bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imaging NF‐κB activity in a murine model of early stage diabetes
Authors: Taghian Toloo , Metelev Valeriy G. , Zhang Surong , Bogdanov Alexei A. 
Published: November 2019

AbstractEarly pro‐inflammatory signaling in the endocrine pancreas involves activation of NF‐κB, which is believed to be important for determining the ultimate fate of β‐cells and hence progression of type 1 diabetes (T1D). Thus, early non‐invasive detection of NF‐κB in pancreatic islets may serve as a potential strategy for monitoring early changes in pancreatic endocrine cells eventually leading to T1D. We investigated the feasibility of optical imaging of NF‐κB transcription factor activation induced by low‐dose streptozocin (LD‐STZ) treatment in the immunocompetent SKH1 mouse model of early stage diabetes. In this model, we showed that the levels of NF‐κB may be visualized and measured by fluorescence intensity of specific near‐infrared (NIR) fluorophore‐labeled oligodeoxyribonucleotide duplex (ODND) probes. In addition, NF‐κB activation following LD‐STZ treatment was validated using immunofluorescence and transgenic animals expressing NF‐κB inducible imaging reporter. We showed that LD‐STZ‐treated SKH1 mice had significantly higher (2‐3 times, P < .01) specific NIR FI in the nuclei and cytoplasm of islets cells than in non‐treated control mice and this finding was corroborated by immunoblotting and electrophoretic mobility shift assays. Finally, using semi‐quantitative confocal analysis of non‐fixed pancreatic islet microscopy we demonstrated that ODND probes may be used to distinguish between the islets with high levels of NF‐κB transcription factor and control islet cells.
Fam20C‐mediated phosphorylation of osteopontin is critical for its secretion but dispensable for its action as a cytokine in the activation of hepatic stellate cells in liver fibrogenesis
Authors: Tibaldi Elena , Brocca Alessandra , Sticca Antonietta , Gola Elisabetta , Pizzi Marco , Bordin Luciana , Pagano Mario Angelo , Mazzorana Marco , Donà Gabriella , Violi Paola , Marin Oriano , Romano Antonella , Angeli Paolo , Carraro Amedeo , Brunati Anna Maria 
Published: November 2019

AbstractOsteopontin (OPN) is a phosphoglycoprotein secreted into the extracellular matrix upon liver injury, acting as a cytokine stimulates the deposition of fibrillary collagen in liver fibrogenesis. In livers of mice subjected to bile duct ligation (BDL) and in cultured activated hepatic stellate cells (HSCs), we show that OPN, besides being overexpressed, is substantially phosphorylated by family with sequence similarity 20, member C (Fam20C), formerly known as Golgi casein kinase (G‐CK), which is exclusively resident in the Golgi apparatus. In both experimental models, Fam20C becomes overactive when associated with a 500‐kDa multiprotein complex, as compared with the negligible activity in livers of sham‐operated rats and in quiescent HSCs. Fam20C knockdown not only confirmed the role of Fam20C itself in OPN phosphorylation, but also revealed that phosphorylation was essential for OPN secretion. However, OPN acts as a fibrogenic factor independently of its phosphorylation state, as demonstrated by the increased expression of Collagen‐I by HSCs incubated with either a phosphorylated or nonphosphorylated form of recombinant OPN. Collectively, our results confirm that OPN promotes liver fibrosis and highlight Fam20C as a novel factor driving this process by favoring OPN secretion from HSCs, opening new avenues for deciphering yet unidentified mechanisms underlying liver fibrogenesis.
The UFM1 cascade times mitosis entry associated with microcephaly
Authors: Yu Li , Li Guangxu , Deng Jing , Jiang Xuan , Xue Jin , Zhu Yingbao , Huang Wen , Tang Beisha , Duan Ranhui 
Published: November 2019

AbstractPosttranslational modifications enhance the functional diversity of the proteome by modifying the substrates. The UFM1 cascade is a novel ubiquitin‐like modification system. The mutations in UFM1, its E1 (UBA5) and E2 (UFC1), have been identified in patients with microcephaly. However, its pathological mechanisms remain unclear. Herein, we observed the disruption of the UFM1 cascade in Drosophila neuroblasts (NBs) decreased the number of NBs, leading to a smaller brain size. The lack of ufmylation in NBs resulted in an increased mitotic index and an extended G2/M phase, indicating a defect in mitotic progression. In addition, live imaging of the embryos revealed an impaired E3 ligase (Ufl1) function resulted in premature entry into mitosis and failed cellularization. Even worse, the embryonic lethality occurred as early as within the first few mitotic cycles following the depletion of Ufm1. Knockdown of ufmylation in the fixed embryos exhibited severe phenotypes, including detached centrosomes, defective microtubules, and DNA bridge. Furthermore, we observed that the UFM1 cascade could alter the level of phosphorylation on tyrosine‐15 of CDK1 (pY15‐CDK1), which is a negative regulator of the G2 to M transition. These findings yield unambiguous evidence suggesting that the UFM1 cascade is a microcephaly‐causing factor that regulates the progression of the cell cycle at mitosis phase entry.
Novel molecular mechanisms for Prph2‐associated pattern dystrophy
Authors: Chakraborty Dibyendu , Strayve Daniel G. , Makia Mustafa S. , Conley Shannon M. , Kakahel Mashal , Al‐Ubaidi Muayyad R. , Naash Muna I. 
Published: November 2019

AbstractMutations in peripherin 2 (PRPH2) have been associated with retinitis pigmentosa (RP) and macular/pattern dystrophies, but the origin of this phenotypic variability is unclear. The majority of Prph2 mutations are located in the large intradiscal loop (D2), a region that contains seven cysteines involved in intra‐ and intermolecular disulfide bonding and protein folding. A mutation at cysteine 213, which is engaged in an intramolecular disulfide bond, leads to butterfly‐shaped pattern dystrophy in humans, in sharp contrast to mutations in the adjacent cysteine at position 214 which result in RP. To help understand this unexpected phenotypic variability, we generated a knockin mouse line carrying the C213Y disease mutation. The mutant Prph2 protein lost the ability to oligomerize with rod outer segment membrane protein 1 (Rom1), but retained the ability to form homotetramers. C213Y heterozygotes had significantly decreased overall Prph2 levels as well as decreased rod and cone function. Critically, supplementation with extra wild‐type Prph2 protein elicited improvements in Prph2 protein levels and rod outer segment structure, but not functional rescue in rods or cones. These findings suggest that not all interruptions of D2 loop intramolecular disulfide bonding lead to haploinsufficiency‐related RP, but rather that more subtle changes can lead to mutant proteins stable enough to exert gain‐of‐function defects in rods and cones. This outcome highlights the difficulty in targeting Prph2‐associated gain‐of‐function disease and suggests that elimination of the mutant protein will be a pre‐requisite for any curative therapeutic strategy.
Genome-wide identification of a regulatory mutation in BMP15 controlling prolificacy in sheep
Authors: Chantepie Louise , Bodin Loys , Sarry Julien , Woloszyn Florent , Plisson-Petit Florence , Ruesche Julien , Drouilhet Laurence , Fabre Stéphane 
Published: November 2019

AbstractThe search for the genetic determinism of prolificacy variability in sheep has evidenced several major mutations in genes playing a crucial role in the control of ovulation rate. In the Noire du Velay (NV) sheep population, a recent genetic study has evidenced the segregation of such a mutation named FecLL. However, based on litter size (LS) records of FecLL non-carrier ewes, the segregation of a second prolificacy major mutation was suspected in this population. In order to identify this mutation, we have combined case/control genome-wide association study with ovine 50k SNP chip genotyping, whole genome sequencing and functional analyses. A new single nucleotide polymorphism (OARX:50977717T>A, NC_019484) located on the X chromosome upstream of the BMP15 gene was evidenced highly associated with the prolificacy variability (P =1.93E-11). The variant allele was called FecXN and shown to segregate also in the Blanche du Massif Central (BMC) sheep population. In both NV and BMC, the FecXN allele frequency was estimated close to 0.10, and its effect on LS was estimated at +0.20 lamb per lambing at heterozygous state. Homozygous FecXN carrier ewes were fertile with increased prolificacy in contrast to numerous mutations affecting BMP15. At the molecular level, FecXN was shown to decrease BMP15 promoter activity and to impact BMP15 expression in oocyte. This regulatory action was proposed as the causal mechanism for the FecXN mutation to control ovulation rate and prolificacy in sheep.Author SummaryIn the genetic etiology of women infertility syndromes, a focus was done on the oocyte-expressed BMP15 and GDF9 genes harboring several mutations associated with ovarian dysfunctions. In sheep also, mutations in these two genes are known to affect the ovarian function leading to sterility or, on the opposite, increasing ovulation rate and litter size constituting the prolificacy trait genetically selected in this species. Through a genome-wide association study with the prolificacy phenotype conducted in the French Noire du Velay sheep breed, we describe a novel mutation located in the regulatory region upstream of the BMP15 gene on the X chromosome. This mutation increases litter size by +0.2 lamb per lambing at the heterozygous state, possibly through an inhibition of BMP15 expression within the oocyte. Our findings suggest a novel kind of BMP15 variant responsible for high prolificacy, in contrast to all other BMP15 variants described so far in the coding sequence.
An alternative spliceosome defined by distinct snRNAs in early zebrafish embryogenesis
Authors: Pagano Johanna F. B. , Dekker Rob J. , Ensink Wim A. , van Olst Marina , Bos Alex , van Leeuwen Selina , de Leeuw Wim C. , Nehrdich Ulrike , Spaink Herman P. , Rauwerda Han , Jonker Martijs J. , Breit Timo M. 
Published: November 2019

ABSTRACTSplicing removes intronic RNA sequences from pre-mRNA molecules and enables, by alternative splicing, the generation of multiple unique RNA molecules from a single gene. As such, splicing is an essential part of the whole translation system of a cell. The spliceosome is a ribonucleoprotein complex in which five small nuclear RNAs (snRNAs) are involved; U1, U2, U4, U5, and U6. For each of these snRNAs there are variant gene copies present in a genome. Furthermore, in many eukaryotic species there is an alternative, minor spliceosome that can splice a small number of specific introns. As we previously discovered an embryogenesis-specific ribosomal system in zebrafish early embryogenesis based on variant rRNA and snoRNA expression, we hypothesized that there may also be an embryogenesis-specific spliceosome. An inventory of zebrafish snRNA genes revealed clustered and dispersed loci for all but U2 major snRNAs. For each minor spliceosome snRNA, just one gene locus was found. Since complete snRNA molecules are hard to sequence, we employed a combined PCR-sequencing approach to measure the individual snRNA-variant presence. Analysis of egg and male-adult samples revealed embryogenesis-specific and somatic-specific variants for each major snRNA. These variants have substantial sequence differences, yet none in their mRNA binding sites. Given that many of the sequence differences are found in loop structures indicate possible alternative protein binding. Altogether, with this study we established that the spliceosome is also an element of the embryogenesis-specific translation system in zebrafish.
Proteoglycan IMPG2 shapes the interphotoreceptor matrix and modulates vision
Authors: Salido Ezequiel M , Ramamurthy Visvanathan 
Published: November 2019

AbstractThe extracellular matrix surrounding the photoreceptor neurons, interphotoreceptor matrix (IPM) is comprised of two unique proteoglycans: IPM proteoglycan 1 and 2 (IMPG1 and IMPG2). Although the functions of the IPM are not understood, patients with mutations in IMPG1/2 develop visual deficits with subretinal material accumulation. Here, we generated mouse models lacking IMPG1/2 to decipher the role of these proteoglycans and the pathological mechanisms that lead to vision loss. IMPG1 and IMPG2 occupy specific locations in the outer retina, and both proteoglycans are fundamental for the constitution of the IPM system. Mice lacking IMPG2 show abnormal accumulation of IMPG1, and in later stages, develop subretinal lesions and reduced visual function. Interestingly, removal of IMPG1-2 showed normal retinal morphology and function, suggesting that the aberrant localization of IMPG1 causes the alterations observed in IMPG2 KO mice. In conclusion, our results demonstrate the role of IMPG2 in shaping the IPM, shed light on the potential mechanisms leading to subretinal lesions, and show that the secreted proteoglycans depend on the extracellular matrix environment to properly integrate into the matrix.
Fractional calculus-based analysis of soil electrical properties
Authors: Liang Guishu , Yang Yulan 
Published: November 2019

Purpose
This paper aims to analyze soil electrical properties based on fractional calculus theory due to the fact that the frequency dependence of soil electrical parameters at high frequencies exhibits a fractional effect. In addition, for the fractional-order formulation, this paper aims to provide a more accurate numerical algorithm for solving the fractional differential equations.

Design/methodology/approach
This paper analyzes the frequency-dependence of soil electrical properties based on fractional calculus theory. A collocation method based on the Puiseux series is proposed to solve fractional differential equations.

Findings
The algorithm proposed in this paper can be used to solve fractional differential equations of arbitrary order, especially for 0.5th-order equations, obtaining accurate numerical solutions. Calculating the impact response of the grounding electrode based on the fractional calculus theory can obtain a more accurate result.

Originality/value
This paper proposes an algorithm for solving fractional differential equations of arbitrary order, especially for 0.5th-order equations. Using fractional calculus theory to analyze the frequency-dependent effect of soil electrical properties, provides a new idea for ground-related transient calculation.
A parallel multi-fidelity optimization approach in induction hardening
Authors: Baldan Marco , Nikanorov Alexander , Nacke Bernard 
Published: November 2019

Purpose
Reliable modeling of induction hardening requires a multi-physical approach, which makes it time-consuming. In designing an induction hardening system, combining such model with an optimization technique allows managing a high number of design variables. However, this could lead to a tremendous overall computational cost. This paper aims to reduce the computational time of an optimal design problem by making use of multi-fidelity modeling and parallel computing.

Design/methodology/approach
In the multi-fidelity framework, the “high-fidelity” model couples the electromagnetic, thermal and metallurgical fields. It predicts the phase transformations during both the heating and cooling stages. The “low-fidelity” model is instead limited to the heating step. Its inaccuracy is counterbalanced by its cheapness, which makes it suitable for exploring the design space in optimization. Then, the use of co-Kriging allows merging information from different fidelity models and predicting good design candidates. Field evaluations of both models occur in parallel.

Findings
In the design of an induction heating system, the synergy between the “high-fidelity” and “low-fidelity” model, together with use of surrogates and parallel computing could reduce up to one order of magnitude the overall computational cost.

Practical implications
On one hand, multi-physical modeling of induction hardening implies a better understanding of the process, resulting in further potential process improvements. On the other hand, the optimization technique could be applied to many other computationally intensive real-life problems.

Originality/value
This paper highlights how parallel multi-fidelity optimization could be used in designing an induction hardening system.
Optimization of the shape of an induction heating device in the presence of skin effect in the coils
Authors: Aiello Giovanni , Alfonzetti Salvatore , Rizzo Santi Agatino , Salerno Nunzio 
Published: November 2019

Purpose
The optimization of the cross section of an axisymmetric induction heating device is performed by means of genetic algorithms (GAs).

Design/methodology/approach
The hybrid finite element method–Dirichlet boundary condition iteration method is used to deal with the unbounded nature of the field. The formulation of the electromagnetic problems takes into account skin and proximity effects in the source currents.

Findings
The convergence of GAs towards the optimum is very fast, since less than a thousand analyses have been necessary.

Originality/value
A special derivation of the finite element global system is presented which allows us to save computing time.
Men and masculinities in a changing world: (de)legitimizing gender ideals in advertising
Authors: Zayer Linda Tuncay , McGrath Mary Ann , Castro-González Pilar 
Published: November 2019

PurposeConversations surrounding gender are sweeping the globe as the voices and lived experiences of people are being heard and shared at unprecedented rates. Discourses about gender in advertising are embedded in cultural narratives and legitimatized by a broad system of institutional structures and actors, at both macro and micro/consumer levels. This study aims to explore how consumers (one type of institutional actor) engage in legitimizing/delegitimizing messages of gender in the marketplace.Design/methodology/approachThis research draws on a qualitative approach, specifically the use of in-depth interviews with men across three global contexts.FindingsThis research identifies the ways in which men engage in (de)legitimizing messages of masculinity in advertising such as reiteration, reframing, ascribing to alternate logics and prioritizing personal norms.Research limitations/implicationsAcross three contexts, this research theorizes the (de)legitimization of gender ideals in advertising and situates consumer narratives within broader institutional forces, providing a holistic understanding of the phenomenon.Practical implicationsUnderstanding the ways in which individuals either accept or reject gendered ideals in media aids advertising and marketing professionals in tailoring messages that resonate with audiences.Social implicationsUnderstanding how individuals negotiate their gender and the messages they deem as legitimate are crucial to understanding gender issues related to consumer welfare and public policy.Originality/valueWhile research has examined advertising practitioners’ views regarding gender from an institutional perspective, research on how consumers construct and maintain the legitimacy of gendered messages in the marketplace is scarce. This research theorizes and illustrates the (de)legitimization of gender ideals across three contexts.
Learning culture in a Chinese SME: the unique role of work-family enrichment
Authors: Xie Lei , Dirani Khalil M. , Beyerlein Michael , Qiu Shaoping 
Published: November 2019

Purpose
Learning and development are critical to a business’s success. This paper aims to focus on organizational factors at multiple organizational levels that facilitate learning culture in a small- and medium-sized enterprise (SME) in northwestern China.

Design/methodology/approach
This study is qualitative in nature. A single case study method is used to explore an SME’s organizational factors that facilitate learning culture.

Findings
This paper categorizes the organizational factors into seven dimensions: shared vision, creating continuous learning opportunities, informal learning that promotes inquiry and dialogue, collaboration and team learning, knowledge management systems, work–family enrichment and encouragement and support. This paper also compares the findings with learning culture models from Western research.

Research limitations/implications
Chinese culture has far-reaching and fundamental effects on many East Asian countries and regions. For SMEs in similar cultural settings with a collectivist orientation, future research may focus on the effect of the work–family enrichment on learning culture.

Originality/value
Work–family enrichment was found to be an important factor that influences learning effectiveness in this Chinese small business based on traditional values in Chinese culture.
Hotel revenue management for the transient segment: taxonomy-based research
Authors: Baker Tim , Eziz Aysajan , Harrington Robert J. 
Published: November 2019

Purpose
This paper aims to (1) organize the open literature on hotel revenue management systems, (2) compare practitioner systems in terms of functionality and (3) integrate (1)-(2) into research stream recommendations for the open literature with an empirical focus.

Design/methodology/approach
The authors use Nickerson’s taxonomy development method from the field of information systems to build the taxonomy.

Findings
New forecasting areas include developing a metric for the degree of strategic fit of a hotel’s pricing strategy and using it in conjunction with quantifications of online reviews for predictions. New price optimization avenues include determining whether a lack of congruence between customer perceptions of fairness and trust and pricing history has a detrimental effect on overall hotel performance and determining which combinations of flexible products, decision-maker risk aversion, nonparametric forecasting and reference effect optimization features work best in which situations.

Originality/value
This is the first study to combine vendor activities outside the technical realms of forecasting and price optimization with an emphasis on the choice modeling technical framework. This study points to several promising studies using qualitative methods, action research and design science.
Disaster risk management approaches in construction and built environment
Authors: Tavakoli Taba Seyedamir , Mojtahedi Mohammad , Newton Sidney 
Published: November 2019

Purpose
Currently there is no analysis of the development of disaster risk management literature in the construction and built environment context, the changes in its research paradigms over time and the role of different key players in the advance of its current body of knowledge. This study aims to address that gap by investigating the longitudinal data of disaster risk management literature published over the past three decades.

Design/methodology/approach
A social network analysis approach is used in this study to show the overall development of the field and specifically the impact of research collaborations between different organisations and countries on research productivity.

Findings
The results indicate that the focus of disaster risk management research in the built environment context is heavily biased towards reactive strategies (response and recovery) over proactive strategies (mitigation and preparedness). The findings also demonstrate that collaboration between disaster risk management researchers has a significant influence on their research productivity.

Originality/value
The findings from this study should be of value to researchers, policymakers and academic strategists. This study for the first time shows the ability of the social networks paradigm to reveal frailties in research connections in the field of disaster risk management in construction and built environment and highlights where networking strategies are needed.