Isosteric ramatroban analogs: selective and potent CRTH-2 antagonists

The chemoattractant receptor-homologous molecule expressed on T(H)2 cells (CRTH-2), also found on eosinophils and basophils, is a prostaglandin D2 receptor involved in the recruitment of these cell types during an inflammatory response. In this report, we describe the synthesis and optimization of a ramatroban isostere that is a selective and potent antagonist of CRTH-2 which may be useful in the treatment of certain diseases.     

Distribution pattern of an expanding Osprey ( Pandion haliaetus) population in a changing environment

We studied the nest site selection and distribution pattern at landscape level of the German Osprey population, and demonstrated how to test the predictions of the ideal free distribution theory and its derivatives on such an expanding population. Information about the location and breeding success of each Osprey nest site between 1995 and 2005 was collected through a long-term monitoring programme. Data of land cover types were acquired from the administrations of each federal state and the CORINE Land Cover database. The results showed that Ospreys preferred landscapes with more water bodies and forests. Such sites were also occupied earlier and had higher local population density. However, in the study period of 11 years, there was a gradual shift from forest-dominated landscapes to agricultural land-dominated landscapes. The breeding success increased over time, with no difference in the breeding success between pairs nesting on trees and poles, whereas there was higher breeding success at nest sites surrounded by more agricultural land and less forest. The more efficient foraging in eutrophic lakes in agricultural landscapes was the most likely cause for the higher breeding success. The distribution pattern of the Ospreys did not match the resource allocation, which deviated from the models tested. We suggested that the proximate cues used for nest site selection mismatched site quality due to anthropogenic environmental changes.     

Optogenetic manipulation of cyclic guanosine monophosphate to probe phosphodiesterase activities in megakaryocytes

Cyclic guanosine monophosphate (cGMP) signalling plays a fundamental role in many cell types, including platelets. cGMP has been implicated in platelet formation, but mechanistic detail about its spatio-temporal regulation in megakaryocytes (MKs) is lacking. Optogenetics is a technique which allows spatio-temporal manipulation of molecular events in living cells or organisms. We took advantage of this method and expressed a photo-activated guanylyl cyclase, Blastocladiella emersonii Cyclase opsin (BeCyclop), after viral-mediated gene transfer in bone marrow (BM)-derived MKs to precisely light-modulate cGMP levels. BeCyclop-MKs showed a significantly increased cGMP concentration after illumination, which was strongly dependent on phosphodiesterase (PDE) 5 activity. This finding was corroborated by real-time imaging of cGMP signals which revealed that pharmacological PDE5 inhibition also potentiated nitric oxide-triggered cGMP generation in BM MKs. In summary, we established for the first-time optogenetics in primary MKs and show that PDE5 is the predominant PDE regulating cGMP levels in MKs. These findings also demonstrate that optogenetics allows for the precise manipulation of MK biology.     

Mapping protein-protein interactions by mass spectrometry

Mass spectrometry is currently at the forefront of technologies for mapping protein-protein interactions, as it is a highly sensitive technique that enables the rapid identification of proteins from a variety of biological samples. When used in combination with affinity purification and/or chemical cross-linking, whole or targeted protein interaction networks can be elucidated. Several methods have recently been introduced that display increased specificity and a reduced occurrence of false-positives. In the future, information gained from human protein interaction studies could lead to the discovery of novel pathway associations and therapeutic targets.     

Consequential Life Cycle Assessment of Pasture‐based Milk Production: A Case Study in the Waikato Region,New Zealand

Farm intensification options in pasture‐based dairy systems are generally associated with increased stocking rates coupled with the increased use of off‐farm inputs to support the additional feed demand of animals. However, as well as increasing milk production per hectare, intensification can also exacerbate adverse impacts on the environment. The objective of the present study was to investigate environmental trade‐offs associated with potential intensification methods for pasture‐based dairy farming systems in the Waikato region, New Zealand. The intensification scenarios selected were (1) increased pasture utilization efficiency (PUE scenario), (2) increased use of nitrogen (N) fertilizer to boost on‐farm pasture production (N fertilizer scenario), and (3) increased use of brought‐in feed as maize silage (MS) (MS scenario). Twelve impact categories were assessed. The PUE scenario was the environmentally preferred intensification method, and the preferred choice between the N fertilizer and MS scenarios depended upon trade‐offs between different environmental impacts. Sensitivity analysis was carried out to test the effects of choice associated with: (1) the approaches used to account for indirect land‐use change (ILUC) and (2) the competing product systems (conventional beef systems) used to handle the co‐product dairy meat for the climate change (CC) indicator. Results showed that the magnitude of the CC indicator results was influenced by the ILUC accounting approaches and the choice associated with a global marginal beef mix, but the relative CC indicator results for the three intensification scenarios remained unchanged.     

Microsatellite markers for Bromus tectorum (cheatgrass)

Bromus tectorum (cheatgrass) is a flourishing invasive weed in the western United States. The objective of our study is to characterize its genetic diversity. We made a B. tectorum genomic library in lambda phage and screened approximately 4000 clones for poly CA and poly CT dinucleotide repeats. Of 38 sequences with dinucleotide repeats isolated from the library, we designed primer sets for 18 loci. A preliminary screen of 40 individuals from four populations indicated that seven loci were polymorphic. These loci will be valuable for elucidation of cheatgrass genetic diversity and population structure.     

Medial and Lateral Entorhinal Cortex Differentially Excite Deep versus Superficial CA1 Pyramidal Neurons

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