4,025 research outputs found

    Challenges and perspectives for naming lipids in the context of lipidomics

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    Introduction: Lipids are key compounds in the study of metabolism and are increasingly studied in biology projects. It is a very broad family that encompasses many compounds, and the name of the same compound may vary depending on the community where they are studied. Objectives: In addition, their structures are varied and complex, which complicates their analysis. Indeed, the structural resolution does not always allow a complete level of annotation so the actual compound analysed will vary from study to study and should be clearly stated. For all these reasons the identification and naming of lipids is complicated and very variable from one study to another, it needs to be harmonized. Methods & Results: In this position paper we will present and discuss the different way to name lipids (with chemoinformatic and semantic identifiers) and their importance to share lipidomic results. Conclusion: Homogenising this identification and adopting the same rules is essential to be able to share data within the community and to map data on functional networks

    Physioxia improves the selectivity of hematopoietic stem cell expansion cultures

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    Hematopoietic stem cells (HSCs) are a rare hematopoietic cell type that can entirely reconstitute the blood and immune systems following transplantation. Allogeneic HSC transplantation (HSCT) is used clinically as a curative therapy for a range of hematolymphoid diseases, but remains a high-risk therapy due to potential side effects including poor graft function and graft-vs-host disease (GvHD). Ex vivo HSC expansion has been suggested as an approach to improve hematopoietic reconstitution from low-cell dose grafts. Here, we demonstrate that we can improve the selectivity of polyvinyl alcohol (PVA)-based mouse HSC cultures through the use of physioxic culture conditions. Single-cell transcriptomic analysis confirmed inhibition of lineage-committed progenitor cells in physioxic cultures. Long-term physioxic expansion also afforded culture-based ex vivo HSC selection from whole bone marrow, spleen, and embryonic tissues. Furthermore, we provide evidence that HSC-selective ex vivo cultures deplete GvHD-causing T cells and that this approach can be combined with genotoxic-free antibody-based conditioning HSCT approaches. Our results offer a simple approach to improve PVA-based HSC cultures and the underlying molecular phenotype, as well as highlight the potential translational implications of selective HSC expansion systems for allogeneic HSCT

    National Cancer Institute Imaging Data Commons:Toward Transparency, Reproducibility, and Scalability in Imaging Artificial Intelligence

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    The remarkable advances of artificial intelligence (AI) technology are revolutionizing established approaches to the acquisition, interpretation, and analysis of biomedical imaging data. Development, validation, and continuous refinement of AI tools requires easy access to large high-quality annotated datasets, which are both representative and diverse. The National Cancer Institute (NCI) Imaging Data Commons (IDC) hosts large and diverse publicly available cancer image data collections. By harmonizing all data based on industry standards and colocalizing it with analysis and exploration resources, the IDC aims to facilitate the development, validation, and clinical translation of AI tools and address the well-documented challenges of establishing reproducible and transparent AI processing pipelines. Balanced use of established commercial products with open-source solutions, interconnected by standard interfaces, provides value and performance, while preserving sufficient agility to address the evolving needs of the research community. Emphasis on the development of tools, use cases to demonstrate the utility of uniform data representation, and cloud-based analysis aim to ease adoption and help define best practices. Integration with other data in the broader NCI Cancer Research Data Commons infrastructure opens opportunities for multiomics studies incorporating imaging data to further empower the research community to accelerate breakthroughs in cancer detection, diagnosis, and treatment. Published under a CC BY 4.0 license

    Waveguide-integrated and portable optomechanical magnetometer

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    Optomechanical magnetometers enable highly sensitive magnetic field sensing. However, all such magnetometers to date have been optically excited and read-out either via free space or a tapered optical fiber. This limits their scalability and integrability, and ultimately their range of applications. Here, we present an optomechanical magnetometer that is excited and read out via a suspended optical waveguide fabricated on the same silicon chip as the magnetometer. Moreover, we demonstrate that thermomechanical noise limited sensitivity is possible using portable electronics and laser. The magnetometer employs a silica microdisk resonator selectively sputtered with a magnetostrictive film of galfenol (FeGa) which induces a resonant frequency shift in response to an external magnetic field. Experimental results reveal the retention of high quality-factor optical whispering gallery mode resonances whilst also demonstrating high sensitivity and dynamic range in ambient conditions. The use of off-the-shelf portable electronics without compromising sensor performance demonstrates promise for applications.Comment: 9 pages, 4 figure

    Body composition and lung cancer-associated cachexia in TRACERx

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    Cancer-associated cachexia (CAC) is a major contributor to morbidity and mortality in individuals with non-small cell lung cancer. Key features of CAC include alterations in body composition and body weight. Here, we explore the association between body composition and body weight with survival and delineate potential biological processes and mediators that contribute to the development of CAC. Computed tomography-based body composition analysis of 651 individuals in the TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study suggested that individuals in the bottom 20th percentile of the distribution of skeletal muscle or adipose tissue area at the time of lung cancer diagnosis, had significantly shorter lung cancer-specific survival and overall survival. This finding was validated in 420 individuals in the independent Boston Lung Cancer Study. Individuals classified as having developed CAC according to one or more features at relapse encompassing loss of adipose or muscle tissue, or body mass index-adjusted weight loss were found to have distinct tumor genomic and transcriptomic profiles compared with individuals who did not develop such features. Primary non-small cell lung cancers from individuals who developed CAC were characterized by enrichment of inflammatory signaling and epithelial‚Äďmesenchymal transitional pathways, and differentially expressed genes upregulated in these tumors included cancer-testis antigen MAGEA6 and matrix metalloproteinases, such as ADAMTS3. In an exploratory proteomic analysis of circulating putative mediators of cachexia performed in a subset of 110 individuals from TRACERx, a significant association between circulating GDF15 and loss of body weight, skeletal muscle and adipose tissue was identified at relapse, supporting the potential therapeutic relevance of targeting GDF15 in the management of CAC

    InterPro in 2022

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    The InterPro database (https://www.ebi.ac.uk/interpro/) provides an integrative classification of protein sequences into families, and identifies functionally important domains and conserved sites. Here, we report recent developments with InterPro (version 90.0) and its associated software, including updates to data content and to the website. These developments extend and enrich the information provided by InterPro, and provide a more user friendly access to the data. Additionally, we have worked on adding Pfam website features to the InterPro website, as the Pfam website will be retired in late 2022. We also show that InterPro's sequence coverage has kept pace with the growth of UniProtKB. Moreover, we report the development of a card game as a method of engaging the non-scientific community. Finally, we discuss the benefits and challenges brought by the use of artificial intelligence for protein structure prediction

    A multi-sensor array for detecting and analyzing nocturnal avian migration

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    Avian migration has fascinated humans for centuries. Insights into the lives of migrant birds are often elusive; however, recent, standalone technological innovations have revolutionized our understanding of this complex biological phenomenon. A future challenge for following these highly mobile animals is the necessity of bringing multiple technologies together to capture a more complete understanding of their movements. Here, we designed a proof-of-concept multi-sensor array consisting of two weather surveillance radars (WSRs), one local and one regional, an autonomous moon-watching sensor capable of detecting birds flying in front of the moon, and an autonomous recording unit (ARU) capable of recording avian nocturnal flight calls. We deployed this array at a field site in central Oklahoma on select nights in March, April, and May of 2021 and integrated data from this array with wind data corresponding to this site to examine the influence of wind on the movements of spring migrants aloft across these spring nights. We found that regional avian migration intensity is statistically significantly negatively correlated with wind velocity, in line with previous research. Furthermore, we found evidence suggesting that when faced with strong, southerly winds, migrants take advantage of these conditions by adjusting their flight direction by drifting. Importantly, we found that most of the migration intensities detected by the sensors were intercorrelated, except when this correlation could not be ascertained because we lacked the sample size to do so. This study demonstrates the potential for multi-sensor arrays to reveal the detailed ways in which avian migrants move in response to changing atmospheric conditions while in flight

    Antioxidant Behavioural Phenotype in the <i>Immp2l</i> Gene Knock-Out Mouse

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    Mitochondrial dysfunction is strongly associated with autism spectrum disorder (ASD) and the Inner mitochondrial membrane protein 2-like (IMMP2L) gene is linked to autism inheritance. However, the biological basis of this linkage is unknown notwithstanding independent reports of oxidative stress in association with both IMMP2L and ASD. To better understand IMMP2L‚Äôs association with behaviour, we developed the Immp2lKD knockout (KO) mouse model which is devoid of Immp2l peptidase activity. Immp2lKD ‚ąí/‚ąí KO mice do not display any of the core behavioural symptoms of ASD, albeit homozygous Immp2lKD ‚ąí/‚ąí KO mice do display increased auditory stimulus-driven instrumental behaviour and increased amphetamine-induced locomotion. Due to reports of increased ROS and oxidative stress phenotypes in an earlier truncated Immp2l mouse model resulting from an intragenic deletion within Immp2l, we tested whether high doses of the synthetic mitochondrial targeted antioxidant (MitoQ) could reverse or moderate the behavioural changes in Immp2lKD ‚ąí/‚ąí KO mice. To our surprise, we observed that ROS levels were not increased but significantly lowered in our new Immp2lKD ‚ąí/‚ąí KO mice and that these mice had no oxidative stress-associated phenotypes and were fully fertile with no age-related ataxia or neurodegeneration as ascertained using electron microscopy. Furthermore, the antioxidant MitoQ had no effect on the increased amphetamine-induced locomotion of these mice. Together, these findings indicate that the behavioural changes in Immp2lKD ‚ąí/‚ąí KO mice are associated with an antioxidant-like phenotype with lowered and not increased levels of ROS and no oxidative stress-related phenotypes. This suggested that treatments with antioxidants are unlikely to be effective in treating behaviours directly resulting from the loss of Immp2l/IMMP2L activity, while any behavioural deficits that maybe associated with IMMP2L intragenic deletion-associated truncations have yet to be determined
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