bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered tRNA processing is linked to a distinct and unusual La protein in Tetrahymena thermophila
Authors: Kerkhofs Kyra , Garg Jyoti , Fafard-Couture Étienne , Abou Elela Sherif , Scott Michelle S. , Pearlman Ronald E. , Bayfield Mark A. 
Published: November 2022

AbstractNascent pre-tRNAs are transcribed by RNA polymerase III and immediately bound by La proteins on the UUU-3’OH sequence, using a tandem arrangement of the La motif and an adjacent RNA recognition motif-1 (RRM1), resulting in protection from 3’-exonucleases and promotion of pre-tRNA folding. The Tetrahymena thermophila protein Mlp1 has been previously classified as a genuine La protein, despite the predicted absence of the RRM1. We find that Mlp1 functions as a La protein through binding of pre-tRNAs, and affects pre-tRNA processing in Tetrahymena thermophila and when expressed in fission yeast. However, unlike in other examined eukaryotes, depletion of Mlp1 results in 3’-trailer stabilization. The 3’-trailers in Tetrahymena thermophila are uniquely short relative to other examined eukaryotes, and 5’-leaders have evolved to disfavour pre-tRNA leader/trailer pairing. Our data indicate that this variant Mlp1 architecture is linked to an altered, novel mechanism of tRNA processing in Tetrahymena thermophila.
Chromatin accessibility dynamics dictate renal tubular epithelial cell response to injury
Authors: Cao Xinyi , Wang Jiuchen , Zhang Tianye , Liu Zhiheng , Liu Lijun , Chen Ying , Li Zehua , Zhao Youlu , Yu Qi , Liu Tong , Nie Jing , Niu Yuanjie , Chen Yupeng , Yang Li , Zhang Lirong 
Published: November 2022

AbstractRenal tubular epithelial cells (TECs) can initiate an adaptive response to completely recover from mild acute kidney injury (AKI), whereas severe injury often leads to persistence of maladaptive repair and progression to kidney fibrosis. Through profiling of active DNA regulatory elements by ATAC-seq, we reveal widespread, dynamic changes in the chromatin accessibility of TECs after ischemia–reperfusion injury. We show that injury-specific domains of regulatory chromatin become accessible prior to gene activation, creating poised chromatin states to activate the consequent gene expression program and injury response. We further identify RXRα as a key transcription factor in promoting adaptive repair. Activation of RXRα by bexarotene, an FDA-approved RXRα agonist, restores the chromatin state and gene expression program to protect TECs against severe kidney injury. Together, our findings elucidate a chromatin-mediated mechanism underlying differential responses of TECs to varying injuries and identify RXRα as a therapeutic target of acute kidney injury.
A p38α-BLIMP1 signalling pathway is essential for plasma cell differentiation
Authors: Wu Jianfeng , Yang Kang , Cai Shaowei , Zhang Xiaohan , Hu Lichen , Lin Fanjia , Wu Su-qin , Xiao Changchun , Liu Wen-Hsien , Han Jiahuai 
Published: November 2022

AbstractPlasma cells (PC) are antibody-secreting cells and terminal effectors in humoral responses. PCs differentiate directly from activated B cells in response to T cell-independent (TI) antigens or from germinal center B (GCB) cells in T cell-dependent (TD) antigen-induced humoral responses, both of which pathways are essentially regulated by the transcription factor BLIMP1. The p38 mitogen-activated protein kinase isoforms have already been implicated in B cell development, but the precise role of p38α in B cell differentiation is still largely unknown. Here we show that PC differentiation and antibody responses are severely impaired in mice with B cell-specific deletion ofp38α, while B cell development and the GCB cell response are spared. By utilizing aBlimp1reporter mouse model, we show thatp38α-deficiency results in decreased BLIMP1 expression. p38α-driven BLIMP1 up-regulation is required for both TI and TD PCs differentiation. By combining CRISPR/Cas9 screening and other approaches, we identify TCF3, TCF4 and IRF4 as downstream effectors of p38α to control PC differentiation viaBlimp1transcription. This study thus identifies an important signalling pathway underpinning PC differentiation upstream of BLIMP1, and points to a highly specialized and non-redundant role for p38α among p38 isoforms.
Targeting APLN/APJ restores blood-testis barrier and improves spermatogenesis in murine and human diabetic models
Authors: Song Ke , Yang Xinyan , An Geng , Xia Xinyu , Zhao Jiexiang , Xu Xiaoheng , Wan Cong , Liu Tianyuan , Zheng Yi , Ren Shaofang , Wang Mei , Chang Gang , Cronin Shane J. F. , Penninger Josef M. , Jing Tao , Ou Xianghong , Rao Shuan , Liu Zhaoting , Zhao Xiao-Yang 
Published: November 2022

AbstractType 2 diabetes mellitus is one of the most prevalent metabolic diseases presenting with systemic pathologies, including reproductive disorders in male diabetic patients. However, the molecular mechanisms that contributing to spermatogenesis dysfunction in diabetic patients have not yet been fully elucidated. Here, we perform STRT-seq to examine the transcriptome of diabetic patients’ testes at single-cell resolution including all major cell types of the testis. Intriguingly, whereas spermatogenesis appears largely preserved, the gene expression profiles of Sertoli cells and the blood-testis barrier (BTB) structure are dramatically impaired. Among these deregulate pathways, the Apelin (APLN) peptide/Apelin-receptor (APJ) axis is hyper-activated in diabetic patients’ testes. Mechanistically, APLN is produced locally by Sertoli cells upon high glucose treatment, which subsequently suppress the production of carnitine and repress the expression of cell adhesion genes in Sertoli cells. Together, these effects culminate in BTB structural dysfunction. Finally, using the small molecule APLN receptor antagonist, ML221, we show that blocking APLN/APJ significantly ameliorate the BTB damage and, importantly, improve functional spermatogenesis in diabetic db/db mice. We also translate and validate these findings in cultured human testes. Our findings identify the APLN/APJ axis as a promising therapeutic target to improve reproduction capacity in male diabetic patients.
Increase in tropical cyclone rain rate with translation speed
Authors: Tu Shifei , Chan Johnny C. L. , Xu Jianjun , Zhong Quanjia , Zhou Wen , Zhang Yu 
Published: November 2022

AbstractIn general, tropical cyclone (TC) rainfall accumulation usually decreases with faster TC translation speed but increases with heavier rain rate. However, how the TC rain rate changes with translation speed is unclear. Here we show that, in all TC basins, the average TC rain rate significantly increases with translation speed. On average, the rain rate in a fast-moving TC is 24% higher than in a slow one. This difference increases with TC intensity, with category 3–5 TCs having a 42% increase while tropical depressions exhibit only a 9% increase. The increase in the average TC rain rate with translation speed is mainly caused by the TC net inflow in the lower troposphere, as well as vertical wind shear. These findings have important implications not only for a deeper understanding of rain rate changes in a translating TC but also for short-term forecasts of TC rainfall and disaster preparedness.
Intelligent certification for quantum simulators via machine learning
Authors: Xiao Tailong , Huang Jingzheng , Li Hongjing , Fan Jianping , Zeng Guihua 
Published: November 2022

AbstractQuantum simulation is a technology of using controllable quantum systems to study new quantum phases of matter. Certification for quantum simulators is a challenging problem whereas identification and properties estimation are two crucial approaches that can be resorted to. In this work, we propose Ab initio end-to-end machine learning certification protocol briefly named MLCP. The learning protocol is trained with a million-level size of randomized measurement samples without relying on the assistance of quantum tomography. In the light of MLCP, we can identify different types of quantum simulators to observe their distinguishability hardness. We also predict the physical properties of quantum states evolved in quantum simulators such as entanglement entropy and maximum fidelity. The impact of randomized measurement samples on the identification accuracy is analyzed to showcase the potential capability of classical machine learning on quantum simulation results. The entanglement entropy and maximum fidelity with varied subsystem partitions are also estimated with satisfactory precision. This work paves the way for large-scale intelligent certification of quantum simulators and can be extended onto an artificial intelligence center to offer easily accessible services for local quantum simulators in the noisy intermediate-size quantum (NISQ) era.
Immune gene expression analysis indicates the potential of a self-amplifying Covid-19 mRNA vaccine
Authors: Ong Eugenia Z. , Yee Jia Xin , Ooi Justin S. G. , Syenina Ayesa , de Alwis Ruklanthi , Chen Shiwei , Sim Jean X. Y. , Kalimuddin Shirin , Leong Yan Shan , Chan Yvonne F. Z. , Sekulovich Rose , Sullivan Brian M. , Lindert Kelly , Sullivan Sean B. , Chivukula Pad , Hughes Steven G. , Low Jenny G. , Ooi Eng Eong , Chan Kuan Rong 
Published: November 2022

AbstractRemarkable potency has been demonstrated for mRNA vaccines in reducing the global burden of the ongoing COVID-19 pandemic. An alternative form of the mRNA vaccine is the self-amplifying mRNA (sa-mRNA) vaccine, which encodes an alphavirus replicase that self-amplifies the full-length mRNA and SARS-CoV-2 spike (S) transgene. However, early-phase clinical trials of sa-mRNA COVID-19 vaccine candidates have questioned the potential of this platform to develop potent vaccines. We examined the immune gene response to a candidate sa-mRNA vaccine against COVID-19, ARCT-021, and compared our findings to the host response to other forms of vaccines. In blood samples from healthy volunteers that participated in a phase I/II clinical trial, greater induction of transcripts involved in Toll-like receptor (TLR) signalling, antigen presentation and complement activation at 1 day post-vaccination was associated with higher anti-S antibody titers. Conversely, transcripts involved in T-cell maturation at day 7 post-vaccination informed the magnitude of eventual S-specific T-cell responses. The transcriptomic signature for ARCT-021 vaccination strongly correlated with live viral vector vaccines, adjuvanted vaccines and BNT162b2 1 day post-vaccination. Moreover, the ARCT-021 signature correlated with day 7 YF17D live-attenuated vaccine transcriptomic responses. Altogether, our findings show that sa-mRNA vaccination induces innate immune responses that are associated with the development of adaptive immunity from other forms of vaccines, supporting further development of this vaccine platform for clinical application.
Quantum affective processes for multidimensional decision-making
Authors: Ho Johnny K. W. , Hoorn Johan F. 
Published: November 2022

AbstractIn modeling the human affective system and applying lessons learned to human–robot interaction, the challenge is to handle ambiguous emotional states of an agency (whether human or artificial), probabilistic decisions, and freedom of choice in affective and behavioral patterns. Moreover, many cognitive processes seem to run in parallel whereas seriality is the standard in conventional computation. Representation of contextual aspects of behavior and processes and of self-directed neuroplasticity are still wanted and so we attempt a quantum-computational construction of robot affect, which theoretically should be able to account for indefinite and ambiguous states as well as parallelism. Our Quantum Coppélia (Q-Coppélia) is a translation into quantum logics of the fuzzy-based Silicon Coppélia system, which simulates the progression of a robot’s attitude towards its user. We show the entire circuitry of the Q-Coppélia framework, aiming at contemporary descriptions of (neuro)psychological processes. Arguably, our work provides a system for simulating and handling affective interactions among various agencies from an understanding of the relations between quantum algorithms and the fundamental nature of psychology.
Serum circulating sirtuin 6 as a novel predictor of mortality after acute ischemic stroke
Authors: Liberale Luca , Ministrini Stefano , Arnold Markus , Puspitasari Yustina M. , Pokorny Thomas , Beer Georgia , Scherrer Natalie , Schweizer Juliane , Christ-Crain Mirjam , Montecucco Fabrizio , Camici Giovanni G. , Katan Kahles Mira 
Published: November 2022

AbstractIn a murine model of acute ischemic stroke, SIRT6 knockdown resulted in larger cerebral infarct size, worse neurological outcome, and higher mortality, indicating a possible neuro-protective role of SIRT6. In this study, we aimed at evaluating the prognostic value of serum SIRT6 levels in patients with acute ischemic stroke (AIS). Serum levels of SIRT6, collected within 72 h from symptom-onset, were measured in 317 consecutively enrolled AIS patients from the COSMOS cohort. The primary endpoint of this analysis was 90-day mortality. The independent prognostic value of SIRT6 was assessed with multivariate logistic and Cox proportional regression models. 35 patients (11%) deceased within 90-day follow-up. After adjustment for established risk factors (age, NIHSS, heart failure, atrial fibrillation, and C reactive protein), SIRT6 levels were negatively associated with mortality. The optimal cut-off for survival was 634 pg/mL. Patients with SIRT6 levels below this threshold had a higher risk of death in multivariable Cox regression. In this pilot study, SIRT6 levels were significantly associated with 90-day mortality after AIS; these results build on previous molecular and causal observations made in animal models. Should this association be confirmed, SIRT6 could be a potential prognostic predictor and therapeutic target in AIS.
Photoacoustic imaging is a novel tool to measure finger artery structure and oxygenation in patients with SSc
Authors: Wilkinson Sarah , Cummings James , Zafar Sakif , Kozar Martin , Manning Joanne , Dinsdale Graham , Berks Michael , Taylor Christopher , Dickinson Mark , Herrick Ariane L. , Murray Andrea K. 
Published: November 2022

AbstractSystemic sclerosis (SSc)-related digital ischaemia is a major cause of morbidity, resulting from a combination of microvascular and digital artery disease. Photoacoustic imaging offers a newly available, non-invasive method of imaging digital artery structure and oxygenation. The aim of this study was to establish whether photoacoustic imaging could detect and measure vasculopathy in digital arteries, including the level of oxygenation, in patients with SSc and healthy controls. 22 patients with SSc and 32 healthy controls (HC) underwent photoacoustic imaging of the fingers. Vascular volume and oxygenation were assessed across eight fingers at the middle phalanx. In addition, oxygenation change during finger occlusion was measured at the non-dominant ring finger and the vascular network was imaged along the length of one finger for qualitative assessment. There was no statistically significant difference in vascular volume between patients with SSc and HC (mean of eight fingers; SSc, median 118.6 IQR [95.0–130.5] vs. HC 115.6 [97.8–158.9]) mm3. However, baseline oxygenation (mean 8 fingers) was lower in SSc vs. HC (0.373 [0.361–0.381] vs. 0.381 [0.373–0.385] arbitrary sO2 units respectively; p = 0.03). Hyperaemic oxygenation response following occlusion release was significantly lower in SSc compared to HC (0.379 [0.376–0.381] vs. 0.382 [0.377–0.385]; p = 0.03). Whilst vascular volume was similar between groups, digital artery oxygenation was decreased in patients with SSc as compared to HC, indicative of functional deficit. Photoacoustic imaging offers an exciting new method to image the vascular network in patients with SSc and the possibility to capture oxygenation as a functional measure.
Organotypic stromal cells impact endothelial cell transcriptome in 3D microvessel networks
Authors: Curtis Matthew B. , Kelly Natalie , Hughes Christopher C. W. , George Steven C. 
Published: November 2022

AbstractEndothelial cells line all major blood vessels and serve as integral regulators of many functions including vessel diameter, cellular trafficking, and transport of soluble mediators. Despite similar functions, the phenotype of endothelial cells is highly organ-specific, yet our understanding of the mechanisms leading to organ-level differentiation is incomplete. We generated 3D microvessel networks by combining a common naïve endothelial cell with six different stromal cells derived from the lung, skin, heart, bone marrow, pancreas, and pancreatic cancer. Single cell RNA-Seq analysis of the microvessel networks reveals five distinct endothelial cell populations, for which the relative proportion depends on the stromal cell population. Morphologic features of the organotypic vessel networks inversely correlate with a cluster of endothelial cells associated with protein synthesis. The organotypic stromal cells were each characterized by a unique subpopulation of cells dedicated to extracellular matrix organization and assembly. Finally, compared to cells in 2D monolayer, the endothelial cell transcriptome from the 3D in vitro heart, skin, lung, and pancreas microvessel networks are more similar to the in vivo endothelial cells from the respective organs. We conclude that stromal cells contribute to endothelial cell and microvessel network organ tropism, and create an endothelial cell phenotype that more closely resembles that present in vivo.
Multi-modal retinal scanning to measure retinal thickness and peripheral blood vessels in multiple sclerosis
Authors: Pearson Thomas , Chen Yingdi , Dhillon Baljean , Chandran Siddharthan , van Hemert Jano , MacGillivray Tom 
Published: November 2022

AbstractOur purpose was to investigate changes to the retina in multiple sclerosis (MS) using established and novel modes of retinal image acquisition and analysis. 72 participants with MS and 80 healthy volunteers underwent retinal scanning with optical coherence tomography (OCT) and ultra-widefield (UWF) scanning laser ophthalmoscopy (SLO), over a two-year period. Changes in retinal nerve fibre layer (RNFL) thickness, macular volume and retinal blood vessel diameter were measured and parameters were then tested for associations with MS. Measurements from OCT showed that individuals with MS had a thinner RNFL and reduced macular volume when compared to healthy volunteers. On UWF images, participants with MS had reduced arterial widths in the inferior nasal quadrant of both eyes and reduced venous widths in the inferior nasal quadrant of right eyes. Longitudinal analysis showed that participants with MS had an accelerated annual rate of RNFL thinning in several regions of the retina. In conclusion, the assessment of OCT showed thinning of the RNFL and macula in concordance with previous reports on MS, while analysis of blood vessels in the retinal periphery from UWF-SLO images revealed novel changes.
Hybrid classical-quantum machine learning based on dissipative two-qubit channels
Authors: Ghasemian E. , Tavassoly M. K. 
Published: November 2022

AbstractAlthough the environmental effects, i.e., dissipation and decoherence seem to be the strongest adversaries in the quantum information realm, here, we address how dissipation can be harnessed for quantum state preparation and universal quantum computation. In this line, we propose a realistic scheme for hybrid classical-quantum neural networks based on dissipative two-qubit channels. In particular, we design a variational quantum circuit consisting of a set of universal quantum gates. We encode classical information in the initial states of a two-qubit system interacting with a global environment. This composite system plays the role of a dissipative quantum channel (DQC). A pooling layer concatenates the output states of the DQCs resulting in the outcome of the circuit. Both the DCQs and the pooling layer provide superposition and entanglement which are the key ingredients of any universal quantum computation protocol. Finally, we investigate the capability and adaptability of this model by doing some machine learning tasks. It is reasonable to postulate that a quantum computer based on DQCs may outperform a classical computer because, in contrast to the latter, the former is capable of producing atypical patterns through non-classical phenomena.
A minimal-complexity light-sheet microscope maps network activity in 3D neuronal systems
Authors: Wysmolek Paulina M. , Kiessler Filippo D. , Salbaum Katja A. , Shelton Elijah R. , Sonntag Selina M. , Serwane Friedhelm 
Published: November 2022

AbstractIn vitro systems mimicking brain regions, brain organoids, are revolutionizing the neuroscience field. However, characterization of their electrical activity has remained a challenge as it requires readout at millisecond timescale in 3D at single-neuron resolution. While custom-built microscopes used with genetically encoded sensors are now opening this door, a full 3D characterization of organoid neural activity has not been performed yet, limited by the combined complexity of the optical and the biological system. Here, we introduce an accessible minimalistic light-sheet microscope to the neuroscience community. Designed as an add-on to a standard inverted microscope it can be assembled within one day. In contrast to existing simplistic setups, our platform is suited to record volumetric calcium traces. We successfully extracted 4D calcium traces at high temporal resolution by using a lightweight piezo stage to allow for 5 Hz volumetric scanning combined with a processing pipeline for true 3D neuronal trace segmentation. As a proof of principle, we created a 3D connectivity map of a stem cell derived neuron spheroid by imaging its activity. Our fast, low complexity setup empowers researchers to study the formation of neuronal networks in vitro for fundamental and neurodegeneration research.
Reliable estimation of internal oscillator properties from a novel, fast-paced tapping paradigm
Authors: Kaya Ece , Henry Molly J. 
Published: November 2022

AbstractRhythmic structure in speech, music, and other auditory signals helps us track, anticipate, and understand the sounds in our environment. The dynamic attending framework proposes that biological systems possess internal rhythms, generated via oscillatory mechanisms, that synchronize with (entrain to) rhythms in the external world. Here, we focused on two properties of internal oscillators: preferred rate, the default rate of an oscillator in the absence of any input, and flexibility, the oscillator’s ability to adapt to changes in external rhythmic context. We aimed to develop methods that can reliably estimate preferred rate and flexibility on an individual basis. The experiment was a synchronization—continuation finger tapping paradigm with a unique design: the stimulus rates were finely sampled over a wide range of rates and were presented only once. Individuals tapped their finger to 5-event isochronous stimulus sequences and continued the rhythm at the same pace. Preferred rate was estimated by assessing the best-performance conditions where the difference between the stimulus rate and continuation tapping rate (tempo-matching error) was minimum. The results revealed harmonically related, multiple preferred rates for each individual. We maximized the differences in stimulus rate between consecutive trials to challenge individuals’ flexibility, which was then estimated by how much tempo-matching errors in synchronization tapping increase with this manipulation. Both measures showed test–retest reliability. The findings demonstrate the influence of properties of the auditory context on rhythmic entrainment, and have implications for development of methods that can improve attentional synchronization and hearing.