bluuebunny/crossref_metadata_2025_split huggingface dataset:
A drop-on-demand bioprinting approach to spatially arrange multiple cell types and monitor their cell-cell interactions towards vascularization based on endothelial cells and mesenchymal stem cells
Authors: Weygant Joshua , Koch Fritz , Adam Katrin , Troendle Kevin , Zengerle Roland , Finkenzeller Günter , Kartmann Sabrina , Koltay Peter , Zimmermann Stefan 
Published: July 2022

AbstractSpheroids, organoids, or highly-dense cell-laden droplets are often used as building blocks for bioprinting, but so far little is known about the spatio-temporal cellular interactions post printing. We present a drop-on-demand approach to study the biological interactions of such building blocks in micrometer dimensions. Droplets (containing approximately 700 cells in 10 nl) of multiple cell types are patterned in a 3D hydrogel matrix with a precision of less than 70 μm. It is applied to investigate interactions of cell types relevant for vascularization approaches. We show that a gap of 200 μm between droplets containing endothelial cells (HUVECs) and adipose-derived mesenchymal stem cells (ASCs) leads to decreased sprouting of HUVECs towards ASCs and increased growth from ASCs towards HUVECs. For mixed aggregates containing both cell types, cellular interconnections of ASCs with up to approximately 0.8 millimeter length and inhibition of HUVEC sprouting are observed. When ASCs are differentiated into smooth muscle cells (SMCs), HUVECs display decreased sprouting towards SMCs in separate aggregates, whereas no cellular interconnections or inhibition of HUVEC sprouting are detected for mixed aggregates. These findings demonstrate that this approach acts as a new tool to investigate cell-cell interactions of different cell types in 3D bioprinted constructs.
Misaligned chromosomes that satisfy the spindle assembly checkpoint are a strong predictor of micronuclei formation in dividing cancer cells
Authors: Gomes Ana Margarida , Orr Bernardo , Novais-Cruz Marco , De Sousa Filipe , Ferrás Cristina , Maiato Helder 
Published: July 2022

SummaryChromosome alignment to the spindle equator is a hallmark of mitosis that is thought to promote chromosome segregation fidelity in metazoans. Yet, chromosome alignment is only indirectly supervised by the spindle assembly checkpoint (SAC) as a byproduct of chromosome bi-orientation, and the consequences of defective chromosome alignment remain unclear. Here we investigated how human cells respond to chromosome alignment defects of distinct molecular nature by following the fate of live HeLa cells after RNAi-mediated depletion of 120 proteins previously implicated in chromosome alignment. Surprisingly, in all cases, cells frequently entered anaphase after a delay with chronically misaligned chromosomes. Using depletion of key proteins as prototypes for defective chromosome alignment, we show that chronically misaligned chromosomes often satisfy the SAC and directly missegregate. In-depth analysis of specific molecular perturbations that prevent proper kinetochore-microtubule attachments revealed that chronically misaligned chromosomes that missegregate frequently result in micronuclei. Higher-resolution live-cell imaging indicated that, contrary to most anaphase lagging chromosomes that correct and reintegrate the main nuclei, chronically misaligned chromosomes are a strong predictor of micronuclei formation in a cancer cell model of chromosomal instability, but not in normal near-diploid cells. We provide evidence supporting that intrinsic differences in kinetochore-microtubule attachment stability on misaligned chromosomes account for this distinct outcome. Thus, chronically misaligned chromosomes that satisfy the SAC may represent a previously overlooked mechanism driving chromosomal/genomic instability during cancer cell division, and we unveil genetic conditions predisposing for these events.
Embryoid bodies facilitate comparative analysis of gene expression in humans and chimpanzees across dozens of cell types
Authors: Barr Kenneth A , Rhodes Katherine L , Gilad Yoav 
Published: July 2022

AbstractComparative gene expression studies in apes are fundamentally limited by the challenges associated with sampling across different tissues. Here, we used single-cell RNA-sequencing of embryoid bodies (EBs) to collect transcriptomic data from over 70 cell types in three humans and three chimpanzees. We found hundreds of genes whose regulation is conserved across cell types, as well as genes whose regulation likely evolves under directional selection in one or a handful of cell types. Using EBs from a human-chimpanzee fused cell line, we also inferred the proportion of inter-species regulatory differences due to changes in cis and trans elements between the species. Thus, we present the most comprehensive dataset of comparative gene expression from humans and chimpanzees to date, including a catalog of regulatory mechanisms associated with inter-species differences.
Reassessing the abundance of miRNAs in the human pancreas and rodent cell lines and its implication
Authors: Sun Guihua , Qi Meirigeng , Kim Alexis S. , Lizhar Elizabeth M. , Al-Abdullah Ismail H , Riggs Arthur D. 
Published: July 2022

AbstractmiRNAs are critical for pancreas development and function. However, we found that there are discrepancies of pancreatic miRNA abundance in published datasets. To obtain a more relevant profile that is close to the true profile, we profiled small RNAs from human islets cells, acini, and four rodent pancreatic cell lines routinely used in diabetes and pancreatic research using a bias reduction protocol for small RNA sequencing. In contrast to the previous notion that miR-375-3p is the sole dominant pancreatic miRNA, we found that miR-148a-3p and miR-7-5p were equally abundant in islets.In silicostudies using predicted and validated targets of these three miRNAs revealed that they possibly work in cooperation to modulate cell differentiation in endocrine and exocrine cells. Our results also suggest, compare to the well characterized miR-375, both miR-148a-3p and miR-7-5p may play more critical roles in human pancreas development and function. Moreover, according toin silicopredicted targets, we found that miR-375-3p had a much broader target spectrum by targeting the coding sequence and the 5’ untranslated region rather than the conventional 3’ untranslated region, suggesting additional unexplored roles for miR-375-3p beyond pancreas. Our study provides a valuable resource for studying miRNAs in pancreas.
PerturbNet predicts single-cell responses to unseen chemical and genetic perturbations
Authors: Yu Hengshi , Welch Joshua D. 
Published: July 2022

AbstractSmall molecule treatment and gene knockout or overexpression induce complex changes in the molecular states of cells, and the space of possible perturbations is too large to measure exhaustively. We present PerturbNet, a deep generative model for predicting the distribution of cell states induced by unseen chemical or genetic perturbations. Our key innovation is to use high-throughput perturbation response data such as Perturb-Seq to learn a continuous mapping between the space of possible perturbations and the space of possible cell states.Using Sci-Plex and LINCS datasets, PerturbNet can accurately predict the distribution of gene expression changes induced by unseen small molecules given only their chemical structures. PerturbNet also accurately predicts gene expression changes induced by shRNA, CRISPRi, or CRISPRa perturbations using a perturbation network trained on gene functional annotations. Furthermore, self-supervised sequence embeddings allow PerturbNet to predict gene expression changes induced by missense mutations. We also use PerturbNet to attribute cell state shifts to specific perturbation features, including atoms and functional gene annotations. Finally, we leverage PerturbNet to design perturbations that achieve a desired cell state distribution. PerturbNet holds great promise for understanding perturbation responses and ultimately designing novel chemical and genetic interventions.
Brain-implanted conductors amplify radiofrequency fields in rodents: advantages and risks
Authors: Vöröslakos Mihály , Yaghmazadeh Omid , Alon Leeor , Sodickson Daniel K. , Buzsáki György 
Published: July 2022

AbstractOver the past few decades, daily exposure to radiofrequency (RF) fields has been increasing due to the rapid development of wireless and medical imaging technologies. Under extreme circumstances, exposure to very strong RF energy can lead to heating of body tissue, even resulting in tissue injury. The presence of implanted devices, moreover, can amplify RF effects on surrounding tissue. Therefore, it is important to understand the interactions of RF fields with tissue in the presence of implants, in order to establish appropriate wireless safety protocols, and also to extend the benefits of medical imaging to increasing numbers of people with implanted medical devices. This study explored the neurological effects of RF exposure in rodents implanted with neuronal recording electrodes. We exposed freely moving and anesthetized rats and mice to 950 MHz RF energy while monitoring their brain activity, temperature, and behavior. We found that RF exposure could induce fast onset firing of single neurons without heat injury. In addition, brain implants enhanced the effect of RF stimulation resulting in reversible behavioral changes. Using an optical temperature measurement system, we found greater than tenfold increase in brain temperature in the vicinity of the implant. On the one hand, our results underline the importance of careful safety assessment for brain implanted devices, but on the other hand, we also show that metal implants may be used for neurostimulation if brain temperature can be kept within safe limits.
Pre-Germinal Center Interactions with T Cells are Natural Checkpoints to Limit Autoimmune B Cell Responses
Authors: Parham Kate A , Tan Xiu Xia Sherry , Morelli Daniel M , Chowdhury Lika , Craig Heather C , Kerfoot Steven M 
Published: July 2022

AbstractInteractions with antigen-specific T cells drive B cells activation and fate choices that ultimately determine the quality of high-affinity antibody responses. As such, thse interactions, and especially the long-lived interactions that occur prior to germinal center formation, may be important checkpoints to regulate undesirable responses. We directly observed interactions between T and B cells responding to the self-antigen Myelin Oligodendrocyte Glycoprotein (MOG) and found that they are of lower quality compared to interactions between cells responding to the model foreign antigen NP-ovalbumin (NP-OVA). This was associated with reduced expression of molecules that facilitate these interactions on the B cells but not on T cells. B cell expression of these molecules was not dictated by the T cell partner, nor could the relative lack of expression on MOG-sp. B cells be reversed by a multivalent antigen. Instead, MOG-sp. B cells were inherently less responsive to B cell Receptor stimulation than MOG-non-sp. cells. However, the phenotype of MOG-sp. B cells was not consistent with previous descriptions of autoimmune B cells that had been tolerized via regular exposure to systemically-expressed self-antigen. This suggests that alternate anergy pathways may exist to limit B cell responses to tissue-restricted self-antigens.
Single nuclei analyses reveal transcriptional profiles and marker genes for diverse supraspinal populations
Authors: Beine Zachary , Wang Zimei , Tsoulfas Pantelis , Blackmore Murray G. 
Published: July 2022

ABSTRACTThe mammalian brain contains numerous neurons distributed across forebrain, midbrain, and hindbrain that project axons to the lower spinal cord and work in concert to control movement and achieve homeostasis. Extensive work has mapped the anatomical location of supraspinal cell types and continues to establish specific physiological functions. The patterns of gene expression that typify and distinguish these disparate populations, however, are mostly unknown. Here we combined retrograde labeling of supraspinal cell nuclei with fluorescence activated nuclei sorting and single nuclei RNA sequencing analyses to transcriptionally profile neurons that project axons from the mouse brain to lumbar spinal cord. We identified fourteen transcriptionally distinct cell types and used a combination of established and newly identified marker genes to assign an anatomical location to each. To validate the putative marker genes, we visualized selected transcripts and confirmed selective expression within lumbar-projecting neurons in discrete supraspinal regions. Finally, we illustrate the potential utility of these data by examining the expression of transcription factors that distinguish different supraspinal cell types and by surveying the expression of receptors for growth and guidance cues that may be present in the spinal cord. Collectively these data establish transcriptional differences between anatomically defined supraspinal populations, identify a new set of marker genes of use in future experiments, and provide insight into potential differences in cellular and physiological activity across the supraspinal connectome.SIGNIFICANCE STATEMENTThe brain communicates with the body through a wide variety of neuronal populations with distinct functions and differential sensitivity to damage and disease. We have employed single nuclei RNA sequencing technology to distinguish patterns of gene expression within a diverse set of neurons that project axons from the mouse brain to the lumbar spinal cord. The results reveal transcriptional differences between populations previously defined on the basis of anatomy, provide new marker genes to facilitate rapid identification of cell type in future work, and suggest distinct responsiveness of different supraspinal populations to external growth and guidance cues.
Drosophila cap-binding protein eiF4EHP promotes translation via a 3’UTR-dependent mechanism under hypoxia and contributes to fruit fly adaptation to oxygen variations
Authors: Liang Manfei , Hody Clara , Yammine Vanessa , Soin Romuald , Sun Yuqiu , Lin Xing , Tian Xiaoying , Meurs Romane , Perdrau Camille , Delacourt Nadège , Andris Fabienne , Conrard Louise , Kruys Véronique , Gueydan Cyril 
Published: July 2022

AbstractHypoxia induces profound modifications in gene expression program enabling eukaryotic cells to adapt to lowered ATP supply resulting from the blockade of oxidative phosphorylation. One major consequence of oxygen deprivation is the massive repression of protein synthesis, leaving a limited set of mRNAs to be translated. D. melanogaster is strongly resistant to oxygen fluctuations, however the mechanisms allowing specific mRNA to be translated in hypoxia are still unknown. Here, we show that Ldh mRNA encoding lactate dehydrogenase is highly translated in hypoxia by a mechanism involving its 3’ untranslated region. Furthermore, we identified the cap-binding protein eiF4HP as a main factor involved in 3’UTR-dependent translation under hypoxia. In accordance with this observation, we show that eiF4EHP is necessary for Drosophila development under low oxygen concentrations and contributes to Drosophila mobility after hypoxic challenge. Altogether, our data bring new insight into mechanisms contributing to Drosophila adaptation to oxygen variations.
Novel methods to identify TCM constitution of hyperlipidemic patients and predict atherosclerotic diseases
Authors: Zeng Liling , Zhang Qixin , Sun Chen , Huang Li , Yuan Jiamin , Tan Fei , Wu Yanhua , Yang Zhimin , Xu Fuping 
Published: July 2022

AbstractHyperlipidemia can accelerate the progression of atherosclerosis, ultimately leading to cardiovascular disease. TCM constitution has been widely used as an indicator of health status and susceptibility to diseases. However, there still lack of objective, credible ways to identify TCM constitution of hyperlipidemic patients, and the connection between TCM constitution and atherosclerotic diseases in individuals with hyperlipidemia is unknown. This study aims to identify differentially expressed microRNAs (DEMs) as biomarkers of the TCM constitution of hyperlipidemic patients and explore the potential connection between TCM constitution and atherosclerotic diseases. In the study, we randomly recruited 10 hyperlipidemic patients with asthenic constitution (HAC), 10 hyperlipidemic patients with strong constitution (HSC), and 10 hyperlipidemic patients with normal constitution (HNC) and collected serum miRNA. After analyzing the miRNA expression profiles, we found that hsa-miR-338-3p may be a potential blood biomarker for the identification of the TCM constitution of hyperlipidemic patients. Moreover, the HSC classification is likely a cardiocerebrovascular disease predisposition and is closely related to the inflammatory process and glucose and lipid metabolism, which contribute to the development of atherosclerotic diseases.
Biopriming of broad bean seeds with entomopathogenic fungusMetarhizium robertsiidoes not affect invertebrate communities of the agroecosystem
Authors: Lyubechanskii I.I. , Novgorodova T.A. , Panina Y. , Kryukov V.V. , Sorokina V.S. , Sadokhina T.A. , Bakshaev D.Ju. , Dudko R.Ju. , Gurina A.A. , Glupov V.V. 
Published: July 2022

AbstractBiopriming, or treatment of seeds with beneficial microorganisms such as beneficial fungi, can be a promising strategy in agricultural cultivation. However, the effects of such treatment on non-target organisms living in the soil and on plants have not been sufficiently studied, and it is not known very well whether such treatment would alter invertebrate communities (e.g., harm them). Here, we addressed the effect of treating broad bean seeds (Vicia fabaL.) with the conidia of entomopathogenic ascomyceteMetarhizium robertsiion the diversity and abundance of invertebrate communities in the agroecosystem in the south part of West Siberia in 2019 and 2020. We have analyzed the effect both on the general invertebrate communities as well as on the main pests of beans. In the case of bean pests, we assessed the rate of plant infestation by aphids (Hemiptera: Aphididae) and the degree of leaf damage by leafminer fliesLiriomyza bryoniae(Diptera: Agromyzidae). In most cases, the treatment did not lead to significant changes in the total abundance of the soil invertebrates and herbivores or the abundance of predominant taxa (Coleoptera: Carabidae, Staphylinidae, Elateridae, Scarabaeidae, Curculionidae; Hemiptera: Miridae, Cicadellidae, Aphididae; larvae of Diptera). A positive effect of treatment on population density of the soil mesofauna was noted for Diptera larvae in June 2019. Regarding aphids and leafminer flies, no significant effect was observed in terms of the proportion of plants with aphids and the density of aphid colonies on individual plants throughout the season, and no significant influence was found on the proportion of plant leaves damaged by leafminer flyLiriomyza bryoniaelarvae. In summary, in Western Siberia, the treatment of broad bean seeds withM. robertsiidid not significantly affect non-target arthropods common for bean fields as well as the main pests of beans, namely aphids and miner flies.
The Universal Endurance Microbiome?
Authors: Olbricht Hope , Twadell Kaitlyn , Sandel Brody , Stephens Craig , Whittall Justen 
Published: July 2022

AbstractBillions of microbial cells sculpt the gut ecosystem, playing essential roles in human physiology. Since endurance athletes’ performance is often physiology-limited, understanding the composition and interactions within these athletes’ gut microbiomes could lead to improved performance. Previous studies describe differences in the relative abundance of bacterial taxa when comparing athletes versus controls or athletes before and after an endurance event, suggesting the existence of an “endurance microbiome”. However, there are inconsistencies among studies in which taxa correlate with extended physical exertion. Although these studies employed similar barcoding methods, variation in downstream bioinformatic analyses makes it difficult to determine whether inconsistencies are due to methodological differences or biological factors. Herein, we created a metagenomic bioinformatics workflow reanalyzing four 16S rDNA sequence datasets reflecting endurance athletes’ gut microbiomes, looking at alpha diversity, changes in relative abundance of gut microbiome genera, changes in pairwise correlations between bacterial genera and compared bacterial association networks. There were no significant differences in alpha diversity between any of the four treatment group comparisons. For relative abundance, there were no consistent differences in all four datasets, and only two genera were significantly different in 50% of the datasets. Although many genera showed changes in pairwise correlations in endurance microbiome samples from individual datasets, none were consistent across datasets. Collectively, these results suggest that either there is no universal endurance microbiome, or that it remains elusive even after controlling for the bioinformatic workflow and statistical analyses. Using this data, a power analysis indicates that sample sizes 150- to 800-fold larger than these published studies would be necessary to detect a 10% difference in relative abundance. Furthermore, 10- to 20-fold more samples will be needed to control for the multitude of covariates (genetic, metabolic, dietary, environmental, and pharmacological factors) that mold the gut microbiome of athletes and non-athletes alike.I’m going to work so that it’s a pure guts race at the end, and if it is, I am the only one who can win it. - Steve Prefontaine
Hydrothermal Vent Species Assemblage Networks Identify Regional Connectivity Patterns in the Northwest Pacific
Authors: Brunner Otis , Chen Chong , Giguere Thomas , Kawagucci Shinsuke , Tunnicliffe Verena , Watanabe Hiromi , Mitarai Satoshi 
Published: July 2022

AbstractThe distribution of species among spatially isolated habitat patches supports regional biodiversity and stability, so understanding the underlying processes and structure is a key target of conservation. Although multivariate statistics can infer the connectivity processes driving species distribution, such as dispersal and habitat suitability, they rarely explore structure. Methods from graph theory, applied to distribution data, give insights into both connectivity pathways and processes by intuitively formatting the data as a network of habitat patches. We apply these methods to empirical data from the hydrothermal vent habitats of the Northwest Pacific. Hydrothermal vents are ‘oases’ of biological productivity and endemicity on the seafloor that are imminently threatened by anthropogenic disturbances with unknown consequences to biodiversity. Here, we describe the structure of hydrothermal vent species assemblage networks, how local and regional parameters affect their structure, and the implications this has for conservation. Two complementary networks were formed from an extensive species assemblage dataset: a bipartite network of species nodes linked to vent site nodes at which they are present, and a similarity network of vent site nodes linked by weighted edges based on their pairwise assemblage similarity. Using these networks, we assessed the role of individual vent sites in linking their network and identified biogeographic sub-regions. The three sub-regions and two outlying sites are separated by their spatial arrangement and local environmental filters. Both networks detected vent sites that play a disproportionately important role in regional pathways, while the bipartite network also identified key vent sites maintaining the distinct species assemblages of their sub-regions. These regional connectivity pathways provide insights into historical colonisation routes, while sub-regional connectivity pathways are of value when selecting sites for conservation and/or estimating the multi-vent impacts from proposed deep-sea mining.