BRCA1 Directs the Repair Pathway to Homologous Recombination by Promoting 53BP1 Dephosphorylation.
AuthorsIsono M, Niimi A, Oike T, Hagiwara Y, Sato H, Sekine R, Yoshida Y, Isobe SY, Obuse C, Nishi R, Petricci E, Nakada S, Nakano T, Shibata A
JournalCell Rep
PubMed ID28076794
'BRCA1 promotes homologous recombination (HR) by activating DNA-end resection. By contrast, 53BP1 forms a barrier that inhibits DNA-end resection. Here, we show that BRCA1 promotes DNA-end resection by relieving the 53BP1-dependent barrier. We show that 53BP1 is phosphorylated by ATM in S/G2 phase, promoting RIF1 recruitment, which inhibits resection. 53BP1 ... More
DRP-1 is required for BH3 mimetic-mediated mitochondrial fragmentation and apoptosis.
AuthorsMilani M, Byrne DP, Greaves G, Butterworth M, Cohen GM, Eyers PA, Varadarajan S
JournalCell Death Dis
PubMed ID28079887
'The concept of using BH3 mimetics as anticancer agents has been substantiated by the efficacy of selective drugs, such as Navitoclax and Venetoclax, in treating BCL-2-dependent haematological malignancies. However, most solid tumours depend on MCL-1 for survival, which is highly amplified in multiple cancers and a major factor determining chemoresistance. ... More
Enhanced CRISPR/Cas9-mediated precise genome editing by improved design and delivery of gRNA, Cas9 nuclease, and donor DNA.
AuthorsLiang X, Potter J, Kumar S, Ravinder N, Chesnut JD
JournalJ Biotechnol
PubMed ID27845164
'While CRISPR-based gene knock out in mammalian cells has proven to be very efficient, precise insertion of genetic elements via the cellular homology directed repair (HDR) pathway remains a rate-limiting step to seamless genome editing. Under the conditions described here, we achieved up to 56% targeted integration efficiency with up ... More
Development of a Bacillus subtilis cell-free transcription-translation system for prototyping regulatory elements.
'Cell-free transcription-translation systems were originally applied towards in vitro protein production. More recently, synthetic biology is enabling these systems to be used within a systematic design context for prototyping DNA regulatory elements, genetic logic circuits and biosynthetic pathways. The Gram-positive soil bacterium, Bacillus subtilis, is an established model organism of ... More
Evaluation of Receptor-Ligand Mechanisms of Dual-Targeted Particles to an Inflamed Endothelium.
AuthorsFromen CA, Fish MB, Zimmerman A, Adili R, Holinstat M, Eniola-Adefeso O
JournalBioeng Transl Med
PubMed ID28066821
'Vascular-targeted carriers (VTCs) are designed as leukocyte mimics, decorated with ligands that target leukocyte adhesion molecules (LAMs) and facilitate adhesion to diseased endothelium. VTCs require different design considerations than other targeted particle therapies; adhesion of VTCs in regions with dynamic blood flow requires multiple ligand-receptor (LR) pairs that provide particle ... More
AuthorsDe Biasi S, Simone AM, Nasi M, Bianchini E, Ferraro D, Vitetta F, Gibellini L, Pinti M, Del Giovane C, Sola P, Cossarizza A
JournalFront Immunol
PubMed ID27965675
Multiple sclerosis (MS), an autoimmune disease with neurodegeneration and inflammation is characterized by several alterations of different T cell subsets. However, few data exist on the role of iNKT lymphocytes. ... More
Virtual screening-driven repositioning of etoposide as CD44 antagonist in breast cancer cells.
AuthorsAguirre-Alvarado C, Segura-Cabrera A, Velázquez-Quesada I, Hernández-Esquivel MA, García-Pérez CA, Guerrero-Rodríguez SL, Ruiz-Moreno AJ, Rodríguez-Moreno A, Pérez-Tapia SM, Velasco-Velázquez MA
JournalOncotarget
PubMed ID27009862
CD44 is a receptor for hyaluronan (HA) that promotes epithelial-to-mesenchymal transition (EMT), induces cancer stem cell (CSC) expansion, and favors metastasis. Thus, CD44 is a target for the development of antineoplastic agents. In order to repurpose drugs as CD44 antagonists, we performed consensus-docking studies using the HA-binding domain of CD44 ... More
Advanced glycosylation end product promotes forkhead box O1 and inhibits Wnt pathway to suppress capacities of epidermal stem cells.
AuthorsZhu J, Wang P, Yu Z, Lai W, Cao Y, Huang P, Xu Q, Yu M, Xu J, Huang Z, Zeng B
JournalAm J Transl Res
PubMed ID28078027
Diabetes mellitus is frequently accompanied by chronic complications like delayed wound healing, which is consider to be attributed to the accumulation of advanced glycosylation end product (AGE). However, the impacts of AGE on epidermal stem cells (ESCs) are largely unknown. This study aims to address the influence and mechanism of ... More
Acute Exposure to Crystalline Silica Reduces Macrophage Activation in Response to Bacterial Lipoproteins.
AuthorsBeamer GL, Seaver BP, Jessop F, Shepherd DM, Beamer CA
JournalFront Immunol
PubMed ID26913035
Numerous studies have examined the relationship between alveolar macrophages (AMs) and crystalline silica (SiO2) using in vitro and in vivo immunotoxicity models; however, exactly how exposure to SiO2 alters the functionality of AM and the potential consequences for immunity to respiratory pathogens remains largely unknown. Because recognition and clearance of ... More
TNFa promotes CAR-dependent migration of leukocytes across epithelial monolayers.
AuthorsMorton PE, Hicks A, Ortiz-Zapater E, Raghavan S, Pike R, Noble A, Woodfin A, Jenkins G, Rayner E, Santis G, Parsons M
JournalSci Rep
PubMed ID27193388
Trans-epithelial migration (TEpM) of leukocytes during inflammation requires engagement with receptors expressed on the basolateral surface of the epithelium. One such receptor is Coxsackie and Adenovirus Receptor (CAR) that binds to Junctional Adhesion Molecule-like (JAM-L) expressed on leukocytes. Here we provide the first evidence that efficient TEpM of monocyte-derived THP-1 ... More
Glucocorticoids regulate the proliferation of T cells via miRNA-155 in septic shock.
AuthorsChen Y, Wang G, Liu Z, Wang S, Wang Y
JournalExp Ther Med
PubMed ID28105104
Although previous studies have evaluated the roles of glucocorticoids and lymphocytes in septic shock, the precise mechanism remains unclear. The present study focused on investigating the influence of glucocorticoids on micro (mi)RNA-155 expression levels and the proliferation of T lymphocytes in septic shock. T cells were harvested from in the ... More
CD4-Transgenic Zebrafish Reveal Tissue-Resident Th2- and Regulatory T Cell-like Populations and Diverse Mononuclear Phagocytes.
AuthorsDee CT, Nagaraju RT, Athanasiadis EI, Gray C, Fernandez Del Ama L, Johnston SA, Secombes CJ, Cvejic A, Hurlstone AF
JournalJ Immunol
PubMed ID27694495
CD4(+) T cells are at the nexus of the innate and adaptive arms of the immune system. However, little is known about the evolutionary history of CD4(+) T cells, and it is unclear whether their differentiation into specialized subsets is conserved in early vertebrates. In this study, we have created ... More
A part toolbox to tune genetic expression in Bacillus subtilis.
AuthorsGuiziou S, Sauveplane V, Chang HJ, Clerté C, Declerck N, Jules M, Bonnet J
JournalNucleic Acids Res
PubMed ID27402159
Libraries of well-characterised components regulating gene expression levels are essential to many synthetic biology applications. While widely available for the Gram-negative model bacterium Escherichia coli, such libraries are lacking for the Gram-positive model Bacillus subtilis, a key organism for basic research and biotechnological applications. Here, we engineered a genetic toolbox ... More
Restored in vivo-like membrane lipidomics positively influence in vitro features of cultured mesenchymal stromal/stem cells derived from human placenta.
AuthorsChatgilialoglu A, Rossi M, Alviano F, Poggi P, Zannini C, Marchionni C, Ricci F, Tazzari PL, Taglioli V, Calder PC, Bonsi L
JournalStem Cell Res Ther
PubMed ID28173875
The study of lipid metabolism in stem cell physiology has recently raised great interest. The role of lipids goes beyond the mere structural involvement in assembling extra- and intra-cellular compartments. Nevertheless, we are still far from understanding the impact of membrane lipidomics in stemness maintenance and differentiation patterns. In the ... More
Selective Inhibitors of Histone Deacetylases 1 and 2 Synergize with Azacitidine in Acute Myeloid Leukemia.
AuthorsMin C, Moore N, Shearstone JR, Quayle SN, Huang P, van Duzer JH, Jarpe MB, Jones SS, Yang M
JournalPLoS One
PubMed ID28060870
Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic stem cell disorders characterized by defects in myeloid differentiation and increased proliferation of neoplastic hematopoietic precursor cells. Outcomes for patients with AML remain poor, highlighting the need for novel treatment options. Aberrant epigenetic regulation plays an important role in the ... More
A human programmed death-ligand 1-expressing mouse tumor model for evaluating the therapeutic efficacy of anti-human PD-L1 antibodies.
AuthorsHuang A, Peng D, Guo H, Ben Y, Zuo X, Wu F, Yang X, Teng F, Li Z, Qian X, Qin FX
JournalSci Rep
PubMed ID28202921
Huge efforts have been devoted to develop therapeutic monoclonal antibodies targeting human Programmed death-ligand 1 (hPD-L1) for treating various types of human cancers. However, thus far there is no suitable animal model for evaluating the anti-tumor efficacy of such antibodies against hPD-L1. Here we report the generation of a robust ... More
Inference of immune cell composition on the expression profiles of mouse tissue.
AuthorsChen Z, Huang A, Sun J, Jiang T, Qin FX, Wu A
JournalSci Rep
PubMed ID28084418
Mice are some of the widely used experimental animal models for studying human diseases. Defining the compositions of immune cell populations in various tissues from experimental mouse models is critical to understanding the involvement of immune responses in various physiological and patho-physiological conditions. However, non-lymphoid tissues are normally composed of ... More
Antimicrobial activity of HL-60 cells compared to primary blood-derived neutrophils against Staphylococcus aureus.
AuthorsYaseen R, Blodkamp S, Lüthje P, Reuner F, Völlger L, Naim HY, von Köckritz-Blickwede M
JournalJ Negat Results Biomed
PubMed ID28214466
The human leukemia cell line HL-60 is considered an alternative cell culture model to study neutrophil differentiation and migration. The aim of this study was to characterize the suitability of HL-60 cells differentiated to neutrophil-like cells (nHL-60) as substitute for blood-derived human neutrophils to investigate the interaction of neutrophils with ... More
Medical School Hotline: Pacific Center for Emerging Infectious Diseases Research.
AuthorsYanagihara R, Nerurkar VR, Hui G, Jacobs GA