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Jill A. Jablonowski Kiev S. Ly Michael Bogenstaetter Curt A. Dvorak Jamin D. Boggs Lisa K. Dvorak Brian Lord Kirsten L. Miller Curt Mazur Sandy J. Wilson Timothy W. Lovenberg Nicholas I. Carruthers 《Bioorganic & medicinal chemistry letters》2009,19(3):903-907
A novel series of imidazole containing histamine H3 receptor ligands were investigated and found to be potent functional antagonists. After improving the stability of these molecules towards liver microsomes, these compounds were found to have no appreciable affinity for CYP P450s. Subsequent in vivo experiments showed significant brain uptake of (4-chloro-phenyl)-[2-(1-isopropyl-piperidin-4-ylmethoxy)-3-methyl-3H-imidazol-4-yl]-methanone 22. 相似文献
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Zizhen Yao Cindy T.J. van Velthoven Thuc Nghi Nguyen Jeff Goldy Adriana E. Sedeno-Cortes Fahimeh Baftizadeh Darren Bertagnolli Tamara Casper Megan Chiang Kirsten Crichton Song-Lin Ding Olivia Fong Emma Garren Alexandra Glandon Nathan W. Gouwens James Gray Lucas T. Graybuck Michael J. Hawrylycz Hongkui Zeng 《Cell》2021,184(12):3222-3241.e26
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Nils Milman Niels Graudal Lillian Staub Nielsen Bjørn Mathiassen Palle Tauris Birgit Lund Jørgen Schøler Kristensen Kirsten Fenger 《Human genetics》1990,85(2):228-232
Summary Pedigree studies were performed based on one Faroese and four Danish probands with overt idiopathic hemochromatosis (IH). The study consisted of HLA typing and determination of biochemical iron status indicators (serum transferrin saturation, serum ferritin). In total, 130 persons were evaluated. The screening identified 6 homozygous (h/h) subjects with preclinical IH, 46 heterozygous (h/n), and 8 normal (n/n) subjects, while 39 subjects were classified as normal or heterozygous (n/h?). One family demonstrated both a homozygous x heterozygous as well as a heterozygous x heterozygous mating. Recombination between the HLA region and IH locus occurred possibly in three subjects in three different families. The significance of detailed screening in families with probands with IH is discussed. 相似文献
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The cellular inhibitory effects of 6-amino-1,2-benzopyrone (6-ABP), a DNA site-specific ligand of adenosine diphosphoribosyl transferase (ADPRT), were determined in a dexamethasone-sensitive EJ-ras gene construct containing cell line (14C cells). Dexamethasone in vitro transforms these cells to a tumorigenic phenotype and also stimulates cell replication. At a non-toxic concentrations (0.2 mM) 6-ABP treatment of intact cells for 4 days inhibits the dexamethasone-stimulated increment of cellular DNA content, depresses replicative DNA synthesis as assayed by thymidine incorporation to the level of cells that were not exposed to dexamethasone, and in permeabilized cells reduces the dexamethasone-stimulated increase of deoxyribonucleotide incorporation into DNA to the level of untreated cells. In situ pulse labeling of cells pretreated with 6-ABP indicated an inhibition of DNA synthesis at a stage prior to the formation of the 10-kb intermediate species. The drug had no direct effect on cellular DNA polymerases as tested in vitro, and the inhibition of DNA synthesis in permeabilized cells following drug treatment for 4 days was abolished by externally added DNA templates. Neither dexamethasone nor the drug influenced the cellular quantity of ADPRT molecules, tested immunochemically. 相似文献
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On September 22, 2017, “Engaging the Forgotten Parent: Conference of Experts on Fathers’ Role in Children’s Weight‐Related Behaviours and Outcomes” brought researchers, students, health professionals, community stakeholders, and knowledge users from Canada, Australia, and the United States together to Toronto, Ontario, for a 1‐day gathering focused on furthering scientific understanding of effective strategies to recruit, engage, and retain fathers in family‐based obesity research. Furthermore this conference focused on identifying key knowledge gaps and opportunities for collaborative research to further our understanding of fathers’ roles in the development of their children’s behaviors and weight outcomes. The following four themes emerged from the conference: (1) underrepresentation of fathers in family‐based obesity research, (2) fathers’ engagement in children’s weight‐related behaviors and desire to participate in research, (3) best practices in recruiting, engaging, and retaining fathers in research, and (4) key lessons learned from fatherhood research in developmental science. 相似文献
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Kirsten M. Ellegaard Silvia Brochet German Bonilla‐Rosso Olivier Emery Natasha Glover Noushin Hadadi Kamil S. Jaron Jan R. van der Meer Marc Robinson‐Rechavi Vladimir Sentchilo Florian Tagini Philipp Engel 《Molecular ecology》2019,28(9):2224-2237
Bacteria that engage in long‐standing associations with particular hosts are expected to evolve host‐specific adaptations that limit their capacity to thrive in other environments. Consistent with this, many gut symbionts seem to have a limited host range, based on community profiling and phylogenomics. However, few studies have experimentally investigated host specialization of gut symbionts and the underlying mechanisms have largely remained elusive. Here, we studied host specialization of a dominant gut symbiont of social bees, Lactobacillus Firm5. We show that Firm5 strains isolated from honey bees and bumble bees separate into deep‐branching host‐specific phylogenetic lineages. Despite their divergent evolution, colonization experiments show that bumble bee strains are capable of colonizing the honey bee gut. However, they were less successful than honey bee strains, and competition with honey bee strains completely abolished their colonization. In contrast, honey bee strains of divergent phylogenetic lineages were able to coexist within individual bees. This suggests that both host selection and interbacterial competition play important roles in host specialization. Using comparative genomics of 27 Firm5 isolates, we found that the genomes of honey bee strains harbour more carbohydrate‐related functions than bumble bee strains, possibly providing a competitive advantage in the honey bee gut. Remarkably, most of the genes encoding carbohydrate‐related functions were not conserved among the honey bee strains, which suggests that honey bees can support a metabolically more diverse community of Firm5 strains than bumble bees. These findings advance our understanding of the genomic changes underlying host specialization. 相似文献
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Joseph Merz Lucius Caldwell Michael Beakes Chris Hammersmark Kirsten Sellheim 《Restoration Ecology》2019,27(3):661-671
Gravel augmentation is often applied to rivers and streams to rehabilitate salmonid spawning and incubation habitat. However, the effect of gravel size on salmon spawning utilization and embryo survival during incubation is not well understood. We conducted an experiment on a regulated and previously mined Northern California salmonid‐bearing stream in which different sized gravel (small, medium, and large) patches were placed into the stream's degraded spawning reach. We documented Oncorhynchus tshawytscha (Chinook salmon) spawning activity within the three gravel sizes for two seasons. In addition, we deployed Chinook salmon embryos into each gravel size patch and allowed them to incubate until estimated emergence time. Although all experimental gravel sizes were predicted to be within the spawning population's mobilization capabilities, model results indicated the probability of salmon building redds decreased as substrate size increased. Conversely, embryo survival increased as gravel size increased. A possible mechanism of disparate Chinook salmon embryo survival is provided by an observed decrease in embryo survival correlating with greater presence of embryo predators (leeches), which are associated with smaller gravel. Our results indicate a parent‐offspring conflict in optimal spawning gravel size for Chinook salmon, and suggest that an intermediate gravel size would maximize overall reproductive success across both spawning and incubation life stages. 相似文献