A Self-Organized ECM-Mimetic Model Based on an Amphiphilic Multiblock Silk-Elastin-Like co-Recombinamer with a Concomitant Dual Physical Gelation Process

Although significant progress has been made in the area of injectable hydrogels for biomedical applications and model cell niches, further improvements are still needed, especially in terms of mechanical performance, stability, and biomimicry of the native fibrillar architecture found in the extracellular matrix (ECM). This work focuses on the design and production of a silk-elastin-based injectable multiblock corecombinamer that spontaneously forms a stable physical nanofibrillar hydrogel under physiological conditions. That differs from previously reported silk-elastin-like polymers on a major content and predominance of the elastin-like part, as well as a more complex structure and behavior of such a part of the molecule, which is aimed to obtain well-defined hydrogels. Rheological and DSC experiments showed that this system displays a coordinated and concomitant dual gelation mechanism. In a first stage, a rapid, thermally driven gelation of the corecombinamer solution takes place once the system reaches body temperature due to the thermal responsiveness of the elastin-like (EL) parts and the amphiphilic multiblock design of the corecombinamer. A bridged micellar structure is the dominant microscopic feature of this stage, as demonstrated by AFM and TEM. Completion of the initial stage triggers the second, which is comprised of a stabilization, reinforcement, and microstructuring of the gel. FTIR analysis shows that these events involve the formation of β-sheets around the silk motifs. The emergence of such β-sheet structures leads to the spontaneous self-organization of the gel into the final fibrous structure. Despite the absence of biological cues, here we set the basis of the minimal structure that is able to display such a set of physical properties and undergo microscopic transformation from a solution to a fibrous hydrogel. The results point to the potential of this system as a basis for the development of injectable fibrillar biomaterial platforms toward a fully functional, biomimetic, artificial extracellular matrix, and cell niches.Este trabajo forma parte de Proyectos de Investigación financiados por la Comisión Europea a través del Fondo Europeo de Desarrollo Regional (ERDF), por el del MINECO (MAT2013-41723-R, MAT2013- 42473-R, PRI-PIBAR-2011-1403 y MAT2012-38043), la Junta de Castilla y León (VA049A11, VA152A12 y VA155A12) y el Instituto de Salud Carlos III bajo el Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León

How to foster citizens' statistical reasoning : implications for genetic counseling

OBJECTIVES: Our aim is to provide an overview of key research findings from cognitive psychology regarding effective ways of communicating statistical information, and to point out the implications of these findings for genetic testing. METHOD: We review the literature on the presentation of statistical information in diagnostic test results, discuss various representations that invite misunderstandings, and propose alternative representations that foster understanding. RESULTS: Single-event probabilities, conditional probabilities and relative risks are easily misunderstood. Specifying the class of events to which a probability refers and using natural frequency statements improve understanding. CONCLUSIONS: Cognitive psychology has identified simple and effective tools for improving statistical reasoning. They can help to improve the public's understanding of diagnostic test results

A mechanistic linkage between oral lichen planus and autoimmune thyroid disease

ObjectiveTo determine the levels of antithyroid antibodies and thyroid hormones in the sera of patients with oral lichen planus (OLP), and to quantify the expression of thyroid proteins in OLP lesions. Subjects and MethodsVenous blood samples were drawn from 110 patients with OLP who had no history of thyroid disease or levothyroxine supplementation (OLP+/LT4-). A random population sample of 657 healthy subjects was used as the control group. Two additional groups were used as comparators. Immunohistochemical and qPCR analyses were performed on tissue specimens collected from the patients with OLP and thyroid disease and healthy subjects. ResultsNo association was found between the presence of antithyroid antibodies and OLP. More patients in the OLP+/LT4- group showed high levels of thyroid-stimulating hormone and low levels of free thyroxine than were seen in the control group. Thyroid-stimulating hormone receptor was more highly expressed in the OLP lesions of patients with thyroid disease than in the healthy oral mucosa. ConclusionsA significant number of patients with OLP who are not previously diagnosed with thyroid disease have thyroid parameters that are compatible with hypothyroidism. The expression of thyroid-stimulating hormone receptor in OLP lesions suggests that mechanisms related to autoimmune thyroid disease are involved in the aetiology of OLP

Chitin-amyloid synergism and their use as sustainable structural adhesives

| openaire: EC/H2020/788489/EU//BioELCellStructural adhesives are relevant to many engineering applications, especially those requiring load-bearing joints with high lap shear strength. Typical adhesives are synthesized from acrylics, epoxies, or urethanes, which may pose a burden to sustainability and the environment. In nature, the interfacial interactions between chitin and proteins are used for structural purposes and as a bio-cement, resulting in materials with properties unmatched by their man-made counterparts. Herein, we show that related supramolecular interactions can be harnessed to develop high strength green adhesives based on chitin nanocrystals (ChNCs), isolated from shrimp shells, and hen egg white lysozyme (HEWL) used in its monomeric or amyloid forms. Consolidation of the bicomponent suspensions, placed between glass substrates, results in long-range ordered superstructures. The formation of these structures is evaluated by surface energy considerations, followed by scanning electron, atomic force, and polarized microscopies of theconsolidated materials. For 0.8 mg of bio-adhesive (lysozyme, ChNCs or their composites), lap shear loads of over 300 N are reached. Such remarkable adhesion reaches maximum values at protein-to-ChNC ratios below 1 : 4, reflecting the synergy established between the components (ca. 25% higher load compared to ChNCs, the strongest single component). We put the observed adhesive performance in perspective by comparing the lap-shear performance with current research on green supramolecular adhesives using natural biopolymers. The results are discussed in the context of current efforts to standardize the measurement of adhesive strength and bond preparation. The latter is key to formalizing the metrology and materials chemistry of bio-based adhesives. The proposed all-green system is expected to expand current developments in the design of bio-based adhesives.Peer reviewe

Models for heritable skin diseases: correlation of morphological and molecular data

International audienceA number of genodermatoses are characterized by distinct morphological markers which have been and are used for classification and diagnosis as well as for identifying causative gene mutations and pathogenetic pathways. Various types of animal models and organotypic cell cultures have been established to provide further insight into disease mechanisms and treatment. Selected examples are: (i) a spontaneous rat model for dominant epidermolysis bullosa revealing similar variability of anchoring fibril expression as in human patients; (ii) PNPLA1 as a new gene involved in autosomal recessive congenital ichthyosis pathology identified from a Golden Retriever breed spontaneously affected by lamellar ichthyosis; (iii) knockout mice for lipoxygenases expressing differential skin barrier defects and compensatory hyperkeratosis; (iv) a long-term skin-humanized mouse model for transglutaminase 1-deficient lamellar ichthyosis, obviously in some respects advantageous to organotypic cell cultures and successfully having been used for enzyme substitution therapy; (v) Persian cat with classical Ehlers-Danlos syndrome. Investigation of such monogenetic disease models can help to understand causal correlations between pathology and clinical manifestations and provide insights towards developing and evaluating novel causal therapies

TiNi-based thin films in MEMS applications: a review

TiNi thin films have attracted much attention in recent years as intelligent and functional materials because of their unique properties. TiNi thin film based micro-actuators will become the actuator of choice in many aspects in the rapidly growing field of micro-electro-mechanical systems (MEMSs). In this review paper, some critical issues and problems in the development of TiNi thin films are discussed, including preparation and characterization considerations, residual stress and adhesion, frequency improvement, fatigue and stability, modeling of behavior as well as functionally graded or composite thin films. Comparison is made of TiNi SMA micro-actuation with other micro-actuation methods. Different types of TiNi thin film based microdevices, such as microgrippers, microswitches, microvalves and pumps, microsensors, etc. are also described and discussed