bluuebunny/crossref_metadata_2025_split huggingface dataset:
Image-guided deployment and monitoring of a novel tungsten nanoparticle–infused radiopaque absorbable inferior vena cava filter in pigs
Authors: San Valentin Erin Marie , Damasco Jossana A. , Bernardino Marvin , Court Karem A. , Godin Biana , Canlas Gino Martin , Melancon Adam , Chintalapani Gouthami , Jacobsen Megan C. , Norton William , Layman Rick R. , Fowlkes Natalie , Chen Stephen R. , Huang Steven Y. , Melancon Marites P. 
Published: February 2023

AbstractThe use of absorbable inferior vena cava filters (IVCFs) constructed with poly-p-dioxanone (PPDO) eliminates risks and complications associated with the use of retrievable metallic filters. Radiopacity of radiolucent PPDO IVCFs can be improved with the incorporation of nanoparticles (NPs) made of high-atomic number materials such as gold and bismuth. In this study, we focused on incorporating tungsten NPs (WNPs), along with polyhydroxybutyrate (PHB), polycaprolactone (PCL), and polyvinylpyrrolidone (PVP) polymers to increase the surface adsorption of the WNPs. We compared the imaging properties of WNPs with single-polymer PHB (W-P) and WNPs with polymer blends consisting of PHB, PCL, and PVP (W-PB). Ourin vitroanalyses using PPDO sutures showed enhanced radiopacity with either W-P or W-PB coating, without compromising the inherent physico-mechanical properties of the PPDO sutures. We observed a more sustained release of WNPs from W-PB-coated sutures than W-P-coated sutures. We successfully deployed W-P- and W-PB-coated IVCFs into the inferior vena cava of pig models, with monitoring by fluoroscopy. At the time of deployment, W-PB-coated IVCFs showed a 2-fold increase in radiopacity compared to W-P-coated IVCFs. Longitudinal monitoring ofin vivoIVCFs over a 12-week period showed a drastic decrease in radiopacity at week 3 for both filters. Results of this study highlight the utility of NPs and polymers for enhancing radiopacity of medical devices; however, different methods of incorporating NPs and polymers can still be explored to improve the efficacy, safety, and quality of absorbable IVCFs.
APOE4drives transcriptional heterogeneity and maladaptive immunometabolic responses of astrocytes
Authors: Lee Sangderk , Williams Holden C. , Gorman Amy A. , Devanney Nicholas A. , Harrison Douglas A. , Walsh Adeline E. , Goulding Danielle S. , Tuck Tony , Schwartz James L. , Zajac Diana J. , Macauley Shannon L. , Estus Steven , Julia TCW , Johnson Lance A. , Morganti Josh M. 
Published: February 2023

SummaryApolipoprotein E4 (APOE4) is the strongest risk allele associated with the development of late onset Alzheimer’s disease (AD). Across the CNS, astrocytes are the predominant expressor ofAPOEwhile also being critical mediators of neuroinflammation and cerebral metabolism. APOE4 has been consistently linked with dysfunctional inflammation and metabolic processes, yet insights into the molecular constituents driving these responses remain unclear. Utilizing complementary approaches across humanized APOE mice and isogenic human iPSC astrocytes, we demonstrate that ApoE4 alters the astrocyte immunometabolic response to pro-inflammatory stimuli. Our findings show that ApoE4-expressing astrocytes acquire distinct transcriptional repertoires at single-cell and spatially-resolved domains, which are driven in-part by preferential utilization of the cRel transcription factor. Further, inhibiting cRel translocation in ApoE4 astrocytes abrogates inflammatory-induced glycolytic shifts and in tandem mitigates production of multiple pro-inflammatory cytokines. Altogether, our findings elucidate novel cellular underpinnings by which ApoE4 drives maladaptive immunometabolic responses of astrocytes.
Arachidonic acid does not grease the exocytotic SNARE machinery
Authors: Fasshauer Dirk 
Published: February 2023

AbstractIt has been proposed that arachidonic acid stimulates neurite outgrowth by specifically activating syntaxin 3, a SNARE proteins that mediates the fusion of transport vesicles with the plasma membrane and is thus instrumental for the insertion of new membrane needed for cell growth and proliferation. Considering the important role of arachidonic acid and other polyunsaturated fatty acids for human health, these findings would have wide implications for everyday life. Here, I have report that the effect of arachidonic acid is caused by a nonspecific, detergent-like action on SNARE proteinsin vitro. The action requires unphysiologically high concentrations, is mimicked by several detergents or detergent-like substances forming micelles regardless of whether arachidonic acid is present or not, and is thus highly unlikely to be of any physiological significance for SNARE function.
SUMOylation of PTEN promotes DNA end resection through directly dephosphorylating 53BP1 in homologous recombination repair
Authors: He Jianfeng , Guo Yanmin , Deng Rong , Li Lian , Huang Caihu , Chen Ran , Wang Yanli , Huang Jian , Cheng Jinke , Chen Guo-Qiang , Zheng Junke , Zhao Xian , Yu Jianxiu 
Published: February 2023

AbstractHomologous recombination (HR) repair for DNA double-strand breaks (DSBs) is critical for maintaining genome stability and cell survival. Nuclear PTEN plays a key role in HR repair, but the underlying mechanism remains largely elusive. We find that SUMOylated PTEN promotes HR repair but represses non-homologous end joining (NHEJ) repair by directly dephosphorylating 53BP1. During DNA damage responses (DDR), p14ARF was phosphorylated and then interacted efficiently with PTEN, thus promoting PTEN SUMOylation as an atypical SUMO E3 ligase. Interestingly, SUMOylated PTEN was subsequently recruited to the chromatin at DNA-break sites. This was because that SUMO1 conjugated to PTEN was recognized and bound by the SUMO-interacting motif (SIM) of BRCA1, which has been located to the core of 53BP1 foci on the chromatin during S/G2 stage. Further, these chromatin-loaded PTEN directly and specifically dephosphorylated pT543 of 53BP1, resulting in the dissociation of 53BP1-complex, which facilitated DNA end resection and ongoing HR repair. The SUMOylation-deficient PTENK254Rmice also showed decreased DNA damage repairin vivo.Blocking PTEN SUMOylation pathway with either an SUMOylation inhibitor or a p14ARF(2-13) peptide sensitized tumor cells to chemotherapy. Our study therefore provides the new mechanistic understanding of PTEN in HR repair and clinical intervention of chemo-resistant tumors.
Towards a more robust non-invasive assessment of functional connectivity
Authors: Westner Britta U. , Kujala Jan , Gross Joachim , Schoffelen Jan-Mathijs 
Published: February 2023

AbstractNon-invasive evaluation of functional connectivity, based on source-reconstructed estimates of phase-difference-based metrics, is notoriously non-robust. This is due to a combination of factors, ranging from a misspecification of seed regions to suboptimal baseline assumptions, and residual signal leakage. In this work, we propose a new analysis scheme of source level phase-difference-based connectivity, which is aimed at optimizing the detection of interacting brain regions. Our approach is based on the combined use of sensor subsampling and dual-source beamformer estimation of all-to-all connectivity on a prespecified dipolar grid. First, a pairwise two-dipole model, to account for reciprocal leakage in the estimation of the localized signals, allows for a usable approximation of the pairwise bias in connectivity due to residual leakage of ‘third party’ noise. Secondly, using sensor array subsampling, the recreation of multiple connectivity maps using different subsets of sensors allows for the identification of consistent spatially localized peaks in the 6-dimensional connectivity maps, indicative of true brain region interactions. These steps are combined with the subtraction of null coherence estimates to obtain the final coherence maps. With extensive simulations, we compared different analysis schemes for their detection rate of connected dipoles, as a function of signal-to-noise ratio, phase difference and connection strength. We demonstrate superiority of the proposed analysis scheme in comparison to single-dipole models, or an approach that discards the zero phase difference component of the connectivity. We conclude that the proposed pipeline allows for a more robust identification of functional connectivity in experimental data, opening up new possibilities to study brain networks with mechanistically inspired connectivity measures in cognition and in the clinic.
Helixer–de novoPrediction of Primary Eukaryotic Gene Models Combining Deep Learning and a Hidden Markov Model
Authors: Holst Felix , Bolger Anthony , Günther Christopher , Maß Janina , Triesch Sebastian , Kindel Felicitas , Kiel Niklas , Saadat Nima , Ebenhöh Oliver , Usadel Björn , Schwacke Rainer , Bolger Marie , Weber Andreas P.M. , Denton Alisandra K. 
Published: February 2023

AbstractGene structural annotation is a critical step in obtaining biological knowledge from genome sequences yet remains a major challenge in genomics projects. Currentde novoHidden Markov Models are limited in their capacity to model biological complexity; while current pipelines are resource-intensive and their results vary in quality with the available extrinsic data. Here, we build on our previous work in applying Deep Learning to gene calling to make a fully applicable, fast and user friendly tool for predicting primary gene models from DNA sequence alone. The quality is state-of-the-art, with predictions scoring closer by most measures to the references than to predictions from otherde novotools. Helixer’s predictions can be used as is or could be integrated in pipelines to boost quality further. Moreover, there is substantial potential for further improvements and advancements in gene calling with Deep Learning.Helixer is open source and available athttps://github.com/weberlab-hhu/HelixerA web interface is available athttps://www.plabipd.de/helixer_main.html
A comprehensivein vivoscreen of yeast farnesyltransferase activity reveals broad reactivity across a majority of CXXX sequences
Authors: Kim June H. , Hildebrandt Emily R. , Sarkar Anushka , Yeung Wayland , Waldon La Ryel A. , Kannan Natarajan , Schmidt Walter K. 
Published: February 2023

AbstractThe current understanding of farnesyltransferase (FTase) specificity was pioneered through investigations of reporters like Ras and Ras-related proteins that possess a C-terminal CaaX motif that consists of 4 amino acid residues: Cysteine – aliphatic1– aliphatic2– variable (X). These studies led to the finding that proteins with the CaaX motif are subject to a 3-step post-translational modification pathway involving farnesylation, proteolysis, and carboxylmethylation. Emerging evidence indicates, however, that FTase can farnesylate sequences outside the CaaX motif and that these sequences do not undergo the canonical 3-step pathway. In this work, we report a comprehensive evaluation of all possible CXXX sequences as FTase targets using the reporter Ydj1, an Hsp40 chaperone that only requires farnesylation for its activity. Our genetic and high throughput sequencing approach reveals an unprecedented profile of sequences that yeast FTase can recognizein vivo, which effectively expands the potential target space of FTase within the yeast proteome. We also document that yeast FTase specificity is majorly influenced by restrictive amino acids at a2and X positions as opposed to the resemblance of CaaX motif as previously regarded. This first complete evaluation of CXXX space expands the complexity of protein isoprenylation and marks a key step forward in understanding the potential scope of targets for this isoprenylation pathway.
Structural basis for inactivation of PRC2 by G-quadruplex RNA
Authors: Song Jiarui , Gooding Anne R. , Hemphill Wayne O. , Kasinath Vignesh , Cech Thomas R. 
Published: February 2023

AbstractThe histone methyltransferase PRC2 (Polycomb Repressive Complex 2) silences genes via successively attaching three methyl groups to lysine 27 of histone H3. PRC2 associates with numerous pre-mRNA and lncRNA transcripts with a binding preference for G-quadruplex RNA. Here, we present a 3.3Å-resolution cryo-EM structure of PRC2 bound to a G-quadruplex RNA. Notably, RNA mediates the dimerization of PRC2 by binding both protomers and inducing a protein interface comprised of two copies of the catalytic subunit EZH2, which limits nucleosome DNA interaction and occludes H3 tail accessibility to the active site. Our results reveal an unexpected mechanism for RNA-mediated inactivation of a chromatin-modifying enzyme. Furthermore, the flexible loop of EZH2 that helps stabilize RNA binding also facilitates the handoff between RNA and DNA, an activity implicated in PRC2 regulation by RNA.One-Sentence SummaryCryo-EM structure of RNA-bound PRC2 dimer elucidates an unexpected mechanism of PRC2 inhibition by RNA.
Mitochondrial Membranes: Model Lipid Compositions, Material Properties and the Changing Curvature of Cardiolipin
Authors: Konar Sukanya , Arif Hina , Allolio Christoph 
Published: February 2023

Mammalian andDrosophila Melanogastermodel mitochondrial membrane compositions are constructed from experimental lipidomics data. Simplified compositions for inner and outer mitochondrial membranes are provided, including an asymmetric inner mitochondrial membrane. We performed atomistic molecular dynamics simulations of these membranes and computed their material properties. When comparing these properties to those obtained by extrapolation from their constituting lipids, we find good overall agreement. Finally, we analyzed the curvature effect of cardiolipin, considering ion concentration effects, oxidation and pH. We draw the conclusion that cardiolipin negative curvature is most likely due to counterion effects, such as cation adsorption, in particular of H3O+. This oft-neglected effect might account for the puzzling behavior of this lipid.SIGNIFICANCEMitochondrial membranes are of fundamental interest to the pathogenesis of neurodegenerative diseases. The biophysics of mitochondrial membranes can be expected to profoundly influence both the electron transport chain and larger-scale mitochondrial morphology. We provide model mitochondrial membrane compositions and examine their mechanic properties. Reconstructing these properties from their constituent lipids, we facilitate the creation of mesoscopic models. Cardiolipin, as the key mitochondrial lipid is given special attention. We find that its mechanical properties, in particular its curvature, are not constant, but highly dependent on specific ion effects, concentration and oxidation state.
Phytoplankton adaptive resilience to climate change collapses in case of extreme events – A modeling study
Authors: Sauterey Boris , Le Gland Guillaume , Cermeño Pedro , Aumont Olivier , Lévy Marina , Vallina Sergio M. 
Published: February 2023

AbstractAs climate change unravels, ecosystems are facing a warming of the climate and an increase in extreme heat events that are unprecedented in recent geological history. We know very little of the ability of oceanic phytoplankton communities, key players in the regulation of Earth’s climate by the oceans, to adapt to these changes. Quantifying the resilience of phytoplankton communities to environmental stressors by means of adaptive evolution is however crucial to accurately predict the response of marine ecosystems to climate change. In this work, we use an eco-evolutionary model to simulate the adaptive response of marine phytoplankton to temperature changes in an initially temperate oligotrophic water-column. By exploring a wide range of scenarios of phytoplankton adaptive capacity, we find that phytoplankton can adapt to temperature increases –even very large ones– as long as they occur over the time scale of a century. However, when rapid and extreme events of temperature change are considered, the phytoplankton adaptive capacity breaks down in a number of our scenarios in which primary productivity plummets as a result. This suggests that current Earth System Models implicitly assuming perfect and instantaneous phytoplankton adaptation to temperature might be overestimating the phytoplankton’s resilience to climate change.
Two novel flavi-like viruses shed light on the plant infecting koshoviruses
Authors: Debat Humberto , Bejerman Nicolás 
Published: February 2023

AbstractThe familyFlaviviridaeis composed of viruses with a positive sense single-stranded RNA genome and includes viruses that are important veterinary and human pathogens. Most members of the family are arthropod and vertebrate-infecting viruses but more recently flavi-like divergent viruses have been identified in marine invertebrate and vertebrate hosts. The striking discovery of gentian Kobu-sho-associated virus (GKaV) expanded the host range of flaviviruses to plants, which was complemented by a recently reported flavi-like virus in carrot, suggesting they could be grouped in a proposed Koshovirus genus. Here, we report the identification in transcriptomic datasets and characterization of two novel RNA viruses from the flowering plantsCoptis teetaandSonchus asper, which have genetic and evolutionary affinity to koshoviruses. These two new viruses are members of novel species which were dubbed Coptis flavi-like virus 1 (CopV1) and Sonchus flavi-like virus 1 (SonV1) and with a viral monopartite RNA of ca. 24 kb, likely have the longest genomes among plant-associated RNA viruses yet. Structural and functional annotations of the polyproteins of all koshoviruses resulted in the detection not only of the expected helicase and RNA-dependent RNA polymerase, but also several additional divergent domains such as AlkB oxigenase, Trypsin-like serine protease, methyltransferase, and envelope E1 flavi-like domains. Phylogenetic analysis groups in a monophyletic clade CopV1, SonV1, GKaV and the carrot flavi-like virus robustly supporting the recently proposed genus Koshovirus of plant infecting flavi-like viruses.
Bilateral asymmetric hip stiffness applied by a robotic hip exoskeleton elicits kinematic and kinetic adaptation
Authors: Abdikadirova Banu , Price Mark , Jaramillo Jonaz Moreno , Hoogkamer Wouter , Huber Meghan E. 
Published: February 2023

AbstractWearable robotic exoskeletons hold great promise for gait rehabilitation as portable, accessible tools. However, a better understanding of the potential for exoskeletons to elicit neural adaptation—a critical component of neurological gait rehabilitation—is needed. In this study, we investigated whether humans adapt to bilateral asymmetric stiffness perturbations applied by a hip exoskeleton, taking inspiration from asymmetry augmentation strategies used in split-belt treadmill training. During walking, we applied torques about the hip joints to repel the thigh away from a neutral position on the left side and attract the thigh toward a neutral position on the right side. Six participants performed an adaptation walking trial on a treadmill while wearing the exoskeleton. The exoskeleton elicited time-varying changes and aftereffects in step length and propulsive/braking ground reaction forces, indicating behavioral signatures of neural adaptation. These responses resemble typical responses to split-belt treadmill training, suggesting that the proposed intervention with a robotic hip exoskeleton may be an effective approach to (re)training symmetric gait.
AnAnaplasma phagocytophilumT4SS effector, AteA, is essential for tick infection
Authors: Park Jason M. , Genera Brittany M. , Fahy Deirdre , Swallow Kyle T. , Nelson Curtis M. , Oliver Jonathan D. , Shaw Dana K. , Munderloh Ulrike G. , Brayton Kelly A. 
Published: February 2023

ABSTRACTPathogens must adapt to disparate environments in permissive host species, a feat that is especially pronounced for vector-borne microbes, which transition between vertebrate hosts and arthropod vectors to complete their lifecycles. Most knowledge about arthropod-vectored bacterial pathogens centers on their life in the mammalian host, where disease occurs. However, disease outbreaks are driven by the arthropod vectors. Adapting to the arthropod is critical for obligate intracellular rickettsial pathogens, as they depend on eukaryotic cells for survival. To manipulate the intracellular environment, these bacteria use Type IV Secretion Systems (T4SS) to deliver effectors into the host cell. To date, few rickettsial T4SS translocated effectors have been identified and have only been examined in the context of mammalian infection. We identified an effector from the tick-borne rickettsial pathogenAnaplasma phagocytophilum, HGE1_02492, as critical for survival in tick cells and acquisition by ticksin vivo. Conversely, HGE1_02492 was dispensable during mammalian cell culture and murine infection. We show HGE1_02492 is translocatable in a T4SS-dependent manner to the host cell cytosol. In eukaryotic cells, the HGE1_02492 localized with cortical actin filaments, which is dependent on multiple sub-domains of the protein. HGE1_02492 is the first arthropod-vector specific T4SS translocated effector identified from a rickettsial pathogen. Moreover, the subcellular target of HGE1_02492 suggests thatA. phagocytophilumis manipulating actin to enable arthropod colonization. Based on these findings, we propose the name AteA forAnaplasma(phagocytophilum) tick effector A. Altogether, we show thatA. phagocytophilumuses distinct strategies to cycle between mammals and arthropods.ImportanceTicks are the number one vector of pathogens for livestock worldwide and for humans in the US. The biology of tick transmission is an understudied area. Understanding this critical interaction could provide opportunities to affect the course of disease spread. In this study we examined the zoonotic tick-borne agentAnaplasma phagocytophilumand identified a secreted protein, AteA, that is expressed in a tick-specific manner. These secreted proteins, termed effectors, are the first proteins to interact with the host environment. AteA is essential for survival in ticks and appears to interact with cortical actin. Most effector proteins are studied in the context of the mammalian host; however, understanding how this unique set of proteins affect tick transmission is critical to developing interventions.
Quantitative analyses of interactions between SpoVG and RNA/DNA
Authors: Saylor Timothy C. , Savage Christina R. , Krusenstjerna Andrew C. , Jusufovic Nerina , Zückert Wolfram R. , Brissette Catherine A. , Motaleb Md. , Schlax Paula J. , Stevenson Brian 
Published: February 2023

1.AbstractTheBorrelia burgdorferiSpoVG protein has previously been found to be a DNA- and RNA-binding protein. To aid in the elucidation of ligand motifs, affinities for numerous RNAs, ssDNAs, and dsDNAs were measured and compared. The loci used in the study werespoVG, glpFKD, erpAB, bb0242, flaB, andospAB, with particular focus on the untranslated 5’ portion of the mRNAs. Performing binding and competition assays yielded that the 5’ end ofspoVGmRNA had the highest affinity while the lowest observed affinity was to the 5’ end offlaBmRNA. Mutagenesis studies ofspoVGRNA and ssDNA sequences suggested that the formation of SpoVG-nucleic acid complexes are not entirely dependent on either sequence or structure. Additionally, exchanging uracil for thymine in ssDNAs did not affect protein-nucleic acid complex formation.