255 research outputs found
La convertibilidad en Argentina: El éxito, fracaso y porqué de su final
This article analyzes the Law of Convertibility approved in Argentina in 1991 and its similarities with the conversion box described by Hanke and Schuler (1993). This work evaluates the effect of this policy on the main macroeconomic indicators. It also discusses the relationship of this measure with the crisis, and it is argued that the increase in public expenditure was the main force behind the weakening of the monetary system. Finally, this work considers the options that the government could have implemented to respond to its obligations. The choice was to default on its debt and devalue its currency, ending with the Law of Convertibility.Este artÃculo analiza la Ley de Convertibilidad aprobada en 1991 en Argentina y su semejanza con la caja de conversión descrita por Hanke y Schuler (1993). Se evalúa el efecto de esta polÃtica sobre los principales indicadores macroeconómicos. Se discute la relación de esta medida con la crisis, y se argumenta que el incremento en el gasto público fue el principal factor que debilitó el sistema monetario. Por último, el artÃculo menciona las opciones que manejaba el gobierno para responder a sus obligaciones. La elección fue el default de su deuda y devaluar la moneda, terminando asà con la Ley de Convertibilidad
High-resolution measurements of the multilayer ultra-structure of articular cartilage and their translational potential
Current musculoskeletal imaging techniques usually target the macro-morphology of articular cartilage or use histological analysis. These techniques are able to reveal advanced osteoarthritic changes in articular cartilage but fail to give detailed information to distinguish early osteoarthritis from healthy cartilage, and this necessitates high-resolution imaging techniques measuring cells and the extracellular matrix within the multilayer structure of articular cartilage. This review provides a comprehensive exploration of the cellular components and extracellular matrix of articular cartilage as well as high-resolution imaging techniques, including magnetic resonance image, electron microscopy, confocal laser scanning microscopy, second harmonic generation microscopy, and laser scanning confocal arthroscopy, in the measurement of multilayer ultra-structures of articular cartilage. This review also provides an overview for micro-structural analysis of the main components of normal or osteoarthritic cartilage and discusses the potential and challenges associated with developing non-invasive high-resolution imaging techniques for both research and clinical diagnosis of early to late osteoarthritis
Artificial intelligence methods enhance the discovery of RNA interactions
Understanding how RNAs interact with proteins, RNAs, or other molecules remains a challenge of main interest in biology, given the importance of these complexes in both normal and pathological cellular processes. Since experimental datasets are starting to be available for hundreds of functional interactions between RNAs and other biomolecules, several machine learning and deep learning algorithms have been proposed for predicting RNA-RNA or RNA-protein interactions. However, most of these approaches were evaluated on a single dataset, making performance comparisons difficult. With this review, we aim to summarize recent computational methods, developed in this broad research area, highlighting feature encoding and machine learning strategies adopted. Given the magnitude of the effect that dataset size and quality have on performance, we explored the characteristics of these datasets. Additionally, we discuss multiple approaches to generate datasets of negative examples for training. Finally, we describe the best-performing methods to predict interactions between proteins and specific classes of RNA molecules, such as circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs), and methods to predict RNA-RNA or RNA-RBP interactions independently of the RNA type
Does reduced employment protection increase the employment disadvantage of workers with low education and poorer health?
Background Declines in employment protection may have disproportionate effects on employment opportunities of workers with low education and poorer health. This study investigates the impact of changes in employment protection levels on employment rates according to education and health in 23 European countries. Methods Data were taken from the 4-year rotating panel European Union Statistics on Income and Living Conditions study. Employed participants aged 29-59 years (n = 334 999) were followed for 1 year over an 11-year period, from 2003 up to 2014. A logistic regression model with country and period fixed effects was used to estimate the association between changes in the Organisation for Economic Co-operation and Development (OECD) employment protection index and labour market outcomes, incorporating interaction terms with education and health. Results 15 of the 23 countries saw their level of employment protection decline between 2003 and 2014. Reduced employment protection of temporary workers increased odds of early retirement (OR 6.29, 95% CI 3.17 to 12.48) and unemployment (OR 1.37, 95% CI 1.07 to 1.76). Reduced employment protection of permanent workers increased odds of early retirement more among workers in poor health (OR 4.46, 95% CI 2.26 to 8.78) than among workers in good health (OR 2.58, 95% CI 1.30 to 5.10). The impact of reduced employment protection of temporary workers on unemployment was stronger among lower-educated workers (OR 1.47, 95% CI 1.13 to 1.90) than among higher-educated workers (OR 1.21, 95% CI 0.95 to 1.54). Conclusion Reduced employment protection increased the odds of early exit from paid employment, especially among workers with lower education and poorer health. Employment protection laws may help reduce the employment disadvantage of workers with low education and poorer health
Alcohol-induced blood-brain barrier impairment: An in vitro study
In recent years, alcohol abuse has dramatically grown with deleterious consequence for people’s health and, in turn, for health care costs. It has been demonstrated, in humans and animals, that alcohol intoxication induces neuroinflammation and neurodegeneration thus leading to brain impairments. Furthermore, it has been shown that alcohol consumption is able to impair the blood– brain barrier (BBB), but the molecular mechanisms underlining this detrimental effect have not been fully elucidated. For this reason, in this study we investigated the effects of alcohol exposure on a rat brain endothelial (RBE4) cell line, as an in vitro-validated model of brain microvascular endothelial cells. To assess whether alcohol caused a concentration-related response, the cells were treated at different times with increasing concentrations (10–1713 mM) of ethyl alcohol (EtOH). Microscopic and molecular techniques, such as cell viability assay, immunofluorescence and Western blotting, were used to examine the mechanisms involved in alcohol-induced brain endothelial cell alterations including tight junction distribution, apoptosis, and reactive oxygen species production. Our findings clearly demonstrate that alcohol causes the formation of gaps between cells by tight junction disassembly, triggered by the endoplasmic reticulum and oxidative stress, highlighted by GRP78 chaperone upregulation and increase in reactive oxygen species production, respectively. The results from this study shed light on the mechanisms underlying alcohol-induced blood–brain barrier dysfunction and a better understanding of these processes will allow us to take advantage of developing new therapeutic strategies in order to prevent the deleterious effects of alcohol
Cannabidiol protects dopaminergic neuronal cells from cadmium
The protective effect of cannabidiol (CBD), the non-psychoactive component of Cannabis sativa, against neuronal toxicity induced by cadmium chloride (CdCl2 10 μM) was investigated in a retinoic acid (RA)-differentiated SH-SY5Y neuroblastoma cell line. CBD (1 μM) was applied 24 h before and removed during cadmium (Cd) treatment. In differentiated neuronal cells, CBD significantly reduced the Cd-dependent decrease of cell viability, and the rapid reactive oxygen species (ROS) increase. CBD significantly prevented the endoplasmic reticulum (ER) stress (GRP78 increase) and the subcellular distribution of the cytochrome C, as well as the overexpression of the pro-apoptotic protein BAX. Immunocytochemical analysis as well as quantitative protein evaluation by western blotting revealed that CBD partially counteracted the depletion of the growth associated protein 43 (GAP43) and of the neuronal specific class III β-tubulin (β3 tubulin) induced by Cd treatment. These data showed that Cd-induced neuronal injury was ameliorated by CBD treatment and it was concluded that CBD may represent a potential option to protect neuronal cells from the detrimental effects of Cd toxicity
Carbonic Anhydrase IV Selective Inhibitors Counteract the Development of Colitis-Associated Visceral Pain in Rats
Persistent pain affecting patients with inflammatory bowel diseases (IBDs) is still very difficult to treat. Carbonic anhydrase (CA) represents an intriguing pharmacological target considering the anti-hyperalgesic efficacy displayed by CA inhibitors in both inflammatory and neuropathic pain models. The aim of this work was to evaluate the effect of inhibiting CA IV, particularly when expressed in the gut, on visceral pain associated with colitis induced by 2,4-di-nitrobenzene sulfonic acid (DNBS) in rats. Visceral sensitivity was assessed by measuring animals’ abdominal responses to colorectal distension. Repeated treatment with the selective CA IV inhibitors AB-118 and NIK-67 effectively counteracted the development of visceral pain induced by DNBS. In addition to pain relief, AB-118 showed a protective effect against colon damage. By contrast, the anti-hyperalgesic activity of NIK-67 was independent of colon healing, suggesting a direct protective effect of NIK-67 on visceral sensitivity. The enzymatic activity and the expression of CA IV resulted significantly increased after DNBS injection. NIK-67 normalised CA IV activity in DNBS animals, while AB-118 was partially effective. None of these compounds influenced CA IV expression through the colon. Although further investigations are needed to study the underlying mechanisms, CA IV inhibitors are promising candidates in the search for therapies to relieve visceral pain in IBDs
Efficacy of a vegetal mixture composed of Zingiber officinale, Echinacea purpurea, and Centella asiatica in a mouse model of neuroinflammation: In vivo and ex vivo analysis
Experimental evidence suggests that neuroinflammation is a key pathological event of many diseases affecting the nervous system. It has been well recognized that these devastating illnesses (e.g., Alzheimer's, Parkinson's, depression, and chronic pain) are multifactorial, involving many pathogenic mechanisms, reason why pharmacological treatments are unsatisfactory. The purpose of this study was to evaluate the efficacy of a vegetal mixture capable of offering a multiple approach required to manage the multifactoriality of neuroinflammation. A mixture composed of Zingiber officinale (150 mg kg(-1)), Echinacea purpurea (20 mg kg(-1)), and Centella asiatica (200 mg kg(-1)) was tested in a mouse model of systemic neuroinflammation induced by lipopolysaccharide (LPS, 1 mg kg(-1)). Repeated treatment with the vegetal mixture was able to completely counteract thermal and mechanical allodynia as reported by the Cold plate and von Frey tests, respectively, and to reduce the motor impairments as demonstrated by the Rota rod test. Moreover, the mixture was capable of neutralizing the memory loss in the Passive avoidance test and reducing depressive-like behavior in the Porsolt test, while no efficacy was shown in decreasing anhedonia as demonstrated by the Sucrose preference test. Finally, LPS stimulation caused a significant increase in the activation of glial cells, of the central complement proteins and of inflammatory cytokines in selected regions of the central nervous system (CNS), which were rebalanced in animals treated with the vegetal mixture. In conclusion, the vegetal mixture tested thwarted the plethora of symptoms evoked by LPS, thus being a potential candidate for future investigations in the context of neuroinflammation
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