bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-molecule RNA sizing enables quantitative analysis of alternative transcription termination
Authors: Patiño-Guillén Gerardo , Pešović Jovan , Panić Marko , Savić-Pavićević Dušanka , Bošković Filip , Keyser Ulrich Felix 
Published: February 2024

AbstractTranscription, a critical process in molecular biology, has found many applications in RNA synthesis, including mRNA vaccines and RNA therapeutics. However, current RNA characterization technologies suffer from amplification and enzymatic biases that lead to loss of native information. Here, we introduce a strategy to quantitatively study both transcription and RNA polymerase behaviour by sizing RNA with RNA nanotechnology and nanopores. To begin, we utilize T7 RNA polymerase to transcribe linear DNA lacking termination sequences. Surprisingly, we discover alternative transcription termination in the origin of replication sequence. Next, we employ circular DNA without transcription terminators to perform rolling circle transcription. This allows us to gain valuable insights into the processivity and transcription behaviour of RNA polymerase at the single-molecule level. Our work demonstrates how RNA nanotechnology and nanopores may be used in tandem for the direct and quantitative analysis of RNA transcripts. This methodology provides a promising pathway for accurate RNA structural mapping by enabling the study of full-length RNA transcripts at the single-molecule level.
Phage-assisted evolution of highly active cytosine base editors with enhanced selectivity and minimal sequence context preference
Authors: Zhang Emily , Neugebauer Monica E. , Krasnow Nicholas A. , Liu David R. 
Published: February 2024

AbstractTadA-derived cytosine base editors (TadCBEs) enable programmable C•G-to-T•A editing while retaining the small size, high on-target activity, and low off-target activity of TadA deaminases. Existing TadCBEs, however, exhibit residual A•T-to-G•C editing at certain positions and lower editing efficiencies at some sequence contexts and with non-SpCas9 targeting domains. To address these limitations, we use phage-assisted evolution to evolve CBE6s from a TadA-mediated dual cytosine and adenine base editor, discovering mutations at N46 and Y73 in TadA that prevent A•T-to-G•C editing and improve C•G-to-T•A editing with expanded sequence-context compatibility, respectively. In E. coli, CBE6 variants offer high C•G-to-T•A editing and no detected A•T-to-G•C editing in any sequence context. In human cells, CBE6 variants exhibit broad Cas domain compatibility and retain low off-target editing despite exceeding BE4max and previous TadCBEs in on-target editing efficiency. Finally, we show that the high selectivity of CBE6 variants is well-suited for therapeutically relevant stop codon installation without creating unwanted missense mutations from residual A•T-to-G•C editing.
Direct contribution of the sensory cortex to the judgment of stimulus duration
Authors: Reinartz Sebastian , Fassihi Arash , Ravera Maria , Paz Luciano , Pulecchi Francesca , Gigante Marco , Diamond Mathew E. 
Published: February 2024

AbstractDecision making frequently depends on monitoring the duration of sensory events. To determine whether, and how, the perception of elapsed time derives from the neuronal representation of the stimulus itself, we recorded and optogenetically modulated vibrissal somatosensory cortical activity as male rats judged vibration duration. Perceived duration was dilated by optogenetic excitation. A second set of rats judged vibration intensity; here, optogenetic excitation amplified the intensity percept, demonstrating sensory cortex to be the common gateway both to time and to stimulus feature processing. A model beginning with the membrane currents evoked by vibrissal and optogenetic drive and culminating in the representation of perceived time successfully replicated rats’ choices. Time perception is thus as deeply intermeshed within the sensory processing pathway as is the sense of touch itself, suggesting that the experience of time may be further investigated with the toolbox of sensory coding.
Mechanically interlocked [c2]daisy chain backbone enabling advanced shape-memory polymeric materials
Authors: Zhou Shang-Wu , Zhou Danlei , Gu Ruirui , Ma Chang-Shun , Yu Chengyuan , Qu Da-Hui 
Published: February 2024

AbstractThe incorporation of mechanically interlocked structures into polymer backbones has been shown to confer remarkable functionalities to materials. In this work, a [c2]daisy chain unit based on dibenzo-24-crown-8 is covalently embedded into the backbone of a polymer network, resulting in a synthetic material possessing remarkable shape-memory properties under thermal control. By decoupling the molecular structure into three control groups, we demonstrate the essential role of the [c2]daisy chain crosslinks in driving the shape memory function. The mechanically interlocked topology is found to be an essential element for the increase of glass transition temperature and consequent gain of shape memory function. The supramolecular host-guest interactions within the [c2]daisy chain topology not only ensure robust mechanical strength and good network stability of the polymer, but also impart the shape memory polymer with remarkable shape recovery properties and fatigue resistance ability. The incorporation of the [c2]daisy chain unit as a building block has the potential to lay the groundwork for the development of a wide range of shape-memory polymer materials.
A streamlined approach to structure elucidation using in cellulo crystallized recombinant proteins, InCellCryst
Authors: Schönherr Robert , Boger Juliane , Lahey-Rudolph J. Mia , Harms Mareike , Kaiser Jacqueline , Nachtschatt Sophie , Wobbe Marla , Duden Rainer , König Peter , Bourenkov Gleb , Schneider Thomas R. , Redecke Lars 
Published: February 2024

AbstractWith the advent of serial X-ray crystallography on microfocus beamlines at free-electron laser and synchrotron facilities, the demand for protein microcrystals has significantly risen in recent years. However, by in vitro crystallization extensive efforts are usually required to purify proteins and produce sufficiently homogeneous microcrystals. Here, we present InCellCryst, an advanced pipeline for producing homogeneous microcrystals directly within living insect cells. Our baculovirus-based cloning system enables the production of crystals from completely native proteins as well as the screening of different cellular compartments to maximize chances for protein crystallization. By optimizing cloning procedures, recombinant virus production, crystallization and crystal detection, X-ray diffraction data can be collected 24 days after the start of target gene cloning. Furthermore, improved strategies for serial synchrotron diffraction data collection directly from crystals within living cells abolish the need to purify the recombinant protein or the associated microcrystals.
High-order sensory processing nanocircuit based on coupled VO2 oscillators
Authors: Yang Ke , Wang Yanghao , Tiw Pek Jun , Wang Chaoming , Zou Xiaolong , Yuan Rui , Liu Chang , Li Ge , Ge Chen , Wu Si , Zhang Teng , Huang Ru , Yang Yuchao 
Published: February 2024

AbstractConventional circuit elements are constrained by limitations in area and power efficiency at processing physical signals. Recently, researchers have delved into high-order dynamics and coupled oscillation dynamics utilizing Mott devices, revealing potent nonlinear computing capabilities. However, the intricate yet manageable population dynamics of multiple artificial sensory neurons with spatiotemporal coupling remain unexplored. Here, we present an experimental hardware demonstration featuring a capacitance-coupled VO2 phase-change oscillatory network. This network serves as a continuous-time dynamic system for sensory pre-processing and encodes information in phase differences. Besides, a decision-making module for special post-processing through software simulation is designed to complete a bio-inspired dynamic sensory system. Our experiments provide compelling evidence that this transistor-free coupling network excels in sensory processing tasks such as touch recognition and gesture recognition, achieving significant advantages of fewer devices and lower energy-delay-product compared to conventional methods. This work paves the way towards an efficient and compact neuromorphic sensory system based on nano-scale nonlinear dynamics.
Elevated extracellular matrix protein 1 in circulating extracellular vesicles supports breast cancer progression under obesity conditions
Authors: Xu Keyang , Fu Ai , Li Zhaoyi , Miao Liangbin , Lou Zhonghan , Jiang Keying , Lau Condon , Su Tao , Tong Tiejun , Bao Jianfeng , Lyu Aiping , Kwan Hiu Yee 
Published: February 2024

AbstractThe cargo content in small extracellular vesicles (sEVs) changes under pathological conditions. Our data shows that in obesity, extracellular matrix protein 1 (ECM1) protein levels are significantly increased in circulating sEVs, which is dependent on integrin-β2. Knockdown of integrin-β2 does not affect cellular ECM1 protein levels but significantly reduces ECM1 protein levels in the sEVs released by these cells. In breast cancer (BC), overexpressing ECM1 increases matrix metalloproteinase 3 (MMP3) and S100A/B protein levels. Interestingly, sEVs purified from high-fat diet-induced obesity mice (D-sEVs) deliver more ECM1 protein to BC cells compared to sEVs from control diet-fed mice. Consequently, BC cells secrete more ECM1 protein, which promotes cancer cell invasion and migration. D-sEVs treatment also significantly enhances ECM1-mediated BC metastasis and growth in mouse models, as evidenced by the elevated tumor levels of MMP3 and S100A/B. Our study reveals a mechanism and suggests sEV-based strategies for treating obesity-associated BC.
The ATR inhibitor ceralasertib potentiates cancer checkpoint immunotherapy by regulating the tumor microenvironment
Authors: Hardaker Elizabeth L. , Sanseviero Emilio , Karmokar Ankur , Taylor Devon , Milo Marta , Michaloglou Chrysis , Hughes Adina , Mai Mimi , King Matthew , Solanki Anisha , Magiera Lukasz , Miragaia Ricardo , Kar Gozde , Standifer Nathan , Surace Michael , Gill Shaan , Peter Alison , Talbot Sara , Tohumeken Sehmus , Fryer Henderson , Mostafa Ali , Mulgrew Kathy , Lam Carolyn , Hoffmann Scott , Sutton Daniel , Carnevalli Larissa , Calero-Nieto Fernando J. , Jones Gemma N. , Pierce Andrew J. , Wilson Zena , Campbell David , Nyoni Lynet , Martins Carla P. , Baker Tamara , Serrano de Almeida Gilberto , Ramlaoui Zainab , Bidar Abdel , Phillips Benjamin , Boland Joseph , Iyer Sonia , Barrett J. Carl , Loembé Arsene-Bienvenu , Fuchs Serge Y. , Duvvuri Umamaheswar , Lou Pei-Jen , Nance Melonie A. , Gomez Roca Carlos Alberto , Cadogan Elaine , Critichlow Susan E. , Fawell Steven , Cobbold Mark , Dean Emma , Valge-Archer Viia , Lau Alan , Gabrilovich Dmitry I. , Barry Simon T. 
Published: February 2024

AbstractThe Ataxia telangiectasia and Rad3-related (ATR) inhibitor ceralasertib in combination with the PD-L1 antibody durvalumab demonstrated encouraging clinical benefit in melanoma and lung cancer patients who progressed on immunotherapy. Here we show that modelling of intermittent ceralasertib treatment in mouse tumor models reveals CD8+ T-cell dependent antitumor activity, which is separate from the effects on tumor cells. Ceralasertib suppresses proliferating CD8+ T-cells on treatment which is rapidly reversed off-treatment. Ceralasertib causes up-regulation of type I interferon (IFNI) pathway in cancer patients and in tumor-bearing mice. IFNI is experimentally found to be a major mediator of antitumor activity of ceralasertib in combination with PD-L1 antibody. Improvement of T-cell function after ceralasertib treatment is linked to changes in myeloid cells in the tumor microenvironment. IFNI also promotes anti-proliferative effects of ceralasertib on tumor cells. Here, we report that broad immunomodulatory changes following intermittent ATR inhibition underpins the clinical therapeutic benefit and indicates its wider impact on antitumor immunity.
Reducing the metabolic burden of rRNA synthesis promotes healthy longevity in Caenorhabditis elegans
Authors: Sharifi Samim , Chaudhari Prerana , Martirosyan Asya , Eberhardt Alexander Otto , Witt Finja , Gollowitzer André , Lange Lisa , Woitzat Yvonne , Okoli Eberechukwu Maryann , Li Huahui , Rahnis Norman , Kirkpatrick Joanna , Werz Oliver , Ori Alessandro , Koeberle Andreas , Bierhoff Holger , Ermolaeva Maria 
Published: February 2024

AbstractRibosome biogenesis is initiated by RNA polymerase I (Pol I)-mediated synthesis of pre-ribosomal RNA (pre-rRNA). Pol I activity was previously linked to longevity, but the underlying mechanisms were not studied beyond effects on nucleolar structure and protein translation. Here we use multi-omics and functional tests to show that curtailment of Pol I activity remodels the lipidome and preserves mitochondrial function to promote longevity in Caenorhabditis elegans. Reduced pre-rRNA synthesis improves energy homeostasis and metabolic plasticity also in human primary cells. Conversely, the enhancement of pre-rRNA synthesis boosts growth and neuromuscular performance of young nematodes at the cost of accelerated metabolic decline, mitochondrial stress and premature aging. Moreover, restriction of Pol I activity extends lifespan more potently than direct repression of protein synthesis, and confers geroprotection even when initiated late in life, showcasing this intervention as an effective longevity and metabolic health treatment not limited by aging.
Self-regulated reversal deformation and locomotion of structurally homogenous hydrogels subjected to constant light illumination
Authors: Guo Kexin , Yang Xuehan , Zhou Chao , Li Chuang 
Published: February 2024

AbstractEnvironmentally adaptive hydrogels that are capable of reconfiguration in response to external stimuli have shown great potential toward bioinspired actuation and soft robotics. Previous efforts have focused mainly on either the sophisticated design of heterogeneously structured hydrogels or the complex manipulation of external stimuli, and achieving self-regulated reversal shape deformation in homogenous hydrogels under a constant stimulus has been challenging. Here, we report the molecular design of structurally homogenous hydrogels containing simultaneously two spiropyrans that exhibit self-regulated transient deformation reversal when subjected to constant illumination. The deformation reversal mechanism originates from the molecular sequential descending-ascending charge variation of two coexisting spiropyrans upon irradiation, resulting in a macroscale volumetric contraction-expansion of the hydrogels. Hydrogel film actuators were developed to display complex temporary bidirectional shape transformations and self-regulated reversal rolling under constant illumination. Our work represents an innovative strategy for programming complex shape transformations of homogeneous hydrogels using a single constant stimulus.
Faecal hsa-miR-7704 inhibits the growth and adhesion of Bifidobacterium longum by suppressing ProB and aggravates hepatic encephalopathy
Authors: Wang Yuchong , Li Yuyu , Lv Longxian , Zhu Liying , Hong Liang , Wang Xueyao , Zhang Yu , Wang Xin , Diao Hongyan 
Published: February 2024

AbstractBoth gut microbiome and microRNAs (miRNAs) play a role in the development of hepatic encephalopathy (HE). However, the functional link between the microbiome and host-derived miRNAs in faeces remains poorly understood. In the present study, patients with HE had an altered gut microbiome and faecal miRNAs compared with patients with chronic hepatitis B. Transferring faeces and faecal miRNAs from patients with HE to the recipient mice aggravated thioacetamide-induced HE. Oral gavage of hsa-miR-7704, a host-derived miRNA highly enriched in faeces from patients with HE, aggravated HE in mice in a microbiome-dependent manner. Mechanistically, hsa-miR-7704 inhibited the growth and adhesion of Bifidobacterium longum by suppressing proB. B. longum and its metabolite acetate alleviated HE by inhibiting microglial activation and ammonia production. Our findings reveal the role of miRNA–microbiome axis in HE and suggest that faecal hsa-miR-7704 are potential regulators of HE progression.
Lumpectomy without radiation for ductal carcinoma in situ of the breast: 20-year results from the ECOG-ACRIN E5194 study
Authors: Wright Jean L. , Gray Robert , Rahbar Habib , Comstock Christopher E. , Tjoe Judy A. , Badve Sunil , Recht Abram , Sparano Joseph A. , Davidson Nancy E. , Wolff Antonio C. 
Published: February 2024

AbstractWe report the 20-year rate of ipsilateral breast event (IBE) for patients with ductal carcinoma in situ (DCIS) treated with lumpectomy without radiation on a non-randomized prospective clinical trial. Patients were enrolled in cohort 1: low- or intermediate-grade DCIS, size ≤ 2.5 cm (n = 561); or cohort 2: high-grade DCIS, size ≤ 1 cm (n = 104). The Kaplan–Meier method was used to estimate time-to-event distributions. Cox proportional hazard methods were used to estimate hazard ratios (HRs) and tests for significance for event times. 561 patients were enrolled in cohort 1 and 104 in cohort 2. After central pathology review, 26% in cohort 1 were recategorized as high-grade and 26% in cohort 2 as low- or intermediate-grade. Mean DCIS size was similar at 7.5 mm in cohort 1 and 7.8 mm in cohort 2. Surgical margin was ≥3 mm in 96% of patients, and about 30% received tamoxifen. Median follow-up was 19.2 years. There were 104 IBEs, of which 54 (52%) were invasive. The IBE and invasive IBE rates increased in both cohorts up to 15 years, then plateaued. The 20-year IBE rates were 17.8% for cohort 1 and 28.7% for cohort 2 (p = 0.005), respectively. Invasive IBE occurred in 9.8% and 15.1% (p = 0.09), respectively. On multivariable analysis, IBE risk increased with size and was higher in cohort 2, but grade and margin width were not significantly associated with IBE. For patients with DCIS treated with excision without radiation, the rate of IBE increased with size and assigned cohort mostly in the first 15 years.
Inter-epitope spacer variation within polytopic L2-based human papillomavirus antigens affects immunogenicity
Authors: Zhang Yueru , Mariz Filipe Colaco , Sehr Peter , Spagnoli Gloria , Koenig Karl Moritz , Çelikyürekli Simay , Kreuziger Tim , Zhao Xueer , Bolchi Angelo , Ottonello Simone , Müller Martin 
Published: February 2024

AbstractThe human papillomavirus minor capsid protein L2 is being extensively explored in pre-clinical studies as an attractive vaccine antigen capable of inducing broad-spectrum prophylactic antibody responses. Recently, we have developed two HPV vaccine antigens – PANHPVAX and CUT-PANHPVAX- both based on heptameric nanoparticle antigens displaying polytopes of the L2 major cross-neutralizing epitopes of eight mucosal and twelve cutaneous HPV types, respectively. Prompted by the variable neutralizing antibody responses against some of the HPV types targeted by the antigens observed in previous studies, here we investigated the influence on immunogenicity of six distinct glycine-proline spacers inserted upstream to a specific L2 epitope. We show that spacer variants differentially influence antigen immunogenicity in a mouse model, with the antigen constructs M8merV6 and C12merV6 displaying a superior ability in the induction of neutralizing antibodies as determined by pseudovirus-based neutralization assays (PBNAs). L2-peptide enzyme-linked immunosorbent assay (ELISA) assessments determined the total anti-L2 antibody level for each antigen variant, showing for the majority of sera a correlation with their repective neutralizing antibody level. Surface Plasmon Resonance revealed that L2 epitope-specific, neutralizing monoclonal antibodies (mAbs) display distinct avidities to different antigen spacer variants. Furthermore, mAb affinity toward individual spacer variants was well correlated with their neutralizing antibody induction capacity, indicating that the mAb affinity assay predicts L2-based antigen immunogenicity. These observations provide insights on the development and optimization of L2-based HPV vaccines.
A simulated ‘sandbox’ for exploring the modifiable areal unit problem in aggregation and disaggregation
Authors: Nieves Jeremiah J. , Gaughan Andrea E. , Stevens Forrest R. , Yetman Greg , Gros Andreas 
Published: February 2024

AbstractWe present a spatial testbed of simulated boundary data based on a set of very high-resolution census-based areal units surrounding Guadalajara, Mexico. From these input areal units, we simulated 10 levels of spatial resolutions, ranging from levels with 5,515–52,388 units and 100 simulated zonal configurations for each level – totalling 1,000 simulated sets of areal units. These data facilitate interrogating various realizations of the data and the effects of the spatial coarseness and zonal configurations, the Modifiable Areal Unit Problem (MAUP), on applications such as model training, model prediction, disaggregation, and aggregation processes. Further, these data can facilitate the production of spatially explicit, non-parametric estimates of confidence intervals via bootstrapping. We provide a pre-processed version of these 1,000 simulated sets of areal units, meta- and summary data to assist in their use, and a code notebook with the means to alter and/or reproduce these data.
Robotic monitoring of dunes: a dataset from the EU habitats 2110 and 2120 in Sardinia (Italy)
Authors: Angelini Franco , Pollayil Mathew J. , Rivieccio Giovanni , Caria Maria Carmela , Bagella Simonetta , Garabini Manolo 
Published: February 2024

AbstractThis data descriptor presents a novel dataset collected using the quadrupedal robot ANYmal C in the Mediterranean coastal dune environment of the European Union (EU) habitats 2110 and 2120 in Sardinia, Italy. The dataset mainly consists of photos, videos, and point clouds of the coastal dunes, providing valuable information on the structure and composition of this habitat. The data was collected by a team of robotic engineers and plant scientists as result of a joint effort towards robotic habitat monitoring. The dataset is publicly available through Zenodo and can be used by researchers working in both the fields of robotics and habitat ecology and conservation. The availability of this dataset has the potential to inform future research and conservation efforts in the EU habitats 2110 and 2120, and it highlights the importance of interdisciplinary collaboration in the field of habitat monitoring. This paper serves as a comprehensive description of the dataset and the methods used to collect it, making it a valuable resource for the scientific community.
Band-by-band spectral radiative kernels based on the ERA5 reanalysis
Authors: Huang Han , Huang Yi , Wei Qiang , Hu Yongyun 
Published: February 2024

AbstractRadiative kernel is a widely adopted method for diagnosing radiation variability and climate feedback. However, most of the existing radiative kernels are broadband flux kernels and lack the spectral information. Motivated by the growing interest in the spectral changes of the Earth radiation budget, we generate a new set of band-by-band radiative kernels based on the fifth generation European Center for Medium-Range Weather Forecasts (ERA5) reanalysis, which can be used for analyzing the spectrally decomposed changes in the top of atmosphere, surface and atmospheric radiation. The radiative sensitivity quantified by the ERA5 band-by-band kernel is compared to another spectral kernel and validated in a spectral radiation closure test. The use and benefits of the new ERA5 kernels are then demonstrated in an analysis of spectral feedbacks of an ensemble of global climate models (GCMs).