bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organoid-based human stomach micro-physiological system to recapitulate the dynamic mucosal defense mechanism
Authors: Jeong Hye-Jin , Park Ji-Hyeon , Kang Joo H. , Kong Seong-Ho , Park Tae-Eun 
Published: March 2022

AbstractSeveral stomach diseases are attributed to the dysregulation of physiological function of gastric mucosal barrier by pathogens. Gastric organoids are a promising tool to develop treatment strategies for gastric infections. However, their functional features of in vivo gastric mucosal barrier and host-microbe interactions are limited due to the lack of physiological stimuli. Herein, we describe the first human stomach micro-physiological system (hsMPS) with physiologically relevant gastric mucosal defense system based on the combination of organoid and MPS technology. A fluid flow enhanced epithelial-mesenchymal interaction in the hsMPS enables functional maturation of gastric epithelial cells, which allows for the recreation of mesh-like mucus layer containing high level of mucus protective peptides and well-developed epithelial junctional complexes. Furthermore, gastroprotection mechanisms against Helicobacter pylori are successfully demonstrated in our system. Therefore, hsMPS represents a new in vitro tool for research where gastric mucosal defense mechanism is pivotal for developing therapeutic strategies.
Partial gene suppression improves identification of cancer vulnerabilities when CRISPR-Cas9 knockout is pan-lethal
Authors: Krill-Burger J. Michael , Dempster Joshua M. , Borah Ashir A. , Paolella Brenton R. , Root David E. , Golub Todd R. , Boehm Jesse S. , Hahn William C. , McFarland James M. , Vazquez Francisca , Tsherniak Aviad 
Published: March 2022

AbstractHundreds of genome-wide loss-of-function screens have been performed, as part of efforts such as The Cancer Dependency Map, to create a catalog of genetic dependencies in a diverse set of cancer contexts. In recent years, large-scale screening efforts have shifted perturbation technology from RNAi to CRISPR-Cas9, due to the superior efficacy and specificity of CRISPR-Cas9-mediated approaches. However, questions remain about the extent to which partial suppression of gene targets could result in selective dependency across cell lines, potentially revealing a larger set of targetable cancer vulnerabilities than can be identified using CRISPR knockout alone. Here, we use CRISPR-Cas9 and RNAi screening data for more than 400 shared cell lines to represent knockout and partial suppression genetic perturbation modalities and evaluate the utility of each for therapeutic target discovery and the inference of gene function. We find that CRISPR screens identify more dependencies, and yield more accurate predictive models and co-dependency relationships overall. However, RNAi outperforms CRISPR in identifying associations (omics, drug, co-dependencies) with genes that are common dependencies for most cell lines (pan-dependencies). As pan-dependencies occur frequently in the CRISPR dataset (~2,000 genes), using results from both RNAi and CRISPR analyses facilitates the discovery of predictive models and associated co-dependencies for a wider range of gene targets than could be detected using either dataset alone. These findings can aid in the interpretation of contrasting results obtained from CRISPR and RNAi screens and reinforce the importance of partial gene suppression methods in building a cancer dependency map.
An initial assessment of the sustainability of waterbird harvest in the United Kingdom
Authors: Ellis Matthew B. , Cameron Tom C. 
Published: March 2022

AbstractThere is a need to assess the sustainability of wild bird harvest in the United
Kingdom (UK), and more widely, across Europe. Yet data on populations and harvest sizes are limited.We used a Demographic Invariant Method (DIM) to estimate Potential Excess Growth (PEG) for populations of UK wintering waterbirds and calculated a Sustainable Harvest Index (SHI) for each. We compared this with population trends and conservation classifications (e.g. Birds of Conservation Concern; BoCC) to assess the sustainability of harvests and the utility of these classifications.Our approach found evidence for potential overharvest of mallard Anas platyrhynchos, Eurasian teal Anas crecca, gadwall Mareca strepera, Canada geese Branta canadensis, greylag geese Anser anser and woodcock Scolopax rusticola. Whether DIM methods predict overharvest is highly dependent on estimates of maximum population growth rates inferring PEG. We found estimates of maximum population growth to be variable across a range of different methods.We found no relationship between SHI and short-term wintering trends or conservation classification under the UK’s BoCC framework. There was however a positive relationship between SHI and long-term wintering trends.Policy Implications: Our results suggest that UK based harvest is unlikely to be a major determinant of population trends for the majority of UK overwintering waterbirds, but harvest rates for some species may exceed that required to maintain stationary population growth. The lack of a relationship between conservation classifications and SHI strongly suggests that such conservation classifications are not an appropriate tool for making decisions about harvest management. Instead, our assessment provides the basis for a framework to make evidence-based decisions on sustainable harvest levels in the face of incomplete data. There is currently no clear policy instrument in the UK to support such a framework via controls on either harvest effort or mortality of waterfowl.
PIF4/HEMERA-mediated daytime thermosensory growth requires the Mediator subunit MED14
Authors: Bajracharya Abhishesh , Xi Jing , Grace Karlie F. , Bayer Eden E. , Grant Chloe A. , Clutton Caroline H. , Baerson Scott R. , Agarwal Ameeta K. , Qiu Yongjian 
Published: March 2022

AbstractWhile moderately elevated ambient temperatures do not trigger stress responses in plants, they do significantly stimulate the growth of specific organs through a process known as thermomorphogenesis. The basic helix-loop-helix transcription factor PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) plays a central role in regulating thermomorphogenetic hypocotyl elongation in various plant species, including Arabidopsis thaliana. Although it is well known that PIF4 promotes plant thermosensory growth by activating genes involved in the biosynthesis and signaling of the phytohormone auxin, the detailed molecular mechanism of such transcriptional activation is not clear. Our previous studies demonstrated that HEMERA (HMR), a transcriptional co-activator of PIF4, promotes the thermo-induced expression of PIF4 target genes through its nine-amino-acid transactivation domain (9aaTAD). In this report, we investigate the role of the Mediator complex in the PIF4/HMR-mediated thermoresponsive gene expression. Through the characterization of various mutants of the Mediator complex, a tail subunit named MED14 is identified as an essential factor for thermomorphogenetic hypocotyl growth. MED14 is required for the thermal induction of PIF4 target genes but has a marginal effect on the levels of PIF4 and HMR. Further transcriptomic analyses confirm that the expression of numerous PIF4/HMR-dependent, auxin-related genes requires MED14 at warm temperatures. Moreover, PIF4 and HMR physically interact with MED14 and both are indispensable for the association of MED14 with the promoters of these thermoresponsive genes. Taken together, these results unveil an important thermomorphogenetic mechanism, in which PIF4 and HMR recruit the Mediator complex to activate auxin-related growth-promoting genes when plants sense moderate increases in ambient temperature.One-sentence summaryThe Mediator subunit MED14 promotes thermomorphogenesis by interacting with PHYTOCHROME-INTERACTING FACTOR 4 and HEMERA to induce the expression of growth-promoting genes at elevated temperatures.
Rapid quantification of polyhydroxyalkanoates accumulated in living cells based on green fluorescence protein labeled phasin: The qPHA method
Authors: Liu Xu , Li Dianjie , Yan Xu , Zhang Zonghao , Zheng Shuang , i Jingpeng Zhang , Wu Fuqing , Li Fangting , Chen Guo-Qiang 
Published: March 2022

AbstractPolyhydroxyalkanoates (PHA), are microbial polyesters with possibility to replace non-biodegradable petro-plastics. No rapid in situ PHA quantitation method has been available for the past 40 years to replace the traditional method which is complicated, time and labor consuming. Quantification of PHA in living cells were finally developed from fluorescence intensities generated from green fluorescence protein (GFP) fused with the Halomonas bluephagenesis phasin proteins attached on the PHA granules. Phasins PhaP1 and PhaP2 were used to fuse with GFP which reflects PHA accumulation with an R-square over 0.9, respectively. Also, a standard correlation was established to calculate PHA contents based on the fluorescence and cell density recorded via a microplate reader with R-square over 0.95 when grown on various substrates, respectively. The PhaP2-GFP containing H. bluephagenesis was applied successfully to quantify PHA synthesis in a 7.5 L fermenter with high precision. The method is named qPHA.
The order Axinellida (Porifera: Demospongiae) in California
Authors: Turner Thomas L. , Pankey M. Sabrina 
Published: March 2022

AbstractSponges are common and diverse in California, but they have received little study in the region, and the identities of many common species remain unclear. Here we combine fresh collections and museum vouchers to revise the order Axinellida for California. Seven new species are described:Endectyon (Endectyon) hispitumulus, Eurypon curvoclavus, Aulospongus viridans, Aulospongus lajollaensis, Halicnemia litorea,Halicnemia montereyensis, andHalicnemia weltoni. One new combination is also described, and two existing species are reduced to junior synonyms, resulting in a total of 13 species; a dichotomous key to differentiate them is provided. DNA data from 9 of the 13 species is combined with publicly available data to produce updated global phylogenies for the order.
Engineering chimeric antigen receptor neutrophils from human pluripotent stem cells for targeted cancer immunotherapy
Authors: Chang Yun , Syahirah Ramizah , Wang Xuepeng , Jin Gyuhyung , Torregrosa-Allen Sandra E. , Elzey Bennett D. , Hummel Sydney N , Wang Tianqi , Lian Xiaojun , Deng Qing , Broxmeyer Hal E. , Bao Xiaoping 
Published: March 2022

SUMMARYNeutrophils, the most abundant white blood cells in the circulation, are closely related to cancer development and progression. Primary neutrophils from healthy donors present potent cytotoxicity against different human cancer cell lines through direct contact and via the generation of reactive oxygen species (ROS). However, due to their short half-life and resistance to genetic modification, neutrophils have not yet been engineered with widely used chimeric antigen receptors (CARs) to enhance their anti-tumor cytotoxicity for targeted immunotherapy. Here, we genetically engineered human pluripotent stem cells (hPSCs) with different synthetic CARs and successfully differentiated them into functional neutrophils by implementing a novel chemically-defined differentiation platform. Neutrophils expressing the chlorotoxin (CLTX)-T-CAR presented specific cytotoxicity against glioblastoma (GBM) cells both in monolayer and 3D cultures. In a GBM xenograft mouse model, systematically-administered CLTX-T-CAR neutrophils also displayed enhanced anti-tumor activity and prolonged animal survival compared with peripheral blood-neutrophils, hPSC-neutrophils and CLTX-NK-CAR natural killer (NK) cells. Collectively, we established a new platform for production of CAR-neutrophils, paving the way to myeloid cell-based therapeutic strategies that would complement and boost current cancer treatment approaches.
Confluence and tight junction dependence of volume regulation in epithelial tissue
Authors: Chmiel Theresa A. , Gardel Margaret L. 
Published: March 2022

AbstractEpithelial cell volume regulation is a key component to tissue stability and dynamics. In particular, how cells respond to osmotic stresses is of significant physiological interest in kidney epithelial tissue. For individual mammalian cells, it is well established that Na-K-2Cl cotransporter (NKCC) channels mediate cell volume homeostasis in response to hyperosmotic stress. However, whether mature epithelium respond similarly is not well known. Here we show that while small colonies of MDCK epithelial cells behave similarly to single cells and exhibit volume homeostasis that is dependent on the NKCC channel function, mature epithelial tissue does not. Instead, the cell volume decreases by 33% when confluent monolayers or acini formed from MDCK are subjected to hyperosmotic stress. We show that the tight junction protein, ZO-1, and Rho-associated kinase (ROCK) are essential for osmotic regulation of cell volume in mature epithelium. Since these both are known to be essential for tight junction assembly, this strongly suggest a role for tight junctions in changing volume response in mature epithelium. Thus, tight junctions act either directly or indirectly in osmotic pressure response of epithelial tissue to suppress volume homeostasis common to isolated epithelial cells.
A chromosome-scale hybrid genome assembly of the extinct Tasmanian tiger (Thylacinus cynocephalus)
Authors: Feigin Charles , Frankenberg Stephen , Pask Andrew 
Published: March 2022

AbstractThe extinct Tasmanian tiger or thylacine (Thylacinus cynocephalus) was a large marsupial carnivore native to Australia. Once ranging across parts of the mainland, the species remained only on the island of Tasmania by the time of European colonization. It was driven to extinction in the early 20th century and is an emblem of native species loss in Australia. The thylacine was a striking example of convergent evolution with placental canids, with which it shared a similar skull morphology. Consequently, it has been the subject of extensive study. While the original thylacine assemblies published in 2018 enabled the first exploration of the species’ genome biology, further progress is hindered by the lack of high-quality genomic resources. Here, we present a new chromosome-scale hybrid genome assembly for the thylacine, which compares favorably with many recent de novo marsupial genomes. Additionally, we provide homology-based gene annotations, characterize the repeat content of the thylacine genome and show that, consistent with demographic decline, the species possessed a low rate of heterozygosity even compared to extant, threatened marsupials.SignificanceThe lack of high-quality genomes for extinct species inhibits research into their biology. Moreover, marsupials are underrepresented among sequenced genomes. Here, we present a new, chromosome-scale thylacine genome. This high-quality assembly is a valuable new resource for studies on marsupial carnivores.
Powering single-cell analyses in the browser with WebAssembly
Authors: Lun Aaron , Kancherla Jayaram 
Published: March 2022

AbstractWe present kana, a web application for interactive single-cell ‘omics data analysis in the browser. Like, literally, in the browser: kana leverages web technologies such as WebAssembly to efficiently perform the relevant computations on the user’s machine, avoiding the need to provision and maintain a backend service. The application provides a streamlined one-click workflow for the main steps in a typical single-cell analysis, starting from a count matrix and finishing with marker detection. Results are presented in an intuitive web interface for further exploration and iterative analysis. Testing on public datasets shows that kana can analyze over 100,000 cells within 5 minutes on a typical laptop.
Cophylogeny and specificity between cryptic coral species (Pocilloporaspp.) at Mo’orea and their symbionts (Symbiodiniaceae)
Authors: Johnston Erika C. , Cunning Ross , Burgess Scott C. 
Published: March 2022

AbstractThe congruence between phylogenies of tightly associated groups of organisms (cophylogeny) reflects evolutionary links between ecologically important interactions. However, despite being a classic example of an obligate symbiosis, tests of cophylogeny between scleractinian corals and their photosynthetic algal symbionts have been hampered in the past because both corals and algae contain genetically unresolved and morphologically cryptic species. Here, we studied co-occurring, crypticPocilloporaspecies from Mo’orea, French Polynesia, that differ in their relative abundance across depth. We constructed new phylogenies of the hostPocillopora(using genomic loci, complete mitochondrial genomes, and thousands of single nucleotide polymorphisms) and their Symbiodiniaceae symbionts (using ITS2 and psbAncrmarkers) and tested for cophylogeny. The analysis supported the presence of fivePocilloporaspecies on the fore-reef at Mo’orea that mostly hosted eitherCladocopium latusorumorC. pacificum.OnlyPocilloporaspecies hostingC. latusorum,and that have similar relative abundances across depths, also hosted taxa fromSymbiodiniumandDurusdinium.In general, theCladocopiumphylogeny mirrored thePocilloporaphylogeny. WithinCladocopiumspecies, lineages also differed in their associations withPocilloporahaplotypes, except those showing evidence of nuclear introgression, and with depth in the two most commonPocilloporaspecies. We also found evidence for a newPocilloporaspecies (haplotype 10), that has so far only been sampled from French Polynesia, that warrants formal identification. The linked phylogenies of thesePocilloporaandCladocopiumspecies and lineages suggest that symbiont speciation is driven by niche diversification in the host, but there is still evidence for symbiont flexibility in rare cases.
Single-cell Spatial Proteomic Imaging for Human Neuropathology
Authors: Vijayaragavan Kausalia , Cannon Bryan J , Tebaykin Dmitry , Bossé Marc , Baranski Alex , Oliveria JP , Mrdjen Dunja , Corces M. Ryan , McCaffrey Erin F , Greenwald Noah F , Sigal Yari , Khair Zumana , Bruce Trevor , Rajaraman Anusha , Bukhari Syed A , Montine Kathleen S. , Angelo R. Michael , Montine Thomas J. , Bendall Sean C. 
Published: March 2022

ABSTRACTNeurodegenerative disorders are characterized by phenotypic changes and hallmark proteopathies. Quantifying these in archival human brain tissues remains indispensable for validating animal models and understanding disease mechanisms. We present a framework for nanometer-scale, spatial proteomics with multiplex ion beam imaging (MIBI) for capturing neuropathological features. MIBI facilitated simultaneous, quantitative imaging of 36 proteins on archival human hippocampus from individuals spanning cognitively normal to dementia. Customized analysis strategies identified cell types and proteopathies in the hippocampus across stages of Alzheimer’s disease (AD) neuropathologic change. We show microglia-pathologic tau interactions in hippocampal CA1 subfield, in AD dementia. Data driven, sample independent creation of spatial proteomic regions identified persistent neurons in pathologic tau neighborhoods expressing mitochondrial protein MFN2, regardless of cognitive status, suggesting a survival advantage. Our study revealed unique insights from multiplexed imaging and data-driven approaches for neuropathologic analysis and serves as a baseline for mechanistic and interventional understanding in human neurodegeneration.
Precocious sperm exchange in the simultaneously hermaphroditic nudibranch,Berghia stephanieae
Authors: Taraporevala Neville F. , Lesoway Maryna P. , Goodheart Jessica A. , Lyons Deirdre C. 
Published: March 2022

AbstractSexual systems vary greatly across molluscs. This diversity includes simultaneous hermaphroditism, with both sexes functional at the same time. Most nudibranch molluscs are thought to be simultaneous hermaphrodites, but detailed studies of reproductive development and timing remain rare as most species cannot be cultured in the lab. The aeolid nudibranch,Berghia stephanieae, is one such species that can be cultured through multiple generations on the benchtop. We studiedB. stephanieaereproductive timing to establish when animals first exchange sperm and how long sperm can be stored. We isolated age- and size-matched individuals at sequential timepoints to learn how early individuals exchange sperm. Individuals isolated at 13 weeks post laying (wpl) can produce fertilized eggs. This is 6 weeks before animals first lay egg masses, indicating that sperm exchange occurs well before individuals are capable of laying eggs. Our results indicate that male gonads become functional for animals between 6 mm (~9 wpl) and 9 mm (~15 wpl) in length. That is much smaller (and sooner) than the size (and age) of individuals at first laying (12-19 mm; ~19 wpl), indicating that male and female functions do not develop simultaneously. We also tracked the number of fertilized eggs in each egg mass, which remained steady for the first 10-15 egg masses, followed by a decline to near-to-no fertilization. This large, novel dataset provides insights into precise timing of the onset of functionality of the male and female reproductive systems inB. stephanieae. These data contribute to a broader understanding of reproductive development and the potential for understanding evolution of diverse sexual systems in molluscs.
Connectomic Analysis of the Drosophila Lateral Neuron Clock Cells Reveals the Synaptic Basis of Functional Pacemaker Classes
Authors: Shafer O.T. , Gutierrez G.J. , Li K. , Mildenhall A. , Spira D. , Marty J. , Lazar A.A. , Fernandez M.P. 
Published: March 2022

AbstractThe circadian clock orchestrates daily changes in physiology and behavior to ensure internal temporal order and optimal timing across the day. In animals, a central brain clock coordinates circadian rhythms throughout the body and is characterized by a remarkable robustness that depends on synaptic connections between constituent neurons. The clock neuron network of Drosophila, which shares network motifs with clock networks in the mammalian brain yet is built of many fewer neurons, offers a powerful model for understanding the network properties of circadian timekeeping. Here we report an assessment of synaptic connectivity within a clock network, focusing on the critical lateral neuron (LN) clock neuron classes. Our results reveal that previously identified anatomical and functional subclasses of LNs represent distinct connectomic types. Moreover, we identify a small number of clock cell subtypes representing highly synaptically coupled nodes within the clock neuron network. This suggests that neurons lacking molecular timekeeping likely play integral roles within the circadian timekeeping network. To our knowledge, this represents the first comprehensive connectomic analysis of a circadian neuronal network.
Relationships among evolutionary distance, the variance–covariance matrix, multidimensional scaling, and principal component analysis
Authors: Misawa Kazuharu 
Published: March 2022

AbstractPrincipal component analyses (PCAs) are often used to visualize patterns of genetic variation in human populations. Previous studies showed a close correspondence between genetic and geographic distances. In such PCAs, the principal components are eigenvectors of the data’s variance-covariance matrix, which is obtained by a genetic relationship matrix (GRM). However, it is difficult to apply GRM to multiallelic sites. In this paper, I showed that a PCA from GRM is equivalent to multidimensional scaling (MDS) from nucleotide differences. Therefore, a PCA can be conducted using nucleotide differences. The new method provided in this study provides a straightforward method to predict the effects of different demographic processes on genetic diversity.