Search results for " protein"
showing 10 items of 12147 documents
Double copies of blaKPC-3::Tn4401a on an IncX3 plasmid in Klebsiella pneumoniae successful clone ST512 from Italy
2015
ABSTRACT A carbapenem-resistant sequence type 512 (ST512) Klebsiella pneumoniae carbapenemase 3 (KPC-3)-producing K. pneumoniae strain showing a novel variant plasmid content was isolated in Palermo, Italy, in 2014. ST512 is a worldwide successful clone associated with the spread of bla KPC genes located on the IncFIIk pKpQIL plasmid. In our ST512 strain, the bla KPC-3 gene was unusually located on an IncX3 plasmid, whose complete sequence was determined. Two copies of bla KPC-3 ::Tn 4401a caused by intramolecular transposition events were detected in the plasmid.
The prolyl-isomerase PIN1 is essential for nuclear Lamin-B structure and function and protects heterochromatin under mechanical stress.
2021
Summary: Chromatin organization plays a crucial role in tissue homeostasis. Heterochromatin relaxation and consequent unscheduled mobilization of transposable elements (TEs) are emerging as key contributors of aging and aging-related pathologies, including Alzheimer’s disease (AD) and cancer. However, the mechanisms governing heterochromatin maintenance or its relaxation in pathological conditions remain poorly understood. Here we show that PIN1, the only phosphorylation-specific cis/trans prolyl isomerase, whose loss is associated with premature aging and AD, is essential to preserve heterochromatin. We demonstrate that this PIN1 function is conserved from Drosophila to humans and prevents…
Hydrogen isotopes (δ2H) of polyunsaturated fatty acids track bioconversion by zooplankton
2022
1. Organisms at the base of aquatic food webs synthesize essential nutrients, such as omega-3 polyunsaturated fatty acids (n-3 PUFA), which are transferred to consumers at higher trophic levels. Many consumers, requiring n-3 long-chain (LC) PUFA, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have limited ability to biosynthesize them from the essential dietary precursor α-linolenic acid (ALA) and thus rely on dietary provision of LC-PUFA. 2. We investigated LC-PUFA metabolism in freshwater zooplankton using stable hydrogen isotopes (δ2H) of fatty acids as tracers. We conducted feeding experiments with the freshwater keystone grazer Daphnia to quantify changes in the δ2…
Dipeptidyl Enoates As Potent Rhodesain Inhibitors That Display a Dual Mode of Action
2015
Dipeptidyl enoates were prepared through a high-yielding two-step synthetic route. They have a dipeptidic structure with a 4-oxoenoate moiety as a warhead with multiple reactive sites. Dipeptidyl enoates were screened against rhodesain and human cathepsins B and L, and were found to be potent and selective inhibitors of rhodesain. Among them (S,E)-ethyl 5-((S)-2-{[(benzyloxy)carbonyl]amino}-3-phenylpropanamido)-7-methyl-4-oxooct-2-enoate (6) was the most potent, with an IC50 value of 16.4 nm and kinact/Ki=1.6×106 m−1 s−1 against rhodesain. These dipeptidyl enoates display a reversible mode of inhibition at very low concentrations and an irreversible mode at higher concentrations. Inhibition…
Experimental Evolution Reveals a Genetic Basis for Membrane-Associated Virus Release
2021
Many animal viruses replicate and are released from cells in close association to membranes. However, whether this is a passive process or is controlled by the virus remains poorly understood. Importantly, the genetic basis and evolvability of membrane-associated viral shedding have not been investigated. To address this, we performed a directed evolution experiment using coxsackievirus B3, a model enterovirus, in which we repeatedly selected the free-virion or the fast-sedimenting membrane-associated viral subpopulations. The virus responded to this selection regime by reproducibly fixing a series of mutations that altered the extent of membrane-associated viral shedding, as revealed by fu…
Autophagy is induced by resistance exercise in young men but unfolded protein response is induced regardless of age
2018
Aim Autophagy and unfolded protein response (UPR) appear to be important for skeletal muscle homoeostasis and may be altered by exercise. Our aim was to investigate the effects of resistance exercise and training on indicators of UPR and autophagy in healthy untrained young men (n = 12, 27 ± 4 years) and older men (n = 8, 61 ± 6 years) as well as in resistance‐trained individuals (n = 15, 25 ± 5 years). Methods Indicators of autophagy and UPR were investigated from the muscle biopsies after a single resistance exercise bout and after 21 weeks of resistance training. Results Lipidated LC3II as an indicator of autophagosome content increased at 48 hours post‐resistance exercise (P < .05) and …
Observation of the Early Structural Changes Leading to the Formation of Protein Superstructures.
2014
Formation of superstructures in protein aggregation processes has been indicated as a general pathway for several proteins, possibly playing a role in human pathologies. There is a severe lack of knowledge on the origin of such species in terms of both mechanisms of formation and structural features. We use equine lysozyme as a model protein, and by combining spectroscopic techniques and microscopy with X-ray fiber diffraction and ab initio modeling of Small Angle X-ray Scattering data, we isolate the partially unfolded state from which one of these superstructures (i.e., particulate) originates. We reveal the low-resolution structure of the unfolded state and its mechanism of formation, hi…
Regulation of type 1 fimbriae synthesis and biofilm formation by the transcriptional regulator LrhA of Escherichia coli
2005
Type 1 fimbriae ofEscherichia colifacilitate attachment to the host mucosa and promote biofilm formation on abiotic surfaces. The transcriptional regulator LrhA, which is known as a repressor of flagellar, motility and chemotaxis genes, regulates biofilm formation and expression of type 1 fimbriae. Whole-genome expression profiling revealed that inactivation oflrhAresults in an increased expression of structural components of type 1 fimbriae.In vitro, LrhA bound to the promoter regions of the twofimrecombinases (FimB and FimE) that catalyse the inversion of thefimApromoter, and to the invertible element itself. TranslationallacZfusions with these genes and quantification offimEtranscript le…
Properties of transmembrane helix TM1 of the DcuS sensor kinase of Escherichia coli, the stator for TM2 piston signaling
2021
Abstract The sensor kinase DcuS of Escherichia coli perceives extracellular fumarate by a periplasmic PASP sensor domain. Transmembrane (TM) helix TM2, present as TM2-TM2′ homo-dimer, transmits fumarate activation in a piston-slide across the membrane. The second TM helix of DcuS, TM1, is known to lack piston movement. Structural and functional properties of TM1 were analyzed. Oxidative Cys-crosslinking (CL) revealed homo-dimerization of TM1 over the complete membrane, but only the central part showed α-helical +3/+4 spacing of the CL maxima. The GALLEX bacterial two-hybrid system indicates TM1/TM1′ interaction, and the presence of a TM1-TM1′ homo-dimer is suggested. The peripheral TM1 regi…
Main protein component of high density lipoprotein, apolipoprotein A1, modulates leukocyte cell respiration
2015
HDL:n (high density lipoprotein) pääproteiinikomponentin, apolipoproteiini A1:n (ApoA1), on todettu lisäävän glykolyysia ja oksidatiivista fosforylaatiota hiiren luurankolihassoluissa. ApoA1:llä oletetaan myös olevan merkittävä rooli lihaksen normaalissa aineenvaihdunnassa ja siihen liittyvissä sairauksissa. ApoA1 vaikuttaa leukosyyttien aktivaatioon ja jakautumiseen säätelemällä solun sisäistä kolesterolitasoa. Nämä muutokset vaikuttavat myös solun aineenvaihduntaan. ApoA1:n suoranaista vaikutusta leukosyyttien soluhengitykseen ei kuitenkaan ole aiemmin tutkittu. Aiemmin on esitetty, että leukosyyttejä voitaisiin käyttää biomarkkerina kuvaamaan muutoksia mitokondrioiden toiminnassa aineenv…