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Found 35038 matches. Displaying 121-130
Nussenzweig PM
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Cas9 Cleavage of Viral Genomes Primes the Acquisition of New

CELL HOST & MICROBE 2019 OCT 9; 26(4):515-526.e6
Type II CRISPR-Cas systems defend prokaryotes from bacteriophage
Kumari N, Abul Hassan M, Lu XD, Roeder RG, Biswas D
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AFF1 acetylation by p300 temporally inhibits transcription during genotoxic stress response

Soon after exposure to genotoxic reagents, mammalian cells inhibit transcription to prevent collisions with repair machinery and to mount a proper DNA damage response. However, mechanisms underlying early transcriptional inhibition are poorly understood. In this report, we show that site-specific acetylation of super elongation complex (SEC) subunit AFF1 by p300 reduces its interaction with other SEC components and impairs P-TEFb-mediated C-terminal domain phosphorylation of RNA polymerase II both in vitro and in vivo. Reexpression of wild-type AFF1, but not an acetylation mimic mutant, restores SEC component recruitment and target gene expression in AFF1 knockdown cells. Physiologically, we show that, upon genotoxic exposure, p300-mediated AFF1 acetylation is dynamic and strongly correlated with concomitant global down-regulation of transcription-and that this can be reversed by over-expression of an acetylation-defective AFF1 mutant. Therefore, we describe a mechanism of dynamic transcriptional regulation involving p300-mediated acetylation of a key elongation factor during genotoxic stress.
Delgobo M, Mendes DAGB, Kozlova E, Rocha EL, Rodrigues-Luiz GF, Mascarin L, Dias G, Patricio DO, Dierckx T, Bicca MA, Bretton G, de Menezes YKT, Starick MR, Rovaris D, Del Moral J, Mansur DS, Van Weyenbergh J, Bafica A
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An evolutionary recent IFN/IL-6/CEBP axis is linked to monocyte expansion and tuberculosis severity in humans

ELIFE 2019 OCT 22; 8(?):? Article e47013
Monocyte counts are increased during human tuberculosis (TB) but it has not been determined whether Mycobacterium tuberculosis (Mtb) directly regulates myeloid commitment. We demonstrated that exposure to Mtb directs primary human CD34(+) cells to differentiate into monocytes/macrophages. In vitro myeloid conversion did not require type I or type II IFN signaling. In contrast, Mtb enhanced IL-6 responses by CD34(+) cell cultures and IL-6R neutralization inhibited myeloid differentiation and decreased mycobacterial growth in vitro. Integrated systems biology analysis of transcriptomic, proteomic and genomic data of large data sets of healthy controls and TB patients established the existence of a myeloid IL-6/IL6R/CEBP gene module associated with disease severity. Furthermore, genetic and functional analysis revealed the IL6/IL6R/CEBP gene module has undergone recent evolutionary selection, including Neanderthal introgression and human pathogen adaptation, connected to systemic monocyte counts. These results suggest Mtb co-opts an evolutionary recent IFN-IL6-CEBP feed-forward loop, increasing myeloid differentiation linked to severe TB in humans.
Sakurai K
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Cutaneous p38 mitogen-activated protein kinase activation triggers

Background: Psoriasis is a chronic inflammatory skin disease
Frew JW
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In silico Analysis of Gamma-Secretase-Complex Mutations in Hidradenitis

FRONTIERS IN MEDICINE 2019 SEP 19; 6(?):? Article 206
Background: Familial Hidradenitis Suppurativa and Familial Alzheimer's
Mukhopadhyay S
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Comparative transcriptome analysis of the human endocervix and

SCIENTIFIC REPORTS 2019 SEP 17; 9(?):? Article 13494
Despite extensive studies suggesting increased susceptibility to HIV
Braunberger TL
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Hemoglobin as an indicator of disease activity in severe hidradenitis

Blus BJ
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Substrate Affinity and Specificity of the ScSth1p Bromodomain Are

STRUCTURE 2019 SEP 3; 27(9):1460-1468.e3
Bromodomains recognize a wide range of acetylated lysines in histones
Perez-Mitta G
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Molecular Design of Solid-State Nanopores: Fundamental Concepts and

ADVANCED MATERIALS 2019 SEP; 31(37):? Article 1901483
Solid-state nanopores are fascinating objects that enable the
Rico CA
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High-Affinity Binding of Chemokine Analogs that Display Ligand Bias at

BIOPHYSICAL JOURNAL 2019 SEP 3; 117(5):903-919
The chemokine receptor CCR5 is a drug target to prevent transmission of