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https://www.readbyqxmd.com/read/28434841/transcriptional-dependencies-in-diffuse-intrinsic-pontine-glioma
#1
Surya Nagaraja, Nicholas A Vitanza, Pamelyn J Woo, Kathryn R Taylor, Fang Liu, Lei Zhang, Meng Li, Wei Meng, Anitha Ponnuswami, Wenchao Sun, Jie Ma, Esther Hulleman, Tomek Swigut, Joanna Wysocka, Yujie Tang, Michelle Monje
Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric cancer with limited therapeutic options. The majority of cases of DIPG exhibit a mutation in histone-3 (H3K27M) that results in oncogenic transcriptional aberrancies. We show here that DIPG is vulnerable to transcriptional disruption using bromodomain inhibition or CDK7 blockade. Targeting oncogenic transcription through either of these methods synergizes with HDAC inhibition, and DIPG cells resistant to HDAC inhibitor therapy retain sensitivity to CDK7 blockade...
April 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28421649/decreased-expression-of-epha5-is-associated-with-fuhrman-nuclear-grade-and-pathological-tumour-stage-in-ccrcc
#2
Xiaolin Wang, Haifei Xu, Zhijun Wu, Xiao Chen, Jiandong Wang
The incidence of renal cell carcinoma is increasing all over the world. The molecular mechanisms for tumorigenesis, progression and prognosis are still unknown. The erythropoietin-producing hepatoma amplified sequence (Eph) receptors have been reported to be expressed aberrantly in many types of human cancers and in particular EphA5 may play a role in certain human cancers. In this study, a set of clear cell renal cell carcinoma (ccRCC) tissues were subjected to immunohistochemistry. The relationship between EphA5 protein expression and clinicopathological parameters was statistically analysed...
April 19, 2017: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/28370426/intramembranous-processing-by-%C3%AE-secretase-regulates-reverse-signaling-of-ephrin-b2-in-migration-of-microglia
#3
Nadja Kemmerling, Patrick Wunderlich, Sandra Theil, Bettina Linnartz-Gerlach, Nils Hersch, Bernd Hoffmann, Michael T Heneka, Bart de Strooper, Harald Neumann, Jochen Walter
The Eph-ephrin system plays pivotal roles in cell adhesion and migration. The receptor-like functions of the ephrin ligands allow the regulation of intracellular processes via reverse signaling. γ-Secretase mediated processing of ephrin-B has previously been linked to activation of Src, a kinase crucial for focal adhesion and podosome phosphorylation. Here, we analyzed the role of γ-secretase in the stimulation of reverse ephrin-B2 signaling in the migration of mouse embryonic stem cell derived microglia...
April 3, 2017: Glia
https://www.readbyqxmd.com/read/28368503/contribution-of-endothelial-to-mesenchymal-transition-to-the-pathogenesis-of-human-cerebral-and-orbital-cavernous-malformations
#4
Shigeki Takada, Masato Hojo, Kenji Tanigaki, Susumu Miyamoto
BACKGROUND: The analysis of gene-targeted mouse mutants has demonstrated that endothelial-to-mesenchymal transition (EndMT) is crucial to the onset and progression of cerebral cavernous malformations (CMs). It has also been shown that Notch and ephrin/Eph signaling are involved in EndMT. However, their roles in the pathogenesis of human intracranial CMs remain unclear. OBJECTIVE: To elucidate the contribution of EndMT, the Notch pathway, and ephrin-B2/EphB4 signaling to the pathogenesis of human intracranial CMs...
March 28, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28366281/neurexin-restricts-axonal-branching-in-columns-by-promoting-ephrin-clustering
#5
Lina Liu, Yao Tian, Xiao-Yan Zhang, Xinwang Zhang, Tao Li, Wei Xie, Junhai Han
Columnar restriction of neurites is critical for forming nonoverlapping receptive fields and preserving spatial sensory information from the periphery in both vertebrate and invertebrate nervous systems, but the underlying molecular mechanisms remain largely unknown. Here, we demonstrate that Drosophila homolog of α-neurexin (DNrx) plays an essential role in columnar restriction during L4 axon branching. Depletion of DNrx from L4 neurons resulted in misprojection of L4 axonal branches into neighboring columns due to impaired ephrin clustering...
April 10, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28360821/combined-ephb2-receptor-knockdown-with-radiation-decreases-cell-viability-and-invasion-in-medulloblastoma
#6
Shilpa Bhatia, Kellen Hirsch, Sanjana Bukkapatnam, Nimrah A Baig, Ayman Oweida, Anastacia Griego, Dylan Calame, Jaspreet Sharma, Andrew Donson, Nicholas Foreman, Christopher Albanese, Sujatha Venkataraman, Rajeev Vibhakar, Sana D Karam
BACKGROUND: Medulloblastoma is one of the most common types of pediatric brain tumor characterized by the subpopulation of cells that exhibit high invasive potential and radioresistant properties. In addition, dysregulated function and signaling by Eph family of receptors have been shown to impart pro-tumorigenic characteristics in this brain malignancy. In the current study, we investigated whether EphB2 knockdown in combination with radiation can alter invasiveness and decrease medulloblastoma tumor growth or viability in vitro...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28351297/epha4-promotes-cell-proliferation-and-cell-adhesion-mediated-drug-resistance-via-the-akt-pathway-in-multiple-myeloma
#7
Linlin Ding, Yaodong Shen, Jing Ni, Yiqing Ou, Yangyu Ou, Hong Liu
Eph receptor A4 (EphA4), a member of the erythropoietin-producing hepatocellular (Eph) family, has been reported to upregulate in several tumors. However, the role of EphA4 in multiple myeloma has not been clarified yet. In this study, we found that EphA4 promoted proliferation of multiple myeloma cells via the regulation of cell cycle. Besides, EphA4 was closely related to cell adhesion of multiple myeloma cells and promoted cell adhesion-mediated drug resistance by enhancing the phosphorylation levels of Akt (p-AKT) expression in multiple myeloma...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28346224/mutant-%C3%AE-2-chimaerin-signals-via-bidirectional-ephrin-pathways-in-duane-retraction-syndrome
#8
Alicia A Nugent, Jong G Park, Yan Wei, Alan P Tenney, Nicole M Gilette, Michelle M DeLisle, Wai-Man Chan, Long Cheng, Elizabeth C Engle
Duane retraction syndrome (DRS) is the most common form of congenital paralytic strabismus in humans and can result from α2-chimaerin (CHN1) missense mutations. We report a knockin α2-chimaerin mouse (Chn1KI/KI) that models DRS. Whole embryo imaging of Chn1KI/KI mice revealed stalled abducens nerve growth and selective trochlear and first cervical spinal nerve guidance abnormalities. Stalled abducens nerve bundles did not reach the orbit, resulting in secondary aberrant misinnervation of the lateral rectus muscle by the oculomotor nerve...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28341121/activation-of-epha1-epha-receptor-axis-attenuates-diabetic-nephropathy-in-mice
#9
Yihui Li, Hongdan Yan, Feng Wang, Shanying Huang, Yun Zhang, Zhihao Wang, Ming Zhong, Wei Zhang
The Eph family of receptor tyrosine kinases serves as key modulators of various cellular functions, including inflammation, hypertrophy and fibrosis. Recent analyses have revealed that a member of the Eph family, EphA1, plays a pivotal role in regulating insulin metabolism and kidney injury. However, the importance of EphA1 in diabetic nephropathy has not been recognized. We established a diabetic nephropathy mouse model using a high-fat diet and streptozotocin (STZ) injection. Then, the recombinant adeno-associated virus type 9 (AAV9) overexpressing EphA1 or a negative control was injected locally into the kidney...
March 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28338017/a-role-of-the-sam-domain-in-epha2-receptor-activation
#10
Xiaojun Shi, Vera Hapiak, Ji Zheng, Jeannine Muller-Greven, Deanna Bowman, Ryan Lingerak, Matthias Buck, Bing-Cheng Wang, Adam W Smith
Among the 20 subfamilies of protein receptor tyrosine kinases (RTKs), Eph receptors are unique in possessing a sterile alpha motif (SAM domain) at their C-terminal ends. However, the functions of SAM domains in Eph receptors remain elusive. Here we report on a combined cell biology and quantitative fluorescence study to investigate the role of the SAM domain in EphA2 function. We observed elevated tyrosine autophosphorylation levels upon deletion of the EphA2 SAM domain (EphA2ΔS) in DU145 and PC3 prostate cancer cells and a skin tumor cell line derived from EphA1/A2 knockout mice...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28322822/asymmetry-at-cell-cell-interfaces-direct-cell-sorting-boundary-formation-and-tissue-morphogenesis
#11
REVIEW
Rosa Ventrella, Nihal Kaplan, Spiro Getsios
During development, cells of seemingly homogenous character sort themselves out into distinct compartments in order to generate cell types with specialized features that support tissue morphogenesis and function. This process is often driven by receptors at the cell membrane that probe the extracellular microenvironment for specific ligands and alter downstream signaling pathways impacting transcription, cytoskeletal organization, and cell adhesion to regulate cell sorting and subsequent boundary formation...
March 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28300720/effect-of-hydrogel-elasticity-and-ephrinb2-immobilized-manner-on-runx2-expression-of-human-mesenchymal-stem-cells
#12
Hiroyuki Toda, Masaya Yamamoto, Hiroshi Uyama, Yasuhiko Tabata
The objective of this study is to design the manner of ephrinB2 immobilized onto polyacrylamide (PAAm) hydrogels with varied elasticity and evaluate the effect of hydrogels elasticity and the immobilized manner of ephrinB2 on the Runx2 expression of human mesenchymal stem cells (hMSC). The PAAm hydrogels were prepared by the radical polymerization of acrylamide (AAm), and N,N'-methylenebisacrylamide (BIS). By changing the BIS concentration, the elasticity of PAAm hydrogels changed from 1 to 70 kPa. For the bio-specific immobilization of ephrinB2, a chimeric protein of ephrinB2 and Fc domain was immobilized onto protein A-conjugated PAAm hydrogels by making use of the bio-specific interaction between the Fc domain and protein A...
March 11, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28294115/phosphorylation-of-rab-coupling-protein-by-lmtk3-controls-rab14-dependent-epha2-trafficking-to-promote-cell-cell-repulsion
#13
Christine Gundry, Sergi Marco, Elena Rainero, Bryan Miller, Emmanuel Dornier, Louise Mitchell, Patrick T Caswell, Andrew D Campbell, Anna Hogeweg, Owen J Sansom, Jennifer P Morton, Jim C Norman
The Rab GTPase effector, Rab-coupling protein (RCP) is known to promote invasive behaviour in vitro by controlling integrin and receptor tyrosine kinase (RTK) trafficking, but how RCP influences metastasis in vivo is unclear. Here we identify an RTK of the Eph family, EphA2, to be a cargo of an RCP-regulated endocytic pathway which controls cell:cell repulsion and metastasis in vivo. Phosphorylation of RCP at Ser(435) by Lemur tyrosine kinase-3 (LMTK3) and of EphA2 at Ser(897) by Akt are both necessary to promote Rab14-dependent (and Rab11-independent) trafficking of EphA2 which generates cell:cell repulsion events that drive tumour cells apart...
March 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28284324/readdressing-the-entity-of-exercise-pulmonary-arterial-hypertension
#14
REVIEW
Boris I Medarov, Sidharth Jogani, Johnathan Sun, Marc A Judson
Exercise pulmonary hypertension (EPH) indicates an abnormally elevated pulmonary artery pressure (PAP) during exercise. The physiological range of PAP during exercise remains poorly defined and, therefore, a universally accepted definition of EPH remains elusive. Nevertheless, previous data concerning the distribution of PAP in normal populations and more recent retrospective clinical data enhanced our ability to define EPH. EPH can impair exercise capacity and cause dyspnea. The underlying pathophysiology of the arterial form of EPH (EPAH) appears to be similar to that seen in resting pulmonary arterial hypertension (PAH), and EPAH individuals are at risk of developing resting PAH...
March 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28276447/ascl1-promotes-tangential-migration-and-confines-migratory-routes-by-induction-of-ephb2-in-the-telencephalon
#15
Yuan-Hsuan Liu, Jin-Wu Tsai, Jia-Long Chen, Wan-Shan Yang, Pei-Ching Chang, Pei-Lin Cheng, David L Turner, Yuchio Yanagawa, Tsu-Wei Wang, Jenn-Yah Yu
During development, cortical interneurons generated from the ventral telencephalon migrate tangentially into the dorsal telencephalon. Although Achaete-scute family bHLH transcription factor 1 (Ascl1) plays important roles in the developing telencephalon, whether Ascl1 regulates tangential migration remains unclear. Here, we found that Ascl1 promoted tangential migration along the ventricular zone/subventricular zone (VZ/SVZ) and intermediate zone (IZ) of the dorsal telencephalon. Distal-less homeobox 2 (Dlx2) acted downstream of Ascl1 in promoting tangential migration along the VZ/SVZ but not IZ...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28272517/evidence-from-single-nucleotide-polymorphism-analyses-of-advance-study-demonstrates-efnb3-as-a-hypertension-risk-gene
#16
Johanne Tremblay, Yujia Wang, John Raelson, Francois-Christophe Marois-Blanchet, Zenghui Wu, Hongyu Luo, Edward Bradley, John Chalmers, Mark Woodward, Stephen Harrap, Pavel Hamet, Jiangping Wu
EPH kinases and their ligands, ephrins (EFNs), have vital and diverse biological functions. We recently reported that Efnb3 gene deletion results in hypertension in female but not male mice. These data suggest that EFNB3 regulates blood pressure in a sex- and sex hormone-dependent way. In the present study, we conducted a human genetic study to assess the association of EFNB3 single nucleotide polymorphisms with human hypertension risks, using 3,448 patients with type 2 diabetes from the ADVANCE study (Action in Diabetes and Vascular Disease: Peterax and Diamicron MR Controlled Evaluation)...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28262839/loss-of-the-eph-receptor-b6-contributes-to-colorectal-cancer-metastasis
#17
Silvia Mateo-Lozano, Sarah Bazzocco, Paulo Rodrigues, Rocco Mazzolini, Elena Andretta, Higinio Dopeso, Yolanda Fernández, Edgar Del Llano, Josipa Bilic, Lucía Suárez-López, Irati Macaya, Fernando Cartón-García, Rocio Nieto, Lizbeth M Jimenez-Flores, Priscila Guimarães de Marcondes, Yaiza Nuñez, Elsa Afonso, Karina Cacci, Javier Hernández-Losa, Stefania Landolfi, Ibane Abasolo, Santiago Ramón Y Cajal, John M Mariadason, Simo Schwartz, Toshimitsu Matsui, Diego Arango
Although deregulation of EPHB signaling has been shown to be an important step in colorectal tumorigenesis, the role of EPHB6 in this process has not been investigated. We found here that manipulation of EPHB6 levels in colon cancer cell lines has no effect on their motility and growth on a solid substrate, soft agar or in a xenograft mouse model. We then used an EphB6 knockout mouse model to show that EphB6 inactivation does not efficiently initiate tumorigenesis in the intestinal tract. In addition, when intestinal tumors are initiated genetically or pharmacologically in EphB6(+/+) and EphB6(-/-) mice, no differences were observed in animal survival, tumor multiplicity, size or histology, and proliferation of intestinal epithelial cells or tumor cells...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28255696/reconstitution-of-tcr-signaling-using-supported-lipid-bilayers
#18
Xiaolei Su, Jonathon A Ditlev, Michael K Rosen, Ronald D Vale
Biochemical reconstitution has served as an important tool for understanding the mechanisms of many cellular processes including DNA replication, transcription, translation, vesicle trafficking, and ubiquitin-mediated proteolysis. Here, we demonstrate that biochemical reconstitution can be applied to studying a complex signaling pathway involving as many as 12 proteins or protein complexes acting at the surface of model membranes. We show that a temporal sequence of events in activated T cells beginning with phosphorylation of the T cell receptor and culminating in the activation of actin polymerization can be replicated in vitro...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28238796/ephrin-b1-mosaicism-drives-cell-segregation-in-craniofrontonasal-syndrome-hipsc-derived-neuroepithelial-cells
#19
Terren K Niethamer, Andrew R Larson, Audrey K O'Neill, Marina Bershteyn, Edward C Hsiao, Ophir D Klein, Jason H Pomerantz, Jeffrey O Bush
Although human induced pluripotent stem cells (hiPSCs) hold great potential for the study of human diseases affecting disparate cell types, they have been underutilized in seeking mechanistic insights into the pathogenesis of congenital craniofacial disorders. Craniofrontonasal syndrome (CFNS) is a rare X-linked disorder caused by mutations in EFNB1 and characterized by craniofacial, skeletal, and neurological anomalies. Heterozygous females are more severely affected than hemizygous males, a phenomenon termed cellular interference that involves mosaicism for EPHRIN-B1 function...
March 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28231684/emergency-peripartum-hysterectomy-a-challenge-or-an-obstetrical-defeat
#20
Aneta Malinowska-Polubiec, Ewa Romejko-Wolniewicz, Julia Zareba-Szczudlik, Agnieszka Dobrowolska-Redo, Agnieszka Sotowska, Roman Smolarczyk, Jan Wilczynski, Krzysztof Czajkowski
OBJECTIVES: Peripartum hysterectomy remains an obstetric nightmare. Most obstetricians consider it a defeat. The aim of our study was to assess the prevalence, indications, procedures and complications of emergency peripartum hysterectomy (EPH) in the 2nd Department of Obstetrics & Gynecology, Medical University of Warsaw during a 7 year period (2007-2013). METHODS: A retrospective evaluation of 21,144 deliveries was performed. We analyzed all cases of EPH, including the maternal characteristics, obstetrical history, course of pregnancy and delivery, type of surgery and complications...
October 2016: Neuro Endocrinology Letters
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