Desmin: molecular interactions and putative functions of the muscle intermediate filament protein

Desmin is the intermediate filament (IF) protein occurring exclusively in muscle and endothelial cells. There are other IF proteins in muscle such as nestin, peripherin, and vimentin, besides the ubiquitous lamins, but they are not unique to muscle. Desmin was purified in 1977, the desmin gene was characterized in 1989, and knock-out animals were generated in 1996. Several isoforms have been described. Desmin IFs are present throughout smooth, cardiac and skeletal muscle cells, but can be more concentrated in some particular structures, such as dense bodies, around the nuclei, around the Z-line or in costameres. Desmin is up-regulated in muscle-derived cellular adaptations, including conductive fibers in the heart, electric organs, some myopathies, and experimental treatments with drugs that induce muscle degeneration, like phorbol esters. Many molecules have been reported to associate with desmin, such as other IF proteins (including members of the membrane dystroglycan complex), nebulin, the actin and tubulin binding protein plectin, the molecular motor dynein, the gene regulatory protein MyoD, DNA, the chaperone alphaB-crystallin, and proteases such as calpain and caspase. Desmin has an important medical role, since it is used as a marker of tumors' origin. More recently, several myopathies have been described, with accumulation of desmin deposits. Yet, after almost 30 years since its identification, the function of desmin is still unclear. Suggested functions include myofibrillogenesis, mechanical support for the muscle, mitochondrial localization, gene expression regulation, and intracellular signaling. This review focuses on the biochemical interactions of desmin, with a discussion of its putative functions.

Disintegrins: integrin selective ligands which activate integrin-coupled signaling and modulate leukocyte functions

Extracellular matrix proteins and cell adhesion receptors (integrins) play essential roles in the regulation of cell adhesion and migration. Interactions of integrins with the extracellular matrix proteins lead to phosphorylation of several intracellular proteins such as focal adhesion kinase, activating different signaling pathways responsible for the regulation of a variety of cell functions, including cytoskeleton mobilization. Once leukocytes are guided to sites of infection, inflammation, or antigen presentation, integrins can participate in the initiation, maintenance, or termination of the immune and inflammatory responses. The modulation of neutrophil activation through integrin-mediated pathways is important in the homeostatic control of the resolution of inflammatory states. In addition, during recirculation, T lymphocyte movement through distinct microenvironments is mediated by integrins, which are critical for cell cycle, differentiation and gene expression. Disintegrins are a family of low-molecular weight, cysteine-rich peptides first identified in snake venom, usually containing an RGD (Arg-Gly-Asp) motif, which confers the ability to selectively bind to integrins, inhibiting integrin-related functions in different cell systems. In this review we show that, depending on the cell type and the microenvironment, disintegrins are able to antagonize the effects of integrins or to act agonistically by activating integrin-mediated signaling. Disintegrins have proven useful as tools to improve the understanding of the molecular events regulated by integrin signaling in leukocytes and prototypes in order to design therapies able to interfere with integrin-mediated effects.

Comparison of anaerobic threshold determined by visual and mathematical methods in healthy women

Several methods are used to estimate anaerobic threshold (AT) during exercise. The aim of the present study was to compare AT obtained by a graphic visual method for the estimate of ventilatory and metabolic variables (gold standard), to a bi-segmental linear regression mathematical model of Hinkley's algorithm applied to heart rate (HR) and carbon dioxide output (VCO2) data. Thirteen young (24 ± 2.63 years old) and 16 postmenopausal (57 ± 4.79 years old) healthy and sedentary women were submitted to a continuous ergospirometric incremental test on an electromagnetic braking cycloergometer with 10 to 20 W/min increases until physical exhaustion. The ventilatory variables were recorded breath-to-breath and HR was obtained beat-to-beat over real time. Data were analyzed by the nonparametric Friedman test and Spearman correlation test with the level of significance set at 5%. Power output (W), HR (bpm), oxygen uptake (VO2; mL kg-1 min-1), VO2 (mL/min), VCO2 (mL/min), and minute ventilation (VE; L/min) data observed at the AT level were similar for both methods and groups studied (P > 0.05). The VO2 (mL kg-1 min-1) data showed significant correlation (P < 0.05) between the gold standard method and the mathematical model when applied to HR (r s = 0.75) and VCO2 (r s = 0.78) data for the subjects as a whole (N = 29). The proposed mathematical method for the detection of changes in response patterns of VCO2 and HR was adequate and promising for AT detection in young and middle-aged women, representing a semi-automatic, non-invasive and objective AT measurement.

Nitric oxide synthesis and biological functions of nitric oxide released from ruthenium compounds

During three decades, an enormous number of studies have demonstrated the critical role of nitric oxide (NO) as a second messenger engaged in the activation of many systems including vascular smooth muscle relaxation. The underlying cellular mechanisms involved in vasodilatation are essentially due to soluble guanylyl-cyclase (sGC) modulation in the cytoplasm of vascular smooth cells. sGC activation culminates in cyclic GMP (cGMP) production, which in turn leads to protein kinase G (PKG) activation. NO binds to the sGC heme moiety, thereby activating this enzyme. Activation of the NO-sGC-cGMP-PKG pathway entails Ca2+ signaling reduction and vasodilatation. Endothelium dysfunction leads to decreased production or bioavailability of endogenous NO that could contribute to vascular diseases. Nitrosyl ruthenium complexes have been studied as a new class of NO donors with potential therapeutic use in order to supply the NO deficiency. In this context, this article shall provide a brief review of the effects exerted by the NO that is enzymatically produced via endothelial NO-synthase (eNOS) activation and by the NO released from NO donor compounds in the vascular smooth muscle cells on both conduit and resistance arteries, as well as veins. In addition, the involvement of the nitrite molecule as an endogenous NO reservoir engaged in vasodilatation will be described.

Silencing HIF-1α reduces the adhesion and secretion functions of acute leukemia hBMSCs

Hypoxia inducible factor-1α (HIF-1α) is an important transcription factor, which plays a critical role in the formation of solid tumor and its microenviroment. The objective of the present study was to evaluate the expression and function of HIF-1α in human leukemia bone marrow stromal cells (BMSCs) and to identify the downstream targets of HIF-1α. HIF-1α expression was detected at both the RNA and protein levels using real-time PCR and immunohistochemistry, respectively. Vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α) were detected in stromal cells by enzyme-linked immunosorbent assay. HIF-1α was blocked by constructing the lentiviral RNAi vector system and infecting the BMSCs. The Jurkat cell/BMSC co-cultured system was constructed by putting the two cells into the same suitable cultured media and conditions. Cell adhesion and secretion functions of stromal cells were evaluated after transfection with the lentiviral RNAi vector of HIF-1α. Increased HIF-1α mRNA and protein was detected in the nucleus of the acute myeloblastic and acute lymphoblastic leukemia compared with normal BMSCs. The lentiviral RANi vector for HIF-1α was successfully constructed and was applied to block the expression of HIF-1α. When HIF-1α of BMSCs was blocked, the expression of VEGF and SDF-1 secreted by stromal cells were decreased. When HIF-1α was blocked, the co-cultured Jurkat cell’s adhesion and migration functions were also decreased. Taken together, these results suggest that HIF-1α acts as an important transcription factor and can significantly affect the secretion and adhesion functions of leukemia BMSCs.

Acute effect of alcohol intake on sine-wave Cartesian and polar contrast sensitivity functions

The aim of this study was to assess contrast sensitivity for angular frequency stimuli as well as for sine-wave gratings in adults under the effect of acute ingestion of alcohol. We measured the contrast sensitivity function (CSF) for gratings of 0.25, 1.25, 2.5, 4, 10, and 20 cycles per degree of visual angle (cpd) as well as for angular frequency stimuli of 1, 2, 4, 24, 48, and 96 cycles/360°. Twenty adults free of ocular diseases, with normal or corrected-to-normal visual acuity, and no history of alcoholism were enrolled in two experimental groups: 1) no alcohol intake (control group) and 2) alcohol ingestion (experimental group). The average concentration of alcohol in the experimental group was set to about 0.08%. We used a paradigm involving a forced-choice method. Maximum sensitivity to contrast for sine-wave gratings in the two groups occurred at 4 cpd sine-wave gratings and at 24 and 48 cycles/360° for angular frequency stimuli. Significant changes in contrast sensitivity were observed after alcohol intake compared with the control condition at spatial frequency of 4 cpd and 1, 24, and 48 cycles/360° for angular frequency stimuli. Alcohol intake seems to affect the processing of sine-wave gratings at maximum sensitivity and at the low and high frequency ends for angular frequency stimuli, both under photopic luminance conditions.

Mathematical modelling of the osmotic dehydration of cherry tomato (Lycopersicon esculentum var. cerasiforme)

Osmotic dehydration of cherry tomato as influenced by osmotic agent (sodium chloride and a mixed sodium chloride and sucrose solutions) and solution concentration (10 and 25% w/w) at room temperature (25°C) was studied. Kinetics of water loss and solids uptake were determined by a two parameter model, based on Fick's second law and applied to spherical geometry. The water apparent diffusivity coefficients obtained ranged from 2.17x10-10 to 11.69x10-10 m²/s.

Multicomponent diffusion during Prato cheese ripening: mathematical modeling using the finite element method

The partial replacement of NaCl by KCl is a promising alternative to produce a cheese with lower sodium content since KCl does not change the final quality of the cheese product. In order to assure proper salt proportions, mathematical models are employed to control the product process and simulate the multicomponent diffusion during the reduced salt cheese ripening period. The generalized Fick's Second Law is widely accepted as the primary mass transfer model within solid foods. The Finite Element Method (FEM) was used to solve the system of differential equations formed. Therefore, a NaCl and KCl multicomponent diffusion was simulated using a 20% (w/w) static brine with 70% NaCl and 30% KCl during Prato cheese (a Brazilian semi-hard cheese) salting and ripening. The theoretical results were compared with experimental data, and indicated that the deviation was 4.43% for NaCl and 4.72% for KCl validating the proposed model for the production of good quality, reduced-sodium cheeses.

Application of mathematical models for the prediction of adsorption isotherms in solid mixture for mango powder refreshment

Solid mixtures for refreshment are already totally integrated to the Brazilian consumers' daily routine, because of their quick preparation method, yield and reasonable price - quite lower if compared to 'ready-to-drink' products or products for prompt consumption, what makes them economically more accessible to low-income populations. Within such a context, the aim of this work was to evaluate the physicochemical and mineral composition, as well as the hygroscopic behavior of four different brands of solid mixture for mango refreshment. The BET, GAB, Oswim and Henderson mathematical models were built through the adjustment of experimental data to the isotherms of adsorption. Results from the physiochemical evaluation showed that the solid mixtures for refreshments are considerable sources of ascorbic acid and reductor sugar; and regarding mineral compounds, they are significant sources of calcium, sodium and potassium. It was also verified that the solid mixtures for refreshments of the four studied brands are considered highly hygroscopic.

Mathematical modeling of dehydration of 'Fuji' and 'Gala' apples slices using infrared

The objective of this work was to determine and model the infrared dehydration curves of apple slices - Fuji and Gala varieties. The slices were dehydrated until constant mass, in a prototype dryer with infrared heating source. The applied temperatures ranged from 50 to 100 °C. Due to the physical characteristics of the product, the dehydration curve was divided in two periods, constant and falling, separated by the critical moisture content. A linear model was used to describe the constant dehydration period. Empirical models traditionally used to model the drying behavior of agricultural products were fitted to the experimental data of the falling dehydration period. Critical moisture contents of 2.811 and 3.103 kgw kgs-1 were observed for the Fuji and Gala varieties, respectively. Based on the results, it was concluded that the constant dehydration rates presented a direct relationship with the temperature; thus, it was possible to fit a model that describes the moisture content variation in function of time and temperature. Among the tested models, which describe the falling dehydration period, the model proposed by Midilli presented the best fit for all studied conditions.

Mathematical modeling of microbial growth in milk

A mathematical model to predict microbial growth in milk was developed and analyzed. The model consists of a system of two differential equations of first order. The equations are based on physical hypotheses of population growth. The model was applied to five different sets of data of microbial growth in dairy products selected from Combase, which is the most important database in the area with thousands of datasets from around the world, and the results showed a good fit. In addition, the model provides equations for the evaluation of the maximum specific growth rate and the duration of the lag phase which may provide useful information about microbial growth.

Evaluation of a new mathematical model to describe Clostridium perfringens growth during the cooling of cooked ground beef

A mathematical model previously developed to study microbial growth in food products under an isothermal environment was adapted to a time-varying temperature regime. The resulting model was applied to study the growth of Clostridium perfringens in meat products. This micro-organism is of particular relevance to public health and economy due to the loss of productivity caused by it. Results showed a similar performance of the model used compared to the Baranyi model under an isothermal situation and a slightly better performance under a non-isothermal temperature profile.

Mathematical modeling of microwave dried celery leaves and determination of the effective moisture diffusivities and activation energy

Celery (Apium graveolens L. var. secalinum Alef) leaves with 50±0.07 g weight and 91.75±0.15% humidity (~11.21 db) were dried using 8 different microwave power densities ranging between 1.8-20 W g-1, until the humidity fell down to 8.95±0.23% (~0.1 db). Microwave drying processes were completed between 5.5 and 77 min depending on the microwave power densities. In this study, measured values were compared with predicted values obtained from twenty thin layer drying theoretical, semi-empirical and empirical equations with a new thin layer drying equation. Within applied microwave power density; models whose coefficient and correlation (R²) values are highest were chosen as the best models. Weibull distribution model gave the most suitable predictions at all power density. At increasing microwave power densities, the effective moisture diffusivity values ranged from 1.595 10-10 to 6.377 10-12 m2 s-1. The activation energy was calculated using an exponential expression based on Arrhenius equation. The linear relationship between the drying rate constant and effective moisture diffusivity gave the best fit.

Nature of the state economic expanded functions in the Brazilian economy*

ABSTRACT The paper discusses the dynamics of capital accumulation in Latin America economies. The hypothesis is that in these economies the role of the State is comparatively broader than in the economies of the centers of the capitalism by structural reasons. The argument is mainly based on Marx and Kalecki, besides historical elements of Latin America economies, particularly the Brazilian economy. Then the paper explores the dynamics consequences of this nature at the national levels, concluding that this condition gives a higher degree of instability.