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.

An empirical comparison of atypical bulimia nervosa and binge eating disorder

The International Classification of Diseases, 10th edition (ICD-10) defines atypical bulimia nervosa (ABN) as an eating disorder that encompasses several different syndromes, including the DSM-IV binge eating disorder (BED). We investigated whether patients with BED can be differentiated clinically from patients with ABN who do not meet criteria for BED. Fifty-three obese patients were examined using the Structured Clinical Interview for DSM-IV and the ICD-10 criteria for eating disorders. All volunteers completed the Binge Eating Scale (BES), the Beck Depression Inventory, and the Symptom Checklist-90 (SCL-90). Individuals fulfilling criteria for both ABN and BED (N = 18), ABN without BED (N = 16), and obese controls (N = 19) were compared and contrasted. Patients with ABN and BED and patients with ABN without BED displayed similar levels of binge eating severity according to the BES (31.05 ± 7.7 and 30.05 ± 5.5, respectively), which were significantly higher than those found in the obese controls (18.32 ± 8.7; P < 0.001 and P < 0.001, respectively). When compared to patients with ABN and BED, patients with ABN without BED showed increased lifetime rates of agoraphobia (P = 0.02) and increased scores in the somatization (1.97 ± 0.85 vs 1.02 ± 0.68; P = 0.001), obsessive-compulsive (2.10 ± 1.03 vs 1.22 ± 0.88; P = 0.01), anxiety (1.70 ± 0.82 vs 1.02 ± 0.72; P = 0.02), anger (1.41 ± 1.03 vs 0.59 ± 0.54; P = 0.005) and psychoticism (1.49 ± 0.93 vs 0.75 ± 0.55; P = 0.01) dimensions of the SCL-90. The BED construct may represent a subgroup of ABN with less comorbities and associated symptoms.

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.

Banking and regional inequality in Brazil: an empirical note

The paper investigates a neglected aspect of regional inequality in Brazil, namely regional inequalities related to financial flows. A synthetic regional financial inequality index is proposed and calculated in a semester basis over the 02-1994/02-2000 period. The inequality measure attempts to capture to what extent deposits in a given state translate into credit operations in that locality. Two main results emerge. First, non-negligible inequality patterns emerge when one considers the segment of private banks and those are consistent with an important proportion of states with a predominantly exporting pattern, for which deposits surpasses loans in that locality. Second, if one focus on the segment of public banks, an opposite pattern appears, that is consistent with decision patterns that might have, in part, a regional development motivation.

Corruption, income, and rule of law: empirical evidence from developing and developed economies

This article presents an empirical analysis based on cross-country data concerned with two points regarding corruption: (i) its effects on income; and (ii) how to mitigate corruption. The findings can be highlighted in two points. Firstly the idea that corruption is intrinsically connected with income is confirmed. Secondly, the traditional argument that an increase in rule of law represents a good strategy in the fight against corruption is valid for developing countries. Furthermore, this study reveals that the search for increasing the human development index represents a rule of thumb for high levels of income and to control corruption.

Price synchronization in retailing: some empirical evidence

The paper investigates the synchronization of price changes in the context of retail tire dealers in São Paulo-Brazil and selected items in supermarkets for cleaning supplies and food in Rio de Janeiro-Brazil. Results indicate similar and non-negligible synchronization for different brands, although magnitudes are distant from a perfect synchronization pattern. We find interesting patterns in inter-firm competition, with similar magnitudes across different tire types. Intra-chain synchronization is substantial, indicating that a common price adjustment policy tends to be sustained for each chain across different products.

Effects of overvaluation and exchange rate volatility over industrial investment: empirical evidence and economic policy proposals for Brazil

The present article aims to analyze the recent behavior of real exchange rate in Brazil and its effects over investment per worker in Brazilian manufacturing and extractive industry. Preliminary estimates presented in the article shows an over-valuation of 48% of real exchange rate in Brazil. The reaction between the level (and volatility) of real exchange rate and investment (per worker) in Brazil is analyzed by means of a panel data econometric model for 30 sectors of Brazilian manufacturing and extractive industry. The empirical results show that the level and volatility of real exchange rate has a strong effect over investment per worker in Brazilian industry. Finally, we conclude the article presenting a proposal for a new macroeconomic regime that aims to produce an acceleration of economic growth of Brazilian economy and, by that, a catching-up process with developed countries.

Overvaluation trend of the Brazilian currency in the 2000s: empirical estimation

The aim of this paper is to discuss the trend of overvaluation of the Brazilian currency in the 2000s, presenting an econometric model to estimate the real exchange rate (RER) and which should be a reference level of the RER to guide long-term economic policy. In the econometric model, we consider long-term structural and short-term components, both of which may be responsible for explaining overvaluation trend of the Brazilian currency. Our econometric exercise confirms that the Brazilian currency had been persistently overvalued throughout almost all of the period under analysis, and we suggest that the long-term reference level of the real exchange rate was reached in 2004. In July 2014, the average nominal exchange rate should have been around 2.90 Brazilian reais per dollar (against an observed nominal rate of 2.22 Brazilian reais per dollar) to achieve the 2004 real reference level (average of the year). That is, according to our estimates, in July 2014 the Brazilian real was overvalued at 30.6 per cent in real terms relative to the reference level. Based on these findings we conclude the paper suggesting a mix of policy instruments that should have been used in order to reverse the overvaluation trend of the Brazilian real exchange rate, including a target for reaching a real exchange rate in the medium and the long-run which would favor resource allocation toward more technological intensive sectors.

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.