Ψl, g s, and ETLYS/ETo in this study were also a linear function of the decrease in volumetric soil water content. The results indicate that even modest water stress can greatly reduce grapevine water use and that short-term measures of vine water status taken at midday are a reflection of daily grapevine water us

Optimizing drip irrigation for eggplant crops in semi-arid zones using evolving thresholds

AbstractField experiments were combined with a numerical model to optimize drip irrigation management based on soil matric potential (SMP) measurements. An experimental crop of eggplant was grown in Burkina Faso from December 2014 to March 2015 and plant response to water stress was investigated by applying four different irrigation treatments. Treatments consisted in using two different irrigation depths (low or high), combined with a water provision of 150%, 100% or 66% (150/100/66) of the maximum crop evapotranspiration (T150low, T66low, T100high, T66high). Soil matric potential measurements at 5, 10 and 15cm depth were taken using a wireless sensor network and were compared with measurements of plant and root biomass and crop yields. Field data were used to calibrate a numerical model to simulate triggered drip irrigation. Different simulations were built using the software HYDRUS 2D/3D to analyze the impact of the irrigation depth and frequency, the irrigation threshold and the soil texture on plant transpiration and water losses. Numerical results highlighted the great impact of the root distribution on the soil water dynamics and the importance of the sensor location to define thresholds. A fixed optimal sensor depth of 10 cm was found to manage irrigation from the vegetative state to the end of fruit development. Thresholds were defined to minimize water losses while allowing a sufficient soil water availability for optimal crop production. A threshold at 10cm depth of −15kPa is recommended for the early growth stage and −40kPa during the fruit formation and maturation phase. Simulations showed that those thresholds resulted in optimal transpiration regardless of the soil texture so that this management system can constitute the basis of an irrigation schedule for eggplant crops and possibly other vegetable crops in semi-arid regions

Phenology, canopy aging and seasonal carbon balance as related to delayed winter pruning of vitis vinifera L. cv. sangiovese grapevines

Manipulating or shifting annual grapevine growing cycle to offset limitations imposed by global warming is a must today, and delayed winter pruning is a tool to achieve it. However, no information is available about its physiological background, especially in relation to modifications in canopy phenology, demography and seasonal carbon budget. Mechanistic hypothesis underlying this work was that very late winter pruning (LWP) can achieve significant postponement of phenological stages so that ripening might occur in a cooler period and, concurrently, ripening potential can be improved due to higher efficiency and prolonged longevity of the canopy. Variability in the dynamics of the annual cycle was created in mature potted cv. Sangiovese grapevines subjected to either standard winter pruning (SWP) or late and very late winter pruning (LWP, VLWP) performed when apical shoots on the unpruned canes were at the stage of 2 and 7 unfolded leaves. Vegetative growth, phenology and canopy net CO2 exchange (NCER) were followed throughout the season. Despite LWP and VLWP induced a bud-burst delay of 17 and 31 days vs. SWP, the delay was fully offset at harvest for LWP and was reduced to 6 days in VLWP. LWP showed notably higher canopy efficiency as shorter time needed to reach maximum NCER/leaf area (22 days vs. 34 in SWP), highest maximum NCER/leaf area (+37% as compared to SWP) and higher NCER/leaf area rates from veraison to end of season. As a result, seasonal cumulated carbon in LWP was 17% higher than SWP. A negative functional relationship was also established between amount of leaf area removed at winter pruning and yield per vine and berry number per cluster. Although retarded winter pruning was not able to postpone late-season phenological stages under the warm conditions of this study, it showed a remarkable potential to limit yield while improving grape quality, thereby fostering the hypothesis that it could be used to replace time-consuming and costly cluster thinning. This preliminary study indicates that proper winter pruning date should be timed so as not to exceed the stage of two unfolded leaves

Drought tolerance in Pinus halepensis seed sources as identified by distinctive physiological and molecular markers

[EN] Drought is one of the main constraints determining forest species growth, survival and productivity, and therefore one of the main limitations for reforestation or afforestation. The aim of this study is to characterize the drought response at the physiological and molecular level of different Pinus halepensis (common name Aleppo pine) seed sources, previously characterized in field trials as drought-sensitive or drought-tolerant. This approach aims to identify different traits capable of predicting the ability of formerly uncharacterized seedlings to cope with drought stress. Gas-exchange, water potential, photosynthetic pigments, soluble sugars, free amino acids, glutathione and proteomic analyses were carried out on control and drought-stressed seedlings in greenhouse conditions. Gas-exchange determinations were also assessed in field-planted seedlings in order to validate the greenhouse experimental conditions. Drought-tolerant seed sources presented higher values of photosynthetic rates, water use efficiency, photosynthetic pigments and soluble carbohydrates concentrations. We observed the same pattern of variation of photosynthesis rate and maximal efficiency of PSII in field. Interestingly drought-tolerant seed sources exhibited increased levels of glutathione, methionine and cysteine. The proteomic profile of drought tolerant seedlings identified two heat shock proteins and an enzyme related to methionine biosynthesis that were not present in drought sensitive seedlings, pointing to the synthesis of sulfur amino acids as a limiting factor for drought tolerance in Pinus halepensis. Our results established physiological and molecular traits useful as distinctive markers to predict drought tolerance in Pinus halepensis provenances that could be reliably used in reforestation programs in drought prone areas.This study is a part of the research project: "Application of molecular biology techniques in forest restoration in Mediterranean environments, PAID-05-11" funded by the Universitat Politecnica de Valencia (UPV), program for supporting R&D of new multidisciplinary research lines. The authors are grateful to the Ministerio de Economia y Competitividad AGL2014-57431-P. AV was supported by project Survive-2 (CGL2015-69773-C2-2-P MINECO/FEDER) by the Spanish Government and Prometeo program (DESESTRES-Generalitat Valenciana). CEAM is funded by Generalitat Valenciana.Taïbi, K.; Campo García, ADD.; Vilagrosa, A.; Belles Albert, JM.; López-Gresa, MP.; Pla, D.; Calvete Chornet, JJ.... (2017). 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Pilot study of losartan for pulmonary hypertension in chronic obstructive pulmonary disease

BACKGROUND: Morbidity in COPD results from a combination of factors including hypoxia-induced pulmonary hypertension, in part due to pulmonary vascular remodelling. Animal studies suggest a role of angiotensin II and acute studies in man concur. Whether chronic angiotensin-II blockade is beneficial is unknown. We studied the effects of an angiotensin-II antagonist losartan, on haemodynamic variables, exercise capacity and symptoms. METHODS: This was a double-blind, randomized, parallel group, placebo- controlled study of 48 weeks duration. Forty patients with COPD and pulmonary hypertension (Tran tricuspid pressure gradient (TTPG) = 30 mmHg) were randomised to losartan 50 mg or placebo. Changes in TTPG were assessed at 3, 6 and 12 months. RESULTS: There was a trend for TTPG to increase in the placebo group (baseline 43.4 versus 48.4 mmHg at endpoint) and stay constant in the losartan group (baseline 42.8 versus 43.6 mmHg). More patients in the losartan group (50%) than in the placebo group (22%) showed a clinically meaningful reduction in TTPG at any timepoint; these effects seemed more marked in patients with higher baseline TTPG. There were no clear improvements in exercise capacity or symptoms. CONCLUSION: In this 12-month pilot study, losartan 50 mg had no statistically significant beneficial effect on TTPG, exercise capacity or symptoms in pulmonary hypertension secondary to obstructive disease. A sub-group of patients with higher TTPG may benefit

Influence of soil water content and atmospheric conditions on leaf water potential in cv. "Touriga Nacional" deep-rooted vineyards

Abstract In this study, the influence of soil and atmosphere conditions on noon and basal leaf water potential of vines ‘‘Touriga Nacional’’ in the Da˜o region submitted to different irrigation treatments is analysed. Both indicators showed to be dependent on environmental conditions at the time of measurement. Leaf water potential at noon of fully watered plants was linearly related with atmospheric conditions, with values registered when vapour pressure deficit (VPD) was higher than approximately 3 kPa being no different from the values registered in stressed plants. Therefore, this indicator cannot be reliably used to distinguish different plant water stress levels when atmospheric conditions induce high evaporative demands. The basal leaf water potential (wb) was also influenced by VPD at the time of measurement for all soil water conditions. In well irrigated plants, it was even possible to establish a baseline that can therefore be used to identify nonwater stressed conditions (wb (MPa) = -0.062–0.0972 VPD (kPa), r2 = 0.78). A good correlation was found between soil humidity and wb. However, more than the average value of the whole thickness of soil monitored, the wb values were dependent on the distribution of soil humidity, with the plants responding to the presence of wet layers