A Mechanistic View of the Role of E3 in Sumoylation

Sumoylation, the covalent attachment of SUMO (Small Ubiquitin-Like Modifier) to proteins, differs from other Ubl (Ubiquitin-like) pathways. In sumoylation, E2 ligase Ubc9 can function without E3 enzymes, albeit with lower reaction efficiency. Here, we study the mechanism through which E3 ligase RanBP2 triggers target recognition and catalysis by E2 Ubc9. Two mechanisms were proposed for sumoylation. While in both the first step involves Ubc9 conjugation to SUMO, the subsequent sequence of events differs: in the first E2-SUMO forms a complex with the target and E3, followed by SUMO transfer to the target. In the second, Ubc9-SUMO binds to the target and facilitates SUMO transfer without E3. Using dynamic correlations obtained from explicit solvent molecular dynamic simulations we illustrate the key roles played by allostery in both mechanisms. Pre-existence of conformational states explains the experimental observations that sumoylation can occur without E3, even though at a reduced rate. Furthermore, we propose a mechanism for enhancement of sumoylation by E3. Analysis of the conformational ensembles of the complex of E2 conjugated to SUMO illustrates that the E2 enzyme is already largely pre-organized for target binding and catalysis; E3 binding shifts the equilibrium and enhances these pre-existing populations. We further observe that E3 binding regulates allosterically the key residues in E2, Ubc9 Asp100/Lys101 E2, for the target recognition

Impacts of climate change on plant diseases – opinions and trends

There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods

PTEN as a Prognostic and Predictive Marker in Postoperative Radiotherapy for Squamous Cell Cancer of the Head and Neck

BACKGROUND: Tumor suppressor PTEN is known to control a variety of processes related to cell survival, proliferation, and growth. PTEN expression is considered as a prognostic factor in some human neoplasms like breast, prostate, and thyroid cancer. METHODOLOGY/PRINCIPAL FINDINGS: In this study we analyzed the influence of PTEN expression on the outcome of a randomized clinical trial of conventional versus 7-days-a-week postoperative radiotherapy for squamous cell cancer of the head and neck. The patients with cancer of the oral cavity, oropharynx, and larynx were randomized to receive 63 Gy in fractions of 1.8 Gy given 5 days a week (CF) or 7 days a week (p-CAIR). Out of 279 patients enrolled in the study, 147 paraffin blocks were available for an immunohistochemical assessment of PTEN. To evaluate the prognostic value of PTEN expression and the effect of fractionation relative to PTEN, the data on the outcome of a randomized clinical trial were analyzed. Tumors with a high intensity of PTEN staining had significant gain in the loco-regional control (LRC) from p-CAIR (5-year LRC 92.7% vs. 70.8%, for p-CAIR vs. CF, p = 0.016, RR = 0.26). By contrast, tumors with low intensity of PTEN did not gain from p-CAIR (5-year LRC 56.2% vs. 47.2%, p = 0.49, RR = 0.94). The intensity of PTEN highly affected the LRC in a whole group of 147 patients (5-year LRC 80.9% vs. 52.3% for high vs. low PTEN, p = 0.0007, RR = 0.32). In multivariate Cox analysis, including neck node involvement, EGFR, nm23, Ki-67, p53, cyclin D1, tumor site and margins, PTEN remained an independent predictor of LRC (RR = 2.8 p = 0.004). CONCLUSIONS/SIGNIFICANCE: These results suggest that PTEN may serve as a potent prognostic and predictive marker in postoperative radiotherapy for high-risk squamous cell cancer of the head and neck

Nestin-GFP Transgene Reveals Neural Precursor Cells in Adult Skeletal Muscle

Background: Therapy for neural lesions or degenerative diseases relies mainly on finding transplantable active precursor cells. Identifying them in peripheral tissues accessible for biopsy, outside the central nervous system, would circumvent the serious immunological and ethical concerns impeding cell therapy. Methodology/Principal Findings: In this study, we isolated neural progenitor cells in cultured adult skeletal muscle from transgenic mice in which nestin regulatory elements control GFP expression. These cells also expressed the early neural marker Tuj1 and light and heavy neurofilament but not S100b, indicating that they express typical neural but not Schwann cell markers. GFP+/Tuj1+ cells were also negative for the endothelial and pericyte markers CD31 and a-smooth muscle actin, respectively. We established their a) functional response to glutamate in patch-clamp recordings; b) interstitial mesenchymal origin; c) replicative capacity; and d) the environment necessary for their survival after fluorescenceactivated cell sorting. Conclusions/Significance: We propose that the decline in nestin-GFP expression in muscle progenitor cells and its persistence in neural precursor cells in muscle cultures provide an invaluable tool for isolating a population of predifferentiated neural cells with therapeutic potential

A review of modelling methodologies for flood source area (FSA) identification

Flooding is an important global hazard that causes an average annual loss of over 40 billion USD and affects a population of over 250 million globally. The complex process of flooding depends on spatial and temporal factors such as weather patterns, topography, and geomorphology. In urban environments where the landscape is ever-changing, spatial factors such as ground cover, green spaces, and drainage systems have a significant impact. Understanding source areas that have a major impact on flooding is, therefore, crucial for strategic flood risk management (FRM). Although flood source area (FSA) identification is not a new concept, its application is only recently being applied in flood modelling research. Continuous improvements in the technology and methodology related to flood models have enabled this research to move beyond traditional methods, such that, in recent years, modelling projects have looked beyond affected areas and recognised the need to address flooding at its source, to study its influence on overall flood risk. These modelling approaches are emerging in the field of FRM and propose innovative methodologies for flood risk mitigation and design implementation; however, they are relatively under-examined. In this paper, we present a review of the modelling approaches currently used to identify FSAs, i.e. unit flood response (UFR) and adaptation-driven approaches (ADA). We highlight their potential for use in adaptive decision making and outline the key challenges for the adoption of such approaches in FRM practises

Ecophysiology and field performance of black spruce (Picea mariana): a review

This paper presents a literature review of black spruce (Picea mariana [Mill] BSP) ecophysiology concerning the response of net photosynthesis and stomata to changes in environmental factors. Current knowledge on root growth, mineral nutrition and response to high temperature, CO2 enrichment and climate change, frosts, water stress and flooding are also covered. The review ends with an overview of stand establishment and field performance of planted seedlings. The authors highlight the need for research on the long-term effects of multiple stresses, such as climate change and air pollution on the black spruce ecosystem.Écophysiologie et performances des plants de l'épinette noire. Revue. Cet article présente une revue de littérature de l'écophysiologie de l'épinette noire (Picea mariana [Mill] BSP) mettant l'accent sur les facteurs environnementaux qui affectent la photosynthèse nette et la réponse des stomates. Cette revue offre une mise à jour sur l'état actuel des connaissances sur la croissance racinaire, sur la nutrition minérale, ainsi que sur la réponse de la plante aux températures élevées, à l'augmentation en CO2 atmosphérique et aux changements climatiques, aux gels, au stress hydrique, et à l'engorgement des sols. Finalement, l'article rapporte différents résultats concernant la régénération naturelle et la performance des plants de l'épinette noire en site de reboisement. Les auteurs soulignent l'importance de poursuivre les recherches sur les effets à long terme de stress multiples comme la pollution de l'air et les changements climatiques sur l'écosystème de la pessière noire

Gas exchange and water relations of 3 sizes of containerized Picea mariana seedlings subjected to atmospheric and edaphic water stress under controlled conditions

Containerized black spruce (Picea mariana [Mill] BSP) seedlings of 3 sizes (heights of 18, 35 and 45 cm) were placed in growth chambers and subjected to conditions of low evaporative (20°C, 60% RH) or high evaporative (30°C, 40% RH) demand, with 3 levels of soil water availability in each environment. The large seedlings had the highest rate of net photosynthesis in the cooler environment, but showed the greatest reduction in net photosynthetic rate in the warmer and drier environment, under conditions of limited water supply. The small seedlings were least affected by the warmer and drier environment in which they maintained photosynthetic rates higher than those of the larger seedlings. The decrease in net photosynthesis experienced by the large seedlings in the warmer and drier environment under conditions of limited water availability was associated with a large decrease in stomatal conductance. However, the maintenance of a high level of intercellular CO2 concentration suggests that most of the limitations to net photosynthesis were of non-stomatal origin. Water content of the root plug was also reduced by increased seedling size, but the differences were least evident under conditions that produced the largest differences in net photosynthetic rates. These results, obtained under controlled conditions, suggest that after outplanting, large seedlings would experience greater reduction in growth than smaller ones only under conditions of high evaporative demand and low water availability.Échanges gazeux et relations hydriques chez des semis de Picea mariana de 3 tailles différentes cultivés en conteneurs et soumis à différentes conditions de sécheresse atmosphérique et édaphique. Nous avons soumis en chambre de croissance des semis d'épinette noire (Picea mariana [Mill] BSP) de 3 tailles différentes (18, 35 et 45 cm de hauteur) et cultivés en conteneurs, à des conditions de demande évaporative faible (20°C, 60% HR) et élevée (30° C, 40% HR) conjointement à 3 niveaux de disponibilité en eau du sol. Les semis de plus forte taille avaient les taux de photosynthèse nette les plus élevés dans l'environnement frais, mais la plus forte réduction de ce paramètre dans l'environnement plus chaud et sec, sous des conditions de faible disponibilité en eau. Cette forte réduction de photosynthèse nette était associée à une fermeture des stomates. Cependant, le taux élevé de concentration intercellulaire en CO2 indique que des facteurs non stomatiques étaient principalement à l'origine de cette réduction. Les semis de plus faible taille ont maintenu en conditions chaudes et sèches des taux de photosynthèse nette supérieurs à ceux des semis de plus forte taille. L'accroissement de la taille des semis a réduit la teneur en eau de la motte racinaire, mais principalement sous des conditions n'engendrant pas de différences dans les taux de photosynthèse nette entre les tailles de semis. Les résultats obtenus en conditions contrôlées indiquent que la croissance des semis d'épinette noire de plus forte taille serait plus affectée à la suite de la plantation que celle des semis de plus faible taille à condition seulement que la demande évaporative soit forte et la disponibilité en eau faible

Morphological versatility of solid C

C60 fullerene may crystallize from benzene solutions as thin yellow plates, whose morphology has suggested the existence of a hcp modification. By means of single crystal X-ray diffraction, we show that these plates crystallize in the cubic system (space group Fm[math]m, a = 14.155 Å). No trace of solvent could be observed by TGA and DSC experiments. Surprisingly, these plates do not exhibit the phase transition near 260 K. Nevertheless, the existence of a hcp variety cannot be discarded since scanning electron microscopy reveals the presence of hexagonal prisms in a sample made of pure C60 powder