Multiple-contrast X-ray micro-CT visualization of colon malformations and tumours in situ in living mice.

The development of new therapeutic approaches against colorectal cancer requires preclinical studies in mice. In vivo imaging could greatly facilitate these trials, but the small size of the animals is a major limitation for the direct visualization of intestinal tissue. Here we report a method of in vivo imaging of the mouse intestine based on X-ray micro-computed tomography using multiple contrast agents.

Sprouty2 inhibits BDNF-induced signaling and modulates neuronal differentiation and survival.

Sprouty (Spry) proteins are ligand-inducible inhibitors of receptor tyrosine kinases-dependent signaling pathways, which control various biological processes, including proliferation, differentiation and survival. Here, we investigated the regulation and the role of Spry2 in cells of the central nervous system (CNS). In primary cultures of immature neurons, the neurotrophic factor BDNF (brain-derived neurotrophic factor) regulates spry2 expression.

The intestine-specific homeobox gene Cdx2 decreases mobility and antagonizes dissemination of colon cancer cells.

The gravity of colorectal cancer is mainly due to the capacity of tumor cells to migrate out of the tumor mass to invade the stroma and disseminate as metastases. The acquisition of a migratory phenotype also occurs during wound healing. Here, we show that several features characterizing invasive colon tumor cells are shared by migrating cells during wound repair in vitro.

Different effects of the Cdx1 and Cdx2 homeobox genes in a murine model of intestinal inflammation.

Aims: The CDX1 and CDX2 homeoproteins are intestine-specific transcription factors regulating homeostasis. We investigated their relevance in experimentally-induced intestinal inflammation.

Methods: The response to intestinal inflammation induced by dextran sodium sulfate (DSS) was compared in wild type, Cdx1(-/-) and Cdx2(+/-) mice.

The human mucin MUC4 is transcriptionally regulated by caudal-related homeobox, hepatocyte nuclear factors, forkhead box A, and GATA endodermal transcription factors in epithelial cancer cells.

The human gene MUC4 encodes a large transmembrane mucin that is developmentally regulated and expressed along the undifferentiated pseudostratified epithelium, as early as 6.5 weeks during fetal development. Immunohistochemical analysis of Muc4 expression in developing mouse lung and gastrointestinal tract showed a different spatio-temporal pattern of expression before and after cytodifferentiation.

A cumulative shear mechanism for tissue damage initiation in shock-wave lithotripsy.

Evidence suggests that inertial cavitation plays an important role in the renal injury incurred during shock-wave lithotripsy. However, it is unclear how tissue damage is initiated, and significant injury typically occurs only after a sufficient dose of shock waves. Although it has been suggested that shock-induced shearing might initiate injury, estimates indicate that individual shocks do not produce sufficient shear to do so.

Precancerous lesions upon sporadic activation of beta-catenin in mice.

Background & Aims: Inappropriate activation of beta-catenin in adult tissues is associated with a wide variety of cancers, especially in the digestive tract. Classic transgenic and knockout murine models in which beta-catenin is activated in large fields of cells have provided experimental support in favor of a role for this molecule in tumorigenesis. However, these models do not reproduce the sporadic nature of the majority of human cancers, beginning with the activation of an oncogene at random in a single cell.

Response of fish and macroinvertebrate bioassessment indices to water chemistry in a mined Appalachian watershed.

Multimetric indices based on fish and benthic macroinvertebrate assemblages are commonly used to assess the biological integrity of aquatic ecosystems. However, their response to specific stressors is rarely known. We quantified the response of a fish-based index (Mid-Atlantic Highlands Index of Biotic Integrity, MAH-IBI) and a benthic invertebrate-based index (West Virginia Stream Condition Index, WV-SCI) to acid mine drainage (AMD)-related stressors in 46 stream sites within the Cheat River watershed, West Virginia.

Identification and characterization of human Mex-3 proteins, a novel family of evolutionarily conserved RNA-binding proteins differentially localized to processing bodies.

In Caenorhabditis elegans, the Mex-3 protein is a translational regulator that specifies the posterior blastomere identity in the early embryo and contributes to the maintenance of the germline totipotency. We have now identified a family of four homologous human Mex-3 genes, called hMex-3A to -3D that encode proteins containing two heterogeneous nuclear ribonucleoprotein K homology (KH) domains and one carboxy-terminal RING finger module. The hMex-3 are phosphoproteins that bind RNA through their KH domains and shuttle between the nucleus and the cytoplasm via the CRM1-dependent export pathway.

The microenvironment controls CDX2 homeobox gene expression in colorectal cancer cells.

The homeobox gene CDX2 plays a major role in development, especially in the gut, and it also acts as a tumor suppressor in the adult colon. Using orthotopic and heterotopic xenografts of human primary colorectal tumor cells and cell lines in nude mice, we addressed the effect of the microenvironment on CDX2 expression. In cells expressing CDX2 at a high level in culture, this level was maintained in subcutaneous grafts but was reduced when implanted into the cecum wall.

Functional interaction between the homeoprotein CDX1 and the transcriptional machinery containing the TATA-binding protein.

We have previously reported that the CDX1 homeoprotein interacts with the TATA-box binding protein (TBP) on the promoter of the glucose-6-phosphatase (G6Pase) gene. We show here that CDX1 interacts with TBP via the homeodomain and that the transcriptional activity additionally requires the N-terminal domain upstream of the homeodomain. CDX1 interacting with TBP is connected to members of the TFIID and Mediator complexes, two major elements of the general transcriptional machinery.

Profound thrombocytopenia related to G-CSF.

Severe thrombocytopenia in association with G-CSF therapy is extremely rare. Here we report a case of profound thrombocytopenia in a 57-year-old male with refractory cardiac ischemia, who received G-CSF during an angiogenesis trial. After 5 days of G-CSF therapy (10 microg/kg/day) the platelet count fell progressively to a nadir of 5x10(9)/L.

Health-e-child: an integrated biomedical platform for grid-based paediatric applications.

There is a compelling demand for the integration and exploitation of heterogeneous biomedical information for improved clinical practice, medical research, and personalised healthcare across the EU. The Health-e-Child project aims at developing an integrated healthcare platform for European Paediatrics, providing seamless integration of traditional and emerging sources of biomedical information. The long-term goal of the project is to provide uninhibited access to universal biomedical knowledge repositories for personalised and preventive healthcare, large-scale information-based biomedical research and training, and informed policy making.

Frequent rearrangements and amplification of the CDX2 homeobox gene in human sporadic colorectal cancers with chromosomal instability.

The expression of the CDX2 gene, a crucial regulator of gut homeostasis, is altered in human colorectal cancers in parallel with de-differentiation. Here, we have investigated the chromosomal status of CDX2 in human sporadic colorectal cancers with the phenotype of chromosomal instability. Allelic imbalance determination showed frequent rearrangements at the CDX2 locus.

Bile acids induce ectopic expression of intestinal guanylyl cyclase C Through nuclear factor-kappaB and Cdx2 in human esophageal cells.

Background & Aims: Although progression to adenocarcinoma at the gastroesophageal junction reflects exposure to acid and bile acids associated with reflux, mechanisms mediating this transformation remain undefined. Guanylyl cyclase C (GC-C), an intestine-specific tumor suppressor, may represent a mechanism-based marker and target of transformation at the gastroesophageal junction. The present studies examine the expression of GC-C in normal tissues and tumors from esophagus and stomach and mechanisms regulating its expression by acid and bile acids.

CDX-2 homeobox gene expression in human gastric carcinoma and precursor lesions.

Background: Recent studies have demonstrated that CDX-2 is expressed in the intestinal metaplasia of the stomach and intestinal-type gastric cancer. To address the role of CDX-2 in carcinogenesis of gastric carcinomas of intestinal type, the expression of CDX-2 in gastric carcinoma and precursor lesions were examined using immunohistochemistry.

Methods: A total of 160 specimens diagnosed as gastric carcinomas or non-invasive neoplasia from 158 patients were analyzed for CDX-2 expression by immunochemical methods.

The effect of LVAD aortic outflow-graft placement on hemodynamics and flow: Implantation technique and computer flow modeling.

Axial-flow ventricular assist devices (VADs) can be implanted either through a left thoracotomy with outflow-graft anastomosis to the descending thoracic aorta or through a midline sternotomy with anastomosis to the ascending aorta. Each method has advantages and disadvantages. Because these VADs produce nonpulsatile flow, their hemodynamic characteristics differ from those of pulsatile devices.

Genome-wide transcriptional analysis of carboplatin response in chemosensitive and chemoresistant ovarian cancer cells.

We have recently described an ex vivo chemoresponse assay for determining chemosensitivity in primary cultures of human tumors. In this study, we have extended these experiments in an effort to correlate chemoresponse data with gene expression patterns at the level of transcription. Primary cultures of cells derived from ovarian carcinomas of individual patients (n=6) were characterized using the ChemoFx assay and classified as either carboplatin sensitive (n=3) or resistant (n=3).

Phosphorylation of the homeotic tumor suppressor Cdx2 mediates its ubiquitin-dependent proteasome degradation.

The Caudal-related homeodomain transcription factor Cdx2 plays a key role in intestinal cell fate determination. Reduction of Cdx2 expression is a feature of many human colon carcinomas and inactivation of one cdx2 allele facilitates the development of invasive adenocarcinoma in the murine colon. Here, we investigated the post-translational regulation of Cdx2.

Information processing in noisy burster models of sensory neurons.

Processing of external stimuli by sensory neurons often involves bursting, when epochs of fast firing alternate with intervals of quiescence. In particular, sensory neurons of electroreceptors in paddlefish (Polyodon spathula) undergo bursting when stimulated externally with broad-band noise, but otherwise fire spontaneously in a quasiperiodic tonic manner. We use a simple phenomenological model for noise-induced bursting to quantify analytically, by means of the Kullback entropy and Fisher information, the gain in information transfer and electroreceptor sensitivity for external noisy stimuli.

Laminin isoforms: biological roles and effects on the intracellular distribution of nuclear proteins in intestinal epithelial cells.

Laminins are structurally and functionally major components of the extracellular matrix. Four isoforms of laminins (laminin-1, -2, -5 and -10) are expressed in a specific pattern along the crypt-villus axis of the intestine. Previous works indicated that expression of these isoforms is developmentally regulated and that laminins could modulate the behaviour of intestinal cells, but the exact role of each isoform remained unclear.

Evaluation of methods for storage of marine macroorganisms with optimal recovery of bacteria.

Marine macroorganisms are a potential source for new bioactive substances. In many cases marine microorganisms--especially bacteria--associated with these macroorganisms are actually producing the bioactive substances. One often is not able to immediately isolate microorganisms from collected macroorganismic materials; we therefore evaluated different methods for storage of such material, e.

Down-regulation of the homeodomain factor Cdx2 in colorectal cancer by collagen type I: an active role for the tumor environment in malignant tumor progression.

The homeobox transcription factor Cdx2 specifies intestinal development and homeostasis and is considered a tumor suppressor in colorectal carcinogenesis. However, Cdx2 mutations are rarely found. Invasion of colorectal cancer is characterized by a transient loss of differentiation and nuclear accumulation of the oncoprotein beta-catenin in budding tumor cells.

SOX9 is an intestine crypt transcription factor, is regulated by the Wnt pathway, and represses the CDX2 and MUC2 genes.

TCF and SOX proteins belong to the high mobility group box transcription factor family. Whereas TCFs, the transcriptional effectors of the Wnt pathway, have been widely implicated in the development, homeostasis and disease of the intestine epithelium, little is known about the function of the SOX proteins in this tissue. Here, we identified SOX9 in a SOX expression screening in the mouse fetal intestine.

Control of differentiation-induced calbindin-D9k gene expression in Caco-2 cells by cdx-2 and HNF-1alpha.

Calbindin D9k (CaBP) is critical for intestinal calcium absorption; its in vivo expression is restricted to differentiated enterocytes of the small intestine. Our goal was to identify factors controlling the transcriptional regulation of this gene in the human intestine. Both the natural gene and a 4600-bp promoter construct were strongly regulated by differentiation (>100-fold) but not by treatment with 1,25(OH)2 vitamin D (<2-fold) in the Caco-2 clone TC7.