LIVIVO - Search results -

Search results

Result 1 - 10 of total 19

Search options

Article ; Online: Measurement and modeling of signaling at the single-cell level.

Kolitz, Sarah E / Lauffenburger, Douglas A

2012 Volume 51, Issue 38, Page(s) 7433–7443

Abstract: It has long been recognized that a deeper understanding of cell function, with respect to execution of phenotypic behaviors and their regulation by the extracellular environment, is likely to be achieved by analyzing the underlying molecular processes ... ...

Abstract	It has long been recognized that a deeper understanding of cell function, with respect to execution of phenotypic behaviors and their regulation by the extracellular environment, is likely to be achieved by analyzing the underlying molecular processes for individual cells selected from across a population, rather than averages of many cells comprising that population. In recent years, experimental and computational methods for undertaking these analyses have advanced rapidly. In this review, we provide a perspective on both measurement and modeling facets of biochemistry at a single-cell level. Our central focus is on receptor-mediated signaling networks that regulate cell phenotypic functions.
MeSH term(s)	Microfluidics ; Models, Molecular ; Signal Transduction
Language	English
Publishing date	2012-09-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	1108-3
ISSN	1520-4995 ; 0006-2960
ISSN (online)	1520-4995
ISSN	0006-2960
DOI	10.1021/bi300846p
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 217: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Eukaryotic initiator tRNA: finely tuned and ready for action.

Kolitz, Sarah E / Lorsch, Jon R

FEBS letters

2009 Volume 584, Issue 2, Page(s) 396–404

Abstract: The initiator tRNA must serve functions distinct from those of other tRNAs, evading binding to elongation factors and instead binding directly to the ribosomal P site with the aid of initiation factors. It plays a key role in decoding the start codon, ... ...

Abstract	The initiator tRNA must serve functions distinct from those of other tRNAs, evading binding to elongation factors and instead binding directly to the ribosomal P site with the aid of initiation factors. It plays a key role in decoding the start codon, setting the frame for translation of the mRNA. Sequence elements and modifications of the initiator tRNA distinguish it from the elongator methionyl tRNA and help it to perform its varied tasks. These identity elements appear to finely tune the structure of the initiator tRNA, and growing evidence suggests that the body of the tRNA is involved in transmitting the signal that the start codon has been found to the rest of the pre-initiation complex.
MeSH term(s)	Anticodon/metabolism ; Codon, Initiator/metabolism ; Eukaryotic Initiation Factor-2/metabolism ; Nucleic Acid Conformation ; Peptide Chain Initiation, Translational ; RNA, Transfer, Met/chemistry ; RNA, Transfer, Met/metabolism ; Ribosomes/metabolism
Chemical Substances	Anticodon ; Codon, Initiator ; Eukaryotic Initiation Factor-2 ; RNA, Transfer, Met
Language	English
Publishing date	2009-11-17
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	212746-5
ISSN	1873-3468 ; 0014-5793
ISSN (online)	1873-3468
ISSN	0014-5793
DOI	10.1016/j.febslet.2009.11.047
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.B 282: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: Measurement and Modeling of Signaling at the Single-Cell Level

Kolitz, Sarah E / Lauffenburger Douglas A

Biochemistry. 2012 Sept. 25, v. 51, no. 38

2012

Abstract	It has long been recognized that a deeper understanding of cell function, with respect to execution of phenotypic behaviors and their regulation by the extracellular environment, is likely to be achieved by analyzing the underlying molecular processes for individual cells selected from across a population, rather than averages of many cells comprising that population. In recent years, experimental and computational methods for undertaking these analyses have advanced rapidly. In this review, we provide a perspective on both measurement and modeling facets of biochemistry at a single-cell level. Our central focus is on receptor-mediated signaling networks that regulate cell phenotypic functions.
Keywords	biochemistry ; models ; phenotype
Language	English
Dates of publication	2012-0925
Size	p. 7433-7443.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	1108-3
ISSN	1520-4995 ; 0006-2960
ISSN (online)	1520-4995
ISSN	0006-2960
DOI	10.1021%2Fbi300846p
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Cologne/Königswinter

Zs.A 217: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Leveraging existing data sets to generate new insights into Alzheimer's disease biology in specific patient subsets.

Fowler, Kevin D / Funt, Jason M / Artyomov, Maxim N / Zeskind, Benjamin / Kolitz, Sarah E / Towfic, Fadi

Scientific reports

2015 Volume 5, Page(s) 14324

Abstract: To generate new insights into the biology of Alzheimer's Disease (AD), we developed methods to combine and reuse a wide variety of existing data sets in new ways. We first identified genes consistently associated with AD in each of four separate ... ...

Abstract	To generate new insights into the biology of Alzheimer's Disease (AD), we developed methods to combine and reuse a wide variety of existing data sets in new ways. We first identified genes consistently associated with AD in each of four separate expression studies, and confirmed this result using a fifth study. We next developed algorithms to search hundreds of thousands of Gene Expression Omnibus (GEO) data sets, identifying a link between an AD-associated gene (NEUROD6) and gender. We therefore stratified patients by gender along with APOE4 status, and analyzed multiple SNP data sets to identify variants associated with AD. SNPs in either the region of NEUROD6 or SNAP25 were significantly associated with AD, in APOE4+ females and APOE4+ males, respectively. We developed algorithms to search Connectivity Map (CMAP) data for medicines that modulate AD-associated genes, identifying hypotheses that warrant further investigation for treating specific AD patient subsets. In contrast to other methods, this approach focused on integrating multiple gene expression datasets across platforms in order to achieve a robust intersection of disease-affected genes, and then leveraging these results in combination with genetic studies in order to prioritize potential genes for targeted therapy.
MeSH term(s)	Algorithms ; Alzheimer Disease/drug therapy ; Alzheimer Disease/genetics ; Apolipoprotein E4/metabolism ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Databases, Protein ; Female ; Gene Expression Regulation/genetics ; Genetic Predisposition to Disease ; Humans ; Male ; Polymorphism, Single Nucleotide/genetics ; Sex Factors ; Synaptosomal-Associated Protein 25/genetics
Chemical Substances	Apolipoprotein E4 ; Basic Helix-Loop-Helix Transcription Factors ; NEUROD6 protein, human ; SNAP25 protein, human ; Synaptosomal-Associated Protein 25
Language	English
Publishing date	2015-09-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep14324
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Full text

Order via subito

Details ▾
- Full text online
- Order with fees

Article ; Online: Kinetic and thermodynamic analysis of the role of start codon/anticodon base pairing during eukaryotic translation initiation.

Kolitz, Sarah E / Takacs, Julie E / Lorsch, Jon R

RNA (New York, N.Y.)

2008 Volume 15, Issue 1, Page(s) 138–152

Abstract: Start codon recognition is a crucial event in the initiation of protein synthesis. To gain insight into the mechanism of start codon recognition in eukaryotes, we used a yeast reconstituted initiation system to isolate the step of Met-tRNA(i)*eIF2*GTP ... ...

Abstract	Start codon recognition is a crucial event in the initiation of protein synthesis. To gain insight into the mechanism of start codon recognition in eukaryotes, we used a yeast reconstituted initiation system to isolate the step of Met-tRNA(i)eIF2GTP ternary complex (TC) binding to the 40S subunit. We examined the kinetics and thermodynamics of this step in the presence of base changes in the mRNA start codon and initiator methionyl tRNA anticodon, in order to investigate the effects of base pairing and sequence on the stability of the resulting 43SmRNA complex. We observed that the formation of three base pairs, rather than their identities, was the key determinant of stability of TC binding, indicating that nothing is inherently special about the sequence AUG for this step. Surprisingly, the rate constant for TC binding to the 40S subunit was strongly codon dependent, whereas the rate constant for TC dissociation from the 43SmRNA complex was not. The data suggest a model in which, after the initial diffusion-limited encounter of TC with the 40S subunit, the formation of three matching start codon/anticodon base pairs triggers a conformational change that locks the complex into a stable state. This induced-fit mechanism supports the proposal that initiation codon recognition by the 43S complex induces a conformational change from an open state to a closed one that arrests movement along the mRNA.
MeSH term(s)	Anticodon/chemistry ; Anticodon/metabolism ; Base Pairing ; Binding Sites ; Codon, Initiator/chemistry ; Codon, Initiator/metabolism ; Eukaryotic Initiation Factor-1/chemistry ; Eukaryotic Initiation Factor-1/metabolism ; Eukaryotic Initiation Factor-2/chemistry ; Eukaryotic Initiation Factor-2/metabolism ; Kinetics ; Models, Biological ; Peptide Chain Initiation, Translational/genetics ; Protein Subunits/chemistry ; Protein Subunits/metabolism ; RNA, Messenger/metabolism ; Ribosome Subunits, Small, Eukaryotic/chemistry ; Ribosome Subunits, Small, Eukaryotic/metabolism ; Thermodynamics
Chemical Substances	Anticodon ; Codon, Initiator ; Eukaryotic Initiation Factor-1 ; Eukaryotic Initiation Factor-2 ; Protein Subunits ; RNA, Messenger
Language	English
Publishing date	2008-11-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1241540-6
ISSN	1469-9001 ; 1355-8382
ISSN (online)	1469-9001
ISSN	1355-8382
DOI	10.1261/rna.1318509
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4777: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Yeast initiator tRNA identity elements cooperate to influence multiple steps of translation initiation.

Kapp, Lee D / Kolitz, Sarah E / Lorsch, Jon R

RNA (New York, N.Y.)

2006 Volume 12, Issue 5, Page(s) 751–764

Abstract: All three kingdoms of life employ two methionine tRNAs, one for translation initiation and the other for insertion of methionines at internal positions within growing polypeptide chains. We have used a reconstituted yeast translation initiation system to ...

Abstract	All three kingdoms of life employ two methionine tRNAs, one for translation initiation and the other for insertion of methionines at internal positions within growing polypeptide chains. We have used a reconstituted yeast translation initiation system to explore the interactions of the initiator tRNA with the translation initiation machinery. Our data indicate that in addition to its previously characterized role in binding of the initiator tRNA to eukaryotic initiation factor 2 (eIF2), the initiator-specific A1:U72 base pair at the top of the acceptor stem is important for the binding of the eIF2.GTP.Met-tRNA(i) ternary complex to the 40S ribosomal subunit. We have also shown that the initiator-specific G:C base pairs in the anticodon stem of the initiator tRNA are required for the strong thermodynamic coupling between binding of the ternary complex and mRNA to the ribosome. This coupling reflects interactions that occur within the complex upon recognition of the start codon, suggesting that these initiator-specific G:C pairs influence this step. The effect of these anticodon stem identity elements is influenced by bases in the T loop of the tRNA, suggesting that conformational coupling between the D-loop-T-loop substructure and the anticodon stem of the initiator tRNA may occur during AUG codon selection in the ribosomal P-site, similar to the conformational coupling that occurs in A-site tRNAs engaged in mRNA decoding during the elongation phase of protein synthesis.
MeSH term(s)	Base Sequence ; Conserved Sequence ; Eukaryotic Initiation Factor-1/isolation & purification ; Eukaryotic Initiation Factor-1/metabolism ; Eukaryotic Initiation Factor-2/isolation & purification ; Eukaryotic Initiation Factor-2/metabolism ; Eukaryotic Initiation Factor-5/isolation & purification ; Eukaryotic Initiation Factor-5/metabolism ; Eukaryotic Initiation Factors/isolation & purification ; Eukaryotic Initiation Factors/metabolism ; Guanosine Triphosphate/metabolism ; Molecular Sequence Data ; Mutation ; Nucleic Acid Conformation ; Peptide Chain Initiation, Translational ; Protein Biosynthesis ; Protein Structure, Tertiary ; Puromycin/analogs & derivatives ; Puromycin/analysis ; Puromycin/biosynthesis ; RNA, Fungal/chemistry ; RNA, Fungal/genetics ; RNA, Fungal/metabolism ; RNA, Transfer, Met/chemistry ; RNA, Transfer, Met/genetics ; RNA, Transfer, Met/isolation & purification ; RNA, Transfer, Met/metabolism ; Ribosomes/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism
Chemical Substances	Eukaryotic Initiation Factor-1 ; Eukaryotic Initiation Factor-2 ; Eukaryotic Initiation Factor-5 ; Eukaryotic Initiation Factors ; RNA, Fungal ; RNA, Transfer, Met ; eukaryotic initiation factor-5B ; eukaryotic peptide initiation factor-1A ; Puromycin (4A6ZS6Q2CL) ; methionylpuromycin (6042-08-6) ; Guanosine Triphosphate (86-01-1)
Language	English
Publishing date	2006-05
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1241540-6
ISSN	1355-8382
ISSN	1355-8382
DOI	10.1261/rna.2263906
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Full text

In stock of ZB MED Cologne/Königswinter

Zs.A 4777: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Conserved residues in yeast initiator tRNA calibrate initiation accuracy by regulating preinitiation complex stability at the start codon.

Dong, Jinsheng / Munoz, Antonio / Kolitz, Sarah E / Saini, Adesh K / Chiu, Wen-ling / Rahman, Hafsa / Lorsch, Jon R / Hinnebusch, Alan G

Genes & development

2014 Volume 28, Issue 5, Page(s) 502–520

Abstract: Eukaryotic initiator tRNA (tRNAi) contains several highly conserved unique sequence features, but their importance in accurate start codon selection was unknown. Here we show that conserved bases throughout tRNAi, from the anticodon stem to acceptor stem, ...

Abstract	Eukaryotic initiator tRNA (tRNAi) contains several highly conserved unique sequence features, but their importance in accurate start codon selection was unknown. Here we show that conserved bases throughout tRNAi, from the anticodon stem to acceptor stem, play key roles in ensuring the fidelity of start codon recognition in yeast cells. Substituting the conserved G31:C39 base pair in the anticodon stem with different pairs reduces accuracy (the Sui(-) [suppressor of initiation codon] phenotype), whereas eliminating base pairing increases accuracy (the Ssu(-) [suppressor of Sui(-)] phenotype). The latter defect is fully suppressed by a Sui(-) substitution of T-loop residue A54. These genetic data are paralleled by opposing effects of Sui(-) and Ssu(-) substitutions on the stability of methionylated tRNAi (Met-tRNA(i)) binding (in the ternary complex [TC] with eIF2-GTP) to reconstituted preinitiation complexes (PICs). Disrupting the C3:G70 base pair in the acceptor stem produces a Sui(-) phenotype and also reduces the rate of TC binding to 40S subunits in vitro and in vivo. Both defects are suppressed by an Ssu(-) substitution in eIF1A that stabilizes the open/P(OUT) conformation of the PIC that exists prior to start codon recognition. Our data indicate that these signature sequences of tRNA(i) regulate accuracy by distinct mechanisms, promoting the open/P(OUT) conformation of the PIC (for C3:G70) or destabilizing the closed/P(IN) state (for G31:C39 and A54) that is critical for start codon recognition.
MeSH term(s)	Base Pairing ; Codon, Initiator/genetics ; Conserved Sequence ; Mutation ; Protein Conformation ; Protein Stability ; RNA, Transfer, Met/genetics ; RNA, Transfer, Met/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Transcription Initiation, Genetic
Chemical Substances	Codon, Initiator ; RNA, Transfer, Met
Language	English
Publishing date	2014-03-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	806684-x
ISSN	1549-5477 ; 0890-9369
ISSN (online)	1549-5477
ISSN	0890-9369
DOI	10.1101/gad.236547.113
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2292: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 54: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Advanced bioinformatics rapidly identifies existing therapeutics for patients with coronavirus disease-2019 (COVID-19).

Kim, Jason / Zhang, Jenny / Cha, Yoonjeong / Kolitz, Sarah / Funt, Jason / Escalante Chong, Renan / Barrett, Scott / Kusko, Rebecca / Zeskind, Ben / Kaufman, Howard

Journal of translational medicine

2020 Volume 18, Issue 1, Page(s) 257

Abstract: ... Vitamin E, ruxolitinib, and glutamine. Glutathione and its precursor glutamine were highly ranked by two ...

Abstract	Background: The recent global pandemic has placed a high priority on identifying drugs to prevent or lessen clinical infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), caused by Coronavirus disease-2019 (COVID-19). Methods: We applied two computational approaches to identify potential therapeutics. First, we sought to identify existing FDA approved drugs that could block coronaviruses from entering cells by binding to ACE2 or TMPRSS2 using a high-throughput AI-based binding affinity prediction platform. Second, we sought to identify FDA approved drugs that could attenuate the gene expression patterns induced by coronaviruses, using our Disease Cancelling Technology (DCT) platform. Results: Top results for ACE2 binding iincluded several ACE inhibitors, a beta-lactam antibiotic, two antiviral agents (Fosamprenavir and Emricasan) and glutathione. The platform also assessed specificity for ACE2 over ACE1, important for avoiding counterregulatory effects. Further studies are needed to weigh the benefit of blocking virus entry against potential counterregulatory effects and possible protective effects of ACE2. However, the data herein suggest readily available drugs that warrant experimental evaluation to assess potential benefit. DCT was run on an animal model of SARS-CoV, and ranked compounds by their ability to induce gene expression signals that counteract disease-associated signals. Top hits included Vitamin E, ruxolitinib, and glutamine. Glutathione and its precursor glutamine were highly ranked by two independent methods, suggesting both warrant further investigation for potential benefit against SARS-CoV-2. Conclusions: While these findings are not yet ready for clinical translation, this report highlights the potential use of two bioinformatics technologies to rapidly discover existing therapeutic agents that warrant further investigation for established and emerging disease processes.
MeSH term(s)	Angiotensin-Converting Enzyme 2 ; Animals ; Betacoronavirus/genetics ; Betacoronavirus/physiology ; COVID-19 ; Computational Biology ; Coronavirus Infections/genetics ; Coronavirus Infections/therapy ; Gene Expression Regulation ; Glutamine/metabolism ; Humans ; Mice ; Pandemics ; Peptidyl-Dipeptidase A/metabolism ; Pneumonia, Viral/genetics ; Pneumonia, Viral/therapy ; SARS-CoV-2 ; Serine Endopeptidases/metabolism
Chemical Substances	Glutamine (0RH81L854J) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Ace2 protein, mouse (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-)
Keywords	covid19
Language	English
Publishing date	2020-06-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2118570-0
ISSN	1479-5876 ; 1479-5876
ISSN (online)	1479-5876
ISSN	1479-5876
DOI	10.1186/s12967-020-02430-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Reconstitution of yeast translation initiation.

Acker, Michael G / Kolitz, Sarah E / Mitchell, Sarah F / Nanda, Jagpreet S / Lorsch, Jon R

Methods in enzymology

2007 Volume 430, Page(s) 111–145

Abstract: To facilitate the mechanistic dissection of eukaryotic translation initiation we have reconstituted the steps of this process using purified Saccharomyces cerevisiae components. This system provides a bridge between biochemical studies in vitro and ... ...

Abstract	To facilitate the mechanistic dissection of eukaryotic translation initiation we have reconstituted the steps of this process using purified Saccharomyces cerevisiae components. This system provides a bridge between biochemical studies in vitro and powerful yeast genetic techniques, and complements existing reconstituted mammalian translation systems (Benne and Hershey, 1978; Pestova and Hellen, 2000; Pestova et al., 1998; Trachsel et al., 1977). The following describes methods for synthesizing and purifying the components of the yeast initiation system and assays useful for its characterization.
MeSH term(s)	Escherichia coli/genetics ; Escherichia coli/metabolism ; Eukaryotic Initiation Factor-1/isolation & purification ; Eukaryotic Initiation Factor-1/metabolism ; Eukaryotic Initiation Factor-2/isolation & purification ; Eukaryotic Initiation Factor-2/metabolism ; Methionine/metabolism ; Methionine-tRNA Ligase/isolation & purification ; Methionine-tRNA Ligase/metabolism ; Protein Biosynthesis ; Protein Isoforms/isolation & purification ; Protein Isoforms/metabolism ; RNA, Fungal/genetics ; RNA, Fungal/isolation & purification ; RNA, Fungal/metabolism ; RNA, Ribosomal/isolation & purification ; RNA, Ribosomal/metabolism ; RNA, Transfer, Met/metabolism ; Ribosome Subunits, Large, Eukaryotic/chemistry ; Ribosome Subunits, Large, Eukaryotic/genetics ; Ribosome Subunits, Large, Eukaryotic/metabolism ; Ribosome Subunits, Small, Eukaryotic/chemistry ; Ribosome Subunits, Small, Eukaryotic/genetics ; Ribosome Subunits, Small, Eukaryotic/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/isolation & purification ; Saccharomyces cerevisiae Proteins/metabolism
Chemical Substances	Eukaryotic Initiation Factor-1 ; Eukaryotic Initiation Factor-2 ; Protein Isoforms ; RNA, Fungal ; RNA, Ribosomal ; RNA, Transfer, Met ; Saccharomyces cerevisiae Proteins ; Methionine (AE28F7PNPL) ; Methionine-tRNA Ligase (EC 6.1.1.10)
Language	English
Publishing date	2007
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	0076-6879
ISSN	0076-6879
DOI	10.1016/S0076-6879(07)30006-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Advanced bioinformatics rapidly identifies existing therapeutics for patients with coronavirus disease-2019 (COVID-19)

Kim, Jason / Zhang, Jenny / Cha, Yoonjeong / Kolitz, Sarah / Funt, Jason / Escalante Chong, Renan / Barrett, Scott / Kusko, Rebecca / Zeskind, Ben / Kaufman, Howard

J Transl Med

Abstract: ... gene expression signals that counteract disease-associated signals. Top hits included Vitamin E, ruxolitinib, and ...

Abstract	BACKGROUND: The recent global pandemic has placed a high priority on identifying drugs to prevent or lessen clinical infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), caused by Coronavirus disease-2019 (COVID-19). METHODS: We applied two computational approaches to identify potential therapeutics. First, we sought to identify existing FDA approved drugs that could block coronaviruses from entering cells by binding to ACE2 or TMPRSS2 using a high-throughput AI-based binding affinity prediction platform. Second, we sought to identify FDA approved drugs that could attenuate the gene expression patterns induced by coronaviruses, using our Disease Cancelling Technology (DCT) platform. RESULTS: Top results for ACE2 binding iincluded several ACE inhibitors, a beta-lactam antibiotic, two antiviral agents (Fosamprenavir and Emricasan) and glutathione. The platform also assessed specificity for ACE2 over ACE1, important for avoiding counterregulatory effects. Further studies are needed to weigh the benefit of blocking virus entry against potential counterregulatory effects and possible protective effects of ACE2. However, the data herein suggest readily available drugs that warrant experimental evaluation to assess potential benefit. DCT was run on an animal model of SARS-CoV, and ranked compounds by their ability to induce gene expression signals that counteract disease-associated signals. Top hits included Vitamin E, ruxolitinib, and glutamine. Glutathione and its precursor glutamine were highly ranked by two independent methods, suggesting both warrant further investigation for potential benefit against SARS-CoV-2. CONCLUSIONS: While these findings are not yet ready for clinical translation, this report highlights the potential use of two bioinformatics technologies to rapidly discover existing therapeutic agents that warrant further investigation for established and emerging disease processes.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #613899
Database	COVID19

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Kategorien

Inter-library loan at ZB MED