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Pathway-Selective Sensitization of Mycobacterium tuberculosis for Target-Based Whole-Cell Screening

Garth L. Abrahams, Anuradha Kumar, Suzana Savvi, Alvin W. Hung, Shijun Wen, Chris Abell, Clifton E. Barry, David R. Sherman, Helena I.M. Boshoff, Valerie Mizrahi
2012 Chemistry and Biology  
Whole-cell screening of Mycobacterium tuberculosis (Mtb) remains a mainstay of drug discovery, but subsequent target elucidation often proves difficult. Conditional mutants that underexpress essential genes have been used to identify compounds with known mechanism of action by target-based wholecell screening (TB-WCS). Here, the feasibility of TB-WCS in Mtb was assessed by generating mutants that conditionally express pantothenate synthetase (panC), diaminopimelate decarboxylase (lysA), and
more » ... itrate lyase (icl1). The essentiality of panC and lysA, and conditional essentiality of icl1 for growth on fatty acids, was confirmed. Depletion of PanC and Icl1 rendered mutants hypersensitive to targetspecific inhibitors. Stable reporter strains were generated for use in high-throughput screening, and their utility was demonstrated by identifying compounds that display greater potency against a PanC-depleted strain. These findings illustrate the power of TB-WCS as a tool for tuberculosis drug discovery.
doi:10.1016/j.chembiol.2012.05.020 pmid:22840772 pmcid:PMC3421836 fatcat:sy5nt6drtndktfefumfpzej2ki

IL-4Rα-Dependent Alternative Activation of Macrophages Is Not Decisive for Mycobacterium tuberculosis Pathology and Bacterial Burden in Mice

Reto Guler, Suraj P. Parihar, Suzana Savvi, Erin Logan, Anita Schwegmann, Sugata Roy, Natalie E. Nieuwenhuizen, Mumin Ozturk, Sebastian Schmeier, Harukazu Suzuki, Frank Brombacher, Martin E Rottenberg
2015 PLoS ONE  
Classical activation of macrophages (caMph or M1) is crucial for host protection against Mycobacterium tuberculosis (Mtb) infection. Evidence suggests that IL-4/IL-13 alternatively activated macrophages (aaMph or M2) are exploited by Mtb to divert microbicidal functions of caMph. To define the functions of M2 macrophages during tuberculosis (TB), we infected mice deficient for IL-4 receptor α on macrophages (LysM cre IL-4Rα -/lox ) with Mtb. We show that absence of IL-4Rα on macrophages does
more » ... play a major role during infection with Mtb H37Rv, or the clinical Beijing strain HN878. This was demonstrated by similar mortality, bacterial burden, histopathology and T cell proliferation between infected wild-type (WT) and LysM cre IL-4Rα -/lox mice. Interestingly, we observed no differences in the lung expression of inducible nitric oxide synthase (iNOS) and Arginase 1 (Arg1), well-established markers for M1/M2 macrophages among the Mtb-infected groups. Kinetic expression studies of IL-4/IL-13 activated bone marrow-derived macrophages (BMDM) infected with HN878, followed by gene set enrichment analysis, revealed that the MyD88 and IL-6, IL-10, G-CSF pathways are significantly enriched, but not the IL-4Rα driven pathway. Together, these results suggest that IL-4Rα-macrophages do not play a central role in TB disease progression.
doi:10.1371/journal.pone.0121070 pmid:25790379 pmcid:PMC4366092 fatcat:wqxp4lulkred5f57rvjmgi7doi

The Worst Class Trip Ever by Dave Barry

Karen Coats
2015 Bulletin of the Center for Children`s Books  
Fortunately, Wyatt's crush, Suzana, is both fearless and fond of intrigue, and between her and a few trusty friends, hair-raising adventure ensues and the day is saved, middleschool style.  ...  The outrageous plotting is the real draw here, though; this is a savvy integration of real-world anxieties with the absurdest of absurd hero fantasies, overlaid with a touch of hey-it-could-happen if,  ... 
doi:10.1353/bcc.2015.0630 fatcat:ar7nekmyfrccpkgqxnqmg3a3ka

Terrible Typhoid Mary: A True Story of the Deadliest Cook in America by Susan Campbell Bartoletti

Elizabeth Bush
2015 Bulletin of the Center for Children`s Books  
Fortunately, Wyatt's crush, Suzana, is both fearless and fond of intrigue, and between her and a few trusty friends, hair-raising adventure ensues and the day is saved, middleschool style.  ...  The outrageous plotting is the real draw here, though; this is a savvy integration of real-world anxieties with the absurdest of absurd hero fantasies, overlaid with a touch of hey-it-could-happen if,  ... 
doi:10.1353/bcc.2015.0651 fatcat:tlon4wf5grb4ta4feroqokhstm

Guest editorial

Chulmo Koo, Luiz Mendes-Filho, Dimitrios Buhalis
2019 Tourism Review  
tech-savvy tourism demand.  ...  The sixth paper, "Mobile technologies and applications towards smart tourism: State of the art", by Jelena Dorcic, Jelena Komsic and Suzana Markovic, provides a systematic literature review of academic  ... 
doi:10.1108/tr-02-2019-208 fatcat:4esaerp2zvfp5c24w723h5rr54

Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells

Erik Arner, Carsten O. Daub, Kristoffer Vitting-Seerup, Robin Andersson, Berit Lilje, Finn Drabløs, Andreas Lennartsson, Michelle Rönnerblad, Olga Hrydziuszko, Morana Vitezic, Tom C. Freeman, Ahmad M. N. Alhendi (+97 others)
2015 Science  
33. The use of microarray data sets to identify alternative mechanisms of TERT reactivation employed by those cell lines that were WT at positions -124 and -146 was unsuccessful. Average mRNA levels were roughly similar for (i) the ETS1 and ETS2 transcription factors (~1.1-fold higher in the WT group), (ii) the c-MYC transcription factor (~1.4-fold higher in the WT group), and (iii) the core components of the Polycomb repressive complex 2 (between~0.91-fold and~1.3-fold higher in the WT group).
more » ... 34. J. Nandakumar et al., Nature 492, 285-289 (2012). ACKNOWLEDGMENTS We thank C. Owens for providing the UC23, as well as detailed information on their origins and growth conditions. This work was supported by NIH grants CA075115 and CA104106 to D.T., Although it is generally accepted that cellular differentiation requires changes to transcriptional networks, dynamic regulation of promoters and enhancers at specific sets of genes has not been previously studied en masse. Exploiting the fact that active promoters and enhancers are transcribed, we simultaneously measured their activity in 19 human and 14 mouse time courses covering a wide range of cell types and biological stimuli. Enhancer RNAs, then messenger RNAs encoding transcription factors, dominated the earliest responses. Binding sites for key lineage transcription factors were simultaneously overrepresented in enhancers and promoters active in each cellular system. Our data support a highly generalizable model in which enhancer transcription is the earliest event in successive waves of transcriptional change during cellular differentiation or activation.
doi:10.1126/science.1259418 pmid:25678556 pmcid:PMC4681433 fatcat:wzkowgz4avg6jmd4pu5rcbnxh4

FANTOM5 CAGE profiles of human and mouse samples

Shuhei Noguchi, Takahiro Arakawa, Shiro Fukuda, Masaaki Furuno, Akira Hasegawa, Fumi Hori, Sachi Ishikawa-Kato, Kaoru Kaida, Ai Kaiho, Mutsumi Kanamori-Katayama, Tsugumi Kawashima, Miki Kojima (+166 others)
2017 Scientific Data  
In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis
more » ... pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.
doi:10.1038/sdata.2017.112 pmid:28850106 pmcid:PMC5574368 fatcat:cel5hhhtardinak67mbl2okvhe

Development of Virtual Surveys for the COVID-19 Wave of the AGELESS Longitudinal Study in Malaysia

Kiirtaara Aravindhan, Sumaiyah Mat, Tengku Aizan Hamid, Suzana Shahar, Abu Bakar Abdul Majeed, Pei-Lee Teh, Kalavathy Ramasamy, Devinder Kaur Ajit Singh, Maw Pin Tan
2021 Gerontology  
Steady rise in tech-savviness among older adults has been observed prior to the pandemic, but a leap in digital literacy oc-curred as a result of lockdown measures due to necessity [10] .  ... 
doi:10.1159/000517946 pmid:34515120 pmcid:PMC8450846 fatcat:ssxorcbwc5dv3ehjeh757pw2hy

Critical Thinking: Way Forward for Human Capital in the Age of Millennial

Zairul Nurshazana Zainuddin, Nurul Ezhawati Abdul Latif, Suzana Sulaiman, Faizal Mohamed Yusof, Mahfuzah Ahmad
2019 International Journal of Academic Research in Business and Social Sciences  
system Liabilities: -Sceptical, distrustful of authority Motivations: -Work on their own Communication: -Voicemail, email Assets: -Collective action, optimism, ability to multi-task, techno-savvy  ...  development opportunities -Flexible work arrangements -Access to coaching- style managers and wise mentors -Access to decision makers Characteristics: -Fast-forward with self- esteem -Extreme techno savvy  ... 
doi:10.6007/ijarbss/v9-i13/6254 fatcat:ar3isfqajfbwxkbwi2xafpy73q


Mrs.D.S.V. Krishna Kumari, Dr. V. Tulasi Das
2020 EPRA International Journal of Economic and Business Review  
For an individual to be emotionally savvy he ought to have the option to see one's own emotions and afterward utilize that data in meeting a far reaching medical services need of people, families and society  ...  Suhaila Haron, Aini Suzana Ariffin, Durrishah Idrus (2019), article entitled "Validating the Development of Instrument for Measuring Nurses'Performance Scale" published in Journal of Management Info, article  ... 
doi:10.36713/epra5628 fatcat:iac7y4fzbrbtfodgdr6odjpad4

Willingness, perceived barriers and motivators in adopting mobile applications for health-related interventions among older adults: a scoping review

Nurul Asilah Ahmad, Arimi Fitri Mat Ludin, Suzana Shahar, Shahrul Azman Mohd Noah, Noorlaili Mohd Tohit
2022 BMJ Open  
process. 1] [52] For older adults, integrating these devices into their lifestyle may be difficult or simply unwanted, particularly for those who have functional deficits or who are not as technologically savvy  ... 
doi:10.1136/bmjopen-2021-054561 pmid:35264349 pmcid:PMC8915330 fatcat:mim2756jwzaf3mdtjn34hmagia

Europe? A speech

Gayatri Chakravorty Spivak
2016 Aletria: Revista de Estudos de Literatura  
I work here with Suzana Milevska.  ...  They illustrate the long itinerary of the desire for continentality and because, apart from the small group I train, the landless illiterate electorate, the largest sector in India, savvy in many ways,  ... 
doi:10.17851/2317-2096.25.3.13-30 fatcat:7dmljcsfwned7hliekaiauef6u

Competitive priorities of manufacturing firms in the Caribbean

Suzana N. Russell, Harvey H. Millar
2014 IOSR Journal of Business and Management  
As Caribbean consumers become more environmentally savvy, sustainability could become a competitive differentiator and a major factor in their purchasing decisions.  ... 
doi:10.9790/487x-161017282 fatcat:zowcm3i7pzabjkt2yfeklhotum

Effect of cell permeability and dehydrogenase expression on octane activation by CYP153A6-based whole cell Escherichia coli catalysts

Bronwyn E. White, Caryn J. Fenner, Martha S. Smit, Susan T. L. Harrison
2017 Microbial Cell Factories  
Biotechnology for construction of plasmids and Suzana Savvi from CeBER for transformation of constructs to create pET28b+/pACYCDuet strains; and to Mariette Smart from CeBER for assistance in creating  ... 
doi:10.1186/s12934-017-0763-0 pmid:28931395 pmcid:PMC5607502 fatcat:m6uzju2z35gwzmjw3g7nefmtsu

Produções de verdade perante as vivências da sexualidade juvenil a partir da troca de fotos em aplicativos de celulares

Tassio Acosta
2020 Revista Periódicus  
O sexting, de acordo com Paula Ribeiro e Suzana Barros (2015) , é uma experimentação e vivência consensual da sexualidade, consistindo na troca virtual de fotos e vídeos íntimos entre pessoas com algum  ...  Foundation (2005) , num estudo dirigido pela Universidade de Stanford, a geração que já nasceu com o desenvolvimento dos dispositivos tecnológico dos computadores e smartphones é conhecida como Geração Tech-Savvy  ... 
doi:10.9771/peri.v1i12.29169 fatcat:st62tvq56na2xpw55ndd6dgst4
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