Transcriptomic changes in human breast cancer progression as determined by serial analysis of gene expression

INTRODUCTION: Genomic and transcriptomic alterations affecting key cellular processes such us cell proliferation, differentiation and genomic stability are considered crucial for the development and progression of cancer. Most invasive breast carcinomas are known to derive from precursor in situ lesions. It is proposed that major global expression abnormalities occur in the transition from normal to premalignant stages and further progression to invasive stages. Serial analysis of gene expression (SAGE) was employed to generate a comprehensive global gene expression profile of the major changes occurring during breast cancer malignant evolution. METHODS: In the present study we combined various normal and tumor SAGE libraries available in the public domain with sets of breast cancer SAGE libraries recently generated and sequenced in our laboratory. A recently developed modified t test was used to detect the genes differentially expressed. RESULTS: We accumulated a total of approximately 1.7 million breast tissue-specific SAGE tags and monitored the behavior of more than 25,157 genes during early breast carcinogenesis. We detected 52 transcripts commonly deregulated across the board when comparing normal tissue with ductal carcinoma in situ, and 149 transcripts when comparing ductal carcinoma in situ with invasive ductal carcinoma (P < 0.01). CONCLUSION: A major novelty of our study was the use of a statistical method that correctly accounts for the intra-SAGE and inter-SAGE library sources of variation. The most useful result of applying this modified t statistics beta binomial test is the identification of genes and gene families commonly deregulated across samples within each specific stage in the transition from normal to preinvasive and invasive stages of breast cancer development. Most of the gene expression abnormalities detected at the in situ stage were related to specific genes in charge of regulating the proper homeostasis between cell death and cell proliferation. The comparison of in situ lesions with fully invasive lesions, a much more heterogeneous group, clearly identified as the most importantly deregulated group of transcripts those encoding for various families of proteins in charge of extracellular matrix remodeling, invasion and cell motility functions

ORESTES are enriched in rare exon usage variants affecting the encoded proteins

A significant fraction of the variability found in the human transcriptome is due to alternative splicing, including alternative exon usage (AEU), intron retention and use of cryptic splice sites. We present a comparison of a large-scale analysis of AEU in the human transcriptome through genome mapping of Open Reading Frame ESTs (ORESTES) and conventional ESTs. It is shown here that ORESTES probe low abundant messages more efficiently. In addition, most of the variants detected by ORESTES affect the structure of the corresponding proteins. (C) 2003 Academie des sciences. Published by Elsevier SAS. All rights reserved.3264195397998

Fortunado’s, Desperado’s and Clandestino’s in Diaspora Labour Markets: The Circular 'Homo Mobilis'

Demographic patterns in our world (e.g., aging processes, birth and death rates) are increasingly influenced by migration movements. A rising number of people is ‘on the move’, in search of a better fortune elsewhere. It is noteworthy that nowadays many migration movements do not show anymore stable patterns, but reflect a high degree of dynamics, for instance, in the form of return migration, circular and temporary migration, or chain migration. There is also a great heterogeneity in the motivations of many migrants that may have significant impacts on the migration choice, the destination place, the migrant’s status, and the duration of stay. Consequently, return migration, temporary migration and circular migration have in recent years become important research and policy issues. This note offers a short review of the dilemma’s and assessment issues inherent in the effects of non-structural or temporary migrants (so-called ‘movers’) on host economies. Particular attention will be paid to circular migration policy in Europe as a vehicle to both mitigate temporary tensions on regional labor markets of host economics and to provide a solid base for sustainable growth in the sending countries. Various research and policy challenges are outlined as well

Does engaging in a group-based intervention increase parental sense of competence in parents of pre-school children?:A Systematic Review of the Current Literature

As the preschool years are a formative period for long-term physical and mental health, this period is recognised as an important window for early effective intervention. Parenting behaviour is a key factor to target in order to optimise child development. Group-based interventions for parents are considered efficient and cost effective methods of early intervention and have been found to improve child behaviour and adjustment. Self-efficacy is key to behaviour change and as such parental self-efficacy should be a consideration in interventions aimed at influencing parenting behaviour. Therefore, the purpose of this systematic review was to examine the impact of group-based early interventions for parents of preschool children on parental self-efficacy. Nine databases were searched (ASSIA, CINAHL, EMBASE, Maternity and Infant Care, Ovid Medline, PsycINFO, Pubmed, Science Direct and Web of Science). Studies were included if they were a randomised controlled trial of a group-based intervention for parents of preschool children and measured change in parental self-efficacy. Fifteen studies were identified. Although changes in parental self-efficacy following a group-based intervention were noted in the majority of studies reviewed, the methodological quality of the studies included in the review means these findings have to be interpreted with caution; only seven studies were rated to be methodologically adequate. Further research is needed to understand the mechanisms by which these interventions may improve parental self-efficacy. Studies specifically examining the impact of such interventions on paternal self-efficacy are also warranted

Prenatal Reflective Functioning and Development of Aggression in Infancy: the Roles of Maternal Intrusiveness and Sensitivity

Maternal reflective functioning (RF) has been associated with quality of parent-child interactions and child development. This study investigated whether prenatal RF predicted the development of infant physical aggression and whether maternal sensitivity and/or intrusiveness mediated or moderated this association. The sample consisted of 96 first-time mothers (M = 22.57 years, SD = 2.13) and their infants (54 % male). Prenatal RF was measured with an interview, maternal behavior was observed during free play at 6 months post-partum, and infant physical aggression was assessed at 6, 12, and 20 months using maternal reports. Multivariate analyses of variance showed that relatively poor prenatal RF was related to relatively high infant physical aggression. These associations were moderated by maternal intrusiveness, with significant differences in physical aggression between RF-groups reportedly only in the absence of intrusiveness. Generally, mothers reported an increase in physical aggression between 6 and 12 months, except when they had both low RF-skills and were relatively less sensitive. It is concluded that prenatal RF is associated with (development of) infant physical aggression, and may be targeted in intervention programs aimed at reducing early physical aggression. Less adequate parenting, however, may counteract the beneficial effects of good RF, or obscure insight into children’s behavioral development

Emotion Socialization in Anxious Youth: Parenting Buffers Emotional Reactivity to Peer Negative Events

Anxious youth exhibit heightened emotional reactivity, particularly to social-evaluative threat, such as peer evaluation and feedback, compared to non-anxious youth. Moreover, normative developmental changes during the transition into adolescence may exacerbate emotional reactivity to peer negative events, particularly for anxious youth. Therefore, it is important to investigate factors that may buffer emotional reactivity within peer contexts among anxious youth. The current study examined the role of parenting behaviors in child emotional reactivity to peer and non-peer negative events among 86 anxious youth in middle childhood to adolescence (Mean age = 11.29, 54% girls). Parenting behavior and affect was observed during a social-evaluative laboratory speech task for youth, and ecological momentary assessment (EMA) methods were used to examine youth emotional reactivity to typical daily negative events within peer and non-peer contexts. Results showed that parent positive behaviors, and low levels of parent anxious affect, during the stressful laboratory task for youth buffered youth negative emotional reactivity to real-world negative peer events, but not non-peer events. Findings inform our understanding of parenting influences on anxious youth's emotional reactivity to developmentally salient negative events during the transition into adolescence