Natural History of Cardiac and Respiratory Involvement,Prognosis and Predictive Factors for Long-Term Survival in Adult Patients with Limb Girdle Muscular Dystrophies Type 2C and 2D

BackgroundType 2C and 2D limb girdle muscular dystrophies (LGMD) are a group of autosomal recessive limb girdle muscular dystrophies manifested by proximal myopathy, impaired respiratory muscle function and cardiomyopathy. The correlation and the prognostic impact of respiratory and heart impairment are poorly described. We aimed to describe the long-term cardiac and respiratory follow-up of these patients and to determine predictive factors of cardio-respiratory events and mortality in LGMD 2C and 2D.MethodsWe reviewed the charts of 34 LGMD patients, followed from 2005 to 2015, to obtain echocardiographic, respiratory function and sleep recording data. We considered respiratory events (acute respiratory failure, pulmonary sepsis, atelectasis or pneumothorax), cardiac events (acute heart failure, significant cardiac arrhythmia or conduction block, ischemic stroke) and mortality as outcomes of interest for the present analysis.ResultsA total of 21 patients had type 2C LGMD and 13 patients had type 2D. Median age was 30 years [IQR 24–38]. At baseline, median pulmonary vital capacity (VC) was 31% of predicted value [20–40]. Median maximal inspiratory pressure (MIP) was 31 cmH₂O [IQR 20.25–39.75]. Median maximal expiratory pressure (MEP) was 30 cm H₂O [20–36]. Median left ventricular ejection fraction (LVEF) was 55% [45–64] with 38% of patients with LVEF <50%. Over a median follow-up of 6 years, we observed 38% respiratory events, 14% cardiac events and 20% mortality. Among baseline characteristics, LVEF and left ventricular end diastolic diameter (LVEDD) were associated with mortality, whilst respiratory parameters (VC, MIP, MEP) and the need for home mechanical ventilation (HMV) were associated with respiratory events.ConclusionIn our cohort of severely respiratory impaired type 2C and 2D LGMD, respiratory morbidity was high. Cardiac dysfunction was frequent in particular in LGMD 2C and had an impact on long-term mortality.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02501083","term_id":"NCT02501083"}}NCT02501083     

Differential physiological and antioxidative responses to drought stress and recovery among four contrasting Argania spinosa ecotypes

Our study was undertaken to ascertain whether the change of the water status and the activation of superoxide dismutase and their isoenzymes in Argan tree can support edaphic drought tolerance and its recovery under rehydration. An experiment was conducted on four contrasting ecotypes of Argania spinosa plants: two contrasting coastal ecotypes (Admine (Adm) and Rabia (Rab)) and two contrasting inland ecotypes (Aoulouz (Alz) and Lakhssas (Lks)). Drought stress significantly decreased the leaf water potential and stomatal conductance in the four contrasted ecotypes. In terms of biochemical responses, significant accumulation of carbonyl groups, hydrogen peroxide and superoxide radical has been recorded in the leaves of stressed plants reflecting oxidative stress. In parallel, the activities of total superoxide dismutase (SOD) and their isoenzymes Cu/Zn-SOD, Cu/Zn-SOD and Fe-SOD were also found to have increased to scavenging ROS and protecting the cell against induced oxidative stress. The recovery kinetics of A. spinosa, as a response to rehydration, were significant and rapid. According to the traits having the most discriminating power, both inland ecotypes (Lks and Alz) showed a better upregulation of its protective mechanisms compared to coastal ecotypes (Rab and Adm). All these adaptive traits make the inland ecotypes as an elite resource of drought tolerance and might become the new focus of domestication research of argan tree in arid and semi-arid environments.     

Role of pyrimidine salvage pathway in the maintenance of organellar and nuclear genome integrity

Nucleotide biosynthesis proceeds through a de novo pathway and a salvage route. In the salvage route, free bases and/or nucleosides are recycled to generate the corresponding nucleotides. Thymidine kinase (TK) is the first enzyme in the salvage pathway to recycle thymidine nucleosides as it phosphorylates thymidine to yield thymidine monophosphate. The Arabidopsis genome contains two TK genes ?TK1a and TK1b? that show similar expression patterns during development. In this work, we studied the respective roles of the two genes during early development and in response to genotoxic agents targeting the organellar or the nuclear genome. We found that the pyrimidine salvage pathway is crucial for chloroplast development and genome replication, as well as for the maintenance of its integrity, and is thus likely to play a crucial role during the transition from heterotrophy to autotrophy after germination. Interestingly, defects in TK activity could be partially compensated by supplementation of the medium with sugar, and this effect resulted from both the availability of a carbon source and the activation of the nucleotide de novo synthesis pathway, providing evidence for a compensation mechanism between two routes of nucleotide biosynthesis that depend on nutrient availability. Finally, we found differential roles of the TK1a and TK1b genes during the plant response to genotoxic stress, suggesting that different pools of nucleotides exist within the cells and are required to respond to different types of DNA damage. Altogether, our results highlight the importance of the pyrimidine salvage pathway, both during plant development and in response to genotoxic stress.     

Contribution of NaCl excretion to salt resistance of Aeluropus littoralis (Willd) Parl

Aeluropus littoralis is a perennial halophyte, native to coastal zones. Although it is usually exposed to high saline, this plant grows normally without toxicity symptoms. In order to assess leaf salt excretion, different growth parameters, Na(+), K(+), Ca(2+), Mg(2+) and Cl(-) concentrations, as well as excreted ions were examined in plants grown for 2 months in the presence of various salinity levels (0-800 mM NaCl). In addition, salt crystals, salt glands and other leaf epidermal structures were investigated. Results showed that total plant growth decreased linearly with increase to medium salinity. This reduction concerns mainly shoot growth. In addition, this species was able to maintain its shoot water content at nearly 50% of the control even when subjected to 800 mM NaCl. Root water content seemed to be unaffected by salt. Sodium and chloride ion contents in shoots and in roots increased with salinity concentrations, in contrast to our observation for potassium. However, calcium and magnesium contents were not greatly affected by salinity. Excreted salts in A. littoralis leaves were in favor of sodium and chloride, but against potassium, calcium and magnesium which were retained in plants. Sodium and chloride were excreted from special salt glands, which were scattered on the both leaf surfaces. In addition to salt glands, papillae were the most frequent epidermal structure found on A. littoralis leaves, and are likely involved in A. littoralis salt resistance.     

Salt impact on photosynthesis and leaf ultrastructure of <Emphasis Type="Italic">Aeluropus littoralis</Emphasis>

The effects of salinity (400 mM NaCl) on growth, biomass partitioning, photosynthesis, and leaf ultrastructure were studied in hydroponically grown plants of Aeluropus littoralis (Willd) Parl. NaCl produced a significant inhibition of the main growth parameters and a reduction in leaf gas exchange (e.g. decreased rates of photosynthesis and stomatal conductance). However, NaCl salinity affected neither the composition of photosynthesis pigments nor leaf water content. The reduction in leaf gas exchange seemed to correlate with a decrease in mesophyll thickness as well as a severe disorganisation of chloroplast structure, with misshapen chloroplasts and dilated thylakoid membranes. Conspicuously, mesophyll chloroplasts were more sensitive to salt treatment than those of bundle sheath cells. The effects of NaCl toxicity on leaf structure and ultrastructure and the associated physiological implications are discussed in relation to the degree of salt resistance of A. littoralis.     

Ultrastructure of Aeluropus littoralis leaf salt glands under NaCl stress

The effects of salt uptake on the morphology and ultrastructure of leaf salt glands were investigated in Aeluropus littoralis plants grown for two months in the presence of 400 mM NaCl. The salt gland is composed of two linked cells, as observed in some other studied Poaceae species. The cap cell, which protrudes from the leaf surface, is smaller than the basal cell, which is embedded in the leaf mesophyll tissues and bears the former. The cuticle over the cap cell is frequently separated from the cell wall to form a cavity where salts accumulate prior to excretion. The basal cell cytoplasm contains an extensive intricate or partitioning membrane system that is probably involved in the excretion process, which is absent from the cap cell. The intricate membrane system seems to be elongated and heavily loaded with salt. The presence of 400 mM NaCl induced the disappearance of the collecting chamber over the glands and an increase in the number of vacuoles and their size in both gland cells. In the basal cell, salt greatly increased both the density and size of the intricate membrane system. The electron density of both gland cells observed under salt treatment reflects a high activity. All these changes probably constitute special adaptations for dealing with salt accumulation in the leaves. Despite the high salt concentration used, no serious damage occurred in A. littoralis salt gland ultrastructure, which consolidates the assumption that they are naturally designated for this purpose.     

Modifications in endopeptidase and 20S proteasome expression and activities in cadmium treated tomato (<Emphasis Type="Italic">Solanum lycopersicum</Emphasis> L.) plants

The effects of cadmium (Cd) on cellular proteolytic responses were investigated in the roots and leaves of tomato (Solanum lycopersicum L., var Ibiza) plants. Three-week-old plants were grown for 3 and 10 days in the presence of 0.3–300 μM Cd and compared to control plants grown in the absence of Cd. Roots of Cd treated plants accumulated four to fivefold Cd as much as mature leaves. Although 10 days of culture at high Cd concentrations inhibited plant growth, tomato plants recovered and were still able to grow again after Cd removal. Tomato roots and leaves are not modified in their proteolytic response with low Cd concentrations (≤3 μM) in the incubation medium. At higher Cd concentration, protein oxidation state and protease activities are modified in roots and leaves although in different ways. The soluble protein content of leaves decreased and protein carbonylation level increased indicative of an oxidative stress. Conversely, protein content of roots increased from 30 to 50%, but the amount of oxidized proteins decreased by two to threefold. Proteolysis responded earlier in leaves than in root to Cd stress. Additionally, whereas cysteine- and metallo-endopeptidase activities, as well as proteasome chymotrypsin activity and subunit expression level, increased in roots and leaves, serine-endopeptidase activities increased only in leaves. This contrasted response between roots and leaves may reflect differences in Cd compartmentation and/or complexation, antioxidant responses and metabolic sensitivity to Cd between plant tissues. The up-regulation of the 20S proteasome gene expression and proteolytic activity argues in favor of the involvement of the 20S proteasome in the degradation of oxidized proteins in plants. This paper is dedicated to Nathalie Galtier (1964–2005), who was senior researcher at the INRA Research Center, Villenave d’Ornon, France.     

On the Use of Leaf Spectral Indices to Assess Water Status and Photosynthetic Limitations in Olea europaea L. during Water-Stress and Recovery

Diffusional limitations to photosynthesis, relative water content (RWC), pigment concentrations and their association with reflectance indices were studied in olive (Olea europaea) saplings subjected to water-stress and re-watering. RWC decreased sharply as drought progressed. Following rewatering, RWC gradually increased to pre-stress values. Photosynthesis (A), stomatal conductance (g_s), mesophyll conductance (g_m), total conductance (g_t), photochemical reflectance index (PRI), water index (WI) and relative depth index (RDI) closely followed RWC. In contrast, carotenoid concentration, the carotenoid to chlorophyll ratio, water content reflectance index (WCRI) and structural independent pigment index (SIPI) showed an opposite trend to that of RWC. Photosynthesis scaled linearly with leaf conductance to CO₂; however, A measured under non-photorespiratory conditions (A_1%O2) was approximately two times greater than A measured at 21% [O₂], indicating that photorespiration likely increased in response to drought. A_1%O2 also significantly correlated with leaf conductance parameters. These relationships were apparent in saturation type curves, indicating that under non-photorespiratory conditions, CO₂ conductance was not the major limitations to A. PRI was significant correlated with RWC. PRI was also very sensitive to pigment concentrations and photosynthesis, and significantly tracked all CO₂ conductance parameters. WI, RDI and WCRI were all significantly correlated with RWC, and most notably to leaf transpiration. Overall, PRI correlated more closely with carotenoid concentration than SIPI; whereas WI tracked leaf transpiration more effectively than RDI and WCRI. This study clearly demonstrates that PRI and WI can be used for the fast detection of physiological traits of olive trees subjected to water-stress.