Identification of novel α7 nicotinic receptor ligands by in silico screening against the crystal structure of a chimeric α7 receptor ligand binding domain

A hierarchical in silico screening procedure using the crystal structure of an agonist bound chimeric α7/Ls-AChBP protein was successfully applied to both proprietary and commercial databases containing drug-like molecules. An overall hit rate of 26% (pK_i ?5.0) was obtained, with an even better hit rate of 35% for the commercial compound collection. Structurally novel and diverse ligands were identified. Binding studies with [³H]epibatidine on chimeric α7/5-HT₃ receptors yielded submicromolar inhibition constants for identified hits. Compared to a previous screening procedure that utilized the wild type Ls-AChBP crystal structure, the current study shows that the recently obtained α7/Ls-AChBP chimeric protein crystal structure is a better template for the identification of novel α7 receptor ligands.     

The effect of sulfur-containing nitrogen fertilizers on the elemental composition of celery (Apium graveolens) grown on a polluted marsh soil

Summary In order to investigate elemental composition of celery, and to quantify the influence of sulfur-containing N-fertilizers on the trace element uptake, a field trial with celery was carried out on marsh soil polluted with municipal wastes. The research yielded the following results:Compared to leaves at harvest time, bulbs showed significantly lower concentrations of Mo, S and Sb, but higher contents of B, Br and Cr and Cu. Since the acidifying effect of the fertilizers was suppressed by the free calcium carbonate in the soil, no significant changes in concentrations of cationic trace elements were detected in plants fertilized with ammonium sulfate compared to those which received urea or calcium ammonium nitrate. On the other hand, in these plants the conspicuous increase in total sulfur was accompanied by a significant decrease in concentrations of up to 30% for B, Br and Sb, 50% for As, 60% for Se and 80% for Mo.According to these results, in plant production on contaminated soils certain plant parts may be marketable due to their low tendency to accumulate toxic elements, and furthermore it may be feasible to reduce the contents of some of these elements in plants by the use of sulfur-containing fertilizers.     

Proton-transfer-reaction mass spectrometry (PTR-MS) for online monitoring of glucose depletion and cell concentrations in HEK 293 gene therapy processes

Biotechnology Letters - The applicability of proton-transfer-reaction mass spectrometry (PTR-MS) as a versatile online monitoring tool to increase consistency and robustness for recombinant...     

Deconvoluting lung evolution: from phenotypes to gene regulatory networks

Speakers in this symposium presented examples of respiratoryregulation that broadly illustrate principles of evolution fromwhole organ to genes. The swim bladder and lungs of aquaticand terrestrial organisms arose independently from a commonprimordial "respiratory pharynx" but not from each other. Pathwaysof lung evolution are similar between crocodiles and birds buta low compliance of mammalian lung may have driven the developmentof the diaphragm to permit lung inflation during inspiration.To meet the high oxygen demands of flight, bird lungs have evolvedseparate gas exchange and pump components to achieve unidirectionalventilation and minimize dead space. The process of "screening"(removal of oxygen from inspired air prior to entering the terminalunits) reduces effective alveolar oxygen tension and potentiallyexplains why nonathletic large mammals possess greater pulmonarydiffusing capacities than required by their oxygen consumption.The "primitive" central admixture of oxygenated and deoxygenatedblood in the incompletely divided reptilian heart is actuallyco-regulated with other autonomic cardiopulmonary responsesto provide flexible control of arterial oxygen tension independentof ventilation as well as a unique mechanism for adjusting metabolicrate. Some of the most ancient oxygen-sensing molecules, i.e.,hypoxia-inducible factor-1alpha and erythropoietin, are up-regulatedduring mammalian lung development and growth under apparentlynormoxic conditions, suggesting functional evolution. Normalalveolarization requires pleiotropic growth factors acting viahighly conserved cell–cell signal transduction, e.g.,parathyroid hormone-related protein transducing at least partlythrough the Wingless/int pathway. The latter regulates morphogenesisfrom nematode to mammal. If there is commonality among thesediverse respiratory processes, it is that all levels of organization,from molecular signaling to structure to function, co-evolveprogressively, and optimize an existing gas-exchange framework.     

Influences of extreme weather,climate and pesticide use on invertebrates in cereal fields over 42 years

Cereal fields are central to balancing food production and environmental health in the face of climate change. Within them, invertebrates provide key ecosystem services. Using 42 years of monitoring data collected in southern England, we investigated the sensitivity and resilience of invertebrates in cereal fields to extreme weather events and examined the effect of long‐term changes in temperature, rainfall and pesticide use on invertebrate abundance. Of the 26 invertebrate groups examined, eleven proved sensitive to extreme weather events. Average abundance increased in hot/dry years and decreased in cold/wet years for Araneae, Cicadellidae, adult Heteroptera, Thysanoptera, Braconidae, Enicmus and Lathridiidae. The average abundance of Delphacidae, Cryptophagidae and Mycetophilidae increased in both hot/dry and cold/wet years relative to other years. The abundance of all 10 groups usually returned to their long‐term trend within a year after the extreme event. For five of them, sensitivity to cold/wet events was lowest (translating into higher abundances) at locations with a westerly aspect. Some long‐term trends in invertebrate abundance correlated with temperature and rainfall, indicating that climate change may affect them. However, pesticide use was more important in explaining the trends, suggesting that reduced pesticide use would mitigate the effects of climate change.     

Cell size control in yeast

Cell size is an important adaptive trait that influences nearly all aspects of cellular physiology. Despite extensive characterization of the cell-cycle regulatory network, the molecular mechanisms coupling cell growth to division, and thereby controlling cell size, have remained elusive. Recent work in yeast has reinvigorated the size control field and suggested provocative mechanisms for the distinct functions of setting and sensing cell size. Further examination of size-sensing models based on spatial gradients and molecular titration, coupled with elucidation of the pathways responsible for nutrient-modulated target size, may reveal the fundamental principles of eukaryotic cell size control.