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https://www.readbyqxmd.com/read/28530709/recognition-of-egf-like-domains-by-the-notch-modifying-o-fucosyltransferase-pofut1
#1
Zhijie Li, Kristina Han, John E Pak, Malathy Satkunarajah, Dongxia Zhou, James M Rini
Protein O-fucosyltransferase 1 (POFUT1) fucosylates the epidermal growth factor (EGF)-like domains found in cell-surface and secreted glycoproteins including Notch and its ligands. Although Notch fucosylation is critical for development, and POFUT1 deficiency leads to human disease, how this enzyme binds and catalyzes the fucosylation of its diverse EGF-like domain substrates has not been determined. Reported here is the X-ray crystal structure of mouse POFUT1 in complex with several EGF-like domains, including EGF12 and EGF26 of Notch...
May 22, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28530241/notch-mediated-conversion-of-activated-t-cells-into-stem-cell-memory-like-t-cells-for-adoptive-immunotherapy
#2
Taisuke Kondo, Rimpei Morita, Yuumi Okuzono, Hiroko Nakatsukasa, Takashi Sekiya, Shunsuke Chikuma, Takashi Shichita, Mitsuhiro Kanamori, Masato Kubo, Keiko Koga, Takahiro Miyazaki, Yoshiaki Kassai, Akihiko Yoshimura
Adoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (TSCM) cells have been proposed as a class of long-lived and highly proliferative memory T cells. CD8(+) TSCM cells can be generated in vitro from naive CD8(+) T cells via Wnt signalling; however, methods do not yet exist for inducing TSCM cells from activated or memory T cells. Here, we show a strategy for generating TSCM-like cells in vitro (iTSCM cells) from activated CD4(+) and CD8(+) T cells in mice and humans by coculturing with stromal cells that express a Notch ligand...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28528349/high-wear-resistance-of-femoral-components-coated-with-titanium-nitride-a-retrieval-analysis
#3
Christian Fabry, Carmen Zietz, Axel Baumann, Reinhard Ehall, Rainer Bader
PURPOSE: The objective of this study was to evaluate the in vivo wear resistance of cobalt-chromium femoral components coated with titanium nitride (TiN). Our null hypothesis was that the surface damage and the thickness of the TiN coating do not correlate with the time in vivo. METHODS: Twenty-five TiN-coated bicondylar femoral retrievals with a mean implantation period of 30.7 ± 11.7 months were subjected to an objective surface damage analysis with a semi-quantitative assessment method...
May 20, 2017: Knee Surgery, Sports Traumatology, Arthroscopy: Official Journal of the ESSKA
https://www.readbyqxmd.com/read/28526832/identification-of-a-novel-chalcone-derivative-that-inhibits-notch-signaling-in-t-cell-acute-lymphoblastic-leukemia
#4
Mattia Mori, Luca Tottone, Deborah Quaglio, Nadezda Zhdanovskaya, Cinzia Ingallina, Marisa Fusto, Francesca Ghirga, Giovanna Peruzzi, Maria Elisa Crestoni, Fabrizio Simeoni, Francesca Giulimondi, Claudio Talora, Bruno Botta, Isabella Screpanti, Rocco Palermo
Notch signaling is considered a rational target in the therapy of several cancers, particularly those harbouring Notch gain of function mutations, including T-cell acute lymphoblastic leukemia (T-ALL). Although currently available Notch-blocking agents are showing anti-tumor activity in preclinical studies, they are not effective in all the patients and often cause severe side-effects, limiting their widespread therapeutic use. Here, by functional and biological analysis of the most representative molecules of an in house library of natural products, we have designed and synthetized the chalcone-derivative 8 possessing Notch inhibitory activity at low micro molar concentration in T-ALL cell lines...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526735/activated-notch-induced-intratumoral-heterogeneity-drives-lung-cancer
#5
(no author information available yet)
Activated NOTCH signaling is both tumor-suppressive and protumorigenic in SCLC.
May 19, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28526588/adam10-and-%C3%AE-secretase-regulate-sensory-regeneration-in-the-avian-vestibular-organs
#6
Mark E Warchol, Jennifer Stone, Matthew Barton, Jeffrey Ku, Rose Veile, Nicolas Daudet, Michael Lovett
The loss of sensory hair cells from the inner ear is a leading cause of hearing and balance disorders. The mammalian ear has a very limited ability to replace lost hair cells, but the inner ears of non-mammalian vertebrates can spontaneously regenerate hair cells after injury. Prior studies have shown that replacement hair cells are derived from epithelial supporting cells and that the differentiation of new hair cells is regulated by the Notch signaling pathway. The present study examined molecular influences on regeneration in the avian utricle, which has a particularly robust regenerative ability...
May 16, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28525978/notch-ligand-delta-like-1-as-a-novel-molecular-target-in-childhood-neuroblastoma
#7
P Bettinsoli, G Ferrari-Toninelli, S A Bonini, C Prandelli, M Memo
BACKGROUND: Neuroblastoma is the most common extracranial solid malignancy in childhood, responsible for 15% of all pediatric cancer deaths. It is an heterogeneous disease that does not always respond to classical therapy; so the identification of new and specific molecular targets to improve existing therapy is needed. We have previously demonstrated the involvement of the Notch pathway in the onset and progression of neuroblastoma. In this study we further investigated the role of Notch signaling and identified Delta-like 1 (DLL1) as a novel molecular target in neuroblastoma cells with a high degree of MYCN amplification, which is a major oncogenic driver in neuroblastoma...
May 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28523980/diverse-endometrial-mrna-signatures-during-the-window-of-implantation-in-patients-with-repeated-implantation-failure
#8
Cheng Shi, Hong Jing Han, Li Juan Fan, Jing Guan, Xing Bang Zheng, Xi Chen, Rong Liang, Xiao Wei Zhang, Kun Kun Sun, Qing Hua Cui, Huan Shen
High endometrial receptivity in the window of implantation (WOI) is essential for successful implantation. However, a diagnostic tool with high specificity for impaired endometrial receptivity remains to be developed. We collected endometrium specimens during the WOI from patients with RIF and women who conceived after one IVF/ICSI attempt. We conducted mRNA microarray on the samples followed by relevant comparative and functional analysis. Microarray analysis revealed 357 dysregulated mRNAs between the two groups...
May 19, 2017: Human Fertility: Journal of the British Fertility Society
https://www.readbyqxmd.com/read/28522881/notch-signaling-and-maintenance-of-sox2-expression-in-rat-anterior-pituitary-cells
#9
Khongorzul Batchuluun, Morio Azuma, Ken Fujiwara, Takashi Yashiro, Motoshi Kikuchi
After publication of reports describing the presence of stem/progenitor cells among non-hormone-producing cells in the pituitary, the mechanism responsible for proliferation and differentiation generated considerable interest. Several studies have suggested that Notch signaling is involved. In the present study, we examined the histochemical relationship between Notch signaling molecules and the transcription factor SOX2 in rat pituitary. Combined in situ hybridization and immunohistochemistry showed that Notch2 mRNA and SOX2 were co-expressed at embryonic day 14...
April 27, 2017: Acta Histochemica et Cytochemica
https://www.readbyqxmd.com/read/28522590/notch-inhibitor-pf-03084014-inhibits-hepatocellular-carcinoma-growth-and-metastasis-via-suppression-of-cancer-stemness-due-to-reduced-activation-of-notch1-stat3
#10
Chuan Xing Wu, Aimin Xu, Cathy C Zhang, Peter Olson, Lin Chen, Terence K Lee, Tan To Cheung, Chung Mau Lo, Xiao Qi Wang
Aberrant activation of the Notch signaling pathway is implicated in many solid tumors, including hepatocellular carcinoma (HCC), indicating a potential use of Notch inhibitors for treatment. In this study, we investigated the antitumor and antimetastasis efficacy of the novel Notch inhibitor (γ-secretase inhibitor) PF-03084014 in HCC. HCC spherical cells (stem-like cancer cells), a sphere-derived orthotopic tumor model and one patient-derived xenograft (PDX) model were used in our experiment. We demonstrated that PF-03084014 inhibited the self-renewal and proliferation of cancer stem cells...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28521941/developmental-mechanism-of-the-tarsus-in-insect-legs
#11
REVIEW
Tetsuya Kojima
Insects show a tremendous morphological variety and have been a subject of studying morphological evolution. In legs, the tarsus is especially variable in the number of subsegments (tarsal segments) and their proportion unlike other leg segments. Recent studies in Drosophila melanogaster have revealed details of the tarsal development: regionalization of the tarsal region through integration of regulatory network and its growth, determination of the joint-forming region in each segment through strict regulation of Notch activity, changes in tissue morphology through regulation of RhoGTPases regulators and localized cell death, and finally, the morphogenetic mechanism of the ball-and-socket joint between tarsal segments...
February 2017: Current Opinion in Insect Science
https://www.readbyqxmd.com/read/28521908/differentiating-between-rhinosinusitis-and-mastoiditis-surgery-from-postmortem-medical-training-a-study-of-two-identified-skulls-and-hospital-records-from-early-20th-century-coimbra-portugal
#12
Bruno M Magalhães, Célia Lopes, Ana Luísa Santos
Differentiating between medical procedures performed antemortem, perimortem or postmortem in skeletal remains can be a major challenge. This work aims to present evidence of procedures to treat rhinosinusitis (RS) and mastoiditis, suggest criteria for the diagnosis of frontal sinus disease, and frame the individuals described in their medical historical context. In the International Exchange collection, the skull (878) of a 24-year-old male, who died in 1933 due to frontal sinusitis and meningitis, presents evidence of a trepanation above the right frontonasal suture, and micro/macroporosity on the superciliary arches...
June 2017: International Journal of Paleopathology
https://www.readbyqxmd.com/read/28521042/induced-pluripotent-stem-cell-modelling-of-hlhs-underlines-the-contribution-of-dysfunctional-notch-signalling-to-impaired-cardiogenesis
#13
Chunbo Yang, Yaobo Xu, Min Yu, David Lee, Sameer Alharti, Nicola Hellen, Noor Ahmad Shaik, Babajan Banaganapalli, Hussein Ali Mohamoud Sheikh, Elango Ramu, Stefan Przyborski, Gennadiy Tenin, Simon Williams, John O'Sullivan, Osman O Al-Radi, Jameel Atta, Sian E Harding, Bernard Keavney, Majlinda Lako, Lyle Armstrong
Hypoplastic left heart syndrome (HLHS) is among the most severe forms of congenital heart disease. Although the consensus view is that reduced flow through the left heart during development is a key factor in the development of the condition, the molecular mechanisms leading to hypoplasia of left heart structures are unknown. We have generated induced pluripotent stem cells (iPSC) from five HLHS patients and two unaffected controls, differentiated these to cardiomyocytes and identified reproducible in vitro cellular and functional correlates of the HLHS phenotype...
May 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28520736/the-bantam-microrna-acts-through-numb-to-exert-cell-growth-control-and-feedback-regulation-of-notch-in-tumor-forming-stem-cells-in-the-drosophila-brain
#14
Yen-Chi Wu, Kyu-Sun Lee, Yan Song, Stephan Gehrke, Bingwei Lu
Notch (N) signaling is central to the self-renewal of neural stem cells (NSCs) and other tissue stem cells. Its deregulation compromises tissue homeostasis and contributes to tumorigenesis and other diseases. How N regulates stem cell behavior in health and disease is not well understood. Here we show that N regulates bantam (ban) microRNA to impact cell growth, a process key to NSC maintenance and particularly relied upon by tumor-forming cancer stem cells. Notch signaling directly regulates ban expression at the transcriptional level, and ban in turn feedback regulates N activity through negative regulation of the Notch inhibitor Numb...
May 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28520516/mesenchymal-stem-cell-migration-and-proliferation-are-mediated-by-hypoxia-inducible-factor-1%C3%AE-upstream-of-notch-and-sumo-pathways
#15
María Ciria, Nahuel A García, Imelda Ontoria-Oviedo, Hernán González-King, Rubén Carrero, José Luis De La Pompa, José Anastasio Montero, Pilar Sepúlveda
Mesenchymal stem cells (MSCs) are effective in treating several pathologies. We and others have demonstrated that hypoxia or hypoxia-inducible factor 1 alpha (HIF-1α) stabilization improves several MSC functions, including cell adhesion, migration, and proliferation, thereby increasing their therapeutic potential. To further explore the mechanisms induced by HIF-1α in MSCs, we studied its relationship with Notch signaling and observed that overexpression of HIF-1α in MSCs increased protein levels of the Notch ligands Jagged 1-2 and Delta-like (Dll)1, Dll3, and Dll4 and potentiated Notch signaling only when this pathway was activated...
May 18, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28515436/nimbolide-upregulates-reck-by-targeting-mir-21-and-hif-1%C3%AE-in-cell-lines-and-in-a-hamster-oral-carcinogenesis-model
#16
Jaganathan Kowshik, Rajakishore Mishra, Josephraj Sophia, Satabdi Rautray, Kumaraswamy Anbarasu, G Deepak Reddy, Madhulika Dixit, Sundarasamy Mahalingam, Siddavaram Nagini
Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a potent inhibitor of matrix metalloproteinases (MMPs) is a common negative target of oncogenic signals and a potential therapeutic target for novel drug development. Here, we show that sequential RECKlessness stimulates angiogenesis and Notch signalling in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model, a paradigm for oral oncogenesis and chemointervention. We also report the chemotherapeutic effect of nimbolide, a limonoid from the neem tree (Azadirachta indica) based on the upregulation of RECK as well as modulation of the expression of key molecules involved in invasion and angiogenesis...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28514688/the-e-id-protein-axis-specifies-adaptive-lymphoid-cell-identity-and-suppresses-thymic-innate-lymphoid-cell-development
#17
Masaki Miyazaki, Kazuko Miyazaki, Kenian Chen, Yi Jin, Jacob Turner, Amanda J Moore, Rintaro Saito, Kenichi Yoshida, Seishi Ogawa, Hans-Reimer Rodewald, Yin C Lin, Hiroshi Kawamoto, Cornelis Murre
Innate and adaptive lymphoid development is orchestrated by the activities of E proteins and their antagonist Id proteins, but how these factors regulate early T cell progenitor (ETP) and innate lymphoid cell (ILC) development remains unclear. Using multiple genetic strategies, we demonstrated that E proteins E2A and HEB acted in synergy in the thymus to establish T cell identity and to suppress the aberrant development of ILCs, including ILC2s and lymphoid-tissue-inducer-like cells. E2A and HEB orchestrated T cell fate and suppressed the ILC transcription signature by activating the expression of genes associated with Notch receptors, T cell receptor (TCR) assembly, and TCR-mediated signaling...
May 16, 2017: Immunity
https://www.readbyqxmd.com/read/28514491/3d-image-based-morphometric-analysis-of-the-scapular-neck-length-in-subjects-undergoing-reverse-shoulder-arthroplasty
#18
P Simon, M Diaz, M Cusick, B Santoni, M Frankle
INTRODUCTION: Scapular notching after RSA may, in part, be related to a patient's scapular morphology. The purpose of this study was to develop a novel 3D measurement technique to describe infraglenoid tubercle morphometry. We hypothesize that the parameters describing infraglenoid tubercle would be normally distributed and would correlate with individual's demographics and glenoid morphometry. MATERIALS AND METHODS: A group of 110 subjects treated with RSA were evaluated...
May 17, 2017: Clinical Anatomy
https://www.readbyqxmd.com/read/28514425/signal-transduction-notch-catches-a-jagged-edge
#19
Stephen C Blacklow
No abstract text is available yet for this article.
May 17, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28513901/transcriptomic-profiling-reveals-disordered-regulation-of-surfactant-homeostasis-in-neonatal-cloned-bovines-with-collapsed-lungs-and-respiratory-distress
#20
Yan Liu, Yifan Rao, Xiaojing Jiang, Fanyi Zhang, Linhua Huang, Weihua Du, Haisheng Hao, Xueming Zhao, Dong Wang, Qiuling Jiang, Huabin Zhu, Xiuzhu Sun
Respiratory distress is a major cause of mortality in cloned neonatal animals, but its pathogenesis remains poorly understood. Here, we used necropsy and histology procedures to evaluate the lungs of cloned neonatal bovines dying of respiratory distress, finding incomplete lung dilation, alveolar collapse, and thickened alveolar walls. Comparison of the transcriptomes between collapsed lungs of cloned bovines and their normal counterparts revealed 1373 differentially expressed genes in collapsed lungs (p < 0...
May 17, 2017: Molecular Reproduction and Development
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