bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ontogeny of collective behaviour
Authors: Muratore Isabella Benter , Garnier Simon 
Published: February 2023

During their lifetime, superorganisms, like unitary organisms, undergo transformations that change the machinery of their collective behaviour. Here, we suggest that these transformations are largely understudied and propose that more systematic research into the ontogeny of collective behaviours is needed if we hope to better understand the link between proximate behavioural mechanisms and the development of collective adaptive functions. In particular, certain social insects engage in self-assemblage, forming dynamic and physically connected architectures with striking similarities to developing multicellular organisms, making them good model systems for ontogenetic studies of collective behaviour. However, exhaustive time series and three-dimensional data are required to thoroughly characterize the different life stages of the collective structures and the transitions between these stages. The well-established fields of embryology and developmental biology offer practical tools and theoretical frameworks that could speed up the acquisition of new knowledge about the formation, development, maturity and dissolution of social insect self-assemblages and, by extension, other superorganismal behaviours. We hope that this review will encourage an expansion of the ontogenetic perspective in the field of collective behaviour and, in particular, in self-assemblage research, which has far-reaching applications in robotics, computer science and regenerative medicine.
This article is part of a discussion meeting issue ‘Collective behaviour through time’.
Discovery of a novel merbecovirus DNA clone contaminating agricultural rice sequencing datasets from Wuhan, China
Authors: Jones Adrian , Zhang Daoyu , Massey Steven E. , Deigin Yuri , Nemzer Louis R. , Quay Steven C. 
Published: February 2023

AbstractHKU4-related coronaviruses are a group of betacoronaviruses belonging to the same merbecovirus subgenus as Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV), which causes severe respiratory illness in humans with a mortality rate of over 30%. The high genetic similarity between HKU4-related coronaviruses and MERS-CoV makes them an attractive subject of research for modeling potential zoonotic spillover scenarios. In this study, we identify a novel coronavirus contaminating agricultural rice RNA sequencing datasets from Wuhan, China. The datasets were generated by the Huazhong Agricultural University in early 2020. We were able to assemble the complete viral genome sequence, which revealed that it is a novel HKU4-related merbecovirus. The assembled genome is 98.38% identical to the closest known full genome sequence,Tylonycteris pachypusbat isolate BtTp-GX2012. Usingin silicomodeling, we identified that the novel HKU4-related coronavirus spike protein likely binds to human dipeptidyl peptidase 4 (DPP4), the receptor used by MERS-CoV. We further identified that the novel HKU4-related coronavirus genome has been inserted into a bacterial artificial chromosome in a format consistent with previously published coronavirus infectious clones. Additionally, we have found a near complete read coverage of the spike gene of the MERS-CoV reference strain HCoV-EMC/2012, and identify the likely presence of a HKU4-related-MERS chimera in the datasets. Our findings contribute to the knowledge of HKU4-related coronaviruses and document the use of a previously unpublished HKU4 reverse genetics system in apparent MERS-CoV related gain-of-function research. Our study also emphasizes the importance of improved biosafety protocols in sequencing centers and coronavirus research facilities.
Fiberbots: Robotic fibers for high-precision minimally invasive surgery
Authors: Abdelaziz Mohamed E. M. K. , Zhao Jinshi , Rosa Bruno Gil , Lee Hyun-Taek , Simon Daniel , Vyas Khushi , Li Bing , Koguna Hanifa , Li Yue , Demircali Ali Anil , Uvet Huseyin , Gencoglan Gulsum , Akcay Arzu , Elriedy Mohamed , Kinross James , Dasgupta Ranan , Takats Zoltan , Yeatman Eric , Yang Guang-Zhong , Temelkuran Burak 
Published: February 2023

AbstractTechnologies that rely on the fundamental principle of thermal expansion have demonstrated high-precision, a growing demand in fields driven by miniaturization. However, scalable production of high aspect ratio devices that harness this capability while facilitating flexibility in design and functionality remains a challenge. We employed the high-throughput fiber thermal drawing technique to readily fabricate multimaterial fiberbots that can precisely and omnidirectionally move by asymmetric thermal expansion. These millimeter-scale fibers (< 2 mm) show excellent repeatability and linearity, negligible hysteresis, and can achieve micron-level resolution over four orders of magnitude motion range. By integrating these robotic fibers with medical devices that can perform cellular-level tissue imaging, diagnosis, and manipulation, we showcase their versatility through benchtop and preclinical animal studies and their overall potential impact on medicine, biomedical engineering, robotics, and beyond.One Sentence SummaryScalable manufacturing and integration of robotic fibers that deliver high-precision motion when heated.
Identification of major quantitative trait loci for parthenocarpic ability in East Asian melon
Authors: Yoshioka Yosuke , Nashiki Akito , Zaelani Ahmad , Isobe Sachiko , Shirasawa Kenta , Shimomura Koichiro , Ohyama Akio 
Published: February 2023

AbstractNatural (genetic) parthenocarpy contributes to fruit yield and quality under unfavorable environmental conditions where there are no effective pollinators or fertile pollen grains. Several old melon cultivars and weedy melon in East Asia are known to have strong parthenocarpic ability, but there has been little progress in intentionally introducing this ability into current F1hybrid cultivars. Here, we examined its inheritance and confirmed the selection accuracy of DNA markers linked to it. We conducted QTL analysis using three F2populations derived from crosses between a non-parthenocarpic cultivar and three parthenocarpic accessions, and detected two major QTLs on chromosomes 2 (par2.1) and 3 (par3.1). The parthenocarpic parent allele at both QTLs enhanced parthenocarpic ability. Phenotypic segregation was well explained bypar2.1andpar3.1in two F2populations derived from Japanese weedy melon and an old Korean cultivar and bypar3.1in one from an old Japanese cultivar. This difference suggests that the effects ofpar2.1andpar 3.1depend on genetic background. Both QTL regions contain several phytohormone-related genes, so we randomly selected SNPs in auxin- and ethylene-related genes to confirm the accuracy of selection for parthenocarpic ability. These SNP markers proved sufficient, though not perfect, to select plants with strong parthenocarpic ability. These results provide new insights into the molecular mechanisms of parthenocarpic ability in melon and will contribute to the development of new cultivars with high parthenocarpic ability.Key messageSeveral oriental melons have strong parthenocarpic ability controlled by one or two loci. DNA markers linked to these loci can select individuals with this ability.
Can mechanistic constraints on recombination reestablishment explain the long-term maintenance of degenerate sex chromosomes?
Authors: Lenormand Thomas , Roze Denis 
Published: February 2023

AbstractY and W chromosomes often stop recombining and degenerate. Most work on recombination suppression has focused on the mechanisms favoring recombination arrest in the short term. Yet, the long-term maintenance of recombination suppression is critical to evolving degenerate sex chromosomes. This long-term maintenance has been little investigated. In the long term, recombination suppression may be maintained for selective reasons (e.g., involving the emergence of nascent dosage compensation), or due to mechanistic constraints preventing the reestablishment of recombination, for instance when complex chromosomal rearrangements evolve on the Y. In this paper, we investigate these ‘constraint’ theories. We show that they face a series of theoretical difficulties: they are not robust to extremely low rates of recombination restoration; they would rather cause population extinction than Y degeneration; they are less efficient at producing a non-recombining and degenerate Y than scenarios adding a selective pressure against recombination, whatever the rate of recombination restoration. Finally, whether such very high constraints exist is questionable. Very low rates of recombination reestablishment are sufficient to prevent Y degeneration, given the large fitness advantage to recover a non-degenerate Y or W for the heterogametic sex. The assumption of a lack of genetic variation to restore recombination seems also implausible given known mechanisms to restore a recombining pair of sex chromosomes.
Precise and efficient C-to-U RNA Base Editing with SNAP-CDAR-S
Authors: Latifi Ngadhnjim , Mack Aline Maria , Tellioglu Irem , Di Giorgio Salvatore , Stafforst Thorsten 
Published: February 2023

AbstractSite-directed RNA base editing enables the transient and dosable change of genetic information and represents a recent strategy to manipulate cellular processes, paving ways to novel therapeutic modalities. While tools to introduce adenosine-to-inosine changes have been explored quite intensively, the engineering of precise and programmable tools for cytidine-to-uridine editing is somewhat lacking behind. Here we demonstrate that the cytidine deaminase domain evolved from the ADAR2 adenosine deaminase, taken from the RESCUE-S tool, provides very efficient and highly programmable editing when changing the RNA targeting mechanism from Cas13-based to SNAP-tag-based. Optimization of the guide RNA chemistry further allowed to dramatically improve editing yields in the difficult-to-edit 5’-CCN sequence context thus improving the substrate scope of the tool. Regarding editing efficiency, SNAP-CDAR-S outcompeted the RESCUE-S tool clearly on all tested targets, and was highly superior in perturbing the β-catenin pathway. NGS analysis showed similar, moderate global off-target A-to-I and C-to-U editing for both tools.
Optogenetic urothelial cell stimulation induces bladder contractions and pelvic nerve afferent firing
Authors: Robilotto Gabriella L , Yang Olivia J , Alom Firoj , Johnson Richard D , Mickle Aaron D 
Published: February 2023

AbstractUrothelial cells, which play an essential role in the barrier function, are also thought to play a sensory role in bladder physiology by releasing signaling molecules in response to sensory stimuli that act upon adjacent sensory neurons. However, it is challenging to study this communication due to the overlap in receptor expression and proximity of urothelial cells to sensory neurons. To overcome this challenge, we have developed a mouse model where we can directly stimulate urothelial cells using optogenetics. We have crossed a uroplakin II-cre mouse (UPK2-Cre) with a mouse that expresses the light-activated cation channel, Channelrhodopsin-2 (ChR2), in the presence of cre-expression. Optogenetic stimulation of urothelial cells cultured from UPK2-ChR2 initiates cellular depolarization and release of adenosine triphosphate. Cystometry recordings demonstrate that optical stimulation of urothelial cells increases bladder pressure and pelvic nerve activity. Increases in bladder pressure persisted, albeit to a lesser extent, when the bladder was excised in anin vitropreparation. The P2X receptor antagonist, PPADS, significantly reduced optically evoked bladder contractionsin vivoandex vivo. Further, corresponding nerve activity was also inhibited with PPADS. Our data suggest that urothelial cells can initiate robust bladder contractions via sensory nerve signaling or contractions through local signaling mechanisms. This data supports a foundation of literature demonstrating communication between sensory neurons and urothelial cells. Importantly, with further use of these optogenetic tools, we hope to scrutinize this signaling mechanism, its importance for normal micturition and nociception, and how it may be altered in pathophysiologic conditions.Animal StudiesAll the procedures involving mice and mouse tissue performed in this study were approved by the University of Florida Institutional Animal Care and Use Committee and in strict accordance with the US National Institute of Health (NIH) Guide for the Care and Use of Laboratory Animals.SignificanceIt has been appreciated for almost two decades that urothelial cells play a sensory role in bladder function. However, it has been particularly challenging to study this communication as both sensory neurons, and urothelial cells express the same sensory receptors. Here we demonstrate an optogenetic technique to specifically stimulate urothelial cells and evaluate the effects on bladder physiology. We used this technique to show that specific urothelial stimulation resulted in bladder contractions. This approach will have a long-lasting impact on how we study urothelial-to-sensory neuron communication and the changes that occur under disease conditions.
Macrophage-targeted lipid nanoparticle delivery of microRNA-146a to mitigate hemorrhagic shock-induced acute respiratory distress syndrome
Authors: Fei Qinqin , Shalosky Emily M. , Barnes Ryelie , Shukla Vasudha C. , Ballinger Megan N. , Farkas Laszlo , Lee Robert J. , Ghadiali Samir N. , Englert Joshua A. 
Published: February 2023

ABSTRACTThe pro-inflammatory response of alveolar macrophages to injurious physical forces during mechanical ventilation is regulated by the anti-inflammatory microRNA, miR-146a. Increasing miR-146a expression to supraphysiologic levels using untargeted lipid nanoparticles reduces ventilator-induced lung injury, but requires a high initial dose of miR-146a making it less clinically applicable. In this study, we developed mannosylated lipid nanoparticles that can effectively mitigate lung injury at the initiation of mechanical ventilation with lower doses of miR-146a. We used a physiologically relevant humanizedin vitroco-culture system to evaluate the cell-specific targeting efficiency of the mannosylated lipid nanoparticle. We discovered that mannosylated lipid nanoparticles preferentially deliver miR-146a to alveolar macrophages and reduce force-induced inflammationin vitro. Ourin vivostudy using a clinically relevant mouse model of hemorrhagic shock-induced acute respiratory distress syndrome demonstrated that delivery of a low dose miR-146a (0.1 nmol) using mannosylated lipid nanoparticles dramatically increases miR-146a in mouse alveolar macrophages and decreases lung inflammation. These data suggest that mannosylated lipid nanoparticles may have therapeutic potential to mitigate lung injury during mechanical ventilation.
Small-molecule targeting of GPCR-independent non-canonical G protein signaling inhibits cancer progression
Authors: Zhao Jingyi , DiGiacomo Vincent , Ferreras-Gutierrez Mariola , Dastjerdi Shiva , de Opakua Alain Ibáñez , Park Jong-Chan , Luebbers Alex , Chen Qingyan , Beeler Aaron , Blanco Francisco J , Garcia-Marcos Mikel 
Published: February 2023

AbstractActivation of heterotrimeric G-proteins (Gαβγ) by G-protein-coupled receptors (GPCRs) is a quintessential mechanism of cell signaling widely targeted by clinically-approved drugs. However, it has become evident that heterotrimeric G-proteins can also be activated via GPCR-independent mechanisms that remain untapped as pharmacological targets. GIV/Girdin has emerged as a prototypical non-GPCR activator of G proteins that promotes cancer metastasis. Here, we introduce IGGi-11, a first-in-class smallmolecule inhibitor of non-canonical activation of heterotrimeric G-protein signaling. IGGi-11 binding to G-protein α-subunits (Gαi) specifically disrupted their engagement with GIV/Girdin, thereby blocking non-canonical G-protein signaling in tumor cells, and inhibiting pro-invasive traits of metastatic cancer cellsin vitroand in mice. In contrast, IGGi-11 did not interfere with canonical G-protein signaling mechanisms triggered by GPCRs. By revealing that small molecules can selectively disable non-canonical mechanisms of G-protein activation dysregulated in disease, these findings warrant the exploration of therapeutic modalities in G-protein signaling that go beyond targeting GPCRs.
Co-localization of antibiotic resistance genes is widespread in the infant gut microbiome and associates with an immature gut microbial composition
Authors: Li Xuanji , Brejnrod Asker , Trivedi Urvish , Russel Jakob , Stokholm Jakob , Thorsen Jonathan , Shah Shiraz A , Vestergaard Gisle Alberg , Rasmussen Morten Arendt , Nesme Joseph , Bisgaard Hans , Sørensen Søren Johannes 
Published: February 2023

AbstractEven in the absence of antibiotic exposure, the gut microbiome of infants has been shown to contain numerous antibiotic resistance genes (ARGs), but the mechanism for this remains unclear. In environmental bacteria, the selective advantage of ARGs can be increased through co-localization with genes such as other ARGs, biocide resistance genes, metal resistance genes, and virulence genes. However, this phenomenon is unknown from the human gut microbiome during early life despite frequent exposures to biocides and metals from an early age. Here, we conducted a comprehensive analysis of genetic co-localization of resistance genes in a cohort of 662 Danish children and examined the association between such co-localization and environmental factors as well as gut microbial maturation. Our study showed that co-localization of ARGs with other resistance and virulence genes is common in the early gut microbiome and is associated with gut bacteria that are indicative of low maturity, especiallyE. coli. The most common forms of co-localization involved tetracycline and fluoroquinolone resistance genes located near other ARGs, and, on plasmids, co-localization predominantly occurred in the form of class 1 integrons. Antibiotic use caused a short-term increase in mobile ARGs, while non-mobile ARGs showed no significant change. Finally, we found that a high abundance of virulence genes was associated with low gut microbial maturity and that virulence genes showed even higher potential for mobility than ARGs. Our study highlights important constraints that need to be considered when developing strategies to combat ARG dissemination.
Microtubule binding of the human HAUS complex is directly controlled by importins and Ran-GTP
Authors: Ustinova Kseniya , Ruhnow Felix , Gili Maria , Surrey Thomas 
Published: February 2023

ABSTRACTMitotic spindle assembly during cell division is a highly regulated process. Ran-GTP produced around chromosomes controls the activity of a multitude of spindle assembly factors by releasing them from inhibitory interaction with importins. A major consequence of Ran-GTP regulation is the stimulation of local microtubule nucleation around chromosomes via augmin/HAUS-mediated branched microtubule nucleation, a process that is critically important for correct spindle assembly. However, augmin is not known to be a direct target of the Ran-GTP pathway, raising the question of how its activity is controlled. Here we present thein vitroreconstitution of Ran-GTP-regulated microtubule binding of the human HAUS complex. We demonstrate that importins directly bind to the HAUS complex, which prevents HAUS from binding to microtubules. Ran-GTP relieves this inhibition. Therefore, the HAUS complex is a direct target of the Ran-GTP pathway, suggesting that branching microtubule nucleation is directly regulated by the Ran-GTP gradient around chromosomes in dividing cells.
Geographic and seasonal variation of theforgene reveal signatures of local adaptation inDrosophila melanogaster
Authors: Perez Dylan J. Padilla 
Published: February 2023

AbstractIn the early 1980s, the observation thatDrosophila melanogasterlarvae differed in their foraging behavior laid the foundation for the work that would later lead to the discovery of the foraging gene (for) and its associated foraging phenotypes, rover and sitter. Since then, the molecular characterization of theforgene and our understanding of the mechanisms that maintain its phenotypic variants in the laboratory have progressed enormously. However, the significance and dynamics of such variation are yet to be investigated in nature. With the advent of next-generation sequencing, it is now possible to identify loci underlying adaptation of populations in response to environmental variation. Here, I present results of a genotype-environment association analysis that quantifies variation at theforgene among samples ofD. melanogasterstructured across space and time. These samples consist of published genomes of adult flies collected worldwide, and at least twice per site of collection (during spring and fall). Both an analysis of genetic differentiation based onFstvalues, and an analysis of population structure revealed an east-west gradient in allele frequency. This gradient may be the result of spatially varying selection driven by the seasonality of precipitation. These results support the hypothesis that different patterns of gene flow as expected under models of isolation by distance and potentially isolation by environment are driving genetic differentiation among populations. Overall, this study is essential for understanding the mechanisms underlying the evolution of foraging behavior inD. melanogaster.
Application of nanotags and nanobodies for live cell single-molecule imaging of the Z-ring inEscherichia coli
Authors: Westlund Emma , Bergenstråle Axel , Pokhrel Alaska , Chan Helena , Skoglund Ulf , Daley Daniel O. , Söderström Bill 
Published: February 2023

AbstractUnderstanding where proteins are localized in a bacterial cell is essential for understanding their function and regulation. This is particularly important for proteins that are involved in cell division, which localize at the division septum and assemble into highly regulated complexes. Current knowledge of these complexes has been greatly facilitated by super-resolution imaging using fluorescent protein fusions. Herein we demonstrate with FtsZ that single-molecule PALM images can be obtainedin-vivousing a genetically fused nanotag (ALFA) and a corresponding nanobody fused to mEos3.2. The methodology presented is applicable to other bacterial proteins.
Isolated nuclei from frozen tissue are the superior source for single cell RNA-seq compared with whole cells
Authors: Jiang Andrew , Lehnert Klaus , Reid Suzanne J. , Handley Renee R. , Jacobsen Jessie C. , Rudiger Syke R. , McLaughlan Clive J. , Verma Paul J. , Bawden C. Simon , Snell Russell G. 
Published: February 2023

AbstractThe isolation of intact single cells from frozen tissue is a challenge due to the mechanical and physical stress inflicted upon the cell during the freeze-thaw process. Ruptured cells release ambient RNA into the cell suspension, which can become encapsulated into droplets during droplet based single cell RNA-seq library preparation methods. The presence of ambient RNA in droplets has been suggested to impact data quality, however there have been limited reports on single cell RNA-seq data from frozen tissue. Here, we compare the results of single cell RNA-seq derived from disaggregated cells from frozen brain tissue with single nuclei RNA-seq derived from purified nuclei of identical tissue using the 10X Genomics Chromium 3’gene expression assay. Our results indicated that presence of ambient RNA in the cell suspension resulted in single cell RNA-seq data with a 25-fold lower gene count, a 5-fold lower UMI count per cell and a 2-fold lower fraction of reads per cell compared with single nuclei RNA-seq data. Cell clustering with the single cell RNA-seq data was unable to resolve the heterogeneity of brain cell types. Our conclusion is that nuclei from frozen tissue are the superior substrate for single cell transcriptome analysis.