Aminomethylmorpholino Nucleosides as Novel Inhibitors of PARP1 and PARP2: Experimental and Molecular Modeling Analyses of Their Selectivity and Mechanism of Action.

Poly(ADP-ribose) polymerases 1 and 2 (PARP1 and PARP2) play a key role in DNA repair. As major sensors of DNA damage, they are activated to produce poly(ADP-ribose). PARP1/PARP2 inhibitors have emerged as effective drugs for the treatment of cancers with BRCA deficiencies.

Menthol-Induced Chirality in Semiconductor Nanostructures: Chiroptical Properties of Atomically Thin 2D CdSe Nanoplatelets Capped with Enantiomeric L-(-)/D-(+)-Menthyl Thioglycolates.

Semiconductor colloidal nanostructures capped with chiral organic molecules are a research hotspot due to their wide range of important implications for photonic and spintronic applications. However, to date, the study of chiral ligands has been limited almost exclusively to naturally occurring chiral amino and hydroxy acids, which typically contain only one stereocenter. Here, we show the pronounced induction of chirality in atomically thin CdSe nanoplatelets (NPLs) by capping them with enantiopure menthol derivatives as multi-stereocenter molecules.

Green Extraction of Reed Lignin: The Effect of the Deep Eutectic Solvent Composition on the UV-Shielding and Antioxidant Properties of Lignin.

Lignin, the second most abundant natural polymer, is a by-product of the biorefinery and pulp and paper industries. This study was undertaken to evaluate the properties and estimate the prospects of using lignin as a by-product of the pretreatment of common reed straw () with deep eutectic solvents (DESs) of various compositions: choline chloride/oxalic acid (ChCl/OA), choline chloride/lactic acid (ChCl/LA), and choline chloride/monoethanol amine (ChCl/EA). The lignin samples, hereinafter referred to as Lig-OA, Lig-LA, and Lig-EA, were obtained as by-products after optimizing the conditions of reed straw pretreatment with DESs in order to improve the efficiency of subsequent enzymatic hydrolysis.

Cas9 is mostly orthogonal to human systems of DNA break sensing and repair.

CRISPR/Cas9 system is а powerful gene editing tool based on the RNA-guided cleavage of target DNA. The Cas9 activity can be modulated by proteins involved in DNA damage signalling and repair due to their interaction with double- and single-strand breaks (DSB and SSB, respectively) generated by wild-type Cas9 or Cas9 nickases. Here we address the interplay between Streptococcus pyogenes Cas9 and key DNA repair factors, including poly(ADP-ribose) polymerase 1 (SSB/DSB sensor), its closest homolog poly(ADP-ribose) polymerase 2, Ku antigen (DSB sensor), DNA ligase I (SSB sensor), replication protein A (DNA duplex destabilizer), and Y-box binding protein 1 (RNA/DNA binding protein).

Lifespans of Fur Color Morphs in Polymorphic Populations of the Mole Vole and the Hypothesis of Adaptive Polymorphism.

Different lifespans were for the first time demonstrated for three (brown, bicolor, and black) fur color morphs in ten mole vole populations of the Volga, Ural, and Trans-Ural regions. With the longest lifespan of 5 years in the species, morphs that numerically dominate in a population can live 1-4 years longer than accompanying morphs. Spearman's correlation coefficient between the longest lifespan of the morphs and their proportion in the population was R = 0.

Can Shrews Avoid Competition When Hutchinson's Ecological Rule Is Disobeyed?

It is established that Hutchinson's ratio of the weights and sizes of the body and foraging organs in similar species is not fully obeyed in shrew species of the genus Sorex. Similarity in the centroid size of the mandible was observed in the large species S. isodon and S.

Human DNA ligases I and IIIα as determinants of accuracy and efficiency of base excision DNA repair.

Mammalian Base Excision Repair (BER) DNA ligases I and IIIα (LigI, LigIIIα) are major determinants of DNA repair fidelity, alongside with DNA polymerases. Here we compared activities of human LigI and LigIIIα on specific and nonspecific substrates representing intermediates of distinct BER sub-pathways. The enzymes differently discriminate mismatches in the nicked DNA, depending on their identity and position, but are both more selective against the 3'-end non-complementarity.

Peculiar Properties of Template-Assisted Aniline Polymerization in a Buffer Solution Using Laccase and a Laccase-Mediator System as Compared with Chemical Polymerization.

The conventional chemical polymerization of aniline has been described in multiple publications, while enzymatic polymerization has been poorly explored. A comparative study of the template-assisted enzymatic and chemical polymerization of aniline in a buffer solution of sodium dodecylbenzenesulfonate micelles was performed for the first time. The high-redox potential laccase from the fungus was used as a catalyst and air oxygen served as an oxidant.

Deep Eutectic Solvents for Biotechnology Applications.

Deep eutectic solvents (DESs) are an alternative to traditional organic solvents and ionic liquids and meet the requirements of "green" chemistry. They are easy to prepare using low-cost constituents, are non-toxic and biodegradable. The review analyzes literature on the use of DES in various fields of biotechnology, provides data on the types of DESs, methods for their preparation, and properties.

Induction of Chirality in Atomically Thin ZnSe and CdSe Nanoplatelets: Strengthening of Circular Dichroism via Different Coordination of Cysteine-Based Ligands on an Ultimate Thin Semiconductor Core.

Chiral nanostructures exhibiting different absorption of right- and left-handed circularly polarized light are of rapidly growing interest due to their potential applications in various fields. Here, we have studied the induction of chirality in atomically thin (0.6-1.

Betaine-Based Deep Eutectic Solvent as a New Media for Laccase-Catalyzed Template-Guided Polymerization/Copolymerization of Aniline and 3-Aminobenzoic Acid.

Deep eutectic solvents (DESs) can compensate for some of the major drawbacks of traditional organic solvents and ionic liquids and meet all requirements of green chemistry. However, the potential of their use as a medium for biocatalytic reactions has not been adequately studied. In this work we used the DES betaine-glycerol with a molar ratio of 1:2 as co-solvent for enzymatic template-guided polymerization/copolymerization of aniline (ANI) and 3-aminobenzoic acid (3ABA).

Functional Roles of PARP2 in Assembling Protein-Protein Complexes Involved in Base Excision DNA Repair.

Poly(ADP-ribose) polymerase 2 (PARP2) participates in base excision repair (BER) alongside PARP1, but its functions are still under study. Here, we characterize binding affinities of PARP2 for other BER proteins (PARP1, APE1, Polβ, and XRCC1) and oligomerization states of the homo- and hetero-associated complexes using fluorescence-based and light scattering techniques. To compare PARP2 and PARP1 in the efficiency of PAR synthesis, in the absence and presence of protein partners, the size of PARP2 PARylated in various reaction conditions was measured.

The contribution of PARP1, PARP2 and poly(ADP-ribosyl)ation to base excision repair in the nucleosomal context.

The regulation of repair processes including base excision repair (BER) in the presence of DNA damage is implemented by a cellular signal: poly(ADP-ribosyl)ation (PARylation), which is catalysed by PARP1 and PARP2. Despite ample studies, it is far from clear how BER is regulated by PARPs and how the roles are distributed between the PARPs. Here, we investigated the effects of PARP1, PARP2 and PARylation on activities of the main BER enzymes (APE1, DNA polymerase β [Polβ] and DNA ligase IIIα [LigIIIα]) in combination with BER scaffold protein XRCC1 in the nucleosomal context.

Analysis of Geographical Variability of Morphogenetic Trajectories Using the Mole Vole (Ellobius talpinus Pall.) as an Example.

ABSTTRACT: -Using the methods of geometric morphometrics, we have revealed the phenomenon of geographical variability of morphogenetic trajectories when doing side-by-side comparisons of mandibular shapes in individuals of different ages from three southern Trans-Ural populations of the mole vole (Ellobius talpinus Pall.) in the common morphospace.

Enzymatic synthesis and electrochemical characterization of sodium 1,2-naphthoquinone-4-sulfonate-doped PEDOT/MWCNT composite.

The development of novel materials with improved functional characteristics for supercapacitor electrodes is of current concern and calls for elaboration of innovative approaches. We report on an eco-friendly enzymatic synthesis of a composite based on poly(3,4-ethylenedioxythiophene) (PEDOT) and multi-walled carbon nanotubes (MWCNTs). The redox active compound, sodium 1,2-naphthoquinone-4-sulfonate (NQS), was used as a dopant for the backbone of the polymer.

[Diseases of biliary tract in the context of association with oncological diseases of the digestive system].

Cancers of the gastrointestinal tract are widespread among the population and cause significant damage to the health care system. In order to improve the strategy of preventive measures and the detection of oncological diseases at the early stages, it is necessary to provide timely impact on possible risk factors contributing to the onset and progression of malignant neoplasms. This review demonstrates the association between the pathology of the biliary tract and oncological diseases of the digestive system, discusses the possible mechanisms of the influence of cholelithiasis and cholecystectomy on the development of malignant neoplasms of various parts of the gastrointestinal tract.

Effect of Human XRCC1 Protein Oxidation on the Functional Activity of Its Complexes with the Key Enzymes of DNA Base Excision Repair.

Base excision repair (BER) ensures correction of most abundant DNA lesions in mammals. The efficiency of this multistep DNA repair process that can occur via different pathways depends on the coordinated action of enzymes catalyzing its individual steps. The scaffold XRCC1 (X-ray repair cross-complementing protein 1) protein plays an important coordinating role in the repair of damaged bases and apurinic/apyrimidinic (AP) sites via short-patch (SP) BER pathway, as well as in the repair of single-strand DNA breaks.

Functional Role of N-Terminal Extension of Human AP Endonuclease 1 In Coordination of Base Excision DNA Repair via Protein-Protein Interactions.

Human apurinic/apyrimidinic endonuclease 1 (APE1) has multiple functions in base excision DNA repair (BER) and other cellular processes. Its eukaryote-specific N-terminal extension plays diverse regulatory roles in interaction with different partners. Here, we explored its involvement in interaction with canonical BER proteins.

Role of Oxidation of XRCC1 Protein in Regulation of Mammalian DNA Repair Process.

The influence of XRCC1 protein oxidation on the modification of proteins catalyzed by poly(ADP-ribose)polymerases (PARP1 and PARP2) was studied for the first time. XRCC1, PARP1, and PARP2, functioning as scaffold proteins, are responsible for coordination of multistep repair of most abundant DNA lesions. We showed that the XRCC1 oxidation reduces the efficiency of its ADP-ribosylation and the protein affinity for poly(ADP-ribose).

Human apurinic/apyrimidinic endonuclease 1 is modified in vitro by poly(ADP-ribose) polymerase 1 under control of the structure of damaged DNA.

Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential multifunctional protein in mammals involved in base excision DNA repair (BER), regulation of gene expression and RNA metabolism. Its major enzymatic function is incision of AP sites. Poly(ADP-ribose) polymerase 1 (PARP1) modifies itself and target proteins with poly(ADP-ribose) (PAR), contributing to regulation of many processes.

Comparative effectiveness of vitamin-mineral complexes with iron in correcting iron deficiency in women in the outpatient setting.

Aim: To compare the efficacy of prophylactic administration of mineral-vitamin complexes "Feroglobin-B12" and "Complivit iron" with different degrees of Fe valence.

Materials And Methods: 120 female subjects were examined. To determine the quality of life, the SF-36 questionnaire was used.

Novel Inhibitors of DNA Repair Enzyme TDP1 Combining Monoterpenoid and Adamantane Fragments.

Background And Objective: The DNA repair enzyme tyrosyl-DNA-phosphodiesterase 1 (TDP1) is a current inhibition target to improve the efficacy of cancer chemotherapy. Previous studies showed that compounds combining adamantane and monoterpenoid fragments are active against TDP1 enzyme. This investigation is focused on the synthesis of monoterpenoid derived esters of 1-adamantane carboxylic acid as TDP1 inhibitors.

Dynamic light scattering study of base excision DNA repair proteins and their complexes.

Base excision repair (BER) involves many enzymes acting in a coordinated fashion at the most common types of DNA damage. The coordination is facilitated by interactions between the enzymes and accessory proteins, X-ray repair cross-complementing protein 1 (XRCC1) and poly(ADP-ribose) polymerase 1 (PARP1). Here we use dynamic light scattering (DLS) technique to determine the hydrodynamic sizes of several BER enzymes and proteins, DNA polymerase β (Polβ), apurinic/apyrimidinic endonuclease 1 (APE1), tyrosyl-DNA phosphodiesterase 1 (TDP1), XRCC1 and PARP1, present alone or in the equimolar mixtures with each other.

Laccase-Catalyzed Heterocoupling of Dihydroquercetin and p-Aminobenzoic Acid: Effect of the Reaction Product on Cultured Cells.

Derivatization of the natural flavonoid dihydroquercetin with p-aminobenzoic acid was carried out in an ethyl acetate/citric buffer biphasic system using laccase from the fungus Trametes hirsuta. The main reaction product yield was ~68 mol %. The product was characterized by H NMR, C NMR, and liquid chromatography-mass spectroscopy, and its structure was elucidated.

Morphogenetic Effects of Resettlement of Mole Voles (Ellobius talpinus Pall., 1770) from the Southern Population to the Northern Boundary of the Species Range.

Geometric morphometry has been used to reveal transformations of mandible morphogenesis in the offspring of mole voles resettled to the northern part of the species range from a southern population. The transformations were new compared to both the original (southern) and the aboriginal (northern) populations. A significant increase in the intragroup morphological disparity estimated by the mean nearest neighbor distance (MNND) in the resettled animals compared to both aboriginal populations is an indirect indication of an increased developmental instability in the resettled animals exposed to new climatic conditions.