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https://www.readbyqxmd.com/read/28642033/atg4b-inhibitors-with-a-benzotropolone-core-structure-block-autophagy-and-augment-efficiency-of-chemotherapy-in-mice
#1
Ammar Kurdi, Matthias Cleenewerck, Christel Vangestel, Sophie Lyssens, Wim Declercq, Jean-Pierre Timmermans, Sigrid Stroobants, Koen Augustyns, Guido R Y De Meyer, Pieter Van Der Veken, Wim Martinet
Autophagy is a cell survival mechanism hijacked by advanced tumors to endure a rough microenvironment. Late autophagy inhibitors such as (hydroxy)chloroquine have been used clinically to halt tumor progression with modest success. However, given the toxic nature of these compounds and their lack of specificity, novel targets should be considered. We recently identified a benzotropolone derivative that significantly inhibited the essential autophagy protein ATG4B. Therefore, we synthesized and tested additional benzotropolone compounds to identify a promising ATG4B inhibitor that impairs autophagy both in vitro and in vivo...
June 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28638875/whole-body-vibration-improves-attention-and-motor-performance-in-mice-depending-on-the-duration-of-the-whole-body-vibration-session
#2
Jan N Keijser, Marieke J G van Heuvelen, Csaba Nyakas, Kata Tóth, Regien G Schoemaker, Edzard Zeinstra, Eddy A van der Zee
BACKGROUND: Whole body vibration (WBV) is a form of physical stimulation via mechanical vibrations transmitted to a subject. It is assumed that WBV induces sensory stimulation in cortical brain regions through the activation of skin and muscle receptors responding to the vibration. The effects of WBV on muscle strength are well described. However, little is known about the impact of WBV on the brain. Recently, it was shown in humans that WBV improves attention in an acute WBV protocol...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28630289/green-mamba-peptide-targets-type-2-vasopressin-receptor-against-polycystic-kidney-disease
#3
Justyna Ciolek, Helen Reinfrank, Loïc Quinton, Say Viengchareun, Enrico A Stura, Laura Vera, Sabrina Sigismeau, Bernard Mouillac, Hélène Orcel, Steve Peigneur, Jan Tytgat, Laura Droctové, Fabrice Beau, Jerome Nevoux, Marc Lombès, Gilles Mourier, Edwin De Pauw, Denis Servent, Christiane Mendre, Ralph Witzgall, Nicolas Gilles
Polycystic kidney diseases (PKDs) are genetic disorders that can cause renal failure and death in children and adults. Lowering cAMP in cystic tissues through the inhibition of the type-2 vasopressin receptor (V2R) constitutes a validated strategy to reduce disease progression. We identified a peptide from green mamba venom that exhibits nanomolar affinity for the V2R without any activity on 155 other G-protein-coupled receptors or on 15 ionic channels. Mambaquaretin-1 is a full antagonist of the V2R activation pathways studied: cAMP production, beta-arrestin interaction, and MAP kinase activity...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28621254/use-of-microcomputed-tomography-to-measure-the-relaxin-induced-expansion-of-intrapubic-ligaments-in-mice
#4
Heather A Zimmerman, Richard P Kennan, Chunlian Zhang, Kashmira Shah, Douglas G Johns, Joseph J Lynch, Maya Dajee
Relaxin is a 6-kDa peptide in the insulin superfamily of hormones. In addition to its effects on reproductive and musculoskeletal ligaments, relaxin has demonstrated beneficial effects on cardiac, renal, and vascular systems in preclinical models. The mouse intrapubic ligament ex vivo bioassay is the current standard for measuring in vivo relaxin bioactivity. However, this bioassay necessitates euthanasia and dissection of large cohorts to measure the intrapubic ligament at specified time points. We hypothesized that μCT imaging could be used to reduce the number of animals necessary for the intrapubic ligament bioassay by enabling a single animal to be followed longitudinally throughout the study rather than euthanizing different cohorts at established time points...
June 15, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28620895/the-standardized-postoperative-checklist-for-bariatric-surgery-a-tool-for-safe-early-discharge
#5
Stefanie R van Mil, Lucia E Duinhouwer, Guido H H Mannaerts, L Ulas Biter, Martin Dunkelgrun, Jan A Apers
BACKGROUND: Morbidly obese patients are at higher risk of complications after surgery. In bariatric surgery, pre- and intra-operative checklists are commonly used to identify high-risk patients preoperatively, to decrease the number of postoperative complications. This pilot study evaluates the effect of a postoperative checklist in bariatric surgery, addressing regularly measured parameters, on the occurrence and early recognition of complications. METHODS: An in-house developed postoperative checklist was used on the first postoperative day after bariatric surgery and included information on nausea, pain, temperature, heart rate, and laboratory markers...
June 15, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28617382/-dimebon-delays-the-onset-of-symptoms-of-fus-proteinopathy-in-transgenic-mice
#6
A V Maltsev, A V Deykin, R K Ovchinnikov, M M Chicheva, E A Kovrazhkina, O D Razinskaya, E V Bronovitsky, A I Budevich, Yu K Kirikovich, S O Bachurin, A A Ustyugov, V I Skvortsova
AIM: To evaluate an effect of dimebon on the onset of symptomatic stage in FUS.1-513 transgenic mice - a new genetic model of neurodegeneration, and to study the dynamics of disease progression in the terminal stage. MATERIAL AND METHODS: The study was carried out on males of line FUS1-513 with the contribution of genes from CD1 strains. Mice of the experimental group (n=28) received dimebon with water in the concentration of 70 mcg/ml starting from the 35th day of life...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28615212/conserved-v%C3%AE-1-binding-geometry-in-a-setting-of-locus-disparate-phla-recognition-by-%C3%AE-%C3%AE-%C3%AE-tcrs-insight-into-recognition-of-hiv-peptides-by-tcr
#7
Yi Shi, Ai Kawana-Tachikawa, Feng Gao, Jianxun Qi, Chuansheng Liu, Jia Gao, Hao Cheng, Takamasa Ueno, Aikichi Iwamoto, George F Gao
Given a limited set of TCR V genes which are used to create TCRs that are reactive to different ligands, such as MHC class I, MHC class II and MHC-like proteins (for example, MIC molecules and CD1 molecules), the Vδ1 segment can be rearranged with Dδ-Jδ-Cδ or Jα-Cα segments, to form classical γδTCR or uncommon αβTCR using a Vδ1 segment (δ/αβTCR). Here we have determined two complex structures of the δ/αβTCRs (S19-2 and TU55) bound to different locus-disparate MHCIs with HIV peptides (HLA-A*2402-Nef138-10 and HLA-B*3501-Pol448-9)...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28606223/murine-astrovirus-infection-and-transmission-in-neonatal-cd1-mice
#8
Susan Compton, Carmen J Booth, James D Macy
Murine astrovirus (MuAstV) is a recently identified, widespread infection among laboratory mice. Our goal was to determine the duration of MuAstV infection, susceptibility of pups, and efficacy of soiled-bedding sentinels and environmental monitoring. Eight CD1 dams and their litters of 3-d-old pups and 8 CD1 dams and their litters of 13-d-old mice were inoculatedorally with MuAstV. Neither dams nor offspring demonstrated any clinical signs, and MuAstV had little to no effect on weight gain in pups. MuAstV RNA was detected in feces from 15 of the 16 dams through postnatal day (PND) 21, and 9 dams were still shedding MuAstV at PND 42...
June 12, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28604784/potential-therapeutic-impact-of-cd13-expression-in-non-small-cell-lung-cancer
#9
Lars Henning Schmidt, Caroline Brand, Janine Stucke-Ring, Christoph Schliemann, Torsten Kessler, Saliha Harrach, Michael Mohr, Dennis Görlich, Alessandro Marra, Ludger Hillejan, Carsten Müller-Tidow, Georg Lenz, Eva Wardelmann, Rainer Wiewrodt, Wolfgang E Berdel, Christian Schwöppe, Wolfgang Hartmann
BACKGROUND: Aminopeptidase N (CD13) is a zinc-binding protease that has functional effects on both cancerogenesis and tumor angiogenesis. Since CD13 is an antigen suitable for molecular targeted therapies (e.g. tTF-NGR induced tumor vascular infarction), we evaluated its impact in NSCLC patients, and tested the effects of the CD13-targeted fusion protein tTF-NGR (truncated tissue factor (tTF) containing the NGR motif: asparagine-glycine-arginine) in vivo in nude mice. METHODS: Expression of both CD13 and CD31 was studied in 270 NSCLC patients by immunohistochemistry...
2017: PloS One
https://www.readbyqxmd.com/read/28604727/bub1-positions-mad1-close-to-knl1-melt-repeats-to-promote-checkpoint-signalling
#10
Gang Zhang, Thomas Kruse, Blanca López-Méndez, Kathrine Beck Sylvestersen, Dimitriya H Garvanska, Simone Schopper, Michael Lund Nielsen, Jakob Nilsson
Proper segregation of chromosomes depends on a functional spindle assembly checkpoint (SAC) and requires kinetochore localization of the Bub1 and Mad1/Mad2 checkpoint proteins. Several aspects of Mad1/Mad2 kinetochore recruitment in human cells are unclear and in particular the underlying direct interactions. Here we show that conserved domain 1 (CD1) in human Bub1 binds directly to Mad1 and a phosphorylation site exists in CD1 that stimulates Mad1 binding and SAC signalling. Importantly, fusion of minimal kinetochore-targeting Bub1 fragments to Mad1 bypasses the need for CD1, revealing that the main function of Bub1 is to position Mad1 close to KNL1 MELT repeats...
June 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28600553/topological-phase-transition-in-single-crystals-of-cd1-xznx-3as2
#11
Hong Lu, Xiao Zhang, Yi Bian, Shuang Jia
Single crystals of (Cd1-xZnx)3As2 were synthesized from high-temperature solutions and characterized in terms of their structural and electrical properties. Based on the measurements of resistivity and Hall signals, we revealed a chemical-doping-controlled transition from a three-dimensional Dirac semimetal to a semiconductor with a critical point xc ~ 0.38. We observed structural transitions from a body-center tetragonal phase to a primitive tetragonal phase then back to a body-center tetragonal phase in the solid solutions as well, which are irrelevant to the topological phase transition...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28597017/folliculotropic-mycosis-fungoides-with-skewed-t-cell-receptor-cdr3-motif-suggestive-of-lipid-antigen-selection
#12
Panagiota Mantaka, Agnieszka Malecka, Gunhild Trøen, Per Helsing, Petter Gjersvik, Klaus Beiske, Jan Delabie
Folliculotropic mycosis fungoides (FMF), a variant of mycosis fungoides (MF) with distinct clinical features, is characterized by infiltration of malignant T cells in hair follicles. This raises the hypothesis that antigens in the hair follicle may contribute to the pathogenesis of FMF. T-cell receptor β gene (TRB) sequences as well as dendritic cell subsets in patients with FMF (n = 21) and control patients with MF (n = 20) were studied to explore this hypothesis. A recurrent usage of the TRB junctional genes TRBJ2-1 and TRBJ2-7 was found in patients with FMF compared with those with MF...
June 9, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28587692/atomic-scale-structural-characterization-of-epitaxial-cd-cr-te-magnetic-semiconductor
#13
Bastien Bonef, Hervé Boukari, Adeline Grenier, Isabelle Mouton, Pierre-Henri Jouneau, Hidekazu Kinjo, Shinji Kuroda
A detailed knowledge of the atomic structure of magnetic semiconductors is crucial to understanding their electronic and magnetic properties, which could enable spintronic applications. Energy-dispersive X-ray spectrometry (EDX) in the scanning transmission electron microscope and atom probe tomography (APT) experiments reveal the formation of Cr-rich regions in Cd1-x Cr x Te layers grown by molecular beam epitaxy. These Cr-rich regions occur on a length scale of 6-10 nm at a nominal Cr composition of x=0.034 and evolve toward an ellipsoidal shape oriented along directions at a composition of x=0...
June 7, 2017: Microscopy and Microanalysis
https://www.readbyqxmd.com/read/28578824/improving-the-malaria-transmission-blocking-activity-of-a-plasmodium-falciparum-48-45-based-vaccine-antigen-by-spytag-spycatcher-mediated-virus-like-display
#14
Susheel K Singh, Susan Thrane, Christoph M Janitzek, Morten A Nielsen, Thor G Theander, Michael Theisen, Ali Salanti, Adam F Sander
Malaria is a devastating disease caused by Plasmodium parasites, resulting in almost 0.5 million deaths per year. The Pfs48/45 protein exposed on the P. falciparum sexual stages is one of the most advanced antigen candidates for a transmission-blocking (TB) vaccine in the clinical pipeline. However, it remains essential to identify an optimal vaccine formulation that can facilitate induction of a long-lasting TB anti-Pfs48/45 response. Here we report on the development and evaluation of two Pfs48/45-based virus-like particle (VLP) vaccines generated using the AP205 SpyTag/Catcher VLP system...
May 31, 2017: Vaccine
https://www.readbyqxmd.com/read/28575276/structural-determinants-of-apobec3b-non-catalytic-domain-for-molecular-assembly-and-catalytic-regulation
#15
Xiao Xiao, Hanjing Yang, Vagan Arutiunian, Yao Fang, Guillaume Besse, Cherie Morimoto, Brett Zirkle, Xiaojiang S Chen
The catalytic activity of human cytidine deaminase APOBEC3B (A3B) has been correlated with kataegic mutational patterns within multiple cancer types. The molecular basis of how the N-terminal non-catalytic CD1 regulates the catalytic activity and consequently, biological function of A3B remains relatively unknown. Here, we report the crystal structure of a soluble human A3B-CD1 variant and delineate several structural elements of CD1 involved in molecular assembly, nucleic acid interactions and catalytic regulation of A3B...
May 30, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28572546/identification-of-a-deleterious-phase-in-photocatalyst-based-on-cd1%C3%A2-%C3%A2-xznxs-zn-oh-2-by-simulated-xrd-patterns
#16
Svetlana Cherepanova, Dina Markovskaya, Ekaterina Kozlova
The X-ray diffraction (XRD) pattern of a deleterious phase in the photocatalyst based on Cd1 - xZnxS/Zn(OH)2 contains two relatively intense asymmetric peaks with d-spacings of 2.72 and 1.56 Å. Very small diffraction peaks with interplanar distances of (d) ≃ 8.01, 5.40, 4.09, 3.15, 2.49 and 1.35 Å are characteristic of this phase but not always observed. To identify this phase, the XRD patterns for sheet-like hydroxide β-Zn(OH)2 and sheet-like hydrozincite Zn5(CO3)2(OH)6 as well as for turbostratic hydrozincite were simulated...
June 1, 2017: Acta Crystallographica Section B, Structural Science, Crystal Engineering and Materials
https://www.readbyqxmd.com/read/28561933/cx36-cx43-and-cx45-in-mouse-and-rat-cerebellar-cortex-species-specific-expression-compensation-in-cx36-null-mice-and-co-localization-in-neurons-vs-glia
#17
J I Nagy, J E Rash
Electrical synapses formed by connexin36 (Cx36)-containing gap junctions between interneurons in the cerebellar cortex have been well characterized, including those formed between basket cells and between Golgi cells, and there is gene reporter-based evidence for the expression of connexin45 (Cx45) in the cerebellar molecular layer. Here, we used immunofluorescence approaches to further investigate expression patterns of Cx36 and Cx45 in this layer, and to examine localization relationships of these connexins with each other and with glial connexin43 (Cx43)...
May 31, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28557390/-the-battery-of-tests-for-behavioral-phenotyping-of-aging-animals-in-the-experiment
#18
Ya V Gorina, Yu K Komleva, O L Lopatina, V V Volkova, A I Chernykh, A A Shabalova, A A Semenchukov, R Ya Olovyannikova, A B Salmina
The purpose of the study was to develop a battery of tests to study social and cognitive impairments for behavioral phenotyping of aging experimental animals with physiological neurodegeneration. Object of the study were outbred CD1 mice in the following groups: 1st group - 12-month old male mice (physiological aging); 2nd group - 2-month old male mice (control group). Social recognition test, elevated plus maze test (EPM), open field test, light-dark box test, and Fear conditioning protocol were used to estimate the neurological status of experimental animals...
2017: Advances in Gerontology, Uspekhi Gerontologii
https://www.readbyqxmd.com/read/28549091/regional-retinal-ganglion-cell-axon-loss-in-a-murine-glaucoma-model
#19
Julie A Schaub, Elizabeth C Kimball, Matthew R Steinhart, Cathy Nguyen, Mary E Pease, Ericka N Oglesby, Joan L Jefferys, Harry A Quigley
Purpose: To determine if retinal ganglion cell (RGC) axon loss in experimental mouse glaucoma is uniform in the optic nerve. Methods: Experimental glaucoma was induced for 6 weeks with a microbead injection model in CD1 (n = 78) and C57BL/6 (B6, n = 68) mice. From epoxy-embedded sections of optic nerve 1 to 2 mm posterior to the globe, total nerve area and regional axon density (axons/1600 μm2) were measured in superior, inferior, nasal, and temporal zones. Results: Control eyes of CD1 mice have higher axon density and more total RGCs than control B6 mice eyes...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28544589/methionine-tumor-starvation-by-erythrocyte-encapsulated-methionine-gamma-lyase-activity-controlled-with-per-os-vitamin-b6
#20
Fabien Gay, Karine Aguera, Karine Sénéchal, Angie Tainturier, Willy Berlier, Delphine Maucort-Boulch, Jérôme Honnorat, Françoise Horand, Yann Godfrin, Vanessa Bourgeaux
Erymet is a new therapy resulting from the encapsulation of a methionine gamma-lyase (MGL; EC number 4.4.1.11) in red blood cells (RBC). The aim of this study was to evaluate erymet potential efficacy in methionine (Met)-dependent cancers. We produced a highly purified MGL using a cGMP process, determined the pharmacokinetics/pharmacodynamics (PK/PD) properties of erymet in mice, and assessed its efficacy on tumor growth prevention. Cytotoxicity of purified MGL was tested in six cancer cell lines. CD1 mice were injected with single erymet product supplemented or not with vitamin B6 vitamer pyridoxine (PN; a precursor of PLP cofactor)...
June 2017: Cancer Medicine
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