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Liang Ma, Omar Salas, Kyle Bowler, Maor Bar-Peled, Amir Sharon
Can accumulation of a normally transient metabolite affect fungal biology? UDP-4-keto-6-deoxyglucose (UDP-KDG) represents an intermediate stage in conversion of UDP-glucose to UDP-rhamnose. Normally, UDP-KDG is not detected in living cells, because it is quickly converted to UDP-rhamnose by the enzyme UDP-4-keto-6-deoxyglucose-3,5-epimerase/-4-reductase (ER). We previously found that deletion of the er gene in Botrytis cinerea resulted in accumulation of UDP-KDG to levels that were toxic to the fungus due to destabilization of the cell wall...
November 21, 2017: MBio
Mohammad Kashif, Shams Tabrez, Atahar Husein, Mohd Arish, Ponnusamy Kalaiarasan, Partha Pratim Manna, Naidu Subbarao, Yusuf Akhter, Abdur Rub
Leishmania, a protozoan parasite that causes leishmaniasis, affects 1-2 million people every year worldwide. Leishmaniasis is a vector born disease and characterized by a diverse group of clinical syndromes. Current treatment is limited because of drug resistance, high cost, poor safety and low efficacy. The urgent need for potent agents against Leishmania has led to significant advances in the development of novel antileishmanial drugs. β-galactofuranose (β-Galf) is an important component of Leishmanial cell surface matrix and plays a critical role in the pathogenesis of parasite...
October 23, 2017: Journal of Cellular Biochemistry
Julia S Martín Del Campo, Meital Eckshtain-Levi, Pablo Sobrado
Aspergillus fumigatus is a human pathogen responsible for deadly infections in immune-compromised patients. A potential strategy for treating A. fumigatus infections is by targeting the biosynthesis of cell wall components, such as galactofuranase, which is absent in humans. Galactofuranose biosynthesis is initiated by the flavoenzyme UDP-galactopyranose mutase (UGM), which converts UDP-galactopyranose (UDP-Galp) to UDP-galactofuranose (UDP-Galf). UGM requires the reduced form of the flavin for activity, which is obtained by reacting with NADPH...
November 4, 2017: Biochemical and Biophysical Research Communications
Jian Fu, Huixiao Fu, Marc Dieu, Iman Halloum, Laurent Kremer, Yufen Xia, Weidong Pan, Stéphane P Vincent
In this study, we report a dynamic combinatorial approach along with highly efficient in situ screening to identify inhibitors of UDP-galactopyranose mutase (UGM), an essential enzyme involved in mycobacterial cell wall biosynthesis. These two technologies converged to the identification of a new UGM inhibitor chemotype. Importantly, the best molecule not only displayed high affinity for the target enzyme but also exhibited in vitro growth inhibition against whole Mycobacterium tuberculosis cells. The strategy described here provides an avenue to explore a novel inhibitor class for UGMs and paves the way for further pharmacological studies on tuberculosis treatment...
September 26, 2017: Chemical Communications: Chem Comm
Julia S Martin Del Campo, Meital Eckshtain-Levi, Nancy J Vogelaar, Pablo Sobrado
Aspergillus fumigatus is an opportunistic human pathogen responsible for deadly, invasive infections in immunocompromised patients. The A. fumigatus cell wall is a complex network of polysaccharides among them galactofuran, which is absent in humans. UDP-galactopyranose mutase (UGM) catalyzes the conversion of UDP-galactofuranose (UDP-Galf) to UDP-galactopyranose (UDP-Galp) and is an important virulence factor. UGM is a flavin-dependent enzyme that requires the reduced flavin for activity; flavin reduction is achieved by reaction with NADPH...
September 7, 2017: Scientific Reports
Matthias Hofer, Kathrin Klein, Bastian Malzkorn, Alice Martin, Christian Weigel, Ole Martin
This article aims to provide useful suggestions for the implementation of new courses with peer-assisted learning (PAL) in undergraduate medical education (UGME). It presents 10 key tips for needs assessment, clarification of goals and objectives for internal marketing, the choice of teaching formats, fund raising, recruiting of educators, qualification of peer tutors, the fun factor, how to establish a structured and longitudinal curriculum, assessment methods and motivation, collecting feedback and the use of its results...
August 2017: Zeitschrift Für Evidenz, Fortbildung und Qualität Im Gesundheitswesen
Valerie J Winton, Alexander M Justen, Helen Deng, Laura L Kiessling
Parasitic nematodes pose a serious threat to agriculture, livestock, and human health. Increasing resistance to antiparasitic agents underscores the need to replenish our anthelmintic arsenal. The nonpathogenic Caenorhabditis elegans, which serves as an effective model of parasitic helminths, has been used to search for new anthelmintic leads. We previously reported small-molecule inhibitors of the essential C. elegans protein UDP-galactopyranose mutase (UGM or Glf). This enzyme is required for the generation of galactofuranose (Galf)-containing glycans and is needed in nematodes for proper cuticle formation...
September 15, 2017: ACS Chemical Biology
Kittikhun Wangkanont, Valerie J Winton, Katrina T Forest, Laura L Kiessling
UDP-galactopyranose mutase (Glf or UGM) catalyzes the formation of uridine 5'-diphosphate-α-d-galactofuranose (UDP-Galf) from UDP-galactopyranose (UDP-Galp). The enzyme is required for the production of Galf-containing glycans. UGM is absent in mammals, but members of the Corynebacterineae suborder require UGM for cell envelope biosynthesis. The need for UGM in some pathogens has prompted the search for inhibitors that could serve as antibiotic leads. Optimizing inhibitor potency, however, has been challenging...
August 1, 2017: Biochemistry
Ankita Srivastava, Deepak Chandra
BACKGROUND: The unsatisfactory treatment options for Visceral Leishmaniasis (VL), needs identification of new drug targets. Among natural products, Alkaloids have been proved to be highly effective against number of diseases. In Leishmania UDP-galactopyranose mutase (UGM) is a critical enzyme required for cell wall synthesis and thus a drug target for structure based drug designing against L. donovani. OBJECTIVE: To build the homology model of UDP galactopyranse mutase and investigate the interaction of selected alkaloids with this modeled UDP galactopyranose mutase by molecular docking...
June 5, 2017: Infectious Disorders Drug Targets
Sydney A Villaume, Jian Fu, Inès N'Go, Hui Liang, Huayong Lou, Laurent Kremer, Weidong Pan, Stéphane P Vincent
This study reports a novel class of inhibitors of uridine 5'-diphosphate (UDP) galactopyranose mutase (UGM) derived from a screening of natural products. This enzyme is an essential biocatalyst involved in the cell wall biosynthesis of Mycobacterium tuberculosis. Flavonoids are potent inhibitors of UGM. The synthesis of novel methylated flavonoids allowed a structure-activity relationship analysis to be performed and which functional groups and structural elements were required for UGM inhibition could be determined...
May 11, 2017: Chemistry: a European Journal
Qinghua Zhu, Qi Chen, Yongxiang Song, Hongbo Huang, Jun Li, Junying Ma, Qinglian Li, Jianhua Ju
Galactose, a monosaccharide capable of assuming two possible configurational isomers (d-/l-), can exist as a six-membered ring, galactopyranose (Galp), or as a five-membered ring, galactofuranose (Galf). UDP-galactopyranose mutase (UGM) mediates the conversion of pyranose to furanose thereby providing a precursor for d-Galf Moreover, UGM is critical to the virulence of numerous eukaryotic and prokaryotic human pathogens and thus represents an excellent antimicrobial drug target. However, the biosynthetic mechanism and relevant enzymes that drive l-Galf production have not yet been characterized...
May 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
Rong Li, Sheng Quan, Xiaofang Yan, Sukumar Biswas, Dabing Zhang, Jianxin Shi
Molecular characterization lays a foundation for safety assessment and subsequent monitoring of genetically modified (GM) crops. Due to the target-specific nature, conventional polymerase chain reaction (PCR)-based methods cannot comprehensively detect unintended gene insertions, let alone unknown GM events. As more and more new developed GM crops including new plant breeding technology (NPBT) generated crops are in the pipeline for commercialization, alternative -omics approaches, particularly next generation sequencing, have been developed for molecular characterization of authorized or unauthorized GM (UGM) crops...
March 2017: Biotechnology Advances
Sweta Misra, Jyoti Gupta, Shailja Misra-Bhattacharya
BACKGROUND: Galactofuranose is an essential cell surface component present in bacteria, fungi and several nematodes such as Caenorhabditis spp., Brugia spp., Onchocerca spp. and Strongyloides spp. This sugar maintains the integrity of parasite surface and is essential for virulence. UDP-Galactopyranose mutase (bmugm) plays a key role in Galf biosynthesis by catalyzing conversion of UDP-Galactopyranose into UDP-galactofuranose and knockout studies of the gene in Leishmania major, Mycobacterium and Aspergillus fumigatus displayed attenuated virulence while RNA interference study in C...
January 19, 2017: Parasites & Vectors
Darryl A Wesener, Matthew R Levengood, Laura L Kiessling
The suborder Corynebacterineae encompasses species like Corynebacterium glutamicum, which has been harnessed for industrial production of amino acids, as well as Corynebacterium diphtheriae and Mycobacterium tuberculosis, which cause devastating human diseases. A distinctive component of the Corynebacterineae cell envelope is the mycolyl-arabinogalactan (mAG) complex. The mAG is composed of lipid mycolic acids, and arabinofuranose (Araf) and galactofuranose (Galf) carbohydrate residues. Elucidating microbe-specific differences in mAG composition could advance biotechnological applications and lead to new antimicrobial targets...
February 17, 2017: Journal of Biological Chemistry
P G Shelton, Irma Corral, Brandon Kyle
Restructuring of undergraduate medical education (UGME) has occurred from time to time over the past century. Many influences, including the persuasive report of Abraham Flexner in 1910, acted to reorganize medical education in the early twentieth century [1, 2]. In his report, Flexner called on American medical schools to enact higher graduation standards and to stringently adhere to the protocols of mainstream science in their teaching. Prior to this report, UGME had changed little over the previous century but over the last several decades, reform within medical education has become routine...
June 2017: Psychiatric Quarterly
Brandon N Kyle, Irma Corral, Nadyah Janine John, P G Shelton
Returning to the original emphasis of higher education, universities have increasingly recognized the value and scholarship of teaching, and medical schools have been part of this educational scholarship movement. At the same time, the preferred learning styles of a new generation of medical students and advancements in technology have driven a need to incorporate technology into psychiatry undergraduate medical education (UGME). Educators need to understand how to find, access, and utilize such educational technology...
June 2017: Psychiatric Quarterly
Colin Hamlin, Kanwar Bhangu, Alexander Villafranca, Manpreet Bhangu, Robert Brown, Marshall Tenenbein, Eric Jacobsohn
PURPOSE: Historically, anesthesiology departments have played a small role in teaching the pre-clerkship component of undergraduate medical education (UGME). The purpose of this study was to measure the current participation of Canadian anesthesiologists in UGME with a focus on pre-clerkship. METHODS: Three surveys were developed in collaboration with the Association of Canadian Departments of Anesthesia. After an initial series of validation procedures, the surveys were distributed to anesthesia department heads, UGME directors, and associate deans at the 17 Canadian medical schools...
January 2017: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
Yousef Sakieh, Abdolrassoul Salmanmahiny, Seyed Hamed Mirkarimi
Continuous surface of urbanization suitability, as an input to many urban growth models (UGM), has a significant role on a proper calibration process. The present study evaluates and compares the simulation success of the Cellular Automata-Markov Chain (CA-MC) model through multiple methods. For this, a series of mapping algorithms are applied ranging from empirical methods such as multi-criteria evaluation (MCE) to statistical algorithms without spatially explicit suitability mapping rules such as logistic regression (LR) and multi-layer perceptron (MLP) neural network and finally statistical and spatially explicit rule-based methods such as SLEUTH-Genetic Algorithm (SLEUTH-GA) model...
November 2016: Environmental Monitoring and Assessment
Christophe J-M Frédéric, Abdellatif Tikad, Jian Fu, Weidong Pan, Ruixiang B Zheng, Akihiko Koizumi, Xiaochao Xue, Todd L Lowary, Stéphane P Vincent
This study reports a new methodology to synthesize exo-glycals bearing both a sulfone and a phosphonate. This synthetic strategy provides a way to generate exo-glycals displaying two electron-withdrawing groups and was applied to eight different carbohydrates from the furanose and pyranose series. The Z/E configurations of these tetrasubstituted enol ethers could be ascertained using NMR spectroscopic techniques. Deprotection of an exo-glycal followed by an UMP (uridine monophosphate) coupling generated two new UDP (uridine diphosphate)-galactofuranose analogues...
September 15, 2016: Chemistry: a European Journal
Valerie J Winton, Claudia Aldrich, Laura L Kiessling
Uridine diphosphate galactopyranose mutase (UGM also known as Glf) is a biosynthetic enzyme required for construction of the galactan, an essential mycobacterial cell envelope polysaccharide. Our group previously identified two distinct classes of UGM inhibitors; each possesses a carboxylate moiety that is crucial for potency yet likely detrimental for cell permeability. To enhance the antimycobacterial potency, we sought to replace the carboxylate with a functional group mimic-an N-acylsulfonamide group. We therefore synthesized a series of N-acylsulfonamide analogs and tested their ability to inhibit UGM...
August 12, 2016: ACS Infectious Diseases
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