Vimentin Is a Novel Anti-Cancer Therapeutic Target; Insights from In Vitro and In Vivo Mice Xenograft Studies

BACKGROUND:Vimentin is a ubiquitous mesenchymal intermediate filament supporting mechano-structural integrity of quiescent cells while participating in adhesion, migration, survival, and cell signaling processes via dynamic assembly/disassembly in activated cells. Soft tissue sarcomas and some epithelial cancers exhibiting "epithelial to mesenchymal transition" phenotypes express vimentin. Withaferin-A, a naturally derived bioactive compound, may molecularly target vimentin, so we sought to evaluate its effects on tumor growth in vitro and in vivo thereby elucidating the role of vimentin in drug-induced responses. METHODS AND FINDINGS:Withaferin-A elicited marked apoptosis and vimentin cleavage in vimentin-expressing tumor cells but significantly less in normal mesenchymal cells. This proapoptotic response was abrogated after vimentin knockdown or by blockade of caspase-induced vimentin degradation via caspase inhibitors or overexpression of mutated caspase-resistant vimentin. Pronounced anti-angiogenic effects of Withaferin-A were demonstrated, with only minimal effects seen in non-proliferating endothelial cells. Moreover, Withaferin-A significantly blocked soft tissue sarcoma growth, local recurrence, and metastasis in a panel of soft tissue sarcoma xenograft experiments. Apoptosis, decreased angiogenesis, and vimentin degradation were all seen in Withaferin-A treated specimens. CONCLUSIONS:In light of these findings, evaluation of Withaferin-A, its analogs, or other anti-vimentin therapeutic approaches in soft tissue sarcoma and "epithelial to mesenchymal transition" clinical contexts is warranted

Erot spatiaalisissa ja ajallisissa reaktionormeissa kevään ja syksyn fenologisille tapahtumille

For species to stay temporally tuned to their environment, they use cues such as the accumulation of degree-days. The relationships between the timing of a phenological event in a population and its environmental cue can be described by a population-level reaction norm. Variation in reaction norms along environmental gradients may either intensify the envi- ronmental effects on timing (cogradient variation) or attenu- ate the effects (countergradient variation). To resolve spatial and seasonal variation in species’ response, we use a unique dataset of 91 taxa and 178 phenological events observed across a network of 472 monitoring sites, spread across the nations of the former Soviet Union. We show that compared to local rates of advancement of phenological events with the advancement of temperature-related cues (i.e., variation within site over years), spatial variation in reaction normsPeer reviewe

Crowdsourcing Fungal Biodiversity : Revision of Inaturalist Observations in Northwestern Siberia

The paper presents the first analysis of crowdsourcing data of all observations of fungi (including lichens) and myxomycetes in Northwestern Siberia uploaded to iNaturalist.org to date (24.02.2022). The Introduction presents an analysis of fungal diversity crowdsourcing globally, in Russia, and in the region of interest. Materials and methods describe the protocol of uploading data to iNaturalist.org, the structure of the crowdsourcing community. initiative to revise the accumulated data. procedures of data analysis, and compilation of a dataset of revised crowdsourced data. The Results present the analysis of accumulated data by several parameters: temporal, geographical and taxonomical scope, observation and identification efforts, identifiability of various taxa, species novelty and Red Data Book categories and the protection status of registered observations. The Discussion provides data on usability of crowdsourcing data for biodiversity research and conservation of fungi, including pros and contras. The Electronic Supplements to the paper include an annotated checklist of observations of protected species with information on Red Data Book categories and the protection status, and an annotated checklist of regional records of new taxa. The paper is supplemented with a dataset of about 15 000 revised and annotated records available through Global Biodiversity Information Facility (GBIF). The tradition of crowdsourcing is rooted in mycological societies around the world, including Russia. In Northwestern Siberia, a regional mycological club was established in 2018, encouraging its members to contribute observations of fungi on iNaturalist.org. A total of about 15 000 observations of fungi and myxomycetes were uploaded so far, by about 200 observers, from three administrative regions (Yamalo-Nenetsky Autonomous Okrug, Khanty-Mansi Autonomous Okrug, and Tyumen Region). The geographical coverage of crowdsourcing observations remains low. However. the observation activity has increased in the last four years. The goal of this study consisted of a collaborative effort of professional mycologists invited to help with the identification of these observations and analysis of the accumulated data. As a result, all observations were reviewed by at least one expert. About half of all the observations have been identified reliably to the species level and received Research Grade status. Of those, 90 species (195 records) represented records of taxa new to their respective regions: 876 records of 53 species of protected species provide important data for conservation programmes. The other half of the observations consists of records still under-identified for various reasons: poor quality photographs, complex taxa (impossible to identify without microscopic or molecular study). or lack of experts in a particular taxonomic group. The Discussion section summarises the pros and cons of the use of crowdsourcing for the study and conservation of regional fungal diversity, and summarises the dispute on this subject among mycologists. Further research initiatives involving crowdsourcing data must focus on an increase in the quality of observations and strive to introduce the habit of collecting voucher specimens among the community of amateurs. The timely feedback from experts is also important to provide quality and the increase of personal involvement.Peer reviewe

Chronicles of nature calendar, a long-term and large-scale multitaxon database on phenology

We present an extensive, large-scale, long-term and multitaxon database on phenological and climatic variation, involving 506,186 observation dates acquired in 471 localities in Russian Federation, Ukraine, Uzbekistan, Belarus and Kyrgyzstan. The data cover the period 1890-2018, with 96% of the data being from 1960 onwards. The database is rich in plants, birds and climatic events, but also includes insects, amphibians, reptiles and fungi. The database includes multiple events per species, such as the onset days of leaf unfolding and leaf fall for plants, and the days for first spring and last autumn occurrences for birds. The data were acquired using standardized methods by permanent staff of national parks and nature reserves (87% of the data) and members of a phenological observation network (13% of the data). The database is valuable for exploring how species respond in their phenology to climate change. Large-scale analyses of spatial variation in phenological response can help to better predict the consequences of species and community responses to climate change.Peer reviewe

Phenological shifts of abiotic events, producers and consumers across a continent

Ongoing climate change can shift organism phenology in ways that vary depending on species, habitats and climate factors studied. To probe for large-scale patterns in associated phenological change, we use 70,709 observations from six decades of systematic monitoring across the former Union of Soviet Socialist Republics. Among 110 phenological events related to plants, birds, insects, amphibians and fungi, we find a mosaic of change, defying simple predictions of earlier springs, later autumns and stronger changes at higher latitudes and elevations. Site mean temperature emerged as a strong predictor of local phenology, but the magnitude and direction of change varied with trophic level and the relative timing of an event. Beyond temperature-associated variation, we uncover high variation among both sites and years, with some sites being characterized by disproportionately long seasons and others by short ones. Our findings emphasize concerns regarding ecosystem integrity and highlight the difficulty of predicting climate change outcomes. The authors use systematic monitoring across the former USSR to investigate phenological changes across taxa. The long-term mean temperature of a site emerged as a strong predictor of phenological change, with further imprints of trophic level, event timing, site, year and biotic interactions.Peer reviewe

ИССЛЕДОВАНИЕ ДИНАМИКИ ТЕРРИТОРИАЛЬНОГО РАСПРОСТРАНЕНИЯ И ЭКОЛОГИИ РЕДКИХ МЛЕКОПИТАЮЩИХ ТАЕЖНОЙ ЕВРАЗИИ (НА ПРИМЕРЕ ЛЕТЯГИ PTEROMYS VOLANS, RODENTIA, PTEROMYIDAE) in English INVESTIGATION OF THE DYNAMICS OF REGIONAL DISTRIBUTION AND ECOLOGY OF RARE MAMMALS TAIGA EURASIA (FOR EXAMPLE Letyago PTEROMYS VOLANS, RODENTIA, PTEROMYIDAE)

This study of the spatial distribution and ecology of the flying squirrel during the turn of the 20th century provides a description of new methods and techniques for detecting and accounting flying squirrels in the forest zone of Eurasia. The flying squirrel population area covers the territory of 61 regions of Russia, including Kamchatsky Krai and Chukotka Autonomous District. The number of flying squirrels in Karelia especially to the east – in the Arkhangelsk region and Western Siberia – significantly exceeds that of Finland, but considerable spatial variability in the number is obvious through all the regions: there are areas where this animal is quite abundant, or inhabits all the territory rather evenly, and there are areas where it is completely absent in vast territories even with seemingly favourable conditions. The flying squirrel is quite difficult to study and the reasons of its absence in obviously favourable areas are still to be explained. Some reasons are: the specificity of favourable landscape, forest coverage pattern, trophic relationships with predators and genetic aspect. A number of hypotheses are supposed to be tested in the nearest future. Key words: accounting, flying squirrel, forest zone, home range, spatial distribution.Peer reviewe

Numerical Study of GaP Nanowires: Individual and Coupled Optical Waveguides and Resonant Phenomena

The development of novel nanophotonic devices and circuits necessitates studies of optical phenomena in nanoscale structures. Catalyzed semiconductor nanowires are known for their unique properties including high crystallinity and silicon compatibility making them the perfect platform for optoelectronics and nanophotonics. In this work, we explore numerically optical properties of gallium phosphide nanowires governed by their dimensions and study waveguiding, coupling between the two wires and resonant field confinement to unveil nanoscale phenomena paving the way for the fabrication of the integrated optical circuits. Photonic coupling between the two adjacent nanowires is studied in detail to demonstrate good tolerance of the coupling to the distance between the two aligned wires providing losses not exceeding 30% for the gap of 100 nm. The dependence of this coupling is investigated with the wires placed nearby varying their relative position. It is found that due to the resonant properties of a nanowire acting as a Fabry–Perot cavity, two coupled wires represent an attractive system for control over the optical signal processing governed by the signal interference. We explore size-dependent plasmonic behaviors of the metallic Ga nanoparticle enabling GaP nanowire as an antenna-waveguide hybrid system. We demonstrate numerically that variation of the structure dimensions allows the nearfield tailoring. As such, we explore GaP NWs as a versatile platform for integrated photonic circuits