1,725,804 research outputs found
Genetic variants of flavin-containing monooxygenases: consequences for drug metabolism
No full textThe metabolism of the anti-tubercular drug, thiacetazone (TAZ) by human FMOs in vitro and
the disposition of TAZ in vivo in mice were studied. Reverse phase chromatography
confirmed TAZ to be a substrate for human FMO1, FMO2.1 and FMO3 with the formation
of TAZ-sulphinic acid and TAZ-carbodiimide via a TAZ- sulphenic acid intermediate. The
products are the same as those formed by the Mycobacterium tuberculosis enzyme EtaA, the
enzyme responsible for TAZ activation. Kinetic studies found FMO2.1 to be significantly
more efficient at TAZ oxygenation than EtaA, FMO1 and FMO3. Asians and Europeans do
not express functional FMO2 in their lungs as a result of a premature stop codon. However
about 28% of African individuals lack this mutation. The products of FMO2 are expected to
be toxic to mammalian cells; therefore individuals expressing FMO2 in their lungs may be at
higher risk of FMO-dependent TAZ bioactivation.
Protein variants of FMO3 were analysed for their ability to catalyse TAZ
oxygenation. Kinetic studies showed that the L360P variant displayed a significantly higher
catalytic activity towards TAZ than the wild type protein. The K158/G308 protein was
inactive towards TAZ, whereas K158 or G308 variants oxygenated TAZ. These findings
may reflect the underlying mechanism of TAZ-dependent liver toxicity reported in patients
taking TAZ as part of treatment for TB.
Mouse liver and lung microsome experiments indicated that both FMOs and
cytochromes P450 (CYPs) metabolise TAZ in vitro. FMO contribution was higher in the lung
than the liver. Kinetic studies using microsomes from Fmo1 knockout mice show FMO1 to
be the predominant contributor to TAZ oxygenation in vitro.
Metabolism of TAZ in liver and lungs of mice in vivo was not observed, however
TAZ, TAZ-sulphenic acid, TAZ-sulphinic acid and TAZ-carbodiimide were identified in
kidney
Fenna–Matthews–Olson (FMO) datasets
No full textThe dynamics of the Fenna–Matthews–Olson (FMO) complex.
FMO-Ia and FMO-Ib data sets: 7-site FMO model Hamiltonian parametrized by Adolphs and Renger solved with local thermalizing Lindblad master equation approach.
FMO-II data set: 7-site FMO model Hamiltonian parametrized by Cho et al. solved with local thermalizing Lindblad master equation approach.
FMO-III data set: 8-site FMO model Hamiltonian parametrized by Jia et al. solved with local thermalizing Lindblad master equation approach.
FMO-IV data set: 8-site FMO model Hamiltonian parametrized by Olbrich et al. and Busch et al. solved with local thermalizing Lindblad master equation approach.
FMO-V data set: FMO trimer based on 8-site model Hamiltonian parametrized by Olbrich et al. and Busch et al. solved with local thermalizing Lindblad master equation approach.
FMO-VI data set: 8-site FMO model Hamiltonian parametrized by by Olbrich et al. and Busch et al. solved solved with hierarchical equations of motion approach.
Each data set contains reduced density matrix of the electronic 7- or 8-site system.
See related materials in Collection at: https://doi.org/10.25452/figshare.plus.c.6389553
Collection description:
Simulations of the dynamics of dissipative quantum systems utilize many methods such as physics-based quantum, semiclassical, and quantum-classical as well as machine learning-based approximations, development and testing of which requires diverse data sets. Here we present a new database QD3SET-1 containing eight data sets of quantum dynamical data for two systems of broad interest, spin-boson (SB) model and the Fenna–Matthews–Olson (FMO) complex, generated with two different methods solving the dynamics, approximate local thermalizing Lindblad master equation (LTLME) and highly accurate hierarchy equations of motion (HEOM). One data set was generated with the SB model which is a two-level quantum system coupled to a harmonic environment using HEOM for 1,000 model parameters. Seven data sets were collected for the FMO complex of different sizes (7- and 8-site monomer and 24-site trimer with LTLME and 8-site monomer with HEOM) for 500–879 model parameters. Our QD3SET-1 database contains both population and coherence dynamics data and part of it has been already used for machine learning-based quantum dynamics studies.
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Requirements of Orbital Phase Continuity Revisited: A FMO Approach
No full text
Cyclic orbital interaction, in which a
series of orbitals interact with each other so as to make a monocyclic system,
affords stabilization if the requirements of orbital phase continuity are
satisfied. Initially, these requirements were derived from the consideration of
a three-body system. Here I propose that these requirements can be easily derived by
considering FMO theory.
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FMO controls.
No full textA representative plot including a sample, and fluorescence minus one (FMO) controls to show how PD-1 and CXCR5 expressing CD4+ T cell populations were identified. (TIF)</p
Flavin-containing monooxygenase (FMO): Beyond xenobiotics
No full textFlavin-containing monooxygenases (FMOs), traditionally known for detoxifying xenobiotics, are now recognized for their involvement in endogenous metabolism. We recently discovered that an isoform of FMO, fmo-2 in Caenorhabditis elegans, alters endogenous metabolism to impact longevity and stress tolerance. Increased expression of fmo-2 in C. elegans modifies the flux through the key pathway known as One Carbon Metabolism (OCM). This modified flux results in a decrease in the ratio of S-adenosyl-methionine (SAM) to S-adenosyl-homocysteine (SAH), consequently diminishing methylation capacity. Here we discuss how FMO-2-mediated formate production during tryptophan metabolism may serve as a trigger for changing the flux in OCM. We suggest formate bridges tryptophan and OCM, altering metabolic flux away from methylation during fmo-2 overexpression. Additionally, we highlight how these metabolic results intersect with the mTOR and AMPK pathways, in addition to mitochondrial metabolism. In conclusion, the goal of this essay is to bring attention to the central role of FMO enzymes but lack of understanding of their mechanisms. We justify a call for a deeper understanding of FMO enzyme’s role in metabolic rewiring through tryptophan/formate or other yet unidentified substrates. Additionally, we emphasize the identification of novel drugs and microbes to induce FMO activity and extend lifespan.The Flavin-containing Monooxygenase, fmo-2, in C. elegans is upregulated under various conditions to promote longevity and enhance stress tolerance. We hypothesize that FMO-2-mediated tryptophan metabolism elevates formate levels, consequently modifying the flux of one-carbon metabolism (OCM) and influencing signaling pathways such as mTOR and AMPK, thereby extending lifespan.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/194013/1/bies202400029.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/194013/2/bies202400029_am.pd
FMO for denoted T cell gates.
No full textA. FMO for CTLA-4+ and PD-1+ populations. Gates preceding CTLA-4 and PD-1 for CD4 T cells denoted in S3 Fig. B. FMO for CD3 and NK1.1. Cells pre-gated on singlets, live cells. (TIF)</p
Blakeney, B F, Fmo Hkrnvr
No full textThis record was harvested from a previous catalogue system and will be withdrawn in 2025. Information in this record may be superseded or incomplete. Visit this record in UMA's new catalogue at: https://archives.library.unimelb.edu.au/nodes/view/372169Surname: BLAKENEY
Given Name(s) or Initials: B F
Military Service Number or Last Known Location: FMO HKRNVR
Missing, Wounded and Prisoner of War Enquiry Card Index Number: 47713183089
Item: [2016.0049.04496] "Blakeney, B F, Fmo Hkrnvr
Benchmarking the MBE, FMO, and CPF GPU-Accelerated Fragmentation Methods for Accuracy and Parallel Time-to-Solution
No full textWe present an accuracy analysis of several fragmenta- tion methods including the embedding-free Many Body Expansion (MBE), the electrostatically-embedded MBE (EE-MBE), the Fragment Molecular Orbital (FMO) and the presently introduced Coulomb Per- turbed Fragmentation (CPF) method. We show that the iterative correction to the electrostatic potential in FMO introduces little to no accuracy gains when com- pared to the non-iterative EE-MBE and CPF methods. Additionally, we present performance comparisons of GPU accelerated implementations of most of these methods and show that MBE4 is not only more ac- curate than FMO3 but, when sufficient parallelism is provided, it is also faster
Bitrate Reduction Using FMO for Video Streaming over Packet Networks
No full textFlexible macroblock ordering (FMO), adopted in the
H.264 standard, allows to partition all macroblocks (MBs) in a frame
into separate groups of MBs called Slice Groups (SGs). FMO can not
only support error-resilience, but also control the size of video packets
for different network types. However, it is well-known that the number
of bits required for encoding the frame is increased by adopting FMO.
In this paper, we propose a novel algorithm that can reduce the bitrate
overhead caused by utilizing FMO. In the proposed algorithm, all MBs
are grouped in SGs based on the similarity of the transform
coefficients. Experimental results show that our algorithm can reduce
the bitrate as compared with conventional FMO
Fluorescence-excitation and emission spectroscopy on single FMO complexes
No full textIn green-sulfur bacteria sunlight is absorbed by antenna structures termed chlorosomes, and transferred to the RC via the Fenna-Matthews-Olson (FMO) complex. FMO consists of three monomers arranged in C3 symmetry where each monomer accommodates eight Bacteriochlorophyll a (BChl a) molecules. It was the first pigment-protein complex for which the structure has been determined with high resolution and since then this complex has been the subject of numerous studies both experimentally and theoretically. Here we report about fluorescence-excitation spectroscopy as well as emission spectroscopy from individual FMO complexes at low temperatures. The individual FMO complexes are subjected to very fast spectral fluctuations smearing out any possible different information from the ensemble data that were recorded under the same experimental conditions. In other words, on the time scales that are experimentally accessible by single-molecule techniques, the FMO complex exhibits ergodic behaviour
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