The RING domain harbours the E3 ubiquitin ligase activity needed by Arkadia to ubiquitinate its substrates such as negative regulators of TGF-beta signaling. The RING finger domain of Arkadia is a RING-H2 type and its structure and stability is strongly dependent on the
presence of two bound Zn(II) ions attached to the protein frame through a defined Cys3-His2-Cys3 motif. In the present paper we transform the RING-H2 type of Arkadia finger domain to nonnative RING sequence, substituting the zinc-binding residues Cys(955) or His(960) to Arginine, through site-directed mutagenesis. The recombinant expression, in Escherichia coli, of the mutants C955R and H960R reveal significant see more lower yield in respect with the native polypeptide of Arkadia RING-H2 finger domain. In particular, only the C955R mutant exhibits expression
yield sufficient for recombinant protein isolation and preliminary studies. Emricasan in vivo Atomic absorption measurements and preliminary NMR data analysis reveal that the C955R point mutation in the RING Finger domain of Arkadia diminishes dramatically the zinc binding affinity, leading to the breakdown of the global structural integrity of the RING construct.”
“Sickle cell disease (SCD) does not occur in the indigenous German population, but with the increasing number of immigrants from countries at high risk for hemoglobinopathies, the question emerges whether or not a newborn screening program (NBS) for SCD disease should be initiated
in Germany anyhow. We have recently shown that in Berlin, a city with a very large immigrant population, the incidence of SCD is considerable, but our findings are insufficient to make a decision for the country as a whole. In this paper we will show that a large body of epidemiological data can be generated in a relatively short period of time, with a very high degree of precision and at relatively little expense-a result that might motivate other working groups to start such a pilot project locally. We examined A-1155463 in vitro previously collected dried blood cards that were up to six months old, using high performance liquid chromatography (HPLC) as first method and capillary electrophoresis (CE) as second method. A single, part-time laboratory technician processed 38,220 samples in a period of 162 working days. The total costs per sample including all incidentals (as well as labor costs) were EUR 1.44.”
“Xeroderma pigmentosum Variant (XP-V) form is characterized by a late onset of skin symptoms. Our aim is the clinical and genetic investigations of XP-V Tunisian patients in order to develop a simple tool for early diagnosis. We investigated 16 suspected XP patients belonging to ten consanguineous families. Analysis of the POLH gene was performed by linkage analysis, long range PCR, and sequencing. Genetic analysis showed linkage to the POLH gene with a founder haplotype in all affected patients.