288 research outputs found
Probing Selectivity and Creating Structural Diversity Through Hybrid Polyketide Synthases
Engineering polyketide synthases (PKS) to produce new metabolites requires an understanding of catalytic points of failure during substrate processing. Growing evidence indicates the thioesterase (TE) domain as a significant bottleneck within engineered PKS systems. We created a series of hybrid PKS modules bearing exchanged TE domains from heterologous pathways and challenged them with both native and nonânative polyketide substrates. Reactions pairing wildtype PKS modules with nonânative substrates primarily resulted in poor conversions to anticipated macrolactones. Likewise, product formation with native substrates and hybrid PKS modules bearing nonâcognate TE domains was severely reduced. In contrast, nonânative substrates were converted by most hybrid modules containing a substrate compatible TE, directly implicating this domain as the major catalytic gatekeeper and highlighting its value as a target for protein engineering to improve analog production in PKS pathways.Improved catalysis with engineered polyketide synthases: Pairing wildâtype polyketide synthases with nonânative substrates largely failed to produce the anticipated products. A series of hybrid modules bearing heterologous thioesterase domains were generated and employed to alleviate the observed catalytic bottleneck, resulting in the efficient processing of nonânative substrates and an unexpected path to product diversity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156208/3/anie202004991-sup-0001-misc_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156208/2/anie202004991_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156208/1/anie202004991.pd
Surprisingly Simple Spectra
The large N limit of the anomalous dimensions of operators in
super Yang-Mills theory described by restricted Schur polynomials, are studied.
We focus on operators labeled by Young diagrams that have two columns (both
long) so that the classical dimension of these operators is O(N). At large N
these two column operators mix with each other but are decoupled from operators
with columns. The planar approximation does not capture the large N
dynamics. For operators built with 2, 3 or 4 impurities the dilatation operator
is explicitly evaluated. In all three cases, in a certain limit, the dilatation
operator is a lattice version of a second derivative, with the lattice emerging
from the Young diagram itself. The one loop dilatation operator is diagonalized
numerically. All eigenvalues are an integer multiple of and there
are interesting degeneracies in the spectrum. The spectrum we obtain for the
one loop anomalous dimension operator is reproduced by a collection of harmonic
oscillators. This equivalence to harmonic oscillators generalizes giant
graviton results known for the BPS sector and further implies that the
Hamiltonian defined by the one loop large dilatation operator is
integrable. This is an example of an integrable dilatation operator, obtained
by summing both planar and non-planar diagrams.Comment: 34 page
Probing Selectivity and Creating Structural Diversity Through Hybrid Polyketide Synthases
Engineering polyketide synthases (PKS) to produce new metabolites requires an understanding of catalytic points of failure during substrate processing. Growing evidence indicates the thioesterase (TE) domain as a significant bottleneck within engineered PKS systems. We created a series of hybrid PKS modules bearing exchanged TE domains from heterologous pathways and challenged them with both native and nonânative polyketide substrates. Reactions pairing wildtype PKS modules with nonânative substrates primarily resulted in poor conversions to anticipated macrolactones. Likewise, product formation with native substrates and hybrid PKS modules bearing nonâcognate TE domains was severely reduced. In contrast, nonânative substrates were converted by most hybrid modules containing a substrate compatible TE, directly implicating this domain as the major catalytic gatekeeper and highlighting its value as a target for protein engineering to improve analog production in PKS pathways.Improved catalysis with engineered polyketide synthases: Pairing wildâtype polyketide synthases with nonânative substrates largely failed to produce the anticipated products. A series of hybrid modules bearing heterologous thioesterase domains were generated and employed to alleviate the observed catalytic bottleneck, resulting in the efficient processing of nonânative substrates and an unexpected path to product diversity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156161/2/ange202004991-sup-0001-misc_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156161/1/ange202004991.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156161/3/ange202004991_am.pd
Exciton-carrier coupling in a metal halide perovskite nanocrystal assembly probed by two-dimensional coherent spectroscopy
The surface chemistry and inter-connectivity within perovskite nanocrystals
play a critical role in determining the electronic interactions. They manifest
in the Coulomb screening of electron-hole correlations and the carrier
relaxation dynamics, among other many-body processes. Here, we characterize the
coupling between the exciton and free carrier states close to the band-edge in
a ligand-free formamidinium lead bromide nanocrystal assembly via
two-dimensional coherent spectroscopy. The optical signatures observed in this
work show: (i) a nonlinear spectral lineshape reminiscent of Fano-like
interference that evidences the coupling between discrete electronic states and
a continuum, (ii) symmetric excited state absorption cross-peaks that suggest
the existence of a coupled exciton-carrier excited state, and (iii) ultrafast
carrier thermalization and exciton formation. Our results highlight the
presence of coherent coupling between exciton and free carriers, particularly
in the sub-100 femtosecond timescales
Effect of connectivity on the carrier transport and recombination dynamics of perovskite quantum dot networks
Quantum dot (QD) solids are being widely exploited as a solution-processable
technology to develop photovoltaic, light-emission, and photo-detection
devices. Charge transport in these materials is the result of a compromise
between confinement at the individual QD level and electronic coupling among
the different nanocrystals in the ensemble. While this is commonly achieved by
ligand engineering in colloidal-based systems, ligand-free QD assemblies have
recently emerged as an exciting alternative where nanostructures can be
directly grown into porous matrices with optical quality as well as control
over their connectivity and hence charge transport properties. In this context,
we present a complete photophysical study comprising fluence and
temperature-dependent time-resolved spectroscopy to study carrier dynamics in
ligand-free QD networks with gradually varying degrees of interconnectivity,
which we achieve by changing the average distance between the QDs. Analysis of
the photoluminescence and absorption properties of the QD assemblies, involving
both static and time-resolved measurements, allows us to identify the weight of
the different recombination mechanisms, both radiative and non-radiative, as a
function of QD connectivity. We propose a picture where carrier diffusion,
which is needed for any optoelectronic application and implies inter-particle
transport, gives rise to the exposure of carriers to a larger defect landscape
than in the case of isolated QDs. The use of a broad range of fluences permits
extracting valuable information for applications demanding either low or high
carrier injection levels and highlighting the relevance of a judicious design
to balance recombination and diffusion.Comment: 16 pages, 5 figures in main manuscript; 11 pages, 11 figures in
Supporting Informatio
Medications as a Potential Source of Exposure to Phthalates in the U.S. Population
Background: Widespread human exposure to phthalates, some of which are developmental and reproductive toxicants in experimental animals, raises concerns about potential human health risks. Underappreciated sources of exposure include phthalates in the polymers coating some oral medications. Objective: The objective of this study was to evaluate whether users of phthalate-containing medications have higher urinary concentrations of phthalate metabolites than do nonusers. Methods: We used publically available files from the National Health and Nutrition Examination Survey for the years 1999â2004. For certain survey periods, participants were asked to recall use of prescription medication during the past 30 days, and for a subsample of individuals, the urinary concentrations of phthalate metabolites were measured. We a priori identified medications potentially containing phthalates as inactive ingredients and then compared the mean urinary concentration of phthalate metabolites between users and nonusers of those medications. Results: Of the 7,999 persons with information on urinary phthalate concentrations, 6 reported using mesalamine formulations, some of which may include dibutyl phthalate (DBP); the mean urinary concentration of monobutyl phthalate, the main DBP metabolite, among these mesalamine users was 50 times higher than the mean for nonusers (2,257 ÎŒg/L vs. 46 ÎŒg/L; p < 0.0001). Users of didanosine, omeprazole, and theophylline products, some of which may contain diethyl phthalate (DEP), had mean urinary concentrations of monoethyl phthalate, the main DEP metabolite, significantly higher than the mean for nonusers. Conclusion: Select medications might be a source of high exposure to some phthalates, one of which, DBP, shows adverse developmental and reproductive effects in laboratory animals. These results raise concern about potential human health risks, specifically among vulnerable segments of the general population and particularly pregnant women and children
Maximal Oxidative Capacity during Exercise Is Associated with Skeletal Muscle Fuel Selection and Dynamic Changes in Mitochondrial Protein Acetylation
SummaryMaximal exercise-associated oxidative capacity is strongly correlated with health and longevity in humans. Rats selectively bred for high running capacity (HCR) have improved metabolic health and are longer-lived than their low-capacity counterparts (LCR). Using metabolomic and proteomic profiling, we show that HCR efficiently oxidize fatty acids (FAs) and branched-chain amino acids (BCAAs), sparing glycogen and reducing accumulation of short- and medium-chain acylcarnitines. HCR mitochondria have reduced acetylation of mitochondrial proteins within oxidative pathways at rest, and there is rapid protein deacetylation with exercise, which is greater in HCR than LCR. Fluxomic analysis of valine degradation with exercise demonstrates a functional role of differential protein acetylation in HCR and LCR. Our data suggest that efficient FA and BCAA utilization contribute to high intrinsic exercise capacity and the health and longevity benefits associated with enhanced fitness
How Substitutional Point Defects in Two-Dimensional WS Induce Charge Localization, Spin-Orbit Splitting, and Strain
Control of impurity concentrations in semiconducting materials is essential
to device technology. Because of their intrinsic confinement, the properties of
two-dimensional semiconductors such as transition metal dichalcogenides (TMDs)
are more sensitive to defects than traditional bulk materials. The
technological adoption of TMDs is dependent on the mitigation of deleterious
defects and guided incorporation of functional foreign atoms. The first step
towards impurity control is the identification of defects and assessment of
their electronic properties. Here, we present a comprehensive study of point
defects in monolayer tungsten disulfide (WS) grown by chemical vapor
deposition (CVD) using scanning tunneling microscopy/spectroscopy, CO-tip
noncontact atomic force microscopy, Kelvin probe force spectroscopy, density
functional theory, and tight-binding calculations. We observe four different
substitutional defects: chromium (Cr) and molybdenum
(Mo) at a tungsten site, oxygen at sulfur sites in both bottom and
top layers (O top/bottom), as well as two negatively charged
defects (CDs). Their electronic fingerprints unambiguously corroborate the
defect assignment and reveal the presence or absence of in-gap defect states.
The important role of charge localization, spin-orbit coupling, and strain for
the formation of deep defect states observed at substitutional defects in
WS as reported here will guide future efforts of targeted defect
engineering and doping of TMDs
Venous Graft-Derived Cells Participate in Peripheral Nerve Regeneration
Background: Based on growing evidence that some adult multipotent cells necessary for tissue regeneration reside in the walls of blood vessels and the clinical success of vein wrapping for functional repair of nerve damage, we hypothesized that the repair of nerves via vein wrapping is mediated by cells migrating from the implanted venous grafts into the nerve bundle. Methodology/Principal Findings: To test the hypothesis, severed femoral nerves of rats were grafted with venous grafts from animals of the opposite sex. Nerve regeneration was impaired when decellularized or irradiated venous grafts were used in comparison to untreated grafts, supporting the involvement of venous graft-derived cells in peripheral nerve repair. Donor cells bearing Y chromosomes integrated into the area of the host injured nerve and participated in remyelination and nerve regeneration. The regenerated nerve exhibited proper axonal myelination, and expressed neuronal and glial cell markers. Conclusions/Significance: These novel findings identify the mechanism by which vein wrapping promotes nerve regeneration. © 2011 Lavasani et al
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