A5010189122- Advanced Electron Microscopy Techniques and Applications
- Endoplasmic Reticulum Stress and Disease
- Advanced X-ray Imaging Techniques
- Dental Education, Practice, Research
- HIV Research and Treatment
- Electron and X-Ray Spectroscopy Techniques
- Photosynthetic Processes and Mechanisms
- Mosquito-borne diseases and control
- Influenza Virus Research Studies
- Viral Infections and Vectors
- Cellular transport and secretion
- Respiratory viral infections research
- Bacteriophages and microbial interactions
- Viral gastroenteritis research and epidemiology
- Fire effects on ecosystems
- Paranormal Experiences and Beliefs
- Lipid Membrane Structure and Behavior
- ATP Synthase and ATPases Research
- RNA regulation and disease
- High Altitude and Hypoxia
- Space Science and Extraterrestrial Life
- Organic Chemistry Cycloaddition Reactions
- Hannah Arendt's Political Philosophy
- Wnt/β-catenin signaling in development and cancer
- Biological Activity of Diterpenoids and Biflavonoids
MRC University of Glasgow Centre for Virus Research
2021-2024
California Institute of Technology
2016-2023
Medical Research Council
2022
University of Alabama at Birmingham
1997-2015
University of Colorado Colorado Springs
2015
Institute of Structural and Molecular Biology
2012
University of Leeds
2010-2012
Clarkson University
2009
University of Alabama
2009
Central Washington University
2009
ABSTRACT Crimean-Congo hemorrhagic fever virus (CCHFV) is an emerging tick-borne of the Bunyaviridae family that responsible for a fatal human disease which preventative or therapeutic measures do not exist. We solved crystal structure CCHFV strain Baghdad-12 nucleocapsid protein (N), potential target, at resolution 2.1 Å. N comprises large globular domain composed both N- and C-terminal sequences, likely involved in RNA binding, protruding arm with conserved DEVD caspase-3 cleavage site its...
TRIM5 proteins are restriction factors that block retroviral infections by binding viral capsids and preventing reverse transcription. Capsid recognition is mediated C-terminal domains on TRIM5α (SPRY) or TRIMCyp (cyclophilin A), which interact weakly with capsids. Efficient capsid also requires the conserved N-terminal tripartite motifs (TRIM), mediate oligomerization create avidity effects. To characterize how recognize capsids, we developed methods for isolating native recombinant...
Mitochondrial diseases produce profound neurological dysfunction via mutations affecting mitochondrial energy production, including the relatively common Leigh syndrome (LS). We recently described an LS case caused by a pathogenic mutation in USMG5, encoding small supernumerary subunit of ATP synthase. This protein is integral for synthase dimerization, and patient fibroblasts revealed almost total loss dimers. Here, we utilize situ cryoelectron tomography (cryo-ET) clinical case-control...
Ribosome-associated vesicles are a novel, dynamic ER-derived organelle.
MINT‐7890784, MINT‐7890776: SH (uniprotkb:P04852) and bind (MI:0407) by electron microscopy (MI:0040)
The signaling network of the unfolded protein response (UPR) adjusts protein-folding capacity endoplasmic reticulum (ER) according to need. most conserved UPR sensor, IRE1α, spans ER membrane and activates through oligomerization. IRE1α oligomers accumulate in dynamic foci. We determined situ structure foci by cryogenic correlated light electron microscopy combined with cryo-tomography complementary immuno–electron mammalian cell lines. localized a narrow anastomosing tubes (diameter, ~28...
Local protein synthesis in axons and dendrites underpins synaptic plasticity. However, the composition of machinery distal neuronal processes mechanisms for its activity-driven deployment to local translation sites remain unclear. Here, we employed cryo-electron tomography, volume electron microscopy, live-cell imaging identify Ribosome-Associated Vesicles (RAVs) as a dynamic platform moving ribosomes processes. Stimulation via chemically-induced long-term potentiation causes RAV...
We study Kleinberg navigation (the search of a target in d-dimensional lattice, where each site is connected to one other random at distance r, with probability proportional r^{-a}) by means an exact master equation for the process. show that asymptotic scaling behavior delivery time T L scales as (ln L)^2 when a=d, and otherwise L^x, x=(d-a)/(d+1-a) a<d, x=a-d d<a<d+1, x=1 a>d+1. These values x exceed rigorous lower-bounds established Kleinberg. also address situation there finite message...
The fibroblast growth factor FGF21 was labeled with molecularly defined gold nanoparticles (AuNPs), applied to human adipocytes, and imaged by cryo-electron tomography (cryo-ET). Most AuNPs were in pairs about 80 Å apart, on the outer cell surface. Pairs of also abundant inside cells clathrin-coated vesicles endosomes. present but no longer paired multivesicular bodies. could thus be tracked along endocytotic pathway. methods developed here visualize signaling coupled endocytosis can a wide...
Significance One of the most notable features TRIM5 proteins is their ability to restrict retroviral infections by binding viral capsids. TRIM5α forms highly dynamic puncta various sizes, and, when purified, hexagonal nets on surface HIV virions, but molecular ultrastructure cellular bodies and relationship in vitro restriction has remained unclear. To define underlying punctate nature YFP-rhTRIM5α bodies, we applied cryogenic correlated light electron microscopy combined with...
Multiple distinct tomograms of a single β cell enable investigation the architecture insulin vesicle neighborhoods.
The
Preparation de (methoxy-2 methyl-5)-benzaldehyde, -acide benzoique et -alcool benzylique -acetophenone
Crimean-Congo haemorrhagic fever virus (CCHFV) is a member of the Nairovirus genus within Bunyaviridae family segmented negative-sense RNA viruses. This paper describes expression, purification and crystallization full-length CCHFV nucleocapsid (N) protein collection 2.1 Å resolution X-ray diffraction data set using synchrotron radiation. Crystals N belonged to space group C2, with unit-cell parameters = 150.38, b 72.06, c 101.23 Å, β 110.70° two molecules in asymmetric unit....
Cryo-electron tomography provides detailed views of macromolecules in situ . However, imaging a large field view to provide more cellular context requires reducing magnification during data collection, which turn restricts the resolution. To circumvent this trade-off between and resolution, we have developed montage collection scheme that uniformly distributes dose throughout specimen. In approach, sets slightly overlapping circular tiles are collected at high stitched form composite...
The title compound (7a) undergoes epimerisation at position 3 of the thietanone ring in presence triethylamine; equilibrium ratio starting material and its epimer (9a) is ca. 1.5 : 1. Methylation compounds or also occurs ring, sodium hydride–methyl iodide; a 1 mixture (3R)-3-methylthietanone (7b) (3S)-3-methylthietanone (9b) produced when tetrahydrofuran used as solvent whereas 2.5 formed NN-dimethylformamide employed. With potassium t-butoxide-t-butyl bromoacetate NN-dimethylformamide,...
Members of the TRIM protein family have been shown to gather into structures in both nucleus and cytoplasm. One member, TRIM5α, has form cytoplasmic bodies involved restricting retroviruses such as HIV-1. Here we applied cryogenic correlated light electron microscopy (cryo-CLEM) intact mammalian cells expressing YFP-rhTRIM5α found hexagonal nets were present whose arm-lengths similar those formed by purified TRIM5α in-vitro. We also observed within a diversity with characteristics expected...
The signaling network of the unfolded protein response (UPR) adjusts folding capacity endoplasmic reticulum (ER) according to need. most conserved UPR sensor, IRE1α, spans ER membrane and activates through oligomerization. IRE1α oligomers accumulate in dynamic foci. We determined in-situ structure foci by cryogenic correlated light electron microscopy (cryo-CLEM), combined with cryo-tomography (cryo-ET) complementary immuno-electron microscopy. localize a narrow anastomosing tubes (diameter...
The phenoxyfurans (4) and (8) undergo a Diels–Alder reaction with dimethyl acetylenedicarboxylate (DMAD) to give the cycloadducts (5) (9) which can be converted into substituted diphenyl ethers (6) (10) respectively.