bluuebunny/crossref_metadata_2025_split huggingface dataset:
AtDAT1 is a key enzyme of D-amino acid stimulated ethylene production inArabidopsis thaliana
Authors: Suarez Juan , Hener Claudia , Lehnhardt Vivien-Alisa , Hummel Sabine , Stahl Mark , Kolukisaoglu Üner 
Published: July 2019

AbstractD-enantiomers of proteinogenic amino acids (D-AAs) are found ubiquitously, but the knowledge about their metabolism and functions in plants is scarce. A long forgotten phenomenon in this regard is the D-AA-stimulated ethylene production in plants. As a starting point to investigate this effect theArabidopsisaccession Landsberg erecta (Ler) got into focus as it was found defective in metabolizing D-AAs. Combining genetics and molecular biology of T-DNA lines and natural variants together with biochemical and physiological approaches we could identify AtDAT1 as a major D-AA transaminase inArabidopsis. Atdat1loss-of-function mutants andArabidopsisaccessions with defectiveAtDAT1alleles were not able to produce D-Ala, D-Glu and L-Met, the metabolites of D-Met, anymore. This result corroborates the biochemical characterization of AtDAT1, which showed highest activity using D-Met as substrate. Germination of seedlings in light and dark led to enhanced growth inhibition ofatdat1mutants on D-Met. Ethylene measurements revealed an enhanced D-AA stimulated ethylene production in these mutants. According to initial working models of this phenomenon D-Met is preferentially malonylated instead of the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC). This decrease of ACC degradation should then lead to the increase of ethylene production. We could observe in our studies a reciprocal relation of malonylated methionine and ACC upon D-Met application and even significantly more malonyl-methionine inatdat1mutants. Unexpectedly, the malonyl-ACC levels did not differ between mutants and wild type in these experiments. With AtDAT1, the first central enzyme of plant D-AA metabolism was characterized biochemically and physiologically. The specific effects of D-Met on ACC metabolization, ethylene production and plant development ofdat1mutants unraveled the impact of AtDAT1 on these processes, but they are not in full accordance to previous working models. Instead, our results imply the influence of additional candidate factors or processes on D-AA-stimulated ethylene production which await to be uncovered.
Meiosis Initiates In The Fetal Ovary Of Mice Lacking All Retinoic Acid Receptor Isotypes
Authors: Vernet Nadège , Mark Manuel , Condrea Diana , Féret Betty , Klopfenstein Muriel , Alunni Violaine , Teletin Marius , Ghyselinck Norbert B. 
Published: July 2019

AbstractGametes are generated through a specialized cell differentiation process, meiosis which, in most mammals, is initiated in ovaries during fetal life. It is widely admitted that all-transretinoic acid (ATRA) is the molecular signal triggering meiosis initiation in mouse female germ cells, but a genetic approach in which ATRA synthesis is impaired disputes this proposal. In the present study, we investigated the contribution of endogenous ATRA to meiosis by analyzing fetuses lacking all RARs ubiquitously, obtained through a tamoxifen-inducible cre recombinase-mediated gene targeting approach. Efficient ablation of RAR-coding genes was assessed by the multiple congenital abnormalities displayed by the mutant fetuses. Unexpectedly, their germ cells robustly expressed STRA8, REC8, SYCP1 and SYCP3, showing that RAR are actually dispensable up to the zygotene stage of meiotic prophase I. Thus our study goes against the current model according to which meiosis is triggered by endogenous ATRA in the developing ovary and revives the identification of the meiosis-preventing substance synthesized by CYP26B1 in the fetal testis.
Higher quality de novo genome assemblies from degraded museum specimens: a linked-read approach to museomics
Authors: Colella Jocelyn P. , Tigano Anna , MacManes Matthew D. 
Published: July 2019

AbstractHigh-throughput sequencing technologies are a proposed solution for accessing the molecular data in historic specimens. However, degraded DNA combined with the computational demands of short-read assemblies has posed significant laboratory and bioinformatics challenges. Linked-read or ‘synthetic long-read’ sequencing technologies, such as 10X Genomics, may provide a cost-effective alternative solution to assemble higher quality de novo genomes from degraded specimens. Here, we compare assembly quality (e.g., genome contiguity and completeness, presence of orthogroups) between four published genomes assembled from a single shotgun library and four deer mouse (Peromyscus spp.) genomes assembled using 10X Genomics technology. At a similar price-point, these approaches produce vastly different assemblies, with linked-read assemblies having overall higher quality, measured by larger N50 values and greater gene content. Although not without caveats, our results suggest that linked-read sequencing technologies may represent a viable option to build de novo genomes from historic museum specimens, which may prove particularly valuable for extinct, rare, or difficult to collect taxa.
Shaky Scaffolding: Age Differences In Cerebellar Activation Revealed Through Activation Likelihood Estimation Meta-Analysis
Authors: Bernard Jessica A. , Nguyen An D. , Hausman Hanna K. , Maldonado Ted , Ballard Hannah K. , Jackson T. Bryan , Eakin Sydney M. , Lokshina Yana , Goen James R.M. 
Published: July 2019

AbstractCognitive neuroscience research has provided foundational insights into aging, but has focused primarily on the cerebral cortex. However, the cerebellum is subject to the effects of aging. Given the importance of this structure in the performance of motor and cognitive tasks, cerebellar differences stand to provide critical insights into age differences in behavior. But, our understanding of cerebellar functional activation in aging is limited. Thus, we completed a meta-analysis of neuroimaging studies across task domains. Unlike in the cortex where an increase in bilateral activation is seen during cognitive task performance with advanced age, there is less overlap in cerebellar activation across tasks in older adults relative to young. Conversely, we see an increase in activation overlap in older adults during motor tasks. We propose that this is due to inputs for comparator processing in the context of control theory (cortical and spinal) that may be differentially impacted in aging. These findings advance our understanding of the aging mind and brain.
Decelerated carbon cycling by ectomycorrhizal fungi is controlled by substrate quality and community composition
Authors: Fernandez Christopher W. , See Craig R. , Kennedy Peter G. 
Published: July 2019

AbstractInteractions between symbiotic ectomycorrhizal (EM) and free-living saprotrophs can result in significant deceleration of leaf litter decomposition. While this phenomenon is widely cited, its generality remains unclear, as both the direction and magnitude of EM fungal effects on leaf litter decomposition have been shown to vary among studies. Here we explicitly examine how contrasting leaf litter types and EM fungal communities may lead to differential effects on C and N cycling. Specifically, we measured the response of soil nutrient cycling, litter decay rates, litter chemistry and fungal community structure to the reduction of EM fungi (via trenching) with a reciprocal litter transplant experiment in adjacentPinus- orQuercus-dominated sites. We found clear evidence of EM fungal suppression of C and N cycling in thePinus-dominated site, but no suppression in theQuercus-dominated site. Additionally, in thePinus-dominated site, only thePinuslitter decay rates were decelerated by EM fungi and were associated with decoupling of litter C and N cycling. Our results support the hypothesis that EM fungi can decelerate C cycling via N competition, but strongly suggest that the ‘Gadgil effect’ is dependent on both substrate quality and EM fungal community composition. We argue that understanding tree host traits as well as EM fungal functional diversity is critical to a more mechanistic understanding of how EM fungi mediate forest soil biogeochemical cycling.
Mass Spectrometry-Based Plasma Proteomics: Considerations from Sample Collection to Achieving Translational Data
Authors: Ignjatovic Vera , Geyer Philipp E , Palaniappan Krishnan K , Chaaban Jessica E , Omenn Gilbert S , Baker Mark S , Deutsch Eric W , Schwenk Jochen M 
Published: July 2019

AbstractThe proteomic analyses of human blood and blood-derived products (e.g. plasma) offers an attractive avenue to translate research progress from the laboratory into the clinic. However, due to its unique protein composition, performing proteomics assays with plasma is challenging. Plasma proteomics has regained interest due to recent technological advances, but challenges imposed by both complications inherent to studying human biology (e.g. inter-individual variability), analysis of biospecimen (e.g. sample variability), as well as technological limitations remain. As part of the Human Proteome Project (HPP), the Human Plasma Proteome Project (HPPP) brings together key aspects of the plasma proteomics pipeline. Here, we provide considerations and recommendations concerning study design, plasma collection, quality metrics, plasma processing workflows, mass spectrometry (MS) data acquisition, data processing and bioinformatic analysis. With exciting opportunities in studying human health and disease though this plasma proteomics pipeline, a more informed analysis of human plasma will accelerate interest whilst enhancing possibilities for the incorporation of proteomics-scaled assays into clinical practice.Abstract Figure
Perturbing neural representations of working memory with task-irrelevant interruption
Authors: Hakim Nicole , Feldmann-Wüstefeld Tobias , Awh Edward , Vogel Edward K. 
Published: July 2019

AbstractWorking memory maintains information so that it can be used in complex cognitive tasks. A key challenge for this system is to maintain relevant information in the face of task-irrelevant perturbations. In this series of experiments, we investigated the impact of task-irrelevant interruptions on neural representations of working memory. We recorded electroencephalogram (EEG) activity in humans while they performed a working memory task. On a subset of trials, we interrupted participants with salient, but task-irrelevant objects. To track the impact of these task-irrelevant interruptions on neural representations of working memory, we measured two well-characterized, temporally sensitive EEG markers that reflect active, prioritized working memory representations: the contralateral delay activity (CDA) and lateralized alpha power (8-12hz). Following interruption, we found that CDA momentarily sustained, but was gone by the end of the trial. Lateralized alpha power was immediately influenced by the interrupters, but recovered by the end of the trial. This suggests that dissociable neural processes contribute to the maintenance of working memory information. Additionally, we found that task expectancy modulated the timing and magnitude of how these two neural signals responded to task-irrelevant interruptions, suggesting that the brain’s response to task-irrelevant interruption is shaped by task context. The distinct time courses of and influence of task context on these two neural signatures of working memory have many interesting theoretical implications about how information is actively maintained in working memory.Significance statementWorking memory plays a central role in intelligent behaviors because it actively maintains relevant information that is easily accessible and manipulatable. In everyday life, we are often interrupted while performing such complex cognitive tasks. Therefore, understanding how working memory responds to and overcomes momentary task-irrelevant interruptions is critical for us to understand how complex cognition works. Here, we unveil how two distinct neural signatures of working memory respond to task-irrelevant interruptions by recording electroencephalogram activity in humans. Our findings raise long-standing theoretical questions about how different neural and cognitive processes contribute to the maintenance of information in working memory.
Replication Timing and Transcription Identifies a Novel Fragility Signature Under Replication Stress
Authors: Sarni Dan , Sasaki Takayo , Miron Karin , Tur-Sinai Michal Irony , Rivera-Mulia Juan Carlos , Magnuson Brian , Lungman Mats , Gilbert David M. , Kerem Batsheva 
Published: July 2019

AbstractCommon fragile sties (CFSs) are regions susceptible to replication stress and are hotspots for chromosomal instability in cancer. Several features characterizing CFSs have been associated with their instability, however, these features are prevalent across the genome and do not account for all known CFSs. Therefore, the molecular mechanism underlying CFS instability remains unclear. Here, we explored the transcriptional profile and temporal order of DNA replication (replication timing, RT) of cells under replication stress conditions. We show that the RT of only a small portion of the genome is affected by replication stress, and that CFSs are enriched for delayed RT. We identified a signature for chromosomal fragility, comprised of replication stress-induced delay in RT of early/mid S-phase replicating regions within actively transcribed large genes. This fragility signature enabled precise mapping of the core fragility region. Furthermore, the signature enabled the identification of novel fragile sites that were not detected cytogenetically, highlighting the improved sensitivity of our approach for identifying fragile sites. Altogether, this study reveals a link between altered DNA replication and transcription of large genes underlying the mechanism of CFS expression. Thus, investigating the RT and transcriptional changes in cancer may contribute to the understanding of mechanisms promoting genomic instability in cancer.
Experimental copper exposure, but not heat stress, leads to elevated intraovarian thyroid hormone levels
Authors: Suvi Ruuskanen , Giovanna Mottola , Katja Anttila 
Published: July 2019

AbstractClimate change and pollution are some of the greatest anthropogenic threats to wild animals. Transgenerational plasticity – when parental exposure to environmental stress leads to changes in offspring phenotype – has been recently highlighted as a potential mechanism to respond to various environmental and anthropogenic changes across taxa. Transgenerational effects may be mediated via multiple mechanisms, such as transfer of maternal hormones to eggs/fetus. However, sources of variation in hormone transfer are poorly understood in fish, and thus the first step is to characterize whether environmental challenges alter transfer of maternal hormones to eggs. To this end, we explored the genetic and environmental variation (in response to temperature and endocrine disrupting copper) in maternal thyroid hormone (TH), transfer to offspring in a common fish model species, the three-spined stickleback (Gasterosteus aculeatus) using multiple approaches: (i) We compared ovarian TH levels among six populations across a wide geographical range in the Baltic Sea, including two populations at high water temperature areas (discharge water areas of nuclear power plants) and we experimentally exposed fish to (ii) environmentally relevant heat stress and (iii) copper for 7 days. We found that populations did not differ in intraovarian TH levels, and short-term heat stress did not influence intraovarian TH levels. However, copper exposure increased both T4 and T3 levels in ovaries. The next step would be to evaluate if such alterations would lead to changes in offspring phenotype.Capsule: We show that experimental copper exposure, but not heat stress (experimental or among-population variation), leads to elevated ovarian thyroid hormone levels in sticklebacks.
Hidden Aspects of the Research-ADOS are Bound to Affect Autism Science
Authors: Torres Elizabeth B , Rai Richa , Mistry Sejal , Gupta Brenda 
Published: July 2019

AbstractThe research-grade ADOS is a broadly used instrument that informs and steers much of the science of Autism. Despite its broad use, little is known about the empirical variability inherently present in the scores of the ADOS scale, or their appropriateness to define change, to repeatedly use this test to characterize neurodevelopmental trajectories. Here we examine the empirical distributions of research-grade ADOS scores from 1,324 records in a cross-section of the population comprising participants with autism between 5-65 years of age. We find that these empirical distributions violate the theoretical requirements of normality and homogeneous variance, essential for independence between bias and sensitivity. Further, we assess a subset of 52 typical controls vs. those with autism and find lack of proper elements to characterize neurodevelopmental trajectories in a coping nervous system changing at non-uniform, non-linear rates. Lastly, longitudinally repeating the assessments over 4 visits in a subset of the participants with autism for whom verbal criteria kept the same appropriate ADOS modules over the timespan of the 4 visits, reveals that switching the clinician, changes the cutoff scores, and consequently, influences the diagnosis, despite maintaining fidelity in the same test’s modules, room conditions and tasks’ fluidity per visit. Given the changes in probability distribution shape and dispersion of these ADOS scores, the lack of appropriate metric spaces, and the impact that these elements have on sensitivity-bias co-dependencies, and on longitudinal tracking of autism, we invite a discussion on the use of this test for scientific purposes.
Depression of substantia nigra dopamine transmission is driven by retrograde neurotensin release and is enhanced by methamphetamine self-administration
Authors: Tschumi Christopher W. , Sharma Ramaswamy , Lynch William B. , Sharpe Amanda L. , Beckstead Michael J. 
Published: July 2019

AbstractMidbrain dopamine neurons play central roles in reward learning and motivated behavior, and inhibition at somatodendritic dopamine D2 receptor (D2R) synapses blunts psychostimulant reinforcement. Release of the neuropeptide neurotensin in the midbrain increases following methamphetamine exposure and induces long-term depression of D2R synaptic currents (LTDDA), however the source of neurotensin that drives LTDDAis not known. Here we show that LTDDAis driven by neurotensin released by dopamine neurons. Optogenetic stimulation of dopamine neurons was sufficient to induce LTDDAin the substantia nigra, but not the ventral tegmental area, and was dependent on neurotensin receptors, postsynaptic calcium, and vacuolar-type H+-ATPase activity in the postsynaptic cell. Further, LTDDAwas enhanced in mice that had self-administered methamphetamine. These findings reveal a novel form of signaling between dopamine neurons involving release of the peptide neurotensin, which may act as a feed forward mechanism to increase dopamine neuron excitability and methamphetamine self-administration.
Reconciling a Model of Core Metabolism with Growth Yield Predicts Biochemical Mechanisms and Efficiency for a Versatile Chemoautotroph
Authors: McNichol Jesse , Sievert Stefan M. 
Published: July 2019

AbstractObligately chemoautotrophicCampylobacteriadominate productivity in dark, sulfidic, and oxygen-depleted environments. However, biochemical mechanisms underlying their growth remain poorly known, limiting understanding of their physiology, ecology, and biogeochemical impact. In this study, we used comparative genomics, conceptual modeling of core metabolism, and chemostat growth yields to derive a model of energy conservation consistent with experimental data for the versatile chemoautotrophSulfurimonas denitrificans. Our model rests on three core mechanisms: Firstly, to allow electrogenic sulfur-based denitrification, we predict that the campylobacterial-type sulfur oxidation enzyme complex must donate electrons to the membrane quinone pool, possibly via a sulfide:quinone oxidoreductase. Secondly, to account for the unexpectedly low growth efficiency of aerobic sulfur oxidation compared to denitrification, we posit the high-affinity campylobacterial-type cbb3cytochrome c oxidase has a relatively low H+/e− of 1, likely due to a lack of proton pumping under physiological conditions. Thirdly, we hypothesize that reductant for carbon fixation by the reverse tricarboxylic acid cycle is produced by a non-canonical complex I that reduces both ferredoxin and NAD(P)H. This complex is conserved among relatedCampylobacteriaand may have allowed for the radiation of organisms likeS. denitrificansinto sulfur-rich environments that became available after the great oxidation event. Our theoretical model has two major implications. Firstly, it sets the stage for future experimental work by providing testable hypotheses about the physiology, biochemistry, and evolution of chemoautotrophicCampylobacteria. Secondly, it provides constraints on the carbon fixation potential of chemoautotrophicCampylobacteriain sulfidic environments worldwide by predicting theoretical ranges of chemosynthetic growth efficiency.SignificanceChemoautotrophicCampylobacteriaare abundant in many low-oxygen, high-sulfide environments where they contribute significantly to dark carbon fixation. Although the overall redox reactions they catalyze are known, the specific biochemical mechanisms that support their growth are mostly unknown. Our study combines conceptual modeling of core metabolic pathways, comparative genomics, and measurements of physiological growth yield in a chemostat to infer the most likely mechanisms of chemoautotrophic energy conservation in the model organismSulfurimonas denitrificans. The hypotheses proposed herein are novel, experimentally falsifiable, and will guide future biochemical, physiological, and environmental modelling studies. Ultimately, investigating the core mechanisms of energy conservation will help us better understand the evolution and physiological diversification of chemoautotrophicCampylobacteriaand their role in modern ecosystems.
Enhanced Population Control in Synthetic Bacterial Consortium by Interconnected Carbon Cross-Feeding
Authors: Losoi Pauli S. , Santala Ville P. , Santala Suvi M. 
Published: July 2019

AbstractEngineered microbial consortia can provide several advantages over monocultures in terms of utilization of mixed substrates, resistance to perturbations, and division of labor in complex tasks. However, maintaining stability, reproducibility, and control over population levels in variable conditions can be challenging in multi-species cultures. In our study, we modeled and constructed a synthetic symbiotic consortium with a genetically encoded carbon cross-feeding system. The system is based on strains ofEscherichia coliandAcinetobacter baylyiADP1, both engineered to be incapable of growing on glucose on their own. In a culture supplemented with glucose as the sole carbon source, growth of the two strains is afforded by the exchange of gluconate and acetate, resulting in inherent control over carbon availability and population balance. We investigated the system robustness in terms of stability and population control under different inoculum ratios, substrate concentrations, and cultivation scales, both experimentally and by modeling. To illustrate how the system might facilitate division of genetic circuits among synthetic microbial consortia, a green fluorescent protein sensitive to pH and a slowly-maturing red fluorescent protein were expressed in the consortium as measures of a circuit’s susceptibility to external and internal variability, respectively. The symbiotic consortium maintained stable and linear growth and circuit performance regardless of the initial substrate concentration or inoculum ratios. The developed cross-feeding system provides simple and reliable means for population control without expression of non-native elements or external inducer addition, being potentially exploitable in consortia applications involving precisely defined cell tasks or division of labor.