Education

Two experiments were demonstrated showing how and where electrical engineering is used. This was to give the students an overall idea about electrical engineering. The first demonstration was to show wireless transmission using microwaves. The second is how electrical engineering is used to read bioelectrical signals from a patient and transmit the readings using the internet to a different location such as the hospital from an ambulance or a patient's home. Both experiment showed how electrical engineering can be used in real society and how it functions to make life easier.

Multiple discrete regions at 8q24 were recently shown to contain alleles that predispose to many cancers including prostate, breast, and colon. These regions are far from any annotated gene and their biological activities have been unknown. Here we profiled a 5-megabase chromatin segment encompassing all the risk regions for RNA expression, histone modifications, and locations occupied by RNA polymerase II and androgen receptor (AR). This led to the identification of several transcriptional enhancers, which were verified using reporter assays. Two enhancers in one risk region were occupied by AR and responded to androgen treatment; one contained a single nucleotide polymorphism (rs11986220) that resides within a FoxA1 binding site, with the prostate cancer risk allele facilitating both stronger FoxA1 binding and stronger androgen responsiveness. The study reported here exemplifies an approach that may be applied to any risk-associated allele in nonprotein coding regions as it emerges from genome-wide association studies to better understand the genetic predisposition of complex diseases. (GAC) . These authors contributed equally to this study.

Recent reports reveal increasing complexity of mechanisms underlying the bone sparing effects of sex steroids. This review focuses on mechanisms by which sex steroids attenuate endocortical and trabecular adult bone turnover, perhaps their most important property as bone mass regulators. Clearly, estrogen withdrawal increases osteoclast number and bone resorption; however, important open questions are the extent to which osteoblasts and their precursors are involved, and the relative contributions of the RANK/RANKL/OPG system, Fas ligand and Runx2. In addition to reviewing these aspects of estrogen action, we also discuss proskeletal effects of androgens on the adult male skeleton, including aromatization to estrogens and male-specific mechanisms. Detailed understanding of skeletal site- and gender-dependent mechanisms by which sex steroids protect the adult skeleton will provide the foundation for improved risk assessment, prevention and management of osteoporosis. J. Cell. Physiol. 224: 305–310, 2010. © 2010 Wiley-Liss, Inc.

Prostate cancers (PCas) become resistant to hormone withdrawal through increased androgen receptor (AR) signaling. Here we show increased AR-mediated transcription efficiency in PCa cells that have acquired the ability to grow in low concentrations of androgen. Compared to androgen-dependent PCa cells, these cells showed increased activity of transiently transfected reporters and increased mRNA synthesis relative to levels of AR occupancy of the prostate-specific antigen (PSA) gene. The locus also displayed up to 10-fold-higher levels of histone H3-K9/K14 acetylation and H3-K4 methylation across the entire body of the gene. Although similar increased mRNA expression and locus-wide histone acetylation were also observed at another kallikrein locus (KLK2), at a third AR target locus (TMPRSS2) increased gene expression and locus-wide histone acetylation were not seen in the absence of ligand. Androgen-independent PCa cells have thus evolved three distinctive alterations in AR-mediated transcription. First, increased RNA polymerase initiation and processivity contributed to increased gene expression. Second, AR signaling was more sensitive to ligand. Third, locus-wide chromatin remodeling conducive to the increased gene expression in the absence of ligand was apparent and depended on sustained AR activity. Therefore, increased AR ligand sensitivity as well as locus-specific chromatin alterations contribute to basal gene expression of a subpopulation of specific AR target genes in androgen-independent PCa cells. These features contribute to the androgen-independent phenotype of these cells.

The transcription factors Runx2 and estrogen receptor-␣ (ER␣) are involved in numerous normal and disease processes, including postmenopausal osteoporosis and breast cancer. Using indirect immunofluorescence microscopy and pull-down techniques, we found them to colocalize and form complexes in a ligand-dependent manner. Estradiol-bound ER␣ strongly interacted with Runx2 directly through its DNAbinding domain and only indirectly through its N-terminal and ligand-binding domains. Runx2's amino acids 417-514, encompassing activation domain 3 and the nuclear matrix targeting sequence, were sufficient for interaction with ER␣'s DNA-binding domain. As a consequence of the interaction, Runx2's transcriptional activation activity was strongly repressed, as shown by reporter assays in COS7 cells, breast cancer cells, and late-stage MC3T3-E1 osteoblast cultures.

The transcription factors Runx2 and estrogen receptor-␣ (ER␣) are involved in numerous normal and disease processes, including postmenopausal osteoporosis and breast cancer. Using indirect immunofluorescence microscopy and pull-down techniques, we found them to colocalize and form complexes in a ligand-dependent manner. Estradiol-bound ER␣ strongly interacted with Runx2 directly through its DNAbinding domain and only indirectly through its N-terminal and ligand-binding domains. Runx2's amino acids 417-514, encompassing activation domain 3 and the nuclear matrix targeting sequence, were sufficient for interaction with ER␣'s DNA-binding domain. As a consequence of the interaction, Runx2's transcriptional activation activity was strongly repressed, as shown by reporter assays in COS7 cells, breast cancer cells, and late-stage MC3T3-E1 osteoblast cultures.

Background Prostate cancer (PCa) cells preferentially metastasize to bone at least in part by acquiring osteomimetic properties. Runx2, an osteoblast master transcription factor, is aberrantly expressed in PCa cells, and promotes their metastatic phenotype. The transcriptional programs regulated by Runx2 have been extensively studied during osteoblastogenesis, where it activates or represses target genes in a context-dependent manner. However, little is known about the gene regulatory networks influenced by Runx2 in PCa cells. We therefore investigated genome wide mRNA expression changes in PCa cells in response to Runx2. Results We engineered a C4-2B PCa sub-line called C4-2B/Rx2dox, in which Doxycycline (Dox) treatment stimulates Runx2 expression from very low to levels observed in other PCa cells. Transcriptome profiling using whole genome expression array followed by in silico analysis indicated that Runx2 upregulated a multitude of genes with prominent cancer associated functions. They included secreted factors (CSF2, SDF-1), proteolytic enzymes (MMP9, CST7), cytoskeleton modulators (SDC2, Twinfilin, SH3PXD2A), intracellular signaling molecules (DUSP1, SPHK1, RASD1) and transcription factors (Sox9, SNAI2, SMAD3) functioning in epithelium to mesenchyme transition (EMT), tissue invasion, as well as homing and attachment to bone. Consistent with the gene expression data, induction of Runx2 in C4-2B cells enhanced their invasiveness. It also promoted cellular quiescence by blocking the G1/S phase transition during cell cycle progression. Furthermore, the cell cycle block was reversed as Runx2 levels declined after Dox withdrawal. Conclusions The effects of Runx2 in C4-2B/Rx2dox cells, as well as similar observations made by employing LNCaP, 22RV1 and PC3 cells, highlight multiple mechanisms by which Runx2 promotes the metastatic phenotype of PCa cells, including tissue invasion, homing to bone and induction of high bone turnover. Runx2 is therefore an attractive target for the development of novel diagnostic, prognostic and therapeutic approaches to PCa management. Targeting Runx2 may prove more effective than focusing on its individual downstream genes and pathways.

EDITORIAL COMMENT: Readers are referred to a recent review(A) of reported results of the Zavanelli manoeuvre in 103 partially-born but undeliverable fetuses (92 cephalic, 11 podalic presentations). Although 7 mothers suffered trauma, including cases of lacerations to the lower uterine segment, and of uterine rupture, there were ‘no maternal deaths or fetal injuries ascribed to the manoeuvre’.

Pseudoaneurysm is a potentially lethal complication after modified Blalock-Taussig shunt. This report describes a frequently misdiagnosed clinical presentation along with noninvasive diagnosis of pseudoaneurysm after a modified Blalock-Taussig shunt. We report a novel single-stage surgical management of the pseudoaneurysm with concomitant complete repair of tetralogy of Fallot.

Pseudoaneurysm is a potentially lethal complication after modified Blalock-Taussig shunt. This report describes a frequently misdiagnosed clinical presentation along with noninvasive diagnosis of pseudoaneurysm after a modified Blalock-Taussig shunt. We report a novel single-stage surgical management of the pseudoaneurysm with concomitant complete repair of tetralogy of Fallot.

Pseudoaneurysm is a potentially lethal complication after modified Blalock-Taussig shunt. This report describes a frequently misdiagnosed clinical presentation along with noninvasive diagnosis of pseudoaneurysm after a modified Blalock-Taussig shunt. We report a novel single-stage surgical management of the pseudoaneurysm with concomitant complete repair of tetralogy of Fallot.

Pseudoaneurysm is a potentially lethal complication after modified Blalock-Taussig shunt. This report describes a frequently misdiagnosed clinical presentation along with noninvasive diagnosis of pseudoaneurysm after a modified Blalock-Taussig shunt. We report a novel single-stage surgical management of the pseudoaneurysm with concomitant complete repair of tetralogy of Fallot.