ABSTRACT
A heterocyclic, sp(3)-rich chemical scaffold was synthesised in just 6 steps via a highly regio- and diastereo-selective tandem nitrone formation/intramolecular nitrone-alkene [3+2] cycloaddition reaction. A library of 543 lead-like compounds based on the scaffold core has been produced.
Subject(s)
Alkenes/chemistry , Heterocyclic Compounds/chemistry , Nitrogen Oxides/chemistry , Cycloaddition ReactionABSTRACT
The Wilms tumor protein WT1 is involved in the development of several organs, including the gonads. WT1 mutations in humans lead to syndromes associated with impaired sexual development and Wt1 knockout mice show regression of gonad anlagen. As a transcription factor, WT1 fulfills its function by regulating a set of target genes. With respect to gonad development only few in vivo WT1 targets, e.g. steroidogenic factor 1 (SF1) have been identified so far. To get a comprehensive view of WT1 targets in the gonad, we compared gene expression in urogenital ridges of wild-type and Wt1(-/-) embryos. We found almost 150 genes differentially expressed higher than factor three, using microarray analysis. To confirm these results we performed quantitative real-time RT-PCR for many genes and observed a high degree of concordance between microarray and real-time RT-PCR results. Employing in situ hybridization we found 'WT1 activated genes' to be expressed in gonads, mesonephroi and coelomic epithelium--those parts of the urogenital ridge with Wt1 expression. Interestingly, many of the differentially expressed genes are known to show sex-specific expression at later time-points. These results provide a basis for investigation of developmental pathways in the urogenital ridge downstream of WT1 and for identification of new candidate genes involved in early urogenital ridge development. For example we provide a first potential target of WT1 in the coelomic epithelium--Muc16, and a gene regulated by the WT1 target SF1--Gata4.
Subject(s)
Gene Expression Regulation, Developmental , Gonads/metabolism , Urogenital System/metabolism , WT1 Proteins/genetics , Animals , Cell Line , Female , GATA4 Transcription Factor/genetics , GATA4 Transcription Factor/metabolism , GATA4 Transcription Factor/physiology , Gonads/embryology , In Situ Hybridization , Male , Mice , Mice, Knockout , Oligonucleotide Array Sequence Analysis , RNA Interference , Reverse Transcriptase Polymerase Chain Reaction , Sex Determination Processes , Urogenital System/embryology , WT1 Proteins/metabolism , WT1 Proteins/physiologyABSTRACT
"The aim of this study is to determine the effect of internal and external migration on the occupational mobility of the heads of households migrating to Medina [Saudi Arabia]....[It] is based on a survey of families in Medina which was conducted by the author in 1986/1987." The results show that "the majority of the migrants were able to achieve positive vocational mobility as a result of their migration. However, there are some distinctions in the extent of this positiveness between Saudi Arabian and non-Saudi Arabian migrants, as well as between urban and rural migrants.... The main factors affecting migration to Medina are difference in income, as well as in the educational level at origin and at destination."
Subject(s)
Educational Status , Emigration and Immigration , Employment , Ethnicity , Family Characteristics , Income , Rural Population , Transients and Migrants , Urban Population , Asia , Asia, Western , Demography , Developing Countries , Economics , Middle East , Population , Population Characteristics , Population Dynamics , Saudi Arabia , Social Class , Socioeconomic FactorsABSTRACT
"The aim of this paper is to study the development of population weights for regions and urban centres in Saudi Arabia through the period 1962-1974. In order to achieve this aim some non-parametric statistical rules have been used such as rank-size rule and the four-city index. The results show non-balanced distribution of population on both regional and urban scales. The concentration of people in urban centres is more pronounced than the concentration in regions. This is due to internal and external movement of population towards large-sized urban centres."
