The Effects of Flooding on Shirakawa Delta Morphology

Floods can significantly alter the morphology of a delta, from inputting increased volumes of sediments to modifying the reach of incoming waves, currents, and other gravity-driven forces occurring within the near shore. Kumamoto experienced flooding in July 2012. This flood event altered the equilibrium profile of the intertidal flat area of the Shirakawa River. This research looks at these modifications and attempts to explain their long-term implications on the overall delta morphology. Data collected over a 30-year period was analyzed and profiles were generated to better analyze and assess the trend in delta morphological changes. Numerical predictions on delta morphology in the presence of gravitydriven sediment transport were applied to investigate the morphological changes related to the flood event. The slope of equilibrium profile is lower and steeper offshore, helping to explain the models created before and after the flood occurred

Flood Risk Management: An Illustrative Approach

Widespread flooding with significant damage in many countries, such as the Philippines in 2013, highlights the ongoing need for effective flood risk management (FRM). This hinges on comprehensive access to and dissemination of information about the elements and the people at risk. Simulations, real-time graphs, and maps illustrate the spatial distribution of flood risks, spatial allocation and dissemination of flood effects, if flood risk reduction measures are not implemented, as well as the benefits to be derived from the effective implementation and maintenance of flood risk management measures not realized. Using precipitation, river water, and tide levels, a real-time monitoring site was set up for the Shirakawa River, Kumamoto, Japan. The data gathered from the July 2012 flood event is used as a demonstrator, illustrating a flood event as well as how to utilize the information provided on this site to determine the future time and possibility of flooding. Additionally, an electronically generated flood hazard map making process is being developed for distribution across Japan. These illustrative approaches can be utilized in cities and communities around the globe

Stromal cell-derived factor 1 (SDF-1) and antenatal human B cell lymphopoiesis: Expression of SDF-1 by mesothelial cells and biliary ductal plate epithelial cells

The chemokine stromal cell-derived factor 1 (SDF-1) stimulates the growth of pre-B cells in vitro, and mice with a disrupted SDF-1 gene have abnormal fetal liver B cell lymphopoiesis. The origin of SDF-1 production has not been determined yet. Using an anti-SDF-1 mAb, we performed immunohistochemical studies in four human embryos and five fetuses to define which cells express the SDF-1 protein at sites of antenatal B cell lymphopoiesis. All mesothelial cells contained SDF-1 at all stages of development, including in the intraembryonic splanchnopleuric mesoderm early into gestation. In fetal lungs and kidneys, SDF-1 was expressed by epithelial cells, and a few B lymphoid precursors, expressing V pre-B chains, were also detected. In the fetal liver, in addition to mesothelial cells, biliary epithelial cells were the only cells to contain SDF-1. Pre-B cells expressing V chains were abundant and exclusively located around the edge of portal spaces, in close contact with biliary ductal plate epithelial cells. They did not colocalize with biliary collecting ducts. Biliary ductal plate epithelial cells and liver B cell lymphopoiesis display a parallel development and disappearance during fetal life. These results indicate that early B cell lymphopoiesis in the splanchnopleura may be triggered by mesothelial cells producing SDF-1. Later into gestation, biliary ductal plate epithelial cells may support B cell lymphopoiesis, thus playing a role similar to that of epithelial cells in the avian bursa of Fabricius, and of thymic epithelial cells for T cell lymphopoiesis

Protective effect of human amniotic fluid stem cells in an immunodeficient mouse model of acute tubular necrosis.

Acute Tubular Necrosis (ATN) causes severe damage to the kidney epithelial tubular cells and is often associated with severe renal dysfunction. Stem-cell based therapies may provide alternative approaches to treating of ATN. We have previously shown that clonal c-kit(pos) stem cells, derived from human amniotic fluid (hAFSC) can be induced to a renal fate in an ex-vivo system. Herein, we show for the first time the successful therapeutic application of hAFSC in a mouse model with glycerol-induced rhabdomyolysis and ATN. When injected into the damaged kidney, luciferase-labeled hAFSC can be tracked using bioluminescence. Moreover, we show that hAFSC provide a protective effect, ameliorating ATN in the acute injury phase as reflected by decreased creatinine and BUN blood levels and by a decrease in the number of damaged tubules and apoptosis therein, as well as by promoting proliferation of tubular epithelial cells. We show significant immunomodulatory effects of hAFSC, over the course of ATN. We therefore speculate that AFSC could represent a novel source of stem cells that may function to modulate the kidney immune milieu in renal failure caused by ATN

CXCR4/CXCL12 expression and signalling in kidney cancer

CXCL12 (SDF-1), a CXC-chemokine, and its specific receptor, CXCR4, have recently been shown to be involved in tumourgenesis, proliferation and angiogenesis. Therefore, we analysed CXCL12α/CXCR4 expression and function in four human kidney cancer cell lines (A-498, CAKI-1, CAKI-2, HA-7), 10 freshly harvested human tumour samples and corresponding normal kidney tissue. While none of the analysed tumour cell lines expressed CXCL12α, A-498 cells were found to express CXCR4. More importantly, real-time RT–PCR analysis of 10 tumour samples and respective adjacent normal kidney tissue disclosed a distinct and divergent downregulation of CXCL12α and upregulation of CXCR4 in primary tumour tissue. To prove that the CXCR4 protein is functionally active, rhCXCL12α was investigated for its ability to induce changes of intracellular calcium levels in A-498 cells. Moreover, we used cDNA expression arrays to evaluate the biological influence of CXCL12α. Comparing gene expression profiles in rhCXCL12α stimulated vs unstimulated A-498 kidney cancer cells revealed specific regulation of 31 out of 1176 genes tested on a selected human cancer array, with a prominent stimulation of genes involved in cell-cycle regulation and apoptosis. The genetic changes reported here should provide new insights into the developmental paths leading to tumour progression and may also aid the design of new approaches to therapeutic intervention

Simultaneous CXCL12 and ESR1 CpG island hypermethylation correlates with poor prognosis in sporadic breast cancer

<p>Abstract</p> <p>Background</p> <p>CXCL12 is a chemokine that is constitutively expressed in many organs and tissues. <it>CXCL12 </it>promoter hypermethylation has been detected in primary breast tumours and contributes to their metastatic potential. It has been shown that the oestrogen receptor α (<it>ESR1</it>) gene can also be silenced by DNA methylation. In this study, we used methylation-specific PCR (MSP) to analyse the methylation status in two regions of the <it>CXCL12 </it>promoter and <it>ESR1 </it>in tumour cell lines and in primary breast tumour samples, and correlated our results with clinicopathological data.</p> <p>Methods</p> <p>First, we analysed <it>CXCL12 </it>expression in breast tumour cell lines by RT-PCR. We also used 5-aza-2'-deoxycytidine (5-aza-CdR) treatment and DNA bisulphite sequencing to study the promoter methylation for a specific region of <it>CXCL12 </it>in breast tumour cell lines. We evaluated <it>CXCL12 </it>and <it>ESR1 </it>methylation in primary tumour samples by methylation-specific PCR (MSP). Finally, promoter hypermethylation of these genes was analysed using Fisher's exact test and correlated with clinicopathological data using the Chi square test, Kaplan-Meier survival analysis and Cox regression analysis.</p> <p>Results</p> <p><it>CXCL12 </it>promoter hypermethylation in the first region (island 2) and second region (island 4) was correlated with lack of expression of the gene in tumour cell lines. In the primary tumours, island 2 was hypermethylated in 14.5% of the samples and island 4 was hypermethylated in 54% of the samples. The <it>ESR1 </it>promoter was hypermethylated in 41% of breast tumour samples. In addition, the levels of ERα protein expression diminished with increased frequency of <it>ESR1 </it>methylation (p < 0.0001). This study also demonstrated that <it>CXCL12 </it>island 4 and <it>ESR1 </it>methylation occur simultaneously at a high frequency (p = 0.0220).</p> <p>Conclusions</p> <p>This is the first study showing a simultaneous involvement of epigenetic regulation for both <it>CXCL12 </it>and <it>ESR1 </it>genes in Brazilian women. The methylation status of both genes was significantly correlated with histologically advanced disease, the presence of metastases and death. Therefore, the methylation pattern of these genes could be used as a molecular marker for the prediction of breast cancer outcome.</p

The CXCL12γ Chemokine Displays Unprecedented Structural and Functional Properties that Make It a Paradigm of Chemoattractant Proteins

The CXCL12γ chemokine arises by alternative splicing from Cxcl12, an essential gene during development. This protein binds CXCR4 and displays an exceptional degree of conservation (99%) in mammals. CXCL12γ is formed by a protein core shared by all CXCL12 isoforms, extended by a highly cationic carboxy-terminal (C-ter) domain that encompass four overlapped BBXB heparan sulfate (HS)-binding motifs. We hypothesize that this unusual domain could critically determine the biological properties of CXCL12γ through its interaction to, and regulation by extracellular glycosaminoglycans (GAG) and HS in particular. By both RT-PCR and immunohistochemistry, we mapped the localization of CXCL12γ both in mouse and human tissues, where it showed discrete differential expression. As an unprecedented feature among chemokines, the secreted CXCL12γ strongly interacted with cell membrane GAG, thus remaining mostly adsorbed on the plasmatic membrane upon secretion. Affinity chromatography and surface plasmon resonance allowed us to determine for CXCL12γ one of the higher affinity for HS (Kd = 0.9 nM) ever reported for a protein. This property relies in the presence of four canonical HS-binding sites located at the C-ter domain but requires the collaboration of a HS-binding site located in the core of the protein. Interestingly, and despite reduced agonist potency on CXCR4, the sustained binding of CXCL12γ to HS enabled it to promote in vivo intraperitoneal leukocyte accumulation and angiogenesis in matrigel plugs with much higher efficiency than CXCL12α. In good agreement, mutant CXCL12γ chemokines selectively devoid of HS-binding capacity failed to promote in vivo significant cell recruitment. We conclude that CXCL12γ features unique structural and functional properties among chemokines which rely on the presence of a distinctive C-ter domain. The unsurpassed capacity to bind to HS on the extracellular matrix would make CXCL12γ the paradigm of haptotactic proteins, which regulate essential homeostatic functions by promoting directional migration and selective tissue homing of cells