bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concurrent optoacoustic tomography and magnetic resonance imaging of resting-state functional connectivity in the mouse brain
Authors: Gezginer Irmak , Chen Zhenyue , Yoshihara Hikari A. I. , Deán-Ben Xosé Luís , Zerbi Valerio , Razansky Daniel 
Published: December 2024

AbstractResting-state functional connectivity (rsFC) has been essential to elucidate the intricacy of brain organization, further revealing clinical biomarkers of neurological disorders. Although functional magnetic resonance imaging (fMRI) remains a cornerstone in the field of rsFC recordings, its interpretation is often hindered by the convoluted physiological origin of the blood-oxygen-level-dependent (BOLD) contrast affected by multiple factors. Here, we capitalize on the unique concurrent multiparametric hemodynamic recordings of a hybrid magnetic resonance optoacoustic tomography platform to comprehensively characterize rsFC in female mice. The unique blood oxygenation readings and high spatio-temporal resolution at depths provided by functional optoacoustic (fOA) imaging offer an effective means for elucidating the connection between BOLD and hemoglobin responses. Seed-based and independent component analyses reveal spatially overlapping bilateral correlations between the fMRI-BOLD readings and the multiple hemodynamic components measured with fOA but also subtle discrepancies, particularly in anti-correlations. Notably, total hemoglobin and oxygenated hemoglobin components are found to exhibit stronger correlation with BOLD than deoxygenated hemoglobin, challenging conventional assumptions on the BOLD signal origin.
DLK-dependent axonal mitochondrial fission drives degeneration after axotomy
Authors: Gómez-Deza Jorge , Nebiyou Matthew , Alkaslasi Mor R. , Nadal-Nicolás Francisco M. , Somasundaram Preethi , Slavutsky Anastasia L. , Li Wei , Ward Michael E. , Watkins Trent A. , Le Pichon Claire E. 
Published: December 2024

AbstractCurrently there are no effective treatments for an array of neurodegenerative disorders to a large part because cell-based models fail to recapitulate disease. Here we develop a reproducible human iPSC-based model where laser axotomy causes retrograde axon degeneration leading to neuronal cell death. Time-lapse confocal imaging revealed that damage triggers an apoptotic wave of mitochondrial fission proceeding from the site of injury to the soma. We demonstrate that this apoptotic wave is locally initiated in the axon by dual leucine zipper kinase (DLK). We find that mitochondrial fission and resultant cell death are entirely dependent on phosphorylation of dynamin related protein 1 (DRP1) downstream of DLK, revealing a mechanism by which DLK can drive apoptosis. Importantly, we show that CRISPR mediated Drp1 depletion protects mouse retinal ganglion neurons from degeneration after optic nerve crush. Our results provide a platform for studying degeneration of human neurons, pinpoint key early events in damage related neural death and provide potential focus for therapeutic intervention.
Higher skeletal muscle mitochondrial oxidative capacity is associated with preserved brain structure up to over a decade
Authors: Tian Qu , Greig Erin E. , Davatzikos Christos , Landman Bennett A. , Resnick Susan M. , Ferrucci Luigi 
Published: December 2024

AbstractImpaired muscle mitochondrial oxidative capacity is associated with future cognitive impairment, and higher levels of PET and blood biomarkers of Alzheimer’s disease and neurodegeneration. Here, we examine its associations with up to over a decade-long changes in brain atrophy and microstructure. Higher in vivo skeletal muscle oxidative capacity via MR spectroscopy (post-exercise recovery rate, kPCr) is associated with less ventricular enlargement and brain aging progression, and less atrophy in specific regions, notably primary sensorimotor cortex, temporal white and gray matter, thalamus, occipital areas, cingulate cortex, and cerebellum white matter. Higher kPCr is also associated with less microstructural integrity decline in white matter around cingulate, including superior longitudinal fasciculus, corpus callosum, and cingulum. Higher in vivo muscle oxidative capacity is associated with preserved brain structure up to over a decade, particularly in areas important for cognition, motor function, and sensorimotor integration.
Human respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interaction
Authors: Li Cun , Yu Yifei , Wan Zhixin , Chiu Man Chun , Huang Jingjing , Zhang Shuxin , Zhu Xiaoxin , Lan Qiaoshuai , Deng Yanlin , Zhou Ying , Xue Wei , Yue Ming , Cai Jian-Piao , Yip Cyril Chik-Yan , Wong Kenneth Kak-Yuen , Liu Xiaojuan , Yu Yang , Huang Lin , Chu Hin , Chan Jasper Fuk-Woo , Clevers Hans , Yuen Kwok Yung , Zhou Jie 
Published: December 2024

AbstractThe lack of a robust system to reproducibly propagate HRV-C, a family of viruses refractory to cultivation in standard cell lines, has substantially hindered our understanding of this common respiratory pathogen. We sought to develop an organoid-based system to reproducibly propagate HRV-C, and characterize virus-host interaction using respiratory organoids. We demonstrate that airway organoids sustain serial virus passage with the aid of CYT387-mediated immunosuppression, whereas nasal organoids that more closely simulate the upper airway achieve this without any intervention. Nasal organoids are more susceptible to HRV-C than airway organoids. Intriguingly, upon HRV-C infection, we observe an innate immune response that is stronger in airway organoids than in nasal organoids, which is reproduced in a Poly(I:C) stimulation assay. Treatment with α-CDHR3 and antivirals significantly reduces HRV-C viral growth in airway and nasal organoids. Additionally, an organoid-based immunofluorescence assay is established to titrate HRV-C infectious particles. Collectively, we develop an organoid-based system to reproducibly propagate the poorly cultivable HRV-C, followed by a comprehensive characterization of HRV-C infection and innate immunity in physiologically active respiratory organoids. The organoid-based HRV-C infection model can be extended for developing antiviral strategies. More importantly, our study has opened an avenue for propagating and studying other uncultivable human and animal viruses.
Cytokine-armed pyroptosis induces antitumor immunity against diverse types of tumors
Authors: Orehek Sara , Ramuta Taja Železnik , Lainšček Duško , Malenšek Špela , Šala Martin , Benčina Mojca , Jerala Roman , Hafner-Bratkovič Iva 
Published: December 2024

AbstractInflammasomes are defense complexes that utilize cytokines and immunogenic cell death (ICD) to stimulate the immune system against pathogens. Inspired by their dual action, we present cytokine-armed pyroptosis as a strategy for boosting immune response against diverse types of tumors. To induce pyroptosis, we utilize designed tightly regulated gasdermin D variants comprising different pore-forming capabilities and diverse modes of activation, representing a toolbox of ICD inducers. We demonstrate that the electrogenic transfer of ICD effector-encoding plasmids into mouse melanoma tumors when combined with intratumoral expression of cytokines IL-1β, IL-12, or IL-18, enhanced anti-tumor immune responses. Careful selection of immunostimulatory molecules is, however, imperative as a combination of IL-1β and IL-18 antagonized the protective effect of pyroptosis by IFNγ-mediated upregulation of several immunosuppressive pathways. Additionally, we show that the intratumoral introduction of armed pyroptosis provides protection against distant tumors and proves effective across various tumor types without inducing systemic inflammation. Deconstructed inflammasomes thus serve as a powerful, tunable, and tumor-agnostic strategy to enhance antitumor response, even against the most resilient types of tumors.
Robust and inducible genome editing via an all-in-one prime editor in human pluripotent stem cells
Authors: Wu Youjun , Zhong Aaron , Sidharta Mega , Kim Tae Wan , Ramirez Bernny , Persily Benjamin , Studer Lorenz , Zhou Ting 
Published: December 2024

AbstractPrime editing (PE) allows for precise genome editing in human pluripotent stem cells (hPSCs), such as introducing single nucleotide modifications, small insertions or deletions at a specific genomic locus. Here, we systematically compare a panel of prime editing conditions in hPSCs and generate a potent prime editor, “PE-Plus”, through co-inhibition of mismatch repair and p53-mediated cellular stress responses. We further establish an inducible prime editing platform in hPSCs by incorporating the PE-Plus into a safe-harbor locus and demonstrated temporal control of precise editing in both hPSCs and differentiated cells. By evaluating disease-associated mutations, we show that this platform allows efficient creation of both monoallelic and biallelic disease-relevant mutations in hPSCs. In addition, this platform enables the efficient introduction of single or multiple edits in one step, demonstrating potential for multiplex editing. Our method presents an efficient and controllable multiplex prime editing tool in hPSCs and their differentiated progeny.
Magnetosensitivity of tightly bound radical pairs in cryptochrome is enabled by the quantum Zeno effect
Authors: Denton Matt C. J. , Smith Luke D. , Xu Wenhao , Pugsley Jodeci , Toghill Amelia , Kattnig Daniel R. 
Published: December 2024

AbstractThe radical pair mechanism accounts for the magnetic field sensitivity of a large class of chemical reactions and is hypothesised to underpin numerous magnetosensitive traits in biology, including the avian compass. Traditionally, magnetic field sensitivity in this mechanism is attributed to radical pairs with weakly interacting, well-separated electrons; closely bound pairs were considered unresponsive to weak fields due to arrested spin dynamics. In this study, we challenge this view by examining the FAD-superoxide radical pair within cryptochrome, a protein hypothesised to function as a biological magnetosensor. Contrary to expectations, we find that this tightly bound radical pair can respond to Earth-strength magnetic fields, provided that the recombination reaction is strongly asymmetric—a scenario invoking the quantum Zeno effect. These findings present a plausible mechanism for weak magnetic field effects in biology, suggesting that even closely associated radical pairs, like those involving superoxide, may play a role in magnetic sensing.
Observation of 1H-1H J-couplings in fast magic-angle-spinning solid-state NMR spectroscopy
Authors: Torodii Daria , Holmes Jacob B. , Grohe Kristof , de Oliveira-Silva Rodrigo , Wegner Sebastian , Sakellariou Dimitrios , Emsley Lyndon 
Published: December 2024

AbstractWhile 1H-1H J-couplings are the cornerstone of all spectral assignment methods in solution-state NMR, they are yet to be observed in solids. Here we observe 1H-1H J-couplings in plastic crystals of (1S)-(−)-camphor in solid-state NMR at magic angle spinning (MAS) rates of 100 kHz and above. This is enabled in this special case because the intrinsic coherence lifetimes at fast MAS rates become longer than the inverse of the 1H-1H J couplings. For example, at 160 kHz MAS the coherence lifetimes are longer than 20 ms, corresponding to refocused linewidths of less than 15 Hz. As a result, we are able to record two-dimensional 1H-1H J resolved spectra that allow the observation and measurement of 1H-1H J-couplings in solid camphor. The J-couplings also lead to unambiguous through-bond correlations in 1H-1H refocused incredible natural abundance double quantum transfer (INADEQUATE) and uniform-sign cross-peak double-quantum-filtered correlation spectroscopy (UC2QFCOSY) experiments.
DNA replication initiation drives focal mutagenesis and rearrangements in human cancers
Authors: Murat Pierre , Guilbaud Guillaume , Sale Julian E. 
Published: December 2024

AbstractThe rate and pattern of mutagenesis in cancer genomes is significantly influenced by DNA accessibility and active biological processes. Here we show that efficient sites of replication initiation drive and modulate specific mutational processes in cancer. Sites of replication initiation impede nucleotide excision repair in melanoma and are off-targets for activation-induced deaminase (AICDA) activity in lymphomas. Using ductal pancreatic adenocarcinoma as a cancer model, we demonstrate that the initiation of DNA synthesis is error-prone at G-quadruplex-forming sequences in tumours displaying markers of replication stress, resulting in a previously recognised but uncharacterised mutational signature. Finally, we demonstrate that replication origins serve as hotspots for genomic rearrangements, including structural and copy number variations. These findings reveal replication origins as functional determinants of tumour biology and demonstrate that replication initiation both passively and actively drives focal mutagenesis in cancer genomes.
Short tandem repeats delineate gene bodies across eukaryotes
Authors: Reinar William B. , Krabberød Anders K. , Lalun Vilde O. , Butenko Melinka A. , Jakobsen Kjetill S. 
Published: December 2024

Abstract
Short tandem repeats (STRs) have emerged as important and hypermutable sites where genetic variation correlates with gene expression in plant and animal systems. Recently, it has been shown that a broad range of transcription factors (TFs) are affected by STRs near or in the DNA target binding site. Despite this, the distribution of STR motif repetitiveness in eukaryote genomes is still largely unknown. Here, we identify monomer and dimer STR motif repetitiveness in 5.1 billion 10-bp windows upstream of translation starts and downstream of translation stops in 25 million genes spanning 1270 species across the eukaryotic Tree of Life. We report that all surveyed genomes have gene-proximal shifts in motif repetitiveness. Within genomes, variation in gene-proximal repetitiveness landscapes correlated to the function of genes; genes with housekeeping functions were depleted in upstream and downstream repetitiveness. Furthermore, the repetitiveness landscapes correlated with TF binding sites, indicating that gene function has evolved in conjunction with cis-regulatory STRs and TFs that recognize repetitive sites. These results suggest that the hypermutability inherent to STRs is canalized along the genome sequence and contributes to regulatory and eco-evolutionary dynamics in all eukaryotes.
Rapid lightsheet fluorescence imaging of whole Drosophila brains at nanoscale resolution by potassium acrylate-based expansion microscopy
Authors: Tian Xuejiao , Lin Tzu-Yang , Lin Po-Ting , Tsai Min-Ju , Chen Hsin , Chen Wen-Jie , Lee Chia-Ming , Tu Chiao-Hui , Hsu Jui-Cheng , Hsieh Tung-Han , Tung Yi-Chung , Wang Chien-Kai , Lin Suewei , Chu Li-An , Tseng Fan-Gang , Hsueh Yi-Ping , Lee Chi-Hon , Chen Peilin , Chen Bi-Chang 
Published: December 2024

AbstractTaking advantage of the good mechanical strength of expanded Drosophila brains and to tackle their relatively large size that can complicate imaging, we apply potassium (poly)acrylate-based hydrogels for expansion microscopy (ExM), resulting in a 40x plus increased resolution of transgenic fluorescent proteins preserved by glutaraldehyde fixation in the nervous system. Large-volume ExM is realized by using an axicon-based Bessel lightsheet microscope, featuring gentle multi-color fluorophore excitation and intrinsic optical sectioning capability, enabling visualization of Tm5a neurites and L3 lamina neurons with photoreceptors in the optic lobe. We also image nanometer-sized dopaminergic neurons across the same intact iteratively expanded Drosophila brain, enabling us to measure the 3D expansion ratio. Here we show that at a tile scanning speed of ~1 min/mm3 with 1012 pixels over 14 hours, we image the centimeter-sized fly brain at an effective resolution comparable to electron microscopy, allowing us to visualize mitochondria within presynaptic compartments and Bruchpilot (Brp) scaffold proteins distributed in the central complex, enabling robust analyses of neurobiological topics.
Time-bin entangled Bell state generation and tomography on thin-film lithium niobate
Authors: Finco Giovanni , Miserocchi Filippo , Maeder Andreas , Kellner Jost , Sabatti Alessandra , Chapman Robert J. , Grange Rachel 
Published: December 2024

AbstractOptical quantum communication technologies are making the prospect of unconditionally secure and efficient information transfer a reality. The possibility of generating and reliably detecting quantum states of light, with the further need of increasing the private data-rate is where most research efforts are focusing. The physical concept of entanglement is a solution guaranteeing the highest degree of security in device-independent schemes, yet its implementation and preservation over long communication links is hard to achieve. Lithium niobate-on-insulator has emerged as a revolutionising platform for high-speed classical telecommunication and is equally suited for quantum information applications owing to the large second-order nonlinearities that can efficiently produce entangled photon pairs. In this work, we generate maximally entangled quantum states in the time-bin basis using lithium niobate-on-insulator photonics at the fibre optics telecommunication wavelength, and reconstruct the density matrix by quantum tomography on a single photonic integrated circuit. We use on-chip periodically-poled lithium niobate as source of entangled qubits with a brightness of 242 MHz/mW and perform quantum tomography with a fidelity of 91.9 ± 1.0 %. Our results, combined with the established large electro-optic bandwidth of lithium niobate, showcase the platform as perfect candidate to realise fibre-coupled, high-speed time-bin quantum communication modules that exploit entanglement to achieve information security.
Variation of gene ratios in mock communities constructed with purified 16S rRNA during processing
Authors: Nammoura Neto Georges Mikhael , Schneider René Peter 
Published: December 2024

Abstract16S ribosomal nucleic acid (16S rRNA) analysis allows to specifically target the metabolically active members of microbial communities. The stability of the ratios between target genes in the workflow, which is essential for the bioprocess-relevance of the data derived from this analysis, was investigated using synthetic mock communities constructed by mixing purified 16S rRNA from Bacillus subtilis (Bs), Staphylococcus aureus (Sa), Pseudomonas aeruginosa (Pa), Klebsiella pneumoniae (Kp) and Burkholderia cepacia (Bc) in different proportions. The RT reaction yielded one copy of cDNA per rRNA molecule for Pa, Bc and Sa but only 2/3 of the expected cDNA from 16S rRNAs of Bs and Kp. The combination of Taq DNA Platinum polymerase with subcycling PCR (scPCR) produced uniform yields of approximately 70% for second strand PCR synthesis from all target cDNAs. The proportion between templates in multicycle PCR was best preserved after 10 cycle scPCR followed by cloning. With MiSeq sequencing, correct proportions for about two thirds of templates were recovered after 10 cycle scPCR with Taq Platinum. 30 cycles standard PCR (stdPCR) or scPCR proved particularly harmful to proportion data and should be avoided.
Rectal mucosal inflammation, microbiome, and wound healing in men who have sex with men who engage in receptive anal intercourse
Authors: Van Doren Vanessa E. , Ackerley Cassie G. , Arthur Robert A. , Murray Phillip M. , Smith S. Abigail , Hu Yi-Juan , Kelley Colleen F. 
Published: December 2024

AbstractMucosal injury is common during consensual intercourse and induces an inflammatory response that could contribute to pathogen transmission including HIV. Here, we compared mucosal immune and microbiome responses to experimentally induced mucosal injury between men who have sex with men engaging in receptive anal intercourse (MSM-RAI) and men who do not engage in RAI (controls), all without HIV. Rectal mucosal secretions were collected from adult MSM-RAI (n = 19) and controls (n = 6) via anoscopy before and up to eight days after experimentally induced injury. Mucosal healing was evaluated by repeated injury surface area measurements with digital imaging. MSM-RAI demonstrated overall significantly higher concentrations of pro-inflammatory cytokines and a distinct rectal microbiome compared with controls. Wound healing was numerically faster in MSM-RAI but did not meet statistical significance (p = 0.09). Different cytokine injury response patterns were observed between MSM-RAI and controls; however, IL-6 and IP-10 were important mediators in both groups. Microbial guilds, particularly from the Lachnospiraceae and Prevotellaceae families, were associated with rectal mucosal inflammation. This work is the first experimental study of rectal mucosal injury and the immune environment in healthy humans and provides a more nuanced understanding of rectal mucosal inflammation after injury, which can inform our understanding of HIV transmission.
Lyophilization of ASFV vaccine candidate ASFV-G-ΔI177L offers long term stability
Authors: Espinoza Nallely , Spinard Edward , Rai Ayushi , Ramirez-Medina Elizabeth , Valladares Alyssa , Meyers Amanda , Borca Manuel V. , Gladue Douglas P. 
Published: December 2024

AbstractFor over a century African swine fever (ASF) has been causing outbreaks leading to devastating losses for the swine industry. The current pandemic of ASF has shown no signs of stopping and continues to spread causing outbreaks in additional countries. Currently control relies mostly on culling infected farms, and strict biosecurity procedures. Recently a vaccine, ASFV-G-ΔI177L was approved for use in Vietnam. In this study we evaluate the long-term stability of lyophilized ASFV-G-ΔI177L. Understanding the stability of different formulations of vaccines is information necessary for deployment of vaccines to ASF outbreak areas, particularly those that do not have a reliable well established cold chain to ensure conservation of vaccine quality. In this report, we determined that ASFV-G-ΔI177L, when lyophilized under specific conditions, is stable for up to one year at 4 °C, with similar vaccine titers after storage. Next-generation sequencing analysis also determined that lyophilization and long-term storage under these conditions had no effect on the genome of ASFV as the genome remained genetically identical to the original non-lyophilized form.
Identifying and understanding the nonlinear behavior of memristive devices
Authors: Yarragolla Sahitya , Hemke Torben , Jalled Fares , Gergs Tobias , Trieschmann Jan , Arul Tolga , Mussenbrock Thomas 
Published: December 2024

AbstractNonlinearity is a crucial characteristic for implementing hardware security primitives or neuromorphic computing systems. The main feature of all memristive devices is this nonlinear behavior observed in their current-voltage characteristics. To comprehend the nonlinear behavior, we have to understand the coexistence of resistive, capacitive, and inertia (virtual inductive) effects in these devices. These effects originate from corresponding physical and chemical processes in memristive devices. A physics-inspired compact model is employed to model and simulate interface-type RRAMs such as Au/BiFeO$$_{3}$$/Pt/Ti, Au/Nb$$_{\textrm{x}}$$O$$_{\textrm{y}}$$/Al$$_{2}$$O$$_{3}$$/Nb, while accounting for the modeling of capacitive and inertia effects. The simulated current-voltage characteristics align well with experimental data and accurately capture the non-zero crossing hysteresis generated by capacitive and inductive effects. This study examines the response of two devices to increasing frequencies, revealing a shift in their nonlinear behavior characterized by a reduced hysteresis range Fourier series analysis utilizing a sinusoidal input voltage of varying amplitudes and frequencies indicates harmonics or frequency components that considerably influence the functioning of RRAMs. Moreover, we propose and demonstrate the use of the frequency spectra as one of the fingerprints for memristive devices.