bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microtubules Regulate Spatial Localization and Availability of Insulin Granules in Pancreatic Beta Cells
Authors: Bracey Kai M. , Ho Kung-Hsien , Yampolsky Dmitry , Gu Guoqiang , Kaverina Irina , Holmes William R. 
Published: March 2019

AbstractTwo key prerequisites for glucose stimulated insulin secretion (GSIS) in Beta cells are the proximity of insulin granules to the plasma membrane and their anchoring or docking to the plasma membrane (PM). While recent evidence has indicated that both of these factors are altered in the context of diabetes, it is unclear what regulates localization of insulin and its interactions with the PM within single cells. Here we demonstrate that microtubule (MT) motor mediated transport dynamics have a critical role in regulating both factors. Super-resolution imaging shows that while the MT cytoskeleton resembles a random meshwork in the cells’ interior, MTs near the cells surface are preferentially aligned with the PM. Computational modeling demonstrates two consequences of this alignment. First, this structured MT network preferentially withdraws granules from the PM. Second, the binding and transport of insulin granules by MT motors prevents their stable anchoring to the PM. The MT cytoskeleton thus negatively regulates GSIS by both limiting the amount of insulin proximal to the PM and preventing/breaking interactions between the PM and the remaining nearby insulin. These results predict that altering MT structure in beta cells can be used to tune GSIS. Thus, our study points to a potential of an alternative therapeutic strategy for diabetes by targeting specific MT regulators.
Estimating narrow-sense heritability from genome-wide data in admixed populations
Authors: Athanasiadis Georgios , Speed Doug , Andersen Mette K. , Appel Emil V. R. , Grarup Niels , Brandslund Ivan , Jørgensen Marit Eika , Lytken Larsen Christina Viskum , Bjerregaard Peter , Hansen Torben , Albrechtsen Anders 
Published: March 2019

AbstractFinding an efficient framework for estimating total narrow-sense heritability in admixed populations remains an open question. In this work, we used extensive simulations to evaluate existing linear mixed model frameworks in estimating total narrow-sense heritability in two population-based cohorts from Greenland and compared the results to data from unadmixed individuals from Denmark. When our analysis focused on Greenlandic sib pairs, the model with two relationship matrices, one capturing identity by descent and one capturing identity by state, returned heritability estimates close to the true simulated value, while using each of the two matrices alone led to downward biases. When phenotypes correlated with ancestry, heritability estimates were inflated. Based on these observations, we propose a post-estimation PCA-based adjustment that recovers successfully the true simulated heritability. We use this knowledge to estimate the heritability of ten quantitative traits from the two Greenlandic cohorts and report differences such as lower heritability for height in Greenlanders compared to Europeans. In conclusion, narrow-sense heritability in admixed populations is best estimated using a mixture of genetic relationship matrices on individuals with at least one first-degree relative included in the sample.
PERK inhibition mitigates restenosis and thrombosis - a potential low-thrombogenic anti-restenotic paradigm
Authors: Wang Bowen , Zhang Mengxue , Urabe Go , Chen Guojun , Wheeler Debra , Dornbos David , Huttinger Allyson , Huang Yitao , Nimjee Shahid , Gong Shaoqin , Guo Lian-Wang , Kent K Craig 
Published: March 2019

AbstractBackgroundDrug-eluting stents (DES) represent the main-stream management of restenosis following treatments of occlusive cardiovascular diseases. However, DES cannot eliminate instent restenosis yet exacerbate thrombogenic risks. To achieve dual inhibition of restenotic smooth muscle cell (SMC) de-differentiation/proliferation and thrombogenic endothelial cell (EC) dysfunction, a common target in both cell types, has been long-sought after. We evaluated the potential of protein kinase RNA-like endoplasmic reticulum kinase (PERK) as such a target for low-thrombogenic anti-restenotic intervention.Methods and ResultsWe used a rat angioplasty model of restenosis and a FeCl3-induced mouse model of thrombosis. Loss-or gain-of-function was achieved by PERK inhibition (GSK2606414, siRNA) or overexpression (adenovirus). Restenosis was robustly mitigated by GSK2606414 administered either via injected (i.v.) lesion-homing platelet membrane-coated nanoclusters or a perivascular hydrogel; it was enhanced by PERK transgene. Whereas PERK inhibition blocked, its overexpression exacerbated PDGF-induced human aortic SMC de-differentiation (reduced smooth muscle α-actin or αSMA) and proliferation (BrdU incorporation). Further, PERK activity promoted STAT3 activation but inhibited SRF transcriptional (luciferase) activity; its protein co-immunoprecipitated with STAT3 and also MRTF-A, the SRF activator for αSMA transcription. Importantly, PERK inhibition also prevented TNFα-induced impairment of human EC growth and upregulation of thrombogenic tissue factor, both in vitro and ex vivo. In vivo, oral gavage of GSK2606414 preserved ~50% of the normal blood flow 60 min after FeCl3-induced vascular injury.ConclusionsPERK inhibition is dual beneficial in mitigating restenosis and thrombosis, thus implicating a potential design for anti-restenotic intervention to overcome the thrombogenicity of DES.
Naturally Produced Lovastatin Modifies the Histology and Proteome Profile of Goat Skeletal Muscle
Authors: Leo Teik Kee , Garba Sani , Abubakar Danmaigoro , Sazili Awis Qurni , Candyrine Su Chui Len , Jahromi Mohammad Faseleh , Goh Yong Meng , Ronimus Ron , Muetzel Stefan , Liang Juan Boo 
Published: March 2019

AbstractEnteric methane formation in ruminants is one of the major contributors to climate change. We have reported that supplementation of naturally produced lovastatin reduced methane emissions in goats without adversely affecting rumen fermentation and animal performance, except that at higher level, lovastatin can have a negative effect on the palatability of the formulated diet. As statins are associated with the development of muscle-related adverse effects at higher than recommended therapeutic doses, this study was conducted to examine the effects of lovastatin on the histology and proteome profile of goat skeletal muscle. A total of 20 intact male Saanen goats were randomly assigned in equal numbers to 4 groups, and fed with a total mixed ration containing 50% rice straw, 22.8% concentrates and 27.2% of various proportions of untreated or treated palm kernel cake (PKC) to achieve the target daily intake levels of 0 (Control), 2 (Low), 4 (Medium) or 6 (High) mg lovastatin/kg body weight (BW). Histological examination discovered that the longissimus thoracis et lumborum muscle of animals from the Medium and High treatment groups showed abnormalities in terms of necrosis, degeneration, interstitial space and vacuolation. Western blot analysis conducted on the myosin heavy chain showed that the immunoreactivity of myosin heavy chain in the High treatment group was significantly lower than the Control, Low and Medium treatment groups. Comparisons between control and lovastatin-treated groups demonstrated that lovastatin supplementation induced complex modifications to the protein expression patterns of the longissimus thoracis et lumborum muscle of the goat. There were 30, 26 and 24 proteins differentially expressed in Low, Medium and High treatment groups respectively, when compared to the Control group. Supplementation of lovastatin down-regulated proteins involved in carbohydrate and creatine metabolism, indicative of reduced energy production, and may have contributed to the skeletal muscle damage. Supplementation of naturally produced lovastatin induced muscle damage in longissimus thoracis et lumborum muscle of goats with increasing dosages, particularly at 6mg/kg BW. In addition, proteomics analysis revealed that lovastatin supplementation induced complex modifications to the protein expressions of skeletal muscle of goats which may have contributed to the observed skeletal muscle damage. Present study suggested that supplementation of naturally-produced lovastatin at 6mg/kg BW could adversely affecting health and wellbeing of the animals.
Sex differences in reward- and punishment-guided actions
Authors: Chowdhury Tara G. , Wallin-Miller Kathryn G. , Rear Alice A. , Park Junchol , Diaz Vanessa , Simon Nicholas W. , Moghaddam Bita 
Published: March 2019

ABSTRACTDifferences in the prevalence and presentation of psychiatric illnesses in men and women suggest that neurobiological sex differences confer vulnerability or resilience in these disorders. Rodent behavioral models are critical for understanding the mechanisms of these differences. Reward processing and punishment avoidance are fundamental dimensions of the symptoms of psychiatric disorders. Here we explored sex differences along these dimensions using multiple and distinct behavioral paradigms. We found no sex difference in reward-guided associative learning but a faster punishment-avoidance learning in females. After learning, females were more sensitive than males to probabilistic punishment but less sensitive when punishment could be avoided with certainty. No sex differences were found in reward-guided cognitive flexibility. Thus, sex differences in goal-directed behaviors emerged selectively when there was an aversive context. These differences were critically sensitive to whether the punishment was certain or unpredictable. Our findings with these new paradigms provide conceptual and practical tools for investigating brain mechanisms that account for sex differences in susceptibility to anxiety and impulsivity. They may also provide insight for understanding the evolution of sex-specific optimal behavioral strategies in dynamic environments.
A quantitative modular modeling approach reveals the consequences of different A20 feedback implementations for the NF-kB signaling dynamics
Authors: Mothes Janina , Ipenberg Inbal , Arslan Seda Çöl , Benary Uwe , Scheidereit Claus , Wolf Jana 
Published: March 2019

AbstractSignaling pathways involve complex molecular interactions and are controlled by non-linear regulatory mechanisms. If details of regulatory mechanisms are not fully elucidated, they can be implemented by different, equally reasonable mathematical representations in computational models. The study presented here focusses on NF-κB signaling, which is regulated by negative feedbacks via IκBα and A20. A20 inhibits NF-κB activation indirectly through interference with proteins that transduce the signal from the TNF receptor complex to activate the IκB kinase (IKK) complex. We focus on the question how different implementations of the A20 feedback impact the dynamics of NF-κB. To this end, we develop a modular modeling approach that allows combining previously published A20 modules with a common pathway core module. The resulting models are based on a comprehensive experimental data set and therefore show quantitatively comparable NF-κB dynamics. Based on defined measures for the initial and long-term behavior we analyze the effects of a wide range of changes in the A20 feedback strength, the IκBα feedback strength and the TNFα stimulation strength on NF-κB dynamics. This shows similarities between the models but also model-specific differences. In particular, the A20 feedback strength and the TNFα stimulation strength affect initial and long-term NF-κB concentrations differently in the analyzed models. We validated our model predictions experimentally by varying TNFα concentrations applied to HeLa cells. These time course data indicate that only one of the A20 feedback models appropriately describes the impact of A20 on the NF-κB dynamics.Author summaryModels are abstractions of reality and simplify a complex biological process to its essential components and regulations while preserving its particular spatial-temporal characteristics. Modelling of biological processes is based on assumptions, in part to implement the necessary simplifications but also to cope with missing knowledge and experimental information. In consequence, biological processes have been implemented by different, equally reasonable mathematical representations in computational models. We here focus on the NF-κB signaling pathway and develop a modular modeling approach to investigate how different implementations of a negative feedback regulation impact the dynamical behavior of a computational model. Our analysis shows similarities of the models with different implementations but also reveals implementation-specific differences. The identified differences are used to design and perform informative experiments that elucidate unknown details of the regulatory feedback mechanism.
Attract customers with a cold look: when do we prefer cold representative
Authors: Xie Zhipeng , Zhao Jing , Wang Tao 
Published: March 2019

Purpose
The purpose of this paper is to examine the contradictory effect of coldness in advertisement and brand logo design.

Design/methodology/approach
The authors conduct four experiments to test the influences of coldness on consumers’ attitude. In the first two experiments, the researchers use real/virtual brand names to test the moderating effect of brand status and customer power; in Study 3, the researchers test the moderating effect of autonomy; while in the last experiment, the findings in the previous experiments are extended to explain similar effect of cold/warm brand logo designs.

Findings
This research finds that coldness also brings benefit to brands under certain circumstances. More specifically, cold endorsers/brand logo designs are only beneficial for brands of high (vs low) status, and can only attract consumers who experience high power (vs low power). Such effects are mediated by consumers’ perceived brand autonomy.

Research limitations/implications
This research urges the managers to analyze the characteristics of the brand and its target consumer. It also points out that the effectiveness of warm/cold representative derives from the customer perceived brand autonomy.

Originality/value
The authors’ contributions to the literature are as follows. First, this research examines the relationship between coldness and autonomy, which enables us to expand the findings to various contexts; second, this research expands the horizon of autonomy theory by identifying customer power and brand status as its moderators.
Pursuing superior performance of service innovation through improved corporate social responsibility
Authors: Li Lan , Li Gang , Yang Xue , Yang Zhilin 
Published: March 2019

PurposeThe purpose of this paper is to investigate the impact of corporate social responsibility (CSR) on the performance of service innovation (PSI), and the mediating effect of knowledge acquisition.Design/methodology/approachDrawing on social exchange and knowledge management theories, this paper establishes a relevant conceptual model and adopts a hierarchical regression analysis to examine the model with a data set of 298 firms from China.FindingsCSR positively affects the PSI; however, the effects vary when firms take responsibility for different stakeholders. CSR for the same group of stakeholders influences differently the short-term financial and long-term non-financial PSI, whereas knowledge acquisition mediates the impact of employee and customer CSR on PSI, but not the impact of community CSR on PSI.Practical implicationsManagers could improve the PSI of the firm by strategically assuming CSR and by managing corporate knowledge acquisition activities.Originality/valueThis study contributes to the service innovation literature by identifying the influence of particular types of CSR on PSI, and by highlighting the influencing mechanism of knowledge acquisition. It extends scholarly understanding of the antecedents of PSI as well as the business returns to CSR.
Celebrity poses and consumer attitudes in endorsement advertisements
Authors: Liu Yongdan , Liu Matthew Tingchi 
Published: March 2019

Purpose
The purpose of this paper is to investigate the effects of celebrity’s poses on consumer attitudes towards the endorsement advertisement by drawing from perceptual fluency hypotheses.

Design/methodology/approach
Study 1 used a single-factor, two-condition (distinctive pose and casual pose) between-subject design. Both Study 2a and Study 2b employed a single-factor, two-condition (distinctive pose, casual pose) between-subject design and tested the mediator of pose matchiness. Study 3 employed a 2 (pose condition: distinctive, casual)×2 (cognitive capacity: no load, load) between-subject design to test the moderator. All data were sourced from more than 600 respondents in China.

Findings
Study 1 illustrated that the existence of a distinctive pose can lead to higher consumer attitudes regarding advertising stimuli and the endorsed brands as well as more positive behavioural intentions towards endorsed products. Study 2a and Study 2b replicated such finding and demonstrated that the feeling of pose matchiness mediates the relationship between celebrities’ pose and endorsement outcomes. Study 3 further revealed that the cognitive capacity moderates such a relationship, that is, that the effect of a distinctive pose is stronger (lesser) when audiences’ cognitive capacity is loaded (not loaded).

Originality/value
Research efforts to date examining the nature of celebrity advertisement have been limited to celebrity’s faces and facial expressions. Little investigation in the marketing domain has considered the consequences of celebrities’ poses. This study takes the first step in revealing the positive effect of distinctive celebrity poses in product endorsement.
The application of multi-attribute utility theory for a market share-based design evaluation
Authors: BuHamdan Samer , Alwisy Aladdin , Bouferguene Ahmed , Al-Hussein Mohamed 
Published: March 2019

PurposeThe purpose of this paper is to use the concepts of the multi-attribute utility theory to develop a model to evaluate the design of low-density residential units to increase the profit of the company from a certain design, by assessing the changes in the market shares as a result of the built unit’s attributes.Design/methodology/approachThe proposed platform consists of two stages: Stage I or relational model development and Stage II or design evaluation. Stage I is concerned with developing a mathematical model that links design variables (e.g. the R-Value of the building envelope and construction material) with the assessment attributes (e.g. price and carbon emissions). Stage II ensures the fulfillment of the corporation’s goals in maximizing profit and market shares using multi-attribute utility theory.FindingsThe application of the proposed model on a case study – a single-family house – shows that reducing the selling price of the unit is not always the best marketing strategy builders should pursue to increase their sales and accordingly their profit, as accounting for other attributes (e.g. performance, operational cost and environmental impact) leads to larger changes in the market shares and accordingly in profit.Research limitations/implicationsThe limitations of this research are manifested in the following points: it does not account for the impact of the marketing campaigns on the market shares; it considers the profit as a percentage of the construction cost; and it has not been validated on high-density residential buildings.Practical implicationsThis research provides speculative builders with a platform that allows the objective evaluation of houses’ designs prior to introducing them to the market so builders can increase their market shares and consequently their profit. The proposed platform also contributes to increasing the sustainable performance of the housing industry, as it allows for the assessment of the design against economic, environmental and social attributes concurrently, which ensures a balanced consideration of the built houses on sustainability pillars.Social implicationsThe proposed platform for design evaluation extends the assessment attributes beyond the traditionally considered economic and environmental attributes. By doing so, it assists decision-makers in evaluating the potential social influence of the proposed design and, as a result, reduces the unwanted impact.Originality/valueThis research combines the concepts of multi-attribute utility with market studies to develop an objective decision support tool for evaluating the design of speculative houses to increase the sustainable performance of the builders without compromising on their profit.
Managers’ views on how intellectual capital is recognized and managed in practice
Authors: Tyskbo Daniel 
Published: March 2019

Purpose
The purpose of this paper is to advance the understanding of how intellectual capital (IC) unfolds in practice in organizations. This is done by answering the research question of how IC is recognized and managed in practice as expressed by managers.

Design/methodology/approach
An explorative, empirical and multiple case study was conducted, investigating four Swedish firms.

Findings
This paper illustrates how IC was recognized and managed in practice despite managers expressing uncertainty of what the IC concept means. More or less direct, formalized and purposeful ways were adopted. The IC elements and practices most important from a management perspective were those aligned with the overall strategy, but were seldom what was visible in financial reports.

Research limitations/implications
The use of an explorative, multiple case study limits the generalizability. However, the rich view gained of how IC unfolds in practice may not always be possible using large sample, survey-studies. Future research is therefore suggested to take this paper’s insights further and investigate IC in other organizations and in other national contexts.

Originality/value
This paper responds to the calls for third stage IC research, by showing how IC management in practice may not be as clear and straightforward as researchers tend to assume. It also adds to the importance debate on IC accountingization, by reflecting on how an accounting dominance may not fully capture IC inside organizations. A number of practical contributions are also made.