Links between biota and climate-related variables in the Baltic region using Lake Onega as an example**This work was supported by Biodiversity Bioresources Programmes grants from the Russian Academy of Sciences.

AbstractThis paper aims to reveal current changes (recent decades) in regional climatic variables like water temperature (WT), the duration of the ice-free period (ICE-FREE) and the precipitation rate (P), as exemplified by Petrozavodsk Bay (Lake Onega, European Russia), and to analyse their relationships with the global climatic indices NAO, AO and structural characteristics of biota (chlorophyll a concentration (Chl a), phytoplankton and zoobenthos abundance/biomass) in the lake ecosystem, which lies within the Baltic Sea catchment area. Spearman’s rank correlations yielded significant (p<0.05) relationships between the NAO and planktonic Cyanobacteria abundance, and also between NAO, AO, WT, P and the abundance and biomass of zoobenthos. Chl a correlates positively (R=0.66; p=0.03) with WT and negatively with ICE-FREE (R=−0.53; p=0.05). At the same time, multiple regression analysis confirmed that the global climate governs primarily the regional climatic variables and productivity level in the lake’s ecosystem, whereas most of the biotic characteristics respond to variability in the regional climate

p63 transcription factor regulates nuclear shape and expression of nuclear envelope-associated genes in epidermal keratinocytes

The maintenance of a proper nuclear architecture and 3D organization of the genes, enhancer elements and transcription machinery plays an essential role in tissue development and regeneration. Here we show that in the developing skin, epidermal progenitor cells of mice lacking p63 transcription factor display alterations in the nuclear shape accompanied by marked decrease in expression of several nuclear envelop-associated components (Lamin B1, Lamin A/C, SUN1, Nesprin-3, Plectin) compared to controls. Furthermore, ChIP-qPCR assay showed enrichment of p63 on Sun1, Syne3 and Plec promoters, suggesting them as p63 targets. Alterations in the nuclei shape and expression of nuclear envelope-associated proteins were accompanied by altered distribution patterns of the repressive histone marks H3K27me3, H3K9me3 and heterochromatin protein 1- alpha in p63-null keratinocytes. These changes were also accompanied by downregulation of the transcriptional activity and relocation of the keratinocyte-specific gene loci away from the sites of active transcription towards the heterochromatin-enriched repressive nuclear compartments in p63-null cells. These data demonstrate functional links between the nuclear envelope organization, chromatin architecture and gene expression in keratinocytes and suggest nuclear envelope-associated genes as important targets mediating p63-regulated gene expression programme in the epidermis

Cbx4 maintains the epithelial lineage identity and cell proliferation in the developing stratified epithelium

During development, multipotent progenitor cells establish lineage-specific programmers of gene activation and silencing underlying their differentiation into specialized cell types. We show that the Polycomb component Cbx4 serves as a critical determinant that maintains the epithelial identity in the developing epidermis by repressing nonepidermal gene expression programs. Cbx4 ablation in mice results in a marked decrease of the epidermal thickness and keratinocyte (KC) proliferation associated with activation of numerous neuronal genes and genes encoding cyclin-dependent kinase inhibitors (p16/p19 and p57). Furthermore, the chromodomain- and SUMO E3 ligase–dependent Cbx4 activities differentially regulate proliferation, differentiation, and expression of nonepidermal genes in KCs. Finally, Cbx4 expression in KCs is directly regulated by p63 transcription factor, whereas Cbx4 overexpression is capable of partially rescuing the effects of p63 ablation on epidermal development. These data demonstrate that Cbx4 plays a crucial role in the p63-regulated program of epidermal differentiation, maintaining the epithelial identity and proliferative activity in KCs via repression of the selected nonepidermal lineage and cell cycle inhibitor genes

p63 regulates Satb1 to control tissue-specific chromatin remodeling during development of the epidermis

Genome organizer Satb1 is regulated by p63 and contributes to epidermal morphogenesis by remodeling chromatin structure and gene expression at the epidermal differentiation complex locus

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

YesMammalian 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.This study was supported by the grants 5R01AR064580 and 1RO1AR071727 to VAB, TKS and AAS, as well as by the grants from MRC (MR/ M010015/1) and BBSRC (BB/K010050/1) to VAB

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. © 2013 Elsevier Ltd

Long-term modification of Arctic lake ecosystems: Reference condition, degradation under toxic impacts and recovery (case study Imandra Lakes, Russia)

AbstractIn this study, published data on Lake Imandra, north-west Russia, have been synthesised to investigate trends in lake contamination and recovery due to changing inputs of heavy metals and nutrients over time. Records of water chemistry, phytoplankton, zooplankton and fish communities have been used to determine the status of aquatic ecosystem health in three distinct phases of Lake Imandra's recent history. Firstly, background (reference) conditions within the lake have been established to determine lake conditions prior to anthropogenic influences. Secondly, a period of ecosystem degradation due to anthropogenic inputs of toxic metals and nutrients has been described. Finally, evidence of lake recovery due to recent decreases of toxic metals and nutrients has been explored. Pollution of Lake Imandra began in the 1930s, reaching a peak in the 1980s. Increases in heavy metal and nutrient inputs transformed the typical Arctic ecosystem. During the contamination phase, there was a decrease in Arctic species and in biodiversity. During the last 10 years, pollution has decreased and the lake has been recolonised by Arctic water species. Ecosystem recovery is indicated by a change of predominant species, an increase in the individual mass of organisms and an increase in the biodiversity index of plankton communities. In accordance with Odum's ecosystem succession theory, this paper demonstrates that the ecosystem has transformed to a more stable condition with new defining parameters. This illustrates that the recovery of Arctic ecosystems towards pre-industrial reference conditions after a reduction in anthropogenic stresses occur, although a complete return to background conditions may not be achievable. Having determined the status of current ecosystem health within Lake Imandra, the effect of global warming on the recovery process is discussed. Climate warming in Arctic regions is likely to move the ecosystem towards a predominance of eurybiontic species in the community structure. These organisms have the ability to tolerate a wider range of environmental conditions than typical Arctic inhabitants and will gain advantages in development. This indicates that the full recovery of Arctic ecosystems in a warming climate may not be possible

Matrix Metalloproteinase-9 Is Involved in the Regulation of Hair Canal Formation.

noHair follicle (HF) morphogenesis is governed by a series of signals exchanged between the epidermal keratinocytes committed to HF-specific differentiation and the mesenchymal cells forming the follicular papilla (Schmidt-Ullrich and Paus, 2005). These interactions lead to the construction of the hair bulb, in which keratinocytes rapidly proliferate and differentiate into several cell populations forming the hair shaft and the inner root sheath. During the final steps of development, the HF elongates up to its maximal length and the hair shaft emerges through the epidermis through the hair canal that is formed at the distal portion of the HF epithelium (Schmidt-Ullrich and Paus, 2005). ...To elucidate a role for MMP-9 in the control of HF development and hair canal formation, its expression was studied by immunohistochemistry in cryosections of embryonic and postnatal skin of C57BL/6 mice (Sharov et al., 2003), and was correlated to the micro-anatomy of the developing hair canal depicted by high-resolution light microscopy, as described previously (Magerl et al., 2001). MMP-9 expression was not observed in the epidermis and developing HF placodes

Nanoscale Electric Field Probing in a Single Nanowire with Raman Spectroscopy and Elastic Strain

In this work we investigate the Raman response of extremely strained gallium phosphide nanowires. We analyze new strain-induced spectral phenomena such as 2-fold and 3-fold phonon peak splitting which arise due to nontrivial internal electric field distribution coupled with inhomogeneous strain. We show that high bending strain acts as a probe allowing us to define the electric field distribution with deep subwavelength resolution using the corresponding changes of the Raman spectra. We investigate the nature of the localization with respect to nanowire diameter, excitation spot position, and light polarization, supporting the experiment with 3D numerical modeling. Based on our findings we propose a research tool allowing to precisely localize the electric field in a certain subwavelength region of the nanophotonic resonator