Characterization of the binding of botulinum type B 16S toxin to human intestinal epithelial cells

Botulinum neurotoxin produced by Clostridium botulinum type B is a complex of 12S and 16S toxins. 12S toxin consists of a neurotoxin and a nontoxic non-HA (NTNH). The 16S toxin consists of a neurotoxin, an NTNH, and a hemagglutinin (HA). Food-borne botulism is caused by these complex toxins, which are ingested orally and absorbed from the digestive tract across the epithelial barrier lining the gut. Here we show that the type B 16S toxin, but not the 12S toxin or the neurotoxin, binds to the T84 human intestinal epithelial cell line. We also demonstrate that the HA moiety in the 16S toxin mediates the toxin binding to the cells. The carbohydrates containing a galactose moiety inhibited the binding of the 16S toxin to the T84 cells, and neuraminidase treatment of the cells increased the 16S toxin binding. The binding of the 16S toxin to the neuraminidase-treated cells was also inhibited by carbohydrates containing a galactose moiety. These results suggest that the type B 16S toxin binds to human intestinal epithelial cells via the galactose moiety in the carbohydrate chain on the cell surface

Threshold and non-linear behavior of lasers of Λ\Lambda and V - configurations

Dynamic properties of closed three level laser systems are investigated. Two schemes of pumping - $\Lambda$ and V - are considered. It is shown that the non-linear behavior of the photon number as a function of pump both near and far above threshold is crucially different for these two configurations. In particular, it is found that in the high pump regime laser can turn off in a phase-transition-like manner in both $\Lambda$ and V schemes.Comment: 9 pages, 5 figure

Metastability, negative specific heat and weak mixing in classical long-range many-rotator system

We perform a molecular dynamical study of the isolated $d=1$ classical Hamiltonian ${\cal H} = {1/2} \sum_{i=1}^N L_i^2 + \sum_{i \ne j} \frac{1-cos(\theta_i-\theta_j)}{r_{ij}^\alpha} ;(\alpha \ge 0)$, known to exhibit a second order phase transition, being disordered for $u \equiv U/N{\tilde N} \ge u_c(\alpha,d)$ and ordered otherwise ($U\equiv$ total energy and ${\tilde N} \equiv \frac{N^{1-\alpha/d}-\alpha/d}{1-\alpha/d}$). We focus on the nonextensive case $\alpha/d \le 1$ and observe that, for $u<u_c$, a basin of attraction exists for the initial conditions for which the system quickly relaxes onto a longstanding metastable state (whose duration presumably diverges with $N$ like ${\tilde N}$) which eventually crosses over to the microcanonical Boltzmann-Gibbs stable state. The temperature associated with the (scaled) average kinetic energy per particle is lower in the metastable state than in the stable one. It is exhibited for the first time that the appropriately scaled maximal Lyapunov exponent $\lambda_{u<u_c}^{max}(metastable) \propto N^{-\kappa_{metastable}} ;(N \to \infty)$, where, for all values of $\alpha/d$, $\kappa_{metastable}$ numerically coincides with {\it one third} of its value for $u>u_c$, hence decreases from 1/9 to zero when $\alpha/d$ increases from zero to unity, remaining zero thereafter. This new and simple {\it connection between anomalies above and below the critical point} reinforces the nonextensive universality scenario.Comment: 9 pages and 4 PS figure

Nonextensivity of the cyclic Lattice Lotka Volterra model

We numerically show that the Lattice Lotka-Volterra model, when realized on a square lattice support, gives rise to a {\it finite} production, per unit time, of the nonextensive entropy $S_q= \frac{1- \sum_ip_i^q}{q-1}$ $(S_1=-\sum_i p_i \ln p_i)$. This finiteness only occurs for $q=0.5$ for the $d=2$ growth mode (growing droplet), and for $q=0$ for the $d=1$ one (growing stripe). This strong evidence of nonextensivity is consistent with the spontaneous emergence of local domains of identical particles with fractal boundaries and competing interactions. Such direct evidence is for the first time exhibited for a many-body system which, at the mean field level, is conservative.Comment: Latex, 6 pages, 5 figure

From Davydov solitons to decoherence-free subspaces: self-consistent propagation of coherent-product states

The self-consistent propagation of generalized $D_{1}$ [coherent-product] states and of a class of gaussian density matrix generalizations is examined, at both zero and finite-temperature, for arbitrary interactions between the localized lattice (electronic or vibronic) excitations and the phonon modes. It is shown that in all legitimate cases, the evolution of $D_{1}$ states reduces to the disentangled evolution of the component $D_{2}$ states. The self-consistency conditions for the latter amount to conditions for decoherence-free propagation, which complement the $D_{2}$ Davydov soliton equations in such a way as to lift the nonlinearity of the evolution for the on-site degrees of freedom. Although it cannot support Davydov solitons, the coherent-product ansatz does provide a wide class of exact density-matrix solutions for the joint evolution of the lattice and phonon bath in compatible systems. Included are solutions for initial states given as a product of a [largely arbitrary] lattice state and a thermal equilibrium state of the phonons. It is also shown that external pumping can produce self-consistent Frohlich-like effects. A few sample cases of coherent, albeit not solitonic, propagation are briefly discussed.Comment: revtex3, latex2e; 22 pages, no figs.; to appear in Phys.Rev.E (Nov.2001

Co-ingestion of cluster dextrin carbohydrate does not increase exogenous protein-derived amino acid release or myofibrillar protein synthesis following a whole-body resistance exercise in moderately trained younger males: a double-blinded randomized controlled crossover trial

Purpose: This study investigates if co-ingestion of cluster dextrin (CDX) augments the appearance of intrinsically labeled meat protein hydrolysate-derived amino acid (D5-phenylalanine), Akt/mTORC1 signaling, and myofibrillar protein fractional synthetic rate (FSR). Methods: Ten moderately trained healthy males (age: 21.5 ± 2.1 years, body mass: 75.7 ± 7.6 kg, body mass index (BMI): 22.9 ± 2.1 kg/m2) were included for a double-blinded randomized controlled crossover trial. Either 75 g of CDX or glucose (GLC) was given in conjunction with meat protein hydrolysate (0.6 g protein * FFM−1) following a whole-body resistance exercise. A primed-continuous intravenous infusion of L-[15N]-phenylalanine with serial muscle biopsies and venous blood sampling was performed. Results: A time × group interaction effect was found for serum D5-phenylalanine enrichment (P 0.05). Tmax serum EAA showed a trend towards a statistical significance favoring CDX over GLC. The phosphorylation of p70S6KThr389, rpS6Ser240/244, ERK1/2Thr202/Tyr204 was greater in CDX compared to GLC (P < 0.05). However, postprandial myofibrillar FSR did not differ between CDX and GLC (P = 0.17). Conclusion: In moderately trained younger males, co-ingestion of CDX with meat protein hydrolysate does not augment the postprandial amino acid availability or myofibrillar FSR as compared to co-ingestion of GLC during the recovery from a whole-body resistance exercise despite an increased intramuscular signaling. Trial registration: ClinicalTrials.gov ID: NCT03303729 (registered on October 3, 2017)

Dynamics of the Density Matrix in Contact with a Thermal Bath and the Quantum Master Equation

We study the structure of the time evolution of the density matrix in contact with a thermal bath in a standard projection operator sheme. The reduced density matrix of the system in the steady state is obtained by tracing out the degree of freedom of the thermal bath from the equilibrium density matrix of the total system. This reduced density matrix is modified by the interaction, and is different from that of the equilibrium of the system alone. We explicitly calculate the contribution of each term in quantum master equation to the realization of the steady state density matrix, and make clear roles of each term. By making use of the role of each term, the properties of the commonly used quantum master equation are examined.Comment: 17 pages, to appear in JPS

Strategies for Diagnosis and Treatment of Suspected Leptospirosis: A Cost-Benefit Analysis

Symptoms and signs of leptospirosis are non-specific. A number of diagnostic tests for leptospirosis are available. We compared the cost-benefit of 5 management strategies: 1) no patients tested or given antibiotic treatment; 2) all patients given empirical doxycycline treatment; patients given doxycycline when a patient is tested positive for leptospirosis using: 3) lateral flow; 4) MCAT; 5) latex test. Outcomes were measured in duration of fever which is then converted to productivity losses to capture the full economic costs. Empirical doxycycline treatment was found to be the most efficient strategy, being both the least costly alternative and the one that resulted in the lowest average duration of fever. The significantly higher relative cost of using a diagnostic test as compared with presumptive treatment, and the limited sensitivity of all the diagnostic tests implied that only the latex test could be considered cost-effective when compared with the no-antibiotic-treatment option, and that all three tests were still inferior to empirical treatment

Gibberellin Biosynthetic Inhibitors Make Human Malaria Parasite Plasmodium falciparum Cells Swell and Rupture to Death

Malaria remains as one of the most devastating infectious disease, and continues to exact an enormous toll in medical cost and days of labor lost especially in the tropics. Effective malaria control and eventual eradication remain a huge challenge, with efficacious antimalarials as important intervention/management tool. Clearly new alternative drugs that are more affordable and with fewer side effects are desirable. After preliminary in vitro assays with plant growth regulators and inhibitors, here, we focus on biosynthetic inhibitors of gibberellin, a plant hormone with many important roles in plant growth, and show their inhibitory effect on the growth of both apicomplexa, Plasmodium falciparum and Toxoplasma gondii. Treatment of P. falciparum cultures with the gibberellin biosynthetic inhibitors resulted in marked morphological changes that can be reversed to a certain degree under hyperosmotic environment. These unique observations suggest that changes in the parasite membrane permeability may explain the pleiotropic effects observed within the intracellular parasites

Two Structures of a Thiazolinyl Imine Reductase from Yersinia enterocolitica Provide Insight into Catalysis and Binding to the Nonribosomal Peptide Synthetase Module of HMWP1

The thiazolinyl imine reductase from Yersinia enterocolitica (Irp3) catalyzes the NADPH-dependent reduction of a thiazoline ring in an intermediate for the formation of the siderophore yersiniabactin. Two structures of Irp3 were determined in the apo- (1.85 Å) and NADP+-bound (2.31 Å) forms. Irp3 shows structural homology to sugar oxidoreductases such as glucose-fructose oxidoreductase and 1,5-anhydro-D-fructose reductase, as well as to biliverdin reductase. A homology model of the thiazolinyl imine reductase from Pseudomonas aeruginosa (PchG) was generated. Extensive loop insertions are observed in the C-terminal domain that are unique to Irp3 and PchG and not found in the structural homologs that recognize small molecular substrates. These loops are hypothesized to be important for binding of the nonribosomal peptide synthetase modules (found in HMWP1 and PchF, respectively) to which the substrate of the reductase is covalently attached. A catalytic mechanism of proton donation from a general acid (either histidine-101 or tyrosine-128) and hydride donation from C4 of nicotinamide of the NADPH cofactor is proposed for reduction of the carbon-nitrogen double bond of the thiazoline