bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconciling Ecogeographical Rules: Rainfall and Temperature Predict Global Colour Variation in the Largest Bird Radiation
Authors: Delhey Kaspar , Dale James , Valcu Mihai , Kempenaers Bart
Published: December 2018

Ecogeographical rules that associate climate with organismal form and function can reveal patterns of climatic adaptation. Two rules link animal coloration with climate: Gloger’s rule (darker coloration where wet and warm), and Bogert’s rule (darker coloration where cold). Whereas Gloger’s rule was proposed for endotherms, and Bogert’s rule for ectotherms, both rules may apply more broadly, despite their seemingly opposing effects. Here we test this contradiction on a global scale across passerine birds. Consistent with Gloger’s rule, birds were darker in wetter areas and, following Bogert’s rule, lighter where warm, although birds became lighter again at very low temperatures. Rainfall and temperature had antagonistic or additive effects depending on their pattern of covariation, and this predicted whether birds followed the rules. We integrate both rules into a general framework to explain heterogeneity in climatic effects on coloration, which has implications to understand patterns of diversification, climatic adaptation and climate change impacts.
Transcriptional logic of cell fate specification and axon guidance in early born retinal neurons revealed by single-cell mRNA profiling
Authors: Giudice Quentin Lo , Leleu Marion , Fabre Pierre J.
Published: December 2018

Retinal ganglion cells (RGC), together with cone photoreceptors, horizontal cells (HC) and amacrine cells (AC), are the first classes of neurons produced in the retina. Here we have profiled 5348 single retinal cells and provided a comprehensive transcriptomic atlas showing the broad diversity of the developing retina at the time when the four early-born cells are being produced. Our results show the transcriptional sequences that establish the hierarchical ordering of early cell fate specification in the retina. RGC maturation follows six waves of gene expression, giving new insight into the regulatory logic of RGC differentiation. Early-generated RGCs transcribe an increasing amount of guidance cues for young peripheral RGC axons that express the matching receptors. Finally, spatial signatures in sub-populations of RGCs allowed to define novel molecular markers that are spatially restricted during the development of the retina. Altogether this study is a valuable resource that identifies new players in mouse retinal development, shedding light on transcription factors sequence and guidance cues dynamics in space and time.
BetaScan2: Standardized statistics to detect balancing selection utilizing substitution data:
Authors: Siewert Katherine M , Voight Benjamin F
Published: December 2018

The recently reported statistic β detects balanced haplotypes without the need for genomic data from an outgroup species. Here we present an extension to the method that incorporates between-species substitution data into the β statistic framework. We show that this approach outperforms existing summary statistics in simulations. We also present the variance of β with and without substitution data, allowing calculation of a standardized score. Besides providing a measure of significance, this enables a proper comparison of β values across varying underlying parameters, a feature lacking from some related methods.
Genomic features of parthenogenetic animals
Authors: Jaron Kamil S. , Bast Jens , Nowell Reuben W. , Ranallo-Benavidez T. Rhyker , Robinson-Rechavi Marc , Schwander Tanja
Published: December 2018

Evolution without sex is predicted to impact genomes in numerous ways. Case studies of individual parthenogenetic animals have reported peculiar genomic features which were suggested to be caused by their mode of reproduction, including high heterozygosity, a high abundance of horizontally acquired genes, a low transposable element load, or the presence of palindromes. We systematically characterized these genomic features in published genomes of 26 parthenogenetic animals representing at least 18 independent transitions to asexuality. Surprisingly, not a single feature was systematically replicated across a majority of these transitions, suggesting that previously reported patterns were lineage specific rather than illustrating general consequences of parthenogenesis. We found that only parthenogens of hybrid origin were characterized by high heterozygosity levels. Parthenogens that were not of hybrid origin appeared to be largely homozygous, independently of the cellular mechanism underlying parthenogenesis. Overall, despite the importance of recombination rate variation for the evolution of sexual animal genomes, the genome-wide absence of recombination does not appear to have had the dramatic effects which are expected from classical theoretical models. The reasons for this are probably a combination of lineage-specific patterns, impact of the origin of parthenogenesis, and a survivorship bias of parthenogenetic lineages.
Whole blood transcriptome analysis in bipolar disorder reveals strong lithium effect
Authors: Krebs Catharine E. , Ori Anil P.S. , Vreeker Annabel , Wu Timothy , Cantor Rita M. , Boks Marco P. , Kahn Rene S. , Olde Loohuis Loes M. , Ophoff Roel A.
Published: December 2018

Bipolar disorder (BD) is a highly heritable mood disorder with complex genetic architecture and poorly understood etiology. We performed a whole blood transcriptome analysis in a BD case-control sample (Nsubjects = 480) by RNA sequencing. While we observed widespread differential gene expression patterns between affected and unaffected individuals, these effects were largely linked to lithium treatment at the time of blood draw (FDR < 0.05, Ngenes = 976) rather than BD diagnosis itself (FDR < 0.05, Ngenes = 6). These lithium-associated genes were enriched for cell signaling and immune response functional annotations, among others, and were associated with neutrophil cell-type proportions, which were elevated in lithium users. Neither genes with altered expression in cases nor in lithium users were enriched for BD, schizophrenia, and depression genetic risk based on information from genome-wide association studies, nor was gene expression associated with polygenic risk scores for BD. Our findings suggest that BD is associated with minimal changes in whole blood gene expression independent of medication use but underline the importance of accounting for medication use and cell type heterogeneity in psychiatric transcriptomic studies. The results of our study add to mounting evidence of lithium's cell signaling and immune-related mechanisms.
Multinomial modelling of TB/HIV co-infection yields a robust predictive signature and generates hypotheses about the HIV+TB+ disease state
Authors: Duffy Fergal J , Thompson Ethan G. , Scriba Thomas J. , Zak Daniel E
Published: December 2018

Background

Current diagnostics are inadequate to meet the challenges presented by coinfection withMycobacterium tuberculosis(Mtb) and HIV, the leading cause of death for HIV-infected individuals. Improved characterisation of Mtb/HIV coinfection as a distinct disease state may lead to better identification and treatment of affected individuals.

Methods

Four previously published TB and HIV co-infection related datasets were used to train and validate multinomial machine learning classifiers that simultaneously predict TB and HIV status. Classifier predictive performance was measured using leave-one-out cross validation on the training set and blind predictive performance on multiple test sets using area under the ROC curve (AUC) as the performance metric. Linear modelling of signature gene expression was applied to systematically classify genes as TB-only, HIV-only or combined TB/HIV.

Results

The optimal signature discovered was a single 10-gene random forest multinomial signature that robustly discriminates active tuberculosis (TB) from other non-TB disease states with improved performance compared with previously published signatures (AUC: 0. 87), and specifically discriminates active TB/HIV co-infection from all other conditions (AUC: 0.88). Signature genes exhibited a variety of transcriptional patterns including both TB-only and HIV-only response genes and genes with expression patterns driven by interactions between HIV and TB infection states, including the CD8+ T-cell receptor LAG3 and the apoptosis-related gene CERKL.

Conclusions

By explicitly including distinct disease states within the machine learning analysis framework, we developed a compact and highly diagnostic signature that simultaneously discriminates multiple disease states associated with Mtb/HIV co-infection. Examination of the expression patterns of signature genes suggests mechanisms underlying the unique inflammatory conditions associated with active TB in the presence of HIV. In particular, we observed that disregulation of CD8+ effector T-cell and NK-cell associated genes may be an important feature of Mtb/HIV co-infection.
Improving the usability and comprehensiveness of microbial databases
Authors: Loeffler Caitlin , Karlsberg Aaron , Martin Lana S. , Eskin Eleazar , Koslicki David , Mangul Serghei
Published: December 2018

Metagenomics studies leverage genomic reference databases to generate discoveries in basic science and translational research. However, current microbial studies use disparate reference databases that lack consistent standards of specimen inclusion, data preparation, taxon labelling and accessibility, hindering their quality and comprehensiveness, and calling for the establishment of recommendations for reference genome database assembly. Here, we analyze existing fungal and bacterial databases and discuss guidelines for the development of a master reference database that promises to improve the quality and quantity of omics research.
Predicting Brain Age Using Structural Neuroimaging and Deep Learning
Authors: Varatharajah Yogatheesan , Baradwaj Sujeeth , Kiraly Atilla , Ardila Diego , Iyer Ravishankar , Shetty Shravya , Kohlhoff Kai
Published: December 2018

Early detection of age-related diseases will greatly benefit from a model of the underlying biological aging process. In this paper, we develop a brain-age predictor by using structural magnetic resonance imaging (SMRI) and deep learning and evaluate the predicted brain age as a marker of brain-aging in Alzheimer's disease. Our approach does not require any domain knowledge in that it trains end-to-end on the SMRI image itself, and has been validated on real SMRI data collected from elderly subjects. We developed two different models by using convolutional neural network (CNN) based regression and bucket classification to predict brain ages from SMRI images. Our models achieved root mean squared errors (RMSE) of 5.54 and 6.44 years in predicting brain ages of healthy subjects. Further analysis showed that there is a substantial difference between the predicted brain ages of cognitively impaired and healthy subjects with similar chronological ages.
Next-generation sequencing based hospital outbreak investigation yields insight into Klebsiella aerogenes population structure and determinants of carbapenem resistance and virulence
Authors: Malek Adel , McGlynn Kelly , Taffner Samantha , Fine Lynn , Tesini Brenda , Wang Jun , Mostafa Heba H , Petry Sharon , Perkins Archibald , Graman Paul , Hardy Dwight J , Pecora Nicole Danielle
Published: December 2018

Klebsiella aerogenes is a nosocomial pathogen associated with drug resistance and outbreaks in intensive care units. In a 5-month period in 2017, we experienced an increased incidence of positive cultures for carbapenem-resistant K. aerogenes (CR-KA) from an adult cardiothoracic intensive care unit (CICU) involving 15 patients. Phylogenomic analysis following whole-genome sequencing (WGS) identified the outbreak CR-KA isolates to group together as a tight clonal cluster (<7 SNPs apart), suggestive of a protracted intra-ward transmission event. No clonal relationships were identified between the CICU CR-KA strains and additional hospital CR-KA patient isolates from different wards and/or previous years. Genes encoding carbapenemases or drug-resistant plasmids were absent in the outbreak strains, and carbapenem resistance was attributed to mutations impacting AmpD activity and membrane permeability. The CICU outbreak strains harbored an integrative conjugative element (ICEKp10), which has been associated with pathogenicity in hypervirulent Klebsiella pneumoniae lineages. Comparative genomics with global K. aerogenes genomes showed our outbreak strains to group closely with global ST4 strains, which along with ST93 likely represent dominant K. aerogenes lineages associated with human infections. WGS is a powerful tool that goes beyond high-resolution tracking of transmission events into identifying the genetic basis of drug-resistance and virulence, which are not part of conventional diagnostic workflows. With an increasing availability of sequenced genomes from across the globe, population structure analysis offers opportunities to identify emerging trends and dominant clones associated with specific syndromes and geographical locations for poorly characterized pathogens.
Warming can destabilise predator-prey interactions by shifting the functional response from Type III to Type II
Authors: Daugaard Uriah , Petchey Owen , Pennekamp Frank
Published: December 2018

The potential for climate change and temperature shifts to affect community stability remains relatively unknown. One mechanism by which temperature may affect stability is by altering trophic interactions. The functional response quantifies the per capita resource consumption by the consumer as a function of resource abundance and is a suitable framework for the description of nonlinear trophic interactions. We studied the effect of temperature on a ciliate predator-prey pair (Spathidium sp. and Dexiostoma campylum) by estimating warming effects on the functional response and on the associated conversion efficiency of the predator. We recorded prey and predator dynamics over 24 hours and at three temperature levels (15, 20 and 25 C). To these data we fitted a population dynamic model including the predator functional response, such that the functional response parameters (space clearance rate, handling time, and density dependence of space clearance rate) were estimated for each temperature separately. To evaluate the ecological significance of temperature effects on the functional response parameters we simulated predator-prey population dynamics. We considered the predator-prey system to be destabilised, if the prey was driven extinct by the predator. Effects of increased temperature included a transition of the functional response from a Type III to a Type II and an increase of the conversion efficiency of the predator. The simulated population dynamics showed a destabilisation of the system with warming, with greater risk of prey extinction at higher temperatures likely caused by the transition from a Type III to a Type II functional response. Warming-induced shifts from a Type III to II are not commonly considered in modelling studies that investigate how population dynamics respond to warming. Future studies should investigate the mechanism and generality of the effect we observed and simulate temperature effects in complex food webs including shifts in the type of the functional response as well as consider the possibility of a temperature dependent conversion efficiency.
Caterpillars on a phytochemical landscape: the case of alfalfa and the Melissa blue butterfly
Authors: Forister Matthew L. , Yoon Su’ad , Philbin Casey S. , Dodson Craig D. , Hart Bret , Harrison Joshua G. , Shelef Oren , Fordyce James A. , Marion Zachary H. , Nice Christopher C. , Richards Lora A. , Buerkle C. Alex , Gompert Zach
Published: December 2018

Modern metabolomic approaches that generate more comprehensive phytochemical profiles than were previously available are providing new opportunities for understanding plant-animal interactions. Specifically, we can characterize the phytochemical landscape by asking how a larger number of individual compounds affect herbivores and how compounds covary among plants. Here we use the recent colonization of alfalfa (Medicago sativa) by the Melissa blue butterfly (Lycaeides melissa) to quantify plant metabolites and the performance of caterpillars as affected by both individual compounds and suites of covarying phytochemicals. We find that survival, development time and adult weight are all associated with variation in nutrition and toxicity, including biomolecules associated with plant cell function as well as putative anti-herbivore action. The plant-insect interface is complex, with clusters of covarying compounds in many cases encompassing divergent effects on different aspects of caterpillar performance. Individual compounds with the strongest associations are largely specialized metabolites, including alkaloids, phenolic glycosides and saponins. The saponins are represented in our data by more than 25 individual compounds with beneficial and detrimental effects onL. melissacaterpillars, which highlights the value of metabolomic data as opposed to approaches that rely on total concentrations within broad defensive classes.
Focussing on resistance to front-line drugs is the most effective way to combat the antimicrobial resistance crisis
Authors: Perry Meghan R , McClean Deirdre , Simonet Camille , Woolhouse Mark , McNally Luke
Published: December 2018

In medical, scientific and political arenas relating to antimicrobial resistance (AMR) there is currently an intense focus on multi-drug resistant pathogens that render last-line antimicrobial treatments ineffective. We question the current emphasis of attention on resistance to last-line antimicrobials, arguing that tackling resistance to front-line antimicrobials has a greater public health benefit. Using AMR monitoring data on 25 drug-pathogen combinations from across Europe, here we show that the presence of front-line pathogen resistance initiates a cascade of resistance selection that ultimately leads to pathogen resistance to last-line antimicrobials. We then interrogate, by modelling the dynamics of resistance evolution, whether 3 key interventions in the strategic response to AMR are more effectively targeted at front-line or last-line treatment. We show that interventions that make front-line therapy more effective by use of antimicrobial adjuvants or front-line resistance diagnostics or by introduction of a novel, front-line antimicrobial all lead to a larger reduction in mortality and morbidity than the same interventions implemented in last-line therapy. Mass use of a newly discovered antimicrobial in front-line infection management to maximise its public health benefit is contrary to current policy but may provide valuable incentives for drug developers. We demonstrate that funding, publications, and attention to those publications do not reflect the importance of front-line antimicrobials and are disproportionately devoted to last-line antimicrobials that account for less than 10% of antimicrobial prescriptions. While studying resistance to last-line drugs is undoubtedly important, our work relays a strong message to public health agencies, funding bodies, and researchers that allocating resources to front-line infections can be a more effective way to combat the antimicrobial resistance crisis.
Macronutrients modulate resistance to infection and immunity in Drosophila
Authors: Ponton Fleur , Morimoto Juliano , Robinson Katie , Kumar Sheemal S , Cotter Sheena , Wilson Kenneth , Simpson Stephen J.
Published: December 2018

Immunity and nutrition are two essential modulators of individual fitness However, while the implications of immune function and nutrition on an individual s lifespan and reproduction are known, the interplay between feeding behaviour, infection, and immune function, remains poorly understood. In this study, we used the fruit fly, Drosophila melanogaster, to investigate how infection through septic injury modulates nutritional intake, and how macronutrient balance affects survival to infection by the pathogenic Gram-positive bacterium Micrococcus luteus. Our results show that infected flies maintain carbohydrate intake, but reduce protein intake, thereby shifting from a protein-to-carbohydrate (P:C) ratio of ~1:4 to ~1:10 relative to non-infected and sham-infected flies. Strikingly, we found that the proportion of flies dying after M. luteus infection was significantly lower when flies were fed a low-P high-C diet, revealing that flies shift their macronutrient intake as means of nutritional self-medication against bacterial infection. This is likely due to the effects of macronutrient balance on the regulation of the constitutive expression of innate immune genes, as a low-P high-C diet was linked to an up-regulation in the expression of key antimicrobial peptides. Together, our results reveal the intricate relationship between macronutrient intake and resistance to infection, and integrate the molecular cross-talk between metabolic and immune pathways into the framework of nutritional immunology.
Metabolic excretion associated with nutrient-growth dysregulation promotes the rapid evolution of an overt metabolic defect
Authors: Green Robin , Sonal  , Wang Lin , Hart Samuel F.M. , Lu Wenyun , Skelding David , Burton Justin C. , Mi Hanbing , Capel Aric , Chen Hung Alex , Lin Aaron , Subramaniam Arvind R. , Rabinowitz Joshua D. , Shou Wenying
Published: December 2018

In eukaryotes, conserved mechanisms ensure that cell growth is coordinated with nutrient availability. Overactive growth during nutrient limitation (“nutrient-growth dysregulation”) can lead to rapid cell death. Here, we demonstrate that cells can adapt to nutrient-growth dysregulation by evolving major metabolic defects. Specifically, when yeast lysine auxotrophic mutant lys- encountered lysine limitation, an evolutionarily novel stress, cells suffered nutrient-growth dysregulation. A sub-population repeatedly evolved to lose the ability to synthesize organosulfurs (lys-orgS-). Organosulfurs, mainly glutathione and glutathione conjugates, were released by lys- cells during lysine limitation when growth was dysregulated, but not during glucose limitation when growth was regulated. Limiting organosulfurs conferred a frequency-dependent fitness advantage to lys-orgS- by eliciting a proper slow growth program including autophagy. Thus, nutrient-growth dysregulation is associated with rapid organosulfur release, which enables the selection of organosulfur auxotrophy to better tune cell growth to the metabolic environment. We speculate that evolutionarily novel stresses can trigger atypical release of certain metabolites, setting the stage for the evolution of new ecological interactions.
Assembly Defects Abrogate Proofreading by Initiation Factors and License the Entry of Premature Ribosomes into the Translation Cycle:
Authors: Sharma Himanshu , Anand B
Published: December 2018

Numerous quality control steps are deployed by the translational machinery to ensure faithful decoding of genetic message to synthesize proteins. However, what transpires to quality control mechanism during protein synthesis when the ribosomes are produced with assembly defects remains enigmatic. In E. coli, we show that ribosomes with assembly defects evade the proofreading steps during translation initiation and participate in the translation cycle. Such ribosomes show severely compromised decoding capabilities that give rise to errors in initiation and elongation. Tracing the genesis, we discovered that the assembly defects compromise the binding of initiation factors, thus licensing the rapid transitioning of 30S (pre) initiation complex to 70S initiation complex by tempering the proofreading mechanism. Overall, our work highlights that a mass balance deficit between premature ribosomes and initiation factors steers the entry of premature ribosomes into the translation cycle.
Believing in one's power: a counterfactual heuristic for goal-directed control
Authors: Chambon Valerian , Thero Heloise , Findling Charles , Koechlin Etienne
Published: December 2018

Most people envision themselves as operant agents endowed with the capacity to bring about changes in the outside world. This ability to monitor one's own causal power has long been suggested to rest upon a specific model of causal inference, i.e., a model of how our actions causally relate to their consequences. What this model is and how it may explain departures from optimal inference, e.g., illusory control and self-attribution biases, are still conjecture. To address this question, we designed a series of novel experiments requiring participants to continuously monitor their causal influence over the task environment by discriminating changes that were caused by their own actions from changes that were not. Comparing different models of choice, we found that participants' behaviour was best explained by a model deriving the consequences of the forgone action from the current action that was taken and assuming relative divergence between both. Importantly, this model agrees with the intuitive way of construing causal power as "difference-making" in which causally efficacious actions are actions that make a difference to the world. We suggest that our model outperformed all competitors because it closely mirrors people's belief in their causal power - a belief that is well-suited to learning action-outcome associations in controllable environments. We speculate that this belief may be part of the reason why reflecting upon one's own causal power fundamentally differs from reasoning about external causes.
Unidirectional response to bidirectional selection on body size. I. Phenotypic, life history and endocrine response
Authors: Renneville Clémentine , Millot Alexis , Agostini Simon , Carmignac David , Maugars Gersende , Dufour Sylvie , Le Rouzic Arnaud , Edeline Eric
Published: December 2018

Anthropogenic perturbations such as harvesting often select against a large body size and are predicted to induce rapid evolution towards smaller body sizes and earlier maturation. However, body-size evolvability and, hence, adaptability to anthropogenic perturbations remain seldom evaluated in wild populations. Here, we use a laboratory experiment over 6 generations to measure the ability of wild-caught medaka fish (Oryzias latipes) to evolve in response to bidirectional size-dependent selection mimicking opposite harvest regimes. Specifically, we imposed selection against a small body size (Large line), against a large body size (Small line) or random selection (Control line), and measured correlated responses across multiple phenotypic, life-history and endocrine traits. As expected, the Large line evolved faster somatic growth and delayed maturation, but also evolved smaller body sizes at hatch, with no change in average levels of pituitary gene expressions of luteinizing, folliclestimulating or growth (GH) hormones. In contrast, the Small medaka line was unable to evolve smaller body sizes or earlier maturation, but evolved smaller body sizes at hatch and showed marginally-significant signs of increased reproductive investment, including larger egg sizes and elevated pituitary GH production. Natural selection on medaka body size was too weak to significantly hinder the effect of artificial selection, indicating that the asymmetric body-size response to size-dependent selection reflected an asymmetry in body-size evolvability. Our results show that trait evolvability may be contingent upon the direction of selection, and that a detailed knowledge of trait evolutionary potential is needed to forecast population response to anthropogenic change.
TORC2 dependent phosphorylation modulates calcium regulation of fission yeast myosin
Authors: Baker Karen , Gyamfi Irene A. , Mashanov Gregory I. , Molloy Justin E. , Geeves Michael A. , Mulvihill Daniel P.
Published: December 2018

All cells have the ability to respond to changes in their environment. Signalling networks modulate cytoskeleton and membrane organisation to impact cell cycle progression, polarised cell growth and multicellular development according to the environmental setting. Using diversein vitro, in vivoand single molecule techniques we have explored the role of myosin-1 signalling in regulating endocytosis during both mitotic and meiotic cell cycles. We have established that a conserved serine within the neck region of the sole fission yeast myosin-1 is phosphorylated in a TORC2 dependent manner to modulate myosin function. Myo1 neck phosphorylation brings about a change in the conformation of the neck region and modifies its interaction with calmodulins, Myo1 dynamics at endocytic foci, and promotes calcium dependent switching between different calmodulin light chains. These data provide insight into a novel mechanism by which myosin neck phosphorylation modulates acto-myosin dynamics to control polarised cell growth in response to mitotic and meiotic cell-cycle progression and the cellular environment.
A metabolic switch from OXPHOS to glycolysis is essential for cardiomyocyte proliferation in the regenerating heart
Authors: Honkoop Hessel , de Bakker Dennis , Aharonov Alla , Kruse Fabian , Shakked Avraham , Nguyen Phong , de Heus Cecilia , Garric Laurence , Muraro Mauro , Shoffner Adam , Tessadori Federico , Peterson Joshua , Noort Wendy , Posthuma George , Grun Dominic , van der Laarse Willem , Klumperman Judith , Jaspers Richard , Poss Kenneth , van Oudenaarden Alexander , Tzahor Eldad , Bakkers Jeroen
Published: December 2018

The capacity to regenerate damaged tissues, such as the heart, various enormously amongst species. While heart regeneration is generally very low in mammals, it can regenerate efficiently in certain amphibian and fish species. Zebrafish has been used extensively to study heart regeneration, resulting in the identification of proliferating cardiomyocytes that drive this process. However, mechanisms that drive cardiomyocyte proliferation are largely unknown. Here, using a single-cell mRNA-sequencing approach, we find a transcriptionally distinct population of dedifferentiated and proliferating cardiomyocytes in regenerating zebrafish hearts. While adult cardiomyocytes are known to rely on mitochondrial oxidative phosphorylation (OXPHOS) for energy production, these proliferating cardiomyocytes show reduced mitochondrial gene expression and decreased OXPHOS activity. Strikingly, we find that genes encoding rate-limiting enzymes of the glycolysis pathway are induced in the proliferating cardiomyocytes, and inhibiting glycolysis impairs cardiomyocyte cell cycle reentry. Mechanistically, glycolytic gene expression is induced by Nrg1/Erbb2 signaling, and this is conserved in a mouse model of enhanced regeneration. Moreover, inhibiting glycolysis in murine cardiomyocytes abrogates the mitogenic effects of Nrg1/ErbB2 signaling. Together these results reveal a conserved mechanism in which cardiomyocytes undergo metabolic reprogramming by activating glycolysis, which is essential for cell cycle reentry and heart regeneration. This could ultimately help develop therapeutic interventions that promote the regenerative capacity of the mammalian heart.
Consensify: a method for generating pseudohaploid genome sequences from palaeogenomic datasets with reduced error rates
Authors: Barlow Axel , Hartmann Stefanie , Gonzalez Javier , Hofreiter Michael , Paijmans Johanna L.A.
Published: December 2018

A standard practise in palaeogenome analysis is the conversion of mapped short read data into pseudohaploid sequences, typically by selecting a single high quality nucleotide at random from the stack of mapped reads. This controls for biases due to differential sequencing coverage but it does not control for differential rates and types of sequencing error, which are frequently large and variable in datasets obtained from ancient samples. These errors have the potential to distort phylogenetic and population clustering analyses, and to mislead tests of admixture using D statistics. We introduce Consensify, a method for generating pseudohaploid sequences which controls for biases resulting from differential sequencing coverage while greatly reducing error rates. The error correction is derived directly from the data itself, without the requirement for additional genomic resources or simplifying assumptions such as contemporaneous sampling. For phylogenetic analysis, we find that Consensify is less affected by branch length artefacts than methods based on standard pseudohaploidisation, and it performs similarly for population clustering analysis based on genetic distances. For D statistics, Consensify is more resistant to false positives and appears to be less affected by biases resulting from different laboratory protocols than other available methods. Although Consensify is developed with palaeogenomic data in mind, it is applicable for any low to medium coverage short read datasets. We predict that Consenify will be a useful tool for future studies of palaeogenomes.
Prevention of chromatin destabilization by FACT is crucial for malignant transformation
Authors: Sandlesh Poorva , Safina Alfiya , Goswami Imon , Prendergust Laura , Rosario Spenser , Gomez Eduardo C , Wang Jianmin , Gurova Katerina V
Published: December 2018

Expression of histone chaperone FACT is increased in tumors and associated with poor prognosis. We investigated why aggressive tumor cells need FACT using a model where FACT could be turned off and confirmed that while FACT is not essential for non-tumor cells, cells become dependent on FACT following oncogene-induced transformation. We compared the phenotypic and transcriptional changes induced by FACT loss and excluded a direct role for FACT in the transcription of genes essential for the viability of transformed cells. Moreover, we established that in immortalized and transformed cells, FACT has a weak negative effect on gene expression. At the same time, we observed a positive correlation between FACT enrichment and the rate of transcription, which was consistent with previous reports. To explain these puzzling observations, we hypothesized that FACT does not facilitate transcription elongation in transformed cells, but prevents nucleosome loss associated with transcription. Indeed, we observed destabilization of chromatin in immortalized and transformed cells upon FACT loss. Furthermore, transformed cells had less stable chromatin than non-transformed cells, which made them vulnerable to FACT loss. However, the mechanisms of cell death upon chromatin destabilization needs to be established. Our data suggest that malignant transformation is accompanied by general chromatin destabilization, and FACT prevents irredeemable chromatin loss.
Microbial contamination in the genome of the domesticated olive
Authors: Reiter Taylor , Brown C. Titus
Published: December 2018

Draft genomes of both the wild and domesticated olive were recently published. While working with these genomes, we identified contamination in the domesticated olive genome representing .06% of basepairs and 1.3% of scaffolds. We used targeted and untargeted approaches to identify the contaminating sequences, the majority of which were *Aureobasidium pullulans*. We applied the same method to the wild olive genome and did not find evidence of contamination. Although contamination in the domesticated olive genome was not prolific, it could lead to biased results either from functional content encoded in the contaminant sequences, or from using it to separate microbial reads from olive reads in microbiome studies.
Dissecting the dilemma betweenin vitroandin vivodrug screening: treating HepG2 cells with Artesunate as a model
Authors: Wong Johnny Kuan-Un , Shi Sophie Ling , Wang Haitao , Xing Fuqiang , Quan Yingyao , Zhao Ming , Zhang Lei , Wong Kristy Hio-Meng , Wong Ada Hang-Heng , Deng Chuxia
Published: December 2018

The dilemma betweenin vitroandin vivodrug screening results persisted to hinder preclinical anti-cancer drug development. In this study, drug screening was initially performed on monolayer cultures of HepG2 cells, whereasin vivodrug testing was performed on the subcutaneous xenograft mouse model of HepG2 cells in athymic nude mice. Results showed that Artesunate inhibited HepG2 cell growthin vitro, but was ineffectivein vivo. Hence, we investigated the difference betweenin vitroandin vivosettings using this cell-drug combination as a model. Immuno-staining of hepatocellular carcinoma (HCC) biomarkers showed that α-fetoprotein (AFP) was unaffected by Artesunate treatmentin vitroorin vivo, suggesting that AFP was neither a biomarker nor response indicator. Alternatively, high albumin was detected in both monolayer and organoid cultures; contrariwise, the xenograft tumors prevailed low albumin, in consistency to human HCC with poor prognosis. Artesunate treatment reduced intracellular albumin expressionin vitro; Artesunate did not alter tissue and serum albumin in xenograft mice, in coincidence with its irresponsivenessin vivo. However, Artesunate binding to albumin was undetectable. Instead, we observed a transient stimulation of Erk1/2 phosphorylation followed by DAPK1 dephosphorylation and apoptosis. Combined treatment of Artesunate with U0126 revoked Erk1/2-DAPK1 phosphorylation and exerted modest proliferative advantage at early time points, but eventually did not rescue HepG2 cells from death. U0126 induced multiploid formation independent of Artesunate, resulting in cell cycle arrest within 24 h post-treatment.

Significance

Systematic investigation of HCC biomarkers AFP and albumin among thein vitromodels of monolayer and organoid cultures, and thein vivomodels of subcutaneous and liver implantation xenograft mice was conducted.
Novel, economically important semi-dwarf and early mutants: Selection and development from Improved White Ponni Rice (Oryza sativa L.)
Authors: Ramchander S. , Leon Andrew Peter , Yasin Jesima Khan , KK Vinod , Pillai Arumugam
Published: December 2018

Rice variety, Improved White Ponni is a medium duration crop, but highly susceptible to lodging impacting maximum yield losses. The present investigation aimed to identify early and early semi-dwarf mutants in Improved White Ponni by inducing variations using gamma rays without altering its native grain quality traits. Seeds were treated with various doses of after fixation of the LD50 value of gamma radiation and reported that most of the traits exhibit variations in the mutants at various levels of irradiation. The selection for earliness and dwarf plant height was imposed in M2 and it was confirmed by evaluation of M3 generation. Apart from semi-dwarf early mutants, high tillering habit, narrow rolled leaf, upper albino leaf and grassy stunt and extreme dwarf mutants were also identified. Characterization of mutants using already reported genic and linked microsatellite markers associated with semi-dwarfism and earliness resulted that PIC value ranges between 0.037 and 0.949 with an average of 0.382. Single marker analysis revealed that RM302 and RM310 on chromosome 1 and 8 had exhibited an association with the traits plant height, culm and internodal lengths. Of these gene-specific markers, GA20Oxi_1 and GA20Oxi_2 have shown polymorphism among mutants. GA20Oxi_2 showed null alleles in the dwarf mutants and this clearly emphasized that there are some base deletions exists in the region of exon 2 of sd1 region. GA3 response study shown that identified mutants were GA3 responsive except IWP 11-2, IWP 48-2, IWP 50-11 and IWP 33-2 which showed very low responsive. Agar plate assay revealed that, IWP 50-11, IWP 33-2, IWP 43-1, IWP 47-2 and IWP 18-1 had low production of α- amylase. Scanning electron microscope examination on confirmed mutants exhibited larger cell size and a lesser number of cells per unit area than the wild-type which shows that these mutants are defective in GA mediated pathway
A quarter of a century after its synthesis and with >200 papers based on its use, `Co(CO3)0.5(OH)·0.11H2O′ proves to be Co6(CO3)2(OH)8·H2O from synchrotron powder diffraction data
Authors: Bhojane Prateek , Le Bail Armel , Shirage Parasharam M.
Published: December 2018

The successful attempt to solve the crystal structure of Co(CO3)0.5(OH)·0.11H2O (denotedCCH), based on synchrotron powder diffraction data, leads to a drastic revision of the chemical formula to Co6(CO3)2(OH)8·H2O [hexacobalt(II) bis(carbonate) octahydroxide monohydrate] and to a hexagonal cell instead of the orthorhombic cell suggested previously [Portaet al.(1992).J. Chem. Soc. Faraday Trans.88, 311–319]. This results in a new structure-type related to malachite involving infinite chains of [CoO6] octahedra sharing edges along a shortcaxis, delimiting tunnels having a three-branched star section. All reports discussing cobalt hydroxycarbonates (CCH) without any structural knowledge and especially its topotactic decomposition into Co3O4have, as a result, to be reconsidered.
Applicant gender and recruiter and organizational characteristics
Authors: Landay Karen , DeArmond Sarah
Published: December 2018

Purpose

The purpose of this study is to understand how applicant gender may interact with recruiter and organizational characteristics to affect organization attraction. Interpreting characteristics of individuals (e.g., recruiters) and organizations requires some degree of interpersonal sensitivity. Evidence shows that women are generally more skilled in this area than men, but women’s skills are not stronger when evaluating characteristics that are male relevant (e.g., dominance, status).

Design/methodology/approach

This study used an experimental between-subjects design in one sample of undergraduate students and one sample of working adults to explore the interaction of applicant gender with two known predictors of organization attraction: recruiter competence and hiring firm reputation.

Findings

As hypothesized, there was a significant interaction between recruiter competence and applicant gender on organization attraction in both samples. Contrary to the hypothesis, there was a significant interaction between hiring firm reputation and applicant gender in the sample of working adults, but not the sample of undergraduate students.

Practical implications

Results suggest that firms wishing to increase the number of women in their workforces should be particularly mindful of how they select and train recruiters as well as how positively their reputation is perceived by potential job applicants.

Originality/value

These results suggest that there may be gender differences in how applicants perceive and react to a variety of factors during the recruitment process that previous research has not considered.
Potential implications of degree apprenticeships for healthcare education
Authors: Baker Denise
Published: December 2018

Purpose

The purpose of this paper is to critically reflect on evidence relating to the development and delivery of apprenticeships and its potential implications for pre-registration healthcare education.

Design/methodology/approach

An iterative review of English language literature published after 1995 to date relating to apprentices and apprenticeships was undertaken. In total, 20 studies were identified for inclusion. Only three related to the most recent apprenticeship initiative in the UK, and the majority were UK based.

Findings

Three key themes were identified: entering an apprenticeship, the learning environment and perceptions of apprenticeships. Successful completion of an apprenticeship relies heavily on both understanding the role the apprentice is seeking to inhabit, as well as well-structured and comprehensive support whilst on the programme. These findings are then discussed with reference to professional body requirements and pre-registration education in healthcare.

Practical implications

Appropriate work experience and support for learning are critical to apprenticeship success and apprenticeships should be given equal status to traditional healthcare education routes.

Originality/value

The introduction of the Apprenticeship Levy in April 2017 (Finance Act, 2016), acknowledgement that all National Health Service Trusts will be levy payers and the introduction of targets relating to apprenticeships for public sector employers have all contributed to growing interest in the apprenticeship agenda in health and social care.
Homeownership and entrepreneurship
Authors: Berggren Bjorn , Fili Andreas , Wilhelmsson Mats
Published: December 2018

Purpose

The purpose of this paper is to analyze the relationship between housing markets and new firm formation in six different industries in all 284 municipalities in Sweden.

Design/methodology/approach

The authors have used data from Statistics Sweden and The Swedish Agency for Economic and Regional Growth to develop a model to analyze the relationship between house prices and industry-specific new firm formation, with the interaction effect of financial infrastructure.

Findings

In the data, stable high house prices have no effect on entrepreneurship. However, a market with rising house prices has a positive effect on new firm formation, in retail, construction, business-to-business services and miscellaneous sectors, but produced no effect in either mining, agriculture and fishing or in manufacturing. The interaction between rising house prices and financial infrastructure does not change the positive effect on retail, business-to-business services and miscellaneous sectors, but within the construction industry, the positive effect on new firm formation disappears. In manufacturing, the authors observe the opposite – a positive effect, instead of no effect previously.

Originality/value

The contribution of this study is to provide evidence of how house prices are associated with entrepreneurship in different industries, as well as analyzing how the interaction between house prices and financial infrastructure is associated with entrepreneurship. By separating observations in time, endogeneity is controlled and a causal relationship where higher house prices is postulated, which leads to an increase in entrepreneurial activity in different industries. By using a spatial Durbin model, the authors control for spatial dependency.
Project work, a challenge to traditional work life institutions
Authors: Ekstedt Eskil
Published: December 2018

Purpose

The purpose of this paper is to illustrate and problematize how the expansion of project and temporary work challenges the traditional industrial work organization and its internal and supportive institutions. It highlights the transformation dilemma, which occurs when traditional industrial institutions are confronted by project organizations. It also discusses how one may prepare to meet these challenges.

Design/methodology/approach

The long-run incremental changes in organizational structures of the economy are described in an economic historical context, focusing on the organizational form of work and the employment regimes. Challenges, at the societal, organizational and individual levels, related to the “projectification” process are illustrated in considering the case of Sweden.

Findings

Project dense industries, like media, entertainment and consultancy, are growing faster than the rest of the economy. The share of project work in permanent organizations is increasing. More than a third of all working hours in industrialized countries, like Germany, was labeled as project work in 2013. This transformation challenges basic conditions for how work is designed and regulated, like the stipulated and uniform work time or the permanent and stable work place. Central institutions of today, like the labor law and the educational system, are challenged.

Social implications

“Projectification” challenges traditional conditions of work and work life institutions and organizations, like the social partners, the educational and law systems.

Originality/value

The paper brings together and problematizes several aspects of “projectification” of work life. It highlights what kind of challenges work and work-related institutions meet and discusses how to handle some of them, like education.