bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromosome-scale assembly of the lablab genome - A model for inclusive orphan crop genomics
Authors: Njaci Isaac , Waweru Bernice , Kamal Nadia , Muktar Meki Shehabu , Fisher David , Gundlach Heidrun , Muli Collins , Muthui Lucy , Maranga Mary , Kiambi Davies , Maass Brigitte L , Emmrich Peter MF , Entfellner Jean-Baka Domelevo , Spannagl Manuel , Chapman Mark A , Shorinola Oluwaseyi , Jones Chris S 
Published: May 2022

AbstractOrphan crops (also described as underutilised and neglected crops) hold the key to diversified and climate-resilient food systems. After decades of neglect, the genome sequencing of orphan crops is gathering pace, providing the foundations for their accelerated domestication and improvement. Recent attention has however turned to the gross under-representation of researchers in Africa in the genome sequencing efforts of their indigenous orphan crops. Here we report a radically inclusive approach to orphan crop genomics using the case of Lablab purpureus (L.) Sweet (syn. Dolichos lablab, or hyacinth bean) – a legume native to Africa and cultivated throughout the tropics for food and forage. Our Africa-led South-North plant genome collaboration produced a high-quality chromosomescale assembly of the lablab genome – the first chromosome-scale plant genome assembly locally sequenced in Africa. We also re-sequenced cultivated and wild accessions of lablab from Africa confirming two domestication events and examined the genetic diversity in lablab germplasm conserved in Africa. Our approach provides a valuable resource for lablab improvement and also presents a model that could be explored by other researchers sequencing indigenous crops particularly from Low and middle income countries (LMIC).
Attention-wise masked graph contrastive learning for predicting molecular property
Authors: Liu Hui , Huang Yibiao , Liu Xuejun , Deng Lei 
Published: May 2022

MotivationAccurate and efficient prediction of the molecular property is one of the fundamental problems in drug research and development. Recent advancements in representation learning have been shown to greatly improve the performance of molecular property prediction. However, due to limited labeled data, supervised learning-based molecular representation algorithms can only search limited chemical space and suffer from poor generalizability.ResultsIn this work, we proposed a self-supervised learning method, ATMOL, for molecular representation learning and properties prediction. We developed a novel molecular graph augmentation strategy, referred to as attention-wise graph masking, to generate challenging positive samples for contrastive learning. We adopted the graph attention network (GAT) as the molecular graph encoder, and leveraged the learned attention weights as masking guidance to generate molecular augmentation graphs. By minimization of the contrastive loss between original graph and augmented graph, our model can capture important molecular structure and higher-order semantic information. Extensive experiments showed that our attention-wise graph mask contrastive learning exhibited state-of-the-art performance in a couple of downstream molecular property prediction tasks. We also verified that our model pretrained on larger scale of unlabeled data improved the generalization of learned molecular representation. Moreover, visualization of the attention heatmaps showed meaningful patterns indicative of atoms and atomic groups important to specific molecular property.
Adversarial interspecies relationships facilitate population suppression by gene drive in spatially explicit models
Authors: Liu Yiran , Teo WeiJian , Yang Haochen , Champer Jackson 
Published: May 2022

AbstractSuppression gene drives are designed to bias their inheritance and increase in frequency in a population, disrupting an essential gene in the process. When the frequency is high enough, the population will be unable to reproduce above the replacement level and could be eliminated. CRISPR suppression drives based on the homing mechanism have already seen success in the laboratory, particularly in malaria mosquitoes. However, several models predict that the use of these drives in realistic populations with spatial structure may not achieve complete success. This is due to the ability of wild-type individuals to escape the drive and reach empty areas with reduced competition, allowing them to achieve high reproductive success and leading to extinction-recolonization cycles across the landscape. Here, we extend our continuous space gene drive framework to include two competing species or predator-prey species pairs. We find that in both general and mosquito-specific models, the presence of a competing species or predator can greatly facilitate drive-based suppression, even for drives with modest efficiency. However, the presence of a competing species also substantially increases the frequency of outcomes in which the drive is lost before suppression is achieved. These results are robust in models with seasonal population fluctuations that mosquito populations often experience. We also found that suppression can be somewhat more difficult if targeting a predator with strong predator-prey interactions. Our results illustrate the difficulty of predicting outcomes of interventions that could substantially affect populations of interacting species in complex ecosystems. However, our results are also potentially promising for the prospects of less powerful suppression gene drives for achieving successful elimination of target mosquito and other pest populations.
m6A epitranscriptomic modification regulates neural progenitor-to-glial cell transition in the retina
Authors: Xin Yanling , He Qinghai , Liang Huilin , Guo Jingyi , Zhong Qi , Zhang Ke , Li Jinyan , Liu Yizhi , Chen Shuyi 
Published: May 2022

AbstractN6-methyladenosine (m6A) is the most prevalent mRNA internal modification and has been shown to regulate the development, physiology and pathology of various tissues. However, the functions of the m6A epitranscriptome in the visual system remain unclear. In this study, using a retina-specific conditional knockout mouse model, we show that retinas deficient in Mettl3, the core component of the m6A methyltransferase complex, exhibit structural and functional abnormalities beginning at the end of retinogenesis. Immunohistological and scRNA-seq analyses of retinogenesis processes reveal that retinal progenitor cells (RPCs) and Müller glial cells are the two cell types primarily affected by Mettl3 deficiency. Integrative analyses of scRNA-seq and MeRIP-seq data suggest that m6A fine-tunes the transcriptomic transition from RPCs to Müller cells by promoting the degradation of RPC transcripts, the disruption of which leads to abnormalities in late retinogenesis and compromises the glial functions of Müller cells. Finally, overexpression of m6A-regulated RPC-enriched transcripts in late RPCs partially recapitulates the Mettl3-deficient retinal phenotype. Collectively, our study reveals an epitranscriptomic mechanism governing progenitor-to-glial cell transition during late retinogenesis, which is essential for the homeostasis of the mature retina. The mechanism revealed in this study might also apply to other nervous systems.
Single-particle studies of the effects of RNA-protein interactions on the self-assembly of RNA virus particles
Authors: Garmann Rees F. , Goldfain Aaron M. , Tanimoto Cheylene R. , Beren Christian E. , Vasquez Fernando F. , Knobler Charles M. , Gelbart William M. , Manoharan Vinothan N. 
Published: May 2022

AbstractUnderstanding the pathways by which simple RNA viruses self-assemble from their coat proteins and RNA is of practical and fundamental interest. Although RNA-protein interactions are thought to play a critical role in the assembly, our understanding of their effects is limited because the assembly process is difficult to observe directly. We address this problem by using interferometric scattering microscopy, a sensitive optical technique with high dynamic range, to follow the in vitro assembly kinetics of over 500 individual particles of brome mosaic virus (BMV)—for which RNA-protein interactions can be controlled by varying the ionic strength of the buffer. We find that when RNA-protein interactions are weak, BMV assembles by a nucleation-and-growth pathway in which a small cluster of RNA-bound proteins must exceed a critical size before additional proteins can bind. As the strength of RNA-protein interactions increases, the nucleation time becomes shorter and more narrowly distributed until the assembly kinetics become indistinguishable from diffusion-limited adsorption. In contrast, the time to grow a capsid after nucleation varies weakly with both salt and protein concentration. These results show that the nucleation rate is controlled by RNA-protein interactions, while the growth process is driven less by RNA-protein interactions and more by protein-protein interactions and intra-protein forces. The nucleated pathway observed with the plant virus BMV is strikingly similar to that previously observed with bacteriophage MS2, a phylogenetically distinct virus with a different host kingdom. These results raise the possibility that nucleated assembly pathways might be common to other RNA viruses.RNA viruses first inspired the term “self-assembly.” Yet much is still not understood about how even the simplest such viruses assemble or if different viruses assemble in similar ways. Theoretical models suggest many possible assembly pathways, with many different roles for the RNA, but until recently measuring these pathways has not been possible. We use a sensitive microscopy technique to follow the assembly of individual particles of BMV, a plant virus. We find evidence of an RNA-mediated nucleation-and-growth pathway that is strikingly similar to that of MS2, a bacterial virus. The last common ancestor of BMV and MS2 existed only in ancient times, suggesting that their assembly pathway might be evolutionarily conserved and other viruses might follow a similar pathway.
Role of intraluteal and intrauterine prostaglandin signaling in LH-induced luteolysis in pregnant rats
Authors: Vashistha Akshi , Rudraiah Medhamurthy 
Published: May 2022

AbstractLuteal dysfunctions lead to fertility disorders and pregnancy complications. Normal luteal function is regulated by many factors, including luteinizing hormone (LH). The luteotropic roles of LH have been widely investigated but its role in the process of luteolysis has received little attention. LH has been shown to have luteolytic effects during pregnancy in rats. Stocco et al. have demonstrated the role of intraluteal prostaglandins (PGs) in LH-mediated luteolysis. However, the status of PG signaling in the uterus during LH-mediated luteolysis remains unexplored. In this study, we have examined the effect of LH-mediated luteolysis on luteal and uterine PG synthesis machinery and genes associated with activated luteal PGF2α signalling and uterine activation during different stages (mid and late) of pregnancy. Further, we analysed the effect of overall PG synthesis machinery blockage on LH-mediated luteolysis during late-pregnancy. Unlike the mid-stage of pregnancy, the expression of genes involved in PG synthesis and responsivity in late-stage pregnant rats’ luteal and uterine tissue increase post repeated administration of LH. Since the cAMP/PKA pathway mediates LH-mediated luteolysis, we analyzed the effect of inhibition of endogenous PG synthesis on the cAMP/PKA/CREB pathway, followed by the analysis of the expression of markers of luteolysis. Inhibition of endogenous PG synthesis did not affect the cAMP/PKA/CREB pathway. However, in the absence of endogenous PGs, luteolysis could not be activated to the full extent. Our results suggest that endogenous PGs may contribute to LH-mediated luteolysis, but this dependency on endogenous PGs is pregnancy stage dependent. These findings advance our understanding of the molecular pathways that regulate luteolysis.
Meta-analysis of transcriptomes in insects showing density-dependent polyphenism
Authors: Toga Kouhei , Yokoi Kakeru , Bono Hidemasa 
Published: May 2022

AbstractWith increasing public data, a statistical analysis approach called meta-analysis, which combines transcriptome results obtained from multiple studies, has succeeded in providing novel insights into targeted biological processes. Locusts and aphids are representative of insect groups that exhibit density-dependent plasticity. Although the physiological mechanisms underlying density-dependent polyphenism have been identified in aphids and locusts, the underlying molecular mechanisms remain largely unknown. In this study, we performed a meta-analysis of public transcriptomes to gain additional insights into the molecular underpinning of density-dependent plasticity. We collected RNA sequencing data of aphids and locusts from public databases and detected differentially expressed genes (DEGs) between crowded and isolated conditions. Gene set enrichment analysis was performed to reveal the characteristics of the DEGs. DNA replication (GO:0006260), DNA metabolic processes (GO:0006259), and mitotic cell cycle (GO:0000278) were enriched in response to crowded conditions. To date, these processes have scarcely been the focus of research. The importance of the oxidative stress response and neurological system modifications under isolated conditions has been highlighted. These biological processes, clarified by meta-analysis, are thought to play key roles in the regulation of density-dependent plasticity.Simple SummaryPopulation density can be an environmental cue to induce modification of insect morphology, physiology, and behavior. This phenomenon is called density-dependent plasticity. Aphids and locusts exhibit textbook examples of density-dependent plasticity but there is a lack of integrative understanding for insect density-dependent plasticity. To address this problem, we combined public gene expression data obtained from multiple studies and re-analyzed them (this process is called meta-analysis). The present study provides additional insight into the regulatory mechanisms of density-dependent plasticity, demonstrating the effectiveness of meta-analyses of public transcriptomes.
Integrative multi-omics analysis reveals molecular subtypes and tumor evolution of synovial sarcoma
Authors: Chen Yi , Su Yanhong , Leo Isabelle Rose , Siavelis Ioannis , Zeng Jianming , Cao Xiaofang , Tsagkozis Panagiotis , Hesla Asle C , Papakonstantinou Andri , Liu Xiao , Huang Wen-Kuan , Ehnman Monika , Johansson Henrik , Lin Yingbo , Lehtiö Janne , Zhang Yifan , Larsson Olle , Haglund de Flon Felix 
Published: May 2022

AbstractSynovial sarcomas (SS) are malignant mesenchymal tumors characterized by the SS18-SSX fusion gene, which drives tumorigenesis by altering the composition of the BAF complex. Secondary genomic alterations that determine variations in tumor phenotype or clinical presentation are largely unknown. Herein, we present transcriptome, targeted DNA-sequencing, and proteomics analysis of 91 synovial sarcomas from 55 patients. We identified three SS clusters (SSCs) characterized by distinct histology, tumor microenvironments, genomic complexities, therapeutic effects, and clinical outcomes. Eight BAF complex components are differentially expressed among SSCs, and their role in mesenchymal-epithelial-transition is supported by single cell sequencing. The epithelial cells of biphasic tumors are more susceptible to developing copy number alterations, including amplification of PDCD1 and TMPRSS2. Our findings explain broad concepts in SS biology and imply that the BAF composition at the start of the tumorigenesis (i.e. the cellular linage) may determine the SS subtype, providing a rationale for individualized treatment strategies.
Multi-color live-cell STED nanoscopy of mitochondria with a gentle inner membrane stain
Authors: Liu Tianyan , Stephan Till , Chen Peng , Chen Jingting , Riedel Dietmar , Yang Zhongtian , Jakobs Stefan , Chen Zhixing 
Published: May 2022

AbstractCapturing mitochondria’s intricate and dynamic structure poses a daunting challenge for optical nanoscopy. Different labeling strategies have been demonstrated for live-cell stimulated emission depletion (STED) microscopy of mitochondria, but orthogonal strategies are yet to be established, and image acquisition has suffered either from photodamage to the organelles or from rapid photobleaching. Therefore, live-cell nanoscopy of mitochondria has been largely restricted to 2D single-color recordings of cancer cells. Here, by conjugation of cyclooctatetraene to a benzo-fused cyanine dye, we report a mitochondrial inner-membrane (IM) fluorescent marker, PK Mito Orange (PKMO), featuring efficient STED at 775 nm, strong photostability and markedly reduced phototoxicity. PKMO enables super-resolution recordings of inner-membrane dynamics for extended periods in immortalized mammalian cell lines, primary cells, and organoids. Photostability and reduced phototoxicity of PKMO open the door to live-cell 3D STED nanoscopy of mitochondria for three-dimensional analysis of the convoluted IM. PKMO is optically orthogonal with green and far-red markers allowing multiplexed recordings of mitochondria using commercial STED microscopes. Using multi-color STED, we demonstrate that imaging with PKMO can capture the sub-mitochondrial localization of proteins, or interactions of mitochondria with different cellular components, such as the ER or the cytoskeleton at sub-100 nm resolution. Thereby, this work offers a versatile tool for studying mitochondrial inner-membrane architecture and dynamics in a multiplexed manner.
The synergistic effects of plants and nitrogen on microbial hitchhiking
Authors: Liu Zhibin , Wang Ziyuan , Xia Qini , Zhou Qin , Wu Xiaobo , Kong Wenqing , Lei Wenyan , Zeng Jiayi , Liu Chao , Wang Yongfeng , Chang Wei , Li Zhi , Yang Yi , Yang Liang , Tan Xiao 
Published: May 2022

AbstractMicrobial hitchhiking demonstrates that some nonmotile microbes utilize trans-species motility to traverse their environment; however, whether driving forces, such as plants and nitrogen, affect microbial hitchhiking is not clear. In our study, we explored the effects of plants and nitrogen fertilizer on Bacillus-hitchhiking by setting filter membranes and different nitrogen fertilizer concentration gradients. In the experimental treatment, we added a filter membrane to the soil to prevent hitchhiking. In the absence of plants, nitrogen alone had little influence on motile bacteria and hitchhiking. However, Bacillus contents were significantly impacted by the nitrogen concentration when the plants were rooted, leading to a great variation in cell motility function according to the functional analysis in the soil microbial community. After applying the filter membrane, there were no significant differences in Bacillus contents, microbial community structure or cell motility functional abundance, which illustrated that hitchhiking impacted the microbial community. Our analysis of co-occurrence between bulk soil motile bacteria (Bacillus) and rhizosphere bacteria also confirmed this. The correlation between bulk soil motile bacteria and the rhizosphere microbial community was strong in the groups with suitable nitrogen concentrations without filter membranes and was weak at all nitrogen levels in the no-membrane treatments. Thus, we concluded that plants and different nitrogen doses synergistically altered the soil microbiome by hitchhiking, whose effect depends on nitrogen.
In-silico identification of Tyr232 in AMPKα2 as a dephosphorylation site for the protein tyrosine phosphatase PTP-PEST
Authors: Manikandan Amrutha , Sreevidya T S , Manoj Narayanan , Vemparala Satyavani , Dixit Madhulika 
Published: May 2022

AbstractThe AMP-activated protein kinase (AMPK) is known to be activated by the protein tyrosine phosphatase non-receptor type 12 (PTP-PEST) under hypoxic conditions. This activation is mediated by tyrosine dephosphorylation of the AMPKα subunit. However, the identity of the phosphotyrosine residues remains unknown. In this study we first predicted the structure of the complex of the AMPKα2 subunit and PTP-PEST catalytic domain using bioinformatics tools and further confirm the stability of the complex using molecular dynamics simulations. Evaluation of the protein-protein interfaces indicates that residue Tyr232 is the most likely site of dephosphorylation on AMPKα2. In addition, we explored the effect of phosphorylation of PTP-PEST residue Tyr64 on the stability of the complex. The phosphorylation of Tyr64, an interface residue, enhances the stability of the complex via the rearrangement of a network of electrostatic interactions in conjunction with conformational changes in the catalytic WPD loop. Our findings present a plausible structural basis of AMPK regulation mediated by PTP-PEST and shows how phosphorylation of PTP-PEST could be involved in its activation.
Cell-type specific transcriptomics reveals roles for root hairs and endodermal barriers in interaction with beneficial rhizobacterium
Authors: Verbon Eline H. , Liberman Louisa M. , Zhou Jiayu , Yin Jie , Pieterse Corné M.J. , Benfey Philip N. , Stringlis Ioannis A. , de Jonge Ronnie 
Published: May 2022

AbstractGrowth-promoting bacteria can boost crop productivity in a sustainable way. Pseudomonas simiae WCS417 is a well-studied bacterium that promotes growth of many plant species. Upon colonization, WCS417 affects root system architecture resulting in an expanded root system. Both immunity and root system architecture, are controlled by root-cell-type specific biological mechanisms, but it is unknown how WCS417 affects these mechanisms. Therefore, here, we transcriptionally profiled five Arabidopsis thaliana root cell types following WCS417 colonization. The cortex and endodermis displayed the most differentially expressed genes, even though they were not in direct contact with this epiphytic bacterium. Many of these genes are associated with reduced cell wall biogenesis, possibly facilitating the root architectural changes observed in WCS417-colonized roots. Comparison of the transcriptome profiles in the two epidermal cell types that were in direct contact with WCS417 – trichoblasts that form root hairs and atrichoblasts that don’t – imply functional specialization. Whereas basal expression levels of nutrient uptake-related genes and defense-related genes are highest in trichoblasts and atrichoblasts, respectively, upon exposure to WCS417 these roles revert. This suggests that root hairs participate in the activation of root immunity, further supported by attenuation of immunity in a root hairless mutant. Furthermore, we observed elevated expression of suberin biosynthesis genes and increased deposition of suberin in the endodermis in WCS417-colonized roots. Using an endodermal barrier mutant we show the importance of endodermal barrier integrity for optimal plant-beneficial bacterium association. Altogether, we highlight the strength of cell-type-specific transcriptional profiling to uncover “masked” biological mechanisms underlying successful plant-microbe associations.