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In this work, we report the systematic investigation of a multiresponsive complex coacervate-based underwater adhesive, obtained by combining polyelectrolyte domains and thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) units. This material exhibits a transition from liquid to solid but, differently from most reactive glues, is completely held together by non-covalent interactions, i.e., electrostatic and hydrophobic. Because the solidification results in a kinetically trapped morphology, the final mechanical properties strongly depend on the preparation conditions and on the surrounding environment. A systematic study is performed to assess the effect of ionic strength and of PNIPAM content on the thermal, rheological and adhesive properties. This study enables the optimization of polymer composition and environmental conditions for this underwater adhesive system. The best performance with a work of adhesion of 6.5 J/m2 was found for the complex coacervates prepared at high ionic strength (0.75 M NaCl) and at an optimal PNIPAM content around 30% mol/mol. The high ionic strength enables injectability, while the hydrated PNIPAM domains provide additional dissipation, without softening the material so much that it becomes too weak to resist detaching stress.

This study aimed at assessing farmers’ perceptions and acceptance of the proposed breeding strategy of Instituto Veterinario de Investigaciones Tropicales y de Altura (IVITA), located in the Central Andes of Peru. A total of 34 farmers, who had received guinea pigs from IVITA, were interviewed. The questionnaire was performed in Spanish language and covered topics about the guinea pig production, feeding, mating system, training, the main products, perception and acceptance of crossbred lines (“cuy RG”), and the farmers’ comment about the terminal crossbred animal (“cuy G”). The preferred feeding strategy was a combination of forage and supplement. All farmers implemented a controlled mating system. Most farmers had received training on feeding, reproduction, management, equipment, and facilities. The main product is animals for slaughter. The 82.40% of farmers reported that they do not purchase guinea pigs from IVITA anymore, because they are highly susceptibility to lymphadenitis, which is a highly contagious disease and causes swollen lymph nodes and affects the meat quality. Most of the respondents classified the “cuy RG” and “cuy G” as suitable for meat production and were satisfied with the performance of the animals. Therefore, 58.80% of respondents already recommended “cuy RG” to other farmers. However, 17.70% of the respondents would not recommend these animals because they are susceptible to disease, especially lymphadenitis. Therefore, IVITA should engage in more structured dialogue with farmers and regularly include their opinion in future improvement of its breeding strategies. This could help to reach higher acceptance rates by farmers.

This study aimed to estimate genetic parameters for four guinea pig lines of a crossbreeding scheme. Two paternal lines are selected for growth rate (P1) and feed conversion rate (P2), whereas two maternal lines are selected for growth rate of litter (M1) and litter size at birth (M2). The heritabilities and genetic correlations were estimated with animal linear models employing multivariate analyses with REML. The heritabilities for birth weight (BW) were 0.21±0.02 and 0.23±0.03 for P1 and P2, respectively, and for weaning weight (WW), the heritability was 0.28±0.03 for P2. The estimates for weight at 60 days of age (W60) were 0.34±0.01 and 0.47±0.04 for P1 and P2, respectively, and for partial feed conversion rate was 0.46±0.03 for P2. Heritabilities for litter weight at birth (LW) were 0.09±0.03 and 0.10±0.03 for P1 and M1, respectively. For litter weight at 10 days of age (LW10), the heritability was 0.15±0.03 for M1. Heritabilities for litter size (LS) were 0.17±0.03, 0.20±0.03 and 0.11±0.03, and for number of pups born alive (BA) were 0.09±0.03, 0.14±0.03 and 0.09±0.03 for P1, M1 and M2, respectively. Similarly, high genetic correlations were found between BW, WW and W60 and between LW, LS, LW10 and BA. The genetic correlation between BW direct and maternal was moderately negative (− 0.24 ± 0.10) for P1. These results show the genetic status for all four guinea pig lines, which is essential for the further improvement of the currently implemented breeding programme and also indicate an opportunity for genetic improvement.

The assembly of iron-sulfur clusters (ISCs) in eukaryotes involves the protein Frataxin. Deficits in this protein have been associated with iron inside the mitochondria and impair ISC biogenesis as it is postulated to act as the iron donor for ISCs assembly in this organelle. A pronounced lack of Frataxin causes Friedreich’s Ataxia, which is a human neurodegenerative and hereditary disease mainly affecting the equilibrium, coordination, muscles and heart. Moreover, it is the most common autosomal recessive ataxia. High similarities between the human and yeast molecular mechanisms that involve Frataxin have been suggested making yeast a good model to study that process. In yeast, the protein complex that forms the central assembly platform for the initial step of ISC biogenesis is composed by yeast frataxin homolog, Nfs1–Isd11 and Isu. In general, it is commonly accepted that protein function involves interaction with other protein partners, but in this case not enough is known about the structure of the protein complex and, therefore, how it exactly functions. The objective of this work is to model the protein complex in order to gain insight into structural details that end up with its biological function. To achieve this goal several bioinformatics tools, modeling techniques and protein docking programs have been used. As a result, the structure of the protein complex and the dynamic behavior of its components, along with that of the iron and sulfur atoms required for the ISC assembly, have been modeled. This hypothesis will help to better understand the function and molecular properties of Frataxin as well as those of its ISC assembly protein partners.

The objective of this study was to characterize the peptide-binding motif of the major histocompatibility complex (MHC) class II HLA-DR8 molecule included in the type 1 diabetes-associated haplotype DRB1 * 0801-DQA1 * 0401/DQB1 * 0402 (DR8-DQ4), and compare it with that of other diabetes-associated MHC class II alleles; DR8-bound peptides were eluted from an HLA-DR homozygous lymphoblastoid cell line. The repertoire was characterized by peptide sequencing using a LTQ ion trap mass spectrometer coupled to a multidimensional liquid chromatography system. After validation of the spectra identification, the definition of the HLA-DR8 peptide-binding motif was achieved from the analysis of 486 natural ligands, based on serial alignments of all possible HLA-DR-binding cores. The DR8 motif showed a strong similarity with the peptide-binding motifs of other MHC class II diabetes-associated alleles, HLA-DQ8 and H-2 I-A g7 . Similar to HLA-DQ8 and H-2 I-A g7 , HLA-DR8 preferentially binds peptides with an acidic residue at position P9 of the binding core, indicating that DR8 is the susceptibility component of the DR8-DQ4 haplotype. Indeed, some DR8 peptides were identical to peptides previously identified as DQ8- or I-A g7 ligands, and several diabetes-specific peptides associated with DQ8 or I-A g7 could theoretically bind to HLA-DR8. These data further strengthen the association of HLA-DR8 with type I diabetes.

Cell-targeting peptides or proteins are appealing tools in nanomedicine and innovative medicines because they increase the local drug concentration and reduce potential side effects. CXC chemokine receptor 4 (CXCR4) is a cell surface marker associated with several severe human pathologies, including colorectal cancer, for which intracellular targeting agents are currently missing. Four different peptides that bind CXCR4 were tested for their ability to internalize a green fluorescent protein-based reporter nanoparticle into CXCR4⁺ cells. Among them, only the 18 mer peptide T22, an engineered segment derivative of polyphemusin II from the horseshoe crab, efficiently penetrated target cells via a rapid, receptor-specific endosomal route. This resulted in accumulation of the reporter nanoparticle in a fully fluorescent and stable form in the perinuclear region of the target cells, without toxicity either in cell culture or in an in vivo model of metastatic colorectal cancer. Given the urgent demand for targeting agents in the research, diagnosis, and treatment of CXCR4-linked diseases, including colorectal cancer and human immunodeficiency virus infection, T22 appears to be a promising tag for the intracellular delivery of protein drugs, nanoparticles, and imaging agents.

BackgroundMultiple factors, in addition to left ventricular ejection fraction (LVEF) influence the risk of mortality in coronary artery disease. The purpose of this study was to evaluate the main causes of syncope after myocardial infarction (MI) and to propose an algorithm of management.Methods356 patients consecutively admitted for syncope and history of MI (>1 month), without ventricular tachycardia (VT), underwent echocardiography, Holter monitoring, head-up tilt test, exercise testing, signal-averaged ECG, electrophysiological study (EPS) and evaluation of coronary status. The mean follow-up was 4±2 years.ResultsMonomorphic VT, ventricular flutter or fibrillation (VF) and supraventricular tachyarrhythmia were respectively induced at EPS in 87, 63 and 39 patients; conduction disturbances were noted in 23 patients, and 57 patients had several abnormalities. Among the 144 patients with negative EPS, coronary ischaemia was identified in 37 patients, and hypervagotonia in 27 patients. All studies remain negative in 84 patients (23.6%), more frequently women (p<0.001). Four patients died suddenly during follow-up. A longer QRS duration, a lower LVEF and grade IVa,b of Lown on Holter ECG were associated with the induction of VT. LVEF<40% and VT/VF induction were predictors of cardiac mortality, VT was a predictor of sudden death, and low LVEF and advanced age were predictors of death by heart failure.ConclusionMyocardial ischaemia, hypervagotonia, conduction abnormalities, ventricular or supraventricular tachyarrhythmias were identified in 76% of patients with syncope after MI. Several factors of syncope were found in 57 patients (16%). Non-invasive rhythmological and systematic coronary status assessment should be recommended in patients with syncope following MI.

Underwater adhesion represents a huge technological challenge as the presence of water compromises the performance of most commercially available adhesives. Inspired by natural organisms, we have designed an adhesive based on complex coacervation, a liquid–liquid phase separation phenomenon. A complex coacervate adhesive is formed by mixing oppositely charged polyelectrolytes bearing pendant thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) chains. The material fully sets underwater due to a change in the environmental conditions, namely temperature and ionic strength. In this work, we incorporate silica nanoparticles forming a hybrid complex coacervate and investigate the resulting mechanical properties. An enhancement of the mechanical properties is observed below the PNIPAM lower critical solution temperature (LCST): this is due to the formation of PNIPAM–silica junctions, which, after setting, contribute to a moderate increase in the moduli and in the adhesive properties only when applying an ionic strength gradient. By contrast, when raising the temperature above the LCST, the mechanical properties are dominated by the association of PNIPAM chains and the nanofiller incorporation leads to an increased heterogeneity with the formation of fracture planes at the interface between areas of different concentrations of nanoparticles, promoting earlier failure of the network—an unexpected and noteworthy consequence of this hybrid system.

Nowadays the challenge for humanity is to find pathways towards sustainable development. Decision makers require a set of sustainability indicators to know if the sustainability strategies are following those pathways. There are more than one hundred sustainability indicators but they differ on their relative importance according to the size of the locality and change on time. The resources needed to follow these sustainability indicators are scarce and in some instances finite, especially in smaller regions. Therefore strategies to select set of these indicators are useful for decision makers responsible for monitoring sustainability. In this paper we propose a model for the identification and selection of a set of sustainability indicators that adequately represents human systems. In developing this model, we applied evolutionary dynamics in a space where sustainability indicators are fundamental entities interconnected by an interaction matrix. we used a fixed interaction that simulates the current context for the city of Cuernavaca, México as an example. We were able to identify and define relevant sets indicators for the system by using the Pareto principle. In this case we identified a set of sixteen sustainability indicators with more than 80% of the total strength. This set presents resilience to perturbations. For the Tangled Nature framework we provided a manner of treating different contexts (i.e., cities, counties, states, regions, countries, continents or the whole planet), dealing with small dimensions. This model provides decision makers with a valuable tool to select sustainability indicators set for towns, cities, regions, countries, continents or the entire planet according to a coevolutionary framework. The social legitimacy can arise from the fact that each individual indicator must be selected from those that are most important for the subject community.

Background/Objectives: Natural products are important in healthcare due to their accessibility and linkage to a healthy lifestyle. However, their effectiveness is uncertain due to insufficient scientific data. Cancer patients are frequent users of natural products to relieve symptoms or for chemoprevention. Eugenia uniflora leaf essential oil (EO), traditionally used for digestive disorders, emerges as a potential antineoplastic agent. We investigated the cytotoxic and antiproliferative effects of E. uniflora EO in human normal CCD 841 CoN and tumoral Caco-2 colonic cell lines. Methods: CCD 841 CoN and Caco-2 cells were exposed to different concentrations of E. uniflora EO, and the cytotoxicity was determined by MTT and Trypan Blue assays. Cell proliferation kinetics were analyzed at a low EO concentration, and the induction of DNA damage and oxidative stress was assessed by Comet and Cellular ROS assays. Results: Both cell lines exhibited cytotoxicity produced by the EO and decreased cell viability of the exposed cells and their progeny. CCD 841 CoN proliferation was impaired by low EO concentration, while the proliferation kinetics of the Caco-2 cells was modified. EO treatment induced variable DNA damage and oxidative stress depending on the cell line. Conclusions: Our results suggest that E. uniflora EO may prevent the proliferation of normal cells, inducing loss of viability. The EO produced cytotoxic and antiproliferative effects in tumoral cells by inducing DNA damage and increased oxidative stress. These effects support the consideration of E. uniflora EO (or its bioactive compounds) as a potential agent for the chemoprevention and treatment of colorectal cancer.