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61.
Hank Rothgerber 《PloS one》2014,9(5)
The present study examined intergroup judgments made between four groups of non-meat eaters: health vegetarians; ethical vegetarians; health vegans, and ethical vegans. Consistent with hypotheses based on horizontal hostility and the need to maintain ingroup distinctiveness, ethical vegetarians gave unfavorable evaluations to health vegetarians relative to vegans, especially when the mainstream omnivore group was made salient. Contrary to expectations, vegans gave relatively more favorable evaluations to ethical vegetarians than health vegetarians when mainstream salience was low. This was especially true for vegans who were motivated primarily by ethical concerns. When mainstream salience was high, vegans did not distinguish between the vegetarian subgroups. Results suggest that one’s motives for abstaining from meat often play a larger role in this type of intergroup perceptions than one’s dietary practices. 相似文献
62.
Selective lysis of target cells by interleukin-2-expanded peripheral blood mononuclear leukocyte clones 总被引:1,自引:0,他引:1
The presence of distinct cytolytic subsets within interleukin-2-expanded peripheral blood leukocytes (IEL) cultures was demonstrated by clonal analysis. Thirty-seven IEL clones were isolated from two healthy blood donors; 21 destroyed both Daudi and K562 cell lines. Of those 21 clones, 1 clone could destroy autologous PBM, 7 clones could destroy fresh allogeneic ovarian carcinoma (OVA-CA) cells, and 6 clones could destroy normal autologous PBM and fresh OVA-CA cells. Twelve of the 37 clones destroyed only one of the four targets tested: 8 clones destroyed K562, 2 clones destroyed Daudi, and 1 clone each was selective for autologous PBM or OVA-CA. Of the remaining 4 clones, 1 destroyed OVA-CA and Daudi cells, 1 destroyed PBM and K562, 1 destroyed PBM and Daudi cells, and 1 destroyed PBM, Daudi, and OVA-CA. These results suggest that these functionally heterogeneous cytolytic clones may use different cell recognition or cytolytic mechanisms to enable these distinct and, at times, reciprocal patterns of target cell selectivity. 相似文献
63.
Sucgang R Kuo A Tian X Salerno W Parikh A Feasley CL Dalin E Tu H Huang E Barry K Lindquist E Shapiro H Bruce D Schmutz J Salamov A Fey P Gaudet P Anjard C Babu MM Basu S Bushmanova Y van der Wel H Katoh-Kurasawa M Dinh C Coutinho PM Saito T Elias M Schaap P Kay RR Henrissat B Eichinger L Rivero F Putnam NH West CM Loomis WF Chisholm RL Shaulsky G Strassmann JE Queller DC Kuspa A Grigoriev IV 《Genome biology》2011,12(2):R20
Background
The social amoebae (Dictyostelia) are a diverse group of Amoebozoa that achieve multicellularity by aggregation and undergo morphogenesis into fruiting bodies with terminally differentiated spores and stalk cells. There are four groups of dictyostelids, with the most derived being a group that contains the model species Dictyostelium discoideum.Results
We have produced a draft genome sequence of another group dictyostelid, Dictyostelium purpureum, and compare it to the D. discoideum genome. The assembly (8.41 × coverage) comprises 799 scaffolds totaling 33.0 Mb, comparable to the D. discoideum genome size. Sequence comparisons suggest that these two dictyostelids shared a common ancestor approximately 400 million years ago. In spite of this divergence, most orthologs reside in small clusters of conserved synteny. Comparative analyses revealed a core set of orthologous genes that illuminate dictyostelid physiology, as well as differences in gene family content. Interesting patterns of gene conservation and divergence are also evident, suggesting function differences; some protein families, such as the histidine kinases, have undergone little functional change, whereas others, such as the polyketide synthases, have undergone extensive diversification. The abundant amino acid homopolymers encoded in both genomes are generally not found in homologous positions within proteins, so they are unlikely to derive from ancestral DNA triplet repeats. Genes involved in the social stage evolved more rapidly than others, consistent with either relaxed selection or accelerated evolution due to social conflict.Conclusions
The findings from this new genome sequence and comparative analysis shed light on the biology and evolution of the Dictyostelia.64.
Jesse E. Hanson Hank La Emile Plise Yung-Hsiang Chen Xiao Ding Taleen Hanania Emily V. Sabath Vadim Alexandrov Dani Brunner Emer Leahy Pascal Steiner Lichuan Liu Kimberly Scearce-Levie Qiang Zhou 《PloS one》2013,8(7)
Suberoylanilide hydroxamic acid (SAHA) is an inhibitor of histone deacetylases (HDACs) used for the treatment of cutaneous T cell lymphoma (CTCL) and under consideration for other indications. In vivo studies suggest reducing HDAC function can enhance synaptic function and memory, raising the possibility that SAHA treatment could have neurological benefits. We first examined the impacts of SAHA on synaptic function in vitro using rat organotypic hippocampal brain slices. Following several days of SAHA treatment, basal excitatory but not inhibitory synaptic function was enhanced. Presynaptic release probability and intrinsic neuronal excitability were unaffected suggesting SAHA treatment selectively enhanced postsynaptic excitatory function. In addition, long-term potentiation (LTP) of excitatory synapses was augmented, while long-term depression (LTD) was impaired in SAHA treated slices. Despite the in vitro synaptic enhancements, in vivo SAHA treatment did not rescue memory deficits in the Tg2576 mouse model of Alzheimer’s disease (AD). Along with the lack of behavioral impact, pharmacokinetic analysis indicated poor brain availability of SAHA. Broader assessment of in vivo SAHA treatment using high-content phenotypic characterization of C57Bl6 mice failed to demonstrate significant behavioral effects of up to 150 mg/kg SAHA following either acute or chronic injections. Potentially explaining the low brain exposure and lack of behavioral impacts, SAHA was found to be a substrate of the blood brain barrier (BBB) efflux transporters Pgp and Bcrp1. Thus while our in vitro data show that HDAC inhibition can enhance excitatory synaptic strength and potentiation, our in vivo data suggests limited brain availability may contribute to the lack of behavioral impact of SAHA following peripheral delivery. These results do not predict CNS effects of SAHA during clinical use and also emphasize the importance of analyzing brain drug levels when interpreting preclinical behavioral pharmacology. 相似文献
65.
Kevin J. Filipski Angel Guzman-Perez Jianwei Bian Christian Perreault Gary E. Aspnes Mary T. Didiuk Robert L. Dow Richard F. Hank Christopher S. Jones Robert J. Maguire Meihua Tu Dongxiang Zeng Shenping Liu John D. Knafels John Litchfield Karen Atkinson David R. Derksen Francis Bourbonais Jeffrey A. Pfefferkorn 《Bioorganic & medicinal chemistry letters》2013,23(16):4571-4578
Glucokinase activators are a class of experimental agents under investigation as a therapy for Type 2 diabetes mellitus. An X-ray crystal structure of a modestly potent agent revealed the potential to substitute the common heterocyclic amide donor–acceptor motif for a pyridone moiety. We have successfully demonstrated that both pyridone and pyrimidone heterocycles can be used as a potent donor–acceptor substituent. Several sub-micromolar analogs that possess the desired partial activator profile were synthesized and characterized. Unfortunately, the most potent activators suffered from sub-optimal pharmacokinetic properties. Nonetheless, these donor–acceptor motifs may find utility in other glucokinase activator series or beyond. 相似文献
66.
Pinguan Zheng Brian P. Lieberman Karl Ploessl Laetitia Lemoine Sara Miller Hank F. Kung 《Bioorganic & medicinal chemistry letters》2013,23(3):869-872
New ligands for in vivo brain imaging of serotonin transporter (SERT) with single photon emission tomography (SPECT) were prepared and evaluated. An efficient synthesis and radiolabeling of a biphenylthiol, FLIP-IDAM, 4, was accomplished. The affinity of FLIP-IDAM was evaluated by an in vitro inhibitory binding assay using [125I]-IDAM as radioligand in rat brain tissue homogenates (Ki = 0.03 nM). New [125I]Flip-IDAM exhibited excellent binding affinity to SERT binding sites with a high hypothalamus to cerebellum ratio of 4 at 30 min post iv injection. The faster in vivo kinetics for brain uptake and a rapid washout from non-specific regions provide excellent signal to noise ratio. This new agent, when labeled with 123I, may be a useful imaging agent for mapping SERT binding sites in the human brain. 相似文献
67.
Kentaro Futatsugi Vincent Mascitti Cristiano R.W. Guimarães Nao Morishita Cuiman Cai Michael P. DeNinno Hua Gao Michael D. Hamilton Richard Hank Anthony R. Harris Daniel W. Kung Sophie Y. Lavergne Bruce A. Lefker Michael G. Lopaze Kim F. McClure Michael J. Munchhof Cathy Preville Ralph P. Robinson Amit S. Kalgutkar 《Bioorganic & medicinal chemistry letters》2013,23(1):194-197
A novel GPR119 agonist based on the 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole scaffold was designed through lead optimization starting from pyrazole-based GPR119 agonist 1. The design is centered on the conformational restriction of the core scaffold, while minimizing the change in spatial relationships of two key pharmacophoric elements (piperidine-carbamate and aryl sulfone). 相似文献
68.
Liu J Zhu L Plössl K Lieberman BP Kung HF 《Bioorganic & medicinal chemistry letters》2011,21(10):2962-2965
A series of novel N-fluoropyridyl-containing tropane derivatives were synthesized and their binding affinities for the dopamine transporter (DAT), serotonin transporter (SERT) and norepinephrine (NET) were determined via competitive radioligand binding assays. Among these derivatives, compound 6d showed the highest binding affinity to DAT (Ki = 4.1 nM), and selectivity for DAT over SERT (5-fold) and NET (16-fold). Compound 6d was radiolabeled with Fluorine-18 in two steps. Regional brain distribution and ex vivo autoradiography studies of [18F]6d demonstrated that the ligand was selectively localized in the striatum region, where DAT binding sites are highly expressed. [18F]6d may be useful as a potential radioligand for imaging DATs with PET. 相似文献
69.
70.
James A. Franke Christoph Müller Sara Minoli Joshua Elliott Christian Folberth Charles Gardner Tobias Hank Roberto Cesar Izaurralde Jonas Jgermeyr Curtis D. Jones Wenfeng Liu Stefan Olin Thomas A.M. Pugh Alex C. Ruane Haynes Stephens Florian Zabel Elisabeth J. Moyer 《Global Change Biology》2022,28(1):167-181
Modern food production is spatially concentrated in global “breadbaskets.” A major unresolved question is whether these peak production regions will shift poleward as the climate warms, allowing some recovery of potential climate-related losses. While agricultural impacts studies to date have focused on currently cultivated land, the Global Gridded Crop Model Intercomparison Project (GGCMI) Phase 2 experiment allows us to assess changes in both yields and the location of peak productivity regions under warming. We examine crop responses under projected end of century warming using seven process-based models simulating five major crops (maize, rice, soybeans, and spring and winter wheat) with a variety of adaptation strategies. We find that in no-adaptation cases, when planting date and cultivar choices are held fixed, regions of peak production remain stationary and yield losses can be severe, since growing seasons contract strongly with warming. When adaptations in management practices are allowed (cultivars that retain growing season length under warming and modified planting dates), peak productivity zones shift poleward and yield losses are largely recovered. While most growing-zone shifts are ultimately limited by geography, breadbaskets studied here move poleward over 600 km on average by end of the century under RCP 8.5. These results suggest that agricultural impacts assessments can be strongly biased if restricted in spatial area or in the scope of adaptive behavior considered. Accurate evaluation of food security under climate change requires global modeling and careful treatment of adaptation strategies. 相似文献