A strongly adhesive hemostatic hydrogel for the repair of arterial and heart bleeds.

Uncontrollable bleeding is a major problem in surgical procedures and after major trauma. Existing hemostatic agents poorly control hemorrhaging from traumatic arterial and cardiac wounds because of their weak adhesion to wet and mobile tissues. Here we design a photo-reactive adhesive that mimics the extracellular matrix (ECM) composition. This biomacromolecule-based matrix hydrogel can undergo rapid gelling and fixation to adhere and seal bleeding arteries and cardiac walls after UV light irradiation. These repairs can withstand up to 290 mm Hg blood pressure, significantly higher than blood pressures in most clinical settings (systolic BP 60-160 mm Hg). Most importantly, the hydrogel can stop high-pressure bleeding from pig carotid arteries with 4~ 5 mm-long incision wounds and from pig hearts with 6 mm diameter cardiac penetration holes. Treated pigs survived after hemostatic treatments with this hydrogel, which is well-tolerated and appears to offer significant clinical advantage as a traumatic wound sealant.

Effects of Gamma and Electron Radiation on the Structural Integrity of Organic Molecules and Macromolecular Biomarkers Measured by Microarray Immunoassays and Their Astrobiological Implications.

High-energy ionizing radiation in the form of solar energetic particles and galactic cosmic rays is pervasive on the surface of planetary bodies with thin atmospheres or in space facilities for humans, and it may seriously affect the chemistry and the structure of organic and biological material. We used fluorescent microarray immunoassays to assess how different doses of electron and gamma radiations affect the stability of target compounds such as biological polymers and small molecules (haptens) conjugated to large proteins. The radiation effect was monitored by measuring the loss in the immunoidentification of the target due to an impaired ability of the antibodies for binding their corresponding irradiated and damaged epitopes (the part of the target molecule to which antibodies bind). Exposure to electron radiation alone was more damaging at low doses (1 kGy) than exposure to gamma radiation alone, but this effect was reversed at the highest radiation dose (500 kGy). Differences in the dose-effect immunoidentification patterns suggested that the amount (dose) and not the type of radiation was the main factor for the cumulative damage on the majority of the assayed molecules. Molecules irradiated with both types of radiation showed a response similar to that of the individual treatments at increasing radiation doses, although the pattern obtained with electrons only was the most similar. The calculated radiolysis constant did not show a unique pattern; it rather suggested a different behavior perhaps associated with the unique structure of each molecule. Although not strictly comparable with extraterrestrial conditions because the irradiations were performed under air and at room temperature, our results may contribute to understanding the effects of ionizing radiation on complex molecules and the search for biomarkers through bioaffinity-based systems in planetary exploration.

Effect of ultrasound treatment during osmotic dehydration on bioactive compounds of cranberries.

The aim of the study was to investigate the influence of ultrasound treatment applied in osmotic solution on bioactive compounds, such as vitamin C, polyphenols, anthocyanins and flavonoids content as well as antioxidant activity in cranberries (Vaccinium oxycoccus). Ultrasound treatment was performed at the frequency of 21kHz for 30 and 60min in two osmotic solutions - 61.5% sucrose and 30% sucrose with an addition of 0.1% of steviol glycosides. Before the ultrasound treatment the material was subjected to cutting or blanching. The obtained results indicated that the influence of ultrasound waves on cranberries depends on a type of bioactive component. The ultrasound treated cranberries as well as the ones subjected to cutting or blanching enhanced by ultrasound were characterized mainly by a lower content of bioactive compounds.

Epitaxy of the bound water phase on hydrophilic surfaces of biopolymers as key mechanism of microwave radiation effects on living objects.

The research investigates the mechanism of microwave radiation effects on biological characteristics and structural-dynamic parameters of a sensor bioluminescence system. The research objects are a sterile growth medium (fish meal hydrolisate) and a bacterial culture. It has been established that irradiation causes changes of the growth medium spectral properties within the range of 200-350nm. Changes take place in the intensity and character of luminescence, as well as in relaxation parameters of nuclear magnetic resonance, growth characteristics of the bacterial culture, its cellular morphology and surface topology. The research results enabled us to establish the mechanisms of primary molecular processes that occur when the bacterial culture is exposed to microwave radiation. Transformation of the dynamic-structural state of adsorbed water phases on biopolymer surfaces has been found to be the key factor in the mechanism of microwave effects on living and water-containing objects.

Temporal control of xyloglucan self-assembly into layered structures by radiation-induced degradation.

Partially degalactosylated xyloglucan from tamarind seeds (Deg-XG) is a very appealing biopolymer for the production of in situ gelling systems at physiological temperature. In this work, we observe that the morphology of hydrogels evolves towards high degrees of structural organization with time, yielding to dense stacks of thin membranes within 24h of incubation at 37°C. We also explore the possibility offered by gamma irradiation of controlling the time scale of this phenomenon, the final morphology and mechanical properties of the system. Structural and molecular modifications of Deg-XG with dose are investigated by FTIR, dynamic light scattering (DLS) and rotational viscosimetry. The impact on gelation ability and gel strength is studied by rheological analysis. The morphology evolution is investigated by SEM analysis, and absence of cytotoxicity verified by MTS assay and optical microscopy of neuroblastoma cells.

High-molecular-weight poly(Gly-Val-Gly-Val-Pro) synthesis through microwave irradiation.

In this study, we synthesized a polypeptide from its pentapeptide unit using microwave irradiation. Effective methods for polypeptide synthesis from unit peptides have not been reported. Here, we used a key elastin peptide, H-GlyValGlyValPro-OH (GVGVP), as the monomer peptide. It is difficult to obtain poly(Gly-Val-Gly-Val-Pro) (poly(GVGVP)) from the pentapeptide unit of elastin, GVGVP, via polycondensation. Poly(GVGVP) prepared from genetically recombinant Escherichia coli is a well-known temperature-sensitive polypeptide, and this temperature sensitivity is known as the lower critical solution temperature. When microwave irradiation was performed in the presence of various additives, the pentapeptide (GVGVP) polycondensation reaction proceeded smoothly, resulting in a product with a high molecular weight in a relatively good yield. The reaction conditions, like microwave irradiation, coupling agents, and solvents, were optimized to increase the reaction efficiency. The product exhibited a molecular weight greater than Mr 7000. Further, the product could be synthesized on a gram scale. The synthesized polypeptide exhibited a temperature sensitivity that was similar to that of poly(GVGVP) prepared from genetically recombinant E. coli. Therefore, this technique offers a facile and quick approach to prepare polypeptides in large amounts. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Contribution of synchrotron radiation to photoactivation studies of biomolecular ions in the gas phase.

Photon activation of ions in the visible and ultraviolet range attracts a growing interest, partly for its promising applications in tandem mass spectrometry. However, this task is not trivial, as it requires notably high brilliance photon sources. Hence, most of the work in that field has been performed using lasers. Synchrotron radiation is a source continuously tunable over a wide photon energy range and which possesses the necessary characteristics for ion activation. This review focuses on the array of applications of synchrotron radiation in photon activation of ions ranging from near UV to soft X-rays.

Electron photodetachment dissociation for structural characterization of synthetic and bio-polymer anions.

Tandem mass spectrometry (MS-MS) is a generic term evoking techniques dedicated to structural analysis, detection or quantification of molecules based on dissociation of a precursor ion into fragments. Searching for the most informative fragmentation patterns has led to the development of a vast array of activation modes that offer complementary ion reactivity and dissociation pathways. Collisional activation of ions using atoms, molecules or surface resulting in unimolecular dissociation of activated ions still plays a key role in tandem mass spectrometry. The discovery of electron capture dissociation (ECD) and then the development of other electron-ion or ion/ion reaction methods, constituted a significant breakthrough, especially for structural analysis of large biomolecules. Similarly, photon activation opened promising new frontiers in ion fragmentation owing to the ability of tightly controlled internal energy deposition and easy implementation on commercial instruments. Ion activation by photons includes slow heating methods such as infrared multiple photon dissociation (IRMPD) and black-body infrared radiative dissociation (BIRD) and higher energy methods like ultra-violet photodissociation (UVPD) and electron photo detachment dissociation (EPD). EPD occurs after UV irradiation of multiply negatively charged ions resulting in the formation of oxidized radical anions. The present paper reviews the hypothesis regarding the mechanisms of electron photo-detachment, radical formation and direct or activated dissociation pathways that support the observation of odd and even electron product ions. Finally, the value of EPD as a complementary structural analysis tool is illustrated through selected examples of synthetic polymers, oligonucleotides, polypeptides, lipids, and polysaccharides.

Assembly of Ni(OH)2 nanoparticle films on aqueous surfaces induced by small amounts of toluene, and the study of their unmediated electrocatalytic oxidation toward some small biomolecules.

A simple strategy for the preparation of a Ni(OH)2 nanoparticle film is described. Ni(OH)2 nanoparticles were synthesized in an aqueous solution of Ni2+ and tert-butylamine in the presence of small amounts of toluene, which induced the nanoparticles to assemble a thin film on the aqueous surface. The obtained Ni(OH)2 nanoparticle film was easily transferred onto the electrode surfaces and exhibited stable electrochemical performance. The electrochemical behavior of various small biomolecules, including cysteine, homocysteine, glutathione, histidine, glycine, cystine, methionine, lysine, aspartic acid, glutamic acid, phenylalanine, ascorbic acid, uric acid and dopamine, were studied at the Ni(OH)2 nanoparticle-film-modified electrode. The Ni(OH)2 nanoparticle film exhibits excellent direct, unmediated electrocatalysis toward the oxidation of cysteine, homocysteine and ascorbic acid in a pH 7.4 buffer solution with a low onset potential and a high oxidation signal. This behavior differs from many reports in which small organic molecules are electrocatalyzed indirectly by the Ni(OH)2/NiOOH redox couple in a strongly alkaline solution.

The effective atomic number revisited in the light of modern photon-interaction cross-section databases.

The effective atomic number, Z(eff), has been calculated for fatty acids and cysteine. It is shown that Z(eff) is a useful parameter for low-Z materials at any energy above 1 keV. Absorption edges of medium-Z elements may complicate the energy dependence of Z(eff) below 10 keV. The notion of Z(eff) is perhaps most useful at energies where Compton scattering is dominating, and where Z(eff) is equal to the mean atomic number, Z, over a wide energy range around 1 MeV.

Nanodosimetry, the metrological tool for connecting radiation physics with radiation biology.

It is generally accepted that the early damage to genes or cells by ionising radiation starts with the early damage to segments of the DNA, at least, to the greater part. This damage is the result of the spatial distribution of inelastic interactions of single ionising particles within the DNA or in its neighbourhood and is, in consequence, determined by the stochastics of particle interactions in volumes a few nanometre in size. Due to the latter fact radiation damage strongly depends on radiation quality and cannot be described satisfactorily in detail by macroscopic quantities like absorbed dose or linear energy transfer (LET). It can, however, be described approximately by the probability distribution of ionisation cluster-size formation in nanometric target volumes of liquid water (nanodosimetry). One aim of nanodosimetry is, therefore, to measure the radiation induced frequency distribution of ionisation cluster-size formation in liquid water, as a substitute for sub-cellular material, in volumes which are comparable in size with those of the most probable radio-sensitive volumes of biological systems. After a short description of the main aspects of cluster-size formation by ionising particles, an overview is given about the measuring principles applied in present-day nanodosimetric measurements. Afterwards, physical principles are discussed which can be used to convert ionisation cluster-size distributions measured in gases into those caused by ionising radiation in liquid water. In a final section, the probability distribution of ionisation cluster-size formation in liquid water is discussed from the point of view of damage formation to segments of the DNA.

Light-induced in situ patterning of DNA-tagged biomolecules and nanoparticles.

We present an in situ method for the selective manipulation of DNA-tagged nano-objects such as vesicles or gold colloids in aqueous solution, at neutral pH. The method makes use of the photosensitizer concept found in photodynamic therapy. Here, single-stranded DNA is immobilized onto a surface via the biotin/streptavidin linkage. If the streptavidin is fluorescently labeled, reactive species will be created during laser-induced photobleaching of the label. These reactive species can then completely or partly suppress the DNA hybridization and cause the removal of the streptavidin. The technique thereby enables a dynamic on-off control over surface density of immobilized DNA-tagged nano-objects. Furthermore, combining this in situ manipulation of DNA with prepatterning of single-stranded DNA in the micro and later in the nano range provides a means for the dynamic patterning required for applications in biosensing and nanotechnology.

Molecular change signal-to-noise criteria for interpreting experiments involving exposure of biological systems to weakly interacting electromagnetic fields.

We describe an approach to aiding the design and interpretation of experiments involving biological effects of weakly interacting electromagnetic fields that range from steady (dc) to microwave frequencies. We propose that if known biophysical mechanisms cannot account for an inferred, underlying molecular change signal-to-noise ratio, (S/N)gen, of a observed result, then there are two interpretation choices: (1) there is an unknown biophysical mechanism with stronger coupling between the field exposure and the ongoing biochemical process, or (2) the experiment is responding to something other than the field exposure. Our approach is based on classical detection theory, the recognition that weakly interacting fields cannot break chemical bonds, and the consequence that such fields can only alter rates of ongoing, metabolically driven biochemical reactions, and transport processes. The approach includes both fundamental chemical noise (molecular shot noise) and other sources of competing chemical change, to be compared quantitatively to the field induced change for the basic case that the field alters a single step in a biochemical network. Consistent with pharmacology and toxicology, we estimate the molecular dose (mass associated with field induced molecular change per mass tissue) resulting from illustrative low frequency field exposures for the biophysical mechanism of voltage gated channels. For perspective, we then consider electric field-mediated delivery of small molecules across human skin and into individual cells. Specifically, we consider the examples of iontophoretic and electroporative delivery of fentanyl through skin and electroporative delivery of bleomycin into individual cells. The total delivered amount corresponds to a molecular change signal and the delivery variability corresponds to generalized chemical noise. Viewed broadly, biological effects due to nonionizing fields may include animal navigation, medical applications, and environmental hazards. Understanding necessary conditions for such effects can be based on a unified approach: quantitative comparison of the estimated chemical change due to a particular electromagnetic field exposure to that due to competing influences, with both estimates based on a biophysical mechanism model within the context of a model of a biological system.

Luminescent radio frequency radiation dosimetry.

Thermoluminescent dosimetry has been the industry standard for ionizing radiation dosimetry because it is inexpensive, sensitive, and accurate. No such system exists for radio frequency radiation. This paper describes the state of the art of efforts toward developing such a system. Thermochemiluminescent (TCL) dosimetry, first reported in 1991, is a first step toward achieving this goal. However, it has had problems in the production of TCL materials and in conversion of the luminescent signal into specific absorption rate (SAR). The former problem has been solved by the development of a genetically engineered Escherichia coli bacterium (JM 109/plC20RNR1.1), described herein, that produces the TCL material in a fermentation process. The latter problem stems from the difficulty in determining the structure of the currently best TCL material diazoluminomelanin. A theoretical approach for the solution of this problem has been achieved by combining equations for delayed fluorescence, temperature determination by TCL, and the free energy equation for equilibrium reactions. It has led to an explanation for the stable display of steady-state energy disposition, illustrated by TCL, in phantoms without the expected disruption by thermal conduction or convection, at frequencies ranging from 2.06 GHz to 35 GHz.

[New aspects of of the effects of low intensity radiation]. / Novye aspekty zakonomernostei deistviia nizkointensivnogo oblucheniia v malykh dozakh.

In paper the new aspects of action regularity of ionizing radiation of low intensity on the biophysical and biochemical characteristics of bio-objects and populations are considered. From the point of view of breaking the connection between occurrence of damages and work of systems of restoration at low intensity irradiation, are described the dose dependence of different types--from threshold up to extreme and a plateau curve, differing among themselves only by a parity of these processes. The features of action of low intensity irradiation on bio-objects and populations--change of structure of a population, sensitivity to action of external stimulus, force of connections between the elements of regulatory systems--allow to consider the low intensity irradiation as the factor capable to cause unpredictable transition of quasistationary systems in new status.

Radiation crosslinking of a bacterial medium-chain-length poly(hydroxyalkanoate) elastomer from tallow.

Pseudomonas resinovorans produces a medium-chain-length poly(hydroxyalkanoate) (MCL-PHA) copolymer when grown on tallow (PHA-tal). This polymer had a repeat unit composition ranging from C4 to C14 with some mono-unsaturation in the C12 and C14 alkyl side chains. Thermal analysis indicated that the polymer was semi-crystalline with a melting temperature (T(m)) of 43.5 +/- 0.2 degrees C and a glass transition temperature (Tg) of -43.4 +/- 2.0 degrees C. The presence of unsaturated side chains allowed crosslinking by gamma-irradiation. Irradiated polymer films had decreased solubility in organic solvents that indicated an increase in the crosslinking density within the film matrix. The addition of linseed oil to the gamma-irradiated film matrix enhanced polymer recovery while minimizing chain scission. Linseed oil also caused a decrease in the enthalpy of fusion (delta Hm) of the films (by an average of 60%) as well as enhanced mineralization. The effects of crosslinking on the mechanical properties and biodegradability of the polymer were determined. Radiation had no effect on the storage modulus (E') of the polymer. However, radiation doses of 25 and 50 kGy did increase the Young modulus of the polymer by 129 and 114%, and the tensile strength of the polymer by 76 and 35%, respectively. Finally, the formation of a higher crosslink density within the polymer matrix decreased the biodegradability of the PHA films.