114 research outputs found
Crosstalk between glial and glioblastoma cells triggers the "go-or-grow" phenotype of tumor cells
Background: Glioblastoma (GBM), the most malignant primary brain tumor, leads to poor and unpredictable clinical outcomes. Recent studies showed the tumor microenvironment has a critical role in regulating tumor growth by establishing a complex network of interactions with tumor cells. In this context, we investigated how GBM cells modulate resident glial cells, particularly their paracrine activity, and how this modulation can influence back on the malignant phenotype of GBM cells.
Methods: Conditioned media (CM) of primary mouse glial cultures unexposed (unprimed) or exposed (primed) to the secretome of GL261 GBM cells were analyzed by proteomic analysis. Additionally, these CM were used in GBM cells to evaluate their impact in glioma cell viability, migration capacity and activation of tumor-related intracellular pathways.
Results: The proteomic analysis revealed that the pre-exposure of glial cells to CM from GBM cells led to the upregulation of several proteins related to inflammatory response, cell adhesion and extracellular structure organization within the secretome of primed glial cells. At the functional levels, CM derived from unprimed glial cells favored an increase in GBM cell migration capacity, while CM from primed glial cells promoted cells viability. These effects on GBM cells were accompanied by activation of particular intracellular cancer-related pathways, mainly the MAPK/ERK pathway, which is a known regulator of cell proliferation.
Conclusions: Together, our results suggest that glial cells can impact on the pathophysiology of GBM tumors, and that the secretome of GBM cells is able to modulate the secretome of neighboring glial cells, in a way that regulates the "go-or-grow" phenotypic switch of GBM cells.Fundação para a Ciência e Tecnologia (IF/00601/2012 to B.M.C.; IF/00111 to A.J.S; SFRH/BD/52287/2013 to A.I.O.; SFRH/BD/81495/2011 to S.I.A.; SFRH/BD/88121/2012 to J.V.C.; projects PTDC/SAU-GMG/113795/2009 to B.M.C.; PTDC/NEU-NMC/0205/2012, PTDC/NEU-SCC/7051/2014, PEst-C/SAU/LA0001/2013–2014 and UID/NEU/04539/2013 to B.M.), Liga Portuguesa Contra o Cancro (B.M.C.), Fundação Calouste Gulbenkian (B.M.C.) and Inter-University Doctoral Programme in Ageing and Chronic Disease (PhDOC; to A.I.O.). Project co-financed by Programa Operacional Regional do Norte (ON.2—O Novo Norte), Quadro de Referência Estratégico Nacional (QREN), Fundo Europeu de Desenvolvimento Regional (FEDER), Programa Operacional Factores de Competitividade (COMPETE), and by The National Mass Spectrometry Network (RNEM) under the contract REDE/1506/REM/2005info:eu-repo/semantics/publishedVersio
Anatomical heterogeneity of tendon: Fascicular and interfascicular tendon compartments have distinct proteomic composition
This study was funded by the BBSRC (BB/K008412/1)
West Highland White Terriers under primary veterinary care in the UK in 2016: demography, mortality and disorders
The West Highland White Terrier (WHWT) is a relatively common breed in the UK, although Kennel Club registrations have declined in recent years. The VetCompass™ Programme collates de-identified clinical data from primary-care veterinary practices in the UK for epidemiological research. Using VetCompass clinical data, this study aimed to characterise the demography, longevity and common disorders of WHWTs under primary veterinary care in the UK
Co-regulation map of the human proteome enables identification of protein functions
This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this recordData availability:
All mass spectrometry raw files generated in-house have been deposited in the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository36 with the dataset identifier PXD008888. The co-regulation map is hosted on our website at www.proteomeHD.net, and pair-wise co-regulation scores are available through STRING (https://string-db.org). A network of the top 0.5% co-regulated protein pairs can be explored interactively on NDEx (https://doi.org/10.18119/N9N30Q).Code availability:
Data analysis was performed in R 3.5.1. R scripts and input files required to reproduce the results of this manuscript are available in the following GitHub repository: https://github.com/Rappsilber-Laboratory/ProteomeHD. R scripts related specifically to the benchmarking of the treeClust algorithm using synthetic data are available in the following GitHub repository: https://github.com/Rappsilber-Laboratory/treeClust-benchmarking. The R package data.table was used for fast data processing. Figures were prepared using ggplot2, gridExtra, cowplot and viridis.Note that the title of the AAM is different from the published versionThe annotation of protein function is a longstanding challenge of cell biology that
suffers from the sheer magnitude of the task. Here we present ProteomeHD, which
documents the response of 10,323 human proteins to 294 biological perturbations,
measured by isotope-labelling mass spectrometry. We reveal functional associations
between human proteins using the treeClust machine learning algorithm, which we
show to improve protein co-regulation analysis due to robust selectivity for close
linear relationships. Our co-regulation map identifies a functional context for many
uncharacterized proteins, including microproteins that are difficult to study with
traditional methods. Co-regulation also captures relationships between proteins
which do not physically interact or co-localize. For example, co-regulation of the
peroxisomal membrane protein PEX11β with mitochondrial respiration factors led us
to discover a novel organelle interface between peroxisomes and mitochondria in
mammalian cells. The co-regulation map can be explored at www.proteomeHD.net .Biotechnology & Biological Sciences Research Council (BBSRC)European Commissio
Trophoblast organoids as a model for maternal-fetal interactions during human placentation.
The placenta is the extraembryonic organ that supports the fetus during intrauterine life. Although placental dysfunction results in major disorders of pregnancy with immediate and lifelong consequences for the mother and child, our knowledge of the human placenta is limited owing to a lack of functional experimental models1. After implantation, the trophectoderm of the blastocyst rapidly proliferates and generates the trophoblast, the unique cell type of the placenta. In vivo, proliferative villous cytotrophoblast cells differentiate into two main sub-populations: syncytiotrophoblast, the multinucleated epithelium of the villi responsible for nutrient exchange and hormone production, and extravillous trophoblast cells, which anchor the placenta to the maternal decidua and transform the maternal spiral arteries2. Here we describe the generation of long-term, genetically stable organoid cultures of trophoblast that can differentiate into both syncytiotrophoblast and extravillous trophoblast. We used human leukocyte antigen (HLA) typing to confirm that the organoids were derived from the fetus, and verified their identities against four trophoblast-specific criteria3. The cultures organize into villous-like structures, and we detected the secretion of placental-specific peptides and hormones, including human chorionic gonadotropin (hCG), growth differentiation factor 15 (GDF15) and pregnancy-specific glycoprotein (PSG) by mass spectrometry. The organoids also differentiate into HLA-G+ extravillous trophoblast cells, which vigorously invade in three-dimensional cultures. Analysis of the methylome reveals that the organoids closely resemble normal first trimester placentas. This organoid model will be transformative for studying human placental development and for investigating trophoblast interactions with the local and systemic maternal environment.Centre for Trophoblast Reearch
Royal Society Dorothy Hodgkin Fellowship
Marie Curie Intra-European Fellowshi
Fungal volatile organic compounds: emphasis on their plant growth-promoting
Fungal volatile organic compounds (VOCs) commonly formed bioactive interface between plants and countless of microorganisms on the above- and below-ground plant-fungus interactions. Fungal-plant interactions symbolize intriguingly biochemical complex and challenging scenarios that are discovered by metabolomic approaches. Remarkably secondary metabolites (SMs) played a significant role in the virulence and existence with plant-fungal pathogen interaction; only 25% of the fungal gene clusters have been functionally identified, even though these numbers are too low as compared with plant secondary metabolites. The current insights on fungal VOCs are conducted under lab environments and to apply small numbers of microbes; its molecules have significant effects on growth, development, and defense system of plants. Many fungal VOCs supported dynamic processes, leading to countless interactions between plants, antagonists, and mutualistic symbionts. The fundamental role of fungal VOCs at field level is required for better understanding, so more studies will offer further constructive scientific evidences that can show the cost-effectiveness of ecofriendly and ecologically produced fungal VOCs for crop welfare
Dynamic pigmentary and structural coloration within cephalopod chromatophore organs
Chromatophores in cephalopod skin are known for fast changes in coloration due to light-scattering pigment granules. Here, authors demonstrate structural coloration facilitated by reflectin in sheath cells and offer insights into the interplay between structural and pigmentary coloration elements
Persistence of single species of symbionts across multiple closelyrelated host species
Some symbiont species are highly host-specific, inhabiting only one or a very few host species, and
typically have limited dispersal abilities. When they do occur on multiple host species, populations of
such symbionts are expected to become genetically structured across these different host species,
and this may eventually lead to new symbiont species over evolutionary timescales. However, a low
number of dispersal events of symbionts between host species across time might be enough to prevent
population structure and species divergence. Overall, processes of evolutionary divergence and the
species status of most putative multi-host symbiont systems are yet to be investigated. Here, we used
DNA metabarcoding data of 6,023 feather mites (a total of 2,225 OTU representative sequences) from
147 infracommunities (i.e., the assemblage consisting of all mites of different species collected from
the same bird host individual) to investigate patterns of population genetic structure and species status
of three different putative multi-host feather mite species Proctophyllodes macedo Vitzthum, 1922,
Proctophyllodes motacillae Gaud, 1953, and Trouessartia jedliczkai (Zimmerman, 1894), each of which
inhabits a variable number of different closely related wagtail host species (genus Motacilla). We show
that mite populations from different host species represent a single species. This pattern was found in
all the mite species, suggesting that each of these species is a multi-host species in which dispersal of
mites among host species prevents species divergence. Also, we found evidence of limited evolutionary
divergence manifested by a low but significant level of population genetic structure among symbiont
populations inhabiting different host species. Our study agrees with previous studies showing a higher
than expected colonization opportunities in host-specific symbionts. Indeed, our results support
that these dispersal events would allow the persistence of multi-host species even in symbionts with
limited dispersal capabilities, though additional factors such as the geographical structure of some bird
populations may also play a role.This work was supported by the MINECO CGL2011-24466 to RJ and
CGL2015-69650-P to RJ and DS
Miniature Schnauzers under primary veterinary care in the UK in 2013: demography, mortality and disorders
Individual dog breeds are often reported as predisposed to specific breed-related disorders but reliable epidemiological data on disease prevalence are sparse. The Miniature Schnauzer in the UK is a popular small breed dog that is often considered as relatively healthy and long-lived, but is this really true? This study aimed to use data from the VetCompass™ Programme at the Royal Veterinary College to characterise the demography, mortality and common disorders of the general population of Miniature Schnauzers under veterinary care in the UK
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