Compositions, Methods And Kits Relating To Remodel

The invention relates to novel nucleic acids encoding a mammalian adventitia inducible and bone expressed gene designated REMODEL, and proteins encoded thereby, whose expression is increased in certain diseases, disorders, or conditions, including, but not limited to, negative remodeling, arterial restenosis, vessel injury, ectopic ossification, fibrosis, and the like. REMODEL also plays a role in cell-cell and cell-matrix adhesion, bone density, bone formation, dorsal closure, and is associated with spina bifida-like phenotype. The invention further relates to methods of treating and detecting these diseases, disorders or conditions, comprising modulating or detecting REMODEL expression and/or production of REMODEL polypeptide

PhyNetLab: An IoT-Based Warehouse Testbed

Future warehouses will be made of modular embedded entities with communication ability and energy aware operation attached to the traditional materials handling and warehousing objects. This advancement is mainly to fulfill the flexibility and scalability needs of the emerging warehouses. However, it leads to a new layer of complexity during development and evaluation of such systems due to the multidisciplinarity in logistics, embedded systems, and wireless communications. Although each discipline provides theoretical approaches and simulations for these tasks, many issues are often discovered in a real deployment of the full system. In this paper we introduce PhyNetLab as a real scale warehouse testbed made of cyber physical objects (PhyNodes) developed for this type of application. The presented platform provides a possibility to check the industrial requirement of an IoT-based warehouse in addition to the typical wireless sensor networks tests. We describe the hardware and software components of the nodes in addition to the overall structure of the testbed. Finally, we will demonstrate the advantages of the testbed by evaluating the performance of the ETSI compliant radio channel access procedure for an IoT warehouse

Suppression of Spry4 enhances cancer stem cell properties of human MDA-MB-231 breast carcinoma cells

BACKGROUND: Cancer stem cells contribute to tumor initiation, heterogeneity, and recurrence, and are critical targets in cancer therapy. Sprouty4 (Spry4) is a potent inhibitor of signal transduction pathways elicited by receptor tyrosine kinases, and has roles in regulating cell proliferation, migration and differentiation. Spry4 has been implicated as a tumor suppressor and in modulating embryonic stem cells. OBJECTIVES: The purpose of this research was to test the novel idea that Spry4 regulates cancer stem cell properties in breast cancer. METHODS: Loss-of function of Spry4 in human MDA-MB-231 cell was used to test our hypothesis. Spry4 knockdown or control cell lines were generated using lentiviral delivery of human Spry4 or non-targeting control shRNAs, and then selected with 2 μg/ml puromycin. Cell growth and migratory abilities were determined using growth curve and cell cycle flow cytometry analyses and scratch assays, respectively. Xenograft tumor model was used to determine the tumorigenic activity and metastasis in vivo. Cancer stem cell related markers were evaluated using immunoblotting assays and fluorescence-activated cell sorting. Cancer stem cell phenotype was evaluated using in vitro mammosphere formation and drug sensitivity tests, and in vivo limiting dilution tumor formation assay. RESULTS: Two out of three tested human Spry4 shRNAs significantly suppressed the expression of endogenous Spry4 in MDA-MB-231 cells. Suppressing Spry4 expression increased MDA-MB-231 cell proliferation and migration. Suppressing Spry4 increased β3-integrin expression, and CD133(+)CD44(+) subpopulation. Suppressing Spry4 increased mammosphere formation, while decreasing the sensitivity of MDA-MB-231 cells to Paclitaxel treatment. Finally, suppressing Spry4 increased the potency of MDA-MB-231 cell tumor initiation, a feature attributed to cancer stem cells. CONCLUSIONS: Our findings provide novel evidence that endogenous Spry4 may have tumor suppressive activity in breast cancer by suppressing cancer stem cell properties in addition to negative effects on tumor cell proliferation and migration

Conditional expression of Spry1 in neural crest causes craniofacial and cardiac defects

<p>Abstract</p> <p>Background</p> <p>Growth factors and their receptors are mediators of organogenesis and must be tightly regulated in a temporal and spatial manner for proper tissue morphogenesis. Intracellular regulators of growth factor signaling pathways provide an additional level of control. Members of the Sprouty family negatively regulate receptor tyrosine kinase pathways in several developmental contexts. To gain insight into the role of Spry1 in neural crest development, we analyzed the developmental effects of conditional expression of Spry1 in neural crest-derived tissues.</p> <p>Results</p> <p>Here we report that conditional expression of Spry1 in neural crest cells causes defects in craniofacial and cardiac development in mice. <it>Spry1;Wnt1-Cre </it>embryos die perinatally and exhibit facial clefting, cleft palate, cardiac and cranial nerve defects. These defects appear to be the result of decreased proliferation and increased apoptosis of neural crest and neural crest-derived cell populations. In addition, the domains of expression of several key transcription factors important to normal craniofacial and cardiac development including <it>AP2</it>, <it>Msx2</it>, <it>Dlx5</it>, and <it>Dlx6 </it>were reduced in <it>Spry1;Wnt1-Cre </it>transgenic embryos.</p> <p>Conclusion</p> <p>Collectively, these data suggest that Spry1 is an important regulator of craniofacial and cardiac morphogenesis and perturbations in Spry1 levels may contribute to congenital disorders involving tissues of neural crest origin.</p

Establishing Research Competitiveness in Biophysical Sciences in Maine

The Maine EPSCoR Research Infrastructure Improvement award is designed to enhance Maine\u27s competitiveness in molecular biophysical sciences through a partnership between the University of Maine and Maine\u27s non-profit research organizations. The proposed Biophysical Sciences Institute brings together University of Maine faculty in physics, chemistry, biology, mathematics, and spatial engineering, with biomedical researchers at the Jackson Laboratory and Maine Medical Center Research Institute. Maine EPSCoR proposes to hire additional tenure-track faculty in the fields of biophysics and advanced optics, biochemistry, structural biology, applied mathematics, computer science, image analysis and visualization, and material science. The new and existing investigators will form research teams to develop new measurement techniques, new sensors, and innovative approaches to data processing and interpretation in intracellular structures and dynamics, functional materials as a means to manipulate cellular reactions, and biocomputing. In addition to establishing the institute, Maine EPSCoR will integrate research and education through improvements to graduate training

Two novel human NUMB isoforms provide a potential link between development and cancer

We previously identified four functionally distinct human NUMB isoforms. Here, we report the identification of two additional isoforms and propose a link between the expression of these isoforms and cancer. These novel isoforms, NUMB5 and NUMB6, lack exon 10 and are expressed in cells known for polarity and migratory behavior, such as human amniotic fluid cells, glioblastoma and metastatic tumor cells. RT-PCR and luciferase assays demonstrate that NUMB5 and NUMB6 are less antagonistic to NOTCH signaling than other NUMB isoforms. Immunocytochemistry analyses show that NUMB5 and NUMB6 interact and complex with CDC42, vimentin and the CDC42 regulator IQGAP1 (IQ (motif) GTPase activating protein 1). Furthermore, the ectopic expression of NUMB5 and NUMB6 induces the formation of lamellipodia (NUMB5) and filopodia (NUMB6) in a CDC42- and RAC1-dependent manner. These results are complemented by in vitro and in vivo studies, demonstrating that NUMB5 and NUMB6 alter the migratory behavior of cells. Together, these novel isoforms may play a role in further understanding the NUMB function in development and cancer

Spry1 Is Expressed in Hemangioblasts and Negatively Regulates Primitive Hematopoiesis and Endothelial Cell Function

Development of the hematopoietic and endothelial lineages derives from a common mesodermal precursor, the Flk1(+) hemangioblast. However, the signaling pathways that regulate the development of hematopoietic and endothelial cells from this common progenitor cell remains incompletely understood. Using mouse models with a conditional Spry1 transgene, and a Spry1 knockout mouse, we investigated the role of Spry1 in the development of the endothelial and hematopoietic lineages during development.Quantitative RT-PCR analysis demonstrates that Spry1, Spry2, and Spry4 are expressed in Flk1(+) hemangioblasts in vivo, and decline significantly in c-Kit(+) and CD41(+) hematopoietic progenitors, while expression is maintained in developing endothelial cells. Tie2-Cre-mediated over-expression of Spry1 results in embryonic lethality. At E9.5 Spry1;Tie2-Cre embryos show near normal endothelial cell development and vessel patterning but have reduced hematopoiesis. FACS analysis shows a reduction of primitive hematopoietic progenitors and erythroblastic cells in Spry1;Tie2-Cre embryos compared to controls. Colony forming assays confirm the hematopoietic defects in Spry1;Tie2-Cre transgenic embryos. Immunostaining shows a significant reduction of CD41 or CD71 and dpERK co-stained cells in Spry1;Tie2-Cre embryos compared to controls, whereas the number of VEC(+) and dpERK co-stained cells is comparable. Compared to controls, Spry1;Tie2-Cre embryos also show a decrease in proliferation and an increase in apoptosis. Furthermore, loss of Spry1 results in an increase of CD41(+) and CD71(+) cells at E9.5 compared with controls.These data indicate that primitive hematopoietic cells derive from Tie2-expressing hemangioblasts and that Spry1 over expression inhibits primitive hematopoietic progenitor and erythroblastic cell development and expansion while having no obvious effect on endothelial cell development

Loss of Spry1 in vascular smooth muscle cells promotes hypercholesterolemiainduced VSMC phenotypic transitions and regulates atherogenesis

Atherosclerosis is an inflammatory disease characterized by arterial wall thickening and plaque accumulation, and is a major cause of death worldwide. Vascular smooth muscle cells (VSMC), which have the unique ability to transition from mature contractile cells to myofibroblasts and macrophagelike foam cells, and adopt a proinflammatory state contribute to atherogenic microenvironment (1). We aimed to investigate how Spry1, a regulator of receptor tyrosine kinase signaling, affects hypercholesterolemia induced plaque formation in mice by manipulating Spry1 expression specifically in VSMC