4:50 From Paddington (Miss Marple Mysteries, Book 8) by Agatha Christie

By Agatha Christie

For an speedy the 2 trains ran jointly, part through facet. In that frozen second, Elspeth witnessed a homicide. Helplessly, she stared out of her carriage window as a guy remorselessly tightened his grip round a woman’s throat. The physique crumpled. Then the opposite teach drew away.

But who, except leave out Marple, could take her tale heavily? finally, there have been no suspects, no different witnesses . . . and no corpse.

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Extra resources for 4:50 From Paddington (Miss Marple Mysteries, Book 8)

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Antibodies against the protein of interest are applied to the membrane with the immobilized proteins. The binding of the specific antibodies to the protein is visualized with a second antibody targeted against the first antibody. , 1995; Couse and Korach, 1999). The direct comparison of the protein structure of ERa and ER~ reveals that the DNA-binding domains of both show an extremely high degree of homology; in fact, the protein structure differs only in three amino acids. On the other hand there is only a 59% homology in the ligand binding domain, which is of great importance for the ligand specificity and, therefore, also of great interest for pharmacological approaches and for the search for ER-subtype specific ligands (agonists and antagonists).

The so-called hinge-region or domain 0 separates the DNA binding domain (DBD) and the LBO and comprises a 40-50 amino acid long 37 "Estrogen's classics" - the genomic pathway of estrogen action c AlB D F E 595 hERa 530 h ER~ Transcriptional 3c:tivat ion AF-2 Af- I DNA binding oacli\'310r binding Corepressor binding Fig. 15. Structural and functional protein domains of ERa and IAdapted from Klinge, 2000) • • ER~ . peptide stretch responsible for the dimerization of the estrogen receptor and for the localization of the receptor dimer to the nucleus (NLS, nuclear localization sequences).

8). Obviously, the mechanism of this regularly occurring cycle is under a tight control of various endocrine feed back and feed forward loops. These interactions are complex enough and would need a much longer discussion for satisfactory understanding. Briefly, during the menstrual cycle estrogen induces massive physiological, morphological and structural changes of the uterus tissue, such as the proliferation of its mucosa. After ovulation, it is the progesterone that changes the physiology and pushes the endometrium into the phase of secretion.

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