New insights into the pathobiology of Down syndrome--hyaluronan synthase-2 overexpression is regulated by collagen VI α2 chain.

Down syndrome (DS) is a common birth defect characterized by the trisomy of chromosome 21. DS-affected umbilical cords (UCs) of fetuses show altered architecture of the extracellular matrix. Overexpression of the chromosome 21 genes encoding the collagen type VI (COLVI) chains α1(VI) and α2(VI), COL6A1 and COL6A2, respectively, has also reported to occur in the nuchal skin of DS fetuses. The aim of this study was therefore to evaluate the COLVI content in euploid and DS-affected UCs and human skin fibroblasts, and to investigate the relationships between COLVI and hyaluronan (HA) and HA synthase-2 (HAS2). We found that the UCs of DS fetuses showed denser staining of COLVI and increased COL6A2 expression at both early and term gestational ages. In vitro expression studies in DS-derived fibroblasts showed similarly increased amounts of α1(VI) and α2(VI) chains at the protein and transcriptional level, supporting the hypothesis of the gene dosage effect. Furthermore, increased levels of HA and HAS2 were also found in DS-derived skin fibroblast cultures. Notably, silencing of COL6A2 in DS-derived cells resulted in downregulation of HAS2, with a simultaneous decrease in secreted HA. Exogenous addition of COLVI to normal fibroblasts did not have any effect on HAS2 expression. In conclusion, UCs and skin fibroblasts in DS show significant increases in COLVI and HA; the overexpression of COL6A2 in DS tissue and cells is closely related to the increased expression of HAS2. These data may explain the DS phenotypes and their effects in organ tissue maturation.

Ms. Ff. Mus. 1238 - Dominica VI. post Trinit. : Liebet eure Feinde; segnet die euch fluchen ; a canto, alto, tenore, basso con i ripieni, 2 violini, 2 hautbois, viola, violoncello,violono, bassono ed organo

di Telemann

Uma carta de lei inédita de D. Alfonso V. onde, entre outros assuntos, se trata das judiaras portuguesas

[von] Mosés Bensabat Amzalak

Torat ṭaʿame ha-miḳra : M. Danielis Weimari s. Doctrina accentuationis Hebraeae VI regulis accurate ÿ& succincte inclusa.../ Ipsam Hanc instauravit ; Gottfried Mathesius adjutor

Text lat. u. hebr.

Abramo Colorni : ingegnere i Alfonso II. d'Este ; memoria letta nell' adunanza 30 marzo 1890

nuove ricerche del G. Jarè

Tôṣe'ôt ḥayyîm : sēfer kôlēl kōl ofnê tefillôt û-taḥanûnîm le-hitpallēl baʿad ha-ḥôlîm we-ham-mētîm ... bi-lšôn ʿivrî û-vi-lšôn aškenazz i

ʿal yedê Yiṣḥāq Ben-Aryê Yôsēf Dōv ...

Institutionum Hebraicarum Libri Sex : I. De Orthographia. II. De Etymologia. III. De Syntaxi. IV. De Prosodia. V. De Masoreth. VI. De Compositis, anomolis & difficilibus

Auctore Valentino Schindlero ...

Aus dem Kohelet-Kommentar des Tanchum Jeruschalmi : Cap. I - VI ; mit Einl. u. Anmerkungen

Leipzig, Univ., Diss. 1888

Sēfer Marʿē mûsār û-vi-lešôn aškenaz ... : kōl ham-mešālîm we-ham-melîkôt ...

Zeligmann Ulma Gintzburg [Seligman Ulma Guenzburg]

Sēfer Maʿaśe H' : ... maʿaśîm gedôlîm we-niflā'îm ... bi-lešôn haq-qôdeš û-vi-lešôn aškenaz

[Simon Akiba Bär Ben-Josef]

Tefillôt yôm kippûr qāṭān : be-taʿanît ʿerev r"ḥ ... ; nidpās bi-lešôn haq-qôdeš û-vi-lešôn aškenaz ... ḥibbûr hap-pêrûš siqqûrîn ṭaiṭš ...

... Nātān de q"q Prostiṣ

Sēfer Maṭṭē Aharôn : bi-šenê ḥalāqîm, kôlēl derûšîm yeqārîm bi-šeʾēlat had-dāt û-vi-šeʾēlat haz-zemān ; we-ḥiddûšê gapa"t ...

hēḵînô Aharôn Dāwid b. R. Ḥayyîm hak-Kōhēn Zeldner