bluuebunny/crossref_metadata_2025 huggingface dataset:
Considering behaviour to ensure the success of a disease control strategy
Authors: McQuaid Christopher Finn , Gilligan Christopher Aidan , van den Bosch Frank
Published: December 2017

The success or failure of a disease control strategy can be significantly affected by the behaviour of individual agents involved, influencing the effectiveness of disease control, its cost and sustainability. This behaviour has rarely been considered in agricultural systems, where there is significant opportunity for impact. Efforts to increase the adoption of control while decreasing oscillations in adoption and yield, particularly through the administration of subsidies, could increase the effectiveness of interventions. We study individual behaviour for the deployment of clean seed systems to control cassava brown streak disease in East Africa, noting that high disease pressure is important to stimulate grower demand of the control strategy. We show that it is not necessary to invest heavily in formal promotional or educational campaigns, as word-of-mouth is often sufficient to endorse the system. At the same time, for improved planting material to have an impact on increasing yields, it needs to be of a sufficient standard to restrict epidemic spread significantly. Finally, even a simple subsidy of clean planting material may be effective in disease control, as well as reducing oscillations in adoption, as long as it reaches a range of different users every season.
Characterization of puma–livestock conflicts in rangelands of central Argentina
Authors: Guerisoli María de las Mercedes , Luengos Vidal Estela , Franchini Marcello , Caruso Nicolás , Casanave Emma Beatriz , Lucherini Mauro
Published: December 2017

Livestock predation is one of the major causes of conflicts between humans and pumas (
Puma concolor
). Using data from interviews with ranchers and kill-site inspections, we characterized puma–livestock conflicts in Villarino and Patagones counties of central Argentinean rangelands. Depredation was considered the major cause of livestock losses, and puma attacks were reported in 46.6% and 35.4% of ranches in Villarino and Patagones, respectively. The majority of ranches underwent losses smaller than 1000 USD. The proportion of livestock lost to predation (0.1–10.4%) and financial losses (5.3–1560.4 USD) per ranch/year varied across ranches, and small sheep ranches in Villarino were affected the most. Depredation was recorded only at night and preferentially in grassland with shrubs and cropland habitats. Although nocturnal enclosures appeared to decrease sheep losses, puma hunting was considered the most effective form of reducing depredation and was implemented by most ranchers. Mortality rates were 3.7 and 1.1–1.56 individuals/year × 100 km
2
for sheep and pumas, respectively. Nocturnal fencing, shepherding and spatial separation from predators may efficiently reduce sheep losses. However, the poor association between the intensity of puma persecution and puma-related livestock losses suggests that conflict mitigation in central Argentina is not only about reducing damage but also about increasing tolerance.
Distribution, composition and functions of gelatinous tissues in deep-sea fishes
Authors: Gerringer Mackenzie E. , Drazen Jeffrey C. , Linley Thomas D. , Summers Adam P. , Jamieson Alan J. , Yancey Paul H.
Published: December 2017

Many deep-sea fishes have a gelatinous layer, or subdermal extracellular matrix, below the skin or around the spine. We document the distribution of gelatinous tissues across fish families (approx. 200 species in ten orders), then review and investigate their composition and function. Gelatinous tissues from nine species were analysed for water content (96.53 ± 1.78% s.d.), ionic composition, osmolality, protein (0.39 ± 0.23%), lipid (0.69 ± 0.56%) and carbohydrate (0.61 ± 0.28%). Results suggest that gelatinous tissues are mostly extracellular fluid, which may allow animals to grow inexpensively. Further, almost all gelatinous tissues floated in cold seawater, thus their lower density than seawater may contribute to buoyancy in some species. We also propose a new hypothesis: gelatinous tissues, which are inexpensive to grow, may sometimes be a method to increase swimming efficiency by fairing the transition from trunk to tail. Such a layer is particularly prominent in hadal snailfishes (Liparidae); therefore, a robotic snailfish model was designed and constructed to analyse the influence of gelatinous tissues on locomotory performance. The model swam faster with a watery layer, representing gelatinous tissue, around the tail than without. Results suggest that the tissues may, in addition to providing buoyancy and low-cost growth, aid deep-sea fish locomotion.
The reproducibility of research and the misinterpretation of
p
-values
Authors: Colquhoun David
Published: December 2017

We wish to answer this question: If you observe a ‘significant’
p
-value after doing a single unbiased experiment, what is the probability that your result is a false positive? The weak evidence provided by
p-
values between 0.01 and 0.05 is explored by exact calculations of false positive risks. When you observe
p
 = 0.05, the odds in favour of there being a real effect (given by the likelihood ratio) are about 3 : 1. This is far weaker evidence than the odds of 19 to 1 that might, wrongly, be inferred from the
p-
value. And if you want to limit the false positive risk to 5%, you would have to assume that you were 87% sure that there was a real effect before the experiment was done. If you observe
p
 
=
 0.001 in a well-powered experiment, it gives a likelihood ratio of almost 100 : 1 odds on there being a real effect. That would usually be regarded as conclusive. But the false positive risk would still be 8% if the prior probability of a real effect were only 0.1. And, in this case, if you wanted to achieve a false positive risk of 5% you would need to observe
p
 = 0.00045. It is recommended that the terms ‘significant’ and ‘non-significant’ should never be used. Rather,
p-
values should be supplemented by specifying the prior probability that would be needed to produce a specified (e.g. 5%) false positive risk. It may also be helpful to specify the minimum false positive risk associated with the observed
p-
value. Despite decades of warnings, many areas of science still insist on labelling a result of
p
 < 0.05 as ‘statistically significant’. This practice must contribute to the lack of reproducibility in some areas of science. This is before you get to the many other well-known problems, like multiple comparisons, lack of randomization and
p-
hacking. Precise inductive inference is impossible and replication is the only way to be sure. Science is endangered by statistical misunderstanding, and by senior people who impose perverse incentives on scientists.
Quantifying intermolecular interactions of ionic liquids using cohesive energy densities
Authors: Lovelock Kevin R. J.
Published: December 2017

For ionic liquids (ILs), both the large number of possible cation + anion combinations and their ionic nature provide a unique challenge for understanding intermolecular interactions. Cohesive energy density,ced, is used to quantify the strength of intermolecular interactions for molecular liquids, and is determined using the enthalpy of vaporization. A critical analysis of the experimental challenges and data to obtaincedfor ILs is provided. For ILs there are two methods to judge the strength of intermolecular interactions, due to the presence of multiple constituents in the vapour phase of ILs. Firstly,cedIP, where the ionic vapour constituent is neutral ion pairs, the major constituent of the IL vapour. Secondly,cedC+A, where the ionic vapour constituents are isolated ions. AcedIPdataset is presented for 64 ILs. For the first time an experimentalcedC+A, a measure of the strength of the total intermolecular interaction for an IL, is presented.cedC+Ais significantly larger for ILs thancedfor most molecular liquids, reflecting the need to break all of the relatively strong electrostatic interactions present in ILs. However, the van der Waals interactions contribute significantly to IL volatility due to the very strong electrostatic interaction in the neutral ion pair ionic vapour. An excellent linear correlation is found betweencedIPand the inverse of the molecular volume. A good linear correlation is found between ILcedIPand IL Gordon parameter (which are dependent primarily on surface tension).cedvalues obtained through indirect methods gave similar magnitude values tocedIP. These findings show thatcedIPis very important for understanding IL intermolecular interactions, in spite ofcedIPnot being a measure of the total intermolecular interactions of an IL. In the outlook section, remaining challenges for understanding IL intermolecular interactions are outlined.
Kidnapping model: an extension of Selten's game
Authors: Iqbal Azhar , Masson Virginie , Abbott Derek
Published: December 2017

Selten's game is a kidnapping model where the probability of capturing the kidnapper is independent of whether the hostage has been released or executed. Most often, in view of the elevated sensitivities involved, authorities put greater effort and resources into capturing the kidnapper if the hostage has been executed, in contrast with the case when a ransom is paid to secure the hostage's release. In this paper, we study the
asymmetric game
when the probability of capturing the kidnapper depends on whether the hostage has been executed or not and find a new uniquely determined perfect equilibrium point in Selten's game.
On modelling the interaction between two rotating bodies with statistically distributed features: an application to dressing of grinding wheels
Authors: Spampinato A. , Axinte D. A.
Published: December 2017

The mechanisms of interaction between bodies with statistically arranged features present characteristics common to different abrasive processes, such as dressing of abrasive tools. In contrast with the current empirical approach used to estimate the results of operations based on attritive interactions, the method we present in this paper allows us to predict the output forces and the topography of a simulated grinding wheel for a set of specific operational parameters (speed ratio and radial feed-rate), providing a thorough understanding of the complex mechanisms regulating these processes. In modelling the dressing mechanisms, the abrasive characteristics of both bodies (grain size, geometry, inter-space and protrusion) are first simulated; thus, their interaction is simulated in terms of grain collisions. Exploiting a specifically designed contact/impact evaluation algorithm, the model simulates the collisional effects of the dresser abrasives on the grinding wheel topography (grain fracture/break-out). The method has been tested for the case of a diamond rotary dresser, predicting output forces within less than 10% error and obtaining experimentally validated grinding wheel topographies. The study provides a fundamental understanding of the dressing operation, enabling the improvement of its performance in an industrial scenario, while being of general interest in modelling collision-based processes involving statistically distributed elements.
The complex and quaternionic quantum bit from relativity of simultaneity on an interferometer
Authors: Garner Andrew J. P. , Müller Markus P. , Dahlsten Oscar C. O.
Published: December 2017

The patterns of fringes produced by an interferometer have long been important testbeds for our best contemporary theories of physics. Historically, interference has been used to contrast quantum mechanics with classical physics, but recently experiments have been performed that test quantum theory against even more exotic alternatives. A physically motivated family of theories are those where the state space of a two-level system is given by a sphere of arbitrary dimension. This includes classical bits, and real, complex and quaternionic quantum theory. In this paper, we consider
relativity of simultaneity
(i.e. that observers may disagree about the order of events at different locations) as applied to a two-armed interferometer, and show that this forbids most interference phenomena more complicated than those of complex quantum theory. If interference must depend on some relational property of the setting (such as path difference), then relativity of simultaneity will limit state spaces to standard complex quantum theory, or a subspace thereof. If this relational assumption is relaxed, we find one additional theory compatible with relativity of simultaneity: quaternionic quantum theory. Our results have consequences for current laboratory interference experiments: they have to be designed carefully to avoid rendering beyond-quantum effects invisible by relativity of simultaneity.
A novel pathway of nutrient absorption in crustaceans: branchial amino acid uptake in the green shore crab (
Carcinus maenas
)
Authors: Blewett Tamzin A. , Goss Greg G.
Published: December 2017

Estuaries are environments enriched with dissolved nutrients such as amino acids. To date, marine arthropods are the only invertebrate group that have not been demonstrated to access this potentially important nutrient resource. Using
in vitro
gill perfusion techniques, we sought to investigate the ability of the green shore crab (
Carcinus maenas
) to take up the amino acid
l
-leucine directly from the water. Investigation of the concentration-dependent transport kinetics of radiolabelled
l
-leucine showed that there are two specific transport pathways across
Carcinus
gills, one with high affinity and low capacity, and the other with high capacity and low affinity. Using putative competitive substrates and reduced sodium preparations, we were able to identify the putative amino acid transport system associated with high-affinity uptake. This is the first study to demonstrate the absorption of dissolved organic nutrients across the gill epithelium of a marine arthropod.
Co-occurrence of related asexual, but not sexual, lineages suggests that reproductive interference limits coexistence
Authors: Whitton Jeannette , Sears Christopher J. , Maddison Wayne P.
Published: December 2017

We used randomizations to analyse patterns of co-occurrence of sexual and apomictic (asexual) members of the North AmericanCrepisagamic complex (Asteraceae). We expect strong asymmetry in reproductive interactions inCrepis: apomicts produce clonal seeds with no need for pollination and are not subject to reproductive interference from co-occurring relatives. However, because they still produce some viable pollen, apomicts can reduce reproductive success of nearby sexual relatives, potentially leading to eventual local exclusion of sexuals. Consistent with this, randomizations reveal that sexuals are over-represented in isolated sites, while apomicts freely co-occur. Incorporation of taxonomic and phylogenetic evidence indicates that this pattern is not driven by local origins of asexuals. Our evidence that patterns of local co-occurrence are structured by reproductive interference suggests an underappreciated role for these interactions in community assembly, and highlights the need for explicit tests of the relative contributions of ecological and reproductive interactions in generating patterns of limiting similarity.
Inter-annual variation in seed production has increased over time (1900–2014)
Authors: Pearse Ian S. , LaMontagne Jalene M. , Koenig Walter D.
Published: December 2017

Mast seeding, or masting, is the highly variable and spatially synchronous production of seeds by a population of plants. The production of variable seed crops is typically correlated with weather, so it is of considerable interest whether global climate change has altered the variability of masting or the size of masting events. We compiled 1086 datasets of plant seed production spanning 1900–2014 and from around the world, and then analysed whether the coefficient of variation (CV) in seed set, a measure of masting, increased over time. Over this 115-year period, seed set became more variable for plants as a whole and for the particularly well-studied taxa of conifers and oaks. The increase in CV corresponded with a decrease in the long-term mean of seed set of plant species. Seed set CV increased to a greater degree in plant taxa with a tendency towards masting. Seed set is becoming more variable among years, especially for plant taxa whose masting events are known to affect animal populations. Such subtle change in reproduction can have wide-ranging effects on ecosystems because seed crops provide critical resources for a wide range of taxa and have cascading effects throughout food webs.
First satellite tracks of South Atlantic sea turtle ‘lost years’: seasonal variation in trans-equatorial movement
Authors: Mansfield Katherine L. , Mendilaharsu Milagros L. , Putman Nathan F. , dei Marcovaldi Maria A. G. , Sacco Alexander E. , Lopez Gustave , Pires Thais , Swimmer Yonat
Published: December 2017

In the South Atlantic Ocean, few data exist regarding the dispersal of young oceanic sea turtles. We characterized the movements of laboratory-reared yearling loggerhead turtles from Brazilian rookeries using novel telemetry techniques, testing for differences in dispersal during different periods of the sea turtle hatching season that correspond to seasonal changes in ocean currents. Oceanographic drifters deployed alongside satellite-tagged turtles allowed us to explore the mechanisms of dispersal (passive drift or active swimming). Early in the hatching season turtles transited south with strong southward currents. Late in the hatching season, when currents flowed in the opposite direction, turtles uniformly moved northwards across the Equator. However, the movement of individuals differed from what was predicted by surface currents alone. Swimming velocity inferred from track data and an ocean circulation model strongly suggest that turtles' swimming plays a role in maintaining their position within frontal zones seaward of the continental shelf. The long nesting season of adults and behaviour of post-hatchlings exposes young turtles to seasonally varying ocean conditions that lead some individuals further into the South Atlantic and others into the Northern Hemisphere. Such migratory route diversity may ultimately buffer the population against environmental changes or anthropologic threats, fostering population resiliency.
Major histocompatibility complex-linked social signalling affects female fertility
Authors: Burger D. , Thomas S. , Aepli H. , Dreyer M. , Fabre G. , Marti E. , Sieme H. , Robinson M. R. , Wedekind C.
Published: December 2017

Genes of the major histocompatibility complex (MHC) have been shown to influence social signalling and mate preferences in many species, including humans. First observations suggest that MHC signalling may also affect female fertility. To test this hypothesis, we exposed 191 female horses (Equus caballus) to either an MHC-similar or an MHC-dissimilar stimulus male around the time of ovulation and conception. A within-subject experimental design controlled for non-MHC-linked male characteristics, and instrumental insemination with semen of other males (n= 106) controlled for potential confounding effects of semen or embryo characteristics. We found that females were more likely to become pregnant if exposed to an MHC-dissimilar than to an MHC-similar male, while overall genetic distance to the stimulus males (based on microsatellite markers on 20 chromosomes) had no effect. Our results demonstrate that early pregnancy failures can be due to maternal life-history decisions (cryptic female choice) influenced by MHC-linked social signalling.
The functional syndrome: linking individual trait variability to ecosystem functioning
Authors: Raffard Allan , Lecerf Antoine , Cote Julien , Buoro Mathieu , Lassus Remy , Cucherousset Julien
Published: December 2017

Phenotypic variability is increasingly assessed through functional response and effect traits, which provide a mechanistic framework for investigating how an organism responds to varying ecological factors and how these responses affect ecosystem functioning. Covariation between response and effect traits has been poorly examined at the intraspecific level, thus hampering progress in understanding how phenotypic variability alters the role of organisms in ecosystems. Using a multi-trait approach and a nine-month longitudinal monitoring of individual red-swamp crayfish (
Procambarus clarkii
), we demonstrated that most of the measured response and effect traits were partially stable during the ontogeny of individuals. Suites of response and effect traits were associated with a response syndrome and an effect syndrome, respectively, which were correlated to form a functional syndrome. Using a bioenergetic model, we predicted that differences in the response syndrome composition of hypothetical populations had important ecological effects on a key ecosystem process (i.e. whole-lake litter decomposition) to a level similar to those induced by doubling population size. Demonstrating the existence of a functional syndrome is likely to improve our understanding of the ecological impacts of phenotypic variation among individuals in wild populations across levels of biological organization, and the linkage between ecosystem and evolutionary ecology.
Rapid evolution rescues hosts from competition and disease but—despite a dilution effect—increases the density of infected hosts
Authors: Strauss Alexander T. , Hite Jessica L. , Shocket Marta S. , Cáceres Carla E. , Duffy Meghan A. , Hall Spencer R.
Published: December 2017

Virulent parasites can depress the densities of their hosts. Taxa that reduce disease via dilution effects might alleviate this burden. However, ‘diluter’ taxa can also depress host densities through competition for shared resources. The combination of disease and interspecific competition could even drive hosts extinct. Then again, genetically variable host populations can evolve in response to both competitors and parasites. Can rapid evolution rescue host density from the harm caused by these ecological enemies? How might such evolution influence dilution effects or the size of epidemics? In a mesocosm experiment with planktonic hosts, we illustrate the joint harm of competition and disease: hosts with constrained evolutionary ability (limited phenotypic variation) suffered greatly from both. However, populations starting with broader phenotypic variation evolved stronger competitive ability during epidemics. In turn, enhanced competitive ability—driven especially by parasites—rescued host densities from the negative impacts of competition, disease, and especially their combination. Interspecific competitors reduced disease (supporting dilution effects) even when hosts rapidly evolved. However, this evolutionary response also elicited a potential problem. Populations that evolved enhanced competitive ability and maintained robust total densities also supported higher densities of infections. Thus, rapid evolution rescued host densities but also unleashed larger epidemics.
Deep pelagic food web structure as revealed by
in situ
feeding observations
Authors: Choy C. Anela , Haddock Steven H. D. , Robison Bruce H.
Published: December 2017

Food web linkages, or the feeding relationships between species inhabiting a shared ecosystem, are an ecological lens through which ecosystem structure and function can be assessed, and thus are fundamental to informing sustainable resource management. Empirical feeding datasets have traditionally been painstakingly generated from stomach content analysis, direct observations and from biochemical trophic markers (stable isotopes, fatty acids, molecular tools). Each approach carries inherent biases and limitations, as well as advantages. Here, using 27 years (1991–2016) of
in situ
feeding observations collected by remotely operated vehicles (ROVs), we quantitatively characterize the deep pelagic food web of central California within the California Current, complementing existing studies of diet and trophic interactions with a unique perspective. Seven hundred and forty-three independent feeding events were observed with ROVs from near-surface waters down to depths approaching 4000 m, involving an assemblage of 84 different predators and 82 different prey types, for a total of 242 unique feeding relationships. The greatest diversity of prey was consumed by narcomedusae, followed by physonect siphonophores, ctenophores and cephalopods. We highlight key interactions within the poorly understood ‘jelly web’, showing the importance of medusae, ctenophores and siphonophores as key predators, whose ecological significance is comparable to large fish and squid species within the central California deep pelagic food web. Gelatinous predators are often thought to comprise relatively inefficient trophic pathways within marine communities, but we build upon previous findings to document their substantial and integral roles in deep pelagic food webs.
Hierarchical social networks shape gut microbial composition in wild Verreaux's sifaka
Authors: Perofsky Amanda C. , Lewis Rebecca J. , Abondano Laura A. , Di Fiore Anthony , Meyers Lauren Ancel
Published: December 2017

In wild primates, social behaviour influences exposure to environmentally acquired and directly transmitted microorganisms. Prior studies indicate that gut microbiota reflect pairwise social interactions among chimpanzee and baboon hosts. Here, we demonstrate that higher-order social network structure—beyond just pairwise interactions—drives gut bacterial composition in wild lemurs, which live in smaller and more cohesive groups than previously studied anthropoid species. Using 16S rRNA gene sequencing and social network analysis of grooming contacts, we estimate the relative impacts of hierarchical (i.e. multilevel) social structure, individual demographic traits, diet, scent-marking, and habitat overlap on bacteria acquisition in a wild population of Verreaux's sifaka (
Propithecus verreauxi
) consisting of seven social groups. We show that social group membership is clearly reflected in the microbiomes of individual sifaka, and that social groups with denser grooming networks have more homogeneous gut microbial compositions. Within social groups, adults, more gregarious individuals, and individuals that scent-mark frequently harbour the greatest microbial diversity. Thus, the community structure of wild lemurs governs symbiotic relationships by constraining transmission between hosts and partitioning environmental exposure to microorganisms. This social cultivation of mutualistic gut flora may be an evolutionary benefit of tight-knit group living.
SciRide Finder: a citation-based paradigm in biomedical literature search
Authors: Volanakis Adam , Konrad Krawczyk
Published: December 2017

There are more than 26 million peer-reviewed biomedical research items according to Medline/PubMed. This breadth of information is indicative of the progress in biomedical sciences on one hand, but an overload for scientists performing literature searches on the other. A major portion of scientific literature search is to find statements, numbers and protocols that can be cited to build an evidence-based narrative for a new manuscript. Because science builds on prior knowledge, such information has likely been written out and cited in an older manuscript. Thus, Cited Statements, pieces of text from scientific literature supported by citing other peer-reviewed publications, carry significant amount of condensed information on prior art. Based on this principle, we propose a literature search service, SciRide Finder (finder.sciride.org), which constrains the search corpus to such Cited Statements only. We demonstrate that Cited Statements can carry different information to this found in titles/abstracts and full text, giving access to alternative literature search results than traditional search engines. We further show how presenting search results as a list of Cited Statements allows researchers to easily find information to build an evidence-based narrative for their own manuscripts.
Sex differences in the genetic architecture of obsessive-compulsive disorder
Authors: Khramtsova Ekaterina A. , Heldman Raphael , Derks Eske M. , Yu Dongmei ,   TS/OCD Psychiatric Genomics Disorders Workgroup, Davis Lea K. , Stranger Barbara E.
Published: December 2017

Obsessive-compulsive disorder (OCD), a highly heritable complex phenotype, demonstrates sexual dimorphism in age of onset and clinical presentation, suggesting a possible sex difference in underlying genetic architecture. We present the first genome-wide characterization of the sex-specific genetic architecture of OCD, utilizing the largest set of OCD cases and controls available from the Psychiatric Genomics Consortium. We assessed evidence for several mechanisms that may contribute to sexual-dimorphism including a sexually dimorphic liability threshold, the presence of individual sex-specific risk variants on the autosomes and the X chromosome, genetic and phenotypic heterogeneity, and sex-specific pleiotropic effects. We observed a strong genetic correlation between male and female OCD and no evidence for a sexually dimorphic liability threshold model. While we did not detect any sex-specific genome-wide associations, we observed that the SNPs with sexually dimorphic effects showed an enrichment of regulatory variants influencing expression of genes in immune tissues. Furthermore, top sex-specific genome-wide associations were enriched for regulatory variants in different tissues, suggesting evidence for potential sex difference in the biology underlying risk for OCD. These findings suggest that future studies with larger sample sizes hold great promise for the identification of sex-specific risk factors for OCD, significantly advancing our understanding of the differences in the genetic basis of sexually dimorphic neuropsychiatric traits.
Serum proteins can successfully predict self-reported ethnicity: Implications for precision-medicine
Authors: Bishnoi Ram J , Palmer Raymond , Royall Donald R
Published: December 2017

The effects of inter-individual variability on disease treatment and prevention are important to the goals of “precision medicine” 1. In biomedical research, consideration of racial or ethnic differences allows generation and exploration of hypotheses about interactions among genetic and environmental factors responsible for differential medical outcomes. The US National Institutes of Health, therefore recommends adequate participation of subjects from ethnic minority groups in research studies. Nevertheless, considerable debate has focused on validity of race or ethnicity as biological construct 2. Inconsistent definition of race/ethnicity and insignificant genetic variations between ethnic groups have invited disregard to this construct 3. On the contrary, differences in prevalence, expression and outcomes of various diseases among ethnic groups argue for continued and focused attention to ethnicity as important predicting variable. In context of Alzheimer’s disease (AD), we have previously reported that ethnicity does moderates the proteomic markers of dementia 4. Here, we attempted to classify and predict selfreported ethnicity (Hispanic or non-Hispanic white, [NHW]) using a limited serum profile of 107 proteins. Random Forest (RF) classification method was able to discriminate those two ethnicities with 95% accuracy and could successfully predict ethnicity in an independent test-set (Area under ROC curve: 0.97). Variable selection method led to a condensed set of six proteins which yielded comparable classification and prediction accuracy. Our results provide preliminary evidence for proteomic variability between ethnic groups, and biological validity of ethnicity construct. Moreover, they also offer an opportunity to exploit these differences towards the objectives of precision medicine.
CREAM: Clustering of genomic REgions Analysis Method
Authors: Tonekaboni Seyed Ali Madani , Mazrooei Parisa , Kofia Victor , Haibe-Kains Benjamin , Lupien Mathieu
Published: December 2017

Cellular identity relies on cell type-specific gene expression profiles controlled by cis-regulatory elements (CREs), such as promoters, enhancers and anchors of chromatin interactions. CREs are unevenly distributed across the genome, giving rise to distinct subsets such as individual CREs and Clusters Of cis-Regulatory Elements (COREs), also known as super-enhancers. Identifying COREs is a challenge due to technical and biological features that entail variability in the distribution of distances between CREs within a given dataset. To address this issue, we developed a new unsupervised machine learning approach termed Clustering of genomic REgions Analysis Method (CREAM) that outperforms the Ranking Of Super Enhancer (ROSE) approach. Specifically CREAM identified COREs are enriched in CREs strongly bound by master transcription factors according to ChIP-seq signal intensity, are proximal to highly expressed genes, are preferentially found near genes essential for cell growth and are more predictive of cell identity. Moreover, we show that CREAM enables subtyping primary prostate tumor samples according to their CORE distribution across the genome. We further show that COREs are enriched compared to individual CREs at TAD boundaries and these are preferentially bound by CTCF and factors of the cohesin complex (e.g.: RAD21 and SMC3). Finally, using CREAM against transcription factor ChIP-seq reveals CTCF and cohesin-specific COREs preferentially at TAD boundaries compared to intra-TADs. CREAM is available as an open source R package (https://CRAN.R-project.org/package=CREAM) to identify COREs from cis-regulatory annotation datasets from any biological samples.
The control of tonic pain by active relief learning
Authors: Zhang Suyi , Mano Hiroaki , Lee Michael , Yoshida Wako , Kawato Mitsuo , Robbins Trevor W , Seymour Ben
Published: December 2017

Tonic pain after injury characterises a behavioural state that prioritises recovery. Although generally suppressing cognition and attention, tonic pain needs to allow effective relief learning so that the cause of the pain can be reduced if possible. Here, we describe a central learning circuit that supports learning of relief and concurrently suppresses the level of ongoing pain. We used computational modelling of behavioural, physiological and neuroimaging data in two experiments in which subjects learned to terminate tonic pain in static and dynamic escape-learning paradigms. In both studies, we show that active relief-seeking involves a reinforcement learning process manifest by error signals observed in the dorsal putamen. Critically, this system also uses an uncertainty (‘associability’) signal detected in pregenual anterior cingulate cortex that both controls the relief learning rate, and endogenously and parametrically modulates the level of tonic pain. The results define a self-organising learning circuit that allows reduction of ongoing pain when learning about potential relief.
Rethinking phylogenetic comparative methods
Authors: Uyeda Josef C. , Zenil-Ferguson Rosana , Pennell Matthew W.
Published: December 2017

As a result of the process of descent with modification, closely related species tend to be similar to one another in a myriad different ways. In statistical terms, this means that traits measured on one species will not be independent of traits measured on others. Since their introduction in the 1980s, phylogenetic comparative methods (PCMs) have been framed as a solution to this problem. In this paper, we argue that this way of thinking about PCMs is deeply misleading. Not only has this sowed widespread confusion in the literature about what PCMs are doing but has led us to develop methods that are susceptible to the very thing we sought to build defenses against — unreplicated evolutionary events. Through three Case Studies, we demonstrate that the susceptibility to singular events is indeed a recurring problem in comparative biology that links several seemingly unrelated controversies. In each Case Study we propose a potential solution to the problem. While the details of our proposed solutions differ, they share a common theme: unifying hypothesis testing with data-driven approaches (which we term “phylogenetic natural history”) to disentangle the impact of singular evolutionary events from that of the factors we are investigating. More broadly, we argue that our field has, at times, been sloppy when weighing evidence in support of causal hypotheses. We suggest that one way to refine our inferences is to re-imagine phylogenies as probabilistic graphical models; adopting this way of thinking will help clarify precisely what we are testing and what evidence supports our claims.
A Basal Ganglia Circuit Sufficient To Guide Birdsong Learning
Authors: Xiao Lei , Chattree Gaurav , Garcia Oscos Francisco , Cao Mou , Wanat Matthew J. , Roberts Todd F.
Published: December 2017

Learning complex vocal behaviors, like speech and birdsong, is thought to rely on continued performance evaluation. Whether candidate performance evaluation circuits in the brain are sufficient to guide vocal learning is not known. Here, we test the sufficiency of VTA projections to the vocal basal ganglia (Area X) in singing zebra finches, a songbird species that learns to produce a complex and stereotyped multi-syllabic courtship song during development. We optogenetically manipulate VTA axon terminals in singing birds contingent on how the pitch of individual song syllables are naturally performed. We find that optical excitation and inhibition of VTA terminals have opponent effects on future performances of targeted song syllables and are each sufficient to reliably guide learned changes in song, consistent with positive and negative reinforcement of performance outcomes. These findings define a central role for reinforcement mechanisms in learning vocalizations and provide the first demonstration of minimal circuit elements for learning vocal behaviors.
Maize GO Annotation - Methods, Evaluation, and Review (maize-GAMER)
Authors: Wimalanathan Kokulapalan , Friedberg Iddo , Andorf Carson M. , Lawrence-Dill Carolyn J.
Published: December 2017

1

We created a new high-coverage, robust, and reproducible functional annotation of maize protein coding genes based on Gene Ontology (GO) term assignments. Whereas the existing Phytozome and Gramene maize GO annotation sets only cover 41% and 56% of maize protein coding genes, respectively, this study provides annotations for 100% of the genes. We also compared the quality of our newly-derived annotations with the existing Gramene and Phytozome functional annotation sets by comparing all three to a manually annotated gold standard set of 1,619 genes where annotations were primarily inferred from direct assay or mutant phenotype. Evaluations based on the gold standard indicate that our new annotation set is measurably more accurate than those from Phytozome and Gramene. To derive this new high-coverage, high-confidence annotation set we used sequence-similarity and protein-domain-presence methods as well as mixed-method pipelines that developed for the Critical Assessment of Function Annotation (CAFA) challenge. Our project to improve maize annotations is called maize-GAMER (GO Annotation Method, Evaluation, and Review) and the newly-derived annotations are accessible via MaizeGDB (http://download.maizegdb.org/maize-GAMER) and CyVerse (B73 RefGen_v3 5b+ at doi: doi.org/10.7946/P2S62P and B73 RefGen_v4 Zm00001d.2 at doi: doi.org/10.7946/P2M925).
Dynamic reorganization of nuclear architecture during human cardiogenesis
Authors: Fields Paul A. , Ramani Vijay , Bonora Giancarlo , Yardimci Gurkan , Bertero Alessandro , Reinecke Hans , Pabon Lil , Noble William S. , Shendure Jay , Murry Charles E.
Published: December 2017

While chromosomal architecture varies among cell types, little is known about how this organization is established or its role in development. We integrated Hi-C, RNA-seq and ATAC-seq during cardiac differentiation from human pluripotent stem cells to generate a comprehensive profile of chromosomal architecture. We identified active and repressive domains that are dynamic during cardiogenesis and recapitulate in vivo cardiomyocytes. During differentiation, heterochromatic regions condense in cis. In contrast, many cardiac-specific genes, such as TTN (titin), decompact and transition to an active compartment coincident with upregulation. Moreover, we identify a network of genes, including TTN, that share the heart-specific splicing factor, RBM20, and become associated in trans during differentiation, suggesting the existence of a 3D nuclear splicing factory. Our results demonstrate both the dynamic nature in nuclear architecture and provide insights into how developmental genes are coordinately regulated.

One Sentence Summary

The three-dimensional structure of the human genome is dynamically regulated both globally and locally during cardiogenesis.
Cardiac metabolic effects of KNa1.2 channel deletion, and evidence for its mitochondrial localization
Authors: Smith Charles O. , Wang Yves T. , Nadtochiy Sergiy M , Miller James H. , Jonas Elizabeth A. , Dirksen Robert T. , Nehrke Keith , Brookes Paul S.
Published: December 2017

Controversy surrounds the molecular identity of mitochondrial K+ channels that are important for protection against cardiac ischemia-reperfusion injury. While KNa1.2 (Kcnt2 gene) is necessary for cardioprotection by volatile anesthetics, electrophysiologic evidence for a channel of this type in mitochondria is lacking. The endogenous physiologic role of a potential mito-KNa1.2 channel is also unclear. Herein, single channel patch-clamp of 27 independent cardiac mitochondrial inner membrane (mitoplast) preparations from wild type (WT) mice yielded 6 channels matching the known ion-sensitivity, ion-selectivity, pharmacology and conductance properties of KNa1.2 (slope conductance 138±1 pS). However, similar experiments on 40 preparations from Kcnt2-/- mice yielded zero such channels. The KNa opener bithionol uncoupled respiration in WT but not Kcnt2-/- cardiomyocytes. Furthermore, when oxidizing only fat as substrate, Kcnt2-/- cardiomyocytes and hearts were less responsive to increases in energetic demand. Kcnt2-/- mice also had elevated body fat, but no baseline differences in the cardiac metabolome. These data support the existence of a cardiac mitochondrial KNa1.2 channel, and a role for cardiac KNa1.2 in regulating metabolism under conditions of high energetic demand.
ZoonoticBabesia microtiin the northeastern U.S.: evidence for the expansion of a specific parasite lineage
Authors: Goethert Heidi K. , Molloy Philip , Berardi Victor , Weeks Karen , Telford Sam R.
Published: December 2017

The recent range expansion of human babesiosis in the northeastern United States, once found only in restricted coastal sites, is not well understood. This study sought to utilize a large number of samples to examine the population structure of the parasites on a fine scale to provide insights into the mode of emergence across the region. 228B. microtisamples collected in endemic northeastern U.S. sites were genotyped using published VNTR markers. The genetic diversity and population structure were analysed on a geographic scale using Phyloviz and TESS. Three distinct populations were detected in northeastern US, each dominated by a single ancestral type. In contrast to the limited range of the Nantucket and Cape Cod populations, the mainland population dominated from New Jersey eastward to Boston. Ancestral populations ofB. microtiwere sufficiently isolated to differentiate into distinct populations. Despite this, a single population was detected across a large geographic area of the northeast that historically had at least 3 distinct foci of transmission, central New Jersey, Long Island and southeastern Connecticut. We conclude that a singleB. microtigenotype has expanded across the northeastern U.S. The biological attributes associated with this parasite genotype that have contributed to such a selective sweep remain to be identified.

Author summary

Babesiosis is a disease caused by a protozoan parasite,Babesia microti,related to malaria. The disease is acquired by the bite of the deer tick, the same tick that transmits Lyme disease. Although Lyme disease rapidly emerged over a wide range within the last 40 years, babesiosis remained rare with an extremely focal distribution. Within the last decade, the number of reports of babesiosis cases has increased from an expanded area of risk, particularly across the mainland of southern New England. We determined whether the expanded risk may be due to local intensification of transmission as opposed to introduction of the parasite. Historical fragmentation of the landscape suggests that sites ofB. microtitransmission should have been isolated and thus evidence of multiple genetically distinct populations should be found. By a genetic fingerprinting method, we found that samples from the new mainland sites were all genetically similar. We conclude that one parasite genetic lineage has recently expanded its distribution and now dominates, suggesting that it has some phenotypic attribute that may confer a selective advantage over others.
Elevated and sustained reactive oxygen species levels facilitate mesoderm formation during earlyXenopusdevelopment
Authors: Han Yue , Chen Yaoyao , Love Nick R. , Ishibashi Shoko , Amaya Enrique
Published: December 2017

Fertilisation triggers embryonic development culminating with the activation of a number of highly co-ordinated and evolutionarily conserved signalling pathways, which induce and pattern the mesoderm of the developing embryo. Previous studies in invertebrates have shown that hydrogen peroxide (H2O2), a reactive oxygen species (ROS), can act as a signalling molecule for axis specification during early development. Using a HyPer transgenicXenopus laevisline that expresses a H2O2-sensitive fluorescent protein sensor maternally, we recently found that fertilisation triggers a rapid increase in ROS production. Here we show that this increase in ROS levels is sustained throughout early embryogenesis, lasting until the tailbud stages. In addition we show that lowering ROS levels from the blastula stage through the gastrula stages via antioxidant treatments disrupts mesoderm formation. Furthermore, we show that attenuating ROS levels during the blastula / gastrula stages affects some, but not all, growth factor signalling pathways involved in mesoderm induction and patterning, including the PI3K/Akt, TGF-β/Nodal, and Wnt/β-catenin signalling pathways. These data suggest that sustained elevated ROS levels during the blastula and gastrula stages are essential for early vertebrate embryonic development, at least partly, through their roles in promoting growth factor signalling.
Engineering a promiscuous pyrrolysyl-tRNA synthetase by a high throughput FACS screen
Authors: Hohl Adrian , Karan Ram , Akal Anstassja , Renn Dominik , Liu Xuechao , Dharamarajnadar Alaguraj , Ghoprade Seema , Groll Michael , Rueping Magnus , Eppinger Jörg
Published: December 2017

The Pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNAPyl are used to facilitate the incorporation of non-canonical amino acids (ncAAs) into the genetic code of bacterial and eukaryotic cells by orthogonally reassigning the amber codon. Currently, the incorporation of new ncAAs requires a cumbersome engineering process composed of several positive and negative selection rounds to select the appropriate PylRS/tRNAPyl pair. Our fast and sensitive engineering approach required only a single FACS selection round to identify 110 orthogonal PylRS variants for the aminoacylation of 20 ncAAs. Pocket-substrate relationship from these variants led to the design of a highly promiscuous PylRS (HpRS), which catalyzed the aminoacylation of 31 structurally diverse lysine derivatives bearing clickable, fluorinated, fluorescent, and biotinylated entities. The high speed and sensitivity of our approach provides a competitive alternative to existing screening methodologies, and delivers insights into the complex PylRS-substrate interactions to facilitate the generation of additional promiscuous variants.