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41.
Mohammad Abdel-Halim Adam B. Keeton Evrim Gurpinar Bernard D. Gary Simon M. Vogel Matthias Engel Gary A. Piazza Frank M. Boeckler Rolf W. Hartmann Ashraf H. Abadi 《Bioorganic & medicinal chemistry》2013,21(23):7343-7356
Derivatives with scaffolds of 1,3,5-tri-substituted pyrazoline and 1,3,4,5-tetra-substituted pyrazoline were synthesized and tested for their inhibitory effects versus the p53+/+ HCT116 and p53?/? H1299 human tumor cell lines. Several compounds were active against the two cell lines displaying IC50 values in the low micromolar range with a clearly more pronounced effect on the p53+/+ HCT116 cells. The compound class shows excellent developability due to the modular synthesis, allowing independent optimization of all three to four key substituents to improve the properties of the molecules. 相似文献
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Dogfish M4 lactate dehydrogenase: reversible inactivation by pyridoxal 5''-phosphate and complete protection in complexes that mimic the active ternary complex. 下载免费PDF全文
Dogfish M4 lactate dehydrogenase, like the corresponding pig enzyme, is inactivated by pyridoxal 5'-phosphate through modification of a single essential lysine residue. The activity is completely protected in the complexes E-NAD+-oxalate, E-NADH-oxamate and E-(NAD+-pyruvate adduct), but only partially protected in E-NAD+, E-NADH, E-NAD+-oxamate and E-NADH-oxalate. 相似文献
44.
Modeling the two‐locus architecture of divergent pollinator adaptation: how variation in SAD paralogs affects fitness and evolutionary divergence in sexually deceptive orchids 下载免费PDF全文
Divergent selection by pollinators can bring about strong reproductive isolation via changes at few genes of large effect. This has recently been demonstrated in sexually deceptive orchids, where studies (1) quantified the strength of reproductive isolation in the field; (2) identified genes that appear to be causal for reproductive isolation; and (3) demonstrated selection by analysis of natural variation in gene sequence and expression. In a group of closely related Ophrys orchids, specific floral scent components, namely n‐alkenes, are the key floral traits that control specific pollinator attraction by chemical mimicry of insect sex pheromones. The genetic basis of species‐specific differences in alkene production mainly lies in two biosynthetic genes encoding stearoyl–acyl carrier protein desaturases (SAD) that are associated with floral scent variation and reproductive isolation between closely related species, and evolve under pollinator‐mediated selection. However, the implications of this genetic architecture of key floral traits on the evolutionary processes of pollinator adaptation and speciation in this plant group remain unclear. Here, we expand on these recent findings to model scenarios of adaptive evolutionary change at SAD2 and SAD5, their effects on plant fitness (i.e., offspring number), and the dynamics of speciation. Our model suggests that the two‐locus architecture of reproductive isolation allows for rapid sympatric speciation by pollinator shift; however, the likelihood of such pollinator‐mediated speciation is asymmetric between the two orchid species O. sphegodes and O. exaltata due to different fitness effects of their predominant SAD2 and SAD5 alleles. Our study not only provides insight into pollinator adaptation and speciation mechanisms of sexually deceptive orchids but also demonstrates the power of applying a modeling approach to the study of pollinator‐driven ecological speciation. 相似文献
45.
Philipp Stöhr Jr. 《Cell and tissue research》1948,34(1):1-54
Zusammenfassung Die interstitielle Zelle läßt sich vielleicht als die kleinste Form einer vegetativen Ganglienzelle betrachten.Im Auerbachschen Plexus des menschlichen Colons kommen Zellen vom Typus 1 und 2 nach Dogiel und viele kleine und mittelgroße, der Form nach sehr mannigfache Gnanglienzellan vor.Der Auerbachsche Plexus zeigt eine Gliederung in ein Primär-, Sekundär- und Tertiärgeflecht. Der mit dem Auerbachschen Plexus kontinuierlich zusammenhängende Plexus muscularis profundus besitzt in verhältnismäßig spärlicher, aber gleichmäßiger Verteilung Ganglienzellen.Die großen Ganglienzellen des Meissnerschen Plexus gehören vorwiegend dem Typus 2 nach Dogiel an; daneben gibt es noch eine Fülle kleiner, teils multipolarer, teils der Form nach schwer bestimmbarer Ganglienzellen.Die an die Muscularis mucosae grenzenden Maschen des Meissnerschen Plexus sind von außerordentlicher Feinheit und enthalten auch interstitielle Zellen.Der Meissnersche Plexus geht mit feinsten, netzartigen Faserzügen ohne scharfe Grenze in den in der Schleimhaut ausgebreiteten Plexus mucosus über. Letzterer enthält zwar in seinem an die Submucosa grenzenden Gebiet noch vereinzelte kleine multipolare Ganglienzellen, weist jedoch in seinen übrigen, dem Epithel genäherten Lagen nur noch interstitielle Zellen auf.Der Plexus mucosus besitzt die Form des Terminalretikulums, den Charakter einer netzartigen Endformation des vegetativen Nervensystems, das hier afferente, efferente und (Sekretorische Nervenelemente in einer gemeinsamen plasmodialen Leitbahn beherbergt.In der Schleimhaut des Processus vermiformis entwickelt der dort ausgebreitete Plexus mucosus eine außerordentliche Zartheit und Reichhaltigkeit seiner nervösen Elemente.In einem Falle von rein neurogener Appandizitis kommen im Plexus mucosus des menschlichen Processus vermiformis bei sonst intakter Schleimhaut neuromatöse Gewebsneubildungen vor, die als das Resultat eines im Terminalretikulum zutage tretenden Wucherungsprozesses gedeutet werden können.In einem Falle von Megacolon werden schwere pathologische Veränderungen, vor allem an den Zellen und Fasern des Auerbachschen Plexus und des Plexus muscularis profundus beschrieben. 相似文献
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47.
Gregor Buch Andreas Schulz Irene Schmidtmann Konstantin Strauch Philipp S. Wild 《Biometrical journal. Biometrische Zeitschrift》2024,66(2):2300063
Variable selection is usually performed to increase interpretability, as sparser models are easier to understand than full models. However, a focus on sparsity is not always suitable, for example, when features are related due to contextual similarities or high correlations. Here, it may be more appropriate to identify groups and their predictive members, a task that can be accomplished with bi-level selection procedures. To investigate whether such techniques lead to increased interpretability, group exponential LASSO (GEL), sparse group LASSO (SGL), composite minimax concave penalty (cMCP), and least absolute shrinkage, and selection operator (LASSO) as reference methods were used to select predictors in time-to-event, regression, and classification tasks in bootstrap samples from a cohort of 1001 patients. Different groupings based on prior knowledge, correlation structure, and random assignment were compared in terms of selection relevance, group consistency, and collinearity tolerance. The results show that bi-level selection methods are superior to LASSO in all criteria. The cMCP demonstrated superiority in selection relevance, while SGL was convincing in group consistency. An all-round capacity was achieved by GEL: the approach jointly selected correlated and content-related predictors while maintaining high selection relevance. This method seems recommendable when variables are grouped, and interpretation is of primary interest. 相似文献
48.
Euskirchen P Skaftnesmo KO Huszthy PC Brekkå N Bjerkvig R Jacobs AH Miletic H 《Experimental cell research》2011,(20):2864-2873
The cell fate determinant NUMB orchestrates asymmetric cell division in flies and mammals and has lately been suggested to have a tumor suppressor function in breast and lung cancer. Here, we studied NUMB in the context of malignant gliomas. We used ectopic expression of NUMB in order to inhibit proliferation and induce differentiation in glioma cells by alteration of Notch, Hedgehog and p53 signaling. We found that NUMB is consistently expressed in glioma biopsies with predominance of NUMB2/4 isoforms as determined by isoform-specific real-time PCR and Western blotting. Upon lentiviral overexpression, in vitro proliferation rate and the grade of differentiation as assessed by morphology and expression of neural and glial markers remained unchanged. Orthotopic xenografts of NUMB-transduced human U87 glioma cells could be established in nude rats without impairing engraftment or causing significant changes in morphology based on magnetic resonance imaging (MRI). The previously reported alteration of Hedgehog and p53 signaling by NUMB could not be recapitulated in glioma cells. We thus show that in experimental gliomas, NUMB overexpression most likely does not exert a tumor suppressor function such as seen in epithelial cancers. 相似文献
49.
To examine the effect of cardiogenic gas mixing on gas exchange we measured arterial tension of O2 (PaO2) and arterial tension of CO2 (PaCO2) during 3- to 5-min breath holds (BH) before and after infusing 50 ml of saline into the pericardial space (PCF) of seven anesthetized, paralyzed, mechanically ventilated dogs. During BH the ventilator was disconnected and a bias flow of 50% O2 at 4-5 l/min was delivered through the side ports of a small catheter whose tip was positioned 1 cm cephalad of the carina. Paired runs, alternately with and without PCF, were performed in triplicate in each dog. Initial PaO2 was similar for control runs [81 +/- 3 mmHg (SE)] and PCF runs (78 +/- 3 mmHg; P greater than 0.1). After 3-min BH, PaO2 in PCF runs (33 +/- 3 mmHg) was less than that in control runs (58 +/- 4 mmHg) (P less than 0.001). In contrast, the pattern of PaCO2 during BH did not differ with PCF. After 3-min BH, PaCO2 was 49 +/- 3 mmHg with PCF and 49 +/- 2 mmHg in the control runs (P greater than 0.7). In two dogs, repeated 50-ml reductions in lung volume, produced by rib cage compression, did not alter the time course of PaO2 during BH. Although cardiac output decreased slightly with PCF, hemodynamic changes due to PCF were unlikely to account for the observed fall in PaO2. Our results indicate a substantial effect of cardiogenic gas mixing on O2 uptake when tracheal gas is O2 enriched during breath holding.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
50.