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Roberta L. Millstein 《Journal of the history of biology》2008,41(2):339-367
Biologists and philosophers have been extremely pessimistic about the possibility of demonstrating random drift in nature,
particularly when it comes to distinguishing random drift from natural selection. However, examination of a historical case
– Maxime Lamotte’s study of natural populations of the land snail, Cepaea nemoralis in the 1950s – shows that while some pessimism is warranted, it has been overstated. Indeed, by describing a unique signature
for drift and showing that this signature obtained in the populations under study, Lamotte was able to make a good case for
a significant role for␣drift. It may be difficult to disentangle the causes of drift and selection acting in a population,
but it is not (always) impossible. 相似文献
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Francesca Passaretta Domenico Bosco Lucia Centurione Maria Antonietta Centurione Fabio Marongiu Roberta Di Pietro 《Journal of cellular and molecular medicine》2020,24(7):4350-4355
Human Amniotic Epithelial Cells (hAEC) isolated from term placenta are a promising source for regenerative medicine. However, it has long been debated whether the hAEC population consists of heterogeneous or homogeneous cells. In a previous study, we investigated the characteristics of hAEC isolated from four different regions of the amniotic membrane finding significant heterogeneity. The aim of this study was to evaluate the hepatic differentiation capability of hAEC isolated from these four regions. Human term placentae were collected after caesarean section and hAEC were isolated from four regions of the amniotic membrane (R1-R4, according to their relative distance from the umbilical cord) and treated in hepatic differentiation conditions for 14 days. hAEC-derived hepatocyte-like cells showed marked differences in the expression of hepatic markers: R4 showed higher levels of Albumin and Hepatocyte Nuclear Factor (HNF) 4α whereas R1 expressed higher Cytochrome P450 enzymes, both at the gene and protein level. These preliminary results suggest that hAEC isolated from R1 and R4 of the amniotic membrane are more prone to hepatic differentiation. Therefore, the use of hAEC from a specific region of the amniotic membrane should be taken into consideration as it could have an impact on the outcome of therapeutic applications. 相似文献
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Synthetic peptides including acidic clusters as substrates and inhibitors of rat liver casein kinase TS (type-2) 总被引:10,自引:0,他引:10
F Meggio F Marchiori G Borin G Chessa L A Pinna 《The Journal of biological chemistry》1984,259(23):14576-14579
The hexapeptides AcSer-Glu-Glu-Glu-Val-Glu and Ser-Glu-Glu-Glu-Glu-Glu, reminiscent of the sites phosphorylated by type-2 casein kinase TS in troponin T and glycogen synthase, respectively, have been synthesized and tested as phosphorylatable substrates for casein kinase TS as well as for other protein kinases. Both peptides are readily phosphorylated by casein kinase TS but not, to any detectable extent, by either cAMP-dependent protein kinase or phosphorylase kinase. Phosphorylation by type-1 casein kinase S was almost negligible. On the other hand the hexapeptide Ser-Glu-Glu-Glu-Ala-Ala is phosphorylated much more slowly and the hexapeptide Ser-Glu-Glu-Ala-Ala-Ala is almost unaffected by casein kinase TS. While the Vmax values of casein kinase TS with the acidic hexapeptides are comparable to those obtained with the corresponding protein substrates, the apparent Km values for the peptides are about two orders of magnitude higher than those for the protein substrates. The heptapeptide Arg-Ser-Glu-Glu-Glu-Val-Glu is a very poor substrate of casein kinase TS in comparison with the corresponding hexapeptide lacking the N-terminal Arg; it is, however, a competitive inhibitor toward the protein substrates, exhibiting a Ki similar to those of Ser-Glu-Glu-Glu-Glu-Glu and (Glu)5 which, in turn, are one order of magnitude higher than that of (Glu)10. It is concluded that the minimum structural requirement of type-2 casein kinases consists of a phosphorylatable residue followed by an acidic cluster, whose length is critical for the binding to the enzyme. Additional residues on the N-terminal side are not required, but their nature can influence the transphosphorylation reaction considerably. 相似文献
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Ca2+ phospholipid-dependent and independent phosphorylation of synthetic peptide substrates by protein kinase C 总被引:1,自引:0,他引:1
Several synthetic peptides reproducing fragments of protamines have been used as model substrates for Ca2+/phospholipid-dependent protein kinase C, tested both in the absence of any effector (basal conditions) and upon activation by either Ca2+ and phosphatidylserine (or diacylglycerol) or limited proteolysis. Only the peptide Arg4-Tyr-Gly-Ser-Arg6-Tyr [Ga(52-65)] shares the unique property of protamines of being readily phosphorylated even under basal conditions. Optimal activity in the absence of effectors is observed with Tris/HCl buffer pH 7.5; Pipes and Hepes are less effective at pH 7.5, and at pH 6.5 basal phosphorylation is reduced. Under the best conditions for basal phosphorylation of Ga(52-65), its derivative with ornithine replaced for arginine and those corresponding to its C-terminal fragments Gly-Ser-Arg6-Tyr [Ga(57-65)] and Gly-Ser-Arg3 [Ga(57-61)], as well as the peptides Pro-Arg5-Ser2-Arg-Pro-Val-Arg [Th(1-12)], Arg4-Tyr-Arg2-Ser-Thr-Val-Ala [Th(13-23)] and Arg2-Leu-Ser2-Leu-Arg-Ala are not significantly affected though all of them, like histones, are more or less readily phosphorylated upon activation of protein kinase C by Ca2+/phosphatidylserine. The peptide Ser2-Arg-Pro-Val-Arg [Th(7-12)] however, corresponding to the C-terminal part of Th(1-12), is not phosphorylated even in the presence of activators. Limited proteolysis can roughly mimic the Ca2+/phosphatidylserine effect inducing however different extents of activation depending on the nature of the peptide substrates. Our results support the following two conclusions. Basal phosphorylation by protein kinase C in the absence of any effector requires peptide substrates whose target residue(s) are included between two extended arginyl blocks and is also dependent on pH and nature of the buffer. Peptides having extended clusters of either arginyl or ornithyl residues on the C-terminal side of serine are also readily phosphorylated, but they need activation of protein kinase by either Ca2+/phosphatidylserine or limited proteolysis. The same is true of peptides having basic residues only on the N-terminal side, or even on both sides but in limited number. 相似文献