Hydrodynamic Properties of Biomacromolecules and Macromolecular Complexes: Concepts and Methods. A Tutorial Mini-review.

This article is intended to be an overview of the current possibilities offered by hydrodynamic methods in the calculation of properties and prediction of the behavior of biomacromolecules in solution. First, we briefly cover the experimental techniques, mentioning their fundamentals and current status. Using a tutorial approach, we provide basic hints to understand conceptual aspects of macromolecular hydrodynamics which underlie the instrumental methods and the modeling and computational procedures. The description is focused on the bead model methodology as implemented in the HYDRO suite of computer programs. For rigid particles, we cover simple models, such as ellipsoids and cylinders, to the most detailed models with atomic resolution. The fundamentals and applicability of the basic random coil and wormlike models for flexible particles are also briefly described. In addition to the simple linear, more or less flexible chain, flexibility may appear in other more specific forms. These cases can be treated by Monte Carlo and Brownian simulation methods, for which computational tools are also available. Finally, we present in some detail the applicability of these tools for unfolded and intrinsically disordered proteins. For the particular case of partially disordered proteins comprising both globular domains and flexible linkers or tails, solution properties can be accurately predicted, and this validation makes the methodology quite promising for future work.

Prediction and analysis of analytical ultracentrifugation experiments for heterogeneous macromolecules and nanoparticles based on Brownian dynamics simulation.

In the prediction of sedimentation profiles in analytical ultracentrifugation, the counterflow due to diffusion must be taken into account for a proper analysis of experimental data in the determination of molecular properties. This is usually achieved by numerical solution of the Lamm equation. This paper presents an alternative approach, in which the displacement of the solute in the cell, resulting from the opposite effects of ultracentrifugal force and diffusional drift, is described by Brownian dynamics simulation of the solute particles. The formalism is developed for heterogeneous solutes, composed of several species, and implemented in computational schemes and tools. The accuracy of the procedure is verified by comparison with other methods based on the Lamm equation, and its efficiency is illustrated. The possibilities offered by the Brownian dynamics methods in the determination of solute properties and sample composition are demonstrated.

Influence of ionic strength on the flexibility of alginate studied by size exclusion chromatography.

SEC measurements of the [η]-M relationship for alginate from Macrocystis pyrifera and the wormlike model can be used to characterize flexibility through two independent treatments (Bohdanecky's equations and HYDFIT program), both providing the same results. Two different assumptions concerning mass per unit of length lead to different conclusions. First: persistence length decreases with ionic strength (the intrinsic component of the persistence length is 11.3 nm and the electrostatic component is 6 nm when ionic strength is 0.01). Second: persistence length is independent of ionic strength (12 nm). Either of these options shows that the wormlike model in itself is not sufficient to explain flexibility over the whole range of chain lengths for these polyelectrolytes. A plausible explanation could be the presence of a combination of short-range and long-range screening effects of the ions of the solutions. This would also explain some data found in the literature regarding alginate flexibility.

Translational diffusion coefficients of macromolecules.

The calculation of the translational diffusion coefficient of a single flexible polymer chain in dilute solution can be basically addressed either a) within the Einstein theory (calculating the time autocorrelation function of the macromolecule center of mass), or b) within the Kirkwood and Riseman theory for irreversible processes of macromolecules in solution. The equations of the latter theory can be solved employing different approximations that give rise to different values of the diffusion coefficient. In general, the value of the diffusion coefficient obtained through the different theories and approaches varies slightly depending on polymer features like flexibility. In this paper, we evaluate the most common procedures to compute the diffusion coefficient of flexible macromolecules via computer simulation and the difference between the values obtained.

Analysis of leakage in IRGA's leaf chambers of open gas exchange systems: quantification and its effects in photosynthesis parameterization.

The measurement of the response of net photosynthesis to leaf internal CO2 (i.e. A-Ci curves) is widely used for ecophysiological studies. Most studies did not consider CO2 exchange between the chamber and the surrounding air, especially at the two extremes of A-Ci curves, where large CO2 gradients are created, leading to erroneous estimations of A and Ci. A quantitative analysis of CO2 leakage in the chamber of a portable open gas exchange system (Li-6400, LI-COR Inc., NE, USA) was performed. In an empty chamber, the measured CO2 leakage was similar to that calculated using the manufacturer's equations. However, in the presence of a photosynthetically inactive leaf, the magnitude of leakage was substantially decreased, although still significant. These results, together with the analysis of the effects of chamber size, tightness, flow rate, and gasket material, suggest that the leakage is larger at the interface between the gaskets than through the gaskets. This differential leakage rate affects the parameterization by photosynthesis models. The magnitude of these errors was assessed in tobacco plants. The results showed that leakage results in a 10% overestimation of the leaf maximum capacity for carboxylation (Vc,max) and a 40% overestimation of day respiration (Rl). Using the manufacturer's equations resulted in larger, non-realistic corrections of the true values. The photosynthetic response to CO2 concentrations at the chloroplast (i.e. A-Cc curves) was significantly less affected by leakage than A-Ci curves. Therefore, photosynthetic parameterization can be improved by: (i) correcting A and Ci values for chamber leakage estimated using a photosynthetically inactive leaf; and (ii) using A-Cc instead of A-Ci curves.

MULTIHYDRO and MONTEHYDRO: conformational search and Monte Carlo calculation of solution properties of rigid or flexible bead models.

A computer program, MULTIHYDRO, has been constructed for the calculation of hydrodynamic coefficients and other solution properties of multiple possible conformations of a bead model. With minimal additional programming to describe the model under study, this program interfaces efficiently with HYDRO for the calculation of solution properties, including hydrodynamic coefficients, radius of gyration, covolume, etc. A useful application is the conformation search of rigid macromolecules, because many possible conformations can be evaluated in a single run of the program. In this paper we also pay attention to the properties of flexible macromolecules, in the so-called Monte Carlo rigid-body approximation, which is virtually exact for the simpler solution properties. The theoretical aspects of the procedure are described, and we show how MULTIHYDRO can be employed for this calculation. However, for flexible molecules, a more general simulation scheme is importance-sampling Monte Carlo generation. We describe how this procedure is implemented in another computer program, MONTEHYDRO. Examples of the usage of these tools are provided.

Pronóstico a corto plazo en pacientes con insuficiencia cardíaca congestiva y función sistólica del ventrículo izquierdo normal / Short term prognosis in patients with congestive heart failure and normal left ventricular systolic function

Existem pocos estudios que describem el prognóstico de los pacientes con insuficiencia cardíaca congestiva (ICC) y función sistólica (FS) del ventrículo izquierdo (VI) intacta. El objetivo de este estudio prospectivo es describir a un grupo de 70 pacientes consecutivos internados en un servicio de medicina interna con ICC, identificar con ecocardiografía el estado contráctil del VI y establecer el pronóstico a corto plazo. Fueron 39 hombres y 31 mujeres con una edad media de 76,4 años. En 38 (54,3 por ciento) se encontró alteración de la FS del VI (Grupo I ) y en 32(45,7 por ciento) se encontraba intacta (Grupo II). El estudio con Doppler cardíaco mostró que 14 del Grupo II tenían alteración de la función diastólica (FD) del VI como único mecanismo responsable de su ICC. Se realizó un seguimiento de 8 meses en promedio, donde 20(28 por ciento) fallecieron. No hubo diferencias significativas en la mortalidad entre los Grupos I y II. Se realizó un análisis multivariado para determinar el riesgo relativo sobre la mortalidad de las variables edad, sexo, FS y diámetros del VI. Ninguna de éstas alcanzó una diferencia estadísticamente significativa. El nuestra serie de pacientes con ICC, 45,7 por ciento tenían FS del VI normal. El pronóstico a corto plazo fue similar al de los pacientes con FS del VI alterada (AU)

Pronóstico a corto plazo en pacientes con insuficiencia cardíaca congestiva y función sistólica del ventrículo izquierdo normal / Short term prognosis in patients with congestive heart failure and normal left ventricular systolic function

Existem pocos estudios que describem el prognóstico de los pacientes con insuficiencia cardíaca congestiva (ICC) y función sistólica (FS) del ventrículo izquierdo (VI) intacta. El objetivo de este estudio prospectivo es describir a un grupo de 70 pacientes consecutivos internados en un servicio de medicina interna con ICC, identificar con ecocardiografía el estado contráctil del VI y establecer el pronóstico a corto plazo. Fueron 39 hombres y 31 mujeres con una edad media de 76,4 años. En 38 (54,3 por ciento) se encontró alteración de la FS del VI (Grupo I ) y en 32(45,7 por ciento) se encontraba intacta (Grupo II). El estudio con Doppler cardíaco mostró que 14 del Grupo II tenían alteración de la función diastólica (FD) del VI como único mecanismo responsable de su ICC. Se realizó un seguimiento de 8 meses en promedio, donde 20(28 por ciento) fallecieron. No hubo diferencias significativas en la mortalidad entre los Grupos I y II. Se realizó un análisis multivariado para determinar el riesgo relativo sobre la mortalidad de las variables edad, sexo, FS y diámetros del VI. Ninguna de éstas alcanzó una diferencia estadísticamente significativa. El nuestra serie de pacientes con ICC, 45,7 por ciento tenían FS del VI normal. El pronóstico a corto plazo fue similar al de los pacientes con FS del VI alterada

[Short-term prognosis in patients with congestive heart failure and normal left ventricular systolic function]. / Pronóstico a corto plazo en pacientes con insuficiencia cardíaca congestiva y función sistólica del ventrículo izquierdo normal.

Congestive heart failure (CHF) has been traditionally associated with impairment of the left ventricular systolic function (LVSF). There are few clinical assays that describe the prognosis of patients with CHF and intact LVSF. The aims of this prospective assay are: to describe a group of 70 patients admitted to an internal medicine department with the clinical syndrome of CHF, to determine the contractile state of the left ventricle with echocardiography and to establish the short term prognosis. There were 39 males and 31 females with a mean age of 76.4. The LVSF was impaired in 38 (54.3%) [Group I] and preserved in 32 (45.7%) [Group II] (Table 1). Sex distribution was different between both groups with women predominating in group II (Figure 1). Fourteen patients belonging to Group II had diastolic function impairment according to cardiac Doppler. There was no other evidence of cardiac abnormality that could justify CHF. During an average of 8 months follow-up 20 (28%) patients died. There were no differences in overall mortality between Groups I and II (Figure 2). Multivariate analysis was used to determine the relative risk in prognosis of the covariates age, gender, systolic function and diameters of the LV. None of these were statistically significant (Table 2). In our series 45.7% of the patients with CHF had normal LVSF. The short term prognosis proved to be the same in patients with and without impaired LVSF.

Pronóstico a corto plazo en pacientes con insuficiencia cardíaca congestiva y función sistólica del ventrículo izquierdo normal. / [Short-term prognosis in patients with congestive heart failure and normal left ventricular systolic function]

Congestive heart failure (CHF) has been traditionally associated with impairment of the left ventricular systolic function (LVSF). There are few clinical assays that describe the prognosis of patients with CHF and intact LVSF. The aims of this prospective assay are: to describe a group of 70 patients admitted to an internal medicine department with the clinical syndrome of CHF, to determine the contractile state of the left ventricle with echocardiography and to establish the short term prognosis. There were 39 males and 31 females with a mean age of 76.4. The LVSF was impaired in 38 (54.3

) [Group I] and preserved in 32 (45.7

) [Group II] (Table 1). Sex distribution was different between both groups with women predominating in group II (Figure 1). Fourteen patients belonging to Group II had diastolic function impairment according to cardiac Doppler. There was no other evidence of cardiac abnormality that could justify CHF. During an average of 8 months follow-up 20 (28

) patients died. There were no differences in overall mortality between Groups I and II (Figure 2). Multivariate analysis was used to determine the relative risk in prognosis of the covariates age, gender, systolic function and diameters of the LV. None of these were statistically significant (Table 2). In our series 45.7

of the patients with CHF had normal LVSF. The short term prognosis proved to be the same in patients with and without impaired LVSF.