MCAM/MUC18 REGULATES MELANOMA PROGRESSION BY MODULATING THE EXPRESSION OF ID-1

The acquisition of the metastatic melanoma phenotype is associated with increased expression of the melanoma cell adhesion molecule MCAM/MUC18 (CD146). However, the mechanism by which MUC18 contributes to melanoma metastasis remains unclear. Herein, we stably silenced MUC18 expression utilizing lentivirus-incorporated small hairpin RNA, in two metastatic melanoma cell lines, A375SM and C8161, and conducted cDNA microarray analysis. We identified and validated that the transcriptional regulator, Inhibitor of DNA Binding-1 (Id-1), previously shown to function as an oncogene in several malignancies, was downregulated by 5.6-fold following MUC18 silencing. Additionally, we found that MUC18 regulated Id-1 expression at the transcriptional level via ATF-3. Interestingly, ATF-3 was upregulated by 6.9 fold in our cDNA microarray analysis following MUC18 silencing. ChIP analysis showed increased binding of ATF-3 to the Id-1 promoter after MUC18 silencing, while mutation of the ATF-3 binding site on the Id-1 promoter increased Id-1 promoter activity in MUC18-silenced cells. These Data suggest that MUC18 silencing promotes inhibition of Id-1 expression by increasing ATF-3 expression and binding to the Id-1 promoter. Rescue of MUC18 reverted the expression of Id-1 and ATF-3, thus validating that they are not off-target effects of MUC18. To further assess the role of Id-1 in melanoma invasion and metastasis, we overexpressed Id-1 in MUC18-silenced cells. Overexpression of Id-1 in MUC18-silenced cells resulted in increased cell invasion, as well as increased expression and activity of MMP-2. Our data further reveal that Id-1 regulates MMP-2 at the transcriptional level through Sp1 and Ets-1. This is the first report to demonstrate that MUC18 does not act exclusively in cell adherence, but is also involved in cell signaling that regulates the expression of genes, such as Id-1 and ATF-3, thus contributing to the metastatic melanoma phenotype.

Strengthening the Reporting of Molecular Epidemiology for Infectious Diseases (STROME-ID): an extension of the STROBE statement

Molecular data are now widely used in epidemiological studies to investigate the transmission, distribution, biology, and diversity of pathogens. Our objective was to establish recommendations to support good scientific reporting of molecular epidemiological studies to encourage authors to consider specific threats to valid inference. The statement Strengthening the Reporting of Molecular Epidemiology for Infectious Diseases (STROME-ID) builds upon the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative. The STROME-ID statement was developed by a working group of epidemiologists, statisticians, bioinformaticians, virologists, and microbiologists with expertise in control of infection and communicable diseases. The statement focuses on issues relating to the reporting of epidemiological studies of infectious diseases using molecular data that were not addressed by STROBE. STROME-ID addresses terminology, measures of genetic diversity within pathogen populations, laboratory methods, sample collection, use of molecular markers, molecular clocks, timeframe, multiple-strain infections, non-independence of infectious-disease data, missing data, ascertainment bias, consistency between molecular and epidemiological data, and ethical considerations with respect to infectious-disease research. In total, 20 items were added to the 22 item STROBE checklist. When used, the STROME-ID recommendations should advance the quality and transparency of scientific reporting, with clear benefits for evidence reviews and health-policy decision making.

Magen Daṿid : Fibel in hebräischer und spaniolischer Sprache

David Moscona

ʻIr Daṿid : Sive De Convenientia Vocabulorum Rabbinicorum; cum Graecis, & quibusdam aliis linguis Europaeis

Auctore David Cohen de Lara

Bigdê Kohanîm id est vestitus sacerdotum Hebræorum, sive commentarius amplissimus in Exodi cap. XXVIII. ac XXXIX. & Levit. cap. XVI. aliaque loca s. scripturae quamplurima : cum indicibus locupletissimis & tabulis aeneis elegantissimis

auctore Johanne Braunio, Palatino

Reshimat otsar ha-sefarim ha-mefuʾar, atsero ṿe-asefo ... Daṿid Oppenhaim ...

Hebr. Text von I. Metz, hebr. Titel und lat. Übers. von L. Emden auf gg.überliegenden Seiten.

Sēfer Menôrat ham-mā'ôr : ... û-le-maʿan gam nāšîm we-yelādîm yiʿidû li-šmôaʿ be-limmûdîm ...

Yiṣḥāq Abôhab

Einige Bemerkungen über Bachjas Stil im Kitab al-hidaja ila fara'id al-qulub und dessen Übersetzung durch J. ibn Tibbon

Moses Sister

Specimen sapientiae Indorum veterum : id est liber ethico-politicus pervetustus ...

[Bearb.: Ibn al-Muqaffa]. Nunc primum Graece ex mss. cod. Holsteiniano prodit, cum versione nova Latina, opera Sebast. Gottofr. Starkii. Aus dem Arab. ins Griech. übers. von Simeon

Oupnek'hat, (id est, Secretum tegendum) : opus ipsa in India rarissimum, continens antiquam et arcanam, seu theologicam et philosophicam, doctrinam, è q. sacris Indorum libris, Rak Beid, Djedjr beid, Sam beid, Athrban beid, excerptam ; ad verbum, è Persico idiomate, Sanscreticis vokabulis intermixto, in Latinum conversum ; dissertationibus et annotationibus, difficiliora explanantibus, illustratum

studio et opera Anquetil Duperron

[Sefer Yetsirah] id est Liber Iezirah, qui Abrahamo patriarchæ adscribitur : unà cum commentario rabi Abraham f. D super 32 Semitis Sapientiæ, à quibus liber Iezirah incipit

translatus & notis illustratus à Joanne Stephano Rittanglio