bluuebunny/crossref_metadata_2025_split huggingface dataset:
OxoScan-MS: Oxonium ion scanning mass spectrometry facilitates plasma glycoproteomics in large scale
Authors: White Matthew E. H. , Jones D. Marc , de Folter Joost , Aulakh Simran Kaur , Flynn Helen R. , Krüger Lynn , Demichev Vadim , Tober-Lau Pinkus , Kurth Florian , Mülleder Michael , Blanchard Véronique , Messner Christoph B. , Ralser Markus 
Published: June 2022

AbstractProtein glycosylation is a complex and heterogeneous post-translational modification. Specifically, the human plasma proteome is rich in glycoproteins, and as protein glycosylation is frequently dysregulated in disease, glycoproteomics is considered an underexplored resource for biomarker discovery. Here, we present OxoScan-MS, a data-independent mass spectrometric acquisition technology and data analysis software that facilitates sensitive, fast, and cost-effective glycoproteome profiling of plasma and serum samples in large cohort studies. OxoScan-MS quantifies glycosylated peptide features by exploiting a scanning quadrupole to assign precursors to oxonium ions, glycopeptide-specific fragments. OxoScan-MS reaches a high level of sensitivity and selectivity in untargeted glycopeptide profiling, such that it can be efficiently used with fast microflow chromatography without a need for experimental enrichment of glycopeptides from neat plasma. We apply OxoScan-MS to profile the plasma glycoproteomic in an inpatient cohort hospitalised due to severe COVID-19, and obtain precise quantities for 1,002 glycopeptide features. We reveal that severe COVID-19 induces differential glycosylation in disease-relevant plasma glycoproteins, including IgA, fibrinogen and alpha-1-antitrypsin. Thus, with OxoScan-MS we present a strategy for quantitatively mapping glycoproteomes that scales to hundreds and thousands of samples, and report glycoproteomic changes in severe COVID-19.
Increased α-ketoglutarate as a missing link from the C3-C4 intermediate state to C4 photosynthesis in the genus Flaveria
Authors: Tang Qiming , Huang Yuhui , Ni Xiaoxiang , Lyu Ming-Ju Amy , Chen Genyun , Sage Rowan , Zhu Xinguang 
Published: June 2022

ABSTRACTAs a complex trait, C4 photosynthesis has multiple independent origins in evolution. Phylogenetic evidence and theoretical analysis suggest that C2 photosynthesis, which is driven by glycine decarboxylation in the bundle sheath cell, may function as a bridge from C3 towards C4 photosynthesis. However, the exact molecular mechanism underlying the transition between C2 photosynthesis towards C4 photosynthesis remains elusive. Here, we provide multiple evidence suggesting a role of higher α-ketoglutarate (AKG) concentration during this transition. Metabolomic data of 12 Flaveria species, including multiple photosynthetic types, show that AKG concentration initially increases in the C3-C4 intermediate with a further increase in C4 species. Petiole feeding of AKG increased the concentrations of C4 related metabolites in C3-C4 and C4 species but not the activity of C4 related enzymes. Sequence analysis shows that glutamate synthase (Fd-GOGAT), which catalyzes the generation of glutamate using AKG, was under strong positive selection during the evolution of C4 photosynthesis. Simulations with a constraint-based model for C3-C4 intermediate further show that decreasing the activity of Fd-GOGAT facilitates the transition from a C2-dominant to a C4-dominant CO2 concentrating mechanisms. All these provide an insight into the mechanistic switch from C3-C4 intermediate to C4 photosynthesis.
TDP 2 modulates the expression of estrogen-responsive oncogenes
Authors: Manguso Nicholas , Kim Minhyung , Joshi Neeraj , Al Mahmud Rasel , Aldaco Juan , Suzuki Ryusuke , Cortes-Ledesma Felipe , Cui Xiaojiang , Yamada Shintaro , Takeda Shunichi , Giuliano Armando , You Sungyong , Tanaka Hisashi 
Published: June 2022

AbstractWith its ligand estrogen, the estrogen receptor (ER) stimulates tumor cell growth by activating a global transcriptional program. This activation involves topoisomerase 2 (TOP2), which resolves topological problems by transiently creating and re-ligating DNA double-strand breaks (DSBs). Recent studies have uncovered the involvement of DNA repair proteins in the repair of TOP2-induced DSBs. These noncanonical repair pathways may serve as backup processes when TOP2 is halted and fails to re-ligate DSBs, but their impact on transcription remains elusive. In this study, we investigated the role of tyrosyl-DNA phosphodiesterase 2 (TDP2), an enzyme that acts for the removal of halted TOP2 from the 5’-end of the DNA, in the estrogen-induced transcriptome. Using TDP2-deficient ER-positive cells and mice, we showed that TDP2 regulates the expression of oncogeneMYC.MYCinduction by estrogen was a very early event (1 hour) and TOP2-dependent. In TDP2-deficient cells, the induction ofMYCby estrogen became prolonged and volatile. Bulk and single-cell RNA-seq identified the oncogenesMYCandCCND1as genes whose estrogen response was regulated by TDP2. These results suggest that TDP2 may play a role in the repair of TOP2-induced DSBs in specific genomic loci and tightly regulates the expression of oncogenes.
Long-read HiFi Sequencing Correctly Assembles Repetitive heavy fibroin Silk Genes in New Moth and Caddisfly Genomes
Authors: Kawahara Akito Y. , Storer Caroline G. , Markee Amanda , Heckenhauer Jacqueline , Powell Ashlyn , Plotkin David , Hotaling Scott , Cleland Timothy P. , Dikow Rebecca B. , Dikow Torsten , Kuranishi Ryoichi B. , Messcher Rebeccah , Pauls Steffen U. , Stewart Russell J. , Tojo Koji , Frandsen Paul B. 
Published: June 2022

AbstractInsect silk is an incredibly versatile biomaterial. Lepidoptera and their sister lineage, Trichoptera, display some of the most diverse uses of silk with varying strength, adhesive qualities and elastic properties. It is well known that silk fibroin genes are long (> 20 kb) and have many repetitive motifs. These features make these genes challenging to sequence. Most research thus far has focused on conserved N- and C-terminal regions of fibroin genes because a full comparison of repetitive regions across taxa has not been possible. Using the PacBio Sequel II system and SMRT sequencing, we generated high fidelity (HiFi) long-read genomic and transcriptomic sequences for the Indianmeal moth (Plodia interpunctella) and genomic sequences for the caddisfly, Eubasilissa regina. Both genomes were highly contiguous (N50 = 9.7 Mbp/32.4 Mbp, L50 = 13/11) and complete (BUSCO Complete = 99.3%/95.2%), with complete and contiguous recovery of silk heavy fibroin gene sequences. This study demonstrates that HiFi long-read sequencing can significantly help our understanding of genes with highly contiguous, repetitive regions.
Beyond the Delay Neural Dynamics: a Decoding Strategy for Working Memory Error Reduction
Authors: Ye Zeyuan , Li Haoran , Tian Liang , Zhou Changsong 
Published: June 2022

AbstractUnderstanding how the brain preserves information despite intrinsic noise is a fundamental question in working memory. Typical working memory tasks consist of delay phase for maintaining information, and decoding phase for retrieving information. While previous works have focused on the delay neural dynamics, it is poorly understood whether and how the neural process during decoding phase reduces memory error. We studied this question by training recurrent neural networks (RNNs) on a color delayed-response task. We found that the trained RNNs reduce the memory error of high-probability-occurring colors (common colors) by decoding/attributing a broader range of neural states to them during decoding phase. This decoding strategy can be further explained by a continuing converging neural dynamics following delay phase and a non-dynamic biased readout process. Our findings highlight the role of the decoding phase in working memory, suggesting that neural systems deploy multiple strategies across different phases to reduce memory errors.SignificancePreserving information under noise is crucial in working memory. A typical working memory task consists of a delay phase for maintaining information, and a decoding phase for decoding the maintained into an output action. While the delay neural dynamics have been intensively studied, the impact of the decoding phase on memory error reduction remains unexplored. We trained recurrent neural networks (RNNs) on a color delayed-response task and found that RNNs reduce memory error of a color by decoding a larger portion of the neural state to that color. This strategy is supported both by a converging neural dynamic, and a non-dynamic readout process. Our results suggest that neural networks can utilize diverse strategies, beyond delay neural dynamics, to reduce memory errors.
Dynamin forms liquid-like condensates at synapses to support ultrafast endocytosis
Authors: Imoto Yuuta , Ma Ye , Itoh Kie , Blumrich Eva-Maria , Matsubayashi Hideaki T. , Liu Jian , Wu Bin , Cousin Michael A. , Ha Taekjip , Inoue Takanari , Watanabe Shigeki 
Published: June 2022

SummaryEndocytosis at synapses is accelerated by the pre-accumulation of Dynamin 1xA at the endocytic zone by Syndapin 1. However, it is unclear how these proteins support the ultrafast kinetics of endocytosis. Here we report that these proteins phase separate at the presynaptic endocytic zone where ultrafast endocytosis takes place. Specifically, the proline-rich motif of Dynamin 1xA interacts with the Src-Homology 3 domain of Syndapin 1 and forms liquid-like condensates. Single-particle tracking of Dynamin 1xA molecules at synapses shows that their diffusion slows down substantially when they are in the condensates, indicating the presence of molecular crowding and intermolecular interaction. When Dynamin 1xA is mutated to disrupt its interaction with Syndapin 1 the condensates do not form. Thus, the liquid-like assembly of these endocytic proteins provides a catalytic platform for ultrafast endocytosis.
Cholecystokinin-expressing (CCK+) basket cells are key controllers of theta-gamma coupled rhythms in the hippocampus
Authors: Chatzikalymniou Alexandra P , Sengupta Spandan , Lefebvre Jeremie , Skinner Frances K 
Published: June 2022

AbstractVarious inhibitory cell types underlie cognitively important brain rhythms and their couplings. Precisely how this is manifest is unclear. Complex network interactions make an understanding of inhibitory cell contributions extremely difficult and using experiments alone is insufficient. Using detailed biophysical models, we obtain hypotheses of how theta and gamma rhythms in the hippocampus are generated and coupled. We find critical contributions by parvalbumin-expressing (PV+) basket cells (BCs), cholecystokinin-expressing (CCK+) BCs and bistratified cells. Based on this, we develop and explore a population rate model and predict that CCK+BCs exert more control relative to PV+BCs for theta-gamma coupling, and that theta frequencies are more strongly affected by PV+BC to CCK+BC coupling relative to CCK+BC to PV+BC. As specific inhibitory cell types can be targeted during behaviour, it is possible to test these predictions. Our work shows that combining models at different scales creates new insights that otherwise would not be revealed.
Ankyrin-B is lipid-modified by S-palmitoylation to promote dendritic membrane scaffolding of voltage-gated sodium channel Nav1.2 in neurons
Authors: Gupta Julie P. , Jenkins Paul M. 
Published: June 2022

ABSTRACTNeuronal ankyrin-B is an intracellular scaffolding protein that plays multiple roles in the axon. By contrast, relatively little is known about the function of ankyrin-B in dendrites, where ankyrin-B is also localized in mature neurons. Recently, we showed that ankyrin-B acts as a scaffold for the voltage-gated sodium channel, NaV1.2, in dendrites of neocortical pyramidal neurons. How ankyrin-B is itself targeted to the dendritic membrane is not well understood. Here, we report that ankyrin-B is lipid-modified by S-palmitoylation to promote dendritic localization of NaV1.2. We identify the palmitoyl acyl transferase zDHHC17 as a key mediator of ankyrin-B palmitoylation in heterologous cells and in neurons. Additionally, we find that zDHHC17 regulates ankyrin-B protein levels independently of its S-acylation function through a conserved binding mechanism between the ANK repeat domain of zDHHC17 and the zDHHC ankyrin-repeat binding motif of ankyrin-B. We subsequently identify five cysteines in the N-terminal ankyrin repeat domain of ankyrin-B that are necessary for ankyrin-B palmitoylation. Mutation of these five cysteines to alanines not only abolishes ankyrin-B palmitoylation, but also prevents ankyrin-B from scaffolding Nav1.2 at dendritic membranes of neurons due to ankyrin-B’s inability to localize properly at dendrites. Thus, we show palmitoylation is critical for localization and function of ankyrin-B at dendrites. Strikingly, loss of ankyrin-B palmitoylation does not affect ankyrin-B-mediated axonal cargo transport of synaptic vesicle synaptotagmin-1 in neurons. This is the first demonstration of S-palmitoylation of ankyrin-B as an underlying mechanism required for ankyrin-B localization and function in scaffolding Nav1.2 at dendrites.
Sentieon DNAscope LongRead – A highly Accurate, Fast, and Efficient Pipeline for Germline Variant Calling from PacBio HiFi reads
Authors: Freed Donald , Rowell William J. , Wenger Aaron M. , Li Zhipan 
Published: June 2022

AbstractPacBio® HiFi sequencing is the first technology to offer economical and highly accurate long-read sequencing, with average read lengths greater than 10kb and average base accuracy of 99.8%1. Here, we present DNAscope LongRead, an accurate and efficient pipeline for germline variant calling from PacBio® HiFi reads. DNAscope LongRead is a modification and extension of Sentieon’s DNAscope tool, a precisionFDA award-winning variant caller. DNAscope LongRead is computationally efficient, calling variants from 30x HiFi samples in under 4 hours on a 16-core machine (120 virtual core-hours) and highly accurate, with precision and recall on the most recent GIAB benchmark dataset exceeding 99.83% for HiFi samples sequenced at 30x coverage, and robust to changes in benchmark dataset and upstream library preparation and sequencing.
Mystery of fatal ‘Staggering disease’ unravelled: Novel rustrela virus causes severe encephalomyelitis in domestic cats
Authors: Matiasek Kaspar , Pfaff Florian , Weissenböck Herbert , Wylezich Claudia , Kolodziejek Jolanta , Tengstrand Sofia , Ecke Frauke , Nippert Sina , Starcky Philip , Litz Benedikt , Nessler Jasmin , Wohlsein Peter , Baumbach Christina , Mundhenk Lars , Aebischer Andrea , Reiche Sven , Weidinger Pia , Olofsson Karin M. , Rohdin Cecilia , Weissenbacher-Lang Christiane , Matt Julia , Rosati Marco , Flegel Thomas , Hörnfeldt Birger , Höper Dirk , Ulrich Rainer G. , Nowotny Norbert , Beer Martin , Ley Cecilia , Rubbenstroth Dennis 
Published: June 2022

ABSTRACT‘Staggering disease’ is a neurological disorder considered a threat to European domestic cats (Felis catus) for almost five decades. However, its aetiology has remained obscure. Rustrela virus (RusV), a relative of rubella virus, has recently been shown to be associated with encephalitis in a broad range of mammalian hosts. Here, we report the detection of RusV RNA and antigen by metagenomic sequencing, RT-qPCR, in-situ hybridization and immunohistochemistry in brain tissues of 28 out of 29 cats with non-suppurative meningoencephalomyelitis and ‘staggering disease’-like neurological disorder from Sweden, Austria, and Germany, but not in non-affected control cats. Screening of possible reservoir hosts in Sweden revealed RusV infection in wood mice (Apodemus sylvaticus). Our work strongly indicates RusV as the long-sought cause of feline ‘staggering disease’. Given its broad host spectrum and considerable geographic range, RusV may be the aetiological agent of neuropathologies in further mammals, possibly even including humans.
Elemental diet enriched in amino acids alters gut microbial community and prevents colonic mucus degradation in mice with colitis
Authors: Zhang Bowei , Zhao Congying , Zhang Yunhui , Zhang Xuejiao , Li Xiang , Liu Xiaoxia , Yin Jia , Li Xinyang , Wang Jin , Wang Shuo 
Published: June 2022

AbstractThe role of dietary amino acids or intact proteins in the progression of colitis remains controversial, and the mechanism involving gut microbes is unclear. Here, we investigated the effects of an elemental diet (ED) enriched in amino acids and a polymeric diet enriched in intact protein on the pathogenesis of DSS-induced colitis in mice. Our results showed that ED induced remission of colitis in mice. Notably, ED treatment reduced the abundance of the mucolytic bacteria Akkermansia and Bacteroides, which was attributed to the decreased colonic protein fermentation. Consistently, the activities of mucolytic enzymes were decreased, leading to the protection of mucus layer degradation and microbial invasion. The fecal microbiota transplantation of ED-fed mice reshaped microbial ecology and alleviated intestinal inflammation in recipient mice. ED failed to induce remission of colitis in pseudo-germ-free mice. Together, we convincingly demonstrated the critical role of gut microbiota in the prevention of ED on colitis.ImportanceThe prevalence of inflammatory bowel disease is rapidly increasing and has become a global burden. Several specific amino acids have been shown to benefit mucosal healing and colitis remission. However, the role of amino acids or intact proteins in diets and enteral nutrition formulas is controversial, and the mechanisms involving gut microbes remain unclear. In this study, we investigated the effects of an elemental diet (ED) enriched in amino acids and a polymeric diet enriched in intact protein on the pathogenesis of colitis in mice. The underlying mechanisms were explored by utilizing fecal microbiota transplantation and pseudo-germ-free mice. ED treatment reduced the abundance of mucolytic bacteria, thereby protecting the mucus layer from microbial invasion and degradation. For the first time, we convincingly demonstrated the critical role of gut microbiota in the effects of ED. This study may provide new insights into the gut microbiota-diet interaction in human health.
Plant signals anticipate the induction of the type III secretion system inPseudomonas syringaepv.actinidiaefacilitating efficient temperature-dependent effector translocation
Authors: Puttilli Maria Rita , Danzi Davide , Correia Cristiana , Brandi Jessica , Cecconi Daniela , Manfredi Marcello , Marengo Emilio , Santos Conceição , Spinelli Francesco , Polverari Annalisa , Vandelle Elodie 
Published: June 2022

AbstractDisease resistance in plants depends on a molecular dialogue with microbes that involves many known chemical effectors, but the time course of the interaction and the influence of the environment are largely unknown. The outcome of host–pathogen interactions is thought to reflect the offensive and defensive capabilities of both players. When plants interact withPseudomonas syringae, several well-characterized virulence factors contribute to early bacterial pathogenicity, including the type III secretion system (T3SS), which must be activated by signals from the plant and environment to allow the secretion of virulence effectors. The manner in which these signals regulate T3SS activity is still unclear. Here, we strengthen the paradigm of the plant–pathogen molecular dialogue by addressing overlooked details concerning the timing of interactions, specifically the role of plant signals and temperature on the regulation of bacterial virulence during the first few hours of the interaction. Whole-genome expression profiling after 1 h revealed that the perception of plant signals from kiwifruit or tomato extracts anticipates T3SS expression inP. syringaepv.actinidiaecompared to apoplast-like conditions, facilitating more efficient effector transportin planta, as revealed by the induction of a temperature-dependent hypersensitive response in the non-host plantArabidopsis thalianaCol-0. Our results show that, in the arms race between plants and bacteria, the temperature-dependent timing of bacterial virulence versus the induction of plant defenses is probably one of the fundamental parameters governing the outcome of the interaction.Abstract importancePlant diseases– their occurrence and severity– result from the impact of three factors: the host, the pathogen, and the environmental conditions, interconnected in the disease triangle. Time was further included as a fourth factor accounting for plant disease, leading to a more realistic three-dimensional disease pyramid to represent the evolution of disease over time. However, this representation still considers time only as a parameter determining when and to which extent a disease will occur, at a scale from days to months. Here, we show that time is a factor regulating the arms race between plants and pathogens, at a scale from minutes to hours, and strictly depends on environmental factors. Thus, besides the arms possessed by pathogens and plants per se, the opportunity and the timing of arms mobilization should make the difference to determine the outcome of an interaction and thus the occurrence of plant disease.
Iron status and the risk of sepsis and severe COVID-19: A two-sample Mendelian randomization study
Authors: Mohus Randi Marie , Flatby Helene , Liyanarachi Kristin V. , DeWan Andrew T. , Solligård Erik , Damås Jan Kristian , Åsvold Bjørn Olav , Gustad Lise T. , Rogne Tormod 
Published: June 2022

AbstractIntroductionObservational studies have indicated an association between iron status and risk of sepsis and severe COVID-19. However, these findings may be affected by residual confounding, reverse causation.MethodsIn a two-sample Mendelian randomization study using inverse variance weighted method, we estimated the effect of genetically-predicted iron biomarkers (serum iron, transferrin saturation (TSAT), total iron binding capacity (TIBC) and ferritin) on risk of sepsis and risk of being hospitalized with COVID-19. For the COVID-19 outcomes we additionally conducted sex-stratified analyses. Weighted median, Weighted mode and MR Egger were used as sensitivity analyses.ResultsFor risk of sepsis, one standard deviation increase in genetically-predicted serum iron was associated with odds ratio (OR) of 1.14 (95% confidence interval [CI] 1.01 to 1.29,P=0.031). The findings were supported in the analyses for transferrin saturation and total iron binding capacity, while the estimate for ferritin was inconclusive. We found a tendency of higher risk of hospitalization with COVID-19 for serum iron; OR 1.29 (CI 0.97–1.72,P=0.08), where sex stratified analyses showed OR 1.63 (CI 0.94–2.86,P=0.09) for women and OR 1.21 (CI 0.92–1.62,P=0.17) for men. Sensitivity analyses supported the main findings and did not suggest bias due to pleiotropy.ConclusionsOur findings suggest a causal effect of genetically-predicted higher iron status and risk of hospitalization due to sepsis and indications of an increased risk of being hospitalized with COVID-19. These findings warrant further studies to assess iron status in relation to severe infections, including the potential of improved management.