bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptive eQTLs reveal the evolutionary impacts of pleiotropy and tissue-specificity, while contributing to health and disease in human populations
Authors: Quiver Melanie H. , Lachance Joseph 
Published: October 2018

AbstractRegulatory DNA has the potential to be adaptive, and large numbers of expression quantitative trait loci (eQTLs) have recently been identified in humans. For the first time, a comprehensive study of adaptive eQTLs is possible. Many eQTLs have large allele frequency differences between populations, and these differences can be due to natural selection. Here, we combined population branch statistics with tissue-specific eQTL data to identify positively selected loci in human populations. Adaptive eQTLs tend to affect fewer tissues than non-adaptive eQTLs. Because the tissue breadth of an eQTL can be viewed as a measure of pleiotropy, these results suggest that pleiotropy can inhibit adaptation. The proportion of eQTLs that are adaptive varies by tissue, and we find that eQTLs that regulate expression in testis, thyroid, blood, or sun-exposed skin are enriched for adaptive outliers. By contrast, eQTLs that regulate expression in the cerebrum or female-specific tissues have a relative lack of adaptive outliers. These results reveal tissues that have been the targets of adaptation during the last 100,000 years of human evolution. The strongest adaptive signal in many regions of the human genome is an eQTL, including an eQTL associated with the Duffy blood group and malaria resistance. Scans of selection also reveal that many adaptive eQTLs are closely linked to disease-associated loci. Taken together, our results indicate that adaptive eQTLs have played an important role in human evolution.
Fast two-photon volumetric imaging of an improved voltage indicator reveals electrical activity in deeply located neurons in the awake brain
Authors: Chavarha Mariya , Villette Vincent , Dimov Ivan K. , Pradhan Lagnajeet , Evans Stephen W. , Shi Dongqing , Yang Renzhi , Chamberland Simon , Bradley Jonathan , Mathieu Benjamin , St-Pierre Francois , Schnitzer Mark J. , Bi Guoqiang , Toth Katalin , Ding Jun , Dieudonné Stéphane , Lin Michael Z. 
Published: October 2018

ABSTRACTImaging of transmembrane voltage deep in brain tissue with cellular resolution has the potential to reveal information processing by neuronal circuits in living animals with minimal perturbation. Multi-photon voltage imaging in vivo, however, is currently limited by speed and sensitivity of both indicators and imaging methods. Here, we report the engineering of an improved genetically encoded voltage indicator, ASAP3, which exhibits up to 51% fluorescence responses in the physiological voltage range, sub-millisecond activation kinetics, and full responsivity under two-photon illumination. We also introduce an ultrafast local volume excitation (ULOVE) two-photon scanning method to sample ASAP3 signals in awake mice at kilohertz rates with increased stability and sensitivity. ASAP3 and ULOVE allowed continuous single-trial tracking of spikes and subthreshold events for minutes in deep locations, with subcellular resolution, and with repeated sampling over multiple days. By imaging voltage in visual cortex neurons, we found evidence for cell type-dependent subthreshold modulation by locomotion. Thus, ASAP3 and ULOVE enable continuous high-speed high-resolution imaging of electrical activity in deeply located genetically defined neurons during awake behavior.
Pixel Quantum Efficiency Differences and Variance Stabilization for sCMOS Single Molecule Localization Microscopy Data Analysis
Authors: Babcock Hazen P. , Huang Fang 
Published: October 2018

ABSTRACTOptimal analysis of single molecule localization microscopy (SMLM) data acquired with a CMOS camera requires compensation for single pixel differences in gain, offset and readout noise. For some CMOS cameras we found that it is also necessary to compensate for pixel differences in sensitivity or relative quantum efficiency (RQE). We present the modifications to the original sCMOS analysis algorithm necessary to correct for these RQE differences. We also discuss the use of the Anscombe transform (AT) for variance stabilization. Removing the variance dependence on the mean allows simpler least squares fitting approaches to achieve the Cramer-Rao bound on the mixed Poisson and Gaussian distributed data typically acquired with an sCMOS camera.
Gastrocnemius fascicles are shorter and more pennate throughout the first month following acute Achilles tendon rupture
Authors: Hullfish Todd J. , O’Connor Kathryn M , Baxter Josh R. 
Published: October 2018

AbstractThe purpose of this study was to characterize the short-term effects of Achilles tendon ruptures on medial gastrocnemius. We hypothesized that the fascicles of the medial gastrocnemius muscle of the injured Achilles tendon would be shorter and more pennate immediately following the injury and would persist throughout 4 weeks post-injury. B-mode longitudinal ultrasound images of the medial gastrocnemius were acquired in 10 adults who suffered acute Achilles tendon ruptures and were treated non-operatively. Ultrasound images were acquired during the initial clinical visit following injury as well as two and four weeks following this initial clinical visit. Resting muscle structure was characterized by measuring fascicle length, pennation angle, muscle thickness, and muscle echo intensity in both the injured and contralateral (control) limbs. Fascicle length was 15% shorter (P< 0.001) and pennation angle was 21% greater (P< 0.001) in the injured muscle compared to the uninjured (control) muscle at the presentation of injury (week 0). These differences in fascicle length and pennation angle persisted throughout the 4 weeks after the injury (P< 0.008). Muscle thickness changes were not detected at any of the post-injury visits (difference < 4%,P> 0.04). Echo intensity of the injured limb was 8% lower at the presentation of the injury and 11% lower (P= 0.008) than the contralateral muscle at 2 weeks following injury (P< 0.001) but returned to within 1% by 4 weeks (P= 0.393). Our results suggest that Achilles tendon ruptures elicit rapid changes in the configuration and quality of the medial gastrocnemius, which may explain long-term functional deficits.
Large-scale neuron cell classification of single-channel and multi-channel extracellularrecordings in the anterior lateral motor cortex
Authors: Parikh Rohan 
Published: October 2018

AbstractIdentification of neuron cell type helps us connect neural circuitry and behavior; greater specificity in cell type and subtype classification provides a clearer picture of specific relationships between the brain and behavior. With the advent of high-density probes, large-scale neuron classification is needed, as typical extracellular recordings are identity-blind to the neurons they record. Current methods for identification of neurons include optogenetic tagging and intracellular recordings, but are limited in that they are expensive, time-consuming, and have a limited scope. Therefore, a more automated, real-time method is needed for large-scale neuron identification. Data from two recordings was incorporated into this research; the single-channel recording included data from three neuron types in the motor cortex: FS, IT, and PT neurons. The multi-channel recording contained data from two neuron subtypes also in the motor cortex: PT_L and PT_U neurons. This allowed for an examination of both general neuron classification and more specific subtype classification, which was done via artificial neural networks (ANNs) and machine learning (ML) algorithms. For the single-channel neuron classification, the ANNs achieved 91% accuracy, while the ML algorithms achieved 98% accuracy, using the raw electrical waveform. The multi-channel classification, which was significantly more difficult due to the similarity between the neuron types, yielded an ineffective ANN, reaching 68% accuracy, while the ML algorithms reached 81% using 8 calculated features from the waveform. Thus, to distinguish between different neuron cell types and subtypes in the motor cortex, both ANNs and specific ML algorithms can facilitate rapid and accurate near real-time large-scale classification.
Independent mechanisms for acquired salt tolerance versus growth resumption induced by mild ethanol pretreatment inSaccharomyces cerevisiae
Authors: McDaniel Elizabeth A. , Stuecker Tara N. , Veluvolu Manasa , Gasch Audrey P. , Lewis Jeffrey A. 
Published: October 2018

ABSTRACTAll living organisms must recognize and respond to various environmental stresses throughout their lifetime. In natural environments, cells frequently encounter fluctuating concentrations of different stressors that can occur in combination or sequentially. Thus, the ability to anticipate an impending stress is likely ecologically relevant. One possible mechanism for anticipating future stress is acquired stress resistance, where cells pre-exposed to a mild sub-lethal dose of stress gain the ability to survive an otherwise lethal dose of stress. We have been leveraging wild strains ofSaccharomyces cerevisiaeto investigate natural variation in the yeast ethanol stress response and its role in acquired stress resistance. Here, we report that a wild vineyard isolate possesses ethanol-induced cross-protection against severe concentrations of salt. Because this phenotype correlates with ethanol-dependent induction of theENAgenes, which encode sodium efflux pumps already associated with salt resistance, we hypothesized that variation inENAexpression was responsible for differences in acquired salt tolerance across strains. Surprisingly, we found that theENAgenes were completely dispensable for ethanol-induced survival of high salt concentrations in the wild vineyard strain. Instead, theENAgenes were necessary for the ability to resume growth on high concentrations of salt following a mild ethanol pretreatment. Surprisingly, this growth acclimation phenotype was also shared by the lab yeast strain despite lack ofENAinduction under this condition. This study underscores that cross protection can affect both viability and growth through distinct mechanisms, both of which likely confer fitness effects that are ecologically relevant.IMPORTANCEMicrobes in nature frequently experience “boom or bust” cycles of environmental stress. Thus, microbes that can anticipate the onset of stress would have an advantage. One way microbes anticipate future stress is through acquired stress resistance, where cells exposed to a mild dose of one stress gain the ability survive an otherwise lethal dose of a subsequent stress. In the budding yeastSaccharomyces cerevisiae,certain stressors can cross protect against high salt concentrations, though the mechanisms governing this acquisition of higher stress resistance are not well understood. In this study, we took advantage of wild yeast strains to understand the mechanism underlying ethanol-induced cross protection against high salt concentrations. We found that mild ethanol stress allows cells to resume growth on high salt, which involves a novel role for a well-studied salt transporter. Overall, this discovery highlights how leveraging natural variation can provide new insights into well-studied stress defense mechanisms.
Predicting Intra- and Intertypic Recombination in Enterovirus 71
Authors: Woodman Andrew , Lee Kuo-Ming , Janissen Richard , Gong Yu-Nong , Dekker Nynke , Shih Shin-Ru , Cameron Craig E. 
Published: October 2018

AbstractEnteroviruses are well known for their ability to cause neurological damage and paralysis. The model enterovirus is poliovirus (PV), the causative agent of poliomyelitis, a condition characterized by acute flaccid paralysis. A related virus, enterovirus 71 (EV-A71), causes similar clinical outcomes in recurrent outbreaks throughout Asia. Retrospective phylogenetic analysis has shown that recombination between circulating strains of EV-A71 produces the outbreak-associated strains which exhibit increased virulence and/or transmissibility. While studies on the mechanism(s) of recombination in PV are ongoing in several laboratories, little is known about factors that influence recombination in EV-A71. We have developed a cell-based assay to study recombination of EV-A71 based upon previously reported assays for poliovirus recombination. Our results show that: (1) EV-A71 strain-type and RNA sequence diversity impacts recombination frequency in a predictable manner that mimics the observations found in nature; (2) recombination is primarily a replicative process mediated by the RNA-dependent RNA polymerase (RdRp); (3) a mutation shown to reduce recombination in PV (L420A) similarly reduces EV-A71 recombination suggesting conservation in mechanism(s); and (4) sequencing of intertypic recombinant genomes indicates that template-switching is by a mechanism that requires some sequence homology at the recombination junction and that the triggers for template-switching may be sequence independent. The development of this recombination assay will permit further investigation on the interplay between replication, recombination and disease.
Processing of grassland soil C-N compounds into soluble and volatile molecules is depth stratified and mediated by genomically novel bacteria and archaea
Authors: Diamond Spencer , Andeer Peter , Li Zhou , Crits-Christoph Alex , Burstein David , Anantharaman Karthik , Lane Katherine R. , Thomas Brian C. , Pan Chongle , Northen Trent , Banfield Jillian F. 
Published: October 2018

AbstractSoil microbial activity drives the carbon and nitrogen cycles and is an important determinant of atmospheric trace gas turnover, yet most soils are dominated by organisms with unknown metabolic capacities. Even Acidobacteria, among the most abundant bacteria in soil, remain poorly characterized, and functions across groups such as Verrucomicrobia, Gemmatimonadetes, Chloroflexi, Rokubacteria are understudied. Here, we resolved sixty metagenomic, and twenty proteomic datasets from a grassland soil ecosystem and recovered 793 near-complete microbial genomes from 18 phyla, representing around one third of all organisms detected. Importantly, this enabled extensive genomics-based metabolic predictions for these understudied communities. Acidobacteria from multiple previously unstudied classes have genomes that encode large enzyme complements for complex carbohydrate degradation. Alternatively, most organisms we detected encode carbohydrate esterases that strip readily accessible methyl and acetyl groups from polymers like pectin and xylan, forming methanol and acetate, the availability of which could explain high prevalences of C1 metabolism and acetate utilization in genomes. Organism abundances among samples collected at three soil depths and under natural and amended rainfall regimes indicate statistically higher associations of inorganic nitrogen metabolism and carbon degradation in deep and shallow soils, respectively. This partitioning decreased in samples under extended spring rainfall indicating long term climate alteration can affect both carbon and nitrogen cycling. Overall, by leveraging natural and experimental gradients with genome-resolved metabolic profiles, we link organisms lacking prior genomic characterization to specific roles in complex carbon, C1, nitrate, and ammonia transformations and constrain factors that impact their distributions in soil.
The glucocorticoid receptor ligand-binding domain confers drug-gated protein regulation inC. elegans
Authors: Monsalve Gabriela C. , Yamamoto Keith R. , Ward Jordan D. 
Published: October 2018

AbstractControlling protein activity and localization is a key tool in modern biology. Mammalian steroid receptor ligand-binding domains (LBDs) fusions have been used in a range of organisms and cell-types to inactivate proteins of interest until the cognate steroid ligand is applied. Here, we demonstrate that the glucocorticoid receptor LBD confers ligand-gated control of a heterologous gene expression system (Q system) and the DAF-16 transcription factor inC. elegans. These experiments demonstrate provide a powerful tool for temporal control of protein activity, and will bolster existing tools used to modulate gene expression and protein activity in this animal.
Smed-egfr-4 is required for planarian eye regeneration
Authors: Emili Elena , Pallarès Maclà Esteve , Romero Rafael , Cebrlà Francesc 
Published: October 2018

ABSTRACTPlanarians are amazing animals that can regenerate a whole body from a tiny piece of them thanks to their pluripotent stem cells, the neoblasts. Planarian neoblasts include both pluripotent stem cells and specialized lineage-committed progenitors that give rise to all the mature cell types during regeneration and homeostatic cell turnover in these plastic animals. Little is known, however, about the mechanisms that regulate neoblast differentiation. Recently, it has been shown that Smed-egfr-1, a homologue of the epidermal growth factor receptor (EGFR) family is required for the final differentiation of the gut progenitors into mature cells but not for their specification. As planarians have several EGFR homologues it has been proposed that they could have diverged functionally to regulate the differentiation of the different cell types found in these animals. Here, we report on the function of Smed-egfr-4 on eye regeneration. The silencing of this gene by RNAi results in animals regenerating smaller eyes compared to controls. The numbers of both eye mature cell types, photoreceptor neurons and eye-cup pigment cells, are significantly decreased in the Smed-egfr-4(RNAi) animals. In contrast, the number of eye progenitor cells expressing the specific markers Smed-ovo and Smed-sp6-9 is increased. These results suggest that Smed-egfr-4 would be required not for the specification of eye progenitor cells but rather for their final differentiation and support the idea that in planarians the EGFR pathway could play a general role regulating the differentiation of lineage-committed progenitors.
Quantitative insights into the cyanobacterial cell economy
Authors: Zavřel Tomáš , Faizi Marjan , Loureiro Cristina , Poschmann Gereon , Stühler Kai , Sinetova Maria , Zorina Anna , Steuer Ralf , Červený Jan 
Published: October 2018

AbstractPhototrophic microorganisms are promising resources for green biotechnology. Compared to heterotrophic microorganisms, however, the cellular economy of phototrophic growth is still insufficiently understood. We provide a quantitative analysis of light-limited, light-saturated, and light-inhibited growth of the cyanobacteriumSynechocystissp. PCC 6803 using a reproducible cultivation setup. We report key physiological parameters, including growth rate, cell size, and photosynthetic activity over a wide range of light intensities. Intracellular proteins were quantified to monitor proteome allocation as a function of growth rate. Among other physiological adaptations, we identify an upregulation of the translational machinery and downregulation of light harvesting components with increasing light intensity and growth rate. The resulting growth laws are discussed in the context of a coarse-grained model of phototrophic growth and available data obtained by a comprehensive literature search. Our insights into quantitative aspects of cyanobacterial adaptations to different growth rates have implications to understand and optimize photosynthetic productivity.
Nitrogen addition pulse has minimal effect in big sagebrush (Artemisia tridentata) communities on the Pinedale Anticline, Wyoming (USA)
Authors: Beltz Christopher W. , Mobley Megan L. , Burke Ingrid C. 
Published: October 2018

ABSTRACTNitrogen additions are known to elicit variable responses in semi-arid ecosystems, with responses increasing with precipitation. The response of semi-arid ecosystems to nitrogen are important to understand due to their large spatial extent worldwide and the global trend of increasingly available nitrogen. In this study, we evaluated the impact of a single nitrogen addition pulse on a semi-arid big sagebrush (Artemisia tridentata) ecosystem in western Wyoming. This is important given that sagebrush ecosystems are poorly understood, despite their prevalence in the western US. In addition, large-scale nitrogen additions have begun on sagebrush landscapes in Wyoming in order to mitigate population declines in mule deer (Odocoileus hemionus). The study objectives were (1) to evaluate the effectiveness of a nitrogen fertilization pulse in increasing sagebrush biomass and forage quality, and (2) to assess effects of nitrogen addition on soil biogeochemistry and vegetation community structure. We fertilized 15 plots across 5 locations in western Wyoming using a single pulse of urea (5.5g N m−2). In addition, we immobilized available nitrogen through surface hay treatments (250g hay/m2). Nitrogen additions failed to increase growth of sagebrush, alter nitrogen content of sagebrush leaders, or alter greenhouse gas efflux from soils. The plant community also remained unchanged; total cover, species richness, and community composition were all unaffected by our treatment application. Over the two years of this study, we did not find indications of nitrogen limitation of ecosystem processes, despite a wet growing season in 2014. Thus, we have found a general lack of response to nitrogen in sagebrush ecosystems and no treatment effect of a single pulse of N to sagebrush biomass or forage quality.
Research challenges in Africa – an exploratory study on the experiences and opinions of African researchers
Authors: Ngongalah Lem , Emerson Wepngong , Rawlings Ngwa Niba , Muleme Musisi James 
Published: October 2018

AbstractBackgroundInsufficient research is a major impediment to growth, development and advancement of health in Africa. Africa produces less than 1% of global research output. Meanwhile, African countries face some of the toughest challenges worldwide, most of which can only be tackled through robust and efficient research. Addressing the barriers to conducting research in Africa is a step towards improving research capacity and output. This study aimed to identify the key challenges affecting research practice and output in Africa; and to highlight priority areas for improvement.MethodsA cross-sectional survey was administered through an online questionnaire, including participants from six countries in Sub-Saharan Africa. Participants included research professionals, research students, research groups and academics.ResultsA total of 424 participants responded to this survey. The ability to conduct and produce high-quality research was seen to be influenced by multiple factors, most of which were related to the research environment in African countries. Priority areas for improvement included providing more training, raising awareness on the importance of research in Africa, encouraging governments to commit to research and increasing collaboration between researchers in Africa.ConclusionThe conditions under which research is done in Africa are severely flawed and do not encourage engagement in research, or continuity of research activity. African governments need to develop initiatives that accelerate and support research and research-based education in Africa, in order to build a solid foundation for research, increase research capacity, and enable institutions to provide valuable training and develop sustainable research opportunities in Africa.