Reconstitution of the adult B cell repertoire after treatment with rituximab

B cells play diverse and fundamental roles in the pathogenesis of autoimmune diseases. Consequently, therapeutic targeting of B cells is gaining prominence in our clinical armamentarium for an ever expanding array of autoimmune and neoplastic disorders. Therefore, it is of great importance to understand the mechanism of action of B cell depletion. Given that the ideal consequence of B cell depletion would be the subsequent re-establishment of immunologic tolerance, a detailed analysis of the properties of the emerging repertoire will be required. The results presented by Rouzière and coworkers in their study of rheumatoid arthritis patients shed some light on this question and are discussed in this commentary.     

Modelling climate change impacts on viticultural yield,phenology and stress conditions in Europe

Viticulture is a key socio‐economic sector in Europe. Owing to the strong sensitivity of grapevines to atmospheric factors, climate change may represent an important challenge for this sector. This study analyses viticultural suitability, yield, phenology, and water and nitrogen stress indices in Europe, for present climates (1980–2005) and future (2041–2070) climate change scenarios (RCP4.5 and 8.5). The STICS crop model is coupled with climate, soil and terrain databases, also taking into account CO₂ physiological effects, and simulations are validated against observational data sets. A clear agreement between simulated and observed phenology, leaf area index, yield and water and nitrogen stress indices, including the spatial differences throughout Europe, is shown. The projected changes highlight an extension of the climatic suitability for grapevines up to 55°N, which may represent the emergence of new winemaking regions. Despite strong regional heterogeneity, mean phenological timings (budburst, flowering, veraison and harvest) are projected to undergo significant advancements (e.g. budburst/harvest can be >1 month earlier), with implications also in the corresponding phenophase intervals. Enhanced dryness throughout Europe is also projected, with severe water stress over several regions in southern regions (e.g. southern Iberia and Italy), locally reducing yield and leaf area. Increased atmospheric CO₂ partially offsets dryness effects, promoting yield and leaf area index increases in central/northern Europe. Future biomass changes may lead to modifications in nitrogen demands, with higher stress in northern/central Europe and weaker stress in southern Europe. These findings are critical decision support systems for stakeholders from the European winemaking sector.     

Neuronal Hyperactivity Disturbs ATP Microgradients,Impairs Microglial Motility,and Reduces Phagocytic Receptor Expression Triggering Apoptosis/Microglial Phagocytosis Uncoupling

Phagocytosis is essential to maintain tissue homeostasis in a large number of inflammatory and autoimmune diseases, but its role in the diseased brain is poorly explored. Recent findings suggest that in the adult hippocampal neurogenic niche, where the excess of newborn cells undergo apoptosis in physiological conditions, phagocytosis is efficiently executed by surveillant, ramified microglia. To test whether microglia are efficient phagocytes in the diseased brain as well, we confronted them with a series of apoptotic challenges and discovered a generalized response. When challenged with excitotoxicity in vitro (via the glutamate agonist NMDA) or inflammation in vivo (via systemic administration of bacterial lipopolysaccharides or by omega 3 fatty acid deficient diets), microglia resorted to different strategies to boost their phagocytic efficiency and compensate for the increased number of apoptotic cells, thus maintaining phagocytosis and apoptosis tightly coupled. Unexpectedly, this coupling was chronically lost in a mouse model of mesial temporal lobe epilepsy (MTLE) as well as in hippocampal tissue resected from individuals with MTLE, a major neurological disorder characterized by seizures, excitotoxicity, and inflammation. Importantly, the loss of phagocytosis/apoptosis coupling correlated with the expression of microglial proinflammatory, epileptogenic cytokines, suggesting its contribution to the pathophysiology of epilepsy. The phagocytic blockade resulted from reduced microglial surveillance and apoptotic cell recognition receptor expression and was not directly mediated by signaling through microglial glutamate receptors. Instead, it was related to the disruption of local ATP microgradients caused by the hyperactivity of the hippocampal network, at least in the acute phase of epilepsy. Finally, the uncoupling led to an accumulation of apoptotic newborn cells in the neurogenic niche that was due not to decreased survival but to delayed cell clearance after seizures. These results demonstrate that the efficiency of microglial phagocytosis critically affects the dynamics of apoptosis and urge to routinely assess the microglial phagocytic efficiency in neurodegenerative disorders.     

Rethinking false spring risk

Temperate plants are at risk of being exposed to late spring freezes. These freeze events—often called false springs—are one of the strongest factors determining temperate plants species range limits and can impose high ecological and economic damage. As climate change may alter the prevalence and severity of false springs, our ability to forecast such events has become more critical, and it has led to a growing body of research. Many false spring studies largely simplify the myriad complexities involved in assessing false spring risks and damage. While these studies have helped advance the field and may provide useful estimates at large scales, studies at the individual to community levels must integrate more complexity for accurate predictions of plant damage from late spring freezes. Here, we review current metrics of false spring, and how, when, and where plants are most at risk of freeze damage. We highlight how life stage, functional group, species differences in morphology and phenology, and regional climatic differences contribute to the damage potential of false springs. More studies aimed at understanding relationships among species tolerance and avoidance strategies, climatic regimes, and the environmental cues that underlie spring phenology would improve predictions at all biological levels. An integrated approach to assessing past and future spring freeze damage would provide novel insights into fundamental plant biology and offer more robust predictions as climate change progresses, which are essential for mitigating the adverse ecological and economic effects of false springs.     

Performance of several models for predicting budburst date of grapevine (<Emphasis Type="Italic">Vitis vinifera</Emphasis> L.)

The budburst stage is a key phenological stage for grapevine (Vitis vinifera L.), with large site and cultivar variability. The objective of the present work was to provide a reliable agro-meteorological model for simulating grapevine budburst occurrence all over France. The study was conducted using data from ten cultivars of grapevine (Cabernet Sauvignon, Chasselas, Chardonnay, Grenache, Merlot, Pinot Noir, Riesling, Sauvignon, Syrah, Ugni Blanc) and five locations (Bordeaux, Colmar, Angers, Montpellier, Epernay). First, we tested two commonly used models that do not take into account dormancy: growing degree days with a base temperature of 10°C (GDD₁₀), and Riou’s model (RIOU). The errors of predictions of these models ranged between 9 and 21 days. Second, a new model (BRIN) was studied relying on well-known formalisms for orchard trees and taking into account the dormancy period. The BRIN model showed better performance in predicting budburst date than previous grapevine models. Analysis of the components of BRIN formalisms (calculation of dormancy, use of hourly temperatures, base temperature) explained the better performances obtained with the BRIN model. Base temperature was the main driver, while dormancy period was not significant in simulating budburst date. For each cultivar, we provide the parameter estimates that showed the best performance for both the BRIN model and the GDD model with a base temperature of 5°C.     

Sawyeria marylandensis (Heterolobosea) has a hydrogenosome with novel metabolic properties

Protists that live under low-oxygen conditions often lack conventional mitochondria and instead possess mitochondrion-related organelles (MROs) with distinct biochemical functions. Studies of mostly parasitic organisms have suggested that these organelles could be classified into two general types: hydrogenosomes and mitosomes. Hydrogenosomes, found in parabasalids, anaerobic chytrid fungi, and ciliates, metabolize pyruvate anaerobically to generate ATP, acetate, CO(2), and hydrogen gas, employing enzymes not typically associated with mitochondria. Mitosomes that have been studied have no apparent role in energy metabolism. Recent investigations of free-living anaerobic protists have revealed a diversity of MROs with a wider array of metabolic properties that defy a simple functional classification. Here we describe an expressed sequence tag (EST) survey and ultrastructural investigation of the anaerobic heteroloboseid amoeba Sawyeria marylandensis aimed at understanding the properties of its MROs. This organism expresses typical anaerobic energy metabolic enzymes, such as pyruvate:ferredoxin oxidoreductase, [FeFe]-hydrogenase, and associated hydrogenase maturases with apparent organelle-targeting peptides, indicating that its MRO likely functions as a hydrogenosome. We also identified 38 genes encoding canonical mitochondrial proteins in S. marylandensis, many of which possess putative targeting peptides and are phylogenetically related to putative mitochondrial proteins of its heteroloboseid relative Naegleria gruberi. Several of these proteins, such as a branched-chain alpha keto acid dehydrogenase, likely function in pathways that have not been previously associated with the well-studied hydrogenosomes of parabasalids. Finally, morphological reconstructions based on transmission electron microscopy indicate that the S. marylandensis MROs form novel cup-like structures within the cells. Overall, these data suggest that Sawyeria marylandensis possesses a hydrogenosome of mitochondrial origin with a novel combination of biochemical and structural properties.     

Social organisational LCA for the academic activity of the University of the Basque Country UPV/EHU

The International Journal of Life Cycle Assessment - This article aims to estimate the social footprint of a higher education institution (HEI) and its potential contribution to Sustainable...