Hepatobiliary and pancreatic imaging in children—techniques and an overview of non-neoplastic disease entities

Imaging plays a major role in the diagnostic work-up of children with hepatobiliary or pancreatic diseases. It consists mainly of US, CT and MRI, with US and MRI being the preferred imaging modalities because of the lack of ionizing radiation. In this review the technique of US, CT and MRI in children will be addressed, followed by a comprehensive overview of the imaging characteristics of several hepatobiliary and pancreatic disease entities most common in the paediatric age group

AtHKT1;1 Mediates Nernstian Sodium Channel Transport Properties in Arabidopsis Root Stelar Cells

The Arabidopsis AtHKT1;1 protein was identified as a sodium (Na+) transporter by heterologous expression in Xenopus laevis oocytes and Saccharomyces cerevisiae. However, direct comparative in vivo electrophysiological analyses of a plant HKT transporter in wild-type and hkt loss-of-function mutants has not yet been reported and it has been recently argued that heterologous expression systems may alter properties of plant transporters, including HKT transporters. In this report, we analyze several key functions of AtHKT1;1-mediated ion currents in their native root stelar cells, including Na+ and K+ conductances, AtHKT1;1-mediated outward currents, and shifts in reversal potentials in the presence of defined intracellular and extracellular salt concentrations. Enhancer trap Arabidopsis plants with GFP-labeled root stelar cells were used to investigate AtHKT1;1-dependent ion transport properties using patch clamp electrophysiology in wild-type and athkt1;1 mutant plants. AtHKT1;1-dependent currents were carried by sodium ions and these currents were not observed in athkt1;1 mutant stelar cells. However, K+ currents in wild-type and athkt1;1 root stelar cell protoplasts were indistinguishable correlating with the Na+ over K+ selectivity of AtHKT1;1-mediated transport. Moreover, AtHKT1;1-mediated currents did not show a strong voltage dependence in vivo. Unexpectedly, removal of extracellular Na+ caused a reduction in AtHKT1;1-mediated outward currents in Columbia root stelar cells and Xenopus oocytes, indicating a role for external Na+ in regulation of AtHKT1;1 activity. Shifting the NaCl gradient in root stelar cells showed a Nernstian shift in the reversal potential providing biophysical evidence for the model that AtHKT1;1 mediates passive Na+ channel transport properties

SOX2 is frequently downregulated in gastric cancers and inhibits cell growth through cell-cycle arrest and apoptosis

SOX transcription factors are essential for embryonic development and play critical roles in cell fate determination, differentiation and proliferation. We previously reported that the SOX2 protein is expressed in normal gastric mucosae but downregulated in some human gastric carcinomas. To clarify the roles of SOX2 in gastric carcinogenesis, we carried out functional characterisation of SOX2 in gastric epithelial cell lines. Exogenous expression of SOX2 suppressed cell proliferation in gastric epithelial cell lines. Flow cytometry analysis revealed that SOX2-overexpressing cells exhibited cell-cycle arrest and apoptosis. We found that SOX2-mediated cell-cycle arrest was associated with decreased levels of cyclin D1 and phosphorylated Rb, and an increased p27Kip1 level. These cells exhibited further characteristics of apoptosis, such as DNA laddering and caspase-3 activation. SOX2 hypermethylation signals were observed in some cultured and primary gastric cancers with no or weak SOX2 expression. Among the 52 patients with advanced gastric cancers, those with cancers showing SOX2 methylation had a significantly shorter survival time than those without this methylation (P=0.0062). Hence, SOX2 plays important roles in growth inhibition through cell-cycle arrest and apoptosis in gastric epithelial cells, and the loss of SOX2 expression may be related to gastric carcinogenesis and poor prognosis

The SOX2 response program in glioblastoma multiforme: an integrated ChIP-seq, expression microarray, and microRNA analysis

<p>Abstract</p> <p>Background</p> <p><it>SOX2 </it>is a key gene implicated in maintaining the stemness of embryonic and adult stem cells. <it>SOX2 </it>appears to re-activate in several human cancers including glioblastoma multiforme (GBM), however, the detailed response program of <it>SOX2 </it>in GBM has not yet been defined.</p> <p>Results</p> <p>We show that knockdown of the <it>SOX2 </it>gene in LN229 GBM cells reduces cell proliferation and colony formation. We then comprehensively characterize the <it>SOX2 </it>response program by an integrated analysis using several advanced genomic technologies including ChIP-seq, microarray profiling, and microRNA sequencing. Using ChIP-seq technology, we identified 4883 <it>SOX2 </it>binding regions in the GBM cancer genome. <it>SOX2 </it>binding regions contain the consensus sequence wwTGnwTw that occurred 3931 instances in 2312 <it>SOX2 </it>binding regions. Microarray analysis identified 489 genes whose expression altered in response to <it>SOX2 </it>knockdown. Interesting findings include that <it>SOX2 </it>regulates the expression of SOX family proteins <it>SOX1 </it>and <it>SOX18</it>, and that <it>SOX2 </it>down regulates <it>BEX1 </it>(brain expressed X-linked 1) and <it>BEX2 </it>(brain expressed X-linked 2), two genes with tumor suppressor activity in GBM. Using next generation sequencing, we identified 105 precursor microRNAs (corresponding to 95 mature miRNAs) regulated by <it>SOX2</it>, including down regulation of miR-143, -145, -253-5p and miR-452. We also show that miR-145 and <it>SOX2 </it>form a double negative feedback loop in GBM cells, potentially creating a bistable system in GBM cells.</p> <p>Conclusions</p> <p>We present an integrated dataset of ChIP-seq, expression microarrays and microRNA sequencing representing the <it>SOX2 </it>response program in LN229 GBM cells. The insights gained from our integrated analysis further our understanding of the potential actions of <it>SOX2 </it>in carcinogenesis and serves as a useful resource for the research community.</p

Deciphering the stem cell machinery as a basis for understanding the molecular mechanism underlying reprogramming

Stem cells provide fascinating prospects for biomedical applications by combining the ability to renew themselves and to differentiate into specialized cell types. Since the first isolation of embryonic stem (ES) cells about 30 years ago, there has been a series of groundbreaking discoveries that have the potential to revolutionize modern life science. For a long time, embryos or germ cell-derived cells were thought to be the only source of pluripotency—a dogma that has been challenged during the last decade. Several findings revealed that cell differentiation from (stem) cells to mature cells is not in fact an irreversible process. The molecular mechanism underlying cellular reprogramming is poorly understood thus far. Identifying how pluripotency maintenance takes place in ES cells can help us to understand how pluripotency induction is regulated. Here, we review recent advances in the field of stem cell regulation focusing on key transcription factors and their functional interplay with non-coding RNAs

Pseudoneoplastic lesions of the testis and paratesticular structures

Pseudotumors or tumor-like proliferations (non-neoplastic masses) and benign mimickers (non-neoplastic cellular proliferations) are rare in the testis and paratesticular structures. Clinically, these lesions (cysts, ectopic tissues, and vascular, inflammatory, or hyperplastic lesions) are of great interest for the reason that, because of the topography, they may be relevant as differential diagnoses. The purpose of this paper is to present an overview of the pseudoneoplasic entities arising in the testis and paratesticular structures; emphasis is placed on how the practicing pathologist may distinguish benign mimickers and pseudotumors from true neoplasia. These lesions can be classified as macroscopic or microscopic mimickers of neoplasia