bluuebunny/crossref_metadata_2025 huggingface dataset:
Megafauna decline have reduced pathogen dispersal which may have increased emergent infectious diseases
Authors: Doughty Christopher E. , Prys-Jones Tomos , Faurby Søren , Abraham Andrew , Hepp Crystal , Leshyk Victor , Fofanov Viacheslav Y. , Nieto Nathan C. , Svenning Jens-Christian , Galetti Mauro
Published: January 2020

The Late Quaternary extinctions of megafauna (defined as animal species >44.5 kg) reduced the dispersal of seeds and nutrients, and likely also microbes and parasites. Here we use body-mass based scaling and range maps for extinct and extant mammal species to show that these extinctions led to an almost seven-fold reduction in the movement of gut-transported microbes, such asEscherichia coli(3.3 km2/day to 0.5 km2/day). Similarly, the extinctions led to a seven-fold reduction in the mean home ranges of vector-borne pathogens (7.8 km2to 1.1 km2). To understand the impact of this, we created an individual-based model where an order of magnitude decrease in home range increased maximum aggregated microbial mutations 4-fold after 20,000 years. We hypothesize that pathogen speciation and hence endemism increased with isolation, as global dispersal distances decreased through a mechanism similar to the theory of island biogeography. To investigate if such an effect could be found, we analysed where 145 zoonotic diseases have emerged in human populations and found quantitative estimates of reduced dispersal of ectoparasites and fecal pathogens significantly improved our ability to predict the locations of outbreaks (increasing variance explained by 8%). There are limitations to this analysis which we discuss in detail, but if further studies support these results, they broadly suggest that reduced pathogen dispersal following megafauna extinctions may have increased the emergence of zoonotic pathogens moving into human populations.
Candida albicans exhibits distinct cytoprotective responses to anti-fungal drugs that facilitate the evolution of drug resistance
Authors: Bettauer V , Massahi S , Khurdia S , Costa ACBP , Omran RP , Khosravi N , Simpson S , Harb M , Dumeaux V , Whiteway M , Hallett MT
Published: January 2020

We developed a modified protocol for nanolitre droplet-based single cell sequencing appropriate for fungal settings, and used it to transcriptionally profiled several thousands cells from a prototrophicCandida albicanspopulation and several drug exposed colonies (incl. fluconazole, caspofungin and nystatin). Thousands of cells from each colony were profiled both at early and late time points post-treatment in order to infer survival trajectories from initial drug tolerance to drug resistance. We find that prototrophicC. albicanspopulations differentially and stochastically express cytoprotective epigenetic programs. For all drugs, there is evidence that tolerant individuals partition into distinct subpopulations, each with a unique survival strategy involving different regulatory programs. These responses are weakly related to changes in morphology (shift from white to opaque forms, or shift from yeast to filamentous forms). In turn, those subpopulations that successfully reach resistance each have a distinct multivariate epigenetic response that coordinates the expression of efflux pumps, chaperones, transport mechanisms, and cell wall maintenance. Live cell fluorescent imaging was used to validate predictions of which molecular responses most often led to survival after drug exposure. Together our findings provide evidence thatC. albicanshas a robust toolkit of short-term epigenetic cytoprotective responses designed to “buy time” and increase the chance of acquiring long-term resistance.
Remodeling of pre-existing myelinated axons and oligodendrocyte differentiation is stimulated by environmental enrichment in the young adult brain
Authors: Nicholson Madeline , Wood Rhiannon J , Fletcher Jessica L , Gonsalvez David G , Hannan Anthony J , Murray Simon S , Xiao Junhua
Published: January 2020

Oligodendrocyte production and central nervous system (CNS) myelination is a protracted process, extending into adulthood. While stimulation of neuronal circuits has been shown to enhance oligodendrocyte production and myelination during development, the extent to which physiological stimuli induces activity-dependent plasticity within oligodendrocytes and myelin is unclear, particularly in the adult CNS. Here, we find that using environmental enrichment (EE) to physiologically stimulate neuronal activity for 6-weeks during young adulthood in C57Bl/6 mice results in an enlargement of callosal axon diameters, with a corresponding increase in thickness of pre-existing myelin sheaths. Additionally, EE uniformly promotes the direct differentiation of pre-existing oligodendroglia in both corpus callosum and somatosensory cortex, while differentially impeding OPC homeostasis in these regions. Furthermore, results of this study indicate that physiologically relevant stimulation in young adulthood exerts little influence upon thede novogeneration of new myelin sheaths on previously unmyelinated segments and does not enhance OPC proliferation. Rather in this context, activity-dependent plasticity involves the coincident structural remodeling of axons and pre-existing myelin sheaths and increases the direct differentiation of pre-existing oligodendroglia, implying constraints on maximalde novoproduction in the adult CNS. Together, our findings of myelinated axon remodeling and increased pre-existing oligodendroglial differentiation constitute a previously undescribed form of adaptive myelination that likely contributes to neuronal circuit maturation and the maintenance of optimum cognitive function in the young adult CNS.

Main points

Environmental enrichment induces the plasticity of myelinated axons, resulting in axon caliber enlargement and increased thickness of pre-existing myelin sheaths

Environmental enrichment increases the direct differentiation of pre-existing oligodendroglia

Environmental enrichment alters OPC homeostasis
Moderate episodic prenatal alcohol does not impact female offspring fertility in rats
Authors: McReight Elizabeth K , Liew Seng H , Steane Sarah E , Hutt Karla J , Moritz Karen M , Akison Lisa K
Published: January 2020

Prenatal alcohol exposure (PAE) has been associated with reproductive dysfunction in offspring. However, studies in females, particularly examining long-term infertility or impacts on ovarian reserve, are lacking. The current study utilised a moderate, episodic exposure model in rats to mimic ‘special occasion’ drinking, which is reported to be common during pregnancy. Our objective was to examine the consequences of this prenatal alcohol exposure on reproductive parameters in female offspring. Pregnant Sprague Dawley rats were treated with either an ethanol gavage (1g EtOH/kg body weight), or an equivalent volume of saline, on embryonic days 13.5 and 14.5 of pregnancy, resulting in a peak blood alcohol concentration of ∼0.04%. Neonatal female offspring were examined for molecular markers regulating early follicle numbers in the ovary and unbiased stereology used to quantify primordial and early growing follicle numbers. Puberty onset (age at vaginal opening and first estrous) was measured post-weaning and estrous cycles, reproductive hormones (progesterone and estradiol) and pregnancy success measured in adults (5-6 months of age). We found no evidence that any of these reproductive parameters were significantly altered by PAE in this model. This animal study provides some reassurance for women who may have consumed a small amount of alcohol during their pregnancy. However, previously published effects on offspring metabolism using this model reinforce avoidance of alcohol during pregnancy.
Structural insight into tanapoxvirus mediated inhibition of apoptosis
Authors: Suraweera Chathura D. , Anasir Mohd Ishtiaq , Chugh Srishti , Javorsky Airah , Impey Rachael E. , Zadeh Mohammad Hasan , Soares da Costa Tatiana P. , Hinds Mark G. , Kvansakul Marc
Published: January 2020

Premature programmed cell death or apoptosis of cells is a strategy utilized by multicellular organisms to counter microbial threats. Tanapoxvirus (TANV) is a large double-stranded DNA virus belonging to thepoxviridaethat causes mild Monkeypox-like infections in humans and primates. TANV encodes for a putative apoptosis inhibitory protein 16L. We show that TANV16L is able to bind to a range of peptides spanning the BH3 motif of human pro-apoptotic Bcl-2 proteins, and is able to counter growth arrest of yeast induced by human Bak and Bax. We then determined the crystal structures of TANV16L bound to three identified interactors, Bax, Bim and Puma BH3. TANV16L adopts a globular Bcl-2 fold comprising 7 α-helices, and utilizes the canonical Bcl-2 binding groove to engage pro-apoptotic host cell Bcl-2 proteins. Unexpectedly, TANV16L is able to adopt both a monomeric as well as a domain-swapped dimeric topology where the α1 helix from one protomer is swapped into a neighbouring unit. Despite adopting two different oligomeric forms, the canonical ligand binding groove in TANV16L remains unchanged from monomer to domain-swapped dimer. Our results provide a structural and mechanistic basis for tanapoxvirus mediated inhibition of host cell apoptosis, and reveal the capacity of Bcl-2 proteins to adopt differential oligomeric states whilst maintaining the canonical ligand binding groove in an unchanged state.
A reference single-cell transcriptomic atlas of human skeletal muscle tissue reveals bifurcated muscle stem cell populations
Authors: De Micheli Andrea J. , Spector Jason A. , Elemento Olivier , Cosgrove Benjamin D.
Published: January 2020

Abstract

Single-cell RNA-sequencing (scRNA-seq) facilitates the unbiased reconstruction of multicellular tissue systems in health and disease. Here, we present a curated scRNA-seq dataset of human muscle samples from 10 adult donors with diverse anatomical locations. We integrated ∼22,000 single-cell transcriptomes using Scanorama to account for technical and biological variation and resolved 16 distinct populations of muscle-resident cells using unsupervised clustering of the data compendium. These cell populations included muscle stem/progenitor cells (MuSCs), which bifurcated into discrete “quiescent” and “early-activated” MuSC subpopulations. Differential expression analysis identified transcriptional profiles altered in the activated MuSCs including genes associated with ageing, obesity, diabetes, and impaired muscle regeneration, as well as long non-coding RNAs previously undescribed in human myogenic cells. Further, we modeled ligand-receptor cell-communication interactions and observed enrichment of the TWEAK-FN14 pathway in activated MuSCs, a characteristic signature of muscle wasting diseases. In contrast, the quiescent MuSCs have enhanced expression of theEGFRreceptor, a recognized human MuSC marker. This work provides a new technical resource to examine human muscle tissue heterogeneity and identify potential targets in MuSC diversity and dysregulation in disease contexts.
Evidence of Absence Regression: A Binomial N-Mixture Model for Estimating Fatalities at Wind Energy Facilities
Authors: McDonald Trent , Bay Kimberly , Studyvin Jared , Leckband Jesse , Schorg Amber , McIvor Jennifer
Published: January 2020

Estimating bird and bat fatalities caused by wind-turbine facilities is challenging when carcass counts are rare and produce counts that are either exactly zero or very near zero. The rarity of found carcasses is exacerbated when live members of a particular species are rare and when carcasses degrade quickly, are removed by scavengers, or are not detected by observers. With few observed carcass counts, common statistical methods like logistic, Poisson, or negative binomial regression are unreliable (statistically biased) and often fail to provide answers (i.e., fail to converge). Here, we propose a binomial N-mixture model that estimates fatality rates as well as the total number of carcass counts when these rates are expanded. Our model extends the ‘evidence of absence’ model (Huso et al., 2015; Dalthorp, Huso, and Dail, 2017) by relating carcass deposition rates to study covariates and by incorporating terms that naturally scale counts from facilities of different sizes. Our model, which we call Evidence of Absence Regression (EoAR), can estimate the total number of birds or bats killed at a single wind energy facility or a fleet of wind energy facilities based on covariate values. Furthermore, with accurate prior distributions the model’s results are extremely robust to sparse data and unobserved combinations of covariate values. In this paper, we describe the model, show its low bias and high precision via computer simulation, and apply it to bat carcass counts observed at 21 wind energy facilities in Iowa.
Modelling the Putative Ancient Distribution of the Coastal Rock Pool MosquitoAedes togoi
Authors: Peach Daniel AH , Matthews Benjamin J
Published: January 2020

The coastal rock pool mosquito,Aedes togoi, is found in coastal east Asia in climates ranging from subtropical to subarctic. However, a disjunct population in the Pacific Northwest of North America has an ambiguous heritage. Two potential models explain the presence ofAe. togoiin North America: ancient Beringian dispersal or modern anthropogenic introduction. Genetic studies have thus far proved inconclusive. Here we described the putative ancient distribution ofAe. togoihabitat in east Asia and examined the climatic feasibility of a Beringian introduction into North America using modern distribution records and ecological niche modeling of bioclimatic data from the last interglacial period (~120,000 BP), the last glacial maximum (~21,000 BP), and the mid-Holocene (~6000 BP). Our results suggest that suitable climatic conditions existed forAe. togoito arrive in North America through natural dispersal as well as to persist there until present times. Furthermore, we find that ancient distributions of suitableAe. togoihabitat in east Asia may explain the genetic relationships betweenAe. togoipopulations identified in other studies. These findings indicate the utility of ecological niche modeling as a complementary tool for studying insect phylogeography.
Use of high-refractive index hydrogels and tissue clearing for large biological sample imaging
Authors: Richardson Alexander , Fok Sandra , Lee Victoria , Rye Kerry-Anne , Di Girolamo Nick , Cochran Blake J.
Published: January 2020

Recent advances in tissue clearing and light sheet fluorescence microscopy have improved insights into and understanding of tissue morphology and disease pathology by imaging large samples without the requirement of histological sectioning. However, sample handling and conservation of sample integrity during lengthy staining and acquisition protocols remains a challenge. This study overcomes these challenges with acrylamide hydrogels synthesised to match the refractive index of solutions typically utilised in aqueous tissue clearing protocols. These hydrogels have a high-water content (82.0±3.7% by weight). The gels are stable over time and FITC-IgG readily permeated into, and effluxed out of them. Whilst the gels deformed and/or swelled over time in some commonly used solutions, this was overcome by using a previously described custom refractive index matched solution. To validate their use, CUBIC cleared mouse tissues and whole embryos were embedded in hydrogels, stained using fluorescent small molecule dyes, labels and antibodies and successfully imaged using light sheet fluorescence microscopy. In conclusion, the high-water content, high refractive index hydrogels described in this study have a broad applicability to research that delves into pathophysiological processes by stabilising and protecting large and fragile samples.
Independent evolution of transcript abundance and gene regulatory dynamics
Authors: Krieger Gat , Lupo Offir , Levy Avraham A. , Barkai Naama
Published: January 2020

Changes in gene expression drive novel phenotypes, raising interest in how gene expression evolves. In contrast to the static genome, cells regulate gene expression to accommodate changing conditions. Previous comparative studies focused on specific conditions, describing inter-species variation in expression levels, but providing limited information about variations in gene regulation. To close this gap, we profiled gene expression of related yeast species in hundreds of conditions, and used co-expression analysis to distinguish variations in transcription regulation from variations in expression levels or environmental perception. The majority of genes whose expression varied between the species maintained a conserved transcriptional regulation. Profiling the interspecific hybrid provided insights into the basis of variations, showed thattrans-varying alleles interact dominantly, and revealed complementation ofcis-variations by variations intrans. Our data suggests that gene expression diverges primarily through changes in promoter strength that do not alter gene positioning within the transcription network.
APPLICATION OF PETRI NETS METHODOLOGY FOR THE EXAMINATION OF THE BIO(PHYSICO)CHEMICAL PARAMETERS OF MITOCHONDRIA FUNCTIONING
Authors: Danylovych Hanna V. , Chunikhin Alexander Yu. , Danylovych Yuriy V. , Kosterin Sergiy O.
Published: January 2020

A mathematical model is developed using Petri net methodology that is able to predict simultaneous changes in bio(physical)chemical parameters of mitochondria, namely hydrodynamic diameter, fluorescence of NADH, DCF fluorescence signal depending on the time of action and concentration of sodium azide and predict these changes for unknown NaN3concentration. The model is created for real experimental conditions, it combines functional changes of mitochondria with a structural representation of learned processes.
Lipid accumulation promotes scission of caveolae
Authors: Hubert Madlen , Larsson Elin , Gayathri Vegesna Naga Venkata , Ahnlund Maria , Johansson Annika I. , Moodie Lindon W. K. , Lundmark Richard
Published: January 2020

Caveolae, bulb-shaped invaginations of the plasma membrane (PM), show distinct behaviors of scission and fusion at the cell surface. Although it is known that caveolae are enriched in cholesterol and sphingolipids, exactly how lipid composition influences caveolae surface stability has not yet been elucidated. Accordingly, we inserted specific lipids into the PM of cells via membrane fusion and studied acute effects on caveolae dynamics. We demonstrate that cholesterol and glycosphingolipids specifically accumulate in caveolae, which decreases their neck diameter and drives their scission from the cell surface. The lipid-induced scission was counteracted by the ATPase EHD2. We propose that lipid accumulation in caveolae generates an intrinsically unstable domain prone to scission if not balanced by the restraining force of EHD2 at the neck. Our work advances the understanding of how lipids contribute to caveolae dynamics, providing a mechanistic link between caveolae and their ability to sense the PM lipid composition.

Caveolae serve as mechanoprotectors and membrane buffers but their specific role in sensing plasma membrane lipid composition remains unclear. Hubert et al. show that cholesterol and glycosphingolipids accumulate in caveolae and drive subsequent scission from the cell surface. These results provide new insight into how lipids contribute to budding and scission of membrane domains in cells.
Linear versus deep learning methods for noisy speech separation for EEG-informed attention decoding
Authors: Das Neetha , Zegers Jeroen , Van hamme Hugo , Francart Tom , Bertrand Alexander
Published: January 2020

Objective

A hearing aid’s noise reduction algorithm cannot infer to which speaker the user intends to listen to. Auditory attention decoding (AAD) algorithms allow to infer this information from neural signals, which leads to the concept of neuro-steered hearing aids. We aim to evaluate and demonstrate the feasibility of AAD-supported speech enhancement in challenging noisy conditions based on electroencephalography (EEG) recordings.

Approach

The AAD performance with a linear versus a deep neural network (DNN) based speaker separation was evaluated for same-gender speaker mixtures using 3 different speaker positions and 3 different noise conditions.

Main results

AAD results based on the linear approach were found to be at least on par and sometimes even better than pure DNN-based approaches in terms of AAD accuracy in all tested conditions. However, when using the DNN to support a linear data-driven beamformer, a performance improvement over the purely linear approach was obtained in the most challenging scenarios. The use of multiple microphones was also found to improve speaker separation and AAD performance over single-microphone systems.

Significance

Recent proof-of-concept studies in this context each focus on a different method in a different experimental setting, which makes it hard to compare them. Furthermore, they are tested in highly idealized experimental conditions, which are still far from a realistic hearing aid setting. This work provides a systematic comparison of a linear and non-linear neuro-steered speech enhancement model, as well as a more realistic validation in challenging conditions.
Short hydrogen bonds enhance non-aromatic protein-related fluorescence
Authors: Stephens Amberley D. , Qaisrani Muhammad Nawaz , Ruggiero Michael T. , Miron Gonzalo Diaz , Morzan Uriel N. , González Lebrero Mariano C. , Jones Saul T.E. , Poli Emiliano , Bond Andrew D. , Woodhams Philippa J. , Kleist Elyse M. , Grisanti Luca , Gebauer Ralph , Zeitler J. Axel , Credgington Dan , Hassanali Ali , Schierle Gabriele S. Kaminski
Published: January 2020

Fluorescence in biological systems is usually associated with the presence of aromatic groups. Here, we show that specific hydrogen bonding networks can significantly affect fluorescence employing a combined experimental and computational approach. In particular, we reveal that the single amino acid L-glutamine, by undergoing a chemical transformation leading to the formation of a short hydrogen bond, displays optical properties that are significantly enhanced compared to L-glutamine itself.Ab initiomolecular dynamics simulations highlight that these short hydrogen bonds prevent the appearance of a conical intersection between the excited and the ground states and thereby significantly decrease non-radiative transition probabilities. Our findings open the doors for the design of new photoactive materials with biophotonic applications.

Significance statement

Intrinsic fluorescence of non-aromatic amino acids is a puzzling phenomenon with an enormous potential for technological and biomedical applications. The physical origins of this effect, however, remain elusive. Herein, we demonstrate how specific hydrogen bond networks can modulate fluorescence. We highlight the key role played by short hydrogen bonds in the networks on the ensuing fluorescence and we provide a detailed molecular mechanism to explain this unusual non-aromatic optical properties. Our findings should benefit the design of novel optically active biomaterials for applications in biosensing and imaging.
Disentangling neocortical alpha/beta and hippocampal theta/gamma oscillations in human episodic memory formation
Authors: Griffiths Benjamin J. , Martín-Buro María Carmen , Staresina Bernhard P. , Hanslmayr Simon
Published: January 2020

To form an episodic memory, we must first process a vast amount of sensory information about a to-be-encoded event and then bind these sensory representations together to form a coherent memory. While these two cognitive capabilities are thought to have two distinct neural origins, with neocortical alpha/beta oscillations supporting information representation and hippocampal theta-gamma phase-amplitude coupling supporting mnemonic binding, evidence for a dissociation between these two neural markers is conspicuously absent. To address this, seventeen human participants completed a sequence-learning task that first involved processing information about three stimuli, and then binding these stimuli together into a coherent memory trace, all the while undergoing MEG recordings. We found that decreases in neocortical alpha/beta power during sequence perception, but not mnemonic binding, correlated with enhanced memory performance. Hippocampal theta/gamma phase-amplitude coupling, however, showed the opposite pattern; increases during mnemonic binding (but not sequence perception) correlated with enhanced memory performance. These results demonstrate that memory-related decreases in neocortical alpha/beta power and memory-related increases in hippocampal theta/gamma phase-amplitude coupling arise at distinct stages of the memory formation process. We speculate that this temporal dissociation reflects a functional dissociation in which neocortical alpha/beta oscillations could support the processing of incoming information relevant to the memory, while hippocampal theta-gamma phase-amplitude coupling could support the binding of this information into a coherent memory trace.
Automated Isoform Diversity Detector (AIDD): A pipeline for investigating transcriptome diversity of RNA-seq data
Authors: Plonski Noel-Marie , Johnson Emily , Frederick Madeline , Mercer Heather , Fraizer Gail , Meindl Richard , Casadesus Gemma , Piontkivska Helen
Published: January 2020

Background

As the number of RNA-seq datasets that become available to explore transcriptome diversity increases, so does the need for easy-to-use comprehensive computational workflows. Many available tools facilitate analyses of one of the two major mechanisms of transcriptome diversity, namely, differential expression of isoforms due to alternative splicing, while the second major mechanism - RNA editing due to post-transcriptional changes of individual nucleotides – remains under-appreciated. Both these mechanisms play an essential role in physiological and diseases processes, including cancer and neurological disorders. However, elucidation of RNA editing events at transcriptome-wide level requires increasingly complex computational tools, in turn resulting in a steep entrance barrier for labs who are interested in high-throughput variant calling applications on a large scale but lack the manpower and/or computational expertise.

Results

Here we present an easy-to-use, fully automated, computational pipeline (Automated Isoform Diversity Detector, AIDD) that contains open source tools for various tasks needed to map transcriptome diversity, including RNA editing events. To facilitate reproducibility and avoid system dependencies, the pipeline is contained within a pre-configured VirtualBox environment. The analytical tasks and format conversions are accomplished via a set of automated scripts that enable the user to go from a set of raw data, such as fastq files, to publication-ready results and figures in one step. A publicly available dataset of Zika virus-infected neural progenitor cells is used to illustrate AIDD’s capabilities.

Conclusions

AIDD pipeline offers a user-friendly interface for comprehensive and reproducible RNA-seq analyses. Among unique features of AIDD are its ability to infer RNA editing patterns, including ADAR editing, and inclusion of Guttman scale patterns for time series analysis of such editing landscapes. AIDD-based results show importance of diversity of ADAR isoforms, key RNA editing enzymes linked with the innate immune system and viral infections. These findings offer insights into the potential role of ADAR editing dysregulation in the disease mechanisms, including those of congenital Zika syndrome. Because of its automated all-inclusive features, AIDD pipeline enables even a novice user to easily explore common mechanisms of transcriptome diversity, including RNA editing landscapes.
Pyphe: A python toolbox for assessing microbial growth and cell viability in high-throughput colony screens
Authors: Kamrad Stephan , Rodríguez-López Maria , Cotobal Cristina , Correia-Melo Clara , Ralser Markus , Bähler Jürg
Published: January 2020

Microbial fitness screens are a key technique in functional genomics. We present an all-in-one solution,pyphe, for automating and improving data analysis pipelines associated with large-scale fitness screens, including image acquisition and quantification, data normalisation, and statistical analysis.Pypheis versatile and processes fitness data from colony sizes, viability scores from phloxine B staining or colony growth curves, all obtained with inexpensive transilluminating flatbed scanners. We applypypheto show that the fitness information contained in late endpoint measurements of colony sizes is similar to maximum growth slopes from time series. We phenotype gene-deletion strains of fission yeast in 59,350 individual fitness assays in 70 conditions, revealing that colony size and viability provide complementary, independent information. Viability scores obtained from quantifying the redness of phloxine-stained colonies accurately reflect the fraction of live cells within colonies.Pypheis user-friendly, open-source and fully-documented, illustrated by applications to diverse fitness analysis scenarios.
Single platelet variability governs population sensitivity and initiates intrinsic heterotypic behaviours
Authors: Jongen Maaike S. A. , MacArthur Ben D. , Englyst Nicola A. , West Jonathan
Published: January 2020

Droplet microfluidics combined with flow cytometry was used for high throughput single platelet function analysis. A large-scale sensitivity continuum was shown to be a general feature of human platelets from individual donors, with hypersensitive platelets coordinating significant sensitivity gains in bulk platelet populations and shown to direct aggregation in droplet-confined minimal platelet systems. Sensitivity gains scaled with agonist potency (convulxin>TRAP-14>ADP) and reduced the collagen and thrombin activation threshold required for platelet population polarization into pro-aggregatory and pro-coagulant states. The heterotypic platelet response results from an intrinsic behavioural program. The method and findings invite future discoveries into the nature of hypersensitive platelets and how community effects produce population level behaviours in health and disease.
A near-term iterative forecasting system successfully predicts reservoir hydrodynamics and partitions uncertainty in real time
Authors: Thomas R. Quinn , Figueiredo Renato J. , Daneshmand Vahid , Bookout Bethany J. , Puckett Laura K. , Carey Cayelan C.
Published: January 2020

Freshwater ecosystems are experiencing greater variability due to human activities, necessitating new tools to anticipate future water quality. In response, we developed and deployed a real-time iterative water temperature forecasting system (FLARE – Forecasting Lake And Reservoir Ecosystems). FLARE is composed of: water quality and meteorology sensors that wirelessly stream data, a data assimilation algorithm that uses sensor observations to update predictions from a hydrodynamic model and calibrate model parameters, and an ensemble-based forecasting algorithm to generate forecasts that include uncertainty. Importantly, FLARE quantifies the contribution of different sources of uncertainty (driver data, initial conditions, model process, and parameters) to each daily forecast of water temperature at multiple depths. We applied FLARE to Falling Creek Reservoir (Vinton, Virginia, USA), a drinking water supply, during a 475-day period encompassing stratified and mixed thermal conditions. Aggregated across this period, root mean squared error (RMSE) of daily forecasted water temperatures was 1.13 C at the reservoir’s near-surface (1.0 m) for 7-day ahead forecasts and 1.62C for 16-day ahead forecasts. The RMSE of forecasted water temperatures at the near-sediments (8.0 m) was 0.87C for 7-day forecasts and 1.20C for 16-day forecasts. FLARE successfully predicted the onset of fall turnover 4-14 days in advance in two sequential years. Uncertainty partitioning identified meteorology driver data as the dominant source of uncertainty in forecasts for most depths and thermal conditions, except for the near-sediments in summer, when model process uncertainty dominated. Overall, FLARE provides an open-source system for lake and reservoir water quality forecasting to improve real-time management.

Key Points

We created a real-time iterative lake water temperature forecasting system that uses sensors, data assimilation, and hydrodynamic modeling

Our water quality forecasting system quantifies uncertainty in each daily forecast and is open-source

16-day future forecasted temperatures were within 1.4°C of observations over 16 months in a reservoir case study
ER stress-mediated BK dysfunction in the DRG underlies pain in a model of multiple sclerosis
Authors: Yousuf Muhammad Saad , Samtleben Samira , Lamothe Shawn M. , Friedman Timothy , Catuneanu Ana , Thorburn Kevin , Desai Mansi , Tenorio Gustavo , Schenk Geert J. , Ballanyi Klaus , Kurata Harley T. , Simmen Thomas , Kerr Bradley J.
Published: January 2020

Neuropathic pain is a common symptom of multiple sclerosis (MS) and current treatment options are ineffective. In this study, we investigated whether endoplasmic reticulum (ER) stress in dorsal root ganglia (DRG) contributes to pain hypersensitivity in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Inflammatory cells and increased levels of ER stress markers are evident in post-mortem DRGs from MS patients. Similarly, we observed ER stress in the DRG of mice with EAE and relieving ER stress with a chemical chaperone, 4-phenylbutyric acid (4-PBA), reduced pain hypersensitivity.In vitro, 4-PBA and the selective PERK inhibitor, AMG44, normalize cytosolic Ca2+transients in putative DRG nociceptors. We went to assess disease-mediated changes in the functional properties of Ca2+-sensitive BK-type K+channels in DRG neurons. We found that the conductance-voltage (GV) relationship of BK channels was shifted to a more positive voltage, together with a more depolarized resting membrane potential in EAE cells. Our results suggest that ER stress in sensory neurons of MS patients and mice with EAE is a source of pain and that ER stress modulators can effectively counteract this phenotype.
BATMAN: fast and accurate integration of single-cell RNA-Seq datasets via minimum-weight matching
Authors: Mandric Igor , Hill Brian L. , Freund Malika K. , Thompson Michael , Halperin Eran
Published: January 2020

Single-cell RNA-Sequencing (scRNA-Seq) is a set of technologies used to profile gene expression at the level of individual cells. Although the throughput of scRNA-Seq experiments is steadily growing in terms of the number of cells, large datasets are not yet commonly used due to prohibitively high costs. Integrating multiple datasets into one can improve power in scRNA-Seq experiments, and efficient integration is very important for downstream analyses such as identifying cell-type-specific eQTLs. State-of-the-art scRNA-Seq integration methods are based on the mutual nearest neighbors paradigm and fail to both correct for batch effects and maintain the local structure of the datasets. In this paper, we propose a novel scRNA-Seq dataset integration method called BATMAN (BATch integration via minimum-weight MAtchiNg). Across multiple simulations and real datasets, we show that our method significantly outperforms state-of-the-art tools with respect to existing metrics for batch effects by up to 80% while retaining cell-to-cell relationships. BATMAN is available athttps://github.com/mandricigor/batman.
Neuroligin3 Splice Isoforms Shape Mouse Hippocampal Inhibitory Synaptic Function
Authors: Uchigashima Motokazu , Leung Ming , Watanabe Takuya , Cheung Amy , Watanabe Masahiko , Kawasawa Yuka Imamura , Futai Kensuke
Published: January 2020

Synapse formation is a dynamic process essential for neuronal circuit development and maturation. At the synaptic cleft, trans-synaptic protein-protein interactions constitute major biological determinants of proper synapse efficacy. The balance of excitatory and inhibitory synaptic transmission (E-I balance) stabilizes synaptic activity. Dysregulation of the E-I balance has been implicated in neurodevelopmental disorders including autism spectrum disorders. However, the molecular mechanisms underlying E-I balance remain to be elucidated. Here, we investigate Neuroligin (Nlgn) genes that encode a family of postsynaptic adhesion molecules known to shape excitatory and inhibitory synaptic function. We demonstrate that Nlgn3 protein differentially regulates inhibitory synaptic transmission in a splice isoform-dependent manner at hippocampal CA1 synapses. Distinct subcellular localization patterns of Nlgn3 isoforms contribute to the functional differences observed among splice variants. Finally, single-cell sequencing analysis reveals thatNlgn1andNlgn3are the majorNlgngenes and that expression ofNlgnsplice isoforms are highly diverse in CA1 pyramidal neurons.
Hesperetin inhibits foam cell formation in macrophages via activating LXRα signal in an AMPK dependent manner
Authors: Chen Xuanjing , Zou Dezhi , Chen Xiaoling , Wu Huanlin , Xu Danping
Published: January 2020

Cholesterol efflux from macrophages is the first step of cholesterol reverse transport (RCT), whose increase inhibits cholesterol accumulation and foam cell formation to suppress atherogenesis. Liver X receptor alpha (LXRα) and adenosine monophosphate activated protein kinases (AMPK) both have the pivotal role in cholesterol homeostasis. However the association between these two molecules in cell model of atherosclerosis is poorly understood. Hesperetin has been reported to possess several protective effects for cardiovascular diseases, while little is known about the role of hesperetin and its underlying mechanism on macrophage foam cell formation. In this study, we sought to investigate the potential effects of hesperetin in cholesterol efflux by using human macrophage derived foam cells, focusing on liver X receptor alpha (LXRα) and adenosine monophosphate activated protein kinases (AMPK) implication. Hesperetin treatment concentration-dependently reduced foam cell formation, intracellular cholesterol level and cholesterol esterification rate, and enhanced cholesterol efflux in THP-1 macrophages. Hesperetin upregulated the protein levels of LXRα and its targets including ABCA1, ABCG1 as well as SR-BI, and phosphorylated-AMPK. Meanwhile, hesperetin-induced upregulation of LXRα expression was enhanced by AMPK agonist and inhibited by AMPK inhibitor. Furthermore, hesperetin increased mRNA level of LXRα and its target genes, all which were depressed by AMPKα1/α2 small interfering RNA (siRNA) transfection. In conclusion, we founded for the first time that hesperetin could active AMPK. And this activation upregulated LXRα and its targets including ABCA1, ABCG1 and SR-BI, which significantly inhibited foam cell formation and promoted cholesterol efflux in THP-1 macrophages. Our results highlight the therapeutic potential of hespretin for the possible reduction in foam cell formation. This new mechanism could contribute the anti-atherogenic effects of hesperetin.
Evaluating India’s energy targets using real options approach
Authors: Das Gupta Supratim , Mosiño Alejandro
Published: January 2020

Purpose

The authors formulate India’s energy targets in light of pushing for renewable energy sources and reducing the dependence on imported coal. Share of imported coal in electricity generation has been approximately 10 per cent in recent years. While investments in renewables have grown in recent years as seen in installed capacities, coal-fired electricity generation has grown because of rising demand for electricity. The purpose of this study is to find a planner solution when high global coal prices force greater investments in renewable energies.

Design/methodology/approach

The authors use real options approach where global coal prices are the stochastic variable. They present an optimal stopping problem and solving the problem backward, the revenues from continuing with the current energy generation mix and those from replacing imported coal with wind and solar is compared for each period.

Findings

The “trigger price” for global coal prices when it is optimal for the social planner to invest in additional wind and solar capacities is found. Trigger prices is the threshold when investment must be undertaken whatever be the future evolution of coal prices; this gives the problem a value of waiting. India cannot afford to wait to invest if faced with strict short-term goals.

Originality/value

The work evaluates India’s domestic targets and its Paris Agreement goals in light of using more of wind and sun and replacing imported coal. Various data sources (government reports, research articles) are consulted to predict shares of electricity from various sources in future and the authors find the operating costs and the investment costs associated with switching to renewables.
Effects of CEO narcissism on decision-making comprehensiveness and speed
Authors: She Zhuolin , Li Quan , London Manuel , Yang Baiyin , Yang Bin
Published: January 2020

Purpose

The purpose of this paper is to examine the relationships between CEO narcissism and strategic decision-making (SDM) processes (decision comprehensiveness and decision speed), and to explore the mediating role of top management team (TMT) members’ participation in decision making and the moderating role of TMT power distance.

Design/methodology/approach

Data were collected from a multisource, time-lagged survey of 103 CEOs and their corresponding TMT members in China. Structural equation modeling was used to test the hypothesized relationships.

Findings

The results indicated that CEO narcissism was negatively related to decision comprehensiveness and positively related to decision speed. These relationships were mediated by TMT members’ participation in decision making, especially when TMT power distance was high.

Practical implications

The results show the potential negative effects of CEOs’ narcissistic personality and suggest ways to attenuate it by increasing TMT participation and decreasing TMT power distance.

Originality/value

This study is an initial attempt to empirically examine how and under what conditions CEOs’ narcissism is a barrier to more comprehensive and more deliberate (slower) SDM.
Evaluating the role of predatory fish controlling the invasion of the Asian golden mussel Limnoperna fortunei in a subtropical river
Authors: González‐Bergonzoni Ivan , Silva Ivana , Teixeira de Mello Franco , D'Anatro Alejandro , Boccardi Lucia , Stebniki Samanta , Brugnoli Ernesto , Tesitore Giancarlo , Vidal Nicolás , Naya Daniel E.
Published: January 2020

The invasive Asian golden mussel Limnoperna fortunei is continuously expanding through South America, altering aquatic ecosystem structure and functioning. While several native fish species predate on this mussel, these interactions, and their consequences for the food web, have not been studied in depth.

We combine a survey of the fish assemblage trophic structure using gut contents and stable isotope analysis with an in situ exclusion experiment in order to: (a) determine the main fish species predating on L. fortunei; (b) estimate the contribution of L. fortunei to the biomass of fish assemblage; and (c) evaluate the role of fish on the density and maximum shell length of L. fortunei in the lower Uruguay River (the Río de La Plata Basin).

We found that about one third of fish species in the assemblage (28 out of 81 species) consumed L. fortunei, which was an important food item (>10% of the dietary volume and >30% of frequency of occurrence) for 11 fish species. Stable isotope mixing models consistently suggested that >14% of the total biomass of the fish assemblage was derived directly from carbon derived from L. fortunei tissues. In addition, the exclusion experiment demonstrated that fish predation reduces the mussel density by c. 70% and the mussel maximum shell length by c. 40%.

Synthesis and applications. Our research suggests a top‐down effect of fish on the invasive Asian golden mussel's abundance. This work highlights the need to preserve the native fish communities, particularly in South America, where many vulnerable migratory fish are of key relevance as Limnoperna fortunei consumers. In the light of these findings, actions such as implementing efficient fish passage technologies in the actual (and projected) dams of the Uruguay River basin and elsewhere become essential to avoid local extinctions of these natural invasion controls upstream of the dams.
The effect of environmental gradient on biodiversity and similarity of invertebrate communities in eelgrass (Zostera marina) beds
Authors: Namba Mizuho , Hashimoto Marina , Ito Minako , Momota Kyosuke , Smith Carter , Yorisue Takefumi , Nakaoka Masahiro
Published: January 2020

Environmental filtering and dispersal limitation are important processes within the metacommunity concept. Non‐random species turnover occurs in places where environmental filtering plays the key role in determining local community structure, whereas dispersal limitation causes nested patterns of species assemblages organized by non‐random colonization processes. However, factors that modify the relative importance of these processes remain unclear for many ecosystems. We tested whether salinity gradient affect the relative importance of environmental filtering and dispersal limitation for structuring epifaunal and infaunal communities in three lagoons in Hokkaido, Japan, that have different salinity gradients. Specifically, we compared patterns of species diversity and similarity of eelgrass‐associated invertebrate assemblages across space. Beta diversity (i.e., species turnover among different sites in each lagoon) was highest in Akkeshi, the lagoon with the salinity gradients. Variation partitioning of similarity components showed that spatial variation in the community assemblage pattern was mostly explained by environmental filtering in Akkeshi, but that it was explained more by species dispersal patterns and the difference in eelgrass biomass and shoot density in Notoro and Saroma, the lagoons without clear salinity gradient. Redundancy analysis showed that spatial variation in community structure was related to salinity and eelgrass biomass in Akkeshi, and to eelgrass aboveground biomass in Notoro and Saroma. Our findings highlight the effects of environmental heterogeneity on beta diversity and community structure and indicate that environmental gradients can be a key factor causing a shift in the relative importance of different metacommunity processes and the role of the foundation species in provisioning habitat.
Culture‐independent tracking of Vibrio cholerae lineages reveals complex spatiotemporal dynamics in a natural population
Authors: Kirchberger Paul C. , Orata Fabini D. , Nasreen Tania , Kauffman Kathryn M. , Tarr Cheryl L. , Case Rebecca J. , Polz Martin F. , Boucher Yann F.
Published: January 2020

Populations of the bacterium Vibrio cholerae consist of dozens of distinct lineages, with primarily (but not exclusively) members of the pandemic generating lineage capable of causing the diarrhoeal disease cholera. Assessing the composition and temporal dynamics of such populations requires extensive isolation efforts and thus only rarely covers large geographic areas or timeframes exhaustively. We developed a culture‐independent amplicon sequencing strategy based on the protein‐coding gene viuB (vibriobactin utilization) to study the structure of a V. cholerae population over the course of a summer. We show that the 26 co‐occurring V. cholerae lineages continuously compete for limited space on nutrient‐rich particles where only a few of them can grow to large numbers. Differential abundance of lineages between locations and size‐fractions associated with a particle‐attached or free‐swimming lifestyle could reflect adaptation to various environmental niches. In particular, a major V. cholerae lineage occasionally grows to large numbers on particles but remain undetectable using isolation‐based methods, indicating selective culturability for some members of the species. We thus demonstrate that isolation‐based studies may not accurately reflect the structure and complex dynamics of V. cholerae populations and provide a scalable high‐throughput method for both epidemiological and ecological approaches to studying this species.