MITF-the first 25 years Goding, Colin R; Arnheiter, Heinz
Genes & development,
08/2019, Letnik:
33, Številka:
15-16
Journal Article
Recenzirano
Odprti dostop
All transcription factors are equal, but some are more equal than others. In the 25 yr since the gene encoding the microphthalmia-associated transcription factor (MITF) was first isolated, MITF has ...emerged as a key coordinator of many aspects of melanocyte and melanoma biology. Like all transcription factors, MITF binds to specific DNA sequences and up-regulates or down-regulates its target genes. What marks MITF as being remarkable among its peers is the sheer range of biological processes that it appears to coordinate. These include cell survival, differentiation, proliferation, invasion, senescence, metabolism, and DNA damage repair. In this article we present our current understanding of MITF's role and regulation in development and disease, as well as those of the MITF-related factors TFEB and TFE3, and highlight key areas where our knowledge of MITF regulation and function is limited.
Microplastics are present throughout the marine environment and ingestion of these plastic particles (<1 mm) has been demonstrated in a laboratory setting for a wide array of marine organisms. Here, ...we investigate the presence of microplastics in two species of commercially grown bivalves: Mytilus edulis and Crassostrea gigas. Microplastics were recovered from the soft tissues of both species. At time of human consumption, M. edulis contains on average 0.36 ± 0.07 particles g−1 (wet weight), while a plastic load of 0.47 ± 0.16 particles g−1 ww was detected in C. gigas. As a result, the annual dietary exposure for European shellfish consumers can amount to 11,000 microplastics per year. The presence of marine microplastics in seafood could pose a threat to food safety, however, due to the complexity of estimating microplastic toxicity, estimations of the potential risks for human health posed by microplastics in food stuffs is not (yet) possible.
•Microplastics are present in two bivalve species cultured for human consumption.•Mussels had an average plastic load of 0.36 ± 0.07 particles per gram tissue (ww).•Oyster had on average 0.47 ± 0.16 particles per gram tissue (ww).•The annual dietary exposure of European consumers can be up to 11,000 microplastics.•Estimating the potential risks for human health is not yet possible.
Microplastics were detected in two commercially grown bivalve species (Mytilus edulis and Crassostrea gigas), enabling us to estimate a preliminary human dietary exposure.
The Cambridge Crystallographic Data Centre (CCDC) was established in 1965 to record numerical, chemical and bibliographic data relating to published organic and metal–organic crystal structures. The ...Cambridge Structural Database (CSD) now stores data for nearly 700 000 structures and is a comprehensive and fully retrospective historical archive of small‐molecule crystallography. Nearly 40 000 new structures are added each year. As X‐ray crystallography celebrates its centenary as a subject, and the CCDC approaches its own 50th year, this article traces the origins of the CCDC as a publicly funded organization and its onward development into a self‐financing charitable institution. Principally, however, we describe the growth of the CSD and its extensive associated software system, and summarize its impact and value as a basis for research in structural chemistry, materials science and the life sciences, including drug discovery and drug development. Finally, the article considers the CCDC’s funding model in relation to open access and open data paradigms.
Crystal‐clear data: The Cambridge Crystallographic Data Centre (CCDC) was established in 1965; its core product, the Cambridge Structural Database (CSD), stores numerical, chemical, and bibliographic data for nearly 700 000 crystal structures. As X‐ray crystallography celebrates its centenary, the CCDC nears its own 50th anniversary. The origins of the CCDC and development of the CSD system is presented. The CCDC's funding model in relation to open access paradigms is also considered.
Vertebrates harbour microbes both internally and externally, and collectively, these microorganisms (the ‘microbiome’) contain genes that outnumber the host's genetic information 10‐fold. The ...majority of the microorganisms associated with vertebrates are found within the gut, where they influence host physiology, immunity and development. The development of next‐generation sequencing has led to a surge in effort to characterize the microbiomes of various vertebrate hosts, a necessary first step to determine the functional role these communities play in host evolution or ecology. This shift away from a culture‐based microbiological approach, limited in taxonomic breadth, has resulted in the emergence of patterns suggesting a core vertebrate microbiome dominated by members of the bacterial phyla Bacteroidetes, Proteobacteria and Firmicutes. Still, there is a substantial variation in the methodology used to characterize the microbiome, from differences in sample type to issues of sampling captive or wild hosts, and the majority (>90%) of studies have characterized the microbiome of mammals, which represent just 8% of described vertebrate species. Here, we review the state of microbiome studies of nonmammalian vertebrates and provide a synthesis of emerging patterns in the microbiome of those organisms. We highlight the importance of collection methods, and the need for greater taxonomic sampling of natural rather than captive hosts, a shift in approach that is needed to draw ecologically and evolutionarily relevant inferences. Finally, we recommend future directions for vertebrate microbiome research, so that attempts can be made to determine the role that microbial communities play in vertebrate biology and evolution.
Stripe rust, caused by
Puccinia striiformis
, has been an important disease of wheat, barley, rye, triticale and certain graminaceous hosts for centuries. The significance of the disease on ...cultivated cereals has waxed and waned according to the vagaries of climate, inoculum levels and susceptible varieties. A progressive understanding of pathogen biology has revealed levels of specialisation between and within host groups, and these had varying impacts on the hosts concerned. The most economically important form is
P. striiformis
f. sp.
tritici
(
Pst
), the causal pathogen of stripe (yellow) rust of wheat, which is the major focus of this paper. The recent discovery of the perfect stage of
Pst
on
Berberis
spp. will encourage further work to uncover the potential importance of the sexual stage in pathogen biology in regions where
Berberis
spp. occur. A review of the evolution of pathotypes within
Pst
over the past 50 years reveals recurrent pandemics emanating from a combination of specific virulence in the pathogen population, wide scale cultivation of genetically similar varieties, and agronomic practices that led to high yield potential. When these factors operate in concert, regional stripe rust epidemics have proven to be dramatic, extensive and serious in terms of the magnitude of losses and the economic hardships endured. A review of these epidemics suggests that little progress has been made in containing the worst effects of epidemics. The current status of stripe rust was gauged from a survey of 25 pathologists and breeders directly associated with the disease. It was evident that
Pst
remains a significant threat in the majority of wheat growing regions of the world with potential to inflict regular regional crop losses ranging from 0.1 to 5%, with rare events giving losses of 5–25%. Regions with current vulnerability include the USA (particularly Pacific North West), East Asia (China north-west and south-west), South Asia (India, Pakistan, Nepal), Oceania (Australia, New Zealand), East Africa (Ethiopia, Kenya), the Arabian Peninsula (Yemen) and Western Europe (east England). The resources deployed to contain the worst effects of
Pst
will need to find a balance between training a new generation of breeders and pathologists in host-pathogen genetics, and an investment in infrastructure in IARCs and NARs.
The hypothesis that ‘microplastic will transfer hazardous hydrophobic organic chemicals (HOC) to marine animals’ has been central to the perceived hazard and risk of plastic in the marine ...environment. The hypothesis is often cited and has gained momentum, turning it into paradigm status. We provide a critical evaluation of the scientific literature regarding this hypothesis. Using new calculations based on published studies, we explain the sometimes contrasting views and unify them in one interpretive framework. One explanation for the contrasting views among studies is that they test different hypotheses. When reframed in the context of the above hypothesis, the available data become consistent. We show that HOC microplastic-water partitioning can be assumed to be at equilibrium for most microplastic residing in the oceans. We calculate the fraction of total HOC sorbed by plastics to be small compared to that sorbed by other media in the ocean. We further demonstrate consistency among (a) measured HOC transfer from microplastic to organisms in the laboratory, (b) measured HOC desorption rates for polymers in artificial gut fluids (c) simulations by plastic-inclusive bioaccumulation models and (d) HOC desorption rates for polymers inferred from first principles. We conclude that overall the flux of HOCs bioaccumulated from natural prey overwhelms the flux from ingested microplastic for most habitats, which implies that microplastic ingestion is not likely to increase the exposure to and thus risks of HOCs in the marine environment.
Advances in the analysis of amplicon sequence datasets have introduced a methodological shift in how research teams investigate microbial biodiversity, away from sequence identity-based clustering ...(producing Operational Taxonomic Units, OTUs) to denoising methods (producing amplicon sequence variants, ASVs). While denoising methods have several inherent properties that make them desirable compared to clustering-based methods, questions remain as to the influence that these pipelines have on the ecological patterns being assessed, especially when compared to other methodological choices made when processing data (e.g. rarefaction) and computing diversity indices. We compared the respective influences of two widely used methods, namely DADA2 (a denoising method) vs. Mothur (a clustering method) on 16S rRNA gene amplicon datasets (hypervariable region v4), and compared such effects to the rarefaction of the community table and OTU identity threshold (97% vs. 99%) on the ecological signals detected. We used a dataset comprising freshwater invertebrate (three Unionidae species) gut and environmental (sediment, seston) communities sampled in six rivers in the southeastern USA. We ranked the respective effects of each methodological choice on alpha and beta diversity, and taxonomic composition. The choice of the pipeline significantly influenced alpha and beta diversities and changed the ecological signal detected, especially on presence/absence indices such as the richness index and unweighted Unifrac. Interestingly, the discrepancy between OTU and ASV-based diversity metrics could be attenuated by the use of rarefaction. The identification of major classes and genera also revealed significant discrepancies across pipelines. Compared to the pipeline's effect, OTU threshold and rarefaction had a minimal impact on all measurements.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
An incomplete view of the mechanisms that drive metastasis, the primary cause of cancer-related death, has been a major barrier to development of effective therapeutics and prognostic diagnostics. ...Increasing evidence indicates that the interplay between microenvironment, genetic lesions, and cellular plasticity drives the metastatic cascade and resistance to therapies. Here, using melanoma as a model, we outline the diversity and trajectories of cell states during metastatic dissemination and therapy exposure, and highlight how understanding the magnitude and dynamics of nongenetic reprogramming in space and time at single-cell resolution can be exploited to develop therapeutic strategies that capitalize on nongenetic tumor evolution.
Coal deposits have attracted much attention in recent years as promising alternative raw sources for rare earth elements and yttrium (REY), not only because the REY concentrations in many coals or ...coal ashes are equal to or higher than those found in conventional types of REY ores but also because of the world-wide demand for REY in recent years has been greater than supply. In addition to anomalies of enrichment or depletion of light-, medium-, and heavy-REY in coal deposits (normalized to Upper Continental Crust, Post-Archean Australian Shale, or North American Shale Composite), anomalies of redox-sensitive Ce and Eu, and, in some cases, of non-redox-sensitive La, Gd, and Y, could be used as geochemical indicators of the sediment-source region, sedimentary environment, tectonic evolution, and post-depositional history of coal deposits. Factors controlling REY anomalies in coal deposits include the geochemistry of terrigenous source rocks, ingress of hydrothermal fluids, influence of marine environments, percolating natural waters, volcanic ashes, and sedimentary environments of peat formation. Additionally, the smoothness of a normalized REY distribution pattern provides a simple but reliable basis for testing the quality of REY chemical analyses for coal and other sedimentary rocks.
•A new technique for the extraction of microplastics from sediments is proposed.•A technique for extracting microplastics from invertebrate tissues was developed.•Extraction efficiencies for various ...types of granules and fibres were determined.•For sediments, considerable high extraction efficiencies were obtained.•Extraction from tissues yielded variable efficiencies, depending on polymer type.
Microplastics have been reported in marine environments worldwide. Accurate assessment of quantity and type is therefore needed. Here, we propose new techniques for extracting microplastics from sediment and invertebrate tissue. The method developed for sediments involves a volume reduction of the sample by elutriation, followed by density separation using a high density NaI solution. Comparison of this methods’ efficiency to that of a widely used technique indicated that the new method has a considerably higher extraction efficiency. For fibres and granules an increase of 23% and 39% was noted, extraction efficiency of PVC increased by 100%. The second method aimed at extracting microplastics from animal tissues based on chemical digestion. Extraction of microspheres yielded high efficiencies (94–98%). For fibres, efficiencies were highly variable (0–98%), depending on polymer type. The use of these two techniques will result in a more complete assessment of marine microplastic concentrations.
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