bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiorespiratory fitness predicts greater hippocampal volume and rate of episodic associative learning in older adults
Authors: Cole Rachel C. , Hazeltine Eliot , Weng Timothy B. , Wharff Conner , DuBose Lyndsey E. , Schmid Phillip , Sigurdsson Gardar , Magnotta Vincent A. , Pierce Gary L. , Voss Michelle W. 
Published: April 2019

ABSTRACTDeclining episodic memory is common among otherwise healthy older adults, in part due to negative effects of aging on hippocampal circuits. However, there is significant variability between individuals in severity of aging effects on the hippocampus and subsequent memory decline. Importantly, variability may be influenced by modifiable protective physiological factors such as cardiorespiratory fitness (CRF). More research is needed to better understand which aspects of cognition that decline with aging benefit most from CRF. The current study evaluated the relation of CRF with learning rate in the Episodic Associative Learning (EAL) task, a task designed specifically to target hippocampal-dependent relational binding and to evaluate learning with repeated occurrences. Results show that higher CRF was associated with larger hippocampal volume and faster learning rate. Larger hippocampal volume was also associated with faster learning rate, and hippocampal volume partially mediated the relationship between CRF and learning rate. Further, to support the distinction between learning item relations and learning higher-order sequences, which declines with aging but is largely reliant on extra-hippocampal learning systems, we found that EAL learning rate was not related to motor sequence learning on the alternating serial reaction time task. Motor sequence learning was also not correlated with hippocampal volume. Thus, for the first time we show that higher CRF in healthy older adults is related to enhanced rate of relational memory acquisition, in part mediated by benefits on the hippocampus.
Deficient stereopsis in the normal population revisited: why current clinical stereo tests may not be adequate
Authors: Hess Robert F , Dillon Rebecca , Ding Rifeng , Zhou Jiawei 
Published: April 2019

AbstractSignificance statementApplied applications for occupational screening, clinical tests should assess sensitivity to the sign as well as the magnitude of disparity.PurposeTo determine why the high incidence of stereo anomaly found using laboratory tests with polarity-based increment judgements (i.e., depth sign) is not reflected in clinical measurements that involve single-polarity incremental judgements (i.e., depth magnitude).MethodsAn iPod-based measurement that involved the detection of an oriented shape defined by a single polarity-depth increment within a random dot display was used. A staircase procedure was used to gather sufficient trials to derive a meaningful measure of variance for the measurement of stereopsis over a large disparity range. Forty-five adults with normal binocular vision (20 - 65 years old) and normal or corrected-to-normal (0 logMAR or better) monocular vision participated in this study.ResultsObservers’ stereo acuities ranged between 10 and 100 arc seconds, and were normally distributed on a log scale (p = 0.90, 2-tailed Shapiro-Wilk test). The present results using a single polarity depth increment task (i.e., depth magnitude) show a similar distribution to those using a similar task using the Randot preschool stereo test on individuals between the ages of 19-35 using either the 4-book test (n = 33) or the 3-book test (n = 40), but very different results when the iPod test involved a polarity-based increment judgement (i.e., depth sign).ConclusionsThe present clinical stereo tests are based on magnitude judgements and are unable to detect the high percentage of stereo anomalous individuals in the normal population revealed using depth sign judgements.
CRISPR-Cas9 Gene Editing in Lizards Through Microinjection of Unfertilized Oocytes
Authors: Rasys Ashley M. , Park Sungdae , Ball Rebecca E. , Alcala Aaron J. , Lauderdale James D. , Menke Douglas B. 
Published: April 2019

AbstractCRISPR-Cas9 mediated gene editing has enabled the direct manipulation of gene function in many species. However, the reproductive biology of reptiles presents unique barriers for the use of this technology, and there are currently no reptiles with effective methods for targeted mutagenesis. Here we present a new approach that enables the efficient production of CRISPR-Cas9 induced mutations in Anolis lizards, an important model for studies of reptile evolution and development.
The mutational landscape of a prion-like domain
Authors: Bolognesi Benedetta , Faure Andre J. , Seuma Mireia , Schmiedel Jörn M. , Tartaglia Gian Gaetano , Lehner Ben 
Published: April 2019

AbstractSpecific insoluble protein aggregates are the hallmarks of many neurodegenerative diseases1–5. For example, cytoplasmic aggregates of the RNA-binding protein TDP-43 are observed in 97% of cases of Amyotrophic Lateral Sclerosis (ALS)6,7. However, it is still unclear for ALS and other diseases whether it is the insoluble aggregates or other forms of the mutated proteins that cause these diseases that are actually toxic to cells8–13. Here we address this question for TDP-43 by systematically mutating14the protein and quantifying the effects on cellular toxicity. We generated >50,000 mutations in the intrinsically disordered prion-like domain (PRD) and observed that changes in hydrophobicity and aggregation potential are highly predictive of changes in toxicity. Surprisingly, however, increased hydrophobicity and cytoplasmic aggregation actually reduce cellular toxicity. Mutations have their strongest effects in a central region of the PRD, with variants that increase toxicity promoting the formation of more dynamic liquid-like condensates. The genetic interactions in double mutants reveal that specific structures exist in this ‘unstructured’ regionin vivo. Our results demonstrate that deep mutagenesis is a powerful approach for probing the sequence-function relationships of intrinsically disordered proteins as well as theirin vivostructural conformations. Moreover, we show that aggregation of TDP-43 is not harmful but actually protects cells, most likely by titrating the protein away from a toxic liquid-like phase.
Microsaccades and attention in a high-acuity visual alignment task
Authors: Nanjappa Rakesh , McPeek Robert M. 
Published: April 2019

ABSTRACTWhile aiming and shooting, we make tiny eye movements called microsaccades that shift gaze between task-relevant objects within a small region. However, in the brief period before pressing trigger, microsaccades are suppressed. This might be due to the lack of the requirement to shift gaze as the retinal images of the two objects start overlapping on fovea. Or we might be actively suppressing microsaccades to prevent any disturbances in visual perception caused by microsaccades around the time of their occurrence and their subsequent effect on shooting performance.In this study we looked at microsaccade rate while participants performed a simulated shooting task under two conditions: normal viewing in which they moved their eyes freely and eccentric condition in which they maintained gaze on a fixed target while performing shooting task at 5° eccentricity. As expected, microsaccade rate dropped at the end of the task in the normal viewing condition. However, we found the same for the eccentric condition in which microsaccade did not shift gaze between the task objects.Microsaccades are also produced in response to shifts in covert attention. To test whether disengagement of covert attention from eccentric shooting location caused the drop in microsaccade rate, we monitored participant’s spatial attention location by employing a RSVP task simultaneously at a location opposite to the shooting task. Target letter detection at RSVP location did not improve during the drop in microsaccade rate, suggesting that covert attention was maintained at the shooting task location.We conclude that in addition to their usual gaze-shifting function, microsaccades during fine acuity tasks might be modulated by cognitive processes other than spatial attention.
Heritability of skewed X-inactivation in female twins is tissue-specific and dependent on age
Authors: Zito Antonino , Davies Matthew N. , Tsai Pei-Chien , Roberts Susanna , Nardone Stefano , Bell Jordana T. , Wong Chloe C. Y. , Small Kerrin S. 
Published: April 2019

AbstractTo balance the X-linked transcriptional dosages between the sexes, one of the two X-chromosomes is randomly selected to be inactivated in somatic tissues of female placental mammals. Non-random, or skewed X-chromosome inactivation (XCI) toward one parental X has been observed in female somatic tissues, and this skewing effect has been associated with several complex human traits. However, the extent of the influence of genetic and environmental factors on XCI skewing is largely unknown. Here, we use RNA-seq and DNA-seq data taken from a large cohort of female twins to quantify the degree of skewing of XCI (DS) in multiple tissues and to study the relationship of XCI with age, genetic factors and complex traits. We show that the XCI patterns are highly tissue-specific with a higher prevalence of skewed XCI in blood-derived tissues than in fat or skin tissue. We also show that the DS in blood-derived tissues is associated with age and that the acquired DS occurs uniquely in blood-derived tissues with an inflection point at approximately 55 years of age. Heritability analysis indicates that the heritability of DS is both age and tissue specific; DS is heritable in blood tissue of females >55 years-old (h2= 0.34) but is not heritable in blood tissues of females <55 years-old (h2= 0), nor in skin and fat tissues at any age. We find a positive association between the DS and smoking status in blood tissues of older females (P= 0.02). The high tissue specificity of XCI patterns in human indicates the existence of tissue-specific mechanisms influencing XCI patterns, including genetic and environmental factors. We conclude that the heritability of XCI skewing in blood-derived tissues is dependent on age, representing a Gene x Age interaction that can shift the functional allelic dosage of an entire chromosome in a tissue-restricted manner.
Neurocognitive reorganization between crystallized intelligence, fluid intelligence and white matter microstructure in two age-heterogeneous developmental cohorts
Authors: Simpson-Kent Ivan L. , Fuhrmann Delia , Bathelt Joe , Achterberg Jascha , Borgeest Gesa Sophia ,   the CALM Team, Kievit Rogier A. 
Published: April 2019

AbstractDespite the reliability of intelligence measures in predicting important life outcomes such as educational achievement and mortality, the exact configuration and neural correlates of cognitive abilities remain poorly understood, especially in childhood and adolescence. Therefore, we sought to elucidate the factorial structure and neural substrates of child and adolescent intelligence using two cross-sectional, developmental samples (CALM: N=551 (N=165 imaging), age range: 5-18 years, NKI-Rockland: N=337 (N=65 imaging), age range: 6-18 years). In a preregistered analysis, we used structural equation modelling (SEM) to examine the neurocognitive architecture of individual differences in childhood and adolescent cognitive ability. In both samples, we found that cognitive ability in lower and typical-ability cohorts is best understood as two separable constructs, crystallized and fluid intelligence, which became more distinct across development, in line with the age differentiation hypothesis. Further analyses revealed that white matter microstructure, most prominently the superior longitudinal fasciculus, was strongly associated with crystallized (gc) and fluid (gf) abilities. Finally, we used SEM trees to demonstrate evidence for developmental reorganization of gc and gf and their white matter substrates such that the relationships among these factors dropped between 7-8 years before increasing around age 10. Together, our results suggest that shortly before puberty marks a pivotal phase of change in the neurocognitive architecture of intelligence.
AlbaTraDIS: Comparative analysis of large datasets from parallel transposon mutagenesis experiments
Authors: Page Andrew J. , Bastkowski Sarah , Yasir Muhammad , Turner A. Keith , Le Viet Thanh , Savva George M. , Webber Mark A. , Charles Ian G. 
Published: April 2019

AbstractBackgroundBacteria have evolved over billions of years to survive in a wide range of environments. Currently, there is an incomplete understanding of the genetic basis for mechanisms underpinning survival in stressful conditions, such as the presence of anti-microbials. Transposon mutagenesis has been proven to be a powerful tool to identify genes and networks which are involved in survival and fitness under a given condition by simultaneously assaying the fitness of millions of mutants, thereby relating genotype to phenotype and contributing to an understanding of bacterial cell biology. A recent refinement of this approach allows the roles of essential genes in conditional stress survival to be inferred by altering their expression. These advancements combined with the rapidly falling costs of sequencing now allows comparisons between multiple experiments to identify commonalities in stress responses to different conditions. This capacity however poses a new challenge for analysis of multiple data sets in conjunction.ResultsTo address this analysis need, we have developed ‘AlbaTraDIS’; a software application for rapid large-scale comparative analysis of TraDIS experiments that predicts the impact of transposon insertions on nearby genes. AlbaTraDIS can identify genes which are up or down regulated, or inactivated, between multiple conditions, producing a filtered list of genes for further experimental validation as well as several accompanying data visualisations. We demonstrate the utility of our new approach by applying it to identify genes used byEscherichia colito survive in a wide range of different concentrations of the biocide Triclosan. AlbaTraDIS automatically identified all well characterised Triclosan resistance genes, including the primary target,fabI. A number of new loci were also implicated in Triclosan resistance and the predicted phenotypes for a selection of these were validated experimentally and results showed high consistency with predictions.ConclusionsAlbaTraDIS provides a simple and rapid method to analyse multiple transposon mutagenesis data sets allowing this technology to be used at large scale. To our knowledge this is the only tool currently available that can perform these tasks. AlbaTraDIS is written in Python 3 and is available under the open source licence GNU GPL 3 fromhttps://github.com/quadram-institute-bioscience/albatradis.
In vitro Evaluation of Antifungal Drug Combinations against Multidrug-resistant Candida auris isolates from New York Outbreak
Authors: O’Brien Brittany , Chaturvedi Sudha , Chaturvedi Vishnu 
Published: April 2019

AbstractSince 2016, New York hospitals and healthcare facilities have faced an unprecedented outbreak of pathogenic yeast Candida auris. We tested over one thousand C. auris isolates from affected facilities and found high-resistance to fluconazole (FLC, MIC50>256 mg/L), and variable resistance to other antifungal drugs. Therefore, we evaluated if two-drug combinations are effective in vitro against multidrug-resistant C. auris. Broth micro-dilution (BMD) plates were custom-designed, and quality controlled by TREK Diagnostic System. We used MIC100 endpoints for the drug combination readings as reported earlier for the intra- and inter-laboratory agreements against Candida species and Aspergillus fumigatus. The study results were derived from 12,960 MIC100 readings, for fifteen C. auris isolates tested against 864 possible two-drug antifungal combinations for nine antifungal drugs. Flucytosine (5FC) at 1.0 mg/L potentiated the most successful combinations with other drugs. Micafungin (MFG), Anidulafungin (AFG), Caspofungin (CAS) at individual concentrations of 0.25 mg/L in combination with 5FC (1.0 mg/L) yielded MIC100 for 14, 13, and 12 of 15 C. auris test isolates. AMB / 5FC (0.25/1.0 mg/L) yielded MIC100 for 13 isolates. None of the combinations were effective for C. auris 18-1, which tested resistant against FLC and 5FC, except POS/5FC (0.12/1.0 mg/L). The simplified two-drug combination susceptibility test format would permit laboratories to provide clinicians and public health experts with additional data to deal with multidrug-resistant C. auris.
Complexity measures of the electroencephalograph capture loss and recovery of consciousness in patients anesthetized with propofol
Authors: Eagleman Sarah L. , Chander Divya , Reynolds Christina , Ouellette Nicholas T. , MacIver M. Bruce 
Published: April 2019

ABSTRACTPropofol is one of the most widely used anesthetics for routine surgical anesthesia. Propofol administration alone produces EEG spectral characteristics similar to most hypnotics; however, inter-individual variation can make spectral measures inconsistent. Complexity measures of EEG signals could offer universal measures to better capture anesthetic depth as brain activity exhibits nonlinear behavior at several scales. We tested the potential of nonlinear dynamics analyses to identify loss and recovery of consciousness at clinically relevant timepoints. Patients undergoing propofol general anesthesia for various surgical procedures were identified as having changes in states of consciousness by the loss and recovery of response to verbal stimuli after induction and upon cessation of anesthesia, respectively. Nonlinear dynamics analyses showed more significant differences between consciousness states than most spectral measures. Thus, complexity measures could provide a means for reliably capturing depth of consciousness based on subtle EEG changes at the beginning and end of anesthesia administration.
Attentive red squirrel mothers have faster-growing pups and higher lifetime reproductive success
Authors: Westrick Sarah E , Taylor Ryan W , Boutin Stan , Lane Jeffrey E , McAdam Andrew G , Dantzer Ben 
Published: April 2019

AbstractParental investment theory predicts that observed levels of parental care afforded to offspring are set by the benefits (to offspring quality and survival) relative to the costs (to parental survival or future reproduction). Although difficult to document in mammals, there is often substantial individual-variation in the amount of parental care within species. We measured the impact of individual variation in maternal care (“attentiveness” towards offspring or maternal motivation) on offspring growth and survival in a wild population of North American red squirrels (Tamiasciurus hudsonicus). We used latency to return to pups following a nest intrusion as a measure of maternal attentiveness to pups. We found this behavior to be repeatable within individuals suggesting this behavior is a personality trait or a “maternal style”. In this population, postnatal growth rate is important for pup overwinter survival. Pups from large litters grew faster if they had a highly attentive mother, indicating that maternal care behavior can mitigate the trade-off between litter size and offspring growth and potentially improve survival of pups. Additionally, more attentive mothers had slightly higher lifetime reproductive success than less attentive mothers. These results highlight important fitness effects of having a highly attentive mother and show that maternal care behavior can alter a fundamental life history trade-off between offspring quantity and quality.Lay SummaryIt pays to be attentive to your pups as a squirrel mom. In a long-term study of a wild population of North American red squirrels, we observed repeatable individual variation in maternal attentiveness towards offspring. Mothers who returned faster to pups following a nest intrusion produced faster growing pups and were able to produce larger fast-growing litters. Over their entire lifetime, attentive mothers also had more offspring recruit into the breeding population.
Methylomic profiles reveal sex-specific shifts in leukocyte composition associated with post-traumatic stress disorder
Authors: Kim Grace S. , Smith Alicia , Xu Fei , Michopoulos Vasiliki , Lori Adriana , Armstrong Don L. , Aiello Allison E. , Koenen Karestan C. , Galea Sandro , Wildman Derek E. , Uddin Monica 
Published: April 2019

ABSTRACTPost-traumatic stress disorder (PTSD) is a debilitating mental disorder precipitated by trauma exposure. However, only some persons exposed to trauma develop PTSD. There are sex differences in risk; twice as many women as men, develop a lifetime diagnosis of PTSD. Methylomic profiles derived from peripheral blood are well-suited for investigating PTSD because DNA methylation (DNAm) encodes individual response to trauma and may play a key role in the immune dysregulation characteristic of PTSD pathophysiology. In the current study, we leveraged recent methodological advances to investigate sex-specific shifts in DNAm-based leukocyte composition that are associated with lifetime PTSD. We estimated leukocyte composition on a combined methylation array dataset (483 participants, ∼450k CpG sites) consisting of two civilian cohorts, the Detroit Neighborhood Health Study and Grady Trauma Project. Sex-stratified Mann-Whitney U test and two-way ANCOVA revealed that lifetime PTSD was associated with a small but significant elevation in monocyte proportions in males, but not in females (Holm-adjusted p-val < 0.05). No difference in monocyte proportions was observed between current and remitted PTSD cases in males, suggesting that this sex-specific peak shift reflects a long-standing trait of lifetime history of PTSD, rather than current state of PTSD. Associations with lifetime PTSD or PTSD status were not observed in any other leukocyte subtype and our finding in monocytes was confirmed using cell estimates based on a different deconvolution algorithm, suggesting that our sex-specific findings are robust across cell estimation approaches. Overall, our main finding of elevated monocyte proportions in males, but not in females with lifetime history of PTSD provides evidence for a sex-specific shift in peripheral blood leukocyte composition that is detectable in methylomic profiles and that reflects long-standing changes associated with PTSD diagnosis.