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31.
Breslin MJ Duggan ME Halczenko W Fernandez-Metzler C Hunt CA Leu CT Merkle KM Naylor-Olsen AM Prueksaritanont T Stump G Wallace A Rodan SB Hutchinson JH 《Bioorganic & medicinal chemistry letters》2003,13(10):1809-1812
Two novel series of small-molecule RGD mimetics containing either a substituted pyridone or pyrazinone central constraint were prepared. Modification of the beta-alanine 3-substituent produced compounds that are potent and selective alpha(v)beta(3) antagonists and exhibit a range of physicochemical properties. 相似文献
32.
Chen CH Li BY Wan JT Sun A Leu JS Chiang CP 《Proceedings of the National Science Council, Republic of China. Part B, Life sciences》2001,25(2):90-96
This study used an immunohistochemical technique to assess the expression of epidermal growth factor (EGF) in 40 specimens of salivary adenoid cystic carcinoma (ACC), 7 specimens of labial glands adjacent to mucocele, and 5 specimens of normal submandibular glands. In normal submandibular glands, immunohistochemically detectable EGF was demonstrated in all ductal segments, including intercalated, striated, and excretory duct cells. No EGF positive staining was found in acinar compartments. including serous and mucous acinar cells. In degenerated labial glands adjacent to mucocele, no EGF staining was detected in the remaining acinar and ductal cells. In salivary ACCs, positive EGF immunostaining was observed in one of the 5 (20%) ACCs with a solid pattern and in 13 of the 35 (37.1%) ACCs with a tubular-cribriform pattern. The overall EGF expression rate in 40 salivary ACCs was 35%. Positive EGF staining was predominantly found in tubular structures in the tubular ACCs and in duct-like structures in large cribriform patterns or in the stroma of the cribriform ACCs. There was no significant correlation between EGF expression in salivary ACCs and any of the clinicopathological parameters including patient age and sex, cancer location, TNM status, clinical stage, histologic type, perivascular or perineural invasion, focal necrosis of tumor, and cellular atypia. We conclude that the duct segments of the normal submandibular gland are the sites of EGF synthesis and secretion. In degenerated labial glands adjacent to mucocele, EGF synthesis is completely inhibited. Furthermore, EGF is mainly biosynthesized in cells forming tubular or duct-like structures in tubular or cribriform salivary ACCs, and EGF may play a biologic role, particularly as a mitogen in salivary ACC growth. 相似文献
33.
The interaction of tumor necrosis factor-alpha with its receptor CD120a (p55) initiates downstream signaling cascades that include the activation of the mitogen-activated protein kinase (MAPK), p42(mapk/erk2). The membrane proximal region of CD120a (p55) is Ser-, Thr-, and Pro-rich and contains four mitogen-activated protein kinase consensus phosphorylation sites. In recent work, we showed that CD120a (p55) itself is a target of phosphorylation by p42(mapk/erk2), and after phosphorylation, the receptor is redistributed from the cell surface and Golgi complex to intracellular tubular structures associated with elements of the endoplasmic reticulum. The goal of this study was to define the specific amino acid residues that are phosphorylated. Deletional mutagenesis of the cytoplasmic domain of CD120a (p55) indicated that two sites located between residues 207-254 and 250-300 were phosphorylated predominantly on Thr and Ser residues, respectively. Site-directed mutagenesis of Ser and Thr residues contained within the extracellular signal-regulated kinase (ERK) consensus sequences indicated that the preferred residues were Thr-236 and Ser-270. Primary phosphorylation at these sites appeared to enable subsequent phosphorylation at Ser-240 and Ser-244, although the level of phosphorylation of these latter two sites was less than the preferred sites. Through the use of specific ligation of CD120a (p55) alone and mice deficient in CD120a (p55), CD120b (p75), or both receptors, CD120a (p55) was shown to be necessary and sufficient for the induction of kinase activity. These findings thus suggest that the phosphorylation of Thr-236 and Ser-270 within the membrane proximal region of CD120a (p55) are the preferred sites of phosphorylation by p42(mapk/erk2) and may set in motion phosphorylation at other sites. 相似文献
34.
Presence or absence of N-acetylneuraminic acid (Neu5Ac) can change a
sialylated glycoprotein's serum half-life and possibly its function. We
evaluated the linearity, sensitivity, reproducibility, and accuracy of a
HPAEC/PAD method to determine its suitability for routine simultaneous
analysis of Neu5Ac and N-glycolylneuraminic acid (Neu5Gc). An effective
internal standard for this analysis is 3-deoxy-d-glycero-d-
galacto-2-nonulosonic acid (KDN). We investigated the effect of the Au
working electrode recession and determined that linear range and
sensitivity were dependent on electrode recession. Using an electrode that
was 350 &mgr;m recessed from the electrode block, the minimum detection
limits of Neu5Ac, KDN, and Neu5Gc were 2, 5, and 2 pmol, respectively, and
were reduced to 1, 2, and 0.5 pmol using a new electrode. The response of
standards was linear from 10 to 500 pmol (r2>0.99) regardless of
electrode recession. When Neu5Ac, KDN, and Neu5Gc (200 pmol each) were
analyzed repetitively for 48 h, area RSDs were <3%. Reproducibility was
unaffected when injections of glycoprotein neuraminidase and acid
digestions were interspersed with standard injections. Area RSDs of Neu5Ac
and Neu5Gc improved when the internal standard was used. We determined the
precision and accuracy of this method for both a recessed and a new working
electrode by analyzing Neu5Ac and Neu5Gc contents of bovine fetuin and
bovine and human transferrins. Results were consistent with published
values and independent of the working electrode. The sensitivity,
reproducibility, and accuracy of this method make it suitable for direct
routine analysis of glycoprotein Neu5Ac and Neu5Gc contents.
相似文献
35.
36.
Arlettaz R Patthey P Baltic M Leu T Schaub M Palme R Jenni-Eiermann S 《Proceedings. Biological sciences / The Royal Society》2007,274(1614):1219-1224
Stress generated by humans on wildlife by continuous development of outdoor recreational activities is of increasing concern for biodiversity conservation. Human disturbance often adds to other negative impact factors affecting the dynamics of vulnerable populations. It is not known to which extent the rapidly spreading free-riding snow sports actually elicit detrimental stress (allostatic overload) upon wildlife, nor what the potential associated fitness and survival costs are. Using a non-invasive technique, we evaluated the physiological stress response induced by free-riding snow sports on a declining bird species of Alpine ecosystems. The results of a field experiment in which radiomonitored black grouse (Tetrao tetrix) were actively flushed from their snow burrows once a day during four consecutive days showed an increase in the concentration of faecal stress hormone (corticosterone) metabolites after disturbance. A large-scale comparative analysis across the southwestern Swiss Alps indicated that birds had higher levels of these metabolites in human-disturbed versus undisturbed habitats. Disturbance by snow sport free-riders appears to elevate stress, which potentially represents a new serious threat for wildlife. The fitness and survival costs of allostatic adjustments have yet to be estimated. 相似文献
37.
Dynamic landscape models have generally assumed random distributions of habitat although real landscapes show spatial organization
at many scales. To explore the role of spatial structure in determining the frequency of dispersal-limited forest species,
we used a cellular landscape model divided into two zones. Zones were distributed in a random, clustered, or regular spatial
pattern. Within each zone habitat cells were randomly destroyed and regenerated, and habitat density and turnover rate were
systematically varied. A hypothetical habitat-limited species dispersed between adjacent habitat cells. All trials showed
a reduced species frequency relative to a static landscape. Reduction was greater at low habitat density (P = 0.30) than at high density (0.90) suggesting the importance of habitat connectivity in controlling species frequency. The
greatest reduction occurred when habitat was concentrated in a small, regularly distributed zone at low habitat density reflecting
the enforced isolation of individual habitat cells. Very little reduction was observed when habitat cells were packed into
a small clustered zone, a situation promoting connectivity between cells. Moderate–severe frequency reduction occurred when
habitat turnover was concentrated in a clustered zone at high habitat density, but little was observed when turnover was widely
distributed in a regular or random pattern. These results can be interpreted in terms of a source-sink function in which spatial
pattern controlled the degree of contact between landscape zones and determined opportunities for dispersal between habitat
cells. We conclude that clustering of forest habitat has the potential to maintain herb species frequency in sparsely forested
landscapes. Conversely, clustering of forest disturbance in heavily forested regions, or regular distribution of forest stands
(as often occurs in agricultural regions) creates areas which are difficult to colonize, and should be avoided. 相似文献
38.
Mate Familiarity Affects Pairing Behaviour in a Long‐Term Monogamous Lizard: Evidence from Detailed Bio‐Logging and a 31‐Year Field Study
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Stephan T. Leu Dale Burzacott Martin J. Whiting C. Michael Bull 《Ethology : formerly Zeitschrift fur Tierpsychologie》2015,121(8):760-768
Long‐term monogamy is most prevalent in birds but is also found in lizards. We combined a 31‐year field study of the long‐lived, monogamous Australian sleepy lizard, Tiliqua rugosa, with continuous behavioural observations through GPS data logging, in 1 yr, to investigate the duration of pair bonds, rates of partner change and whether either the reproductive performance hypothesis or the mate familiarity hypothesis could explain this remarkable long‐term monogamy. The reproductive performance hypothesis predicts higher reproductive success in more experienced parents, whereas the mate familiarity hypothesis suggests that effects of partner familiarity select for partner retention and long‐term monogamy. Rates of partner change were below 34% over a 5‐yr period and most sleepy lizards formed long‐term pair bonds: 31 partnerships lasted for more than 15 yr, 110 for more than 10 yr, and the recorded maximum was 27 yr (ongoing). In the year when we conducted detailed observations, familiar pairs mated significantly earlier than unfamiliar pairs. Previous pairing experience (total number of years paired with previous partners) had no significant effect. Early mating often equates to higher reproductive success, and we infer that is the case in sleepy lizards. Early mating of familiar pairs was not due to better body condition. We propose two suggestions about the proximate mechanisms that may allow familiar pair partners to mate earlier than unfamiliar partners. First, they may have improved coordination of their reproductive sexual cycles to reach receptivity earlier and thereby maximise fertilisation success. Second, they may forage more efficiently, benefiting from effective information transfer and/or cooperative predator detection. Those ideas need empirical testing in the future. Regardless of the mechanism, our observations of sleepy lizard pairing behaviour support the mate familiarity hypothesis, but not the reproductive performance hypothesis, as an explanation for its long‐term monogamous mating system. 相似文献
39.
Christoph Gerhardt Johanna Maria Lier Stephan Burmühl Andreas Struchtrup Kathleen Deutschmann Maik Vetter Tristan Leu Sandra Reeg Tilman Grune Ulrich Rüther 《The Journal of cell biology》2015,210(1):1027-1045
Mutations in RPGRIP1L result in severe human diseases called ciliopathies. To unravel the molecular function of RPGRIP1L, we analyzed Rpgrip1l−/− mouse embryos, which display a ciliopathy phenotype and die, at the latest, around birth. In these embryos, cilia-mediated signaling was severely disturbed. Defects in Shh signaling suggested that the Rpgrip1l deficiency causes an impairment of protein degradation and protein processing. Indeed, we detected a cilia-dependent decreased proteasomal activity in the absence of Rpgrip1l. We found different proteasomal components localized to cilia and identified Psmd2, a component of the regulatory proteasomal 19S subunit, as an interaction partner for Rpgrip1l. Quantifications of proteasomal substrates demonstrated that Rpgrip1l regulates proteasomal activity specifically at the basal body. Our study suggests that Rpgrip1l controls ciliary signaling by regulating the activity of the ciliary proteasome via Psmd2. 相似文献
40.
Chia-Chen Hsu Yu-Wei Leu Min-Jen Tseng Kuan-Der Lee Tzen-Yu Kuo Jia-Yi Yen Yen-Ling Lai Yi-Chen Hung Wei-Sheng Sun Chien-Min Chen Pei-Yi Chu Kun-Tu Yeh Pearlly S Yan Yu-Sun Chang Tim H-M Huang Shu-Huei Hsiao 《Journal of biomedical science》2011,18(1):12