The BioSamples database at EMBL-EBI is the central institutional repository for sample metadata storage and connection to EMBL-EBI archives and other resources. The technical improvements to our infrastructure described in our last update have enabled us to scale and accommodate an increasing number of communities, resulting in a higher number of submissions and more heterogeneous data. The BioSamples database now has a valuable set of features and processes to improve data quality in BioSamples, and in particular enriching metadata content and following FAIR principles. In this manuscript, we describe how BioSamples in 2021 handles requirements from our community of users through exemplar use cases: increased findability of samples and improved data management practices support the goals of the ReSOLUTE project, how the plant community benefits from being able to link genotypic to phenotypic information, and we highlight how cumulatively those improvements contribute to more complex multi-omics data integration supporting COVID-19 research. Finally, we present underlying technical features used as pillars throughout those use cases and how they are reused for expanded engagement with communities such as FAIRplus and the Global Alliance for Genomics and Health. Availability: The BioSamples database is freely available at http://www.ebi.ac.uk/biosamples. Content is distributed under the EMBL-EBI Terms of Use available at https://www.ebi.ac.uk/about/terms-of-use. The BioSamples code is available at https://github.com/EBIBioSamples/biosamples-v4 and distributed under the Apache 2.0 license.

Background: Anesthetic preconditioning (APC) of the myocardium is mediated in part by reversible alteration of mitochondrial function. Nitric oxide (NO) inhibits mitochondrial respiration and may mediate APC-induced cardioprotection. In this study, the effects of isoflurane on different states of mitochondrial respiration during the oxidation of complex I-linked substrates and the role of NO were investigated. Methods: Mitochondria were isolated from Sprague-Dawley rat hearts. Respiration rates were measured polarographically at 28ºC with a computer-controlled Clark-type O₂ electrode in the mitochondria (0.5 mg/mL) with complex I substrates glutamate/malate (5 mM). Isoflurane (0.25 mM) was administered before or after adenosine diphosphate (ADP)-initiated state 3 respiration. The NO synthase (NOS) inhibitor L-N⁵-(1-iminoethyl)-ornithine (L-NIO, 10 μM) and the NO donor S-nitroso-N-acetylpenicillamine (SNAP, 1 μM) were added before or after the addition of ADP. Results: Isoflurane administered in state 2 increased state 2 respiration and decreased state 3 respiration. This attenuation of state 3 respiration by isoflurane was similar when it was given during state 3. L-NIO did not alter mitochondrial respiration or the effect of isoflurane. SNAP only, added in state 3, decreased state 3 respiration and enhanced the isoflurane-induced attenuation of state 3 respiration. Conclusion: Isoflurane has clearly distinguishable effects on different states of mitochondrial respiration during the oxidation of complex I substrates. The uncoupling effect during state 2 respiration and the attenuation of state 3 respiration may contribute to the mechanism of APC-induced cardioprotection. These effects of isoflurane do not depend on endogenous mitochondrial NO, as the NOS inhibitor L-NIO did not alter the effects of isoflurane on mitochondrial respiration.

The present study aimed to determine the occurrence of autophagy following ischemia/reperfusion (I/R) injury in the rat spinal cord and whether autophagy inhibition contributes to neural tissue damage and locomotor impairment. A spinal cord I/R model was induced via descending thoracic aorta occlusion for 10 min using systemic hypotension (40 mmHg) in adult male Sprague-Dawley rats. Then, 600 nmol 3-methyladenine (3-MA) or vehicle was intrathecally administered. Ultrastructural spinal cord changes were observed via transmission electron microscopy (TEM) and immunofluorescent double-labeling. Western blots were used to determine the protein expression of microtubule-associated protein light chain 3 (LC3) and Beclin 1. Spinal cord ischemia/reperfusion (I/R) injury may induce paralysis, which represents the underlying pathological cause of patient mortality and morbidity.1) Spinal cord I/R injury triggers pathophysiological changes that involve excitotoxicity, free radical production, inflammation, and apoptosis.2-4) In recent years, evidence has indicated that autophagy may play an important role in various spinal disease models, including spinal cord contusion injury, spinal cord hemisection injury, and cervical spondylotic myelopathy.5-7) However, the occurrence and role of autophagy in neural tissues following spinal cord I/R injury have not been clearly illustrated.Autophagy comprises an evolutionarily conserved process wherein damaged or dysfunctional cytoplasmic components undergo autophagosomal-lysosomal pathway clearance/degradation to facilitate the maintenance of homeostasis. 8,9) Microtubule-associated protein light chain 3 (LC3) and Beclin 1 are two key proteins involved in the autophagic cascade. LC3 occurs in cytosolic (LC3-I) and membrane-bound (LC3-II) forms, and the extent of autophagosome formation is correlated with the ratio of LC3-I to LC3-II conversion. 10)Beclin 1 is a mammalian homolog of yeast Atg6 that was initially described as a Bcl-2-interacting protein and has been demonstrated to promote autophagy. 11) Autophagy is activated during different stress responses, including starvation, oxidative stress, and hypoxia.12,13) Abnormal autophagy has been linked to many pathophysiological events and is involved in disease development.14) The presence of autophagosomes in dying cells indicates that autophagy may play a role in cell death (i.e., "autophagic cell death").15) Autophagy is a critical regulator of cell death and survival and interacts with necrosis and apoptosis in determining the outcome of injured cells. In recent years, the role of autophagy in the pathogenesis of cerebral ischemia had been clearly demonstrated. [16][17][18] Investigations of autophagy-related cures to alleviate the hardships of spinal I/R injury include interventions that attenuate the secondary injury cascade, enhance endogenous repair mechanisms, and replace lost cells.3-Methyladenine (3-MA) is a pharmacological inhibitor of autophagy. It blocks class III phosphoinositide 3-kinase (PI3K) to inhibit autophagosom...

The COVID-19 pandemic has highlighted the need for FAIR (Findable, Accessible, Interoperable, and Reusable) data more than any other scientific challenge to date. We developed a flexible, multi-level, domain-agnostic FAIRification framework, providing practical guidance to improve the FAIRness for both existing and future clinical and molecular datasets. We validated the framework in collaboration with several major public-private partnership projects, demonstrating and delivering improvements across all aspects of FAIR and across a variety of datasets and their contexts. We therefore managed to establish the reproducibility and far-reaching applicability of our approach to FAIRification tasks.

Background: The FAIR Principles explicitly require the use of FAIR vocabularies, but what precisely constitutes a FAIR vocabulary remains unclear. Being able todefine FAIR vocabularies, identify features of FAIR vocabularies, and provide assessment approaches against the features can guide the development of vocabularies.Results: We differentiate data, data resources and vocabularies used for FAIR, examine the application of the FAIR Principles to vocabularies, align their requirements with the Open Biomedical Ontologies (OBO) Principles, and propose FAIR Vocabulary Features (FVFs). We also design assessment approaches for FAIR vocabularies by mapping the FVFs with existing FAIR assessment indicators. Finally, we demonstrate how FVFs can be used for evaluating and improving vocabularies using exemplar biomedical vocabularies.Conclusions: The FAIR Vocabulary Features and corresponding indicators can be used to assess the FAIR levels of different types of vocabularies, identify use cases for vocabulary engineers, and guide the evolution of vocabularies.