bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Network Reconstruction using Mixed Integer Programming
Authors: Bosdriesz Evert , Prahallad Anirudh , Klinger Bertram , Sieber Anja , Bosma Astrid , Bernards René , Blüthgen Nils , Wessels Lodewyk FA 
Published: January 2018

AbstractNew anti-cancer drugs that specifically target oncogenes involved in signalling show great clinical promise. However, the effectiveness of such targeted treatments is often hampered by innate or acquired resistance due to feedbacks, crosstalks or network adaptations in response to drug treatment. Addressing this problem requires an understanding of these networks and how they differ between cells with different oncogenic mutations or between sensitive and resistant cells. Here, we present Comparative Network Reconstruction (CNR), a computational method to reconstruct signaling networks based on incomplete perturbation data, and to identify which edges differ quantitatively between two or more signalling networks. Prior knowledge about network topology is not required but can straightforwardly be incorporated. We extensively tested our approach using simulated data and applied it to perturbation data from a BRAF mutant cell line that developed resistance to BRAF inhibition. Comparing the reconstructed networks of sensitive and resistant cells suggests that the resistance mechanism involves re-establishing wildtype MAPK signaling, possibly through an alternative RAF-isoform.
Graph theory approaches to functional network organization in brain disorders: A critique for a brave new small-world
Authors: Hallquist Michael N. , Hillary Frank G. 
Published: January 2018

AbstractOver the past two decades, resting-state functional connectivity (RSFC) methods have provided new insights into the network organization of the human brain. Studies of brain disorders such as Alzheimer’s disease or depression have adapted tools from graph theory to characterize differences between healthy and patient populations. Here, we conducted a review of clinical network neuroscience, summarizing methodological details from 106 RSFC studies. Although this approach is prevalent and promising, our review identified four challenges. First, the composition of networks varied remarkably in terms of region parcellation and edge definition, which are fundamental to graph analyses. Second, many studies equated the number of connections across graphs, but this is conceptually problematic in clinical populations and may induce spurious group differences. Third, few graph metrics were reported in common, precluding meta-analyses. Fourth, some studies tested hypotheses at one level of the graph without a clear neurobiological rationale or considering how findings at one level (e.g., global topology) are contextualized by another (e.g., modular structure). Based on these themes, we conducted network simulations to demonstrate the impact of specific methodological decisions on case-control comparisons. Finally, we offer suggestions for promoting convergence across clinical studies in order to facilitate progress in this important field.
Environmental and evolutionary drivers of the modular gene regulatory network underlying phenotypic plasticity for stress resistance in the nematodeCaenorhabditis remanei
Authors: Sikkink Kristin L. , Reynolds Rose M. , Ituarte Catherine M. , Cresko William A. , Phillips Patrick C. 
Published: January 2018

ABSTRACTIn response to changing environmental conditions, organisms can acclimate through phenotypic plasticity or adapt by evolving mechanisms to cope with novel stressors. Changes in gene expression, whether dynamic or evolved, are an important way in which environmental responses are mediated; however, much is still unknown about how the molecular networks underlying plastic phenotypes evolve. Here, we compare transcriptional responses to acute heat stress among four populations of the nematodeCaenorhabditis remanei—one selected to withstand heat stress, one selected under oxidative stress, an unselected control, and the ancestral population. We used a weighted gene coexpression network analysis within these lines to identify transcriptional modules, which are sets of genes that respond similarly to stress via plastic responses, evolutionary responses, or both. The transcriptional response to acute heat stress is dominated by a plastic response that is shared in the ancestor and all evolved populations. However, we also identified several modules that respond to artificial selection by (1) changing the baseline level of expression, (2) altering the magnitude of the plastic response, or (3) a combination of the two. Our findings reveal that while it is possible to perturb the nature of the transcriptional response network with short bouts of intense selection, the overall structure of transcriptional plasticity is dominated by inherent, ancestral regulatory systems.
Spiking network optimized for noise robust word recognition approaches human-level performance and predicts auditory system hierarchy
Authors: Khatami Fatemeh , Escabí Monty A. 
Published: January 2018

AbstractThe auditory neural code is resilient to acoustic variability and capable of recognizing sounds amongst competing sound sources, yet, the transformations enabling noise robust abilities are largely unknown. We report that a hierarchical spiking neural network (HSNN) trained to maximize word recognition accuracy in noise and multiple talkers approaches human-level performance. Intriguingly, comparisons with data from auditory nerve, midbrain, thalamus and cortex reveals that the organization and nonlinear transformations of the optimal network predict several properties of the ascending auditory pathway including a sequential loss of temporal resolution, increasing sparseness and selectivity. The optimal organizational scheme is critical for noise robustness since an identical network arranged to enable high information transfer does not predict auditory pathway organization and has substantially poorer performance. Furthermore, conventional linear and nonlinear receptive field-based models fail to achieve similar noise robust performance. The findings suggest that the auditory pathway hierarchy and its sequential nonlinear feature extraction computations may form a near optimal code capable of efficiently detecting sounds in noise impoverished conditions.Significance StatementThe brain’s ability to recognize sounds in the presence of competing sounds or background noise is essential for everyday hearing tasks. How the brain accomplishes noise resiliency, however, is poorly understood. Using neural recording from the ascending auditory pathway and an auditory spiking network model trained for optimal sound recognition in noise we explore the computational strategies that enable noise robustness. Our results suggest that the hierarchical organization of the auditory pathway and the resulting nonlinear transformations may form a near optimal strategy that is essential for sound recognition in the presence of noise.
Testing the phylogenetic gambit: how much functional diversity can we reliably conserve if we prioritize phylogenetic diversity?
Authors: Mazel Florent , Pennell Matthew W. , Cadotte Marc , Diaz Sandra , Dalla Riva Giulio Valentino , Grenyer Richard , Leprieur Fabien , Mooers Arne O. , Mouillot David , Tucker Caroline M. , Pearse William D. 
Published: January 2018

AbstractIn the face of the biodiversity crisis, it is argued that we should prioritize species in order to capture high functional diversity (FD). Because species traits often reflect shared evolutionary history, many researchers have advocated for a “phylogenetic gambit”: maximizing phylogenetic diversity (PD) should indirectly capture FD. For the first time, we empirically test this gambit using data from >15,000 vertebrate species and ecologically-relevant traits. Maximizing PD results in an average gain of 18% of FD relative to random choice. However, this average gain hides the fact that in over 1/3 of the comparisons, maximum PD sets contain less FD than randomly chosen sets of species. These results suggest that, while maximizing PD protection can help to protect FD, it represents a risky strategy.Statement of authorshipFM, MP, MC, SD, GVDR, RG, AOM, CT and WP conceived the design of the study. FM and GVDR conducted the analysis. FM, RG, MP and WP interpreted the results and wrote the first draft of the manuscript. All authors edited the final version.Data accessibility statementMost of the data is publicly available (see methods). The Fish data is available upon request.Code accessibility statementR functions developed in this paper are available at https://github.com/FloMazel/FD_PD_Max
Cross-feeding modulates antibiotic tolerance in bacterial communities
Authors: Adamowicz Elizabeth M. , Flynn Jeffrey , Hunter Ryan C. , Harcombe William R. 
Published: January 2018

AbstractMicrobes frequently rely on metabolites excreted by other bacterial species, but little is known about how this cross-feeding influences the effect of antibiotics. We hypothesized that when species rely on each other for essential metabolites, the minimum inhibitory concentration (MIC) for all species will drop to that of the “weakest link” - the species least resistant in monoculture. We tested this hypothesis in an obligate cross-feeding system that was engineered betweenEscherichia coli, Salmonella enterica, andMethylobacterium extorquens. The effect of tetracycline and ampicillin were tested on both liquid and solid media. In all cases, resistant species were inhibited at significantly lower antibiotic concentrations in the cross-feeding community than in monoculture or a competitive community. However, deviation from the “weakest link” hypothesis was also observed in cross-feeding communities apparently as result of changes in the timing of growth and cross-protection. Comparable results were also observed in a clinically relevant system involving facultative cross-feeding betweenPseudomonas aeruginosaand an anaerobic consortium found in the lungs of cystic fibrosis patients.P. aeruginosawas inhibited by lower concentrations of ampicillin when cross-feeding than when grown in isolation. These results suggest that cross-feeding significantly alters tolerance to antibiotics in a variety of systems.
A new look at multi-stage models of cancer incidence
Authors: Lian Tyler , Durrett Rick 
Published: January 2018

AbstractMulti-stage models have long been used in combination with SEER data to make inferences about the mechanisms underlying cancer initiation. The main method for studying these models mathematically has been the computation of generating functions by solving hyperbolic partial differential equations. Here, we analyze these models using a probabilistic approach similar to the one Durrett and Moseley [7] used to study branching process models of cancer. This more intuitive approach leads to simpler formulas and new insights into the behavior of these models. Unfortunately, the examples we consider suggest that fitting multi-stage models has very little power to make inferences about the number of stages unless parameters are constrained to take on realistic values.
A three-dimensional staging system of mouse endometrial gland morphogenesis
Authors: Vue Zer , Gonzalez Gabriel , Stewart C. Allison , Mehra Shyamin , Behringer Richard R. 
Published: January 2018

AbstractEndometrial or uterine glands secrete substances essential for uterine receptivity to the embryo, implantation, conceptus survival, development, and growth. Adenogenesis is the process of gland formation within the stroma of the uterus that occurs after birth. In the mouse, uterine gland formation initiates at postnatal day (P) 5. Subsequently, the developing uterine glands invade into the adjacent stroma. Mouse uterine gland morphology is poorly understood because it is based on two-dimensional (2D) histological observations. To more fully describe uterine gland morphogenesis, we generated three-dimensional (3D) models of postnatal uterine glands from P0 to P21, using light sheet microscopy. At birth (P0), there were no glands. At P8, we found bud- and teardrop-shaped epithelial invaginations. By P11, the forming glands were elongated epithelial tubes. By P21, the elongated tubes had a sinuous morphology. These morphologies are homogeneously distributed along the anterior-posterior axis of the uterus. To facilitate uterine gland analyses, we propose a novel 3D staging system of uterine gland morphology during postnatal development in the mouse. We define 6 stages: Stage 0: Aglandular, Stage 1: Bud, Stage 2: Teardrop, Stage 3: Elongated, Stage 4: Sinuous, and Stage 5: Primary Branches. This staging system provides a standardized key to assess and quantify uterine gland morphology that can be used for studies of uterine gland development and pathology. In addition, our studies suggest that gland formation initiation occurs during P8 and P11. However, between P11 and P21 gland formation initiation stops and all glands elongate and become sinuous.
Muscle stem cell intramuscular delivery within hyaluronan methylcellulose improves engraftment efficiency and dispersion
Authors: Davoudi Sadegh , Chin Chih-Ying , Cooke Michael C. , Tam Roger Y. , Shoichet Molly S. , Gilbert Penney M. 
Published: January 2018

AbstractAdult skeletal muscle tissue harbors the capacity for self-repair due to the presence of tissue resident muscle stem cells (MuSCs). Advances in the area of prospective MuSC isolation demonstrated the potential of cell transplantation therapy as a regenerative medicine strategy to restore strength and long-term regenerative capacity to aged, injured, or diseased skeletal muscle tissue. However, cell loss during ejection, limits to post-injection proliferation, and poor donor cell dispersion distal to the injection site are amongst hurdles to overcome to maximize MuSC transplant impact. Here, we assess a physical blend of hyaluronan and methylcellulose (HAMC) as a bioactive, shear thinning hydrogel cell delivery system to improve MuSC transplantation efficiency. Using in vivo transplantation studies, we found that the HAMC delivery system results in a >45% increase in the number of donor-derived fibers as compared to saline delivery. Furthermore, we observed a significant improvement in donor fiber dispersion when transplanted MuSCs were delivered in the HAMC hydrogel. Studies to assess primary myoblast and MuSC viability in HAMC culture revealed no differences compared to the media control even when the cells were first ejected through a syringe and needle or exposed to regenerating skeletal muscle extract to mimic the transplantation procedure. However, when we quantified absolute numbers, we found that more cells pass through the syringe and needle when delivered in HAMC. Culture in HAMC also increased the proportion of MuSCs in cell cycle, via a CD44-independent mechanism. An effect on myoblast proliferation was not observed, suggesting a hierarchical effect. Finally, a series of transplant studies indicated that HAMC delivery does not influence passive cell clearance or alter the host immune response, but instead may serve to support in vivo expansion by delaying differentiation following transplant. Therefore, we conclude that MuSC engraftment efficacy is improved by delivering the therapeutic cell population within HAMC.
Transcription factor dynamics reveals a circadian code for fat cell differentiation
Authors: Bahrami-Nejad Zahra , Zhao Michael L. , Tholen Stefan , Hunerdosse Devon , Tkach Karen E. , van Schie Sabine , Chung Mingyu , Teruel Mary N. 
Published: January 2018

SUMMARYGlucocorticoid and other adipogenic hormones are secreted in mammals in circadian oscillations. Loss of this circadian oscillation pattern during stress and disease correlates with increased fat mass and obesity in humans, raising the intriguing question of how hormone secretion dynamics affect the process of adipocyte differentiation. By using live, single-cell imaging of the key adipogenic transcription factors CEBPB and PPARG, endogenously tagged with fluorescent proteins, we show that pulsatile circadian hormone stimuli are rejected by the adipocyte differentiation control system, leading to very low adipocyte differentiation rates. In striking contrast, equally strong persistent signals trigger maximal differentiation. We identify the mechanism of how hormone oscillations are filtered as a combination of slow and fast positive feedback centered on PPARG. Furthermore, we confirm in mice that flattening of daily glucocorticoid oscillations significantly increases the mass of subcutaneous and visceral fat pads. Together, our study provides a molecular mechanism for why stress, Cushing’s disease, and other conditions for which glucocorticoid secretion loses its pulsatility can lead to obesity. Given the ubiquitous nature of oscillating hormone secretion in mammals, the filtering mechanism we uncovered may represent a general temporal control principle for differentiation.HIGHLIGHTWe found that the fraction of differentiated cells is controlled by rhythmic and pulsatile hormone stimulus patterns.Twelve hours is the cutoff point for daily hormone pulse durations below which cells fail to differentiate, arguing for a circadian code for hormone-induced cell differentiation.In addition to fast positive feedback such as between PPARG and CEBPA, the adipogenic transcriptional architecture requires added parallel slow positive feedback to mediate temporal filtering of circadian oscillatory inputs
Multi-regional Neurodegeneration in Alzheimer’s disease: Meta-analysis and data integration of transcriptomics data
Authors: Reza Karbalaei , Mostafa Rezaei-Tavirani , Bahareh Torkzaban , Sadegh Azimzadeh 
Published: January 2018

AbstractAlzheimer’s disease (AD) is a complex neurodegenerative disease with various deleterious perturbations in regulatory pathways of various brain regions. Thus, it would be critical to understanding the role of different regions of the brain in initiation and progression of AD, However, owing to complex and multifactorial nature of this disease, the molecular mechanism of AD has yet to be fully elucidated. To confront with this challenge, we launched a meta-analytical study of current transcriptomics data in four different regions of the brain in AD (Entorhinal, Hippocampus, Temporal and Frontal) with systems analysis of identifying involved signaling and metabolic pathways. We found different regulatory patterns in Entorhinal and Hippocampus regions to be associated with progression of AD. We also identified shared versus unique biological pathways and critical proteins among different brain regions. ACACB, GAPDH, ACLY, and EGFR were the most important proteins in Entorhinal, Frontal, Hippocampus and Temporal regions, respectively. Moreover, eight proteins including CDK5, ATP5G1, DNM1, GNG3, AP2M1, ALDOA, GPI, and TPI1 were differentially expressed in all four brain regions, among which, CDK5 and ATP5G1 were enriched in KEGG Alzheimer’s disease pathway as well.
Testing a dynamic model of the impact of psychological capital on work engagement and job performance
Authors: Alessandri Guido , Consiglio Chiara , Luthans Fred , Borgogni Laura 
Published: January 2018

PurposePsychological Capital (PsyCap), consisting of hope, efficacy, resilience, and optimism, is a positive state associated with attitudes, behaviors and performance. The purpose of this paper is to investigate a dynamic mediational model posing work engagement as the mediator of the longitudinal relation between PsyCap and job performance.Design/methodology/approachData came from all white collar employees who responded to this study’s variables (n=420) from a comprehensive data set drawn from a large communications service company over two consecutive years. Job performance was rated at the end of each year by the direct supervisor as part of the organizational appraisal system.FindingsStructural equation modeling analysis found that both absolute levels and increases in PsyCap predicted subsequent work engagement increases which in turn predicted job performance increases. Moreover, the mediating role of the changes in work engagement between previous PsyCap and performance change was confirmed over time.Research limitations/implicationsThere is much to gain in conceptualizing the relations among PsyCap, work engagement and job performance as dynamic, rather than static. The results support the conservation of resources theory, in which employees are motivated to acquire, protect and foster their valued (psychological) resources to attain successful performance outcomes, in order to create a gain cycle of resources (Salanova et al., 2010). Moreover, it provide further empirical validation for the idea that processes, like work engagement, are sustained by personal resources, and that these latter exerts mostly an indirect effect on organizational behavior outcomes (Xanthopoulouet al., 2009b).Practical implicationsThese results are important from a practical point of view, because they point to the importance of training interventions aimed at developing and sustaining PsyCap as an important determinant of workers’ motivation and behavior within the organization. Considerable literature offers practical insights and guidelines for developing PsyCap (Luthanset al., 2006, 2015; Luthans and Youssef-Morgan, 2017).Originality/valueDespite the demonstrated state-like, dynamic nature of PsyCap, its relationship with performance has mainly been statically analyzed and the role of possible mediating mechanisms largely ignored. This study begins to fill this research gap by investigating the dynamic nature of PsyCap in relation to work engagement and job performance and whether over time engagement mediates the relationship between PsyCap and job performance.
The informativeness of short sellers: an insider’s perspective
Authors: Gao George , Ma Qingzhong , Ng David 
Published: January 2018

Purpose
The purpose of this paper is to empirically examine whether corporate insiders extract information from activity of outsiders, specifically the short sellers.

Design/methodology/approach
Using portfolio approach and Fama-MacBeth regressions, this study examines the relation between short interest and subsequent insider trading activities.

Findings
The following results are reported. First, there is a strong inverse relation between short selling and subsequent insider trading, which is partially due to common private information and same target firm characteristics. Second, insiders extract information from shorts. This information extraction effect is more pronounced for firms whose insiders have stronger incentives to extract shorts information (insider purchases, higher short sale constraints, and better information environments). Third, during the September 2008 shorting ban, the information extraction affect disappeared among the large banned firms, whose shorting activities were distorted.

Research limitations/implications
The findings contradict the of-cited accusations corporate executives hold against short sellers. Instead, corporate insiders appear to trade in the same direction as suggested by shorting activities.

Practical implications
Among the vocal critics of short sellers are corporate insiders, who allege that short sellers beat down their stock prices. Many corporations even engage in stock repurchases to show confidence that the stock will perform well going forward despite the short sellers’ actions. This paper’s analysis on their personal portfolios suggests the other way around.

Originality/value
By focusing on how corporate insider trading is related to shorts information, this paper sheds new light on whether corporate decisions convey the true information the corporate insiders possess.