bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptional Analysis ofColletotrichum fructicolafrom Different Geographic Regions Inoculated toCamellia oleifera
Authors: Tan Shimeng , Chen Yanying , Zhou Guoying , Liu Junang
Published: July 2020

Anthracnose, caused by Colletotrichum. Spp., is an important disease affecting oil tea (Camellia oleifera). Extensive molecular studies have demonstrated thatColletotrichum fructicolais the dominant pathogen of oil tea anthracnose in China. The study aims to investigate differences in molecular processes and regulatory genes at different stages of infection ofC. fructicola, to aide in understanding differences in pathogenic mechanisms ofC. fructicolaof different geographic populations. Materials and Methods: We compared the pathogenicity ofC. fructicolafrom different populations (Wuzhishan, Hainan province and Shaoyang, Hunan province), and gene expression of representative strains of the two populations before and after inoculation in oil tea using RNA sequencing. In results we found thatC. fructicolafrom Wuzhishan has a stronger ability to infect and impact oil tea leaf tissue. Up-regulated genes in oil tea following infection with the two geographic populations were associated with a number of ribosome-related GO terms and ribosome metabolic related KEGG pathways, and were significantly enriched in galactosidase activity, glutamine family amino acid metabolism, arginine and proline metabolism. In addition, up-regulated gene lists associated with infection in the Wuzhishan strains were significantly enriched purine metabolism pathways as well, while Shaoyang strains were not significantly enriched in these processes. Differences in gene expression were indicative of greater active transcription and translation in the Wuzhishan population while more active glycoprotein metabolism was observed following inoculation with strains from Shaoyang. These results indicate thatC. fructicolaobtained sugars and amino acids from oil tea tissue to resist host immune pressure. Moreover, more active in transcriptional and translational activity and the greater regulation of purine metabolism pathway in the Wuzhishan strain might contribute to its stronger pathogenicity.
Analysis of Distributed Neural Synchrony through State-Space Coherence Analysis
Authors: Fard Reza Saadati , Arai Kensuke , Eden Uri T. , Brown Emery N. , Yousefi Ali
Published: July 2020

Established methods to track the dynamics of neural representations focus at the level of individual neurons for spiking data, and individual or pair of channels for local field potentials. However, our understanding of neural function and computation has moved toward an integrative view, based upon coordinated activity of multiple neural populations across brain areas. To draw network-level inferences of brain function, we propose a new modeling framework that combines the state-space model and cross-spectral matrix estimates – this is called state-space coherence (SSCoh). We define elements of the SSCoh and derive system identification and approximate filter solution for multivariate space processes. We expand SCoh for mixed observation processes, where the observation includes different modalities of neural data including local filed potential and spiking activity. Finally, we show an application of the framework to study neural synchrony across different brain nodes of a task participant performing Stroop task under different distraction levels.
Comparative analysis of chloroplast genomes indicated different origin for Indian Tea (Camellia assamica) cv TV-1 as compared to Chinese tea
Authors: Rawal Hukam C. , Mazumder Abhishek , Borchetia Sangeeta , Bera Biswajit , Soundararajan S. , Ilango R Victor J , Barooah Anoop Kumar , Singh Nagendra Kumar , Mondal Tapan Kumar
Published: July 2020

Tea is an important plantation crop of some Asian and African countries. Based upon the morphological characteristics, tea is classified botanically into 2 main types i.e. Assam and China, which are morphologically very distinct. Further, they are so easily pollinated among themselves, that a third category, Cambod type is also described. Although the general consensus of origin of tea is India, Burma and China joining area, yet specific origin of China and Assam tea are not yet clear. In the present study, we made an attempt to understand the origin of Indian tea through the comparative analysis of different chloroplast (cp) genomes under the Camellia genus. Cp genome based phylogenetic analysis indicated that Indian Assam Tea, TV-1 formed a different group from that of China tea, indicating that TV-1 might have undergone different domestication and hence owe different origin. The simple sequence repeats (SSRs) analysis and codon usage distribution pattern also supported the clustering order in the cp genome based phylogenetic tree.
Ex vivoobservation of granulocyte activity during thrombus formation
Authors: Morozova Daria S. , Martyanov Alexey A. , Obydennyi Sergei I. , Korobkin Julia-Jessica D. , Sokolov Alexey V. , Shamova Ekaterina V. , Gorudko Irina V. , Shcherbina Anna , Panteleev Mikhail A. , Sveshnikova Anastasia N.
Published: July 2020

Infiltration of growing thrombi by leukocytes, being the key part of the thromboinflammation, is well establishedin vivo. The study was aimed at the development of anex vivosimulation of this phenomenon. Thrombus formation in anticoagulated whole blood from healthy volunteers and patients was visualized by fluorescent microscopy in parallel-plate flow chambers with fibrillar collagen type I coverslips.

Moving CD66b-positive cells (granulocytes) were observed in hirudinated or recalcified blood under low wall shear rate conditions (<200 s−1). These cells crawled around thrombi in a step-wise manner with an average rate of 70 nm/s. Pre-incubation of blood with leukocyte priming agents lead to a significant increase in average cell velocity. On the contrary, leukocytes from Wiskott-Aldrich syndrome patients demonstrated a 1.5-fold lower average velocity, in line with their impaired actin polymerization.

Thereby, the observed features of granulocytes crawling are consistent with the neutrophil chemotaxis phenomenon. We conclude that the proposedex vivoexperimental setting allows us to observe granulocytes activity in near-physiological conditions.
A simple and efficient metric quantifying druggable property of chemical small molecules
Authors: Huang Chuanbo , Yang Jichun , Cui Qinghua
Published: July 2020

One big class of drugs are chemical small molecules (CSMs), but the majority of CSMs are in very low druggable potential. Therefore, it is quite important to predict drug-related properties (druggable properties) for candidate CSMs. Currently, although a number of druggable properties (e.g. logP and pKa) can be calculated by in silico methods, the identification of druggable CSMs is still at high risk and new quantitative metrics for the druggable potential of CSMs are increasingly needed. Here, we presented normalized bond energy (NBE), a new metric for the above purpose. By applying NBE to the DrugBank CSMs whose properties are largely known, we revealed that NBE is able to describe a number of critical druggable properties including logP, pKa, membrane permeability, blood-brain barrier penetration, and human intestinal absorption. Moreover, given that the human endogenous metabolites could be served as an important resource for drug discovery, we applied NBE to the metabolites in the Human Metabolome Database. As a result, NBE shows a significant difference in metabolites from various body fluids and is correlated with some important properties including melting point and water solubility.
IP6K1 upregulates the formation of processing bodies by promoting proteome remodeling on the mRNA cap
Authors: Shah Akruti , Bhandari Rashna
Published: July 2020

Inositol hexakisphosphate kinases (IP6Ks) are ubiquitously expressed small molecule kinases that catalyze the conversion of the inositol phosphate IP6 to 5-IP7. IP6Ks have been reported to influence cellular functions by protein-protein interactions independent of their enzymatic activity. Here, we show that IP6K1 regulates the formation of processing bodies (P-bodies), which are cytoplasmic ribonucleoprotein granules that serve as sites for storage of translationally repressed mRNA. Cells with reduced levels of IP6K1 display a dramatic reduction in the number of P-bodies, which can be restored by the expression of active or catalytically inactive IP6K1. IP6K1 does not localize to P-bodies, but instead facilitates the formation of P-bodies by promoting translation suppression. We demonstrate that IP6K1 is present on ribosomes, where it interacts with proteins that constitute the mRNA decapping complex – the scaffold protein EDC4, activator proteins DCP1A/B, and the decapping enzyme DCP2. IP6K1 also interacts with components of the eIF4F translation initiation complex – the scaffolding protein eIF4G1, the RNA helicase eIF4A2, and the cap binding protein eIF4E. The RNA helicase DDX6 and the eIF4E binding protein 4E-T are known to promote translation suppression to facilitate P-body formation. We show that IP6K1 binds to DDX6 and promotes the interaction of DDX6 and 4E-T with the cap binding protein eIF4E, and also enhances the binding between DDX6 and EDC4, thus acting to suppress mRNA translation and promote mRNA decapping. Our findings unveil IP6K1 as a novel facilitator of proteome remodelling on the mRNA cap, tipping the balance in favour of translation repression over initiation, and thus leading to the formation of P-bodies.
Intraneuronal chloride accumulation via NKCC1 is not essential for hippocampal network developmentin vivo
Authors: Graf Jürgen , Zhang Chuanqiang , Marguet Stephan Lawrence , Herrmann Tanja , Flossmann Tom , Hinsch Robin , Rahmati Vahid , Guenther Madlen , Frahm Christiane , Urbach Anja , Neves Ricardo Melo , Witte Otto W. , Kiebel Stefan J. , Isbrandt Dirk , Hübner Christian A. , Holthoff Knut , Kirmse Knut
Published: July 2020

NKCC1 is the primary transporter mediating chloride uptake in immature principal neurons, but its role in the development ofin vivonetwork dynamics and cognitive abilities remains unknown. Here, we address the function of NKCC1 in developing mice using electrophysiological, optical and behavioral approaches. We report that NKCC1 deletion from telencephalic glutamatergic neurons decreasesin-vitroexcitatory GABA actions and impairs neuronal synchrony in neonatal hippocampal brain slices.In vivo, it has a minor impact on correlated spontaneous activity in the hippocampus and does not affect network activity in the intact visual cortex. Moreover, long-term effects of the developmental NKCC1 deletion on synaptic maturation, network dynamics and behavioral performance are subtle. Our data reveal a neural network function of depolarizing GABA in the hippocampusin vivo, but challenge the hypothesis that NKCC1 is essential for major aspects of hippocampal development.
How robust are cross-population signatures of polygenic adaptation in humans?
Authors: Refoyo-Martínez Alba , Liu Siyang , Jørgensen Anja Moltke , Jin Xin , Albrechtsen Anders , Martin Alicia R. , Racimo Fernando
Published: July 2020

Over the past decade, summary statistics from genome-wide association studies (GWASs) have been used to detect and quantify polygenic adaptation in humans. Several studies have reported signatures of natural selection at sets of SNPs associated with complex traits, like height and body mass index. However, more recent studies suggest that some of these signals may be caused by biases from uncorrected population stratification in the GWAS data with which these tests are performed. Moreover, past studies have predominantly relied on SNP effect size estimates obtained from GWAS panels of European ancestries, which are known to be poor predictors of phenotypes in non-European populations. Here, we collated GWAS data from multiple anthropometric and metabolic traits that have been measured in more than one cohort around the world, including the UK Biobank, FINRISK, Chinese NIPT, Biobank Japan, APCDR and PAGE. We then evaluated how robust signals of polygenic score overdispersion (which have been interpreted as suggesting polygenic adaptation) are to the choice of GWAS cohort used to identify associated variants and their effect size estimates. We did so while using the same panel to obtain population allele frequencies (The 1000 Genomes Project). We observe many discrepancies across tests performed on the same phenotype and find that association studies performed using multiple different cohorts, like meta-analyses and mega-analyses, tend to produce polygenic scores with strong overdispersion across populations. This results in apparent signatures of polygenic adaptation which are not observed when using effect size estimates from biobank-based GWASs of homogeneous ancestries. Indeed, we were able to artificially create score overdispersion when taking the UK Biobank cohort and simulating a meta-analysis on multiple subsets of the cohort. Finally, we show that the amount of overdispersion in scores for educational attainment - a trait with strong social implications and high potential for misinterpretation - is also strongly dependent on the specific GWAS used to build them. This suggests that extreme caution should be taken in the execution and interpretation of future tests of polygenic score overdispersion based on population differentiation, especially when using summary statistics from a GWAS that combines multiple cohorts.
A gustatory receptor tuned to the steroid plant hormone brassinolide inPlutella xylostella(Lepidoptera: Plutellidae)
Authors: Yang Ke , Gong Xin-Lin , Li Guo-Cheng , Huang Ling-Qiao , Ning Chao , Wang Chen-Zhu
Published: July 2020

Feeding and oviposition deterrents help phytophagous insects to identify host plants. The taste organs of phytophagous insects contain bitter gustatory receptors (GRs). To explore their function, we focused on PxylGr34, a bitter GR inPlutella xylostella(L.). We detected abundantPxylGr34transcripts in the larval head and specific expression ofPxylGr34in the antennae of females. Analyses using theXenopusoocyte expression system and two-electrode voltage-clamp recording showed that PxylGr34 is specifically tuned to the plant hormone brassinolide (BL) and its analog 24-epibrassinolide. Electrophysiological analyses revealed that the medial sensilla styloconica on the maxillary galea of the 4thinstar larvae are responsive to BL. Dual-choice bioassays demonstrated that BL inhibits larval feeding and female ovipositing. Knock-down of PxylGr34 by RNAi abolished BL-induced feeding inhibition. These results shed light on gustatory coding mechanisms and deterrence of insect feeding and ovipositing, and may be useful for designing plant hormone-based pest management strategies.
Testing two competing hypotheses for Eurasian jays’ caching for the future: planning versus compensatory caching
Authors: Amodio Piero , Brea Johanni , Farrar Benjamin G. , Ostojic Ljerka , Clayton Nicola S.
Published: July 2020

Previous research reported that corvids preferentially cache food in a location where no food will be available or cache more of a specific food in a location where this food will not be available. Here, we consider possible explanations for these prospective caching behaviours and directly compare two competing hypotheses. The Compensatory Caching Hypothesis suggests that birds learn to cache more of a particular food in places where that food was less frequently available in the past. In contrast, the Future Planning Hypothesis suggests that birds recall what-when-where features of specific past events to predict the future availability of food. We designed a protocol in which the two hypotheses predict different caching patterns across different caching locations such that the two explanations can be disambiguated. We formalised the hypotheses in a Bayesian model comparison and tested this protocol in two experiments with one of the previously tested species, namely Eurasian jays. Consistently across the two experiments, the observed caching pattern did not support either hypothesis; rather it was best explained by a uniform distribution of caches over the different caching locations. Future research is needed to gain more insight into the cognitive mechanism underpinning corvids’ caching for the future.
Extracellular matrix supports excitation-inhibition balance in neuronal networks by stabilizing inhibitory synapses
Authors: Dzyubenko Egor , Fleischer Michael , Manrique-Castano Daniel , Borbor Mina , Kleinschnitz Christoph , Faissner Andreas , Hermann Dirk M
Published: July 2020

Maintaining the balance between excitation and inhibition is essential for the appropriate control of neuronal network activity. Sustained excitation-inhibition (E-I) balance relies on the orchestrated adjustment of synaptic strength, neuronal activity and network circuitry. While growing evidence indicates that extracellular matrix (ECM) of the brain is a crucial regulator of neuronal excitability and synaptic plasticity, it remains unclear whether and how ECM contributes to neuronal circuit stability. Here we demonstrate that the integrity of ECM supports the maintenance of E-I balance by retaining inhibitory connectivity. Depletion of ECM in mature neuronal networks preferentially decreases the density of inhibitory synapses and the size of individual inhibitory postsynaptic scaffolds. After ECM depletion, inhibitory synapse strength homeostatically increases via the reduction of presynaptic GABABreceptors. However, the inhibitory connectivity reduces to an extent that inhibitory synapse scaling is no longer efficient in controlling neuronal network activity. Our results indicate that the brain ECM preserves the balanced network state by stabilizing inhibitory synapses.

Significance statement

The question how the brain’s extracellular matrix (ECM) controls neuronal plasticity and network activity is key for an appropriate understanding of brain functioning. In this study, we demonstrate that ECM depletion much more strongly affects the integrity of inhibitory than excitatory synapses in vitro and in vivo. We revealed that by retaining inhibitory connectivity, ECM ensures the efficiency of inhibitory control over neuronal network activity. Our work significantly expands our current state of knowledge about the mechanisms of neuronal network activity regulation. Our findings are similarly relevant for researchers working on the physiological regulation of neuronal plasticity in vitro and in vivo and for researchers studying the remodeling of neuronal networks upon brain injury, where prominent ECM alterations occur.
Early Medieval Genetic Data from Ural Region Evaluated in the Light of Archaeological Evidence of Ancient Hungarians
Authors: Csáky Veronika , Gerber Dániel , Szeifert Bea , Egyed Balázs , Stégmár Balázs , Botalov Sergej Gennad’evich , Grudochko Ivan Valer’evich , Matvejeva Natalja Petrovna , Zelenkov Alexander Sergejevich , Slepcova Anastasija Viktorovna , Goldina Rimma D. , Danich Andrey V. , Mende Balázs G. , Türk Attila , Szécsényi-Nagy Anna
Published: July 2020

The ancient Hungarians originated from the Ural region of Russia, and migrated through the Middle-Volga region and the Eastern European steppe into the Carpathian Basin during the 9th century AD. Their Homeland was probably in the southern Trans-Ural region, where the Kushnarenkovo culture disseminated. In the Cis-Ural region Lomovatovo and Nevolino cultures are archaeologically related to ancient Hungarians. In this study we describe maternal and paternal lineages of 36 individuals from these regions and nine Hungarian Conquest period individuals from today’s Hungary, as well as shallow shotgun genome data from the Trans-Uralic Uyelgi cemetery. We point out the genetic continuity between the three chronological horizons of Uyelgi cemetery, which was a burial place of a rather endogamous population. Using phylogenetic and population genetic analyses we demonstrate the genetic connection between Trans-, Cis-Ural and the Carpathian Basin on various levels. The analyses of this new Uralic dataset fill a gap of population genetic research of Eurasia, and reshape the conclusions previously drawn from 10-11th century ancient mitogenomes and Y-chromosomes from Hungary.
Divergence and Remarkable Diversity of the Y Chromosome in Guppies
Authors: Almeida Pedro , Sandkam Benjamin A. , Morris Jake , Darolti Iulia , Breden Felix , Mank Judith E.
Published: July 2020

The guppy sex chromosomes show an extraordinary diversity in divergence across populations and closely related species. In order to understand the dynamics of the guppy Y chromosome, we used linked-read sequencing to assess Y chromosome evolution and diversity across upstream and downstream population pairs that vary in predator and food abundance in three replicate watersheds. Based on our population-specific genome assemblies, we first confirmed and extended earlier reports of two strata on the guppy sex chromosomes. Stratum I shows significant accumulation of male-specific sequence, consistent with Y divergence, and predates the colonization of Trinidad. In contrast, Stratum II shows divergence from the X, but no Y-specific sequence, and this divergence is greater in three replicate upstream populations compared to their downstream pair. Despite longstanding assumptions that sex chromosome recombination suppression is achieved through inversions, we find no evidence of inversions associated with either Stratum I or Stratum II. Instead, we observe a remarkable diversity in Y chromosome haplotypes within each population, even in the ancestral Stratum I. This diversity is likely due to gradual mechanisms of recombination suppression, which, unlike an inversion, allow for the maintenance of multiple haplotypes. In addition, we show that this Y diversity is dominated by low-frequency haplotypes segregating in the population, suggesting a link between haplotype diversity and female-preference for rare Y-linked colour variation. Our results reveal the complex interplay between recombination suppression and Y chromosome divergence at the earliest stages of sex chromosome divergence.
Pan-genome analyses of peach and its wild relatives provide insights into the genetics of disease resistance and species adaptation
Authors: Cao Ke , Peng Zhen , Zhao Xing , Li Yong , Liu Kuozhan , Arus Pere , Zhu Gengrui , Deng Shuhan , Fang Weichao , Chen Changwen , Wang Xinwei , Wu Jinlong , Fei Zhangjun , Wang Lirong
Published: July 2020

As a foundation to understand the molecular mechanisms of peach evolution and high-altitude adaptation, we performedde novogenome assembling of four wild relatives ofP. persica, P. mira, P. kansuensis, P. davidianaandP. ferganensis. Through comparative genomic analysis, abundant genetic variations were identified in four wild species when compared toP. persica. Among them, a deletion, located at the promoter ofPrupe.2G053600inP. kansuensis, was validated to regulate the resistance to nematode. Next, a pan-genome was constructed which comprised 15,216 core gene families among four wild peaches andP. perisca. We identified the expanded and contracted gene families in different species and investigated their roles during peach evolution. Our results indicated thatP. mirawas the primitive ancestor of cultivated peach, and peach evolution was non-linear and a cross event might have occurred betweenP. miraandP. dulcisduring the process. Combined with the selective sweeps identified using accessions ofP. miraoriginating from different altitude regions, we proposed that nitrogen recovery was essential for high-altitude adaptation ofP. mirathrough increasing its resistance to low temperature. The pan-genome constructed in our study provides a valuable resource for developing elite cultivars, studying the peach evolution, and characterizing the high-altitude adaptation in perennial crops.
Differential transcriptional reprogramming by wild type and lymphoma-associated mutant MYC proteins as B-cells convert to lymphoma-like cells
Authors: Mahani Amir , Arvidsson Gustav , Sadeghi Laia , Grandien Alf , Wright Anthony P.
Published: July 2020

The transcription factor MYC regulates the expression of a vast number of genes and is implicated in various human malignancies, for which it’s deregulation by genomic events such as translocation or amplification can be either disease-defining or associated with poor prognosis. In hematological malignancies MYC is frequently subject to missense mutations and one such hot spot where mutations have led to increased protein stability and elevated transformation activity exists within its transactivation domain. Here we present and characterize a model system for studying the effects of gradually increasing MYC levels as B-cells progress to lymphoma-like cells. Inclusion of two frequent lymphoma-associated MYC mutants (T58A and T58I) allowed for discrimination of changes in the MYC regulatory program according to mutation status. Progressive increase in MYC levels significantly altered the transcript levels of 7569 genes and subsets of these were regulated differently in mutant MYC proteins compared to WT MYC or between the mutant MYC proteins. Functional classification of the differentially regulated genes based on expression levels across different MYC levels confirmed previously found MYC regulated functions such as ribosome biogenesis and purine metabolism while other functional groups such as the downregulation of genes involved in B-cell differentiation and chemotaxis were novel. Gene sets that were differently regulated in cells overexpressing mutant MYC proteins contained an over-representation of genes involved in DNA Replication and transition from the G2 phase to mitosis. The cell model presented here mimics changes seen during lymphoma development in the Eμ-Myc mouse model as well as MYC-dependent events associated with poor prognosis in a wide range of human cancer types and therefore constitutes a relevant cell model forin vitromechanistic studies of wild type and mutant MYC proteins in relation to lymphoma development.
A quantised cyclin-based cell cycle model
Authors: Emerson Chris , Bennie Lindsey , Green Dermot , Currell Fred , Coulter Jonathan A.
Published: July 2020

Computational modelling is an important research tool, helping predict the outcome of proposed treatment plans or to illuminate the mechanics of tumour growth.In silicomodelling has been used in every aspect of cancer research from DNA damage and repair, tumour growth, drug/tumour interactions, and mutational status. Indeed, modelling even holds potential in understanding the interactions between individual proteins on a single cell basis. Here, we present a computational model of the cell cycle network of the cyclin family of proteins (cyclin A, B, D and E). This model has been quantised using western blot and flow cytometry data from a synchronised HUVEC line to enable the determination of the absolute number of cyclin protein molecules per cell. This quantification allows the model to have stringent controls over the thresholds between transitions. The results show that the peak values obtained for the four cyclins are similar with cyclin B having a peak values of 5×106to 9×106molecules per cell. Comparing this value with the number of actin proteins, 5E8, shows that despite their importance, the level of cyclin family proteins are approximately 2 orders of magnitude lower. The efficiency of the model presented would also allow for its use as an internal component in more complex models such as a tumour growth model, in which each individual cell would have its own cell cycle calculated independently from neighbouring cells. Additionally, the model can also be used to help understand the impact of novel therapeutic interventions on cell cycle progression.

Author Summary

Protein and gene networks control every physiological behaviour of cells, with the cell cycle being controlled by the network of genes that promote the cyclin family of proteins. These networks hold the key to creating accurate and relevant biological models. Normally these models are presented with relative protein concentrations without any real world counterpart to their outputs. The model presented within shows and advancement of this approach by calculating the absolute concentration of each cyclin protein in one cell as it progresses through the cell cycle. This model employs Boolean variables to represent the genetic network, either the gene is active or not, and continuous variables to represent the concentrations of the proteins. This hybridised approach allows for rapid calculations of the protein concentrations and of the cell cycle progression allowing for a model that could be easily incorporated into larger tumour models, allowing for the tracking of discrete cells within the tumour.
Resolving phylogeny and polyploid parentage using genus-wide genome-wide sequence data from birch trees
Authors: Wang Nian , Kelly Laura J. , McAllister Hugh A. , Zohren Jasmin , Buggs Richard J. A.
Published: July 2020

Numerous plant genera have a history including frequent hybridisation and polyploidisation, which often means that their phylogenies are not yet fully resolved. The genusBetula, which contains many ecologically important allopolyploid tree species, is a case in point. We generated genome-wide sequence data for 27 diploid and 31 polyploidBetulaspecies or subspecies using restriction site associated DNA (RAD) sequences assembled into contigs with a mean length of 675 bp. We reconstructed the evolutionary relationships among diploidBetulaspecies using both supermatrix and species tree methods. We identified progenitors of the polyploids according to the relative rates at which their reads mapped to contigs from different diploid species. We sorted the polyploid reads into different putative sub-genomes and used the extracted contigs, along with the diploid sequences, to build new phylogenies that included the polyploid sub-genomes. This approach yielded a highly evidenced phylogenetic hypothesis for the genusBetula, including the complex reticulate origins of the majority of its polyploid taxa. The genus was split into two well supported clades, which differ in their seed-wing morphology. We propose a new taxonomy forBetula, splitting it into two subgenera. We have resolved the parentage of many widespread and economically important polyploid tree species, opening the way for their population genomic study.
A cell non-autonomous mechanism of yeast chronological aging regulated by caloric restriction and one-carbon metabolism
Authors: Enriquez-Hesles Elisa , Smith Daniel L. , Maqani Nazif , Wierman Margaret B. , Sutcliffe Matthew , Fine Ryan D. , Kalita Agata , Santos Sean M. , Muehlbauer Michael J. , Bain James R. , Janes Kevin A. , Hartman John L. , Hirschey Matthew D. , Smith Jeffrey S.
Published: July 2020

Caloric restriction (CR) improves healthspan and lifespan of organisms ranging from yeast to mammals. Understanding the mechanisms involved will uncover future interventions for aging associated diseases. In budding yeast,Saccharomyces cerevisiae, CR is commonly defined by reduced glucose in the growth medium, which extends both replicative and chronological lifespan (CLS). We found that conditioned media collected from stationary phase CR cultures extended CLS when supplemented into non-restricted (NR) cultures, suggesting a potential cell non-autonomous mechanism of CR-induced lifespan regulation. Chromatography and untargeted metabolomics of the conditioned media, as well as transcriptional responses associated with the longevity effect, pointed to specific amino acids enriched in the CR conditioned media (CRCM) as functional molecules, with L-serine being a particularly strong candidate. Indeed, supplementing L-serine into NR cultures extended CLS through a mechanism dependent on the one-carbon metabolism pathway, thus implicating this conserved and central metabolic hub in lifespan regulation.
Multi-Task Learning based 3-Dimensional Striatal Segmentation of MRI – a Multi-modal Objective Assessment
Authors: Serrano-Sosa Mario , Van Snellenberg Jared X. , Meng Jiayan , Spuhler Karl , Weinstein Jodi J. , Abi-Dargham Anissa , Slifstein Mark , Huang Chuan
Published: July 2020

The human striatum is a collection of subcortical nuclei that serves as a critical node in an information processing network. Recent studies have established a clear topographical and functional organization of projections to and from striatal regions that involves detailed and complex subdivisions of the striatum. Manual segmentation of these functional subdivisions is labor-intensive and time-consuming, yet automated methods have also been a challenging computational problem. Recently, deep learning has emerged as a powerful tool for various tasks, including semantic segmentation. Multi-Task Learning (MTL) is a machine learning technique that allows latent representations between related tasks to be shared during model prediction of multiple tasks with better accuracy. We utilized MTL to segment subregions of the striatum consisting of pre-commissural putamen (prePU), pre-commissural caudate (preCA), post-commissural putamen (postPU), post-commissural caudate (postCA), and ventral striatum (VST). Dice similarity coefficients (DSC) demonstrate excellent spatial agreement between manual and MTL-generated segmentations (≥ 0.72 across all striatal subregions). Further quantitative task-based analysis was also conducted. Binding potential values, BPND, of [11C]raclopride PET, and ROI time-series and whole-brain connectivity using fMRI images were compared between results generated from manual segmentations and MTL-generated segmentations. BPNDvalues from MTL-generated segmentations were shown to correlate well with manual segmentations with R2≥ 0.91 in all caudate and putamen subregions, and R2=0.69 in VST. Mean Pearson correlation coefficients of the fMRI data between MTL-generated and manual segmentations were also high in time-series (≥0.86) and whole-brain connectivity (≥0.89) across all subregions. We conclude that the MTL approach is a fast, robust and reliable method for 3D striatal subregion segmentation with results comparable to manually segmented ROIs.
The impact of dominance on adaptation in changing environments
Authors: Devi Archana , Jain Kavita
Published: July 2020

Natural environments are seldom static and therefore it is important to ask how a population adapts in a changing environment. We consider a finite, diploid population evolving in a periodically changing environment and study how the fixation probability of a rare mutant depends on its dominance coefficient and the rate of environmental change. We find that in slowly changing environments, the effect of dominance is the same as in the static environment, that is, if a mutant is beneficial (deleterious) when it appears, it is more (less) likely to fix if it is dominant. But in fast changing environments, the effect of dominance can be different from that in the static environment and is determined by the mutant’s fitness at the time of appearance as well as that in the time-averaged environment. We find that in a rapidly varying environment which is neutral on average, an initially beneficial (deleterious) mutant that arises while selection is decreasing (increasing) has a fixation probability lower (higher) than that for a neutral mutant as a result of which the recessive (dominant) mutant is favored. If the environment is beneficial (deleterious) on average but the mutant is deleterious (beneficial) when it appears in the population, the dominant (recessive) mutant is favored in a fast changing environment. We also find that when recurrent mutations occur, dominance does not have a strong influence on evolutionary dynamics.
Causal inference in environmental sound recognition
Authors: Traer James , Norman-Haignere Sam V. , McDermott Josh H.
Published: July 2020

Sound is caused by physical events in the world. Do humans infer these causes when recognizing sound sources? We tested whether the recognition of common environmental sounds depends on the inference of a basic physical variable – the source intensity (i.e., the power that produces a sound). A source’s intensity can be inferred from the intensity it produces at the ear and its distance, which is normally conveyed by reverberation. Listeners could thus use intensity at the ear and reverberation to constrain recognition by inferring the underlying source intensity. Alternatively, listeners might separate these acoustic cues from their representation of a sound’s identity in the interest of invariant recognition. We compared these two hypotheses by measuring recognition accuracy for sounds with typically low or high source intensity (e.g., pepper grinders vs. trucks) that were presented across a range of intensities at the ear or with reverberation cues to distance. The recognition of low-intensity sources (e.g., pepper grinders) was impaired by high presentation intensities or reverberation that conveyed distance, either of which imply high source intensity. Neither effect occurred for high-intensity sources. The results suggest that listeners implicitly use the intensity at the ear along with distance cues to infer a source’s power and constrain its identity. The recognition of real-world sounds thus appears to depend upon the inference of their physical generative parameters, even generative parameters whose cues might otherwise be separated from the representation of a sound’s identity.
scReQTL: an approach to correlate SNVs to gene expression from individual scRNA-seq datasets
Authors: Liu Hongyu , Prashant N M , Spurr Liam F. , Bousounis Pavlos , Alomran Nawaf , Ibeawuchi Helen , Sein Justin , Słowiński Piotr , Tsaneva-Atanasova Krasimira , Horvath Anelia
Published: July 2020

Recently, pioneering eQTLs studies on single cell RNA-seq (scRNA-seq) data have revealed new and cell-specific regulatory SNVs. Because eQTLs correlate genotypes and gene expression across multiple individuals, they are confined to SNVs with sufficient population frequency. Here, we present an alternative sc-eQTL approach – scReQTL - wherein we substitute the genotypes with expressed Variant Allele Fraction (VAFRNA) at heterozygous SNV sites. Our approach employs the advantage that, when estimated from multiple cells, VAFRNAcan be used to assess effects of rare SNVs in a single individual. ScReQTLs are enriched in known genetic interactions, therefore can be used to identify novel regulatory SNVs.
Linear vector models of time perception account for saccade and stimulus novelty interactions
Authors: Ghaderi Amirhossein , Niemeier Matthias , Crawford John Douglas
Published: July 2020

Various models (e.g., scalar, state-dependent network, and vector models) have been proposed to explain the global aspects of time perception, but they have not been tested against specific visual phenomena like perisaccadic time compression and novel stimulus time dilation. Here, in two separate experiments (N=31), we tested how the perceived duration of a novel stimulus is influenced by 1) a simultaneous saccade, in combination with 2) a prior series of repeated stimuli in human participants. This yielded a novel behavioral interaction: pre-saccadic stimulus repetition neutralizes perisaccadic time compression. We then tested these results against simulations of the above models. Our data yielded low correlations against scalar model simulations, high but non-specific correlations for our feedforward neural network, and correlations that were both high and specific for a vector model based on identity of objective and subjective time. These results demonstrate the power of global time perception models in explaining disparate empirical phenomena and suggest that subjective time has a similar essence to time’s physical vector.
Cell-wall-deficient Bacteria in Oral Biofilm: Association with Periodontitis
Authors: Germano Francesco , Testi Davide , Campagnolo Luisa , Scimeca Manuel , Arcuri Claudio
Published: July 2020

Cell-wall-deficient bacteria are those that lack cell walls and live in a pleomorphic state. The genus Mycoplasma and L-form bacteria are both members of this group. The aim of this study was to search cell-wall-deficient bacteria in periodontal biofilm and link their presence to periodontal disease. Eighty-nine individuals were recruited and divided into three groups: periodontally healthy individuals, individuals with chronic periodontitis, and those with aggressive periodontitis. The presence of cell-wall-deficient bacteria was detected in freshly collected biofilm by light microscopy, transmission electron microscopy (TEM) with and without electron microscopy in situ hybridization, atomic force microscopy and DNA stain (Hoechst). A new dichotomic index of classification for prevalence and morphologic variants was developed to classify cell-wall-deficient bacteria in periodontal biofilm. Cell-wall-deficient bacteria were found in periodontal biofilm and classified into Protoplastic, Everted, Filament and Intracellular forms, the last one mainly associated with aggressive periodontitis. We also assessed the prevalence of periodontopathic bacteria by means of polymerase chain-reaction (PCR) and found no clear, statistically significant, correlation among periodontal pathogens tested (except T. denticola) that allowed individuals with chronic periodontitis to be distinguished from those with aggressive periodontitis. Association between cell-wall-deficient bacteria and periodontal condition was: periodontally healthy, 3.3% (1/30); individuals with chronic periodontitis, 30.6% (11/36); and those with aggressive periodontitis, 100% (23/23). Cell-wall-deficient bacteria were detected in periodontal biofilm and linked to aggressive periodontitis.
Regional Differences in the Ghrelin-Growth Hormone Secretagogue Receptor Signalling System in Human Heart Disease
Authors: Sullivan Rebecca , Randhawa Varinder K , Lalonde Tyler , Yu Tina , Kiaii Bob , Luyt Leonard , Wisenberg Gerald , Dhanvantari Savita
Published: July 2020

The hormone ghrelin and its receptor, the growth hormone secretagogue receptor (GHSR) are expressed in myocardium. GHSR binding activates signalling pathways coupled to cardiomyocyte survival and contractility. These properties have made the ghrelin-GHSR axis a candidate for a biomarker of cardiac function. The dynamics of ghrelin-GHSR are altered significantly in late stages of heart failure and cardiomyopathy, when left ventricular (LV) function is failing. We examined the relationship of GHSR with ghrelin in cardiac tissue from patients with valvular disease with no detectable changes in LV function. Biopsy samples from the LV and left atrium (LA) were obtained from 25 patients with valvular disease (of whom 13 also had coronary artery disease) and preserved LV ejection fraction, and compared control samples obtained via autopsy. Using quantitative confocal fluorescence microscopy, levels of GHSR were determined using a fluorescent peptide analog of ghrelin, Cy5-ghrelin(1-19); ghrelin, the heart failure marker natriuretic peptide type-b (BNP), and contractility marker sarcoplasmic reticulum ATPase pump (SERCA2a) were measured by immunofluorescence. A positive correlation between GHSR and ghrelin was apparent in only diseased tissue. Ghrelin and BNP significantly correlated in the LV and strongly co-localized to the same intracellular compartment in both diseased and control tissue. GHSR, ghrelin and BNP all strongly and significantly correlated with SERCA2a in the LV of diseased tissue only. Our results suggest that the dynamics of the myocardial ghrelin/GHSR axis is altered in cardiovascular disease in the absence of measurable changes in heart function, and may accompany a regional shift in endocrine programming.
Maximizing cooperation in the prisoner’s dilemma evolutionary game via optimal control
Authors: Newton P.K. , Ma Y.
Published: July 2020

The prisoner’s dilemma (PD) game offers a simple paradigm of competition between two players who can either cooperate or defect. Since defection is a strict Nash equilibrium, it is an asymptotically stable state of the replicator dynamical system that uses the PD payoff matrix to define the fitness landscape of two interacting evolving populations. The dilemma arises from the fact that the average payoff of this asymptotically stable state is sub-optimal. Coaxing the players to cooperate would result in a higher payoff for both. Here we develop an optimal control theory for the prisoner’s dilemma evolutionary game in order to maximize cooperation (minimize the defector population) over a given cycle-timeT, subject to constraints. Our two time-dependent controllers are applied to the off-diagonal elements of the payoff matrix in a bang-bang sequence that dynamically changes the game being played by dynamically adjusting the payoffs, with optimal timing that depends on the initial population distributions. Over multiple cyclesnT(n> 1), the method is adaptive as it uses the defector population at the end of thenthcycle to calculate the optimal schedule over then+ 1stcycle. The control method, based on Pontryagin’s maximum principle, can be viewed as determining the optimal way to dynamically alter incentives and penalties in order to maximize the probability of cooperation in settings that track dynamic changes in the frequency of strategists, with potential applications in evolutionary biology, economics, theoretical ecology, and other fields where the replicator system is used.

PACS numbers

02.50.Le; 02.30.Yy; 05.45.-a; 87.23.Kg; 87.23.Cc
The National Early Warning Score (NEWS2) systematically underestimates the risk of in-hospital mortality in unplanned COVID-19 admissions to hospital
Authors: Richardson Donald , Faisal Muhammad , Fiori Massimo , Beatson Kevin , Mohammed Mohammed A
Published: July 2020

Background

Although the National Early Warning Score (NEWS) and its latest version NEWS2 are recommended for monitoring for deterioration in patients admitted to hospital, little is known about their performance in COVID-19 patients. We analysed the performance of National Early Warning Score (NEWS2) during the first phase of the COVID-19 pandemic.

Methods

Adult non-elective admissions discharged between 11-March-2020 to 13-June-2020 with an index NEWS2 electronically recorded within ±24 hours of admission are used to predict mortality at four time points (in-hospital, 24hours, 48hours, and 72hours) in COVID-19 versus non-COVID-19 admissions.

Results

Out of 6480 non-elective admissions, 620 (9.6%) had a diagnosis of COVID-19. They were older (73.3 vs 67.7yrs), more often male (54.7% vs 50.1%), had higher index NEWS (4 vs 2.5) and NEWS2 (4.6 vs 2.8) scores and higher in-hospital mortality (32.1% vs 5.8%). The c-statistics for predicting in-hospital mortality in COVID-19 admissions was significantly lower using NEWS (0.64 vs 0.74) or NEWS2 (0.64 vs 0.74), however these differences reduced at 72hours (NEWS: 0.75 vs 0.81; NEWS2: 0.71 vs 0.81), 48 hours (NEWS: 0.78 vs 0.81; NEWS2: 0.76 vs 0.82) and 24hours (NEWS: 0.84 vs 0.84; NEWS2: 0.86 vs 0.84). Increasing NEWS2 values reflected increased mortality, but for any given value the absolute risk was on average 24% higher (e.g.NEWS2=5: 36% vs 9%).

Interpretation

NEWS2 is a valid predictor of the mortality risk but substantially underestimates the absolute mortality risk in COVID-19 patients. Clinical staff and escalation protocols based on NEWS2 need to make note of this finding.