bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short Linear Motifs In Intrinsically Disordered Regions Modulate HOG Signaling Capacity
Authors: Strome Bob , Hsu Ian , Li Cheong Man Mitchell , Zarin Taraneh , Nguyen Ba Alex , Moses Alan M 
Published: October 2017

AbstractThe effort to characterize intrinsically disordered regions of signaling proteins is rapidly expanding. An important class of disordered interaction modules are ubiquitous and functionally diverse elements known as short linear motifs (SLiMs). To further examine the role of SLiMs in signal transduction, we used a previously devised bioinformatics method to predict evolutionarily conserved SLiMs within a well-characterized pathway in S. cerevisiae. Using a single cell, reporter-based flow cytometry assay in conjunction with a fluorescent reporter driven by a pathway-specific promoter, we quantitatively assessed pathway output via systematic deletions of individual motifs. We found that, when deleted, 34% (10/29) of predicted SLiMs displayed a significant decrease in pathway output, providing evidence that these motifs play a role in signal transduction. In addition, we show that perturbations of parameters in a previously published stochastic model of HOG signaling could reproduce the quantitative effects of 4 out of 7 mutations in previously unknown SLiMs. Our study suggests that, even in well-characterized pathways, large numbers of functional elements remain undiscovered, and that challenges remain for application of systems biology models to interpret the effects of mutations in signalling pathways.One-sentence SummaryMutations of short conserved elements in disordered regions have quantitative effects on a model signaling pathway.
Eye opening differentially modulates inhibitory synaptic transmission in the developing visual cortex
Authors: Guan Wuqiang , Cao Jun-Wei , Liu Lin-Yun , Zhao Zhi-Hao , Fu Yinghui , Yu Yong-Chun 
Published: October 2017

AbstractEye opening, a natural and timed event during animal development, influences cortical circuit assembly and maturation; yet, little is known about its precise effect on inhibitory synaptic connections. Here we show that coinciding with eye opening, the strength of unitary inhibitory postsynaptic currents (uIPSCs) from somatostatin-expressing interneurons (SST-INs) to nearby excitatory neurons, but not interneurons, sharply decreases in layer 2/3 of the mouse visual cortex. In contrast, the strength of uIPSCs from fast-spiking interneurons (FS-INs) to excitatory neurons significantly increases during eye opening. More importantly, these developmental changes can be prevented by dark rearing or binocular lid suture, and reproduced by artificial opening of sutured lids. Mechanistically, this differential maturation of synaptic transmission is accompanied by a significant change in the postsynaptic quantal size. Together, our study reveals a differential regulation in GABAergic circuits in the cortex driven by eye opening likely crucial for cortical maturation and function.
Transgenerational dynamics of rDNA copy number inDrosophilamale germline stem cells
Authors: Lu Kevin L. , Nelson Jonathan O. , Warsinger-Pepe Natalie , Yamashita Yukiko M. 
Published: October 2017

AbstractrDNA loci, composed of hundreds of tandemly duplicated arrays of rRNA genes, are known to be among the most unstable genetic elements due to their repetitive nature. rDNA instability underlies aging (replicative senescence) in yeast cells, however, its contribution to the aging of multicellular organisms is poorly understood. In this study, we investigate the dynamics of rDNA loci during aging in theDrosophilamale germline stem cell (GSC) lineage, and show that rDNA copy number decreases during aging. Our study further reveals that this age-dependent decrease in rDNA copy number is heritable from generation to generation, yet GSCs in animals that inherit reduced rDNA copy number are capable of recovering normal rDNA copy number. Based on these findings, we propose that rDNA loci are dynamic genetic elements, where rDNA copy number changes dynamically yet is maintained through a recovery mechanism in the germline.
Electrophysiological indices of anterior cingulate cortex function reveal changing levels of cognitive effort and reward valuation that sustain task performance
Authors: Umemoto Akina , Inzlicht Michael , Holroyd Clay B. 
Published: October 2017

AbstractSuccessful execution of goal-directed behaviors often requires the deployment of cognitive control, which is thought to require cognitive effort. Recent theories have proposed that anterior cingulate cortex (ACC) regulates control levels by weighing the reward-related benefits of control against its effort-related costs. However, given that the sensations of cognitive effort and reward valuation are available only to introspection, this hypothesis is difficult to investigate empirically. We have proposed that two electrophysiological indices of ACC function, frontal midline theta and the reward positivity (RewP), provide objective measures of these functions. To investigate this issue, we recorded the electroencephalogram (EEG) from participants engaged in an extended, cognitively-demanding task. Participants performed a time estimation task for 2 hours in which they received reward and error feedback according to their task performance. We observed that the amplitude of the RewP, a feedback-locked component of the event related brain potential associated with reward processing, decreased with time-on-task. Conversely, frontal midline theta power, which consists of 4-8 Hz EEG oscillations associated with cognitive effort, increased with time-on-task. We also examined how these phenomena changed over time by conducting within-participant multi-level modeling analyses. Our results suggest that extended execution of a cognitively-demanding task is characterized by an early phase in which high control levels combine with strong reward valuation to foster rapid improvements in task performance, and a later phase in which high control levels counteract waning reward valuation to maintain stable task performance.
Enhancer identification and activity evaluation in the red flour beetle,Tribolium castaneum
Authors: Lai Yi-Ting , Deem Kevin D. , Borràs-Castells Ferran , Sambrani Nagraj , Rudolf Heike , Suryamohan Kushal , El-Sherif Ezzat , Halfon Marc S. , McKay Daniel J. , Tomoyasu Yoshinori 
Published: October 2017

ABSTRACTEvolution ofcis-properties (such as enhancers) often plays an important role in the production of diverse morphology. However, a mechanistic understanding is often limited by the absence of methods to study enhancers in species outside of established model systems. Here, we sought to establish methods to identify and test enhancer activity in the red flour beetle,Tribolium castaneum. To identify possible enhancer regions, we first obtained genome-wide chromatin profiles from various tissues and stages ofTriboliumvia FAIRE (Formaldehyde Assisted Isolation of Regulatory Elements)-sequencing. Comparison of these profiles revealed a distinct set of open chromatin regions in each tissue and stage. Second, we established the first reporter assay system that works in bothDrosophilaandTribolium, usingnubbinin the wing andhunchbackin the embryo as case studies. Together, these advances will be useful to study the evolution ofcis-language and morphological diversity inTriboliumand other insects.
Idiosyncratic genome degradation in a bacterial endosymbiont of periodical cicadas
Authors: Campbell Matthew A. , Łukasik Piotr , Simon Chris , McCutcheon John P. 
Published: October 2017

SummaryWhen a free-living bacterium transitions to a host-beneficial endosymbiotic lifestyle, it almost invariably loses a large fraction of its genome [1, 2]. The resulting small genomes often become unusually stable in size, structure, and coding capacity [3-5].CandidatusHodgkinia cicadicola (Hodgkinia), a bacterial endosymbiont of cicadas, sometimes exemplifies this genomic stability. TheHodgkiniagenome has remained completely co-linear in some cicadas diverged by tens of millions of years [6, 7]. But in the long-lived periodical cicadaMagicicada tredecim, theHodgkiniagenome has split into dozens of tiny, gene-sparse genomic circles that sometimes reside in distinctHodgkiniacells [8]. Previous data suggested that otherMagicicadaspecies harbor similarly complexHodgkiniapopulations, but the timing, number of origins, and outcomes of the splitting process were unknown. Here, by sequencingHodgkiniametagenomes from the remaining sixMagicicadaspecies and two sister species, we show that allMagicicadaspecies harborHodgkiniapopulations of at least twenty genomic circles each. We find little synteny among the 256Hodgkiniacircles analyzed except between the most closely related species. Individual gene phylogenies show thatHodgkiniafirst split in the common ancestor ofMagicicadaand its closest known relatives, but that most splitting has occurred withinMagicicadaand has given rise to highly variableHodgkiniagene dosages between cicada species. These data show thatHodgkiniagenome degradation has proceeded down different paths in differentMagicicadaspecies, and support a model of genomic degradation that is stochastic in outcome and likely nonadaptive for the host. These patterns mirror the genomic instability seen in some mitochondria.
Myosin II filament dynamics in actin networks revealed with interferometric scattering microscopy
Authors: Mosby L. S. , Hundt N. , Young G. , Fineberg A. , Polin M. , Mayor S. , Kukura P. , Köster D. V. 
Published: October 2017

AbstractThe plasma membrane and the underlying cytoskeletal cortex constitute active platforms for a variety of cellular processes. Recent work has shown that the remodeling acto-myosin network modifies local membrane organization, but the molecular details are only partly understood due to difficulties with experimentally accessing the relevant time and length scales. Here, we use interferometric scattering (iSCAT) microscopy to investigate a minimal acto-myosin network linked to a supported lipid bilayer membrane. Using the magnitude of the interferometric contrast, which is proportional to molecular mass, and fast acquisition rates, we detect, and image individual membrane attached actin filaments diffusing within the acto-myosin network and follow individual myosin II filament dynamics. We quantify myosin II filament dwell times and processivity as a function of ATP concentration, providing evidence for the predicted ensemble behavior of myosin head domains. Our results show how decreasing ATP concentrations lead to both increasing dwell times of individual myosin II filaments and a global change from a remodeling to a contractile state of the acto-myosin network.Statement of SignificanceHere, we show that interferometric scattering microscopy in combination with single particle tracking enables label-free, high contrast imaging of filament dynamics on surfaces, while distinguishing different species based on their mass. These results significantly broaden the available toolkit, and associated capabilities of researchers studying dynamics of biological machines at interfaces.
Cryptic phylogeographic history sheds light on the generation of species diversity in sky-island mountains
Authors: He Kai , Wan Tao , Koepfli Klaus-Peter , Jin Wei , Liu Shao-Ying , Jiang Xue-Long 
Published: October 2017

ABSTRACTBiodiversity hotspots should be given high priority for conservation under the situation of global climate change. The sky islands in southwestern China are characterized by extraordinarily high species diversity and are among one of the world’s top biodiversity hotspots. However, neither the actual species diversity in this region or mechanisms generating this diversity are well explored. Here, we report on the phylogeographic analysis of the long-tailed mole (Scaptonyx fusicaudus), a semi-fossorial mammal that inhabits the montane cool forests across the Chinese sky islands and is considered to represent one species divided into two subspecies. Analyses using DNA sequence data from one mitochondrial and six nuclear genes revealed that populations inhabiting different mountains exhibited exceptionally strong geographic structure. The lowlands and large rivers act as “soft” and “hard” barriers to dispersal, respectively, isolating evolutionary lineages for up to 11 million years. Our results suggest that the mountain ranges act as interglacial refugia buffering populations from climate fluctuations, further facilitating allopatric diversification. Strikingly, species delimitation analyses suggests that the long-tailed mole may comprise 18 operational taxonomic units and 17 putative species. Our results suggest that for low-vagility species, the complex topography of the Chinese sky islands has shaped genetic diversity and structure and promoted exceptional diversification through a combination of eco-environmental stability as well as geographic fragmentation. The patterns observed in S. fusicaudus may be representative for other cold- adapted species, reflecting the generation of mammalian faunal diversity in the sky-island mountains of southwestern China.
Temperature and Water Quality-Related Patterns in Sediment-AssociatedSymbiodiniumCommunities Impact Symbiont Uptake and Fitness of Juvenile Acroporid Corals
Authors: Quigley Kate M. , Bay Line K. , Willis Bette L. 
Published: October 2017

AbstractThe majority of corals acquire their photo-endosymbiontSymbiodiniumfrom environmental sources anew each generation. Despite the critical role that environmental availability ofSymbiodiniumplays in the potential for corals to acclimate and adapt to changing environments, little is known about the diversity of free-livingSymbiodiniumcommunities and how variation in these communities influences uptake andin hospitecommunities in juvenile corals. Here we characterizeSymbiodiniumcommunity diversity in sediment samples collected from eight reefs representing latitudinal and cross-shelf variation in water quality and temperature regimes. Sediment-associatedSymbiodiniumcommunities were then compared toin hospitecommunities acquired byA. tenuisandA. milleporajuveniles following 11 – 145 days of experimental exposure to sediments from each of the reefs. Communities associated with juveniles and sediments differed substantially, with sediments harbouring four times more unique OTUs than juveniles (1125 OTUs vs. 271). Moreover, only 10.6% of these OTUs were shared between juveniles and sediments, indicating selective uptake by acroporid juveniles. The diversity and abundance ofSymbiodiniumtypes differed among sediment samples from different temperature and water quality environments.Symbiodiniumcommunities acquired by juveniles also differed among the sediment treatments, despite juveniles having similar parentage. Moreover,Symbiodiniumcommunities displayed different rates of infection, mortality, and photochemical efficiencies. This study demonstrates that the biogeography of free-livingSymbiodiniumtypes found within sediment reservoirs follows patterns along latitudinal and water quality environmental gradients on the Great Barrier Reef. We also demonstrate a bipartite strategy forSymbiodiniumuptake by juvenile corals of two horizontally-transmitting acroporid species, whereby uptake is selective within the constraints of environmental availability.
Investigating genetic correlations and causal effects between caffeine consumption and sleep behaviours
Authors: Treur Jorien L. , Gibson Mark , Taylor Amy E , Rogers Peter J , Munafò Marcus R 
Published: October 2017

AbstractStudy Objectives:Higher caffeine consumption has been linked to poorer sleep and insomnia complaints. We investigated whether these observational associations are the result of genetic risk factors influencing both caffeine consumption and poorer sleep, and/or whether they reflect (possibly bidirectional) causal effects.Methods:Summary-level data were available from genome-wide association studies (GWAS) on caffeine consumption (n=91,462), sleep duration, and chronotype (i.e., being a ‘morning’ versus an ‘evening’ person) (both n=128,266), and insomnia complaints (n=113,006). Linkage disequilibrium (LD) score regression was used to calculate genetic correlations, reflecting the extent to which genetic variants influencing caffeine consumption and sleep behaviours overlap. Causal effects were tested with bidirectional, two-sample Mendelian randomization (MR), an instrumental variable approach that utilizes genetic variants robustly associated with an exposure variable as an instrument to test causal effects. Estimates from individual genetic variants were combined using inverse-variance weighted meta-analysis, weighted median regression and MR Egger regression methods.Results:There was no clear evidence for genetic correlation between caffeine consumption and sleep duration (rg=0.000,p=0.998), chronotype (rg=0.086,p=0.192) or insomnia (rg=-0.034,p=0.700). Two-sample Mendelian randomization analyses did not support causal effects from caffeine consumption to sleep behaviours, or the other way around.Conclusions:We found no evidence in support of genetic correlation or causal effects between caffeine consumption and sleep. While caffeine may have acute effects on sleep when taken shortly before habitual bedtime, our findings suggest that a more sustained pattern of high caffeine consumption is likely associated with poorer sleep through shared environmental factors.
A strategy to exploit surrogate sire technology in livestock breeding programs
Authors: Gottardo Paolo , Gorjanc Gregor , Battagin Mara , Gaynor R Chris , Jenko Janez , Ros-Freixedes Roger , Whitelaw C Bruce A , Mileham Alan J , Herring William O , Hickey John M 
Published: October 2017

AbstractIn this work, we performed simulations to develop and test a strategy for exploiting surrogate sire technology in animal breeding programs. Surrogate sire technology allows the creation of males that lack their own germline cells, but have transplanted spermatogonial stem cells from donor males. With this technology, a single elite male donor could give rise to huge numbers of progeny, potentially as much as all the production animals in a particular time period.One hundred replicates of various scenarios were performed. Scenarios followed a common overall structure but differed in the strategy used to identify elite donors and how these donors were used in the product development part.The results of this study showed that using surrogate sire technology would significantly increase the genetic merit of commercial sires, by as much as 6.5 to 9.2 years’ worth of genetic gain compared to a conventional breeding program. The simulations suggested that a strategy involving three stages (an initial genomic test followed by two subsequent progeny tests) was the most effective of all the strategies tested.The use of one or a handful of elite donors to generate the production animals would be very different to current practice. While the results demonstrate the great potential of surrogate sire technology there are considerable risks but also other opportunities. Practical implementation of surrogate sire technology would need to account for these.
El Niño Southern Oscillation influences the abundance and movements of a marine top predator in coastal waters
Authors: Sprogis Kate R. , Christiansen Fredrik , Wandres Moritz , Bejder Lars 
Published: October 2017

AbstractLarge‐scale climate modes such as El Niño Southern Oscillation (ENSO) influence population dynamics in many species, including marine top predators. However, few quantitative studies have investigated the influence of large‐scale variability on resident marine top predator populations. We examined the effect of climate variability on the abundance and temporary emigration of a resident bottlenose dolphin (Tursiops aduncus) population off Bunbury, Western Australia (WA). This population has been studied intensively over six consecutive years (2007–2013), yielding a robust dataset that captures seasonal variations in both abundance and movement patterns. In WA, ENSO affects the strength of the Leeuwin Current (LC), the dominant oceanographic feature in the region. The strength and variability of the LC affects marine ecosystems and distribution of top predator prey. We investigated the relationship between dolphin abundance and ENSO, Southern Annular Mode, austral season, rainfall, sea surface salinity and sea surface temperature (SST). Linear models indicated that dolphin abundance was significantly affected by ENSO, and that the magnitude of the effect was dependent upon season. Dolphin abundance was lowest during winter 2009, when dolphins had high temporary emigration rates out of the study area. This coincided with the single El Niño event that occurred throughout the study period. Coupled with this event, there was a negative anomaly in SST and an above average rainfall. These conditions may have affected the distribution of dolphin prey, resulting in the temporary emigration of dolphins out of the study area in search of adequate prey. This study demonstrated the local effects of large‐scale climatic variations on the short‐term response of a resident, coastal delphinid species. With a projected global increase in frequency and intensity of extreme climatic events, resident marine top predators may not only have to contend with increasing coastal anthropogenic activities, but also have to adapt to large‐scale climatic changes.
Re‐evaluating pathogenicity of variants associated with the long QT syndrome
Authors: Kaltman Jonathan R. , Evans Frank , Fu Yi‐Ping 
Published: October 2017

AbstractIntroductionGenetic testing for congenital long QT syndrome (LQTS) has become common. Recent studies have shown that some variants labelled as pathogenic might be misclassified due to sparse case reports and relatively common allele frequencies (AF) in the general population. This study aims to evaluate the presence of LQTS‐associated variants in the Genome Aggregation Database (gnomAD) population, and assess the functional impact of these variants.Methods and resultsVariants associated with LQTS from the Human Gene Mutation Database were extracted and matched to the gnomAD to evaluate population‐based AF. We used MetaSVM to predict the function of LQTS variants. Allele distribution by protein topology in KCNQ1, KCNH2, and SCN5A was compared between gnomAD (n = 123,136) and a cohort of LQTS patients aggregated from eight published studies (n = 2,683). Among the 1,415 LQTS‐associated single nucleotide variants in 30 genes, 347 (25%) are present in gnomAD; 24% of the 347 variants were predicted as functionally tolerated compared with 4% of variants not present in gnomAD (P < 0.001). Of the 347 pathogenic variants in gnomAD, seven (2%) had an AF of ≥ 0.001 and 65 (19%) variants had an AF of ≥ 0.0001. In KCNQ1, KCNH2, and SCN5A, allele distribution by protein functional region was significantly different with gnomAD alleles appearing less frequently in highly pathogenic domains than case alleles.ConclusionA significant number of LQTS variants have insufficient evidence for pathogenicity and relatively common AF in the general population. Caution should be used when ascribing pathogenicity to these variants.