bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving yield and fruit quality traits in sweet passion fruit: evidence for genotype by environment interaction and cross-compatibility in selected genotypes
Authors: Chavarría-Perez Lourdes Maria , Giordani Willian , das Graças Dias Kaio Olimpio , da Costa Zirlane Portugal , Ribeiro Carolina Albuquerque Massena , Benedetti Anderson Roberto , Cauz-Santos Luiz Augusto , da Silva Pereira Guilherme , Rosa João Ricardo Bachega Feijó , Garcia Antonio Augusto Franco , Vieira Maria Lucia Carneiro 
Published: July 2019

AbstractBreeding for yield and fruit quality traits in passion fruits is complex due to the polygenic nature of these traits and the existence of genetic correlations among them. Therefore, studies focused on crop management practices and breeding using modern quantitative genetic approaches are still needed, especially for Passiflora alata, an understudied crop, popular known as the sweet passion fruit. It is assumed to be a self-incompatible species and is highly appreciated for its typical aroma and flavor characteristics. With the aim of estimating the genetic and phenotypic parameters related to fruit traits, our group has already investigated a sweet passion fruit progeny consisting of 100 individuals from which 30 genotypes were selected. In this study, we reevaluated these superior genotypes in three environmental conditions. The results of the multi-environment trial analysis indicate that the genotypes do not behave consistently across these environments, and this was taken into account when selecting genotypes. Pairwise genetic correlations among the fruit traits were evaluated, and different genotype rankings obtained depending on the trait and environment, providing further evidence of genotype by environment interaction. Finally, we used a multiplicative selection index to select 20% of genotypes for weight of pulp and against thickness and weight of the fruit skin. The response to selection was positive for all traits except soluble solids, and the superior (six) genotypes were ranked. The consensus is that open-pollinated populations can be used as commercial varieties in crop species that are sensitive to inbreeding depression or within breeding programs that are not well developed. For these reasons, we performed a complete diallel cross for evaluating the capability of the selected genotypes to be fertilized and set fruits. Most of the crosses were compatible, resulting in over 50% fruit set. It is worth noting that all genotypes produce fruits if used as females, which is essential to guarantee yields in commercial orchards.
Tissue of Origin Dictates GOT1 Dependence and Confers Synthetic Lethality to Radiotherapy
Authors: Nelson Barbara S. , Lin Lin , Kremer Daniel M. , Sousa Cristovão M. , Cotta-Ramusino Cecilia , Myers Amy , Ramos Johanna , Gao Tina , Kovalenko Ilya , Wilder-Romans Kari , Dresser Joseph , Davis Mary , Lee Ho-Joon , Nwosu Zeribe C. , Campit Scott , Mashadova Oksana , Nicolay Brandon N. , Tolstyka Zachary P. , Halbrook Christopher J. , Chandrasekaran Sriram , Asara John M. , Crawford Howard C. , Cantley Lewis C. , Kimmelman Alec C. , Wahl Daniel R. , Lyssiotis Costas A. 
Published: July 2019

AbstractMetabolic programs in cancer cells are influenced by genotype and the tissue of origin. We have previously shown that central carbon metabolism is rewired in pancreatic ductal adenocarcinoma (PDA) to support proliferation through a glutamate oxaloacetate transaminase 1 (GOT1)-dependent pathway. Here we tested if tissue type impacted GOT1 dependence by comparing PDA and colorectal cancer (CRC) cell lines and tumor models of similar genotype. We found CRC to be insensitive to GOT1 inhibition, contrasting markedly with PDA, which exhibit profound growth inhibition upon GOT1 knockdown. Utilizing a combination of metabolomics strategies and computational modeling, we found that GOT1 inhibition disrupted glycolysis, nucleotide metabolism, and redox homeostasis in PDA but not CRC. These insights were leveraged in PDA, where we demonstrate that radiotherapy potently enhanced the effect of GOT1 inhibition on tumor growth. Taken together, these results illustrate the role of tissue type in dictating metabolic dependencies and provide new insights for targeting metabolism to treat PDA.
Non-spherical coacervate shapes in an enzyme driven active system
Authors: Spoelstra Willem Kasper , van der Sluis Eli O. , Dogterom Marileen , Reese Louis 
Published: July 2019

AbstractCoacervates are polymer-rich droplets that form through liquid-liquid phase separation in polymer solutions. Liquid-liquid phase separation and coacervation have recently been shown to play an important role in the organization of biological systems. Such systems are highly dynamic and under continuous influence of enzymatic and chemical processes. However, it is still unclear how enzymatic and chemical reactions affect the coacervation process. Here, we present and characterize a system of enzymatically active coacervates containing spermine, RNA, free nucleotides, and the template independent RNA (de)polymerase PNPase. We find that these RNA coacervates display transient non-spherical shapes, and we systematically study how PNPase concentration, UDP concentration and temperature affect coacervate morphology. Furthermore, we show that PNPase localizes predominantly into the coacervate phase and that its depolymerization activity in high-phosphate buffer causes coacervate degradation. Our observations of non-spherical coacervate shapes may have broader implications for the relationship between (bio-)chemical activity and coacervate biology.
Short-term block of CRH receptor in adults mitigates age-related memory impairments provoked by early-life adversity
Authors: Short Annabel K. , Maras Pamela M. , Pham Aidan L. , Ivy Autumn S. , Baram Tallie Z. 
Published: July 2019

AbstractIn humans, early-life adversity (ELA) is associated with impairments in learning and memory that may emerge later in life. In rodent models, ELA directly impacts hippocampal neuron structure and connectivity with progressive deficits in long-term potentiation and spatial memory function. Previous work has demonstrated that augmented release and actions of the stress-activated neuropeptide, CRH, contribute to the deleterious effects of ELA on hippocampal structure and memory-function. Early-life adversity increases CRH production and levels, and blocking CRH receptor type 1 (CRHR1) within the hippocampus immediately following adversity prevented the memory and LTP problems caused by ELA. Here we queried if blocking CRHR1 during adulthood ameliorates the adverse impact of ELA on memory in middle age. Blocking CRHR1 for a week in two month old male rats prevented ELA-induced deficits in object recognition memory that emerge during middle age. The intervention failed to mitigate the reduction of spatial memory at 4 and 8 months, but restored hippocampus-dependent location memory in ELA-experiencing rats during middle age (12 months of age).Notably, neither ELA nor blocking CRHR1 influenced anxiety- or depression-related behaviors These findings suggest a sensitive period during which interventions can fully prevent long-lasting effects of ELA, yet indicate that interventions later in life offer significant benefits.
Cortical encoding of melodic expectations in human temporal cortex
Authors: Di Liberto Giovanni M. , Pelofi Claire , Bianco Roberta , Patel Prachi , Mehta Ashesh D. , Herrero Jose L. , de Cheveigné Alain , Shamma Shihab , Mesgarani Nima 
Published: July 2019

SummaryHumans engagement in music rests on underlying elements such as the listeners’ cultural background and general interest in music, all shaping the way music is processed in the brain and perceived. Crucially, these factors modulate how listeners anticipate musical events, a process inducing instantaneous neural responses as the music confronts these expectations. Measuring such neural correlates would represent a direct window into high-level brain processing of music. Here we recorded electroencephalographic and electrocorticographic brain responses as participants listened to Bach melodies. We assessed the relative contributions of the acoustic versus melodic components of the music to the neural signal. Acoustic features included envelope and its derivative. Melodic features included information on melodic progressions (pitch) and their tempo (onsets), which were extracted from a Markov model predicting the next note based on a corpus of Western music and the preceding proximal musical context. We related the music to brain activity with a linear temporal response function, and demonstrated that cortical responses to music encode melodic expectations. Specifically, individual-subject neural signals were better predicted by a combination of acoustic and melodic expectation features than by either alone. This effect was most pronounced at response latencies up to 350ms, and in both planum temporale and Heschl’s gyrus. Finally, expectations of pitch and onset-time of musical notes exerted independent cortical effects, and such influences were modulated by the listeners’ musical expertise. Overall, this study demonstrates how the interplay of experimental and theoretical approaches can yield novel insights into the cortical encoding of melodic expectations.
How to make “number lines” stable in the mind’s eye
Authors: Pinto Mario , Pellegrino Michele , Marson Fabio , Lasaponara Stefano , Cestari Vincenzo , Doricchi Fabrizio 
Published: July 2019

AbstractHumans are prone to mentally organise the ascending series of integers according to reading habits, so that in western cultures small numbers are positioned to the left of larger ones on a mental number line (MNL, Dehaene et al., 1993). Despite 140 years since seminal observations made by Sir Francis Galton in human observers that experienced vivid MNLs (Galton, 1880a,b), the neural and functional mechanisms that give rise to MNLs remain elusive. Here, in a series of three experiments we show that spatially organised MNLs are not “all or none” phenomena and that MNLs get progressively less noisy and more stable in the mind’s eye, the more an observer fully combines left/right spatial codes with small/large magnitude codes to operate on numbers. These results show that conceptualising the ascending series of integers in spatial terms depends on contextual clues rather than being inherent to the semantic representation of numbers.
Transcription-mediated organization of the replication initiation program across large genes sets up common fragile sites genome-wide
Authors: Brison Olivier , EL-Hilali Sami , Azar Dana , Koundrioukoff Stéphane , Schmidt Mélanie , Naehse-Kumpf Viola , Jaszczyszyn Yan , Lachages Anne-Marie , Dutrillaux Bernard , Thermes Claude , Debatisse Michelle , Chen Chun-Long 
Published: July 2019

ABSTRACTCommon Fragile Sites (CFSs) are chromosome regions prone to breakage under replication stress, known to drive chromosome rearrangements during oncogenesis. Most CFSs nest in large expressed genes, suggesting that transcription elicits their instability but the underlying mechanisms remained elusive. Analyses of genome-wide replication timing of human lymphoblasts here show that stress-induced delayed/under-replication is the hallmark of CFSs. Extensive genome-wide analyses of nascent transcripts, replication origin positioning and fork directionality reveal that 80% of CFSs nest in large transcribed domains poor in initiation events, thus replicated by long-traveling forks. In contrast to formation of sequence-dependent fork barriers or head-on transcription-replication conflicts, traveling-long in late S phase explains CFS replication features. We further show that transcription inhibition during the S phase, which excludes the setting of new replication origins, fails to rescue CFS stability. Altogether, results show that transcription-dependent suppression of initiation events delays replication of large gene body, committing them to instability.
Uncovering Staphylococcus aureus genes with roles in pathogenicity by silkworm infection model
Authors: Paudel Atmika , Hamamoto Hiroshi , Panthee Suresh , Matsumoto Yasuhiko , Sekimizu Kazuhisa 
Published: July 2019

AbstractThe regulatory network of virulence factors production by Staphylococcus aureus, an opportunistic pathogen, is incompletely understood, and the functions of many uncharacterized genes in its genome remain to be uncovered. We screened 380 function unassigned genes disrupted mutants of the community-acquired methicillin-resistant S. aureus USA300 for pathogenicity using silkworms and identified 11 strains with reduced silkworm killing ability. Nine out of the 11 strains displayed reduced virulence in the mouse model as evidenced by reduced colony-forming units in organs of the infected mice. Three of the identified gene-disrupted mutants had reduced hemolytic activity, one among the three also had reduced proteolytic activity and pigment production. These results suggest that silkworm model could identify the genes required for virulence in the mouse model. The newly identified genes involved in virulence in this study facilitates the further understanding of the pathogenicity of S. aureus.ImportanceWe performed a large scale screening of mutants of Staphylococcus aureus with disruption in function unassigned genes using silkworm infection model and identified eleven genes required for full virulence in silkworm. Nine of the eleven genes were involved in virulence in mice and were previously not known to aggravate virulence of S. aureus. The results suggest that silkworm model is suitable for quantitative measurement of virulence, which is shared between silkworms and mammals.
NET4 modulates the compactness of vacuoles in Arabidopsis thaliana
Authors: Kaiser Sabrina , Eisa Ahmed , Kleine-Vehn Jürgen , Scheuring David 
Published: July 2019

AbstractThe dimension of the plants largest organelle – the vacuole, plays a major role in defining cellular elongation rates. The morphology of the vacuole is controlled by the actin cytoskeleton but the mechanistic connection between them remains largely elusive. Recently, the NETWORKED (NET) family of membrane-associated, actin-binding proteins has been identified and represent potential candidates to impact on vacuolar morphology. Here, we show that NET4A localizes to highly constricted regions in the vacuolar membrane and contributes to the compactness of the vacuole. Using genetic interference, we found that deregulation of NET4 abundance impacts on vacuole morphogenesis and overexpression leads to more compact vacuoles. We moreover show that the NET4A-induced changes in vacuolar shape correlates with reduced cellular and organ growth in Arabidopsis thaliana. Our results demonstrate that NET4 modulates the compactness of vacuoles and reveal higher complexity in the regulation of actin-reliant vacuolar morphology.
JASS: Command Line and Web interface for the joint analysis of GWAS results
Authors: Julienne Hanna , Lechat Pierre , Guillemot Vincent , Lasry Carla , Yao Chunzi , Laville Vincent , Vilhjalmsson Bjarni , Ménager Hervé , Aschard Hugues 
Published: July 2019

AbstractGenome Wide Association Study (GWAS) has been the driving force for identifying association between genetic variants and human phenotypes. Thousands of GWAS summary statistics covering a broad range of human traits and diseases are now publicly available, and studies have demonstrated their utility for a range of secondary analyses. This includes in particular the joint analysis of multiple GWAS to identify new genetic variants missed by univariate screenings. However, although several methods have been proposed, there are very few large scale applications published so far because of challenges in implementing these methods on real data. Here, we present JASS (Joint Analysis of Summary Statistics), a polyvalent Python package that addresses this need. Our package solves all practical and computational barriers for large-scale multivariate analysis of GWAS summary statistics. This includes data cleaning and harmonization tools, an efficient algorithm for fast derivation of various joint statistics, an optimized data management process, and a web interface for exploration purposes. Benchmark analyses confirmed the strong performances of JASS. We also performed multiple real data analyses demonstrating the strong potential of JASS for the detection of new associated genetic variants across various scenarios. Our package is freely available at https://gitlab.pasteur.fr/statistical-genetics/jass.
Dopamine-dependent loss aversion during effort-based decision-making
Authors: Chen Xiuli , Voets Sarah , Jenkinson Ned , Galea Joseph M. 
Published: July 2019

AbstractFrom psychology to economics there has been substantial interest in how costs (e.g., delay, risk) are represented asymmetrically during decision-making when attempting to gain reward or to avoid punishment. For example, in decision-making under risk, individuals show a tendency to prefer to avoid punishment than to acquire the equivalent reward (loss aversion). Although the cost of physical effort has received significant recent attention due to the evaluation of motor costs being crucial in our daily decisions, it remains unclear whether loss aversion exists during effort-based decision-making. On the one hand, loss aversion may be hardwired due to asymmetric evolutionary pressure on losses and gains and therefore exists across decision-making contexts. On the other hand, distinct brain regions are involved with different decision costs, making it questionable whether similar asymmetries exist. Here, we demonstrate that young healthy participants exhibit loss aversion during effort-based decision-making by exerting more physical effort in order to avoid punishment than to gain a same-size reward. Next, we show that medicated Parkinson’s disease (PD) patients show a reduction in loss aversion compared to age-matched controls. Behavioural and computational analysis revealed that people with PD exerted similar physical effort in return for a reward, but were less willing to produce effort in order to avoid punishment. Therefore, loss aversion is present during effort-based decision-making and can be modulated by altered dopaminergic state. This finding could have important implications for our understanding of clinical disorders that show a reduced willingness to exert effort in the pursuit of reward.Significance StatementLoss aversion – preferring to avoid punishment than to acquire equivalent reward – is an important concept in decision-making under risk. However, little is known about whether loss aversion also exists during decisions where the cost is physical effort. This is surprising given that motor cost shapes human behaviour, and a reduced willingness to exert effort is a characteristic of many clinical disorders. Here, we show that healthy individuals exert more effort to minimise punishment than to maximise reward (loss aversion). We also demonstrate that loss aversion is modulated by altered dopaminergic state by showing that medicated Parkinson’s disease patients exert similar effort to gain reward but less effort to avoid punishment. Therefore, dopamine-dependent loss aversion is crucial for explaining effort-based decision-making.
Pre-warming before general anesthesia with isoflurane delays the onset of hypothermia in rats
Authors: Rufiange Maxime , Leung Vivian SY , Simpson Keith , Pang Daniel SJ 
Published: July 2019

AbstractGeneral anesthesia causes hypothermia by impairing normal thermoregulatory mechanisms. Redistribution of warm blood from the core to the periphery is the primary mechanism in the development of hypothermia and begins following induction of anesthesia. Raising skin temperature before anesthesia reduces the temperature gradient between core and periphery, decreasing the transfer of heat. This prospective, crossover study (n = 17 adult male and female SD rats) compared three treatment groups: PW1% (pre-warming to increase core temperature 1% over baseline), PW40 (pre-warming to increase core temperature to 40°C) and NW (no warming). The PW1% group was completed first to ensure tolerance of pre-warming. Treatment order was then randomized and alternated after a washout period. Once target temperature was achieved, anesthesia was induced and maintained with isoflurane in oxygen without further external temperature support. Pre-warming was effective at delaying the onset of hypothermia, with a significant difference between PW1% (11.2 minutes) and PW40 (14.7 minutes, p = 0.0044 (95%CI −12 to −2.2), PW40 and NW (6.0 minutes, p = 0.003 (95%CI 1.8 to 8.7) and PW1% and PW40 (p = 0.004, 95%CI −12 to −2.2). The rate of heat loss in the pre-warmed groups exceed that of the NW group: PW1% versus NW (p = 0.005, 95%CI 0.004 to 0.027), PW40 versus NW (p < 0.0001, 95%CI 0.014 to 0.036) and PW1% versus PW40 (p = 0.07, 95%CI −0.021 to 0.00066). Pre-warming alone confers a protective effect against hypothermia during volatile anesthesia; however, longer duration procedures would require additional heating support.
Pharmacological evidence for the implication of noradrenaline in effort
Authors: Borderies Nicolas , Mattioni Julia , Bornert Pauline , Gilardeau Sophie , Bouret Sébastien 
Published: July 2019

AbstractThe trade-off between effort and reward is one of the main determinants of behavior and its alteration is at the heart of major disorders such as depression or Parkinson’s disease. Monoaminergic neuromodulators are thought to play a key role in this trade-off, but their relative contribution remains unclear. Rhesus monkeys (Macaca mulatta) performed a choice-task requiring a trade-off between the volume of fluid reward and the amount of force to be exerted on a grip. In line with a causal role of noradrenaline in effort, decreasing noradrenaline levels with systemic clonidine injections (0.01mg/kg) decreased exerted force and enhanced the weight of upcoming force on choices, without any effect on reward sensitivity. Computational modeling demonstrated that NA acted on a single hidden variable, which affected both choices (as a variable of decision) and force production (as a driving force). Thus, our data strongly support noradrenaline’s implication in effort processing.
SMAD3 Determines Conventional versus Plasmacytoid Dendritic Cell Fates
Authors: Yoon Jeong-Hwan , Bae Eunjin , Sudo Katsuko , Han Jin Soo , Park Seok Hee , Nakae Susumu , Yamashita Tadashi , Lee In-Kyu , Ju Ji Hyeon , Matsumoto Isao , Sumida Takayuki , Kuroda Masahiko , Miyazawa Keiji , Kato Mitsuyasu , Mamura Mizuko 
Published: July 2019

SUMMARYTransforming growth factor (TGF)-β plays crucial roles in differentiation of dendritic cells (DC). However, molecular mechanisms how TGF-β regulates DC differentiation remain largely unknown. Here, we show that selective repression of one of the TGF-β receptor-regulated SMADs (R-SMADs), SMAD3 directs conventional DC (cDC) differentiation, whereas maintenance of SMAD3 is indispensable for plasmacytoid DC (pDC) differentiation. Expression of SMAD3 was specifically downregulated in CD115+common DC progenitor (CDP), pre-cDCs and cDCs. SMAD3 deficient mice showed a significant reduction in pre-pDCs and pDCs with increased CDP, pre-cDCs and cDCs. SMAD3 upregulated the pDC-related genes: SPI-B, E2-2 and IKAROS, while it repressed FLT3 and the cDC-related genes: IRF4 and ID2. STAT3 and a SMAD transcriptional co-repressor, c-SKI repressed SMAD3 for cDC differentiation, whereas canonical SMAD-mediated TGF-β signalling maintained SMAD3 for pDC differentiation. Thus, SMAD3 is the pivotal determinant to bifurcate cDC and pDC differentiation in the steady-state condition.