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Cryo-EM snapshots of mycobacterial arabinosyltransferase complex Embb2-AcpM2

Protein & Cell 2020年第7期11卷 505-517页

作者： Lu Zhang Yao Zha Ruogu Gao Jun Li Xiuna Yang Yan Gao Wei Zhao sudagar s.Gurcha Natacha Veerapen sarah M.batt Kajelle Kaur besra Wenqing Xu Lijun bi Xian'en Zhang Luke W.Guddat Haitao Yang Quan Wang gurdyal s.b.sra Zihe Rao state Key Laboratory of Medicinal Chemical biology College of Life Sciences and College of PharmacyNankai UniversityTianjin 300353China shanghai Institute for Advanced Immunochemical studies and school of Life science and Technology ShanghaiTech UniversityShanghai 201210China CAs Center for Excellence in Molecular Cell science Shanghai Institute of Biochemistry and Cell BiologyChinese Academy of Sciences(CAS)Shanghai 200031China University of Chinese Academy of sciences Beijing 100101China National Laboratory of biomacromolecules and Key Laboratory of RNA biology CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsCASBeijing 100101China Laboratory of structural biology Tsinghua UniversityBeijing 100084China school of biosciences Institute of Microbiology and InfectionUniversity of BirminghamBirmingham B152TTUK school of Chemistry and Molecular biosciences The University of QueenslandBrisbaneQLD 4072Australia

Inhibition of Mycobacterium tuberculosis(Mtb)cell wall assembly is an established strategy for anti-Tb *** Embb,which catalyzes the transfer of arabinose from the donor decaprenyl-phosphate-arabinose(DPA)to its arabinosyl acceptor is an essential enzyme for Mtb cell wall *** of drug resistance mutations suggests that Embb is the main target of the front-line anti-Tb drug,***,we report the cryo-EM structures of Mycobacterium smegmatis Embb in its"resting state"and DPA-bound"active state".Embb is a fifteen-transmembrane-spanning protein,assembled as a *** protomer has an associated acyl-carrier-protein(AcpM)on their cytoplasmic ***-mational changes upon DPA binding indicate an asym-metric movement within the Embb dimer during *** studies have identified critical residues in substrate recognition and catalysis,and demonstrated that ethambutol inhibits transferase activity of Embb by competing with *** structures represent the first step directed towards a rational approach for anti-Tb drug discovery.

关键词： Mycobacterium tuberculosis Embb cryo-EM ethambutol cell wall synthesis arabinoglacatan arabinosyltransferase acyl-carrier-protein drug discovery

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Identification of arylamine N-acetyltransferase inhibitors as an approach towards novel anti-tuberculars

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Protein & Cell 2010年第1期1卷 82-95页

作者： Isaac M.Westwood sanjib bhakta Angela J.Russell Elizabeth Fullam Matthew C.Anderton Akane Kawamura Andrew W.Mulvaney Richard J.Vickers Veemal bhowruth gurdyal s.b.sra Ajit Lalvani stephen G.Davies Edith sim Department of Pharmacology University of OxfordOxford OX13QTUnited Kingdom Chemistry Research Laboratory Department of Organic ChemistryUniversity of OxfordOxford OX13QLUnited Kingdom school of biosciences University of BirminghamEdgbastonBirmingham B152TTUnited Kingdom Tuberculosis Immunology Group Department of Respiratory MedicineNational Heart and Lung InstituteWright Fleming Institute of Infection and ImmunityImperial College LondonNorfolk PlaceLondon W21PGUnited Kingdom structure-based Drug Design Team Sections of Structural Biology and Cancer TherapeuticsInstitute of Cancer ResearchChester Beatty LaboratoriesLondon SW36JBUnited Kingdom Institute of structural and Molecular biology Department of Biological ScienceBirkbeckUniversity of LondonLondon WC1E 7HXUnited Kingdom

New anti-tubercular drugs and drug targets are urgently needed to reduce the time for treatment and also to identify agents that will be effective against Mycobacterium tuberculosis persisting *** have a unique cell *** of the gene for arylamine N-acetyltransferase(NAT)decreases mycobacterial cell wall lipids,particularly the distinctive mycolates,and also increases antibiotic susceptibility and killing within macrophage of Mycobacterium bovis *** nat gene and its associated gene cluster are almost identical in sequence in *** bCG and *** gene cluster is essential for intracellular survival of *** have therefore used pure NAT protein for high-throughput screening to identify several classes of small molecules that inhibit NAT ***,we characterize one class of such molecules—triazoles—in relation to its effects on the target enzyme and on both *** bCG and *** most potent triazole mimics the effects of deletion of the nat gene on growth,lipid disruption and intracellular *** also present the structure-activity relationship between NAT inhibition and effects on mycobacterial growth,and use ligand-protein analysis to give further insight into the structure-activity *** conclude that screening a chemical library with NAT protein yields compounds that have high potential as anti-tubercular agents and that the inhibitors will allow further exploration of the biochemical pathway in which NAT is involved.

关键词： N-acetyltransferase Mycobacterium tuberculosis triazoles screening

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sperm chromatin condensation as an in vivo fertility biomarker in bulls:a flow cytometry approach

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Journal of Animal science and biotechnology 2022年第2期13卷 418-429页

作者： Marc Llavanera Jordi Ribas-Maynou Ariadna Delgado-bermúdez sandra Recuero Rodrigo Muiño Carlos OHidalgo Carolina Tamargo sergi bonet Yentel Mateo-Otero Marc Yeste biotechnology of Animal and Human Reproduction(Technosperm) Faculty of SciencesUniversity of GironaC/Maria Aurèlia Campany69ES-17003 GironaSpain Department of biology Unit of Cell BiologyFaculty of SciencesUniversity of GironaES-17003 GironaSpain Department of Animal Pathology Faculty of Veterinary MedicineUniversity of Santiago de CompostelaES-15705 LugoSpain Department of Animal selection and Reproduction The Regional Agri-Food Research and Development Service of Asturias(SERIDA)E-33394 GijónSpain

background:Genetic selection in cattle has been directed to increase milk ***,coupled to the fact that the vast majority of bovine artificial inseminations(AI)are performed using cryopreserved sperm,have led to a reduction of fertility rates over the ***,seeking sensitive and specific sperm biomarkers able to predict fertility rates is of vital importance to improve cattle reproductive *** humans,sperm chromatin condensation evaluated through chromomycin A3(CMA3)has recently been purported to be a powerful biomarker for sperm functional status and male *** objectives of the present study were:a)to set up a flow cytometry method for simultaneously evaluating chromatin condensation and sperm viability,and b)to test whether this parameter could be used as a predictor of in vivo fertility in *** study included pools of three independent cryopreserved ejaculates per bull from 25 Holstein *** outcomes of each sire were determined by non-return rates,which were used to classify bulls into two groups(highly fertile and subfertile).Results:Chromatin condensation status of bovine sperm was evaluated through the combination of CMA3 and Yo-Pro-1 staining and flow *** quality parameters(morphology,viability,total and progressive motility)were also *** correlation coefficients and ROC curves were calculated to assess their capacity to predict in vivo *** morphology,viability and total motility presented an area under the ROC curve(AUC)of 0.54,0.64 and 0.68,respectively(P>0.05),and thus were not able to discriminate between fertile and subfertile ***,while the percentage of progressively motile sperm showed a significant predictive value,with an AUC of 0.73(P=0.05),CMA3/Yo-Pro-1 staining even depicted superior results for the prediction of in vivo fertility in ***,the percentage of viable sperm with poor chromatin condensation showed better accura

关键词： bull Chromatin Chromomycin A3 Condensation Fertility Flow cytometry sperm

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IMPLEMENTATION OF COLORIMETRIC MEAsUREMENT sYsTEM AT INMETRO

IMPLEMENTATION OF COLORIMETRIC MEASUREMENT SYSTEM AT INMETRO

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26th session of the CIE

作者： J.F.s.Gomes G.s.Araǘjo H.P.Grieneisen I.b.Couceiro brazilian National Institute of Metrology-INMETRO Optical Metrology Division-DIOPT Radiometry Laboratory-LARAD Av.N.sra.das Graas 50-Xerém-Duque de CaxiasRJCEP 25250-020Brazil brazilian National Institute of Metrology-INMETRO Optical Metrology Division-DIOPT Radiometry Laboratory-LARAD Av.N.sra.das Graas 50-Xerém-Duque de CaxiasRJCEP 25250-020Brazil brazilian National Institute of Metrology-INMETRO Optical Metrology Division-DIOPT Radiometry Laboratory-LARAD Av.N.sra.das Graas 50-Xerém-Duque de CaxiasRJCEP 25250-020Brazil brazilian National Institute of Metrology-INMETRO Optical Metrology Division-DIOPT Radiometry Laboratory-LARAD Av.N.sra.das Graas 50-Xerém-Duque de CaxiasRJCEP 25250-020Brazil

＜正＞The Radiometry Laboratory of brazilian National Institute of Metrology,according CIE standards, has implemented a setup for colorimetric materials and color tile characterization with high *** the main purpose to check the preliminary performance of the reference system two sets of ceramic color standards were obtained and the characterization of the samples has been done using a PR-650 Photoresearch *** reflectance measurements are done for the common configuration of illumination and observation geometry,0/45,for colorimetric characterization of color tiles.

关键词： colorimetry colorimetric measurements material characterization

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A boronic acid-based fluorescent hydrogel for monosaccharide detection

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Frontiers of Chemical science and Engineering 2020年第1期14卷 112-116页

作者： suying Xu Adam C.sedgwick souad A.Elfeky Wenbo Chen Ashley s.Jones George T.Williams A.Toby A.Jenkins steven D.bull John s.Fossey Tony D.James Department of biochemistry Faculty of ScienceBeijing University of Chemical TechnologyBeijing 100029China Department of Chemistry University of BathBath BA27AYUK Department of Chemistry University of Texas at AustinTX 78712-1224USA school of Chemistry University of BirminghamBirmingham B152TTUK National Institute of Laser Enhanced sciences Cairo UniversityGiza 12613Egypt Higher Institute for Optics Technology SheratonCairo 17361Egypt shanghai Key Laboratory of Materials Protection and Advanced Materials in Electric Power Shanghai University of Electric PowerShanghai 200090China

A boronic acid-based anthracene fluorescent probe was functionalised with an acrylamide unit to incorporate into a hydrogel system for monosaccharide *** solution,the fluorescent probe displayed a strong fluorescence turn-on response upon exposure to fructose,and an expected trend in apparent binding constants,as judged by a fluorescence response where D-fructose>D-galactose>D-mannose>*** hydrogel incorporating the boronic acid monomer demonstrated the ability to detect monosaccharides by fluorescence with the same overall trend as the monomer in solution with the addition of D-fructose resulting in a 10-fold enhancement(≤0.25 mol/L).

关键词： boron hydrogel monomer

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COMPLIANCE AND TEsTING OF HID-LAMPs FOR MINIMUM LUMINOUs FLUX LEVELs

COMPLIANCE AND TESTING OF HID-LAMPS FOR MINIMUM LUMINOUS FLU...

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26th session of the CIE

作者： A.s.P.Timmins C.T.Coelho H.P.H.Grieneisen I.A.Oliveira I.b.Couceiro National Institute of Metrology standardization and Industrial Quality-Inmetro Optical Metrology Division-Diopt Photometry Laboratory-Lafot Av.N.Sra.das Graas50-Xerém-Duque de CaxiasRJCEP 25250-020Brazil National Institute of Metrology standardization and Industrial Quality-Inmetro Optical Metrology Division-Diopt Photometry Laboratory-Lafot Av.N.Sra.das Graas50-Xerém-Duque de CaxiasRJCEP 25250-020Brazil National Institute of Metrology standardization and Industrial Quality-Inmetro Optical Metrology Division-Diopt Photometry Laboratory-Lafot Av.N.Sra.das Graas50-Xerém-Duque de CaxiasRJCEP 25250-020Brazil National Institute of Metrology standardization and Industrial Quality-Inmetro Optical Metrology Division-Diopt Photometry Laboratory-Lafot Av.N.Sra.das Graas50-Xerém-Duque de CaxiasRJCEP 25250-020Brazil National Institute of Metrology standardization and Industrial Quality-Inmetro Optical Metrology Division-Diopt Photometry Laboratory-Lafot Av.N.Sra.das Graas50-Xerém-Duque de CaxiasRJCEP 25250-020Brazil

＜正＞The lamps manufactures in brazil have a demand to determining minimum luminous flux performance of high intensity discharge lamps - HID using integrating sphere photometers.A method is presented here to measured HID lamps of different lamp types,such as sodium,metal vapor and mercury lamps,each exhibiting a different emission spectrum using two different methodologies:with an integrating sphere and a ***,we are going to compare the found results and determine the best methodology to be used by the industry.

关键词： luminous flux goniophotometry HID-lamp

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An adhesive and resilient hydrogel for the sealing and treatment of gastric perforation

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bioactive Materials 2022年第8期7卷 52-60页

作者： Jing Chen Julia s.Caserto Ida Ang Kaavian shariati James Webb bo Wang Xi Wang Nikolaos bouklas Minglin Ma College of Pharmacy Nanjing University of Chinese MedicineNanjing210023China Department of biological and Environmental Engineering Cornell UniversityIthacaNY14853USA Robert Frederick smith school of Chemical and biomolecular Engineering Cornell UniversityIthacaNY14853USA sibley school of Mechanical and Aerospace Engineering Cornell UniversityIthacaNY14853USA

Adhesive hydrogels have been recently proposed as a potential option to seal and treat gastric perforation(GP)which causes high mortality despite advancements in surgical ***,to be effective,the hydrogels must have sufficient tissue adhesiveness,tough mechanical property,tunable biodegradability and ideally are easy to apply and ***,we report an adhesive and resilient hydrogel for the sealing and treatment of gastric *** hydrogel consists of a bioactive,transglutaminase(TG)-crosslinked gelatin network and a dynamic,borate-crosslinked poly-N-[Tris(hydroxymethyl)methyl]acrylamide(PTH)*** hydrogel can be formed in situ,facilitating easy delivery to the GP and allowing for precise sealing of the *** vivo experiments,using a perforated stomach mouse model,shows that the adhesive hydrogel plug effectively seals GP defects and promotes gastric mucosa ***,this hydrogel represents a promising biomaterial for GP treatment.

关键词： Adhesive hydrogel plug Gastric perforation Thermo-responsive Regeneration

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Malignant Cerebral Edema secondary to Gliadel Wafers in the Early Postsurgical Period

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Open Journal of Anesthesiology 2015年第4期5卷 72-74页

作者： Ana b. Fernández Antonio Garcia Eglis Lazo Department of Anesthesiology Intensive Care and Pain Treatment Nuestra Sra de Cande-laria University Hospital Santa Cruz de Tenerife Spain Department of Neurosurgery Nuestra Sra de Candelaria University Hospital Santa Cruz de Tenerife Spain

High grade gliomas are the commonest intrinsic brain tumours and account for more average years of life lost than all the common cancers. It has become the commonest cause of cancer death in men under the age of 45 and women under the age of 35. Although surgical resection can greatly reduce tumour bulk, complete excision is virtually impossible due to the infiltrative nature of these tumours. In an attempt to treat the infiltrating tumour cells, there has been much interest in using local therapies inserted at the time of surgery. The authors report a case of fatal cerebral edema unresponsive to aggressive medical and surgical assessment that finally evolved to premature death in the early postsurgical period, after the craniotomy and implantation of Gliadel wafers. They note that high doses of dexamethasone were insufficient to prevent cerebral edema and death. A search for corticosteroid use and dosing for patients treated with Gliadel wafers in the published literature revealed no recommendations on the doses of steroids to be administered. In our opinion this is a very important issue and maybe the key point for the treatment of this disease, and may need to be addressed with treatment guidelines in the near future in order to ensure better results on patient’s survival. Prior to this case review there had been two similar report but a later presentation. so we think that this is the first case report of acute fulminant cerebral edema secondary to gliadel wafers in the early period.

关键词： Malignant Glioma Carmustine Wafer Cerebral Edema Cytotoxic Effect

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Critical role of OX40 signaling in the TCR-independent phase of human and murine thymic Treg generation

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Cellular & Molecular Immunology 2019年第2期16卷 138-153页

作者： Prabhakaran Kumar Alejandra Marinelarena Divya Raghunathan Vandhana K Ragothaman shikha saini Palash bhattacharya Jilao Fan Alan L Epstein Ajay V Maker bellur s Prabhakar Department of Microbiology and Immunology University of Illinois-College of MedicineChicagoILUSA Department of Pathology University of Southern California Keck School of MedicineLos AngelesCAUSA Department of surgery Division of Surgical OncologyUniversity of Illinois-College of MedicineChicagoILUSA

Regulatory T cells(Tregs)play a pivotal role in immune-tolerance,and loss of Treg function can lead to the development of *** Tregs generated in the thymus substantially contribute to the Treg pool in the periphery,where they suppress self-reactive effector T cells(Teff)***,we showed that OX40L(TNFsF4)is able to drive selective proliferation of peripheral Tregs independent of canonical antigen presentation(CAP-independent)in the presence of low-dose ***,we hypothesized that OX40 signaling might be integral to the TCR-independent phase of murine and human thymic Treg(tTreg)*** of tTregs is a two-step process:strong T-cell receptor(TCR)signals in combination with co-signals from the TNFRsF members facilitate tTreg precursor selection,followed by a TCR-independent phase of tTreg development in which their maturation is driven by ***,we investigated whether OX40 signaling could also play a critical role in the TCR-independent phase of tTreg ***40−/−mice had significantly reduced numbers of CD25−Foxp3low tTreg precursors and CD25+Foxp3+mature tTregs,while OX40L treatment of WT mice induced significant proliferation of these cell *** to tTeff cells,OX40 was expressed at higher levels in both murine and human tTreg precursors and mature *** ex vivo cultures,OX40L increased tTreg maturation and induced CAP-independent proliferation of both murine and human tTregs,which was mediated through the activation of AKT-mTOR *** novel findings show an evolutionarily conserved role for OX40 signaling in tTreg development and proliferation,and might enable the development of novel strategies to increase Tregs and suppress autoimmunity.

关键词： Thymic Tregs OX40L IL-2 Treg proliferation maturation

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