bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonlinear sensitivity to acoustic context is a stable feature of neuronal responses to complex sounds in auditory cortex of awake mice
Authors: Akritas Marios , Armstrong Alex G. , Lebert Jules M. , Meyer Arne F. , Sahani Maneesh , Linden Jennifer F. 
Published: April 2023

AbstractThe perceptual salience of a sound depends on the acoustic context in which it appears, and can vary on a timescale of milliseconds. At the level of single neurons in the auditory cortex, spectrotemporal tuning for particular sounds is shaped by a similarly fast and systematic nonlinear sensitivity to acoustic context. Does this neuronal context sensitivity “drift” over time in awake animals, or is it a stable feature of sound representation in the auditory cortex? We used chronically implanted tetrode arrays in awake mice to measure the electrophysiological responses of auditory cortical neurons to spectrotemporally complex, rapidly varying sounds across many days. For each neuron in each recording session, we applied the nonlinear-linear “context model” to estimate both a principal (spectrotemporal) receptive ﬁeld and a “contextual gain ﬁeld” describing the neuron’s nonlinear sensitivity to acoustic context. We then quantiﬁed the stability of these ﬁelds within and across days, using spike waveforms to match neurons recorded in multiple sessions. Contextual gain ﬁelds of auditory cortical neurons in awake mice were remarkably stable across many days of recording, and comparable in stability to principal receptive ﬁelds. Interestingly, there were small but signiﬁcant effects of changes in locomotion or pupil size on the ability of the context model to ﬁt temporal fluctuations in the neuronal response.We conclude that both spectrotemporal tuning and nonlinear sensitivity to acoustic context are stable features of neuronal sound representation in the awake auditory cortex, which can be modulated by behavioral state.
Functional divergences of natural variations ofTaNAM-A1controlling leaf senescence initiation during wheat grain filling
Authors: Zhou Longxi , Shen Chuncai , Teng Wan , He Xue , Zhao Xueqiang , Jing Yanfu , Huang Zhixiong , Tong Yiping 
Published: April 2023

SummaryLeaf senescence is an essential physiological process related to grain yield potential and nutritional quality. Green leaf duration (GLD) after anthesis directly reflects the leaf senescence process and exhibits large genotypic differences in common wheat; however, the underlying gene regulatory mechanism is still lacking up to now. Here, we reportTaNAM-A1as the causal gene of major lociqGLD-6Afor GLD during grain filling by map-based cloning. The role of TaNAM-A1 in regulating leaf senescence, spike length, and grain size was proved by transgenic assay and TILLING mutants analyses. Furthermore, the functional divergences amongTaNAM-A1three haplotypes were systematically evaluated. Wheat varieties withTaNAM-A1d(containing two mutations in CDS ofTaNAM-A1) had longer GLD and advantages in yield-related traits than those with the wild typeTaNAM-A1a. All three haplotypes were functional in transactivating the expression of genes involved in macromolecular degradation and mineral nutrient remobilization, with TaNAM-A1a the strongest activity and TaNAM-A1d the weakest. TaNAM-A1 modulates the expression ofTaNAC016-3AandTaNAC-S-7Ato trigger senescence initiation. TaNAC016-3A enhances TaNAM-A1 transcriptional activation ability by protein-protein interaction. Our study provides new insights into fine-tuning the leaf functional period and grain yield formation for wheat breeding under different geographical climatic conditions.
Automated whole-organ histological imaging assisted with ultraviolet-excited sectioning tomography and deep learning
Authors: Kang Lei , Yu Wentao , Zhang Yan , Wong Terence T. W. 
Published: April 2023

AbstractThree-dimensional (3D) histopathology involves the microscopic examination of a specimen, which plays a vital role in studying tissue’s 3D structures and the signs of diseases. However, acquiring high-quality histological images of a whole organ is extremely time-consuming (e.g., several weeks) and laborious, as the organ has to be sectioned into hundreds or thousands of slices for imaging. Besides, the acquired images are required to undergo a complicated image registration process for 3D reconstruction. Here, by incorporating a recently developed vibratome-assisted block-face imaging technique with deep learning, we developed a pipeline termed HistoTRUST that can rapidly and automatically generate subcellular whole organ’s virtual hematoxylin and eosin (H&E) stained histological images which can be reconstructed into 3D by simple image stacking (i.e., without registration). The performance and robustness of HistoTRUST have been successfully validated by imaging all vital mouse organs (brain, liver, kidney, heart, lung, and spleen) within 1–3 days depending on the size. The generated 3D dataset has the same color tune as the traditional H&E stained histological images. Therefore, the virtual H&E stained images can be directly analyzed by pathologists. HistoTRUST has a high potential to serve as a new standard in providing 3D histology for research or clinical applications.
Competitive performance and superior noise robustness of a non-negative deep convolutional spiking network
Authors: Rotermund David , Garcia-Ortiz Alberto , Pawelzik Klaus R. 
Published: April 2023

AbstractNetworks of spiking neurons promise to combine energy efficiency with high performance. However, spiking models that match the performance of current state-of-the-art networks while requiring moderate computational resources are still lacking. Here we present an alternative framework to deep convolutional networks (CNNs), the ”Spike by Spike” network (SbS), together with an efficient backpropagation algorithm. SbS implements networks based on non-negative matrix factorisation (NNMF), but uses discrete events as signals instead of real values. On clean data, the performance of CNNs is matched by both NNMF-based networks and SbS. SbS are found to be most robust when the data is corrupted by noise, specially when this noise was not seen before.
A DRG genetic toolkit reveals molecular, morphological, and functional diversity of somatosensory neuron subtypes
Authors: Qi Lijun , Iskols Michael , Shi David , Reddy Pranav , Walker Christopher , Lezgiyeva Karina , Voisin Tiphaine , Pawlak Mathias , Kuchroo Vijay K. , Chiu Isaac , Ginty David D. , Sharma Nikhil 
Published: April 2023

SummaryMechanical and thermal stimuli acting on the skin are detected by morphologically and physiologically distinct sensory neurons of the dorsal root ganglia (DRG). Achieving a holistic view of how this diverse neuronal population relays sensory information from the skin to the central nervous system (CNS) has been challenging with existing tools. Here, we used transcriptomic datasets of the mouse DRG to guide development and curation of a genetic toolkit to interrogate transcriptionally defined DRG neuron subtypes. Morphological analysis revealed unique cutaneous axon arborization areas and branching patterns of each subtype. Physiological analysis showed that subtypes exhibit distinct thresholds and ranges of responses to mechanical and/or thermal stimuli. The somatosensory neuron toolbox thus enables comprehensive phenotyping of most principal sensory neuron subtypes. Moreover, our findings support a population coding scheme in which the activation thresholds of morphologically and physiologically distinct cutaneous DRG neuron subtypes tile multiple dimensions of stimulus space.
Frontal-midline theta and posterior alpha oscillations index early processing of spatial representations during active navigation
Authors: Du Yu Karen , Liang Mingli , McAvan Andrew S. , Wilson Robert C. , Ekstrom Arne D. 
Published: April 2023

AbstractPrevious research has demonstrated that humans combine multiple sources of spatial information such as self-motion and landmark cues, while navigating through an environment. However, it is unclear whether this involves comparing multiple representations obtained from different sources during navigation (parallel hypothesis) or building a representation first based on self-motion cues and then combining with landmarks later (serial hypothesis). We tested these two hypotheses (parallel vs. serial) in an active navigation task using wireless mobile scalp EEG recordings. Participants walked through an immersive virtual hallway with or without conflicts between self-motion and landmarks (i.e., intersections) and pointed toward the starting position of the hallway. We employed the oscillatory signals recorded during mobile wireless scalp EEG as means of identifying when participant representations based on self-motion vs. landmark cues might have first emerged. We found that path segments, including intersections present early during navigation, were more strongly associated with later pointing error, regardless of when they appeared during encoding. We also found that there was sufficient information contained within the frontal-midline theta and posterior alpha oscillatory signals in the earliest segments of navigation involving intersections to decode condition (i.e., conflicting vs. not conflicting). Together, these findings suggest that intersections play a pivotal role in the early development of spatial representations, suggesting that memory representations for the geometry of walked paths likely develop early during navigation, in support of the parallel hypothesis.
Drug combinations proposed by machine learning on genes/proteins to improve the efficacy of Tecovirimat in the treatment of Monkeypox: A Systematic Review and Network Meta-analysis
Authors: Boush Mahnaz , Kiaei Ali A. , Safaei Danial , Abadijou Sadegh , Salari Nader , Mohammadi Masoud 
Published: April 2023

ABSTRACTBackgroundThe World Health Organization (WHO) describes Monkeypox as a viral zoonosis, or an animal-to-human virus transmission, with symptoms comparable to those of past smallpox patients but clinically less severe. This study’s objective is to assess the results of previous investigations on the best drug combinations for treating Monkeypox.MethodThe pharmacological combinations used to treat monkeypox sickness have been researched in two stages for this systematic review and network meta-analysis. To begin with, a certain machine learning technique is used to extract the medication combinations from the researched articles offered on science databases, including Scopus, PubMed, Web of Science (ISI), Science Direct, Embase, and Google Scholar. Second, the tested medicine combinations will have been proven.ResultsThe results of this study show that the p-value between the proposed drug combination and Monkeypox for scenarios 1 to 5 were 0.108, 0.042, 0.023, 0.018, and 0.015, respectively. Scenarioiis the combination of the firstisuggested drugs for treating Monkeypox. This has led to a 720 percent increase in the proposed drug combination’s efficacy in treating Monkeypox.ConclusionThe suggested drug combination decreases the p-value between MonkeyPox and the genes as potential targets for Monkeypox progression, which leads to an improvement in the treatment of Monkeypox. Therefore, using the right combination of drugs is important in improving the community’s health and reducing per capita treatment costs.
IL-15 priming alters IFN-γ regulation in murine NK cells
Authors: Cimpean Maria , Keppel Molly P. , Gainullina Anastasiia , Fan Changxu , Schedler Nathan C. , Swain Amanda , Kolicheski Ana , Shapiro Hannah , Young Howard A. , Wang Ting , Artyomov Maxim N. , Cooper Megan A. 
Published: April 2023

AbstractNatural killer (NK) effector functions can be triggered by inflammatory cytokines and engagement of activating receptors. NK cell production of IFN-γ, an important immunoregulatory cytokine, exhibits activation-specific IFN-γ regulation. Resting murine NK cells exhibit activation-specific metabolic requirements for IFN-γ production, which are reversed for activating receptor-mediated stimulation following IL-15 priming. While both cytokine and activating receptor stimulation leads to similar IFN-γ protein production, only cytokine stimulation upregulatesIfngtranscript, suggesting that protein production is translationally regulated after receptor stimulation. Based on these differences in IFN-γ regulation, we hypothesized that ex vivo IL-15 priming of murine NK cells allows a switch to IFN-γ transcription upon activating receptor engagement. Transcriptional analysis of primed NK cells compared to naïve cells or cells cultured with low-dose IL-15 demonstrated that primed cells strongly upregulatedIfngtranscript following activating receptor stimulation. This was not due to chromatin accessibility changes in theIfnglocus or changes in ITAM signaling, but was associated with a distinct transcriptional signature induced by ITAM stimulation of primed compared to naïve NK cells. Transcriptional analyses identified a common signature of c-Myc (Myc) targets associated withIfngtranscription. While Myc marked NK cells capable ofIfngtranscription, Myc itself was not required forIfngtranscription using a genetic model of Myc deletion. This work highlights altered regulatory networks in IL-15 primed cells, resulting in distinct gene expression patterns and IFN-γ regulation in response to activating receptor stimulation.
Localized estimation of electromagnetic sources underlying event-related fields using recurrent neural networks
Authors: O’Reilly Jamie A. , Zhu Judy D. , Sowman Paul F. 
Published: April 2023

AbstractObjectiveTo use a recurrent neural network (RNN) to reconstruct neural activity responsible for generating noninvasively measured electromagnetic signals.ApproachOutput weights of an RNN were fixed as the lead field matrix from volumetric source space computed using the boundary element method with co-registered structural magnetic resonance images and magnetoencephalography (MEG). Initially, the network was trained to minimize mean-squared-error loss between its outputs and MEG signals, causing activations in the penultimate layer to converge towards putative neural source activations. Subsequently, L1 regularization was applied to the final hidden layer, and the model was fine-tuned, causing it to favour more focused activations. Estimated source signals were then obtained from the outputs of the last hidden layer. We developed and validated this approach with simulations before applying it to real MEG data, comparing performance with three existing methods: beamformers, minimum-norm estimate, and dynamical statistical parametric mapping.Main resultsThe proposed method had higher output signal-to-noise ratios than the others and comparable correlation and error between estimated and simulated sources. Reconstructed MEG signals were also equal or superior to the other methods in terms of their similarity to ground-truth. When applied to MEG data recorded during an auditory roving oddball experiment, source signals estimated with the RNN were generally consistent with expectations from the literature and qualitatively smoother and more reasonable-looking than estimates from the other methods.SignificanceThis work builds on recent developments of RNNs for modelling event-related neural responses by incorporating biophysical constraints from the forward model, thus taking a significant step towards greater biological realism and introducing the possibility of exploring how input manipulations may influence localized neural activity.
Temporal variability can promote migration between habitats
Authors: Jaggi Harman , Steinsaltz David , Tuljapurkar Shripad 
Published: April 2023

AbstractUnderstanding the conditions that promote the evolution of migration is important in ecology and evolution. When environments are fixed and there is one most favorable site, migration to other sites lowers overall growth rate and is not favored. Here we ask, can environmental variability favor migration when there is one best site on average? Previous work suggests that the answer is yes, but a general and precise answer remained elusive. Here we establish new, rigorous inequalities to show (and use simulations to illustrate) how stochastic growth rate can increase with migration when fitness (dis)advantages fluctuate over time across sites. The effect of migration between sites on the overall stochastic growth rate depends on the difference in expected growth rates and the variance of the fluctuating difference in growth rates. When fluctuations (variance) are large, a population can benefit from bursts of higher growth in sites that are worse on average. Such bursts become more probable as the between-site variance increases. Our results apply to many (≥ 2) sites, and reveal an interplay between the length of paths between sites, the average differences in site-specific growth rates, and the size of fluctuations. Our findings have implications for evolutionary biology as they provide conditions for departure from the reduction principle, and for ecological dynamics: even when there are superior sites in a sea of poor habitats, variability and habitat quality across space determine the importance of migration.
Mechanism of the Covalent Inhibition of Human Transmembrane Protease Serine 2 as an Original Antiviral Strategy
Authors: Spinello Angelo , D’Anna Luisa , Bignon Emmanuelle , Miclot Tom , Grandemange Stéphanie , Terenzi Alessio , Barone Giampaolo , Barbault Florent , Monari Antonio 
Published: April 2023

AbstractThe Transmembrane Protease Serine 2 (TMPRSS2) is a human enzyme which is involved in the maturation and post-translation of different proteins. In addition of being overexpressed in cancer cells, TMPRSS2 plays a further fundamental role in favoring viral infections by allowing the fusion of the virus envelope and the cellular membrane, notably in SARS-CoV-2. In this contribution we resort to multiscale molecular modeling to unravel the structural and dynamical features of TMPRSS2 and its interaction with a model lipid bilayer. Furthermore, we shed light into the mechanism of action of a potential inhibitor (Nafamostat), determining the free-energy profile associated with the inhibition reaction, and showing the facile poisoning of the enzyme. Our study, while providing the first atomistically resolved mechanism of TMPRSS2 inhibition, is also fundamental in furnishing a solid framework for further rational design targeting transmembrane proteases in a host-directed antiviral strategy.TOC GRAPHICS
Mechanistic characterization of aDrosophilamodel of paraneoplastic nephrotic syndrome
Authors: Xu Jun , Liu Ying , Chen Weihang , Shun Li Joshua Shing , Comjean Aram , Hu Yanhui , Perrimon Norbert 
Published: April 2023

AbstractParaneoplastic syndromes occur in cancer patients and originate from dysfunction of organs at a distance from the tumor or its metastasis. A wide range of organs can be affected in paraneoplastic syndromes; however, the pathological mechanisms by which tumors influence host organs are poorly understood. Recent studies in the fly uncovered that tumor secreted factors target host organs, leading to pathological effects. In this study, using aDrosophilagut tumor model, we characterized a mechanism of tumor-induced kidney dysfunction. Specifically, we found that Pvf1, a PDGF/VEGF signaling ligand, secreted by gut tumors activates the PvR/JNK/Jra signaling pathway in the principal cells of the kidney, leading to mis-expression of renal genes and paraneoplastic renal syndrome-like phenotypes. Our study describes a novel mechanism by which gut tumors perturb the function of the kidney, which might be of clinical relevance for the treatment of paraneoplastic syndromes.
State-dependent role of interhemispheric pathway for motor recovery in primates
Authors: Mitsuhashi Masahiro , Yamaguchi Reona , Kawasaki Toshinari , Ueno Satoko , Sun Yiping , Isa Kaoru , Takahashi Jun , Kobayashi Kenta , Onoe Hirotaka , Takahashi Ryosuke , Isa Tadashi 
Published: April 2023

AbstractWhether and how the interhemispheric pathway is involved in post-injury motor recovery is controversial. Unidirectional chemogenetic blockade of the interhemispheric pathway from the contralesional to ipsilesional premotor cortex impaired dexterous hand movements during the early recovery stage after lesioning the lateral corticospinal tract in macaques. Furthermore, electrocorticographical recording showed that the low frequency band activity of the ipsilesional premotor cortex around the movement onset was decreased by the blockade during the early recovery stage, while it was increased by blockade during the intact state and the late recovery stage. These results demonstrate that the action of the interhemispheric pathway changed from inhibition to facilitation, leading to the involvement of the ipsilesional sensorimotor cortex in hand movements during the early recovery stage. The present study offers new insights into the state-dependent role of the interhemispheric pathway and a therapeutic target in the early recovery stage after lesioning of the corticospinal tract.
Male nurses’ adaptation experiences after turnover to community institutions in Korea
Authors: Kim Ja-Sook , Kim Suhyun , Chung Hyang-In Cho 
Published: April 2023

AbstractWe aimed to develop a substantive theory according to the associations between adaptation experience-related factors identified in male nurses after turnover to community institutions. From April through August 2019, data were collected through direct observations and in-depth interviews of 22 male nurse participants who were recruited purposively and analyzed simultaneously with the method proposed by Strauss and Corbin. Furthermore, 29 subcategories were derived from 11 categories, including: (1) leaving the clinical sector and changing jobs, (2) shaking while settling, (3) characteristics of the new job, (4) personal disposition, (5) support system, (6) finding my place, (7) solidifying my place, (8) demonstrating my professional competence, (9) stable settlement in my place, (10) preparing for a better future, and (11) still confused. The core category was identified as “putting down roots in another place for myself.” The verification of this theory in this study’s results indicates a need for research into the evaluation and development of professional development programs and related policies to provide support to male nurses who are pursuing opportunities in community institutions to maintain their nursing identity and further their efforts for developing a nursing specialty. Keywords: nurses, male, turnover, adaptation, grounded theory, qualitative research
Computation of Expected Epidemic Duration
Authors: González Alejandro Alarcón , Pérez Guillermo A. 
Published: April 2023

AbstractThis paper discusses the mean duration of a closed epidemic modeled by a discrete-time Markov chain. We develop a methodology for the efficient computation of the quantity of interest. The Markov chain model in consideration is bivariate, and is formally handled. We derive explicit terms for the probability to transition from one state to another, and prove that the chain is absorbing. The computation of the mean duration is translated to the computation of the expected hitting times to the set of absorbing states. We use the theory of absorbing Markov chains to derive a matrix formulation that gives way to an efficient algorithm to solve for the expected hitting times. This approach is instantiated in the form of a concrete algorithm, which is further optimized by using dynamic programming. Finally, we have implemented the method and tested it against the use of simulations to estimate mean durations.