Read by QxMD icon Read


Kristine Hardy, Corey Smith, Wen Juan Tu, Robert McCuaig, Archana Panikkar, Vijayendra Dasari, Fan Wu, Siok-Keen Tey, Geoffrey R Hill, Rajiv Khanna, Sudha Rao
Immune reconstitution following hematopoietic stem cell transplantation (HSCT) is critical in preventing harmful sequelae in recipients with cytomegalovirus (CMV) infection. To understand the molecular mechanisms underlying immune reconstitution kinetics, we profiled the transcriptome-chromatin accessibility landscape of CMV-specific CD8+ T cells from HCST recipients with different immune reconstitution efficiencies. CMV-specific T cells from HSCT recipients with stable antiviral immunity expressed higher levels of interferon/defense response and cell cycle genes in an interconnected network involving PI3KCG , STAT5B , NFAT , RBPJ , and lower HDAC6 , increasing chromatin accessibility at the enhancer regions of immune and T-cell receptor signaling pathway genes...
March 27, 2018: Blood Advances
Agnieszka Szymula, Richard D Palermo, Amr Bayoumy, Ian J Groves, Mohammed Ba Abdullah, Beth Holder, Robert E White
The Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) is the first viral latency-associated protein produced after EBV infection of resting B cells. Its role in B cell transformation is poorly defined, but it has been reported to enhance gene activation by the EBV protein EBNA2 in vitro. We generated EBNA-LP knockout (LPKO) EBVs containing a STOP codon within each repeat unit of IR1. EBNA-LP-mutant EBVs established lymphoblastoid cell lines (LCLs) from adult B cells at reduced efficiency, but not from umbilical cord B cells, which died approximately two weeks after infection...
February 20, 2018: PLoS Pathogens
Lars la Cour Poulsen, Reidunn Jetne Edelmann, Stig Krüger, Rodrigo Diéguez-Hurtado, Akshay Shah, Tor Espen Stav-Noraas, Anastasia Renzi, Monika Szymanska, Junbai Wang, Manuel Ehling, Rui Benedito, Monika Kasprzycka, Espen Bækkevold, Olav Sundnes, Kim S Midwood, Helge Scott, Philippe Collas, Christian W Siebel, Ralf H Adams, Guttorm Haraldsen, Eirik Sundlisæter, Johanna Hol
OBJECTIVE: Endothelial upregulation of adhesion molecules serves to recruit leukocytes to inflammatory sites and appears to be promoted by NOTCH1; however, current models based on interactions between active NOTCH1 and NF-κB components cannot explain the transcriptional selectivity exerted by NOTCH1 in this context. APPROACH AND RESULTS: Observing that Cre/Lox-induced conditional mutations of endothelial Notch modulated inflammation in murine contact hypersensitivity, we found that IL (interleukin)-1β stimulation induced rapid recruitment of RELA to genomic sites occupied by NOTCH1-RBPJ and that NOTCH1 knockdown reduced H3K27 acetylation at a subset of NF-κB-directed inflammatory enhancers...
February 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Tal Golan-Lagziel, Yair E Lewis, Omer Shkedi, Guy Douvdevany, Lilac H Caspi, Izhak Kehat
Cardiac fibroblasts play key roles in both health and disease. Their regulatory elements, transcription factors (TFs), and mechanisms of expression control have not been fully elucidated. We used a differential open chromatin approach, coupled with active enhancer mark, transcriptomic, and computational TFs binding analysis to map cell-type-specific active enhancers in cardiac fibroblasts and cardiomyocytes, and outline the TFs families that control them. This approach was validated by its ability to uncover the known cardiomyocyte TF biology in an unbiased manner, and was then applied to cardiac fibroblasts...
February 5, 2018: Journal of Molecular and Cellular Cardiology
Jesús A Prieto-Ruiz, Rafael Alis, Sandra García-Benlloch, Sara Sáez-Atiénzar, Ignacio Ventura, José M Hernández-Andreu, José Hernández-Yago, José R Blesa
The TIM23 protein is a key component of the mitochondrial import machinery in yeast and mammals. TIM23 is the channel-forming subunit of the translocase of the inner mitochondrial membrane (TIM23) complex, which mediates preprotein translocation across the mitochondrial inner membrane. In this paper, we aimed to characterize the promoter region of the highly similar human TIM23 orthologs: TIMM23 and TIMM23B. Bioinformatic analysis revealed putative sites for the GA-binding protein (GABP) and the recombination signal binding protein for immunoglobulin kappa J (RBPJ) transcription factors in both promoters...
January 30, 2018: Biochimica et Biophysica Acta
Anca Florentina Mitroi, Mariana Aschie, Adriana Apostol, Costel Brinzan, Georgeta Cozaru, Adrian Nelutu Mitroi
RATIONALE: To date, >40 cases have been described with interstitial deletions involving the 4p15 region. PATIENT CONCERNS AND DIAGNOSIS: We report a case of a 3-year-old boy with an interstitial de novo deletion of approximately 13.34 Mb in 4p15.1-15.31 having mild developmental delay and multiple minor congenital abnormalities. LESSONS: This case presents a clinical manifestation that is similar but not identical to other reported cases...
December 2017: Medicine (Baltimore)
Anna Engler, Chiara Rolando, Claudio Giachino, Ichiko Saotome, Andrea Erni, Callum Brien, Runrui Zhang, Ursula Zimber-Strobl, Freddy Radtke, Spyros Artavanis-Tsakonas, Angeliki Louvi, Verdon Taylor
Neurogenesis continues in the ventricular-subventricular zone (V-SVZ) of the adult forebrain from quiescent neural stem cells (NSCs). V-SVZ NSCs are a reservoir for new olfactory bulb (OB) neurons that migrate through the rostral migratory stream (RMS). To generate neurons, V-SVZ NSCs need to activate and enter the cell cycle. The mechanisms underlying NSC transition from quiescence to activity are poorly understood. We show that Notch2, but not Notch1, signaling conveys quiescence to V-SVZ NSCs by repressing cell-cycle-related genes and neurogenesis...
January 23, 2018: Cell Reports
Sara Duarte, Petter S Woll, Natalija Buza-Vidas, Desmond Wai Loon Chin, Hanane Boukarabila, Tiago C Luís, Laura Stenson, Tiphaine Bouriez-Jones, Helen Ferry, Adam J Mead, Deborah Atkinson, Shaobo Jin, Sally-Ann Clark, Bishan Wu, Emmanouela Repapi, Nicki Gray, Stephen Taylor, Anders P Mutvei, Yat Long Tsoi, Claus Nerlov, Urban Lendahl, Sten Eirik W Jacobsen
While an essential role for canonical Notch signaling in generation of hematopoietic stem cells in the embryo and in thymic T cell development is well established, its role in adult bone marrow (BM) myelopoiesis remains unclear. Some studies, analyzing myeloid progenitors in adult mice with inhibited Notch signaling, implicated distinct roles of canonical Notch signaling in regulation of progenitors for the megakaryocyte, erythroid and granulocyte-macrophage cell lineages. However, these studies might also have targeted other pathways...
January 16, 2018: Blood
Christian J M Antila, Vilma Rraklli, Henri A Blomster, Käthe M Dahlström, Tiina A Salminen, Johan Holmberg, Lea Sistonen, Cecilia Sahlgren
The Notch signaling pathway is a key regulator of stem cells during development, and its deregulated activity is linked to developmental defects and cancer. Transcriptional activation of Notch target genes requires cleavage of the Notch receptor in response to ligand binding, production of the Notch intracellular domain (NICD1), NICD1 migration into the nucleus, and assembly of a transcriptional complex. Post-translational modifications of Notch regulate its trafficking, turnover, and transcriptional activity...
January 5, 2018: Cell Death and Differentiation
Anup K Nair, Jeff R Sutherland, Michael Traurig, Paolo Piaggi, Peng Chen, Sayuko Kobes, Robert L Hanson, Clifton Bogardus, Leslie J Baier
PTF1 complex is critical for pancreatic development and maintenance of adult exocrine pancreas. As a part of our ongoing studies to identify genetic variation that contributes to type 2 diabetes (T2D) in American Indians, we analyzed variation in genes that form this complex, namely PTF1A, RBPJ, and its paralogue RBPJL. A c.839C>T (p.(Thr280Met)) variant (rs200998587:C>T, risk allele frequency = 0.03) in RBPJL, identified only in Amerindian-derived populations, associated with T2D (OR = 1.60[1...
January 4, 2018: European Journal of Human Genetics: EJHG
Jatin Patel, Betoul Baz, Ho Yi Wong, James S Lee, Kiarash Khosrotehrani
Skin wound healing in adults is characterised by a peak of angiogenesis followed by regression of the excessive vasculature in parallel with collagen deposition and fibrosis in the wound. We hypothesized that regressing vessels in healing wounds were in fact entering an endothelial to mesenchymal transition (EndMT) contributing to scarring. Using vascular specific fate tracking (Cdh5-creERt2 /ROSA-YFP mice), full-thickness excisional wounds were analysed to reveal a time dependent transition from endothelial phenotype characterised by VE-Cadherin, CD31 and CD34 towards a mesenchymal phenotype characterised by alpha-smooth muscle actin and FSP1 expression...
December 14, 2017: Journal of Investigative Dermatology
Michael R Strug, Ren-Wei Su, Tae Hoon Kim, Alessandro Mauriello, Carlo Ticconi, Bruce A Lessey, Steven L Young, Jeong Mook Lim, Jae-Wook Jeong, Asgerally T Fazleabas
Unexplained recurrent pregnancy loss (uRPL) is associated with repeated embryo loss and endometrial repair with elevated endometrial expression of inflammatory cytokines, including IFN-γ. Notch signaling through its transcription factor recombination signal binding protein Jκ (RBPJ) regulates mechanisms including the immune response and repair after tissue injury. Initially, null mutation of RBPJ in the mouse uterus ( Pgrcre/+ Rbpjf/f ; Rbpj c-KO) results in subfertility, but we have found that these mice become infertile after pregnancy as a result of dysfunctional postpartum uterine repair, including delayed endometrial epithelial and myometrial regeneration...
January 8, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Gregory J Logan, Margaret C Wright, Adam C Kubicki, Stephen M Maricich
Merkel cells are mechanosensitive skin cells derived from the epidermal lineage whose development requires expression of the basic helix-loop-helix transcription factor Atoh1. The genes and pathways involved in regulating Merkel cell development during embryogenesis are poorly understood. Notch pathway signaling antagonizes Atoh1 expression in many developing body regions, so we hypothesized that Notch signaling might inhibit Merkel cell development. We found that conditional, constitutive overexpression of the Notch intracellular domain (NICD) in mouse epidermis significantly decreased Merkel cell numbers in whisker follicles and touch domes of hairy skin...
February 15, 2018: Developmental Biology
Rebecca Kohnken, Jing Wen, Bethany Mundy-Bosse, Kathleen McConnell, Ashleigh Keiter, Leah Grinshpun, Alex Hartlage, Max Yano, Betina McNeil, Nitin Chakravarti, Basem William, James E Bradner, Michael A Caligiuri, Pierluigi Porcu, Anjali Mishra
MicroRNA (miRNA) dysregulation is a hallmark of cutaneous T-cell lymphoma (CTCL), an often-fatal malignancy of skin-homing CD4+ T cells for which there are few effective therapies. The role of microRNAs (miRs) in controlling epigenetic modifier-dependent transcriptional regulation in CTCL is unknown. In this study, we characterize a novel miR dysregulation that contributes to overexpression of the epigenetic reader bromodomain-containing protein 4 (BRD4). We used patient CD4+ T cells to show diminished levels of miR-29b compared with healthy donor cells...
February 15, 2018: Blood
Rexxi D Prasasya, Kelly E Mayo
The Notch pathway is a highly conserved juxtacrine signaling mechanism that is important for many cellular processes during development, including differentiation and proliferation. While Notch is important during ovarian follicle formation and early development, its functions during the gonadotropin-dependent stages of follicle development are largely unexplored. We observed positive regulation of Notch activity and expression of Notch ligands and receptors following activation of the LH-receptor in prepubertal mouse ovary...
November 8, 2017: Endocrinology
Ahmed Raafat, Sharon Bargo, David McCurdy, Robert Callahan
Transgenic mice expressing the Notch-4 intracellular domain (designated Int3) in the mammary gland have two phenotypes exhibited with 100% penetrance: arrest of mammary alveolar/lobular development and mammary tumorigenesis. Notch-4 signaling is mediated primarily through the interaction of Int3 with the transcription repressor/activator Rbpj. Interestingly, WAP-Int3/Rbpj knockout mice have normal mammary gland development but still developed mammary tumors with a slightly longer latency than the WAP-Int3 mice...
October 20, 2017: Scientific Reports
Kashyap Krishnasamy, Anne Limbourg, Tamar Kapanadze, Jaba Gamrekelashvili, Christian Beger, Christine Häger, Vladimir J Lozanovski, Christine S Falk, L Christian Napp, Johann Bauersachs, Matthias Mack, Hermann Haller, Christian Weber, Ralf H Adams, Florian P Limbourg
Ischemia causes an inflammatory response that is intended to restore perfusion and homeostasis yet often aggravates damage. Here we show, using conditional genetic deletion strategies together with adoptive cell transfer experiments in a mouse model of hind limb ischemia, that blood vessels control macrophage differentiation and maturation from recruited monocytes via Notch signaling, which in turn promotes arteriogenesis and tissue repair. Macrophage maturation is controlled by Notch ligand Dll1 expressed in vascular endothelial cells of arteries and requires macrophage canonical Notch signaling via Rbpj, which simultaneously suppresses an inflammatory macrophage fate...
October 16, 2017: Nature Communications
Tao Xu, Sung-Soo Park, Benedetto Daniele Giaimo, Daniel Hall, Francesca Ferrante, Diana M Ho, Kazuya Hori, Lucas Anhezini, Iris Ertl, Marek Bartkuhn, Honglai Zhang, Eléna Milon, Kimberly Ha, Kevin P Conlon, Rork Kuick, Brandon Govindarajoo, Yang Zhang, Yuqing Sun, Yali Dou, Venkatesha Basrur, Kojo Sj Elenitoba-Johnson, Alexey I Nesvizhskii, Julian Ceron, Cheng-Yu Lee, Tilman Borggrefe, Rhett A Kovall, Jean-François Rual
Notch signaling is an evolutionarily conserved signal transduction pathway that is essential for metazoan development. Upon ligand binding, the Notch intracellular domain (NOTCH ICD) translocates into the nucleus and forms a complex with the transcription factor RBPJ (also known as CBF1 or CSL) to activate expression of Notch target genes. In the absence of a Notch signal, RBPJ acts as a transcriptional repressor. Using a proteomic approach, we identified L3MBTL3 (also known as MBT1) as a novel RBPJ interactor...
November 2, 2017: EMBO Journal
Sung Hee Choi, Eric Severson, Warren S Pear, Xiaole S Liu, Jon C Aster, Stephen C Blacklow
Notch is a major oncogenic driver in T cell acute lymphoblastic leukemia (T-ALL), in part because it binds to an enhancer that increases expression of MYC. Here, we exploit the capacity of activated NOTCH1 and NOTCH3 to induce T-ALL, despite substantial divergence in their intracellular regions, as a means to elucidate a broad, common Notch-dependent oncogenomic program through systematic comparison of the transcriptomes and Notch-bound genomic regulatory elements of NOTCH1- and NOTCH3-dependent T-ALL cells...
2017: PloS One
Katherine K Slemmons, Lisa E S Crose, Stefan Riedel, Manuela Sushnitha, Brian Belyea, Corinne M Linardic
Rhabdomyosarcoma (RMS), a cancer characterized by skeletal muscle features, is the most common soft-tissue sarcoma of childhood. While low- and intermediate-risk groups have seen improved outcomes, high-risk patients still face a 5-year survival rate of <30%, a statistic that has not changed in over 40 years. Understanding the biologic underpinnings of RMS is critical. The developmental pathways of Notch and YAP have been identified as potent but independent oncogenic signals that support the embryonal variant of RMS (eRMS)...
December 2017: Molecular Cancer Research: MCR
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"