Comparison of the Gene Expression Profiles from Normal and Fgfrl1 Deficient Mouse Kidneys Reveals Downstream Targets of Fgfrl1 Signaling

Fgfrl1 (fibroblast growth factor receptor-like 1) is a transmembrane receptor that is essential for the development of the metanephric kidney. It is expressed in all nascent nephrogenic structures and in the ureteric bud. Fgfrl1 null mice fail to develop the metanephric kidneys. Mutant kidney rudiments show a dramatic reduction of ureteric branching and a lack of mesenchymal-to-epithelial transition. Here, we compared the expression profiles of wildtype and Fgfrl1 mutant kidneys to identify genes that act downstream of Fgfrl1 signaling during the early steps of nephron formation. We detected 56 differentially expressed transcripts with 2-fold or greater reduction, among them many genes involved in Fgf, Wnt, Bmp, Notch, and Six/Eya/Dach signaling. We validated the microarray data by qPCR and whole-mount in situ hybridization and showed the expression pattern of candidate genes in normal kidneys. Some of these genes might play an important role during early nephron formation. Our study should help to define the minimal set of genes that is required to form a functional nephron

Clinicopathological significance of homeoprotein Six1 in hepatocellular carcinoma

Tumour recurrence and metastases of hepatocellular carcinoma (HCC) after hepatectomy are the major obstacles of long-term survival. The present study investigated the clinicopathological significance of a possible metastasis regulator Six1 in HCC patients who were undergone hepatectomy. Seventy-two pairs of RNA and 103 pairs of protein from tumour and adjacent nontumour liver tissues of HCC patients were examined. About 85 and 60% of HCC tumour tissues were found to overexpress Six1 mRNA and protein, respectively, compared with nontumour liver tissues. No Six1 protein was detected in HCC nontumour liver tissues and normal liver tissues. Increased Six1 protein expression in HCC patients was significantly correlated with pathologic tumour-node-metastasis (pTNM) stage (P=0.002), venous infiltration (P=0.004) and poor overall survival (P=0.0423). We concluded that Six1 is frequently overexpressed in HCC patients and elevated Six1 protein in HCC patients may be an indication of advanced stage and poor overall survival after hepatectomy

Epithelial-Mesenchymal Transition in Cancer: Parallels Between Normal Development and Tumor Progression

From the earliest stages of embryonic development, cells of epithelial and mesenchymal origin contribute to the structure and function of developing organs. However, these phenotypes are not always permanent, and instead, under the appropriate conditions, epithelial and mesenchymal cells convert between these two phenotypes. These processes, termed Epithelial-Mesenchymal Transition (EMT), or the reverse Mesenchymal-Epithelial Transition (MET), are required for complex body patterning and morphogenesis. In addition, epithelial plasticity and the acquisition of invasive properties without the full commitment to a mesenchymal phenotype are critical in development, particularly during branching morphogenesis in the mammary gland. Recent work in cancer has identified an analogous plasticity of cellular phenotypes whereby epithelial cancer cells acquire mesenchymal features that permit escape from the primary tumor. Because local invasion is thought to be a necessary first step in metastatic dissemination, EMT and epithelial plasticity are hypothesized to contribute to tumor progression. Similarities between developmental and oncogenic EMT have led to the identification of common contributing pathways, suggesting that the reactivation of developmental pathways in breast and other cancers contributes to tumor progression. For example, developmental EMT regulators including Snail/Slug, Twist, Six1, and Cripto, along with developmental signaling pathways including TGF-β and Wnt/β-catenin, are misexpressed in breast cancer and correlate with poor clinical outcomes. This review focuses on the parallels between epithelial plasticity/EMT in the mammary gland and other organs during development, and on a selection of developmental EMT regulators that are misexpressed specifically during breast cancer

The more we know, the more we have to discover: an exciting future for understanding cilia and ciliopathies

Contains fulltext : 154216.pdf (publisher's version ) (Open Access)The Cilia 2014 conference was organised by four European networks: the Ciliopathy Alliance, the Groupement de Recherche CIL, the Nordic Cilia and Centrosome Network and the EU FP7 programme SYSCILIA. More than 400 delegates from 27 countries gathered at the Institut Pasteur conference centre in Paris, including 30 patients and patient representatives. The meeting offered a unique opportunity for exchange between different scientific and medical communities. Major highlights included new discoveries about the roles of motile and immotile cilia during development and homeostasis, the mechanism of cilium construction, as well as progress in diagnosis and possible treatment of ciliopathies. The contributions to the cilia field of flagellated infectious eukaryotes and of systems biology were also presented

Primary cilia control telencephalic patterning and morphogenesis via Gli3 proteolytic processing

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Inseminate without hormonal treatment in dairy sheep farms: exploring the consequences on the sustainability of several contrasted production systems

International audienceAlternatives to hormonal treatments (HTs) in dairy sheep reproduction management are being explored in response to increasing societal concerns regarding animal welfare and food safety. However, hormonefree reproduction implies higher variability in flock performances and additional constraints for timely synchronised artificial insemination (AI) in the flock, impacting the diffusion of genetic progress. The use of the male effect, a well-known practice to induce synchronised oestrus, combined with precision tools (e.g., heat detector), is a plausible way to implement AI without HT in dairy sheep farms. To date, the consequences of such alternative reproduction management on the whole farm sustainability remain unknown. To anticipate these potential impacts, a multiagent model (REPRIN’OV) was used to simulate dairy sheep farms’ sustainability indicators (biotechnical, economic, environmental and workload). A reproduction management scenario, including the use of the male effect followed by AI on the adult ewes (HFAI), was simulated and compared to the current reproduction management of four case study farms (Early_conv, Late_conv, Early_org and Late_org). They were selected to represent the different agricultural models (Conventional or Organic) and reproduction seasons (Early during spring, out of ewes’ natural reproduction season or Late from early summer to the end of autumn) of the Roquefort Basin’s farms in Southern France. Simulation results showed that the HFAI scenario had different consequences depending on the farm’s production system type. A negative effect on most key sustainability indicators of the Conv farms was observed, as a significant reduction in the fertility rate, in the proportion of young ewes born from AI( 54%inbothfarms;P<0.05)and intheflock’s milk production were observed; while the workload and greenhouse gas (GHG) emissions were increased compared to the initial scenario. In the Org farms, HFAI had neutral to positive effects on most indicators as the fertility, milk production of the f lock, workload during milking and GHG emissions were barely affected by this scenario, while an increase in the proportion of young ewes born from AI was observed (+39% and + 43% in each farm, respectively; P < 0.05), allowing a better farm gross margin. Still, the workload during lambing was increased in Early_org (+18%; P < 0.05), as Early farms, tended to be more negatively impacted by HFAI than Late ones. Overall, our simulation approach provides interesting elements to exchange with stakeholders on how to progress towards a socially acceptable reproduction management system, for the dairy sheep sector

The effect of room temperature ionic liquids on the selective biocatalytic hydrolysis of chitin via sequential or simultaneous strategies

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