1,025 research outputs found
Purification and structural characterization of the Na<sup>+</sup>-translocating ferredoxin: NAD<sup>+</sup> reductase (Rnf) complex of Clostridium tetanomorphum
Various microbial metabolisms use H+/Na+-translocating ferredoxin:NAD+ reductase (Rnf) either to exergonically oxidize reduced ferredoxin by NAD+ for generating a transmembrane electrochemical potential or reversely to exploit the latter for producing reduced ferredoxin. For cryo-EM structural analysis, we elaborated a quick four-step purification protocol for the Rnf complex from Clostridium tetanomorphum and integrated the homogeneous and active enzyme into a nanodisc. The obtained 4.27 Å density map largely allows chain tracing and redox cofactor identification complemented by biochemical data from entire Rnf and single subunits RnfB, RnfC and RnfG. On this basis, we postulated an electron transfer route between ferredoxin and NAD via eight [4Fe-4S] clusters, one Fe ion and four flavins crossing the cell membrane twice related to the pathway of NADH:ubiquinone reductase. Redox-coupled Na+ translocation is provided by orchestrating Na+ uptake/release, electrostatic effects of the assumed membrane-integrated FMN semiquinone anion and accompanied polypeptide rearrangements mediated by different redox steps
Facilitated spin models: recent and new results
Facilitated or kinetically constrained spin models (KCSM) are a class of
interacting particle systems reversible w.r.t. to a simple product measure.
Each dynamical variable (spin) is re-sampled from its equilibrium distribution
only if the surrounding configuration fulfills a simple local constraint which
\emph{does not involve} the chosen variable itself. Such simple models are
quite popular in the glass community since they display some of the peculiar
features of glassy dynamics, in particular they can undergo a dynamical arrest
reminiscent of the liquid/glass transitiom. Due to the fact that the jumps
rates of the Markov process can be zero, the whole analysis of the long time
behavior becomes quite delicate and, until recently, KCSM have escaped a
rigorous analysis with the notable exception of the East model. In these notes
we will mainly review several recent mathematical results which, besides being
applicable to a wide class of KCSM, have contributed to settle some debated
questions arising in numerical simulations made by physicists. We will also
provide some interesting new extensions. In particular we will show how to deal
with interacting models reversible w.r.t. to a high temperature Gibbs measure
and we will provide a detailed analysis of the so called one spin facilitated
model on a general connected graph.Comment: 30 pages, 3 figure
Analytical solution of a one-dimensional Ising model with zero temperature dynamics
The one-dimensional Ising model with nearest neighbour interactions and the
zero-temperature dynamics recently considered by Lefevre and Dean -J. Phys. A:
Math. Gen. {\bf 34}, L213 (2001)- is investigated. By introducing a
particle-hole description, in which the holes are associated to the domain
walls of the Ising model, an analytical solution is obtained. The result for
the asymptotic energy agrees with that found in the mean field approximation.Comment: 6 pages, no figures; accepted in J. Phys. A: Math. Gen. (Letter to
the Editor
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Dorsal GPi/GPe Stimulation Induced Dyskinesia in a Patient with Parkinson’s Disease
Clinical vignette: A 68-year-old man with Parkinson’s disease (PD) had bilateral GPi DBS placed for management of his motor fluctuations. He developed stimulation-induced dyskinesia (SID) with left dorsal GPi stimulation.
Clinical dilemma: What do we know about SID in PD patients with GPi DBS? What are the potential strategies used to maximize the DBS therapeutic benefit and minimize the side effects of stimulation?
Clinical solution: Avoiding the contact implicated in SID and programming more ventral contacts, using lower voltage, frequency and pulse width and programming in bipolar configuration all appear to help minimize the SID and provide appropriate symptomatic motor control.
Gap in knowledge: Little is known about SID in patients with PD who had GPi DBS therapy. More studies using volume of tissue activated and diffusion tensor imaging MRI are needed to localize specific tracts in or around the GPi that may be implicated in SID
On the Sets of Real Numbers Recognized by Finite Automata in Multiple Bases
This article studies the expressive power of finite automata recognizing sets
of real numbers encoded in positional notation. We consider Muller automata as
well as the restricted class of weak deterministic automata, used as symbolic
set representations in actual applications. In previous work, it has been
established that the sets of numbers that are recognizable by weak
deterministic automata in two bases that do not share the same set of prime
factors are exactly those that are definable in the first order additive theory
of real and integer numbers. This result extends Cobham's theorem, which
characterizes the sets of integer numbers that are recognizable by finite
automata in multiple bases.
In this article, we first generalize this result to multiplicatively
independent bases, which brings it closer to the original statement of Cobham's
theorem. Then, we study the sets of reals recognizable by Muller automata in
two bases. We show with a counterexample that, in this setting, Cobham's
theorem does not generalize to multiplicatively independent bases. Finally, we
prove that the sets of reals that are recognizable by Muller automata in two
bases that do not share the same set of prime factors are exactly those
definable in the first order additive theory of real and integer numbers. These
sets are thus also recognizable by weak deterministic automata. This result
leads to a precise characterization of the sets of real numbers that are
recognizable in multiple bases, and provides a theoretical justification to the
use of weak automata as symbolic representations of sets.Comment: 17 page
Ligand binding and conformational dynamics of the E. coli nicotinamide nucleotide transhydrogenase revealed by hydrogen/deuterium exchange mass spectrometry
Nicotinamide nucleotide transhydrogenases are integral membrane proteins that utilizes the proton motive force to reduce NADP+ to NADPH while converting NADH to NAD+. Atomic structures of various transhydrogenases in different ligand-bound states have become available, and it is clear that the molecular mechanism involves major conformational changes. Here we utilized hydrogen/deuterium exchange mass spectrometry (HDX-MS) to map ligand binding sites and analyzed the structural dynamics of E. coli transhydrogenase. We found different allosteric effects on the protein depending on the bound ligand (NAD+, NADH, NADP+, NADPH). The binding of either NADP+ or NADPH to domain III had pronounced effects on the transmembrane helices comprising the proton-conducting channel in domain II. We also made use of cyclic ion mobility separation mass spectrometry (cyclic IMS-MS) to maximize coverage and sensitivity in the transmembrane domain, showing for the first time that this technique can be used for HDX-MS studies. Using cyclic IMS-MS, we increased sequence coverage from 68 % to 73 % in the transmembrane segments. Taken together, our results provide important new insights into the transhydrogenase reaction cycle and demonstrate the benefit of this new technique for HDX-MS to study ligand binding and conformational dynamics in membrane proteins
Microscopic simulation of membrane molecule diffusion on corralled membrane surfaces
The current understanding of how receptors diffuse and cluster in the plasma membrane is limited. Data from single-particle tracking and laser tweezer experiments have suggested that membrane molecule diffusion is affected by the presence of barriers dividing the membrane into corrals. Here, we have developed a stochastic spatial model to simulate the effect of corrals on the diffusion of molecules in the plasma membrane. The results of this simulation confirm that a fence barrier (the ratio of the transition probability for diffusion across a boundary to that within a corral) on the order of 103–104 recreates the experimentally measured difference in diffusivity between artificial and natural plasma membranes. An expression for the macroscopic diffusivity of receptors on corralled membranes is derived to analyze the effects of the corral parameters on diffusion rate. We also examine whether the lattice model is an appropriate description of the plasma membrane and look at three different sets of boundary conditions that describe diffusion over the barriers and whether diffusion events on the plasma membrane may occur with a physically relevant length scale. Finally, we show that to observe anomalous (two-timescale) diffusion, one needs high temporal (microsecond) resolution along with sufficiently long (more than milliseconds) trajectories
Obesity and STING1 genotype associate with 23-valent pneumococcal vaccination efficacy
© 2020, Sebastian etal. BACKGROUND. Obesity has been associated with attenuated vaccine responses and an increased risk of contracting pneumococcal pneumonia, but no study to our knowledge has assessed the impact of obesity and genetics on 23-valent pneumococcal vaccine (PPSV23) efficacy. We assessed the relationship of obesity (primary analysis) and stimulator of interferon genes (STING1) genotype (secondary analysis) on PPSV23 efficacy. METHODS. Nonobese (BMI 22-25 kg/m2) and obese participants (BMI ≥30 kg/m2) were given a single dose of PPSV23. Blood was drawn immediately prior to and 4-6 weeks after vaccination. Serum samples were used to assess PPSV23-specific antibodies. STING1 genotypes were identified using PCR on DNA extracted from peripheral blood samples. RESULTS. Forty-six participants were categorized as nonobese (n = 23; 56.5% women; mean BMI 23.3 kg/m2) or obese (n = 23; 65.2% women; mean BMI 36.3 kg/m2). Obese participants had an elevated fold change in vaccine-specific responses compared with nonobese participants (P \u3c 0.0001). The WT STING1 group (R232/R232) had a significantly higher PPSV23 response than individuals with a single copy of HAQ-STING1 regardless of BMI (P = 0.0025). When WT was assessed alone, obese participants had a higher fold serotype-specific response compared with nonobese participants (P \u3c 0.0001), but no difference was observed between obese and nonobese individuals with 1 HAQ allele (P = 0.693). CONCLUSIONS. These observations demonstrate a positive association between obesity and PPSV23 efficacy specifically in participants with the WT STING1 genotype. TRIAL REGISTRATION. ClinicalTrials.gov NCT02471014. FUNDING. This research was supported by the NIH and the University of Florida MD-PhD Training Program
Glassy timescale divergence and anomalous coarsening in a kinetically constrained spin chain
We analyse the out of equilibrium behavior of an Ising spin chain with an
asymmetric kinetic constraint after a quench to a low temperature T. In the
limit T\to 0, we provide an exact solution of the resulting coarsening process.
The equilibration time exhibits a `glassy' divergence \teq=\exp(const/T^2)
(popular as an alternative to the Vogel-Fulcher law), while the average domain
length grows with a temperature dependent exponent, \dbar ~ t^{T\ln 2}. We show
that the equilibration time \teq also sets the timescale for the linear
response of the system at low temperatures.Comment: 4 pages, revtex, includes two eps figures. Proof of energy barrier
hierarchy added. Version to be published in Phys Rev Let
Leguminosae do Campus da Universidade Federal de Santa Maria, Santa Maria, RS, Brasil
This work presents a floristic survey of the Leguminosae speciesfounded in the Campus of Universidade Federal de Santa Maria (UFSM). Eigthyseventaxa were recognized, of which 51,72% are Papilionoideae, 25,28%Caesalpinioideae and 22,98% Mimosoideae. Among the identified species 52are native from Rio Grande do Sul State and 31 are exotic. This work alsopresents a key for identification of the species.Key words: Leguminosae, floristic, Mimosoideae, Caesalpinioideae,Papilionoideae.Este trabalho apresenta um levantamento florístico da famíliaLeguminosae realizado no Campus da Universidade Federal de Santa Maria(UFSM), Rio Grande do Sul. Foram encontrados 87 táxons, sendo 51,72% pertencentesà Papilionoideae, 25,28% à Caesalpinioideae e 22,98% à Mimosoideae.Das espécies identificadas, 52 são nativas do Rio Grande do Sul e 31 exóticas.São apresentadas chaves analíticas para espécies, individualizadas porsubfamília.Palavras-chave: Leguminosae, florística, Mimosoideae, Caesalpinioideae,Papilionoideae
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