bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional divergence of Plexin B structural motifs in distinct steps ofDrosophilaolfactory circuit assembly
Authors: Guajardo Ricardo , Luginbuhl David J , Han Shuo , Luo Liqun , Li Jiefu 
Published: May 2019

AbstractPlexins exhibit multitudinous, evolutionarily conserved functions in the development of nervous systems. However, how Plexins employ their diverse structural motifsin vivoto perform distinct roles in the stepwise assembly of neural circuits is unclear. Here, we systematically mutagenized structural motifs ofDrosophilaPlexin B (PlexB) and examined the function of these variants at multiple PlexB-mediated neurodevelopmental processes in olfactory receptor neurons: axon fasciculation, trajectory choice, and synaptic partner selection. We found that the extracellular Sema domain is essential for all three processes, the catalytic site of the intracellular RapGAP is engaged in none, and the intracellular GTPase-binding motifs are essential for trajectory choice and synaptic partner selection, but are dispensable for fasciculation. Moreover, extracellular PlexB cleavage serves as a regulatory mechanism of PlexB signaling. Thus, PlexB structural motifs have divergent roles in distinct steps of neural development, altogether contributing to the functional versatility of PlexB in neural circuit assembly.
Fighting antimicrobial resistance in Pseudomonas aeruginosa with machine learning-enabled molecular diagnostics
Authors: Khaledi Ariane , Weimann Aaron , Schniederjans Monika , Asgari Ehsaneddin , Kuo Tzu-Hao , Oliver Antonio , Cabot Gabriel , Kola Axel , Gastmeier Petra , Hogardt Michael , Jonas Daniel , Mofrad Mohammad R.K. , Bremges Andreas , McHardy Alice C. , Häussler Susanne 
Published: May 2019

AbstractThe growing importance of antibiotic resistance on clinical outcomes and cost of care underscores the need for optimization of current diagnostics. For a number of bacterial species antimicrobial resistance can be unambiguously predicted based on their genome sequence. In this study, we sequenced the genomes and transcriptomes of 414 drug-resistant clinical Pseudomonas aeruginosa isolates. By training machine learning classifiers on information about the presence or absence of genes, their sequence variation, and gene expression profiles, we generated predictive models and identified biomarkers of susceptibility or resistance to four commonly administered antimicrobial drugs. Using these data types alone or in combination resulted in high (0.8-0.9) or very high (>0.9) sensitivity and predictive values, where the relative contribution of the different categories of biomarkers strongly depended on the antibiotic. For all drugs except for ciprofloxacin, gene expression information substantially improved diagnostic performance. Our results pave the way for the development of a molecular resistance profiling tool that reliably predicts antimicrobial susceptibility based on genomic and transcriptomic markers. The implementation of a molecular susceptibility test system in routine clinical microbiology diagnostics holds promise to provide earlier and more detailed information on antibiotic resistance profiles of bacterial pathogens and thus could change how physicians treat bacterial infections.
The rapid regenerative response of a model sea anemone speciesExaiptasia pallidais characterised by tissue plasticity and highly coordinated cell communication
Authors: van der Burg Chloé A. , Pavasovic Ana , Gilding Edward K. , Pelzer Elise S. , Surm Joachim M. , Smith Hayden L. , Walsh Terence P. , Prentis Peter J. 
Published: May 2019

AbstractRegeneration of a limb or tissue can be achieved through multiple different pathways and mechanisms. The sea anemoneExaiptasia pallidahas been observed to have excellent regenerative proficiency but this has not yet been described transcriptionally. In this study we examined the genetic expression changes during a regenerative timecourse and report key genes involved in regeneration and wound healing. We found that the major response was an early upregulation of genes involved in cellular movement and cell communication, which likely contribute to a high level of tissue plasticity resulting in the rapid regeneration response observed in this species. We find the immune system is only transcriptionally active in the first eight hours post-amputation and conclude, in accordance with previous literature, that the immune system and regeneration have an inverse relationship. Fifty-nine genes (3.8% of total) differentially expressed during regeneration were identified as having no orthologues in other species, indicating that regeneration inE. pallidamay rely on the activation of species-specific novel genes. Additionally, taxonomically-restricted novel genes, including species-specific novels, and highly conserved genes were identified throughout the regenerative timecourse, showing that both may work in concert to achieve complete regeneration. We conclude thatE. pallidabehaves similarly to other anemone species such asNematostella vectensisandCalliactis polypusbut with some notable novel differences.
Parental care shapes evolution of aposematism and provides lifelong protection against predators
Authors: Lindstedt C. , Boncoraglio G. , Cotter S.C. , Gilbert J.D.J. , Kilner R.M 
Published: May 2019

ABSTRACTSocial interactions within species can modulate the response to selection and determine the extent of evolutionary change. Yet relatively little work has determined whether the social environment can influence the evolution of traits that are selected by interactions with other species - a major source of natural selection. Here we show that the amount of parental care received as an offspring can influence the expression, and potential evolution, of warning displays deployed against predators in adulthood. In theory, warning displays by prey are selected by predators for uniformity and to reliably advertise the extent to which individuals are chemically defended. However, the correlated evolution of intensity of the visual display and strength of the chemical defense is only possible if there is a genetic correlation between them. Adult burying beetlesNicrophorus vespilloidesbear bright orange elytral markings which advertise their chemical defenses. We experimentally manipulated the level of maternal care that individuals received when they were larvae and then measured the strength of the correlation between the component parts of the warning display when they reached adulthood. We found that under limited care individuals were smaller and produced less conspicuous warning displays. The underlying family (genetic) correlation between the visual display and the chemical defense was weaker in individuals that received little care as larvae. We conclude that parenting by burying beetles modulates the evolvability of aposematic defense, making correlated evolutionary change in signal intensity and chemical defense less likely when they restrict care to their young.Significance StatementParental care can improve early offspring survival against predators. However, we have little knowledge of how its effects shape the evolution of predator-prey interactions later in the offspring’s life. We tested this with carrion beetles who provide care for offspring and who carry warning coloration to advertise to predators that they are chemically defended. We show that more parental care resulted in larger, more brightly coloured and chemically defended adult beetles. Furthermore, when parents had provided little care for their young we found weaker genetic correlations between warning signal salience and chemical defense. Over time, this could result in untrustworthy warning signals, which could render them ineffective against predators.
Consistency in macroscopic human brain responses to noisy time-varying visual inputs
Authors: Kitajo Keiichi , Sase Takumi , Mizuno Yoko , Suetani Hiromichi 
Published: May 2019

AbstractIt is an open question as to whether macroscopic human brain responses to repeatedly presented external inputs show consistent patterns across trials. We here provide experimental evidence that human brain responses to noisy time-varying visual inputs, as measured by scalp electroencephalography (EEG), show a signature of consistency. The results indicate that the EEG-recorded responses are robust against fluctuating ongoing activity, and that they respond to visual stimuli in a repeatable manner. This consistency presumably mediates robust information processing in the brain. Moreover, the EEG response waveforms were discriminable between individuals, and were invariant over a number of days within individuals. We reveal that time-varying noisy visual inputs can harness macroscopic brain dynamics and can manifest hidden individual variations.
Comparing statistical and mechanistic models to identify the drivers of mortality within a rear-edge beech population
Authors: Petit-Cailleux Cathleen , Davi Hendrik , Lefèvre François , Garrigue Joseph , Magdalou Jean-André , Hurson Christophe , Magnanou Elodie , Oddou-Muratorio Sylvie 
Published: May 2019

AbstractSince several studies have been reporting an increase in the decline of forests, a major issue in ecology is to better understand and predict tree mortality. The interactions between the different factors and the physiological processes giving rise tree mortality, as well as the inter-individual variability in mortality risk, still need to be better assessed.This study investigates mortality in a rear-edge population of European beech (Fagus sylvaticaL.) using a combination of statistical and process-based modelling approaches. Based on a survey of 4323 adult beeches since 2002 within a natural reserve, we first used statistical models to quantify the effects of competition, tree growth, size, defoliation and fungi presence on mortality. Secondly, we used an ecophysiological process-based model (PBM) to separate out the different mechanisms giving rise to temporal and inter-individual variations in mortality by simulating depletion of carbon stocks, loss of hydraulic conductance and damage due to late frosts in response to climate.The combination of all these simulated processes was associated with the temporal variations in the population mortality rate. The individual probability of mortality decreased with increasing mean growth, and increased with increasing crown defoliation, earliness of budburst, fungi presence and increasing competition, in the statistical model. Moreover, the interaction between tree size and defoliation was significant, indicating a stronger increase in mortality associated to defoliation in smaller than larger trees. Finally, the PBM predicted a higher conductance loss together with a higher level of carbon reserves for trees with earlier budburst, while the ability to defoliate the crown was found to limit the impact of hydraulic stress at the expense of the accumulation of carbon reserves.We discuss the convergences and divergences obtained between statistical and process-based approaches and we highlight the importance of combining them to characterize the different processes underlying mortality, and the factors modulating individual vulnerability to mortality.
No effect of triple-pulse TMS medial to intraparietal sulcus on online correction for target perturbations during goal-directed hand and foot reaches
Authors: Marigold Daniel S. , Lajoie Kim , Heed Tobias 
Published: May 2019

AbstractPosterior parietal cortex (PPC) is central to sensorimotor processing for goal-directed hand and foot movements. Yet, the specific role of PPC subregions in these functions is not clear. Previous human neuroimaging and transcranial magnetic stimulation (TMS) work has suggested that PPC lateral to the intraparietal sulcus (IPS) is involved in directing the arm, shaping the hand, and correcting both finger-shaping and hand trajectory during movement. The lateral localization of these functions agrees with the comparably lateral position of the hand and fingers within the motor and somatosensory homunculi along the central sulcus; this might suggest that, in analogy, (goal-directed) foot movements would be mediated by medial portions of PPC. However, foot movement planning activates similar regions for both hand and foot movement along the caudal-to-rostral axis of PPC, with some effector-specificity evident only rostrally, near the central regions of sensorimotor cortex. Here, we attempted to test the causal involvement of PPC regions medial to IPS in hand and foot reaching as well as online correction evoked by target displacement. Participants made hand and foot reaches towards identical visual targets. Sometimes, the target changed position 100-117 ms into the movement. We disturbed cortical processing over four positions medial to IPS with three pulses of TMS separated by 40 ms, both during trials with and without target displacement. We timed TMS to disrupt reach execution and online correction. TMS did not affect endpoint error, endpoint variability, or reach trajectories for hand or foot. While these negative results await replication with different TMS timing and parameters, we conclude that regions medial to IPS are involved in planning, rather than execution and online control, of goal-directed limb movements.
Enabling high-accuracy long-read amplicon sequences using unique molecular identifiers with Nanopore or PacBio sequencing
Authors: Karst Søren M. , Ziels Ryan M. , Kirkegaard Rasmus H. , Sørensen Emil A. , McDonald Daniel , Zhu Qiyun , Knight Rob , Albertsen Mads 
Published: May 2019

AbstractHigh-throughput amplicon sequencing of large genomic regions remains challenging for short-read technologies. Here, we report a high-throughput amplicon sequencing approach combining unique molecular identifiers (UMIs) with Oxford Nanopore Technologies or Pacific Biosciences CCS sequencing, yielding high accuracy single-molecule consensus sequences of large genomic regions. Our approach generates amplicon and genomic sequences of >10,000 bp in length with a mean error-rate of 0.0049-0.0006% and chimera rate <0.022%.
Technical Note: Efficient and accurate estimation of genotype odds ratios in biobank-based unbalanced case-control studies
Authors: Dey Rounak , Lee Seunggeun 
Published: May 2019

AbstractIn genome-wide association studies (GWASs), genotype log-odds ratios (LORs) quantify the effects of the variants on the binary phenotypes, and calculating the genotype LORs for all of the markers is required for several downstream analyses. Calculating genotype LORs at a genome-wide scale is computationally challenging, especially when analyzing large-scale biobank data, which involves performing thousands of GWASs phenome-wide. Since most of the binary phenotypes in biobank-based studies have unbalanced (case : control = 1 : 10) or often extremely unbalanced (case : control = 1 : 100) case-control ratios, the existing methods cannot provide a scalable and accurate way to estimate the genotype LORs. The traditional logistic regression provides biased LOR estimates in such situations. Although the Firth bias correction method can provide unbiased LOR estimates, it is not scalable for genome-wide or phenome-wide scale association analyses typically used in biobank-based studies, especially when the number of non-genetic covariates is large. On the other hand, the saddlepoint approximation-based test (fastSPA), which can provide accurate p values and is scalable to analyse large-scale biobank data, does not provide the genotype LOR estimates as it is a score-based test. Here, we propose a scalable method based on score statistics, to accurately estimate the genotype LORs, adjusting for non-genetic covariates. Comparing to the Firth method, our proposed method reduces the computational complexity from O(nK2 + K3) to O(n), where n is the sample-size, and K is the number of non-genetic covariates. Our method is ~ 10x faster than the Firth method when 15 covariates are being adjusted for. Through extensive numerical simulations, we show that the proposed method is both scalable and accurate in estimating the genotype ORs in genome-wide or phenome-wide scale.
Next generation sequencing to investigate genomic diversity in Caryophyllales
Authors: Pucker Boas , Feng Tao , Brockington Samuel F. 
Published: May 2019

AbstractCaryophyllales are a highly diverse and large order of plants with a global distribution. While some species are important crops like Beta vulgaris, many others can survive under extreme conditions. This order is well known for the complex pigment evolution, because the pigments anthocyanins and betalains occur with mutual exclusion in species of the Caryophyllales. Here we report about genome assemblies of Kewa caespitosa (Kewaceae), Macarthuria australis (Macarthuriaceae), and Pharnaceum exiguum (Molluginaceae) which are representing different taxonomic groups in the Caryophyllales. The availability of these assemblies enhances molecular investigation of these species e.g. with respect to certain genes of interest.
Tomato root transformation followed by inoculation with Ralstonia solanacearum for straightforward genetic analysis of bacterial wilt disease
Authors: Morcillo Rafael J. L. , Zhao Achen , Tamayo-Navarrete María I. , García-Garrido José M. , Macho Alberto P. 
Published: May 2019

ABSTRACTRalstonia solanacearum is a devastating soil borne vascular pathogen that is able to infect a large range of plant species, causing an important threat to agriculture. However, the Ralstonia model is considerably under-explored in comparison to other models involving bacterial plant pathogens, such as Pseudomonas syringae in Arabidopsis. Research targeted to understanding the interaction between Ralstonia and crop plants is essential to develop sustainable solutions to fight against bacterial wilt disease, but is currently hindered by the lack of straightforward experimental assays to characterize the different components of the interaction in native host plants. In this scenario, we have developed an easy method to perform genetic analysis of Ralstonia infection of tomato, a natural host of Ralstonia. This method is based on Agrobacterium rhizogenes-mediated transformation of tomato roots, followed by Ralstonia soil-drenching inoculation of the resulting plants, containing transformed roots expressing the construct of interest. The versatility of the root transformation assay allows performing either gene overexpression or gene silencing mediated by RNAi. As a proof of concept, we used this method to show that RNAi-mediated silencing of SlCESA6 of tomato roots conferred resistance to Ralstonia. Here, we describe this method in detail, enabling genetic approaches to understand bacterial wilt disease in a relative short time and with small requirements of equipment and plant growth space.SUMMARYA versatile method for tomato root transformation followed by inoculation with Ralstonia solanacearum to perform straightforward genetic analysis for the study of bacterial wilt disease.
Murine norovirus virulence factor 1 (VF1) protein contributes to viral fitness during persistent infection
Authors: Borg Constantina , Jahun Aminu S. , Thorne Lucy , Sorgeloos Frédéric , Bailey Dalan , Goodfellow Ian 
Published: May 2019

AbstractBackgroundMurine norovirus (MNV) is widely used as a model for studying norovirus biology. While MNV isolates vary in their pathogenesis, infection of immunocompetent mice mostly results in persistent infection. The ability of a virus to establish a persistent infection is dependent on its ability to subvert or avoid the host immune response. Previously, we described the identification and characterization of virulence factor 1 (VF1) in MNV, and established that it acts as an innate immune antagonist. Here, we explore the role of VF1 during persistent MNV infection in an immunocompetent host.MethodsUsing reverse genetics, we generated VF1-knockout MNV-3 that contained a single or a triple termination codon inserted in the VF1 open reading frame.ResultsVF1-knockout MNV-3 replicated to comparable levels to the wildtype virus in tissue culture. Comparative studies between MNV-3 and an acute MNV-1 strain show that MNV-3 VF1 exerts the same functions as MNV-1 VF1, but with reduced potency. Mice infected with VF1-knockout MNV-3 showed significantly reduced replication kinetics during the acute phase of the infection, but viral loads rapidly reached the levels seen in mice infected with wildtype virus after phenotypic restoration of VF1 expression. Infection with an MNV-3 mutant that had three termination codons inserted into VF1, in which reversion was suppressed, resulted in consistently lower replication throughout a three-month persistent infection in mice, suggesting a role for VF1 in viral fitness in vivo.ConclusionOur results indicate that VF1 expressed by a persistent strain of MNV also functions to antagonise the innate response to infection. We found that VF1 is not essential for viral persistence, but instead contributes to viral fitness in mice. These data fit with the hypothesis that noroviruses utilise multiple mechanisms to avoid and/or control the host response to infection and that VF1 is just one component of this.
Parkinson’s disease: a systemic inflammatory disease accompanied by bacterial inflammagens
Authors: Adams Büin , Nunes J Massimo , Page Martin J , Roberts Timothy , Carr Jonathan , Nell Theo A , Kell Douglas B , Pretorius Etheresia 
Published: May 2019

ABSTRACTParkinson’s disease (PD) is a well-known neurodegenerative disease. Recently, the role of gingipains fromPorphyromonas gingivaliswas implicated in Alzheimer’s disease. Here we present evidence of systemic inflammation, accompanied by hypercoagulation; we also show that ginipains fromP. gingivalisand its LPS may foster abnormal clotting, and that ginipains are present in PD blood, and thus that ginipain’s action on blood may be relevant to PD pathology. Bloods from both PD and healthy blood samples were analysed using thromboelastography (TEG), confocal and electron microscopies, and for cytokine and other circulating biomarkers. We also probed PD and healthy plasma clots with a polyclonal antibody for the bacterial protease, gingipain R1, fromP. gingivalis. Low concentrations of recombinant gingipain R1 were also added to purified fluorescent fibrinogen. TEG, fibrin(ogen) amyloid formation and platelet ultrastructure analysis confirmed profound hypercoagulation, while the biomarker analysis confirmed significantly increased levels of circulating proinflammatory cytokines. We provide evidence for the presence of the protease, gingipain R1 in PD blood, implicating inflammatory microbial cell wall products in PD.
The lottery of spermatogenesis
Authors: Kalirad Ata , Safdari Hadiseh , Sadeghi Mehdi 
Published: May 2019

AbstractThe causes of male infertility are yet to be fully understood. Here, we propose that male infertility can be partly attributed to the insufficiency of cytoplasmically-inherited proteins in sperms. Using a simple stochastic model of spermatogenesis, we show that in a range of parameters, the proportion of viable sperms can be reduced simply due to stochastic transmission of proteins from spermatogonia to spermatids.