bluuebunny/crossref_metadata_2025_split huggingface dataset:
Awakening prime editing for precision engineering of probioticEscherichia coliNissle 1917
Authors: Chen Pei-Ru , Wei Ying , Li Xin , Yu Hai-Yan , Wang Shu-Guang , Yuan Xian-Zheng , Xia Peng-Fei 
Published: October 2024

AbstractCRISPR-Cas systems are transforming precision medicine with engineered probiotics as next-generation diagnostics and therapeutics. To promote human health and treat disease, engineering probiotic bacteria demands maximal versatility to enable non-natural functionalities while minimizing undesired genomic interferences. Here, we present a streamlined prime editing approach tailored for probioticEscherichia coliNissle 1917 utilizing only essential genetic modules and an optimized workflow. This was realized by assembling a prime editor consisting of the CRISPR-Cas system fromStreptococcus pyogeneswith its native codons and a codon-optimized reverse transcriptase, and by orchestrating the induction levels. As a result, we achieved all types of prime editing in every individual round of experiments with efficiencies of 25.0%, 52.0% and 66.7% for DNA deletion, insertion, and substitution, respectively. A comprehensive evaluation of off-target effects revealed a significant reduction in unintended mutations, particularly in comparison to two different base editing methods. Leveraging the prime editing system, we developed a barcoding system for strain tracking and an antibiotic-resistance-gene-free platform to enable non-natural functionalities. Our prime editing strategy awakens back-to-basics CRISPR-Cas systems devoid of complex or extraneous designs, paving the way for future innovations in engineered probiotics.
The aberrant language network dynamics in autism ages 5–40 years
Authors: Hu Zhe , Guo Xiaolin , Yang Junjie , Qu Zhiheng , Li Zhongqi , Li Junjing , Gao Xiaowei , Liu Jiaxuan , Wang Yaling , Li Wanchun , Li Wanjing , Huang Yien , Chen Jiali , Wang Xin , Yuan Binke 
Published: October 2024

AbstractBackgroundLanguage impairments, which affect both structural aspects of language and pragmatic use, are frequently observed in autism spectrum disorder (ASD). These impairments are often associated with atypical brain development and unusual network interaction patterns. However, a neurological framework remains elusive to explain them.MethodsIn this study, we utilized the dynamic "meta-networking" framework of language—a theoretical model that describes the domain-segregation dynamics during resting states—to investigate cortical language network abnormalities in ASD aged 5–40 years.ResultsOur findings revealed distinct developmental trajectories for three domain-specific language subnetworks in ASD, characterized by unique patterns of hypo-and hyper-connectivity that vary with age. Notably, these language network abnormalities proved to be strong predictors of verbal Intelligence Quotient and communication deficits, though they did not predict social abilities or stereotypical behaviors.LimitationsDue to the limited availability of linguistic data, our study was unable to assess the language deficit profiles of individuals with ASD.ConclusionsCollectively, these findings refined our understanding of the network mechanisms for language and communication deficits in ASD.
Should I stay or should I go? Generalized marginal value theorem with temporal discounting
Authors: Zylberberg Joel 
Published: October 2024

AbstractConsider a person in an environment containing patchy rewards. Under what circumstances should they stay in a given reward patch or leave that patch to seek out a new one? In a landmark 1976 study, Charnov derived the action policy that maximizes the expected rate at which this person gathers rewards. This result is called the Marginal Value Theorem (MVT), and decades of study have shown that humans’ and other animals’ behaviors qualitatively follow MVT, but with notable and systematic deviations. These deviations have been hypothesized to arise from the fact that MVT does not incorporate temporal discounting whereas humans and other animals tend to value current rewards more than future ones. Rigorously testing that hypothesis has been challenging because there is no mathematical theory that determines optimal patch foraging decision policies for agents who use temporal discounting. To fill this knowledge gap, I derived the optimal patch foraging policy for agents who exponentially discount future rewards and studied how that optimal policy depends upon their temporal discount rate, and upon the structure of their environment. Notably there are conditions under which the optimal policy with temporal discounting is to leaveearlierthan is predicted by MVT (under-staying), while under other conditions the optimal policy is to stay longer than is predicted by MVT (over-staying). The theory presented here delineates when each situation arises and may help to interpret the otherwise-puzzling ways in which human and animal behaviors deviate from MVT.
Mechanisms and purpose of lowered action potential firing threshold in fast-spiking interneurons in the human neocortex
Authors: Bakos Emoke , Tiszlavicz Ádám , Szegedi Viktor , Douida Abdennour , Furdan Szabina , Welter Daphne , Landry Jonathan , Bende Balazs , Hutoczki Gabor , Barzo Pal , Tamas Gabor , Benes Vladimir , Szucs Attila , Lamsa Karri 
Published: October 2024

AbstractThe mammalian brain exhibits various interspecies differences. Microanatomical and molecular differences in homologous neurons between species are best characterized in the neocortical mantle, but the purpose of these differences remains poorly understood. We performed whole-cell microelectrode recordings and microanatomical and molecular analyses of human fast-spiking parvalbumin (pvalb)-expressing interneurons in neocortical tissue resected during brain surgery. Fast-spiking interneurons exhibited a lower action potential (AP) firing threshold in humans than in mice. Compared with mouse neurons, human neurons displayed an elongated axon initial segment (AIS), and the human AIS was deficient in low-voltage activated inhibitory Kv1 potassium channels. Contrarily, Kv1 ion channels were prominent in mouse neurons. Computational fast-spiking interneuron model simulations revealed that human-type AIS lowers the AP threshold and shortens the time lag for AP generation. Thus, human AIS supports fast in–fast out electrical circuit function in human pvalb neurons, which have electrically slow membrane potential kinetics in somata.TeaserFast-spiking neurons in the human neocortex have structural and molecular adaptations in the axon to shorten IN-OUT delay
On reconstruction of cortical functional maps using subject-specific geometric and connectome eigenmodes
Authors: Olsen Anders S. , Mansour L. Sina , Pang James C. , Zalesky Andrew , Van De Ville Dimitri , Behjat Hamid 
Published: October 2024

ABSTRACTUnderstanding the interplay between human brain structure and function is crucial to discern neural dynamics. This study explores the relation between brain structure and macroscale functional activity using subject-specific structural connectome eigenmodes, complementing prior work that focused on group-level models and geometry. Leveraging data from the Human Connectome Project, we assess accuracy in reconstructing various functional MRI-based cortical maps using individualised eigenmodes, specifically, across a range of connectome construction parameters. Our results show only minor differences in performance between surface geometric eigenmodes, a local neighborhood graph, a highly smoothed null model, and individual and group-level connectomes at modest smoothing and density levels. Furthermore, our results suggest that spatially smooth eigenmodes best explain functional data. The absence of improvement of individual connectomes and surface geometry over smoothed null models calls for further methodological innovation to better quantify and understand the degree to which brain structure constrains brain function.
Coordinated conformational changes in the Tad pilus ATPase CpaF facilitate a rotary mechanism of catalysis
Authors: Yen Ian Y. , Whitfield Gregory B. , Rubinstein John L. , Burrows Lori L. , Brun Yves V. , Howell P. Lynne 
Published: October 2024

ABSTRACTThe type IV pilus family uses PilT-like ATPases to rapidly assemble and disassemble pilin subunits. Among them, the tight adherence (Tad) pilus performs both functions using a single bifunctional ATPase, CpaF. How ATP catalysis by CpaF facilitates both assembly and disassembly of the Tad pilus remains unclear. Here, we determined electron cryo-microscopy structures of CpaF in three distinct conformations and nucleotide occupancies. Packing unit analyses revealed differences in nucleotide coordination in the active sites, as well as synchronized domain movements during the catalytic cycle. Alphafold3 modeling demonstrated that CpaF and other motors within the type IV filament superfamily use a similar binding interface to engage their respective platform proteins. From these data, we propose that CpaF employs a clockwise, rotary mechanism of catalysis, which couples chemical energy to mechanical force during the biogenesis of Tad pili, a process broadly applicable to other single motor systems.
Rapid adaptation and increased genetic parallelism in experimental metapopulations ofPseudomonas aeruginosa
Authors: Chakraborty Partha Pratim , Kassen Rees 
Published: October 2024

AbstractNatural populations are often spatially structured, meaning they are best described as metapopulations composed of subpopulations connected by migration. We know little about how the topology of connections in metapopulations impacts adaptive evolution. Topologies that concentrate dispersing individuals through a central hub can accelerate adaptation above that of a well-mixed system in some models, however empirical support is lacking. We provide evidence to support this claim and show acceleration is accompanied by high rates of parallel evolution resulting from a reduced probability that rare beneficial mutations are stochastically lost. Our results suggest metapopulation topology can be a potent force driving evolutionary dynamics and patterns of genomic repeatability in structured landscapes such as those involving the spread of pathogens or invasive species.
Screening Envelope Genes Across Primate Genomes Reveals Evolution and Diversity Patterns of Endogenous Retroviruses
Authors: Chabukswar Saili , Grandi Nicole , Soddu Elena , Lin Liang-Tzung , Tramontano Enzo 
Published: October 2024

AbstractEndogenous Retroviruses (ERVs) are integrated into the host DNA as result of ancient germ line infections, majorly by now extinct exogenous retroviruses. Accordingly, vertebrates’ genomes contain thousands of ERV copies, providing “fossil” records for the ancestral retroviral diversity and its evolution within the host. Like exogenous retroviruses, ERV proviral sequence consists ofgag, pro-pol, andenvgenes flanked by long terminal repeats (LTRs). In particular, the characterization ofenvgene changes over time allows both to understand ERVs evolutionary trajectory and to infer their potential role in host physiology, including their pathological involvement. Despite their potential impact on the host, a detailed characterization has been performed for few domesticatedenvgenes, while a comprehensive survey of their abundance and diversity among primates’ genomes is still lacking. The study primarily focused on ERVs’envthat are known to be present in hominoid species, given their well-characterized nature and availability in public databases. Hence using theseenvsequences, we reconstructed 32 Env sequences representing the prototypes of these ancestral proteins in Class I, Class II, and Class III HERVs. These reconstructed Envs were then used for similarity search, phylogenetic analysis, and examination of recombination events occurred within primates’ genomes that were applied to 55 primate species across theCatarrhiniandPlatyrrhiniparvorders. Through such comprehensive pipeline, we reconstituted a phylogenetic distribution of ERV based specifically on theenvgenes, showing that the ERVs have been prevalent and widely distributed across the primate lineage. We observed for the first time the presence of the HML (human mouse mammary tumor virus-like) group in thePlatyrrhiniparvorder, indicating initiation of spread of HML supergroup before the split between New World Monkeys (NWM) and Old World Monkeys (OWM) i.e. even before 40 mya. Importantly, we confirmed interclass and intra-classenvrecombination events confirming the phenomenon of “envsnatching” among primates’ ERVs. As a result, we demonstrate that tracing the diversity patterns of ERVs’envprovides relevant insights into the retroviral evolutionary history of ERVs inCatarrhiniandPlatyrrhiniparvorders. Overall, our findings reveal thatenvrecombination contributes to the diversification of ERVs, thereby broadening our comprehension of retroviral and primate evolution.
Alzheimer’s Disease Patient Brain Extracts Induce Multiple Pathologies in Vascularized Neuroimmune Organoids for Disease Modeling and Drug Discovery
Authors: Ji Yanru , Chen Xiaoling , Joseph Meek Connor , McLean Jenna Lillie , Yang Yang , Yuan Chongli , Rochet Jean-Christophe , Liu Fei , Xu Ranjie 
Published: October 2024

AbstractAlzheimer’s Disease (AD) is the most common cause of dementia afflicting 55 million individuals worldwide, with limited treatment available. Current AD models mainly focus on familial AD (fAD), which is due to genetic mutations. However, models for studying sporadic AD (sAD), which represents over 95% of AD cases without specific genetic mutations, are severely limited. Moreover, the fundamental species differences between humans and animals might significantly contribute to clinical failures for AD therapeutics that have shown success in animal models, highlighting the urgency to develop more translational human models for studying AD, particularly sAD. In this study, we developed a complex human pluripotent stem cell (hPSC)-based vascularized neuroimmune organoid model, which contains multiple cell types affected in human AD brains, including human neurons, microglia, astrocytes, and blood vessels. Importantly, we demonstrated that brain extracts from individuals with sAD can effectively induce multiple AD pathologies in organoids four weeks post-exposure, including amyloid beta (Aβ) plaques-like aggregates, tau tangles-like aggregates, neuroinflammation, elevated microglial synaptic pruning, synapse/neuronal loss, and impaired neural network. Furthermore, after treatment with Lecanemab, an FDA-approved drug targeting Aβ, AD brain extract exposed organoids showed a significant reduction of amyloid burden. Thus, the neuroimmune organoid model provides a unique opportunity to study AD, particularly sAD under a pathophysiological relevant three-dimensional (3D) human cell environment. It also holds great promise to facilitate AD drug development, particularly for immunotherapies.
Light tunes a novel long-term threat avoidance behavior
Authors: Aranda Marcos L. , Min Eric , Liu Lucy T. , Schipma Anika E. , Schmidt Tiffany M. 
Published: October 2024

SummaryAnimals must constantly scan their environment for imminent threats to their safety. However, they must also integrate their past experiences across long timescales to assess the potential recurrence of new threats. Though visual inputs are critical for the detection of environmental danger, whether and how visual information shapes an animal’s assessment of whether a new threat is likely to reappear in a given context is unknown. Using a novel behavioral assessment of long-term threat avoidance behavior, we find that animals will avoid a familiar location where they previously experienced a single exposure to an innately threatening visual stimulus. This avoidance behavior is highly sensitive and lasts for multiple days. Intriguingly, we find that the melanopsin-expressing, intrinsically photosensitive retinal ganglion cells tune this behavior via a perihabenular-nucleus accumbens circuit distinct from the canonical visual threat detection circuits. These findings define a specific retinal cell type driving a new long-term threat avoidance behavior driven by prior visual experience.
Reductions ofGrin2ain adolescent dopamine neurons confers aberrant salience and related psychosis phenotype
Authors: Kielhold Michelle L. , Jacobs David S. , Torrado-Pacheco Alejandro , Lebowitz Joseph J. , Langdon Angela J. , Williams John T. , Zweifel Larry S. , Moghaddam Bita 
Published: October 2024

AbstractPsychosis is a hallmark of schizophrenia. It typically emerges in late adolescence and is associated with dopamine abnormalities and aberrant salience. Most genes associated with schizophrenia risk involve ubiquitous targets that may not explain delayed emergence of dopaminergic disruptions. This includesGRIN2A,the gene encoding the GluN2A subunit of the NMDA receptor. Both common and rare variants ofGRIN2Aare considered genetic risk factors for schizophrenia diagnosis. We find thatGrin2aknockout in dopamine neurons during adolescence is sufficient to produce a behavioral phenotype that mirrors aspects of psychosis. These include disruptions in effort optimization, salience attribution, and ability to utilize feedback to guide behavior. We also find a selective effect of this manipulation on dopamine release during prediction error signaling. These data provide mechanistic insight into how variants ofGRIN2Amay lead to the latent presentation of aberrant salience and abnormalities in dopamine dynamics. This etiologically relevant model may aid future discovery of course altering treatments for schizophrenia.
CRISPR-enabled control of gene expression sets the isotopic composition of microbial methane
Authors: Gropp Jonathan , Bill Markus , Lloyd Max K. , Stein Rebekah , Nayak Dipti D. , Stolper Daniel A. 
Published: October 2024

AbstractThe stable isotopic composition of biogenic methane varies substantially in the environment and is routinely used to fingerprint its source. However, the underlying cause of this variation is debated. Here, we experimentally manipulate the growth rate of the model methanogen,Methanosarcina acetivorans, using CRISPR mutagenesis to generate a tunable version of the key and final enzyme in methanogenesis, methyl-coenzyme M reductase (MCR). We demonstrate that the carbon and hydrogen isotopic composition of methane change as a function of MCR expression and growth rate. Using an isotope enabled metabolic model we show that these changes stem from a substrate-independent increase in reversibility of methanogenic enzymes. Overall, these data provide a novel framework for calibrating growth coupled changes in the isotopic composition of biogenic methane.
Mu opioid receptor expression by nucleus accumbens inhibitory interneurons promotes affiliative social behavior
Authors: Toddes Carlee , Lefevre Emilia M. , Retzlaff Cassandra L. , Zugschwert Lauryn , Khan Sameer , Myhre Erin , Gauthier Elysia A. , Fernandez de Velasco Ezequiel Marron , Kieffer Brigitte L. , Rothwell Patrick E. 
Published: October 2024

ABSTRACTMu opioid receptors in the nucleus accumbens regulate motivated behavior, including pursuit of natural rewards like social interaction as well as exogenous opioids. We used a suite of genetic and viral strategies to conditionally delete mu opioid receptor expression from all major neuron types in the nucleus accumbens. We pinpoint inhibitory interneurons as an essential site of mu opioid receptor expression for typical social behavior, independent from exogenous opioid sensitivity.
Measurement of differential collisional excitation cross sections for the
Kα
emission of He-like oxygen
Authors: Grilo Filipe , Shah Chintan , Marques José , Santos José Paulo , Crespo López-Urrutia José R. , Amaro Pedro 
Published: October 2024

We measure the energy-differential cross sections for collisional excitation of the soft x-ray electric-dipole Kα (x+y+w) emission from He-like oxygen (O ), using an electron beam ion trap. Values near their excitation thresholds were extracted from the observed emissivity by rapidly cycling the energy of the exciting electron beam. This allows us to subtract time-dependent contributions of the forbidden z-line emission to the multiplet. We develop a time-dependent collisional-radiative model to further demonstrate the method and predict all spectral features. We then compare the extracted x+y+w cross sections with calculations based on distorted-wave and R-matrix methods from the literature and our own predictions using the . All R-matrix results are validated by our measurements of direct and resonant excitation, supporting the use of such state-of-the-art codes for astrophysical and plasma physics diagnostics.

Published by the American Physical Society
2024
Supply chain resilience in the construction industry: a bibliometric review on operations management practices from Industry 4.0 to Industry 5.0
Authors: Bello Jummai Okikiola , Stephen Seyi , Adetoro Pelumi , Mogaji Iseoluwa Joanna 
Published: October 2024

PurposeThe purpose of this research was to conduct a comprehensive bibliometric analysis to explore supply chain resilience and operations management practices in the construction industry, with a particular focus on the transition from Industry 4.0 to Industry 5.0. The study addressed a significant gap in the literature regarding the impact of these advanced technologies on the construction sector’s ability to anticipate, respond to and recover from disruptions.Design/methodology/approachThe methodology employed a bibliometric analysis using the Scopus database to identify key trends, influential publications and emerging research areas using keywords such as “supply chain”, “operations management”, “Industry 4.0”, “Industry 5.0” and “construction”. This approach allowed for a quantitative evaluation of existing literature, offering insights into the intellectual structure of the field.FindingsThe findings revealed that while Industry 4.0 technologies, such as IoT and AI, have enhanced the construction industry’s supply chain visibility and efficiency, the shift towards the Industry 5.0 paradigm introduces a human-centric approach that further strengthens resilience through collaboration and sustainability.Practical implicationsThe study’s practical implications suggest to both industry and academia that embracing Industry 5.0 principles could significantly enhance the construction industry’s resilience, enabling it to withstand disruptions better and maintain project quality, timelines, and budgets in an increasingly complex global environment.Originality/valueThis research examines the shift from Industry 4.0 to Industry 5.0 within construction supply chains, offering a novel perspective on integrating these technologies.