One-Pot Synthesis of Oxidation-Sensitive Supramolecular Gels and Vesicles

Polypeptide-based nanoparticles offer unique advantages from a nanomedicine perspective such as biocompatibility, biodegradability, and stimuli-responsive properties to (patho)physiological conditions. Conventionally, self-assembled polypeptide nanostructures are prepared by first synthesizing their constituent amphiphilic polypeptides followed by postpolymerization self-assembly. Herein, we describe the one-pot synthesis of oxidation-sensitive supramolecular micelles and vesicles. This was achieved by polymerization-induced self-assembly (PISA) of the N-carboxyanhydride (NCA) precursor of methionine using poly(ethylene oxide) as a stabilizing and hydrophilic block in dimethyl sulfoxide (DMSO). By adjusting the hydrophobic block length and concentration, we obtained a range of morphologies from spherical to wormlike micelles, to vesicles. Remarkably, the secondary structure of polypeptides greatly influenced the final morphology of the assemblies. Surprisingly, wormlike micellar morphologies were obtained for a wide range of methionine block lengths and solid contents, with spherical micelles restricted to very short hydrophobic lengths. Wormlike micelles further assembled into oxidation-sensitive, self-standing gels in the reaction pot. Both vesicles and wormlike micelles obtained using this method demonstrated to degrade under controlled oxidant conditions, which would expand their biomedical applications such as in sustained drug release or as cellular scaffolds in tissue engineering

Combinatorial entropy behaviour leads to range selective binding in ligand-receptor interactions

From viruses to nanoparticles, constructs functionalized with multiple ligands display peculiar binding properties that only arise from multivalent effects. Using statistical mechanical modelling, we describe here how multivalency can be exploited to achieve what we dub range selectivity, that is, binding only to targets bearing a number of receptors within a specified range. We use our model to characterise the region in parameter space where one can expect range selective targeting to occur, and provide experimental support for this phenomenon. Overall, range selectivity represents a potential path to increase the targeting selectivity of multivalent constructs

Dynamics of magnetic assembly of binary colloidal structures

"This is an author-created, un-copyedited version of an article published in Europhysics Letters. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at 10.1209/0295-5075/111/37002."Magnetic field (MF)-directed assembly of colloidal particles provides a step towards the bottom-up manufacturing of smart materials whose properties can be precisely modulated by non-contact forces. Here, we study the MF-directed assembly in binary colloids made up of strong ferromagnetic and diamagnetic microparticles dispersed in ferrofluids. We present observations of the aggregation of pairs and small groups of particles to build equilibrium assemblies. We also develop a theoretical model capable of solving the aggregation dynamics and predicting the particle trajectories, a key factor to understand the physics governing the MF-directed assembly.The project MINECO FIS2013-41821-R (Spain) is acknowledged for financial support

Desafios do projeto transição produtiva e serviços ambientais na qualificação de políticas públicas voltadas ao setor rural.

Três medidas político-institucionais ocorridas no Brasil nas duas últimas décadas devem ser destacadas: (1) Lei 12.651/2012 (Novo Código Florestal), (2) Projeto de Lei (PL) 792/2007 (Serviços Ambientais) e (3) Lei 9.126/1995 (Taxa de Juros de Longo Prazo). Mas a falta de informações cientificamente validadas impede a operacionalização de incentivos econômicos para transição produtiva com pagamento de serviços ambientais. Nesse sentido, a Embrapa e entidades parceiras conceberam o Projeto Transição Produtiva e Serviços Ambientais, com o objetivo geral de "gerar e validar instrumentos e metodologias para apoiar políticas públicas de incentivo econômico a processos de transição produtiva de Sistemas Produtivos Integrados (SPIs) com capacidade de geração de renda e prestação de serviços ambientais em escala de paisagem rural". A fase I do projeto será executada entre 09/2013 e 09/2017, tendo como resultados esperados (1) validação científica de desenhos agronômicos de SPIs, (2) validação científica de coeficientes financeiros para potencializar adoção de SPIs via crédito rural, (3) validação científica de indicadores de serviços ambientais prestados e valoração de serviços ambientais por SPIs para viabilizar rebate ecológico no crédito rural e comercialização de produtos em mercados institucionais com preços diferenciados, (4) validação participativa de indicadores de serviços ambientais e de metodologia de certificação de serviços ambientais para atestar condicionalidades em políticas públicas e reduzir custos de transação do PSA, (5) análise comportamental sobre adoção de SPIs para subsidiar recomendações técnicas de TT e ATER e (6) disponibilização de banco de dados de acesso público

Risk factors for bronchiolitis hospitalization during the first year of life in a multicenter Italian birth cohort

BACKGROUND: Respiratory Syncytial Virus (RSV) is one of the main causes of respiratory infections during the first year of life. Very premature infants may contract more severe diseases and 'late preterm infants' may also be more susceptible to the infection. The aim of this study is to evaluate the risk factors for hospitalization during the first year of life in children born at different gestational ages in Italy. METHODS: A cohort of 33-34 weeks gestational age (wGA) newborns matched by sex and age with two cohort of newborns born at 35-37 wGA and > 37 wGA were enrolled in this study for a three-year period (2009-2012). Hospitalization for bronchiolitis (ICD-9 code 466.1) during the first year of life was assessed through phone interview at the end of the RSV season (November-March) and at the completion of the first year of life. RESULTS: The study enrolled 2314 newborns, of which 2210 (95.5 %) had a one year follow-up and were included in the analysis; 120 (5.4 %) were hospitalized during the first year of life for bronchiolitis. Children born at 33-34 wGA had a higher hospitalization rate compared to the two other groups. The multivariate analysis carried out on the entire population associated the following factors with higher rates for bronchiolitis hospitalization: male gender; prenatal treatment with corticosteroids; prenatal exposure to maternal smoking; singleton delivery; respiratory diseases in neonatal period; surfactant therapy; lack of breastfeeding; siblings <10 years old; living in crowded conditions and/or in unhealthy households and early exposure to the epidemic RSV season. When analysis was restricted to preterms born at 33-34 wGA the following variables were associated to higher rates of bronchiolitis hospitalization: male gender, prenatal exposure to maternal smoking, neonatal surfactant therapy, having siblings <10 years old, living in crowded conditions and being exposed to epidemic season during the first three months of life. CONCLUSION: Our study identified some prenatal, perinatal and postnatal conditions proving to be relevant and independent risk factors for hospitalization for bronchiolitis during the first year of life. The combination of these factors may lead to consider palivizumab prophylaxis in Italy

A Weakly Supervised Deep Learning Approach for Detecting Malaria and Sickle Cells in Blood Films

Machine vision analysis of blood films imaged under a brightfield microscope could provide scalable malaria diagnosis solutions in resource constrained endemic urban settings. The major bottleneck in successfully analyzing blood films with deep learning vision techniques is a lack of object-level annotations of disease markers such as parasites or abnormal red blood cells. To overcome this challenge, this work proposes a novel deep learning supervised approach that leverages weak labels readily available from routine clinical microscopy to diagnose malaria in thick blood film microscopy. This approach is based on aggregating the convolutional features of multiple objects present in one hundred high resolution image fields. We show that this method not only achieves expert-level malaria diagnostic accuracy without any hard object-level labels but can also identify individual malaria parasites in digitized thick blood films, which is useful in assessing disease severity and response to treatment. We demonstrate another application scenario where our approach is able to detect sickle cells in thin blood films. We discuss the wider applicability of the approach in automated analysis of thick blood films for the diagnosis of other blood disorders

Blockade of T-cell activation by dithiocarbamates involves novel mechanisms of inhibition of nuclear factor of activated T cells.

Dithiocarbamates (DTCs) have recently been reported as powerful inhibitors of NF-kappaB activation in a number of cell types. Given the role of this transcription factor in the regulation of gene expression in the inflammatory response, NF-kappaB inhibitors have been suggested as potential therapeutic drugs for inflammatory diseases. We show here that DTCs inhibited both interleukin 2 (IL-2) synthesis and membrane expression of antigens which are induced during T-cell activation. This inhibition, which occurred with a parallel activation of c-Jun transactivating functions and expression, was reflected by transfection experiments at the IL-2 promoter level, and involved not only the inhibition of NF-kappaB-driven reporter activation but also that of nuclear factor of activated T cells (NFAT). Accordingly, electrophoretic mobility shift assays (EMSAs) indicated that pyrrolidine DTC (PDTC) prevented NF-kappaB, and NFAT DNA-binding activity in T cells stimulated with either phorbol myristate acetate plus ionophore or antibodies against the CD3-T-cell receptor complex and simultaneously activated the binding of AP-1. Furthermore, PDTC differentially targeted both NFATp and NFATc family members, inhibiting the transactivation functions of NFATp and mRNA induction of NFATc. Strikingly, Western blotting and immunocytochemical experiments indicated that PDTC promoted a transient and rapid shuttling of NFATp and NFATc, leading to their accelerated export from the nucleus of activated T cells. We propose that the activation of an NFAT kinase by PDTC could be responsible for the rapid shuttling of the NFAT, therefore transiently converting the sustained transactivation of this transcription factor that occurs during lymphocyte activation, and show that c-Jun NH2-terminal kinase (JNK) can act by directly phosphorylating NFATp. In addition, the combined inhibitory effects on NFAT and NF-KB support a potential use of DTCs as immunosuppressants

Composite Polymer Hydrogels with high and Reversible Elongation under Magnetic Stimuli

The field of soft actuators is dominated by elastomers that experience mechanical deformations in response to external stimuli. In this context, magnetic stimuli attract considerable interest because of their easy application, tunability, fast response, remote actuation, and safe penetration in biological environments. Since very recently, research interests in the field are being redirected towards hydrogels, which could virtually replace elastomers, overcoming their limitations and expanding the field of application of soft actuators. The mechanical actuation of hydrogels is a nascent field full of challenges, such as achieving reliable and significant responsiveness. Here we demonstrate that the combination of a physical polymer hydrogel with a dispersed phase consisting of clusters of magnetic particles, results in magnetic hydrogel composites that exhibit high and reversible elongation in response to magnetic stimuli. Our analyses show that this response is strongly dependent on the matrix elasticity, the concentration of magnetic particles, and the particle distribution within the network of polymer nanofibres. Our strategy for the maximization of the response of magnetic hydrogels should be a catalyst for the development of novel applications of composite hydrogels, such as a valve remotely actuated by a magnetic field that we also present here as a proof-of-concept. © 2021 The Author(s).Dr. Mariusz Barczak is acknowledged for help with SEM imaging of iron particles. Ms. Laura Quesada de la Torre is acknowledged for help with design of graphical abstract. This study was supported by project FIS2017-85954-R (Ministerio de Economía, Industria y Competitividad, MINECO, and Agencia Estatal de Investigación, AEI, Spain, cofunded by Fondo Europeo de Desarrollo Regional, FEDER, European Union ). CGV acknowledges financial support by Ministerio de Ciencia, Innovación y Universidades and University of Granada, Spain, for her FPU17/00491 grant. AZ thanks the Russian Science Foundation, project 20-12-00031, for the financial support. LRA thanks the Spanish State Research Agency (Spanish Ministry of Science and Innovation ) through Juan de la Cierva Incorporacion Fellowship ( IJC2018-037951-I ). Funding for open access charge: Universidad de Granada / CBUA

Dynamic and wear study of an extremely bidisperse magnetorheological fluid

Acceso a la versión publicada en Smart Mater. Struct. 24(12) 127001 (http://iopscience.iop.org/0964-1726/24/12/127001)"This is an author-created, un-copyedited version of an article accepted for publication/published in Smart Materials and Structures. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at http://dx.doi.org/10.1088/0964-1726/24/12/127001."In this work the friction and wear properties of five magnetorheologicalfluids (MRFs)with varying compositions are investigated. Considering that many of the proposed applications for these fluids involve lubricated contact between mobile metal –metal or polymer– metal parts, the relationship between MR response and wear behavior appears to be of fundamental importance. One of the fluids(MR#1)contains only the iron microparticles and base oil; the second and third ones(MR#2 and MR#3) contain an anti-wear additive as well. The fourth one(MR#4)is a well known commercial MRF. Finally, MR#5 is stabilized by dispersing the iron particles in a magnetite ferrofluid. The MR response of the latter fluid is better(higher yield stress and post-yield viscosity)than that of the others. More importantly, it remains(and even improves)after the wear test: the pressure applied in the four-ball apparatus produces a compaction of the magnetite layer around the iron microparticles. Additionally, the friction coefficient is larger, which seems paradoxical in principle, but can be explained by considering the stability of MR#5 in comparison to the other four MRs, which appear to undergo partial phase separation during the test. In fact, electron and optical microscope observations confirm a milder wear effect of MR#5, with almost complete absence of scars from the steel test spheres and homogeneous and shallow grooves on them. Comparatively, MR#2, MR#3 and, particularly, MR#1 produce a much more significant wear.MINECO Ramón y Cajal Programme (RYC-2014-16901)MINECO FIS 2013-07666-C3-1-RCEI Biotic BS27.2015Junta de Andalucía, PE2012-FQM-069

Carbon nanomaterials for targeted cancer therapy drugs: a critical review.

Cancer represents one of the main causes of human death in developed countries. Most current therapies, unfortunately, carry a number of side effects, such as toxicity and damage to healthy cells, as well as the risk of resistance and recurrence. Therefore, cancer research is trying to develop therapeutic procedures with minimal negative consequences. The use of nanomaterial-based systems appears to be one of them. In recent years, great progress has been made in the field of possible use of nanomaterials with high potential in biomedical applications. Carbon nanomaterials, thanks to their unique physicochemical properties, are gaining more and more popularity in cancer therapy. They are valued especially for their ability to deliver drugs or small therapeutic molecules to these cells. Through surface functionalization, they can specifically target tumor tissues, increasing the therapeutic potential and significantly reducing the adverse effects of therapy. Their potential future use could, therefore, as vehicles for drug delivery. This review presents the latest findings of research studies using carbon nanomaterials in the treatment of various types of cancer. To carry out this study, different databases such as Web of Science, PubMed, MEDLINE and Google Scholar were employed. The findings of research studies chosen from more than 2000 viewed scientific publications from the last 15 years were compared