Monitoring of optical properties of tumors during laser plasmon photothermal therapy.

We studied grafted tumors obtained by subcutaneous implantation of kidney cancer cells into male white rats. Gold nanorods with a plasmon resonance of about 800 nm were injected intratumorally for photothermal heating. Experimental irradiation of tumors was carried out percutaneously using a near-infrared diode laser. Changes in the optical properties of the studied tissues in the spectral range 350-2200 nm under plasmonic photothermal therapy (PPT) were studied. Analysis of the observed changes in the absorption bands of water and hemoglobin made it possible to estimate the depth of thermal damage to the tumor. A significant decrease in absorption peaks was observed in the spectrum of the upper peripheral part and especially the tumor capsule. The obtained changes in the optical properties of tissues under laser irradiation can be used to optimize laboratory and clinical PPT procedures.

Darwin, Haeckel, and the "Mikluskan gas organ theory".

A previously unknown reference to the Russian ethnologist, biologist, and traveler Nikolai N. Miklucho-Maclay (1846-1888) was discovered in correspondence between Charles Darwin (1809-1882) and Ernst Haeckel (1834-1919). This reference has remained unknown to science, even to Miklucho-Maclay's biographers, probably because Darwin used the Russian nickname "Mikluska" when alluding to this young scientist. Here, we briefly outline the story behind the short discussion between Darwin and his German counterpart Haeckel, and highlight its importance for the history of science. Miklucho-Maclay's discovery of a putative swim bladder anlage in sharks, published in 1867, was discussed in four letters between the great biologists. Whereas, Haeckel showed enthusiasm for the finding because it supported (his view on) evolutionary theory, Darwin was less interested, which highlights the conceptual differences between the two authorities. We discuss the scientific treatment of Miklucho-Maclay's observation in the literature and discuss the homology, origin, and destiny of gas organs-swim bladders and lungs-in vertebrate evolution, from an ontogenetic point of view. We show that the conclusions reached by Miklucho-Maclay and Haeckel were rather exaggerated, although they gave rise to fundamental insights, and we illustrate how tree-thinking may lead to differences in the conceptualization of evolutionary change.

Selection of Aptamers for Use as Molecular Probes in AFM Detection of Proteins.

Currently, there is great interest in the development of highly sensitive bioanalytical systems for diagnosing diseases at an early stage, when pathological biomarkers are present in biological fluids at low concentrations and there are no clinical manifestations. A promising direction is the use of molecular detectors-highly sensitive devices that detect signals from single biomacromolecules. A typical detector in this class is the atomic force microscope (AFM). The high sensitivity of an AFM-based bioanalysis system is determined by the size of the sensing element of an atomic force microscope-the cantilever-the radius of the curvature of which is comparable to that of a biomolecule. Biospecific molecular probe-target interactions are used to ensure detection system specificity. Antibodies, aptamers, synthetic antibodies, and peptides can be used as molecular probes. This study has demonstrated the possibility of using aptamers as molecular probes for AFM-based detection of the ovarian cancer biomarker CA125. Antigen detection in a nanomolar solution was carried out using AFM chips with immobilized aptamers, commercially available or synthesized based on sequences from open sources. Both aptamer types can be used for antigen detection, but the availability of sequence information enables additional modeling of the aptamer structure with allowance for modifications necessary for immobilization of the aptamer on an AFM chip surface. Information on the structure and oligomeric composition of aptamers in the solution was acquired by combining small-angle X-ray scattering and molecular modeling. Modeling enabled pre-selection, before the experimental stage, of aptamers for use as surface-immobilized molecular probes.

Nucleoid-Associated Proteins HU and IHF: Oligomerization in Solution and Hydrodynamic Properties.

Structure and function of bacterial nucleoid is controlled by the nucleoid-associated proteins (NAP). In any phase of growth, various NAPs, acting sequentially, condense nucleoid and facilitate formation of its transcriptionally active structure. However, in the late stationary phase, only one of the NAPs, Dps protein, is strongly expressed, and DNA-protein crystals are formed that transform nucleoid into a static, transcriptionally inactive structure, effectively protected from the external influences. Discovery of crystal structures in living cells and association of this phenomenon with the bacterial resistance to antibiotics has aroused great interest in studying this phenomenon. The aim of this work is to obtain and compare structures of two related NAPs (HU and IHF), since they are the ones that accumulate in the cell at the late stationary stage of growth, which precedes formation of the protective DNA-Dps crystalline complex. For structural studies, two complementary methods were used in the work: small-angle X-ray scattering (SAXS) as the main method for studying structure of proteins in solution, and dynamic light scattering as a complementary one. To interpret the SAXS data, various approaches and computer programs were used (in particular, the evaluation of structural invariants, rigid body modeling and equilibrium mixture analysis in terms of the volume fractions of its components were applied), which made it possible to determine macromolecular characteristics and obtain reliable 3D structural models of various oligomeric forms of HU and IHF proteins with ~2 nm resolution typical for SAXS. It was shown that these proteins oligomerize in solution to varying degrees, and IHF is characterized by the presence of large oligomers consisting of initial dimers arranged in a chain. An analysis of the experimental and published data made it possible to hypothesize that just before the Dps expression, it is IHF that forms toroidal structures previously observed in vivo and prepares the platform for formation of DNA-Dps crystals. The results obtained are necessary for further investigation of the phenomenon of biocrystal formation in bacterial cells and finding ways to overcome resistance of various pathogens to external conditions.

Electrokinetic and Electroconvective Effects in Ternary Electrolyte Near Ion-Selective Microsphere.

The paper presents theoretical and experimental investigations of the behavior of an electrolyte solution with three types of ions near an ion-selective microparticle with electrokinetically and pressure-driven flow. A special experimental cell has been developed for the investigations. An anion-selective spherical particle composed of ion-exchange resin is fixed in the center of the cell. An enriched region with a high salt concentration appears at the anode side of the particle when an electric field is turned on, according to the nonequilibrium electrosmosis behavior. A similar region exists near a flat anion-selective membrane. However, the enriched region near the particle produces a concentration jet that spreads downstream akin to a wake behind an axisymmetrical body. The fluorescent cations of Rhodamine-6G dye are chosen as the third species in the experiments. The ions of Rhodamine-6G have a 10-fold lower diffusion coefficient than the ions of potassium while bearing the same valency. This paper shows that the concentration jet behavior is described accurately enough with the mathematical model of a far axisymmetric wake behind a body in a fluid flow. The third species also forms an enriched jet, but its distribution turns out to be more complex. The concentration of the third species increases in the jet with an increase in pressure gradient. The pressure-driven flow stabilizes the jet, yet electroconvection has been observed near the microparticle for sufficiently strong electric fields. The electrokinetic instability and the electroconvection partially destroy the concentration jet of salt and the third species. The conducted experiments show good qualitative agreement with the numerical simulations. The presented results could be used in future for implementing microdevices based on membrane technology for solving problems of detection and preconcentration, and thus simplifying chemical and medical analyses utilizing the superconcentration phenomenon. Such devices are called membrane sensors, and are actively being studied.

Cytotoxicity, Dermal Toxicity, and In Vivo Antifungal Effect of Griseofulvin-Loaded Vaterite Carriers Administered via Sonophoresis.

The search for novel therapeutic strategies to treat fungal diseases is of special importance nowadays given the emerging threat of drug resistance. Various particulate delivery systems are extensively being developing to enhance bioavailability, site-specific penetration, and therapeutic efficacy of antimycotics. Recently, we have designed a novel topical formulation for griseofulvin (Gf) drug, which is currently commercially available in oral dosage forms due to its limited skin permeation. The proposed formulation is based on vaterite carriers that enabled effective incorporation and ultrasonically assisted delivery of Gf to hair follicles improving its dermal bioavailability. Here, we evaluated the effect of ultrasound on the viability of murine fibroblasts co-incubated with either Gf-loaded carriers or a free form of Gf and investigated the influence of both forms on different subpopulations of murine blood cells. The study revealed no sufficient cyto- and hemotoxicity of the carriers, even at the highest investigated concentrations. We also conducted a series of in vivo experiments to assess their multi-dose dermal toxicity and antifungal efficiency. Visual and histological examinations of the skin in healthy rabbits showed no obvious adverse effects after US-assisted application of the Gf-loaded carriers. At the same time, investigation of therapeutic efficiency for the designed formulation in comparison with free Gf and isoconazole drugs in a guinea pig model of trichophytosis revealed that the vaterite-based form of Gf provided the most rapid and effective cure of infected animals together with the reduction in therapeutic procedure number. These findings pave the way to improving antifungal therapy of superficial mycoses and justifying further preclinical studies.

Template-Directed Polymerization Strategy for Producing rGO/UHMWPE Composite Aerogels with Tunable Properties.

In this paper, we suggest a previously unknown template-directed polymerization strategy for producing graphene/polymer aerogels with elevated mechanical properties, preservation of the nanoscale pore structure, an extraordinary crystallite structure, as well as tunable electrical and hydrophobic properties. The suggested approach is studied using the reduced graphene oxide (rGO)/ultrahigh molecular weight polyethylene (UHMWPE) system as an example. We also develop a novel method of ethylene polymerization with formation of UHMWPE directly on the surface of rGO sheets prestructured as the aerogel template. At a UHMWPE content smaller than 20 wt %, composite materials demonstrate completely reversible deformation and good conductivity. An ultrahigh polymer content (more than 80 wt %) results in materials with pronounced plasticity, improved hydrophobic properties, and a Young's modulus that is more than 200 times larger than that of pure rGO aerogel. Variation of the polymer content makes it possible to tune the electro-conductive properties of the aerogel in the range from 4.8 × 10-6 to 4.9 × 10-1 S/m and adjust its hydrophobic properties. The developed approach would make it possible to create composite materials with highly developed nanostructural morphology and advanced properties controlled by the thickness of the polymer layer on the surface of graphene sheets.

Immersion optical clearing of adipose tissue in rats: ex vivo and in vivo studies.

Optical clearing (OC) of adipose tissue has not been studied enough, although it can be promising in medical applications, including surgery and cosmetology, for example, to visualize blood vessels or increase the permeability of tissues to laser beams. The main objective of this work is to develop technology for OC of abdominal adipose tissue in vivo using hyperosmotic optical clearing agents (OCAs). The maximum OC effect (77%) was observed for ex vivo rat adipose tissue samples exposed to OCA on fructose basis for 90 minutes. For in vivo studies, the maximum effect of OC (65%) was observed when using OCA based on diatrizoic acid and dimethylsulfoxide for 120 minutes. Histological analysis showed that in vivo application of OCAs may induce a limited local necrosis of fat cells. The efficiency of OC correlated with local tissue damage through cell necrosis due to accompanied cell lipolysis.

The biogenetic law and the Gastraea theory: From Ernst Haeckel's discoveries to contemporary views.

More than 150 years ago, in 1866, Ernst Haeckel published a book in two volumes called Generelle Morphologie der Organismen (General Morphology of Organisms) in the first volume of which he formulated his biogenetic law, famously stating that ontogeny recapitulates phylogeny. Here, we describe Haeckel's original idea as first formulated in the Generelle Morphologie der Organismen and later further developed in other publications until the present situation in which molecular data are used to test the "hourglass model," which can be seen as a modern version of the biogenetic law. We also tell the story about his discovery, while traveling in Norway, of an unknown organism, Magosphaera planula, that was important in that it helped to precipitate his ideas into what was to become the Gastraea theory. We also follow further development and reformulations of the Gastraea theory by other scientists, notably the Russian school. Elias Metchnikoff developed the Phagocytella hypothesis for the origin of metazoans based on studies of a colonial flagellate. Alexey Zakhvatin focused on deducing the ancestral life cycle and the cell types of the last common ancestor of all metazoans, and Kirill V. Mikhailov recently pursued this line of research further.

Heteroleptic Crown-Substituted Tris(phthalocyaninates) as Dynamic Supramolecular Scaffolds with Switchable Rotational States and Tunable Magnetic Properties.

Herein we report single-crystal X-ray diffraction characterization and complementary solution studies of supramolecular interaction between potassium salts and heteroleptic homo- and heteronuclear triple-decker crown phthalocyaninates [(15C5)4Pc]M*[(15C5)4Pc]M(Pc) or [M*,M], where M* and M = Y and/or Tb. Our results evidence that, in contrast to the previously studied crown-substituted phthalocyanines, the interaction of K+ cations with [M*,M] does not induce their intermolecular aggregation. Instead, the cations reversibly intercalate between the crown-substituted phthalocyanine ligands, resulting in switching of the coordination polyhedron of the metal center M* from square-antiprismatic to square-prismatic. In the case of terbium(III) complexes, such a switching alters their magnetic properties, which can be read-out by 1H NMR spectroscopy. For [Tb*,Y], such a switching causes an almost 25% increase in the axial component of the magnetic susceptibility tensor. Even though the polyhedron of the paramagnetic center in [Y*,Tb] is not switched, minor structural perturbations associated with the overall reorganization of the receptor also cause smaller, but nevertheless appreciable, growth of the axial anisotropy. The observed effects render the studied complexes as molecular switches with tunable magnetic properties.

Microphase separation of stimuli-responsive interpenetrating network microgels investigated by scattering methods.

Polymer stimuli-responsive microgels find their use in various applications. The knowledge of its internal structure is of importance for further improvement and expanding the scope. Interpenetrating network (IPN) microgels may possess a remarkable feature of strongly non-uniform inner architecture, even microphase separation, in conditions of a selective solvent. In this research, we, for the first time, use a combination of static light scattering (SLS) and small-angle X-ray scattering (SAXS) techniques to collect the structure factors of aqueous dispersions of poly(N-isopropylacrylamide)-polyacrylic acid IPN microgels on the broad scale ofqvalues. We study the influence of solvent quality on microgel conformations and show that in a selective solvent, such a system undergoes microphase separation: the sub-network in a poor solvent conditions forms dense small aggregates inside the large swollen sub-network in a good solvent. We propose the microstructured sphere model for the IPN microgel structure factor interpretation and perform additional analysis and verification through coarse-grained molecular dynamics computer simulations.

Tobacco use and exposure to second-hand smoke among high school students in Ernakulum district, Kerala: A cross-sectional study.

Objectives: Tobacco use and exposure to second-hand smoke (SHS) in the home setting are major health hazards for adolescents. The objectives of this study were to estimate tobacco use and exposure to SHS among high school students in Ernakulam district of Kerala, India, and to investigate associated factors. Study design: Cross-sectional study. Methods: A school-based cross-sectional study was carried out in 25 randomly selected high schools from 210 schools in the Ernakulam educational district of Kerala, India. The minimum calculated sample size for ever-use of tobacco and SHS exposure was determined to be 2500, with 95% confidence interval (CI) and 10% relative precision. Data were collected using a semi-structured, pre-tested questionnaire from 2585 high school students. Data analyses were performed using SPSS version 20. Results: The ever-use of tobacco was reported to be 3.9% (95% CI 3.16 to 4.54) and the mean age of the participants was 13.97 ± 0.77 years. One-fifth of participants had tried a tobacco product before the age of 10 years. SHS exposure at home was reported by one in every 5 respondents (20.3%). Male gender (adjusted odds ratio [aOR] 8.79; 95% CI 3.16, 24.53), presence of a family member who smokes within the home (aOR 4.28; 95% CI 2.58, 7.12), lack of awareness about the harmful effects of SHS exposure (aOR 2.47; 95% CI 1.41, 5.18) and having seen an advertisement or promotion at point of sale (aOR 2.16; 95% CI 1.29, 3.60) were found to be independent predictors for tobacco use.Participants with respiratory infections were three times more likely to have experienced SHS exposure at home (aOR 2.87; 95% CI 2.21, 3.74), there was an 86% protective effect of SHS exposure for participants with a father in a professional occupation compared with unskilled profession (aOR 0.14; 95% CI 0.02, 0.67; p < 0.15) and participants with ever-use of tobacco were two times more likely to have experienced SHS exposure at home (aOR 1.63; 95% CI 3.13, 8.98). Conclusions: SHS exposure in the home environment continues to be high. Urgent innovative measures are necessary for the implementation of tobacco smoke-free homes and to reduce tobacco use in this vulnerable population. Further studies are necessary to determine ways to reduce smoking within homes and to increase population awareness.

Cation-Induced Dimerization of Heteroleptic Crown-Substituted Trisphthalocyaninates as Revealed by X-ray Diffraction and NMR Spectroscopy.

We report comprehensive X-ray diffraction and NMR studies of potassium-induced dimerization of heteroleptic triple-decker crown-phthalocyaninates [(15C5)4Pc]M(Pc)M(Pc) (1M, M = Y and Tb). Characterization of the crystalline dimer 2(1Y)·4KBPh4·12CH3CN·10CHCl3 gave the first structural evidence of the formation of a six-decker structure with four rare earth metal ions perfectly aligned near the symmetry axis. NMR studies of soluble supramolecular dimers 2(1M)·4KOAc provided a spectral-structural model that allowed us to assign the NMR spectra of related complexes with paramagnetic lanthanides and to further evaluate their structure and long-range interaction between the Ln(III) centers in multinuclear tetrapyrrolic complexes. The obtained results are promising for elaboration of new supramolecular magnetic materials.

Ernst Haeckel, Nikolai Miklucho-Maclay and the racial controversy over the Papuans.

BACKGROUND: The "German Darwin" Ernst Haeckel (1834-1919) was a key figure during the first "Darwinian revolution", a time when the foundations of the modern evolutionary theory were laid. It was Haeckel, who crucially contributed to the visualization of the Darwinian theory by designing "genealogical-trees" illustrating the evolution of various species, including humans. Although the idea of explaining human evolution by natural selection belongs to Darwin, Haeckel was the first who attempted to create a new exact anthropology based on the Darwinian method. DISCUSSION: Trying to immediately reconstruct human evolution proceeding from the description of modern populations led Haeckel to the views which, from the contemporary perspective, are definitely racist. Haeckel created racial anthropology intending to prove human origins from a lower organism, but without the intention of establishing a discriminatory racial praxis. Although hierarchical in its outcome, the Haeckelian method did not presuppose the necessity of a racial hierarchy of currently living humans. It is crucial to grasp in what sense Haeckel's theoretical explorations in human evolution were racist, and in what sense they were not. Our argument flows as follows. One of Haeckel's pupils was the Russian ethnographer, anthropologist and zoologist Nikolai Nikolajewitsch Miklucho-Maclay (1846-1888). Maclay and Haeckel worked closely together for several years; they traveled jointly and Maclay had enough time to learn the major methodological principles of Haeckel's research. Yet in contrast to Haeckel, Maclay is regarded as one of the first scientific anti-racists, who came to anti-racist views using empirical field studies in Papua-New Guinea. CONCLUSIONS: We claim that while conducting these studies Maclay applied scientific principles to a significant extent acquired from Haeckel. The paper contributes to the view that Haeckel's theoretical racism did not follow the Darwinian method he used.

Integrated effects of fractional laser microablation and sonophoresis on skin immersion optical clearing in vivo.

This study is aimed to find an approach for effective skin optical clearing in vivo using polyethylene glycol 300 (PEG-300) as an optical clearing agent in combination with physical enhancers: fractional laser microablation (FLMA) and/or low-frequency sonophoresis. In this study albino outbred rats were used. Light attenuation coefficient and optical clearing potential (OCP) of these approaches were evaluated in upper (from ~70 to ~200 µm) and middle (from ~200 to ~400 µm) dermis separately using optical coherence tomography. In 30 minutes, OCP of sonophoresis in combination with FLMA and PEG-300 in the upper dermis was the maximal (2.3 ± 0.4) in comparison with other treatments in this time point. The most effective approach for optical clearing of middle dermis was PEG-300 and sonophoresis; but the maximal value of OCP (1.6 ± 0.1) was achieved only in 90 minutes.

Continuous phase-shifting holography.

A scanning full-field interferometer is a key device in the optical scheme of digital hyperspectral hologram registration. Behind the theory of hyperspectral holography is Fourier transform spectroscopy, wherein the set of spectrally resolved complex amplitudes of the object's hyperspectral field is obtained via the Fourier transform of a series of interferograms registered in incoherent radiation. Several established approaches in digital holography, based on discrete phase-shifting techniques as well as continuous phase modulation of the reference signal by a scanning mirror, are special cases of Fourier transform spectroscopy, where a coherent light source is used for hologram registration. The proposed algorithm was found to apply to processing holograms registered by various phase-shifting techniques and can give a greater signal-to-noise ratio.

Formation of high-intensity axially symmetric and ribbon beams of low-energy metal ions.

Low-energy metal ion beams are of considerable interest in developing a high-intensity implantation method that modifies the elemental composition, microstructure, and properties of various materials at depths many times exceeding the projective range of ions. This study presents the results of experiments on plasma-immersion formation followed by spherical and cylindrical ballistic focusing of aluminum and titanium ion beams. The features of the formation, transport, and ballistic focusing of an ion beam are discussed based on the parameters of the vacuum-arc plasma, conditions of its preliminary injection into the drift space and beam focusing, amplitude, duration, and frequency of the bias potential pulses. The optimal conditions to form high-intensity beams of metal ions purified from the macroparticle debris of a vacuum-arc with a current of higher than 1 A and a current density of up to 0.5 A/cm2 are determined.

Optimized skin optical clearing for optical coherence tomography monitoring of encapsulated drug delivery through the hair follicles.

Hair follicles (HF) represent a drug delivery reservoir for improved treatment of skin disorders. Although various particulate systems play an important role in HF-targeting, their optical monitoring in skin is challenging due to strong light scattering. Optical clearing is an effective approach allowing the increasing of particle detection depth in skin. The enhancement of optical probing depth (OPD) and optical detection depth (ODD) of particle localization using optical coherence tomography (OCT) was evaluated under application of various optical clearing agents (OCAs) together with skin permeability enhancers ex vivo in rats. Efficient OPD increasing was demonstrated for all investigated OCAs. However, skin dehydration under action of hyperosmotic agents led to the worsening of OCT-contrast in dermis decreasing the ODD. Lipophilic agents provided optical clearing of epidermis without its dehydration. The highest ODD was obtained at application of a PEG-400/oleic acid mixture. This OCA was tested in vivo showing beneficial ODD and OPD enhancement.

Ernst Haeckel in the history of biology.

The German zoologist Ernst Haeckel (1834-1919) was arguably the most influential champion of Darwin's theory of evolution on the European continent and one of the most significant worldwide. As his biographer Robert Richards emphasized: "More people at the turn of the century learned of evolutionary theory from his pen than from any other source, including Darwin's own writings" [1]. Furthermore, Darwin himself considered Haeckel a crucial proponent of his theory. How can we explain the mismatch between Haeckel's extraordinary influence among his contemporaries and his relatively modest place in the current historiography of biology? Why are Haeckel-studies nothing like the 'Darwin-industry'? To answer these questions, we outline Haeckel's contribution to evolutionary biology and anthropology and - to a lesser extent - the general history of ideas. We argue that Haeckel is currently underestimated, because history written by the advocates of the modern synthesis focused on neo-Darwinian schools of thought and neglected 'old-school-Darwinism' which Haeckel was part of. Besides, Haeckel's militant anti-clericalism and his exotic philosophy of 'monism' made him an uncomfortable figure in European intellectual history. In contrast to Darwin, Haeckel from the very beginning tried to turn Darwinism into a universal worldview, thus jeopardizing his credibility as a scientist.