bluuebunny/crossref_metadata_2025_split huggingface dataset:
A discrete subpopulation of PFC-LHb neurons govern cocaine place preference
Authors: Abdel-Hay Nur , Kabirova Marina , Yaka Rami 
Published: July 2024

AbstractAddiction is a complex behavioral disorder characterized by compulsive drug-seeking and drug use despite harmful consequences. The prefrontal cortex (PFC) plays a crucial role in cocaine addiction, involving decision-making, impulse control, memory, and emotional regulation. The PFC interacts with the brain’s reward system, including the ventral tegmental area (VTA) and nucleus accumbens (NAc). The PFC also projects to the lateral habenula (LHb), a brain region critical for encoding negative reward and regulating the reward system. In the current study, we examined the role of PFC-LHb projections in regulating cocaine reward-related behaviors. We found that optogenetic stimulation of the PFC-LHb circuit during cocaine conditioning abolished cocaine preference without causing aversion. In addition, increased c-fos expression in LHb neurons was observed in animals that received optic stimulation during cocaine conditioning, supporting the circuit’s involvement in cocaine preference regulation. Molecular analysis in animals that received optic stimulation revealed that cocaine-induced alterations in the expression of GluA1 subunit of AMPA receptor was normalized to saline levels in a region-specific manner. Moreover, GluA1 serine phosphorylation on S845 and S831 were differentially altered in LHb and VTA but not in the PFC. Together these findings highlight the critical role of the PFC-LHb circuit in controlling cocaine reward-related behaviors and shed light on the underlying mechanisms. Understanding this circuit’s function may provide valuable insights into addiction and contribute to developing targeted treatments for substance use disorders.
The anti-tumor effect of trifluridine via induction of aberrant mitosis is unaffected by mutations modulating p53 activity
Authors: Wakasa Takeshi , Nonaka Kentaro , Harada Akihito , Ohkawa Yasuyuki , Kikutake Chie , Suyama Mikita , Kobunai Takashi , Tsunekuni Kenta , Matsuoka Kazuaki , Kataoka Yuki , Ochiiwa Hiroaki , Miyadera Kazutaka , Sagara Takeshi , Oki Eiji , Ohdo Shigehiro , Maehara Yoshihiko , Iimori Makoto , Kitao Hiroyuki 
Published: July 2024

AbstractThe fluorinated thymidine analog trifluridine (FTD) is a chemotherapeutic drug commonly used to treat cancer; however, the mechanism by which FTD induces cytotoxicity is not fully understood. In addition, the effect of gain-of-function (GOF) missense mutations of the TP53 gene (encoding p53), which promote cancer progression and chemotherapeutic drug resistance, on the chemotherapeutic efficacy of FTD is unclear. Here, we revealed the mechanisms by which FTD-induced aberrant mitosis and contributed to cytotoxicity in both p53-null and p53-GOF missense mutant cells. In p53-null mutant cells, FTD-induced DNA double-stranded breaks, single-stranded DNA accumulation, and the associated DNA damage responses during the G2 phase. Nevertheless, FTD-induced DNA damage and the related responses were not sufficient to trigger strict G2/M checkpoint arrest. Thus, these features were carried over into mitosis, resulting in chromosome breaks and bridges, and subsequent cytokinesis failure. Improper mitotic exit eventually led to cell apoptosis, caused by the accumulation of extensive DNA damage and the presence of micronuclei encapsulated in the disrupted nuclear envelope. Upon FTD treatment, the behavior of the p53-GOF-missense mutant, isogenic cell lines, generated by CRISPR/Cas9 genome editing, was similar to that of p53-null mutant cells. Thus, our data suggest that FTD treatment overrode the effect on gene expression induced by p53-GOF mutants and exerted its anti-tumor activity in a manner that was independent of the p53 function.
Perirhinal cortex learns a predictive map of the task environment
Authors: Lee David G. , McLachlan Caroline A. , Nogueira Ramon , Kwon Osung , Carey Alanna E. , House Garrett , Lagani Gavin D. , LaMay Danielle , Fusi Stefano , Chen Jerry L. 
Published: July 2024

AbstractGoal-directed tasks involve acquiring an internal model, known as a predictive map, of relevant stimuli and associated outcomes to guide behavior. Here, we identified neural signatures of a predictive map of task behavior in perirhinal cortex (Prh). Mice learned to perform a tactile working memory task by classifying sequential whisker stimuli over multiple training stages. Chronic two-photon calcium imaging, population analysis, and computational modeling revealed that Prh encodes stimulus features as sensory prediction errors. Prh forms stable stimulus-outcome associations that can progressively be decoded earlier in the trial as training advances and that generalize as animals learn new contingencies. Stimulus-outcome associations are linked to prospective network activity encoding possible expected outcomes. This link is mediated by cholinergic signaling to guide task performance, demonstrated by acetylcholine imaging and systemic pharmacological perturbation. We propose that Prh combines error-driven and map-like properties to acquire a predictive map of learned task behavior.
Accelerating glacier volume loss on Juneau Icefield driven by hypsometry and melt-accelerating feedbacks
Authors: Davies Bethan , McNabb Robert , Bendle Jacob , Carrivick Jonathan , Ely Jeremy , Holt Tom , Markle Bradley , McNeil Christopher , Nicholson Lindsey , Pelto Mauri 
Published: July 2024

AbstractGlobally, glaciers and icefields contribute significantly to sea level rise. Here we show that ice loss from Juneau Icefield, a plateau icefield in Alaska, accelerated after 2005 AD. Rates of area shrinkage were 5 times faster from 2015–2019 than from 1979–1990. Glacier volume loss remained fairly consistent (0.65–1.01 km3 a−1) from 1770–1979 AD, rising to 3.08–3.72 km3 a−1 from 1979–2010, and then doubling after 2010 AD, reaching 5.91 ± 0.80 km3 a−1 (2010–2020). Thinning has become pervasive across the icefield plateau since 2005, accompanied by glacier recession and fragmentation. Rising equilibrium line altitudes and increasing ablation across the plateau has driven a series of hypsometrically controlled melt-accelerating feedbacks and resulted in the observed acceleration in mass loss. As glacier thinning on the plateau continues, a mass balance-elevation feedback is likely to inhibit future glacier regrowth, potentially pushing glaciers beyond a dynamic tipping point.
A unified model-based framework for doublet or multiplet detection in single-cell multiomics data
Authors: Hu Haoran , Wang Xinjun , Feng Site , Xu Zhongli , Liu Jing , Heidrich-O’Hare Elisa , Chen Yanshuo , Yue Molin , Zeng Lang , Rong Ziqi , Chen Tianmeng , Billiar Timothy , Ding Ying , Huang Heng , Duerr Richard H. , Chen Wei 
Published: July 2024

AbstractDroplet-based single-cell sequencing techniques rely on the fundamental assumption that each droplet encapsulates a single cell, enabling individual cell omics profiling. However, the inevitable issue of multiplets, where two or more cells are encapsulated within a single droplet, can lead to spurious cell type annotations and obscure true biological findings. The issue of multiplets is exacerbated in single-cell multiomics settings, where integrating cross-modality information for clustering can inadvertently promote the aggregation of multiplet clusters and increase the risk of erroneous cell type annotations. Here, we propose a compound Poisson model-based framework for multiplet detection in single-cell multiomics data. Leveraging experimental cell hashing results as the ground truth for multiplet status, we conducted trimodal DOGMA-seq experiments and generated 17 benchmarking datasets from two tissues, involving a total of 280,123 droplets. We demonstrated that the proposed method is an essential tool for integrating cross-modality multiplet signals, effectively eliminating multiplet clusters in single-cell multiomics data—a task at which the benchmarked single-omics methods proved inadequate.
Intrinsic signaling pathways modulate targeted protein degradation
Authors: Mori Yuki , Akizuki Yoshino , Honda Rikuto , Takao Miyu , Tsuchimoto Ayaka , Hashimoto Sota , Iio Hiroaki , Kato Masakazu , Kaiho-Soma Ai , Saeki Yasushi , Hamazaki Jun , Murata Shigeo , Ushijima Toshikazu , Hattori Naoko , Ohtake Fumiaki 
Published: July 2024

AbstractTargeted protein degradation is a groundbreaking modality in drug discovery; however, the regulatory mechanisms are still not fully understood. Here, we identify cellular signaling pathways that modulate the targeted degradation of the anticancer target BRD4 and related neosubstrates BRD2/3 and CDK9 induced by CRL2VHL- or CRL4CRBN -based PROTACs. The chemicals identified as degradation enhancers include inhibitors of cellular signaling pathways such as poly-ADP ribosylation (PARG inhibitor PDD00017273), unfolded protein response (PERK inhibitor GSK2606414), and protein stabilization (HSP90 inhibitor luminespib). Mechanistically, PARG inhibition promotes TRIP12-mediated K29/K48-linked branched ubiquitylation of BRD4 by facilitating chromatin dissociation of BRD4 and formation of the BRD4–PROTAC–CRL2VHL ternary complex; by contrast, HSP90 inhibition promotes BRD4 degradation after the ubiquitylation step. Consequently, these signal inhibitors sensitize cells to the PROTAC-induced apoptosis. These results suggest that various cell-intrinsic signaling pathways spontaneously counteract chemically induced target degradation at multiple steps, which could be liberated by specific inhibitors.
Non-invasive and noise-robust light focusing using confocal wavefront shaping
Authors: Aizik Dror , Levin Anat 
Published: July 2024

AbstractWavefront-shaping is a promising approach for imaging fluorescent targets deep inside scattering tissue despite strong aberrations. It enables focusing an incoming illumination into a single spot inside tissue, as well as correcting the outgoing light scattered from the tissue. Previously, wavefront shaping modulations have been successively estimated using feedback from strong fluorescent beads, which have been manually added to a sample. However, such algorithms do not generalize to neurons whose emission is orders of magnitude weaker. We suggest a wavefront shaping approach that works with a confocal modulation of both the illumination and imaging arms. Since the aberrations are corrected in the optics before the detector, the low photon budget is directed into a single sensor spot and detected with high signal-noise ratio. We derive a score function for modulation evaluation from mathematical principles, and successfully use it to image fluorescence neurons, despite scattering through thick tissue.
Tamm-cavity terahertz detector
Authors: Tu Xuecou , Zhang Yichen , Zhou Shuyu , Tang Wenjing , Yan Xu , Rui Yunjie , Wang Wohu , Yan Bingnan , Zhang Chen , Ye Ziyao , Shi Hongkai , Su Runfeng , Wan Chao , Dong Daxing , Xu Ruiying , Zhao Qing-Yuan , Zhang La-Bao , Jia Xiao-Qing , Wang Huabing , Kang Lin , Chen Jian , Wu Peiheng 
Published: July 2024

AbstractEfficiently fabricating a cavity that can achieve strong interactions between terahertz waves and matter would allow researchers to exploit the intrinsic properties due to the long wavelength in the terahertz waveband. Here we show a terahertz detector embedded in a Tamm cavity with a record Q value of 1017 and a bandwidth of only 469 MHz for direct detection. The Tamm-cavity detector is formed by embedding a substrate with an Nb5N6 microbolometer detector between an Si/air distributed Bragg reflector (DBR) and a metal reflector. The resonant frequency can be controlled by adjusting the thickness of the substrate layer. The detector and DBR are fabricated separately, and a large pixel-array detector can be realized by a very simple assembly process. This versatile cavity structure can be used as a platform for preparing high-performance terahertz devices and opening up the study of the strong interactions between terahertz waves and matter.
Accurate Prediction of Protein Structural Flexibility by Deep Learning Integrating Intricate Atomic Structures and Cryo-EM Density Information
Authors: Song Xintao , Bao Lei , Feng Chenjie , Huang Qiang , Zhang Fa , Gao Xin , Han Renmin 
Published: July 2024

AbstractThe dynamics of proteins are crucial for understanding their mechanisms. However, computationally predicting protein dynamic information has proven challenging. Here, we propose a neural network model, RMSF-net, which outperforms previous methods and produces the best results in a large-scale protein dynamics dataset; this model can accurately infer the dynamic information of a protein in only a few seconds. By learning effectively from experimental protein structure data and cryo-electron microscopy (cryo-EM) data integration, our approach is able to accurately identify the interactive bidirectional constraints and supervision between cryo-EM maps and PDB models in maximizing the dynamic prediction efficacy. Rigorous 5-fold cross-validation on the dataset demonstrates that RMSF-net achieves test correlation coefficients of 0.746 ± 0.127 at the voxel level and 0.765 ± 0.109 at the residue level, showcasing its ability to deliver dynamic predictions closely approximating molecular dynamics simulations. Additionally, it offers real-time dynamic inference with minimal storage overhead on the order of megabytes. RMSF-net is a freely accessible tool and is anticipated to play an essential role in the study of protein dynamics.
Acquisition of non-olfactory encoding improves odour discrimination in olfactory cortex
Authors: Federman Noel , Romano Sebastián A. , Amigo-Duran Macarena , Salomon Lucca , Marin-Burgin Antonia 
Published: July 2024

AbstractOlfaction is influenced by contextual factors, past experiences, and the animal’s internal state. Whether this information is integrated at the initial stages of cortical odour processing is not known, nor how these signals may influence odour encoding. Here we revealed multiple and diverse non-olfactory responses in the primary olfactory (piriform) cortex (PCx), which dynamically enhance PCx odour discrimination according to behavioural demands. We performed recordings of PCx neurons from mice trained in a virtual reality task to associate odours with visual contexts to obtain a reward. We found that learning shifts PCx activity from encoding solely odours to a regime in which positional, contextual, and associative responses emerge on odour-responsive neurons that become mixed-selective. The modulation of PCx activity by these non-olfactory signals was dynamic, improving odour decoding during task engagement and in rewarded contexts. This improvement relied on the acquired mixed-selectivity, demonstrating how integrating extra-sensory inputs in sensory cortices can enhance sensory processing while encoding the behavioural relevance of stimuli.
The mastery of details in the workflow of materials machine learning
Authors: Ma Yingying , Xu Pengcheng , Li Minjie , Ji Xiaobo , Zhao Wenyue , Lu Wencong 
Published: July 2024

AbstractAs machine learning (ML) continues to advance in the field of materials science, the variation in strategies for the same steps of the ML workflow becomes increasingly significant. These details can have a substantial impact on results, yet they have not received the deserved attention. This review aims to explore the various strategies available for each detail within the general workflow of materials ML. Firstly, the general workflow of materials ML will be introduced to help readers gain an understanding of potential details. Subsequently, different strategies of details within each step of the workflow will be presented through state-of-the-art case studies. The potential outcomes associated with choosing different strategies to details will be explored. Following this, suitable strategies for details will be recommended based on distinct application scenarios. Finally, directions for the future development of materials ML concerning details will be proposed. Through these discussions, we aspire to offer a comprehensive understanding of the nuances in details within materials ML. This will serve as valuable reference and guidance for researchers in both materials science and ML.
Calcium-rich dairy matrix protects better than mineral calcium against colonic luminal haem-induced alterations in male rats
Authors: Olier Maïwenn , Naud Nathalie , Fouché Edwin , Tondereau Valérie , Ahn Ingrid , Leconte Nadine , Blas-Y-Estrada Florence , Garric Gilles , Heliès-Toussaint Cécile , Harel-Oger Marielle , Marmonier Corinne , Théodorou Vassilia , Guéraud Françoise , Jan Gwénaël , Pierre Fabrice 
Published: July 2024

AbstractThe haemoglobin content in meat is consistently associated with an increased risk of colorectal cancer, whereas calcium may play a role as a chemopreventive agent. Using rodent models, calcium salts have been shown to prevent the promotion of haem-induced and red meat-induced colorectal carcinogenesis by limiting the bioavailability of the gut luminal haem iron. Therefore, this study aimed to compare impacts of dietary calcium provided as calcium salts or dairy matrix on gut homoeostasis perturbations by high haeminic or non-haeminic iron intakes. A 3-week intervention study was conducted using Fischer 344 rats. Compared to the ferric citrate-enriched diet, the haemoglobin-enriched diet led to increased faecal, mucosal, and urinary lipoperoxidation-related biomarkers, resulting from higher gut luminal haem iron bioavailability. This redox imbalance was associated to a dysbiosis of faecal microbiota. The addition of calcium to haemoglobin-enriched diets limited haem iron bioavailability and counteracted redox imbalance, with improved preventive efficacy when calcium was provided in dairy matrix. Data integration revealed correlations between haem-induced lipoperoxidation products and bacterial communities belonging to Peptococcaceae, Eubacterium coprostanoligenes group, and Bifidobacteriaceae. This integrated approach provides evidence of the benefits of dairy matrix as a dietary calcium vehicle to counteract the deleterious side-effects of meat consumption.
Point-of-use filtration units as drinking water distribution system sentinels
Authors: Bai Weiliang , Xu Ruizhe , Podar Mircea , Swift Cynthia M. , Saleh Navid B. , Löffler Frank E. , Alvarez Pedro J. J. , Kumar Manish 
Published: July 2024

AbstractMunicipal drinking water distribution systems (DWDSs) and associated premise plumbing (PP) systems are vulnerable to proliferation of opportunistic pathogens, even when chemical disinfection residuals are present, thus presenting a public health risk. Monitoring the structure of microbial communities of drinking water is challenging because of limited continuous access to faucets, pipes, and storage tanks. We propose a scalable household sampling method, which uses spent activated carbon and reverse osmosis (RO) membrane point-of-use (POU) filters to evaluate mid- to long-term occurrence of microorganisms in PP systems that are relevant to consumer exposure. As a proof of concept, POU filter microbiomes were collected from four different locations and analyzed with 16S rRNA gene amplicon sequencing. The analyses revealed distinct microbial communities, with occasional detection of potential pathogens. The findings highlight the importance of local, and if possible, continuous monitoring within and across distribution systems. The continuous operation of POU filters offers an advantage in capturing species that may be missed by instantaneous sampling methods. We suggest that water utilities, public institutions, and regulatory agencies take advantage of end-of-life POU filters for microbial monitoring. This approach can be easily implemented to ensure drinking water safety, especially from microbes of emerging concerns; e.g., pathogenic Legionella and Mycobacterium species.
Sustained increases in atmospheric oxygen and marine productivity in the Neoproterozoic and Palaeozoic eras
Authors: Stockey Richard G. , Cole Devon B. , Farrell Una C. , Agić Heda , Boag Thomas H. , Brocks Jochen J. , Canfield Don E. , Cheng Meng , Crockford Peter W. , Cui Huan , Dahl Tais W. , Del Mouro Lucas , Dewing Keith , Dornbos Stephen Q. , Emmings Joseph F. , Gaines Robert R. , Gibson Timothy M. , Gill Benjamin C. , Gilleaudeau Geoffrey J. , Goldberg Karin , Guilbaud Romain , Halverson Galen , Hammarlund Emma U. , Hantsoo Kalev , Henderson Miles A. , Henderson Charles M. , Hodgskiss Malcolm S. W. , Jarrett Amber J. M. , Johnston David T. , Kabanov Pavel , Kimmig Julien , Knoll Andrew H. , Kunzmann Marcus , LeRoy Matthew A. , Li Chao , Loydell David K. , Macdonald Francis A. , Magnall Joseph M. , Mills N. Tanner , Och Lawrence M. , O’Connell Brennan , Pagès Anais , Peters Shanan E. , Porter Susannah M. , Poulton Simon W. , Ritzer Samantha R. , Rooney Alan D. , Schoepfer Shane , Smith Emily F. , Strauss Justin V. , Uhlein Gabriel Jubé , White Tristan , Wood Rachel A. , Woltz Christina R. , Yurchenko Inessa , Planavsky Noah J. , Sperling Erik A. 
Published: July 2024

AbstractA geologically rapid Neoproterozoic oxygenation event is commonly linked to the appearance of marine animal groups in the fossil record. However, there is still debate about what evidence from the sedimentary geochemical record—if any—provides strong support for a persistent shift in surface oxygen immediately preceding the rise of animals. We present statistical learning analyses of a large dataset of geochemical data and associated geological context from the Neoproterozoic and Palaeozoic sedimentary record and then use Earth system modelling to link trends in redox-sensitive trace metal and organic carbon concentrations to the oxygenation of Earth’s oceans and atmosphere. We do not find evidence for the wholesale oxygenation of Earth’s oceans in the late Neoproterozoic era. We do, however, reconstruct a moderate long-term increase in atmospheric oxygen and marine productivity. These changes to the Earth system would have increased dissolved oxygen and food supply in shallow-water habitats during the broad interval of geologic time in which the major animal groups first radiated. This approach provides some of the most direct evidence for potential physiological drivers of the Cambrian radiation, while highlighting the importance of later Palaeozoic oxygenation in the evolution of the modern Earth system.
Quantifying short-range order using atom probe tomography
Authors: He Mengwei , Davids William J. , Breen Andrew J. , Ringer Simon P. 
Published: July 2024

AbstractMedium- and high-entropy alloys are an emerging class of materials that can exhibit outstanding combinations of strength and ductility for engineering applications. Computational simulations have suggested the presence of short-range order (SRO) in these alloys, and recent experimental evidence is also beginning to emerge. Unfortunately, the difficulty in quantifying the SRO under different heat treatment conditions has generated much debate on the atomic preferencing and implications of SRO on mechanical properties. Here we develop an approach to measure SRO using atom probe tomography. This method balances the limitations of atom probe tomography with the threshold values of SRO to map the regimes where the required atomistic neighbourhood information is preserved and where it is not. We demonstrate the method with a case study of the CoCrNi alloy and use this to monitor SRO changes induced by heat treatments. These species-specific SRO measurements enable the generation of computational simulations of atomic neighbourhood models that are equivalent to the experiment and can contribute to the further understanding and design of medium- and high-entropy alloys and other materials systems where SRO may occur.