Identity crisis in pulmonary arterial hypertension

International audiencePulmonary arterial hypertension (PAH) shares many hallmarks with cancer. Cancer cells acquire their hallmarks by a pathological Darwinian evolution process built on the so-called cancer cell ''identity crisis.'' Here we demonstrate that PAH shares the most striking features of the cancer identity crisis: the ectopic expression of normally silent tissue-specific genes

More Insights into the Association between RVX-208 and Pulmonary Arterial Hypertension Reply

Therapeutic cell differentiatio

BET Signaling:A Novel Therapeutic Target for Pulmonary Hypertension? Reply

Therapeutic cell differentiatio

Bound and free waves in non-collinear second harmonic generation

We analyze the relationship between the bound and the free waves in the noncollinear SHG scheme, along with the vectorial conservation law for the different components arising when there are two pump beams impinging on the sample with two different incidence angles. The generated power is systematically investigated, by varying the polarization state of both fundamental beams, while absorption is included via the Herman and Hayden correction terms. The theoretical simulations, obtained for samples which are some coherence length thick show that the resulting polarization mapping is an useful tool to put in evidence the interference between bound and free waves, as well as the effect of absorption on the interference patternComment: 10 pages, 7 figure. to be published on Optics Expres

Proceed with caution: The need to raise the publication bar for microplastics research

This is an Accepted Manuscript. Embargo until December 12 2022.Plastic is a ubiquitous contaminant of the Anthropocene. The highly diverse nature of microplastic pollution means it is not a single contaminant, but a suite of chemicals that include a range of polymers, particle sizes, colors, morphologies, and associated contaminants. Microplastics research has rapidly expanded in recent years and has led to an overwhelming consideration in the peer-reviewed literature. While there have been multiple calls for standardization and harmonization of the research methods used to study microplastics in the environment, the complexities of this emerging field have led to an exploration of many methods and tools. While different research questions require different methods, making standardization often impractical, it remains import to harmonize the outputs of these various methodologies. We argue here that in addition to harmonized methods and quality assurance practices, journals, editors and reviewers must also be more proactive in ensuring that scientific papers have clear, repeatable methods, and contribute to a constructive and factual discourse on plastic pollution. This includes carefully considering the quality of the manuscript submissions and how they fit into the larger field of research. While comparability and reproducibility is critical in all fields, we argue that this is of utmost importance in microplastics research as policy around plastic pollution is being developed in real time alongside this evolving scientific field, necessitating the need for rigorous examination of the science being published.acceptedVersio

Diversity and Keratin Degrading Ability of Fungi Isolated from Canadian Arctic Marine Bird Feathers

We present the first records of fungi associated with feathers from seabirds and sea ducks in the Canadian Arctic and sub-Arctic. Birds sampled in Nunavut and Newfoundland (Canada) included the Common Eider (Somateria mollissima), King Eider (S. spectabilis), Black-legged Kittiwake (Rissa tridactyla), Northern Fulmar (Fulmarus glacialis), Glaucous Gull (Larus hyperboreus), Black Guillemot (Cepphus grylle), and Thick-billed Murre (Uria lomvia). In total 19 fungal species were cultured from feathers, identified using ITS rDNA barcoding, and screened for their ability to degrade keratin using a keratin azure assay. Our results indicate that 1) of the 19 isolates, 74% were ascomycetes, while the remaining 26% were basidiomycetes (yeasts); 2) 21% of the ascomycete isolates demonstrated keratinolytic activity (a known pathogenicity factor for fungi that may potentially be harmful to birds); 3) the largest number of fungi were cultured from the sampled Thick-billed Murre; and 4) based on a multiple correspondence analysis, there is some indication that both the King Eider and the Thick-billed Murre collected in the low Arctic had distinct fungal communities that were different from each other and from the other birds sampled. Although our sample sizes were small, initial trends in point (4) do demonstrate that additional study is merited to assess whether the fungal community differences are influenced by variation in the known ecologies of the avian hosts and fungi identified.Nous présentons les premiers enregistrements de champignons se rapportant aux plumes d’oiseaux et de canards de mer dans l’Arctique et la région subarctique du Canada. Parmi les oiseaux échantillonnés au Nunavut et à Terre-Neuve (Canada), notons l’eider à duvet (Somateria mollissima), l’eider à tête grise (S. spectabilis), la mouette tridactyle (Rissa tridactyla), le fulmar boréal (Fulmarus glacialis), le goéland bourgmestre (Larus hyperboreus), le guillemot à miroir (Cepphus grylle) et le guillemot de Brünnich (Uria lomvia). En tout, 19 espèces de champignons ont été prélevées à partir de plumes. Elles ont été identifiées au moyen de codes à barres ITS ADNr et examinées afin de déterminer si elles sont capables de dégrader la kératine, et ce, à l’aide d’une épreuve de dégradation de la kératine au bleu azur. Nos résultats indiquent : 1) que parmi les 19 isolats, 74 % étaient des ascomycètes et que les 26 % restants étaient des basidiomycètes (levures); 2) que 21 % des isolats d’ascomycètes ont affiché une activité kératinolytique (un facteur de pathogénicité pour les champignons, facteur susceptible de nuire aux oiseaux); 3) que le plus grand nombre de cultures de champignons a été prélevé chez le guillemot de Brünnich; et 4) que d’après une analyse de correspondance multiple, il y a une certaine indication que les échantillons de l’eider à tête grise et du guillemot de Brünnich recueillis dans le Bas-Arctique comprenaient des communautés fongiques distinctes qui différaient les unes des autres ainsi que des autres oiseaux échantillonnés. Même si la taille de nos échantillons était petite, les premières tendances ressortant du point (4) démontrent qu’il y a lieu de faire des études plus poussées afin de déterminer si les différences entre les communautés fongiques sont influencées par la variation des écologies connues des hôtes aviaires et des champignons identifiés

Current efforts on microplastic monitoring in Arctic fish and how to proceed

In this review, we investigated published data on the occurrence of microplastic in Arctic fish, and the suitability of the data and species for risk assessment and monitoring. As of 11.11.2021, we found nine studies in the peer-reviewed literature, one thesis and one report, confirming the occurrence of microplastic in fishes from multiple Arctic regions. The studies varied in methodology, detection and quantification limitations, reported categories of size, shape, and chemical identity. All these factors influence the numbers of microplastic reported, thus limiting comparability and hindering integrative analysis. The physiological impacts of the reported microplastic contamination cannot be determined, as all studies targeted stomach/intestine contents and did not use methods with limits of detection low enough to determine particle translocation from the intestine to other organs, tissues or body fluids within the fish. Furthermore, there is a fundamental lack of understanding the transfer and the effects of plastic additives to Arctic fishes. In addition to discussing methodological challenges and knowledge gaps, we consider ecosystem needs, commercial interests, Indigenous people’s subsistence, food safety and food sovereignty concerns, and developed a framework to harmonize and facilitate pan-Arctic microplastic monitoring.Current efforts on microplastic monitoring in Arctic fish and how to proceedacceptedVersio

Linking plastic ingestion research with marine wildlife conservation

Plastic is an increasingly pervasive marine pollutant. Concomitantly, the number of studies documenting plastic ingestion in wildlife is accelerating. Many of these studies aim to provide a baseline against which future levels of plastic ingestion can be compared, and are motivated by an underlying interest in the conservation of their study species and ecosystems. Although this research has helped to raise the profile of plastic as a pollutant of emerging concern, there is a disconnect between research examining plastic pollution and wildlife conservation. We present ideas to further discussion about how plastic ingestion research could benefit wildlife conservation by prioritising studies that elucidates the significance of plastic pollution as a population-level threat, identifies vulnerable populations, and evaluates strategies for mitigating impacts. The benefit of plastic ingestion research to marine wildlife can be improved by establishing a clearer understanding of how discoveries will be integrated into conservation and policy actions

Cumulative mutagenesis of the basic residues in the 201-218 region of insulin-like growth factor (IGF)-binding protein-5 results in progressive loss of both IGF-I binding and inhibition of IGF-I biological action

We have reported previously that mutation of two conserved nonbasic amino acids (G203 and Q209) within the highly basic 201–218 region in the C-terminal domain of IGF-binding protein-5 (IGFBP-5) decreases binding to IGFs. This study reveals that cumulative mutagenesis of the 10 basic residues in this region, to create the C-Term series of mutants, ultimately results in a 15-fold decrease in the affinity for IGF-I and a major loss in heparin binding. We examined the ability of mutants to inhibit IGF-mediated survival of MCF-7 cells and were able to demonstrate that this depended not only upon the affinity for IGF-I, but also the kinetics of this interaction, because IGFBP-5 mutants with similar affinity constants (KD) values, but with different association (Ka) and dissociation (Kd) rate values, had markedly different inhibitory properties. In contrast, the affinity for IGF-I provided no predictive value in terms of the ability of these mutants to enhance IGF action when bound to the substratum. Instead, these C-Term mutants appeared to enhance the actions of IGF-I by a combination of increased dissociation of IGF-IGFBP complexes from the substratum, together with dissociation of IGF-I from IGFBP-5 bound to the substratum. These effects of the IGFBPs were dependent upon binding to IGF-I, because a non-IGF binding mutant (N-Term) was unable to inhibit or enhance the actions of IGF-I. These results emphasize the importance of the kinetics of association/dissociation in determining the enhancing or inhibiting effects of IGFBP-5 and demonstrate the ability to generate an IGFBP-5 mutant with exclusively IGF-enhancing activity

Bridging Indigenous and science-based knowledge in coastal and marine research, monitoring, and management in Canada

This work is licensed under a Creative Commons Attribution 4.0 International License.Background Drawing upon multiple types of knowledge (e.g., Indigenous knowledge, local knowledge, science-based knowledge) strengthens the evidence-base for policy advice, decision making, and environmental management. While the benefits of incorporating multiple types of knowledge in environmental research and management are many, doing so has remained a challenge. This systematic map examined the extent, range, and nature of the published literature (i.e., commercially published and grey) that seeks to respectively bridge Indigenous and science-based knowledge in coastal and marine research and management in Canada. Methods This systematic map applied standardized search terms across four databases focused on commercially published literature, carefully selected specialist websites, and two web-based search engines. In addition, reference sections of relevant review articles were cross-checked to identify articles that may not have been found using the search strategy. Search results were screened in two sequential stages; (1) at title and abstract; and (2) at full text following a published protocol. All case studies included were coded using a standard questionnaire. A narrative synthesis approach was used to identify trends in the evidence, knowledge gaps, and knowledge clusters. Results A total of 62 articles that spanned 71 Canadian case studies were included in the systematic map. Studies across the coastal and marine regions of Inuit Nunangat accounted for the majority of the studies. Whether the focus is on management and decision making or research and monitoring, the predominant ecological scale was at the species level, accounting for over two-thirds of the included studies. There were 24 distinct coastal and marine species of central focus across the studies. Nunavut had the greatest taxonomic coverage as studies conducted to date cover 13 different genera. The predominant methodology employed for combining and/or including Indigenous knowledge was case study design, which accounted for over half of the studies. Other methodologies employed for combining and/or including different ways of knowing included: (i) community-based participatory research; (ii) mixed methods; (iii) ethnography; and (iv) simulation modelling. There are a suite of methods utilized for documenting and translating Indigenous knowledge and an equally diverse tool box of methods used in the collection of scientific data. Over half of the case studies involved Indigenous knowledge systems of the Inuit, while another significant proportion involved Indigenous knowledge systems of First Nations, reflecting 21 unique nations. We found that demographics of knowledge holders were generally not reported in the articles reviewed. Conclusions The results of this systematic map provide key insights to inform and improve future research. First, a variety of methodologies and methods are used in these types of studies. Therefore, there is a need to consider in more detail how Indigenous and science-based knowledge systems can be respectively bridged across subjects while also recognizing specific place-based needs of Indigenous communities. Second, the work highlights the need to better report the demographics of knowledge holders. Further inquiry focused on the extent of knowledge co-production and assessing Indigenous participation across different stages of the research process would serve the research community well to improve future research and monitoring in support of, and to strengthen, evidence-based environmental management