Designing bioactive porous titanium interfaces to balance mechanical properties and in vitro cells behavior towards increased osseointegration

Titanium implant failures are mainly related to stress shielding phenomenon and the poor cell interaction with host bone tissue. The development of bioactive and biomimetic Ti scaffolds for bone regeneration remains a challenge which needs the design of Ti implants with enhanced osseointegration. In this context, 4 types of titanium samples were fabricated using conventional powder metallurgy, fully dense, dense etched, porous Ti, and porous etched Ti. Porous samples were manufactured by space holder technique, using ammonium bicarbonate particles as spacer in three different ranges of particle size (100–200 μm, 250–355 μm and 355–500 μm). Substrates were chemically etched by immersion in fluorhydric acid at different times (125 and 625 s) and subsequently, were characterized from a micro-structural, topographical and mechanical point of view. Etched surfaces showed an additional roughness preferentially located inside pores. In vitro tests showed that all substrates were biocompatible (80% of cell viability), confirming cell adhesion of premioblastic cells. Similarly, osteoblast showed similar cell proliferation rates at 4 days, however, higher cell metabolic activity was observed in fully dense and dense etched surfaces at 7 days. In contrast, a significant increase of alkaline phosphatase enzyme expression was observed in porous and porous etched samples compared to control surfaces (dense and dense etched), noticing the suitable surface modification parameters (porosity and roughness) to improve cell differentiation. Furthermore, the presence of pores and rough surfaces of porous Ti substrates remarkably decreased macrophage activation reducing the M1 phenotype polarization as well M1 cell marker expression. Thus, a successful surface modification of porous Ti scaffolds has been performed towards a reduction on stress shielding phenomenon and enhancement of bone osseointegration, achieving a biomechanical and biofunctional equilibrium.Ministry of Economy and Competitiveness of Spain grant MAT2015-71284-PJunta de Andalucía – FEDER (Spain) Project Ref. P12-TEP-140

Bifocal dual reflectarray with curved main surface

This paper presents a novel approach to synthesizing curved reflectarrays using Geometrical Optics (GO). It introduces the concepts of virtual normal and path length shift, which enable a vector-based formulation of the problem that can be solved using ray tracing techniques. The formulation is applied for the design of two different versions of a Dual Bifocal Reflectarray with a parabolic main surface and a flat subreflectarray. The first version aims to enhance the performance of the multibeam antenna by providing a focal ring located at the feed cluster plane. The second version focuses on improving the scanning characteristics of the antenna in the horizontal plane by incorporating two foci. The synthesis procedure yields samples of the path length shift or its derivatives. To reconstruct the phase distribution, an interpolation scheme is employed and described in this paper. Numerical results are presented for both the focal-ring and two-foci configurations, demonstrating the feasibility of this solution for multibeam or scanning satellite antennas operating in the Ka.European Space Research and Technology Centre | Ref. 4000117113/16/NL/AFMinisterio de Economía y Competitividad | Ref. PDC2021-120959-C21/C22Ministerio de Ciencia e Innovación | Ref. RYC2021-033593-IXunta de Galicia | Ref. GRC-ED431C-2019/2

Numerical and Experimental Analyses of Hybrid Composites Made from Amazonian Natural Fibers

The application of lignocellulosic fibers as reinforcements in composite materials has found increasing use in recent years, due to the attractive characteristics of natural fibers such as their low cost, high specific modulus, biodegradability, abundance and with many technical qualities. Natural fiber hybrid composites are very frequently used in automotive aerospace and other industries. In this work, numerical and experimental analysis is carried out to compare curauá, jute and sisal fibers in epoxy composites for use in industry. The most appropriate hybridization effect by establishing the amounts of each fiber on the mechanical properties was considered. Finite Element Models were designed and validated through mechanical tests. The number of Finite Element models and specimens performed was determined through the design of experiments using the Taguchi Method and then the results were statistically validated. Higher strength was obtained in composites made with curauá fiber, followed by jute and sisal fibers. Such behavior was achieved by FEM and experimental tests, revealing an increase in tensile strength by increasing the amount of fibers up to 35% in total. Higher strength was achieved when the composite was made with curauá (20 wt.%), jute (10 wt.%) and sisal (5 wt.%) fibers. The results show a good agreement between the FEM and the experimental tests. Furthermore, the results of the present study were compared with those obtained previously mentioned in the open literature

Integrated tsunami vulnerability and risk assessment: application to the coastal area of El Salvador

ABSTRACT. Advances in the understanding and prediction of tsunami impacts allow for the development of risk reduction strategies for tsunami-prone areas. This paper presents a tsunami vulnerability and risk assessment for the case study of El Salvador, the applied methodology dealing with the complexity and variability of coastal zones by means of (i) an integral approach to cover the entire risk-related process from the hazard, vulnerability and risk assessments to the final risk management; (ii) an integrated approach to combine and aggregate the information stemming from the different dimensions of coupled human and natural systems; and (iii) a dynamic and scale-dependent approach to integrate the spatiotemporal variability considerations. This work also aims at establishing a clear connection to translate the vulnerability and risk assessment results into adequate target-oriented risk reduction measures, trying to bridge the gap between science and management for the tsunami hazard. The approach is applicable to other types of hazards, having been successfully applied to climate-change-related flooding hazard

Importance of a deficiency in S-adenosyl-L-methionine synthesis in the pathogenesis of liver injury

One of the features of liver cirrhosis is an abnormal metabolism of methionine--a characteristic that was described more than a half a century ago. Thus, after an oral load of methionine, the rate of clearance of this amino acid from the blood is markedly impaired in cirrhotic patients compared with that in control subjects. Almost 15 y ago we observed that the failure to metabolize methionine in cirrhosis was due to an abnormally low activity of the enzyme methionine adenosyltransferase (EC 2.5.1.6). This enzyme converts methionine, in the presence of ATP, to S-adenosyl-L-methionine (SAMe), the main biological methyl donor. Since then, it has been suspected that a deficiency in hepatic SAMe may contribute to the pathogenesis of the liver in cirrhosis. The studies reviewed here are consistent with this hypothesis

A methodology for tsunami hazard and risk assessment: application to the coastal area of El Salvador

Advances in the understanding and prediction of tsunami impacts allow the development of adaptation and mitigation strategies to reduce risk on coastal areas. This work, funded by the Spanish Agency for International Development Cooperation (AECID) during the period 2009-2012, presents a comprehensive methodology for tsunami risk assessment at any coastal area worldwide applied specifically in this case to the coast of El Salvador

S-Adenosylmethionine revisited: its essential role in the regulation of liver function

Dietary methionine is mainly metabolized in the liver where it is converted into S-adenosylmethionine (AdoMet), the main biologic methyl donor. This reaction is catalyzed by methionine adenosyltransferase I/III (MAT I/III), the product of MAT1A gene, which is exclusively expressed in this organ. It was first observed that serum methionine levels were elevated in experimental models of liver damage and in liver cirrhosis in human beings. Results of further studies showed that this pathological alteration was due to reduced MAT1A gene expression and MAT I/III enzyme inactivation associated with liver injury. Synthesis of AdoMet is essential to all cells in the organism, but it is in the liver where most of the methylation reactions take place. The central role played by AdoMet in cellular function, together with the observation that AdoMet administration reduces liver damage caused by different agents and improves survival of alcohol-dependent patients with cirrhosis, led us to propose that alterations in methionine metabolism could play a role in the onset of liver disease and not just be a consequence of it. In the present work, we review the recent findings that support this hypothesis and highlight the mechanisms behind the hepatoprotective role of AdoMet

The Development of the Bengamides as New Antibiotics against Drug-Resistant Bacteria

The bengamides comprise an interesting family of natural products isolated from sponges belonging to the prolific Jaspidae family. Their outstanding antitumor properties, coupled with their unique mechanism of action and unprecedented molecular structures, have prompted an intense research activity directed towards their total syntheses, analogue design, and biological evaluations for their development as new anticancer agents. Together with these biological studies in cancer research, in recent years, the bengamides have been identified as potential antibiotics by their impressive biological activities against various drug-resistant bacteria such as Mycobacterium tuberculosis and Staphylococcus aureus. This review reports on the new advances in the chemistry and biology of the bengamides during the last years, paying special attention to their development as promising new antibiotics. Thus, the evolution of the bengamides from their initial exploration as antitumor agents up to their current status as antibiotics is described in detail, highlighting the manifold value of these marine natural products as valid hits in medicinal chemistry.Supported by grants RTI2018-098296-BI00 (Ministerio de Ciencia e Innovación), PI19/01478 from Instituto de Salud Carlos III (ISCIII) (FEDER), P20_00540 (Andalusian Government and FEDER), K99GM138758 and R35GM136286 (National Institute of General Medical Sciences of the National Institutes of Health), A-CTS-666-UGR20 (University of Granada) (FEDER), CTS-107 (Andalusian Government) and 2021-GRIN-30998 (University of Castilla-La Mancha). Partial funding for open access charge: Universidad de Málag

Defining a novel leptin–melanocortin–kisspeptin pathway involved in the metabolic control of puberty

Objective Puberty is a key developmental phenomenon highly sensitive to metabolic modulation. Worrying trends of changes in the timing of puberty have been reported in humans. These might be linked to the escalating prevalence of childhood obesity and could have deleterious impacts on later (cardio-metabolic) health, but their underlying mechanisms remain unsolved. The neuropeptide α-MSH, made by POMC neurons, plays a key role in energy homeostasis by mediating the actions of leptin and likely participates in the control of reproduction. However, its role in the metabolic regulation of puberty and interplay with kisspeptin, an essential puberty-regulating neuropeptide encoded by Kiss1, remain largely unknown. We aim here to unveil the potential contribution of central α-MSH signaling in the metabolic control of puberty by addressing its role in mediating the pubertal effects of leptin and its potential interaction with kisspeptin. Methods Using wild type and genetically modified rodent models, we implemented pharmacological studies, expression analyses, electrophysiological recordings, and virogenetic approaches involving DREADD technology to selectively inhibit Kiss1 neurons, in order to interrogate the physiological role of a putative leptin→α-MSH→kisspeptin pathway in the metabolic control of puberty. Results Stimulation of central α-MSH signaling robustly activated the reproductive axis in pubertal rats, whereas chronic inhibition of melanocortin receptors MC3/4R, delayed puberty, and prevented the permissive effect of leptin on puberty onset. Central blockade of MC3/4R or genetic elimination of kisspeptin receptors from POMC neurons did not affect kisspeptin effects. Conversely, congenital ablation of kisspeptin receptors or inducible, DREADD-mediated inhibition of arcuate nucleus (ARC) Kiss1 neurons resulted in markedly attenuated gonadotropic responses to MC3/4R activation. Furthermore, close appositions were observed between POMC fibers and ARC Kiss1 neurons while blockade of α-MSH signaling suppressed Kiss1 expression in the ARC of pubertal rats. Conclusions Our physiological, virogenetic, and functional genomic studies document a novel α-MSH→kisspeptin→GnRH neuronal signaling pathway involved in transmitting the permissive effects of leptin on pubertal maturation, which is relevant for the metabolic (and, eventually, pharmacological) regulation of puberty onsetThis work was supported by grants BFU2011-025021 & BFU2014-57581-P (Ministerio de Economía y Competitividad, Spain; co-funded with EU funds from FEDER Program); project PIE-00005 (Flexi-Met, Instituto de Salud Carlos III, Ministerio de Sanidad, Spain); Projects P08-CVI-03788 and P12-FQM-01943 (Junta de Andalucía, Spain); EU research contract DEER FP7-ENV-2007-1 and the New Zealand Health Research Council. CIBER Fisiopatología de la Obesidad y Nutrición is an initiative of Instituto de Salud Carlos III. Senior authors are indebted with Dr. R.A. Steiner (University of Washington, Seattle, USA) and Dr. U. Boehm (University of Saarland School of Medicine, Homburg, Germany) for provision of relevant mouse lines, essential for conduction of some of the experiments included in this studyS

Regulation of mammalian liver methionine adenosyltransferase

S-adenosylmethionine (SAM) is an essential metabolite in all cells. SAM is the most important biological methyl group donor and is a precursor in the synthesis of polyamines. Methionine adenosyltransferase (MAT; EC 2.5.1.6) catalyzes the only known SAM biosynthetic reaction from methionine and ATP. In mammalian tissues, three different forms of MAT (MAT I, MAT III and MAT II) have been identified that are the product of two different genes (MAT1A and MAT2A). Although MAT2A is expressed in all mammalian tissues, the expression of MAT1A is primarily restricted to adult liver. In mammals, up to 85% of all methylation reactions and as much as 48% of methionine metabolism occurs in the liver, which indicates the important role of this organ in the regulation of blood methionine. Recent evidence indicates that not only is SAM the main biological methyl group donor and an intermediate metabolite in methionine catabolism, but it is also an intracellular control switch that regulates essential hepatic functions such as liver regeneration and differentiation as well as the sensitivity of this organ to injury. Therefore, knowledge of factors that regulate the activity of MAT I/III, the specific liver enzyme, is essential to understand how cellular SAM levels are controlled