bluuebunny/crossref_metadata_2025_split huggingface dataset:
Astrocytic TDP-43 dysregulation impairs memory by modulating antiviral pathways and interferon-inducible chemokines
Authors: Licht-Murava Avital , Meadows Samantha M. , Palaguachi Fernando , Song Soomin C. , Bram Yaron , Zhou Constance , Jackvony Stephanie , Schwartz Robert E. , Froemke Robert C. , Orr Adam L. , Orr Anna G. 
Published: September 2022

AbstractTDP-43 pathology is prevalent in dementia but the cell type-specific effects of TDP-43 are not clear and therapeutic strategies to alleviate TDP-43-linked cognitive decline are lacking. We found that patients with Alzheimer’s disease (AD) or frontotemporal dementia (FTD) have aberrant TDP-43 accumulation in hippocampal astrocytes. In mouse models, induction of widespread or hippocampus-targeted accumulation in astrocytic TDP-43 caused progressive memory loss and localized changes in antiviral gene expression. These changes were cell-autonomous and correlated with impaired astrocytic defense against infectious viruses. Among the changes, astrocytes had elevated levels of interferon-inducible chemokines and neurons had elevated levels of the corresponding chemokine receptor CXCR3 in presynaptic terminals. CXCR3 stimulation altered presynaptic function and promoted neuronal hyperexcitability, akin to the effects of astrocytic TDP-43, and blockade of CXCR3 reduced this activity. Ablation of CXCR3 also prevented TDP-43-linked memory loss. Thus, astrocytic TDP-43 dysfunction contributes to cognitive impairment through aberrant chemokine-mediated astrocytic-neuronal interactions.SummaryIn dementia, protein buildup in glia enhances chemokine signaling to synapses and impairs specific aspects of neurocognitive function.
Assessing the utility of death assemblages as reference conditions in a common benthic index (M-AMBI) with simulations
Authors: Smith Jansen A. , Pruden Matthew J. , Handley John C. , Durham Stephen R. , Dietl Gregory P. 
Published: September 2022

ABSTRACTIncorporating paleontological data into the methods and formats already familiar to conservation practitioners may facilitate greater use of paleontological data in conservation practice. Benthic indices (e.g., Multivariate - AZTI Marine Biotic Index; M-AMBI) already incorporate reference conditions and are a good candidate for integration. In simulations of living communities under constant and changing environmental conditions, we evaluate the capacity of death assemblage reference conditions to replicate M-AMBI values when used in place of reference conditions from the final ten generations of the simulation or all five hundred simulated generations.Reference conditions from all death assemblage scenarios successfully replicated correct remediation decisions in the majority of simulation runs with environmental change and stability. Variations in M-AMBI values were due to overestimated richness and diversity in the death assemblages but effects of changes to these parameters varied across scenarios, emphasizing the importance of evaluating multiple metrics. Time averaging was largely beneficial, particularly when environmental change occurred and short-term ecological observations (ten generations) produced incorrect remediation decisions. When the duration of time averaging is known, death assemblages can provide valuable long-term perspectives with the potential to outperform temporally constrained baseline information from monitoring the living community.Supplementary materialAll R code used to produce the simulation, analyze outputs, and create figures is available at: https://doi.org/10.5281/zenodo.6355921. The simulated data is also available at this location. Supplementary figures and analyses referred to in the text are available at the end of this document.
Targeted multi-omic analysis of human skin tissue identifies alterations of conventional and unconventional T cells associated with burn injury
Authors: Labuz Daniel , Lewis Giavonni , Fleming Irma D. , Thompson Callie M. , Zhai Yan , Firpo Matthew A. , Leung Daniel T. 
Published: September 2022

AbstractBurn injuries are a leading cause of unintentional injury, associated with a dysfunctional immune response and an increased risk of infections. Despite this, little is known about the role of T cells in human burn injury. In this study, we compared the activation and function of conventional T cells and unconventional T cell subsets in skin tissue from acute burn (within 7 days from initial injury) burn, late phase burn (beyond 7 days from initial injury), and non-burn patients. We compared T cell functionality by a combination of flow cytometry and a multi-omic single-cell approach with targeted transcriptomics and protein expression. We found a significantly lower proportion of CD8+ T cells in burn skin compared to non-burn skin, with CD4+ T cells making up the bulk of the T cell population. Both conventional and unconventional burn tissue T cells show significantly higher IFN-γ and TNF-α levels after stimulation than non-burn skin T cells. In sorted T cells, clustering showed that burn tissue had significantly higher expression of homing receptors CCR7, S1PR1, and SELL compared to non-burn skin. In unconventional T cells, including mucosal-associated invariant T (MAIT) and γδ T cells, we see significantly higher expression of cytotoxic molecules GZMB, PRF1, and GZMK. Multi-omics analysis of conventional T cells suggests a shift from tissue-resident T cells in non-burn tissue to a circulating T cell phenotype in burn tissue. In conclusion, by examining skin tissue from burn patients, our results suggest that T cells in burn tissue have a pro-inflammatory rather than a homeostatic tissue-resident phenotype, and that unconventional T cells have a higher cytotoxic capacity. Our findings have the potential to inform the development of novel treatment strategies for burns.
An oligogenic architecture underlying ecological and reproductive divergence in sympatric populations
Authors: Briševac Dušica , Peralta Carolina M. , Kaiser Tobias S. 
Published: September 2022

AbstractThe evolutionary trajectories and genetic architectures underlying ecological divergence with gene flow are poorly understood. Sympatric timing types of the intertidal insect Clunio marinus (Diptera) from Roscoff (France) differ in lunar reproductive timing. One type reproduces at full moon, the other at new moon, controlled by a circalunar clock of yet unknown molecular nature. Lunar reproductive timing is a magic trait for a sympatric speciation process, as it is both ecologically relevant and entails assortative mating. Here we show that the difference in reproductive timing is controlled by at least four quantitative trait loci (QTL) on three different chromosomes. They are partly associated with complex inversions, but differentiation of the inversion haplotypes cannot explain the different phenotypes. The most differentiated locus in the entire genome, with QTL support, is the period locus, implying that this gene could not only be involved in circadian timing but also in lunar timing. Our data indicate that magic traits can be based on an oligogenic architecture and can be maintained by selection on several unlinked loci.
Spatial Transcriptomics Using Multiplexed Deterministic Barcoding in Tissue
Authors: Wirth Johannes , Compera Nina , Yin Kelvin , Brood Sophie , Chang Simon , Martinez-Jimenez Celia P. , Meier Matthias 
Published: September 2022

SummaryIn this study, we present a multiplexed version of deterministic barcoding in tissue (xDbit) to acquire spatially resolved transcriptomes of nine tissue sections in parallel. New microfluidic chips were developed to spatially encode mRNAs over a total tissue area of 1.17 cm2 with spots of 50 μm×50 μm. Optimization of the biochemical protocol increased read and gene counts per spot by one order of magnitude compared with previous reports. Furthermore, the introduction of alignment markers allows seamless registration of images and spatial transcriptomic spot coordinates. Together with technological advances, we provide an open-source computational pipeline to transform raw sequencing data from xDbit experiments into the AnnData format. The functionality of xDbit was demonstrated by the acquisition of 18 spatially resolved transcriptomic datasets from five different murine organs, including cerebellum, liver, kidney, spleen, and heart. Factor analysis and deconvolution of xDbit spatial transcriptomes allowed for in-depth characterization of the murine kidney.
Label-free imaging of 3D pluripotent stem cell differentiation dynamics on chip
Authors: Atwell Scott , Waibel Dominik J. E. , Boushehri Sayedali Shetab , Marr Carsten , Meier Matthias 
Published: September 2022

AbstractThe dynamic chemical and architectural microenvironments of 3D stem cell cultures can be controlled by integration into a microfluidic chip. Massive parallelized 3D stem cell cultures for engineering in vitro human cell types require new imaging methods with high time and spatial resolution to fully exploit technological advances in cell culture. Here, we introduce a label-free deep learning method called Bright2Nuc to predict in silico nuclear staining in 3D from bright-field images obtained using traditional confocal microscopy. Bright2Nuc was trained and applied to several hundred 3D human induced pluripotent stem cell cultures differentiating towards definitive endoderm on a microfluidic platform. Combined with existing image analysis tools, Bright2Nuc segmented individual nuclei from bright-field images, quantified their morphological properties, predicted stem cell differentiation state, and tracked the cells over time. Our methods are available in an open-source pipeline that enables researchers to upscale 3D cell phenotyping in stem cell culture.
Incidental Temporal Binding in Rats: A Novel Behavioral Task Relevant to Episodic Memory
Authors: Radostova Dominika , Kuncicka Daniela , Krajcovic Branislav , Hejtmanek Lukas , Petrasek Tomas , Svoboda Jan , Stuchlik Ales , Brozka Hana 
Published: September 2022

ABSTRACTWe designed a behavioral task called One-Trial Trace Escape Reaction (OTTER), in which rats incidentally associate two temporally discontinuous stimuli: a neutral acoustic cue (CS) with an aversive stimulus (US) which occurs two seconds later (CS-2s-US sequence). Rats are first habituated to two similar environmental contexts (A and B), each consisting of an interconnected dark and light chamber. Next, rats experience the CS-2s-US sequence in the dark chamber of one of the contexts (either A or B); the US is terminated immediately after a rat escapes into the light chamber. The CS-2s-US sequence is presented only once to ensure the incidental acquisition of the association. The recall is tested 24 h later when rats are presented with only the CS in the alternate context (B or A), and their behavioral response is observed. Our results show that 59 % of the rats responded to the CS by escaping to the light chamber, although they experienced only one CS-2s-US pairing. The OTTER task offers a flexible high throughput tool to study memory acquired incidentally after a single experience. Incidental acquisition of association between temporally discontinuous events is highly relevant to episodic memory formation.
Characterizing the targets of transcription regulators by aggregating ChIP-seq and perturbation expression data sets
Authors: Morin Alexander , Chu Eric Ching-Pan , Sharma Aman , Adrian-Hamazaki Alex , Pavlidis Paul 
Published: September 2022

AbstractMapping the gene targets of chromatin-associated transcription regulators (TRs) is a major goal of genomics research. ChIP-seq of TRs and experiments that perturb a TR and measure the differential abundance of gene transcripts are a primary means by which direct relationships are tested on a genomic scale. It has been reported that there is poor overlap in the evidence across gene regulation strategies, emphasizing the need for integrating results from multiple experiments. While research consortia interested in gene regulation have produced a valuable trove of high-quality data, there is an even greater volume of TR-specific data throughout the literature. In this study, we demonstrate a workflow for the identification, uniform processing, and aggregation of ChIP-seq and TR perturbation experiments for the ultimate purpose of ranking human and mouse TR-target interactions. Focusing on an initial set of eight regulators (ASCL1, HES1, MECP2, MEF2C, NEUROD1, PAX6, RUNX1, and TCF4), we identified 497 experiments suitable for analysis. We used this corpus to examine data concordance, to identify systematic patterns of the two data types, and to identify putative orthologous interactions between human and mouse. We build upon commonly used strategies to forward a procedure for aggregating and combining these two genomic methodologies, assessing these rankings against independent literature-curated evidence. Beyond a framework extensible to other TRs, our work also provides empirically ranked TR-target listings, as well as transparent experiment-level gene summaries for community use.
A cross-species study of sex chromosome dosage effects on mammalian brain anatomy
Authors: Guma Elisa , Beauchamp Antoine , Liu Siyuan , Levitis Elizabeth , Clasen Liv S. , Torres Erin , Blumenthal Jonathan , Lalonde Francois , Qiu Lily R. , Hrncir Haley , MacKenzie-Graham Allan , Yang Xia , Arnold Arthur P. , Lerch Jason P , Raznahan Armin 
Published: September 2022

SummaryAll eutherian mammals show chromosomal sex determination with contrasting sex chromosome dosages (SCDs) between males (XY) and females (XX). Studies in transgenic mice and humans with sex chromosome trisomy (SCT) have revealed direct SCD effects on regional mammalian brain anatomy, but we lack a formal test for cross-species conservation of these effects. Here, we develop a harmonized framework for comparative structural neuroimaging and apply this to systematically profile SCD effects on regional brain anatomy in both humans and mice by contrasting groups with SCT (XXY and XYY) vs. XY controls. We show that total brain size is substantially altered by SCT in humans (significantly decreased by XXY and increased by XYY), but not in mice. Controlling for global effects reveals robust and spatially convergent effects of XXY and XYY on regional brain volume in humans, but not mice. However, mice do show subtle effects of XXY and XYY on regional volume, although there is not a general spatial convergence in these effects within mice or between species. Notwithstanding this general lack of conservation in SCT effects, we detect several brain regions that show overlapping effects of XXY and XYY both within and between species (cerebellum, parietal, and orbitofrontal cortex) - thereby nominating high priority targets for future translational dissection of SCD effects on the mammalian brain. Our study introduces a generalizable framework for comparative neuroimaging in humans and mice and applies this to achieve a cross-species comparison of SCD effects on the mammalian brain through the lens of SCT.HighlightsParallel structural neuroimaging in humans and mice with sex chromosome trisomiesDivergent X- and Y-chromosome effects on human brain size, but convergent effects on regional anatomyMuted impact of additional X or Y on mouse brain, but subtle regional effects evidentEvidence for conserved cross-species impact of X and Y on fronto-parietal cortices and cerebellum
Hemisynthetic derivatives of the natural alkaloid trilobine are fast-acting antimalarial compounds with sustained activity in multi-drug resistant P. falciparum isolates
Authors: Nardella Flore , Dobrescu Irina , Hassan Haitham , Rodrigues Fabien , Thiberge Sabine , Silva Liliana Mancio , Tafit Ambre , Jallet Corinne , Cadet-Daniel Véronique , Goussin Stéphane , Lorthiois Audrey , Menon Yoann , Molinier Nicolas , Pechalrieu Dany , Long Christophe , Sautel François , Matondo Mariette , Duchateau Magalie , Medard Guillaume , Witkowski Benoit , Scherf Artur , Halby Ludovic , Arimondo Paola B. 
Published: September 2022

AbstractMalaria eradication requires the development of new drugs to combat drug-resistant parasites. The search for new chemical scaffolds that target novel pathways of the human malaria parasite Plasmodium falciparum is of highest priority. We identified bisbenzylisoquinoline alkaloids isolated from Cocculus hirsutus. (trilobine derivatives) as active in the nanomolar range against P. falciparum blood stages. Synthesis of a library of 94 hemi-synthetic derivatives allowed us to identify compound 84 that kills multi-drug resistant clinical isolates in the nanomolar range (median IC50 ranging from 35-88nM). Efforts were made to obtain compounds with significantly improved preclinical properties. Out of those, compound 125 delays the onset of parasitemia in P. berghei infected mice and inhibits P. falciparum transmission stages in vitro (culture assays) and in vivo using membrane feeding assay in the Anopheles stephensi vector. Compound 125 also impairs P. falciparum development in sporozoite-infected hepatocytes, in the low micromolar range. Finally, we used a chemical pull-down strategy to identify potential protein targets of this chemical family. Mass spectrometry analysis identified the parasite interactome with trilobine derivatives, identifying protein partners belonging to metabolic pathways that have not been previously targeted by antimalarial drugs or implicated in drug-resistance mechanisms.
Extending Conway’s Game of Life
Authors: Getz Wayne M , Salter Richard 
Published: September 2022

AbstractWe introduce an extension to Conway’s Game of Life (GoL) that allows more than 2 states (dead/alive; 0/1) to be specified. State 0 is reserved for dead or lifeless cells, and states 1 to n − 1 for cells that are “alive.” Associated with state σ is the value vσ of cells such that v0 = 0, v1 = 1, and for σ = 2, …, n − 1 the cell value vσ is free to be assigned any positive integer value. The value Vij of the Moore neighborhood surrounding cells at array locations (i, j) (i = 1, …, r rows, j = 1, …, c) is the sum of state values of the 8 cells that touch the cell at location (i, j) (4 north, south, east and west side cells and 4 NE, NW, SE, and SW corner cells; except for boundary cells, which have 5 neighbors on an edge or 3 neighbors on a corner, and noting that torroidal arrays have no boundaries). The game is based on a set of rules involving the values Vij that determine whether cells at locations (i, j) in state σ, stay in this state or progress to state σ + 1, σ = 0, …, n − 2, or die (remain dead in the case of dead cells). Specifically, for two non-negative constants 0 ≤ pσL ≤ pσU, if Vij< pσL, Vij ∈ [pσL, pσU] or Vij> pσU then a cell in state σ at location (i, j) respectively stays in state σ, progresses to state σ + 1, or dies. In this paper, we illustrate some of the properties of such games of life with three, four and six states, identifying still-life, oscillator, glider and replicator pattern sequences. We also examine the long term behavior of patterns arising from random and regular (stripped diagonals) starting configurations, as well as set-piece motifs. Most importantly, we introduce two freely downloadable, Numerus runtime alterable model platforms (Numerus RAMPs) that can be used to simulate the three and four state GoLs discussed in this paper, and provide a guide on how these RAMPs can be used to explore the behavior of our GoLs.
General cognitive performance declines with female age and is negatively related to fledging success in a wild bird
Authors: Soravia Camilla , Ashton Benjamin J. , Thornton Alex , Ridley Amanda R. 
Published: September 2022

ABSTRACTIdentifying the causes and fitness consequences of intraspecific variation in cognitive performance is fundamental to understand how cognition evolves. Selection may act on different cognitive traits separately or jointly as part of the general cognitive performance of the individual. To date, few studies have examined simultaneously whether individual cognitive performance covaries across different cognitive tasks, the relative importance of individual and social attributes in determining cognitive variation, and its fitness consequences in the wild. Here, we tested 38 wild southern pied babblers (Turdoides bicolor) on a cognitive test battery targeting associative learning, reversal learning and inhibitory control. We found that a single factor explained 59.5% of the variation in individual cognitive performance across tasks, suggestive of a general cognitive factor. General cognitive performance varied by age and sex; declining with age in females but not males. Older females also tended to produce a higher average number of fledglings per year compared to younger females. Analysing over 10 years of breeding data, we found that individuals with lower general cognitive performance produced more fledglings per year. Collectively, our findings support the existence of a trade-off between cognitive performance and reproductive success in a wild bird.
Multiset partial least squares with rank order of groups for integrating multi-omics data
Authors: Yamamoto Hiroyuki 
Published: September 2022

AbstractAs more multi-omics data such as metabolome, proteome and transcriptome data are acquired, statistical analyses to integrate multi-omics data has been required. Multivariate analysis for integration of multi-omics data has been proposed such as multiset partial least squares (PLS). However, when we want to extract scores about the rank order of groups such as severity of disease as well as difference of groups, we could not always extract scores with rank order of groups by using multiset PLS. Therefore, we proposed multiset PLS with rank order of groups (multiset PLS-ROG) to integrate multiple omics dataset. We visualized multiple omics data by using multiset PLS-ROG in two studies of multi-omics and multi-organ derived metabolome data. After we visualize data and focus on a specific score with phenotype of interest, it is important to select compounds to identify biomarker candidates or make biological inferences. In ordinary principal component analysis (PCA) or PLS, we could select statistical significantly compounds correlated with PC or PLS score by using PC or PLS loadings. However, multiset PLS loading has not been used because its statistical property has not been clarified. Then, we clarified statistical property of multiset PLS and multiset PLS-ROG loading, and we could identify statistically significant compounds by using statistical hypothesis testing. We implemented multiset PLS-ROG to R loadings package, freely available in CRAN.