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The presence of a 22q11.2 microdeletion (22q11.2 deletion syndrome [22q11DS]) ranks among the greatest known genetic risk factors for the development of psychotic disorders. There is emerging evidence that the cerebellum is important in the pathophysiology of psychosis. However, there is currently limited information on cerebellar neuroanatomy in 22q11DS specifically.High-resolution 3T magnetic resonance imaging was acquired in 79 individuals with 22q11DS and 70 typically developing control subjects (N = 149). Lobar and lobule-level cerebellar volumes were estimated using validated automated segmentation algorithms, and subsequently group differences were compared. Hierarchical clustering, principal component analysis, and graph theoretical models were used to explore intercerebellar relationships. Cerebrocerebellar structural connectivity with cortical thickness was examined via linear regression models.Individuals with 22q11DS had, on average, 17.3% smaller total cerebellar volumes relative to typically developing subjects (p.0001). The lobules of the superior posterior cerebellum (e.g., VII and VIII) were particularly affected in 22q11DS. However, all cerebellar lobules were significantly smaller, even after adjusting for total brain volumes (all cerebellar lobules p.0002). The superior posterior lobule was disproportionately associated with cortical thickness in the frontal lobes and cingulate cortex, brain regions known be affected in 22q11DS. Exploratory analyses suggested that the superior posterior lobule, particularly Crus I, may be associated with psychotic symptoms in 22q11DS.The cerebellum is a critical but understudied component of the 22q11DS neuroendophenotype.

We analyzed the diversity of bacterial communities, metabolic activity, pH, and anthropogenic impact in the water of the estuaries and estuarine waters of the rivers in Southern Baikal in 2018 with different chemical composition. The chemical composition of waters and values of total microbial count (TMC), organotrophic bacteria (OB), and bacterial production (BP) depended on the geographical position, length of the rivers, and their water quality. In rivers with water acidification, we did not detect an effect of pH on TMC, abundance of OB, or total amount of mesophilic aerobic and facultative anaerobic microorganisms (PC). In rivers with a discharge of untreated domestic sewage, there was an increase in the content of dissolved organic carbon (DOC), concentration of nutrients, number of fecal and mesophilic bacteria, and high metabolic activity of microorganisms. The value of bacterioplankton production reached 0.26 to 12.41 per day−1; TMC – 0.155 ± 0.002 to 3.474 ± 0.044 million cells/mL. Using the massive parallel sequencing of fragments encoding the V2–V3 region of the 16S rRNA gene, we studied the diversity of bacteria and estimated the influence of chemical composition on the diversity of communities. As in other freshwater ecosystems and the pelagic zone of Lake Baikal, the members of freshwater Proteobacteria, Actinobacteria, Bacteroidetes, Cyanobacteria, and Verrucomicrobia predominated in the estuaries and estuarine waters of the rivers. The obtained data on the number and diversity of hygiene indicator bacteria suggested fecal pollution of the rivers of Southern Baikal.

The potato (Solanum tuberosum L.) has been the focus of dietary research in recent decades due to its ability to accumulate phenolic substances (anthocyanins) in tubers. In Russia, such varieties have been created for a number of regions, but in the Far East, the program to increase the content of anthocyanins in potato tubers has recently begun. In the presented study using liquid chromatography and second-order mass spectrometry methods, we profiled anthocyanins and quantified their accumulation for potato varieties of different origin (Russia, Ukraine, Belarus, Kazakhstan, Germany, the Netherlands), which had not previously been characterized by this feature. For the first time, four dietary Russian varieties with an increased content of anthocyanins have been identified. This work aimed to determine the profiles of anthocyanins and their content in tubers in the conditions of the Russian Far East. We used 22 varieties selected for early maturity, productivity, low starch content and different color of tubers and flowers. The anthocyanin profile was double-identified, by the retention time on a C18 reverse phase column with detection of absorbance at wavelength range 400-700 nm and ESI-MS/MS in positive ionization mode. Anthocyanins were quantified spectrophotometrically. The anthocyanins identified in the tubers were delphinidin, petunidin, malvidin, cyanidin, and pelargonidin. Delphinidin and cyanidin were found in mono- and diglycosylated forms. It was revealed that petunidin-3-glucoside is the most common anthocyanin which is present in almost all of the studied varieties. In tubers, depending on varietal specificity, there were from 1 to 5 anthocyanins of those found. Varieties with yellow skin and pink spots on the yellow tuber skin were characterized by a low content of anthocyanins. The pink and dark pink color of the skin positively correlates with the content of pelargonidin-3-glucoside, while petunidin-3-glucoside and cyanidin-3-glucoside give a purple and blue-violet color to the skin of the tuber. The anthocyanin level was the highest in Phioletovii variety (310 mg/kg cyanidin-3-glucoside, 50 mg/kg malvidin, 30 mg/kg delphinidin), Vasilyok variety (150 mg/kg petunidin), and in Mayak (95 mg/kg pelargonidin) and Kuznechanka (78 mg/kg pelargonidin) varieties. In the Phioletovii variety, the cyanidin-3-glucoside prevailed. We recommend to involve varieties with pink, dark pink, purple and blue-purple tuber skin in selection for an increased content of anthocyanins.

Relevance. A number of scientific studies confirm that consumption of fruits and vegetables can reduce the risk of certain chronic diseases, such as cancer and cardiovascular diseases, for example, consumption of fresh tomatoes and tomato products is inversely proportional to the development of certain types of cancer. Tomato Solanum lycopersicum L. contains a large number of polyphenolic complexes, which are biologically active compounds. In this article, the authors have attempted for the first time to present the complete metabolomic composition of Solanum lycopersicum extracts.Materials and methods: As an object of research, authors used the extracts of Solanum lycopersicum L., from the collection of the Federal Research Center N.I. Vavilov All-Russian Institute of Plant Genetic Resources, grown and collected at the Far Eastern Experiment Station Branch of the Federal State Budgetary Scientific Institution in September 2020 (varieties: k-5351 Ont77 13, Canada; k-3149 Rehovoth, Israel; 2698 Ukraine). High performance liquid chromatography (HPLC) in combination with a BRUKER DALTONIKS ion trap (tandem mass spectrometry) was used to identify target analytes in extracts obtained by the maceration method.Discussion: The results of initial studies revealed the presence of 36 biologically active compounds, of which 22 were identified for the first time in Solanum lycopersicum L. These are Apigenin, Luteolin, Kaempferol, Taxifolin, Myricetin, Coutaric acid, Caffeoylmalic acid, Caftaric acid, Dicaffeoylquinic acid, coumarins Fraxetin, and Fraxetin-7-O-beta-glucuronide, Pelargonidin, Salvianolic acid D, Rosmanol, Colnelenic acid, Ethyl rosemary, lignan Medioresinol-O-hexoside, Squalene, etc. The findings will help to intensify future research into the development and production of various functional food products containing targeted extracts of Solanum lycopersicum L.

We studied the microbial communities associated with the Baikal ostracods, Candona sp. (Candonidae). Bacterial biofilms were identified on the shell valves of the ostracods localized near epibiotic ciliates of the genus Lagenophrys (Ciliophora: Lagenoprydae). In situ hybridization confirmed the presence of eubacterial cells in different parts of the ostracod’s body. Bacteria of two morphotypes were detected in bacterial biofilms, including filamentous bacteria. Next-generation sequencing of 16S rRNA bacterial gene fragment allowed us to identify representatives of five bacterial phyla. Members of the phyla Proteobacteria and Bacteroidetes typical of non-marine epibiotic associations of ostracods were dominant taxa in the ostracod microbiomes. Members of other taxa (Actinobacteria, Gracilibacteria and Cyanobacteria) are likely facultative and consumed by ostracods together with detritus. In the ostracod microbiome, a significant proportion (20% of all reads) belonged to the sequences of the genus Rickettsia related to intracellular parasites.

Diversity of methano- and methylotrophic bacteria in enrichments from the oxidized sediment layer maintained at 10°C in mineral media with nitrogen compounds ( $${\text{NO}}_{3}^{ - }$$ and $${\text{NH}}_{4}^{ + }$$ ) and methanol was studied using high-throughput sequencing of the V2–V3 region of the 16S rRNA gene. Methanotrophs of the bottom sediment belonged to the order Methylococcales, with predominance of the genus Methylobacter (6.4 and 4.6% of the total number of sequences, respectively). Members of the methylotrophic community belonged to the genus Methylotenera (family Methylophilaceae). Enrichments in the medium with ammonium and methane were characterized by the highest diversity of methanotrophs, containing 22 OTUs of the family Methylococcaceae, nine of which were not detected under other cultivation conditions. Altogether, only six out of 28 OTUs of methanotrophic bacteria exhibited similarity to cultured members of Methylobacter, Metyloglobulus, and Methylomicrobium, while others showed different levels of similarity (94–99%) to uncultured members of the family Methylococcaceae. The presence of 0.01% methanol promoted preferential development of methylotrophic bacteria, while 0.5% methanol suppressed the growth of methanotrophic bacteria irrespective of the nitrogen source added.

The article reflects the results of a study of the morphological composition of blood, indicators of metabolism and the content of hormones in the blood plasma of gonadectomized cockerels of the Adler silvery breed. In the experiment, 40 males were used at the age of 6 weeks, of which two groups were formed, a control and an experimental, 20 heads each. It was found that during the preparatory (leveling) period, the clinical state, morphological composition of blood and metabolic parameters in the experimental group of males did not differ from each other and were within the limits of their physiological values. There were also no differences in blood glucose concentration, protein content, triglycerol, cholesterol, uric acid, as well as the activity of alkaline phosphatase, alanine and aspartate aminotransferase in the blood plasma of cockerels in the experimental and control groups during the preparatory period. Gonadectomy of males by surgical intervention at the age of six weeks did not significantly affect the morphology of their blood on the third day, with the exception of ESR, the value of which in birds of the experimental group was 1.9 times higher than in the control. In gonadectomized males, the number of platelets in the blood decreased by 30.7% compared to the control, which indicates a decrease in platelet activity and is probably associated with their participation in blood coagulation processes in the body after gonadectomy. Other indicators of the morphological composition of blood, namely, the number of erythrocytes, leukocytes, lymphocytes, eosinophils and neutrophils in gonadectomized males did not change compared with the control. It was found that the concentration of glucose in the blood, as well as total protein and uric acid in the blood plasma of males who underwent gonadectomy on the third day of the research period were at the level of the values of the control group birds and corresponded to the physiological values of these parameters in clinically healthy birds. On the 125th day of the main period in gonadectomized males, the level of glucose and protein, as well as indicators of lipid metabolism, namely, the concentration of triglycerol and cholesterol in the blood plasma did not change, while the content of uric acid increased by 23.7% compared with the control. It was found that the content of cortisol in the blood plasma of gonadectomized males was 3.2 times lower, and testosterone 10.2 times lower than in the control. So, gonadectomy of cockerels does not affect the morphological composition of the blood, indicators of the metabolic status of the bird, but it helps to reduce the content of cortisol and testosterone in the blood plasma. Key words: roosters, gonadectomy, blood morphology, metabolic parameters, enzyme activity, cortisol, testosterone.

The effect of gonadoectomy (removal of the testicles) in Adler's silver roosters on the clinical condition, live weight, slaughter rates and chemical composition of the pectoral muscle was studied. The experiment was performed on 40 roosters of 6-weeks, which according to the principle of analogues were divided into two groups: control and experimental 20 heads each. It was found that in the preparatory period, which lasted 10 days indicators of the clinical condition – body temperature, pulse and respiration, as well as live weight of the roosters of the experimental group did not differ from the control. Gonadoectomy of roosters of the experimental group, conducted at the age of 45 days by a specially developed method, increased the body temperature of the poultry on the second day after surgical intervention by 1.03°C, and on the third – by 1.15°, while other indicators of clinical condition – pulse, number respiratory movements and live weight did not change compared to control. The duration of the postoperative period in the roosters of the experimental group was 3-4 days and ended with the healing of the wound on the skin. Subsequently, body temperature, pulse and the number of respiratory movements in gonadoectomized roosters corresponded to similar indicators of poultry in the control group. The live weight of gonadoectomized roosters in the rearing process, which was monitored decadelly from the 65th to the 95th day compared to the control did not change, on 105th and 115th day had a tendency to increase, and 125th day increased by 4.8 %. Slaughter rates of gonadoectomized roosters corresponded to similar indicators of poultry of the control group. The weight of the gutted carcass was higher by 5.2% and that of the muscular stomach by 7.8%. Differences in the chemical composition of the pectoral muscle of gonadoectomized roosters compared with control, namely: on the content of dry matter, moisture, fat, protein and ash were not found. Thus, gonadoectomy of roosters of the Adler's silver meat-egg breed does not affect their clinical condition, the chemical composition of the pectoral muscles, but increases the live weight of the bird on the 125th day of rearing

The effect of the antibiotic chlortetracycline and the anthelmintic albendazole on morphological features, internal organs, alkaline phosphatase activity and protein content in the gills of two-year-old carp was studied. It was found that chlortetracycline and albendazole at the studied concentrations in water and short-term action do not affect the morphological features, behavior and internal organs, but change the alkaline phosphatase activity of the gills of two-year-old carp. The antibiotic chlortetracycline at concentrations of 1.10, 3.15, and 6.30 mg/dm3 of water and fish exposure for 72 h reduced the alkaline phosphatase activity of gills in carp of the first experimental group by 2.5 times, in the second – by 2.8 times and in the third – by 2.7 times regard the control; it did not affect the protein content in the gills, morphological features and internal organs of fish. We registered an increase in alkaline phosphatase activity of gills in two-year-old carp under effect of anthelmintic albendazole at at the concentration of 1.0 mg/dm3 by 28.2%, while albendazole concentration of 0.2 and 0.5 mg/dm3 did not affect the alkaline phosphatase activity as well as the level of protein in fish body. Our results indicate an important role of gill alkaline phosphatase in assessing the negative effects of antibiotics and water anthelmintics in freshwater fish. Key words: freshwater fish, morphological features, respiratory organs, antibiotic, anthelmintic, protein. References Bartikova H., Skalova L., Stuchlikova L., Vok

Hybrid molecules created from different pharmacophores of natural and synthetic equivalents are successfully used in pharmaceutical practice. One promising target for anticancer therapy is tyrosyl-DNA phosphodiesterase 1 (Tdp1) because it can repair DNA lesions caused by DNA-topoisomerase 1 (Top1) inhibitors, resulting in drug resistance. In this study, new hybrid compounds were synthesized by combining the pharmacophoric moiety of a set of natural compounds with inhibitory properties against Tdp1, particularly, phenolic usnic acid and a set of different monoterpenoid fragments. These fragments were connected through a hydrazinothiazole linker. The inhibitory properties of the new compounds mainly depended on the structure of the terpenoid moieties. The two most potent compounds, 9a and 9b, were synthesized from citral and citronellal, which contain acyclic fragments with IC50 values in the range of 10-16 nM. Some synthesized derivatives showed low cytotoxicity against HeLa cells and increased the effect of the Top1 inhibitor topotecan in vitro by three to seven times. These derivatives may be considered as potential agents for the development of anticancer therapies when combined with Top1 inhibitors.

The current review focuses on the connection of telomerase and telomeres with aging. In this review, we describe the changes in telomerase and telomere length (TEL) during development, their role in carcinogenesis processes, and the consequences of reduced telomerase activity. More specifically, the connection of TEL in peripheral blood cells with the development of aging-associated diseases is discussed. The review provides systematic data on the role of telomerase in mitochondria, the biology of telomeres in stem cells, as well as the consequences of the forced expression of telomerase (telomerization) in human cells. Additionally, it presents the effects of chronic stress exposure on telomerase activity, the effect of TEL on fertility, and the effect of nutraceutical supplements on TEL. Finally, a comparative review of the chronographic theory of aging, presented by Olovnikov is provided based on currently available scientific research on telomere, telomerase activity, and the nature of aging by multicellular organisms.

Graphical abstract, Highlights • Carbon nanofibers had no pronounced pathomorphic effect on freshwater insects. • Carbon nanofibers were absorbed in the intestine of freshwater insects. • Biodegradation of carbon nanofibers was detected in the digestive tract of insects., Carbon nanofibers (CNFs) are widely used in consumer products today. In this study, we assessed the effects of CNFs on the digestive system of three freshwater invertebrate species (Gammaridae, Ephemerellidae, and Chironomidae). The aquatic insects Diamesa sp., Drunella cryptomeria, and Gammarus suifunensis were incubated with the CNFs at the concentration of 100 mg/L during the 7-days period. Histological examination of the whole specimens and the longitudinal sections revealed no toxic effects of CNFs. However, a noticeable change in the structure of the CNFs accumulated in the intestines of the aquatic insects was found by Raman spectroscopy. The registered decrease in the relative proportion of amorphous carbon included in the CNF sample was found in the intestines of Diamesa sp. and D. cryptomeria. The registered effect can indicate a biodegradation of amorphous carbon in the digestive tract of these two insect species. In contrast, the decrease of highly structured carbons and the decrease of G-bonds intensity were registered in the digestive tract of G. suifunensis. This observation demonstrates the partial biodegradation of CNFs in the digestive tract of G. suifunensis.

Vehicle emission particles (VEPs) represent a significant part of air pollution in urban areas. However, the toxicity of this category of particles in different aquatic organisms is still unexplored. This work aimed to extend the understanding of the toxicity of the vehicle exhaust particles in two species of marine diatomic microalgae, the planktonic crustacean Artemia salina, and the sea urchin Strongylocentrotus intermedius. These aquatic species were applied for the first time in the risk assessment of VEPs. Our results demonstrated that the samples obtained from diesel-powered vehicles completely prevented egg fertilization of the sea urchin S. intermedius and caused pronounced membrane depolarization in the cells of both tested microalgae species at concentrations between 10 and 100 mg/L. The sample with the highest proportion of submicron particles and the highest content of polycyclic aromatic hydrocarbons (PAHs) had the highest growth rate inhibition in both microalgae species and caused high toxicity to the crustacean. The toxicity level of the other samples varied among the species. We can conclude that metal content and the difference in the concentrations of PAHs by itself did not directly reflect the toxic level of VEPs, but the combination of both a high number of submicron particles and high PAH concentrations had the highest toxic effect on all the tested species.

A comparative analysis of molecular genetic phenotypes of mucous membrane cells in five anatomical regions of the colon in a group of healthy donors was conducted by comparing mRNA expression profiles of 62 genes involved in the regulation of vital cellular function. We used 181 biopsy samples of morphologically unchanged colonic mucosa, obtained from the colon (ascending, transverse-colon, descending, sigmoid) and rectum sections during prophylactic colonoscopy of 58 donors with no colon pathology. The mRNA levels for 62 genes involved in the regulation of apoptosis, proliferation, transcription, differentiation, cell-cell adhesion, and immune response were assessed by RT-PCR. Statistically significant differences were found for the molecular phenotypes of five sections of the colon. The results of the study can serve as a basis for creating a reference database (values of expression profiles), developing methods of differential diagnostics and screening of various pathologies of the colon.Proveden sravnitel'nyĭ analiz molekuliarno-geneticheskikh fenotipov kletok slizistoĭ obolochki v piati anatomicheskikh otdelakh tolstoĭ kishki v gruppe uslovno zdorovykh donorov. Profili ékspressii mRNK 62 genov, uchastvuiushchikh v reguliatsii zhiznenno vazhnykh kletochnykh funktsiĭ, issledovali v biopsiĭnom materiale morfologicheski neizmenennoĭ slizistoĭ obolochki tolstoĭ kishki 181 obraztsa, poluchennogo iz osnovnykh otdelov obodochnoĭ (voskhodiashchaia, poperechno-obodochnaia, niskhodiashchaia, sigmovidnaia) i priamoĭ kishki v khode profilakticheskoĭ kolonoskopii 58 donorov, u kotorykh otsutstvovala patologiia tolstoĭ kishki. Ékspressiiu mRNK 62 genov, reguliruiushchikh apoptoz, proliferatsiiu, transkriptsiiu, differentsirovku, mezhkletochnuiu adgeziiu i immunnyĭ otvet, otsenivali metodom OT-PTsR. Ustanovleny statisticheski znachimye otlichiia molekuliarnykh fenotipov piati otdelov tolstoĭ kishki. Rezul'taty provedennogo issledovaniia mogut sluzhit' osnovaniem dlia sozdaniia referensnoĭ bazy dannykh (znacheniĭ ékspressionnykh profileĭ), razrabotki metodov differentsial'noĭ diagnostiki i skrininga razlichnykh patologiĭ tolstoĭ kishki.

Usnic acid (UA) is a secondary metabolite of lichens that exhibits a wide range of biological activities. Previously, we found that UA derivatives are effective inhibitors of tyrosyl-DNA phosphodiesterase 1 (TDP1). It can remove covalent complex DNA-topoisomerase 1 (TOP1) stabilized by the TOP1 inhibitor topotecan, neutralizing the effect of the drugs. TDP1 removes damage at the 3′ end of DNA caused by other anticancer agents. Thus, TDP1 is a promising therapeutic target for the development of drug combinations with topotecan, as well as other drugs for cancer treatment. Ten new UA enamino derivatives with variation in the terpene fragment and substituent of the UA backbone were synthesized and tested as TDP1 inhibitors. Four compounds, 11a-d, had IC50 values in the 0.23–0.40 μM range. Molecular modelling showed that 11a-d, with relatively short aliphatic chains, fit to the important binding domains. The intrinsic cytotoxicity of 11a-d was tested on two human cell lines. The compounds had low cytotoxicity with CC50 ≥ 60 μM for both cell lines. 11a and 11c had high inhibition efficacy and low cytotoxicity, and they enhanced topotecan’s cytotoxicity in cancerous HeLa cells but reduced it in the non-cancerous HEK293A cells. This “protective” effect from topotecan on non-cancerous cells requires further investigation.

Several different mitochondrial clades have been found in natural populations of Drosophila melanogaster. Most often, the difference is in single nucleotide substitutions, some of which are conservative. Some clades are rare, and others dominate. It has been reported that clade III dominates over clades V and VI in seven populations of D. melanogaster. We compared D. melanogaster strains with different mitotypes by locomotor activity (using TriKinetics Drosophila Activity Monitor), energy expenditure (by indirect calorimetry, based on measuring oxygen consumption) and life span (under extreme conditions at 29 °C). The nuclear genomes of these strains were aligned for several generations by backcrosses. According to our data, individuals with the mitotype from clade III had a higher level of locomotor activity and longer life span. In terms of energy expenditure, the strains studied did not differ. However, the same level of energy expenditure may be differently distributed between the state of activity and the state of rest or sleep. If the energy expenditure during the sleep in flies with different locomotor activity is the same, then an individual with the same overall energy expenditure can move a greater distance or be active longer. This can be interpreted as an advantage of the strain with the mitotype from clade III compared to the other two mitotypes studied. If individuals have different energy expenditure values at rest, the strains with lower energy expenditure at rest spend less energy during forced inactivity. In this case, the mitotype from clade III should also be advantageous. What nucleotide substitutions in the mitotype from clade III can provide an adaptive advantage is not clear yet. We assume that individuals with widespread clade М(III) may have adaptive advantages compared to other mitotypes due to their greater locomotor activity even with the same energy expenditure. Further studies are required, for mitotypes are polymorphic for single nucleotide polymorphism not only between but also within the clades.

Persistent organic pollutants (POPs) constitute a wide range of chemicals. Their release into the environment has raised great concern due to their potentially harmful impact in humans and wildlife species. The aim of this current study was to detect selected POPs in hair samples of wild terrestrial mammals from Primorsky Krai, Russia, so as to assess potential environmental exposure. The tested wild species were leopard cat, musk deer, wolf, amur hedgehog, and raccoon dog. The targeted organochlorines were hexachlorobenzene (HCB) and DDTs (opDDE, ppDDE, and opDDD), polychlorinated biphenyl (PCB) congeners (28, 52, 101, 118, 138, 153, and 180), and polycyclic aromatic hydrocarbons (PAHs) (acenaphylene (ACEN), fluorene (FLU), anthracene (ANTH) phenathrene (PHEN), and pyrene (PYR)). The detection of POPs was conducted in hair samples by a one-step hair extraction method, by using a headspace solid-phase microextraction technique (HS-SPME) and analyzed then by GC-MS. The majority of the wild animal hair samples were found positive in all tested pollutants. More specifically, the percentage of positive hair samples for HCB was 93.3% and for DDTs, PCBs, and PAHs, 20.0 to 100.0%, 6.7 to 100.0%, and 75.0 to 100.0%, respectively. DDT, PCB, and PAH detection ranged from 1.26 to 52.06 pg mg−1, 0.73 to 31.34 pg mg−1, and 2.59 to 35.00 pg mg−1, respectively. The highest mean concentration levels of all tested pollutants were found for musk deer (PCBs 12.41 pg mg−1, DDTs 21.87 pg mg−1, PAHs 22.12 pg mg−1) compared to the other wild species. To the best of our knowledge, this is the first study that provides results regarding contamination in different terrestrial mammals by POP exposure. The use of hair as a matrix is proven to be an effective tool for nondestructive biological monitoring of POP contamination in terrestrial ecosystems.

Using the Illumina MiSeq platform, we have studied the diversity of bacteria and archaea in three rivers of the southeastern end of Lake Baikal in the under-ice period of 2018. In analysed 16S rRNA gene libraries of all rivers, we have identified sequences of 12 bacterial phyla: Actinobacteria, Bacteroidetes, Cyanobacteria, Elusimicrobia, Epsilonbacteraeota, Fibrobacteres, Firmicutes, Omnitrophicaeota, Patescibacteria, Planctomycetes, Proteobacteria, and Verrucomicrobia. The contribution of minor taxa to the microbiomes from the estuaries of the rivers Solzan and Bolshaya Osinovka is more significant. Three phyla (Thaumarchaeota, Euryarchaeota and Crenarchaeota) and one superphylum (DPANN) represent archaea. The diversity of bacteria and archaea in the investigated ecotopes has its specifics and is not identical to that found in the pelagic zone of Southern Baikal. Bacteria show phylogenetic diversity at the level of families and genera, whereas archaea – at the level of phyla. In the microbiomes, we have identified microorganisms involved in various stages of transformation of organic and inorganic substances.

This work represents a comparative metabolomic study of extracts of wild grapes obtained from six different places in the Primorsky and Khabarovsk territories (Far East Russia) and extracts of grapes obtained from the collection of N.I. Vavilov All-Russian Institute of Plant Genetic Resources (St. Petersburg). The metabolome analysis was performed by liquid chromatography in combination with ion trap mass spectrometry. The results showed the presence of 118 compounds in ethanolic extracts of V. amurensis grapes. In addition, several metabolites were newly annotated in V. amurensis. The highest diversity of phenolic compounds was identified in the samples of the V. amurensis grape collected in the vicinity of Vyazemsky (Khabarovsk Territory) and the floodplain of the Arsenyevka River (Primorsky Territory), compared to the other wild samples and cultural grapes obtained in the collection of N.I. Vavilov All-Russian Institute of Plant Genetic Resources.

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a promising target for anticancer therapy due to its ability to counter the effects topoisomerase 1 (Top1) poison, such as topotecan, thus, decreasing their efficacy. Compounds containing adamantane and monoterpenoid residues connected via 1,2,4-triazole or 1,3,4-thiadiazole linkers were synthesized and tested against Tdp1. All the derivatives exhibited inhibition at low micromolar or nanomolar concentrations with the most potent inhibitors having IC50 values in the 0.35–0.57 µM range. The cytotoxicity was determined in the HeLa, HCT-116 and SW837 cancer cell lines, moderate CC50 (µM) values were seen from the mid-teens to no effect at 100 µM. Furthermore, citral derivative 20c, α-pinene-derived compounds 20f, 20g and 25c, and the citronellic acid derivative 25b were found to have a sensitizing effect in conjunction with topotecan in the HeLa cervical cancer and colon adenocarcinoma HCT-116 cell lines. The ligands are predicted to bind in the catalytic pocket of Tdp1 and have favorable physicochemical properties for further development as a potential adjunct therapy with Top1 poisons.

Simple Summary Given the complexity of the human reproduction system and the numerous limitations imposed on human studies, a fruit fly model was used to investigate whether the effects of high temperature on fertility and sleep correlate one with another. No evidence was provided for a causal link of temperature-sensitive sterility with sleep disturbance under high temperature in infertile females born from females of Canton-S strain and males of Harwich strain. However, sensitivity of sleep of these females to high temperature differed from that in fertile females born from females of Harwich strain and males of Canton-S strain and in males of either cross. Abstract Humans and fruit flies demonstrate similarity in sleep-wake behavior, e.g., in the pattern of sleep disturbances caused by an exposure to high temperature. Although research has provided evidence for a clear connection between sleeping problems and infertility in women, very little is known regarding the mechanisms underlying this connection. Studies of dysgenic crosses of fruit flies revealed that an exposure to elevated temperature induces sterility in female intra-specific hybrids exclusively in one of two cross directions (progeny of Canton-S females crossed with Harwich males). Given the complexity and limitations of human studies, this fruit flies’ model of temperature-sensitive sterility might be used for testing whether the effects of high temperature on fertility and on 24-h sleep pattern are inter-related. To document this pattern, 315 hybrids were kept for at least five days in constant darkness at 20 °C and 29 °C. No evidence was found for a causal link between sterility and sleep disturbance. However, a diminished thermal responsiveness of sleep was shown by females with temperature-induced sterility, while significant responses to high temperature were still observed in fertile females obtained by crossing in the opposite direction (i.e., Canton-S males with Harwich females) and in fertile males from either cross.

A new type of berberine derivatives was obtained by the reaction of berberrubine with aliphatic sulfonyl chlorides. The new polycyclic compounds have a sultone ring condensed to C and D rings of a protoberberine core. The reaction conditions were developed to facilitate the formation of sultones with high yields without by-product formation. Thus, it was shown that the order of addition of reagents affects the composition of the reaction products: when sulfochlorides are added to berberrubine, their corresponding 9-O-sulfonates are predominantly formed, when berberrubine is added to pre-generated sulfenes, sultones are the only products. The reaction was shown to proceed stereo-selectively and the cycle configuration was confirmed by 2D NMR spectroscopy. The inhibitory activity of the synthesized sultones and their 12-brominated analogs against the DNA-repair enzyme tyrosyl-DNA phosphodiesterase 1 (Tdp1), an important target for a potential antitumor therapy, was studied. All derivatives were active in the micromolar and submicromolar range, in contrast to the acyclic analogs and 9-O-sulfonates, which were inactive. The significance of the sultone cycle and bromine substituent in binding with the enzyme was confirmed using molecular modeling. The active inhibitors are mostly non-toxic to the HeLa cancer cell line, and several ligands show synergy with topotecan, a topoisomerase 1 poison in clinical use. Thus, novel berberine derivatives can be considered as candidates for adjuvant therapy against cancer.

The plant Rhodiola rosea L. of family Crassulaceae was extracted using the supercritical CO2-extraction method. Several experimental conditions were investigated in the pressure range of 200–500 bar, with the used volume of cosolvent ethanol in the amount of 1% in the liquid phase at a temperature in the range of 31–70°C. The most effective extraction conditions are pressure 350 bar and temperature 60°C. The extracts were analyzed by HPLC with MS/MS identification. 78 target analytes were isolated from Rhodiola rosea (Russia) using a series of column chromatography and mass spectrometry experiments. The results of the analysis showed a spectrum of the main active ingredients Rh. rosea: salidroside, rhodiolosides (B and C), rhodiosin, luteolin, catechin, quercetin, quercitrin, herbacetin, sacranoside A, vimalin, and others. In addition to the reported metabolites, 29 metabolites were newly annotated in Rh. rosea. There were flavonols: dihydroquercetin, acacetin, mearnsetin, and taxifolin-O-pentoside; flavones: apigenin-O-hexoside derivative, tricetin trimethyl ether 7-O-hexosyl-hexoside, tricin 7-O-glucoronyl-O-hexoside, tricin O-pentoside, and tricin-O-dihexoside; flavanones: eriodictyol-7-O-glucoside; flavan-3-ols: gallocatechin, hydroxycinnamic acid caffeoylmalic acid, and di-O-caffeoylquinic acid; coumarins: esculetin; esculin: fraxin; and lignans: hinokinin, pinoresinol, L-ascorbic acid, glucaric acid, palmitic acid, and linolenic acid. The results of supercritical CO2-extraction from roots and rhizomes of Rh. rosea, in particular, indicate that the extract contained all biologically active components of the plant, as well as inert mixtures of extracted compositions.

The effect of iron deficiency (ID) without anemia on the reproductive health of women in contrast to iron deficiency anemia is still insufficiently evaluated from a clinical point of view, despite a weighty theoretical basis and a large pool of clinical observations. The purpose of this review is to systematize the ID causes without anemia in women associated and not associated with reproductive disorders, the effects of ID without anemia on reproductive health, and modern approaches to the diagnosis and treatment of this pathology. ID without anemia affects most of the physiological processes in a woman's body, including hormonal regulation, immune processes and functions of the nervous system. The negative effect of ID without anemia on a woman's reproductive function is realized through hormone-mediated and immune mechanisms. ID without anemia is currently underestimated in terms of somatic and reproductive health of women, as well as quality of life. Сlinical manifestations of ID without anemia are mostly nonspecific, which is why clinicians, focusing only on hematological parameters are often explaining them by other reasons, which leads to late diagnosis. Assessment of hematological parameters alone is accompanied by significant underdiagnosis of ID without anemia. Diagnosis of ID without anemia should be carried out in women with risk factors (abnormal uterine bleeding, heavy menstrual bleeding, etc.), as well as with dyshormonal disorders, recurrent inflammatory processes in combination with ID symptoms by assessing the ferritin and transferrin saturation. To treat ID without anemia it is necessary to eliminate the etiological factor and carry out a sufficiently long-term supplementation with oral iron preparations with good tolerance and bioavailability. Iron bisglycinate is the form of iron intake that does not affect the mucous membrane of the gastrointestinal tract and is absorbed by the small intestine mucosa unchanged, which ensures its good tolerability and high efficiency for the correction of ID.

BackgroundLake Baikal is the largest body of liquid freshwater on Earth. Previous studies have described the microbial composition of this habitat, but the viral communities from this ecosystem have not been characterized in detail.ResultsHere, we describe the viral diversity of this habitat across depth and seasonal gradients. We discovered 19,475 bona fide viral sequences, which are derived from viruses predicted to infect abundant and ecologically important taxa that reside in Lake Baikal, such as Nitrospirota, Methylophilaceae, and Crenarchaeota. Diversity analysis revealed significant changes in viral community composition between epipelagic and bathypelagic zones. Analysis of the gene content of individual viral populations allowed us to describe one of the first bacteriophages that infect Nitrospirota, and their extensive repertoire of auxiliary metabolic genes that might enhance carbon fixation through the reductive TCA cycle. We also described bacteriophages of methylotrophic bacteria with the potential to enhance methanol oxidation and the S-adenosyl-L-methionine cycle.ConclusionsThese findings unraveled new ways by which viruses influence the carbon cycle in freshwater ecosystems, namely, by using auxiliary metabolic genes that act upon metabolisms of dark carbon fixation and methylotrophy. Therefore, our results shed light on the processes through which viruses can impact biogeochemical cycles of major ecological relevance.

A series of berberine and tetrahydroberberine sulfonate derivatives were prepared and tested against the tyrosyl-DNA phosphodiesterase 1 (Tdp1) DNA-repair enzyme. The berberine derivatives inhibit the Tdp1 enzyme in the low micromolar range; this is the first reported berberine based Tdp1 inhibitor. A structure–activity relationship analysis revealed the importance of bromine substitution in the 12-position on the tetrahydroberberine scaffold. Furthermore, it was shown that the addition of a sulfonate group containing a polyfluoroaromatic moiety at position 9 leads to increased potency, while most of the derivatives containing an alkyl fragment at the same position were not active. According to the molecular modeling, the bromine atom in position 12 forms a hydrogen bond to histidine 493, a key catalytic residue. The cytotoxic effect of topotecan, a clinically important topoisomerase 1 inhibitor, was doubled in the cervical cancer HeLa cell line by derivatives 11g and 12g; both displayed low toxicity without topotecan. Derivatives 11g and 12g can therefore be used for further development to sensitize the action of clinically relevant Topo1 inhibitors.

With the increasing annual production of nanoparticles (NPs), the risks of their harmful influence on the environment and human health are rising. However, our knowledge about the mechanisms of interaction between NPs and living organisms is limited. Prior studies have shown that echinoderms, and especially sea urchins, represent one of the most suitable models for risk assessment in environmental nanotoxicology. To the best of the authors&rsquo, knowledge, the sea urchin Strongylocentrotus intermedius has not been used for testing the toxicity of NPs. The present study was designed to determine the effect of 10 types of common NPs on spermatozoa activity, egg fertilization, and early stage of embryo development of the sea urchin S. intermedius. In this research, we used two types of multiwalled carbon nanotubes (CNT-1 and CNT-2), two types of carbon nanofibers (CNF-1 and CNF-2), two types of silicon nanotubes (SNT-1 and SNT-2), nanocrystals of cadmium and zinc sulfides (CdS and ZnS), gold NPs (Au), and titanium dioxide NPs (TiO2). The results of the embryotoxicity test showed the following trend in the toxicity level of used NPs: Au &gt, SNT-2 &gt, SNT-1 &gt, CdS &gt, ZnS &gt, CNF-2 &gt, CNF-1 &gt, TiO2 &gt, CNT-1 &gt, CNT-2. This research confirmed that the sea urchin S. intermedius can be considered as a sensitive and stable test model in marine nanotoxicology.

Woody liana Schisandra chinensis contains valuable lignans, which are phenylpropanoids with valuable biological activity. Among green and selective extraction methods, supercritical carbon dioxide (SC-CO2) was shown to be the method of choice for the recovery of these naturally occurring compounds. Carbon dioxide (CO2) was the solvent with the flow rate (10&minus, 25 g/min) with 2% ethanol as co-solvent. In this piece of work operative parameters and working conditions were optimized by experimenting with different pressures (200&ndash, 400 bars) and temperatures (40&ndash, 60 &deg, C). The extraction time varied from 60 to 120 min. HPLC-SPD-ESI -MS/MS techniques were applied to detect target analytes. Twenty-six different lignans were identified in the S. chinensis SC-CO2 extracts.

Four new conjugates, esters of polyhydroxysteroids with long-chain fatty acids (1&ndash, 4), were isolated from the deep-water Far Eastern starfish Ceramaster patagonicus. The structures of 1&ndash, 4 were established by NMR and ESIMS techniques as well as chemical transformations. Unusual compounds 1&ndash, 4 contain the same 5&alpha, cholestane-3&beta, 6&beta, 15&alpha, 16&beta, 26-pentahydroxysteroidal moiety and differ from each other in the fatty acid units: 5'Z,11'Z-octadecadienoic (1), 11'Z-octadecenoic (2), 5'Z,11'Z-eicosadienoic (3), and 7'Z-eicosenoic (4) acids. Previously, only one such steroid conjugate with a fatty acid was known from starfish. After 72 h of cell incubation, using MTS assay it was found that the concentrations of compounds 1, 2, and 3 that caused 50% inhibition of growth (IC50) of JB6 Cl41 cells were 81, 40, and 79 &micro, M, respectively, for MDA-MB-231 cells, IC50 of compounds 1, 2, and 3 were 74, 33, and 73 &micro, for HCT 116 cells, IC50 of compounds 1, 2, and 3 were 73, 31, and 71 &micro, M, respectively. Compound 4 was non-toxic against tested cell lines even in three days of treatment. Compound 2 (20 &micro, M) suppressed colony formation and migration of MDA-MB-231 and HCT 116 cells.

Simple Summary The growing nanotechnology industry disposes of a variety of nanoparticles with different physiochemical properties in everyday life. However, the dependence of the safety and toxicity of nanoparticles on their physicochemical properties remains unclear. Bivalve molluscs represent an efficient model for the investigation of nanoparticle toxicity owing to their filtrating ability and feeding on particles suspended in the water. Moreover, the blood cells of bivalve molluscs, the hemocytes, have been suggested as a good analog test-object to mammalian immune cells, phagocytes. In this study, we used hemocytes of three marine bivalve species, namely, Crenomytilus grayanus, Modiolus modiolus, and Arca boucardi, to evaluate and compare the toxic effects of 10 different types of nanoparticles. We gave short-term exposure of the nanoparticles to the hemocytes and registered viability and changes in their cell membrane polarization by employing flow cytometry. Metal-based nanoparticles were the most toxic to the cells of all three tested bivalve mollusc species. However, the sensitivity to different nanoparticle types varied between species. Moreover, the registered cell membrane depolarization indicated an early toxic response and raised concern that chronic long-term exposure of nanoparticles (even if they were previously declared as safe) is a serious threat for aquatic organisms. Abstract Nanoparticles (NPs) have broad applications in medicine, cosmetics, optics, catalysis, environmental purification, and other areas nowadays. With increasing annual production of NPs, the risks of their harmful influence on the environment and human health are also increasing. Currently, our knowledge about the mechanisms of the interaction between NPs and living organisms is limited. The marine species and their habitat environment are under continuous stress owing to the anthropogenic activities, which result in the release of NPs in the aquatic environment. We used a bioassay model with hemocytes of three bivalve mollusc species, namely, Crenomytilus grayanus, Modiolus modiolus, and Arca boucardi, to evaluate the toxicity of 10 different types of NPs. Specifically, we compared the cytotoxic effects and cell-membrane polarization changes in the hemocytes exposed to carbon nanotubes, carbon nanofibers, silicon nanotubes, cadmium and zinc sulfides, Au-NPs, and TiO2 NPs. Viability and the changes in hemocyte membrane polarization were measured by the flow cytometry method. The highest aquatic toxicity was registered for metal-based NPs, which caused cytotoxicity to the hemocytes of all the studied bivalve species. Our results also highlighted different sensitivities of the used tested mollusc species to specific NPs.

This study reports the differences in toxic action between cadmium sulfide (CdS) and zinc sulfide (ZnS) nanoparticles (NPs) prepared by recently developed xanthate-mediated method. The aquatic toxicity of the synthesized NPs on four marine microalgae species was explored. Growth rate, esterase activity, membrane potential, and morphological changes of microalgae cells were evaluated using flow cytometry and optical microscopy. CdS and ZnS NPs demonstrated similar level of general toxicity and growth-rate inhibition to all used microalgae species, except the red algae P. purpureum. More specifically, CdS NPs caused higher inhibition of growth rate for C. muelleri and P. purpureum, while ZnS NPs were more toxic for A. ussuriensis and H. akashiwo species. Our findings suggest that the sensitivity of different microalgae species to CdS and ZnS NPs depends on the chemical composition of NPs and their ability to interact with the components of microalgal cell-wall. The red microalga was highly resistant to ZnS NPs most likely due to the presence of phycoerythrin proteins in the outer membrane bound Zn2+ cations defending their cells from further toxic influence. The treatment with CdS NPs caused morphological changes and biochemical disorder in all tested microalgae species. The toxicity of CdS NPs is based on their higher photoactivity under visible light irradiation and lower dissociation in water, which allows them to generate more reactive oxygen species and create a higher risk of oxidative stress to aquatic organisms. The results of this study contribute to our understanding of the parameters affecting the aquatic toxicity of semiconductor NPs and provide a basis for further investigations.

Mice with mutant ATG16L develop spontaneous, severe Alzheimer’s-like disease with age, despite normal autophagy., Noncanonical functions of autophagy proteins have been implicated in neurodegenerative conditions, including Alzheimer’s disease (AD). The WD domain of the autophagy protein Atg16L is dispensable for canonical autophagy but required for its noncanonical functions. Two-year-old mice lacking this domain presented with robust β-amyloid (Aβ) pathology, tau hyperphosphorylation, reactive microgliosis, pervasive neurodegeneration, and severe behavioral and memory deficiencies, consistent with human disease. Mechanistically, we found this WD domain was required for the recycling of Aβ receptors in primary microglia. Pharmacologic suppression of neuroinflammation reversed established memory impairment and markers of disease pathology in this novel AD model. Therefore, loss of the Atg16L WD domain drives spontaneous AD in mice, and inhibition of neuroinflammation is a potential therapeutic approach for treating neurodegeneration and memory loss. A decline in expression of ATG16L in the brains of human patients with AD suggests the possibility that a similar mechanism may contribute in human disease.

Nanoparticles (NPs) have various applications in medicine, cosmetics, optics, catalysis, environmental purification, and other areas nowadays. With an increasing annual production of NPs, the risks of their harmful influence to the environment and human health is rising. Currently, our knowledge about the mechanisms of interaction between NPs and living organisms is limited. Additionally, poor understanding of how physical and chemical characteristic and different conditions influence the toxicity of NPs restrict our attempts to develop the standards and regulations which might allow us to maintain the safe living conditions. The marine species and their habitat environment are under continuous stress due to anthropogenic activities which result in the appearance of NPs in the aquatic environment. Our study aimed to evaluate and compare biochemical effects caused by the influence of different types of carbon nanotubes, carbon nanofibers, and silica nanotubes on four marine microalgae species. We have evaluated the changes in growth-rate, esterase activity, membrane polarization, and size changes of microalgae cells using flow cytometry method. Our results demonstrated that toxic effects caused by the carbon nanotubes strongly correlated with the content of heavy metal impurities in the NPs. More hydrophobic carbon NPs with less ordered structure had a higher impact on the red microalgae P. purpureum because of higher adherence between the particles and mucous covering of the algae; silica NPs caused significant inhibition of microalgae growth-rate predominantly produced by mechanical influence.

Progressive ventricular enlargement, a key feature of several neurologic and psychiatric diseases, is mediated by unknown mechanisms. Here, using murine models of 22q11-deletion syndrome (22q11DS), which is associated with schizophrenia in humans, we found progressive enlargement of lateral and third ventricles and deceleration of ciliary beating on ependymal cells lining the ventricular walls. The cilia-beating deficit observed in brain slices and in vivo is caused by elevated levels of dopamine receptors (Drd1), which are expressed in motile cilia. Haploinsufficiency of the microRNA-processing gene Dgcr8 results in Drd1 elevation, which is brought about by a reduction in Drd1-targeting microRNAs miR-382-3p and miR-674-3p. Replenishing either microRNA in 22q11DS mice normalizes ciliary beating and ventricular size. Knocking down the microRNAs or deleting their seed sites on Drd1 mimicked the cilia-beating and ventricular deficits. These results suggest that the Dgcr8–miR-382-3p/miR-674-3p–Drd1 mechanism contributes to deceleration of ciliary motility and age-dependent ventricular enlargement in 22q11DS., Schizophrenia is associated with brain ventricular enlargement. Here, the authors show in mice that 22q11 deletion, which is associated with schizophrenia, causes ventricular enlargement and motility abnormalities in cilia lining ventricle walls via a microRNA mechanism.

We have assessed the diversity of bacteria near oil-methane (area I) and methane (area II) seeps in the pelagic zone of Lake Baikal using massive parallel sequencing of 16S rRNA, pmoA, and mxaF gene fragments amplified from total DNA. At depths from the surface to 100 m, sequences belonging to Cyanobacteria dominated. In the communities to a depth of 200 m of the studied areas, Proteobacteria dominated the deeper layers of the water column. Alphaproteobacteria sequences were predominant in the community near the oil-methane seep, while the community near the methane seep was characterized by the prevalence of Alpha- and Gammaproteobacteria. Among representatives of these classes, type I methanotrophs prevailed in the 16S rRNA gene libraries from the near-bottom area, and type II methanotrophs were detected in minor quantities at different depths. In the analysis of the libraries of the pmoA and mxaF functional genes, we observed the different taxonomic composition of methanotrophic bacteria in the surface and deep layers of the water column. All pmoA sequences from area I were type II methanotrophs and were detected at a depth of 300 m, while sequences of type I methanotrophs were the most abundant in deep layers of the water column of area II. All mxaF gene sequences belonged to Methylobacterium representatives. Based on comparative analyses of 16S rRNA, pmoA, and mxaF gene fragment libraries, we suggest that there must be a wider spectrum of functional genes facilitating methane oxidation that were not detected with the primers used.

Antibiotic-associated diarrhea remains an unresolved problem in current medicine. In the last decade, in addition to idiopathic antibiotic-associated diarrhea, diseases caused by cytotoxin-producing Klebsiella oxytoca strains are becoming increasingly detected. Clinical manifestations of this infection may vary from relatively mild diarrhea without signs of hemocolitis to severe antibiotic-associated hemorrhagic colitis with predominant involvement of the right hemicolon. High prevalence of resistance to ciprofloxacin, tetracycline, gentamicin, amikacyne, and trimethoprim/sulfamethoxazole is associated with the presence of all adhesion genes of K. oxytoca and its greater cytotoxicity. The genes encoding the K. oxytoca cytotoxin (tilivalline) are a part of the pathogenicity island (PAI) and are similar to the clusters responsible for the biosynthesis of pyrrolobenzodiazepine and found in gram-positive bacteria. The most important pathogenicity factor related to the development of K. oxytoca -associated hemorrhagic colitis is a cytotoxin kleboxymycin, which is a tilivalline metabolite. The treatment strategy in K. oxytoca -associated hemorrhagic colitis is to withdraw the trigger antimicrobial agent, to refrain from administration of new antimicrobials, to administer rehydration and rational pathogenetically based therapy. Studies on the development of therapeutic bacteriophages against K. oxytoca are of pilot nature.

The effect of carbon and silicon nanotubes (CNTs and SiNTs) and carbon nanofibers (CNFs) to microscopic marine algae Heterosigma akashiwo was studied, using algal growth inhibition for 3 days (acute effect) and 7 days (chronic effect) as toxicity endpoints. The criterion of the toxic effect was the statistically significant reduction of the number of algal cells in the exposed samples compared to the control. Samples did not demonstrate toxic effects at doses 1 mg/l and 10 mg/l. CNTs and SiNTs samples at 100 mg/l exhibited both acute and chronic toxic effects. We assume that the main cause of cell death in these samples was related to the mechanical damage of cell integrity. CNFs at concentrations of 100 mg/l did not inhibit algal growth, but cells with irregular shapes were observed, which were not observed after exposure to CNTs and SiNTs. Nickel impurities present in CNFs samples are presumably the main cause of observed cell deformations.

In current work unique hexagonal microparticles of silicon oxide (phytolite), isolated from the red algae Tichocarpus crinitus, which grows in the Sea of Japan described. The structures of poytolites are characterized by the methods of optical microscopy and scanning electron microscopy. The role of these formations in plant life and the mechanism of their synthesis remains unclear.

Massive parallel sequencing of the 16S rRNA gene fragments was used to investigate the composition and diversity of microbial communities in sediments from Southern Baikal to a depth of 9 cm with 1-cm step. In the layers from the sediment surface to the lower border of oxygen penetration (2 cm), organotrophic bacteria with high similarity to the heterotrophic species Luteolibacter luojiensis constituted the largest fraction of the community. In the formation zone of Fe/Mn crusts (3–5 cm), Proteobacteria and Actinobacteria predominated in the community, while the share of Cyanobacteria was considerable. The lower reduced layers showed an increased contribution of the Bacteroidetes, while the shares of the taxa predominant in the higher layers remained significant. Analysis of archaeal 16S rRNA gene amplicons revealed predominance of the soil and aquatic Thaumarchaeota (Marine Group I lineage), which are involved in anaerobic ammonium oxidation, practically in all sediment layers. The buried oxidized layer (6–7 cm), where members of the uncultured Marine Benthic Group D lineage of the order Thermoplasmatales (Euryarchaeota) predominated, was an exception in this regard. Small numbers of archaea of the Baikal-1 lineages (below 1%) were observed in the communities from the 6–7 and 7–8 cm layers, while the archaea involved in anaerobic methane oxidation (including the ANME-2d group) were not detected.

We show for the first time that natural 2,5-diketopiperazines (cyclic dipeptides) can suppress the activity of the important anticancer target poly(ADP-ribose)polymerase (PARP). Cyclo(L-Ala-L-Ala) and cyclo(L-Ala-D-Ala) can interact with the key residues of the PARP-1 active site, as demonstrated using docking and molecular dynamics simulations. One of the amide groups of cyclo(L-Ala-L-Ala) and cyclo(L-Ala-D-Ala) forms hydrogen bonds with the Gly863 residue, while the second amide group can form a hydrogen bond with the catalytic residue Glu988, and the side chain can make a hydrophobic contact with Ala898. Newly identified diketopiperazine inhibitors are promising basic structures for the design of more effective inhibitors of PARP family enzymes. The piperazine core with two chiral centers provides many opportunities for structural optimization.

The ability of a number of nitrogen-containing compounds that simultaneously carry the adamantane and monoterpene moieties to inhibit Tdp1, an important enzyme of the DNA repair system, is studied. Inhibition of this enzyme has the potential to overcome chemotherapeutic resistance of some tumor types. Compound (+)-3c synthesized from 1-aminoadamantane and (+)-myrtenal, and compound 4a produced from 2-aminoadamantane and citronellal were found to be most potent as they inhibited Tdp1 with IC50 values of 6 and 3.5 µM, respectively. These compounds proved to have low cytotoxicity in colon HCT-116 and lung A-549 human tumor cell lines (CC50 > 50 µM). It was demonstrated that compound 4a at 10 µM enhanced cytotoxicity of topotecan, a topoisomerase 1 poison in clinical use, against HCT-116 more than fivefold and to a lesser extent of 1.5 increase in potency for A-549.

Meldonium is used clinically as an anti-ischaemic drug to treat myocardial infarction and chronic heart failure, and it had become a news making substance after the banning several elite athletes i...

Using the FISH method and PCR analysis, the presence of canonical P element was studied in the genomes of a number of laboratory lines isolated from nature in different years from the Zaprionus genus (Z. indianus) and Drosophila genus, Sophophora subgenus (D. ananassae, D. eugracilis, D. simulans, D. immigrans), Drosophila subgenus (D. virilis, D. mercatorum, D. hydei, D. funebris, D. pseudoobscura), Lordiphosa subgenus (L. magnipectinata), and Dorsilopha subgenus (D. busckii) in a search for new cases of horizontal transfer. According to our data, the L. magnipectinata genome contains sequences homologous to terminal regions of canonical P element, as well as the sequence with a weak homology from the central part of canonical P element. The P-element hybridization sites adjacent to the chromocenter were found in the D. pseudoobscura genome; this can indicate an ancient origin of the sequences homologous to the P element. The P element is absent in old D. simulans lines, except for the line isolated from nature in 2014 (in which the P element was found); this confirms data of other researchers about recent cases of horizontal P-element transfer in this species. No new cases of horizontal transfer were detected in the analyzed lines.