bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two groups ofArabidopsisreceptor kinases preferentially regulate the growth of intraspecies pollen tubes in the female reproductive tract
Authors: Lee Hyun Kyung , Goring Daphne R. 
Published: March 2020

SummaryIn flowering plants, continuous cell-cell communication between the compatible male pollen grain/growing pollen tube and the female pistil is required for successful sexual reproduction. InArabidopsis thaliana, the later stages of this dialogue are mediated by several peptide ligands and receptor kinases that guide pollen tubes to the ovules for the release of sperm cells. Despite a detailed understanding of these processes, a key gap remains on the nature of the regulators that function at the earlier stages. Here, we report on two groups ofA. thalianareceptor kinases, theLRR-VIII-2 RKsubclass and theSERKs, that function in the female reproductive tract to regulate the compatible pollen grains and early pollen tube growth, both essential steps for the downstream processes leading to fertilization. MultipleA. thaliana LRR-VIII-2 RKandSERKknockout mutant combinations were created, and several phenotypes were observed such as reduced wild-type pollen hydration and reduced pollen tube travel distances. As these mutant pistils displayed a wild-type morphology, the observed altered responses of the wild-type pollen are proposed to result from the loss of these receptor kinases leading to an impaired pollen-pistil dialogue at these early stages. Furthermore, using pollen from related Brassicaceae species, we also discovered that these receptor kinases are required in the female reproductive tract to establish a reproductive barrier to interspecies pollen. Thus, we propose that theLRR-VIII-2 RKs and theSERKs play a dual role in the preferential selection and promotion of intraspecies pollen over interspecies pollen.
Sox2 controls neural stem cell self-renewal through a Fos-centered gene regulatory network
Authors: Pagin Miriam , Pernebrink Mattias , Giubbolini Simone , Barone Cristiana , Sambruni Gaia , Zhu Yanfen , Chiara Matteo , Ottolenghi Sergio , Pavesi Giulio , Wei Chia-Lin , Cantù Claudio , Nicolis Silvia K. 
Published: March 2020

AbstractThe Sox2 transcription factor is necessary for the long-term self-renewal of neural stem cells (NSC). Its mechanism of action is still poorly defined. To identify molecules regulated by Sox2, and acting in mouse NSC maintenance, we transduced, into Sox2-deleted NSC, genes whose expression is strongly downregulated following Sox2 loss (Fos, Jun, Egr2), individually or in combination. Fos alone rescued long-term proliferation, as shown by in vitro cell growth and clonal analysis. Further, pharmacological inhibition of the FOS/JUN AP1 complex binding to its targets, decreased cell proliferation and expression of the putative target Suppressor of cytokine signaling 3 (Socs3). Additionally, Fos requirement for efficient long-term proliferation was demonstrated by the reduction of NSC clones capable of long-term expansion following CRISPR/Cas9-mediated Fos inactivation. Previous work showed that the Socs3 gene is strongly downregulated following Sox2 deletion, and its reexpression by lentiviral transduction rescues long-term NSC proliferation. Fos appears to be an upstream regulator of Socs3, possibly together with Jun and Egr2; indeed, Sox2 reexpression in Sox2-deleted NSC progressively activates both Fos and Socs3 expression; in turn, Fos transduction activates Socs3 expression. Based on available SOX2 ChIPseq and ChIA-PET data, we propose a model whereby Sox2 is a direct activator of both Socs3 and Fos, as well as possibly Jun and Egr2; further, we provide direct evidence for FOS and JUN binding onSocs3promoter, suggesting direct transcriptional regulation. These results provide the basis for developing a model of a network of interactions, regulating critical effectors of NSC proliferation and long-term maintenance.Significance statementProliferation and maintenance of NSC are essential during normal brain development, and, postnatally, for the maintenance of hippocampal function and memory until advanced age. Little is known about the molecular mechanisms that maintain the critical aspects of NSC biology (quiescence and proliferation) in postnatal age. Our work provides a methodology, transduction of genes deregulated following Sox2 deletion, that allows to test many candidate genes for their ability to sustain NSC proliferation. In principle, this may have interesting implications for identifying targets for pharmacological manipulations.Abstract Figure
Temporal context actively shapes EEG signatures of time perception
Authors: Damsma Atser , Schlichting Nadine , van Rijn Hedderik 
Published: March 2020

AbstractOur subjective perception of time is optimized to temporal regularities in the environment. This is illustrated by the central tendency effect: when estimating a range of intervals, short intervals are overestimated whereas long intervals are underestimated to reduce the overall estimation error. Most models of interval timing ascribe this effect to the weighting of the current interval with previous memory tracesafterthe interval has been perceived. Alternatively, theperceptionof the duration could already be flexibly tuned to its temporal context. We investigated this hypothesis using an interval reproduction task in which human participants (both sexes) reproduced a shorter and longer interval range. As expected, reproductions were biased towards the subjective mean of each presented range. EEG analyses showed that temporal context indeed affected neural dynamics during the perception phase. Specifically, longer previous durations decreased CNV and P2 amplitude and increased beta power. In addition, multivariate pattern analysis showed that it is possible to decode context from the transient EEG signal quickly after both onset and offset of the perception phase. Together, these results suggest that temporal context creates dynamic expectations which actively affect theperceptionof duration.Significance StatementThe subjective sense of duration does not arise in isolation, but is informed by previous experiences. This is demonstrated by abundant evidence showing that the production of duration estimates is biased towards previously experienced time intervals. However, it is yet unknown whether this temporal context actively affects perception or only asserts its influence in later, post-perceptual stages as proposed by most current formal models of this task. Using an interval reproduction task, we show that EEG signatures flexibly adapt to the temporal context during perceptual encoding. Furthermore, interval history can be decoded from the transient EEG signal even when the current duration was identical. Thus, our results demonstrate that context actively influences perception.
YAP and TAZ promote periosteal osteoblast precursor expansion and differentiation for fracture repair
Authors: Kegelman Christopher D. , Nijsure Madhura P. , Moharrer Yasaman , Pearson Hope B. , Dawahare James H. , Jordan Kelsey M. , Qin Ling , Boerckel Joel D. 
Published: March 2020

ABSTRACTIn response to bone fracture, periosteal progenitor cells proliferate, expand, and differentiate to form cartilage and bone in the fracture callus. These cellular functions require the coordinated activation of multiple transcriptional programs, and the transcriptional regulators Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) regulate osteochondroprogenitor activation during endochondral bone development. However, recent observations raise important distinctions between the signaling mechanisms used to control bone morphogenesis and repair. Here, we tested the hypothesis that YAP and TAZ regulate osteochondroprogenitor activation during endochondral bone fracture healing. Constitutive YAP and/or TAZ deletion from Osterix-expressing cells impaired both cartilage callus formation and subsequent mineralization. However, this could be explained either by direct defects in osteochondroprogenitor differentiation after fracture, or by developmental deficiencies in the progenitor cell pool prior to fracture. Consistent with the second possibility, we found that developmental YAP/TAZ deletion produced long bones with impaired periosteal thickness and cellularity. Therefore, to remove the contributions of developmental history, we next generated adult onset-inducible knockout mice (using Osx1-CretetOff) in which YAP and TAZ were deleted prior to fracture, but after normal development. Adult onset-induced YAP/TAZ deletion had no effect on cartilaginous callus formation, but impaired bone formation at 14 days post-fracture (dpf). Earlier, at 4 dpf, adult onset-induced YAP/TAZ deletion impaired the proliferation and expansion of osteoblast precursor cells located in the shoulder of the callus. Further, activated periosteal cells isolated from this region at 4 dpf exhibited impaired osteogenic differentiationin vitroupon YAP/TAZ deletion. Finally, confirming the effects on osteoblast functionin vivo, adult onset-induced YAP/TAZ deletion impaired bone formation in the callus shoulder at 7 dpf, prior to the initiation of endochondral ossification. Together, these data show that YAP and TAZ promote the expansion and differentiation of periosteal osteoblast precursors to accelerate bone fracture healing.
High-order interdependencies in the aging brain
Authors: Gatica Marilyn , Cofré Rodrigo , Mediano Pedro A.M. , Rosas Fernando E. , Orio Patricio , Diez Ibai , Swinnen S.P. , Cortes Jesus M. 
Published: March 2020

AbstractBrain interdependencies can be studied either from a structural/anatomical perspective (“structural connectivity”, SC) or by considering statistical interdependencies (“functional connectivity”, FC). Interestingly, while SC is typically pairwise (white-matter fibers start in a certain region and arrive at another), FC is not; however, most FC analyses focus only on pairwise statistics and neglect high-order interactions. A promising tool to study high-order interdependencies is the recently proposedO-Information, which can quantify the intrinsic statistical synergy and redundancy in groups of three or more interacting variables. In this paper we used the O-Information to investigate how high-order statistical interdependencies are affected by age. For this, we analised functional magnetic resonance imaging (fMRI) data at rest obtained from 164 healthy participants, ranging from 10 to 80 years old. Our results show that older subjects (age ranging from 60 to 80 years) exhibit a higher predominance of redundant dependencies than younger subjects; moreover, this effect seems to be pervasive, taking place at all interaction orders. Additionally, we found that these effects are highly heterogeneous across brain regions, and suggest the existence of a “redundancy core” formed by the prefrontal and motor cortices – thus involving functions such as working memory, executive and motor functions. Our methodology to assess high-order interdependencies in fMRI data has unlimited applications. The code to calculate these metrics is freely available.
The giant sequoia genome and proliferation of disease resistance genes
Authors: Scott Alison D. , Zimin Aleksey V. , Puiu Daniela , Workman Rachael , Britton Monica , Zaman Sumaira , Caballero Madison , Read Andrew C. , Bogdanove Adam J. , Burns Emily , Wegrzyn Jill , Timp Winston , Salzberg Steven L. , Neale David B. 
Published: March 2020

ABSTRACTThe giant sequoia (Sequoiadendron giganteum) of California are massive, long-lived trees that grow along the U.S. Sierra Nevada mountains. As they grow primarily in isolated groves within a narrow range, conservation of existing trees has been a national goal for over 150 years. Genomic data are limited in giant sequoia, and the assembly and annotation of the first giant sequoia genome has been an important goal to allow marker development for restoration and management. Using Illumina and Oxford Nanopore sequencing combined with Dovetail chromosome conformation capture libraries, 8.125 Gbp of sequence was assembled into eleven chromosome-scale scaffolds. This giant sequoia assembly represents the first genome sequenced in the Cupressaceae family, and lays a foundation for using genomic tools to aid in giant sequoia conservation and management. Beyond conservation and management applications, the giant sequoia assembly is a resource for answering questions about the life history of this enigmatic and robust species. Here we provide an example by taking an inventory of the large and complex family of NLR type disease resistance genes.
Structure of population activity in primary motor cortex for single finger flexion and extension
Authors: Arbuckle Spencer A. , Weiler Jeff , Kirk Eric A. , Rice Charles L. , Schieber Marc , Pruszynski J. Andrew , Ejaz Naveed , Diedrichsen Jörn 
Published: March 2020

AbstractHow is the primary motor cortex (M1) organized to control fine finger movements? We investigated the population activity in M1 for single finger flexion and extension, using 7T functional magnetic resonance imaging (fMRI) in female and male human participants, and compared these results to the neural spiking patterns recorded in two male monkeys performing the identical task. fMRI activity patterns were distinct for movements of different fingers, but quite similar for flexion and extension of the same finger. In contrast, spiking patterns in monkeys were quite distinct for both fingers and directions, similar to what was found for muscular activity patterns. The discrepancy between fMRI and electrophysiological measurements can be explained by two (non-mutually exclusive) characteristics of the organization of finger flexion and extension movements. Given that fMRI reflects predominantly input and recurrent activity, the results can be explained by an architecture in which neural populations that control flexion or extension of the same finger produce distinct outputs, but interact tightly with each other and receive similar inputs. Additionally, neurons tuned to different movement directions for the same finger (or combination of fingers) may cluster closely together, while neurons that control different finger combinations may be more spatially separated. When measuring this organization with fMRI at a coarse spatial scale, the activity patterns for flexion and extension of the same finger would appear very similar. Overall, we suggest that the discrepancy between fMRI and electrophysiological measurements provides new insights into the general organization of fine finger movements in M1.Significance statementThe primary motor cortex (M1) is important for producing individuated finger movements. Recent evidence shows that movements that commonly co-occur are associated with more similar activity patterns in M1. Flexion and extension of the same finger, which never co-occur, should therefore be associated with distinct representations. However, using carefully controlled experiments and multivariate analyses, we demonstrate that human fMRI activity patterns for flexion or extension of the same finger are highly similar. In contrast, spiking patterns measured in monkey M1 are clearly distinct. This suggests that populations controlling opposite movements of the same finger, while producing distinct outputs, may cluster together and share inputs and local processing. These results provide testable hypotheses about the organization of hand control in M1.
Novel genes required for surface-associated motility inAcinetobacter baumannii
Authors: Blaschke Ulrike , Skiebe Evelyn , Wilharm Gottfried 
Published: March 2020

AbstractAcinetobacter baumanniiis an opportunistic and increasingly multi-drug resistant human pathogen rated as a critical priority 1 pathogen for the development of new antibiotics by the WHO in 2017. Despite the lack of flagella,A. baumanniican move along wet surfaces in 2 different ways: via twitching motility and surface-associated motility. While twitching motility is known to depend on type IV pili, the mechanism of surface-associated motility is poorly understood. In this study we established a library of 30A. baumanniiATCC 17978 mutants that displayed deficiency in surface-associated motility. By making use of natural competence we also introduced these mutations into strain 29D2 to differentiate strain-specific versus species-specific effects of mutations. Mutated genes were associated with purine/pyrimidine/folate biosynthesis (e.g.purH,purF,purM,purE), alarmone/stress metabolism (e.g. Ap4A hydrolase), RNA modification/regulation (e.g. methionyl-tRNA synthetase), outer membrane proteins (e.g.ompA), and genes involved in natural competence (comEC). All tested mutants originally identified as motility-deficient in strain ATCC 17978 also displayed a motility-deficient phenotype in 29D2. By contrast, further comparative characterization of the mutant sets of both strains regarding pellicle biofilm formation, antibiotic resistance, and virulence in theGalleria mellonellainfection model revealed numerous strain-specific mutant phenotypes. Our studies highlight the need for comparative analyses to characterize gene functions inA. baumanniiand for further studies on the mechanisms underlying surface-associated motility.
A cross-kingdom conserved ER-phagy receptor maintains endoplasmic reticulum homeostasis during stress
Authors: Stephani Madlen , Picchianti Lorenzo , Gajic Alexander , Beveridge Rebecca , Skarwan Emilio , de Medina Hernandez Victor Sanchez , Mohseni Azadeh , Clavel Marion , Zeng Yonglung , Naumann Christin , Matuszkiewicz Mateusz , Turco Eleonora , Loefke Christian , Li Baiying , Durnberger Gerhard , Schutzbier Michael , Chen Hsiao Tieh , Abdrakhmanov Alibek , Savova Adriana , Chia Khong-Sam , Djamei Armin , Schaffner Irene , Abel Steffen , Jiang Liwen , Mechtler Karl , Ikeda Fumiyo , Martens Sascha , Clausen Tim , Dagdas Yasin 
Published: March 2020

SummaryEukaryotes have evolved various quality control mechanisms to promote proteostasis in the ER. Selective removal of certain ER domains via autophagy (termed as ER-phagy) has emerged as a major quality control mechanism. However, the degree to which ER-phagy is employed by other branches of ER-quality control remains largely elusive. Here, we identify a cytosolic protein, C53, that is specifically recruited to autophagosomes during ER-stress, in both plant and mammalian cells. C53 interacts with ATG8 via a distinct binding epitope, featuring a shuffled ATG8 interacting motif (sAIM). C53 senses proteotoxic stress in the ER lumen by forming a tripartite receptor complex with the ER-associated ufmylation ligase UFL1 and its membrane adaptor DDRGK1. The C53/UFL1/DDRGK1 receptor complex is activated by stalled ribosomes and induces the degradation of internal or passenger proteins in the ER. Consistently, the C53 receptor complex and ufmylation mutants are highly susceptible to ER stress. Thus, C53 forms an ancient quality control pathway that bridges selective autophagy with ribosome-associated quality control at the ER.
Integrated lipidomics and proteomics network analysis highlights lipid and immunity pathways associated with Alzheimer’s disease
Authors: Xu Jin , Bankov Giulia , Kim Min , Wretlind Asger , Lord Jodie , Green Rebecca , Hodges Angela , Hye Abdul , Aarsland Dag , Velayudhan Latha , Dobson Richard J.B. , Proitsi Petroula , Legido-Quigley Cristina ,   on behalf of the AddNeuroMed Consortium
Published: March 2020

AbstractINTRODUCTIONThere is an urgent need to understand the molecular mechanisms underlying Alzheimer’s Disease (AD) to enable early diagnosis and develop effective treatments. Here we aim to investigate Alzheimer’s dementia using an unsupervised lipid, protein and gene multi-omic integrative approach.METHODSA lipidomics dataset (185 AD, 40 MCI and 185 controls) and a proteomics dataset (201 AD patients, 104 MCI individuals and 97 controls) were utilised for weighted gene co-expression network analyses (WGCNA). An additional proteomics dataset (94 AD, 55 MCI and 100 controls) was included for external proteomics validation. Modules created within each modality were correlated with clinical AD diagnosis, brain atrophy measures and disease progression, as well as with each other. Gene Ontology (GO) enrichment analysis was employed to examine the biological processes and molecular and cellular functions for protein modules associated with AD phenotypes. Lipid species were annotated in the lipid modules associated with AD phenotypes. Associations between established AD risk loci and lipid/protein modules that showed high correlation with AD phenotypes were also explored.RESULTSFive of the 20 identified lipid modules and five of the 17 identified protein modules were correlated with AD phenotypes. Lipid modules comprising of phospholipids, triglycerides, sphingolipids and cholesterol esters, correlated with AD risk loci involved in immune response and lipid metabolism. Five protein modules involved in positive regulation of cytokine production, neutrophil mediated immunity, humoral immune responses were correlated with AD risk loci involved in immune and complement systems.DISCUSSIONWe have shown the first multi-omic study linking genes, proteins and lipids to study pathway dysregulation in AD. Results identified modules of tightly regulated lipids and proteins that were strongly associated with AD phenotypes and could be pathology drivers in lipid homeostasis and innate immunity.Research in ContextLipid and protein modules were preserved amongst Alzheimer’s disease (AD) patients, participants with mild cognitive impairment (MCI) and controls. Protein modules were also externally validated.Five lipid and five protein modules out of a total of thirty-seven correlated with clinical AD diagnosis, brain atrophy measurements and the rate of cognitive decline in AD.Lipid and protein modules associated with AD phenotypes showed associations with established AD risk loci involved in lipid and immune pathways.
Cooperative Chikungunya virus membrane fusion and its sub-stoichiometric inhibition by CHK-152 antibody
Authors: Blijleven Jelle S. , Bouma Ellen M. , van Duijl Mareike K.S. , Smit Jolanda M. , van Oijen Antoine M. 
Published: March 2020

AbstractChikungunya virus (CHIKV) presents a major burden on healthcare systems worldwide, but specific treatment remains unavailable. Attachment and fusion of CHIKV to the host cell membrane is mediated by the E1/E2 protein spikes. We used an in vitro single-particle fusion assay to study the effect of the potent, neutralizing antibody CHK-152 on CHIKV binding and fusion. We find that CHK-152 shields the virions, inhibiting interaction with the target membrane and inhibiting fusion. Analysis of the ratio of bound antibodies to epitopes implied that CHIKV fusion is a highly cooperative process. Further, dissociation of the antibody at lower pH results in a finely balanced kinetic competition between inhibition and fusion, suggesting a window of opportunity for the spike proteins to act and mediate fusion even in the presence of antibody.