Modelled biophysical impacts of conservation agriculture on local climates

Including the parameterization of land management practices into Earth System Models has been shown to influence the simulation of regional climates, particularly for temperature extremes. However, recent model development has focused on implementing irrigation where other land management practices such as conservation agriculture (CA) has been limited due to the lack of global spatially explicit datasets describing where this form of management is practiced. Here, we implement a representation of CA into the Community Earth System Model and show that the quality of simulated surface energy fluxes improves when including more information on how agricultural land is managed. We also compare the climate response at the subgrid scale where CA is applied. We find that CA generally contributes to local cooling (~1°C) of hot temperature extremes in mid‐latitude regions where it is practiced, while over tropical locations CA contributes to local warming (~1°C) due to changes in evapotranspiration dominating the effects of enhanced surface albedo. In particular, changes in the partitioning of evapotranspiration between soil evaporation and transpiration are critical for the sign of the temperature change: a cooling occurs only when the soil moisture retention and associated enhanced transpiration is sufficient to offset the warming from reduced soil evaporation. Finally, we examine the climate change mitigation potential of CA by comparing a simulation with present‐day CA extent to a simulation where CA is expanded to all suitable crop areas. Here, our results indicate that while the local temperature response to CA is considerable cooling (>2°C), the grid‐scale changes in climate are counteractive due to negative atmospheric feedbacks. Overall, our results underline that CA has a nonnegligible impact on the local climate and that it should therefore be considered in future climate projections.     

Combination of a Proteomics Approach and Reengineering of Meso Scale Network Models for Prediction of Mode-of-Action for Tyrosine Kinase Inhibitors

In drug discovery, the characterisation of the precise modes of action (MoA) and of unwanted off-target effects of novel molecularly targeted compounds is of highest relevance. Recent approaches for identification of MoA have employed various techniques for modeling of well defined signaling pathways including structural information, changes in phenotypic behavior of cells and gene expression patterns after drug treatment. However, efficient approaches focusing on proteome wide data for the identification of MoA including interference with mutations are underrepresented. As mutations are key drivers of drug resistance in molecularly targeted tumor therapies, efficient analysis and modeling of downstream effects of mutations on drug MoA is a key to efficient development of improved targeted anti-cancer drugs. Here we present a combination of a global proteome analysis, reengineering of network models and integration of apoptosis data used to infer the mode-of-action of various tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) cell lines expressing wild type as well as TKI resistance conferring mutants of BCR-ABL. The inferred network models provide a tool to predict the main MoA of drugs as well as to grouping of drugs with known similar kinase inhibitory activity patterns in comparison to drugs with an additional MoA. We believe that our direct network reconstruction approach, demonstrated on proteomics data, can provide a complementary method to the established network reconstruction approaches for the preclinical modeling of the MoA of various types of targeted drugs in cancer treatment. Hence it may contribute to the more precise prediction of clinically relevant on- and off-target effects of TKIs.     

Temporal sampling,resetting, and adaptation orchestrate gradient sensing in sperm

Sperm, navigating in a chemical gradient, are exposed to a periodic stream of chemoattractant molecules. The periodic stimulation entrains Ca²⁺ oscillations that control looping steering responses. It is not known how sperm sample chemoattractant molecules during periodic stimulation and adjust their sensitivity. We report that sea urchin sperm sampled molecules for 0.2–0.6 s before a Ca²⁺ response was produced. Additional molecules delivered during a Ca²⁺ response reset the cell by causing a pronounced Ca²⁺ drop that terminated the response; this reset was followed by a new Ca²⁺ rise. After stimulation, sperm adapted their sensitivity following the Weber–Fechner law. Taking into account the single-molecule sensitivity, we estimate that sperm can register a minimal gradient of 0.8 fM/µm and be attracted from as far away as 4.7 mm. Many microorganisms sense stimulus gradients along periodic paths to translate a spatial distribution of the stimulus into a temporal pattern of the cell response. Orchestration of temporal sampling, resetting, and adaptation might control gradient sensing in such organisms as well.     

Comparative study of hydrogel-immobilized l-glutamate oxidases for a novel thick-film biosensor and its application in food samples

Novel, thick-film biosensors have been developed for the determination of l-glutamate in foodstuffs. The sensors were prepared by immobilization of l-glutamate oxidase by using polycarbamylsulfonate-hydrogel on a thick-film sensor. l-Glutamate oxidases obtained from Streptomyces sp. with different degree of purification were compared with their characteristic response to l-glutamate at different conditions and for their specificity, inhibition, and storage properties. These sensors were applied to determine monosodium glutamate in soy sauce samples and show good correlation with colorimetric method.     

Integrating Pathways of Parkinson's Disease in a Molecular Interaction Map

Parkinson's disease (PD) is a major neurodegenerative chronic disease, most likely caused by a complex interplay of genetic and environmental factors. Information on various aspects of PD pathogenesis is rapidly increasing and needs to be efficiently organized, so that the resulting data is available for exploration and analysis. Here we introduce a computationally tractable, comprehensive molecular interaction map of PD. This map integrates pathways implicated in PD pathogenesis such as synaptic and mitochondrial dysfunction, impaired protein degradation, alpha-synuclein pathobiology and neuroinflammation. We also present bioinformatics tools for the analysis, enrichment and annotation of the map, allowing the research community to open new avenues in PD research. The PD map is accessible at http://minerva.uni.lu/pd_map.     

Mnl2, a novel component of the ER associated protein degradation pathway

In eukaryotes, membrane and soluble proteins of the secretory pathway enter the endoplasmic reticulum (ER) after synthesis in an unfolded state. Directly after entry, most proteins are modified with glycans at suitable glycosylation sites and start to fold. A protein that cannot fold properly will be degraded in a process called ER associated degradation (ERAD). Failures in ERAD, either by loss of function or by premature degradation of proteins, are a cause of severe diseases. Therefore, the search for novel ERAD components to gain better insight in this process is of high importance. Carbohydrate trimming is a relevant process in ER quality control. In this work a novel putative yeast mannosidase encoded by the open reading frame YLR057W was identified and named Mnl2. Deletion of MNL2 diminished the degradation efficiency of misfolded CPY^* in the absence of the cognate mannosidase Mnl1, indicating a specific role in ERAD.     

Short-term variation of nutritive and metabolic parameters in <Emphasis Type="Italic">Temora longicornis</Emphasis> females (Crustacea,Copepoda) as a response to diet shift and starvation

Changes in fatty acid patterns, digestive and metabolic enzyme activities and egg production rates (EPR) were studied in the small calanoid copepod Temora longicornis. Female copepods were collected in spring 2005 off Helgoland (North Sea). In the laboratory one group of copepods was fed with the cryptophycean Rhodomonas baltica for a period of 3 days. Another group of copepods was maintained without food. According to the fatty acid patterns, animals from the field were feeding on a more detrital, animal-based and to a minor extent to a diatom-based diet. Under laboratory conditions, females rapidly accumulated fatty acids such as 18:4 (n-3), 18:3 (n-3) and 18:2 (n-6) which are specific of R. baltica. Diatom-specific fatty acids such as 16:1 (n-7) were strongly reduced. In fed animals the activities of digestive and metabolic enzymes remained constant and egg production rates were highest on day 2. Starving animals, in contrast, showed significantly reduced faecal pellet production and EPR. Proteolytic enzyme activity decreased rapidly within 24 h and remained at a low level until the end of the experiment. Citrate synthase decreased continuously as well. T. longicornis rapidly reacts to dietary changes and food depletion. It has limited energy stores and, thus, strongly depends on continuous food supply.