bluuebunny/crossref_metadata_2025_split huggingface dataset:
A weaponized phage suppresses competitors in historical and modern metapopulations of pathogenic bacteria
Authors: Backman Talia , Latorre Sergio M. , Symeonidi Efthymia , Muszyński Artur , Bleak Ella , Eads Lauren , Martinez-Koury Paulina I. , Som Sarita , Hawks Aubrey , Gloss Andrew D. , Belnap David M. , Manuel Allison M. , Deutschbauer Adam M. , Bergelson Joy , Azadi Parastoo , Burbano Hernán A. , Karasov Talia L. 
Published: April 2023

AbstractBacteriophages, the viruses of bacteria, are proposed to drive bacterial population dynamics, yet direct evidence of their impact on natural populations is limited. Here we identified viral sequences in a metapopulation of wild plant-associatedPseudomonasspp. genomes. We discovered that the most abundant viral cluster does not encode an intact phage but instead encodes a tailocin - a phage-derived element that bacteria use to kill competitors for interbacterial warfare. Each pathogenicPseudomonassp. strain carries one of a few distinct tailocin variants, which target variable polysaccharides in the outer membrane of co-occurring pathogenic strains. Analysis of historic herbarium samples from the last 170 years revealed that the same tailocin and receptor variants have persisted in thePseudomonaspopulations for at least two centuries, suggesting the continued use of a defined set of tailocin haplotypes and receptors. These results indicate that tailocin genetic diversity can be mined to develop targeted “tailocin cocktails” for microbial control.One-Sentence SummaryBacterial pathogens in a host-associated metapopulation use a repurposed prophage to kill their competitors.
Histone divergence inTrypanosoma bruceiresults in unique alterations to nucleosome structure
Authors: Deák Gauri , Wapenaar Hannah , Sandoval Gorka , Chen Ruofan , Taylor Mark R. D. , Burdett Hayden , Watson James A. , Tuijtel Maarten W. , Webb Shaun , Wilson Marcus D. 
Published: April 2023

AbstractEukaryotes have a multitude of diverse mechanisms for organising and using their genomes, but the histones that make up chromatin are highly conserved. Unusually, histones from kinetoplastids are highly divergent. The structural and functional consequences of this variation are unknown. Here, we have biochemically and structurally characterised nucleosome core particles (NCPs) from the kinetoplastid parasiteTrypanosoma brucei. A structure of theT. bruceiNCP reveals that global histone architecture is conserved, but specific sequence alterations lead to distinct DNA and protein interaction interfaces. TheT. bruceiNCP is unstable and has weakened overall DNA binding. However, dramatic changes at the H2A-H2B interface introduce local reinforcement of DNA contacts. TheT. bruceiacidic patch has altered topology and is refractory to known binders, indicating that the nature of chromatin interactions inT. bruceimay be unique. Overall, our results provide a detailed molecular basis for understanding evolutionary divergence in chromatin structure.
CamoTSS: analysis of alternative transcription start sites for cellular phenotypes and regulatory patterns from 5’ scRNA-seq data
Authors: Hou Ruiyan , Hon Chung-Chau , Huang Yuanhua 
Published: April 2023

AbstractFive-prime single-cell RNA-seq (scRNA-seq) has been widely employed to profile cellular transcriptomes, however, its power of analysing transcription start sites (TSS) has not been fully utilised. Here, we present a computational method suite, CamoTSS, to precisely identify TSS and quantify its expression by leveraging the cDNA on read 1, which enables effective detection of alternative TSS usage. With various experimental data sets, we have demonstrated that CamoTSS can accurately identify TSS and the detected alternative TSS usages showed strong specificity in different biological processes, including cell types across human organs, the development of human thymus, and cancer conditions. As evidenced in nasopharyngeal cancer, alternative TSS usage can also reveal regulatory patterns including systematic TSS dysregulations.
Impact of light pollution at night on male reproductive success in Japanese medaka (Oryzias latipes)
Authors: Closs Lauren E. , Royan Muhammad Rahmad , Sayyari Amin , Mayer Ian , Weltzien Finn-Arne , Baker Dianne M. , Fontaine Romain 
Published: April 2023

ABSTRACTEnvironmental light is perceived and anticipated by organisms to synchronize their biological cycles. Therefore, exposure to artificial light at night could disrupt diurnal and seasonal rhythmicity. Reproduction is a complex physiological process involving integration of environmental signals by the brain, and release of endocrine signals by the pituitary that regulate gametogenesis and spawning. In addition, males from many species form a dominance hierarchy that, through a combination of aggressive and protective behavior, influences their reproductive success. In this study, we investigated the effect of different light regimes, including light pollution at night and continuous light, on the fitness of male fish within a dominance hierarchy using a model fish, the Japanese medaka. In normal light/dark rhythm conditions, we observed that dominant males are more aggressive, remain closer to the female, and spend ten-fold more time spawning than subordinates. By using males with different genotypes, we determined the paternity of the progeny and found that even though subordinate males spend less time with the females, they are equally successful at fertilizing eggs in normal light conditions due to an efficient sneaking behavior. However, when exposed to light at night, dominant males fertilize more eggs. We indeed found that when exposed to nocturnal light pollution, dominant males produce higher quality sperm than subordinate males. Surprisingly, we did not find differences in circulating sex steroid levels, pituitary gonadotropin levels, or gonadosomatic index between dominant and subordinate males, neither in control nor night light condition. Continuous light was found to completely inhibit establishment of male hierarchy. This study is the first to report an effect of light pollution on sperm quality with an impact on male fertilization success in any vertebrate. It has broad implications for fish ecology in urban areas with potential impacts on the genetic diversity of these fish populations.GRAPHICAL ABSTRACT:Highlights:In a triadic relationship, subordinate medaka show sneaking behavior during female spawning, allowing them to produce about 50% of the offspring.Continuous light inhibits establishment of male hierarchy.Light pollution at night shifts the balance of reproductive efficiency between dominant and subordinate males, benefiting dominant males.Exposure to light pollution at night improves sperm quality in dominant fish relative to subordinates, but does not clearly affect reproductive hormone levels.
Colocalization of Protein and microRNA Markers Reveals Unique Extracellular Vesicle Sub-Populations for Early Cancer Detection
Authors: Li Zongbo , Guo Kaizhu , Gao Ziting , Chen Junyi , Ye Zuyang , Wang Shizhen Emily , Yin Yadong , Zhong Wenwan 
Published: April 2023

AbstractExtracellular vesicles (EVs) play important roles in cell-cell communication but they are highly heterogeneous, and each vesicle has dimensions smaller than 200 nm thus encapsulates very limited amounts of cargos. We report the technique of NanOstirBar (NOB)-EnabLed Single Particle Analysis (NOBEL-SPA) that utilizes NOBs, which are superparamagnetic nanorods easily handled by a magnet or a rotating magnetic field, to act as isolated “islands” for EV immobilization and cargo confinement. NOBEL-SPA permits rapid inspection of single EV with high confidence by confocal fluorescence microscopy, and can assess the colocalization of selected protein/microRNA (miRNA) pairs in the EVs produced by various cell lines or present in clinical sera samples. Specific EV sub-populations marked by the colocalization of unique protein and miRNA combinations have been revealed by the present work, which can differentiate the EVs by their cells or origin, as well as to detect early-stage breast cancer (BC). We believe NOBEL-SPA can be expanded to analyze the co-localization of other types of cargo molecules, and will be a powerful tool to study EV cargo loading and functions under different physiological conditions, and help discover distinct EV subgroups valuable in clinical examination and therapeutics development.
mRNA Localization and Local Translation of the Microtubule Severing Enzyme, Fidgetin-Like 2, in Polarization, Migration and Outgrowth
Authors: Birnbaum Rayna , Biswas Jeetayu , Singer Robert H. , Sharp David J. 
Published: April 2023

SUMMARYCell motility requires strict spatiotemporal control of protein expression. During cell migration, mRNA localization and local translation in subcellular areas like the leading edge and protrusions are particularly advantageous for regulating the reorganization of the cytoskeleton. Fidgetin-Like 2 (FL2), a microtubule severing enzyme (MSE) that restricts migration and outgrowth, localizes to the leading edge of protrusions where it severs dynamic microtubules. FL2 is primarily expressed during development but in adulthood, is spatially upregulated at the leading edge minutes after injury. Here, we show mRNA localization and local translation in protrusions of polarized cells are responsible for FL2 leading edge expression after injury. The data suggests that the RNA binding protein IMP1 is involved in the translational regulation and stabilization of FL2 mRNA, in competition with the miRNA let-7. These data exemplify the role of local translation in microtubule network reorganization during migration and elucidate an unexplored MSE protein localization mechanism.Graphical AbstractHighlightsThe microtubule severing enzyme FL2 RNA is localized to the leading edgeFL2 mRNA localization leads to FL2 translation within protrusionsThe IMP family works in concert with Let-7 miRNA to regulate FL2 mRNA
RNA editing of AZIN1 coding sites is catalyzed by ADAR1 p150 after splicing
Authors: Xing Yanfang , Nakahama Taisuke , Wu Yuke , Inoue Maal , Kim Jung In , Todo Hiroyuki , Shibuya Toshiharu , Kato Yuki , Kawahara Yukio 
Published: April 2023

AbstractAdenosine-to-inosine RNA editing is catalyzed by nuclear ADAR1 p110 and ADAR2, and cytoplasmic ADAR1 p150 in mammals, all of which recognize double-stranded RNAs (dsRNAs) as targets. Although its frequency is quite rare, RNA editing occurs in coding regions, which alters protein functions by exchanging amino acid sequences, and is therefore physiologically significant. In general, such coding sites are edited by ADAR1 p110 and ADAR2 prior to splicing, given that the corresponding exon forms a dsRNA structure with an adjacent intron. We previously found that RNA editing at two coding sites of antizyme inhibitor 1 (AZIN1) is sustained inAdar1 p110/Aadr2double knockout mice. However, the molecular mechanisms underlying RNA editing of AZIN1 remain unknown. Here, we showed that Azin1 editing levels were increased upon type I interferon treatment, which activated Adar1 p150 transcription, in mouse Raw264.7 cells. Azin1 RNA editing was observed in mature mRNA but not precursor mRNA. Furthermore, we revealed that the two coding sites were editable only by ADAR1 p150 in both mouse Raw264.7 and human HEK293T cells. This unique editing was achieved by forming a dsRNA structure with a downstream exon after splicing and the intervening intron suppressed RNA editing. Therefore, deletion of a nuclear export signal from ADAR1 p150, shifting its localization to the nucleus, decreased Azin1 editing levels. Finally, we demonstrated that Azin1 RNA editing was completely absent inAdar1 p150knockout mice. Thus, these findings indicate that RNA editing of AZIN1 coding sites is exceptionally catalyzed by ADAR1 p150 after splicing.
Single worm long read sequencing reveals genome diversity in free-living nematodes
Authors: Lee Yi-Chien , Lee Hsin-Han , Ke Huei-Mien , Liu Yu-Ching , Wang Min-Chen , Tseng Yung-Che , Kikuchi Taisei , Tsai Isheng Jason 
Published: April 2023

AbstractObtaining sufficient genetic material from a limited biological source is currently the primary operational bottleneck in studies investigating biodiversity and genome evolution. In this study, we employed multiple displacement amplification (MDA) and Smartseq2 to amplify nanograms of genomic DNA and mRNA, respectively from individualCaenorhabditis elegans. Although reduced genome coverage was observed in repetitive regions, we produced assemblies covering 98% of the reference genome using long-read sequences generated with Oxford Nanopore Technologies (ONT). Annotation with the sequenced transcriptome coupled with the available assembly revealed that gene predictions were more accurate, complete and contained far fewer false positives thande novotranscriptome assembly approaches. We sampled and sequenced the genomes and transcriptomes of 13 nematodes from Dorylaimia, Enoplia, and early-branching species in Chromadoria. These free-living species had larger genome sizes, ranging from 147-792 Mb, compared to those of the parasitic lifestyle. Nine mitogenomes were fully assembled and displaying a complete lack of synteny to other species. Phylogenomic analyses based on the new annotations revealed strong support for Enoplia as sister to the rest of Nematoda. Our result demonstrates the robustness of MDA in combination with ONT, paving the way for the study of genome diversity in the phylum Nematoda and beyond.
Modulation of Pain Perceptions Following Treadmill Running with Different Intensities and The Potential Mechanisms of Exercise-induced Hypoalgesia
Authors: Xu Zi-Han , An Nan , Chang Jeremy Rui , Yang Yong-Long 
Published: April 2023

AbstractObjectiveThis study aimed to compare the effects of three intensities of treadmill running on pain perceptions in healthy individuals. And investigate the role of endogenous pain modulation in the exercise-induced hypoalgesia (EIH) effects.MethodsSixty-six healthy female individuals were included in this study and were randomly assigned to one of three treadmill running intensities for 35 minutes: 40% of their reserve heart rate (HRR), 55% HRR, or 70% HRR. The EIH effects were assessed by the changes of pressure pain thresholds (PPT) and pressure pain tolerance thresholds (PPTol) at multiple time points. The assessments were conducted prior to the treadmill running session every 5 minutes during the exercise bout, and at 5 minutes, 10 minutes, and 24 hours post-exercise. The conditioned pain modulation (CPM) was also measured to determine the functions of endogenous pain modulation.ResultsCompared with baseline, there was a significant increase of PPT and PPTol at arm and leg in all groups during running and 5-10min follow-ups. The PPT and PPTol changes of moderate and low intensity groups were significantly higher than the high intensity group during running and 24h after running. While the CPM responses of high intensity group were significantly reduced compared with other groups at 24h follow-up.ConclusionModerate and low intensity running may trigger the endogenous descending inhibition and elicit significant EIH effects following running and persisting over 24h. While the high intensity running only induced limited EIH effects for the activation of both descending pain inhibition and facilitation, with reduced CPM responses. Thus, the pain perception changes following exercises may reveal the potential mechanisms of EIH induced via exercises with different intensities.New findingsWhat is the central question of this study?Both the primary analgesia effect (EIH) and secondary pain allodynia (delayed onset muscle soreness) may occur following exercises, possibly due to the interaction between endogenous pain modulation and exercise intensities. What is the difference in the changes of primary and secondary pain perceptions following exercise with different intensities?What is the main finding and its importance?Moderate and low intensity running induced acute and long-lasting EIH effects via the effective activation of descending inhibition, while the high intensity running may trigger the descending facilitation and attenuate both the acute and long-lasting EIH effects. This result preliminarily explained the non-liner effect of exercise intensity on the acute EIH responds.
Single-nucleus profiling identifies accelerated oligodendrocyte precursor cell senescence in a mouse model of Down Syndrome
Authors: Rusu Bianca , Kukreja Bharti , Wu Taiyi , Dan Sophie J. , Feng Min Yi , Kalish Brian T. 
Published: April 2023

AbstractDown Syndrome (DS), the most common genetic cause of intellectual disability, is associated with lifelong cognitive disability. However, the mechanisms by which triplication of human chromosome 21 genes drive neuroinflammation and cognitive dysfunction are poorly understood. Here, using the Ts65Dn mouse model of DS, we performed an integrated single-nucleus RNA and ATAC-seq analysis of the cortex. We identify cell type-specific transcriptional and chromatin-associated changes in the Ts65Dn cortex, including regulators of neuroinflammation, transcription and translation, myelination, and mitochondrial function. We discover enrichment of a senescence-associated transcriptional signature in Ts65Dn oligodendrocyte precursor cells (OPCs) and epigenetic changes consistent with a loss of heterochromatin. We find that senescence is restricted to a subset of cortical OPCs concentrated in deep cortical layers. Treatment of Ts65Dn mice with a senescence-reducing flavonoid rescues cortical OPC proliferation, restores microglial homeostasis, and improves contextual fear memory. Together, these findings suggest that cortical OPC senescence may be an important driver of neuropathology in DS.
Biotic interactions explain seasonal dynamics of the alpine soil microbiome
Authors: Fiore-Donno Anna Maria , Freudenthal Jule , Borg Dahl Mathilde , Rixen Christian , Urich Tim , Bonkowski Michael 
Published: April 2023

AbstractBackgroundThe soil alpine microbiome is dependent on season and elevation, yet there is limited understanding of how complex communities are differentially shaped by abiotic and biotic factors. Here we investigated the spring-to-summer dynamics of soil microbiomes in alpine grasslands, focussing on soil food web interactions. To this end, we conducted a survey along altitudinal transects in three mountains in the Alps, in spring at snowmelt and in the following summer, recorded vegetation and topographic, climatic and edaphic parameters for 158 soil samples. By using metatranscriptomics, we simultaneously assessed prokaryotic and eukaryotic communities, further classified by nutrition guilds.ResultsOur results show: (i) that biotic interactions could explain more variation of the microbial communities than topographic and edaphic variables, more for consumers than for preys, and this effect was stronger in summer than in spring; (ii) a seasonal dynamic in biotic interactions: the consumers’ pressure on preys increases from spring to summer, resulting in a higher diversity and evenness of preys.ConclusionIn alpine grasslands, consumers effectively contribute to maintain the diverse soil bacterial and fungal community essential for ecosystem functioning.
Detection of spatially-localized sounds is robust to saccades and concurrent eye movement-related eardrum oscillations (EMREOs)
Authors: Bröhl Felix , Kayser Christoph 
Published: April 2023

AbstractHearing is an active process and recent studies show that even the ear is affected by cognitive states or motor actions. One example are movements of the eardrum induced by saccadic eye movements - known as “eye movement-related eardrum oscillations” (EMREOs). While these are systematically shaped by the direction and size of saccades, the consequences of saccadic eye movements and their resulting EMREOs for hearing remain unclear. We here studied their implications for the detection of near-threshold clicks in human participants. Across three experiments sound detection was not affected by their time of presentation relative to saccade onset, by saccade amplitude or direction. While the EMREOs were shaped by the direction and amplitude of the saccadic movement, inducing covert shifts in spatial attention did not affect the EMREO, suggesting that this signature of active sensing is restricted to overt changes in visual focus. Importantly, in our experiments fluctuations in the EMREO amplitude were not related to detection performance, at least when monaural cues are sufficient. Hence while eye movements may shape the transduction of acoustic information the behavioral implications remain unclear.
On-demand low-frequency stimulation for seizure control: efficacy and behavioral implications
Authors: Paschen Enya , Kleis Piret , Vieira Diego M. , Heining Katharina , Boehler Christian , Egert Ulrich , Häussler Ute , Haas Carola A. 
Published: April 2023

AbstractMesial temporal lobe epilepsy (MTLE), the most common form of focal epilepsy in adults, is often refractory to medication and associated with hippocampal sclerosis. Deep brain stimulation represents an alternative treatment option for drug-resistant patients who are ineligible for resective brain surgery. In clinical practice, closed-loop stimulation at high frequencies is applied to interrupt ongoing seizures, yet with a high incidence of false detections, the drawback of delayed seizure-suppressive intervention and limited success in sclerotic tissue. More recently, hippocampal low-frequency stimulation (LFS) has been shown to reduce excitability in clinical settings and prevent seizures in experimental MTLE when applied continuously. However, as the hippocampus is important for navigation and memory, it would be beneficial to stimulate it only on-demand to reduce its exposure to LFS pulses, and to investigate LFS-related effects on cognition.Using the intrahippocampal kainate mouse model, which recapitulates the key features of MTLE, we developed an on-demand LFS setup and investigated its effects on spontaneous seizure activity and hippocampal function. Specifically, our online detection algorithm monitored epileptiform activity in hippocampal local field potential recordings and identified short epileptiform bursts preceding focal seizure clusters, triggering hippocampal LFS to stabilize the network state. In addition, we investigated the acute influence of LFS on behavioral performance, including anxiety-like behavior in the light-dark box test, spatial and non-spatial memory in the object location memory and novel object recognition test, as well as spatial navigation and long-term memory in the Barnes maze.Compared to open-loop stimulation protocols, on-demand LFS was more efficient in preventing focal seizure clusters, as the strong anti-epileptic effect was achieved with a reduced stimulation load. In behavioral tests, chronically epileptic mice were as mobile as healthy controls but showed increased anxiety, an altered spatial learning strategy and impaired memory performance. Most importantly, our experiments ruled out deleterious effects of hippocampal LFS on cognition and even showed alleviation of deficits in long-term memory recall. Taken together, our findings may provide a promising alternative to current therapies, overcoming some of their major limitations, and inspire further investigation of LFS for seizure control in MTLE.