Exploiting the downhill folding regime via experiment.

Traditionally, folding experiments have been directed at determining equilibrium and relaxation rate constants of proteins that fold with two-state-like kinetics. More recently, the combination of free energy surface approaches inspired by theory with the discovery of proteins that fold in the downhill regime has greatly widened the battlefield for experimentalists. Downhill folding proteins cross very small or no free energy barrier at all so that all relevant partially folded conformations become experimentally accessible.

Social phobia and sexual problems: A comparison of social phobic, sexually dysfunctional and normal individuals.

Objectives: This study sought to test the putative link between social phobia and sexual functioning.

Methods: Three groups consisting of 106 social phobic, 164 sexually dysfunctional and 111 normal participants were assessed in terms of sexual functioning, social anxiety, social functioning and general psychopathology.

Results: Although social phobic men were less sexually active than normal men, they were as sexually satisfied.

A designed protein as experimental model of primordial folding.

How do proteins accomplish folding during early evolution? Theoretically the mechanism involves the selective stabilization of the native structure against all other competing compact conformations in a process that involves cumulative changes in the amino acid sequence along geological timescales. Thus, an evolved protein folds into a single structure at physiological temperature, but the conformational competition remains latent. For natural proteins such competition should emerge only near cryogenic temperatures, which places it beyond experimental testing.

Diversity driven unbiased search of minimum energy cluster configurations.

The determination of the spatial distributions that atoms adopt to form condensed matter is a problem of crucial importance, since most physical properties depend on the atomic arrangement. This is especially relevant for clusters, where periodicity is nonexistent. Several optimization procedures have been implemented to tackle this problem, with ever increasing success.

[Cerebral sinovenous thrombosis and acquired antithrombin, protein C and S deficiency during chemotherapy in a young man: report of a case].

L-asparaginase is commonly used in the chemotherapy regimens for acute lymphoblastic leukaemia. Its use is associated with thrombotic complications in 1 to 14 % of the cases. The pathogenesis of this complication is still unclear.

Protein folding rates and stability: how much is there beyond size?

An intriguing feature of protein folding is that the overall behavior obeys simple physical rules, but the finer details show a great deal of complexity. The scaling of thermodynamic and kinetic properties with protein size is one such rule. However, it is not clear to what extent biologically relevant folding properties (i.

Dynamics of one-state downhill protein folding.

The small helical protein BBL has been shown to fold and unfold in the absence of a free energy barrier according to a battery of quantitative criteria in equilibrium experiments, including probe-dependent equilibrium unfolding, complex coupling between denaturing agents, characteristic DSC thermogram, gradual melting of secondary structure, and heterogeneous atom-by-atom unfolding behaviors spanning the entire unfolding process. Here, we present the results of nanosecond T-jump experiments probing backbone structure by IR and end-to-end distance by FRET. The folding dynamics observed with these two probes are both exponential with common relaxation times but have large differences in amplitude following their probe-dependent equilibrium unfolding.

Optimal control in a noisy system.

We describe a simple method to control a known unstable periodic orbit (UPO) in the presence of noise. The strategy is based on regarding the control method as an optimization problem, which allows us to calculate a control matrix A. We illustrate the idea with the Rossler system, the Lorenz system, and a hyperchaotic system that has two exponents with positive real parts.

Quantitative description of realistic wealth distributions by kinetic trading models.

Data on wealth distributions in trading markets show a power law behavior x(-)(1+alpha) at the high end, where, in general, alpha is greater than 1 (Pareto's law). Models based on kinetic theory, where a set of interacting agents trade money, yield power law tails if agents are assigned a saving propensity. In this paper we are solving the inverse problem, that is, in finding the saving propensity distribution which yields a given wealth distribution for all wealth ranges.

Electrotonic myofibroblast-to-myocyte coupling increases propensity to reentrant arrhythmias in two-dimensional cardiac monolayers.

In pathological conditions such as ischemic cardiomyopathy and heart failure, differentiation of fibroblasts into myofibroblasts may result in myocyte-fibroblast electrical coupling via gap junctions. We hypothesized that myofibroblast proliferation and increased heterocellular coupling significantly alter two-dimensional cardiac wave propagation and reentry dynamics. Co-cultures of myocytes and myofibroblasts from neonatal rat ventricles were optically mapped using a voltage-sensitive dye during pacing and sustained reentry.

Large-scale modulation of thermodynamic protein folding barriers linked to electrostatics.

Protein folding barriers, which range from zero to the tens of RT that result in classical two-state kinetics, are primarily determined by protein size and structural topology [Plaxco KW, Simons KT, Baker D (1998) J Mol Biol 277:985-994]. Here, we investigate the thermodynamic folding barriers of two relatively large proteins of the same size and topology: bovine alpha-lactalbumin (BLA) and hen-egg-white lysozyme (HEWL). From the analysis of differential scanning calorimetry experiments with the variable-barrier model [Muñoz V, Sanchez-Ruiz JM (2004) Proc Natl Acad Sci USA 101:17646-17651] we obtain a high barrier for HEWL and a marginal folding barrier for BLA.

Determining denaturation midpoints in multiprobe equilibrium protein folding experiments.

Multiprobe equilibrium unfolding experiments in the downhill regime (i.e., maximal barrier < 3 RT) can resolve the folding process with atomic resolution [ Munoz ( 2002) Int.

The structure and properties of small Pd clusters.

The zero-temperature minimal energy structure of small free-standing Pd clusters (14≤N≤21, where N is the number of atoms in the cluster), their characteristics and their magnetic configurations are investigated. Results obtained using five different phenomenological many-body potentials (implemented in combination with a genetic algorithm search) are refined by means of various density functional theory (DFT) techniques. The agreement and differences between the results obtained with our procedure, using these five potentials, are displayed in detail.

Expanding the realm of ultrafast protein folding: gpW, a midsize natural single-domain with alpha+beta topology that folds downhill.

All ultrafast folding proteins known to date are either very small in size (less than 45 residues), have an alpha-helix bundle topology, or have been artificially engineered. In fact, many of them share two or even all three features. Here we show that gpW, a natural 62-residue alpha+beta protein expected to fold slowly in a two-state fashion, folds in microseconds (i.

Binding of tau protein to the ends of ex vivo paired helical filaments.

Human recombinant tau can bind to the end of isolated human paired helical filaments (PHF). The sequential binding of tau protein to PHF could result in an elongation of the previously polymerized PHF. However, we have observed that the elongation takes place in a different way on different types of PHF.

[Not Available].

Objective: To evaluate changes in quality over a 5-year period from the perspective of patients, in an attempt to meet their expectations in a new hospital.

Method: The procedure takes as a reference the results of an opinion survey carried out in the hospital in 2001 and compares these results with those of annual surveys and completes them with information from written complaints and demands for accountability.

Results: During the period studied, 821 surveys (a response rate of 22.

Estimating free-energy barrier heights for an ultrafast folding protein from calorimetric and kinetic data.

Differential scanning calorimetry was used to measure the temperature dependence of the absolute heat capacity of the 35-residue subdomain of the villin headpiece, a protein that folds in 5 mus and is therefore assumed to have a small free-energy barrier separating folded and unfolded states. To obtain an estimate of the barrier height from the calorimetric data, two models, a variable-barrier model and an Ising-like model, were used to fit the heat capacity in excess of the folded state over the temperature range 15-125 degrees C. The variable-barrier model is based on an empirical mathematical form for the density of states, with four adjustable parameters and the enthalpy (H) as a reaction coordinate.

Recognition and diagnosis of mucopolysaccharidosis II (Hunter syndrome).

Mucopolysaccharidosis II, also known as Hunter syndrome, is a rare, X-linked disorder caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase, which catalyzes a step in the catabolism of glycosaminoglycans. In patients with mucopolysaccharidosis II, glycosaminoglycans accumulate within tissues and organs, contributing to the signs and symptoms of the disease. Mucopolysaccharidosis II affects multiple organs and physiologic systems and has a variable age of onset and variable rate of progression.

Roux-en-Y gastric bypass: major complications.

Learning Objectives: To describe normal anatomy of Roux-en-Y gastric bypass (GBP) surgery. To know the spectrum of major complications, time of appearance and imaging findings.

Background: Roux-en-Y GBP surgery nowadays represents a successful treatment of morbid obesity.

[Predictors of the level of patient satisfaction in a university hospital].

Background: Client satisfaction is an important indicator of the quality of services, and health care is not an exemption.

Aim: To explore and establish the predictors that exert the greater influence on the level of satisfaction with the service offered in a University Hospital.

Material And Method: The source of the study is a data base, obtained from a survery made to 355 patients of the Hospital Clínico de la Pontificia Universidad Católica de Chile prior to discharge.

Differential resistance of melanoma cells to treatment with recombinant IFN-alpha2b and leukocyte IFN.

Background: Interferon-alpha (IFN-alpha) subtypes bind to the same receptor and are expected to have the same biological functions. Whether or not leukocyte IFN, containing six major IFN-alpha proteins had the same anti-tumor effect as one subtype, recombinant IFN-alpha2b, was investigated.

Materials And Methods: Three melanoma lines were treated with both types of IFN, and the effect on proliferation and survival was estimated both after short-term and prolonged treatment.

Relationships among production systems, preschool nutritional status, and pesticide-related toxicity in seven ecuadorian communities: a multi-case study approach.

Background: Among small Andean potato farmers, greater pesticide use and better linkage to markets are promoted as ways to improve farm outputs and incomes. The health of household members is assumed to improve with higher incomes, although evidence to support such an assumption remains scarce.

Objective: Using a multidisciplinary approach, we sought to characterize agricultural systems producing potatoes and to assess relationships between these characteristics and farm household health indicators.