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

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.Besra 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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RIP1 （ROP Interactive Partner 1）/IcR1 Marks Pollen Germination Sites and May Act in the ROP1 Pathway in the control of Polarized Pollen Growth

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Molecular Plant 2008年第6期1卷 1021-1035页

作者： Shundai Li Ying Gu An Yan elizabeth Lord Zhen-Biao Yang center for Plant cell Biology Institute of Integrative Genome Biology and Department of Botany and Plant Sciences University of California Riverside CA92521 USA Present address: Energy Biosciences Institute University of California Berkeley Berkeley CA 94720 USA

Rho family small GTPases are universal signaling switches in the control of cell polarity in eukaryotic cells. Their polar distribution to the cell cortex is critical for the execution of their functions, yet the mechanism for this distribution is poorly understood. Using a yeast two-hybrid method, we identified RIP1 （ROP interactive partner 1）, which belongs to a family of five members of novel proteins that share a c-terminal region that interacts with ROP. When expressed in Arabidopsis pollen, green fluorescence protein GFP-tagged RIP1 was localized to the nucleus of mature pollen. When pollen grains were hydrated in germination medium, GFP-RIP1 switched from the nucleus to the cell cortex at the future pollen germination site and was maintained in the apical cortex of germinating pollen and growing pollen tubes. RIP1 was found to interact with ROP1 in pollen tubes, and the cortical RIP1 localization was influenced by the activity of ROP1. Overexpression of RIP1 induced growth depolarization in pollen tubes, a phenotype similar to that induced by ROP1 overexpression. Interestingly, RIP1 overexpression enhanced GFP-ROP1 recruitment to the plasma membrane （PM） of pollen tubes. Based on these observations, we hypothesize that RIP1 is involved in the positive feedback regulation of ROP1 localization to the PM, leading to the establishment of a polar site for pollen germination and pollen tube growth.

关键词： Pollen Tube Retinopathy of Prematurity RIPK1 gene FEEDBAcK REGULATION Nucleus Pollen pollen germination Two-Hybrid System Techniques cell Polarity

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Synthesis and evaluation as cO2 chemisorbent of the Li5(Al1-xFex)O4 solid solution materials:Effect of oxygen addition

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Journal of Energy chemistry 2017年第5期26卷 948-955页

作者： Paulina Olavarría elizabeth Vera Enrique J.Lima Heriberto Pfeiffer Laboratorio de Fisicoquímica y Reactividad de Superficies(LaFReS) Instituto de Investigaciones en MaterialesUniversidad Nacional Autońoma de MexicoCircuito exterior s/nCd.UniversitariaDel.Coyoacan C.P.04510Ciudad de MéxicoMexico

Pentalithium aluminate（β-LiAlO） and the corresponding iron-containing solid solution(Li(AlFe)O)were synthetized by solid-state reaction. All the samples were characterized structural and microstructurally by X-ray diffraction, solid-state nuclear magnetic resonance, scanning electron microscopy, Nadsorption-desorption and temperature-programmed desorption of cO. Results showed that 30 mol% of iron can be incorporated into the β-LiAlOcrystalline structure at aluminum positions. Moreover, iron addition induced morphological and superficial reactivity variations. Li(AlFe)Osamples chemisorbed cObetween 200 and 700 °c, where the superficial chemisorption presented the highest enhancement,in comparison to β-LiAlO. Additionally, Li(AlFe)Osamples sintered at higher temperatures thanβ-LiAlO. Isothermal cOchemisorption experiments of β-LiAlOand Li(AlFe)Owere fitted to a first order reaction model, corroborating that iron enhances the cOchemisorption, kinetically. When oxygen was added to the gas flow, cOchemisorption process was mainly enhanced between 400 and 600 °c for the Li(AlFe)Osample in comparison to β-LiAlO. Hence, Li(AlFe)Osolid solution presented an enhanced cOchemisorption process, in the presence and absence of oxygen, in comparison to β-LiAlO.

关键词： Lithium aluminate cO2 chemisorption Solid solution Thermogravimetry

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Intensivist-based deep sedation using propofol for pediatric outpatient flexible bronchoscopy

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World Journal of critical care Medicine 2017年第4期6卷 179-184页

作者： Kamal Abulebda Samer Abu-Sultaneh Sheikh Sohail Ahmed elizabeth A S Moser Renee c McKinney Riad Lutfi Department of Pediatrics Section of Critical CareIndiana University School of MedicineRiley Hospital for Children at Indiana University Health Department of Biostatistics Indiana University School of Medicine and Richard M Fairbanks School of Public Health

AIM To evaluate the safety and efficacy of sedating pediatric patients for outpatient flexible *** A retrospective chart review was conducted for all children, age 17 years or under who underwent flexible bronchoscopy under deep sedation in an outpatient hospital-based setting. Two sedation regimens were used; propofol only or ketamine prior to propofol. Patients were divided into three age groups; infants(less than 12 mo), toddlers(1-3 years) and children(4-17 years). Demographics, indication for bronchoscopy, sedative dosing, sedation and recovery time and adverse events were *** Of the total 458 bronchoscopies performed, propofol only regimen was used in 337(74%) while propofol and ketamine was used in 121(26%). About 99% of the procedures were successfully completed. children in the propofol + ketamine group tend to be youngerand have lower weight compared to the propofol only group. Adverse events including transient hypoxemia and hypotension occurred in 8% and 24% respectively. Median procedure time was 10 min while the median discharge time was 35 min. There were no differences in the indication of the procedure, propofol dose, procedure or recovery time in either sedative regimen. When compared to other age groups, infants had a higher incidence of *** children can be effectively sedated for outpatient flexible bronchoscopy with high rate of success. This procedure should be performed under vigilance of highly trained providers.

关键词： Pediatric flexible bronchoscopy Propofol Deep sedation Procedural sedation Sedation time Hypoxemia

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Nat Immunol:科学家阐明如何有效抑制自身免疫疾病的发生

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现代生物医学进展 2017年第8期17卷 I0002-I0003页

作者： Thomas H auml ggl #x000F6 f, Saikiran K Sedimbi Mikael c I Karlsson Jennifer L Yates elizabeth A Leadbetter Roham Parsa Robert A Harris Briana Hauff Salas elizabeth A Leadbetter Department of Microbiology Tumor and Cell Biology Karolinska Institutet Solna Sweden. Trudeau Institute Saranac Lake New York USA. Department of clinical Neuroscience Karolinska Institutet Centre for Molecular Medicine Karolinska University Hospital at Solna Solna Sweden. Department of Microbiology Immunology and Molecular Genetics University of Texas Health Science Center at San Antonio San Antonio Texas USA.

机体免疫系统中一种未知的安全机制能够保持机体免于自身免疫疾病，日前一项刊登于国际杂志Nature Immunology上的研究报告中，来自瑞典卡罗琳学院的研究人员通过研究发现。机体先天性免疫系统中的细胞能够阻止后天性的免疫系统对机体... 详细信息

机体免疫系统中一种未知的安全机制能够保持机体免于自身免疫疾病，日前一项刊登于国际杂志Nature Immunology上的研究报告中，来自瑞典卡罗琳学院的研究人员通过研究发现。机体先天性免疫系统中的细胞能够阻止后天性的免疫系统对机体固有的细胞产生反应，否则就会引发诸如系统性红斑狼疮等自身免疫疾病的发生。

关键词：自身免疫疾病机体免疫系统 Nat 科学家系统性红斑狼疮安全机制研究人员后天性

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Investigational growth factors utilized in animal models of spinal fusion: Systematic review

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World Journal of Orthopedics 2019年第4期10卷 176-191页

作者： Ethan cottrill A Karim Ahmed Noah Lessing Zachary Pennington Wataru Ishida Alexander Perdomo-Pantoja Sheng-fu Lo elizabeth Howell christina Holmes c Rory Goodwin Nicholas Theodore Daniel M Sciubba Timothy F Witham Department of Neurosurgery The Johns Hopkins Hospital Department of Neurosurgery Duke University Medical Center

BAcKGROUND Over 400000 Americans annually undergo spinal fusion surgeries, yet up to 40%of these procedures result in pseudoarthrosis even with iliac crest autograft, the current "gold standard" treatment. Tissue engineering has the potential to solve this problem via the creation of bone grafts involving bone-promoting growth factors(e.g., bone morphogenetic protein 2). A broad assessment of experimental growth factors is important to inform future work and clinical potential in this area. To date, however, no study has systematically reviewed the investigational growth factors utilized in preclinical animal models of spinal *** To review all published studies assessing investigational growth factors for spinal fusion in animal models and identify promising agents for *** We conducted a systematic review of the literature using PubMed, Embase,cochrane Library, and Web of Science databases with searches run on May 29 th,2018. The search query was designed to include all non-human, preclinical animal models of spinal fusion reported in the literature without a timespan limit. Extracted data for each model included surgical approach, level of fusion,animal species and breed, animal age and sex, and any other relevant characteristics. The dosages/sizes of all implant materials, spinal fusion rates,and follow-up time points were recorded. The data were analyzed and the results reported in tables and text. PRISMA guidelines were followed for this systematic *** Twenty-six articles were included in this study, comprising 14 experimental growth factors: AB204(n = 1); angiopoietin 1(n = 1); calcitonin(n = 3);erythropoietin(n = 1); basic fibroblast growth factor(n = 1); growth differentiation factor 5(n = 4), combined insulin-like growth factor 1 +transforming growth factor beta(n = 4); insulin(n = 1); NELL-1(n = 5); noggin(n= 1); P-15(n = 1); peptide B2 A(n = 2); and secreted phosphoprotein 24(n = 1).The fusion rates of the current gold sta

关键词： Spinal fusion Growth factor Pseudoarthrosis Systematic review

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Experiences with a violence and mental health safety protocol for a randomized controlled trial to support youth living with HIV

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Global Health Research and Policy 2021年第1期6卷 87-96页

作者： Katherine G.Merrill Jonathan K.Mwansa Sam Miti Virginia M.Burke elizabeth A.Abrams christiana Frimpong Michele R.Decker Jacquelyn c.campbell Julie A.Denison Department of International Health Johns Hopkins Bloomberg School of Public Health615 N.Wolfe StreetBaltimoreMD 21205USA Arthur Davison children’s Hospital NdolaZambia Department of Population Family and Reproductive HealthJohns Hopkins Bloomberg School of Public HealthBaltimoreMDUSA Department of community-Public Health Johns Hopkins School of NursingBaltimoreMDUSA Present Address:Department of Medicine University of Illinois at ChicagoChicagoILUSA

Background:Safety protocols are an essential component of studies addressing violence and mental health but are rarely described in the published literature from Sub-Saharan *** designed and implemented a safety protocol within Project YES!(Youth Engaging for Success),which enrolled 276 youth living with HIV(ages 15–24 years)in a randomized controlled trial of a peer-mentoring intervention across four HIV clinics in Ndola,***:Youth who reported severe violence and/or suicidal thoughts on research surveys or during meetings with youth peer mentors(YPM)were referred to designated healthcare providers(HcP).We explored experiences with the safety protocol using:a)monitoring data of referrals,and b)in-depth interviews with youth(n=82),HcP(n=10),YPM(n=8),and staff(n=6).Descriptive statistics were generated and thematic analysis of coded transcripts and written memos ***:Nearly half of youth enrolled(48%of females,41%of males)were referred to a HcP at least *** first referral was most often for sexual violence(35%)and/or suicidal ideation/depression(29%).All referred youth aged 15–17 years and over 80%of referred youth aged 18+agreed to see a *** referred 15%for additional services outside the ***-nine youth,all HcP,all YPM,and all staff interviewed discussed the safety *** youth felt“encouraged,”“helped,”“unburdened,”and“relieved”by their meetings with HcP;some expressed concerns about meeting with *** safety protocol helped HcP recognize the need to integrate care for violence and mental health with medication adherence ***,YPM,and study staff raised implementation challenges,including youth choosing not to open up to HcP,time and resource constraints,deficiencies in HcP training,and stigma and cultural norms inhibiting referrals outside the clinic for emotional trauma and mental ***:Implementing a safety protocol within an HIV clinic-based research study is possible and beneficial for

关键词： Safety protocol Referral Violence Mental health HIV Youth Zambia

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The Use of the cuisenaire Rule in the classroom

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Journal of Mathematics and System Science 2020年第2期10卷 23-26页

作者： caudana elizabeth de Lourdes School IPEM 116“Manuel Belgrano”Rural Annex Punta del Agua Department Tercero Arriba CórdobaRepública Argentina

This pedagogical proposal was implemented in the curricular space of mathematics,in the first year of the basic cycle of the pluricurso in IPEM 116“Manuel Belgrano”Rural Annex Punta del Agua,with Orientation Agro Ambiente,Department Third Arriba,province of córdoba,República *** was developed according to the difficulties shown by students in not being able to establish the relationship that exists between natural,fractional,decimal and percentage *** with this situation,it is proposed to develop the cuisenaire Rule as a teaching resource in order to stimulate and develop the logical capacities in students within the framework of thoughtful and operational mathematical thinking by applying it in the resolution of specific learning *** construction and application of this resource allowed them to develop the understanding and assimilation of concepts in which they presented difficulties promoted learning and taking of.

关键词： didactic resource fractions decimals percentage

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Evaluation of phytochemical properties and in-vitro antibacterial activity of the aqueous extracts of leaf,seed and root of Abrus precatorius Linn. against Salmonella and Shigella

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Asian Pacific Journal of Tropical Biomedicine 2016年第9期6卷 755-759页

作者： Ojo Joseph Sunday Shola Kola Babatunde Adeyinka elizabeth Ajiboye Racheal Majekodunmi Adedayo Mufutau Adeyemi Ajao Busayo Isreal Ajuwon Department of Biosciences and Biotechnology Kwara State University

Objective:To investigate the phytochemical components of Abrus precatorius(***) and the in-vitro susceptibility of Salmonella typhi and Shigella dysenteriae to the aqueous extracts of *** leaf,seed and ***:The leaf,seed and root of *** were collected and homogenized separately after drying at 40℃ for seven days in hot-air *** aqueous extracts of each of the parts were prepared and subjected to phytochemical *** of 400,300,200,100 mg/mL,of each of the extracts were used for broth dilution in minimum inhibitory concentration(MIc) determination against clinical isolates of Salmonella typhi and Shigella dysenteriae,while 50,40,30,20,and 10 mg/mL dilutions were used for the agar diffusion test and 100 mg/mL and 10 mg/mL of gentamycin were used as controls for broth dilution in MIc determination and agar diffusion test,***:Qualitative study reveals that tannin,saponins,alkaloids,flavonoids,terpenoids,steroids and phenols were present in all of the plant *** leaf has the highest quantities of tannin and *** root generally showed the lowest quantity of all the *** pathogens were susceptible to aqueous extracts of the leaf,stem and root of *** at 50 mg/*** concentrations of 40,30 and 20 mg/mL,all the aqueous extracts of *** showed variation in MIc,but produced no minimum bactericide effect upon *** were variations in diameter of zone of inhibition against the organisms at lower ***:These findings suggest that *** is a valuable source of phytochemicals with promising antibacterial *** this bioactivity,*** could be probed further for toxicity,and to obtain some novel antibacterial molecules.

关键词： Abrus precatorius Phytochemicals Antibacterial susceptibility Salmonella Shigella

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Impact of sustained virologic response on chronic kidney disease progression in hepatitis c

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World Journal of Hepatology 2017年第36期9卷 1352-1360页

作者： elizabeth S Aby Tien S Dong Jenna Kawamoto Joseph R Pisegna Jihane N Benhammou Division of Gastroenterology Hepatology and Parenteral Nutrition Department of Medicine VA Greater Los Angeles Healthcare System the Vatche and Tamar Manoukian Division of Digestive Diseases UCLA Los Angeles Department of Medicine University of California David Geffen School of Medicine

AIM To determine how sustained virological response at 12 wk(SVR12) with direct acting antivirals(DAAs) for the treatment of hepatitis c virus(HcV) infection affects chronic kidney disease(cKD) progression. METHODS A retrospective analysis was performed in patients aged ≥ 18 years treated for HcV with DAAs at the VA Greater Los Angeles Healthcare System from 2014-2016. The treatment group was compared to patients with HcV from 2011-2013 who did not undergo HcV treatment, prior to the introduction of DAAs; the control group was matched to the study group in terms of age, gender, and ethnicity. Analysis of variance and co-variance was performed to compare means between SVR12 subgroups adjusting for *** Five hundred and twenty-three patients were evaluated. When comparing the rate of change in estimated glomerular filtration rate(e GFR) one-year after HcV treatment to one-year before treatment, patients who achieved SVR12 had a decline in GFR of 3.1 m L/min ± 0.75 m L/min per 1.73 m^2 compared to a decline in e GFR of 11.0 m L/min ± 2.81 m L/min per 1.73 m^2 in patients who did not achieve SVR12(P = 0.002). There were no significant clinical differences between patients who achieved SVR12 compared to those who did not in terms of cirrhosis, treatment course, treatment experience, cKD stage prior to treatment, diuretic use or other co-morbidities. The decline in e GFR in those with untreated HcV over 2 years was 2.8 m L/min ± 1.0 m L/min per 1.73 m^2, which was not significantly different from the e GFR decline noted in HcV-treated patients who achieved SVR12(P = 0.43).cONcLUSION Patients who achieve SVR12 have a lesser decline in renal function, but viral eradication in itself may not be associated improvement in renal disease progression.

关键词： Hepatitis c Direct-acting antivirals chronic kidney disease End stage renal disease Sustained virological response

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