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101.
Palucki BL Park MK Nargund RP Tang R MacNeil T Weinberg DH Vongs A Rosenblum CI Doss GA Miller RR Stearns RA Peng Q Tamvakopoulos C Van der Ploeg LH Patchett AA 《Bioorganic & medicinal chemistry letters》2005,15(8):1993-1996
We report the discovery and optimization of substituted 2-piperazinecarboxamides as potent and selective agonists of the melanocortin subtype-4 receptor. The 5- and 6-alkylated piperazine compounds exhibit low bioactivation potential as measured by covalent binding in microsome preparations. 相似文献
102.
Annexin II is a novel receptor for Pseudomonas aeruginosa 总被引:1,自引:0,他引:1
Kirschnek S Adams C Gulbins E 《Biochemical and biophysical research communications》2005,327(3):900-906
Infections with Pseudomonas aeruginosa (P. aeruginosa) are critical in ventilated and poly-traumatized patients. Most important, these bacteria cause frequent and chronic pulmonary infections in patients with cystic fibrosis. Therefore, identification of molecular mechanisms that mediate the infection of mammalian cells with P. aeruginosa is urgently required. Here, we aimed to identify novel receptors that are involved in internalization of P. aeruginosa into mammalian epithelial cells. Employing SDS-PAGE purification and mass spectrometry we demonstrate that annexin II specifically binds to P. aeruginosa. The significance of the interaction of annexin II with P. aeruginosa for the infection of mammalian cells is indicated by the finding that neutralization of the ligands on P. aeruginosa by incubation of the bacteria with recombinant, soluble annexin II prevents internalization of P. aeruginosa into human epithelial cells. 相似文献
103.
Gimenes D Constantin J Comar JF Kelmer-Bracht AM Broetto-Biazon AC Bracht A 《Cell biochemistry and function》2006,24(4):313-325
The perfused rat liver responds intensely to NAD+ infusion (20-100 microM). Increases in portal perfusion pressure and glycogenolysis and transient inhibition of oxygen consumption are some of the effects that were observed. The aim of the present work was to investigate the distribution of the response to extracellular NAD+ along the hepatic acinus. The bivascularly perfused rat liver was used. Various combinations of perfusion directions (antegrade and retrograde) and infusion routes (portal vein, hepatic vein and hepatic artery) were used in order to supply NAD+ to different regions of the liver parenchyma, also taking advantage of the fact that its extracellular transformation generates steep concentration gradients. Oxygen uptake was stimulated by NAD+ in retrograde perfusion (irrespective of the infusion route) and transiently inhibited in antegrade perfusion. This indicates that the signal causing oxygen uptake inhibition is generated in the periportal area. The signal responsible for oxygen uptake stimulation is homogenously distributed. Stimulation of glucose release was more intense when NAD+ was infused into the portal vein or into the hepatic artery, indicating that stimulation of glycogenolysis predominates in the periportal area. The increases in perfusion pressure were more pronounced when the periportal area was supplied with NAD+ suggesting that the vasoconstrictive elements responding to NAD+ predominate in this region. The response to extracellular NAD+ is thus unequally distributed in the liver. As a paracrine agent, NAD+ is likely to be released locally. It can be concluded that its effects will be different depending on the area where it is released. 相似文献
104.
105.
Endonucleolytic function of MutLalpha in human mismatch repair 总被引:8,自引:0,他引:8
Half of hereditary nonpolyposis colon cancer kindreds harbor mutations that inactivate MutLalpha (MLH1*PMS2 heterodimer). MutLalpha is required for mismatch repair, but its function in this process is unclear. We show that human MutLalpha is a latent endonuclease that is activated in a mismatch-, MutSalpha-, RFC-, PCNA-, and ATP-dependent manner. Incision of a nicked mismatch-containing DNA heteroduplex by this four-protein system is strongly biased to the nicked strand. A mismatch-containing DNA segment spanned by two strand breaks is removed by the 5'-to-3' activity of MutSalpha-activated exonuclease I. The probable endonuclease active site has been localized to a PMS2 DQHA(X)(2)E(X)(4)E motif. This motif is conserved in eukaryotic PMS2 homologs and in MutL proteins from a number of bacterial species but is lacking in MutL proteins from bacteria that rely on d(GATC) methylation for strand discrimination in mismatch repair. Therefore, the mode of excision initiation may differ in these organisms. 相似文献
106.
M. Bocakova R. Constantin L. Bocak 《Cladistics : the international journal of the Willi Hennig Society》2012,28(2):117-129
The melyrid lineage of beetles form a distinct group of the superfamily Cleroidea with a high level of soft‐bodiedness. Here we present the first molecular phylogenetic analysis of this group. The data matrix included partial sequences of the small and large subunits of rRNA, the mitochondrial large subunit rRNA, and cytochrome oxidase subunit I of 67 melyrid and eight outgroup taxa. The concatenated sequences were analysed using maximum‐parsimony (MP), maximum‐likelihood (ML) and Bayesian analysis (BA) approach. The results strongly supported the monophyly of the melyrid lineage splitting into six major clades: Rhadalidae, Mauroniscidae, Prionoceridae, Melyridae sensu stricto, Dasytidae and Malachiidae. The rhadalids were placed in the most basal position, followed by mauroniscids and prionocerids. Three terminal lineages—the true melyrids, dasytids, and malachiids—are well supported by all analyses, but their mutual relationships remain uncertain as MP analysis proposed alternative topologies to that of the ML and BA trees, with often low node support in the latter two methods. The monophyly of the subfamily Danacaeinae (Dasytidae) with respect to the danacaeine genera of the southern hemisphere (Hylodanacaea, Listrocerus, Amecocerus) was challenged as they were found to be polyphyletic. Similarly, the monophyly of Attalus was rejected by our analyses and shown to be polyphyletic. Based on the preferred phylogenetic hypothesis, the subfamilies Rhadalinae, Dasytinae and Malachiinae are elevated to family rank. © The Willi Hennig Society 2011. 相似文献
107.
Disrupting tumor-mediated mechanisms suppressing host immunity represents a novel approach to tumor immunotherapy. Depletion
of regulatory T cells (Tregs) increases endogenous anti-tumor immunity and the efficacy of active immunotherapy in experimental
tumor models. HLA-A2.1/HLA-DR1 (A2.1/DR1) × BALB- neuT
+ (neuT
+) triple transgenic mice represent an improvement over neuT
+ mice for evaluating vaccination regimens to overcome tolerance against HER-2/neu. We questioned whether depletion of Tregs with Denileukin diftitox (Ontak) enhances the efficacy of a therapeutic vaccine
consisting of HER-2(85–94) (p85) CTL and HER-2(776–790) (p776) Th peptides against the growth of TUBO.A2 transplantable tumor
in male A2.1/DR1 × neuT
+ Tg mice. While the therapeutic vaccine primed the tumor-reactive CD8+ CTLs and CD4+ effector T lymphocytes (Teffs) compartment, inducing activation, tumor infiltration, and tumor rejection or delay in tumor
growth, treatment with Ontak 1 day prior to vaccination resulted in enhanced CD4+ and CD8+ T-cell-mediated vaccine-specific immune responses in the periphery. This was closely associated with greater infiltration
and a striking change in the intratumor balance of Tregs and vaccine-specific CTLs/Teffs that directly correlated with markedly
enhanced antitumor activity. The data suggest that Tregs control both CD4+ and CD8+ T-cell activity within the tumor, emphasize the importance of the intratumor ratio of vaccine-specific lymphocytes to Tregs,
and demonstrate significant inversion of this ratio and correlation with tumor rejection during Ontak/vaccine immunotherapy. 相似文献
108.
Gibrat G Assairi L Craescu CT Hui Bon Hoa G Loew D Lombard B Blouquit L Bellissent-Funel MC 《Biochimica et biophysica acta》2012,1824(10):1097-1106
Apo-calmodulin, a small, mainly α, soluble protein is a calcium-dependent protein activator. It is made of two N- and C-terminal domains having a sequence homology of 70%, an identical folding but different stabilities, and is thus an interesting system for unfolding studies. The use of small angle neutron scattering (SANS) and other biophysical techniques has permitted to reveal conformational difference between native and thermal denatured states of apo-calmodulin. The results show that secondary and tertiary structures of apo-calmodulin evolve in a synchronous way, indicating the absence in the unfolding pathway of molten-globule state sufficiently stable to affect transition curves. From SANS experiments, at 85 °C, apo-calmodulin adopts a polymer chain conformation with some residual local structures. After cooling down, apo-calmodulin recovers a compact state, with a secondary structure close to the native one but with a higher radius of gyration and a different tyrosine environment. In fact on a timescale of few minutes, heat denaturation of apo-calmodulin is partially reversible, but on a time scale of hours (for SANS experiments), the long exposure to heat may lead to a non-reversibility due to some chemical perturbation of the protein. In fact, from Mass Spectrometry measurements, we got evidence of dehydration and deamidation of heated apo-calmodulin. 相似文献
109.
Background
Many human interactions are built on trust, so widespread confidence in first impressions generally favors individuals with trustworthy-looking appearances. However, few studies have explicitly examined: 1) the contribution of unfakeable facial features to trust-based decisions, and 2) how these cues are integrated with information about past behavior.Methodology/Principal Findings
Using highly controlled stimuli and an improved experimental procedure, we show that unfakeable facial features associated with the appearance of trustworthiness attract higher investments in trust games. The facial trustworthiness premium is large for decisions based solely on faces, with trustworthy identities attracting 42% more money (Study 1), and remains significant though reduced to 6% when reputational information is also available (Study 2). The face trustworthiness premium persists with real (rather than virtual) currency and when higher payoffs are at stake (Study 3).Conclusions/Significance
Our results demonstrate that cooperation may be affected not only by controllable appearance cues (e.g., clothing, facial expressions) as shown previously, but also by features that are impossible to mimic (e.g., individual facial structure). This unfakeable face trustworthiness effect is not limited to the rare situations where people lack any information about their partners, but survives in richer environments where relevant details about partner past behavior are available. 相似文献110.
Constantin T. Yiannoutsos Ming-Wen An Constantine E. Frangakis Beverly S. Musick Paula Braitstein Kara Wools-Kaloustian Daniel Ochieng Jeffrey N. Martin Melanie C. Bacon Vincent Ochieng Sylvester Kimaiyo 《PloS one》2008,3(12)