bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokinin response induces immunity and fungal pathogen resistance in tomato by modulating cellular trafficking of PRRs
Authors: Gupta Rupali , Pizarro Lorena , Leibman-Markus Meirav , Marash Iftah , Bar Maya 
Published: March 2020

AbstractPlant immunity is often defined by the “immunity hormones”: salicylic acid (SA), jasmonic acid (JA), and ethylene (ET). These hormones are well known for differentially regulating defense responses against pathogens. In recent years, the involvement of other plant growth hormones such as auxin, gibberellic acid, abscisic acid, and cytokinins (CKs) in biotic stresses has been recognized. Previous reports have indicated that endogenous and exogenous CK treatment can result in pathogen resistance. We show here that CK induces systemic tomato immunity, modulating cellular trafficking of the PRR LeEIX2 and promoting biotrophic and necrotrophic pathogen resistance in an SA and ET dependent mechanism. CK perception within the host underlies its protective effect. Our results support the notion that CK acts as a priming agent, promoting pathogen resistance by inducing immunity in the host.
Accelerating Maximal-Exact-Match Seeding with Enumerated Radix Trees
Authors: Subramaniyan Arun , Wadden Jack , Goliya Kush , Ozog Nathan , Wu Xiao , Narayanasamy Satish , Blaauw David , Das Reetuparna 
Published: March 2020

ABSTRACTMotivationRead alignment is a time-consuming step in genome sequence analysis. In the read alignment software BWA-MEM and the recently published faster version BWA-MEM2, the seeding step is a major bottleneck, for instance, contributing 38% to the overall execution time in BWA-MEM2 when aligning single-end whole human genome reads from the Platinum Genomes dataset. This is because both BWA-MEM and BWA-MEM2 use a compressed index structure called the FMD-Index, which results in high memory bandwidth requirements for seeding, primarily due to its character-by-character processing of reads.ResultsWe propose a memory bandwidth-aware data structure for maximal-exact-match seeding called Enumerated Radix Tree (ERT). ERT trades off memory capacity to improve seeding performance (∼60 GB index for human genome). Together with optimizations to the seeding algorithm and mate-rescue step, ERT when integrated into BWA-MEM2 speeds up overall read alignment by 1.28× and provides up to 2.1× higher seeding performance while guaranteeing identical output to the original software. Furthermore, we prototype an FPGA implementation of ERT on Amazon EC2 F1 cloud and observe 1.6× higher seeding throughput over a 48-thread optimized CPU-ERT implementation.Availability and implementationhttps://github.com/arun-sub/bwa-mem2Contactarunsub@umich.edu,reetudas@umich.edu
Conspicuous candidate alleles point tocis-regulatory divergence underlying rapidly evolving craniofacial phenotypes
Authors: McGirr Joseph A. , Martin Christopher H. 
Published: March 2020

AbstractDeveloping a mechanistic understanding of genetic variation contributing to variation in complex craniofacial traits is a major goal of both basic and translational research. Investigating closely related species that evolved divergent feeding morphology is a powerful approach to identify genetic variation underlying natural and clinical variation in human craniofacial phenotypes. We combined whole-genome resequencing of 258 individuals with 50 transcriptomes to identify candidatecis-acting genetic variation influencing rapidly evolving craniofacial phenotypes within an adaptive radiation ofCyprinodonpupfishes. This radiation consists of a dietary generalist species and two derived trophic niche specialists – a molluscivore and a scale-eating species. Despite extensive morphological divergence, these species only diverged 10 kya and produce fertile hybrids in the laboratory. Out of 9.3 million genome-wide SNPs and 80,012 structural variants, we found very few alleles fixed between species – only 157 SNPs and 87 deletions. Comparing gene expression across 38 purebred F1 offspring sampled at three early developmental stages, we identified 17 fixed variants within 10 kb of 12 genes that were highly differentially expressed between species. By measuring allele-specific expression in F1 hybrids from multiple crosses, we found strong evidence for twocis-regulatory alleles affecting expression divergence of two genes with putative effects on skeletal development (dync2li1andpycr3). These results suggest that SNPs and structural variants contribute to the evolution of novel traits and highlight the utility of the San Salvador pupfish system as an evolutionary model for craniofacial development.
WalkingDrosophilanavigate complex plumes using stochastic decisions biased by the timing of odor encounters
Authors: Demir Mahmut , Kadakia Nirag , Anderson Hope D. , Clark Damon A. , Emonet Thierry 
Published: March 2020

ABSTRACTInsects find food, mates, and egg-laying sites by tracking odor plumes swept by complex wind patterns. Previous studies have shown that moths and flies localize plumes by surging upwind at odor onset and turning cross- or downwind at odor offset. Less clear is how, once within the expanding cone of the odor plume, insects use their brief encounters with individual odor packets, whose location and timing are random, to progress towards the source. Experiments and theory have suggested that the timing of odor encounters might assist navigation, but connecting behaviors to individual encounters has been challenging. Here, we imaged complex odor plumes simultaneous with freely-walking flies, allowing us to quantify how behavior is shaped by individual odor encounters. Combining measurements, dynamical models, and statistical inference, we found that within the plume cone, individual encounters did not trigger reflexive surging, casting, or counterturning. Instead, flies turned stochastically with stereotyped saccades, whose direction was biased upwind by the timing of prior odor encounters, while the magnitude and rate of saccades remained constant. Odor encounters did not strongly affect walking speed. Instead, flies used encounter timing to modulate the rate of transitions between walks and stops. When stopped, flies initiated walks using information from multiple odor encounters, suggesting that integrating evidence without losing position was part of the strategy. These results indicate that once within the complex odor plume, where odor location and timing are unpredictable, animals navigate with biased random walks shaped by the entire sequence of encounters.
Glycoengineering of NK cells with glycan ligands of CD22 and selectins for B-cell lymphoma therapy
Authors: Hong Senlian , Yu Chenhua , Wang Peng , Shi Yujie , Cheng Bo , Chen Mingkuan , Chapla Digantkumar G. , Reigh Natalie , Narimatsu Yoshiki , Chen Xing , Clausen Henrik , Moremen Kelly W. , Macauley Matthew Scott , Paulson James C. , Wu Peng 
Published: March 2020

ABSTRACTCD22, a member of Siglec family of sialic acid binding proteins, has restricted expression on B cells. Antibody-based agents targeting CD22 or CD20 (Rituxan™) on B lymphoma and leukemia cells exhibit clinical efficacy for treating these malignancies, but also attack normal B cells leading to immune deficiency. Here, we report a chemoenzymatic glycocalyx editing strategy to introduce high-affinity and specific CD22 ligands onto NK-92MI and cytokine-induced killer (CIK) cells to achieve tumor-specific CD22 targeting. These CD22-ligand modified cells exhibited significantly enhanced tumor cell binding and killingin vitrowithout harming healthy B cells. For effective lymphoma cell killing in vivo we further functionalized CD22 ligand-modified NK-92MI cells with the E-selectin ligand sialyl Lewis X to promote trafficking to bone marrow. The cells containing the ligands of both CD22 and selectins resulted in the efficient suppression of B lymphoma in a xenograft model. Our results suggest that NK cells modified with glycan ligands to CD22 and selectins promote both targeted killing of B lymphoma cells and improved trafficking to sites where the cancer cells reside, respectively.
Characterization of amyloid β fibril formation under microgravity conditions
Authors: Yagi-Utsumi Maho , Yanaka Saeko , Song Chihong , Satoh Tadashi , Yamazaki Chiaki , Kasahara Haruo , Shimazu Toru , Murata Kazuyoshi , Kato Koichi 
Published: March 2020

AbstractAmyloid fibrils are self-assembled and ordered proteinaceous supramolecules structurally characterized by the cross-β spine. Amyloid formation is known to be related to various diseases typified by neurogenerative disorders and involved in a variety of functional roles. Whereas common mechanisms for amyloid formation have been postulated across diverse systems, the mesoscopic morphology of the fibrils is significantly affected by the type of solution condition in which it grows. Amyloid formation is also thought to share a phenomenological similarity with protein crystallization. While many studies have demonstrated the effect of gravity on protein crystallization, its effect on amyloid formation has not been reported. In this study, we conducted an experiment at the International Space Station (ISS) to characterize fibril formation of 40-residue amyloid β (Aβ(1-40)) under microgravity conditions. Our comparative analyses revealed that the Aβ(1-40) fibrilization progresses much more slowly on the ISS than on the ground, similarly to protein crystallization. Furthermore, microgravity promoted the formation of distinct morphologies of Aβ(1-40) fibrils. Our findings demonstrate that the ISS provides an ideal experimental environment for detailed investigations of amyloid formation mechanisms by eliminating the conventionally uncontrollable factors derived from gravity.
HELLO: A hybrid variant calling approach
Authors: Ramachandran Anand , Lumetta Steven S. , Klee Eric , Chen Deming 
Published: March 2020

AbstractNext Generation Sequencing (NGS) technologies that cost-effectively characterize genomic regions and identify sequence variations using short reads are the current standard for genome sequencing. However, calling small indels in low-complexity regions of the genome using NGS is challenging. Recent advances in Third Generation Sequencing (TGS) provide long reads, which call large-structural variants accurately. However, these reads have context-dependent indel errors in low-complexity regions, resulting in lower accuracy of small indel calls compared to NGS reads. When both small and large-structural variants need to be called, both NGS and TGS reads may be available. Integration of the two data types with unique error profiles could improve robustness of small variant calling in challenging cases. However, there isn’t currently such a method integrating both types of data. We present a novel method that integrates NGS and TGS reads to call small variants. We leverage the Mixture of Experts paradigm which uses an ensemble of Deep Neural Networks (DNN), each processing a different data type to make predictions. We present improvements in our DNN design compared to previous work such as sequence processing using one-dimensional convolutions instead of image processing using two-dimensional convolutions and an algorithm to efficiently process sites with many variant candidates, which help us reduce computations. Using our method to integrate Illumina and PacBio reads, we find a reduction in the number of erroneous small variant calls of up to ~30%, compared to the state-of-the-art using only Illumina data. We also find improvements in calling small indels in low-complexity regions.
Genetic Diversity and Population Structure in the Ryukyu Flying Fox Inferred from Remote Sampling in the Yaeyama Archipelago
Authors: Taki Yuto , Vincenot Christian E. , Sato Yu , Inoue-Murayama Miho 
Published: March 2020

AbstractThe Ryukyu flying fox (Pteropus dasymallus) is distributed throughout the island chain spanning across southern Japan, Taiwan, and possibly the Philippines. AlthoughP. dasymallusis listed as VU (vulnerable) in the IUCN Red List, only few genetic works have been conducted to support its conservation. In this study we analyzed 19 markers (mtDNA haplotypes and 18 microsatellite markers) to evaluate genetic diversity and investigate the genetic structure of this species.mtDNA analysis was conducted with 142 DNA remote samples, mostly from feces, and wing tissues collected on eight islands (Miyako, Ishigaki, Kohama, Kuroshima, Hateruma, Taketomi, Iriomote, Yonaguni). 39 haplotypes were identified in 526bp of the control region, and haplotype network showed no clear genetic structure.Microsatellite analysis was also conducted with 155 samples collected on six islands (Miyako, Ishigaki, Kohama, Taketomi, Iriomote, Yonaguni). It showed that the Yonaguni population exhibits low genetic diversity, high inbreeding, and clear genetic differentiation from other populations. Gene flow between Ishigaki and Miyako through small stepstone islands might be preventing inbreeding of the Miyako population.We provide for the first time indirect proof of long-distance inter-island dispersal in the Ryukyu flying fox and revealed genetic diversity, gene flow and genetic differentiation among populations of the archipelago. These results will be useful for delineating conservation units and designing specific conservation policies for each island based on metapopulation genetic structure.
Reusable and Sensitive Detection Method for Exonuclease III Activity by DNB Nanoarrays Based on cPAS Sequencing Technology
Authors: Chen Ying , Wang Hui , Yang Jin , Yang Huanming , Drmanac Radoje , Xu Chongjun , Zhang Wenwei 
Published: March 2020

AbstractionIn this article, we have designed a sensitive and recycled DNB (DNA nanoball) nanoarrays sequencing complex structures based on BGISEQ-500RS sequencer for the monitoring performance of Exo III activity. In the shortage of Exo III, the effective number ratio of DNB would be captured by an optical system due to one fluorescent. In contrast, in the presence of Exo III, some DNB would disappear or discard from the fields of the optical system by fluorescence extinction and uncleaned fluorescent, respectively. As a result, the effective number of DNB of this strategy was relative to the concentration of Exo III. For Exo III, our strategy showed a highly sensitive linear response in the low detection range of 0.01 U/mL to 0.5 U/mL, with detection limits below 0.01 U/mL. With the comparison between DNB nanoarrays and other fluorescent sensors, this study possessed superior sensitivity, selectivity, and reusability, accompanying with the low cost and simple setup.
IL8 Drives an Elaborate Signal Transduction Process for CD38 to Produce NAADP from NAAD and NADP+in Endolysosomes to Effect Cell Migration
Authors: Nam Tae-Sik , Park Dae-Ryoung , Rah So-Young , Woo Tae-Gyu , Chung Hun Taeg , Brenner Charles , Kim Uh-Hyun 
Published: March 2020

AbstractNicotinic acid adenine dinucleotide phosphate (NAADP) is an obligate driver of calcium signaling whose formation from other metabolites of nicotinamide adenine dinucleotide (NAD+) has remained elusive.In vitro, CD38-mediated NAADP synthesis requires an acidic pH and a nonphysiological concentration of nicotinic acid (NA). We discovered that the type II membrane form of CD38 catalyzes synthesis of NAADP by exchanging the nicotinamide moiety of nicotinamide adenine dinucleotide phosphate (NADP+) for the NA group of nicotinic acid adenine dinucleotide (NAAD) inside endolysosomes of interleukin 8 (IL8)-treated lymphokine-activated killer cells. Upon IL8 stimulation, cytosolic NADP+is transported to acidified endolysosomes via connexin 43 via cAMP-EPAC-RAP1-PP2A signaling. Luminal CD38 then performs a base exchange reaction with the donor NA group deriving from NAAD, produced by newly described endolysosomal activities of NA phosphoribosyltransferase and NMN adenyltransferase 3. Thus, the membrane organization of endolysosomal CD38, a signal-mediated transport system for NADP+and luminal NAD+biosynthetic enzymes integrate signals from a chemokine and cAMP to specify the spatiotemporal mobilization of calcium to drive cell migration.
An allosteric interaction controls the activation mechanism of SHP2 tyrosine phosphatase
Authors: Anselmi Massimiliano , Hub Jochen S. 
Published: March 2020

ABSTRACTSHP2 is a protein tyrosine phosphatase (PTP) involved in multiple signaling pathways. Mutations of SHP2 can result in Noonan syndrome or pediatric malignancies. Inhibition of wild-type SHP2 represents a novel strategy against several cancers. SHP2 is activated by binding of a phosphopeptide to the N-SH2 domain of SHP2, thereby favoring dissociation of the N-SH2 domain and exposing the active site on the PTP domain. The conformational transitions controlling ligand affinity and PTP dissociation remain poorly understood. Using molecular simulations, we revealed an allosteric interaction restraining the N-SH2 domain into a SHP2-activating and a stabilizing state. Only ligands selecting for the activating N-SH2 conformation, depending on ligand sequence and binding mode, are effective activators. We validate the model of SHP2 activation by rationalizing modified basal activity and responsiveness to ligand stimulation of several N-SH2 variants. This study provides mechanistic insight into SHP2 activation and may open routes for SHP2 regulation.
Protective effect of agmatine against cisplatin-induced apoptosis in an auditory cell line
Authors: Park Euyhyun , Lee Se Hee , Lee Hoyoung , Kim Young-Chan , Jung Hak Hyun , Im Gi Jung 
Published: March 2020

AbstractObjectivesAgmatine, an endogenous metabolite of arginine, is known to have antioxidant activity, protect mitochondrial function, and confer resistance to cellular apoptosis. The aim of this study was to evaluate the protective effects of agmatine against cisplatin-induced cellular apoptosis in an auditory cell line.MethodsHEI-OC1 cells were co-treated with agmatine at different concentrations and 15 µM cisplatin for 48 h. Cell viability was measured and annexin V-FITC/propidium iodide (PI) staining was performed to analyze apoptosis. The levels of intracellular reactive oxygen species (ROS) were measured using flow cytometry. The expression of BAX (Bcl2-associated X protein) and the enzymatic activity of caspase-3 were measured to examine the pathway of apoptosis induction.ResultsCo-treatment with 8 mM agmatine protected HEI-OC1 cells against cisplatin-induced cell apoptosis. Agmatine exerted a significant protective effect against 15 µM cisplatin when applied for 48 h and reduced the proportion of necrotic and late apoptotic cells. Agmatine did not reduce the cisplatin-induced increase in ROS but decreased the expression of BAX and the activity of caspase-3.ConclusionsAgmatine protected against cisplatin-induced cellular apoptosis in an auditory cell line. These effects were mediated by the protection of mitochondrial function and inhibition of apoptosis.
Phylogenetic diversity of 200+ isolates of the ectomycorrhizal fungusCenococcum geophilumassociated withPopulus trichocarpasoils in the Pacific Northwest, USA and comparison to globally distributed representatives
Authors: Vélez Jessica M. , Morris Reese M. , Vilgalys Rytas , Labbé Jessy , Schadt Christopher W. 
Published: March 2020

AbstractThe ectomycorrhizal fungal symbiontCenococcum geophilumis of great interest as it is globally distributed, associates with many plant species, and has resistance to multiple environmental stressors.C. geophilumis only known from asexual states but is often considered a cryptic species complex, since extreme phylogenetic divergence is often observed within morphologically identical strains. Alternatively,C. geophilummay represent a highly diverse single species, which would suggest cryptic but frequent recombination. Here we describe a new isolate collection of 229C. geophilumisolates from soils underPopulus trichocarpaat 123 collection sites spanning a ~283 mile north-south transect in Washington and Oregon, USA (PNW). To further understanding of the phylogenetic relationships withinC. geophilum, we performed maximum likelihood phylogenetic analyses to assess divergence within the PNW isolate collection, as well as a globalGAPDHphylogenetic analysis of 789 isolates with publicly available data from the United States, Europe, Japan, and other countries. Phylogenetic analyses of the PNW isolates revealed three distinct phylogenetic groups, with 15 clades that strongly resolved at >80% bootstrap support based on aGAPDHphylogeny and one clade segregating strongly in two principle component analyses. The abundance and representation of PNW isolate clades varied greatly across the North-South range, including a monophyletic group of isolates that spanned nearly the entire gradient at ~250 miles. A direct comparison between theGAPDHand ITS phylogenies combined with additional analyses revealed stark incongruence between the ITS andGAPDHgene regions, implicating probable intra-species recombination between PNW isolates. In the global isolate collection phylogeny, 34 clades were strongly resolved at >80% bootstrap support, with some clades having intra- and intercontinental distributions. These data are highly suggestive of divergence within multiple cryptic species, however additional analyses such as higher resolution genotype-by-sequencing approaches are needed to distinguish potential species boundaries and recombination patterns.
Supertertiary protein structure affects an allosteric network
Authors: Laursen Louise , Kliche Johanna , Gianni Stefano , Jemth Per 
Published: March 2020

AbstractThe notion that protein function is allosterically regulated by structural or dynamic changes in proteins has been extensively investigated in several protein domains in isolation. In particular, PDZ domains have represented a paradigm for these studies, despite providing conflicting results. Furthermore, it is still unknown how the association between protein domains in supramodules, consitituting so-called supertertiary structure, affects allosteric networks. Here, we experimentally mapped the allosteric network in a PDZ:ligand complex, both in isolation and in the context of a supramodular structure, and show that allosteric networks in a PDZ domain are highly dependent on the supertertiary structure in which they are present. This striking sensitivity of allosteric networks to presence of adjacent protein domains is likely a common property of supertertiary structures in proteins. Our findings have general implications for prediction of allosteric networks from primary and tertiary structure and for quantitative descriptions of allostery.