bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncovering 2-D toroidal representations in grid cell ensemble activity during 1-D behavior
Authors: Hermansen Erik , Klindt David A. , Dunn Benjamin A. 
Published: June 2024

AbstractMinimal experiments, such as head-fixed wheel-running and sleep, offer experimental advantages but restrict the amount of observable behavior, making it difficult to classify functional cell types. Arguably, the grid cell, and its striking periodicity, would not have been discovered without the perspective provided by free behavior in an open environment. Here, we show that by shifting the focus from single neurons to populations, we change the minimal experimental complexity required. We identify grid cell modules and show that the activity covers a similar, stable toroidal state space during wheel running as in open field foraging. Trajectories on grid cell tori correspond to single trial runs in virtual reality and path integration in the dark, and the alignment of the representation rapidly shifts with changes in experimental conditions. Thus, we provide a methodology to discover and study complex internal representations in even the simplest of experiments.
Alkylamine-tethered molecules recruit FBXO22 for targeted protein degradation
Authors: Kagiou Chrysanthi , Cisneros Jose A. , Farnung Jakob , Liwocha Joanna , Offensperger Fabian , Dong Kevin , Yang Ka , Tin Gary , Horstmann Christina S. , Hinterndorfer Matthias , Paulo Joao A. , Scholes Natalie S. , Sanchez Avila Juan , Fellner Michaela , Andersch Florian , Hannich J. Thomas , Zuber Johannes , Kubicek Stefan , Gygi Steven P. , Schulman Brenda A. , Winter Georg E. 
Published: June 2024

AbstractTargeted protein degradation (TPD) relies on small molecules to recruit proteins to E3 ligases to induce their ubiquitylation and degradation by the proteasome. Only a few of the approximately 600 human E3 ligases are currently amenable to this strategy. This limits the actionable target space and clinical opportunities and thus establishes the necessity to expand to additional ligases. Here we identify and characterize SP3N, a specific degrader of the prolyl isomerase FKBP12. SP3N features a minimal design, where a known FKBP12 ligand is appended with a flexible alkylamine tail that conveys degradation properties. We found that SP3N is a precursor and that the alkylamine is metabolized to an active aldehyde species that recruits the SCFFBXO22 ligase for FKBP12 degradation. Target engagement occurs via covalent adduction of Cys326 in the FBXO22 C-terminal domain, which is critical for ternary complex formation, ubiquitylation and degradation. This mechanism is conserved for two recently reported alkylamine-based degraders of NSD2 and XIAP, thus establishing alkylamine tethering and covalent hijacking of FBXO22 as a generalizable TPD strategy.
MRE11 and TREX1 control senescence by coordinating replication stress and interferon signaling
Authors: Técher Hervé , Gopaul Diyavarshini , Heuzé Jonathan , Bouzalmad Nail , Leray Baptiste , Vernet Audrey , Mettling Clément , Moreaux Jérôme , Pasero Philippe , Lin Yea-Lih 
Published: June 2024

AbstractOncogene-induced senescence (OIS) arrests cell proliferation in response to replication stress (RS) induced by oncogenes. OIS depends on the DNA damage response (DDR), but also on the cGAS-STING pathway, which detects cytosolic DNA and induces type I interferons (IFNs). Whether and how RS and IFN responses cooperate to promote OIS remains unknown. Here, we show that the induction of OIS by the H-RASV12 oncogene in immortalized human fibroblasts depends on the MRE11 nuclease. Indeed, treatment with the MRE11 inhibitor Mirin prevented RS, micronuclei formation and IFN response induced by RASV12. Overexpression of the cytosolic nuclease TREX1 also prevented OIS. Conversely, overexpression of a dominant negative mutant of TREX1 or treatment with IFN-β was sufficient to induce RS and DNA damage, independent of RASV12 induction. These data suggest that the IFN response acts as a positive feedback loop to amplify DDR in OIS through a process regulated by MRE11 and TREX1.
Selection and horizontal gene transfer underlie microdiversity-level heterogeneity in resistance gene fate during wastewater treatment
Authors: Brown Connor L. , Maile-Moskowitz Ayella , Lopatkin Allison J. , Xia Kang , Logan Latania K. , Davis Benjamin C. , Zhang Liqing , Vikesland Peter J. , Pruden Amy 
Published: June 2024

AbstractActivated sludge is the centerpiece of biological wastewater treatment, as it facilitates removal of sewage-associated pollutants, fecal bacteria, and pathogens from wastewater through semi-controlled microbial ecology. It has been hypothesized that horizontal gene transfer facilitates the spread of antibiotic resistance genes within the wastewater treatment plant, in part because of the presence of residual antibiotics in sewage. However, there has been surprisingly little evidence to suggest that sewage-associated antibiotics select for resistance at wastewater treatment plants via horizontal gene transfer or otherwise. We addressed the role of sewage-associated antibiotics in promoting antibiotic resistance using lab-scale sequencing batch reactors fed field-collected wastewater, metagenomic sequencing, and our recently developed bioinformatic tool Kairos. Here, we found confirmatory evidence that fluctuating levels of antibiotics in sewage are associated with horizontal gene transfer of antibiotic resistance genes, microbial ecology, and microdiversity-level differences in resistance gene fate in activated sludge.
Tracking single hiPSC-derived cardiomyocyte contractile function using CONTRAX an efficient pipeline for traction force measurement
Authors: Pardon Gaspard , Vander Roest Alison S. , Chirikian Orlando , Birnbaum Foster , Lewis Henry , Castillo Erica A. , Wilson Robin , Denisin Aleksandra K. , Blair Cheavar A. , Holbrook Colin , Koleckar Kassie , Chang Alex C. Y. , Blau Helen M. , Pruitt Beth L. 
Published: June 2024

AbstractCardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are powerful in vitro models to study the mechanisms underlying cardiomyopathies and cardiotoxicity. Quantification of the contractile function in single hiPSC-CMs at high-throughput and over time is essential to disentangle how cellular mechanisms affect heart function. Here, we present CONTRAX, an open-access, versatile, and streamlined pipeline for quantitative tracking of the contractile dynamics of single hiPSC-CMs over time. Three software modules enable: parameter-based identification of single hiPSC-CMs; automated video acquisition of >200 cells/hour; and contractility measurements via traction force microscopy. We analyze >4,500 hiPSC-CMs over time in the same cells under orthogonal conditions of culture media and substrate stiffnesses; +/− drug treatment; +/− cardiac mutations. Using undirected clustering, we reveal converging maturation patterns, quantifiable drug response to Mavacamten and significant deficiencies in hiPSC-CMs with disease mutations. CONTRAX empowers researchers with a potent quantitative approach to develop cardiac therapies.
Microglia contribute to neuronal synchrony despite endogenous ATP-related phenotypic transformation in acute mouse brain slices
Authors: Berki Péter , Cserép Csaba , Környei Zsuzsanna , Pósfai Balázs , Szabadits Eszter , Domonkos Andor , Kellermayer Anna , Nyerges Miklós , Wei Xiaofei , Mody Istvan , Kunihiko Araki , Beck Heinz , Kaikai He , Ya Wang , Lénárt Nikolett , Wu Zhaofa , Jing Miao , Li Yulong , Gulyás Attila I. , Dénes Ádám 
Published: June 2024

AbstractAcute brain slices represent a workhorse model for studying the central nervous system (CNS) from nanoscale events to complex circuits. While slice preparation inherently involves tissue damage, it is unclear how microglia, the main immune cells and damage sensors of the CNS react to this injury and shape neuronal activity ex vivo. To this end, we investigated microglial phenotypes and contribution to network organization and functioning in acute brain slices. We reveal time-dependent microglial phenotype changes influenced by complex extracellular ATP dynamics through P2Y12R and CX3CR1 signalling, which is sustained for hours in ex vivo mouse brain slices. Downregulation of P2Y12R and changes of microglia-neuron interactions occur in line with alterations in the number of excitatory and inhibitory synapses over time. Importantly, functional microglia modulate synapse sprouting, while microglial dysfunction results in markedly impaired ripple activity both ex vivo and in vivo. Collectively, our data suggest that microglia are modulators of complex neuronal networks with important roles to maintain neuronal network integrity and activity. We suggest that slice preparation can be used to model time-dependent changes of microglia-neuron interactions to reveal how microglia shape neuronal circuits in physiological and pathological conditions.
Comparative optimization of polysaccharide-based nanoformulations for cardiac RNAi therapy
Authors: Gao Han , Li Sen , Lan Zhengyi , Pan Da , Naidu Gonna Somu , Peer Dan , Ye Chenyi , Chen Hangrong , Ma Ming , Liu Zehua , Santos Hélder A. 
Published: June 2024

AbstractIonotropic gelation is widely used to fabricate targeting nanoparticles (NPs) with polysaccharides, leveraging their recognition by specific lectins. Despite the fabrication scheme simply involves self-assembly of differently charged components in a straightforward manner, the identification of a potent combinatory formulation is usually limited by structural diversity in compound collections and trivial screen process, imposing crucial challenges for efficient formulation design and optimization. Herein, we report a diversity-oriented combinatory formulation screen scheme to identify potent gene delivery cargo in the context of precision cardiac therapy. Distinct categories of cationic compounds are tested to construct RNA delivery system with an ionic polysaccharide framework, utilizing a high-throughput microfluidics workstation coupled with streamlined NPs characterization system in an automatic, step-wise manner. Sequential computational aided interpretation provides insights in formulation optimization in a broader scenario, highlighting the usefulness of compound library diversity. As a result, the out-of-bag NPs, termed as GluCARDIA NPs, are utilized for loading therapeutic RNA to ameliorate cardiac reperfusion damages and promote the long-term prognosis. Overall, this work presents a generalizable formulation design strategy for polysaccharides, offering design principles for combinatory formulation screen and insights for efficient formulation identification and optimization.
Stabilizing atomic Ru species in conjugated sp2 carbon-linked covalent organic framework for acidic water oxidation
Authors: Jia Hongnan , Yao Na , Jin Yiming , Wu Liqing , Zhu Juan , Luo Wei 
Published: June 2024

AbstractSuppressing the kinetically favorable lattice oxygen oxidation mechanism pathway and triggering the adsorbate evolution mechanism pathway at the expense of activity are the state-of-the-art strategies for Ru-based electrocatalysts toward acidic water oxidation. Herein, atomically dispersed Ru species are anchored into an acidic stable vinyl-linked 2D covalent organic framework with unique crossed π-conjugation, termed as COF-205-Ru. The crossed π-conjugated structure of COF-205-Ru not only suppresses the dissolution of Ru through strong Ru-N motifs, but also reduces the oxidation state of Ru by multiple π-conjugations, thereby activating the oxygen coordinated to Ru and stabilizing the oxygen vacancies during oxygen evolution process. Experimental results including X-ray absorption spectroscopy, in situ Raman spectroscopy, in situ powder X-ray diffraction patterns, and theoretical calculations unveil the activated oxygen with elevated energy level of O 2p band, decreased oxygen vacancy formation energy, promoted electrochemical stability, and significantly reduced energy barrier of potential determining step for acidic water oxidation. Consequently, the obtained COF-205-Ru displays a high mass activity with 2659.3 A g−1, which is 32-fold higher than the commercial RuO2, and retains long-term durability of over 280 h. This work provides a strategy to simultaneously promote the stability and activity of Ru-based catalysts for acidic water oxidation.
Phage predation accelerates the spread of plasmid-encoded antibiotic resistance
Authors: Ruan Chujin , Ramoneda Josep , Kan Anton , Rudge Timothy J. , Wang Gang , Johnson David R. 
Published: June 2024

AbstractPhage predation is generally assumed to reduce microbial proliferation while not contributing to the spread of antibiotic resistance. However, this assumption does not consider the effect of phage predation on the spatial organization of different microbial populations. Here, we show that phage predation can increase the spread of plasmid-encoded antibiotic resistance during surface-associated microbial growth by reshaping spatial organization. Using two strains of the bacterium Escherichia coli, we demonstrate that phage predation slows the spatial segregation of the strains during growth. This increases the number of cell-cell contacts and the extent of conjugation-mediated plasmid transfer between them. The underlying mechanism is that phage predation shifts the location of fastest growth from the biomass periphery to the interior where cells are densely packed and aligned closer to parallel with each other. This creates straighter interfaces between the strains that are less likely to merge together during growth, consequently slowing the spatial segregation of the strains and enhancing plasmid transfer between them. Our results have implications for the design and application of phage therapy and reveal a mechanism for how microbial functions that are deleterious to human and environmental health can proliferate in the absence of positive selection.
Chameleon-inspired tunable multi-layered infrared-modulating system via stretchable liquid metal microdroplets in elastomer film
Authors: Zhang Yingyue , Zhu Hanrui , An Shun , Xing Wenkui , Fu Benwei , Tao Peng , Shang Wen , Wu Jianbo , Dickey Michael D. , Song Chengyi , Deng Tao 
Published: June 2024

AbstractThis report presents liquid metal-based infrared-modulating materials and systems with multiple modes to regulate the infrared reflection. Inspired by the brightness adjustment in chameleon skin, shape-morphing liquid metal droplets in silicone elastomer (Ecoflex) matrix are used to resemble the dispersed “melanophores”. In the system, Ecoflex acts as hormone to drive the deformation of liquid metal droplets. Both total and specular reflectance-based infrared camouflage are achieved. Typically, the total and specular reflectances show change of ~44.8% and 61.2%, respectively, which are among the highest values reported for infrared camouflage. Programmable infrared encoding/decoding is explored by adjusting the concentration of liquid metal and applying areal strains. By introducing alloys with different melting points, temperature-dependent infrared painting/writing can be achieved. Furthermore, the multi-layered structure of infrared-modulating system is designed, where the liquid metal-based infrared modulating materials are integrated with an evaporated metallic film for enhanced performance of such system.
Asthma and COPD management of patients with intellectual disabilities in general practice
Authors: Mastebroek Mathilde , Everlo Nadeem C. M. , Cuypers Maarten , Bischoff Erik W. M. A. , Schalk Bianca W. M. 
Published: June 2024

AbstractPeople with intellectual disabilities experience overall poorer health and healthcare access than the general population. It is largely unknown how this applies to asthma and chronic obstructive pulmonary disease (COPD) management by general practitioners (GPs). In a 10-year retrospective matched cohort study, n = 34,429, we examined year prevalence of asthma and COPD in adult patients with and without intellectual disabilities and potential differences in the delivery of asthma and COPD disease management activities in Dutch general practices (2010–2019). We collected information on patient characteristics, comorbidity, consultation patterns, use and outcomes of asthma/COPD control questionnaires, spirometry measurement, pulmonology referrals, and prescribed medication. Asthma patients with intellectual disabilities suffered more frequently from obesity (53.2% vs. 39.5% without intellectual disabilities), and both asthma and COPD patients with intellectual disabilities were more frequently current smokers (45.2% vs. 22.1% without intellectual disabilities, and 76.6% vs. 51.4% without intellectual disabilities, respectively). Also, a statistically significant larger number of asthma patients with intellectual disabilities were prescribed antibiotics (69.9% vs. 54.5%). COPD patients with intellectual disabilities, compared with matched controls without intellectual disabilities, received significantly more often either no COPD-related practice consultation at all (respectively 20.8% vs. 8.5%, p = 0.004) or a large number of practice consultations (>31 consultations, respectively 16.7% vs. 5.3%, p = 0.004). For asthma, there was no statistical difference between patients with or without intellectual disabilities regarding the number and type of consultations. The asthma year point prevalence in patients with intellectual disabilities was, from 2014 onward, significantly higher, and in 2019 was 8.7% vs. 6.0% for people without intellectual disabilities. For COPD, it was comparable in both groups. Both asthma and COPD patients with intellectual disabilities appeared considerably younger in age than patients without intellectual disabilities. Our findings warrant further research into the causes of the differences found for asthma and COPD and whether they also infer differences in the quality or the effectiveness of GP disease management, especially for young adults with intellectual disabilities.
National-scale 10-m maps of cropland use intensity in China during 2018–2023
Authors: Qiu Bingwen , Liu Baoli , Tang Zhenghong , Dong Jinwei , Xu Weiming , Liang Juanzhu , Chen Nan , Chen Jiangping , Wang Laigang , Zhang Chengming , Li Zhengrong , Wu Fangzheng 
Published: June 2024

AbstractThe amount of actively cultivated land in China is increasingly threatened by rapid urbanization and rural population aging. Quantifying the extent and changes of active cropland and cropping intensity is crucial to global food security. However, national-scale datasets for smallholder agriculture are limited in spatiotemporal continuity, resolution, and precision. In this paper, we present updated annual Cropland Use Intensity maps in China (China-CUI10m) with descriptions of the extent of fallow/abandoned, actively cropped fields and cropping intensity at a 10-m resolution in recent six years (2018–2023). The dataset is produced by robust algorithms with no requirements for regional adjustments or intensive training samples, which take full advantage of the Sentinel-1 (S1) SAR and Sentinel-2 (S2) MSI time series. The China-CUI10m maps have achieved high accuracy when compared to ground truth data (Overall accuracy = 90.88%) and statistical data (R2 > 0.94). This paper provides the recent trends in cropland abandonment and agricultural intensification in China, which contributes to facilitating geographic-targeted cropland use control policies towards sustainable intensification of smallholder agricultural systems in developing countries.
An integrated remote sensing, petrology, and field geology analyses for Neoproterozoic basement rocks in some parts of the southern Egyptian-Nubian Shield
Authors: El-Desoky Hatem M. , Bachri Imane , El Mezayen Ahmed M. , Abdel-Rahman Ahmed M. , El-Awny Hamada , El-Gammal Arafa A. , Alshehri Fahad , Almadani Sattam 
Published: June 2024

AbstractThe main objective of this study was to use deep learning, and convolutional neural networks (CNN), integrated with field geology to identify distinct lithological units. The Samadia-Tunduba region of the South Eastern Desert of Egypt was mapped geologically for the first time thanks to the use of processed developed CNN algorithms using Landsat 9 OLI-2, which were further enhanced by geological fieldwork, spectral measurements of field samples, and petrographic examination. According to previously published papers, a significant difference was observed in the distribution of rocks and their boundaries, as well as the previously published geological maps that were not accurately compatible with the nature of the area. The many lithologic units in the region are refined using principal component analysis, color ratio composites, and false-color composites. These techniques demonstrated the ability to distinguish between various igneous and metamorphic rock types, especially metavolcanics, metasediments, granodiorite, and biotite monzogranite. The Key structural trends, lithological units, and wadis affecting the area under study are improved by the principal component analysis approach (PC 3, 2, 1), (PC 2, 3, 4), (PC 4, 3, 2), (PC 5, 4, 3), and (PC 6, 5, 4) in RGB, respectively. The best band ratios recorded in the area are recorded the good discrimination (6/5, 4/3, and 2/1), (4/2, 6/7, and 5/6), and (3/2, 5/6, and 4/6) for RGB. The classification map achieved an overall accuracy of 95.27%, and these results from Landsat-9 data were validated by field geology and petrographical studies. The results of this survey can make a significant difference to detailed geological studies. A detailed map of the new district has been prepared through a combination of deep learning and fieldwork.
Multiple talker processing in autistic adult listeners
Authors: Alispahic Samra , Pellicano Elizabeth , Cutler Anne , Antoniou Mark 
Published: June 2024

AbstractAccommodating talker variability is a complex and multi-layered cognitive process. It involves shifting attention to the vocal characteristics of the talker as well as the linguistic content of their speech. Due to an interdependence between voice and phonological processing, multi-talker environments typically incur additional processing costs compared to single-talker environments. A failure or inability to efficiently distribute attention over multiple acoustic cues in the speech signal may have detrimental language learning consequences. Yet, no studies have examined effects of multi-talker processing in populations with atypical perceptual, social and language processing for communication, including autistic people. Employing a classic word-monitoring task, we investigated effects of talker variability in Australian English autistic (n = 24) and non-autistic (n = 28) adults. Listeners responded to target words (e.g., apple, duck, corn) in randomised sequences of words. Half of the sequences were spoken by a single talker and the other half by multiple talkers. Results revealed that autistic participants’ sensitivity scores to accurately-spotted target words did not differ to those of non-autistic participants, regardless of whether they were spoken by a single or multiple talkers. As expected, the non-autistic group showed the well-established processing cost associated with talker variability (e.g., slower response times). Remarkably, autistic listeners’ response times did not differ across single- or multi-talker conditions, indicating they did not show perceptual processing costs when accommodating talker variability. The present findings have implications for theories of autistic perception and speech and language processing.