bluuebunny/crossref_metadata_2025 huggingface dataset:
Specifying precision in visual-orthographic prediction error representations for a better understanding of efficient reading
Authors: Fu Wanlu , Gagl Benjamin
Published: March 2024

Efficient visual word recognition presumably relies on orthographic prediction error (oPE) representations. Based on a transparent neurocognitive computational model rooted in the principles of the predictive coding framework, we postulated that readers optimize their percept by removing redundant visual signals, allowing them to focus on the informative aspects of the sensory input (i.e., the oPE). Here, we explore alternative oPE implementations, testing whether increased precision by assuming all-or-nothing signaling and more realistic word lexicons results in adequate representations underlying efficient word recognition. We used behavioral and electrophysiological data (i.e., EEG) for model evaluation. More precise oPE representations (i.e., implementing a binary signaling and a frequency-sorted lexicon with the 500 most common five-letter words) explained variance in behavioral responses and electrophysiological data 300 ms after stimulus onset best. The original less-precise oPE representation still best explains early brain activation. This pattern suggests a dynamic adaption of represented visual-orthographic information, where initial graded prediction errors convert into binary representations, allowing accurate retrieval of word meaning. These results offer a neuro-cognitive plausible account of efficient word recognition, emphasizing visual-orthographic information in the form of prediction error representations central to the transition from perceptual processing to the access of word meaning.
Delineating Transdiagnostic Subtypes in Neurodevelopmental Disorders via Contrastive Graph Machine Learning of Brain Connectivity Patterns
Authors: Wang Xuesong , Zhao Kanhao , Yao Lina , Fonzo Gregory A , Satterthwaite Theodore D , Rekik Islem , Zhang Yu
Published: March 2024

Neurodevelopmental disorders, such as Attention Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD), are characterized by comorbidity and heterogeneity. Identifying distinct subtypes within these disorders can illuminate the underlying neurobiological and clinical characteristics, paving the way for more tailored treatments. We adopted a novel transdiagnostic approach across ADHD and ASD, using cutting-edge contrastive graph machine learning to determine subtypes based on brain network connectivity as revealed by resting-state functional magnetic resonance imaging. Our approach identified two generalizable subtypes characterized by robust and distinct functional connectivity patterns, prominently within the frontoparietal control network and the somatomotor network. These subtypes exhibited pronounced differences in major cognitive and behavioural measures. We further demonstrated the generalizability of these subtypes using data collected from independent study sites. Our data-driven approach provides a novel solution for parsing biological heterogeneity in neurodevelopmental disorders.
Sex differences in the distribution and density of regulatory interneurons in the striatum
Authors: Van Zandt Meghan , Flanagan Deirdre , Pittenger Christopher
Published: March 2024

Dysfunction of the cortico-basal circuitry – including its primary input nucleus, the striatum – contributes to neuropsychiatric disorders, including autism and Tourette Syndrome (TS). These conditions show marked sex differences, occurring more often in males than in females. Regulatory interneurons, including cholinergic interneurons (CINs) and parvalbumin-expressing GABAergic fast spiking interneurons (FSIs), are implicated in human neuropsychiatric disorders such as TS, and ablation of these interneurons produces relevant behavioral pathology in male mice, but not in females. Here we investigate sex differences in the density and distribution of striatal interneurons, using stereological quantification of CINs, FSIs, and somatostatin-expressing (SOM) GABAergic interneurons in the dorsal striatum (caudate-putamen) and the ventral striatum (nucleus accumbens) in male and female mice. Males have a higher density of CINs than females, especially in the dorsal striatum; females have equal distribution between dorsal and ventral striatum. FSIs showed similar effects, with a greater dorsal-ventral density gradient in males than in females. SOM interneurons were denser in the ventral than in the dorsal striatum, with no sex differences. These sex differences in the density and distribution of FSIs and CINs may contribute to sex differences in basal ganglia function, including in the context of psychopathology.
Reduction Midpoint Potential of a Paradigm Light-Oxygen-Voltage Receptor and its Modulation by Methionine Residues
Authors: García de Fuentes Andrés , Möglich Andreas
Published: March 2024

Light-dependent adaptations of organismal physiology, development, and behavior abound in nature and depend on sensory photoreceptors. As one class, light-oxygen-voltage (LOV) photoreceptors harness flavin-nucleotide chromophores to sense blue light. Photon absorption drives the LOV receptor to its signaling state, characterized by a metastable thioadduct between the flavin and a conserved cysteine residue. With this cysteine absent, LOV receptors instead undergo photoreduction to the flavin semiquinone which however can still elicit downstream physiological responses. Irrespective of the cysteine presence, the LOV photochemical response thus entails a formal reduction of the flavin. Against this backdrop, we here investigate the reduction midpoint potentialE0in the paradigm LOV2 domain fromAvena sativaphototropin 1 (AsLOV2), and how it can be deliberately varied. Replacements of residues at different sites near the flavin by methionine consistently increaseE0from its value of around –280 mV by up to 40 mV. Moreover, methionine introduction invariably impairs photoactivation efficiency and thus renders the resultantAsLOV2 variants less light-sensitive. Although individual methionine substitutions also affect the stability of the signaling state and downstream allosteric responses, no clear-cut correlation with the redox properties emerges. With a reduction midpoint potential near –280 mV,AsLOV2 and, by inference, other LOV receptors may be partially reduced inside cells which directly affects their light responsiveness. The targeted modification of the chromophore environment, as presently demonstrated, may mitigate this effect and enables the design of LOV receptors with stratified redox sensitivities.
A Combination of Environmental and Landscape Variables Drive Movement and Habitat use in TwoAnaxyrussp. in the Eastern Coastal Plain
Authors: Ferentinos Alexander M. , Check Courtney E. , Windorf Olivia , Leu Matthias
Published: March 2024

Amphibians are one of the most endangered taxa and are largely threatened by habitat loss. Little work has been conducted on the movement and habitat use of amphibians outside of the breeding season. In this study, we examined the movement patterns of two species of toads inhabiting the Eastern Coastal Plain of Virginia: the Eastern American Toad (Anaxyrus americanus americanus) and the Fowler’s Toad (Anaxyrus fowleri). Based on three years of movement data, we estimated the median migration distance of toads from their breeding location and the propensity for site fidelity, related variation in distance traveled to environmental (e.g., rain, temperature, humidity) and landscape variables (e.g., coniferous forests, distance to trails, terrain ruggedness index), and compared microhabitat selection for daytime refugia between the two species. We found the median distance from breeding grounds to be similar between the two species, 63 m for the Eastern American Toad and 64 m for the Fowler’s Toad, but Eastern American Toads had a greater range of moved distances (3rdquartiles were 122 m for Eastern American and 73 m for Fowler’s Toads). We also found that both species exhibit site fidelity. Distance to trails, proportion of conifer forest, minimum temperature, and 3-day cumulative rainfall related positively with increased movements. Compared to Fowler’s Toads, Eastern American Toads favored woody structures and leaf litter for daytime refugia. Our research provides crucial information for two toad species about the extent of their movements and habitat use during the nonbreeding season. To lessen the decline of amphibians, habitat occupied during the nonbreeding season needs to be included in conservation strategies at biologically relevant distances.
Segmentation aware probabilistic phenotyping of single-cell spatial protein expression data
Authors: Lee Yuju , Chen Edward L. Y. , Chan Darren C. H. , Dinesh Anuroopa , Afiuni-Zadeh Somaieh , Klamann Conor , Selega Alina , Mrkonjic Miralem , Jackson Hartland W. , Campbell Kieran R.
Published: March 2024

Spatial protein expression technologies can map cellular content and organization by simultaneously quantifying the expression of >40 proteins at subcellular resolution within intact tissue sections and cell lines. However, necessary image segmentation to single cells is challenging and error prone, easily confounding the interpretation of cellular phenotypes and cell clusters. To address these limitations, we present STARLING, a novel probabilistic machine learning model designed to quantify cell populations from spatial protein expression data while accounting for segmentation errors. To evaluate performance we developed a comprehensive benchmarking workflow by generating highly multiplexed imaging data of cell line pellet standards with controlled cell content and marker expression and additionally established a novel score to quantify the biological plausibility of discovered cellular phenotypes on patient derived tissue sections. Moreover, we generate spatial expression data of the human tonsil – a densely packed tissue prone to segmentation errors – and demonstrate cellular states captured by STARLING identify known cell types not visible with other methods and enable quantification of intra- and inter- individual heterogeneity. STARLING is available athttps://github.com/camlab-bioml/starling.
Leukemia aggressiveness is driven by chromatin remodeling and expression changes of core regulators
Authors: Bonilla Gracia , Morris Alexander , Kundu Sharmistha , DuCasse Anthony , Kirkpatrick Grace , Jeffries Nathan E. , Chetal Kashish , Yvanovich Emma E. , Milosevic Jelena , Zhao Ting , Xia Jun , Barghout Rana , Scadden David , Mansour Michael K. , Kingston Robert E. , Sykes David B. , Mercier Francois E. , Sadreyev Ruslan I.
Published: March 2024

Molecular mechanisms driving clonal aggressiveness in leukemia are not fully understood. We tracked and analyzed MLL-rearranged leukemic clones independently evolving towards higher aggressiveness. More aggressive subclones lost their growth differential ex vivo but restored it upon secondary transplantation, suggesting molecular memory of aggressiveness. Development of aggressiveness was associated with clone-specific gradual modulation of chromatin states and expression levels across the genome, with a surprising preferential trend of reversing the earlier changes between normal and leukemic progenitors. To focus on the core aggressiveness program, we identified genes with consistent changes of expression and chromatin marks that were maintained in vivo and ex vivo in both clones. Overexpressing selected core genes (Smad1 as aggressiveness driver, Irx5 and Plag1 as suppressors) affected leukemic progenitor growth in the predicted way and had convergent downstream effects on central transcription factors and repressive epigenetic modifiers, suggesting a broader regulatory network of leukemic aggressiveness.
Activation of locus coeruleus noradrenergic neurons rapidly drives homeostatic sleep pressure
Authors: Silverman Daniel , Chen Changwan , Chang Shuang , Bui Lillie , Zhang Yufan , Raghavan Rishi , Jiang Anna , Darmohray Dana , Sima Jiao , Ding Xinlu , Li Bing , Ma Chenyan , Dan Yang
Published: March 2024

Homeostatic sleep regulation is essential for optimizing the amount and timing of sleep, but the underlying mechanism remains unclear. Optogenetic activation of locus coeruleus noradrenergic neurons immediately increased sleep propensity following transient wakefulness. Fiber photometry showed that repeated optogenetic or sensory stimulation caused rapid declines of locus coeruleus calcium activity and noradrenaline release. This suggests that functional fatigue of noradrenergic neurons, which reduces their wake-promoting capacity, contributes to sleep pressure.
Low protein diet protects liver function upon Salmonella infection by metabolic reprogramming of macrophages
Authors: Wojtowicz Edyta E , Hampton Katherine , Moreno-Gonzalez Mar , Utting Charlotte L , Lan Yuxuan , Ruiz Paula , Beasy Gemma , Bone Caitlin , Hellmich Charlotte , Maynard Rebecca , Acton Luke , Telatin Andrea , Kingsley Robert A , Macaulay Iain C , Rushworth Stuart A , Beraza Naiara
Published: March 2024

Background & Aims

Western diets are the underlying cause of metabolic and liver diseases. Recent trend to limit the consumption of protein-rich animal products has become more prominent. This dietary change entails decreased protein consumption; however, it is still unknown how this affects innate immunity. Here, we studied the influence of a low protein diet (LPD) on the liver response to bacterial infection.

Methods

Mice were fed a LPD and exposed toSalmonella entericaserotype Typhimurium infection. Mechanistic studies were donein vitrowhere bone marrow derived macrophages were cultured in a low-aa media to mimicin vivoreduction of protein availability and challenged with bacterial endotoxin.

Results

We found that a LPD protects fromSTyphimurium-induced liver damage. Bulk- and 10xsingle cell-RNA sequencing of liver tissues and isolated immune cells showed reduced activation of myeloid cells in mice fed with LPD afterSTyphimurium infection. Mechanistically, we found reduced activation of the mammalian target of rapamycin (mTOR) pathway whilst increased phagocytosis and activation of autophagy in LPD-programmed macrophages. Dietary restoration of leucine reverted the protective effects of a LPD and restored the damaging effects of Salmonella on liver parenchyma in mice.

Conclusions

Low protein diet protects the liver formSTyphimurium-induced tissue damage via modulating macrophage autophagy and phagocytosis. Our result support the causal role of dietary components on the fitness of the immune system.

SYNOPSIS

Low protein diet protects the liver from Salmonella-mediated liver injury that associates with reduced mTOR activation and increased autophagy in macrophages. Restoration of the mTOR pathway with aminoacid supplementation reverses the protection of a low protein diet from Salmonella-liver damage.
Effects of input image size on the accuracy of fish identification using deep learning
Authors: Iwahara Yuka , Shibata Yasutoki , Manano Masahiro , Nishino Tomoya , Kariya Ryosuke , Yaemori Hiroki
Published: March 2024

The length composition of catches by species is important for stock assessment. However, length measurement is performed manually, jeopardizing the future of continuous measurement because of likely labor shortages. We focused on applying deep learning to estimate length composition by species from images of fish caught for sustainable management. In this study, input image sizes were varied to evaluate the effect of input image size on detection and classification accuracy, as a method for improving the accuracy. The images (43,226 fish of 85 classes) were captured on conveyor belts to sort set-net catches. Fish detection and classification were performed using Mask R-CNN. The effect of input image size on accuracy was examined using three image sizes of 1333×888, 2000×1333, and 2666×1777 pixels, achieving an mAP50-95 of 0.580 or higher. The accuracy improved with increasing image size, attaining a maximum improvement of 4.3% compared to the smallest size. However, increasing the image size too far from the default size may not improve the accuracy of models with fine-tuning. Improvements in accuracy were primarily observed for the species with low accuracy at the smallest image size. Increasing image size would be a useful and simple way to improve accuracy for these species.
Targeting GFPT2 to reinvigorate immunotherapy in EGFR-mutated NSCLC
Authors: Ao Luyao , Jia Wenjing , Gong Qixing , Cui Jiawen , Wang Jun , Yu Ying , Fu Chenghao , Li Haobin , Wei Jia , Wang Ruiqi , Wang Feiyi , Shang Xin , Li Yantong , Fang Shencun , Wang Guangji , Zhou Fang , Liu Jiali
Published: March 2024

In the evolving field of cancer immunotherapy, EGFR-mutated NSCLC presents a significant challenge, demonstrating marked innate resistance to established treatments. An effective method to counter this resistance remains elusive. Through comprehensive genetic and pharmacological analyses across various models, we have identified glutamine fructose-6-phosphate transaminase 2 (GFPT2) as a key facilitator of immune evasion in EGFR-mutated NSCLC. Mechanistically, under EGFR mutation condition, GFPT2 expression, which is typically low in normal tissues, is highly induced via EGFR/IRE1α/Xbp1s signaling axis, leading to a significant increase in intracellular UDP-GlcNAc and consequently, an altered N-glycosylation profile. GFPT2 escalates the expression and glycosylation of PD-L1, PVR and CD276, bolstering their interactions with CD8+T cells, and amplifies CD73 glycosylation, thereby intensifying adenosine-mediated CD8+T cells suppression. These actions collectively reduce tumor cell vulnerability to CD8+T cell-mediated death. Moreover, GFPT2 regulates EGFR glycosylation, which consequentially modulates the EGFR-dependent secretion of CXCL10 and VEGF, thus impeding CD8+T cell infiltration within tumors. We further identified a GFPT2 isoform-specific inhibitor that potentiates PD-1 blockade therapy beyond that of existing strategy, corroborated by results in xenografts and patient-derived organoids. Together, these findings illuminate the promising therapeutic potential of GFPT2 as a metabolic checkpoint, offering an innovative approach to invigorate immunotherapy in NSCLC with EGFR mutations.
A locally administered single cycle influenza vaccine expressing a non-fusogenic stabilised haemagglutinin stimulates strong T-cell and neutralising antibody immunity
Authors: Sadler Holly L. , Rijal Pramila , Tan Tiong Kit , Townsend Alain R. M.
Published: March 2024

Current influenza vaccination approaches protect against specific viral strains, but do not consistently induce broad and long-lasting protection to the diversity of circulating influenza viruses. Single cycle viruses delivered to the respiratory tract may offer a promising solution as they safely express a diverse array of viral antigens by undergoing just one round of cell infection in their host and stimulate broadly protective resident memory T-cell responses in the lung. We have previously developed a vaccine candidate called S-FLU that is limited to a single cycle of infection by inactivation of the hemagglutinin signal sequence and induces a broadly cross-reactive T-cell response and antibodies to neuraminidase, but fails to induce neutralising antibodies to hemagglutinin after intranasal administration.

This study describes the development of CLEARFLU, a derivative of S-FLU that is designed to add a neutralising antibody response to hemagglutinin. In contrast to S-FLU, which does not express a hemagglutinin molecule at the infected cell surface, CLEARFLU viruses express a stabilised non-fusogenic hemagglutinin. They are equally limited to a single cycle of infection, but induce a neutralising antibody response to the expressed hemagglutinin in addition to the cytotoxic T lymphocyte (CTL) responses to internal proteins and antibodies to neuraminidase induced by S-FLU. This represents a notable advantage as CLEARFLU viruses may provide sterile immunity against strain-matched challenge as well as non-sterile protection against a broad range of influenza viruses.

Importance

Influenza is a serious public health concern, causing seasonal epidemics as well as pandemics in people. Influenza can also cause severe agricultural losses due to its circulation in farmed poultry and swine. A major challenge in the control of influenza is the diversity of circulating viruses. Developing vaccines which stimulate immunity to a wide array of influenza viruses is therefore important for protecting human and animal populations from disease and death. In this study, we describe an approach for developing influenza vaccines which trigger immune mechanisms shown to induce broad protection against a diversity of viruses, while also conserving the strong protection against specific strains observed in existing vaccines.
Genotypic and phenotypic characterization of a nosocomial outbreak ofCandida aurisin Spain during five years
Authors: Mulet-Bayona Juan Vicente , Cancino-Muñoz Irving , Salvador-García Carme , Tormo-Palop Nuria , Guna Remedios , González-Candelas Fernando , Gimeno-Cardona Concepción
Published: March 2024

Objectives

The investigation ofCandida aurisoutbreaks is needed to provide insights into its population structure and transmission dynamics. We genotypically and phenotypically characterized aC. aurisnosocomial outbreak occurred at the Consorcio Hospital General Universitario de Valencia (CHGUV), Spain.

Methods

Data and isolates were collected at CHGUV from September 2017 (first case) until September 2021. Thirty-five isolates, one from an environmental source, were selected for whole genome sequencing (WGS), and the genomes were analyzed along with 335 publicly available genomes, assigning them to one of the five major clades. In order to identify polymorphisms associated with drug resistance, we used the fully susceptible GCA_003014415.1 strain as reference sequence. Known mutations in geneserg11andfks1conferring resistance to fluconazole and echinocandins, respectively, were investigated. Isolates were classified into aggregating or non-aggregating.

Results

All isolates belonged to clade III and were from an outbreak with a single origin. They clustered close to 3 publicly available genomes from a hospital from where the first patient was transferred, being the probable origin. The mutation VF125AL in theERG11protein, conferring resistance to fluconazole, was present in all the isolates and one isolate also carried the mutation S639Y in theFKS1protein. All the isolates had a non-aggregating phenotype.

Conclusions

Isolates are genotypically related and phenotypically identical but one with resistance to echinocandins, which seems to indicate that they all belong to an outbreak originated from a single isolate, remaining largely invariable over the years. This result stresses the importance of implementing infection control practices as soon as the first case is detected or when a patient is transferred from a setting with known cases.
α7 nicotinic acetylcholine receptors are necessary for basal forebrain activation to increase expression of the nerve growth factor receptor TrkA
Authors: Kumro Jacob , Tripathi Ashutosh , Terry Alvin V. , Pillai Anilkumar , Blake David T
Published: March 2024

Activation of the basal forebrain leads to increases in the expression of the nerve growth factor receptor, Tropomyosin receptor kinase A (TrkA) and decreases in expression of the beta amyloid cleavage enzyme 1 (BACE1) in the cerebral cortex of both sexes of 5xFAD mice. The studies described in this report were designed to determine if these changes were dependent on acetylcholine receptors. Mice were stimulated unilaterally in the basal forebrain for two weeks. Animals were administered a cholinergic antagonist, or saline, 30 minutes prior to stimulation. Animals administered saline exhibited significant increases in TrkA expression and decreases in BACE1 in the stimulated hemisphere relative to the unstimulated. While both nonselective nicotinic and muscarinic acetylcholine receptor blockade attenuated the BACE1 decline, only the nicotinic receptor antagonism blocked the TrkA increase. Next, we applied selective nicotinic antagonists, and the α7 antagonist blocked the TrkA increases, but the α4β2 antagonist did not. BACE1 declines were not blocked by either intervention. Mice with a loxP conditional knockout of the gene for the α7 nicotinic receptor were also employed in these studies. Animals were either stimulated bilaterally for two weeks, or left unstimulated. With or without stimulation, the expression of TrkA receptors was lower in the cortical region with the α7 nicotinic receptor knockdown. We thus conclude that α7 nicotinic receptor activation is necessary for normal expression of TrkA and increases caused by basal forebrain activation, while BACE1 declines caused by stimulation have dependency on a broader array of receptor subtypes.
Analysis of justification for and gender bias in author order among those contributing equally
Authors: Mattoon Ellie Rose , Miles Maisha , Broderick Nichole A , Casadevall Arturo
Published: March 2024

The practice of designating two or more authors as equal contributors (EC) on a scientific publication is increasingly common as a form of sharing credit. However, EC authors are often unclearly attributed on CVs or citation engines, and it is unclear how research teams determine author order within an EC listing. In response to studies showing that male authors were more likely to be placed first in an EC listing, the American Society of Microbiology (ASM) required that authors explain the reasons for author order beginning in 2020. In this study we analyze data from over 2500 ASM publications to see how this policy affected gender bias and how research teams are making decisions on author order. Data on publications from 2018-2021 show that gender bias was largely nonsignificant both before and after authors were asked by ASM to provide an EC statement. The most likely reasons for EC order included alphabetical order, seniority, and chance, although there were differences for publications from different geographic regions. However, many research teams used unique methods in order selection, highlighting the importance of EC statements to provide clarity for readers, funding agencies, and tenure committees.
Creation and manipulation of bipartite expression transgenes inC. elegansusing phiC31 recombinase
Authors: Nonet Michael L.
Published: March 2024

Bipartite expression systems are widely used in model organisms to express specific gene products in a cell-specific context. They are typically encoded as two independent, unlinked transgenic insertions: a driver and a reporter. Herein, I outline an efficient method namedrecombination-mediated homologexchange (RMHE) that uses genetically encoded phiC31 recombinase to convert driver and reporter transgenes integrated at the same genetic position from atransconfiguration where one component is on each chromosome, to acisconfiguration where the driver and reporter are on the same chromosome. This approach is based upon the development of a set of 3’attBtagged driver lines and 5’attPtagged reporter lines. This genetic based approach leverages both the power of combinatorial re-assortment of drivers and reporters and the simplicity of single locus genetics. I also describe a novel microinjection-based approach namedrecombination-mediated integration (RMI) that utilizes the individualattBdriver andattPreporter lines as landing site for the phiC31 recombinase mediated integration of whole driver and reporter plasmids into the existing reporter and driver lines, respectively. Thus, this work outlines both a novel genetic based and a novel microinjection-based method to create cis-linked driver/reporter pairs. These new tools increase the utility of bipartite systems forC. elegansgenetics by reducing the complexity of reporter system segregation in crosses and thus can greatly simplify the use of bipartite reporter systems during genetic analysis.
Time Cells in the Retrosplenial Cortex
Authors: Subramanian Dev Laxman , Smith David M.
Published: March 2024

The retrosplenial cortex (RSC) is a key component of the brain’s memory systems, with anatomical connections to the hippocampus, anterior thalamus, and entorhinal cortex. This circuit has been implicated in episodic memory and many of these structures have been shown to encode temporal information, which is critical for episodic memory. For example, hippocampal time cells reliably fire during specific segments of time during a delay period. Although RSC lesions are known to disrupt temporal memory, time cells have not been observed there. In the present study, we examined the firing patterns of RSC neurons during the intertrial delay period of two behavioral tasks, a blocked alternation task and a cued T-maze task. For the blocked alternation task, rats were required to approach the east or west arm of a plus maze for reward during different blocks of trials. Because the reward locations were not cued, the rat had to remember the goal location for each trial. In the cued T-maze task, the reward location was explicitly cued with a light and the rats simply had to approach the light for reward, so there was no requirement to hold a memory during the intertrial delay. Time cells were prevalent in the blocked alternation task, and most time cells clearly differentiated the east and west trials. We also found that RSC neurons could exhibit off-response time fields, periods of reliably inhibited firing. Time cells were also observed in the cued T-maze, but they were less prevalent and they did not differentiate left and right trials as well as in the blocked alternation task, suggesting that RSC time cells are sensitive to the memory demands of the task. These results suggest that temporal coding is a prominent feature of RSC firing patterns, consistent with an RSC role in episodic memory.
Synfire Chain Dynamics Unravelling Theta-nested Gamma Oscillations for Balancing Prediction and Dodge in Navigation
Authors: Li Kwan Tung , Wei Yina , Gong Pulin , Yang Dongping
Published: March 2024

Theta-nested gamma oscillations, widely observed in experiments, play a crucial role in navigation, yet their functional roles and the origin of the positive correlation between theta frequency and motion velocity remain unclear. We propose that the object’s survival relies on both prediction and dodge – predicting future events and staying alert to unpredictable ones, the latter of which has seldom been considered in goal-navigation tasks. By building a biologically plausible spiking neuronal network model and reproducing experimental results, we leverage synfire chain properties – length and separation – to elucidate the functional roles of theta-nested gamma oscillations: theta oscillations for self-location awareness, gamma oscillations for predictive capabilities and their coupling for enhancing functionality. The positive correlation between theta frequency and motion velocity is demonstrated to optimally balance representing predictable events for planning and staying alert to unexpected events. Our study offers a new avenue for unravelling the neural mechanisms of navigation.
Inferring stability and persistence in the vaginal microbiome: A stochastic model of ecological dynamics
Authors: Ponciano José M. , Gómez Juan P. , Ravel Jacques , Forney Larry J.
Published: March 2024

The interplay of stochastic and ecological processes that govern the establishment and persistence of host-associated microbial communities is not well understood. Here we illustrate the conceptual and practical advantages of fitting stochastic population dynamics models to multi-species bacterial time series data. We show how the stability properties, fluctuation regimes and persistence probabilities of human vaginal microbial communities can be better understood by explicitly accommodating three sources of variability in ecological stochastic models of multi-species abundances: 1) stochastic biotic and abiotic forces, 2) ecological feedback and 3) sampling error. Rooting our modeling tool in stochastic population dynamics modeling theory was key to apply standardized measures of a community’s reaction to environmental variation that ultimately depends on the nature and intensity of the intra-specific and inter-specific interaction strengths. Using estimates of model parameters, we developed a Risk Prediction Monitoring (RPM) tool that estimates temporal changes in persistence probabilities for any bacterial group of interest. This method mirrors approaches that are often used in conservation biology in which a measure of extinction risks is periodically updated with any change in a population or community. Additionally, we show how to use estimates of interaction strengths and persistence probabilities to formulate hypotheses regarding the molecular mechanisms and genetic composition that underpin different types of interactions. Instead of seeking a definition of “dysbiosis” we propose to translate concepts of theoretical ecology and conservation biology methods into practical approaches for the management of human-associated bacterial communities.
Systematics of the fleshy-fruited Sonerileae (Melastomataceae)
Authors: Quakenbush J. Peter , Chen Luo , Penneys Darin S. , Barkman Todd J. , Liu Ying , Yakandawala Deepthi , Veranso-Libalah Marie-Claire , Kadereit Gudrun
Published: March 2024

With approximately 1080 species, Sonerileae is the second largest tribe in the Melastomataceae. Approximately 40% of Sonerileae species belong to fleshy-fruited genera (Catanthera,Heteroblemma,Kendrickia,Medinilla,Pachycentria, andPlethiandra). Relatively few species, especially of the fleshy-fruited taxa, have been sampled for phylogenetic study. Consequently, there is huge uncertainty resulting in many unanswered questions about their evolutionary history, including the monophyly of the largest genus,Medinilla. In this study, the phylogeny of the fleshy-fruited Sonerileae was reconstructed using 385 nuclear and 81 plastid protein-coding loci recovered from target capture. Our study revealed that the fleshy fruited Sonerileae are polyphyletic and belong to three lineages.Kendrickiais sister to an Afrotropical endemic clade.HeteroblemmaandCatantherabelong to a second clade and are most closely related to somePhyllagathisandDriesseniaspecies.Medinillaforms a third clade, and includesPachycentriaandPlethiandra. WithinMedinilla, fifteen clades are identified and characterized. To makeMedinillamonophyletic, the genus is redefined to includePachycentriaandPlethiandra. Major lineages identified withinMedinillalay the groundwork for an infrageneric classification system. Areas of the phylogenetic tree with high conflict or weak sampling are identified to aid further studies in the tribe.
Multiple resistance factors collectively promote inoculum-dependent dynamic survival during antimicrobial peptide exposure inEnterobacter cloacae
Authors: Murtha Andrew N. , Kazi Misha , Kim Eileen , Rosch Kelly M. , Torres Facundo , Dörr Tobias
Published: March 2024

Antimicrobial peptides (AMPs) are a promising tool with which to fight rising antibiotic resistance. However, pathogenic bacteria are equipped with several AMP defense mechanisms, whose contributions to AMP resistance are often poorly defined. Here, we evaluate the genetic determinants of resistance to an insect AMP, cecropin B, in the opportunistic pathogenEnterobacter cloacae. Single-cell analysis ofE. cloacae’sresponse to cecropin revealed marked heterogeneity in cell survival, phenotypically reminiscent of heteroresistance (the ability of a subpopulation to grow in the presence of supra-MIC concentration of antimicrobial). The magnitude of this response was highly dependent on initialE. cloacaeinoculum. We identified 3 genetic factors which collectively contribute toE. cloacaeresistance in response to the AMP cecropin: The PhoPQ-two-component system, OmpT-mediated proteolytic cleavage of cecropin, and Rcs-mediated membrane stress response. Altogether, this evidence suggests that multiple, independent mechanisms contribute to AMP resistance inE. cloacae.
Neuronal lysosome transfer to oligodendrocyte precursor cells: a novel mechanism of neuron-glia communication and its role in neurodegenerative diseases
Authors: Fang Li-Pao , Lin Ching-Hsin , Medlej Yasser , Zhao Renping , Chang Hsin-Fang , Su Yixun , Zhao Na , Gobbo Davide , Guo Qilin , Wyatt Amanda , Wahl Vanessa , Boehm Ulrich , Huang Wenhui , Lauterbach Marcel A. , Yi Chenju , Niu Jianqin , Scheller Anja , Kirchhoff Frank , Bai Xianshu
Published: March 2024

Oligodendrocyte precursor cells (OPCs) shape brain function through intricate regulatory mechanisms. Here, we observed that OPC processes establish connections with neuronal somata, with smaller lysosomes positioned near these contact sites. Tracking lysosomes demonstrated neuronal lysosomes were attracted to and released at these contact points, eventually becoming incorporated into OPC processes, suggesting a selective, OPC-evoked release of lysosomes from neuronal soma and their ingestion by OPCs, highlighting a unique lysosome-mediated communication between neurons and OPCs. Diminished branching of OPC processes resulted in fewer neuron-OPC contacts, fostering larger lysosome accumulation in neurons, altered neuronal activity and escalated prevalence of senescent neurons during aging. A similar reduction in OPC branching and neuronal lysosome accumulation was evident in an early-stage Alzheimer’s disease mouse model. Together, these findings underscore the pivotal role of OPC processes in modulating neuronal activity through direct somatic contact and lysosome ingestion, presenting a prospective therapeutic avenue for addressing neurodegenerative diseases.
Developing Bioactive Hydrogels Containing Cell-derived Extracellular Matrix: Implications in Drug and Cell-free Bone and Cartilage Repair
Authors: Coyle Ali , Chakraborty Aishik , Huang Jiaqi , Shamiya Yasmeen , Luo Wei , Paul Arghya
Published: March 2024

The prevalence of osteoarthritis has been increasing in aging populations, which has necessitated the use of advanced biomedical treatments. These involve grafts or delivering drug molecules entrapped in scaffolds. However, such treatments often show suboptimal therapeutic effects due to poor half-life and off-target effects of drug molecules. This study aims to overcome these limitations by 3D printing gelatin-based hydrogel scaffolds containing cell-derived extracellular matrix (ECM) as the bioactive therapeutic cargo. Here, pre-osteoblastic and pre-chondrogenic murine cells were differentiatedin vitro, decellularized, and incorporated into methacrylated gelatin (GelMA) solutions to form osteogenic (GelO) and chondrogenic (GelC) hydrogels, respectively. The integration of the bioactive decellularized extracellular matrix (dECM) allows GelO and GelC to induce differentiation in human adipose-derived stem cells (hADSCs) toward osteogenic and chondrogenic lineages. GelO and GelC can be covalently adhered using carbodiimide coupling reaction, forming bioactive osteochondral plug. Moreover, this osteochondral plug can also induce differentiation of hADSCs. To conclude, this ECM-based bioactive hydrogel offers a promising new drug-free and cell-free treatment strategy for bone and cartilage repair, and future osteoarthritis management.
Broadband detection of 18 teeth in an 11-dB squeezing comb
Authors: Wilken Dennis , Junker Jonas , Heurs Michèle
Published: March 2024

Squeezed vacuum is a versatile resource of bipartite entanglement for quantum metrology and information. Optical parametric oscillators generate these states in a frequency comb structure. We show the simultaneous detection of 18 teeth with 11 dB of squeezing each. We built a 1.5-m-long optical resonator to increase the spectral teeth density and significantly increase the detection bandwidth by employing unbalanced homodyne detection instead of balanced. Our approach can be a crucial step in using the scaling potential of high-frequency squeezed states in quantum information.

Published by the American Physical Society
2024
Master formulas for
N
-photon tree level amplitudes in plane wave backgrounds
Authors: Copinger Patrick , Edwards James P. , Ilderton Anton , Rajeev Karthik
Published: March 2024

The presence of strong electromagnetic fields adds huge complexity to QED Feynman diagrams, such that new methods are required to calculate higher-loop and higher-multiplicity scattering amplitudes. Here we use the worldline formalism to present “master formulas” for all tree level amplitudes of two massive particles and an arbitrary number of photons, in a plane wave background, in both scalar and spinor QED. The plane wave is treated without approximation throughout, meaning in particular that our formulas are valid in the strong-field regime of current theoretical and experimental interest. We check our results against literature expressions obtainable at low multiplicity via direct Feynman diagram calculations.

Published by the American Physical Society
2024
Entropy and chirality in sphinx tilings
Authors: Huber Greg , Knecht Craig , Trump Walter , Ziff Robert M.
Published: March 2024

As a toy model of chiral interactions in crowded spaces, we consider sphinx tilings in finite regions of the triangular lattice. The sphinx tiles, hexiamonds composed of six equilateral triangles in the shape of a stylized sphinx, come in left and right enantiomorphs. Regions scaled up from the unit sphinx by an integer factor () require tiles of both chiral forms to produce tilings, including crystalline, quasicrystalline, and fully disordered tilings. For frames up to order 13, we describe methods that permit exact enumeration and computation of partition functions using , , and algorithms. For larger frames, we introduce a Monte Carlo method to sample typical tilings. The key to the latter is the identification of fundamental shapes () that admit multiple tilings and which allow a rejection-free MC simulation.

Published by the American Physical Society
2024
Calculation of screened Coulomb interaction parameters for the charge-disproportionated insulator
CaFeO3
Authors: Merkel Maximilian E. , Ederer Claude
Published: March 2024

We calculate the screened electron-electron interaction for the charge-disproportionated insulator CaFeO3 using the constrained random-phase approximation (cRPA). While in many correlated materials the formation of a Mott-insulating state is driven by a large local Coulomb repulsion, represented by the Hubbard U, several cases have been identified more recently in which U is strongly screened and instead the Hund's interaction J dominates the physics. Our results confirm a strong screening of the local Coulomb repulsion U in CaFeO3, whereas J is much less screened and can thus stabilize a charge-disproportionated insulating state. This is consistent with the case of the rare-earth nickelates, where similar behavior has been demonstrated. In addition, we validate some common assumptions used for parametrizing the local electron-electron interaction in first-principles calculations based on density-functional theory (DFT), we assess the dependence of the interaction on the choice of correlated orbitals, and we discuss the use of the calculated interaction parameters in DFT+U calculations of CaFeO3. Our work also highlights certain limitations for the direct use of cRPA results in DFT-based first-principles calculations, in particular for systems with strong entanglement between the correlated and uncorrelated bands.

Published by the American Physical Society
2024
Experimental realization of quantum walks near synthetic horizons on photonic lattices
Authors: He Runqiu , Zhao Yule , Sheng Chong , Duan Jiachen , Wei Ying , Sun Changwei , Lu Liangliang , Gong Yan-Xiao , Zhu Shining , Liu Hui
Published: March 2024

Entanglement plays crucial roles in quantum optics, providing a prerequisite for these recent unprecedented leaps. Nevertheless, the study of quantum entanglement under the influence of relativity, an important ingredient of quantum optics, still needs to be explored. In parallel, integrated photonic chips, particularly those with the aid of transformation optics, have simulated various relativity phenomena including gravitational lensing and Unruh radiation. However, thus far, studying relativistic quantum optics on this type of platform has not yet occurred. Here, we propose and experimentally realize quantum walks of entangled photons near an emulated Rindler horizon. Remarkably, we find that quantum interference near the synthetic horizon leads to a counterintuitive phenomenon of optical escape. Our study paves the way to a tabletop platform for studying quantum phenomena in various relativistic space-time metrics, and may bring an implication for the test of quantum theory in relativity.

Published by the American Physical Society
2024
Demonstration of spontaneous symmetry breaking in self-modulated ring resonators
Authors: Rah Yoonhyuk , Yu Kyoungsik
Published: March 2024

The demonstration of spontaneous symmetry breaking in a system consisting of a pair of self-modulated ring resonators is performed. In addition, the critical effect of thermal heating induced by optical absorption is studied, where experimental results with numerical calculations reveal that optical absorption contributing as an optical nonlinearity is greatly dominant over the optical Kerr effect under certain operation speeds, depicting a significant impact on the system performance. Our analysis of the operation characteristics outlines important characteristics of self-modulated nonlinear resonators and their function as an optical binary state system.

Published by the American Physical Society
2024
Nonlocal thermoelectric detection of interaction and correlations in edge states
Authors: Braggio Alessandro , Carrega Matteo , Sothmann Björn , Sánchez Rafael
Published: March 2024

Nonlocal thermoelectricity is proposed as a direct probe of interactions, nonthermal states, and the effect of correlations in the nonequilibrium heat transport between 1D quantum channels. In copropagating quantum Hall edge states contacted at different temperatures, the nonlocal thermoelectrical response is expected if the electron-electron interaction mediates the heat exchange directly measuring the interaction strength. Considering the low-energy limit of zero-range interactions, we analytically solve the charge and energy currents of a nonequilibrium interacting system, determining the universal scaling law in terms of an interaction-dependent energy-relaxation length. Further, a setup with two controllable quantum point contacts allows thermoelectricity to monitor the thermalization of an interacting system as well as the fundamental role of cross-correlations in the heat exchange at intermediate length scales.

Published by the American Physical Society
2024