LIVIVO - Search results -

Search results

Result 1 - 10 of total 63

Search options

Article ; Online: An esophagus cell atlas reveals dynamic rewiring during active eosinophilic esophagitis and remission.

Ding, Jiarui / Garber, John J / Uchida, Amiko / Lefkovith, Ariel / Carter, Grace T / Vimalathas, Praveen / Canha, Lauren / Dougan, Michael / Staller, Kyle / Yarze, Joseph / Delorey, Toni M / Rozenblatt-Rosen, Orit / Ashenberg, Orr / Graham, Daniel B / Deguine, Jacques / Regev, Aviv / Xavier, Ramnik J

Nature communications

2024 Volume 15, Issue 1, Page(s) 3344

Abstract: Coordinated cell interactions within the esophagus maintain homeostasis, and disruption can lead to eosinophilic esophagitis (EoE), a chronic inflammatory disease with poorly understood pathogenesis. We profile 421,312 individual cells from the ... ...

Abstract	Coordinated cell interactions within the esophagus maintain homeostasis, and disruption can lead to eosinophilic esophagitis (EoE), a chronic inflammatory disease with poorly understood pathogenesis. We profile 421,312 individual cells from the esophageal mucosa of 7 healthy and 15 EoE participants, revealing 60 cell subsets and functional alterations in cell states, compositions, and interactions that highlight previously unclear features of EoE. Active disease displays enrichment of ALOX15
MeSH term(s)	Humans ; Eosinophilic Esophagitis/genetics ; Eosinophilic Esophagitis/pathology ; Endothelial Cells/metabolism ; Interleukin-13 ; Inflammation/genetics
Chemical Substances	Interleukin-13
Language	English
Publishing date	2024-04-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-47647-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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.

Article ; Online: The landscape of immune dysregulation in Crohn's disease revealed through single-cell transcriptomic profiling in the ileum and colon.

Kong, Lingjia / Pokatayev, Vladislav / Lefkovith, Ariel / Carter, Grace T / Creasey, Elizabeth A / Krishna, Chirag / Subramanian, Sathish / Kochar, Bharati / Ashenberg, Orr / Lau, Helena / Ananthakrishnan, Ashwin N / Graham, Daniel B / Deguine, Jacques / Xavier, Ramnik J

Immunity

2023 Volume 56, Issue 2, Page(s) 444–458.e5

Abstract: Crohn's disease (CD) is a chronic gastrointestinal disease that is increasing in prevalence worldwide. CD is multifactorial, involving the complex interplay of genetic, immune, and environmental factors, necessitating a system-level understanding of its ... ...

Abstract	Crohn's disease (CD) is a chronic gastrointestinal disease that is increasing in prevalence worldwide. CD is multifactorial, involving the complex interplay of genetic, immune, and environmental factors, necessitating a system-level understanding of its etiology. To characterize cell-type-specific transcriptional heterogeneity in active CD, we profiled 720,633 cells from the terminal ileum and colon of 71 donors with varying inflammation status. Our integrated datasets revealed organ- and compartment-specific responses to acute and chronic inflammation; most immune changes were in cell composition, whereas transcriptional changes dominated among epithelial and stromal cells. These changes correlated with endoscopic inflammation, but small and large intestines exhibited distinct responses, which were particularly apparent when focusing on IBD risk genes. Finally, we mapped markers of disease-associated myofibroblast activation and identified CHMP1A, TBX3, and RNF168 as regulators of fibrotic complications. Altogether, our results provide a roadmap for understanding cell-type- and organ-specific differences in CD and potential directions for therapeutic development.
MeSH term(s)	Humans ; Crohn Disease ; Transcriptome ; Colon ; Ileum ; Inflammation/genetics ; Ubiquitin-Protein Ligases/genetics
Chemical Substances	RNF168 protein, human (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2023-01-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2023.01.002
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4227: 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 69: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The landscape of immune dysregulation in Crohn's disease revealed through single-cell transcriptomic profiling in the ileum and colon.

Immunity

2023 Volume 56, Issue 12, Page(s) 2855

Language	English
Publishing date	2023-11-21
Publishing country	United States
Document type	Published Erratum
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2023.10.017
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4227: 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 69: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Using analyses of amino Acid coevolution to understand protein structure and function.

Ashenberg, Orr / Laub, Michael T

Methods in enzymology

2013 Volume 523, Page(s) 191–212

Abstract: Determining which residues of a protein contribute to a specific function is a difficult problem. Analyses of amino acid covariation within a protein family can serve as a useful guide by identifying residues that are functionally coupled. Covariation ... ...

Abstract	Determining which residues of a protein contribute to a specific function is a difficult problem. Analyses of amino acid covariation within a protein family can serve as a useful guide by identifying residues that are functionally coupled. Covariation analyses have been successfully used on several different protein families to identify residues that work together to promote folding, enable protein-protein interactions, or contribute to an enzymatic activity. Covariation is a statistical signal that can be measured in a multiple sequence alignment of homologous proteins. As sequence databases have expanded dramatically, covariation analyses have become easier and more powerful. In this chapter, we describe how functional covariation arises during the evolution of proteins and how this signal can be distinguished from various background signals. We discuss the basic methodology for performing amino acid covariation analysis, using bacterial two-component signal transduction proteins as an example. We provide practical suggestions for each step of the process including assembly of protein sequences, construction of a multiple sequence alignment, measurement of covariation, and analysis of results.
MeSH term(s)	Amino Acids/chemistry ; Evolution, Molecular ; Proteins/chemistry ; Signal Transduction
Chemical Substances	Amino Acids ; Proteins
Language	English
Publishing date	2013
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	1557-7988 ; 0076-6879
ISSN (online)	1557-7988
ISSN	0076-6879
DOI	10.1016/B978-0-12-394292-0.00009-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: A cellular and spatial atlas of

bioRxiv : the preprint server for biology

2024

Abstract: ... ...

Abstract	TP53
Language	English
Publishing date	2024-02-14
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.06.28.546977
Database	MEDical Literature Analysis and Retrieval System OnLINE

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 ▾

Article ; Online: Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA.

Ashenberg, Orr / Padmakumar, Jai / Doud, Michael B / Bloom, Jesse D

PLoS pathogens

2017 Volume 13, Issue 3, Page(s) e1006288

Abstract: The innate-immune restriction factor MxA inhibits influenza replication by targeting the viral nucleoprotein (NP). Human influenza virus is more resistant than avian influenza virus to inhibition by human MxA, and prior work has compared human and avian ... ...

Abstract	The innate-immune restriction factor MxA inhibits influenza replication by targeting the viral nucleoprotein (NP). Human influenza virus is more resistant than avian influenza virus to inhibition by human MxA, and prior work has compared human and avian viral strains to identify amino-acid differences in NP that affect sensitivity to MxA. However, this strategy is limited to identifying sites in NP where mutations that affect MxA sensitivity have fixed during the small number of documented zoonotic transmissions of influenza to humans. Here we use an unbiased deep mutational scanning approach to quantify how all single amino-acid mutations to NP affect MxA sensitivity in the context of replication-competent virus. We both identify new sites in NP where mutations affect MxA resistance and re-identify mutations known to have increased MxA resistance during historical adaptations of influenza to humans. Most of the sites where mutations have the greatest effect are almost completely conserved across all influenza A viruses, and the amino acids at these sites confer relatively high resistance to MxA. These sites cluster in regions of NP that appear to be important for its recognition by MxA. Overall, our work systematically identifies the sites in influenza nucleoprotein where mutations affect sensitivity to MxA. We also demonstrate a powerful new strategy for identifying regions of viral proteins that affect inhibition by host factors.
MeSH term(s)	DNA Mutational Analysis ; High-Throughput Nucleotide Sequencing ; Humans ; Influenza A Virus, H1N1 Subtype/genetics ; Influenza A Virus, H1N1 Subtype/immunology ; Mutation ; Myxovirus Resistance Proteins/immunology ; Nucleoproteins/genetics ; Nucleoproteins/immunology ; Polymerase Chain Reaction
Chemical Substances	MX1 protein, human ; Myxovirus Resistance Proteins ; Nucleoproteins
Language	English
Publishing date	2017-03-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7366
ISSN (online)	1553-7374
ISSN	1553-7366
DOI	10.1371/journal.ppat.1006288
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Site-Specific Amino Acid Preferences Are Mostly Conserved in Two Closely Related Protein Homologs.

Doud, Michael B / Ashenberg, Orr / Bloom, Jesse D

Molecular biology and evolution

2015 Volume 32, Issue 11, Page(s) 2944–2960

Abstract: Evolution drives changes in a protein's sequence over time. The extent to which these changes in sequence lead to shifts in the underlying preference for each amino acid at each site is an important question with implications for comparative sequence- ... ...

Abstract	Evolution drives changes in a protein's sequence over time. The extent to which these changes in sequence lead to shifts in the underlying preference for each amino acid at each site is an important question with implications for comparative sequence-analysis methods, such as molecular phylogenetics. To quantify the extent that site-specific amino acid preferences shift during evolution, we performed deep mutational scanning on two homologs of human influenza nucleoprotein with 94% amino acid identity. We found that only a modest fraction of sites exhibited shifts in amino acid preferences that exceeded the noise in our experiments. Furthermore, even among sites that did exhibit detectable shifts, the magnitude tended to be small relative to differences between nonhomologous proteins. Given the limited change in amino acid preferences between these close homologs, we tested whether our measurements could inform site-specific substitution models that describe the evolution of nucleoproteins from more diverse influenza viruses. We found that site-specific evolutionary models informed by our experiments greatly outperformed nonsite-specific alternatives in fitting phylogenies of nucleoproteins from human, swine, equine, and avian influenza. Combining the experimental data from both homologs improved phylogenetic fit, partly because measurements in multiple genetic contexts better captured the evolutionary average of the amino acid preferences for sites with shifting preferences. Our results show that site-specific amino acid preferences are sufficiently conserved that measuring mutational effects in one protein provides information that can improve quantitative evolutionary modeling of nearby homologs.
MeSH term(s)	Amino Acid Sequence ; Amino Acids/genetics ; Animals ; Biological Evolution ; Computer Simulation ; Evolution, Molecular ; Horses ; Humans ; Molecular Sequence Data ; Mutation ; Phylogeny ; Proteins/genetics ; Sequence Homology, Amino Acid ; Swine
Chemical Substances	Amino Acids ; Proteins
Language	English
Publishing date	2015-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	998579-7
ISSN	1537-1719 ; 0737-4038
ISSN (online)	1537-1719
ISSN	0737-4038
DOI	10.1093/molbev/msv167
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.A 2137: 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 ▾

Article ; Online: Helix bundle loops determine whether histidine kinases autophosphorylate in cis or in trans.

Ashenberg, Orr / Keating, Amy E / Laub, Michael T

Journal of molecular biology

2013 Volume 425, Issue 7, Page(s) 1198–1209

Abstract: Bacteria frequently use two-component signal transduction pathways to sense and respond to environmental and intracellular stimuli. Upon receipt of a stimulus, a homodimeric sensor histidine kinase autophosphorylates and then transfers its phosphoryl ... ...

Abstract	Bacteria frequently use two-component signal transduction pathways to sense and respond to environmental and intracellular stimuli. Upon receipt of a stimulus, a homodimeric sensor histidine kinase autophosphorylates and then transfers its phosphoryl group to a cognate response regulator. The autophosphorylation of histidine kinases has been reported to occur both in cis and in trans, but the molecular determinants dictating which mechanism is employed are unknown. Based on structural considerations, one model posits that the handedness of a loop at the base of the helical dimerization domain plays a critical role. Here, we tested this model by replacing the loop from Escherichia coli EnvZ, which autophosphorylates in trans, with the loop from three PhoR orthologs that autophosphorylate in cis. These chimeric kinases autophosphorylated in cis, indicating that this small loop is sufficient to determine autophosphorylation mechanism. Further, we report that the mechanism of autophosphorylation is conserved in orthologous sets of histidine kinases despite highly dissimilar loop sequences. These findings suggest that histidine kinases are under selective pressure to maintain their mode of autophosphorylation, but they can do so with a wide range of sequences.
MeSH term(s)	Amino Acid Sequence ; Bacterial Outer Membrane Proteins/chemistry ; Bacterial Outer Membrane Proteins/genetics ; Bacterial Outer Membrane Proteins/metabolism ; Bacterial Proteins/chemistry ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Electrophoresis, Polyacrylamide Gel ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Escherichia coli Proteins/chemistry ; Escherichia coli Proteins/genetics ; Escherichia coli Proteins/metabolism ; Fluorescence Resonance Energy Transfer ; Histidine Kinase ; Kinetics ; Luminescent Proteins/genetics ; Luminescent Proteins/metabolism ; Models, Molecular ; Molecular Sequence Data ; Multienzyme Complexes/chemistry ; Multienzyme Complexes/genetics ; Multienzyme Complexes/metabolism ; Mutation ; Phosphorylation ; Protein Conformation ; Protein Kinases/chemistry ; Protein Kinases/genetics ; Protein Kinases/metabolism ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Sequence Homology, Amino Acid
Chemical Substances	Bacterial Outer Membrane Proteins ; Bacterial Proteins ; Escherichia coli Proteins ; Luminescent Proteins ; Multienzyme Complexes ; PhoR protein, Bacteria (107121-16-4) ; Protein Kinases (EC 2.7.-) ; Histidine Kinase (EC 2.7.13.1) ; envZ protein, E coli (EC 2.7.3.-)
Language	English
Publishing date	2013-01-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	80229-3
ISSN	1089-8638 ; 0022-2836
ISSN (online)	1089-8638
ISSN	0022-2836
DOI	10.1016/j.jmb.2013.01.011
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.A 867: 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 ▾

Article ; Online: Mutational effects on stability are largely conserved during protein evolution.

Ashenberg, Orr / Gong, L Ian / Bloom, Jesse D

Proceedings of the National Academy of Sciences of the United States of America

2013 Volume 110, Issue 52, Page(s) 21071–21076

Abstract: Protein stability and folding are the result of cooperative interactions among many residues, yet phylogenetic approaches assume that sites are independent. This discrepancy has engendered concerns about large evolutionary shifts in mutational effects ... ...

Abstract	Protein stability and folding are the result of cooperative interactions among many residues, yet phylogenetic approaches assume that sites are independent. This discrepancy has engendered concerns about large evolutionary shifts in mutational effects that might confound phylogenetic approaches. Here we experimentally investigate this issue by introducing the same mutations into a set of diverged homologs of the influenza nucleoprotein and measuring the effects on stability. We find that mutational effects on stability are largely conserved across the homologs. We reach qualitatively similar conclusions when we simulate protein evolution with molecular-mechanics force fields. Our results do not mean that proteins evolve without epistasis, which can still arise even when mutational stability effects are conserved. However, our findings indicate that large evolutionary shifts in mutational effects on stability are rare, at least among homologs with similar structures and functions. We suggest that properly describing the clearly observable and highly conserved amino acid preferences at individual sites is likely to be far more important for phylogenetic analyses than accounting for rare shifts in amino acid propensities due to site covariation.
MeSH term(s)	Computer Simulation ; Evolution, Molecular ; Mutation/genetics ; Nucleoproteins/genetics ; Phylogeny ; Protein Folding ; Protein Stability ; Proteins/genetics
Chemical Substances	Nucleoproteins ; Proteins
Language	English
Publishing date	2013-12-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1314781111
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1148: 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: Helix Bundle Loops Determine Whether Histidine Kinases Autophosphorylate in cis or in trans

Ashenberg, Orr / Keating, Amy E / Laub, Michael T

Journal of molecular biology. 2013 Apr. 12, v. 425, no. 7

2013

Abstract	Bacteria frequently use two-component signal transduction pathways to sense and respond to environmental and intracellular stimuli. Upon receipt of a stimulus, a homodimeric sensor histidine kinase autophosphorylates and then transfers its phosphoryl group to a cognate response regulator. The autophosphorylation of histidine kinases has been reported to occur both in cis and in trans, but the molecular determinants dictating which mechanism is employed are unknown. Based on structural considerations, one model posits that the handedness of a loop at the base of the helical dimerization domain plays a critical role. Here, we tested this model by replacing the loop from Escherichia coli EnvZ, which autophosphorylates in trans, with the loop from three PhoR orthologs that autophosphorylate in cis. These chimeric kinases autophosphorylated in cis, indicating that this small loop is sufficient to determine autophosphorylation mechanism. Further, we report that the mechanism of autophosphorylation is conserved in orthologous sets of histidine kinases despite highly dissimilar loop sequences. These findings suggest that histidine kinases are under selective pressure to maintain their mode of autophosphorylation, but they can do so with a wide range of sequences.
Keywords	Escherichia coli ; bacteria ; dimerization ; histidine kinase ; models ; signal transduction
Language	English
Dates of publication	2013-0412
Size	p. 1198-1209.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	80229-3
ISSN	1089-8638 ; 0022-2836
ISSN (online)	1089-8638
ISSN	0022-2836
DOI	10.1016/j.jmb.2013.01.011
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Bonn / Germany

Z 4' 63/108: Show issues

Order via subito

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 ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

Order via subito

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

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Full text online

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

In stock of ZB MED Bonn / Germany

Order via subito

Inter-library loan at ZB MED