bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the evolution of functional redundancy in metabolic networks
Authors: Sambamoorthy Gayathri , Raman Karthik 
Published: July 2018

Abstract

Motivation
Metabolic networks have evolved to reduce the disruption of key metabolic pathways by the establishment of redundant genes/reactions. Synthetic lethals in metabolic networks provide a window to study these functional redundancies. While synthetic lethals have been previously studied in different organisms, there has been no study on how the synthetic lethals are shaped during adaptation/evolution.

Results
To understand the adaptive functional redundancies that exist in metabolic networks, we here explore a vast space of ‘random’ metabolic networks evolved on a glucose environment. We examine essential and synthetic lethal reactions in these random metabolic networks, evaluating over 39 billion phenotypes using an efficient algorithm previously developed in our lab, Fast-SL. We establish that nature tends to harbour higher levels of functional redundancies compared with random networks. We then examined the propensity for different reactions to compensate for one another and show that certain key metabolic reactions that are necessary for growth in a particular growth medium show much higher redundancies, and can partner with hundreds of different reactions across the metabolic networks that we studied. We also observe that certain redundancies are unique to environments while some others are observed in all environments. Interestingly, we observe that even very diverse reactions, such as those belonging to distant pathways, show synthetic lethality, illustrating the distributed nature of robustness in metabolism. Our study paves the way for understanding the evolution of redundancy in metabolic networks, and sheds light on the varied compensation mechanisms that serve to enhance robustness.

Supplementary information
Supplementary data are available at Bioinformatics online.
Down‐regulation of acid sphingomyelinase and neutral sphingomyelinase‐2 inversely determines the cellular resistance to plasmalemmal injury by pore‐forming toxins
Authors: Schoenauer Roman , Larpin Yu , Babiychuk Eduard B. , Drücker Patrick , Babiychuk Viktoriia S. , Avota Elita , Schneider-Schaulies Sibylle , Schumacher Fabian , Kleuser Burkhard , Köffel René , Draeger Annette 
Published: July 2018

ABSTRACTBacterial pore‐forming toxins compromise plasmalemmal integrity, leading to Ca2+ influx, leakage of the cytoplasm, and cell death. Such lesions can be repaired by microvesicular shedding or by the endocytic uptake of the injured membrane sites. Cells have at their disposal an entire toolbox of repair proteins for the identification and elimination of membrane lesions. Sphingomyelinases catalyze the breakdown of sphingomyelin into ceramide and phosphocholine. Sphingomyelin is predominantly localized in the outer leaflet, where it is hydrolyzed by acid sphingomyelinase (ASM) after lysosomal fusion with the plasma membrane. The magnesium‐dependent neutral sphingomyelinase (NSM)‐2 is found at the inner leaflet of the plasmalemma. Because either sphingomyelinase has been ascribed a role in the cellular stress response, we investigated their role in plasma membrane repair and cellular survival after treatment with the pore‐forming toxins listeriolysin O (LLO) or pneumolysin (PLY). Jurkat T cells, in which ASM or NSM‐2 was down‐regulated [ASM knockdown (KD) or NSM‐2 KD cells], showed inverse reactions to toxin‐induced membrane damage: ASM KD cells displayed reduced toxin resistance, decreased viability, and defects in membrane repair. In contrast, the down‐regulation of NSM‐2 led to an increase in viability and enhanced plasmalemmal repair. Yet, in addition to the increased plasmalemmal repair, the enhanced toxin resistance of NSM‐2 KD cells also appeared to be dependent on the activation of p38/MAPK, which was constitutively activated, whereas in ASM KD cells, the p38/MAPK activation was constitutively blunted.—Schoenauer, R., Larpin, Y., Babiychuk, E. B., Drücker, P., Babiychuk, V. S., Avota, E., Schneider‐Schaulies, S., Schumacher, F., Kleuser, B., Köffel, R., Draeger, A. Down‐regulation of acid sphingomyelinase and neutral sphingomyelinase‐2 inversely determines the cellular resistance to plasmalemmal injury by pore‐forming toxins. FASEB J. 33, 275–285 (2019). www.fasebj.org
STAU1 binds to IBDV genomic double‐stranded RNA and promotes viral replication via attenuation of MDA5‐dependent β interferon induction
Authors: Ye Chengjin , Yu Zhaoli , Xiong Yiwei , Wang Yu , Ruan Yina , Guo Yueping , Chen Mianmian , Luan Shilu , Zhang Enli , Liu Hebin 
Published: July 2018

ABSTRACTInfectious bursal disease virus (IBDV) infection triggers the induction of type IIFN, which is mediated by melanoma differentiation‐associated protein 5 recognition of the viral genomic double‐stranded RNA (dsRNA). However, the mechanism of IBDV overcoming the type I IFN antiviral response remains poorly characterized. Here, we show that IBDV genomic dsRNA selectively binds to the host cellular RNA binding protein Staufen1 (STAU1) in vitro and in vivo. The viral dsRNA binding region was mapped to the N‐terminal moiety of STAU1 (residues 1–468). Down‐regulation of STAU1 impaired IBDV replication and enhanced IFN‐β transcription in response to IBDV infection, while having little effect on the viral attachment to the host cells and cellular entry. Conversely, over‐expression of STAU1 but not the IBDV dsRNA–binding deficient STAU1 mutant (469–702) led to a suppression of IBDV dsRNA–induced IFN‐β promoter activity. Moreover, we found that the binding of STAU1 to IBDV dsRNA decreased the association of melanoma differentiation‐associated protein 5 but not VP3 with the IBDV dsRNA in vitro. Finally, we showed that STAU1 and VP3 suppressed IFN‐β gene transcription in response to IBDV infection in an additive manner. Collectively, these findings provide a novel insight into the evasive strategies used by IBDV to escape the host IFN antiviral response.—Ye, C., Yu, Z., Xiong, Y., Wang, Y., Ruan, Y., Guo, Y., Chen, M., Luan, S., Zhang, E., Liu, H. STAU1 binds to IBDV genomic double‐stranded RNA and promotes viral replication via attenuation of MDA5‐dependent β interferon induction. FASEB J. 33, 286–300 (2019). www.fasebj.org
SFRP3 negatively regulates placental extravillous trophoblast cell migration mediated by the GCM1‐WNT10B‐FZD7 axis
Authors: Wang Liang‐Jie , Lo Hsiao‐Fan , Lin Cheng‐Fu , Ng Pui‐Sze , Wu Yi‐Hung , Lee Yun‐Shien , Cheong Mei‐Leng , Chen Hungwen 
Published: July 2018

ABSTRACTMigration of placental extravillous trophoblast (EVT) cells into uterine decidua facilitates the establishment of blood circulation between mother and fetus and is modulated by EVT‐decidual cell interaction. Poor or excessive EVT migration is associated with pregnancy complications such as preeclampsia or placenta accreta. Glial cells missing 1 (GCM1) transcription factor is essential for placental development, and decreased GCM1 activity is detected in preeclampsia. To study whether GCM1 regulates trophoblast cell migration, here we showed that GCM1 promotes BeWo and JAR trophoblast cell migration through a novel target gene, WNT10B. Moreover, WNT10B signaling stimulated cytoskeletal remodeling via Rac1 and frizzled 7 (FZD7) was identified as the cognate receptor for WNT10B to up‐regulate cell migration. We further showed that secreted frizzled‐related protein 3 (SFRP3) is expressed in uterine decidual cells by immunohistochemistry and that SFRP3 expression in telomerase‐transformed human endometrial stromal cells (T‐HESCs) is elevated under decidualization stimuli and further enhanced by bone morphogenetic protein 2 via SMAD1. SFRP3 blocked the interaction between FZD7 and WNT10B to decrease BeWo cell migration, which corroborated the elevated BeWo cell migration when cocultured with decidualized and SFRP3‐knockdown T‐HESC monolayer. Our results suggest that GCM1 up‐regulates EVT cell migration through WNT10B and FZD7, which is negatively modulated by decidual SFRP3.—Wang, L.‐J., Lo, H.‐F., Lin, C.‐F., Ng, P.‐S., Wu, Y.‐H., Lee, Y.‐S., Cheong, M.‐L., Chen, H. SFRP3 negatively regulates placental extravillous trophoblast cell migration mediated by the GCM1‐WNT10B‐FZD7 axis. FASEB J. 33, 314–326 (2019). www.fasebj.org
α‐Galactosidase A‐deficient rats accumulate glycosphingolipids and develop cardiorenal phenotypes of Fabry disease
Authors: Miller James J. , Aoki Kazuhiro , Mascari Carly A. , Beltrame Angela K. , Sokumbi Olayemi , North Paula E. , Tiemeyer Michael , Kriegel Alison J. , Dahms Nancy M. 
Published: July 2018

ABSTRACTFabry disease is an X‐linked lysosomal storage disease caused by α‐galactosidase A (α‐Gal A) deficiency. Kidney and heart failure are frequent complications in adulthood and greatly contribute to patient morbidity and mortality. Because α‐Gal A‐deficient mouse models do not recapitulate cardiorenal findings observed in patients, a nonmouse model may be beneficial to our understanding of disease pathogenesis. In this study, we evaluated disease processes in a recently generated Fabry rat model. We found that male Fabry rats weighed significantly less than wild‐type (WT) males, whereas female Fabry rats weighed significantly more than WT females. Whereas no difference in female survival was detected, we observed that male Fabry rats had a decreased lifespan. Skin histology revealed that inflammation and lipoatrophy may be chief disease mediators in patients. With respect to the kidney and heart, we found that both organs accumulate α‐Gal A substrates, including the established biomarkers, globotriaosylceramide and globotriaosylsphingosine. Longitudinal serum and urine chemistry panels demonstrated pronounced renal tubule dysfunction, which was confirmed histologically. Mitral valve thickening was observed in Fabry rats using echocardiography. We conclude that Fabry rats recapitulate important kidney and heart phenotypes experienced by patients and can be further used to study disease mechanisms and test therapies.—Miller, J. J., Aoki, K., Mascari, C. A., Beltrame, A. K., Sokumbi, O., North, P. E., Tiemeyer, M., Kriegel, A. J., Dahms, N. M., α‐Galactosidase A‐deficient rats accumulate glycosphingolipids and develop cardiorenal phenotypes of Fabry disease. FASEB J. 33, 418–429 (2019). www.fasebj.org
Microbial subnetworks related to short-term diel O2fluxes within geochemically distinct freshwater wetlands
Authors: Horton Dean J. , Cooper Matthew J. , Wing Anthony J. , Kourtev Peter S. , Uzarski Donald G. , Learman Deric R. 
Published: July 2018

ABSTRACTO2concentrations often fluctuate over diel timescales within wetlands, driven by temperature, sunlight, photosynthesis, and respiration. These daily fluxes have been shown to impact biogeochemical transformations (e.g. denitrification), which are mediated by the residing microbial community. However, little is known about how resident microbial communities respond to diel dramatic physical and chemical fluxes in freshwater wetland ecosystems. In this study, total microbial (bacterial and archaeal) community structure was significantly related to diel time points in just one out of four distinct freshwater wetlands sampled. This suggests that daily environmental shifts may influence wetlands differentially based upon the resident microbial community and specific physical and chemical conditions of a freshwater wetland. However, when exploring at finer resolutions of the microbial communities within each wetland, subcommunities within two wetlands were found to correspond to fluctuating O2levels. Microbial taxa that were found to be susceptible to fluctuating O2levels within these subnetworks may have intimate ties to metabolism and/or diel redox cycles. This study highlights that freshwater wetland microbial communities are often stable in community structure when confronted with short-term O2fluxes, however, specialist taxa may be sensitive to these same fluxes.
Phenotypic Age: a novel signature of mortality and morbidity risk
Authors: Liu Zuyun , Kuo Pei-Lun , Horvath Steve , Crimmins Eileen , Ferrucci Luigi , Levine Morgan 
Published: July 2018

AbstractBackground:A person’s rate of aging has important implications for his/her risk of death and disease, thus, quantifying aging using observable characteristics has important applications for clinical, basic, and observational research. We aimed to validate a novel aging measure, “Phenotypic Age”, constructed based on routine clinical chemistry measures, by assessing its applicability for differentiating risk for morbidity and mortality in both healthy and unhealthy populations of various ages.Methods:A nationally representative US sample, NHANES III, was used to derive “Phenotypic Age” based on a linear combination of chronological age and nine multi-system clinical chemistry measures, selected via cox proportional elastic net. Mortality predictions were validated using an independent sample (NHANES IV), consisting of 11,432 participants, for whom we observed a total of 871 deaths, ascertained over 12.6 year of follow-up. Proportional hazard models and ROC curves were used to evaluate predictions.Results:Phenotypic Age was significantly associated with all-cause mortality and cause-specific mortality. These results were robust to age and sex stratification, and remained even when excluding short-term mortality. Similarly, Phenotypic Age was associated with mortality among seemingly “healthy” participants—defined as those who were disease-free and had normal BMI at baseline—as well as the oldest-old (aged 85+)—a group with high disease burden.Conclusions:Phenotypic Age is a reliable predictor of all-cause and cause-specific mortality in multiple subgroups of the population. Risk stratification by this composite measure is far superior to that of the individual measures that go into it, as well as traditional measures of health. It is able to differentiate individuals who appear healthy, who may have otherwise been missed using traditional health assessments. Further, it can differentiate risk among persons with shared disease burden. Overall, this easily measured metric may be useful in the clinical setting and facilitate secondary and tertiary prevention strategies.
An Internet of Things (IoT)-based risk monitoring system for managing cold supply chain risks
Authors: Tsang Y.P. , Choy K.L. , Wu C.H. , Ho G.T.S. , Lam Cathy H.Y. , Koo P.S. 
Published: July 2018

Purpose
Since the handling of environmentally sensitive products requires close monitoring under prescribed conditions throughout the supply chain, it is essential to manage specific supply chain risks, i.e. maintaining good environmental conditions, and ensuring occupational safety in the cold environment. The purpose of this paper is to propose an Internet of Things (IoT)-based risk monitoring system (IoTRMS) for controlling product quality and occupational safety risks in cold chains. Real-time product monitoring and risk assessment in personal occupational safety can be then effectively established throughout the entire cold chain.

Design/methodology/approach
In the design of IoTRMS, there are three major components for risk monitoring in cold chains, namely: wireless sensor network; cloud database services; and fuzzy logic approach. The wireless sensor network is deployed to collect ambient environmental conditions automatically, and the collected information is then managed and applied to a product quality degradation model in the cloud database. The fuzzy logic approach is applied in evaluating the cold-associated occupational safety risk of the different cold chain parties considering specific personal health status. To examine the performance of the proposed system, a cold chain service provider is selected for conducting a comparative analysis before and after applying the IoTRMS.

Findings
The real-time environmental monitoring ensures that the products handled within the desired conditions, namely temperature, humidity and lighting intensity so that any violation of the handling requirements is visible among all cold chain parties. In addition, for cold warehouses and rooms in different cold chain facilities, the personal occupational safety risk assessment is established by considering the surrounding environment and the operators’ personal health status. The frequency of occupational safety risks occurring, including cold-related accidents and injuries, can be greatly reduced. In addition, worker satisfaction and operational efficiency are improved. Therefore, it provides a solid foundation for assessing and identifying product quality and occupational safety risks in cold chain activities.

Originality/value
The cold chain is developed for managing environmentally sensitive products in the right conditions. Most studies found that the risks in cold chain are related to the fluctuation of environmental conditions, resulting in poor product quality and negative influences on consumer health. In addition, there is a lack of occupational safety risk consideration for those who work in cold environments. Therefore, this paper proposes IoTRMS to contribute the area of risk monitoring by means of the IoT application and artificial intelligence techniques. The risk assessment and identification can be effectively established, resulting in secure product quality and appropriate occupational safety management.
When did fun become so much work
Authors: Loiacono Eleanor , McCoy Scott 
Published: July 2018

Purpose
The purpose of this paper is to investigate the negative impact the invasive nature of social media technologies (SMTs) can have on a user’s continued intention to use it.

Design/methodology/approach
In order to understand the impact technology invasiveness (TI) has on people’s continued SMT behavior, a research model and corresponding survey were developed based on a comprehensive literature review and data collected from actual SMT users.

Findings
The authors found perceived usefulness has a large impact on user’s attitudes. Additionally, social networking (SN) has a significant and direct impact on both attitude toward the use of the SMT and its continued use. Another interesting finding is how strongly SN increases a user’s TI. The negative impact technology has on users’ lives comes from the need users feel to continue to update and manage their online persona.

Practical implications
Social media tools are becoming part of the workplace environment. If not careful, companies may introduce increased pressures on their workers to constantly be “connected” to SMTs. In order to obtain the advantages of SMT usage, companies would be wise to set expectation standards that alleviate some of this pressure.

Social implications
This growth in social media would lead one to assume that all is well with SMTs and their usage is similar to other web-based technologies. However, there are some negative effects of SMT that warrant society and companies pausing to rethink the focus on these technologies.

Originality/value
Previous research has looked at IT from system success and acceptance. In this paper, we investigate the negative impact the invasive nature of SMTs can have on a user’s continued intention to use it.
Bridging past and present entrepreneurial marketing research
Authors: Most Fabian , Conejo Francisco J. , Cunningham Lawrence F. 
Published: July 2018

PurposeLiterature in entrepreneurial marketing (EM) continues to grow in volume and diversity. This paper aims to examine the topical structure of EM’s literature toward guiding research in the field.Design/methodology/approachA four-phase bibliometric research design is implemented, encompassing co-citation and bibliographic-coupling analyses, network analysis, factor analysis and correspondence analysis.FindingsIn total, 14 EM literature clusters, comprising 7 topical meta-clusters, are mapped and discussed: the 7 clusters are resources and capabilities, entrepreneurial orientation (EO), measurement, EO/marketing orientation (MO) integration, MO, international entrepreneurship and social entrepreneurship.Originality/valueThese topical streams confirm, refine and extend prior bibliometric studies. A more comprehensive, extensive and reliable picture of EM’s literature is provided, the result of using over twice as many references as prior studies and peer-reviewed journals only. Results will help guide EM research, contributing toward the field’s empirical/theoretical development.
Structural investigation of spunlace nonwoven
Authors: Jain Ravi Kumar , Sinha Sujit Kumar , Das Apurba 
Published: July 2018

Purpose
Spunlacing is a promising nonwoven technology for the production of fabric with good handle and better structural integrity. Structural parameters such as pore size, thickness and number of binding point/entanglement between fibres are decisive for good mechanical and comfort properties of nonwoven fabrics. This study aims to focus on the effect of different process parameters on the structural change in spunlace fabrics.

Design/methodology/approach
Spunlacing is purely a mechanical bonding technology where high-speed jets of water strike a web to entangle the fibres. Different spunlace nonwoven structures were produced by varying processing parameters such as waterjet pressure, delivery speed, web mass and web composition as per four-factor, three-level Box–Behnken design. The effect of these parameters on the structural arrangement was studied using scanning electron microscopy. An attempt has also been made to study the changes in pore geometry and thickness of the fabrics by using response surface methodology with backward elimination.

Findings
Significant structural changes were observed with variation in water pressure, web mass and web composition. The test results showed that fabric produced at higher waterjet pressure has lower mean pore diameter and lower thickness. The variation in mean pore diameter and mean thickness due to waterjet pressure is around 26 and 34 per cent, respectively, at 95 per cent significance level. The web composition and web mass also significantly influence the mean pore diameter and thickness at 95 per cent significance level. There is a strong positive correlation (r = 0.523) between mean air permeability and mean pore diameter of fabric, and this correlation is significantly linear. A strong negative correlation (r = −0.627) is found between weight and air permeability of fabric.

Research limitations/implications
The delivery speed failed to show any significant effect; this is in contrary to the general expectation.

Originality/value
The effect of concurrent variation in waterjet pressure, web mass, delivery speed and web composition on the structure of spunlace nonwoven is studied, which was not reported in the literature. The effect of web composition on pore diameter of spunlace nonwoven is interesting finding. This study is expected to help in designing the spunlace nonwoven as per end uses and specifically for apparel application.