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“Heterozygous coding mutations in the INS gene that encodes preproinsulin were recently shown to be an important cause of permanent neonatal diabetes. These dominantly acting mutations prevent normal folding of proinsulin, which leads to beta-cell death through endoplasmic reticulum stress and apoptosis. We now report 10 different recessive INS mutations in 15 probands BAY 57-1293 with neonatal diabetes. Functional studies showed

that recessive mutations resulted in diabetes because of decreased insulin biosynthesis through distinct mechanisms, including gene deletion, lack of the translation initiation signal, and altered mRNA stability because of the disruption of a polyadenylation signal. A subset of recessive mutations caused abnormal INS transcription,

including the deletion of the C1 and E1 cis regulatory elements, or three different single base-pair substitutions in a CC dinucleotide sequence located between E1 and A1 elements. In keeping with click here an earlier and more severe beta-cell defect, patients with recessive INS mutations had a lower birth weight (-3.2 SD score vs.-2.0 SD score) and were diagnosed earlier (median 1 week vs. 10 weeks) compared to those with dominant INS mutations. Mutations in the insulin gene can therefore result in neonatal diabetes as a result of two contrasting pathogenic mechanisms. Moreover, the recessively inherited mutations provide a genetic demonstration of the essential role of multiple sequence

elements that regulate the biosynthesis of insulin in man.”
“A combination of analytical techniques capable of elemental and microstructural characterisation was used for the identification of ancient gilding technology and bronze metallurgy. EDXRF, micro-EDXRF, SEM-EDS analysis and metallographic examinations were applied in the study of artefacts dating to the end of the second millennium BC from Crasto de So Romo in Central Portugal. Results report to the finding of an exceptional gilded copper nail among bronze GS-9973 cost artefacts with 9 wt.% to15 wt.% tin and minute other metallic impurities. Additionally, analysis of a crucible fragment points out for bronze production at the archaeological site. EDXRF and micro-EDXRF analysis made on the copper nail showed that it was gilded only on the front side of the head, and that the gold layer has been lost in the most exposed areas. SEM-EDS analysis showed that the gold layer has 5-8 A mu m in thickness and is covered with a thick corrosion layer. The gilding technique is discussed based on the gold layer composition and gold/copper substrate interface. So far, this object seems to be the first diffusion gilded artefact identified in the Portuguese territory dated to Late Bronze Age.