Time-course Of Transcriptomic Responses In Skeletal Muscle During Recovery From Endurance Exercise Indicates Prolonged Muscular Inflammation

Introduction Re-programming of gene expression is fundamental for skeletal muscle adaptations in response to endurance exercise. Although inflammatory responses in muscle following muscle-damaging exercise can persist for days, there is a paucity of global gene expression data beyond 48 hours following exercise. This study aimed to investigate the changes in the transcriptome of skeletal muscle until 96 hours after an endurance exercise trial (EXTRI; one hour of cycling followed by one hour of running). Data on the transcriptome of circulating neutrophils from participants in the current study indicated that the neutrophil transcriptional activity was related to the muscle-damaging component of the EXTRI (Neubauer et al. 2013, J Appl Physiol.). We hypothesised that the muscular transcriptome would particularly reflect interactions between muscle and infiltrating leukocytes. Methods Eight healthy, endurance-trained, male individuals participated. Skeletal muscle samples were taken one week before the EXTRI, 3, 48, and 96 hours post-EXTRI. RNA was extracted from muscle tissue. Differential gene expression was evaluated using Illumina microarrays, and validated with q-PCR. Gene set enrichment analysis identified functionally related gene sets chosen from the Molecular Signatures Database. Results Significantly (FWER p-value Conclusions The current data indicate that many of the coordinated gene expression responses in skeletal muscle, particularly at 96 hours post-EXTRI, were related with exercise-induced muscle damage, and the subsequent accumulation of muscle leukocytes. The substantial transcriptional activity 96 h post-EXTRI was strongly associated with inflammatory and immune responses, and suggests that muscular recovery, from a transcriptional perspective, is incomplete 96 hours after exercise

Viral to metazoan marine plankton nucleotide sequences from the Tara Oceans expedition

A unique collection of oceanic samples was gathered by the Tara Oceans expeditions (2009-2013), targeting plankton organisms ranging from viruses to metazoans, and providing rich environmental context measurements. Thanks to recent advances in the field of genomics, extensive sequencing has been performed for a deep genomic analysis of this huge collection of samples. A strategy based on different approaches, such as metabarcoding, metagenomics, single-cell genomics and metatranscriptomics, has been chosen for analysis of size-fractionated plankton communities. Here, we provide detailed procedures applied for genomic data generation, from nucleic acids extraction to sequence production, and we describe registries of genomics datasets available at the European Nucleotide Archive (ENA, www.ebi.ac.uk/ena). The association of these metadata to the experimental procedures applied for their generation will help the scientific community to access these data and facilitate their analysis. This paper complements other efforts to provide a full description of experiments and open science resources generated from the Tara Oceans project, further extending their value for the study of the world's planktonic ecosystems

CEERS Key Paper VII: Emission Line Ratios from NIRSpec and NIRCam Wide-Field Slitless Spectroscopy at z>2

We use James Webb Space Telescope Near-Infrared Camera Wide Field Slitless Spectroscopy (NIRCam WFSS) and Near-Infrared spectrograph (NIRSpec) in the Cosmic Evolution Early Release survey (CEERS) to measure rest-frame optical emission-line of 155 galaxies at z>2. The blind NIRCam grism observations include a sample of galaxies with bright emission lines that were not observed on the NIRSpec masks. We study the changes of the Ha, [OIII]/Hb, and [NeIII]/[OII] emission lines in terms of redshift by comparing to lower redshift SDSS and CLEAR samples. We find a significant (>3$\sigma$) correlation between [OIII]/Hb with redshift, while [NeIII]/[OII] has a marginal (2$\sigma$) correlation with redshift. We compare [OIII]/Hb and [NeIII]/[OII] to stellar mass and Hb SFR. We find that both emission-line ratios have a correlation with Hb SFR and an anti-correlation with stellar mass across the redshifts 0<z<9. Comparison with MAPPINGS~V models indicates that these trends are consistent with lower metallicity and higher ionization in low-mass and high-SFR galaxies. We additionally compare to IllustriousTNG predictions and find that they effectively describe the highest [OIII]/Hb ratios observed in our sample, without the need to invoke MAPPINGS models with significant shock ionizionation components.Comment: 16 pages, 11 figure

Functional repertoire convergence of distantly related eukaryotic plankton lineages abundant in the sunlit ocean

Marine planktonic eukaryotes play critical roles in global biogeochemical cycles and climate. However, their poor representation in culture collections limits our understanding of the evolutionary history and genomic underpinnings of planktonic ecosystems. Here, we used 280 billion Tara Oceans metagenomic reads from polar, temperate, and tropical sunlit oceans to reconstruct and manually curate more than 700 abundant and widespread eukaryotic environmental genomes ranging from 10 Mbp to 1.3 Gbp. This genomic resource covers a wide range of poorly characterized eukaryotic lineages that complement long-standing contributions from culture collections while better representing plankton in the upper layer of the oceans. We performed the first, to our knowledge, comprehensive genome-wide functional classification of abundant unicellular eukaryotic plankton, revealing four major groups connecting distantly related lineages. Neither trophic modes of plankton nor its vertical evolutionary history could completely explain the functional repertoire convergence of major eukaryotic lineages that coexisted within oceanic currents for millions of years

US-triggered Microbubble Destruction for Augmenting Hepatocellular Carcinoma Response to Transarterial Radioembolization: A Randomized Pilot Clinical Trial.

Combined US-triggered microbubble destruction and hepatocellular carcinoma radioembolization showed improved treatment response compared with radioembolization alone and no changes in vital signs or liver function. Background US contrast agents are gas-filled microbubbles (MBs) that can be locally destroyed by using external US. Among other bioeffects, US-triggered MB destruction, also known as UTMD, has been shown to sensitize solid tumors to radiation in preclinical models through localized insult to the vascular endothelial cells. Purpose: To evaluate the safety and preliminary efficacy of combining US-triggered MB destruction and transarterial radioembolization (TARE) in participants with hepatocellular carcinoma (HCC). Materials and Methods: In this pilot clinical trial, participants with HCC scheduled for sublobar TARE were randomized to undergo either TARE or TARE with US-triggered MB destruction 1–4 hours and approximately 1 and 2 weeks after TARE. Enrollment took place between July 2017 and February 2020. Safety of US-triggered MB destruction was evaluated by physiologic monitoring, changes in liver function tests, adverse events, and radiopharmaceutical distribution. Treatment efficacy was evaluated by using modified Response Evaluation Criteria in Solid Tumors (mRECIST) on cross-sectional images, time to required next treatment, transplant rates, and overall survival. Differences across mRECIST reads were compared by using a Mann-Whitney U test, and the difference in prevalence of tumor response was evaluated by Fisher exact test, whereas differences in time to required next treatment and overall survival curves were compared by using a log-rank (Mantel-Cox) test. Results: Safety results from 28 participants (mean age, 70 years ± 10 [standard deviation]; 17 men) demonstrated no significant changes in temperature (P = .31), heart rate (P = .92), diastolic pressure (P = .31), or systolic pressure (P = .06) before and after US-triggered MB destruction. No changes in liver function tests between treatment arms were observed 1 month after TARE (P \u3e .15). Preliminary efficacy results showed a greater prevalence of tumor response (14 of 15 [93%; 95% CI: 68, 100] vs five of 10 [50%; 95% CI: 19, 81]; P = .02) in participants who underwent both US-triggered MB destruction and TARE (P = .02). Conclusion: The combination of US-triggered microbubble destruction and transarterial radioembolization is feasible with an excellent safety profile in this patient population and appears to result in improved hepatocellular carcinoma treatment response

Independent Regulation of Reovirus Membrane Penetration and Apoptosis by the μ1 ϕ Domain

Apoptosis plays an important role in the pathogenesis of reovirus encephalitis. Reovirus outer-capsid protein μ1, which functions to penetrate host cell membranes during viral entry, is the primary regulator of apoptosis following reovirus infection. Ectopic expression of full-length and truncated forms of μ1 indicates that the μ1 ϕ domain is sufficient to elicit a cell death response. To evaluate the contribution of the μ1 ϕ domain to the induction of apoptosis following reovirus infection, ϕ mutant viruses were generated by reverse genetics and analyzed for the capacity to penetrate cell membranes and elicit apoptosis. We found that mutations in ϕ diminish reovirus membrane penetration efficiency by preventing conformational changes that lead to generation of key reovirus entry intermediates. Independent of effects on membrane penetration, amino acid substitutions in ϕ affect the apoptotic potential of reovirus, suggesting that ϕ initiates apoptosis subsequent to cytosolic delivery. In comparison to wild-type virus, apoptosis-defective ϕ mutant viruses display diminished neurovirulence following intracranial inoculation of newborn mice. These results indicate that the ϕ domain of μ1 plays an important regulatory role in reovirus-induced apoptosis and disease