1,334 research outputs found
A General, Practical Palladium-Catalyzed Cyanation of (Hetero)Aryl Chlorides and Bromides
Playing it safe: The nontoxic cyanide source K[subscript 4][Fe(CN)[subscript 6]⋅3 H[subscript 2]O can be used for the cyanation of (hetero)aryl halides. The application of palladacycle catalysts prevents poisoning during catalyst formation, thereby allowing for low catalyst loadings, fast reaction times, and wide heterocyclic substrate scope.National Institutes of Health (U.S.) (Award GM46059
Activation of TRPA1 by membrane permeable local anesthetics
<p>Abstract</p> <p>Background</p> <p>Low concentrations of local anesthetics (LAs) suppress cellular excitability by inhibiting voltage-gated Na<sup>+ </sup>channels. In contrast, LAs at high concentrations can be excitatory and neurotoxic. We recently demonstrated that LA-evoked activation of sensory neurons is mediated by the capsaicin receptor TRPV1, and, to a lesser extent by the irritant receptor TRPA1. LA-induced activation and sensitization of TRPV1 involves a domain that is similar, but not identical to the vanilloid-binding domain. Additionally, activation of TRPV1 by LAs involves PLC and PI(4,5)P<sub>2</sub>-signalling. In the present study we aimed to characterize essential structural determinants for LA-evoked activation of TRPA1.</p> <p>Results</p> <p>Recombinant rodent and human TRPA1 were expressed in HEK293t cells and investigated by means of whole-cell patch clamp recordings. The LA lidocaine activates TRPA1 in a concentration-dependent manner. The membrane impermeable lidocaine-derivative QX-314 is inactive when applied extracellularly. Lidocaine-activated TRPA1-currents are blocked by the TRPA1-antagonist HC-030031. Lidocaine is also an inhibitor of TRPA1, an effect that is more obvious in rodent than in human TRPA1. This species-specific difference is linked to the pore region (transmembrane domain 5 and 6) as described for activation of TRPA1 by menthol. Unlike menthol-sensitivity however, lidocaine-sensitivity is not similarly determined by serine- and threonine-residues within TM5. Instead, intracellular cysteine residues known to be covalently bound by reactive TRPA1-agonists seem to mediate activation of TRPA1 by LAs.</p> <p>Conclusions</p> <p>The structural determinants involved in activation of TRPA1 by LAs are disparate from those involved in activation by menthol or those involved in activation of TRPV1 by LAs.</p
Force dependent fragility in RNA hairpins
We apply Kramers theory to investigate the dissociation of multiple bonds
under mechanical force and interpret experimental results for the
unfolding/refolding force distributions of an RNA hairpin pulled at different
loading rates using laser tweezers. We identify two different kinetic regimes
depending on the range of forces explored during the unfolding and refolding
process. The present approach extends the range of validity of the two-states
approximation by providing a theoretical framework to reconstruct free-energy
landscapes and identify force-induced structural changes in molecular
transition states using single molecule pulling experiments. The method should
be applicable to RNA hairpins with multiple kinetic barriers.Comment: Latex file, 4 pages+3 figure
Snowier Winters Extend Autumn Availability of High-quality Forage for Caribou in Arctic Alaska
Caribou (Rangifer tarandus) rely on the short Arctic growing season to restore body condition, support the demands of lactation, and prepare for the long arctic winter, making them susceptible to even small changes in forage availability or quality. Body condition in the summer and autumn is linked to winter survival rates and fecundity in cows, critical factors in the productivity of caribou populations. Climate change predictions of warmer and wetter northern winters suggest increased snowfall over Alaska’s North Slope, which has recently been verified between 1995 and 2017. However, a comprehensive analysis of how deeper snow will affect caribou forage quality is absent across Alaska. In this study, we quantify how snow depth alters the quality and seasonality of caribou forage using a long-term (24 yr) International Tundra Experiment snow depth manipulation to evaluate how winter climate change scenarios may affect tussock tundra systems in northern Alaska. Deeper snow in prior winters leads to increases in growing season leaf N and digestible protein (DP) in deciduous shrubs (and Betula spp.) and graminoids (Carex spp. and Eriophorum spp.), but not evergreen dwarf shrubs (Rhododendron spp. and Vaccinium spp.). Dry matter digestibility varied among species with small differences (\u3c5%) associated with snow depth. Most striking was the discovery that deeper snow in the prior winter increased the duration of DP levels above the minimum threshold for protein gain in caribou by as much as 25 d in Salix pulchra and 6–9 d in Betula nana and Carex bigelowii in late summer and early autumn. Consequently, deeper winter snow may provide an extended window of opportunity for foraging and the accumulation of lean body mass and fat reserves which promote winter survival and successful calving the following spring and potentially improve the productivity of caribou in northern Alaska
Invasion is Contingent on Species Assemblage and Invasive Species Identity inExperimental Rehabilitation Plots
Ecological studies often suggest that diverse communities are most resistant to invasion by exotic plants, but relatively few local species may be available to a rehabilitation practitioner. We examine the ability of monocultures and diverse assemblages to resist invasion by an exotic annual grass (cheatgrass) and an exotic biennial forb (dyer’s woad) in experimental rehabilitation plots. We constructed seven assemblages that included three monocultures of grass, forb, or shrub; three four-species mixtures of grasses, forbs, or shrubs; and a three-species mixture of one species from each growth form in an experimental field setting to test resistance to invasion. Assemblages were seeded with cheatgrass and dyer’s woad for two consecutive years and quantified as biomass and density of individuals from each exotic species. Soil NO3 and leaf-area index were examined as predictors of invasive plant abundance. Cheatgrass invasion was greatest in forb and shrub assemblages, and least in mixed grass or grass monoculture; dyer’s woad invasion was greatest into mixed grass or grass monoculture, but least into monoculture or mixedspecies assemblages composed of forbs or shrubs. The community composed of grasses, forbs, and shrubs suppressed invasion by both species. Consequently, assemblages were most resistant to invasion by species of the same growth form. Moreover, these monocultures and mixtures were generally similar in conferring resistance to invasion, but a monoculture of big sagebrush was more resistant than a mixture of shrubs. Soil NO3 was correlated with invasion by cheatgrass, whereas LAI was correlated with invasion by dyer’s woad, suggesting these species were more limited by belowground and aboveground resources, respectively. Overall, increasing diversity with limited species did not necessarily enhance resistance to invasion
Salivary Gluten Degradation and Oral Microbial Profiles in Healthy Individuals and Celiac Disease Patients
Solution of generalized fractional reaction-diffusion equations
This paper deals with the investigation of a closed form solution of a
generalized fractional reaction-diffusion equation. The solution of the
proposed problem is developed in a compact form in terms of the H-function by
the application of direct and inverse Laplace and Fourier transforms.
Fractional order moments and the asymptotic expansion of the solution are also
obtained.Comment: LaTeX, 18 pages, corrected typo
Fractional reaction-diffusion equations
In a series of papers, Saxena, Mathai, and Haubold (2002, 2004a, 2004b)
derived solutions of a number of fractional kinetic equations in terms of
generalized Mittag-Leffler functions which provide the extension of the work of
Haubold and Mathai (1995, 2000). The subject of the present paper is to
investigate the solution of a fractional reaction-diffusion equation. The
results derived are of general nature and include the results reported earlier
by many authors, notably by Jespersen, Metzler, and Fogedby (1999) for
anomalous diffusion and del-Castillo-Negrete, Carreras, and Lynch (2003) for
reaction-diffusion systems with L\'evy flights. The solution has been developed
in terms of the H-function in a compact form with the help of Laplace and
Fourier transforms. Most of the results obtained are in a form suitable for
numerical computation.Comment: LaTeX, 17 pages, corrected typo
Forced-unfolding and force-quench refolding of RNA hairpins
Using coarse-grained model we have explored forced-unfolding of RNA hairpin
as a function of and the loading rate (). The simulations and
theoretical analysis have been done without and with the handles that are
explicitly modeled by semiflexible polymer chains. The mechanisms and time
scales for denaturation by temperature jump and mechanical unfolding are vastly
different. The directed perturbation of the native state by results in a
sequential unfolding of the hairpin starting from their ends whereas thermal
denaturation occurs stochastically. From the dependence of the unfolding rates
on and we show that the position of the unfolding transition state
(TS) is not a constant but moves dramatically as either or is
changed. The TS movements are interpreted by adopting the Hammond postulate for
forced-unfolding. Forced-unfolding simulations of RNA, with handles attached to
the two ends, show that the value of the unfolding force increases (especially
at high pulling speeds) as the length of the handles increases. The pathways
for refolding of RNA from stretched initial conformation, upon quenching
to the quench force , are highly heterogeneous. The refolding times, upon
force quench, are at least an order of magnitude greater than those obtained by
temperature quench. The long -dependent refolding times starting from
fully stretched states are analyzed using a model that accounts for the
microscopic steps in the rate limiting step which involves the trans to gauche
transitions of the dihedral angles in the GAAA tetraloop. The simulations with
explicit molecular model for the handles show that the dynamics of force-quench
refolding is strongly dependent on the interplay of their contour length and
the persistence length, and the RNA persistence length.Comment: 42 pages, 15 figures, Biophys. J. (in press
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