bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterizing the polarization continuum of macrophage subtypes M1, M2a and M2c
Authors: Oates TCL , Moura PL , Cross SJ , Roberts K , Baum HE , Haydn-Smith KL , Wilson MC , Heesom KJ , Severn CE , Toye AM 
Published: June 2022

AbstractMacrophages are vital components of the inflammatory response and exhibit phenotypical plasticity through active conversion between pro- and anti-inflammatory cell subtypes, a feature which can be reproduced inex vivoculture. We employed a multifaceted approach utilizing proteomics, flow cytometry, activity assays and livecell microscopy imaging to characterize four cultured macrophage subtypes: unstimulated MØ, classically activated M1, alternatively activated M2a, and deactivated M2c macrophages. Whole cell proteomics identified a total of 5435 proteins, with >50% of these proteins exhibiting significant alterations in abundance between the different subtypes. This confirms that four distinct macrophage subtypes are induced from the same originating donor material through stimulation with specific cytokines. Additional surfaceome analysis revealed that M2c macrophages significantly upregulate pro-inflammatory markers compared to the MØ baseline and thus appear to be activated or primed to activate, similar to M1. Surface protein expression provided further subtype characterization, in particular distinguishing between the M2a and M2c macrophages.We next explored the re-polarization capabilities of macrophages using dexamethasone, an anti-inflammatory glucocorticoid known to induce macrophage polarization towards the M2c de-activated phenotype. We show that activated M1 macrophages treated with dexamethasone for 48-hours upregulate the levels of CD163 and CD206, markers synonymous with a phenotypical shift from M1 to M2c yet retain key surface markers and display the functional phenotype of M1 macrophages. The observed repolarization of M1 pro-inflammatory macrophages provides a potential mechanism through which dexamethasone treatment improves COVID-19 prognosis and constitutes evidence of partial repolarization along the macrophage continuum. These proteomic and functionalex vivomacrophage datasets provide a valuable resource for studying macrophage polarity and the impact of dexamethasone on macrophage phenotype and function.
Automated non-lethal moth traps can be used for robust estimates of moth abundance
Authors: Möglich Jonas Mielke , Lampe Patrick , Fickus Mario , Gottwald Jannis , Nauss Thomas , Brandl Roland , Brändle Martin , Friess Nicolas , Freisleben Bernd , Heidrich Lea 
Published: June 2022

AbstractRecent reports of insect decline highlight the need for extensive large-scale insect monitoring. However, obtaining abundance or species richness data at high spatial and temporal resolution is difficult due to personnel, maintenance, and post-processing costs as well as ethical considerations. Non-invasive automated insect monitoring systems could provide a solution to address these constraints. However, every new insect monitoring design needs to be evaluated with respect to reliability and bias based on comparisons with conventional methods.In this study, we evaluate the effectiveness of an automated moth trap (AMT), built from off-the-shelf-hardware, in capturing variations in moth abundance, by comparing it to a conventional, lethal trap. Both trap types were operated five times on 16 plots from the beginning of July 2021 to the end of August 2021.Moth abundance scaled isometrically between the two trap types. Consequently, the respective seasonal patterns in abundance determined over the monitoring period were similar.The AMT samples phenological patterns using a robust and non-lethal method. However, an initial quantitative in-field test revealed that its long-term applicability must be preceded by several adjustments to the power supply and to data transfer. Depending on the software implementation, the AMT can be used to address a broad range of research questions while also reducing both energy expenditure and the disturbance of non-target animals.
Distinct sequencing success at non-B-DNA motifs
Authors: Weissensteiner Matthias H. , Cremona Marzia A. , Guiblet Wilfried , Stoler Nicholas , Harris Robert S. , Cechova Monika , Eckert Kristin A. , Chiaromonte Francesca , Huang Yi-Fei , Makova Kateryna D. 
Published: June 2022

AbstractModern sequencing technologies are not error-free, and might have elevated error rates at some locations of the genome. A potential cause for such elevated error rates is the formation of alternative DNA structures (non-B DNA), such as G-quadruplexes (G4s), Z-DNA, or cruciform structures, during sequencing. Approximately 13% of the human genome has the potential to form such structures, which have been previously shown to affect the activity of DNA polymerases and helicases. Here we tested whether motifs with the potential to form non-B DNA (non-B motifs) influence the sequencing success of three major sequencing technologies—Illumina, Pacific Biosciences (PacBio) HiFi, and Oxford Nanopore Technologies (ONT). We estimated sequencing success by computing the rates of single-nucleotide, insertion, and deletion errors, as well as by evaluating mean read depth and mean base quality. Overall, all technologies exhibited altered sequencing success for most non-B motif types. Single-nucleotide error rates were generally increased for G-quadruplexes (G4s) and Z-DNA motifs in all three technologies. Illumina and PacBio HiFi deletion error rates were also increased for all non-B types except for Z-DNA motifs, while in ONT they were increased substantially only for G4 motifs. Insertion error rates for non-B motifs were highly elevated in Illumina, moderately elevated in PacBio HiFi, and only slightly elevated in ONT. Using Poisson regression modeling, we evaluated how non-B DNA motifs and other factors influence sequencing error profiles. Using the error rates at non-B motifs, we developed a probabilistic approach to determine the number of false-positive single-nucleotide variants (SNVs) in different sample size and variant frequency cutoff scenarios, as well as in previously generated sequencing data sets (1000Genomes, Simons Genome Diversity Project, and gnomAD). Overall, the effect of non-B DNA on sequencing should be considered in downstream analyses, particularly in studies with limited read depth—e.g., single-cell and ancient DNA sequencing, as well as sequencing of pooled population samples—and when scoring variants with low frequency (e.g., singletons). Because each sequencing technology analyzed has a unique error profile at non-B motifs, a combination of different technologies should be considered in future sequencing studies of such motifs, to maximize accuracy.
MicroRNA-27a is essential for bone remodeling by modulating p62-mediated osteoclast signaling
Authors: Wang Shumin , Maruyama Eri O , Martinez John , Lopes Justin , Hsu Trunee , Wu Wencheng , Hsu Wei , Maruyama Takamitsu 
Published: June 2022

AbstractThe ability to simultaneously modulate a set of genes for lineage-specific development has made microRNA an ideal master regulator for organogenesis. However, most microRNA deletions do not exhibit obvious phenotypic defects possibly due to functional redundancy. MicroRNAs are known to regulate skeletal lineages as the loss of their maturation enzyme Dicer impairs bone remodeling processes. Therefore, it is important to identify specific microRNA essential for bone homeostasis. We report the loss of miR-27a causing severe osteoporosis in mice. MiR-27a affects osteoclast-mediated bone resorption but not osteoblast-mediated bone formation during skeletal remodeling. Gene profiling and bioinformatics further identify the specific targets of miR-27a in osteoclast cells. MiR-27a exerts its effects on osteoclast differentiation through modulation of Squstm1/p62 whose mutations have been linked to Paget’s disease of bone. Our findings reveal a new miR-27a-p62 axis necessary and sufficient to mediate osteoclast differentiation and highlight a therapeutic implication for osteoporosis.
Disentanglement of Resting State Brain Networks for Localizing Epileptogenic Zone in Focal Epilepsy
Authors: Ye Shuai , Bagić Anto , He Bin 
Published: June 2022

AbstractResting state electromagnetic recordings have been analyzed in epilepsy patients aiding presurgical evaluation. However, it has been rarely explored how pathological networks can be separated and thus used for epileptogenic focus localization purpose. We proposed here a resting state EEG/MEG analysis framework, to disentangle brain functional networks represented by electrophysiological oscillations. Firstly, by using an Embedded Hidden Markov Model (EHMM), we constructed a state space for resting state recordings consisting of brain states with different spatiotemporal patterns. After that, functional connectivity analysis along with graph theory were applied on the extracted brain states to quantify the network features of the extracted brain states, and we determine the source location of pathological states based on these features. The EHMM model was rigorously evaluated using computer simulations. Our simulation results revealed the proposed framework can extract brain states with high accuracy regarding both spatial and temporal profiles. We than validated the entire framework as compared with clinical ground truth in 10 patients with drug-resistant focal epilepsy who underwent MEG recordings. We segmented the resting state MEG recordings into a few brain states with diverse connectivity patterns and extracted pathological brain states by applying graph theory on the constructed functional networks. We showed reasonable localization results using the extracted pathological brain states in 6/10 patients, as compared to the invasive clinical findings. The framework can serve as an objective tool in extracting brain functional networks from noninvasive resting state electromagnetic recordings. It promises to aid presurgical evaluation guiding intracranial EEG electrodes implantation.
Epac2 in midbrain dopamine neurons contributes to cocaine reinforcement via enhancement of dopamine release
Authors: Liu Xiaojie , Vickstrom Casey R. , Yu Hao , Liu Shuai , Snarrenberg Shana Terai , Friedman Vladislav , Mu Lianwei , Chen Bixuan , Kelly Thomas J. , Baker David A. , Liu Qing-song 
Published: June 2022

AbstractRepeated exposure to drugs of abuse results in an upregulation of cAMP signaling in the mesolimbic dopamine system, a molecular adaptation thought to be critically involved in the development of drug dependence. Exchange protein directly activated by cAMP (Epac2) is a major cAMP effector abundantly expressed in the brain. However, it remains unknown whether Epac2 contributes to cocaine reinforcement. Here, we report that Epac2 in the mesolimbic dopamine system promotes cocaine reinforcement via enhancement of dopamine release. Conditional knockout of Epac2 from midbrain dopamine neurons (Epac2-cKO) and the selective Epac2 inhibitor ESI-05 decreased cocaine self-administration in mice under both fixed-ratio and progressive-ratio reinforcement schedules and across a broad range of cocaine doses. In addition, Epac2-cKO led to reduced evoked dopamine release, whereas Epac2 agonism robustly enhanced dopamine release in the nucleus accumbens in vitro. This mechanism is central to the behavioral effects of Epac2 disruption, as chemogenetic activation of ventral tegmental area (VTA) dopamine neurons increased dopamine release and reversed the impairment of cocaine self-administration in Epac2-cKO mice. Conversely, chemogenetic inhibition of VTA dopamine neurons reduced dopamine release and cocaine self-administration in wild-type mice. Epac2-mediated enhancement of dopamine release may therefore represent a novel and powerful mechanism that contributes to cocaine reinforcement.
Prenatal arsenic exposure stymies gut butyrate production and enhances gut permeability in post natal life even in absence of arsenic deftly through miR122-Occludin pathway
Authors: Chakraborty Mainak , Gautam Anupam , Das Oishika , Masid Aaheli , Bhaumik Moumita 
Published: June 2022

AbstractThis discourse attempts to capture a few important dimensions of gut physiology like microbial homeostasis, short chain fatty acid (SCFA) production, occludin expression and gut permeability in post-natal life of mice those received arsenic only during pre-natal life (pAs-mice). The pAs-mice showed a striking reduction in Firmicutes to Bacteroidetes (F/B) ratio coupled with decrease in tight junction protein, occludin resulting in increase in gut permeability, increased infiltration of inflammatory cells in the colon and decrease in common SCFAs in which butyrate reduction was quite prominent in fecal samples as compared to normal control. The above phenotypes of pAs-mice were mostly reversed by supplementing butyrate with food. The talismanic ability of butyrate in enhancing occludin expression, in particular, was dissected further. As miR122 causes degradation of Occludin mRNA, we transiently overexpressed miR122 by injecting appropriate plasmids and showed reversal of butyrate effects in pAs-mice. Thus, pre-natal arsenic exposure orchestrates variety of effects by decreasing in butyrate in pAs-mice leading to increased permeability due to reduced occludin expression. Our research adds a new dimension to our understanding that pre-natal arsenic exposure imprints in post-natal life while there was no further arsenic exposure.HighlightsPrenatal Arsenic exposure decreases prevalence of butyrate producing bacteria and butyrate production in gut.Lack of butyrate production in the gut is responsible for increased permeability and decreased occludin expression.Oral supplementation with butyrate reverses the prenatal arsenic induced changes in the gut.Butyrate increases Occludin gene expression by downregulating miR122 in the gut.
Collective Decision-making in Response to Visual Looming Stimuli in Medaka Fish
Authors: Nakahata Ryohei , Takeuchi Hideaki 
Published: June 2022

AbstractVarious social animals synchronously make behavioral choices among alternatives (i.e., collective decision-making) to efficiently migrate, forage, or escape from predators. Here, we demonstrated that medaka fish, Oryzias latipes, make collective decisions in response to visual looming stimuli (LS), a simulated predator attack. The group-level response to the LS could be classified into 2 patterns: freezing synchronously or not freezing, indicating that medaka selected their response to the LS from 2 alternative choices. Furthermore, the behavioral response to the LS persisted over multiple behavioral trials for 3 days, indicating that each group made a consistent decision to freeze or not to freeze. Finally, we showed that the group response could be predicted by the maximum swimming speed among individuals during the LS presentation. If a group included at least 1 individual that responded to the LS with high-speed movement (>7.4 cm/s), the group tended to freeze synchronously in response to the LS. If no member of the group was moving at high-speed during the LS presentation, the group tended to continue moving after the LS presentation. Our findings suggest that the presence of 1 or more individual medaka with a strong fear response in a group determines the group-level decision of how to respond to a threatening stimulus.
Distinct trajectories in low-dimensional neural oscillation state space track dynamic decision-making in humans
Authors: Thiery Thomas , Rainville Pierre , Cisek Paul , Jerbi Karim 
Published: June 2022

ABSTRACTThe brain evolved to govern behavior in a dynamic world, in which pertinent information about choices is often in flux. Thus, the commitment to an action choice must reflect a balance between monitoring that information and the necessity to act before opportunities are lost. Here, we investigate the mechanisms of dynamic decision-making in humans using low dimensional space representation of brain wide magnetoencephalography recordings. We show that the principal components (PCs) of alpha (9-13 Hz) and beta power (16-24 Hz) are involved in tracking sensory information evolving over time in the sensorimotor and visual cortex. We also found that alpha PCs reflect the commitment to a particular choice, while beta PCs reflect motor execution. Finally, higher frequency components in subcortical areas reflect the adjustment of speed- accuracy tradeoff policies. These results provide a new detailed characterization of the distributed oscillatory brain processes underlying dynamic decision-making in humans.
Optimized intramuscular immunization with VSV-vectored spike protein triggers a superior protective humoral immune response to SARS-CoV-2
Authors: Taddeo Adriano , Veiga Inês Berenguer , Devisme Christelle , Boss Renate , Plattet Philippe , Weigang Sebastian , Kochs Georg , Thiel Volker , Benarafa Charaf , Zimmer Gert 
Published: June 2022

SummaryImmunization with vesicular stomatitis virus (VSV)-vectored COVID-19 vaccine candidates expressing the SARS-CoV-2 spike protein in place of the VSV glycoprotein relies implicitly on expression of the ACE2 receptor at the muscular injection site. Here, we report that such a viral vector vaccine did not induce protective immunity following intramuscular immunization of K18-hACE2 transgenic mice. However, when the viral vector was trans-complemented with the VSV glycoprotein, intramuscular immunization resulted in high titers of spike-specific neutralizing antibodies. The vaccinated animals were fully protected following infection with a lethal dose of SARS-CoV-2-SD614G via the nasal route, and partially protected if challenged with the SARS-CoV-2Delta variant. While dissemination of the challenge virus to the brain was completely inhibited, replication in the lung with consequent lung pathology was not entirely controlled. Thus, intramuscular immunization was clearly enhanced by trans-complementation of the VSV-vectored vaccines by the VSV glycoprotein and led to protection from COVID-19, although not achieving sterilizing immunity.
Chromosome-level genome and the identification of sex chromosomes in Uloborus diversus
Authors: Miller Jeremiah , Zimin Aleksey V , Gordus Andrew 
Published: June 2022

AbstractThe orb-web is a remarkable example of animal architecture that is observed in families of spiders that diverged over 200 million years ago. While several genomes exist for Araneid orb-weavers, none exist for other orb-weaving families, hampering efforts to investigate the genetic basis of this complex behavior. Here we present a chromosome-level genome assembly for the cribellate orb-weaving spider Uloborus diversus. The assembly reinforces evidence of an ancient arachnid genome duplication and identifies complete open reading frames for every class of spidroin gene, which encode the proteins that are the key structural components of spider silks. We identified the two X chromosomes for U. diversus and identify candidate sex-determining genes. This chromosome-level assembly will be a valuable resource for evolutionary research into the origins of orb-weaving, spidroin evolution, chromosomal rearrangement, and chromosomal sex-determination in spiders.
Subventricular zone cytogenesis provides trophic support for neural repair
Authors: Williamson Michael R. , Le Stephanie P. , Franzen Ronald L. , Donlan Nicole A. , Rosow Jill L. , Dunn Andrew K. , Jones Theresa A. , Drew Michael R. 
Published: June 2022

AbstractStroke enhances proliferation of neural precursor cells within the subventricular zone (SVZ) and induces ectopic migration of newborn cells towards the site of injury. Here we characterize the identity of cells arising from the SVZ after stroke and provide insight into their function by uncovering a mechanism through which they facilitate neural repair and functional recovery. Using genetic lineage tracing, we show that SVZ-derived cells that migrate towards stroke- induced cortical lesions in mice are predominantly undifferentiated precursors, suggesting that the main function of post-injury cytogenesis is not cell replacement. We find that SVZ-derived cells are a unique cellular source of trophic factors that instruct neural repair. Chemogenetic ablation of neural precursor cells or conditional knockout of VEGF in the adult neural stem cell lineage impairs neuronal and vascular reparative responses and worsens functional recovery after stroke. In addition, normal aging markedly diminishes the cytogenic response to stroke, resulting in worse functional recovery. Therapeutic replacement of VEGF in peri-infarct cortex is sufficient to induce neural repair and functional recovery in mice with arrested cytogenesis. These findings indicate that the SVZ cytogenic response following brain injury is a source of trophic support that drives neural repair and recovery.
A novel method to selectively elicit cold sensations without touch
Authors: Ezquerra-Romano Ivan , Chowdhury Maansib , Leone Caterina Maria , Iannetti Gian Domenico , Haggard Patrick 
Published: June 2022

AbstractBackgroundThermal and tactile stimuli are transduced by different receptor classes. However, mechano- and thermo-sensitive afferents interact at spinal and supraspinal levels. Yet, most studies on responses to cooling stimuli are confounded by mechanical contact, making these interactions difficult to isolate. Methods for precise control of non-mechanical thermal stimulations remain challenging, particularly in the cold range.New MethodWe developed a non-tactile, focal, temperature-controlled, multi-purpose cooling stimulator. This method controls the exposure of a target skin region to a dry-ice source. Using a thermal camera to monitor skin temperature, and adjusting the source-skin distance accordingly, we could deliver non-tactile cooling stimuli with customisable profiles, for studying different aspects of cold sensation.ResultsTo validate our method, we measured absolute and relative thresholds for cold sensation without mechanical contact in 13 human volunteer participants, using the method of limits. We found that the absolute cold detection threshold was 32.71°C ± 0.88 °C. This corresponded to a threshold relative to each participant’s baseline skin temperature of -1.08 °C ± 0.37 °C.Comparisons with Existing MethodOur method allows cooling stimulation without the confound of mechanical contact, in a controllable and focal manner.ConclusionsWe report a non-contact cooling stimulator and accompanying control system. We used this to measure cold thresholds in the absence of confounding touch. Our method enables more targeted studies of both cold sensory pathways, and of cold-touch interactions.HighlightsMost studies on cold sensation fail to control for concomitant tactile input.A method to deliver non-tactile cooling stimuli was developed.The method combines dry ice, a thermal camera, and motorised stages.The method delivers rapid ramps and feedback-controlled pulses.Thresholds for contactless cold perception were estimated in humans.