bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the role of root exudates in recruitingStreptomycesbacteria to theArabidopsis thalianaroot microbiome
Authors: Worsley Sarah F. , Macey Michael , Prudence Sam , Wilkinson Barrie , Murrell J. Colin , Hutchings Matthew I. 
Published: September 2020

AbstractStreptomycesspecies are saprophytic soil bacteria that produce a diverse array of specialised metabolites, including half of all known antibiotics. They are also rhizobacteria and plant endophytes that can promote plant growth and protect against disease. Several studies have shown that streptomycetes are enriched in the rhizosphere and endosphere of the model plantArabidopsis thaliana. Here, we set out to test the hypothesis that they are attracted to plant roots by root exudates, and specifically by the plant phytohormone salicylate, which they might use as a nutrient source. We confirmed a previously published report that salicylate over-producingcpr5plants are colonised more readily by streptomycetes but found that salicylate-deficientsid2-2andpad4plants had the same levels of root colonisation byStreptomycesbacteria as the wild-type plants. We then tested eight genome sequencedStreptomycesendophyte strainsin vitroand found that none were attracted to or could grow on salicylate as a sole carbon source. We next used13CO2DNA stable isotope probing to test whetherStreptomycesspecies can feed off a wider range of plant metabolites but found thatStreptomycesbacteria were outcompeted by faster growing proteobacteria and did not incorporate photosynthetically fixed carbon into their DNA. We conclude that, given their saprotrophic nature and under conditions of high competition, streptomycetes most likely feed on more complex organic material shed by growing plant roots. Understanding the factors that impact the competitiveness of strains in the plant root microbiome could have consequences for the effective application of biocontrol strains.ImportanceStreptomycesbacteria are ubiquitous in soil but their role as rhizobacteria is less well studied. Our recent work demonstrated that streptomycetes isolated fromA. thalianaroots can promote growth and protect against disease across plant species and that plant growth hormones can modulate the production of bioactive specialised metabolites by these strains. Here we used13CO2DNA stable isotope probing to identify which bacteria feed on plant metabolites in theA. thalianarhizosphere and, for the first time, in the endosphere. We found thatStreptomycesspecies are outcompeted for these metabolites by faster growing proteobacteria and instead likely subsist on more complex organic material such as cellulose derived from plant cell material that is shed from the roots. This work thus reveals the “winners and losers” in the battle between soil bacteria for plant metabolites and could inform the development of methods to apply streptomycetes as plant growth-promoting agents.
A simple permutation-based test of intermodal correspondence
Authors: Weinstein Sarah M. , Vandekar Simon N. , Adebimpe Azeez , Tapera Tinashe M. , Robert-Fitzgerald Timothy , Gur Ruben C. , Gur Raquel E. , Raznahan Armin , Satterthwaite Theodore D. , Alexander-Bloch Aaron F. , Shinohara Russell T. 
Published: September 2020

AbstractMany key findings in neuroimaging studies involve similarities between brain maps, but statistical methods used to measure these findings have varied. Current state-of-the-art methods involve comparing observed group-level brain maps (after averaging intensities at each image location across multiple subjects) against spatial null models of these group-level maps. However, these methods typically make strong and potentially unrealistic statistical assumptions, such as covariance stationarity. To address these issues, in this paper we propose using subject-level data and a classical permutation testing framework to test and assess similarities between brain maps. Our method is comparable to traditional permutation tests in that it involves randomly permuting subjects to generate a null distribution of intermodal correspondence statistics, which we compare to an observed statistic to estimate ap-value. We apply and compare our method in simulated and real neuroimaging data from the Philadelphia Neurodevelopmental Cohort. We show that our method performs well for detecting relationships between modalities known to be strongly related (cortical thickness and sulcal depth), and it is conservative when an association would not be expected (cortical thickness and activation on then-back working memory task). Notably, our method is the most flexible and reliable for localizing intermodal relationships within subregions of the brain and allows for generalizable statistical inference.
The phosphatase inhibitor LB-100 acts synergistically with the NPR2 agonist BMN-111 to improve bone growth
Authors: Shuhaibar Leia C. , Kaci Nabil , Egbert Jeremy R. , Loisay Léa , Vigone Giulia , Uliasz Tracy F. , Dambroise Emilie , Swingle Mark R. , Honkanen Richard E. , Jaffe Laurinda A. , Legeai-Mallet Laurence 
Published: September 2020

ABSTRACTActivating mutations in fibroblast growth factor receptor 3 (FGFR3) and inactivating mutations in the natriuretic peptide receptor 2 (NPR2) guanylyl cyclase both result in decreased production of cyclic GMP (cGMP) in chondrocytes and severe short stature, causing achondroplasia (ACH) and acrosomelic dysplasia type Maroteaux, respectively. Previously we showed that an NPR2 agonist BMN-111 (vosoritide) increases bone growth in mice mimicking ACH (Fgfr3Y367C/+), and that in control growth plate chondrocytes, FGFR3 signaling decreases NPR2 activity by dephosphorylating the NPR2 protein. Here we tested whether a phosphatase inhibitor (LB-100) could enhance bone growth in ACH. Inex vivoimaging experiments using a FRET sensor to measure cGMP production in chondrocytes of living tibias from newborn mice, LB-100 counteracts the FGF-induced dephosphorylation and inactivation of NPR2. Inex vivoexperiments withFgfr3Y367C/+mice, LB-100 in combination with BMN-111 increases the rate of femur growth by ∼25% vs BMN-111 alone, restores chondrocyte terminal differentiation, increases the proliferative growth plate area of the femur, and reduces the activity of the MAP kinase pathway. Our results provide a proof of concept that a phosphatase inhibitor could be used together with an NPR2 agonist to enhance cGMP production as a therapy for ACH.GRAPHICAL ABSTRACT
Coordination of two enhancers drives expression of olfactory trace amine-associated receptors
Authors: Fei Aimei , Wu Wanqing , Tan Longzhi , Tang Cheng , Xu Zhengrong , Huo Xiaona , Bao Hongqiang , Johnson Mark , Hartmann Griffin , Talay Mustafa , Yang Cheng , Riegler Clemens , Joseph Kristian , Engert Florian , Xie X. Sunney , Barnea Gilad , Liberles Stephen D. , Yang Hui , Li Qian 
Published: September 2020

SummaryOlfactory sensory neurons (OSNs) are functionally defined by their expression of a unique odorant receptor (OR). Mechanisms underlying singular OR expression are well studied, and involve a massive cross-chromosomal enhancer interaction network. Trace amine-associated receptors (TAARs) form a distinct family of olfactory receptors, and here we find that mechanisms regulatingTaargene choice display many unique features. The epigenetic signature ofTaargenes in TAAR OSNs is different from that in OR OSNs. We further identify that two TAAR enhancers conserved across placental mammals are absolutely required for expression of the entireTaargene repertoire. Deletion of either enhancer dramatically decreases the expression probabilities of differentTaargenes, while deletion of both enhancers completely eliminates the TAAR OSN populations. In addition, both of the enhancers are sufficient to drive transgene expression in the partially overlapped TAAR OSNs. We also show that the TAAR enhancers operate incisto regulateTaargene expression. Our findings reveal a coordinated control ofTaargene choice in OSNs by two remote enhancers, and provide an excellent model to study molecular mechanisms underlying formation of an olfactory subsystem.
Quantification and demonstration of the constriction-by-rachet mechanism in the dynamin molecular motor
Authors: Ganichkin Oleg , Vancraenenbroeck Renee , Rosenblum Gabriel , Hofmann Hagen , Mikhailov Alexander S. , Daumke Oliver , Noel Jeffrey K. 
Published: September 2020

AbstractDynamin oligomerizes into helical filaments on tubular membrane templates and, through constriction, cleaves them in a GTPase-driven way. Structural observations of GTP-dependent cross-bridges between neighboring filament turns have led to the suggestion that dynamin operates as a molecular ratchet motor. However, the proof of such mechanism remains absent. Particularly, it is not known whether a powerful enough stroke is produced and how the motor modules would cooperate in the constriction process. Here, we characterized the dynamin motor modules by single molecule (sm) FRET and found strong nucleotide-dependent conformational changes. Integrating smFRET with molecular dynamics simulations allowed us to determine the forces generated in a power stroke. Subsequently, the quantitative force data and the measured kinetics of the GT-Pase cycle were incorporated into a model including both a dynamin filament, with explicit motor cross-bridges, and a realistic deformable membrane template. In our simulations, collective constriction of the membrane by dynamin motor modules, based on the ratchet mechanism, is directly reproduced and analyzed. Functional parallels between the dynamin system and actomyosin in the muscle are seen. Through concerted action of the motors, tight membrane constriction to the hemifission radius can be reached. Our experimental and computational study provides an example of how collective motor action in megadalton molecular assemblies can be approached and explicitly resolved.
Heterogeneous aggregation of amyloid-β 42 from single-molecule spectroscopy
Authors: Meng Fanjie , Yoo Janghyun , Chung Hoi Sung 
Published: September 2020

AbstractProtein aggregation is implicated as the cause of pathology in various diseases such as Alzheimer’s and Parkinson’s disease. Polymorphism in the structure of fibrils formed by aggregation suggests the existence of many different assembly pathways and therefore a heterogeneous ensemble of soluble oligomers. Characterization of this heterogeneity is the key to understanding the aggregation mechanism and toxicity of specific oligomers, but in practice it is extremely difficult because oligomers cannot be readily separated. Here, we investigate highly heterogeneous oligomerization and fibril formation of the 42-residue amyloid-β peptide (Aβ42). We developed and used new single-molecule fluorescence spectroscopic and fluorescence lifetime imaging methods, combined with deep learning for image analysis. We found that the concentration of oligomers, including dimers, is extremely low and that the dimer is conformationally diverse. Aggregation to form fibrils is also highly heterogeneous in terms of the number of strands in a fibril and the elongation speed and conformation of fibrils. This heterogeneity in all stages of aggregation explains diverse and sometimes irreproducible results of experimental studies of amyloid-β. Based on our observations and analysis, we propose a new model for aggregation of Aβ42.
Phosphodiesterase Type 4 anchoring regulates cAMP signaling to Popeye domain-containing proteins
Authors: Tibbo Amy J , Dobi Sara , McFall Aisling , Tejeda Gonzalo S , Blair Connor , MacLeod Ruth , MacQuaide Niall , Gök Caglar , Fuller William , Smith Brian O , Smith Godfrey L , Brand Thomas , Baillie George S 
Published: September 2020

AbstractCyclic AMP is a ubiquitous second messenger used to transduce intracellular signals from a variety of Gs-coupled receptors. Compartmentalisation of protein intermediates within the cAMP signaling pathway underpins receptor-specific responses. The cAMP effector proteins protein-kinase A and EPAC are found in complexes that also contain phosphodiesterases whose presence ensures a coordinated cellular response to receptor activation events. Popeye proteins are the most recent class of cAMP effectors to be identified and have crucial roles in cardiac pacemaking and conduction. We report the first observation that Popeye proteins exist in complexes with members of the PDE4 family in cardiac myocytes thus restricting cAMP signaling. We show that POPDC1 preferentially binds the PDE4A sub-family via a specificity motif in the PDE4 UCR1 region and that PDE4s bind to the Popeye domain of POPDC1 in a region known to be susceptible to a mutation that causes human disease. Using a cell-permeable disruptor peptide that displaces the POPDC1-PDE4 complex we show that PDE4 activity localized to POPDC1 is essential to maintain action potential duration in beating cardiac myocytes.
The atypical Rho GTPase Rnd2 is critical for dentate granule neuron development and anxiety-like behavior during adult but not neonatal neurogenesis
Authors: Kerloch Thomas , Farrugia Fanny , Maître Marlène , Terral Geoffrey , Koehl Muriel , Heng Julian Ik-Tsen , Blanchard Mylène , Doat Hélène , Leste-Lasserre Thierry , Goron Adeline , Gonzales Delphine , Guillemot François , Abrous Djoher Nora , Pacary Emilie 
Published: September 2020

ABSTRACTDespite the central role of Rho GTPases in neuronal development, their functions in adult hippocampal neurogenesis remain poorly explored. Here, by using a retrovirus-based loss-of-function approachin vivo, we show that the atypical Rho GTPase Rnd2 is crucial for the survival, positioning, somatodendritic morphogenesis and functional maturation of adult-born dentate granule neurons. Interestingly, most of these functions are specific to granule neurons generated during adulthood since the deletion ofRnd2in neonatally-born granule neurons only affects dendritogenesis. In addition, suppression ofRnd2in adult-born dentate granule neurons increases anxiety-like behaviour whereas its deletion in pups has no such effect, a finding supporting the adult neurogenesis hypothesis of anxiety disorders. Thus, our results provide mechanistic insight into the differential regulation of hippocampal neurogenesis during development and adulthood, and establishes a causal relationship between Rnd2 expression and anxiety.
Genome-wide association and prediction study in grapevine deciphers the genetic architecture of multiple traits and identifies genes under many new QTLs
Authors: Flutre Timothée , Le Cunff Loïc , Fodor Agota , Launay Amandine , Romieu Charles , Berger Gilles , Bertrand Yves , Terrier Nancy , Beccavin Isabelle , Bouckenooghe Virginie , Roques Maryline , Pinasseau Lucie , Verbaere Arnaud , Sommerer Nicolas , Cheynier Véronique , Bacilieri Roberto , Boursiquot Jean-Michel , Lacombe Thierry , Laucou Valérie , This Patrice , Péros Jean-Pierre , Doligez Agnès 
Published: September 2020

AbstractTo cope with the challenges faced by agriculture, speeding-up breeding programs is a worthy endeavor, especially for perennials such as grapevine, but requires understanding the genetic architecture of target traits. To go beyond the mapping of quantitative trait locus (QTL) in bi-parental crosses, we exploited a diverse panel of 279Vitis viniferaL. cultivars. This panel planted in five blocks in the vineyard was phenotyped over several years for 127 traits including yield components, organic acids, aroma precursors, polyphenols, and a water stress indicator. The panel was genotyped for 63k single nucleotide polymorphisms (SNPs) by combining an 18K microarray and genotyping-by-sequencing (GBS). The experimental design allowed to reliably assess the genotypic values for most traits. Marker densification via GBS markedly increased the proportion of genetic variance explained by SNPs, and two multi-SNP models identified QTLs not found by a SNP-by-SNP model. Overall, 489 reliable QTLs were detected for 41% more response variables than by a SNP-by-SNP model with microarray-only SNPs, many new ones compared to the results from bi-parental crosses. Prediction accuracy higher than 0.42 was obtained for 50% of the response variables. Our overall approach as well as QTL and prediction results provide insights into the genetic architecture of target traits. New candidate genes and the application in breeding are discussed.
The inhibitory activity of glycine transporter 2 targeting bioactive lipid analgesics are influenced by formation of a deep lipid cavity
Authors: Wilson Katie A. , Mostyn Shannon N. , Frangos Zachary J. , Shimmon Susan , Rawling Tristan , Vandenberg Robert J. , O’Mara Megan L. 
Published: September 2020

AbstractThe human glycine transporter 2 (GlyT2 or SLC6A5) has emerged as a promising drug target for the development of new analgesics to manage chronic pain. N-acyl amino acids inhibit GlyT2 through binding to an allosteric binding site to produce analgesia in vivo with minimal overt side effects. In this paper we use a combination of medicinal chemistry, electrophysiology, and computational modelling to explore the molecular basis of GlyT2 inhibition at the allosteric site. We show how N-acyl amino acid head group stereochemistry, tail length and double bond position promote enhanced inhibition by deep penetration into the binding pocket. This work provides new insights into the interaction of lipids with transport proteins and will aid in future rational design of novel GlyT2 inhibitors.
Wheat developmental traits as affected by the interaction betweenEps-7Dand temperature under contrasting photoperiods with insensitivePpd-D1background
Authors: Basavaraddi Priyanka A. , Savin Roxana , Griffiths Simon , Slafer Gustavo A. 
Published: September 2020

AbstractEarlinessper se(Eps) genes are important to fine tune adaptation, and studying their probable pleiotropic effect on wheat yield traits is worthwhile. In addition, it has been shown that some Eps genes interact with temperature. We studied two NILs differing in the newly identifiedEps-7Dbut carrying insensitivePpd-D1 in the background under three temperature regimes (9, 15 and 18 °C) and two photoperiods (12 h and 24 h).Eps-7Daffected time to anthesis as expected and theEps-7D-lateallele extended both the period before and after terminal spikelet. The interaction effect ofEps-7D× temperature was significant but not cross-over: the magnitude and level of significance of the difference between NILs with thelateorearlyallele was affected by the growing temperature (i.e. difference was least at 18 °C and largest at 9 °C), and differences in temperature sensitivity was influenced by photoperiod. Rate of leaf initiation was faster in NIL withEps-7D-earlythan with thelateallele which compensated for the shorter duration of leaf initiation resulting in similar final leaf number between two NILs.Eps-7D-late consistently increased spike fertility through improving floret primordia survival as a consequence of extending the late reproductive phase.
Decreased calmodulin recruitment triggers PMCA4 dysfunction and pancreatic injury in cystic fibrosis
Authors: Madácsy Tamara , Varga Árpad , Papp Noémi , Deák Barnabás , Tél Bálint , Pallagi Petra , Szabó Viktória , Fanczal Júlia , Rakonczay Zoltan , Rázga Zsolt , Hohwieler Meike , Kleger Alexander , Gray Mike , Hegyi Péter , Maléth József 
Published: September 2020

ABSTRACTExocrine pancreatic damage is a common complication of cystic fibrosis (CF), which can significantly debilitate the quality of life and life expectancy of CF patients. The cystic fibrosis transmembrane conductance regulator (CFTR) has a major role in pancreatic ductal ion secretion, however, it presumably has an influence on intracellular signaling as well. Here we describe in multiple model systems, including iPSC-derived human pancreatic organoids from CF patients, that the activity of PMCA4 is impaired by the decreased expression of CFTR in ductal cells. The regulation of PMCA4, which colocalizes and physically interacts with CFTR on the apical membrane of the ductal cells, is dependent on the calmodulin binding ability of CFTR. Moreover, CFTR seems to be involved in the process of the apical recruitment of calmodulin, which enhances its role in calcium signaling and homeostasis. Sustained intracellular Ca2+ elevation in CFTR KO cells undermined the mitochondrial function and increased apoptosis. Based on these, the prevention of sustained intracellular Ca2+ overload may improve the exocrine pancreatic function and may have a potential therapeutic aspect in CF.
Neural representations of task context and temporal order during action sequence execution
Authors: Shahnazian Danesh , Senoussi Mehdi , Krebs Ruth M. , Verguts Tom , Holroyd Clay B. 
Published: September 2020

AbstractSince routine action sequences can share a great deal of similarity in terms of their stimulus response mappings, their correct execution relies crucially on the ability to preserve contextual and temporal information (Lashley, 1951). However, there are few empirical studies on the neural mechanism and the brain areas maintaining such information. To address this gap in the literature, we recently recorded the blood-oxygen level dependent (BOLD) response in a newly developed coffee-tea making task (Holroyd et al., 2018). The task involves the execution of 4 action sequences that each feature 6 decision states. Here we report a reanalysis of this dataset using a data-driven approach, namely multivariate pattern analysis (MVPA), that examines context-dependent neural activity across several predefined regions of interest. Results highlight involvement of the inferior-temporal gyrus and lateral prefrontal cortex in maintaining temporal and contextual information for the execution of hierarchically-organized action sequences. Furthermore, temporal information seems to be more strongly encoded in areas over the left hemisphere.
CycleFlow quantifies cell-cycle heterogeneityin vivo
Authors: Jolly Adrien , Fanti Ann-Kathrin , Gräßer Ines , Becker Nils B. , Höfer Thomas 
Published: September 2020

AbstractWhile the average cell-cycle length in a cell population can be derived from pulse-chase experiments, proliferative heterogeneity has been difficult to quantify. Here we describe CycleFlow, a broadly applicable method that applies Bayesian inference to combined measurements of EdU incorporation and DNA content. CycleFlowaccurately quantifies the fraction of proliferating versus quiescent cells and the durations of cell-cycle phases of the proliferating cellsin vitroandin vivo.