bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination of structural and functional connectivity explains unique variation in specific domains of cognitive function
Authors: Litwińczuk Marta Czime , Trujillo-Barreto Nelson , Muhlert Nils , Cloutman Lauren , Woollams Anna 
Published: October 2021

AbstractThe relationship between structural and functional brain networks has been characterised as complex: the two networks mirror each other and show mutual influence but they also diverge in their organisation. This work explored whether a combination of structural and functional connectivity can improve predictive models of cognitive performance. Principal Component Analysis (PCA) was first applied to cognitive data from the Human Connectome Project to identify components reflecting five cognitive domains: Executive Function, Self-regulation, Language, Encoding and Sequence Processing. A Principal Component Regression (PCR) approach was then used to fit predictive models of each cognitive domain based on structural (SC), functional (FC) or combined structural-functional (CC) connectivity. Self-regulation, Encoding and Sequence Processing were best modelled by FC, whereas Executive Function and Language were best modelled by CC. The present study demonstrates that integrating structural and functional connectivity can help predict cognitive performance, but that the added explanatory value may be (cognitive) domain-specific. Implications of these results for studies of the brain basis of cognition in health and disease are discussed.HighlightsWe assessed the relationship between cognitive domains and structural, functional and combined structural-functional connectivity.We found that Executive Function and Language components were best predicted by combined models of functional and structural connectivity.Self-regulation, Encoding and Sequence Processing were best predicted by functional connectivity alone.Our findings provide insight into separable contributions of functional, structural and combined connectivity to different cognitive domains.
Metastatic profiling of HER2-positive breast cancer cell lines in xenograft models
Authors: Han Yuxuan , Azuma Kazushi , Watanabe Shinya , Semba Kentaro , Nakayama Jun 
Published: October 2021

AbstractMost studies on breast cancer metastasis have been performed using triple-negative breast cancer (TNBC) cells; thus, subtype-dependent metastatic ability of breast cancer is poorly understood. In this research, we performed intravenous injection (IVI) and intra-caudal arterial injections (CAI) using nine human epidermal growth factor receptor-2 (HER2)-positive breast cancer cell lines for evaluating their metastatic abilities. Our results showed that MDA-MB-453, UACC-893, and HCC-202 had strong bone metastatic abilities, whereas HCC-2218 and HCC-1419 did not show bone metastasis. HER2-positive cell lines could hardly metastasize to the lung through IVI. From the genomic analysis, gene signatures were extracted according to the breast cancer subtypes and their metastatic preferences. The UACC-893 cell line was identified as a useful model for the metastasis study of HER2-positive breast cancer. Combined with our previous result on brain proliferation ability, we provide a characteristic metastasis profile of HER2-positive breast cancer cell lines in this study.Statements and DeclarationsFundingThis study was supported by JSPS KAKENHI (grant no. 18K16269: Grant-in-Aid for Early-Career Scientist to J.N.; grant no. 20J01794, Grant-in-Aid for JSPS fellows to J.N.; grant no. 20J23297, Grant-in-Aid for JSPS fellows to Y.H.) and partially supported by the grants for translational research programs from Fukushima Prefecture (S.W. and K.S.).AuthorshipYH and KA performed the in vivo experiments and bioinformatical analyses. SW, and KS interpreted the data. YH, KA, and JN wrote the manuscript. JN conceived and designed the study. All the authors reviewed and edited the manuscript.Competing InterestsThe authors declare that they have no competing interests.Ethical approvalThe animal experiments were conducted under the approval of the ethics committee of Waseda University (2020-A067, 2021-A074).
A multimodal imaging and analysis pipeline for creating a cellular census of the human cerebral cortex
Authors: Costantini Irene , Morgan Leah , Yang Jiarui , Balbastre Yael , Varadarajan Divya , Pesce Luca , Scardigli Marina , Mazzamuto Giacomo , Gavryusev Vladislav , Castelli Filippo Maria , Roffilli Matteo , Silvestri Ludovico , Laffey Jessie , Raia Sophia , Varghese Merina , Wicinski Bridget , Chang Shuaibin , Chen I-Chun Anderson , Wang Hui , Cordero Devani , Vera Matthew , Nolan Jackson , Nestor Kim , Mora Jocelyn , Iglesias Juan Eugenio , Pallares Erendira Garcia , Evancic Kathryn , Augustinack Jean , Fogarty Morgan , Dalca Adrian V. , Frosch Matthew , Magnain Caroline , Frost Robert , van der Kouwe Andre , Chen Shih-Chi , Boas David A. , Pavone Francesco Saverio , Fischl Bruce , Hof Patrick R. 
Published: October 2021

AbstractCells are not uniformly distributed in the human cerebral cortex. Rather, they are arranged in a regional and laminar fashion that span a range of scales. Here we demonstrate an innovative imaging and analysis pipeline to construct a reliable cell census across the human cerebral cortex. Magnetic resonance imaging (MRI) is used to establish a macroscopic reference coordinate system of laminar and cytoarchitectural boundaries. Cell counting is obtained with both traditional immunohistochemistry, to provide a stereological gold-standard, and with a custom-made inverted confocal light-sheet fluorescence microscope (LSFM) for 3D imaging at cellular resolution. Finally, mesoscale optical coherence tomography (OCT) enables the registration of the distorted histological cell typing obtained with LSFM to the MRI-based atlas coordinate system.
Single-cell Stereo-seq enables cell type-specific spatial transcriptome characterization in Arabidopsis leaves
Authors: Xia Keke , Sun Hai-Xi , Li Jie , Li Jiming , Zhao Yu , Chen Ruiying , Liu Guangyu , Chen Zhiyong , Yin Ruilian , Hao Shijie , Wang Jing , Xie Qing , Xu Jiangshan , Li Yuxiang , Chen Ao , Liu Longqi , Yin Ye , Yang Huanming , Wang Jian , Gu Ying , Xu Xun 
Published: October 2021

SummaryUnderstanding the complex functions of plant leaves requires spatially resolved gene expression profiling with single-cell resolution. However, although in situ gene expression profiling technologies have been developed, this goal has not yet been achieved. Here, we present the first in situ single-cell transcriptome profiling in plant, scStereo-seq (single-cell SpaTial Enhanced REsolution Omics-sequencing), which enabled the bona fide single-cell spatial transcriptome of Arabidopsis leaves. We successfully characterized subtle but significant transcriptomic differences between upper and lower epidermal cells. Furthermore, with high-resolution location information, we discovered the cell type-specific spatial gene expression gradients from main vein to leaf edge. By reconstructing those spatial gradients, we show for the first time the distinct spatial developmental trajectories of vascular cells and guard cells. Our findings show the importance of incorporating spatial information for answering complex biological questions in plant, and scStereo-seq offers a powerful single cell spatially resolved transcriptomic strategy for plant biology.
Arnold tongue entrainment reveals dynamical principles of the embryonic segmentation clock
Authors: Sanchez Paul Gerald Layague , Mochulska Victoria , Denis Christian Mauffette , Mönke Gregor , Tomita Takehito , Tsuchida-Straeten Nobuko , Petersen Yvonne , Sonnen Katharina F. , François Paul , Aulehla Alexander 
Published: October 2021

Living systems exhibit an unmatched complexity, due to countless, entangled interactions across scales. Here we aim to understand a complex system, i.e. segmentation timing in mouse embryos, without a reference to these detailed interactions. To this end, we develop a coarse-grained approach, in which theory guides the experimental identification of the segmentation clock entrainment responses.We demonstrate period- and phase-locking of the segmentation clock across a wide range of entrainment parameters, including higher-order coupling. These quantifications allow to derive the phase response curve (PRC) and Arnold tongues of the segmentation clock, revealing its essential dynamical properties. Our results indicate that the somite segmentation clock has characteristics reminiscent of a highly non-linear oscillator close to an infinite period bifurcation and suggests the presence of long-term feedbacks.Combined, this coarse-grained theoretical-experimental approach reveals how we can derive simple, essential features of a highly complex dynamical system, providing precise experimental control over the pace and rhythm of the somite segmentation clock.
hyperTRIBER: a flexible R package for the analysis of differential RNA editing
Authors: Rennie Sarah , Magnusson Daniel Heidar , Andersson Robin 
Published: October 2021

AbstractRNA editing by ADAR (adenosine deaminase acting on RNA) is gaining an increased interest in the field of post-transcriptional regulation. Fused to an RNA-binding protein (RBP) of interest, the catalytic activity of ADAR results in A-to-I RNA edits, whose identification will determine RBP-bound RNA transcripts. However, the computational tools available for their identification and differential RNA editing statistical analysis are limited or too specialised for general-purpose usage. Here we presenthyperTRIBER, a flexible suite of tools, wrapped into a convenient R package, for the detection of differential RNA editing.hyperTRIBERis applicable to complex scenarios and experimental designs, and provides a robust statistical framework allowing for the control for coverage of reads at a given base, the total expression level and other co-variates. We demonstrate the capabilities of our approach on HyperTRIBE RNA-seq data for the detection of bound RNAs by theN6-methyladenosine (m6A) reader protein ECT2 in Arabidopsis roots. We show thathyperTRIBERfinds edits with a high statistical power, even where editing proportions and RNA transcript expression levels are low, together demonstrating its usability and versatility for analysing differential RNA editing.
Pavlovian fear conditioning does not readily occur in rats in naturalistic environments
Authors: Zambetti Peter R. , Schuessler Bryan P. , Lecamp Bryce E. , Shin Andrew , Kim Eun Joo , Kim Jeansok J. 
Published: October 2021

AbstractPavlovian fear conditioning, which offers the advantage of simplicity in both the control of conditioned and unconditioned stimuli (CS, US) presentation and the analysis of specific conditioned and unconditioned responses (CR, UR) in a controlled laboratory setting, has been the standard model in basic and translational fear research. Despite 100 years of experiments, the utility of fear conditioning has not been trans-situationally validated in real-life contexts. We thus investigated whether fear conditioning readily occurs and guides the animal’s future behavior in an ecologically-relevant environment. To do so, Long-Evans rats foraging for food in an open arena were presented with a tone CS paired with electric shock US to their dorsal neck/body that instinctively elicited escape UR to the safe nest. On subsequent test days, the tone-shock paired animals failed to exhibit fear CR to the CS. In contrast, animals that encountered a realistic agent of danger (a looming artificial owl) paired with a shock, simulating a realistic predatory strike, instantly fled to the nest when presented with a tone for the first time. These results illustrate the survival function and precedence of a nonassociative process, rather than associative conditioning, in life-threatening situations that animals are likely to encounter in nature.
Rating enrichment items by group-housed laboratory mice in multiple binary choice tests using an RFID-based tracking system
Authors: Hobbiesiefken Ute , Urmersbach Birk , Jaap Anne , Diederich Kai , Lewejohann Lars 
Published: October 2021

AbstractThere is growing evidence that enrichment of housing conditions of laboratory animals has positive effects on behavior, growth, and health. Laboratory mice spend most of their lives in their housing rather than in experimental apparatus, so improving housing conditions is a first-choice approach to improving their welfare. Despite the increasing popularity of enrichment, little is known about whether it is also perceived as being beneficial from the animal’s point of view. This is especially true due to the fact that ‘enrichment’ has become an umbrella term that encompasses a wide variety of different elements. Therefore, we categorized enrichment items according to their prospective use into the categories ‘structural’, ‘housing’, and ‘foraging’. In multiple binary choice tests we let 12 female C57BL/6J mice chose and rank 5 enrichment items per category. All possible pair combinations of enrichment items within each category were presented counterbalanced for a 46-hour period in a home cage based system consisting of two interconnected cages. A new analyzing method combined the binary decisions and ranked the enrichment items within each category by calculating worth values and consensus errors. Mice ranked the lattice ball (foraging), the rope (structural) and the second plane (structural) in upper positions. No clear preferences were determined for different types of housing enrichment during inactive times (light phase) whereas these objects were actively explored during the dark phase. Here the floorhouse and the paperhouse revealed high worth values. Overall, a high consensus error in ranking positions was observed reflecting strong individual differences in preferences. This highlights the importance of a varied enrichment approach as not all mice prefer the same item at all times. Given the known overall beneficial effects of enrichment, these data will help to provide appropriate enrichment elements to improve animal welfare and refine animal experimentation.
Cell responses to simulated microgravity and hydrodynamic stress can be distinguished by using comparative transcriptomic analysis
Authors: Kouznetsov Nikolai V. 
Published: October 2021

AbstractThe human immune system is compromised in microgravity (MG) conditions during an orbital flight and upon return to Earth. T cells are critical for the immune response and execute their functions via actin mediated immune cell-cell interactions that could be disturbed by MG conditions. Here, we have applied two rotational platforms to simulate MG conditions: fast rotating clinostat (CL) and random positioning machine (RPM) followed by global T cell transcriptome analysis using RNA sequencing. We demonstrate that the T cell transcriptome profile in response to simulated MG treatment was clearly distinguishable from the T cell transcriptome response to hydrodynamic stress (HS) induced by shear forces upon cell movement in cultural medium. Gene expression profiling of genes related to or involved in actin cytoskeleton networks using RT-qPCR confirmed two sets of differentially regulated genes in the T cell response to MG or to HS. Several key genes potentially involved in T cell gravisensing (Fam163b, Dnph1, Trim34, Upk-1b) were identified. A number of candidate biomarker genes of the response to MG (VAV1, VAV2, VAV3, and NFATC2) and of the response to HS (ITGAL, ITGB1, ITGB2, RAC1 and RAC2) could be used to distinguish between these processes on the gene transcription level. Together, MG induces changes in the overall transcriptome of T cells leading to specific shifts in expression of cytoskeletal network genes.
Nuclear alpha-synuclein is present in the human brain and is modified in dementia with Lewy bodies
Authors: Koss David J. , Erskine Daniel , Porter Andrew , Palmoski Pawel , Leite Marta , Attems Johannes , Outeiro Tiago F. 
Published: October 2021

AbstractDementia with Lewy bodies is pathologically defined by the cytoplasmic accumulation of alpha-synuclein within neuronal cells in the brain. Alpha-synuclein is predominately pre-synaptic, but has been reported present in various subcellular compartments in cell and animal models. In particular, nuclear alpha-synuclein is evident in-vitro and in disease models and has been associated with altered DNA integrity, gene transcription, nuclear homeostasis. However, owing to various factors, the presence of alpha-synuclein in the nuclei of human brain cells remains controversial, as does its role in synucleinopathies.Here, we close this gap and provide a unique demonstration confirming the presence of nuclear alpha-synuclein in post-mortem brain tissue obtained from cases of dementia with Lewy bodies as well as from controls via immunohistochemistry, immunoblot, and label-free mass-spectrometry.Discrete intra-nuclear alpha-synuclein puncta reactive against phosphorylated serine 129-alpha-synuclein and pan-alpha-synuclein antibodies were observed in cortical neurons and non-neuronal cells in fixed brain sections and in isolated nuclear preparations from Dementia with Lewy bodies cases and matched controls. Subsequent biochemical analysis of subcellular fractionated tissue confirmed alpha-synuclein as present in a nuclear fraction at levels ~ 10-fold lower than in the cytoplasm. Critically, however, an increase in monomeric nuclear alpha-synuclein phosphorylated as serine 129 was observed in cases of dementia with Lewy bodies alongside higher molecular weight pan- and phosphorylation reactive alpha-synuclein species, consistent with the formation of intranuclear phosphorylated alpha-synuclein oligomers. Furthermore, the presence of nuclear alpha-synuclein was confirmed via label free mass spectrometry, as 6 unique alpha-synuclein derived peptide sequences were identified in nuclear fractions (71.4% sequence coverage).Collectively, our data confirm the presence of nuclear alpha-synuclein in human brain tissue and describe nuclear pathology associated with dementia with Lewy bodies. These findings address a major controversy in the synucleinopathy field by confirming the presence of nuclear alpha-synuclein in autoptic human brain tissue and, for the first time, identify that alpha-synuclein is aggregated into novel and potentially pathological assemblies in the nucleus as part of the disease process associated with dementia with Lewy bodies and thus may contribute to the disease phenotype.
Systematic identification of yeast mutants with increased rates of cell death reveals rapid stochastic necrosis associated with cell division
Authors: Alexandrov Alexander I. , Grosfeld Erika V. , Mitkevich Olga V. , Bidyuk Victoria A. , Nostaeva Arina V. , Kukhtevich Igor V. , Schneider Robert , Shilov Evgeniy S. , Kushnirov Vitaliy V. , Dmitriev Sergey E. , Gladyshev Vadim N. 
Published: October 2021

AbstractCell death plays a major role in development, pathology and aging and can be triggered by various types of acute stimuli which arrest cell growth. However, little is known about chronic cell death in the context of continuing cell division. Here, we performed a genome-wide search for mutants with this type of death in dividing baker’s yeast by assaying staining with phloxine B, which accumulates in dead cells. This screen yielded 83 essential and 43 non-essential gene mutants. Three contrasting types of spatial distribution of dead cells in colonies were observed, which corresponded to gene ontology enrichment for (i) DNA replication and repair, RNA processing, chromatin organization, and nuclear transport; (ii) mitosis and cytokinesis; and (iii) vesicular transport and glycosylation/cell wall homeostasis. To study dynamics of cell death in these mutants, we developed methods for analyzing the death of newborn cells (DON) and cell death in real time using microfluidics-based microscopy. These revealed rapid stochastic necrosis during bud generation or cytokinesis without prior division arrest. Increased death during division was associated with common sensitivity to plasma membrane and cell-wall perturbing agents, and could be mitigated by neutral pH stabilization of the medium. This suggests a common downstream type of cell death caused by a wide range of genetic perturbations.
Fibrosis protein-protein interactions from Google matrix analysis of MetaCore network
Authors: Kotelnikova Ekaterina , Frahm Klaus M. , Shepelyansky Dima L. , Kunduzova Oksana 
Published: October 2021

AbstractProtein-protein interactions is a longstanding challenge in cardiac remodeling processes and heart failure. Here we use the MetaCore network and the Google matrix algorithms for prediction of protein-protein interactions dictating cardiac fibrosis, a primary causes of end-stage heart failure. The developed algorithms allow to identify interactions between key proteins and predict new actors orchestrating fibroblast activation linked to fibrosis in mouse and human tissues. These data hold great promise for uncovering new therapeutic targets to limit myocardial fibrosis.
Immune, endothelial and neuronal network map in human lymph node and spleen
Authors: Currlin Seth , Nick Harry S. , Jorgensen Marda , Nick Jerelyn A. , Brusko Maigan A. , Hakimian Hunter , Penaloza-Aponte Jesus , Rodriguez Natalie , Medina-Serpas Miguel , Yang Mingder , Seifert Robert P. , Kusmartseva Irina , Brusko Todd M. , Otto Kevin , Posgai Amanda L. , Wasserfall Clive H. , Atkinson Mark A. 
Published: October 2021

SummaryThe spleen and lymph node represent important hubs for both innate and adaptive immunity1,2. Herein, we map immune, endothelial, and neuronal cell networks within these tissues from “normal”/non-diseased organ donors, collected through the NIH Human BioMolecular Atlas Program (HuBMAP)3, using highly multiplexed CODEX (CO-Detection by indEXing) imaging and 3D light sheet microscopy of cleared tissues. Building on prior reports4–6, we observed the lymph node subcapsular sinus expressing podoplanin, smooth muscle actin, and LYVE1. In the spleen, LYVE1 was expressed by littoral cells lining venous sinusoids, whereas podoplanin was restricted to arteries and trabeculae. 3D visualization of perivascular innervation revealed a subset of axonal processes expressing choline acetyl transferase in both tissues, in contrast with prior literature on human spleen7. We further report our novel observations regarding the distinct localization of GAP43 and β3-tubulin within the vascular anatomy of both lymph node and spleen, with Coronin-1A+ cells forming a dense cluster around β3-tubulin positive GAP43 low/negative segments of large vessels in spleen. These data provide an unprecedented 2D and 3D visualization of cellular networks within secondary lymphoid tissues, laying the groundwork for future disease-specific and system-wide studies of neural regulation of immunity in human lymphatics.