bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nicotine measurement on Cambridge Filter PADs: an interlaboratory comparison to evaluate exposure by different electronic devices and traditional cigarette
Authors: Zuccarello Pietro , Emma Rosalia , Caruso Massimo , Pulvirenti Roberta , Rust Sonja , Poulas Konstantinos , Zadjali Fahad , Boffo Silvia , Volarevic Vladislav , Lesmana Ronny , Abdulkhakov Sayar R , Mesiakaris Konstantinos , Tobi Mohammed Al , Giordano Antonio , Arsenijevic Aleksandar , Barliana Melisa I , Kitaeva Kristina V , Polosa Riccardo , Volti Giovanni Li , Ferrante Margherita 
Published: April 2022

AbstractInter-laboratory comparison is widely used to ensure quality control among laboratories. In in vitro toxicology studies for tobacco harm reduction (THR), exposure system performance and laboratory proficiency along with product smoke and aerosol stream are tested for variability to assess accuracy. Here we aim to test a novel inter-laboratory setup created in a new collaborative research group using identical and small footprint systems- in order to minimize variability factors and increase reproducibility.Seven independent laboratories from different geographical areas tested the aerosol and smoke stream and exposure system performance (LM1 and LM4E) using Cambridge Filter Pad (CFP) trapping techniques. We tested 1R6F reference cigarettes, two electronic cigarettes (Vype e-Pen and Vype e-Stick Maxx), and two tobacco heating products (IQOS and Glo™) under the appropriate ISO and/or HCI regimes. Nicotine quantification was performed by GC-FID at the laboratory of the leading center. The performance of participant laboratories was assessed by z-score values obtained from results either in relation to the mean and standard deviation of total participants or in relation to the reference leading center. Z-Scores were satisfactory when |z| ≤ 2, questionable when 2 < |z| < 3 and, unsatisfactory when |z| ≥ 3. In the first evaluation, for all the tested devices, Z- scores values generated by dosimetry data ranged from -2 to +2. However, high intra-laboratory variability (RSD> 10%) was observed for almost all laboratories. In the second, data showed borderline and unsatisfactory exposure performances versus LAB-A. Particularly, Z-scores ≥ 3 were observed once for LAB-B (e-Stick exposure) and LAB-G (e-Pen exposure), twice for LAB-C (1R6F-ISO and e-Stick exposures) and LAB-E (e-Pen and e-Stick exposures), and three times for LAB-F (1R6F-HCI, e-Pen, and Glo exposures).This study demonstrates that nicotine dosimetry is a fundamental method for quality assurance of smoke/vapor run exposure in the early stage of an interlaboratory study, allowing the identification and possibly the resolution of gaps. Extended practice sessions on exposure runs and several rounds of nicotine dosimetry testing should be planned to keep in check overall equipment and operator performance.
Genetically defined nucleus incertus neurons differ in connectivity and function
Authors: Spikol Emma D. , Cheng Ji , Macurak Michelle , Subedi Abhignya , Halpern Marnie E. 
Published: April 2022

AbstractThe nucleus incertus (NI), a conserved hindbrain structure implicated in the stress response, arousal, and memory, is a major site for production of the neuropeptide relaxin-3. On the basis ofgoosecoid homeobox 2(gsc2) expression, we identified a neuronal cluster that lies adjacent torelaxin 3a(rln3a) neurons in the zebrafish analogue of the NI. To delineate the characteristics of thegsc2andrln3aNI neurons, we used CRISPR/Cas9 targeted integration to drive gene expression specifically in each neuronal group, and found that they differ in their efferent and afferent connectivity, spontaneous activity, and functional properties.gsc2andrln3aNI neurons have widely divergent projection patterns and innervate distinct subregions of the midbrain interpeduncular nucleus (IPN). Whereasgsc2neurons are activated by electric shock,rln3aneurons exhibit spontaneous fluctuations in calcium signaling and regulate locomotor activity. Our findings define heterogeneous neurons in the NI and provide new tools to probe its diverse functions.
A macroecological perspective on genetic diversity in the human gut microbiome
Authors: Shoemaker William R. 
Published: April 2022

AbstractWhile the human gut microbiome has been intensely studied, we have yet to obtain a sufficient understanding of the genetic diversity that it harbors. Research efforts have demonstrated that a considerable fraction of within-host genetic variation in the human gut is driven by the ecological dynamics of co-occurring strains belonging to the same species, suggesting that an ecological lens may provide insight into empirical patterns of genetic diversity. Indeed, an ecological model of self-limiting growth and environmental noise known as the Stochastic Logistic Model (SLM) was recently shown to successfully predict the temporal dynamics of strains within a single human host. However, its ability to predict patterns of genetic diversity across human hosts has yet to be tested. In this manuscript I determine whether the predictions of the SLM explain patterns of genetic diversity across unrelated human hosts for 22 common microbial species. Specifically, the stationary distribution of the SLM explains the distribution of allele frequencies across hosts and predicts the fraction of hosts harboring a given allele (i.e., prevalence) for a considerable fraction of sites. The accuracy of the SLM was correlated with independent estimates of strain structure, suggesting that patterns of genetic diversity in the gut microbiome follow statistically similar forms across human hosts due to the existence of strain-level ecology.
Assessing the importance of resistance, persistence and hyper-mutation for antibiotic treatment success with stochastic modelling
Authors: Witzany Christopher , Regoes Roland R. , Igler Claudia 
Published: April 2022

AbstractAntimicrobial resistance poses a rising threat to global health, making it crucial to understand the routes of bacterial survival during antimicrobial treatments. Treatment failure can result from genetic or phenotypic mechanisms, which diminish the effect of antibiotics. By assembling empirical data, we find that, for example, Pseudomonas aeruginosa infections in cystic fibrosis patients frequently contain persisters, transiently non-growing and antibiotic-refractory subpopulations, and hyper-mutators, mutants with elevated mutation rates and thus higher probability of genetic resistance emergence. Resistance, persistence and hyper-mutation dynamics are difficult to disentangle experimentally. Hence, we use stochastic population modelling and deterministic fitness calculations of bacterial evolution under antibiotic treatment to investigate how genetic resistance and phenotypic mechanisms affect treatment success. We find that treatment failure is caused by resistant mutants at lower antibiotic concentrations (with high final bacterial numbers), but by persistence phenotypes at higher antibiotic concentrations (with low final bacterial numbers). Facilitation of resistance occurs through hyper-mutators during treatment, but through persistence only after treatment is discontinued, which allows for persisters to resume growth and evolve resistance in the absence of antibiotics. Our findings highlight the time- and concentration-dependence of different bacterial mechanisms to escape antibiotic killing, which should be considered when designing ‘resistance-proof’ antimicrobial treatments.
Quantitative MRI maps of human neocortex explored using cell type-specific gene expression analysis
Authors: Edwards Luke J. , McColgan Peter , Helbling Saskia , Zarkali Angeliki , Vaculčiaková Lenka , Pine Kerrin J. , Dick Fred , Weiskopf Nikolaus 
Published: April 2022

AbstractQuantitative MRI (qMRI) allows extraction of reproducible and robust parameter maps. However, the connection to underlying biological substrates remains murky, especially in the complex, densely packed cortex. We investigated associations in human neocortex between qMRI parameters and neocortical cell types by comparing the spatial distribution of the qMRI parameters longitudinal relaxation rate (R1), effective transverse relaxation rate (R2∗), and magnetization transfer saturation (MTsat) to gene expression from the Allen Human Brain Atlas, then combining this with lists of genes enriched in specific cell types found in the human brain. As qMRI parameters are magnetic field strength-dependent, the analysis was performed on MRI data at 3T and 7T. All qMRI parameters significantly covaried with genes enriched in GABA- and glutamatergic neurons, i.e. they were associated with cytoarchitecture. The qMRI parameters also significantly covaried with the distribution of genes enriched in astrocytes (R2∗ at 3T, R1 at 7T), endothelial cells (R1 and MTsat at 3T), microglia (R1 and MTsat at 3T, R1 at 7T), and oligodendrocytes (R1 at 7T). These results advance the potential use of qMRI parameters as biomarkers for specific cell types.
Caenorhabditis elegansMES-3 is a highly divergent ortholog of the canonical PRC2 component SUZ12
Authors: Snel Berend , van den Heuvel Sander , Seidl Michael F. 
Published: April 2022

SUMMARYPolycomb Repressive Complex 2 (PRC2) catalyzes the mono-, di, and trimethylation of histone protein H3 on lysine 27 (H3K27), which is strongly associated with transcriptionally silent chromatin. The functional core of PRC2 is highly conserved in animals and consists of four subunits. One of these, SUZ12, has not been identified in the genetic modelCaenorhabditis elegans, whereasC. elegansPRC2 contains the clade-specific MES-3 protein. Through unbiased sensitive sequence similarity searches complemented by high-quality structure predictions of monomers and multimers, we here demonstrate that MES-3 is a highly divergent ortholog of SUZ12. MES-3 shares protein folds and conserved residues of key domains with SUZ12 and is predicted to interact with core PRC2 members similar to SUZ12 in human PRC2. Thus, in agreement with previous genetic and biochemical studies, we provide evidence thatC. eleganscontains a diverged yet evolutionary conserved core PRC2, like other animals.
Probing Notch1-Dll4 Signaling in Regulating Osteogenic Differentiation of Human Mesenchymal Stem Cells using Single Cell Nanobiosensor
Authors: Zhao Yuwen , Yang Rui , Bousraou Zoe , Richardson Kiarra , Wang Shue 
Published: April 2022

AbstractHuman mesenchymal stem cells (hMSCs) have great potential in cell-based therapies for tissue engineering and regenerative medicine due to their self-renewal and multipotent properties. Recent studies indicate that Notch1-Dll4 signaling is an important pathway in regulating osteogenic differentiation of hMSCs. However, the fundamental mechanisms that govern osteogenic differentiation are poorly understood due to a lack of effective tools to detect gene expression at single cell level. Here, we established a double-stranded locked nucleic acid (LNA)/DNA (LNA/DNA) nanobiosensor for gene expression analysis in single hMSC in both 2D and 3D microenvironments. We first characterized this LNA/DNA nanobiosensor and demonstrated the Dll4 mRNA expression dynamics in hMSCs during osteogenic differentiation. By incorporating this nanobiosensor with live hMSCs imaging during osteogenic induction, we performed dynamic tracking of hMSCs differentiation and Dll4 mRNA gene expression profiles of individual hMSC during osteogenic induction. Our results showed the dynamic expression profile of Dll4 during osteogenesis, indicating the heterogeneity of hMSCs during this dynamic process. We further investigated the role of Notch1-Dll4 signaling in regulating hMSCs during osteogenic differentiation. Pharmacological perturbation is applied to disrupt Notch1-Dll4 signaling to investigate the molecular mechanisms that govern osteogenic differentiation. In addition, the effects of Notch1-Dll4 signaling on hMSCs spheroids differentiation were also investigated. Our results provide convincing evidence supporting that Notch1-Dll4 signaling is involved in regulating hMSCs osteogenic differentiation. Specifically, Notch1-Dll4 signaling is active during osteogenic differentiation. Our results also showed that Dll4 is a molecular signature of differentiated hMSCs during osteogenic induction. Notch inhibition mediated osteogenic differentiation with reduced Alkaline Phosphatase (ALP) activity. Lastly, we elucidated the role of Notch1-Dll4 signaling during osteogenic differentiation in a 3D spheroid model. Our results showed that Notch1-Dll4 signaling is required and activated during osteogenic differentiation in hMSCs spheroids. Inhibition of Notch1-Dll4 signaling mediated osteogenic differentiation and enhanced hMSCs proliferation, with increased spheroid sizes. Taken together, the capability of LNA/DNA nanobiosensor to probe gene expression dynamics during osteogenesis, combined with the engineered 2D/3D microenvironment, enables us to study in detail the role of Notch1-Dll4 signaling in regulating osteogenesis in 2D and 3D microenvironment. These findings will provide new insights to improve cell-based therapies and organ repair techniques.
Genome structures resolve the early diversification of teleost fishes
Authors: Parey Elise , Louis Alexandra , Montfort Jerome , Bouchez Olivier , Roques Céline , Iampietro Carole , Lluch Jerome , Castinel Adrien , Donnadieu Cécile , Desvignes Thomas , Bucao Christabel Floi , Jouanno Elodie , Wen Ming , Mejri Sahar , Dirks Ron , Jansen Hans , Henkel Christiaan , Chen Wei-Jen , Zahm Margot , Cabau Cédric , Klopp Christophe , Thompson Andrew W. , Robinson-Rechavi Marc , Braasch Ingo , Lecointre Guillaume , Bobe Julien , Postlethwait John H. , Berthelot Camille , Crollius Hugues Roest , Guiguen Yann 
Published: April 2022

AbstractAccurate species phylogenies are a prerequisite for evolutionary research. Teleosts are by far the largest and the most diversified group of extant vertebrates, but relationships among the three oldest lineages of extant teleosts remain unresolved. Based on seven high-quality new genome assemblies in Elopomorpha (tarpons, eels), we revisited the topology of the deepest branches of the teleost phylogeny using independent gene sequence and chromosomal rearrangement phylogenomic approaches. These analyses converged to a single scenario that unambiguously places the Elopomorpha and Osteoglossomorpha (bony-tongues) in a monophyletic group sister to all other teleosts, i.e., the Clupeocephala lineage. This finding resolves over 50 years of controversy on the evolutionary relationships of these lineages and highlights the power of combining different levels of genome-wide information to solve complex phylogenies.One-Sentence SummaryWhole-genome analyses place Elopomorpha (tarpons, eels) and Osteoglossomorpha (bony-tongues) as sister groups at the deepest branching of crown teleosts.
mulEEG: A Multi-View Representation Learning on EEG Signals
Authors: Kumar Vamsi , Reddy Likith , Sharma Shivam Kumar , Dadi Kamalakar , Yarra Chiranjeevi , Raju Bapi , Rajendran Srijithesh 
Published: April 2022

AbstractModeling effective representations using multiple views that positively influence each other is challenging, and the existing methods perform poorly on Electroencephalogram (EEG) signals for sleepstaging tasks. In this paper, we propose a novel multi-view self-supervised method (mulEEG) for unsupervised EEG representation learning. Our method attempts to effectively utilize the complementary information available in multiple views to learn better representations. We introduce diverse loss that further encourages complementary information across multiple views. Our method with no access to labels, beats the supervised training while outperforming multi-view baseline methods on transfer learning experiments carried out on sleep-staging tasks. We posit that our method was able to learn better representations by using complementary multi-views. †
Parvalbumin basket cell myelination accumulates axonal mitochondria to internodes
Authors: Kole Koen , Voesenek Bas J. B. , Brinia Maria E. , Petersen Naomi , Kole Maarten H. P. 
Published: April 2022

AbstractParvalbumin-expressing (PV+) basket cells are fast-spiking interneurons that exert critical control over local neuronal circuit activity and oscillations. PV+interneuron axons are partially myelinated but the electrical and metabolic roles of myelin in axonal functions remain poorly understood. Here, we developed Cre-dependent AAV vectors for cell type-specific investigation of mitochondria with genetically encoded fluorescent probes. Single-cell reconstructions and mining of ultrastructural data revealed that mitochondria selectively cluster to myelinated segments of PV+basket cell axons. Cuprizone-induced demyelination abolished mitochondrial clustering in PV+axons but increased axonal mitochondrial densities in excitatory axons. The internodal clustering of mitochondria was preserved with genetic deletion of myelin basic protein, suggesting that noncompacted myelin is sufficient. Finally, two-photon imaging of action potential-evoked mitochondrial calcium (mt-Ca2+) responses showed that internodal mitochondria did not contribute in buffering activity-dependent Ca2+influx. These findings suggest that oligodendrocyte-PV+axon signaling assembles mitochondria to branch selectively fine-tune metabolic demands.
Lipidoid nanoparticles increase ATP uptake into hypoxic brain endothelial cells
Authors: Khare Purva , Conway James F. , Manickam Devika S 
Published: April 2022

AbstractLipidoid nanoparticles (LNPs) are clinically successful carriers for nucleic acid delivery to liver and muscle targets. Their ability to load and deliver small molecule drugs has not been reported yet. We propose that the delivery of adenosine triphosphate (ATP) to brain endothelial cells (BECs) lining the blood-brain barrier may increase cellular energetics of the injured BECs. We formulated and studied the physicochemical characteristics of ATP-loaded LNPs using the C12-200 ionizable cationic lipid and other helper lipids. Polyethylene glycol-dimyristoyl glycerol (PEG-DMG), one of the helper lipids, played a crucial role in maintaining colloidal stability of LNPs over time whereas the inclusion of both ATP and PEG-DMG maintained the colloidal stability of LNPs in the presence of serum proteins. ATP-LNPs formulated with PEG-DMG resulted in a 7.7- and 6.6-fold increased uptake of ATP into normoxic and hypoxic BECs, respectively. Altogether, our results demonstrate the potential of LNPs as a novel carrier for the delivery of small molecular mass actives to BECs—a CNS target.HighlightsLNPs were formulated with ATP, a small molecule drugPEG-DMG plays a critical role in maintaining particle stability over timATP and PEG-DMG play a critical role in maintaining particle stability in 10% serumATP-LNPs were internalized by normoxic and hypoxic brain endothelial cells (BECs)LNP delivery to BECs broadens its applicability to CNS targetsGraphical Abstract
Subtractive proteomics analysis to uncover the potent drug targets for distinctive drug design of Candida auris
Authors: Islam Bappy Md. Nazmul , Robin Tanjin Barketullah , Prome Anindita Ash , Laskar Fayeza Sadia , Roy Anindita , Akter Hafsa , Zinnah Kazi Md. Ali 
Published: April 2022

AbstractCandida auris is a serious health concern of current world that possess serious global health threat and is emerging at a high rate. Available antifungal drugs are failing to combat this pathogen as they are growing resistance toward those drugs and some strains have already showed resistant to all three available antifungal drugs in the market. Finding alternative treatments is a must, therefore, to save lives from this foe. To make the way easier for developing new treatments, we have made some insilico analysis of this pathogen to identify suitable targets for designing drugs and also suggested some potential metabolites to test in vivo condition after some computational analysis. After the subtraction of duplicate, non-essential, human homologs, non-metabolic, human microbiome similar and druggable proteins we ended up with three proteins (XP_028890156.1, XP_028891672.1 and XP_028891858.1) from a total of 5441 C. auris proteins. Blocking those proteins will result in the destruction of the pathogen while the host will remain safe from unintentional blocking. Their subcellular locations and interaction with high number of proteins also indicate their suitability as drug target candidates. After analyzing in silico docking of 29 potential antifungal from plant origin with those three proteins we selected Caledonixanthone E, Viniferin, Glaucine, Jatrorrhizine as the most potent weapon to block those proteins as they showed higher binding affinity. Furthermore, they were predicted to be safe and also showed proper ADME properties (Figure 1).
Neuronal HLH-30/TFEB modulates muscle mitochondrial fragmentation to improve thermoresistance in C. elegans
Authors: Wong Shi Quan , Ryan Catherine J , Lapierre Louis R 
Published: April 2022

ABSTRACTTranscription factor EB (TFEB) is a conserved master transcriptional activator of autophagy and lysosomal genes that modulates organismal lifespan regulation and stress resistance. As neurons can coordinate organism-wide mechanisms, we investigated the role of neuronal TFEB in stress resistance and longevity. To this end, the C. elegans TFEB orthologue, hlh-30, was rescued panneuronally in hlh-30 loss of function mutants. While important in the long lifespan of daf-2 animals, neuronal hlh-30 was not sufficient to restore normal lifespan in short-lived hlh-30 mutants. However, neuronal HLH-30/TFEB rescue mediated robust improvements in the heat stress resistance of wild-type but not daf-2 animals. Notably, these mechanisms can be uncoupled, as neuronal HLH-30/TFEB regulates longevity and thermoresistance dependently and independently of DAF-16/FOXO respectively. Through transcriptomics profiling and functional analysis, we identified the uncharacterized gene W06A11.1 as a bona fide mediator of heat stress resistance via the induction of mitochondrial fragmentation in distal muscles. Neuron-to-muscle communication occurred through a modulation of neurotransmission. Taken together, this study uncovers a novel mechanism of heat stress protection mediated by neuronal HLH-30/TFEB.