bluuebunny/crossref_metadata_2025 huggingface dataset:
Trophic niche breadth of pond zooplankton species using stable isotope analysis and the relationship with the abiotic and biotic factors
Authors: Doi Hideyuki , Chang Kwang-Hyeon , Nakano Shin-ichi
Published: January 2019

Zooplankton species have different feeding habits, but the diversity of their food resources and the factors governing them are still largely unknown. We here estimated the differences in the trophic niche breadths of dominant zooplankton species in ponds, using stable isotopes. To understand the differences in trophic niches of different zooplankton species, we measured the carbon and nitrogen stable isotope ratios and calculated the nearest-neighbour distance (NND), and standard deviation of NND (SDNND) of the bi-plot space of stable carbon and nitrogen isotopes in pond zooplankton. We tested the relationship between the NND/SDNND and environmental factors, as well as the zooplankton biomass, using generalized linear models (GLMs). For cladocerans, including
Bosmina, Ceriodaphnia
and
Daphnia,
the NNDs were significantly correlated with the biomass, pond morphology (volume and depth), total phosphorous (TP) and fish presence. For copepod species, including
Eodiaptomus
and cyclopoids, NNDs were significantly correlated with pond morphology, TP and fish presence, but not with biomass. In GLMs of SDNND, significant correlated factors were less than those for NND, and for some species, pond morphology and TP were significantly correlated with SDNND. Here, we found that the NND and SDNND of zooplankton species were related to various factors, including their biomass, predator presence, pond size and water quality. For cladocerans, biomass may be supported by trophic niche breadth, probably because of the consequences of resource competition. Also, predation and ecosystem size may influence trophic niche breadth due to changes in zooplankton behaviours.
Thermal decomposition characteristics of foundry sand for cast iron in nitrogen atmosphere
Authors: Xu Qingwei , Xu Kaili , Yao Xiwen , Li Jishuo , Li Li
Published: January 2019

Sand casting, currently the most popular approach to the casting production, has wide adaptability and low cost. The thermal decomposition characteristics of foundry sand for cast iron were determined for the first time in this study. Thermogravimetry was monitored by simultaneous thermal analyser to find that there was no obvious oxidation or combustion reaction in the foundry sand; the thermal decomposition degree increased as the heating rate increased. There was an obvious endothermic peak at about 846 K due to the transition of quartz from
β
to
α
phase. A novel technique was established to calculate the starting temperature of volatile emission in determining the volatile release parameter of foundry sand for cast iron. Foundry sand does not readily evaporate because its volatile content is only about 2.68 wt% and its main components have high-temperature stability. The thermal decomposition kinetics parameters of foundry sand, namely activation energy and pre-exponential factor, were obtained under kinetics theory. The activation energy of foundry sand for cast iron was small, mainly due to the wide temperature range of thermal decomposition in the foundry sand.
Screening of cytotoxic or cytostatic flavonoids with quantitative Fluorescent Ubiquitination-based Cell Cycle Indicator-based cell cycle assay
Authors: Go Young-Hyun , Lee Hyo-Ju , Kong Hyeon-Joon , Jeong Ho-Chang , Lee Dong Young , Hong Soon-Ki , Sung Sang Hyun , Kwon Ok-Seon , Cha Hyuk-Jin
Published: January 2019

The Fluorescent Ubiquitination-based Cell Cycle Indicator (FUCCI) system can be used not only to study gene expression at a specific cell cycle stage, but also to monitor cell cycle transitions in real time. In this study, we used a single clone of FUCCI-expressing HeLa cells (FUCCI-HeLa cells) and monitored the cell cycle in individual live cells over time by determining the ratios between red fluorescence (RF) of RFP-Cdt1 and green fluorescence (GF) of GFP-Geminin. Cytotoxic and cytostatic compounds, the latter of which induced G2 or mitotic arrest, were identified based on periodic cycling of the RF/GF and GF/RF ratios in FUCCI-HeLa cells treated with anti-cancer drugs. With this cell cycle monitoring system, ten flavonoids were screened. Of these, apigenin and luteolin, which have a flavone backbone, were cytotoxic, whereas kaempferol, which has a flavonol backbone, was cytostatic and induced G2 arrest. In summary, we developed a system to quantitatively monitor the cell cycle in real time. This system can be used to identify novel compounds that modulate the cell cycle and to investigate structure–activity relationships.
Soundscapes influence the settlement of the common Caribbean coral
Porites astreoides
irrespective of light conditions
Authors: Lillis Ashlee , Apprill Amy , Suca Justin J. , Becker Cynthia , Llopiz Joel K. , Mooney T. Aran
Published: January 2019

The settlement of reef-building corals is critical to the survival and recovery of reefs. Recent evidence indicates that coral larvae orient towards reef sound, yet the components of the acoustic environment that may attract coral larvae and induce settlement are unknown. Here we investigated the effects of ambient soundscapes on settlement of
Porites astreoides
coral larvae using
in situ
chambers on reefs differing in habitat quality (coral and fish abundance). Mean larval settlement was twice as high in an acoustic environment with high levels of low-frequency sounds, typical of a high-quality, healthy reef; this result was observed in both natural light and dark treatments. Overall, the enhancement of coral settlement by soundscapes typical of healthy reefs suggests a positive feedback where soundscape properties of reefs with elevated coral and fish abundance may facilitate coral recruitment.
No place like home? A test of the natal habitat-biased dispersal hypothesis in Scandinavian wolves
Authors: Sanz-Pérez Ana , Ordiz Andrés , Sand Håkan , Swenson Jon E. , Wabakken Petter , Wikenros Camilla , Zimmermann Barbara , Åkesson Mikael , Milleret Cyril
Published: January 2019

Natal dispersal is an important mechanism for the viability of populations. The influence of local conditions or experience gained in the natal habitat could improve fitness if dispersing individuals settle in an area with similar habitat characteristics. This process, defined as ‘natal habitat-biased dispersal’ (NHBD), has been used to explain distribution patterns in large carnivores, but actual studies evaluating it are rare. We tested whether grey wolf
Canis lupus
territory establishment was influenced by the habitat characteristics of the natal territory using the long-term monitoring of the Scandinavian wolf population. We paired the locations of natal and established territories, accounted for available habitats along the dispersing route, and compared their habitat characteristics for 271 wolves during 1998–2012. Wolves with the shortest dispersal distances established in natal-like habitat types more than expected by chance, whereas wolves that dispersed longer distances did not show NHBD. The pattern was consistent for male and female wolves, with females showing more NHBD than males. Chances to detect NHBD increased with the size of habitat defined as available. This highlights the importance of considering the biological characteristics of the studied species when defining habitat availability. Our methodological approach can prove useful to inform conservation and management to identify habitats to be selected by reintroduced or naturally expanding populations.
Density-dependent changes in neophobia and stress-coping styles in the world's oldest farmed fish
Authors: Champneys T. , Castaldo G. , Consuegra S. , Garcia de Leaniz C.
Published: January 2019

Farmed fish are typically reared at densities much higher than those observed in the wild, but to what extent crowding results in abnormal behaviours that can impact welfare and stress coping styles is subject to debate. Neophobia (i.e. fear of the ‘new’) is thought to be adaptive under natural conditions by limiting risks, but it is potentially maladapted in captivity, where there are no predators or novel foods. We reared juvenile Nile tilapia (Oreochromis niloticus) for six weeks at either high (50 g l−1) or low density (14 g l−1), assessed the extent of skin and eye darkening (two proxies of chronic stress), and exposed them to a novel object in an open test arena, with and without cover, to assess the effects of density on neophobia and stress coping styles. Fish reared at high density were darker, more neophobic, less aggressive, less mobile and less likely to take risks than those reared at low density, and these effects were exacerbated when no cover was available. Thus, the reactive coping style shown by fish at high density was very different from the proactive coping style shown by fish at low density. Our findings provide novel insights into the plasticity of fish behaviour and the effects of aquaculture intensification on one of the world's oldest farmed and most invasive fish, and highlight the importance of considering context. Crowding could have a positive effect on the welfare of tilapia by reducing aggressive behaviour, but it can also make fish chronically stressed and more fearful, which could make them less invasive.
Ratiometric analysis using Raman spectroscopy as a powerful predictor of structural properties of fatty acids
Authors: Jamieson Lauren E. , Li Angela , Faulds Karen , Graham Duncan
Published: January 2019

Raman spectroscopy has been used extensively for the analysis of biological samplesin vitro,ex vivoandin vivo. While important progress has been made towards using this analytical technique in clinical applications, there is a limit to how much chemically specific information can be extracted from a spectrum of a biological sample, which consists of multiple overlapping peaks from a large number of species in any particular sample. In an attempt to elucidate more specific information regarding individual biochemical species, as opposed to very broad assignments by species class, we propose a bottom-up approach beginning with a detailed analysis of pure biochemical components. Here, we demonstrate a simple ratiometric approach applied to fatty acids, a subsection of the lipid class, to allow the key structural features, in particular degree of saturation and chain length, to be predicted. This is proposed as a starting point for allowing more chemically and species-specific information to be elucidated from the highly multiplexed spectrum of multiple overlapping signals found in a real biological sample. The power of simple ratiometric analysis is also demonstrated by comparing the prediction of degree of unsaturation in food oil samples using ratiometric and multivariate analysis techniques which could be used for food oil authentication.
High quality statistical shape modelling of the human nasal cavity and applications
Authors: Keustermans William , Huysmans Toon , Danckaers Femke , Zarowski Andrzej , Schmelzer Bert , Sijbers Jan , Dirckx Joris J. J.
Published: January 2019

The human nose is a complex organ that shows large morphological variations and has many important functions. However, the relation between shape and function is not yet fully understood. In this work, we present a high quality statistical shape model of the human nose based on clinical CT data of 46 patients. A technique based on cylindrical parametrization was used to create a correspondence between the nasal shapes of the population. Applying principal component analysis on these corresponded nasal cavities resulted in an average nasal geometry and geometrical variations, known as principal components, present in the population with a high precision. The analysis led to 46 principal components, which account for 95% of the total geometrical variation captured. These variations are first discussed qualitatively, and the effect on the average nasal shape of the first five principal components is visualized. Hereafter, by using this statistical shape model, two application examples that lead to quantitative data are shown: nasal shape in function of age and gender, and a morphometric analysis of different anatomical regions. Shape models, as the one presented here, can help to get a better understanding of nasal shape and variation, and their relationship with demographic data.
Accelerated and natural carbonation of concrete with high volumes of fly ash: chemical, mineralogical and microstructural effects
Authors: Van den Heede Philip , De Schepper Mieke , De Belie Nele
Published: January 2019

Today, a rather poor carbonation resistance is being reported for high-volume fly ash (HVFA) binder systems. This conclusion is usually drawn from accelerated carbonation experiments conducted at CO
2
levels that highly exceed the natural atmospheric CO
2
concentration of 0.03–0.04%. However, such accelerated test conditions may change the chemistry of the carbonation reaction (and the resulting amount of CH and C–S–H carbonation), the nature of the mineralogical phases formed (stable calcite versus metastable vaterite, aragonite) and the resulting porosity and pore size distribution of the microstructure after carbonation. In this paper, these phenomena were studied on HVFA and fly ash + silica fume (FA + SF) pastes after exposure to 0.03–0.04%, 1% and 10% CO
2
using thermogravimetric analysis, quantitative X-ray diffraction and mercury intrusion porosimetry. It was found that none of these techniques unambiguously revealed the reason for significantly underestimating carbonation rates at 1% CO
2
from colorimetric carbonation test results obtained after exposure to 10% CO
2
that were implemented in a conversion formula that solely accounts for the differences in CO
2
concentration. Possibly, excess water production due to carbonation at too high CO
2
levels with a pore blocking effect and a diminished solubility for CO
2
plays an important role in this.
Guided electromagnetic waves for periodic arrays of thin metallic wires near an interface between two dielectric media
Authors: Zalipaev V. V. , Kosulnikov S. Yu.
Published: January 2019

Guided localized electromagnetic waves propagating along one-dimensional (1D) arrays of thin metallic parallel wires, finite and infinite, are studied. The arrays are embedded into the upper dielectric half-space close to the interface separating it from the lower dielectric medium with different permittivity and the same permeability. Firstly, a dependence of resonance frequencies of excited wave modes for finite array with respect to the array height above the interface is studied. The array is excited by a normally incident plane wave. It is important that the order of the resonance modes changes if the distance between the array and the interface becomes small. An analysis, based on the Pocklington system of integral equations to evaluate resonance frequencies and compute the fields of excited modes above the array, was applied. This approach is based on the longwave approximation of thin wires. Secondly, the waves propagating along infinite 1D array of thin metallic wires that is close to the interface are studied. Dispersion curves are presented for the lowest case of half-wave resonance for different heights of the array over the interface. When the array approaches very close to the interface an anomalous dispersion is observed. The results of the numerical analysis were tested against computations obtained by means of other independent CST Studio Suite simulations.
Animal movement drives variation in seed dispersal distance in a plant–animal network
Authors: Rehm E. , Fricke E. , Bender J. , Savidge J. , Rogers H.
Published: January 2019

Frugivores play differing roles in shaping dispersal patterns yet seed dispersal distance is rarely quantified across entire communities. We model seed dispersal distance using gut passage times and bird movement for the majority (39 interactions) of known bird–tree interactions on the island of Saipan to highlight differences in seed dispersal distances provided by the five avian frugivores. One bird species was found to be a seed predator rather than a disperser. The remaining four avian species dispersed seeds but differences in seed dispersal distance were largely driven by interspecific variation in bird movement rather than intraspecific variation in gut passage times. The median dispersal distance was at least 56 m for all species-specific combinations, indicating all species play a role in reducing high seed mortality under the parent tree. However, one species—the Micronesian Starling—performed 94% of dispersal events greater than 500 m, suggesting this species could be a key driver of long-distance dispersal services (e.g. linking populations, colonizing new areas). Assessing variation in dispersal patterns across this network highlights key sources of variation in seed dispersal distances and suggests which empirical approaches are sufficient for modelling how seed dispersal mutualisms affect populations and communities.
The demography of a resource specialist in the tropics:
Cecropia
trees and the fitness of three-toed sloths
Authors: Garcés-Restrepo Mario F. , Peery M. Zachariah , Pauli Jonathan N.
Published: January 2019

Resource specialists persist in a narrow range of resources. Consequently, the abundance of key resources should drive vital rates, individual fitness, and population viability. While Neotropical forests feature both high levels of biodiversity and numbers of specialist species, no studies have directly evaluated how the variation of key resources affects the fitness of a tropical specialist. Here, we quantified the effect of key tree species density and forest cover on the fitness of three-toed sloths (
Bradypus variegatus
), an arboreal folivore strongly associated with
Cecropia
trees in Costa Rica, using a multi-year demographic, genetic, and space-use dataset. We found that the density of
Cecropia
trees was strongly and positively related to both adult survival and reproductive output. A matrix model parametrized with
Cecropia
–demography relationships suggested positive growth of sloth populations, even at low densities of
Cecropia
(0.7 trees ha
−1
). Our study shows the first direct link between the density of a key resource to demographic consequences of a tropical specialist, underscoring the sensitivity of tropical specialists to the loss of a single key resource, but also point to targeted conservation measures to increase that resource. Finally, our study reveals that previously disturbed and regenerating environments can support viable populations of tropical specialists.
Toxins or medicines? Phytoplankton diets mediate host and parasite fitness in a freshwater system
Authors: Sánchez Kristel F. , Huntley Naomi , Duffy Meghan A. , Hunter Mark D.
Published: January 2019

Diets must satisfy the everyday metabolic requirements of organisms and can also serve as medicines to combat disease. Currently, the medicinal role of diets is much better understood in terrestrial than in aquatic ecosystems. This is surprising because phytoplankton species synthesize secondary metabolites with known antimicrobial properties. Here, we investigated the medicinal properties of phytoplankton (including toxin-producing cyanobacteria) against parasites of the dominant freshwater herbivore,
Daphnia.
We fed
Daphnia dentifera
on green algae and toxic cyanobacteria diets known to vary in their nutritional quality and toxin production, and an additional diet of
Microcystis
with added pure microcystin-LR. We then exposed
Daphnia
to fungal and bacterial parasites.
Anabaena
,
Microcystis
and
Chlorella
diets prevented infection of
Daphnia
by the fungal parasite
Metschnikowia
, while
Nodularia
toxins increased offspring production by infected hosts. In contrast to their medicinal effects against
Metschnikowia
, toxic phytoplankton generally decreased the fitness of
Daphnia
infected with the bacterial parasite,
Pasteuria
. We also measured the amount of toxin produced by phytoplankton over time. Concentrations of anatoxin-a produced by
Anabaena
increased in the presence of
Metschnikowia
, suggesting parasite-induced toxin production. Our research illustrates that phytoplankton can serve as toxins or medicines for their consumers, depending upon the identity of their parasites.
Burgess Shale fossils shed light on the agnostid problem
Authors: Moysiuk J. , Caron J.-B.
Published: January 2019

Agnostids (agnostinids and eodiscinids) are a widespread and biostratigraphically important group of Cambro-Ordovician euarthropods whose evolutionary affinities have been highly controversial. Their dumbbell-shaped calcified tergum was traditionally suggested to unite them with trilobites, but agnostinids have alternatively been interpreted as stem-crustaceans, based on Orsten larval material from the Cambrian of Sweden. We describe exceptionally preserved soft tissues from mature individuals of the agnostinidsPeronopsisandPtychagnostusfrom the middle Cambrian (Wuliuan Stage) Burgess Shale (Walcott Quarry and Marble Canyon, British Columbia, Canada), facilitating the testing of alternative hypotheses. The digestive tract includes conspicuous ramifying cephalic diverticulae. The cephalon carries one pair of elongate spinous antennules projecting to the front, two pairs of appendages with distally setose, oar-like exopods, and three pairs of presumably biramous appendages with endopods sporting club-shaped exites. The trunk bears five appendage pairs, at least the first two of which are similar to the posteriormost cephalic pairs. The combined evidence supports a nektobenthic and detritivorous lifestyle for agnostinids. A head with six appendiferous segments contrasts strikingly with the four known in trilobites and five typical of mandibulates. Agnostinids are retrieved as the sister group to polymeroid trilobites in our phylogeny, implying that crustacean-like morphologies evolved homoplastically. This result highlights the variability in segmental composition of the artiopodan head. Finally, our study emphasizes the continued role of Burgess Shale-type fossils in resolving the affinities of problematic biomineralizing taxa.
Phenotypic evolution shaped by current enzyme function in the bioluminescent courtship signals of sea fireflies
Authors: Hensley Nicholai M. , Ellis Emily A. , Gerrish Gretchen A. , Torres Elizabeth , Frawley John P. , Oakley Todd H. , Rivers Trevor J.
Published: January 2019

Mating behaviours are diverse and noteworthy, especially within species radiations where they may contribute to speciation. Studying how differences in mating behaviours arise between species can help us understand how diversity is generated at multiple biological levels. The bioluminescent courtship displays of cypridinid ostracods (or sea fireflies) are an excellent system for this because amazing variety evolves while using a conserved biochemical mechanism. We find that the evolution of one aspect in this behavioural phenotype—the duration of bioluminescent courtship pulses—is shaped by biochemical function. First, by measuring light production from induced bioluminescence in 38 species, we discovered differences between species in their biochemical reactions. Then, for 16 species for which biochemical, phylogenetic and behavioural data are all available, we used phylogenetic comparative models to show that differences in biochemical reaction are nonlinearly correlated with the duration of courtship pulses. This relationship indicates that changes to both enzyme (c-luciferase) function and usage have shaped the evolution of courtship displays, but that they differentially contribute to these phenotypic changes. This nonlinear dynamic may have consequences for the disparity of signalling phenotypes observed across species, and demonstrates how unappreciated diversity at the biochemical level can lead to inferences about behavioural evolution.
Crystal Structure of the putative tail fiber protein gp53 from theAcinetobacter baumanniibacteriophage AP22
Authors: Sycheva Lada V. , Shneider Mikhail M. , Popova Anastasia V. , Ziganshin Rustam H. , Volozhantsev Nikolay V. , Miroshnikov Konstantin A. , Leiman Petr G.
Published: January 2019

This report describes the structure of a putative tail fiber protein of theAcinetobacter baumanniibacteriophage AP22. The target host range of strictly lytic bacteriophage AP22 includes many clinical isolates ofA. baumanniifrom hospitals in Chelyabinsk, Nizhny Novgorod, Moscow and St. Petersburg (Russia), but its host cell binding apparatus remains uncharacterized. Here, we report the crystal structure of the C-terminal fragment of AP22 gene product 53 (gp53) one of its two putative host cell-binding proteins. We show that gp53 forms a trimeric fiber and binds ethylene glycol and glycerol molecules that represent known surrogates of the oligosaccharide backbone. However, despite its structural similarities to other phage/virus host cell-binding fibers and its binding to small sugar-like molecules, gp53 did not inhibit AP22 infection and its role in the infection process remains unclear.
The self as a generative, teleological, and subjective prior: Mutually-modulated temporal agency
Authors: Asai Tomohisa , Imaizumi Shu , Imamizu Hiroshi
Published: January 2019

How can we certify our existence? Recent theoretical studies have suggested that, in the brain, the effect inversely infers the possibility of the existence of the self as the cause. While this Bayesian view of the sense of agency is widely accepted, empirical evidence in support of this theory is still lacking. The current study examined outcome-modulated agency in terms of time perception in seven experiments, with a total of 90 participants. It was hypothesized that perceptual generation, not termination, should subjectively infer the existence of the self, even though both include the same stimuli and are driven by the same teleological action. Results suggest support for the hypothesis (Experiments 1 and 2). Participants judged stronger self-agency, detected less delay, or felt shorter duration for auditory generation, compared with termination, which was driven by the same volitional key-press. Furthermore, the main experiment, Experiment 3, focused on temporal probability distributions both for action and outcome (e.g., standard deviations or relative entropy), and concluded that the observed contrast in onset/offset agency indicates a mutual or bidirectional relationship between cause and effect only during agentive action, characterized by active (i.e., teleological) generation. Finally, the concurrent theoretical models for volitional action-modulated time perception are discussed on the basis of the suggested triplet (generativity, teleology, and subjectivity) dimensions of agency.
Macroevolution of dimensionless life history metrics in tetrapods
Authors: Morrow Cecina Babich , Ernest S. K. Morgan , Kerkhoff Andrew J.
Published: January 2019

Life history traits represent organism’s strategies to navigate the fitness trade-offs between survival and reproduction. Eric Charnov developed three dimensionless metrics to quantify fundamental life history trade-offs. Lifetime reproductive effort (LRE), relative reproductive lifespan (RRL), and relative offspring size (ROS), together with body mass, can be used classify life history strategies across the four major classes of tetrapods: amphibians, reptiles, mammals, and birds. First, we investigate how the metrics have evolved in concert with body mass. In most cases, we find evidence for correlated evolution between body mass and the three metrics. Finally, we compare life history strategies across the four classes of tetrapods and find that LRE, RRL, and ROS delineate a space in which the major tetrapod clades occupy mostly unique subspaces. These distinct combinations of life history strategies provide us with a framework to understand the impact of major evolutionary transitions in energetics, physiology, and ecology.
Alveolar macrophages up-regulate a non-classical innate response toMycobacterium tuberculosisinfectionin vivo
Authors: Rothchild A. C. , Olson G. S. , Nemeth J. , Amon L. M. , Mai D. , Gold E. S. , Diercks A. H. , Aderem A.
Published: January 2019

Alveolar macrophages (AMs) are the first cells to be infected duringMycobacterium tuberculosis(Mtb) infection. Thus the AM response to infection is the first of many steps leading to initiation of the adaptive immune response, which is required for efficient control of infection. A hallmark of Mtb infection is the delay of the adaptive response, yet the mechanisms responsible for this delay are largely unknown. We developed a system to identify, sort and analyze Mtb-infected AMs from the lung within the first 10 days of infection. In contrast to what has been previously described usingin vitrosystems, we find that Mtb-infected AMs up-regulate a cell-protective antioxidant transcriptional signature that is dependent on the lung environment and not dependent on bacterial virulence. Computational approaches including pathway analysis and transcription factor binding motif enrichment analysis identify Nrf2 as a master regulator of the response of AMs to Mtb infection. Using knock-out mouse models, we demonstrate that Nrf2 drives the expression of the cell protective transcriptional program and impairs the ability of the host to control bacterial growth over the first 10 days of infection. Mtb-infected AMs exhibit a highly delayed pro-inflammatory response, and comparisons with uninfected AMs from the same infected animals demonstrate that inflammatory signals in the lung environment are blocked in the Mtb-infected cells. Thus, we have identified a novel lung-specific transcriptional response to Mtb infection that impedes AMs from responding rapidly to intracellular infection and thereby hinders the overall immune response.

One Sentence Summary

In response to Mtb infectionin vivo, alveolar macrophages fail to up-regulate the canonical pro-inflammatory innate response and instead induce an Nrf2-dependent cell protective transcriptional program, which in turn impairs the host’s control of bacterial growth.
JuLI: accurate detection of DNA fusions in clinical sequencing for precision oncology
Authors: Shin Hyun-Tae , Kim Nayoung K. D. , Yun Jae Won , Lee Boram , Kyung Sungkyu , Lee Ki-Wook , Ryu Daeun , Kim Jinho , Bae Joon Seol , Park Donghyun , Choi Yoon-La , Lee Se-Hoon , Ahn Myung-Ju , Park Keunchil , Park Woong-Yang
Published: January 2019

Accurate detection of genomic fusions by high-throughput sequencing in clinical samples with inadequate tumor purity and formalin-fixed paraffin embedded (FFPE) tissue is an essential task in precise oncology. We developed the fusion detection algorithm Junction Location Identifier (JuLI) for optimization of high-depth clinical sequencing. We implemented novel filtering steps to minimize false positives and a joint calling function to increase sensitivity in clinical setting. We comprehensively validated the algorithm using high-depth sequencing data from cancer cell lines and clinical samples and whole genome sequencing data from NA12878. We showed that JuLI outperformed state-of-the-art fusion callers in cases with high-depth clinical sequencing and rescued a driver fusion from false negative in plasma cell-free DNA. JuLI is freely available via GitHub (https://github.com/sgilab/JuLI).
Distinguishing biological from technical sources of variation by leveraging multiple methylation datasets
Authors: Thompson Mike , Chen Zeyuan Johnson , Rahmani Elior , Halperin Eran
Published: January 2019

DNA methylation remains one of the most widely studied epigenetic markers. One of the major challenges in population studies of methylation is the presence of global methylation effects that may mask local signals. Such global effects may be due to either technical effects (e.g., batch effects) or biological effects (e.g., cell-type composition, genetics). Many methods have been developed for the detection of such global effects, typically in the context of epigenome-wide association studies. However, current unsupervised methods do not distinguish between biological and technical effects, resulting in a loss of highly relevant information. Though supervised methods can be used to estimate known biological effects, it remains difficult to identify and estimate unknown biological effects that globally affect the methylome. Here, we proposeCONFINED,a reference-free method based on sparse canonical correlation analysis that captures replicable sources of variation—such as age, sex, and cell-type composition—across multiple methylation datasets and distinguishes them from dataset-specific sources of variability (e.g., technical effects). Consequently, we demonstrate through simulated and real data that by leveraging multiple datasets simultaneously, our approach captures several replicable sources of biological variation better than previous reference-free methods and is considerably more robust to technical noise than previous reference-free methods.CONFINEDis available as an R package as detailed athttps://github.com/cozygene/CONFINED.
Investigation of the transcriptional profile of human kidneys during machine perfusion reveals potential benefits of haemoadsorption
Authors: Ferdinand John R. , Hosgood Sarah A. , Moore Tom , Ward Christopher J. , Castro-Dopico Tomas , Nicholson Michael L. , Clatworthy Menna R.
Published: January 2019

Transplantation is the optimal treatment for most patients with end stage kidney disease but organ shortage is a major challenge. Normothermic machine perfusion (NMP) has been used to re-condition marginal organs but the mechanisms by which NMP might benefit transplant kidneys are not fully understood. Furthermore, the question of whether removal of pro-inflammatory mediators from the perfusate might offer additional benefits in optimising kidneys prior to transplantation has not been addressed. Using pairs of human kidneys obtained from the same donor, we compared the effect of NMP with that of cold storage on the global transcriptome of kidneys, and then went on to investigate the impact of adding a haemoadsorption device to the NMP circuit. We found that cold storage significantly reduced the expression of inflammatory genes, but also of genes required for energy generation such as those encoding oxidative phosphorylation (OXPHOS) enzymes. In contrast, during NMP, there was marked upregulation OXPHOS genes, as well as a number of immune and inflammatory pathway genes. The induction of inflammatory genes during NMP was substantially attenuated by the addition of a haemoadsorber to the perfusion circuit, which also further increased OXPHOS pathway gene expression. Together, our data suggest that absorption of pro-inflammatory mediators from the perfusate represents a useful intervention that may further improve organ viability and should be tested in clinical practice.

Single sentence summary: The use of a haemoadsorber during machine perfusion reduces inflammatory gene expression, with potential benefits for kidney transplantation.
Rapid microbial interaction network inference in microfluidic droplets
Authors: Hsu Ryan H. , Clark Ryan L. , Tan Jin Wen , Romero Philip A. , Venturelli Ophelia S.
Published: January 2019

Microbial interactions are major drivers of microbial community dynamics and functions. However, microbial interactions are challenging to decipher due to limitations in parallel culturing of sub-communities across many environments and accurate absolute abundance quantification of constituent members of the consortium. To this end, we developed Microbial Interaction Network Inference in microdroplets (MINI-Drop), a high-throughput method to rapidly infer microbial interactions in microbial consortia in microfluidic droplets. Fluorescence microscopy coupled to automated computational droplet and cell detection was used to rapidly determine the absolute abundance of each strain in hundreds to thousands of droplets per experiment. We show that MINI-Drop can accurately infer pairwise as well as higher-order interactions using a microbial interaction toolbox of defined microbial interactions mediated by distinct molecular mechanisms. MINI-Drop was used to investigate how the molecular composition of the environment alters the interaction network of a three-member consortium. To provide insight into the variation in community states across droplets, we developed a probabilistic model of cell growth modified by microbial interactions. In sum, we demonstrate a robust and generalizable method to probe cellular interaction networks by random encapsulation of sub-communities into microfluidic droplets.
PIK3CA inKrasG12D/Trp53R172HTumor Cells Promotes Immune Evasion by Limiting Infiltration of T Cells in a Model of Pancreatic Cancer
Authors: Sivaram Nithya , McLaughlin Patrick A. , Han Han V. , Petrenko Oleksi , Jiang Ya-Ping , Ballou Lisa M. , Pham Kien , Liu Chen , Velden Adrianus W.M. van der , Lin Richard Z.
Published: January 2019

The presence of tumor-infiltrating T cells is associated with favorable patient outcomes, yet most pancreatic cancers are immunologically silent and resistant to currently available immunotherapies. Here we show using a syngeneic orthotopic implantation model of pancreatic cancer thatPik3caregulates tumor immunogenicity. Genetic silencing ofPik3cainKrasG12D/Trp53R172H-driven pancreatic tumors leads to infiltration of T cells, complete tumor regression, and 100% survival of immunocompetent host mice. By contrast,Pik3ca-null tumors implanted in T cell-deficient mice progress and kill all of the animals. Adoptive transfer of tumor antigen-experienced T cells eliminatesPik3ca-null tumors in immunodeficient mice. Loss of PIK3CA or inhibition of its effector, AKT, increases the expression of MHC Class I and CD80 on tumor cells. These changes contribute to the increased susceptibility ofPik3ca-null tumors to T cell surveillance. These results indicate that tumor cell PIK3CA-AKT signaling limits T cell recognition and clearance of pancreatic cancer cells. Strategies that target this pathway may yield an effective immunotherapy for this cancer.

SIGNIFICANCE

PIK3CA-AKT signaling in pancreatic cancer cells limits T cell infiltration and clearance of tumors by suppressing the surface expression of MHC Class I and CD80. Targeting the PIK3CA-AKT pathway in tumor cells provides a new avenue for discovery of novel pancreatic cancer immunotherapies.
Efficient variance components analysis across millions of genomes
Authors: Pazokitoroudi Ali , Wu Yue , Burch Kathryn S. , Hou Kangcheng , Zhou Aaron , Pasaniuc Bogdan , Sankararaman Sriram
Published: January 2019

Variance components analysis has emerged as a powerful tool in complex trait genetics, with applications ranging from heritability estimation to association mapping. While the application of these methods to large-scale genetic datasets can potentially reveal important insights into genetic architecture, existing methods for fitting variance components do not scale well to these datasets. Here, we present a new algorithm for variance components analysis that is accurate and highly efficient, capable of estimating one hundred variance components on a million individuals genotyped at a million SNPs in a few hours. We illustrate the utility of our method in estimating variation in a trait explained by genotyped SNPs (SNP heritability) as well in partitioning heritability across population and functional genomic annotations. Analyzing 22 diverse traits with genotypes from 300, 000 individuals across about 8 million common and low frequency SNPs (minor allele frequency > 0.1%), we observe that the allelic effect size increases with decreasing MAF (minor allele frequency) and LD (linkage disequilibrium) across the analyzed traits consistent with the action of negative selection. Partitioning heritability across 28 functional annotations, we observe enrichment of heritability in FANTOM5 enhancers in asthma, eczema, thyroid and autoimmune disorders.
Stochastic modelling reveals mechanisms of metabolic heterogeneity
Authors: Tonn Mona K. , Thomas Philipp , Barahona Mauricio , Oyarzún Diego A.
Published: January 2019

Phenotypic variation is a hallmark of cellular physiology. Metabolic heterogeneity, in particular, underpins single-cell phenomena such as microbial drug tolerance and growth variability. Much research has focussed on transcriptomic and proteomic heterogeneity, yet it remains unclear if such variation permeates to the metabolic state of a cell. Here we propose a stochastic model to show that complex forms of metabolic heterogeneity emerge from fluctuations in enzyme expression and catalysis. The analysis predicts clonal populations to split into two or more metabolically distinct subpopulations. We reveal mechanisms not seen in deterministic models, in which enzymes with unimodal expression distributions lead to metabolites with a bimodal or multimodal distribution across the population. Based on published data, the results suggest that metabolite heterogeneity may be more pervasive than previously thought. Our work casts light on links between gene expression and metabolism, and provides a theory to probe the sources of metabolite heterogeneity.
The neural mechanism of fluency-based memory illusions: the role of fluency context
Authors: Gomes Carlos Alexandre , Mecklinger Axel , Zimmer Hubert
Published: January 2019

Recognition memory judgments can be influenced by a variety of signals including fluency. Here, we investigated whether the neural correlates of memory illusions (i.e., misattribution of fluency to prior study) can be modulated by fluency context. Using a masked priming/recognition memory paradigm, we found memory illusions for low confidence decisions. When fluency varied randomly across trials, we found reductions in perirhinal cortex (PrC) activity for primed trials, as well as a (pre)cuneus-PrC (BA 35) connectivity. When the fluency context was unchanging, there was increased PrC activity for primed trials, with the (pre)cuneus showing greater connectivity with PrC (BA 36). Thus, our results tentatively suggest two neural mechanisms via which fluency can lead to memory illusions.
Digital platforms in Russia: competition between national and foreign multi-sided platforms stimulates growth and innovation
Authors: Eferin Yaroslav , Hohlov Yuri , Rossotto Carlo
Published: January 2019

Purpose

This paper aims to test the “winner-takes-all” vs the “winner-takes-some” scenarios in digital platform competition dynamics in emerging markets.

Design/methodology/approach

This paper uses an analytical reference framework to assess the emergence of digital platforms in Russia, including four elements: definition of multi-sided platforms (MSPs), platform enablers, business models and competitive dynamics.

Findings

This paper concludes that Russia shows that a healthy competition between national and foreign MSPs led to the emergence of a shared equilibrium, where local platforms were able to retain a significant, often majority, share vis-à-vis foreign and global platforms.

Research limitations/implications

This paper stands as a counterpoint to the widespread conviction that digital platform dynamics will result into a “winner-takes-all” scenario and dominance of global platforms.

Practical implications

This case study offers practical data and analysis that can be used to create a baseline and evaluate the dynamics of digital platforms in emerging markets. It offers data, trends and evidence on Russia’s digital economy.

Social implications

This research provides a logical framework to help policymakers take decisions on a policy framework to regulate platforms in emerging markets. The good outcome of competition between local and foreign platforms should emerge as a policy objective to achieve in most emerging markets.

Originality/value

This case study is the first baseline to assess the dynamics of competition between national and foreign digital platforms in the Russian market. It is one of the first papers to tackle the market of digital platforms in an emerging and developing economy. It tries to address the debate between “winner-takes-all” and “winner-takes some” competition equilibrium through a concrete case study in an important G20 emerging market economy.
The whirlpool algorithm based on physical phenomenon for solving optimization problems
Authors: Zou Yuanyang
Published: January 2019

Purpose

This paper aims to propose a novel nature-inspired optimization algorithm, called whirlpool algorithm (WA), which imitates the physical phenomenon of whirlpool.

Design/methodology/approach

The idea of this algorithm stems from the fact that the whirlpool has a descent direction and a vertex.

Findings

WA is tested with two types of models: 29 typical mathematical optimization models and three engineering problems (tension/compression spring design, welded-beam design, pressure vessel design).

Originality/value

The results shown that the WA is vying compared to the state-of-art algorithms likewise conservative approaches.
Specific HR practices and employee commitment: the mediating role of job satisfaction
Authors: Mahmood Arshad , Akhtar Muhammad Naseer , Talat Usman , Shuai Chuanmin , Hyatt James C.
Published: January 2019

Purpose

The purpose of this paper is to increase understanding of the influence mechanisms of specific HR practices variables – salary, job stability and job enrichment – upon employee commitment, through the mediating role of job satisfaction, in a developing country context. Crucially, these indicate employee commitment.

Design/methodology/approach

The study analyzed three specific HR practices with a sample of 263 employees in the banking industry of Pakistan. A structural equation modeling methodology is adopted.

Findings

The findings indicate that remuneration strategies were positively related to job satisfaction and employee commitment. Regarding the intervening impact of job satisfaction, this study found that it mediates only for non-monetary strategies between job satisfaction and employee commitment.

Research limitations/implications

A key limitation is that this is a cross-sectional study, perhaps not generalizable over longitudinal approaches. Another limit is posed by the developing country context of this study, perhaps not applicable to some developed countries.

Practical implications

From an HR perspective, managing salary structure is an ongoing issue. The proposed model suggests the use of specific practices about satisfaction and commitment as intermediate steps to manage employee commitment.

Originality/value

The research offers a unique understanding from the developing country context of Pakistan. This provides a novel study conducted to examine employee commitment using the high-performance work practices model.