539 research outputs found
Optical properties of in-vitro biomineralised silica
This is the final version of the article. Available from the publisher via the DOI in this record.Silicon is the second most common element on the Earth's crust and its oxide (SiO(2)) the most abundant mineral. Silica and silicates are widely used in medicine and industry as well as in micro- and nano-optics and electronics. However, the fabrication of glass fibres and components requires high temperature and non-physiological conditions, in contrast to biosilica structures in animals and plants. Here, we show for the first time the use of recombinant silicatein-α, the most abundant subunit of sponge proteins catalyzing biosilicification reactions, to direct the formation of optical waveguides in-vitro through soft microlithography. The artificial biosilica fibres mimic the natural sponge spicules, exhibiting refractive index values suitable for confinement of light within waveguides, with optical losses in the range of 5-10 cm(-1), suitable for application in lab-on-chips systems. This method extends biosilicification to the controlled fabrication of optical components by physiological processing conditions, hardly addressed by conventional technologies.This work is financially supported by the BIO-LITHO European project (6th Framework
Program, NMP). W.E.G. Muller is holder of an ERC Advanced Research Grant
Characteristics of clinical-pharmacological recommendations in psychiatry.
OBJECTIVE
Psychiatric patients in general, and elderly psychiatric patients in particular, are at risk of adverse drug reactions due to comorbidities and inappropriate polypharmacy. Interdisciplinary and clinical-pharmacologist-led medication reviews may contribute to medication safety in the field of psychiatry. In this study, we reported the frequency and characteristics of clinical-pharmacological recommendations in psychiatry, with a particular focus on geriatric psychiatry.
METHOD
A clinical pharmacologist, in collaboration with the attending psychiatrists and a consulting neurologist, conducted interdisciplinary medication reviews in a general psychiatric ward with a geropsychiatric focus at a university hospital over a 25-week period. All clinical and pharmacological recommendations were recorded and evaluated.
RESULTS
A total of 316 recommendations were made during 374 medication reviews. Indications/contraindications of drugs were the most frequently discussed topics (59/316; 18.7 %), followed by dose reductions (37/316; 11.7 %), and temporary or permanent discontinuation of medications (36/316; 11.4 %). The most frequent recommendations for dose reduction involvedbenzodiazepines (9/37; 24.3 %). An unclear or absent indication was the most common reason for recommending temporary or permanent discontinuation of the medication (6/36; 16.7 %).
CONCLUSION
Interdisciplinary clinical pharmacologist-led medication reviews represented a valuable contribution to medication management in psychiatric patients, particularly the elderly ones
Evagination of Cells Controls Bio-Silica Formation and Maturation during Spicule Formation in Sponges
The enzymatic-silicatein mediated formation of the skeletal elements, the spicules of siliceous sponges starts intracellularly and is completed extracellularly. With Suberites domuncula we show that the axial growth of the spicules proceeds in three phases: (I) formation of an axial canal; (II) evagination of a cell process into the axial canal, and (III) assembly of the axial filament composed of silicatein. During these phases the core part of the spicule is synthesized. Silicatein and its substrate silicate are stored in silicasomes, found both inside and outside of the cellular extension within the axial canal, as well as all around the spicule. The membranes of the silicasomes are interspersed by pores of ≈2 nm that are likely associated with aquaporin channels which are implicated in the hardening of the initial bio-silica products formed by silicatein. We can summarize the sequence of events that govern spicule formation as follows: differential genetic readout (of silicatein) → fractal association of the silicateins → evagination of cells by hydro-mechanical forces into the axial canal → and finally processive bio-silica polycondensation around the axial canal. We termed this process, occurring sequentially or in parallel, bio-inorganic self-organization
The group law on the tropical Hesse pencil
We show that the addition of points on the tropical Hesse curve can be
realized via the intersection with a tropical line. Then the addition formula
for the tropical Hesse curve is reduced from those for the level-three theta
functions through the ultradiscretization procedure. A tropical analogue of the
Hessian group, the group of linear automorphisms acting on the Hesse pencil, is
also investigated; it is shown that the dihedral group of degree three is the
group of linear automorphisms acting on the tropical Hesse pencil.Comment: 17 pages, 1 figure, submitted to Special Issue of the Journal
Mathematics and Computers in Simulation on "Nonlinear Waves: Computation and
Theory
Sponge spicules as blueprints for the biofabrication of inorganic–organic composites and biomaterials
While most forms of multicellular life have developed a calcium-based skeleton, a few specialized organisms complement their body plan with silica. However, of all recent animals, only sponges (phylum Porifera) are able to polymerize silica enzymatically mediated in order to generate massive siliceous skeletal elements (spicules) during a unique reaction, at ambient temperature and pressure. During this biomineralization process (i.e., biosilicification) hydrated, amorphous silica is deposited within highly specialized sponge cells, ultimately resulting in structures that range in size from micrometers to meters. Spicules lend structural stability to the sponge body, deter predators, and transmit light similar to optic fibers. This peculiar phenomenon has been comprehensively studied in recent years and in several approaches, the molecular background was explored to create tools that might be employed for novel bioinspired biotechnological and biomedical applications. Thus, it was discovered that spiculogenesis is mediated by the enzyme silicatein and starts intracellularly. The resulting silica nanoparticles fuse and subsequently form concentric lamellar layers around a central protein filament, consisting of silicatein and the scaffold protein silintaphin-1. Once the growing spicule is extruded into the extracellular space, it obtains final size and shape. Again, this process is mediated by silicatein and silintaphin-1, in combination with other molecules such as galectin and collagen. The molecular toolbox generated so far allows the fabrication of novel micro- and nanostructured composites, contributing to the economical and sustainable synthesis of biomaterials with unique characteristics. In this context, first bioinspired approaches implement recombinant silicatein and silintaphin-1 for applications in the field of biomedicine (biosilica-mediated regeneration of tooth and bone defects) or micro-optics (in vitro synthesis of light waveguides) with promising results
The role of thyroid hormone nuclear receptors in the heart: evidence from pharmacological approaches
This review evaluates the hypothesis that the cardiac effects of amiodarone can be explained—at least partly—by the induction of a local ‘hypothyroid-like condition’ in the heart. Evidence supporting the hypothesis comprises the observation that amiodarone exerts an inhibitory effect on the binding of T3 to thyroid hormone receptors (TR) alpha-1 and beta-1 in vitro, and on the expression of particular T3-dependent genes in vivo. In the heart, amiodarone decreases heart rate and alpha myosin heavy chain expression (mediated via TR alpha-1), and increases sarcoplasmic reticulum calcium-activated ATPase and beta myosin heavy chain expression (mediated via TR beta-1). Recent data show a significant similarity in expression profiles of 8,435 genes in the heart of hypothyroid and amiodarone-treated animals, although similarities do not always exist in transcripts of ion channel genes. Induction of a hypothyroid cardiac phenotype by amiodarone may be advantageous by decreasing energy demands and increasing energy availability
Antimicrobial Peptides and Skin: A Paradigm of Translational Medicine
Antimicrobial peptides (AMPs) are small, cationic, amphiphilic peptides with broad-spectrum microbicidal activity against both bacteria and fungi. In mammals, AMPs form the first line of host defense against infections and generally play an important role as effector agents of the innate immune system. The AMP era was born more than 6 decades ago when the first cationic cyclic peptide antibiotics, namely polymyxins and tyrothricin, found their way into clinical use. Due to the good clinical experience in the treatment of, for example, infections of mucus membranes as well as the subsequent understanding of mode of action, AMPs are now considered for treatment of inflammatory skin diseases and for improving healing of infected wounds. Based on the preclinical findings, including pathobiochemistry and molecular medicine, targeted therapy strategies are developed and first results indicate that AMPs influence processes of diseased skin. Importantly, in contrast to other antibiotics, AMPs do not seem to propagate the development of antibiotic-resistant micro-organisms. Therefore, AMPs should be tested in clinical trials for their efficacy and tolerability in inflammatory skin diseases and chronic wounds. Apart from possible fields of application, these peptides appear suited as an example of the paradigm of translational medicine for skin diseases which is today seen as a `two-way road' - from bench to bedside and backwards from bedside to bench. Copyright (c) 2012 S. Karger AG, Base
CAR-T cell. the long and winding road to solid tumors
Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles
Correlation of cell growth and heterologous protein production by Saccharomyces cerevisiae
With the increasing demand for biopharmaceutical proteins and industrial enzymes, it is necessary to optimize the production by microbial fermentation or cell cultures. Yeasts are well established for the production of a wide range of recombinant proteins, but there are also some limitations; e.g., metabolic and cellular stresses have a strong impact on recombinant protein production. In this work, we investigated the effect of the specific growth rate on the production of two different recombinant proteins. Our results show that human insulin precursor is produced in a growth-associated manner, whereas alpha-amylase tends to have a higher yield on substrate at low specific growth rates. Based on transcriptional analysis, we found that the difference in the production of the two proteins as function of the specific growth rate is mainly due to differences in endoplasmic reticulum processing, protein turnover, cell cycle, and global stress response. We also found that there is a shift at a specific growth rate of 0.1 h(-1) that influences protein production. Thus, for lower specific growth rates, the alpha-amylase and insulin precursor-producing strains present similar cell responses and phenotypes, whereas for higher specific growth rates, the two strains respond differently to changes in the specific growth rate
Supramolecular binding and separation of hydrocarbons within a functionalised porous metal-organic framework
Supramolecular interactions are fundamental to host-guest binding in chemical and biological processes. Direct visualisation of such supramolecular interactions within host-guest systems is extremely challenging but crucial for the understanding of their function. We report a comprehensive study combining neutron scattering with synchrotron X-ray and neutron diffraction, coupled with computational modelling, to define the detailed binding at a molecular level of acetylene, ethylene and ethane within the porous host NOTT-300. This study reveals the simultaneous and cooperative hydrogen-bonding, π···π stacking interactions and inter-molecular dipole interactions in the binding of acetylene and ethylene to give up to twelve individual weak supramolecular interactions aligned within the host to form an optimal geometry for intelligent, selective binding of hydrocarbons. We also report, for the first time, the cooperative binding of a mixture of acetylene and ethylene within the porous host together with the corresponding breakthrough experiment and analysis of mixed gas adsorption isotherms
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