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https://www.readbyqxmd.com/read/29213081/pak2-is-essential-for-the-function-of-foxp3-regulatory-t-cells-through-maintaining-a-suppressive-treg-phenotype
#1
Kyle L O'Hagan, Stephen D Miller, Hyewon Phee
Foxp3, a key transcription factor that drives lineage differentiation of regulatory T cells (Tregs), was thought to imprint a unique and irreversible genetic signature within Tregs. Recent evidence, however, suggests that loss or attenuation of Foxp3 expression can cause Tregs to de-differentiate into effector T cells capable of producing proinflammatory cytokines. Herein, we report that the signaling kinase, p21-activated kinase 2 (Pak2), is essential for maintaining Treg stability and suppressive function...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29200164/neuropilin-1-cd304-expression-by-flow-cytometry-in-pediatric-precursor-b-acute-lymphoblastic-leukemia-a-minimal-residual-disease-and-potential-prognostic-marker
#2
Hala M Abaza, Mervat A A Alfeky, Deena S Eissa, Mona F Abdel Fattah, Laila M Annaka, Fatma S Ebeid
Flow cytometry (FCM) is used for quantification of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) through discriminating leukemic B-lymphoblasts from normal B-cell precursor counterparts "hematogones." Neuropilin-1 (NRP-1)/CD304 is a vascular endothelial growth factor receptor implicated in the progression of hematological malignancies. We evaluated NRP-1/CD304 as MRD and prognostic marker in pediatric precursor B-ALL using FCM. Seventy children with precursor B-ALL and 40 control children were enrolled...
December 1, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29183999/autopolysialylation-of-polysialyltransferases-is-required-for-polysialylation-and-polysialic-acid-chain-elongation-on-select-glycoprotein-substrates
#3
Gaurang P Bhide, Joseph L Zapater, Karen J Colley
Polysialic acid (polySia) is a large glycan polymer that is added to some glycoproteins by two polysialyltransferases (polySTs), ST8Sia-II and ST8Sia-IV. As polySia modulates cell adhesion and signaling, immune cell function, and tumor metastasis, it is of interest to determine how the polySTs recognize their select substrates. We have recently identified residues within the ST8Sia-IV polybasic region (PBR) that are required for neural cell adhesion molecule (NCAM) recognition and subsequent polysialylation...
November 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29179185/vegf-a-neuropilin-1-pathway-confers-cancer-stemness-via-activating-wnt-%C3%AE-catenin-axis-in-breast-cancer-cells
#4
Lansheng Zhang, Hongmei Wang, Caihong Li, Yang Zhao, Langjie Wu, Xiuping Du, Zhengxiang Han
BACKGROUND/AIMS: Targeting cancer stem cells (CSCs) is emerging as a promising method for cancer treatment. We previously indicated that knockdown of Neuropilin 1(NRP-1) could inhibit breast cancer cell proliferation. Here, we continue exploring the roles and mechanisms of VEGF-A/NRP-1 axis in breast CSCs formation. METHODS: qRT-PCR was used to detect the levels of VEGF-A and NRP-1 in breast cancer sphere cells and wild-type cells. Mammospheres formation, flow cytometry, soft agar colony and tumor formation assays were performed to evaluate the effects of VEGF-A/NRP-1 on breast cancer stemness...
November 28, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29178242/deceased-organ-donor-screening-for-human-immunodeficiency-virus-hepatitis-b-and-hepatitis-c-viruses-discordant-serology-and-nucleic-acid-testing-results
#5
Nicole Theodoropoulos, Marek J Nowicki, Claudia Chinchilla-Reyes, Sara Dionne, Andrés Jaramillo, Tom Mone, Richard Hasz, Martin D Jendrisak, Daniela P Ladner, Michael G Ison
BACKGROUND: Before the 2014 policy change pertaining to infectious disease screening, many organ procurement organizations (OPOs) were supplementing serologic screening of deceased organ donors with nucleic acid testing (NAT) for human immunodeficiency virus (HIV-1), hepatitis B virus (HBV), and hepatitis C virus (HCV). The number of seronegative, NAT-positive donors has not been directly measured. METHODS: HIV, HBV, and HCV screening results of 11 229 donor referrals evaluated from 2010 to 2013 were obtained from three OPO-affiliated laboratories, capturing 35% of all donors in the United States...
November 27, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/29175650/the-asparagine-rich-protein-nrp-facilitates-the-degradation-of-the-pp6-type-phosphatase-fypp3-to-promote-aba-response-in-arabidopsis
#6
Tong Zhu, Yanying Wu, Xiaotong Yang, Wenli Chen, Qingqiu Gong, Xinqi Liu
The phytohormone abscisic acid (ABA) plays critical roles in abiotic stress responses and plant development. In germinating seeds, the phytochrome-associated protein phosphatase, FyPP3, regulates ABA signaling negatively by dephosphorylating the transcription factor ABI5. However, whether and how the FyPP3 protein level is regulated is unknown previously. Here, we report that an asparagine-rich protein, NRP, interacts with FyPP3 both in vitro and in vivo, and that NRP tethers FyPP3 to SYP41/61-positive endosomes and facilitates its degradation in the vacuole...
November 23, 2017: Molecular Plant
https://www.readbyqxmd.com/read/29173394/outcome-after-heart-transplantation-from-donation-after-circulatory-determined-death-donors
#7
Simon Messer, Aravinda Page, Richard Axell, Marius Berman, Jules Hernández-Sánchez, Simon Colah, Barbora Parizkova, Kamen Valchanov, John Dunning, Evgeny Pavlushkov, Sendhil K Balasubramanian, Jayan Parameshwar, Yasir Abu Omar, Martin Goddard, Stephen Pettit, Clive Lewis, Anna Kydd, David Jenkins, Christopher J Watson, Catherine Sudarshan, Pedro Catarino, Marie Findlay, Ayyaz Ali, Steven Tsui, Stephen R Large
BACKGROUND: The requirement for heart transplantation is increasing, vastly outgrowing the supply of hearts available from donation after brain death (DBD) donors. Transplanting hearts after donation after circulatory-determined death (DCD) may be a viable additive alternative to DBD donors. This study compared outcomes from the largest single-center experience of DCD heart transplantation against matched DBD heart transplants. METHODS: DCD hearts were retrieved using normothermic regional perfusion (NRP) or direct procurement and perfusion (DPP)...
December 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/29173319/impact-of-the-neonatal-resuscitation-program-recommended-low-oxygen-strategy-on-outcomes-of-infants-born-preterm
#8
Vishal S Kapadia, Charitharth V Lal, Venkat Kakkilaya, Roy Heyne, Rashmin C Savani, Myra H Wyckoff
OBJECTIVE: To evaluate the impact of the Neonatal Resuscitation Program (NRP)-recommended low oxygen strategy (LOX) on neonatal morbidities, mortality, and neurodevelopmental outcomes in neonates born preterm. STUDY DESIGN: In March 2011, Parkland Hospital changed from a high oxygen strategy (HOX) of resuscitation with initial 100% oxygen and targeting 85%-94% oxygen saturation for delivery room resuscitation to a LOX with initial 21% oxygen and titrating oxygen to meet NRP-recommended transitional target saturations...
December 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/29169039/heteromultivalent-targeting-of-integrin-%C3%AE-v%C3%AE-3-and-neuropilin-1-promotes-cell-survival-via-the-activation-of-the-igf-1-insulin-receptors
#9
Tao Jia, Jungyoon Choi, Jéremy Ciccione, Maxime Henry, Ahmad Mehdi, Jean Martinez, Béatrice Eymin, Gilles Subra, Jean-Luc Coll
Angiogenesis strongly depends on the activation of integrins, especially integrin αvβ3, and of neuropilin-1 (NRP-1), a co-receptor of VEGFR2. Dual-targeted molecules that simultaneously block both of them are expected have increased anti-angiogenic and antitumor activity. Toward this goal, we generated bifunctional 40 nm-sized silica nanoparticles (NPs) coated with controlled amounts of cRGD and ATWLPPR peptides and studied their affinity, selectivity and biological activity in HUVECs. Sub-nanomolar concentrations of NPs grafted either with ATWLPPR alone or in combination with cRGD exhibit potent and specific antagonist activity against VEGFR2/AKT signaling...
October 29, 2017: Biomaterials
https://www.readbyqxmd.com/read/29156489/an-adherent-mucus-layer-attenuates-the-genotoxic-effect-of-colibactin
#10
Christian Reuter, Mona Alzheimer, Heike Walles, Tobias A Oelschlaeger
The human gastrointestinal tract is a complex ecosystem in which epithelial cells and microorganisms of the intestinal microbiota live in symbiosis. Certain members of the microbiota, in particular Escherichia coli strains of the B2 phylotype, carry the polyketide synthase (pks)-island encoding the genotoxin colibactin. Colibactin is a non-ribosomal peptide (NRP) or polyketide (PK)-NRP hybrid of still unsolved structure, which induces DNA double strand breaks (DSBs) in eukaryotic cells. However, direct contact between live bacteria and host cell is required in order to elicit these genotoxic effects...
November 20, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/29120882/donation-after-circulatory-death-and-its-expansion-in-spain
#11
Eduardo Miñambres, Juan J Rubio, Elisabeth Coll, Beatriz Domínguez-Gil
PURPOSE OF REVIEW: Donation after circulatory death (DCD) is still performed in a limited number of countries. This article summarizes the development of DCD in Spain and presents recent Spanish contributions to gain knowledge on the potential benefits and the practical use of normothermic regional perfusion (nRP). RECENT FINDINGS: DCD now contributes to 24% of deceased donors in Spain. The development of DCD has been based on an assessment of practices in the treatment of cardiac arrest and end-of-life care to accommodate the option of DCD; the creation of an adequate regulatory framework; and institutional support, professional training and public education...
November 7, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/29120740/breaking-the-barrier-host-cell-invasion-by-lujo-virus
#12
Stefan Kunz, Juan Carlos de la Torre
Lujo virus (LUJV) is an arenavirus that emerged in 2008 associated with a cluster of human cases of severe hemorrhagic fever. In this issue of Cell Host & Microbe, Raaben et al. (2017) identify neuropilin (NRP)-2 as cell surface receptor and the tetraspannin protein CD63 as intracellular entry factor for LUJV.
November 8, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29120534/joint-effects-of-prenatal-air-pollutant-exposure-and-maternal-folic-acid-supplementation-on-risk-of-autism-spectrum-disorder
#13
Amanda J Goodrich, Heather E Volk, Daniel J Tancredi, Rob McConnell, Fred W Lurmann, Robin L Hansen, Rebecca J Schmidt
Independent studies report that periconceptional folic acid (FA) may decrease the risk of autism spectrum disorder (ASD) while exposure to air pollution may increase ASD risk. We examined the joint effects of gestational FA and air pollution exposures in association with ASD. We studied 346 ASD cases and 260 typically developing controls from the CHARGE case-control study. Self-reported FA intake for each month of pregnancy was quantified. Estimates of exposure to near roadway air pollution (NRP) and criteria air pollutant measures were assigned based on maternal residential history...
November 9, 2017: Autism Research: Official Journal of the International Society for Autism Research
https://www.readbyqxmd.com/read/29118857/analysis-of-predictive-parameters-for-the-development-of-radiation-induced-pneumonitis
#14
Toru Yamagishi, Norio Kodaka, Yoshiyuki Kurose, Kayo Watanabe, Chihiro Nakano, Kumiko Kishimoto, Takeshi Oshio, Kumiko Niitsuma, Hiroto Matsuse
INTRODUCTION: Prevention and effective treatment of radiation-induced pneumonitis (RP) could facilitate greater use of radiation therapy (RT) for lung cancer. The purpose of this study was to determine clinical parameters useful for early prediction of RP. METHODS: Blood sampling, pulmonary function testing, chest computed tomography, and bronchoalveolar lavage (BAL) were performed in patients with pathologically confirmed lung cancer who had completed ≥60 Gy of RT, at baseline, shortly after RT, and at 1 month posttreatment...
October 2017: Annals of Thoracic Medicine
https://www.readbyqxmd.com/read/29111348/nrpa-308-a-new-neuropilin-1-antagonist-exerts-in%C3%A2-vitro-anti-angiogenic-and-anti-proliferative-effects-and-in%C3%A2-vivo-anti-cancer%C3%A2-effects-in-a-mouse-xenograft-model
#15
Wang-Qing Liu, Yves Lepelletier, Matthieu Montès, Lucia Borriello, Rafika Jarray, Renaud Grépin, Bertrand Leforban, Ali Loukaci, Rachid Benhida, Olivier Hermine, Sylvie Dufour, Gilles Pagès, Christiane Garbay, Françoise Raynaud, Reda Hadj-Slimane, Luc Demange
Neuropilin-1 (NRP-1) is an extra-cellular receptor for the main Vascular Endothelial Growth Factor over-expressed in tumour tissues, VEGF-A165. Consequently, NRP-1 is involved in angiogenesis and in tumour growth, and its over-expression is related to a clinical poor prognosis. NRP-1 appears as a major target in oncology, which remains poorly exploited. Herein, we report a new series of 18 small-sized fully organic VEGF-A165/NRP-1 antagonists (NRPas). These compounds share an original scaffold, including two linkers (sulphonamide and amide) and three aromatic cores...
October 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29067211/pilot-assessment-of-vascular-endothelial-growth-factor-receptors-and-trafficking-pathways-in-recurrent-and-metastatic-canine-subcutaneous-mast-cell-tumours
#16
Lucas Da Silva, Carlos E Fonseca-Alves, Jennifer J Thompson, Robert A Foster, Geoffrey A Wood, Renee L Amorim, Brenda L Coomber
Canine subcutaneous mast cell tumour (scMCT) shows less aggressive biological behaviour than cutaneous MCT. Vascular endothelial growth factor receptor 2 (VEGFR2) is expressed by neoplastic cells in canine scMCT, but the relevance of this signalling pathway for disease pathobiology is not clear. The objective of this study was to quantify VEGF-A, VEGFR2, pVEGFR2, the VEGF co-receptor Neuropilin 1 (NRP-1) and the E3 ubiquitin protein ligase c-Cbl in canine scMCT, and to evaluate their association with disease outcome...
August 2017: Veterinary Medicine and Science
https://www.readbyqxmd.com/read/29026302/ultrasmall-aguix-theranostic-nanoparticles-for-vascular-targeted-interstitial-photodynamic-therapy-of-glioblastoma
#17
Eloïse Thomas, Ludovic Colombeau, Mickaël Gries, Thibaut Peterlini, Clélia Mathieu, Noémie Thomas, Cédric Boura, Céline Frochot, Régis Vanderesse, François Lux, Muriel Barberi-Heyob, Olivier Tillement
Despite combined treatments, glioblastoma outcome remains poor with frequent local recurrences, indicating that a more efficient and local therapy is needed. In this way, vascular-targeted photodynamic therapy (VTP) could help tumor eradication by destroying its neovessels. In this study, we designed a polysiloxane-based nanoparticle (NP) combining a magnetic resonance imaging (MRI) contrast agent, a photosensitizer (PS) and a new ligand peptide motif (KDKPPR) targeting neuropilin-1 (NRP-1), a receptor overexpressed by angiogenic endothelial cells of the tumor vasculature...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29018206/tumor-penetrating-delivery-of-sirna-against-tnf%C3%AE-to-human-vestibular-schwannomas
#18
Yin Ren, Jessica E Sagers, Lukas D Landegger, Sangeeta N Bhatia, Konstantina M Stankovic
Vestibular schwannoma (VS) is the most common tumor of the cerebellopontine angle, and it typically presents with sensorineural hearing loss. The genomic landscape of schwannoma is complex and many of the molecules implicated in VS pathogenesis represent targets not amenable to antibody-based or small molecule therapeutics. Tumor-targeted delivery of small interfering RNA (siRNA) therapeutics provides a direct and effective means to interrogate targets while minimizing off-target effects. To establish a preclinical model for therapeutic inhibition of putative targets in VS, archived tumor specimens, fresh tumor cells derived from patients with sporadic VS, and an established schwannoma cell line were screened...
October 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29018120/an-engineered-synthetic-pathway-for-discovering-nonnatural-nonribosomal-peptides-in-escherichia%C3%A2-coli
#19
Sara Cleto, Timothy K Lu
Peptides that are synthesized independently of the ribosome in plants, fungi, and bacteria can have clinically relevant anticancer, antihemochromatosis, and antiviral activities, among many other. Despite their natural origin, discovering new natural products is challenging, and there is a need to expand the chemical diversity that is accessible. In this work, we created a novel, compressed synthetic pathway for the heterologous expression and diversification of nonribosomal peptides (NRPs) based on homologs of siderophore pathways from Escherichia coli and Vibrio cholerae To enhance the likelihood of successful molecule production, we established a selective pressure via the iron-chelating properties of siderophores...
October 10, 2017: MBio
https://www.readbyqxmd.com/read/28977999/platelet-derived-growth-factor-c-promotes-human-melanoma-aggressiveness-through-activation-of-neuropilin-1
#20
Federica Ruffini, Lauretta Levati, Grazia Graziani, Simona Caporali, Maria Grazia Atzori, Stefania D'Atri, Pedro M Lacal
Despite recent progress in advanced melanoma therapy, identification of signalling pathways involved in melanoma switch from proliferative to invasive states is still crucial to uncover new therapeutic targets for improving the outcome of metastatic disease. Neuropilin-1 (NRP-1), a co-receptor for vascular endothelial growth factor-A (VEGF-A) tyrosine kinase receptors (VEGFRs), has been suggested to play a relevant role in melanoma progression. NRP-1 can be activated by VEGF-A also in the absence of VEGFRs, triggering specific signal transduction pathways (e...
September 15, 2017: Oncotarget
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