bluuebunny/crossref_metadata_2025_split huggingface dataset:
SpaDecon: cell-type deconvolution in spatial transcriptomics with semi-supervised learning
Authors: Coleman Kyle , Hu Jian , Schroeder Amelia , Lee Edward B. , Li Mingyao 
Published: February 2023

AbstractSpatially resolved transcriptomics (SRT) has advanced our understanding of the spatial patterns of gene expression, but the lack of single-cell resolution in spatial barcoding-based SRT hinders the inference of specific locations of individual cells. To determine the spatial distribution of cell types in SRT, we present SpaDecon, a semi-supervised learning approach that incorporates gene expression, spatial location, and histology information for cell-type deconvolution. SpaDecon was evaluated through analyses of four real SRT datasets using knowledge of the expected distributions of cell types. Quantitative evaluations were performed for four pseudo-SRT datasets constructed according to benchmark proportions. Using mean squared error and Jensen-Shannon divergence with the benchmark proportions as evaluation criteria, we show that SpaDecon performance surpasses that of published cell-type deconvolution methods. Given the accuracy and computational speed of SpaDecon, we anticipate it will be valuable for SRT data analysis and will facilitate the integration of genomics and digital pathology.
Proposed Methodology for Reducing Bias in Structural MRI Analysis in the Presence of Lesions: Data from a Pediatric Traumatic Brain Injury Cohort
Authors: Griffiths-King Daniel , Shephard Adam , Novak Jan , Catroppa Cathy , Anderson Vicki A. , Wood Amanda G. 
Published: February 2023

AbstractTraumatic brain injury can lead to multiple pathologic features, including brain lesions, which are visible on magnetic resonance imaging (MRI). These resulting heterogenous lesions can present a difficulty for several standard approaches to neuroimaging, resulting in bias and error in subsequent quantitative measurements. Thus, cases presenting with lesions on MRI may be excluded from analyses, biasing samples across the research field. We outline a potential solution to this issue in the case of Freesurfer, a popular neuroimaging tool for surface-based segmentation of brain tissue from structural MRI. The proposed solution involves two-steps, a) Pre-processing: Enantiomorphic Lesion-Filling and b) Post-processing: Lesion Labelling. We applied this methodology to 14 pediatric TBI cases which presented with lesions on T1w MRI. Following qualitative inspection of these cases after implementation of the approach, 8 out of 14 cases were retained as being of sufficient quality. In brief, we have presented here an adapted pipeline for processing structural MRI (sMRI) of patients who have experienced a TBI using the Freesurfer software package. This approach aims to mitigate potential lesion-induced biases that exist beyond the locality of the pathological tissue, even in the contralesioned hemisphere.
Coupling allows robust redox circadian rhythms despite heterogeneity and noise
Authors: del Olmo Marta , Kalashnikov Anton , Schmal Christoph , Kramer Achim , Herzel Hanspeter 
Published: February 2023

AbstractCircadian clocks are endogenous oscillators present in almost all cells that drive daily rhythms in physiology and behavior. There are two mechanisms that have been proposed to explain how circadian rhythms are generated in mammalian cells: through a transcription-translation feedback loop (TTFL) and based on oxidation/reduction reactions, both of which are intrinsically stochastic and heterogeneous at the single cell level. In order to explore the emerging properties of stochastic and heterogeneous redox oscillators, we simplify a recently developed kinetic model of redox oscillations to an amplitude-phase oscillator with ‘twist’ (period-amplitude correlation) and subject to Gaussian noise. We show that noise and heterogeneity alone lead to fast desynchronization, and that coupling between noisy oscillators can establish robust and synchronized rhythms with amplitude expansions and tuning of the period due to twist. Coupling a network of redox oscillators to a simple model of the TTFL also contributes to synchronization, large amplitudes and fine-tuning of the period for appropriate interaction strengths. These results provide insights into how the circadian clock compensates randomness from intracellular sources and highlight the importance of noise, heterogeneity and coupling in the context of circadian oscillators.
Two dimensions of chemical variation of the human microbiome across body sites and in COVID-19 patients
Authors: Dick Jeffrey M. 
Published: February 2023

AbstractA better understanding of dysbiosis is a major goal of human microbiome studies, but more knowledge about chemical effects on microbial communities is needed. Oxidation-reduction and hydration-dehydration reactions are chemical processes that are important for physiological functions and, it is hypothesized here, may also influence the elemental composition of microbial proteins. Chemical metrics of biomolecules relevant to these processes are carbon oxidation state (ZC) and stoichiometric hydration state. I calculated these metrics for protein sequences derived from microbial genomes (multiplied by 16S rRNA-based taxonomic abundances to obtain community reference proteomes), shotgun metagenomes, and metaproteomes. Metaproteomes of gut communities are reduced (i.e., have lowerZC) compared to oral communities. In contrast, community reference proteomes have lowerin gut compared to nasal, skin, and oral communities, and metagenomes for gut and oral communities exhibit the same trend. The chemical differences for metaproteomes may be explained by physiological adjustment of protein expression levels to anaerobic, reducing conditions in the gut, whereas metagenomes and reference proteomes may reflect evolutionary adaptation to dehydrating conditions brought on by intestinal absorption of water. Community reference proteomes, metagenome-assembled genomes (MAGs), and metaproteomes compiled from various studies yield a common trend of more reduced proteins in gut communities of COVID-19 patients compared to controls. These chemical differences imply more reducing conditions in the guts of COVID-19 patients, a finding that contrasts with oxidative conditions that have been previously associated with dysbiosis in inflammatory bowel disease and HIV infection. These results reveal how the human microbiome is shaped by multiple chemical factors over a range of timescales and suggest a new strategy for using multi-omics data to infer changes in gut redox conditions in COVID-19 patients.
Divergent patterns of meiotic double strand breaks and synapsis initiation dynamics suggest an evolutionary shift in the meiosis program between American and Australian marsupials
Authors: Valero-Regalón F. Javier , Solé Mireia , López-Jiménez Pablo , Valerio-de Arana María , Martín-Ruiz Marta , de la Fuente Roberto , Marín-Gual Laia , Renfree Marilyn B. , Shaw Geoff , Berríos Soledad , Fernández-Donoso Raúl , Waters Paul D. , Ruiz-Herrera Aurora , Gómez Rocío , Page Jesús 
Published: February 2023

ABSTRACTIn eutherian mammals, hundreds of programmed DNA double-strand breaks (DSBs) are generated at the onset of meiosis. The DNA damage response is then triggered. Although the dynamics of this response is well studied in eutherian mammals, recent findings have revealed different patterns of DNA damage signaling and repair in marsupial mammals. To better characterize these differences, here we analyzed synapsis and the chromosomal distribution of meiotic DSBs markers in three different marsupial species (Thylamys elegans, Dromiciops gliorides, andMacropus eugenii) that represent South American and Australian Orders. Our results revealed inter-specific differences in the chromosomal distribution of DNA damage and repair proteins, which were associated with differing synapsis patterns. In the American speciesT. elegansandD. gliroides, synapsis progressed exclusively from the chromosomal ends towards interstitial regions. This was accompanied by sparse H2AX phosphorylation, mainly accumulating at chromosomal ends, which appeared conspicuously polarized in abouquetconfiguration at early stages of prophase I. Accordingly, RAD51 and RPA were mainly localized at chromosomal ends throughout prophaseI in both American marsupials, likely resulting in reduced recombination rates at interstitial positions. In sharp contrast, synapsis initiated at both interstitial and distal chromosomal regions in the Australian representativeM. eugenii, γH2AX had a broad nuclear distribution, and RAD51 and RPA foci displayed an even chromosomal distribution. Given the basal evolutionary position ofT. elegans, it is likely that the meiotic features reported in this species represent an ancestral pattern in marsupials and that a shift in the meiotic program occurred after the split ofD. gliroidesand the Australian marsupial clade. Our results open intriguing questions about the regulation and homeostasis of meiotic DSBs in marsupials. The low recombination rates observed at the interstitial chromosomal regions in American marsupials can result in the formation of large linkage groups, thus having an impact in the evolution of their genomes.
Measuring chondrocyte viability of articular cartilage based on label-free two-photon microscopy and deep learning image analysis
Authors: Fan Hongming , Xu Pei , Chen Xun , Li Yang , Hsu Jennifer , Le Michael , Zhang Zhao , Ye Emily , Gao Bruce , Ye Tong 
Published: February 2023

SummaryObjectiveChondrocyte viability (CV) is an important indicator of articular cartilage health. Two-photon excitation autofluorescence (TPAF) and second harmonic generation (SHG) microscopy provide a label-free method for imaging chondrocytes. In this study, we propose an automated assessment of CV using deep learning cell segmentation and counting based on acquired TPAF/SHG images.DesignLabel-free TPAF/SHG images of cartilage samples from rats and porcine were acquired using both commercial and home-built two-photon microscopes, respectively. TPAF/SHG images were merged to form RGB color images with red, green, and blue channels assigned to TPAF (two channels) and SHG signals, respectively. To make the training datasets for the deep learning networks, individual chondrocyte areas on the RGB color images were manually circled and live or dead chondrocytes were validated by using Calcein-AM and Ethidium homodimer-1 dye labeling. We first built a chondrocyte viability network (MCV-Net) using the Mask R-CNN architecture, which could provide individual segmented cellular areas with live or dead status. Wiener deconvolution preprocessing was added before the input of MCV-Net to improve the accuracy of the CV analysis, forming the Wiener deconvolution CV network (wMCV-Net).ResultsTraining (300 images) and test (120 images) datasets were built for rats and porcine cartilage respectively. Wiener deconvolution could improve the Peak Signal-to-Noise Ratio (PSNR) for 30-40%. We demonstrated that both MCV-Net and wMCV-Net significantly improved the accuracy of the CV measurement.ConclusionA custom desktop TPAF/SHG microscope was used in collaboration with deep learning algorithm wMCV-Net based label-free method to assess the CV and get 95% accuracy with both rats and porcine samples.
Chronic morphine induces adaptations in opioid receptor signaling in a thalamo-cortico-striatal circuit that are projection-dependent, sex-specific and regulated by mu opioid receptor phosphorylation
Authors: Jaeckel Elizabeth R. , Arias-Hervert Erwin R. , Perez-Medina Alberto L. , Herrera Yoani N. , Schulz Stefan , Birdsong William T. 
Published: February 2023

ABSTRACTChronic opioid exposure induces tolerance to the pain-relieving effects of opioids but sensitization to some other effects. While the occurrence of these adaptations is well-understood, the underlying cellular mechanisms are less clear. This study aimed to determine how chronic treatment with morphine, a prototypical opioid agonist, induced adaptations to subsequent morphine signaling in different subcellular contexts. Opioids acutely inhibit glutamatergic transmission from medial thalamic (MThal) inputs to the dorsomedial striatum (DMS) and anterior cingulate cortex (ACC) via activity at μ-opioid receptors (MORs). MORs are present in somatic and presynaptic compartments of MThal neurons terminating in both the DMS and ACC. We investigated the effects of chronic morphine treatment on subsequent morphine signaling at MThal-DMS synapses, MThal-ACC synapses, and MThal cell bodies in male and female mice. Surprisingly, chronic morphine treatment increased subsequent morphine inhibition of MThal-DMS synaptic transmission (morphine facilitation), but decreased subsequent morphine inhibition of transmission at MThal-ACC synapses (morphine tolerance) in a sex-specific manner; these adaptations were present in male but not female mice. Additionally, these adaptations were not observed in knockin mice expressing phosphorylation-deficient MORs, suggesting a role of MOR phosphorylation in mediating both facilitation and tolerance to morphine within this circuit. The results of this study suggest that the effects of chronic morphine exposure are not ubiquitous; rather adaptations in MOR function may be determined by multiple factors such as subcellular receptor distribution, influence of local circuitry and sex.
Motor “laziness” constrains fixation selection in real-world tasks
Authors: Burlingham Charlie S. , Sendhilnathan Naveen , Komogortsev Oleg , Murdison T. Scott , Proulx Michael J. 
Published: February 2023

AbstractPeople coordinate their eye, head, and body movements to gather information from a dynamic environment while maximizing reward and minimizing biomechanical and energetic costs. Such natural behavior is not possible in a laboratory setting where the head and body are usually restrained and the tasks and stimuli used often lack ecological validity. Therefore, it’s unclear to what extent principles of fixation selection derived from lab studies, such as inhibition-of-return (IOR), apply in a real-world setting. To address this gap, participants performed nine real-world tasks, including driving, grocery shopping, and building a lego set, while wearing a mobile eye tracker (169 recordings; 26.6 hours). Surprisingly, spatial and temporal IOR were absent in all tasks. Instead, participants most often returned to what they just viewed, and saccade latencies were shorter preceding return than forward saccades. We hypothesized that participants minimize the time their eyes spend in an eccentric position to conserve eye and head motor effort. Correspondingly, we observed center biases in the distributions of fixation location and duration, relative to the head’s orientation. A model that generates scanpaths by randomly sampling these distributions reproduced the spatial and temporal return phenomena seen in the data, including distinct 3-fixation sequences for forward versus return saccades. The amount of the orbit used in each task traded off with fixation duration, as if both incur costs in the same space. Conservation of effort (“laziness”) explains all these behaviors, demonstrating that motor costs shape how people extract and act on relevant visual information from the environment.Significance StatementHumans display remarkably precise yet flexible control of eye and body movements, allowing for a wide range of activities. However, most studies of gaze behavior use the same setup: a head-restrained participant views small images on a computer. Such lab studies find that people avoid looking at the same thing twice, and hesitate in cases when they do. We had people perform nine everyday activities while wearing glasses with embedded eye tracking, and surprisingly found that they did the opposite, often returning to what they just viewed and expediting these “return” eye movements over others. A tendency to keep the eyes centered in the head, which we speculate helps to conserve motor effort, explained these behaviors for all tasks.
Botulinum neurotoxin A modulates the axonal release of pathological tau in hippocampal neurons
Authors: Panzi Chiara , Surana Sunaina , De La-Rocque Samantha , Moretto Edoardo , Lazo Oscar Marcelo , Schiavo Giampietro 
Published: February 2023

AbstractPathological tau aggregates propagate across functionally connected neuronal networks in human neurodegenerative pathologies, such as Alzheimer’s disease. However, the mechanism underlying this process is poorly understood. Several studies have showed that tau release is dependent on neuronal activity and that pathological tau is found in the extracellular space in free form, as well as in the lumen of extracellular vesicles. We recently showed that metabotropic glutamate receptor activity and the SNAP25 integrity modulate the release of pathological tau from human and mouse synaptosomes. Here, we have leveraged botulinum neurotoxins (BoNTs), which impair neurotransmitter release by cleaving specific synaptic SNARE proteins, to dissect molecular mechanisms related to tau release at synapses. In particular, we have tested the effect of botulinum neurotoxin A (BoNT/A) on the synaptic release of tau in primary mouse neurons. Hippocampal neurons were grown in microfluidic chambers and transduced with lentiviruses expressing human tau (hTau). We found that neuronal stimulation significantly increases the release of mutant hTau, whereas wild-type hTau is unaffected. Importantly, BoNT/A blocks mutant hTau release, indicating that this process is modulated by SNAP25 in intact neurons. These results suggest that BoNTs are potent tools to study the spreading of pathological proteins in neurodegenerative diseases and will play a central role in identifying novel molecular targets for the development of therapeutic interventions to treat tauopathies.
Role of maternal, fetal and placental histopathology factors in the pathogenesis of retinopathy of prematurity
Authors: Kaur Tarandeep , Sharma Neha , Jakati Saumya , Bagga Nitasha , Mitra Sanchita , Bhargavi K Katamtreddy , Jalali Subhadra , Kaur Inderjeet 
Published: February 2023

AbstractPurposeTo investigate if maternal, fetal and placental vascular and/or molecular changes predict the risk for retinopathy of prematurity in preterm infants.MethodologyThe postnatal and antenatal data and placental histopathological changes; H&E staining of placental sections and molecular findings; gene expression analysis by qRT-PCR and protein expression by IHC at the maternal-fetal interface were collected from 20 placental samples and categorized into 3 groups: full-term (n=10), preterm without ROP (n=7) and preterm with ROP (n=6).ResultsThe correlation analysis indicated significant association of increased monocytes (p=0.042), fetal growth retardation (p=0.000), apnoeic spell (p=0.033), ventilation (p=0.009), length in hospital stay (p=0.001) and decreased RBC (p=0.02), Hb (p=0.048), PCV (p=0.010), gestational age (p=0.003), birth weight (p=0.000) with increased risk of ROP. Along with these factors, placental weight(p=0.001), diameter (p=0.019), Tenny-Parker changes (p=0.025), alternating area of small and short hyper mature villi (p=0.033) are also found to be significant determinants of the disease. Gene expression analysis revealed significant increase in hypoxia (HIF-1gene expression; p=0.007) and non-significant increase in the pro-inflammatory markerIL-6. The protein expression also showed the significantly increased activation of complement pathway (CFH) and NF- ΚB at maternal-fetal interface.ConclusionsOur preliminary results support the changes in the maternal-fetal factors, placental histopathology and molecular alterations related to hypoxia, inflammation and complement activation at maternal-fetal interface in preterm with ROP placentas. These changes have the potential to predict the risk of the disease but the results are required to be further validated in larger cohort.
Redefinition of archetypal phytoplankton-associated bacteria taxa based on globally distributed dinoflagellates and diatoms
Authors: Yang Xiaoyu , Cai Guanjing , Cai Runlin , Gu Haifeng , Chen Yuerong , Xie Jianmin , Hu Zhong , Wang Hui 
Published: February 2023

AbstractBacteria colonizing in the phycosphere formed by phytoplankton exudates play important roles in marine ecosystems, yet their taxonomy is poorly defined. Here, we customized the analytical approaches for the microalga-attached microbiotas from 110 diatom and 86 dinoflagellate samples to reveal key bacterial players and their ecological significance in the phycosphere. The results demonstrated a co-occurrence of host-specificity and conservation of phytoplankton-associated bacterial communities, defined 8 diatom- and 23 dinoflagellate-affiliated characteristic genera, as well as identifying 14 core genera prevalent with phytoplankton populations. Further classification of these 14 core genera into three tiers showed their distinct ecological features regarding occupancy, connectivity and community-stabilizing, whilst also matching their inherent metabolic properties. Our study redefines the archetypal phytoplankton-associated bacteria taxa more specifically up to the genus level, highlighting the significance of rarely noticed bacteria in the phycosphere, which is invaluable when selecting target bacteria for studying phytoplankton-bacteria interactions.
Judging the difficulty of perceptual decisions
Authors: Löffler Anne , Zylberberg Ariel , Shadlen Michael N. , Wolpert Daniel M. 
Published: February 2023

AbstractDeciding how difficult it is going to be to perform a task allows us to choose between tasks, allocate appropriate resources, and predict future performance. To be useful for planning, difficulty judgments should not require completion of the task. Here we examine the processes underlying difficulty judgments in a perceptual decision making task. Participants viewed two patches of dynamic random dots, which were colored blue or yellow stochastically on each appearance. Stimulus coherence (the probability,pblue, of a dot being blue) varied across trials and patches thus establishing difficulty, |pblue− 0.5|. Participants were asked to indicate for which patch it would be easier to decide the dominant color. Accuracy in difficulty decisions improved with the difference in the stimulus difficulties, whereas the reaction times were not determined solely by this quantity. For example, when the patches shared the same difficulty, reaction times were shorter for easier stimuli. A comparison of several models of difficulty judgment suggested that participants compare the absolute accumulated evidence from each stimulus and terminate their decision when they differed by a set amount. The model predicts that when the dominant color of each stimulus is known, reaction times should depend only on the difference in difficulty, which we confirm empirically. We also show that this model is preferred to one that compares the confidence one would have in making each decision. The results extend evidence accumulation models, used to explain choice, reaction time and confidence to prospective judgments of difficulty.