bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lung macrophages mediate helminth resistance through differential activation of recruited monocyte-derived alveolar macrophages and arginine depletion
Authors: Chen Fei , El-Naccache Darine W. , Ponessa John J. , Lemenze Alexander , Espinosa Vanessa , Wu Wenhui , Lothstein Katherine , Jin Linhua , Antao Olivia , Weinstein Jason S. , Damani-Yokota Payal , Khanna Kamal , Murray Peter , Rivera Amariliz , Siracusa Mark C. , Gause William C. 
Published: October 2020

AbstractMacrophages are known to mediate anti-helminth responses, but it remains uncertain which subsets are involved or how macrophages actually kill helminths. Here we show rapid monocyte recruitment to the lung after infection with the nematode parasite,Nippostrongylus brasiliensis. In this inflamed tissue microenvironment these monocytes differentiate into an alveolar-like macrophage (AM) phenotype, expressing both Siglec-F and CD11c, surround invading parasitic larvae and preferentially kill parasites in vitro. Monocyte-derived AMs (Mo-AMs) express type 2-associated markers and show distinct remodeling of the chromatin landscape relative to tissue-derived AMs. In particular, they express high amounts of Arg1 (arginase-1), which we demonstrate mediates helminth killing through L-arginine depletion. These studies indicate that recruited monocytes are selectively programmed in the pulmonary environment to express AM markers and an anti-helminth phenotype.
Unsupervised cellular phenotypic hierarchy enables spatial intratumor heterogeneity characterization, recurrence-associated microdomains discovery, and harnesses network biology from hyperplexed in-situ fluorescence images of colorectal carcinoma
Authors: Furman Samantha A. , Stern Andrew M. , Uttam Shikhar , Taylor D. Lansing , Pullara Filippo , Chennubhotla S. Chakra 
Published: October 2020

AbstractLEAPH is an unsupervised machinelearningalgorithm for characterizing in situphenotypicheterogeneity in tissue samples. LEAPH builds a phenotypic hierarchy of cell types, cell states and their spatial configurations. The recursive modeling steps involve determining cell types with low-ranked mixtures of factor analyzers and optimizing cell states with spatial regularization. We applied LEAPH to hyperplexed (51 biomarkers) immunofluorescence images of colorectal carcinoma primary tumors (N=213). LEAPH, combined with pointwise mutual information (PMI), enables the discovery of phenotypically distinctmicrodomains, composed of spatially configured computational phenotypes. LEAPH identified a subset of microdomains visualized as the spatial configuration of recurrence-specific signaling networks whose intracellular and intercellular interactions support cancer stem cell maintenance and immunosuppression in the evolving tumor microenvironment. The LEAPH framework, when combined with microdomain discovery and microdomain-specific network biology, has the potential to provide insights into pathophysiological mechanisms, identify novel drug targets and inform therapeutic strategies for individual patients.
ScRNA-seq reveals tumor microenvironment remodeling induced by local intervention-based immunotherapy
Authors: Hoover Ashley R. , Liu Kaili , DeVette Christa I. , Krawic Jason R. , West Connor L. , Medcalf Delaney , Welm Alana L. , Sun Xiao-Hong , Hildebrand William H. , Chen Wei R. 
Published: October 2020

ABSTRACTLaser immunotherapy (LIT) combines local photothermal therapy (PTT), to disrupt tumor homeostasis and release tumor antigens, and an intratumorally administered immunostimulant, N-dihydrogalactochitosan (GC), to induce antitumor immune responses. We performed single-cell RNA sequencing on tumor-infiltrating leukocytes of MMTV-PyMT mouse mammary tumors to characterize LIT-induced myeloid and lymphoid compartment remodeling. Analysis of 49,380 single cell transcriptomes from different treatment groups revealed that proinflammatory IFNα, IFNγ, and TNFα cytokine signaling pathways were enriched in both lymphoid and myeloid cells isolated from LIT-treated tumors. The CD4+and CD8+T cells in LIT treated tumors resided in an activated state while immune cells in untreated and PTT-treated tumors remained in a neutral/resting state. Additionally, monocytes recruited into the LIT-treated tumors were driven towards proinflammatory M1-like macrophage phenotypes or monocyte-derived dendritic cells. Our results reveal that LIT prompts immunological remodeling of the tumor microenvironment by initiating broad proinflammatory responses to drive antitumor immunity.STATEMENT OF SIGNIFICANCETranscriptome profiling of tumor infiltrating leukocytes revealed that localized laser immunotherapy (LIT) greatly enhanced antitumor T cell activity by promoting proinflammatory myeloid cell responses within the tumor microenvironment. This manuscript demonstrates that LIT broadly stimulates antitumor immunity and has great potential to synergize with current immunotherapies to increase their efficacy.
Cellular Anatomy of the Mouse Primary Motor Cortex
Authors: Muñoz-Castañeda Rodrigo , Zingg Brian , Matho Katherine S. , Wang Quanxin , Chen Xiaoyin , Foster Nicholas N. , Narasimhan Arun , Li Anan , Hirokawa Karla E. , Huo Bingxing , Bannerjee Samik , Korobkova Laura , Park Chris Sin , Park Young-Gyun , Bienkowski Michael S. , Chon Uree , Wheeler Diek W. , Li Xiangning , Wang Yun , Kelly Kathleen , An Xu , Attili Sarojini M. , Bowman Ian , Bludova Anastasiia , Cetin Ali , Ding Liya , Drewes Rhonda , D’Orazi Florence , Elowsky Corey , Fischer Stephan , Galbavy William , Gao Lei , Gillis Jesse , Groblewski Peter A. , Gou Lin , Hahn Joel D. , Hatfield Joshua T. , Hintiryan Houri , Huang Jason , Kondo Hideki , Kuang Xiuli , Lesnar Philip , Li Xu , Li Yaoyao , Lin Mengkuan , Liu Lijuan , Lo Darrick , Mizrachi Judith , Mok Stephanie , Naeemi Maitham , Nicovich Philip R. , Palaniswamy Ramesh , Palmer Jason , Qi Xiaoli , Shen Elise , Sun Yu-Chi , Tao Huizhong , Wakemen Wayne , Wang Yimin , Xie Peng , Yao Shenqin , Yuan Jin , Zhu Muye , Ng Lydia , Zhang Li I. , Lim Byung Kook , Hawrylycz Michael , Gong Hui , Gee James C. , Kim Yongsoo , Peng Hanchuan , Chuang Kwanghun , Yang X William , Luo Qingming , Mitra Partha P. , Zador Anthony M. , Zeng Hongkui , Ascoli Giorgio A. , Huang Z Josh , Osten Pavel , Harris Julie A. , Dong Hong-Wei 
Published: October 2020

AbstractAn essential step toward understanding brain function is to establish a cellular-resolution structural framework upon which multi-scale and multi-modal information spanning molecules, cells, circuits and systems can be integrated and interpreted. Here, through a collaborative effort from the Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based description of one brain structure - the primary motor cortex upper limb area (MOp-ul) of the mouse. Applying state-of-the-art labeling, imaging, computational, and neuroinformatics tools, we delineated the MOp-ul within the Mouse Brain 3D Common Coordinate Framework (CCF). We defined over two dozen MOp-ul projection neuron (PN) types by their anterograde targets; the spatial distribution of their somata defines 11 cortical sublayers, a significant refinement of the classic notion of cortical laminar organization. We further combine multiple complementary tracing methods (classic tract tracing, cell type-based anterograde, retrograde, and transsynaptic viral tracing, high-throughput BARseq, and complete single cell reconstruction) to systematically chart cell type-based MOp input-output streams. As PNs link distant brain regions at synapses as well as host cellular gene expression, our construction of a PN type resolution MOp-ul wiring diagram will facilitate an integrated analysis of motor control circuitry across the molecular, cellular, and systems levels. This work further provides a roadmap towards a cellular resolution description of mammalian brain architecture.
New evidence concerning the genome designations of the AC(DC) tetraploidAvenaspecies
Authors: Yan Honghai , Ren Zichao , Deng Di , Yang Kehan , Yang Chuang , Zhou Pingping , Wight Charlene , Ren Changzhong , Peng Yuanying 
Published: October 2020

AbstractThe tetraploidAvenaspecies in the sectionPachycarpaBaum, includingA. insularis, A. maroccana, andA. murphyi, are thought to be involved in the evolution of hexaploid oats; however, their genome designations are still being debated. Repetitive DNA sequences play an important role in genome structuring and evolution, so understanding the chromosomal organization and distribution of these sequences inAvenaspecies could provide valuable information concerning genome evolution in this genus. In this study, the chromosomal organizations and distributions of six repetitive DNA sequences (including three SSR motifs (TTC, AAC, CAG), one 5S rRNA gene fragment, and two oat A and C genome specific repeats) were investigated using non-denaturing fluorescence in situ hybridization (ND-FISH) in the three tetraploid species mentioned above and in two hexaploid oat species. Preferential distribution of the SSRs in centromeric regions was seen in the A and D genomes, whereas few signals were detected in the C genomes. Some intergenomic translocations were observed in the tetraploids; such translocations were also detected between the C and D genomes in the hexaploids. These results provide robust evidence for the presence of the D genome in all three tetraploids, strongly suggesting that the genomic constitution of these species is DC and not AC, as had been thought previously.
Proton-Dependent Inhibition, Inverted Voltage Activation, and Slow Gating of CLC-0 Chloride Channel
Authors: Kwon Hwoi Chan , Yu Yawei , Fairclough Robert H. , Chen Tsung-Yu 
Published: October 2020

AbstractCLC-0, a prototype Cl−channel in the CLC family, employs two gating mechanisms that control its ion-permeation pore: fast gating and slow gating. The negatively-charged sidechain of a pore glutamate residue, E166, is known to be the fast gate, and the swinging of this sidechain opens or closes the pore of CLC-0 on the millisecond time scale. The other gating mechanism, slow gating, operates with much slower kinetics in the range of seconds to tens or even hundreds of seconds, and it is thought to involve still-unknown conformational rearrangements. Here, we find that low intracellular pH (pHi) facilitates the closure of the CLC-0’s slow gate, thus generating current inhibition. The rate of low pHi-induced current inhibition increases with intracellular H+concentration ([H+]i)—the time constants of current inhibition by low pHi= 4.5, 5.5 and 6 are roughly 0.1, 1 and 10 sec, respectively, at room temperature. In comparison, the time constant of the slow gate closure at pHi= 7.4 at room temperature is hundreds of seconds. The inhibition by low pHiis significantly less prominent in mutants favoring the slow-gate open state (such as C212S and Y512A), further supporting the fact that intracellular H+enhances the slow-gate closure in CLC-0. A fast inhibition by low pHicauses an apparent inverted voltage-dependent activation in the wild-type CLC-0, a behavior similar to those in some channel mutants such as V490W in which only membrane hyperpolarization can open the channel. Interestingly, when V490W mutation is constructed in the background of C212S or Y512A mutation, the inverted voltage-dependent activation disappears. We propose that the slow kinetics of CLC-0’s slow-gate closure may be due to low [H+]irather than due to the proposed large conformational change of the channel protein. Our results also suggest that the inverted voltage-dependent opening observed in some mutant channels may result from fast closure of the slow gate by the mutations.
Social Information use Shapes the Coevolution of Sociality and Virulence
Authors: Ashby Ben , Farine Damien R 
Published: October 2020

AbstractSocial contacts can facilitate the spread of both survival-related information and infectious diseases, but little is known about how these processes combine to shape host and parasite evolution. Here, we use a theoretical model that captures both infection and information transmission processes to investigate how host sociality (contact effort) and parasite virulence (disease-associated mortality rate) (co)evolve. We show that selection for sociality (and in turn, virulence) depends on both the intrinsic costs and benefits of social information and infection as well as their relative prevalence in the population. Specifically, greater sociality and lower virulence evolve when the risk of infection is either low or high and social information is neither very common nor too rare. Lower sociality and higher virulence evolve when the prevalence patterns are reversed. When infection and social information are both at moderate levels in the population, the direction of selection depends on the relative costs and benefits of being infected or informed. We also show that sociality varies inversely with virulence, and that parasites may be unable to prevent runaway selection for higher contact efforts. Together, these findings provide new insights for our understanding of group living and how apparently opposing ecological processes can influence the evolution of sociality and virulence in a range of ways.
Transferrin receptor (Tfr1) ablation in satellite cells impacts skeletal muscle regeneration through the activation of ferroptosis
Authors: Ding Hongrong , Chen Shujie , Pan Xiaohan , Dai Xiaoshuang , Pan Guihua , Li Ze , Mai Xudong , Tian Ye , Zhang Susu , Liu Bingdong , Cao Guangchao , Yao Zhicheng , Yao Xiangping , Gao Liang , Yang Li , Chen Xiaoyan , Sun Jia , Chen Hong , Han Mulan , Yin Yulong , Xu Guohuan , Li Huijun , Wu Weidong , Chen Zheng , Lin Jingchao , Xiang Liping , Lu Yan , Zhu Xiao , Xie Liwei 
Published: October 2020

AbstractSatellite cells (SCs) are critical to the postnatal development and skeletal muscle regeneration. Inactivation of SCs is linked with the skeletal muscle loss. Leveraging on the RNAseq screening, transferrin receptor (Tfr1) is identified to be associated with muscle/SC ageing and the declined regeneration potential. Muscle-specific deletion ofTfr1results in the growth retardation, metabolic disorder and lethality, shedding light on the importance of Tfr1 in skeletal muscle physiology. Here, our investigation reported that conditional SC-ablation ofTfr1leads to the SCs inactivation and skeletal muscle regeneration defects, followed by the labile iron accumulation,de novolipogenesis via fibroadipogenic progenitors (FAPs) and Gpx4/Nrf2-mediated ROS-scavenger defects. These abnormal phenomena, such as Hmox1-mediated myoglobin degradation, Tfr1-Slc39a14 functional switch and the activation of unsaturated fatty acid biosynthesis pathway are orchestrated with the occurrence of ferroptosis in skeletal muscle. Ferroptosis may further prevent SC proliferation and skeletal muscle regeneration. Ferrostatin-1, a ferroptosis inhibitor could not rescue Tfr1-ablation induced ferroptosis. However, intramuscular administration of lentivirus expressing Tfr1 could partially reduce labile iron accumulation, decreasede novolipogenesis and promote skeletal muscle regeneration. Most importantly, Tfr1/Slc39a14 functional switch, labile iron accumulation and fatty acid biosynthesis are recapitulated in aged skeletal muscle of rodents, indicating that ferroptosis occurs in the skeletal muscles of aged rodents. The present study also bridges the gap between pathogenesis of iron and functional defects in the skeletal muscle, providing mechanistic information to develop anti-aging strategies.One Sentence SummaryConditional ablation ofTfr1in satellite cells (SCs) results in the SC inactivation, skeletal muscle regeneration defects, labile iron accumulation, and unsaturated fatty acid biosynthesis, leading to the activation of ferroptosis, which is recapitulated in skeletal muscles of aged rodents to be a new cell death form identified in skeletal muscle and sheds light on the development of novel anti-ageing strategies.
Transmission of SARS-COV-2 from China to Europe and West Africa: a detailed phylogenetic analysis
Authors: Wruck Wasco , Adjaye James 
Published: October 2020

AbstractBackgroundSARS-CoV-2, the virus causing the Covid-19 pandemic emerged in December 2019 in China and raised fears that it could overwhelm healthcare systems worldwide. In June 2020, all African countries registered human infections with SARS-CoV-2.The virus is mutating steadily and this is monitored by a well curated database of viral nucleotide sequences from samples taken from infected individual thus enabling phylogenetic analysis and phenotypic associations.MethodsWe downloaded from the GISAID database, SARS-CoV-2 sequences established from four West African countries Ghana, Gambia, Senegal and Nigeria and then performed phylogenetic analysis employing the nextstrain pipeline. Based on mutations found within the sequences we calculated and visualized statistics characterizing clades according to the GISAID nomenclature.ResultsWe found country-specific patterns of viral clades: the later Europe-associated G-clades predominantly in Senegal and Gambia, and combinations of the earlier (L, S, V) and later clades in Ghana and Nigeria. Contrary to our expectations, the later Europe-associated G-clades emerged before the earlier clades. Detailed analysis of distinct samples showed that some of the earlier clades might have circulated latently and some reflect migration routes via Mali and Tunisia.ConclusionsThe distinct patterns of viral clades in the West African countries point at its emergence from Europe and China via Asia and Europe. The observation that the later clades emerged before the earlier clades could be simply due to founder effects or due to latent circulation of the earlier clades. Only a marginal correlation of the G-clades associated with the D614G mutation could be identified with the relatively low case fatality (0.6-3.2).Key messagesGhana and Nigeria have a combination of earlier (L, V, S) and later Europe-associated G-clades of SARS-CoV-2, therefore pointing to multiple introductions while in Senegal and Gambia Europe-associated G-clades predominate pointing to introductions mainly from Europe.Surprisingly, the later G-clades emerged before the earlier clades (L, V, S)Detailed phylogenetic analysis points at latent circulation of earlier clades before the first registered cases.Phylogenetic analysis of some cases points at migration routes to Europe via Tunisia, Egypt and Mali.A marginal correlation of r=0.28 between the percentage of the D614G mutation defining the G-clades and case-fatality can be detected.
Plasmodium falciparumAtg18 localizes to the food vacuole via interaction with the multi-drug resistance protein 1 and phosphatidylinositol 3-phosphate
Authors: Sudhakar Renu , Das Divya , Thanumalayan Subramanian , Gorde Somesh , Sijwali Puran Singh 
Published: October 2020

AbstractAutophagy is a lysosome-dependent degradative process involving over 35 Atg proteins. The autophagy repertoire in malaria parasites is limited and does not appear to be a major degradative process. To better understand the autophagy process, we investigatedPlasmodium falciparumAtg18 (PfAtg18), a PROPPIN family protein, whose members likeS. cerevisiaeAtg18 (ScAtg18) and human WIPI2 are essential for autophagy. Wild type and mutant PfAtg18 were expressed inP. falciparumand assessed for localization, the effect of various inhibitors and antimalarials on PfAtg18 localization, and identification of PfAtg18-interacting proteins. PfAtg18 is expressed in asexual erythrocytic stages and localized to the food vacuole, which was also observed with otherPlasmodiumAtg18 proteins, indicating that food vacuole localization is a conserved feature. Interaction of PfAtg18 with the food vacuole-associated PI3P is essential for localization, as PfAtg18 mutants of PI3P-binding motifs neither bound PI3P nor localized to the food vacuole. Interestingly, ScAtg18 showed complete cytoplasmic localization despite binding with PI3P, indicating additional requirement for PfAtg18 localization. The food vacuole multi-drug resistance protein 1 (MDR1) was consistently identified in the PfAtg18 immunoprecipitate, and also interacted with PfAtg18. In contrast to PfAtg18, ScAtg18 did not interact with the MDR1, which, in addition to PI3P, could play a critical role in localization of PfAtg18. Chloroquine and amodiaquine greatly affected PfAtg18 localization, suggesting that these quinolines target PfAtg18 or the proteins that might be involved in its localization. Thus, PI3P and MDR1are critical mediators of PfAtg18 localization, and PfAtg18 may modulate MDR1 activity.
Native cyclase-associated protein and actin fromXenopus laevisoocytes form a 4:4 complex with a tripartite structure
Authors: Kodera Noriyuki , Abe Hiroshi , Ono Shoichiro 
Published: October 2020

AbstractCyclase-associated protein (CAP) is a conserved actin-binding protein that regulates multiple aspects of actin filament dynamics, including polymerization, depolymerization, filament severing, and nucleotide exchange. Intriguingly, CAP has been isolated from different cells and tissues as an equimolar complex with actin, and previous studies have shown that a CAP-actin complex contains six molecules each of CAP and actin. Here, we successfully isolated a complex ofXenopuscyclase-associated protein 1 (XCAP1) and actin from oocyte extracts and demonstrated that the complex contained four molecules each of XCAP1 and actin. The XCAP1-actin complex remained stable as a single population of 340 kDa in hydrodynamic analysis using gel filtration or analytical ultracentrifugation. Examination of the XCAP1-actin complex by high-speed atomic force microscopy revealed a tripartite structure: a middle globular domain and two globular arms. The two arms were connected with the middle globular domain by a flexible linker and observed in two states with different heights, presumably representing the presence or absence of G-actin. We hypothesize that the middle globular domain corresponds to a tetramer of the N-terminal helical-folded domain of XCAP1, and that each arm in the high state corresponds to a hetero-tetramer containing a dimer of the C-terminal CARP domain of XCAP1 and two G-actin molecules. This novel configuration of a CAP-actin complex may represent a functionally important aspect of this complex.