bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling phylogenetic biome shifts on a planet with a past
Authors: Landis Michael J. , Edwards Erika J. , Donoghue Michael J. 
Published: November 2019

AbstractThe spatial distribution of biomes has changed considerably over deep time, so the geographical opportunity for an evolutionary lineage to shift into a new biome may depend on how the availability and connectivity of biomes has varied temporally. To better understand how lineages shift between biomes in space and time, we developed a phylogenetic biome shift model in which each lineage shifts between biomes and disperses between regions at rates that depend on the lineage’s biome affinity and location relative to the spatiotemporal distribution of biomes at any given time. To study the behavior of the biome shift model in an empirical setting, we developed a literature-based representation of paleobiome structure for three mesic forest biomes, six regions, and eight time strata, ranging from the Late Cretaceous (100 Ma) through the present. We then fitted the model to a time-calibrated phylogeny of 119Viburnumspecies to compare how the results responded to various realistic or unrealistic assumptions about paleobiome structure.Ancestral biome estimates that account for paleobiome dynamics reconstructed a warm temperate (or tropical) origin ofViburnum, which is consistent with previous fossil-based estimates of ancestral biomes. Imposing unrealistic paleobiome distributions led to ancestral biome estimates that eliminated support for tropical origins, and instead inflated support for cold temperate ancestry throughout the warmer Paleocene and Eocene. The biome shift model we describe is applicable to the study of evolutionary systems beyondViburnum, and the core mechanisms of our model are extensible to the design of richer phylogenetic models of historical biogeography and/or lineage diversification. We conclude that biome shift models that account for dynamic geographical opportunities are important for inferring ancestral biomes that are compatible with our understanding of Earth history.
Host-dependent induction of disease tolerance to infection by tetracycline antibiotics
Authors: Colaço Henrique G. , Barros André , Neves-Costa Ana , Seixas Elsa , Pedroso Dora , Velho Tiago R. , Willmann Katharina , Yi Hyon-Seung , Shong Minho , Benes Vladimir , Weis Sebastian , Köcher Thomas , Moita Luís F. 
Published: November 2019

SummarySynergy of resistance and disease tolerance mechanisms is necessary for an effective immune response leading to survival and return to homeostasis when an organism is challenged by infection. Antibiotics are used for their resistance enhancement capabilities by decreasing pathogen load, but several classes have long been known to have beneficial effects that cannot be explained strictly on the basis of their capacity to control the infectious agent. Here we report that tetracycline antibiotics, a class of ribosome-targeting drugs, robustly protects against sepsis by inducing disease tolerance, independently from their direct antibiotic properties. Mechanistically, we find that mitochondrial inhibition of protein synthesis perturbs the electron transfer chain and leads to improved damage repair in the lung and fatty acid oxidation and glucocorticoid sensitivity in the liver. Using a partial and acute deletion ofCRIF1in the liver, a critical mitoribosomal component for protein synthesis, we find that mice are protected against bacterial sepsis, an observation which is phenocopied by the transient inhibition of complex I of ETC by phenformin. Together, we demonstrate that ribosome-targeting antibiotics are beneficial beyond their antibacterial activity and that mitochondrial protein synthesis inhibition leading to ETC perturbation is a novel mechanism for the induction of disease tolerance.
How Array Design affects SNP Ascertainment Bias
Authors: Geibel Johannes , Reimer Christian , Weigend Steffen , Weigend Annett , Pook Torsten , Simianer Henner 
Published: November 2019

AbstractSingle nucleotide polymorphisms (SNPs), genotyped with SNP arrays, have become a widely used marker type in population genetic analyses over the last 10 years. However, compared to whole genome re-sequencing data, arrays are known to lack a substantial proportion of globally rare variants and tend to be biased towards variants present in populations involved in the development process of the respective array. This affects population genetic estimators and is known as SNP ascertainment bias. We investigated factors contributing to ascertainment bias in array development by redesigning the Axiom™ Genome-Wide Chicken Arrayin silicoand evaluating changes in allele frequency spectra and heterozygosity estimates in a stepwise manner. A sequential reduction of rare alleles during the development process was shown with main influencing factors being the identification of SNPs in a limited set of populations and a within-population selection of common SNPs when aiming for equidistant spacing. These effects were shown to be less severe with a larger discovery panel. Additionally, a generally massive overestimation of expected heterozygosity for the ascertained SNP sets was shown. This overestimation was 24% higher for populations involved in the discovery process than not involved populations in case of the original array. The same was observed after the SNP discovery step in the redesign. However, an unequal contribution of populations during the SNP selection can mask this effect but also adds uncertainty. Finally, we make suggestions for the design of specialized arrays for large scale projects where whole genome re-sequencing techniques are still too expensive.
A statistical nonparametric method for identifying consistently important features across samples
Authors: Sauerwald Natalie , Kingsford Carl 
Published: November 2019

AbstractIn many applications, a consistently high measurement across many samples can indicate particularly meaningful or useful information for quality control or biological interpretation. Identification of these strong features among many others can be challenging especially when the samples cannot be expected to have the same distribution or range of values. We present a general method called conserved feature discovery (CFD) for identifying features with consistently strong signals across multiple conditions or samples. Given any real-valued data, CFD requires no parameters, makes no assumptions on the shape of the underlying sample distributions, and is robust to differences across these distributions.We show that with high probability CFD identifies all true positives and no false positives under certain assumptions on the median and variance distributions of the feature measurements. Using simulated data, we show that CFD is tolerant to a small percentage of poor quality samples and robust to false positives. Applying CFD to RNA sequencing data from the Human Body Map project and GTEx, we identify housekeeping genes as highly expressed genes across tissue types and compare to housekeeping gene lists from previous methods. CFD is consistent between the Human Body Map and GTEx data sets, and identifies lists of genes enriched for basic cellular processes as expected. The framework can be easily adapted for many data types and desired feature properties.AvailabilityCode for CFD and scripts to reproduce the figures and analysis in this work are available at https://github.com/Kingsford-Group/cfd.Supplementary informationSupplementary data are available at https://github.com/Kingsford-Group/cfd.
The thermodynamics of thinking: connections between neural activity, energy metabolism and blood flow
Authors: Buxton Richard B. 
Published: November 2019

SummarySeveral current functional neuroimaging methods are sensitive to cerebral metabolism and cerebral blood flow (CBF) rather than the underlying neural activity itself. Empirically, the connections between metabolism, flow and neural activity are complex and somewhat counterintuitive: CBF and glycolysis increase more than seems to be needed to provide oxygen and pyruvate for oxidative metabolism, and the oxygen extraction fraction is relatively low in the brain anddecreaseswhen oxygen metabolism increases. This work lays a foundation for the idea that this unexpected pattern of physiological changes is consistent with basic thermodynamic considerations related to metabolism. In the context of this thermodynamic framework, the apparent mismatches in metabolic rates and CBF are related to preserving the entropy change of oxidative metabolism, specifically the O2/CO2ratio in the mitochondria. However, the mechanism supporting this CBF response is likely not due to feedback from a hypothetical O2sensor in tissue, but rather is consistent with feed-forward control by signals from both excitatory and inhibitory neural activity. Quantitative predictions of the thermodynamic framework, based on models of O2and CO2transport and possible neural drivers of CBF control, are in good agreement with a wide range of experimental data, including responses to neural activation, hypercapnia, hypoxia and high-altitude acclimatization.
A tradeoff between robustness to environmental fluctuations and speed of evolution
Authors: Schmid Max , Paniw Maria , Postuma Maarten , Ozgul Arpat , Guillaume Frédéric 
Published: November 2019

AbstractOrganisms must cope with both short- and long-term environmental changes to persist. In this study we investigated whether life histories trade-off between their robustness to short-term environmental perturbations and their ability to evolve directional trait changes. We could confirm the tradeoff by modeling the eco-evolutionary dynamics of life-histories along the fast-slow pace-of-life continuum. Offspring dormancy and high adult survival rates allowed for large population sizes to be maintained in face of interannual environmental fluctuations but limited the speed of trait evolution with ongoing environmental change. In contrast, precocious offspring maturation and short-living adults promoted evolvability while lowering demographic robustness. This tradeoff had immediate consequences on extinction dynamics in variable environments. High evolvability allowed short-lived species to cope with long-lasting gradual environmental change, but came at the expense of more pronounced population declines and extinction rates from environmental variability. Higher robustness of slow life-histories helped them persist better on short timescales.
Detection of interictal epileptiform discharges: A comparison of on-scalp MEG and conventional MEG measurements
Authors: Westin Karin , Pfeiffer Christoph , Andersen Lau M. , Ruffieux Silvia , Cooray Gerald , Kalaboukhov Alexei , Winkler Dag , Ingvar Martin , Schneiderman Justin , Lundqvist Daniel 
Published: November 2019

AbstractMagnetoencephalography (MEG) is an important part of epilepsy evaluations because of its unsurpassed ability to detect interictal epileptiform discharges (IEDs). This ability may be improved by next-generation MEG sensors, where sensors are placed directly on the scalp instead of in a fixed-size helmet, as in today’s conventional MEG systems. In order to investigate the usefulness of on-scalp MEG measurements we performed the first-ever measurements of on-scalp MEG on an epilepsy patient. The measurement was conducted as a benchmarking study, with special focus on IED detection. An on-scalp high-temperature SQUID system was utilized alongside a conventional low-temperature “in-helmet” SQUID system. EEG was co-registered during both recordings. Visual inspection of IEDs in the raw on-scalp MEG data was unfeasible why a novel machine learning-based IED-detection algorithm was developed to guide IED detection in the on-scalp MEG data. A total of 24 IEDs were identified visually from the conventional in-helmet MEG session (of these, 16 were also seen in the EEG data; eight were detected only by MEG). The on-scalp MEG data contained a total of 47 probable IEDs of which 16 IEDs were co-registered by the EEG, and 31 IEDs were on-scalp MEG-unique IEDs found by the IED detection algorithm. We present a successful benchmarking study where on-scalp MEG are compared to conventional in-helmet MEG in a temporal lobe epilepsy patient. Our results demonstrate that on-scalp MEG measurements are feasible on epilepsy patients, and indicate that on-scalp MEG might capture IEDs not seen by other non-invasive modalities.
NF1 regulates mesenchymal glioblastoma plasticity and aggressiveness through the AP-1 transcription factor FOSL1
Authors: Marques Carolina , Unterkircher Thomas , Kroon Paula , Izzo Annalisa , Dramaretska Yuliia , Kling Eva , Oldrini Barbara , Schnell Oliver , Nelander Sven , Wagner Erwin F. , Bakiri Latifa , Gargiulo Gaetano , Carro Maria Stella , Squatrito Massimo 
Published: November 2019

AbstractThe molecular basis underlying Glioblastoma (GBM) heterogeneity and plasticity are not fully understood. Using transcriptomic data of patient-derived brain tumor stem cell lines (BTSCs), classified based on GBM-intrinsic signatures, we identify the AP-1 transcription factorFOSL1as a key regulator of the mesenchymal (MES) subtype. We provide a mechanistic basis to the role of the Neurofibromatosis type 1 gene (NF1), a negative regulator of the RAS/MAPK pathway, in GBM mesenchymal transformation through the modulation ofFOSL1expression. Depletion ofFOSL1inNF1-mutant human BTSCs andKras-mutant mouse neural stem cells results in loss of the mesenchymal gene signature, reduction in stem cell properties andin vivotumorigenic potential. Our data demonstrate thatFOSL1controls GBM plasticity and aggressiveness in response toNF1alterations.
Polycysteine-encoding leaderless short ORFs function as cysteine-responsive attenuators of operonic gene expression in mycobacteria
Authors: Canestrari Jill G. , Lasek-Nesselquist Erica , Upadhyay Ashutosh , Rofaeil Martina , Champion Matthew M. , Wade Joseph T. , Derbyshire Keith M. , Gray Todd A. 
Published: November 2019

ABSTRACTGenome-wide transcriptomic analyses have revealed abundant expressed short open reading frames (ORFs) in bacteria. Whether these short ORFs, or the small proteins they encode, are functional remains an open question. One quarter of mycobacterial mRNAs are leaderless, beginning with a 5’-AUG or GUG initiation codon. Leaderless mRNAs often encode unannotated short ORFs as the first gene of a polycistronic transcript. Here we show that polycysteine-encoding leaderless short ORFs function as cysteine-responsive attenuators of operonic gene expression. Detailed mutational analysis shows that one polycysteine short ORF controls expression of the downstream genes. Our data indicate that ribosomes stalled in the polycysteine tract block mRNA structures that otherwise sequester the ribosome-binding site of the 3’gene. We assessed endogenous proteomic responses to cysteine limitation inMycobacterium smegmatisusing mass spectrometry. Six cysteine metabolic loci having unannotated polycysteine-encoding leaderless short ORF architectures responded to cysteine limitation, revealing widespread cysteine-responsive attenuation in mycobacteria. Individual leaderless short ORFs confer independent operon-level control, while their shared dependence on cysteine ensures a collective response mediated by ribosome pausing. We propose the term ribulon to classify ribosome-directed regulons. Regulon-level coordination by ribosomes on sensory short ORFs illustrates one utility of the many unannotated short ORFs expressed in bacterial genomes.
Stochastic Sampling of Structural Contexts Improves the Scalability and Accuracy of RNA 3D Module Identification
Authors: Sarrazin-Gendron Roman , Yao Hua-Ting , Reinharz Vladimir , Oliver Carlos G. , Ponty Yann , Waldispühl Jérôme 
Published: November 2019

AbstractRNA structures possess multiple levels of structural organization. Secondary structures are made of canonical (i.e. Watson-Crick and Wobble) helices, connected by loops whose local conformations are critical determinants of global 3D architectures. Such local 3D structures consist of conserved sets of non-canonical base pairs, called RNA modules. Their prediction from sequence data is thus a milestone toward 3D structure modelling. Unfortunately, the computational efficiency and scope of the current 3D module identification methods are too limited yet to benefit from all the knowledge accumulated in modules databases. Here, we introduceBayesPairing 2, a new sequence search algorithm leveraging secondary structure tree decomposition which allows to reduce the computational complexity and improve predictions on new sequences. We benchmarked our methods on 75 modules and 6380 RNA sequences, and report accuracies that are comparable to the state of the art, with considerable running time improvements. When identifying 200 modules on a single sequence,BayesPairing 2is over 100 times faster than its previous version, opening new doors for genome-wide applications.
The Hippo pathway oncoprotein YAP promotes melanoma cell invasion and spontaneous metastasis
Authors: Zhang Xiaomeng , Yang Lie , Szeto Pacman , Zhang Youfang , Amarasinghe Kaushalya , Li Jason , McLean Catriona , Shackleton Mark , Harvey Kieran F. 
Published: November 2019

ABSTRACTMelanoma is a deadly form of skin cancer that accounts for a disproportionally large proportion of cancer-related deaths in younger people. Compared to most other skin cancers, a feature of melanoma is its high metastatic capacity, although molecular mechanisms that confer this are not well understood. The Hippo pathway is a key regulator of organ growth and cell fate that is deregulated in many cancers. To analyse the Hippo pathway in cutaneous melanoma, we generated a transcriptional signature of pathway activity in melanoma cells. Hippo-mediated transcriptional activity varied in melanoma cell lines but failed to cluster with known genetic drivers of melanomagenesis such asBRAFandNRASmutation status. Instead, it correlated strongly with published gene expression profiles linked to melanoma cell invasiveness. Consistent with this, the central Hippo oncogene, YAP, was both necessary and sufficient for melanoma cell invasion in vitro. In in vivo murine studies, YAP promoted spontaneous melanoma metastasis, whilst the growth of YAP-expressing primary tumours was impeded. Finally, we identified the YAP target genesAXL,THBS1andCYR61as key mediators of YAP-induced melanoma cell invasion. These data suggest that the Hippo pathway is a critical regulator of melanoma metastasis.
An extensively optimized chromatin immunoprecipitation protocol for quantitatively comparable and robust results
Authors: de Jonge Wim J. , Brok Mariël , Kemmeren Patrick , Holstege Frank C.P. 
Published: November 2019

AbstractChromatin immunoprecipitation (ChIP) is a commonly used technique to investigate which parts of a genome are bound by a particular protein. The result of ChIP is often interpreted in a binary manner: bound or not bound. Due to this focus, ChIP protocols frequently lack the ability to quantitatively compare samples with each other, for example in a time series or under different growth conditions. Here, using the yeast S. cerevisiae transcription factors Cbf1, Abf1, Reb1, Mcm1 and Sum1, we optimized the five major steps of a commonly used ChIP protocol: cross-linking, quenching, cell lysis, fragmentation and immunoprecipitation. Quenching with glycine is inefficient and can lead to large degrees of variability, an issue that is resolved by using tris(hydroxymethyl)aminomethane (Tris). Another source of variability is degradation of the protein of interest during the procedure. Enzymatic cell lysis with zymolyase can lead to extensive protein degradation, which is greatly reduced by mechanical lysis through bead beating. Degradation also occurs during sonication of chromatin, affecting large proteins in particular. An optimal mix of protease inhibitors and cross-linking with a higher percentage of formaldehyde reduces the extent of this degradation. Finally we also show that the immunoprecipitation step itself can be greatly improved with magnetic beads and optimized incubation/washing steps. The study results in a highly optimized protocol, which is shorter, easier to perform and has a stronger, more reproducible signal with less background. This protocol is presented in detail. In addition, the results highlight the greatest sources of variability in many other protocols, showing which steps are important to focus on for reproducible and quantitatively comparable ChIP experiments.
IFRS adoption and accounting regulation in Ethiopia
Authors: Wagaw Yitayew Mihret , Mihret Dessalegn Getie , Obo Degefe Duressa 
Published: November 2019

Purpose
The purpose of this study is to examine international financial reporting standards (IFRSs) adoption in Ethiopia to explain transnational political-economic antecedents of this change and its associated consequences on the regulatory landscape of accounting.

Design/methodology/approach
Using a neo-Gramscian theory of globalization and the state, the study examines interview and document review evidence pertaining to IFRS adoption in Ethiopia by focusing on the period from 1991 to 2014.

Findings
The study illustrates that a dialectical rather than deterministic interaction between global and national forces explains IFRS adoption in Ethiopia, i.e. IFRS adoption falls within the broader scheme of universalizing regulatory institutions in the globalizing world economy. Compared to the commonly understood trends of IFRS adoption circumscribed within a pre-existing regulatory framework, this study illustrates IFRS adoption as a primary driver of major reforms to the accounting regulatory landscape.

Originality/value
This study contributes original theoretically grounded insights into the transnational political-economic rationale for IFRS adoption and consequences of the adoption on the accounting regulatory landscape.
Stock price synchronicity and dividend policy: evidence from an emerging market
Authors: Farooq Omar , ElBannan Mona A. 
Published: November 2019

Purpose
The purpose of this paper is to document the impact of stock price synchronicity (SYNCH) on the dividend payout ratio.

Design/methodology/approach
The authors use data from India for the period between 2000 and 2012 and the panel regression approach to test their arguments.

Findings
This paper documents that the relationship between synchronicity and dividend payout ratio is positive until a turning point is reached. After that point, synchronicity has a negative impact on dividend payout ratio. The authors argue that firms with low synchronicity have higher information asymmetries. As a result, they have an incentive to develop a reputation as better-governed firms by paying high dividends. However, as synchronicity increases further, information asymmetries go down and as a result incentive to use dividend payouts as a mechanism to reduce information asymmetries goes down. Therefore, positive relationship between synchronicity and dividend payout ratios breaks down at high levels of synchronicity.

Originality/value
The authors provide evidence regarding the role played by SYNCH – a publicly available measure – on dividend polices adopted by firms within the context of emerging markets.