bluuebunny/crossref_metadata_2025_split huggingface dataset:
Limits to Genomic Divergence Under Sexually Antagonistic Selection
Authors: Kasimatis Katja R. , Ralph Peter L. , Phillips Patrick C. 
Published: March 2019

AbstractSince the autosomal genome is shared between the sexes, sex-specific fitness optima present an evolutionary challenge. While sexually antagonistic selection might favor different alleles within females and males, segregation randomly reassorts alleles at autosomal loci between sexes each generation. This process of homogenization during transmission thus prevents between-sex allelic divergence generated by sexually antagonistic selection from accumulating across multiple generations. However, recent empirical studies have reported high male-femaleFSTstatistics. Here, we use a population genetic model to evaluate whether these observations could plausibly be produced by sexually antagonistic selection. To do this, we use both a single-locus model with nonrandom mate choice, and individual-based simulations to study the relationship between strength of selection, degree of between-sex divergence, and the associated genetic load. We show that selection must be exceptionally strong to create measurable divergence between the sexes and that the decrease in population fitness due to this process is correspondingly high. Individual-based simulations with selection genome-wide recapitulate these patterns and indicate that small sample sizes and sampling variance can easily generate substantial male-female divergence. We therefore conclude that caution should be taken when interpreting autosomal allelic differentiation between the sexes.
Identification of novel neuroprotective loci modulating ischemic stroke volume in a cross between wild-derived inbred mouse strains
Authors: Lee Han Kyu , Widmayer Samuel J. , Huang Min-Nung , Aylor David L. , Marchuk Douglas A. 
Published: March 2019

AbstractTo identify genes involved in cerebral infarction we have employed a forward genetic approach in inbred mouse strains, using quantitative trait locus (QTL) mapping for cerebral infarct volume after middle cerebral artery occlusion. We had previously observed that infarct volume is inversely correlated with cerebral collateral vessel density in the strains. In this study, we expanded the pool of allelic variation among classical inbred mouse strains by utilizing the eight founder strains of the Collaborative Cross and found a wild-derived strain, WSB/EiJ, that breaks this general rule that collateral vessel density inversely correlates with infarct volume. WSB/EiJ and another wild-derived strain, CAST/EiJ, show the highest collateral vessel densities of any inbred strain, but infarct volume of WSB/EiJ mice is 8.7-fold larger than that of CAST/EiJ mice. QTL mapping between these strains identified four new neuroprotective loci modulating cerebral infarct volume while not affecting collateral vessel phenotypes. To identify causative variants in genes we surveyed non-synonymous coding SNPs between CAST/EiJ and WSB/EiJ and found 96 genes harboring coding SNPs predicted to be damaging and mapping within one of the four intervals. In addition, we performed RNA sequencing for brain tissue of CAST/EiJ and WSB/EiJ mice and identified 79 candidate genes mapping in one of the four intervals showing strain-specific differences in expression. The identification of the genes underlying these neuroprotective loci will provide new understanding of genetic risk factors of ischemic stroke which may provide novel targets for future therapeutic intervention of human ischemic stroke.
Mitochondria supply ATP to the ER through a mechanism antagonized by cytosolic Ca2+
Authors: Yong Jing , Bischof Helmut , Siirin Marina , Murphy Anne , Malli Roland , Kaufman Randal J. 
Published: March 2019

AbstractThe endoplasmic reticulum (ER) imports ATP and uses energy from ATP hydrolysis for protein folding and trafficking. However, little is known about this vital ATP transport process across the ER membrane. Here, using three commonly used cell lines (CHO, INS1 and HeLa), we report that ATP enters the ER lumen through a cytosolic Ca2+-antagonized mechanism, orCaATiER(Ca2+-AntagonizedTransport intoER) mechanism for brevity. Significantly, we observed that a Ca2+gradient across the ER membrane is necessary for ATP transport into the ER. Therefore Ca2+signaling in the cytosol is inevitably coupled with ATP supply to the ER. We propose that under physiological conditions, cytosolic Ca2+inhibits ATP import into the ER lumen to limit ER ATP consumption. Furthermore, the ATP level in the ER is readily depleted by oxidative phosphorylation (OxPhos) inhibitors, and that ER protein misfolding increases ATP trafficking from mitochondria into the ER. These findings suggest that ATP usage in the ER may increase mitochondrial OxPhos while decreasing glycolysis, i.e., an “anti-Warburg” effect.Significance StatementWe report that ATP enters the ER lumen through an AXER-dependent, cytosolic Ca2+-antagonized mechanism, orCaATiER(Ca2+-Antagonized Transport into ER) mechanism. In addition, our findings suggest that ATP usage in the ER may render an “anti-Warburg” effect by increasing ATP regeneration from mitochondrial OxPhos while decreasing the portion of ATP regeneration from glycolysis.
Hierarchy of connectivity-function relationship of the human cortex revealed through predicting activity across functional domains
Authors: Wu Dongya , Fan Lingzhong , Song Ming , Wang Haiyan , Chu Congying , Yu Shan , Jiang Tianzi 
Published: March 2019

AbstractMany studies showed that anatomical connectivity supports both anatomical and functional hierarchies that span across the primary and association cortices in the cerebral cortex. However, it remains unclear whether a hierarchy of connectivity-function relationship (CFR) exists across the human cortex as well as how to characterize the hierarchy of this CFR if it exists. We first addressed whether anatomical connectivity could be used to predict functional activations across different functional domains using multilinear regression models. Then we characterized the CFR by predicting activity from anatomical connectivity throughout the cortex. We found that there is a hierarchy of CFR across the human cortex. Moreover, this CFR hierarchy was correlated to the functional and anatomical hierarchy reflected in functional flexibility, functional variability, and the myelin map. Our results suggest a shared hierarchical mechanism in the cortex, a finding which provides important insights into the anatomical and functional organization of the human brain.
Inhibition of mTORC1 signaling in aged rats counteracts the decline in muscle mass and reverses multiple parameters of muscle signaling associated with sarcopenia
Authors: Joseph Giselle A. , Wang Sharon , Zhou Weihua , Kimble Garrett , Tse Herman , Eash John , Shavlakadze Tea , Glass David J. 
Published: March 2019

AbstractThere is a lack of pharmacological interventions available for sarcopenia, a progressive age-associated loss of muscle mass, leading to a decline in mobility and quality of life. We found mTORC1 (mammalian target of rapamycin complex 1), a well-established critical positive modulator of mass, to be hyperactivated in sarcopenic muscle. Furthermore, inhibition of the mTORC1 pathway counteracted sarcopenia as determined by observing an increase in muscle mass and fiber type cross sectional area, surprising because mTORC1 signaling has been shown to be required for muscle mass gains in some settings. Additionally, several genes related to senescence were downregulated, while gene expression indicators of neuromuscular junction denervation were diminished using a low dose of a rapalog. Therefore mTORC1 inhibition may delay the progression of sarcopenia by directly and indirectly modulating multiple age-associated pathways, implicating mTORC1 as a therapeutic target to treat sarcopenia.
Modeling latent flows on single-cell data using the Hodge decomposition
Authors: Maehara Kazumitsu , Ohkawa Yasuyuki 
Published: March 2019

AbstractSingle-cell analysis is a powerful technique used to identify a specific cell population of interest during differentiation, aging, or oncogenesis. Individual cells occupy a particular transient state in the cell cycle, circadian rhythm, or during cell death. An appealing concept of pseudo-time trajectory analysis of single-cell RNA sequencing data was proposed in the software Monocle, and several methods of trajectory analysis have since been published to date. These aim to infer the ordering of cells and enable the tracing of gene expression profile trajectories in cell differentiation and reprogramming. However, the methods are restricted in terms of time structure because of the pre-specified structure of trajectories (linear, branched, tree or cyclic) which contrasts with the mixed state of single cells.Here, we propose a technique to extract underlying flows in single-cell data based on the Hodge decomposition (HD). HD is a theorem of vector fields on a manifold which guarantees that any given flow can decompose into three types of orthogonal component: gradient-flow (acyclic), curl-, and harmonic-flow (cyclic). HD is generalized on a simplicial complex (graph) and the discretized HD has only a weak assumption that the graph is directed. Therefore, in principle, HD can extract flows from any mixture of tree and cyclic time flows of observed cells. The decomposed flows provide intuitive interpretations about complex flow because of their linearity and orthogonality. Thus, each extracted flow can be focused on separately with no need to consider crosstalk.We developed ddhodge software, which aims to model the underlying flow structure that implies unobserved time or causal relations in the hodge-podge collection of data points. We demonstrated that the mathematical framework of HD is suitable to reconstruct a sparse graph representation of diffusion process as a candidate model of differentiation while preserving the divergence of the original fully-connected graph. The preserved divergence can be used as an indicator of the source and sink cells in the observed population. A sparse graph representation of the diffusion process transforms data analysis of the non-linear structure embedded in the high-dimensional space of single-cell data into inspection of the visible flow using graph algorithms. Hence, ddhodge is a suitable toolkit to visualize, inspect, and subsequently interpret large data sets including, but not limited to, high-throughput measurements of biological data.The beta version of ddhodge R package is available at:https://github.com/kazumits/ddhodge
A general mathematical framework for understanding the behavior of heterogeneous stem cell regeneration
Authors: Lei Jinzhi 
Published: March 2019

AbstractStem cell heterogeneity is essential for the homeostasis in tissue development. This paper established a general formulation for understanding the dynamics of stem cell regeneration with cell heterogeneity and random transitions of epigenetic states. The model generalizes the classical G0 cell cycle model, and incorporates the epigenetic states of stem cells that are represented by a continuous multidimensional variable and the kinetic rates of cell behaviors, including proliferation, differentiation, and apoptosis, that are dependent on their epigenetic states. Moreover, the random transition of epigenetic states is represented by an inheritance probability that can be described as a conditional beta distribution. This model can be extended to investigate gene mutation-induced tumor development. The proposed formula is a generalized formula that helps us to understand various dynamic processes of stem cell regeneration, including tissue development, degeneration, and abnormal growth.
Nitro-fatty acids formation in Virgin Olive Oil during gastric digestion and its relationship to cultivar and fruit ripening
Authors: Sánchez-Calvo Beatriz , Mastrogiovanni Mauricio , Conde-Innamorato Paula , Arias-Sibillotte Mercedes , Trostchansky Andrés , Rubbo Homero 
Published: March 2019

AbstractVirgin olive oil (VOO) represents the main source of unsaturated lipids in the Mediterranean diet associated with low mortality. Health benefits of VOO rely on its composition, mainly fatty acids and minor components such as polyphenols. In addition, VOO contains nitro-fatty acids (NO2-FA), novel signaling mediators exhibiting pleiotropic anti-inflammatory responses. Previous work from our group reported the presence of nitro-oleic acid (NO2-OA), nitro-linoleic acid (NO2-LA) and nitro-conjugated linoleic acid (NO2-cLA) in extra virgin olive oil under gastric conditions. Herein, we analyzed the fatty acid profile, phenol, pigment and NO2-FA formation in two contrasting Uruguayan olive cultivars, Arbequina and Coratina at two ripening conditions. We demonstrate that VOO fatty acid nitration is dependent on olive cultivar as well as fruit ripening. Under gastric nitration conditions, the presence of polyphenols in Arbequina VOO promoted fatty acid nitration. In contrast, the absence of polyphenols favor lipid oxidation, decreasing fatty acid nitration. In Coratina, where the content of polyphenolic compounds is higher than in Arbequina, their absence did not affect the formation of NO2-FA. Coratina contains other bioactive constituents such as pigments that could play an important role in protection of VOO from lipid oxidation. Overall, we postulate that unsaponifiable constituents of VOO, e.g. polyphenols and pigments, contribute to the formation of NO2-FA in gastric conditions, thus potentiating their health beneficial
Apical transport of Crumbs maintains epithelial cell polarity
Authors: Aguilar-Aragon M , Fletcher G , Thompson BJ 
Published: March 2019

AbstractCrumbs (Crb inDrosophila; CRB1-3 in mammals) is a transmembrane determinant of epithelial cell polarity and a regulator of Hippo signalling. Crb is normally localized to apical cell-cell contacts, just above adherens junctions, but how apical trafficking of Crb is regulated in epithelial cells remains unclear. We use theDrosophilafollicular epithelium to demonstrate that polarized trafficking of Crb is mediated by transport along microtubules by the motor protein Dynein and along actin filaments by the motor protein Myosin-V (MyoV). Blocking transport of Crb-containing vesicles by Dynein or MyoV leads to accumulation of Crb within Rab11 endosomes, rather than apical delivery. The final steps of Crb delivery and stabilisation at the plasma membrane requires the exocyst complex and three apical FERM domain proteins – Merlin, Moesin and Expanded – whose simultaneous loss disrupts apical localization of Crb. Accordingly, a knock-in deletion of the Crb FERM-binding motif (FBM) also impairs apical localization. Finally, overexpression of Crb challenges this system, creating a sensitized background to identify components involved in cytoskeletal polarization, apical membrane trafficking and stabilisation of Crb at the apical domain.
New insights on the GeSe

x

Te1−x
phase diagram from theory and experiment
Authors: Herrmann Markus Guido , Stoffel Ralf Peter , Küpers Michael , Ait Haddouch Mohammed , Eich Andreas , Glazyrin Konstantin , Grzechnik Andrzej , Dronskowski Richard , Friese Karen 
Published: March 2019

The high-pressure and low-temperature behaviour of the GeSe
x
Te1−x
system (x = 0, 0.2, 0.5, 0.75, 1) was studied using a combination of powder diffraction measurements and first-principles calculations. Compounds in the stability field of the GeTe structure type (x = 0, 0.2, 0.5) follow the high-pressure transition pathway: GeTe-I (R3m) → GeTe-II (f.c.c.) → GeTe-III (Pnma). The newly determined GeTe-III structure is isostructural to β-GeSe, a high-pressure and high-temperature polymorph of GeSe. Pressure-dependent formation enthalpies and stability regimes of the GeSe
x
Te1−x
polymorphs were studied by DFT calculations. Hexagonal Ge4Se3Te is stable up to at least 25 GPa. Significant differences in the high-pressure and low-temperature behaviour of the GeTe-type structures and the hexagonal phase are highlighted. The role of Ge...Ge interactions is elucidated using the crystal orbital Hamilton population method. Finally, a sketch of the high-pressure phase diagram of the system is provided.
Investor attention is a risk pricing factor? Evidence from Chinese investors for self-selected stocks
Authors: Dong Dayong , Wu Keke 
Published: March 2019

Purpose
The purpose of this paper is to empirically examine whether investor attention is a significant risk pricing factor.

Design/methodology/approach
Using investor attention data from Eastmoney.com, which provides for each stock the number of investors whose watch list includes that stock on a daily basis, this paper constructs a “heat” factor based on the change in investor attention and a “market exposure” factor based on the proportion of attention on a given stock over the attention to all stocks. Using the Fama−MacBeth two-step regression and a rolling analysis, this study examines the ability of the investor attention factor to explain market returns.

Findings
The empirical results show that there exists a risk premium for the “heat” factor and “market exposure” factor that is significantly different from zero. This finding shows that investor attention can systematically influence stock returns, making it a significant risk pricing factor.

Practical implications
This paper’s research on the risk pricing factors of investor attention can help investors to rationally build investment portfolios, avoid risks and form a sound investment concept, which will further reveal the information recognition mechanism of the capital market and standardize the information disclosure behavior of listed companies.

Originality/value
This paper provides evidence that investor attention is a risk pricing factor for the stock market. There are “heat” factors and “market exposure” factors in the Chinese stock market that significantly affect the purchasing behavior of individual investors.
Analytical modelling of the transient thermal field of a tubular bus in nominal rating
Authors: Gołębiowski Jerzy , Zaręba Marek 
Published: March 2019

Purpose
The purpose of this paper is to analyse the dynamics of a thermal field generated in a tubular bus with rated current by using two models of electrical resistivity of copper.

Design/methodology/approach
The boundary-initial problem of the modified heat equation was formulated for the tubular bus. Analytical solutions were obtained by means of Green’s functions as the kernels of the integral operator inverse to the corresponding differential operator. The results were presented graphically and verified using the finite element method. The calculations were made by considering the example of the Storm Power Components tubular bus (USA).

Findings
Analytical field models were used to determine time- and space-variable heating curves, time constants and steady-state current ratings.

Research limitations/implications
This paper is related to the structure of a hollow cylinder. Other bus sections can be taken into account by using the coordinate systems of different curvilinear orthogonal symmetry.

Originality/value
Using the analytical method, the influence of the variable (temperature dependent) electrical resistivity on some important parameters and characteristics of the tubular bus was investigated. The system was considered as an element with distributed parameters.
V-Xpress: B2B marketing in the logistics industry
Authors: Pandey Neeraj , Shinde Sandesha 
Published: March 2019

Learning outcomes
The learning objectives of this case study are to understand business-to-business (B2B) marketing in a logistics organization; apply go-to-market (GTM) strategy in the logistics industry; design B2B distribution strategy so as to enhance geographic penetration; and develop digital marketing strategies in the logistics industry.

Case Overview/Synopsis
V-Xpress is a leading B2B player in the express cargo category in the Indian logistics industry. In March 2017, Sachin Nair, Head of V-Xpress Marketing, was presenting three different GTM strategies to the CEO for the new Assured Timely Movement services. He wanted CEO views on each of them so that he can choose the best one. Sachin was also trying to find a solution to backhaul problem in eastern India. The resolution of this problem would have helped V-Xpress to become a truly pan-India B2B logistics company. Sachin was also revamping the digital marketing strategy as part of ambitious V-Xpress marketing strategy. These initiatives were taken as part of CEO’s vision for reaching annual revenue of INR 10bn by 2020. Sachin was thinking about various options so as to implement these changes with least investments.

Complexity academic level
This case study can be used in B2B marketing, marketing management and marketing strategy course of an MBA program.

Supplementary materials
Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS: 8: Marketing
Articulating entrepreneurial competencies in the undergraduate curricular
Authors: Dinning Track 
Published: March 2019

Purpose
The purpose of this paper is to explore the level enterprise language is articulated within programme level documentation, and then, using EntreComp (Bacigalupo et al., 2016) as a framework, investigate the extent by which curricula is underpinned by enterprise competencies.

Design/methodology/approach
This study adopted a qualitative approach firstly through a desk analysis of undergraduate programme documentation across one UK University (n=60), followed by face-to-face interviews with programme leaders (n=25).

Findings
Findings revealed a lack of reference to enterprise in programme documentation as well as a confusion of the language associated with enterprise and entrepreneurship. However, all participants in the study were able to articulate opportunities afforded to students within the programme to practise entrepreneurial competencies from the EntreComp framework.

Originality/value
Whilst the limitation of this study is that it has been carried out in just one university, the practical implication of these findings provide supporting evidence that the EntreComp framework can be used to build a whole programme approach to embedding enterprise. This remains to be tested in future research. As the EntreComp framework is relatively new, then this piece of research is original as it is amongst the first to report on the framework.