5C analysis of the Epidermal Differentiation Complex locus reveals distinct chromatin interaction networks between gene-rich and gene-poor TADs in skin epithelial cells.

Mammalian genomes contain several dozens of large (>0.5 Mbp) lineage-specific gene loci harbouring functionally related genes. However, spatial chromatin folding, organization of the enhancer-promoter networks and their relevance to Topologically Associating Domains (TADs) in these loci remain poorly understood. TADs are principle units of the genome folding and represents the DNA regions within which DNA interacts more frequently and less frequently across the TAD boundary. Here, we used Chromatin Conformation Capture Carbon Copy (5C) technology to characterize spatial chromatin interaction network in the 3.1 Mb Epidermal Differentiation Complex (EDC) locus harbouring 61 functionally related genes that show lineage-specific activation during terminal keratinocyte differentiation in the epidermis. 5C data validated by 3D-FISH demonstrate that the EDC locus is organized into several TADs showing distinct lineage-specific chromatin interaction networks based on their transcription activity and the gene-rich or gene-poor status. Correlation of the 5C results with genome-wide studies for enhancer-specific histone modifications (H3K4me1 and H3K27ac) revealed that the majority of spatial chromatin interactions that involves the gene-rich TADs at the EDC locus in keratinocytes include both intra- and inter-TAD interaction networks, connecting gene promoters and enhancers. Compared to thymocytes in which the EDC locus is mostly transcriptionally inactive, these interactions were found to be keratinocyte-specific. In keratinocytes, the promoter-enhancer anchoring regions in the gene-rich transcriptionally active TADs are enriched for the binding of chromatin architectural proteins CTCF, Rad21 and chromatin remodeler Brg1. In contrast to gene-rich TADs, gene-poor TADs show preferential spatial contacts with each other, do not contain active enhancers and show decreased binding of CTCF, Rad21 and Brg1 in keratinocytes. Thus, spatial interactions between gene promoters and enhancers at the multi-TAD EDC locus in skin epithelial cells are cell type-specific and involve extensive contacts within TADs as well as between different gene-rich TADs, forming the framework for lineage-specific transcription.

Biomarkers in bivalve mollusks and amphipods for assessment of effects linked to cyanobacteria and elodea: Mesocosm study.

The effects of cyanobacteria (Aphanizomenon flos-aquae (90%), Microcystis aeruginosa) and dense Elodea canadensis beds on the health endpoints of the amphipod Gmelinoides fasciatus and bivalve mollusc Unio pictorum were examined in mesocosms with simulated summer conditions (July-August 2018) in the environment of the Rybinsk Reservoir (Volga River Basin, Russia). Four treatments were conducted, including one control and three treatments with influencing factors, cyanobacteria and dense elodea beds (separately and combined). After 20 days of exposure, we evaluated the frequency of malformed and dead embryos in amphipods, heart rate (HR) and its recovery (HRR) after stress tests in molluscs as well as heat tolerance (critical thermal maximum or CTMax) in both amphipods and molluscs. The significant effect, such as elevated number of malformed embryos, was recorded after exposure with cyanobacteria (separately and combined with elodea) and presence of microcystins (MC) in water (0.17 µg/l, 40% of the most toxic MC-LR contribution). This study provided evidence that an elevated number (>5% of the total number per female) of malformed embryos in amphipods showed noticeable toxicity effects in the presence of cyanobacteria. The decreased oxygen under the influence of dense elodea beds led to a decrease in HR (and an increase in HRR) in molluscs. The notable effects on all studied biomarkers, embryo malformation frequency and heat tolerance in the amphipod G. fasciatus, as well as the heat tolerance and heart rate in the mollusc U. pictorum, were found when both factors (elodea and cyanobacteria) were combined. The applied endpoints could be further developed for environmental monitoring, but the obtained results support the importance of the combined use of several biomarkers and species, especially in the case of multi-factor environmental stress.

p63 and Brg1 control developmentally regulated higher-order chromatin remodelling at the epidermal differentiation complex locus in epidermal progenitor cells.

Chromatin structural states and their remodelling, including higher-order chromatin folding and three-dimensional (3D) genome organisation, play an important role in the control of gene expression. The role of 3D genome organisation in the control and execution of lineage-specific transcription programmes during the development and differentiation of multipotent stem cells into specialised cell types remains poorly understood. Here, we show that substantial remodelling of the higher-order chromatin structure of the epidermal differentiation complex (EDC), a keratinocyte lineage-specific gene locus on mouse chromosome 3, occurs during epidermal morphogenesis. During epidermal development, the locus relocates away from the nuclear periphery towards the nuclear interior into a compartment enriched in SC35-positive nuclear speckles. Relocation of the EDC locus occurs prior to the full activation of EDC genes involved in controlling terminal keratinocyte differentiation and is a lineage-specific, developmentally regulated event controlled by transcription factor p63, a master regulator of epidermal development. We also show that, in epidermal progenitor cells, p63 directly regulates the expression of the ATP-dependent chromatin remodeller Brg1, which binds to distinct domains within the EDC and is required for relocation of the EDC towards the nuclear interior. Furthermore, Brg1 also regulates gene expression within the EDC locus during epidermal morphogenesis. Thus, p63 and its direct target Brg1 play an essential role in remodelling the higher-order chromatin structure of the EDC and in the specific positioning of this locus within the landscape of the 3D nuclear space, as required for the efficient expression of EDC genes in epidermal progenitor cells during skin development.

Lhx2 differentially regulates Sox9, Tcf4 and Lgr5 in hair follicle stem cells to promote epidermal regeneration after injury.

The Lhx2 transcription factor plays essential roles in morphogenesis and patterning of ectodermal derivatives as well as in controlling stem cell activity. Here, we show that during murine skin morphogenesis, Lhx2 is expressed in the hair follicle (HF) buds, whereas in postnatal telogen HFs Lhx2(+) cells reside in the stem cell-enriched epithelial compartments (bulge, secondary hair germ) and co-express selected stem cell markers (Sox9, Tcf4 and Lgr5). Remarkably, Lhx2(+) cells represent the vast majority of cells in the bulge and secondary hair germ that proliferate in response to skin injury. This is functionally important, as wound re-epithelization is significantly retarded in heterozygous Lhx2 knockout (+/-) mice, whereas anagen onset in the HFs located closely to the wound is accelerated compared with wild-type mice. Cell proliferation in the bulge and the number of Sox9(+) and Tcf4(+) cells in the HFs closely adjacent to the wound in Lhx2(+/-) mice are decreased in comparison with wild-type controls, whereas expression of Lgr5 and cell proliferation in the secondary hair germ are increased. Furthermore, acceleration of wound-induced anagen development in Lhx2(+/-) mice is inhibited by administration of Lgr5 siRNA. Finally, Chip-on-chip/ChIP-qPCR and reporter assay analyses identified Sox9, Tcf4 and Lgr5 as direct Lhx2 targets in keratinocytes. These data strongly suggest that Lhx2 positively regulates Sox9 and Tcf4 in the bulge cells, and promotes wound re-epithelization, whereas it simultaneously negatively regulates Lgr5 in the secondary hair germ and inhibits HF cycling. Thus, Lhx2 operates as an important regulator of epithelial stem cell activity in the skin response to injury.

Pathobiology of chemotherapy-induced hair loss.

Hair loss can be a psychologically devastating adverse effect of chemotherapy, but satisfactory management strategies for chemotherapy-induced alopecia remain elusive. In this Review we focus on the complex pathobiology of this side-effect. We discuss the clinical features and current management approaches, then draw upon evidence from mouse models and human hair-follicle organ-culture studies to explore the main pathobiology principles and explain why chemotherapy-induced alopecia is so challenging to manage. P53-dependent apoptosis of hair-matrix keratinocytes and chemotherapy-induced hair-cycle abnormalities, driven by the dystrophic anagen or dystrophic catagen pathway, play important parts in the degree of hair-follicle damage, alopecia phenotype, and hair-regrowth pattern. Additionally, the degree of hair-follicle stem-cell damage determines whether chemotherapy-induced alopecia is reversible. We highlight the need for carefully designed preclinical research models to generate novel, clinically relevant pointers to how this condition may be overcome.

Inhibition of the CoREST Repressor Complex Promotes Wound Re-Epithelialization through the Regulation of Keratinocyte Migration.

Wound healing is a complex process involving phases of hemostasis, inflammation, proliferation, and remodeling. The regenerative process in the skin requires coordination between many regulators, including signaling molecules, transcription factors, and the epigenetic machinery. In this study, we show that chromatin regulators HDAC1 and LSD1, key components of the CoREST repressor complex, are upregulated in the regenerating epidermis during wound repair. We also show that corin, a synthetic dual inhibitor of the CoREST complex and HDAC1/LSD1 activities, significantly accelerates wound closure through enhanced re-epithelialization in a mouse tail wound model. Acetylated H3K9 (methylation of histone H3 at lysine 9) expression, a histone modification targeted by HDAC1, is increased in keratinocytes after topical treatment with 100 nM and 1 µM of corin. In vitro experiments demonstrate that corin promotes migration and inhibits the proliferation of human keratinocytes. Furthermore, expression levels of genes promoting keratinocyte migration, such as AREG, CD24, EPHB2, ITGAX, PTGS, SCT1, SERPINB2, SERPINE1, SLPI, SNAI2, and TWIST, increased in keratinocytes treated with corin. These data demonstrate that dual inhibition of class I histone deacetylases and LSD1 by corin may serve as a new approach for promoting wound re-epithelialization and provide a platform for further applications of corin for the treatment of chronic wounds.

Responses of zebra and quagga mussels to copper and tribytiltin exposure: Bioconcentration, metabolic and cardiac biomarkers.

One of the top ecological priorities is to find sensitive indicators for pollution monitoring. This study focuses on the bioconcentration and responses (condition index, survival, oxygen consumption, heart rates, and oxidative stress and neurotoxic effect biomarkers) of mussels from the Volga River basin, Dreissena polymorpha and Dreissena bugensis, to long-term exposure to toxic chemicals such as tributyltin (TBT, 25 and 100 ng/L) and copper (Cu, 100 and 1000 µg/L). We found that TBT was present in the tissues of zebra and quagga mussels in comparable amounts, whereas the bioconcentration factor of Cu varied depending on its concentration in water. Differences in responses between the two species were revealed. When exposed to high Cu concentrations or a Cu-TBT mixture, quagga mussels had a lower survival rate and a longer heart rate recovery time than zebra mussels. TBT treatment caused neurotoxicity (decreased acetylcholinesterase activity) and oxidative stress (increased levels of thiobarbituric acid reactive substances) in both species. TBT and Cu levels in mussel tissues correlated positively with the condition index, but correlated with the level of acetylcholinesterase in the mussel gills. The principal component analysis revealed three main components: the first consists of linear combinations of 14 variables reflecting TBT water pollution, TBT and Cu levels in mussel tissues, and biochemical indicators; the second includes Cu water concentration, cardiac tolerance, and mussel size; and the third combines weight, metabolic rate, and heart rates. Quagga mussels are less tolerable to contaminants than zebra mussels, so they may be used as a sensitive indicator.

Seasonal Diet Changes and Trophic Links of Cold-Water Fish (Coregonus albula) within a Northern Lake Ecosystem.

The seasonal feeding patterns of the cold-adapted fish, Coregonus albula, are poorly studied in high-latitude lakes but could provide insight for predicting the effects of global warming. We examined vendace's diet composition, traced the carbon and nitrogen isotope ratios from producers to consumers in the food web, and estimated vendace's trophic position in a subarctic lake (the White Sea basin). Results showed the vendace to be a typical euryphagous fish, but clear seasonal differences were found in the relative importance of plankton and benthos in the diet. The vendace consumed primarily benthic amphipods in the summer, planktonic cladocerans in the autumn, and copepods in the winter-spring (under ice); larvae of aquatic insects were the second-most important food items throughout the year. Because of the substantial proportion of fish embryos in its diet, the vendace had a trophic position similar to that of a predatory fish (perch). The Bayesian food source-mixing model revealed that the majority of vendace energy derives from planktonic copepods. The dominant Cyclops had the lowest carbon isotope values, suggesting a carbon-depleted diet typical for methanotrophic bacteria, as its probable food source was in a lake under ice. Understanding the feeding patterns of vendace provides information to better predict the potential biotic effects of environmental change on lake ecosystems.

MicroRNA-21 is an important downstream component of BMP signalling in epidermal keratinocytes.

Bone morphogenetic proteins (BMPs) play essential roles in the control of skin development, postnatal tissue remodelling and tumorigenesis. To explore whether some of the effects of BMP signalling are mediated by microRNAs, we performed genome-wide microRNA (miRNA) screening in primary mouse keratinocytes after BMP4 treatment. Microarray analysis revealed substantial BMP4-dependent changes in the expression of distinct miRNAs, including miR-21. Real-time PCR confirmed that BMP4 dramatically inhibits miR-21 expression in the keratinocytes. Consistently, significantly increased levels of miR-21 were observed in transgenic mice overexpressing the BMP antagonist noggin under control of the K14 promoter (K14-noggin). By in situ hybridization, miR-21 expression was observed in the epidermis and hair follicle epithelium in normal mouse skin. In K14-noggin skin, miR-21 was prominently expressed in the epidermis, as well as in the peripheral portion of trichofolliculoma-like hair follicle-derived tumours that contain proliferating and poorly differentiated cells. By transfecting keratinocytes with a miR-21 mimic, we identified the existence of two groups of the BMP target genes, which are differentially regulated by miR-21. These included selected BMP-dependent tumour-suppressor genes (Pten, Pdcd4, Timp3 and Tpm1) negatively regulated by miR-21, as well as miR-21-independent Id1, Id2, Id3 and Msx2 that predominantly mediate the effects of BMPs on cell differentiation. In primary keratinocytes and HaCaT cells, miR-21 prevented the inhibitory effects of BMP4 on cell proliferation and migration. Thus, our study establishes a novel mechanism for the regulation of BMP-induced effects in the skin and suggests miRNAs are important modulators of the effects of growth factor signalling pathways on skin development and tumorigenesis.

Algicidal Activity and Microcystin-LR Destruction by a Novel Strain Penicillium sp. GF3 Isolated from the Gulf of Finland (Baltic Sea).

The present article focuses on a strain of ascomycete GF3 isolated from a water sample taken in the Gulf of Finland. Based on phylogenetic analysis data, the isolate was identified as Penicillium sp. GF3. The fungus GF3 demonstrates algicidal activity towards cyanobacteria (98-100%). The algicidal effect on green algae did not exceed 50%. The isolate GF3 exhibits an indirect attack mode by releasing metabolites with algicidal and/or lytic activity into the environment. Moreover, the strain Penicillium sp. GF3 is able to degrade MC-LR. After 72 h of GF3 cultivation, the MC-LR content was reduced by 34.1% and 26.7% at initial 0.1 µg/mL and 0.45 µg/mL concentrations, respectively. The high stress resistance of the GF3 to toxic MC-LR is provided by a 1.5-fold activation of catalase activity and a change in the reduced glutathione content. Additionally, during the MC-LR biotransformation, a MC-LR-GSH conjugate and linearized MC-LR were identified. The linearized MC-LR in the presence of fungi capable of degrading MCs was revealed for the first time. Using Daphnia magna as a bioindicator, it was shown that the MC-LR biotransformation led to the formation of less toxic intermediates. The toxicity of the fungal filtrate is reduced by five times compared to the abiotic control. Our findings enhance the understanding of the role that ascomycete fungi have as potential bioagents for cyanoHABs to control and detoxify water bodies.

Effects of Algicidal Macrophyte Metabolites on Cyanobacteria, Microcystins, Other Plankton, and Fish in Microcosms.

To control harmful algae blooms (HABs), methods based on natural mechanisms are now required. We investigated the effects of an algicide derived from macrophyte metabolites, namely mixtures of gallic, tetradecanoic, heptanoic, and octanoic acids (1:1:1:1 mass ratio, a total concentration of 14 mg/L), on the biomass of cyanobacteria and other plankton and the production of microcystins under experimental conditions. Two types of microcosms have been created: simple (microalgae, cyanobacteria, and zooplankton) and complex (microalgae, cyanobacteria, zooplankton, and planktivorous fish). We observed the dynamics of the phytoplankton structure, the concentrations of microcystins and chlorophyll-a, hydrochemistry, and the status of zooplankton and fish in both types of microcosms with and without algicide for one month (from 19 July to 19 August 2021). The introduction of algicide caused changes in phytoplankton structure, a drop in cyanobacterial biomass, and a decrease in the total concentration of microcystins. Surprisingly, the contributions of the most toxic microcystins (LR form) were higher in both types of microcosms exposed to algicide than in microcosms without algicide. The inhibitory effect on the cyanobacterial biomass was most significant in complex ecosystems (containing fish), while it was only observed at the end of the exposure in simple ecosystems. Not only algicide but also phytoplankton consumed by fish and zooplankton, as well as nutrient excretory activity by both consumers, seem to have impact on cyanobacterial biomass. This study found that the using chemical substances similar to macrophyte metabolites can help regulate HABs and cyanotoxins. However, the results differ depending on ecosystem type.

DNA dioxygenases Tet2/3 regulate gene promoter accessibility and chromatin topology in lineage-specific loci to control epithelial differentiation.

Execution of lineage-specific differentiation programs requires tight coordination between many regulators including Ten-eleven translocation (TET) family enzymes, catalyzing 5-methylcytosine oxidation in DNA. Here, by using Keratin 14-Cre-driven ablation of Tet genes in skin epithelial cells, we demonstrate that ablation of Tet2/Tet3 results in marked alterations of hair shape and length followed by hair loss. We show that, through DNA demethylation, Tet2/Tet3 control chromatin accessibility and Dlx3 binding and promoter activity of the Krt25 and Krt28 genes regulating hair shape, as well as regulate interactions between the Krt28 gene promoter and distal enhancer. Moreover, Tet2/Tet3 also control three-dimensional chromatin topology in Keratin type I/II gene loci via DNA methylation-independent mechanisms. These data demonstrate the essential roles for Tet2/3 in establishment of lineage-specific gene expression program and control of Dlx3/Krt25/Krt28 axis in hair follicle epithelial cells and implicate modulation of DNA methylation as a novel approach for hair growth control.

Biodiversity of aquatic organisms in the Mekong Delta, Vietnam.

Background: The Mekong River is the 10th largest river in the world. It is recognised as the most productive river in Southeast Asia and economically essential to the region, with an estimated 60-65 million people living in the lower Mekong Basin. The Mekong Delta within Vietnam is considered a highly vulnerable ecosystem under threat from increasing anthropogenic pressure, such as dam construction and, as a consequence, the Delta is sinking and altering the natural hydrological cycle. Dams also lead to eutrophication and pollution of downstream water from regulated water flux and water stagnation. Another threat is climate change coupled with the lower rainfall, which could lead to an increased risk of drought in the Mekong Delta Basin. Thus, these project data represent an important baseline reference. The ecological health of the Mekong Delta's environment, as indicated by the quality and availability of its water and biological resources, largely determines the economic and social development of the region, which produces about half of the agriculture and aquaculture products of Vietnam. New information: This paper reports quantitative data on the biodiversity of six groups of aquatic organisms: bottom and pelagic fish, macrozoobenthos, microorganisms, phyto- and zooplankton in the Mekong Delta within Vietnam, as well as data on the physicochemical parameters of water and bottom sediments. The data were collected during 2018-2022 as part of the Ecolan E-3.4 programme within the framework of the research plan of the Joint Russian-Vietnamese Tropical Research and Technological Center. All presented datasets are published for the first time.

Histone Deacetylases in the Control of Epidermal Homeostasis: From Chromatin Biology toward Therapy.

Histone deacetylases (HDACs) induce gene repression and modify the activity of nonhistone proteins. In a new article in the Journal of Investigative Dermatology, Zhu et al. (2021) demonstrate essential roles for HDAC1/2 in maintaining keratinocyte proliferation and survival in adult epidermis and basal cell carcinoma, thus providing a rationale for using HDAC inhibitors for the treatment of hyperproliferative and neoplastic skin disorders.

Effects of Diclofenac on the Reproductive Health, Respiratory Rate, Cardiac Activity, and Heat Tolerance of Aquatic Animals.

Diclofenac is an important pharmaceutical present in the water cycle of wastewater treatment and one of the most distributed drugs in aquatic ecosystems. Despite the great interest in the fate of diclofenac in freshwaters, the effects of environmentally relevant concentrations on invertebrates are still unclear. Two species of freshwater invertebrates, the amphipod Gmelinoides fasciatus and the bivalve mollusk Unio pictorum, were exposed to diclofenac concentrations of 0.001-2 µg/L (environmentally relevant levels) for 96 h. A set of biological endpoints (survival, fecundity, embryo abnormalities, respiration and heart rates, heat tolerance, and cardiac stress tolerance) were estimated in exposed invertebrates. Effects of diclofenac on amphipod metabolic rate and reproduction (number and state of embryos) and adaptive capacity (cardiac stress tolerance) in both species were evident. The oxygen consumption of amphipods exposed to diclofenac of 0.1-2 µg/L was 1.5-2 times higher than in the control, indicating increased energy requirements for standard metabolism in the presence of diclofenac (>0.1 µg/L). The heart rate recovery time in mollusks after heating to critical temperature (30 °C) was 1.7 and 9 times greater in mollusks exposed to 0.1 and 0.9 µg/L, respectively, than in the control (24 min). A level of diclofenac >0.9 µg/L adversely affected amphipod embryos, leading to an increase in the number of embryos with impaired development, which subsequently died. Thus, the lowest effective concentration of diclofenac (0.1 µg/L) led to increased energy demands of animals while reducing cardiac stress tolerance, and at a level close to 1 µg/L reproductive disorders (elevated mortality of the embryos) occurred. Environ Toxicol Chem 2022;41:677-686. © 2021 SETAC.

Genotoxicity of Natural Water during the Mass Development of Cyanobacteria Evaluated by the Allium Test Method: A Model Experiment with Microcosms.

Cyanobacteria, which develop abundantly in aquatic ecosystems, can be harmful to humans and animals not only by releasing toxins that cause poisoning but also by provoking cytogenetic effects. The influence of the mass development of cyanobacteria on the genotoxic properties of natural water has been studied in model ecosystems (microcosms) with different compositions of biotic components (zooplankton, amphipods and fish). The validated plant test system "Allium test" was used in this study. Genotoxic effects were detected at microcystin concentrations below those established by the World Health Organization (WHO) for drinking water. In all experimental treatments, cells with disorders such as polyploidy and mitotic abnormalities associated with damage to the mitotic spindle, including c-mitosis, as well as lagging chromosomes were found. Genotoxic effects were associated with the abundance of cyanobacteria, which, in turn, depended on the composition of aquatic organisms in the experimental ecosystem. Fish, to a greater extent than other aquatic animals, maintain an abundance of cyanobacteria. After one month, in microcosms with fish, mitotic abnormalities and polyploidy continued to be detected, whereas in other treatments, there were no statistically significant genotoxic effects. In microcosms with amphipods, the number and biomass of cyanobacteria decreased to the greatest extent, and only one parameter of genotoxic activity (frequency of polyploidy) significantly differed from the control.

Skin Aging in Long-Lived Naked Mole-Rats Is Accompanied by Increased Expression of Longevity-Associated and Tumor Suppressor Genes.

Naked mole-rats (NMRs) (Heterocephalus glaber) are long-lived mammals that possess a natural resistance to cancer and other age-related pathologies, maintaining a healthy life span >30 years. In this study, using immunohistochemical and RNA-sequencing analyses, we compare skin morphology, cellular composition, and global transcriptome signatures between young and aged (aged 3‒4 vs. 19‒23 years, respectively) NMRs. We show that similar to aging in human skin, aging in NMRs is accompanied by a decrease in epidermal thickness; keratinocyte proliferation; and a decline in the number of Merkel cells, T cells, antigen-presenting cells, and melanocytes. Similar to that in human skin aging, expression levels of dermal collagens are decreased, whereas matrix metalloproteinase 9 and matrix metalloproteinase 11 levels increased in aged versus in young NMR skin. RNA-sequencing analyses reveal that in contrast to human or mouse skin aging, the transcript levels of several longevity-associated (Igfbp3, Igf2bp3, Ing2) and tumor-suppressor (Btg2, Cdkn1a, Cdkn2c, Dnmt3a, Hic1, Socs3, Sfrp1, Sfrp5, Thbs1, Tsc1, Zfp36) genes are increased in aged NMR skin. Overall, these data suggest that specific features in the NMR skin aging transcriptome might contribute to the resistance of NMRs to spontaneous skin carcinogenesis and provide a platform for further investigations of NMRs as a model organism for studying the biology and disease resistance of human skin.

Micro-RNA-31 controls hair cycle-associated changes in gene expression programs of the skin and hair follicle.

The hair follicle is a cyclic biological system that progresses through stages of growth, regression, and quiescence, which involves dynamic changes in a program of gene regulation. Micro-RNAs (miRNAs) are critically important for the control of gene expression and silencing. Here, we show that global miRNA expression in the skin markedly changes during distinct stages of the hair cycle in mice. Furthermore, we show that expression of miR-31 markedly increases during anagen and decreases during catagen and telogen. Administration of antisense miR-31 inhibitor into mouse skin during the early- and midanagen phases of the hair cycle results in accelerated anagen development, and altered differentiation of hair matrix keratinocytes and hair shaft formation. Microarray, qRT-PCR and Western blot analyses revealed that miR-31 negatively regulates expression of Fgf10, the components of Wnt and BMP signaling pathways Sclerostin and BAMBI, and Dlx3 transcription factor, as well as selected keratin genes, both in vitro and in vivo. Using luciferase reporter assay, we show that Krt16, Krt17, Dlx3, and Fgf10 serve as direct miR-31 targets. Thus, by targeting a number of growth regulatory molecules and cytoskeletal proteins, miR-31 is involved in establishing an optimal balance of gene expression in the hair follicle required for its proper growth and hair fiber formation.

Shifted mineral ions transport in the mollusk Unio pictorum exposed to environmental concentrations of diclofenac.

Previous studies showed that diclofenac (DCF), when released in the environment, can be toxic to aquatic animals (fish and mollusks), affecting gills, which are the main organ of ionic regulation. This study focuses on detecting the effects of relevant environmental concentrations of DCF (0.1-1 µg L-1) on the transport of main mineral cations, i.e. sodium (Na), potassium (K), calcium (Ca), and magnesium (Mg), by widely distributed freshwater bivalve mollusks Unio pictorum. After 96-h exposure to river aerated water at 25 °C with DCF concentrations of 0 (control), 0.1 (treatment I), and 1 µg L-1 (treatment II), the mollusks were transferred to deionized water, and daily (for 7 days) concentrations of these cations in the medium have been measured. Animals exposed to 1 µg L-1 DCF maintained the ionic balance between the organism and the diluted medium at a significantly higher level of Na, K, and Mg ions in water compared to the control and animals exposed to 0.1 µg L-1 DCF. At 0.1 µg L-1 DCF, the greater loss concerning the control (p < 0.05) was found only for Na ion. There were no differences in the dynamics of Ca ions between control and both treatments. This study showed that detectable environmental concentrations of DCF in natural waters can influence the transport of main cations required by freshwater animals to maintain their ionic balance, and the observed effect (elevated ion loss) is ion-specific and also dose-dependent.

Hazardous substances in the sediments and their pathways from potential sources in the eastern Gulf of Finland.

Contamination by hazardous substances is one of the main environmental problems in the eastern Gulf of Finland, Baltic Sea. A trilateral effort to sample and analyse heavy metals (HMs), polycyclic aromatic hydrocarbons (PAHs), and organotins from bottom sediments in 2019-2020 were conducted along with harvesting historical data in Russian, Estonian and Finnish waters. We suggest that the input of organotins still occurs along the ship traffic routes. The tributyltin content exceeded the established quality criteria up to more than 300 times. High contamination by PAHs found near the ports, most likely originate from incomplete fuel incineration processes. The Neva River Estuary and Luga Bay might potentially suffer from severe cadmium contamination. The high ecological risk attributed to the HMs was detected at deep offshore areas. The simulated accumulation pattern qualitatively agrees with field observations of HMs in sediments, demonstrating the potential of numerical tools to tackle the hazardous substances problems.