DNA Methylation Signatures of Bone Metabolism in Osteoporosis and Osteoarthritis Aging-Related Diseases: An Updated Review

DNA methylation is one of the most studied epigenetic mechanisms that play a pivotal role in regulating gene expression. The epigenetic component is strongly involved in aging-bone diseases, such as osteoporosis and osteoarthritis. Both are complex multi-factorial late-onset disorders that represent a globally widespread health problem, highlighting a crucial point of investigations in many scientific studies. In recent years, new findings on the role of DNA methylation in the pathogenesis of aging-bone diseases have emerged. The aim of this systematic review is to update knowledge in the field of DNA methylation associated with osteoporosis and osteoarthritis, focusing on the specific tissues involved in both pathological conditions.     

Hepatitis C virus RNA in serum of blood donors with or without elevated transaminase levels

The pattern of hepatitis C virus (HCV) viremia in blood donors who are positive for antibody to HCV (anti-HCV) according to the level of transaminase activity is unclear. A polymerase chain reaction-based HCV RNA detection method was used to study two clearly defined groups of anti-HCV-positive blood donors with repeatedly normal (n = 27) and elevated (n = 17) alanine aminotransferase (ALT) levels. HCV RNA was detected in only 4 of 27 blood donors with normal ALT values and 15 of 17 with elevated ALT values. These results indicate that anti-HCV-positive blood donors with normal ALT levels constitute a heterogeneous group, as HCV viremia is detectable in only a small proportion of cases. Polymerase chain reaction should be useful in the surveillance of anti-HCV-positive blood donors with normal ALT levels, by identifying those who might benefit from further investigation and treatment.     

A genetic algorithm for the optimisation of assembly sequences

This paper describes a Genetic Algorithm (GA) designed to optimise the Assembly Sequence Planning Problem (ASPP), an extremely diverse, large scale and highly constrained combinatorial problem. The modelling of the ASPP problem, which has to be able to encode any industrial-size product with realistic constraints, and the GA have been designed to accommodate any type of assembly plan and component. A number of specific modelling issues necessary for understanding the manner in which the algorithm works and how it relates to real-life problems, are succinctly presented, as they have to be taken into account/adapted/solved prior to Solving and Optimising (S/O) the problem. The GA has a classical structure but modified genetic operators, to avoid the combinatorial explosion. It works only with feasible assembly sequences and has the ability to search the entire solution space of full-scale, unabridged problems of industrial size. A case study illustrates the application of the proposed GA for a 25-components product.     

Mechanisms of insulin resistance in experimental hyperinsulinemic dogs

The aim of this work was to identify which proteins in horse dander extracts are allergens and to characterise them. Two-dimensional PAGE showed that horse dander preparations are composed of up to 50 proteins, all having acidic isoelectric points in the pH range 3-4.5. Immunoblots of two-dimensional PAGE were used to compare the reactivity of the proteins with IgE from 23 allergic patients. Patient sera were divided into two main groups recognising either allergens of 18.5 kDa or proteins of 27-29 and 31 kDa. The proteins of 27-29 kDa and 31 kDa were all N-glycosylated and their glycan chains seem to play a role in the binding of IgE from allergic patients. The sugar composition of their carbohydrate moiety was determined and lectin-binding experiments indicated presence of terminal sialic acid linked alpha-(2-->6) to galactose, galactose linked beta-(1-->4) to N-acetylglucosamine, and possibly presence of sialic acid linked alpha-(2-->3) to galactose. The 27-29-kDa glycoproteins had heterogeneous isoelectric points, most probably due to different degrees of sialylation in their oligosaccharide chains. The two 18.5-kDa allergens exhibited slightly different isoelectric points and their N-terminal sequences were identical, showing that they most likely were isoforms of the same protein. Sequence analyses revealed that their N-terminal sequences are similar to proteins belonging to the lipocalin family. We named the two 18.5-kDa proteins Equ c 2.0101 and Equ c 2.0102, according to International Allergen Nomenclature recommendations [King, T. P., Hoffman, D., Lowenstein, H., Marsh, D. G., Platts-Mills, T. A. E. & Thomas, W. (1995) J. Allergy Clin. Immunol. 96, 5-14]. The N-terminal of the allergens of 27-29 kDa were blocked and their sequences were not determined. Their amino acid compositions were determined and comparison with acidic mammalian proteins in the Swiss-Prot database revealed high scores with lipocalin proteins. This suggests that the glycosylated horse dander allergens belong to the lipocalin family, like Equ c 2.0101 and Equ c 2.0102.     

A globally stable discrete-time controller for current-fed induction motors

In this short paper we present a discrete-time field oriented controller (FOC) for current-fed induction motors which insures global asymptotic speed regulation as well as rotor flux norm tracking. To the best of our knowledge, this is the first time such a result is rigorously established for a controller implemented in discrete-time. To insure global stability a condition on the reference for the rotor flux norm, which is time-varying, is imposed. This condition disappears as the sampling period goes to zero, hence allowing for independent speed regulation and rotor flux norm tracking. One important feature of our scheme is that, compared with the first-difference approximation of the classical indirect FOC, the additional computational burden is negligible. It is also shown that the result can easily be extended to the case of tracking time-varying references in speed or position.     

Residuated bilattices

We introduce a new product bilattice construction that generalizes the well-known one for interlaced bilattices and others that were developed more recently, allowing to obtain a bilattice with two residuated pairs as a certain kind of power of an arbitrary residuated lattice. We prove that the class of bilattices thus obtained is a variety, give a finite axiomatization for it and characterize the congruences of its members in terms of those of their lattice factors. Finally, we show how to employ our product construction to define first-order definable classes of bilattices corresponding to any first-order definable subclass of residuated lattices.     

Mutual Prodrugs of 5-Fluorouracil: From a Classic Chemotherapeutic Agent to Novel Potential Anticancer Drugs

The development of potent antitumor agents with a low toxicological profile against healthy cells is still one of the greatest challenges facing medicinal chemistry. In this context, the “mutual prodrug” approach has emerged as a potential tool to overcome undesirable physicochemical features and mitigate the side effects of approved drugs. Among broad-spectrum chemotherapeutics available for clinical use today, 5-fluorouracil (5-FU) is one of the most representative, also included in the World Health Organization model list of essential medicines. Unfortunately, severe side effects and drug resistance phenomena are still the primary limits and drawbacks in its clinical use. This review describes the progress made over the last ten years in developing 5-FU-based mutual prodrugs to improve the therapeutic profile and achieve targeted delivery to cancer tissues.