bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of TRIB1 abundance in hepatoma models
Authors: Soubeyrand Sébastien , Lau Paulina , McPherson Ruth 
Published: July 2022

AbstractTribbles related homolog 1 (TRIB1) contributes to lipid and glucose homeostasis by facilitating the degradation of cognate cargos by the proteasome. We previously reported that TRIB1 was unstable in non-hepatic cellular models. Moreover, inclusion of proteasome inhibitors failed to prevent TRIB1 loss, consistent with the involvement of proteasome independent degradative processes. In view of the key role of TRIB1 in liver function, we continue our exploration of TRIB1 regulation pathways in two commonly used human hepatocyte models, HuH-7 and HepG2 cells. Proteasome inhibitors potently upregulated both endogenous and recombinant TRIB1 mRNA and protein levels. Increased transcript abundance was independent of MAPK activation while ER stress was a relatively mild inducer. Despite increasing TRIB1 protein abundance and stabilizing bulk ubiquitination, proteasome inhibition failed to stabilize TRIB1, pointing to the predominance of proteasome independent protein degradation processes controlling TRIB1 protein abundance in hepatomas. Proteasome inhibition via downregulation of its PSMB3 regulatory subunit, in contrast to its chemical inhibition, had minimal impact on TRIB1 levels. Moreover, immunoprecipitation experiments showed no evidence of TRIB1 ubiquitination. Cytoplasmic retained TRIB1 was unstable, indicating that TRIB1 lability is regulated prior to its nuclear import. Substitution of the TRIB1 PEST-like region with a GST helical region or N-terminal deletions failed to fully stabilize TRIB1. Finally, inclusion of protease or autophagy inhibitors in vivo did not rescue TRIB1 stability. This work excludes proteasome-mediated degradation as a significant contributor to TRIB1 instability and identifies transcriptional regulation as a prominent mechanism regulating TRIB1 abundance in liver models in response to proteasome inhibition.
Structural Characterisation of Nanoparticle-Supported Lipid Bilayers by Grazing Incidence X-ray and Neutron Scattering
Authors: Paracini Nicolò , Gutfreund Philipp , Welbourn Rebecca , Gonzalez Juan Francisco , Zhu Kexin , Miao Yansong , Yepuri Nageshwar , Darwish Tamim A , Garvey Christopher , Waldie Sarah , Larsson Johan , Wolff Max , Cárdenas Marité 
Published: July 2022

AbstractThe structure of supported lipid bilayers formed on a monolayer of nanoparticles was determined using a combination of grazing incidence X-ray and neutron scattering techniques. Ordered nanoparticle arrays assembled on a silicon crystal using a Langmuir-Schaefer deposition were shown to be suitable and stable substrates for the formation of curved and fluid lipid bilayers that retained lateral mobility, as shown by fluorescence recovery after photobleaching. A comparison between the structure of the curved bilayer assembled around the nanoparticles with the planar lipid membrane formed on the flat underlying silicon oxide surface revealed a ∼5 Å thinner bilayer on the curved interface, resolving the effects of curvature on the lipid packing and overall bilayer structure. The combination of neutron scattering techniques, which grant access to sub-nanometre scale structural information at buried interfaces, and nanoparticle-supported lipid bilayers, offers a novel approach to investigate the effects of membrane curvature on lipid bilayers.
Pseudouridine-dependent ribosome biogenesis regulates translation of polyglutamine proteins during Drosophila oogenesis
Authors: Breznak Shane , Peng Yingshi , Deng Limin , Kotb Noor M. , Flamholz Zachary , Rapisarda Ian T. , Martin Elliot T. , LaBarge Kara A. , Fabris Dan , Gavis Elizabeth R. , Rangan Prashanth 
Published: July 2022

AbstractStem cells in many systems, including Drosophila germline stem cells (GSCs), increase ribosome biogenesis and translation during terminal differentiation. Here, we show that pseudouridylation of ribosomal RNA (rRNA) mediated by the H/ACA box is required for ribosome biogenesis and oocyte specification. Reducing ribosome levels during differentiation decreased the translation of a subset of mRNAs that are enriched for CAG repeats and encode polyglutamine-containing proteins, including differentiation factors such as RNA-binding Fox protein 1. Moreover, ribosomes were enriched at CAG repeats within transcripts during oogenesis. Increasing TOR activity to elevate ribosome levels in H/ACA box-depleted germlines suppressed the GSC differentiation defects, whereas germlines treated with the TOR inhibitor rapamycin had reduced levels of polyglutamine-containing proteins. Thus, ribosome biogenesis and ribosome levels can control stem cell differentiation via selective translation of CAG repeat-containing transcripts.
Meditators probably show increased behaviour-monitoring related neural activity
Authors: Bailey Neil W , Geddes Harry , Zannettino Isabella , Humble Gregory , Payne Jake , Baell Oliver , Emonson Melanie , Chung Sung Wook , Hill Aron T , Rogasch Nigel , Hohwy Jakob , Fitzgerald Paul B 
Published: July 2022

AbstractObjectivesMindfulness meditation is associated with better attention function. Performance monitoring and error-processing are important aspects of attention. We investigated whether experienced meditators showed different neural activity related to performance monitoring and error-processing. Previous research has produced inconsistent results. This study used more rigorous analyses and a larger sample to resolve the inconsistencies.MethodsWe used electroencephalography (EEG) to measure the error-related negativity (ERN) and error positivity (Pe) following correct and incorrect responses to a Go/Nogo task from 27 experienced meditators and 27 non-meditators.ResultsNo differences were found in the ERN (all p > 0.05). Meditators showed larger global field potentials (GFP) in the Pe after both correct responses and errors, indicating stronger neural responses (p = 0.0190, FDR-p = 0.152, np2 = 0.0951, BFincl = 2.691). This effect did not pass multiple comparison controls. However, single electrode analysis of the Pe did pass multiple comparison controls (p = 0.002, FDR-p = 0.016, np2 = 0.133, BFincl = 220.659). Meditators also showed a significantly larger Pe GFP for errors only, which would have passed multiple comparison controls, but was not a primary analysis (p = 0.0028, np2 = 0.1493, BF10 = 9.999).ConclusionsMeditation may strengthen neural responses related to performance monitoring (measured by the Pe), but not specifically to error monitoring (although measurements of the Pe after errors may be more sensitive to group differences). However, only the single electrode analysis passed multiple comparison controls, while analysis including all electrodes did not, so this conclusion remains tentative.
Associative nitrogen fixation could be common in South African mesic grassland
Authors: Morris Craig D , Ramesar Danvir R , Burgdorf Richard J 
Published: July 2022

AbstractNon-symbiotic nitrogen-fixing bacterial diazotrophs closely associated with the roots of grasses probably contribute most of the new nitrogen acquired to sustain productive natural grasslands, yet their ecology is poorly understood, especially in southern Africa. We looked for genetic evidence, using qPCR and gel electrophoresis, for the presence of the bacterial nifH gene associated with the roots of four grass species (20 plants each) in a mesic grassland in South Arica, which would indicate the potential for N fixation by diazotrophs. Grasses most tolerant of low N (Aristida junciformis) were predicted to harbour the most diazotrophs, especially compared to those most responsive to fertiliser N (Eragrostis curvula). However, the nifH gene was found in all 80 root samples and did not differ in copy number between species. Sequencing of a representative sample confirmed the identity of the nifH gene. The recently burned half of the grassland had 60% more nifH genes than the area burned 15 months previously, suggesting that grass growth stimulated by fire could recruit diazotrophs. Given their ubiquity and importance in the N economy of grasslands, research is required to characterise root-associated diazotroph communities, quantify their N fixation rates, and understand their environmental controls.
Energy-based Advection Modelling Using Bond Graphs
Authors: Gawthrop Peter J. , Pan Michael 
Published: July 2022

AbstractAdvection, the transport of a substance by the flow of a fluid, is a key process in biological systems. The energy-based bond graph approach to modelling chemical transformation within reaction networks is extended to include transport and thus advection. The approach is illustrated using a simple model of advection via circulating flow and by a simple pharmacokinetic model of anaesthetic gas uptake.This extension provides a physically-consistent framework for linking advective flows with the fluxes associated with chemical reactions within the context of physiological systems in general and the human physiome in particular.
Impact of AMPK on cervical carcinoma progression and metastasis
Authors: Konieczny Paweł , Adamus Tomasz , Sulkowski Maciej , Majka Marcin 
Published: July 2022

ABSTRACTCervical cancer (CC) is the fourth most common malignant neoplasm among women. Late diagnosis is directly associated with the incidence of metastatic disease and remarkably limits the effectiveness of conventional anticancer therapies at the advanced tumor stage. In this study, we investigated the role of 5’AMP-activated kinase (AMPK) in the metastatic progression of cervical cancer. Since the epithelial mesenchymal transition (EMT) is known as major mechanism enabling cancer cell metastasis, cell lines, which accurately represent this process, have been used as a research model. We used C-4I and HTB-35 cervical cancer cell lines representing distant stages of the disease, in which we genetically modified the expression of the AMPK catalytic subunit α. We have shown that tumor progression leads to metabolic deregulation which results in reduced expression and activity of AMPK. We also demonstrated that AMPK is related to the ability of cells to acquire invasive phenotype and potential for in vivo metastases, and its activity may inhibit these processes. Our findings support the hypothesis that AMPK is a promising therapeutic target and modulation of its expression and activity may improve the efficacy of cervical cancer treatment.
A fully phased interspecific grapevine rootstock genome sequence representingV. ripariaandV. cinereaand allele-aware annotation of the phylloxera resistance locusRdv1
Authors: Frommer Bianca , Hausmann Ludger , Holtgräwe Daniela , Viehöver Prisca , Hüttel Bruno , Reinhardt Richard , Töpfer Reinhard , Weisshaar Bernd 
Published: July 2022

AbstractThe phylloxera resistant rootstock cultivar ‘Börner’ is an interspecific hybrid derived fromVitis ripariaandV. cinereaand a valuable resource forVitisdisease resistances. We created a fully phased, high-quality ‘Börner’ genome sequence named BoeRC using long PacBio reads. Comprehensive gene annotation of both ‘Börner’ haplotypes, designated BoeRip and BoeCin, was applied to describe the phylloxera resistance locusRdv1. Using a mapping population derived from a susceptibleV. viniferabreeding line and ‘Börner’, theRdv1locus was further delimited.Rdv1, which is derived fromV. cinereaand included in the haplotype BoeCin, was compared with sequences of phylloxera-susceptible and phylloxera-tolerant cultivars. Between flanking regions that display high synteny, we detected and precisely characterized a diverse sequence region that covers between 202 to 403 kbp in different haplotypes. In BoeCin, five putative disease resistance genes were identified that represent likely candidates for conferring resistance to phylloxera.
A fitness trade-off explains the early fate of yeast aneuploids with chromosome gains
Authors: Pompei Simone , Lagomarsino Marco Cosentino 
Published: July 2022

AbstractThe early development of aneuploidy from an accidental chromosome missegregation shows contrasting effects. On the one hand, it is associated to significant cellular stress and decreased fitness. On the other hand, it often carries a beneficial effect and provides a quick (but typically transient) solution to external stress. These apparently controversial trends emerge in several experimental contexts, particularly in the presence of duplicated chromosomes. However, we lack a mathematical evolutionary modeling framework that comprehensively captures these trends from the mutational dynamics and the trade-offs involved in the early stages of aneuploidy. Here, focusing on chromosome gains, we address this point by introducing a fitness model where a fitness cost of chromosome duplications is contrasted by a fitness advantage from the dosage of specific genes. The model successfully captures the experimentally measured probability of emergence of extra chromosomes in a laboratory evolution setup. Additionally, using phenotypic data collected in rich media, we explored the fitness landscape, finding evidence supporting the existence of a per-gene cost of extra chromosomes. Finally, we show that the substitution dynamics of our model, evaluated in the empirical fitness landscape, explains the relative abundance of duplicated chromosomes observed in yeast population genomics data. These findings lay a firm framework for the understanding of the establishment of newly duplicated chromosomes, providing testable quantitative predictions for future observations.
Modbamtools: Analysis of single-molecule epigenetic data for long-range profiling, heterogeneity, and clustering
Authors: Razaghi Roham , Hook Paul W. , Ou Shujun , Schatz Michael C. , Hansen Kasper D. , Jain Miten , Timp Winston 
Published: July 2022

AbstractThe advent of long-read sequencing methods provides new opportunities for profiling the epigenome - especially as the methylation signature comes for “free” when native DNA is sequenced on either Oxford Nanopore or Pacific Biosciences instruments. However, we lack tools to visualize and analyze data generated from these new sources. Recent efforts from the GA4GH consortium have standardized methods to encode modification location and probabilities in the BAM format. Leveraging this standard format, we developed a technology-agnostic tool, modbamtools to visualize, manipulate and compare base modification/methylation data in a fast and robust way. modbamtools can produce high quality, interactive, and publication-ready visualizations as well as provide modules for downstream analysis of base modifications. Modbamtools comprehensive manual and tutorial can be found at https://rrazaghi.github.io/modbamtools/.
Synthetic analysis of chromatin tracing and live-cell imaging indicates pervasive spatial coupling between genes
Authors: Bohrer Christopher H. , Larson Daniel R. 
Published: July 2022

AbstractThe role of the spatial organization of chromosomes in directing transcription remains an outstanding question in gene regulation. Here, we analyze two recent single-cell imaging methodologies applied across hundreds of genes to systematically analyze the contribution of chromosome conformation to transcriptional regulation. Those methodologies are: 1) single-cell chromatin tracing with super-resolution imaging in fixed cells; 2) high throughput labeling and imaging of nascent RNA in living cells. Specifically, we determine the contribution of physical distance to the coordination of transcriptional bursts. We find that individual genes adopt a constrained conformation and reposition toward the centroid of the surrounding chromatin upon activation. Leveraging the variability in distance inherent in single-cell imaging, we show that physical distance – but not genomic distance – between genes on individual chromosomes is the major factor driving co-bursting. By combining this analysis with live-cell imaging, we arrive at a corrected transcriptional correlation of ϕ ≈ 0.3 for genes separated by < 400 nm. We propose that this surprisingly large correlation represents a physical property of human chromosomes and establishes a benchmark for future experimental studies.
Correlation of Alpha-1 Antitrypsin Levels and Exosome Associated Neutrophil Elastase Endothelial Injury in Subjects with SARS-CoV2 Infection
Authors: Lascano Jorge , Oshins Regina , Eagan Christina , Wadood Zerka , Qiang Xiao , Flagg Tammy , Scindia Yogesh , Mehrad Borna , Brantly Mark , Khodayari Nazli 
Published: July 2022

AbstractBackgroundSevere acute respiratory syndrome caused by a novel coronavirus 2 (SARS-CoV-2) has infected more than 18 million people worldwide. The activation of endothelial cells is a hallmark of signs of SARS-CoV-2 infection that includes altered integrity of vessel barrier and endothelial inflammation.ObjectivesPulmonary endothelial activation is suggested to be related to the profound neutrophil elastase (NE) activity, which is necessary for sterilization of phagocytosed bacterial pathogens. However, unopposed activity of NE increases alveolocapillary permeability and extracellular matrix degradation. The uncontrolled protease activity of NE during the inflammatory phase of lung diseases might be due to the resistance of exosome associated NE to inhibition by alpha-1 antitrypsin.Method31 subjects with a diagnosis of SARS-CoV2 infection were recruited in the disease group and samples from 30 voluntaries matched for age and sex were also collected for control.ResultsWe measured the plasma levels of exosome-associated NE in SARS-CoV-2 patients which, was positively correlated with the endothelial damage in those patients. Notably, we also found strong correlation with plasma levels of alpha-1 antitrypsin and exosome-associated NE in SARS-CoV-2 patients. Using macrovascular endothelial cells, we also observed that purified NE activity is inhibited by purified alpha-1 antitrypsin while, NE associated with exosomes are resistant to inhibition and show less sensitivity to alpha-1 antitrypsin inhibitory activity, in vitro.ConclusionsOur results point out the role of exosome-associated NE in exacerbation of endothelial injury in SARS-CoV-2 infection. We have demonstrated that exosome-associated NE could be served as a new potential therapeutic target of severe systemic manifestations of SARS-CoV-2 infection.
Cigarette smoke exposed airway epithelial cell-derived EVs promote pro-inflammatory macrophage activation in alpha-1 antitrypsin deficiency
Authors: Khodayari Nazli , Oshins Regina , Mehrad Borna , Lascano Jorge E. , Qiang Xiao , West Jesse R. , Holliday L. Shannon , Lee Jungnam , Wiesemann Gayle , Eydgahi Soroush , Brantly Mark 
Published: July 2022

AbstractBackgroundAlpha-1 antitrypsin deficiency (AATD) is a genetic disorder most commonly secondary to a single mutation in the SERPINA1 gene (PI*Z) that causes misfolding and accumulation of alpha-1 antitrypsin (AAT) in hepatocytes and mononuclear phagocytes which reduces plasma AAT and creates a toxic gain of function. This toxic gain of function promotes a pro-inflammatory phenotype in macrophages that contributes to lung inflammation and early-onset COPD, especially in individuals who smoke cigarettes. The aim of this study is to determine the role of cigarette exposed AATD macrophages and bronchial epithelial cells in AATD-mediated lung inflammation.MethodsPeripheral blood mononuclear cells from AATD and healthy individuals were differentiated into alveolar-like macrophages and exposed to air or cigarette smoke while in culture. Macrophage endoplasmic reticulum stress was quantified and secreted cytokines were measured using qPCR and cytokine ELISAs. To determine whether there is “cross talk” between epithelial cells and macrophages, macrophages were exposed to extracellular vesicles released by airway epithelial cells exposed to cigarette smoke and their inflammatory response was determined.ResultsAATD macrophages spontaneously produce several-fold more pro-inflammatory cytokines as compared to normal macrophages. AATD macrophages have an enhanced inflammatory response when exposed to cigarette smoke-induced extracellular vesicles (EVs) released from airway epithelial cells. Cigarette smoke-induced EVs induce expression of GM-CSF and IL-8 in AATD macrophages but have no effect on normal macrophages. Release of AAT polymers, potent neutrophil chemo attractants, were also increased from AATD macrophages after exposure to cigarette smoke-induced EVs.ConclusionsThe expression of mutated AAT confers an inflammatory phenotype in AATD macrophages which disposes them to an exaggerated inflammatory response to cigarette smoke-induced EVs, and thus could contribute to progressive lung inflammation and damage in AATD individuals.
Synaptotagmin 7 outperforms synaptotagmin 1 to promote the formation of large, stable fusion pores via robust membrane penetration
Authors: Courtney Kevin C. , Mandal Taraknath , Mehta Nikunj , Wu Lanxi , Li Yueqi , Das Debasis , Cui Qiang , Chapman Edwin R. 
Published: July 2022

AbstractSynaptotagmin-1 and synaptotagmin-7 are two prominent Ca2+sensors that regulate exocytosis in neuronal and neuroendocrine cells. Upon binding Ca2+, both proteins partially penetrate lipid bilayers that bear anionic phospholipids, but the specific underlying mechanisms that enable them to trigger exocytosis remain controversial. Here, we examined the biophysical properties of these two synaptotagmin isoforms and compared their interactions with phospholipid membranes. We discovered that synaptotagmin-1•membrane interactions are greatly influenced by membrane order; tight packing of phosphatidylserine inhibits binding due to impaired membrane penetration. In contrast, synaptotagmin-7 exhibits robust membrane binding and penetration activity regardless of phospholipid acyl chain structure. Thus, synaptotagmin-7 is a “super-penetrator”. We exploited these observations to specifically isolate and examine the role of membrane penetration in synaptotagmin function. Using nanodisc-black lipid membrane electrophysiology, we demonstrate that membrane penetration is a critical component that underlies how synaptotagmin proteins regulate reconstituted, exocytic fusion pores in response to Ca2+.