Berberis vulgaris L. extract supplementation exerts regulatory effects on the lifespan and healthspan of Drosophila through its antioxidant activity depending on the sex.

Worldwide the aging population continues to increase, so the concept of healthy longevity medicine has become increasingly significant in modern society. Berberis vulgaris L. fruits serve as a functional food supplement with a high concentration of bioactive compounds, which offer numerous health-promoting benefits. The goal of this study was to investigate the geroprotective effect of Berberis vulgaris L. extract. Here we show that extract of Berberis vulgaris L. can, depending on concentrate, increases lifespan up to 6%, promote healthspan (stress resistance up to 35%, locomotor activity up to 25%, integrity of the intestinal barrier up to 12%, metabolic rate up to 5%) of Drosophila melanogaster (in vitro) and exhibits antioxidant (using red blood cell tests) and antiglycation activity (using glycation of bovine serum albumin) (in vitro). In addition to this, the extract does not exhibit cytotoxic properties in vitro, unlike the well-known polyphenolic compound quercetin. qRT-PCR has revealed the involvement of metabolic, heat shock response and lipid metabolism genes in the observed effects.

Complexes of Cationic Pyridylphenylene Dendrimers with Anionic Liposomes: The Role of Dendrimer Composition in Membrane Structural Changes.

In the last decades, dendrimers have received attention in biomedicine that requires detailed study on the mechanism of their interaction with cell membranes. In this article, we report on the role of dendrimer structure in their interaction with liposomes. Here, the interactions between cationic pyridylphenylene dendrimers of the first, second, and third generations with mixed or completely charged pyridyl periphery (D16+, D215+, D229+, and D350+) with cholesterol-containing (CL/Chol/DOPC) anionic liposomes were investigated by microelectrophoresis, dynamic light scattering, fluorescence spectroscopy, and conductometry. It was found that the architecture of the dendrimer, namely the generation, the amount of charged pyridynium groups, the hydrophobic phenylene units, and the rigidity of the spatial structure, determined the special features of the dendrimer-liposome interactions. The binding of D350+ and D229+ with almost fully charged peripheries to liposomes was due to electrostatic forces: the dendrimer molecules could be removed from the liposomal surfaces by NaCl addition. D350+ and D229+ did not display a disruptive effect toward membranes, did not penetrate into the hydrophobic lipid bilayer, and were able to migrate between liposomes. For D215+, a dendrimer with a mixed periphery, hydrophobic interactions of phenylene units with the hydrocarbon tails of lipids were observed, along with electrostatic complexation with liposomes. As a result, defects were formed in the bilayer, which led to irreversible interactions with lipid membranes wherein there was no migration of D215+ between liposomes. A first-generation dendrimer, D16+, which was characterized by small size, a high degree of hydrophobicity, and a rigid structure, when interacting with liposomes caused significant destruction of liposomal membranes. Evidently, this interaction was irreversible: the addition of salt did not lead to the dissociation of the complex.

An Experimental Model of Proton-Beam-Induced Radiation Dermatitis In Vivo.

Radiation dermatitis (RD) is one of the most common side effects of radiation therapy. However, to date, there is a lack of both specific treatments for RD and validated experimental animal models with the use of various sources of ionizing radiation (IR) applied in clinical practice. The aim of this study was to develop and validate a model of acute RD induced using proton radiation in mice. Acute RD (Grade 2-4) was obtained with doses of 30, 40, and 50 Gy, either with or without depilation. The developed model of RD was characterized by typical histological changes in the skin after irradiation. Moreover, the depilation contributed to a skin histology alteration of the irradiated mice. The assessment of animal vital signs indicated that there was no effect of proton irradiation on the well-being or general condition of the animals. This model can be used to develop effective therapeutic agents and study the pathogenesis of radiation-induced skin toxicity, including that caused by proton irradiation.

Ni Nanoparticles Stabilized by Hyperbranched Polymer: Does the Architecture of the Polymer Affect the Nanoparticle Characteristics and Their Performance in Catalysis?

Heat-up and hot-injection methods were employed to synthesize Ni nanoparticles (NPs) with narrow size distribution in the presence of hyperbranched pyridylphenylene polymer (PPP) as a stabilizing agent. It was shown that depending on the synthetic method, Ni NPs were formed either in a cross-linked polymer network or stabilized by a soluble hyperbranched polymer. Ni NPs were characterized by a combination of transmission electron microscopy (TEM), scanning TEM, thermogravimetric analysis, powder X-ray diffraction, X-ray photoelectron spectroscopy, energy dispersive X-ray analysis, and magnetic measurements. The architecture of polymer support was found to significantly effect Ni NPs characteristics and behavior. The Ni NPs demonstrated a high catalytic activity in a model Suzuki-Miyaura cross-coupling reaction. No significant drop in activity was observed upon repeated use after magnetic separation in five consecutive catalytic cycles. We believe that hyperbranched PPP can serve as universal platform for the controllable synthesis of Ni NPs, acting as highly active and stable catalysts.

Ru@hyperbranched Polymer for Hydrogenation of Levulinic Acid to Gamma-Valerolactone: The Role of the Catalyst Support.

Hydrogenation of levulinic acid (LA) obtained from cellulose biomass is a promising path for production of γ-valerolactone (GVL)-a component of biofuel. In this work, we developed Ru nanoparticle containing nanocomposites based on hyperbranched pyridylphenylene polymer, serving as multiligand and stabilizing matrix. The functionalization of the nanocomposite with sulfuric acid significantly enhances the activity of the catalyst in the selective hydrogenation of LA to GVL and allows the reaction to proceed under mild reaction conditions (100 °C, 2 MPa of H2) in water and low catalyst loading (0.016 mol.%) with a quantitative yield of GVL and selectivity up to 100%. The catalysts were successfully reused four times without a significant loss of activity. A comprehensive physicochemical characterization of the catalysts allowed us to assess structure-property relationships and to uncover an important role of the polymeric support in the efficient GVL synthesis.

Multicore iron oxide mesocrystals stabilized by a poly(phenylenepyridyl) dendron and dendrimer: role of the dendron/dendrimer self-assembly.

We report the formation of multicore iron oxide mesocrystals using the thermal decomposition of iron acetyl acetonate in the presence of the multifunctional and rigid poly(phenylenepyridyl) dendron and dendrimer. We thoroughly analyze the influence of capping molecules of two different architectures and demonstrate for the first time that dendron/dendrimer self-assembly leads to multicore morphologies. Single-crystalline ordering in multicore NPs leads to cooperative magnetic behavior: mesocrystals exhibit ambient blocking temperatures, allowing subtle control over magnetic properties using a minor temperature change.

The Effect of Chromosomes on Courtship Behavior in Sibling Species of the Drosophila virilis Group.

Prezygotic isolation mechanisms, particularly courtship behavior, play a significant role in the formation of reproductive barriers. The action of these mechanisms leads to the coexistence of numerous closely related insect species with specific adaptations in a shared or adjacent territory. The genetic basis of these mechanisms has been studied using closely related Drosophila species, such as the D. virilis group. However, the investigation of individual courtship behavior elements has been limited until recently, and the effect of genotype on the species-specific features of courtship as a whole has not been thoroughly examined. It should be noted that courtship behavior is not a typical quantitative trait that can be easily measured or quantified in both females and males, similar to traits like wing length or bristle number. Each courtship element involves the participation of both female and male partners, making the genetic analysis of this behavior complex. As a result, the traditional approach of genetic analysis for quantitative traits, which involves variance decomposition in a set of crosses, including parental species, F1 and F2 hybrids, and backcrosses of F1 to parental species, is not suitable for analyzing courtship behavior. To address this, we employed a modified design by introducing what we refer to as 'reference partners' during the testing of hybrid individuals from F1, F2, and backcrosses. These reference partners represented one of the parental species. This approach allowed us to categorize all possible test combinations into four groups based on the reference partner's sex (female or male) and their constant genotype towards one of the parental species (D. virilis or D. americana). The genotype of the second partner in the within-group test combinations varied from completely conspecific to completely heterospecific, based on the parental chromosomal sets. To assess the contribution of partner genotypes to the variability of courtship-element parameters, we employed structural equation modeling (SEM) instead of the traditional analysis of variance (ANOVA). SEM enabled us to estimate the regression of the proportion of chromosomes of a specific species type on the value of each courtship-element parameter in partners with varying genotypes across different test combinations. The aim of the current study was to analyze the involvement of sex chromosomes and autosomes in the formation of courtship structure in D. virilis and D. americana. The genetic analysis was complemented by video recording and formalization of courtship-ritual elements. D. virilis was found to be more sensitive to mate stimuli compared to D. americana. The majority of species-specific parameters, such as latency and duration of courtship elements (e.g., male and female song, following, licking, and circling), were shown to be influenced by the D. virilis genotype. However, not all of these parameters significantly impact copulation success, with the male song, licking, and following being the most significant. In females, the female song was found to have a significant relationship only with copulation duration. The influence of the female genotype on the species-specific parameters of courtship elements is primarily related to autosomes, while the male genotype is associated with the X chromosomes. The study suggests that sexual selection primarily occurs through acoustic and chemoreceptor channels.

Ultramicroporous Polyphenylenes via Diels-Alder Polycondensation Approach.

Development of new microporous organic polymers attracts significant attention due to a wide scope of promising applications. In addition, the synthesis of soluble, non-crosslinking polymers of high surface area and uniform microporosity is very challenging, and the methods for soluble microporous polymers formation are rather limited. In this work, we report a new approach to construct porous polyphenylenes which employs the Diels-Alder polycondensation of multifunctional ethynyl-containing monomers of different spatial architecture with bis(cyclopentadienone)s. The resulting polymers were soluble in common organic solvents, and their structure and properties were assessed by NMR, TGA, DSC, and SEC studies. The polymers demonstrated a specific surface area up to 751 m2·g-1 and ultramicroporous (pore size ≤ 0.6 nm) structure. N2 and CO2 adsorption-desorption data revealed that porosity parameters, e.g., specific surface area and pore sizes, can be tuned selectively by varying the type of monomers and reaction conditions.

Highly Selective CO2 Hydrogenation to Methanol over Complex In/Co Catalysts: Effect of Polymer Frame.

The growing demand for new energy sources governs the intensive research into CO2 hydrogenation to methanol, a valuable liquid fuel. Recently, indium-based catalysts have shown promise in this reaction, but they are plagued by shortcomings such as structural instability during the reaction and low selectivity. Here, we report a new strategy of controlling the selectivity and stability of bimetallic magnetically recoverable indium-based catalysts deposited onto a solid support. This was accomplished by the introduction of a structural promoter: a branched pyridylphenylene polymer (PPP). The selectivity of methanol formation for this catalyst reached 98.5%, while in the absence of PPP, the catalysts produced a large amount of methane, and the selectivity was about 70.2%. The methanol production rate was higher by a factor of twelve compared to that of a commercial Cu-based catalyst. Along with tuning selectivity, PPP allowed the catalyst to maintain a high stability, enhancing the CO2 sorption capacity and the protection of In against sintering and over-reduction. A careful evaluation of the structure-activity relationships allowed us to balance the catalyst composition with a high level of structural control, providing synergy between the support, magnetic constituent, catalytic species, and the stabilizing polymer layer. We also uncovered the role of each component in the ultimate methanol activity and selectivity.

Dendrimers as Antiamyloid Agents.

Dendrimer-protein conjugates have significant prospects for biological applications. The complexation changes the biophysical behavior of both proteins and dendrimers. The dendrimers could influence the secondary structure of proteins, zeta-potential, distribution of charged regions on the surface, the protein-protein interactions, etc. These changes offer significant possibilities for the application of these features in nanotheranostics and biomedicine. Based on the dendrimer-protein interactions, several therapeutic applications of dendrimers have emerged. Thus, the formation of stable complexes retains the disordered proteins on the aggregation, which is especially important in neurodegenerative diseases. To clarify the origin of these properties and assess the efficiency of action, the mechanism of protein-dendrimer interaction and the nature and driving force of binding are considered in this review. The review outlines the antiamyloid activity of dendrimers and discusses the effect of dendrimer structures and external factors on their antiamyloid properties.

Atomic-Scale Modification of Oxidation Phenomena on the Ge(100) Surface by Si Alloying.

Properties of Ge oxides are significantly different from those of widely used Si oxides. For example, the instability of GeO x at device junctions causes electronic defect levels that degrade the performance of Ge-containing devices (e.g., transistors and infrared detectors). Therefore, the passivating Si layers have been commonly used at Ge interfaces to reduce the effects of Ge oxide instability and mimic the successful strategy of Si oxidation. To contribute to the atomic-scale knowledge and control of oxidation of such Si-alloyed Ge interfaces (O/Si/Ge), we present a synchrotron radiation core-level study of O/Si/Ge, which is combined with scanning probe microscopy measurements. The oxidation processes and electronic properties of O/Si/Ge(100) are examined as functions of Si amount and oxidation doses. In particular, the incorporation of Si into Ge is shown to cause the strengthening of Ge-O bonds and the increase of incorporated oxygen amount in oxide/Ge junctions, supporting that the method is useful to decrease the defect-level densities.

Magnetically Recoverable Nanoparticulate Catalysts for Cross-Coupling Reactions: The Dendritic Support Influences the Catalytic Performance.

Carbon-carbon cross-coupling reactions are among the most important synthetic tools for the preparation of pharmaceuticals and bioactive compounds. However, these reactions are normally carried out using copper, phosphines, and/or amines, which are poisonous for pharmaceuticals. The use of nanocomposite catalysts holds promise for facilitating these reactions and making them more environmentally friendly. In the present work, the PEGylated (PEG stands for poly(ethylene glycol) pyridylphenylene dendrons immobilized on silica loaded with magnetic nanoparticles have been successfully employed for the stabilization of Pd2+ complexes and Pd nanoparticles. The catalyst developed showed excellent catalytic activity in copper-free Sonogashira and Heck cross-coupling reactions. The reactions proceeded smoothly in green solvents at low palladium loading, resulting in high yields of cross-coupling products (from 80% to 97%) within short reaction times. The presence of magnetic nanoparticles allows easy magnetic separation for repeated use without a noticeable decrease of catalytic activity due to the strong stabilization of Pd species by rigid and bulky dendritic ligands. The PEG dendron periphery makes the catalyst hydrophilic and better suited for green solvents. The minor drop in activity upon the catalyst reuse is explained by the formation of Pd nanoparticles from the Pd2+ species during the catalytic reaction. The magnetic separation and reuse of the nanocomposite catalyst reduces the cost of target products as well as energy and material consumption and diminishes residual contamination by the catalyst. These factors as well as the absence of copper in the catalyst makeup pave the way for future applications of such catalysts in cross-coupling reactions.

The effects of the sex chromosomes on the inheritance of species-specific traits of the copulatory organ shape in Drosophila virilis and Drosophila lummei.

The shape of the male genitalia in many taxa is the most rapidly evolving morphological structure, often driving reproductive isolation, and is therefore widely used in systematics as a key character to distinguish between sibling species. However, only a few studies have used the genital arch of the male copulatory organ as a model to study the genetic basis of species-specific differences in the Drosophila copulatory system. Moreover, almost nothing is known about the effects of the sex chromosomes on the shape of the male mating organ. In our study, we used a set of crosses between D. virilis and D. lummei and applied the methods of quantitative genetics to assess the variability of the shape of the male copulatory organ and the effects of the sex chromosomes and autosomes on its variance. Our results showed that the male genital shape depends on the species composition of the sex chromosomes and autosomes. Epistatic interactions of the sex chromosomes with autosomes and the species origin of the Y-chromosome in a male in interspecific crosses also influenced the expression of species-specific traits in the shape of the male copulatory system. Overall, the effects of sex chromosomes were comparable to the effects of autosomes despite the great differences in gene numbers between them. It may be reasonably considered that sexual selection for specific genes associated with the shape of the male mating organ prevents the demasculinization of the X chromosome.

Pd Catalyst Based on Hyperbranched Polypyridylphenylene Formed In Situ on Magnetic Silica Allows for Excellent Performance in Suzuki-Miyaura Reaction.

Here, for the first time, we developed a catalytic composite by forming a thin layer of a cross-linked hyperbranched pyridylphenylene polymer (PPP) on the surface of mesoporous magnetic silica (Fe3O4-SiO2, MS) followed by complexation with Pd species. The interaction of Pd acetate (PdAc) with pyridine units of the polymer results in the formation of Pd2+ complexes which are evenly distributed through the PPP layer. The MS-PPP-PdAc catalyst was tested in the Suzuki-Miyaura cross-coupling reaction with four different para-Br-substituted arenes, demonstrating enhanced catalytic properties for substrates containing electron withdrawing groups, and especially, for 4-bromobenzaldehyde. In this case, 100% selectivity and conversion were achieved with TOF of >23 000 h-1 at a very low Pd loading (0.032 mol %), a remarkable performance in this reaction. We believe these exceptional catalytic properties are due to the hyperbranched polymer architecture, which allows excellent stabilization of catalytic species as well as a favorable space for reacting molecules. Additionally, the magnetic character of the support allows for easy magnetic separation during the catalyst synthesis, purification, and reuse, resulting in energy and materials savings. These factors and excellent reusability of MS-PPP-PdAc in five consecutive uses make this catalyst promising for a variety of catalytic reactions.

Disruption of Amyloid Prion Protein Aggregates by Cationic Pyridylphenylene Dendrimers.

Disruption of amyloid protein aggregates is one of the potential therapies for treatment of neurodegenerative disorders such as prion diseases. Here, for the first time we report that pH-independent cationic pyridylphenylene dendrimers are able to disrupt amyloid protein aggregates at physiological pH as exemplified by inclusion bodies of ovine prion protein. The results show that exposure of inclusion bodies to the dendrimers leads to its partial disaggregation and release of the nanosize protein-dendrimer complexes. The complexes were characterized by SDS PAGE, DLS, and Western blotting methods. Thioflavin T fluorescence clearly demonstrated a decrease of amyloidogenic capability of the prion protein upon exposure to the dendrimers. The complexes formed are stable and do not show further aggregation.

A novel clean catalytic method for waste-free modification of polysaccharides by oxidation.

A practical, clean, single step oxidative modification of polysaccharides by H(2)O(2) catalysed by water soluble iron phthalocyanine, exemplified with starch, allows quantitative preparation of a range of tailor made materials without producing any waste.

Relative biological efficiency of protons at low and therapeutic doses in induction of 53BP1/γH2AX foci in lymphocytes from umbilical cord blood.

PURPOSE: In order to evaluate DNA damage induced by protons at low and radiotherapeutic doses at the therapeutic proton complex at Ruzomberok, Slovak Republic, lymphocytes from umbilical cord blood (UCB) of the same four probands were irradiated in the dose range of 1-200 cGy with γ-rays and protons (200 MeV, irradiation in the Bragg peak). MATERIALS AND METHODS: DNA repair γH2AX/53BP1 foci were analyzed by fluorescent microscopy and flow cytometry. RESULTS: Statistically significant effects of radiations were detected by fluorescent microscopy at all doses higher 1 cGy. Almost all distributions of foci in irradiated cells fitted to the Poisson distribution. In general, there was no difference in the levels of γH2AX and 53BP1 foci in irradiated cells. Flow cytometry was less sensitive and detected radiation induced effects at doses of 50 cGy and higher. Factorial analysis of variance in the whole studied dose range has shown no significant effect of radiation quality on number of γH2AX and 53BP1 foci. The ratio of proton-induced foci to γ-ray-induced foci was 0.86 ± 0.16 (53BP1) and 0.99 ± 0.34 (γH2AX) as measured by fluorescent microscopy and 0.99 ± 0.16 (γH2AX) as measured by flow cytometry at the radiotherapeutic dose of 2 Gy. CONCLUSIONS: Both flow cytometry and fluorescent microscopy indicated that the average value of relative biological efficiency (RBE) at radiation doses ≥ 20 cGy was about 1.0. Our data that RBE increased at low doses ≤ 20 cGy are relevant both to the development of treatment modalities and exposures that take place during space exploration and should be verified by further studies.

A combined approach to drug metabolism and toxicity assessment.

The challenge of predicting the metabolism or toxicity of a drug in humans has been approached using in vivo animal models, in vitro systems, high throughput genomics and proteomics methods, and, more recently, computational approaches. Understanding the complexity of biological systems requires a broader perspective rather than focusing on just one method in isolation for prediction. Multiple methods may therefore be necessary and combined for a more accurate prediction. In the field of drug metabolism and toxicology, we have seen the growth, in recent years, of computational quantitative structure-activity relationships (QSARs), as well as empirical data from microarrays. In the current study we have further developed a novel computational approach, MetaDrug, that 1) predicts metabolites for molecules based on their chemical structure, 2) predicts the activity of the original compound and its metabolites with various absorption, distribution, metabolism, excretion, and toxicity models, 3) incorporates the predictions with human cell signaling and metabolic pathways and networks, and 4) integrates networks and metabolites, with relevant toxicogenomic or other high throughput data. We have demonstrated the utility of such an approach using recently published data from in vitro metabolism and microarray studies for aprepitant, 2(S)-((3,5-bis(trifluoromethyl)benzyl)-oxy)-3(S)phenyl-4-((3-oxo-1,2,4-triazol-5-yl)methyl)morpholine (L-742694), trovofloxacin, 4-hydroxytamoxifen, and artemisinin and other artemisinin analogs to show the predicted interactions with cytochromes P450, pregnane X receptor, and P-glycoprotein, and the metabolites and the networks of genes that are affected. As a comparison, we used a second computational approach, MetaCore, to generate statistically significant gene networks with the available expression data. These case studies demonstrate the combination of QSARs and systems biology methods.