bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silver-spoon upbringing improves early-life fitness but promotes reproductive ageing in a wild bird
Authors: Spagopoulou Foteini , Teplitsky Celine , Lind Martin I. , Gustafsson Lars , Maklakov Alexei A. 
Published: January 2019

SummaryEarly-life conditions can have long-lasting effects and organisms that experience a poor start in life are often expected to age at a faster rate. Alternatively, individuals raised in high-quality environments can overinvest in early-reproduction resulting in rapid ageing. Here we use a long-term experimental manipulation of early-life conditions in a natural population of collared flycatchers (Ficedula albicollis), to show that females raised in a low-competition environment (artificially reduced broods) have higher early-life reproduction but lower late-life reproduction than females raised in high-competition environment (artificially increased broods). Reproductive success of high-competition females peaked in late-life, when low-competition females were already in steep reproductive decline and suffered from a higher mortality rate. Our results demonstrate that “silver-spoon” natal conditions increase female early-life performance at the cost of faster reproductive ageing and increased late-life mortality. These findings demonstrate experimentally that natal environment shapes individual variation in reproductive and demographic ageing in nature.
Lobule-specific dosage considerations for cerebellar transcranial direct current stimulation during healthy aging – a computational modeling study using age-specific MRI templates
Authors: Rezaee Zeynab , Dutta Anirban 
Published: January 2019

AbstractThe world population aged 60 years and older is expected to double between 2015 and 2050. Aging is associated with a decline in cognitive and motor performances which are a part of geriatric syndromes. Aging is also associated with the loss of cerebellar volume where the cerebellum has a considerable contribution in cognitive and motor functions. Therefore, cerebellar transcranial direct current stimulation (ctDCS) has been proposed to study and facilitate cerebellar function during aging. However, the one-size-fits-all approach used for ctDCS can lead to variability in the cerebellar lobule-specific dosing due to age-related changes in the cerebellar structure. Therefore, we investigated lobular electric field (EF) distribution during healthy aging for age groups of 18 to 89 years where computational modeling was based on age-appropriate human brain magnetic resonance imaging (MRI) templates (http://jerlab.psych.sc.edu/NeurodevelopmentalMRIDatabase/). A fully automated open-source pipeline (Realistic vOlumetric-Approach to Simulate Transcranial Electric Stimulation – ROAST) was used for the age-group specific EF modeling. Then, we extracted the EF distribution at the 28 cerebellar lobules based on a spatially unbiased atlas (SUIT) for the cerebellum. Our computational results showed that the EF strength increased significantly at certain important cerebellar lobules (e.g., Crus I and Crus II relevant for cognitive function) contralateral (contra) to the targeted (ipsi) cerebellar hemisphere at an older age that reduced the ctDCS specificity. Specifically, two-way ANOVA showed that the lobules as well as the age-group (and their interaction term) had a significant effect (p<0.01). Post-hoc multiple comparison tests at Alpha=0.01 using Bonferroni critical values showed that Right (Ipsi) Crus I, Right (Ipsi) Crus II, Right (Ipsi) VI, Vermis VIIb, Vermis VIIIa, Right (Ipsi) VIIb, Left (Contra) VIIIb, Left (Contra) IX, Right (Ipsi) VIIIa, Right (Ipsi) VIIIb, Vermis VIIIb, Right (Ipsi) IX, and Vermis IX, and the age-group 18, 18.5, 19, 20-24, 45-49, 50-54, 70-74, 75-79, 85-89 years experienced higher electric field strength (>0.11V/m). Since there is a dichotomy between the sensorimotor cerebellum and the cognitive cerebellum, therefore, subject-specific MRI based head modeling for lobule-specific dosage considerations will be necessary for clinical translation of ctDCS to address geriatric cerebellar syndromes.
Stable transgenesis in Astyanax mexicanus using the Tol2 transposase system
Authors: Stahl Bethany A. , Peuß Robert , McDole Brittnee , Kenzior Alexander , Jaggard James B. , Gaudenz Karin , Krishnan Jaya , McGaugh Suzanne E. , Duboue Erik R. , Keene Alex C. , Rohner Nicolas 
Published: January 2019

AbstractAstyanax mexicanus is a well-established and widely used fish model system for evolutionary and developmental biology research. These fish exist as surface forms that inhabit rivers and 30 different populations of cavefish. The establishment of A. mexicanus as an emergent model organism for understanding the evolutionary basis of development and behavior has been accelerated by an increasing availability of genomic approaches to identify genotype-phenotype associations. Despite important progress in the deployment of new technologies, deep mechanistic insights into A. mexicanus evolution and development have been limited by a lack of transgenic lines commonly used in genetic model systems. Here, we expand the toolkit of transgenesis by characterizing two novel stable transgenic lines that were generated using the highly efficient Tol2 system, commonly used to generate transgenic zebrafish. A stable transgenic line consisting of the zebrafish ubiquitin promoter fused to eGFP expressed eGFP ubiquitously throughout development in a surface population of Astyanax. To define specific cell-types, we injected fish with a Cntnap2-mCherry construct that labels lateral line mechanosensory neurons in zebrafish. Strikingly, both constructs appear to label the predicted cell types, suggesting many genetic tools and defined promoter regions in zebrafish are directly transferrable to cavefish. The lines provide proof-of-principle for the application of Tol2 transgenic technology in A. mexicanus. Expansion on these initial transgenic lines will provide a platform to address broadly important problems in the quest to bridge the genotype to phenotype gap.
Human Myosin 1e tail but not motor domain replaces fission yeast Myo1 domains to support myosin-I function during endocytosis
Authors: Barger Sarah R. , James Michael L. , Pellenz Christopher D. , Krendel Mira , Sirotkin Vladimir 
Published: January 2019

ABSTRACTIn both unicellular and multicellular organisms, long-tailed class I myosins function in clathrin-mediated endocytosis. Myosin 1e (Myo1e) in vertebrates and Myo1 in fission yeast have similar domain organization, yet whether these proteins or their individual protein domains are functionally interchangeable remains unknown. In an effort to assess functional conservation of class I myosins, we tested whether human Myo1e could replace Myo1 in fission yeastSchizosaccharomyces pombeand found that it was unable to substitute for yeast Myo1. To determine if any individual protein domain is responsible for the inability of Myo1e to function in yeast, we created human-yeast myosin-I chimeras. By functionally testing these chimeric myosinsin vivo,we concluded that the Myo1e motor domain is unable to function in yeast, even when combined with the yeast Myo1 tail and a full complement of yeast regulatory light chains. Conversely, the Myo1e tail, when attached to the yeast Myo1 motor domain, supports localization to actin patches and partially rescues the endocytosis defect inmyo1Δcells. Further dissection showed that both the TH1 and TH2-SH3 domains in the human Myo1e tail are required for localization and function of chimeric myosin-I at endocytic sites. Overall, this study provides insights into the role of individual myosin-I domains, expands the utility of fission yeast as a simple model system to study the effects of disease-associatedMYO1Emutations, and supports a model of co-evolution between a myosin motor and its actin track.
Focused natural product elucidation by prioritizing high-throughput metabolomic studies with machine learning
Authors: Tobias Nicholas J. , Parra-Rojas César , Shi Yan-Ni , Shi Yi-Ming , Simonyi Svenja , Thanwisai Aunchalee , Vitta Apichat , Chantratita Narisara , Hernandez-Vargas Esteban A. , Bode Helge B. 
Published: January 2019

AbstractBacteria of the genera Photorhabdus and Xenorhabdus produce a plethora of natural products to support their similar symbiotic lifecycles. For many of these compounds, the specific bioactivities are unknown. One common challenge in natural product research when trying to prioritize research efforts is the rediscovery of identical (or highly similar) compounds from different strains. Linking genome sequence to metabolite production can help in overcoming this problem. However, sequences are typically not available for entire collections of organisms. Here we perform a comprehensive metabolic screening using HPLC-MS data associated with a 114-strain collection (58 Photorhabdus and 56 Xenorhabdus) from across Thailand and explore the metabolic variation among the strains, matched with several abiotic factors. We utilize machine learning in order to rank the importance of individual metabolites in determining all given metadata. With this approach, we were able to prioritize metabolites in the context of natural product investigations, leading to the identification of previously unknown compounds. The top three highest-ranking features were associated with Xenorhabdus and attributed to the same chemical entity, cyclo(tetrahydroxybutyrate). This work addresses the need for prioritization in high-throughput metabolomic studies and demonstrates the viability of such an approach in future research.
Turning a green alga red: engineering astaxanthin biosynthesis by intragenic pseudogene revival in Chlamydomonas reinhardtii
Authors: Perozeni Federico , Cazzaniga Stefano , Baier Thomas , Zanoni Francesca , Zoccatelli Gianni , Lauersen Kyle J. , Wobbe Lutz , Ballottari Matteo 
Published: January 2019

SummaryThe green alga Chlamydomonas reinhardtii does not synthesize high-value ketocarotenoids like canthaxanthin and astaxanthin, however, a β-carotene ketolase (CrBKT) can be found in its genome. CrBKT is poorly expressed, contains a long C-terminal extension not found in homologues and likely represents a pseudogene in this alga. Here, we used synthetic re-design of this gene to enable its constitutive overexpression from the nuclear genome of C. reinhardtii. Overexpression of the optimized CrBKT extended native carotenoid biosynthesis to generate ketocarotenoids in the algal host causing noticeable changes the green algal colour to a reddish-brown. We found that up to 50% of native carotenoids could be converted into astaxanthin and more than 70% into other ketocarotenoids by robust CrBKT overexpression. Modification of the carotenoid metabolism did not impair growth or biomass productivity of C. reinhardtii, even at high light intensities. Under different growth conditions, the best performing CrBKT overexpression strain was found to reach ketocarotenoid productivities up to 4.5 mg L-1 day-1. Astaxanthin productivity in engineered C. reinhardtii shown here is competitive with that reported for Haematococcus lacustris (formerly pluvialis) which is currently the main organism cultivated for industrial astaxanthin production. In addition, the extractability and bio-accessibility of these pigments was much higher in cell wall deficient C. reinhardtii than the resting cysts of H. lacustris. Engineered C. reinhardtii strains could thus be a promising alternative to natural astaxanthin producing algal strains and may open the possibility of other tailor-made pigments from this host.
Non-Invasive Detection of Viral Antibodies Using Oral Flocked Swabs
Authors: Speicher David J. , Luinstra Kathy , Smith Emma J. , Castriciano Santina , Smieja Marek 
Published: January 2019

AbstractSalivary antibodies are useful in surveillance and vaccination studies. However, low antibody levels and degradation by endonucleases are problematic. Oral flocked swabs are a potential non-invasive alternative to blood for detecting viral antibodies. Serum and saliva collected from 50 healthy volunteers were stored at −80°C; dried swabs at room temperature. Seroprevalence for Cytomegalovirus (CMV), Varicella-Zoster virus (VZV), Epstein-Barr virus (EBV), Measles and Mumps IgG antibodies were determined using commercial ELISAs and processed on an automated platform. For each antibody, swabs correlated well with saliva. For CMV IgG, VZV IgG, and EBV EBNA-1 IgG and VCA IgG, the swab sensitivities compared to serum were 95.8%, 96%, 92.1% and 95.5% respectively. For Measles IgG, swab sensitivity was 84.5%. Mumps IgG displayed poor sensitivity for oral swabs (60.5%) and saliva (68.2%). Specificities for IgG antibodies were 100% for CMV, EBV and Mumps. Specificities for VZV and Measles could not be determined due to seropositive volunteers. As oral flocked swabs correlate well with serum, are easy to self-collect and stable at room temperature further research is warranted.HighlightsOral flocked swabs are an easy, self-collection method for measuring viral antibodies.Viral IgG is stable on dried oral flocked swabs for at least two years.Oral swabs are highly sensitive for CMV, VZV, and EBV IgG.Oral swabs are potentially useful for surveillance and clinical microbiology.
The network underlying human higher-order motor control: Insights from machine learning-based lesion-behaviour mapping in apraxia
Authors: Sperber Christoph , Wiesen Daniel , Goldenberg Georg , Karnath Hans-Otto 
Published: January 2019

AbstractNeurological patients with apraxia of pantomime provide us with a unique opportunity to study the neural correlates of higher-order motor function. Previous studies using lesion-behaviour mapping methods led to inconsistent anatomical results, reporting various lesion locations to induce this symptom. We hypothesised that the inconsistencies might arise from limitations of mass-univariate lesion-behaviour mapping approaches if our ability to pantomime the use of objects is organised in a brain network. Thus, we investigated apraxia of pantomime by using multivariate lesion behaviour mapping based both on support vector regression and sparse canonical correlations in a sample of 130 left-hemisphere stroke patients. Both multivariate methods identified multiple areas to underlie high-order motor control, including inferior parietal lobule, precentral gyrus, posterior parts of middle temporal cortex, and insula. Further, long association fibres were affected, such as the superior longitudinal fascicle, inferior occipito-frontal fascicle, uncinated fascicle, and superior occipito-frontal fascicle. The findings thus not only underline the benefits of multivariate lesion-behaviour mapping in brain networks, but they also uncovered that higher-order motor control indeed is based on a common anatomical network.
Re-curation and Rational Enrichment of Knowledge Graphs in Biological Expression Language
Authors: Hoyt Charles Tapley , Domingo-Fernández Daniel , Aldisi Rana , Xu Lingling , Kolpeja Kristian , Spalek Sandra , Wollert Esther , Bachman John , Gyori Benjamin M. , Greene Patrick , Hofmann-Apitius Martin 
Published: January 2019

AbstractThe rapid accumulation of new biomedical literature not only causes curated knowledge graphs to become outdated and incomplete, but also makes manual curation an impractical and unsustainable solution. Automated or semi-automated workflows are necessary to assist in prioritizing and curating the literature to update and enrich knowledge graphs.We have developed two workflows: one for re-curating a given knowledge graph to assure its syntactic and semantic quality and another for rationally enriching it by manually revising automatically extracted relations for nodes with low information density. We applied these workflows to the knowledge graphs encoded in Biological Expression Language from the NeuroMMSig database using content that was pre-extracted from MEDLINE abstracts and PubMed Central full text articles using text mining output integrated by INDRA. We have made this workflow freely available at https://github.com/bel-enrichment/bel-enrichment.Database URLhttps://github.com/bel-enrichment/results
Dual pathway for metabolic engineering of E. coli metabolism to produce the highly valuable hydroxytyrosol
Authors: Trantas Emmanouil , Navakoudis Eleni , Pavlidis Theofilos , Nikou Theodora , Halabalaki Maria , Skaltsounis Leandros , Ververidis Filippos 
Published: January 2019

AbstractOne of the most abundant phenolic compounds traced in olive tissues is Hydroxytyrosol (HT), a molecule that has been attributed with a pile of beneficial effects, well documented by many epidemiological studies and thus adding value to products containing it. Strong antioxidant capacity and protection from cancer are only some of its exceptional features making it ideal as a potential supplement or preservative to be employed in the nutraceutical, agrochemical, cosmeceutical, and food industry. The HT biosynthetic pathway in plants (e.g. olive fruit tissues) is not well apprehended yet. In this contribution we employed a metabolic engineering strategy by constructing a dual pathway introduced inEscherichia coliand proofing its significant functionality leading it to produce HT. Our primary target was to investigate whether such a metabolic engineering approach could benefit the metabolic flow of tyrosine introduced to the conceived dual pathway, leading to the maximalization of the HT productivity. Various gene combinations derived from plants or bacteria were used to form a newly-inspired, artificial biosynthetic dual pathway managing to redirect the carbon flow towards the production of HT directly from glucose. Various biosynthetic bottlenecks faced due tofeaBgene function, resolved through the overexpression of a functional aldehyde reductase. Currently, we have achieved equimolar concentration of HT to tyrosine as precursor when overproduced straight from glucose, reaching the level of 1.76 mM (270.8 mg/L) analyzed by LC-HRMS. This work realizes the existing bottlenecks of the metabolic engineering process that was dependent on the utilized host strain, growth medium as well as to other factors studied in this work.
Mutational analysis of field cancerization in bladder cancer
Authors: Strandgaard Trine , Nordentoft Iver , Lamy Philippe , Christensen Emil , Houlberg Thomsen Mathilde Borg , Jensen Jørgen Bjerggaard , Dyrskjøt Lars 
Published: January 2019

AbstractThe multifocal and recurrent nature of bladder cancer has been explained by field cancerization of the bladder urothelium. To shed light on field cancerization in the bladder, we investigated the mutational landscape of normal appearing urothelium and paired bladder tumors from four patients. Sequencing of 509 cancer driver genes revealed the presence of 2-16 mutations exclusively localized in normal tissue (average target read depth 634x). Furthermore, 6-13 mutations were shared between tumor and normal samples and 8-75 mutations were exclusively detected in tumor samples. More mutations were observed in normal samples from patients with multifocal disease compared to patients with unifocal disease. Mutations in normal samples had low allele frequencies compared to tumor mutations (p<2.2*10−16). Furthermore, significant differences in the type of nucleotide changes between tumor, normal and shared mutations (p=2.7*10−8) were observed, and mutations in APOBEC context were observed primarily among tumor mutations (p=0.026). No differences in functional impact between normal, shared and tumor mutations were observed (p=0.23). Overall, these findings support the theory of multiple fields in the bladder, and document non-tumor specific driver mutations to be present in normal appearing bladder tissue.
Doc2b Ca2+-binding site mutants act as a gain of function at rest and loss of function during neuronal activity
Authors: Bourgeois-Jaarsma Quentin , Verhage Matthijs , Groffen Alexander J. 
Published: January 2019

AbstractCommunication between neurons involves presynaptic neurotransmitter release which can be evoked by action potentials or occur spontaneously as a result of stochastic vesicle fusion. The Ca2+-binding double C2proteins Doc2a and –b regulate both spontaneous and asynchronous evoked release, but the mechanism remains unclear. Here, we compared wildtype Doc2b with two Ca2+binding site mutants named DN and 6A, respectively considered gain-and loss-of function mutants and carrying the substitutions D218,220N or D163,218,220,303,357,359A. We found that both mutants bound phospholipids at low free Ca2+concentrations and were membrane-associated in neurons at rest, mimicking a Ca2+activated state. Their overexpression in hippocampal primary neurons culture had similar effects on spontaneous and evoked release, inducing higher mEPSC frequencies and increased short-term depression. Together, these data suggest that the DN and 6A mutants both act as gain-of-function mutants at resting conditions but as loss-of-function during neuronal activity.
Cortical and subcortical T1 white/gray contrast, chronological age, and cognitive performance
Authors: Lewis John D. , Fonov Vladimir S. , Louis Collins D. , Evans Alan C. , Tohka Jussi ,   for the Brain Development Cooperative Group, and the Pediatric Imaging, Neurocognition, and Genetics Study
Published: January 2019

AbstractThe maturational schedule of typical brain development is tightly constrained; deviations from it are associated with cognitive atypicalities, and are potentially predictive of developmental disorders. Previously, we have shown that the white/gray contrast at the inner border of the cortex is a good predictor of chronological age, and is sensitive to aspects of brain development that reflect cognitive performance. Here we extend that work to include the contrast at the white/gray border of subcortical structures. We show that cortical and subcortical contrast together yield better age-predictions than any non-kernel-based method based on a single image-type, and that the residuals of the improved predictions provide new insight into unevenness in cognitive performance. We demonstrate the improvement in age predictions in two large datasets: the NIH Pediatric Data, with 831 scans of typically developing individuals between 4 and 22 years of age; and the Pediatric Imaging, Neurocognition, and Genetics data, with 909 scans of individuals in a similar age-range. Assessment of the relation of the residuals of these age predictions to verbal and performance IQ revealed correlations in opposing directions, and a principal component analysis of the residuals of the model that best fit the contrast data produced components related to either performance IQ or verbal IQ. Performance IQ was associated with the first principle component, reflecting increased cortical contrast, broadly, with almost no subcortical presence; verbal IQ was associated with the second principle component, reflecting reduced contrast in the basal ganglia and increased contrast in the bilateral arcuate fasciculi.