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https://www.readbyqxmd.com/read/28820943/the-active-site-flexibility-of-mycobacterium-tuberculosis-isocitrate-lyase-in-dimer-form
#1
Yie-Vern Lee, Sybing Choi, Habibah Wahab, Yee Siew Choong
Tuberculosis (TB) still remains as global threat due to the emerging of drug resistant strain. Instead of focus on drug target of active stage TB, we are highlighting the isocitrate lyase (ICL) at the dormant stage TB. ICL is one of the persistent factors for Mycobacterium tuberculosis (MTB) to survive during dormant phase. In addition, the absent of ICL in human has made ICL a potential drug target for TB therapy. However, the dynamics details of ICL which could give insights to the ICL-ligand interaction is yet to be solved...
August 18, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28792090/distinct-activation-mechanisms-trigger-the-trypanocidal-activity-of-dna-damaging-prodrugs
#2
Emma Louise Meredith, Ambika Kumar, Aya Konno, Joanna Szular, Sam Alsford, Karin Seifert, David Horn, Shane R Wilkinson
Quinone-based compounds have been exploited to treat infectious diseases and cancer, with such chemicals often functioning as inhibitors of key metabolic pathways or as prodrugs. Here, we screened an aziridinyl-1,4-benzoquinone (ABQ) library against the causative agents of trypanosomiasis, and cutaneous leishmaniasis, identifying several potent structures that exhibited EC50 values of <100 nM. However, these compounds also displayed significant toxicity towards mammalian cells indicating that they are not suitable therapies for systemic infections...
August 9, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28790537/refractive-outcomes-of-posterior-chamber-phakic-intraocular-lens-implantation-for-correction-of-myopia-and-myopic-astigmatism
#3
Melisa Ahmedbegovic Pjano, Ajla Pidro, Alma Biscevic, Senad Grisevic, Bojana Pandzic, Vesna Cerovic
OBJECTIVES: The aim was to examine efficacy and safety after Implantable Collamer Lens (ICL) implantation for correction of myopia et myopic astigmatism. METHODS: This prospective clinical study included 28 eyes of 16 patients which underwent implantation of ICL for correction of myopia up to -18,00 diopters (D) and myopic astigmatism up to -6,00 D in the Eye Clinic Svjetlost Sarajevo, from January 2013 to January 2016. Uncorrected distance visual acuity (UDVA), spherical equivalent (SE), corrected distance visual acuity (CDVA), intraocular pressure (IOP), endothelial cell (EC) density were evaluated at one, six and twelve months...
April 2017: Medical Archives
https://www.readbyqxmd.com/read/28774525/v4b-implantable-collamer-lens-versus-intacs-corneal-rings-to-manage-anisometropic-myopic-amblyopia-in-children
#4
Sherif Ahmed Eissa, Mohamed Wagih El-Deeb, Mahmoud Salah Hendawi
OBJECTIVE: To compare the safety and efficacy of phakic intraocular lens (PIOL) versus intrastromal corneal ring segments (Intacs), for correcting high myopic anisometropia in amblyopic children. DESIGN: Nonrandomized prospective multi-center study. PARTICIPANTS: Thirty children, aged between 4 and 12 years, with unilateral high myopic anisometropic amblyopia were included in this study. METHODS: Patients who were prospectively subdivided into group A, with mean preoperative manifest refraction spherical equivalent (MRSE) of -12...
August 2017: Canadian Journal of Ophthalmology. Journal Canadien D'ophtalmologie
https://www.readbyqxmd.com/read/28746729/pleurotus-sajor-caju-can-be-used-to-synthesize-silver-nanoparticles-with-anti-fungal-activity-against-candida-albicans
#5
Siti Fadhilah Musa, Ting Seng Yeat, Laina Zarisa Mohd Kamal, Yasser M Tabana, Mowaffaq Adam Ahmed, Ahmad El Ouweini, Lim Vuangao, Lee Chee Keong, Doblin Sandai
BACKGROUND: Green synthesis of silver nanoparticles (AgNPs) has become widely practiced worldwide. In this study, AgNPs were synthesized using a hot-water extract of the edible mushroom, Pleurotus sajor-caju. The product, PSC-AgNPs, was characterized by using UV-Vis spectra, DLS analysis, TEM, XRD and FTIR spectrometry. To assess its antifungal activity against C. albicans, gene transcription and protein expression analyses were conducted for CaICL1 and its product, ICL using RT-qPCR and western blot, respectively...
July 26, 2017: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/28740486/evolution-of-acinetobacter-baumannii-in-vivo-international-clone-ii-more-resistance-to-ceftazidime-mutation-in-ptk
#6
Xiaoting Hua, Zhihui Zhou, Qing Yang, Qiucheng Shi, Qingye Xu, Jianfeng Wang, Keren Shi, Feng Zhao, Long Sun, Zhi Ruan, Yan Jiang, Yunsong Yu
Acinetobacter baumannii is an important nosocomial pathogen worldwide. A more comprehensive understanding of the within-host genomic evolution of A. baumannii would provide a molecule basis for improving treatment of A. baumannii infection. To understand the evolutionary mechanism facilitating A. baumannii survived in human body, we here reported the genomic analysis of A. baumannii isolated sampled from Chinese patients. We used whole-genome sequence of A. baumannii isolates from the same patient to determine single-nucleotide variants, insertion sequence mapping, and gene change...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28740361/matched-population-comparison-of-visual-outcomes-and-patient-satisfaction-between-3-modalities-for-the-correction-of-low-to-moderate-myopic-astigmatism
#7
Sri Ganesh, Sheetal Brar, Archana Pawar
PURPOSE: To compare toric implantable collamer lens (T-ICL), femto-LASIK, and ReLEx SMILE for the treatment of low to moderate myopic astigmatism in terms of long-term visual and refractive outcomes and predictability of astigmatic correction. MATERIALS AND METHODS: The study included 30 eyes from 30 patients between the age groups of 21 and 40 years, undergoing bilateral surgery with any of the three procedures - T-ICL, femto-LASIK, or ReLEx SMILE - for correction of myopic astigmatism within the range of -3 to -8 D spherical equivalent (SE), with a minimum astigmatism of -0...
2017: Clinical Ophthalmology
https://www.readbyqxmd.com/read/28729370/anterior-segment-optical-coherence-tomography-angle-and-vault-analysis-after-toric-and-non-toric-implantable-collamer-lens-v4c-implantation-in-patients-with-high-myopia
#8
Guillermo Garcia-De la Rosa, Andrew Olivo-Payne, Juan Carlos Serna-Ojeda, Maria Sandra Salazar-Ramos, Alejandro Lichtinger, Arturo Gomez-Bastar, Arturo Ramirez-Miranda, Alejandro Navas, Enrique O Graue-Hernandez
OBJECTIVE: To assess anterior segment changes, including iridocorneal angle and vault, after toric and non-toric implantable collamer lens (ICL) V4c (STAAR Surgical AG) implantation under different lighting conditions. METHODS: Longitudinal, prospective, case series. Patients with high myopia (>6 dioptres) underwent toric and non-toric ICL V4c implantation. Optical coherence tomography measurements were taken under different lighting conditions preoperatively and at 1 week and 1, 6 and 12 months of follow-up...
July 20, 2017: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/28694253/implementing-the-compassion-intervention-a-model-for-integrated-care-for-people-with-advanced-dementia-towards-the-end-of-life-in-nursing-homes-a-naturalistic-feasibility-study
#9
Kirsten J Moore, Bridget Candy, Sarah Davis, Anna Gola, Jane Harrington, Nuriye Kupeli, Victoria Vickerstaff, Michael King, Gerard Leavey, Irwin Nazareth, Rumana Z Omar, Louise Jones, Elizabeth L Sampson
BACKGROUND: Many people with dementia die in nursing homes, but quality of care may be suboptimal. We developed the theory-driven 'Compassion Intervention' to enhance end-of-life care in advanced dementia. OBJECTIVES: To (1) understand how the Intervention operated in nursing homes in different health economies; (2) collect preliminary outcome data and costs of an interdisciplinary care leader (ICL) to facilitate the Intervention; (3) check the Intervention caused no harm...
July 10, 2017: BMJ Open
https://www.readbyqxmd.com/read/28687272/interstrand-crosslink-repair-as-a-target-for-hdac-inhibition
#10
REVIEW
Teodora Nikolova, Nicole Kiweler, Oliver H Krämer
DNA interstrand crosslinks (ICLs) covalently connect complementary DNA strands. Consequently, DNA replication and transcription are hampered, DNA damage responses (DDR) are initiated, and cell death is triggered. Therefore, drugs inducing ICLs are effective against rapidly growing cancer cells. However, tumors engage a complicated enzymatic machinery to repair and survive ICLs. Several factors, including the post-translational acetylation/deacetylation of lysine residues within proteins, control this network...
July 4, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28684355/studies-of-protein-protein-interactions-in-fanconi-anemia-pathway-to-unravel-the-dna-interstrand-crosslink-repair-mechanism
#11
Mohd Quadir Siddiqui, Yogendra S Rajpurohit, Pankaj S Thapa, Ganesh Kumar Maurya, Kuheli Banerjee, Mudassar Ali Khan, Pragnya Panda, Syed K Hasan, Nikhil Gadewal, Hari S Misra, Ashok K Varma
Fanconi anemia (FA), a cancer predisposition syndrome exhibits hallmark feature of radial chromosome formation, and hypersensitivity to DNA crosslinking agents. A set of FA pathway proteins mainly FANCI, FANCD2 and BRCA2 are expressed to repair the covalent crosslink between the dsDNA. However, FA, BRCA pathways play an important role in DNA ICL repair as well as in homologous recombination repair, but the presumptive role of FA-BRCA proteins has not clearly explored particularly in context to function associated protein-protein interactions (PPIs)...
July 3, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28679637/mechanism-based-inactivator-of-isocitrate-lyases-1-and-2-from-mycobacterium-tuberculosis
#12
Truc V Pham, Andrew S Murkin, Margaret M Moynihan, Lawrence Harris, Peter C Tyler, Nishant Shetty, James C Sacchettini, Hsiao-Ling Huang, Thomas D Meek
Isocitrate lyase (ICL, types 1 and 2) is the first enzyme of the glyoxylate shunt, an essential pathway for Mycobacterium tuberculosis (Mtb) during the persistent phase of human TB infection. Here, we report 2-vinyl-d-isocitrate (2-VIC) as a mechanism-based inactivator of Mtb ICL1 and ICL2. The enzyme-catalyzed retro-aldol cleavage of 2-VIC unmasks a Michael substrate, 2-vinylglyoxylate, which then forms a slowly reversible, covalent adduct with the thiolate form of active-site Cys191 2-VIC displayed kinetic properties consistent with covalent, mechanism-based inactivation of ICL1 and ICL2 with high efficiency (partition ratio, <1)...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28668303/ca-2-activated-cl-current-is-antiarrhythmic-by-reducing-both-spatial-and-temporal-heterogeneity-of-cardiac-repolarization
#13
Bence Hegyi, Balázs Horváth, Krisztina Váczi, Mónika Gönczi, Kornél Kistamás, Ferenc Ruzsnavszky, Roland Veress, Leighton T Izu, Ye Chen-Izu, Tamás Bányász, János Magyar, László Csernoch, Péter P Nánási, Norbert Szentandrássy
The role of Ca(2+)-activated Cl(-) current (ICl(Ca)) in cardiac arrhythmias is still controversial. It can generate delayed afterdepolarizations in Ca(2+)-overloaded cells while in other studies incidence of early afterdepolarization (EAD) was reduced by ICl(Ca). Therefore our goal was to examine the role of ICl(Ca) in spatial and temporal heterogeneity of cardiac repolarization and EAD formation. Experiments were performed on isolated canine cardiomyocytes originating from various regions of the left ventricle; subepicardial, midmyocardial and subendocardial cells, as well as apical and basal cells of the midmyocardium...
August 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28662940/impacts-of-implantable-collamer-lens-v4c-placement-on-angle-measurements-made-by-optical-coherence-tomography-two-year-follow-up
#14
José Ignacio Fernández-Vigo, Ana Macarro-Merino, Cristina Fernández-Vigo, José Ángel Fernández-Vigo, Lucía De-Pablo-Gómez-de-Liaño, Cristina Fernández-Pérez, Julián García-Feijóo
PURPOSE: To determine iridocorneal angle changes produced after two years of implantable collamer lens(®) (ICL) V4c (STAAR Surgical AG) placement by Fourier-domain optical coherence tomography (FD-OCT). DESIGN: Prospective interventional case series. METHODS: In 54 eyes of 27 myopic subjects FD-OCT (RTVue(®), Optovue Inc.) iridocorneal angle measurements were made before, and 1 month, 3 months, 1 year and 2 years after ICL implant. Trabecular-iris angle (TIA), angle opening distance 500 μm from the scleral spur (AOD500) and iridotrabecular contact length (TICL) were compared among these time points and the quadrants nasal, temporal and inferior...
June 26, 2017: American Journal of Ophthalmology
https://www.readbyqxmd.com/read/28654754/potential-strategies-to-target-protein-protein-interactions-in-the-dna-damage-response-and-repair-pathways
#15
Naoaki Fujii
This review article discusses some insights about generating novel mechanistic inhibitors of the DNA damage response and repair (DDR) pathways by focusing on protein-protein interactions (PPIs) of the key DDR components. General requirements for PPI strategies, such as selecting the target PPI site on the basis of its functionality, are discussed first. Next, on the basis of functional rationale and biochemical feasibility to identify a PPI inhibitor, 26 PPIs in DDR pathways (BER, MMR, NER, NHEJ, HR, TLS, and ICL repair) are specifically discussed for inhibitor discovery to benefit cancer therapies using a DNA-damaging agent...
July 12, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28652643/hybrid-tandem-quantum-dot-organic-photovoltaic-cells-with-complementary-near-infrared-absorption
#16
Taesoo Kim, Elenita Palmiano, Ru-Ze Liang, Hanlin Hu, Banavoth Murali, Ahmad R Kirmani, Yuliar Firdaus, Yangqin Gao, Arif Sheikh, Mingjian Yuan, Omar F Mohammed, Sjoerd Hoogland, Pierre M Beaujuge, Edward H Sargent, Aram Amassian
Monolithically integrated hybrid tandem solar cells that effectively combine solution-processed colloidal quantum dot (CQD) and organic bulk heterojunction subcells to achieve tandem performance that surpasses the individual subcell efficiencies have not been demonstrated to date. In this work, we demonstrate hybrid tandem cells with a low bandgap PbS CQD subcell harvesting the visible and near-infrared photons and a polymer:fullerene-poly (diketopyrrolopyrrole-terthiophene) (PDPP3T):[6,6]-phenyl-C60-butyric acid methyl ester (PC61BM)-top cell absorbing effectively the red and near-infrared photons of the solar spectrum in a complementary fashion...
May 29, 2017: Applied Physics Letters
https://www.readbyqxmd.com/read/28650856/a-rare-case-of-pupillary-block-glaucoma-following-centraflow-implantable-collamer-lens-surgery
#17
Isha G Grover, Sirisha Senthil, Somasheila Murthy, Jagadesh C Reddy
A 28-year-old lady with a refractive error of -11.0 D sphere/-1.50 D cylinder at 160 degrees in the right eye underwent an uneventful Implantable Collamer Lens surgery (ICL) with a V4c model, which uses a central Aquaport. This ICL does not require preoperative laser iridotomy or surgical iridectomy, as the centraflow opening is designed to prevent pupillary block. At postoperative day 1, her visual acuity in the right eye was 20/400, with diffuse microcystic corneal edema with fixed, dilated pupil and high intraocular pressure...
August 2017: Journal of Glaucoma
https://www.readbyqxmd.com/read/28645378/preparation-of-stable-nitrogen-mustard-dna-interstrand-cross-link-analogs-for-biochemical-and-cell-biological-studies
#18
Alejandra Castaño, Upasana Roy, Orlando D Schärer
Nitrogen mustards (NMs) react with two bases on opposite strands of a DNA duplex to form a covalent linkage, yielding adducts called DNA interstrand cross-links (ICLs). This prevents helix unwinding, blocking essential processes such as replication and transcription. Accumulation of ICLs causes cell death in rapidly dividing cells, especially cancer cells, making ICL-forming agents like NMs valuable in chemotherapy. However, the repair of ICLs can contribute to chemoresistance through a number of pathways that remain poorly understood...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28640145/comparison-of-implantable-collamer-lens-visian-icl-v4-and-icl-v4c-for-high-myopia-a-cohort-study
#19
COMPARATIVE STUDY
Ying Tian, Hai-Bo Jiang, Jian Jiang, Dan Wen, Xiao-Bo Xia, Wei-Tao Song
The aim of this study was to investigate the visual quality of the 2 kinds of intraocular lens: Visian implantable collamer lens (ICL) V4 and Visian ICL V4c implantations for high myopia.Twenty cases (20 eyes) with high myopia who received Visian ICL V4 implantation and 18 cases (18 eyes) with high myopia who received Visian ICL V4c implantation in our hospital from April 1, 2014 to November 31, 2016 were enrolled. In 1-month follow-up, near vision, best corrected distant visual acuity (BCVA), uncorrected distant visual acuity (UDVA), and wavefront aberrations were measured, and compensation factor was calculated...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28638843/susceptibility-to-cryptococcal-meningoencephalitis-associated-with-idiopathic-cd4-lymphopenia-and-secondary-germline-or-acquired-defects
#20
Anil A Panackal, Lindsey B Rosen, Gulbu Uzel, Michael J Davis, Guowu Hu, Adebowale Adeyemo, Fasil Tekola-Ayele, Andrea Lisco, Christopher Diachok, Jonathan D Kim, Dawn Shaw, Irini Sereti, Jennifer Stoddard, Julie Niemela, Sergio D Rosenzweig, John E Bennett, Peter R Williamson
Idiopathic CD4(+) lymphopenia (ICL) predisposes to opportunistic infections (OIs) but can often remain asymptomatic and does not have a strong association with monogenic mutations. Likewise, cryptococcal meningoencephalitis, the most common OI in ICL, is not strongly associated with monogenic mutations. In this study, we describe 2 patients with ICL plus an additional immune defect: one from an E57K genetic mutation in the nuclear factor-κβ essential modulator, and the other with acquired autoantibodies to granulocyte-macrophage colony-stimulating factor...
2017: Open Forum Infectious Diseases
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