bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disentangling primer interactions improves SARS-CoV-2 genome sequencing by the ARTIC Network’s multiplex PCR
Authors: Itokawa Kentaro , Sekizuka Tsuyoshi , Hashino Masanori , Tanaka Rina , Kuroda Makoto 
Published: March 2020

AbstractSince December 2019, the coronavirus disease 2019 (COVID-19) caused by a novel coronavirus SARS-CoV-2 has rapidly spread to almost every nation in the world. Soon after the pandemic was recognized by epidemiologists, a group of biologists comprising the ARTIC Network, has devised a multiplexed polymerase chain reaction (PCR) protocol and primer set for targeted whole-genome amplification of SARS-CoV-2. The ARTIC primer set amplifies 98 amplicons, which are separated only in two PCRs, across a nearly entire viral genome. The original primer set and protocol showed a fairly small amplification bias when clinical samples with relatively high viral loads were used. However, when sample’s viral load was low, several amplicons, especially amplicons 18 and 76, exhibited low coverage or complete dropout. We have determined that these dropouts were due to a dimer formation between the forward primer for amplicon 18, 18_LEFT, and the reverse primer for amplicon 76, 76_RIGHT. Replacement of 76_RIGHT with an alternatively designed primer was sufficient to produce a drastic improvement in coverage of both amplicons. Based on this result, we replaced 12 primers in total in the ARTIC primer set that were predicted to be involved in 14 primer interactions. The resulting primer set, version N1 (NIID-1), exhibits improved overall coverage compared to the ARTIC Network’s original (V1) and modified (V3) primer set.
Repeatable ecological dynamics govern response of experimental community to antibiotic pulse perturbation
Authors: Cairns Johannes , Jokela Roosa , Becks Lutz , Mustonen Ville , Hiltunen Teppo 
Published: March 2020

AbstractIn an era of pervasive anthropogenic ecological disturbances, there is a pressing need to understand the factors constituting community response and resilience. A detailed understanding of disturbance response needs to go beyond associations and incorporate features of disturbances, species traits, rapid evolution and dispersal. Multispecies microbial communities experiencing antibiotic perturbation represent a key system with important medical dimensions. However, previous microbiome studies on the theme have relied on high-throughput sequencing data from uncultured species without the ability to explicitly account for the role of species traits and immigration. Here we serially passaged a 34-species defined bacterial community through different levels of pulse antibiotic disturbance, manipulating the presence or absence of species immigration. To understand the ecological community response measured by amplicon sequencing, we combined initial trait data measured for each species separately and metagenome sequencing data revealing adaptive mutations during the experiment. We found that the ecological community response was highly repeatable within the experimental treatments, owing to an increasingly strong yet canalized response at increasing antibiotic levels, which could be partly attributed to key species traits (antibiotic susceptibility and growth rate). Increasing antibiotic levels were also coupled with increasing species extinction probability, making species immigration preventing this critical for community resilience. Moreover, we could detect signals of antibiotic resistance evolution occurring within species at the same time scale, leaving evolutionary changes in communities despite recovery at the species compositional level. Together these observations reveal a disturbance response which appears as classic species sorting but is nevertheless accompanied by rapid within-species evolution.
The periphery is the dominant site of B-cell deletion in a polyclonal repertoire
Authors: Brooks Jeremy F. , Steptoe Raymond J. 
Published: March 2020

AbstractThe concerted actions of multiple tolerance checkpoints limit the possibility of immune attack against self-antigens. For B cells, purging of autoreactivity from the developing repertoire has been almost exclusively studied using B-cell receptor transgenic models. Analyses have generally agreed that central and peripheral tolerance occurs in the form of deletion, receptor editing and anergy. However, when and where these processes occur in a normal polyclonal repertoire devoid of B-cell receptor engineering remain unclear. Here, employing sensitive tools that alleviate the need for B-cell receptor engineering, we track the development of self-reactive B cells and challenge whether deletion plays a meaningful role in B-cell tolerance. We find self-reactive B cells can mature unperturbed by ubiquitous self-antigen expression but, even in the presence of T-cell help, are robustly anergic in the periphery. These studies query the prominence attributed to central and peripheral deletion by most BCR transgenic studies and suggest that other mechanisms predominantly govern B cell tolerance.
The design and implementation of restraint devices for the injection of pathogenic microorganisms intoGalleria mellonella
Authors: Fredericks Lance R. , Roslund Cooper R. , Lee Mark D. , Crabtree Angela M. , Allen Peter B. , Rowley Paul A. 
Published: March 2020

AbstractThe injection of laboratory animals with pathogenic microorganisms poses a significant safety risk because of the potential for injury by accidental needlestick. This is especially true for researchers using invertebrate models of disease due to the small size of the animals and the required precision and accuracy of the injection. The immobilization of the greater wax moth larvae (Galleria mellonella) is often achieved by grasping a larva firmly between finger and thumb. Needle resistant gloves or forceps can be used to reduce the risk of a needlestick but can result in animal injury, a loss of throughput, and inconsistencies in experimental data. Immobilization devices are commonly used for the manipulation of small mammals, and in this manuscript, we describe the construction of injection chambers that can be used to entrap and restrainG. mellonellalarvae prior to injection with pathogenic microbes. These devices significantly reduce the manual handling of larvae and provide an engineering control to protection against accidental needlestick injury, while maintaining a high rate of injection.
Dissecting the role of Amerindian genetic ancestry andApoEε4 allele on Alzheimer disease in an admixed Peruvian population
Authors: Cornejo-Olivas M. , Rajabli F. , Marca V. , Whitehead P.G. , Hofmann N. , Ortega O. , Milla-Neyra K. , Veliz-Otani D. , Custodio N. , Montesinos R. , Castro-Suarez S. , Meza M. , Adams L.D. , Mena P.R. , Isasi R. , Cuccaro M.L. , Vance J.M. , Beecham G.W. , Mazzetti P. , Pericak-Vance M.A. 
Published: March 2020

AbstractAlzheimer disease (AD) is the leading cause of dementia in the elderly and occurs in all ethnic and racial groups.ApoE ε4is the most significant genetic risk factor for late-onset AD and shows the strongest effect among East Asian populations followed by non-Hispanic White populations and has a relatively lower effect in African descent populations. Admixture analysis in the African American and Puerto Rican populations showed that the variation inε4risk is correlated with the genetic ancestral background local to theApoEgene. Native American populations are substantially underrepresented in AD genetic studies. The Peruvian population with up to ∼80 of Amerindian ancestry provides a unique opportunity to assess the role of Amerindian ancestry in Alzheimer disease. In this study we assess the effect of theApoEε4 allele on AD in the Peruvian population.A total of 78 AD cases and 128 unrelated cognitive healthy controls were included in the study. Genome-wide genotyping was performed using the Illumina Global screening array. Global ancestry and local ancestry analyses were assessed. The effect of theApoE ε4allele on Alzheimer disease was tested using a logistic regression model by adjusting for age, gender, and population substructure (first three principal components). Logistic regression results showed thatApoE ε4allele is significantly associated with AD in Peruvian population with the high-risk effect (OR = 5.02, CI: 2.3-12.5, p-value = 2e-4). The average values of the local ancestries surrounding theApoEgene (chr19:44Mb-46Mb) have the highest proportion of Amerindian (60.6%), followed by European (33.9%) and African (5.5%) ancestral backgrounds.Our results showed that the risk for AD fromApoE ε4in Peruvians is higher than we have observed in non-Hispanic White populations. Given the high admixture of Amerindian ancestry in the Peruvian population, it suggests that the Amerindian local ancestry is contributing to a strong risk for AD inApoEε4 carriers. Our data also support the findings of an interaction between the genetic risk alleleApoE ε4and the ancestral backgrounds located around the genomic region ofApoEgene.
Linkage Analysis in Caribbean Hispanic Families with Puerto Rican Ancestry Idenitfies an Alzheimer Disease Locus on chromosome 9
Authors: Rajabli Farid , Feliciano-Astacio Briseida E. , Cukier Holly N. , Wang Liyong , Griswold Anthony , Hamilton-Nelson Kara L. , Adams Larry D. , Rodriguez Vanessa C. , Mena Pedro Ramon , Tejada Sergio , Celis Katrina , Whitehead Patrice L. , Van Booven Derek J , Hofmann Natalia K. , Bussies Parker , Prough Michael , Chinea Angel , Feliciano Nereida I , Acosta Heriberto , Dalgard Clifton L. , Vance Jeffery M. , Cuccaro Michael C. , Beecham Gary W. , Pericak-Vance Margaret A. 
Published: March 2020

AbstractBackgroundThe ancestral genetic heterogeneity (admixture) of Caribbean Hispanics makes studies of this population critical to the discovery of ancestry-specific genetic factors in Alzheimer disease. In this study, we performed whole genome sequencing in multiplex Caribbean Hispanic Puerto Rican families to identify rare causal variants influencing Alzheimer disease through linkage and segregation-based approaches.MethodsAs part of the Puerto Rican Alzheimer Disease Initiative, whole genome sequencing data were generated for 100 individuals (61 affected) from 23 Puerto Rican families. To identify the genetic loci likely to carry risk variants, we performed a parametric multipoint affected individuals-only linkage analysis using MERLIN software. Following the linkage analysis, we identified the consensus region (heterogeneity logarithm of the odds score (HLOD) > 5.1), annotated variants using Ensembl Variant Effect Predictor, and combined annotation dependent depletion score (CADD). Finally, we prioritized variants according to allele frequency (< 0.01), function (CADD > 10), and complete segregation among affected individuals.ResultsA locus at 9p21 produced a linkage HLOD score of 5.1 in the parametric affecteds-only multipoint affected individuals-only model supported by 9 families. Through the prioritization step, we selected 36 variants (22 genic variants). Candidate genes in the regions includeC9orf72, UNC13B, andELAVL2.ConclusionsLinkage analysis of Caribbean Hispanics Puerto Rican families confirmed previously reported linkage to9p21in non-Hispanic White and Israeli-Arap families. Our results suggest several candidates in the region as conferring AD risk. Identified putative damaging rare variants in multiplex families indicates the critical role of rare variation in Alzheimer disease etiology.
Lipid-associated PML domains regulate CCTα, Lipin1 and lipid homeostasis
Authors: Lee Jonghwa , Salsman Jayme , Foster Jason , Dellaire Graham , Ridgway Neale D. 
Published: March 2020

ABSTRACTNuclear LDs (nLDs) originate at the inner nuclear membrane by a mechanism that involves the promyelocytic leukemia (PML) protein. Here we demonstrate that nLDs in oleate-treated U2OS cells are associated withLipid-AssociatedPML (LAP) domains that differ from canonical PML nuclear bodies by the relative absence of SUMO1, SP100 and DAXX. nLDs were also enriched in CTP:phosphocholine cytidylyltransferase α (CCTα), the phosphatidic acid phosphatase Lipin1 and diacylglycerol (DAG). High resolution imaging revealed that LAP domains and CCTα occupy distinct polarized regions on nLDs, and that loss of LAP domains in PML knockout U2OS cells reduced the recruitment of CCTα onto nLDs by its amphipathic α-helical M-domain. The association of Lipin1 and DAG with nLDs was also LAP domain-dependent. The disruption of CCTα and Lipin1 localization on nLDs in PML knockout cells resulted in the inhibition of phosphatidylcholine and triacylglycerol synthesis indicating that LAP domains are a unique PML subdomain involved in nLD assembly and regulation of lipid metabolism.
Economic policy uncertainty and Bitcoin. Is Bitcoin a safe-haven asset?
Authors: Paule-Vianez Jessica , Prado-Román Camilo , Gómez-Martínez Raúl 
Published: March 2020

PurposeThe goal of this work is to determine whether Bitcoin behaves as a safe-haven asset. In order to do so, the influence of Economic Policy Uncertainty (EPU) on Bitcoin returns and volatility was studied.Design/methodology/approachIt is evaluated whether, when compared with the evolution of EPU, Bitcoin's returns and volatility show behaviours typical of safe havens or rather, those of conventional speculative assets. When faced with an increase in EPU, safe havens – such as gold – can be expected to increase their returns and volatility, while conventional speculative assets will increase their volatility and reduce their returns. This study uses simple linear regression and quantile regression models on a daily data sample from 19 July 2010 to 11 April 2019, to analyse the influence of EPU on the returns and volatility of Bitcoin and gold.FindingsBitcoin's returns and volatility increase during more uncertain times, just like gold, showing that Bitcoin acts not only as a means of exchange but also shows characteristics of investment assets, specifically of safe havens. These findings provide useful information to investors by allowing Bitcoin to be considered as a tool to protect savings in times of economic uncertainty and to diversify portfolios.Originality/valueThis study complements and expands current research by aiming to answer the question of whether Bitcoin is a simple speculative asset or a safe haven. The most significant contribution is to show that Bitcoin is not a mere speculative asset but behaves like a safe haven.
Do we innovate as we believe we do?
Authors: McLaughlin Laura , McLaughlin James F. 
Published: March 2020

PurposeThis research study assessed the mindset of individuals regarding their perception of innovation as a means for successful product or process improvement and their perception of thought processes that underpin innovative practices. It investigated the attitudinal foundation for the development of training, development and assessment of structured innovation methodologies.Design/methodology/approachA combination of qualitative and quantitative research gathered through an anonymous survey designed to explore the basic understanding of innovation and included open-ended questions supported more integrated perceptions of innovation in the sampled population's own experiences. The participants of the survey and research were drawn from the public, but it focused more specifically on demographic groups known for their interest in innovation, either as practitioners or teachers.FindingsThe results found, overwhelmingly, survey participants believed innovation is a skill; however, they also believed, inconsistently, that innovation itself is an unpredictable, unstructured and unsystematic process.Practical implicationsAt a practical level, exploring the propensity for individuals or groups to believe defined innovation practices can be effective and that these practices can be learned, measured and improved drives the overall effectiveness of training and organizational leadership. With research, we can make training professionals aware that the mindset of potential innovators is to favor a belief in brainstorming and random success. Doing so can significantly impact the preparation of training and development programs for developing structured innovation capabilities.Originality/valueTraining a new generation of innovators, especially young children, requires care so that they internalize the right mindset and the right tool strategy to be the best innovators possible.
Combined cues of male competition influence spermatozoal investment in a moth
Authors: Liu Junyan , Zhang Yujing , Zheng Xia‐Lin , He Xiong Z. , Wang Qiao 
Published: March 2020

Abstract

Male animals usually raise their sperm allocation after detecting sperm competition risk. To date, only a few studies have investigated the cues used by males to sense and respond to rivals. Yet, it is still largely unknown whether males respond to single or combined cues and whether they can increase their lifetime spermatozoal investment after a perception of rival cue(s).

Here we postulate that males increase ejaculation and production of sperm after detecting combined cues from rivals, but such response quickly diminishes after the cues are removed. We exposed newly emerged and virgin focal males of the moth Ephestia kuehniella to various rival cues and then permanently removed the cues. We introduced a virgin female to an exposed focal male and an unexposed focal male, respectively, per day and counted the number of sperm transferred by the focal males in each mating and recovered in their body after death.

We demonstrate that males significantly increased their lifetime sperm allocation and production after premating detection of either single (acoustic or chemical) or combined cues (acoustic + chemical or acoustic + chemical + tactile) from their rivals with combined cues (acoustic + chemical + tactile) somewhat strengthening such response in eupyrene production.

The number of sperm ejaculated by males significantly decreased over successive matings in their lifetime regardless of whether they were exposed to rival cues, but the decline was significantly faster in rival‐cue‐exposed males than in unexposed ones. This suggests that the increase in spermatogenesis cannot fully compensate for that of sperm expenditure in response to rival cues.

We show that 10‐hr premating rival exposure was sufficient to maximize males' response in sperm ejaculation and production. The impact of the rival perception on sperm transfer persisted for most of males' reproductive life, suggesting that the moth males have a long‐term memory of sperm competition risk experienced in the early adulthood.

A free Plain Language Summary can be found within the Supporting Information of this article.
Common image gather conditioning using cycle generative adversarial networks
Authors: O'Brien G.S. 
Published: March 2020

ABSTRACTSeismically derived amplitude‐versus‐angle attributes along with well constraints are the base inputs into inverting seismic into subsurface properties. Conditioning the common image gathers is a common workflow in quantitative inversion and leads to a more accurate inversion product due to the removal of post‐migration artefacts. Here, we apply a neural network to condition the post‐migration gathers. The network is a cycle generative adversarial network, CycleGAN, which was designed for image‐to‐image translation. This can be considered the same problem as translating an artefact rich seismic gather to an artefact free seismic gather. To assess the feasibility of applying the network to pre‐stack conditioning, synthetic data sets were generated to train different networks for different tasks. The networks were trained to remove white noise, residual de‐multiples, gather flattening and a combination of the above for conditioning. The results show that a trained network was able remove white noise providing a more robust amplitude‐versus‐offset calculation. Another network trained using synthetic gathers with and without multiples assisted in multiple removal. However, instability around primary preservation has been observed so the network works better as a residual de‐multiple method. For gather conditioning, a network was trained with the unpaired artefact‐rich and artefact‐free training data where the artefacts included complex moveout, noise and multiples. When applied to the test data sets, the networks cleaned the artefact‐rich test data and translated complex moveout into flat gathers whilst preserving the amplitude response. Finally, two networks are applied to real data where a gather based on the well logs is used to quantify the match between the conditioned gathers and the raw gathers. The first network used synthetic data to train the network and, when applied to real data, provided a better tie with the well. The second network was trained with synthetic gathers whose properties were constrained by real seismic gathers from near the well. As anticipated, the network trained on the representative training data outperforms the network trained using the unconstrained data. However, the ability of the first network to condition the gather indicates that a sweep of networks can be trained without the need for real data and applied in a manner analogous to the way parameters are adjusted in traditional geophysical methods. The results show that the different neural networks can offer an alternative or augmentation to the existing geophysical workflow for conditioning pre‐stack seismic gathers.
Territoriality drives preemptive habitat selection in recovering wolves: Implications for carnivore conservation
Authors: O'Neil Shawn T. , Vucetich John A. , Beyer Dean E. , Hoy Sarah R. , Bump Joseph K. 
Published: March 2020

Abstract

According to the ideal‐free distribution (IFD), individuals within a population are free to select habitats that maximize their chances of success. Assuming knowledge of habitat quality, the IFD predicts that average fitness will be approximately equal among individuals and between habitats, while density varies, implying that habitat selection will be density dependent. Populations are often assumed to follow an IFD, although this assumption is rarely tested with empirical data, and may be incorrect when territoriality indicates habitat selection tactics that deviate from the IFD (e.g. ideal‐despotic distribution or ideal‐preemptive distribution).

When territoriality influences habitat selection, species' density will not directly reflect components of fitness such as reproductive success or survival. In such cases, assuming an IFD can lead to false conclusions about habitat quality. We tested theoretical models of density‐dependent habitat selection on a species known to exhibit territorial behaviour in order to determine whether commonly applied habitat models are appropriate under these circumstances.

We combined long‐term radiotelemetry and census data from grey wolves Canis lupus in the Upper Peninsula of Michigan, USA to relate spatiotemporal variability in wolf density to underlying classifications of habitat within a hierarchical state‐space modelling framework. We then iteratively applied isodar analysis to evaluate which distribution of habitat selection best described this recolonizing wolf population.

The wolf population in our study expanded by >1,000% during our study (~50 to >600 individuals), and density‐dependent habitat selection was most consistent with the ideal‐preemptive distribution, as opposed to the ideal‐free or ideal‐despotic alternatives.

Population density of terrestrial carnivores may not be positively correlated with the fitness value of their habitats, and density‐dependent habitat selection patterns may help to explain complex predator–prey dynamics and cascading indirect effects. Source–sink population dynamics appear likely when species exhibit rapid growth and occupy interspersed habitats of contrasting quality. These conditions are likely and have implications for large carnivores in many systems, such as areas in North America and Europe where large predator species are currently recolonizing their former ranges.