bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of fixational tremor on the retinal image
Authors: Bowers Norick R. , Boehm Alexandra E. , Roorda Austin 
Published: August 2018

AbstractThe study of fixational eye motion (FEM) has implications for the neural and computational underpinnings of vision. One component of FEM is tremor, a high-frequency oscillatory jitter reported to be anywhere from ∼5 to 60 seconds of arc in amplitude. In order to isolate the effects of tremor on the retinal image directly and in the absence of optical blur, high-frequency, high-resolution eye traces were collected in 6 subjects from videos recorded with an Adaptive Optics Scanning Laser Ophthalmoscope. Videos were acquired while subjects engaged in an active fixation task where they fixated on a tumbling E stimulus and reported changes in its orientation. Spectral analysis was conducted on isolated segments of optical drift. The resultant amplitude spectra showed a slight deviation from the traditional 1/f nature of optical drift in the frequency range of 50-100 Hz, which is indicative of tremor; however, the amplitude of this deviation rarely exceeded one second of arc, smaller than any magnitude previously reported.
BIOLOGICAL SCIENCES: Genetics
Authors: Hsiao Jack S. , Germain Noelle D. , Wilderman Andrea , Stoddard Christopher , Wojenski Luke A. , Villafano Geno J. , Core Leighton , Cotney Justin , Chamberlain Stormy J. 
Published: August 2018

ABSTRACTAngelman syndrome (AS) is a severe neurodevelopmental disorder caused by the loss of function from the maternal allele of UBE3A, a gene encoding an E3 ubiquitin ligase. UBE3A is only expressed from the maternally-inherited allele in mature human neurons due to tissue-specific genomic imprinting. Imprinted expression of UBE3A is restricted to neurons by expression of UBE3A antisense transcript (UBE3A-ATS) from the paternally-inherited allele, which silences the paternal allele of UBE3A in cis. However, the mechanism restricting UBE3A-ATS expression and UBE3A imprinting to neurons is not understood. We used CRISPR/Cas9-mediated genome editing to functionally define a bipartite boundary element critical for neuron-specific expression of UBE3A-ATS in humans. Removal of this element led to upregulation of UBE3A-ATS without repressing paternal UBE3A. However, increasing expression of UBE3A-ATS in the absence of the boundary element resulted in full repression of paternal UBE3A, demonstrating that UBE3A imprinting requires both the loss of function from the boundary element as well as upregulation of UBE3A-ATS. These results suggest that manipulation of the competition between UBE3A-ATS and UBE3A may provide a potential therapeutic approach for AS.SIGNIFICANCE STATEMENTAngelman syndrome is a neurodevelopmental disorder caused by loss of function from the maternal allele of UBE3A, an imprinted gene. The paternal allele of UBE3A is silenced by a long, non-coding antisense transcript in mature neurons. We have identified a boundary element that stops the transcription of the antisense transcript in human pluripotent stem cells, and thus restricts UBE3A imprinted expression to neurons. We further determined that UBE3A imprinting requires both the loss of the boundary function and sufficient expression of the antisense transcript to silence paternal UBE3A. These findings provide essential details about the mechanisms of UBE3A imprinting that may suggest additional therapeutic approaches for Angelman syndrome.
Rapid detection of cytochromecd1-containing nitrite reductase encoding genenirSwith loop-mediated isothermal amplification assay
Authors: Yang Qianqian , Zhang Xuzhi , Jiang Xiaoyu , Wang Xiaochun , Li Yang , Zhao Jun , Hao Zhihui , Wang Pingping , Qu Keming 
Published: August 2018

AbstractThe cytochromecd1-containing nitrite reductase,nirS, plays an important role in biological denitrification. Consequently, investigating the presence and abundance ofnirSis a commonly used approach to understand the distribution and potential activity of denitrifying bacteria, in addition to denitrifier communities. Herein, a new molecular biology technique termed loop-mediated isothermal amplification (LAMP) was developed to rapidly detectnirSgene using those ofPseudomonas aeruginosato optimize the assay. The LAMP assay relied on a set of four primers that were designed to recognize six target sequence sites, resulting in high target specificity. The specificity of the assay was confirmed by the lack of amplification when using DNA from 15 other bacterial species lackingnirSgene. The limit of detection for the LAMP assay under optimized conditions was 1.87 pg/reaction of genomic DNA, which was an order of magnitude lower than that required by conventional PCR assays. Moreover, a cell-template based LAMP assay was also developed for detectingnirSgene that directly used bacterial cells as template rather than genomic DNA. Only 1 h was needed from the addition of bacterial cells to the reaction to the verification of amplification success, and bulky and sophisticated equipment were not needed. Further, thenirSgene ofP. aeruginosain spiked seawater samples could be detected with both the DNA-template based LAMP assay and the cell-template based LAMP assay, thereby demonstrating the practicality of in-field use of them. In summary, the LAMP assays described here represent a rapid, user-friendly, and cost-effective alternative to conventional PCR.
Genetic continuity in the last seven Millennia in human hepatitis B viruses
Authors: Lei Xiaoyun , Zhang Ye , Huang Shi 
Published: August 2018

AbstractHepatitis B virus (HBV) is a major human pathogen and yet the evolution history of HBV has largely remained uncertain. With a better theoretical understanding of genetic diversity, we here used a new method to examine the previously published ancient and present day HBV genomes. We identified an informative region in the HBV polymerase that is slow evolving and used it to study genetic distances among HBVs. Three ancient human HBV isolates from 4488-7074 years ago in Germany were identified as genotype G that is also presently common in the same country. We constructed a new phylogenetic tree of HBVs that placed genotype D as the most basal branch with an inferred age of ~20500 years, which is remarkably consistent with the worldwide distribution and a most parsimonious migration route of HBV genotypes today. These results help resolve the evolutionary history of HBV and provide a useful method for studying the phylogenetics of HBV and other viruses in general.
Spatial distribution of mammography adherence in a Swiss urban population and its association with socioeconomic status
Authors: Sandoval José Luis , Himsl Rebecca , Theler Jean-Marc , Gaspoz Jean-Michel , Joost Stéphane , Guessous Idris 
Published: August 2018

ABSTRACTPurposeLocal physical and social environment has a defining influence on individual behaviour and health-related outcomes. However, it remains undetermined if its impact is independent of individual socioeconomic status. In this study, we evaluated the spatial distribution of mammography adherence in the state of Geneva (Switzerland) using individual-level data and assessed its independence from socioeconomic status (SES).MethodsGeo-referenced individual-level data from the population-based cross-sectional Bus Santé study (n = 5,002) were used to calculate local indicators of spatial association (LISA) and investigate the spatial dependence of mammography adherence. Spatial clusters are reported without adjustment; adjusted for neighbourhood income and individual educational attainment; and demographic factors (age and Swiss nationality). The association between adjusted clusters and the proximity to the nearest screening centre was also evaluated.ResultsMammography adherence was not randomly distributed throughout Geneva with clusters geographically coinciding with known SES distributions. After adjustment for SES indicators, clusters were reduced to 56.2% of their original size (n = 1,033). Adjustment for age and nationality further reduced the number of individuals exhibiting spatially dependent behaviour (36.5% of the initial size). The identified SES-independent hot spots and cold-spots of mammography adherence were not explained by proximity to the nearest screening centre.ConclusionsSES and demographic factors play an important role in shaping the spatial distribution of mammography adherence. However, the spatial clusters persisted after confounder adjustment indicating that additional neighbourhood-level determinants could influence mammography adherence and be the object of targeted public health interventions.
Calcium nanodomains in spindles
Authors: Mo Guolong , Li Ruizhen , Swider Zachary , Tao Yong , Mikoshiba Katsuhiko , Bement William M. , Liu X. Johné 
Published: August 2018

SummaryThe role of calcium signaling in specific events of animal cell meiosis or mitosis (M-phase) is a subject of enduring controversy. Early efforts suggested that increases in intracellular free calcium ([Ca2+]i) promote spindle disassembly 1, 2 while subsequent work suggested that global [Ca2+]i increases trigger nuclear envelope breakdown, spindle assembly, the metaphase-anaphase transition, and cytokinesis 3-6. However, further studies led to the conclusion that elevation of [Ca2+]i either has no role in these events, plays a permissive role in these events, or functions as an auxiliary signaling pathway that supplements other mechanisms 7. One potential explanation of the controversy is that specific M-phase events might depend on highly localized increases in [Ca2+]i, variously referred to as microdomains 8 or nanodomains 9, as proposed recently 10. Such domains are hypothesized to arise from rapid shuttling of calcium between closely positioned sources and sinks, rendering them potentially difficult to detect with traditional dyes and largely insensitive to slow chelators such as EGTA 9. Here a novel microtubule-binding calcium sensor—TubeCamp--was used to test the hypothesis 10 that spindles are associated with calcium nanodomains. TubeCamp imaging revealed that spindles in Xenopus eggs, Xenopus embryos, and HeLa cells were all associated with calcium nanodomains at the spindle poles. Calcium nanodomains also formed in spindles assembled in cell extracts and at the center of monopolar spindles, suggesting that they are a basic feature of spindle self-assembly. Disruption of calcium nanodomains via perturbation of inositol-1,4,5-trisphosphate signaling or rapid chelation of [Ca2+]i resulted in spindle disassembly in vivo and vitro. The results demonstrate the existence of spindle-associated calcium nanodomains and indicate that such domains are an essential and common feature of spindles in vertebrates.
Evaluation of rearing parameters of a self-limiting strain of the Mediterranean fruit fly,Ceratitis capitata(Diptera: Tephritidae)
Authors: Rachid Elaini , Asadi Romisa , Naish Neil , Koukidou Martha , Ahmed Mazih 
Published: August 2018

AbstractThe Mediterranean fruit fly,Ceratitis capitata, (medfly) is an important pest of stone and pome fruit, causing significant economic losses worldwide. Current control is primarily based on insecticides, often mixed with protein baits. Chemical approaches are effective but there are label limits to avoid residues in fruits and harm to the environment and sustained use will lead to pesticide resistance in the medfly pest. In recent years, emphasis has been placed on environmentally friendly methods to control medfly.Oxitec has developed a self-limiting medfly strain (OX3864A) that demonstrates conditional female-specific mortality in the early life stages. Sustained release of OX3864A males offers a mating-based approach to medfly control, which should lead to significant economic benefits in area-wide programmes. Furthermore, a heritable fluorescent marker provides quick and accurate identification of released OX3864A males for efficient monitoring in the field.An important prerequisite of mating-based control programmes is the availability of adequate numbers of high-quality male flies in a sustainable and cost-effective manner. This paper summarises rearing optimisations for the OX3864A strain and the production of OX3864A males.
A Tale of Two Positivities and the N400: Distinct neural signatures are evoked by confirmed and violated predictions at different levels of representation
Authors: Kuperberg Gina R. , Brothers Trevor , Wlotko Edward W. 
Published: August 2018

AbstractIt has been proposed that hierarchical prediction is a fundamental computational principle underlying neurocognitive processing. Here we ask whether the brain engages distinct neurocognitive mechanisms in response to inputs that fulfillversusviolate strong predictions at different levels of representation during language comprehension. Participants read three-sentence scenarios in which the third sentence constrained for a broad event structure, e.g. {Agent caution animate-Patient}.High constraintcontexts additionally constrained for a specific event/lexical item, e.g. a two-sentence context about a beach, lifeguards and sharks constrained for the event, {Lifeguards cautioned Swimmers} and the specific lexical item, “swimmers”.Low constraintcontexts did not constrain for any specific event/lexical item. We measured ERPs on critical nouns that fulfilled and/or violated each of these constraints. We found clear, dissociable effects to fulfilled semantic predictions (a reduced N400), to event/lexical prediction violations (an increasedlate frontal positivity), and to event structure/animacy prediction violations (an increasedlate posterior positivity/P600). We argue that thelate frontal positivityreflects a large change in activity associated with successfully updating the comprehender’s current situation model with new unpredicted information. We suggest that thelate posterior positivity/P600is triggered when the comprehender detects a conflict between the input and her model of the communicator and communicative environment. This leads to an initial failure to incorporate new unpredicted input, which may be followed by second-pass attempts to make sense of the discourse through reanalysis, repair, or reinterpretation. Together, these findings provide strong evidence that confirmed and violated predictions at different levels of representation manifest as distinct spatiotemporal neural signatures.
Increased frequency of travel in the presence of cross-immunity may act to decrease the chance of a global pandemic
Authors: Thompson R.N. , Thompson C.P. , Pelerman O. , Gupta S. , Obolski U. 
Published: August 2018

ABSTRACTThe high frequency of modern travel has led to concerns about a devastating pandemic since a lethal pathogen strain could spread worldwide quickly. Many historical pandemics have arisen following pathogen evolution to a more virulent form. However, some pathogen strains invoke immune responses that provide partial cross-immunity against infection with related strains. Here, we consider a mathematical model of successive outbreaks of two strains – a low virulence strain outbreak followed by a high virulence strain outbreak. Under these circumstances, we investigate the impacts of varying travel rates and cross-immunity on the probability that a major epidemic of the high virulence strain occurs, and the size of that outbreak. Frequent travel between subpopulations can lead to widespread immunity to the high virulence strain, driven by exposure to the low virulence strain. As a result, major epidemics of the high virulence strain are less likely, and can potentially be smaller, with more connected subpopulations. Cross-immunity may be a factor contributing to the absence of a global pandemic as severe as the 1918 influenza pandemic in the century since.
Cross-cancer pleiotropic associations with lung cancer risk in African Americans
Authors: Jones Carissa C. , Bradford Yuki , Amos Christopher I. , Blot William J. , Chanock Stephen J. , Harris Curtis C. , Schwartz Ann G. , Spitz Margaret R. , Wiencke John K. , Wrensch Margaret R. , Wu Xifeng , Aldrich Melinda C. 
Published: August 2018

ABSTRACTBackgroundIdentifying genetic variants with pleiotropic associations across multiple cancers can reveal shared biologic pathways. Prior pleiotropic studies have primarily focused on European descent individuals. Yet population-specific genetic variation can occur and potential pleiotropic associations among diverse racial/ethnic populations could be missed. We examined cross-cancer pleiotropic associations with lung cancer risk in African Americans.MethodsWe conducted a pleiotropic analysis among 1,410 African American lung cancer cases and 2,843 controls. We examined 36,958 variants previously associated (or in linkage disequilibrium) with cancer in prior genome-wide association studies. Logistic regression analyses were conducted, adjusting for age, sex, global ancestry, study site, and smoking status.ResultsWe identified three novel genomic regions significantly associated (FDR-corrected p-value < 0.10) with lung cancer risk (rs336958 on 5q14.3, rs7186207 on 16q22.2, and rs11658063 on 17q12). On chromosome16q22.2, rs7186207 was significantly associated with increased risk (OR=1.24, 95% CI: 1.12-1.38) and functional annotation using GTEx showed rs7186207 modifiesDHODHgene expression. The risk allele at rs336958 on 5q14.3 was associated with reduced lung cancer risk (OR=0.68, 95% CI: 0.56-0.82), while the risk allele at rs11658063 on 17q12 was associated with increased risk (OR=1.24, 95% CI: 1.11-1.39).ConclusionWe identified novel associations on chromosomes 5q14.3, 16q22.2, and 17q12, which containHNF1B, DHODH,andHAPLN1genes, respectively. SNPs within these regions have been previously associated with multiple cancers. This is the first study to examine cross-cancer pleiotropic associations for lung cancer in African Americans.ImpactOur findings demonstrate novel cross-cancer pleiotropic associations with lung cancer risk in African Americans.
Molecular and evolutionary strategies of meiotic cheating by selfish centromeres
Authors: Akera Takashi , Trimm Emily , Lampson Michael A. 
Published: August 2018

SummaryAsymmetric division in female meiosis creates selective pressure favoring selfish centromeres that bias their transmission to the egg. This centromere drive can explain the paradoxical rapid evolution of both centromere DNA and centromere-binding proteins despite conserved centromere function. Here, we define a molecular pathway linking expanded centromeres to histone phosphorylation and recrui™ent of microtubule destabilizing factors in an intraspecific hybrid, leading to detachment of selfish centromeres from spindle microtubules that would direct them to the polar body. We also introduce a second hybrid model, exploiting centromere divergence between species, and show that winning centromeres in one hybrid become losers in the other. Our results indicate that increasing destabilizing activity is a general strategy for drive, but centromeres have evolved distinct strategies to increase that activity. Furthermore, we show that drive depends on slowing meiotic progression, suggesting that a weakened meiotic spindle checkpoint evolved as a mechanism to suppress selfish centromeres.
On the role of different age groups during pertussis epidemics in California, 2010 and 2014
Authors: Mahmud Ayesha , Lipsitch Marc , Goldstein Edward 
Published: August 2018

AbstractBackgroundThere is limited information on the roles of different age groups in propagating pertussis outbreaks, and the temporal changes in those roles since the introduction of acellular pertussis vaccines.MethodsThe relative roles of different age groups in propagating the 2010 and the 2014 pertussis epidemics in California were evaluated using the RR statistic that measures the change in the group’s proportion among all detected cases before-vs.-after the epidemic peak.ResultsFor the 2010-11 epidemic, evidence for a predominant transmission age group was weak, with the largest RR estimates being 1.26(95%CI (1.08,1.46)) (aged 11-13y); 1.19(1.01,1.4) (aged 9-10y); 1.17(0.86,1.59) (aged 14-15y); 1.12(0.86,1.46) (aged 16-19y); and 1.1(0.89,1.36) (aged 7-8y). The 2014 epidemic showed a strong signal of the role of older adolescents, with the highest RR estimate being in those aged 14-15y (RR=1.83(1.61,2.07)), followed by adolescents aged 16-19y (RR=1.41(1.24,1.61)) and 11-13y (RR=1.26(1.12,1.41)), with lower RR estimates in other age groups.ConclusionsAs the time following introduction of acellular pertussis vaccines in California progressed, older adolescents played an increasing role in transmission during the major pertussis outbreaks. Booster pertussis vaccination for older adolescents with vaccines effective against pertussis transmission should be considered with the aim of mitigating future pertussis epidemics in the community.
Environmental association identifies candidates for tolerance to low temperature and drought
Authors: Lei Li , Poets Ana M. , Liu Chaochih , Wyant Skylar R. , Hoffman Paul J. , Carter Corey K. , Trantow Richard M. , Shaw Brian G. , Li Xin , Muehlbauer Gary J. , Katagiri Fumiaki , Morrell Peter L. 
Published: August 2018

AbstractBarley(Hordeum vulgaressp.vulgare)is cultivated from the equator to the Arctic Circle. The wild progenitor species,Hordeum vulgare ssp. spontaneum, occupies a relatively narrow latitudinal range (~30 – 40° N) primarily at low elevation (< 1,500 m). Adaptation to the range of cultivation has occurred over ~8,000 years. The genetic basis of this adaptation is amenable to study through environmental association. Using genotyping from 7,864 SNPs in 803 barley landraces, we performed mixed model association analysis relative to bioclimatic variables and analysis of allele frequency differentiation across multiple partitions of the data. Using resequencing data from a subset of these landraces, we tested for linkage disequilibrium (LD) between SNPs queried in genotyping and SNPs in neighboring loci. Six loci previously reported to contribute to adaptive differences in flowering time and abiotic stress in barley and six loci previously identified in other plant species were identified in our analyses. In many cases, patterns of LD are consistent with the causative variant occurring in the immediate vicinity of the queried SNP. The identification of barley orthologs to well characterized genes may provide new understanding of the nature of adaptive variation and could permit a more targeted use of potentially adaptive variants in barley breeding and germplasm improvement.