bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural insights into ligand efficacy and activation of the glucagon receptor
Authors: Hilger Daniel , Kumar Kaavya Krishna , Hu Hongli , Pedersen Mie Fabricius , Giehm Lise , Mathiesen Jesper Mosolff , Skiniotis Georgios , Kobilka Brian K. 
Published: June 2019

AbstractThe glucagon receptor family comprises Class B G protein-coupled receptors (GPCRs) that play a crucial role in regulating blood sugar levels. Receptors of this family represent important therapeutic targets for the treatment of diabetes and obesity. Despite intensive structural studies, we only have a poor understanding of the mechanism of peptide hormone-induced Class B receptor activation. This process involves the formation of a sharp kink in transmembrane helix 6 that moves out to allow formation of the nucleotide-free G protein complex. Here, we present the cryo-EM structure of the glucagon receptor (GCGR), a prototypical Class B GPCR, in complex with an engineered soluble glucagon derivative and the heterotrimeric G-protein, Gs. Comparison with the previously determined crystal structures of GCGR bound to a partial agonist reveals a structural framework to explain the molecular basis of ligand efficacy that is further supported by mutagenesis data.
Non-coding RNAs control metabolic state in mycobacteria
Authors: Mehta Dolly , Anjali K , Achuthan A , Gupta Ritu , Ramesh Arati 
Published: June 2019

ABSTRACTNon-coding RNAs play pivotal roles in bacterial signaling. However, RNAs from certain phyla (specially high-GC actinobacteria) remain elusive. Here, by revamping existing approaches we discover a family of structurally conserved RNAs in actinobacteria. These RNAs function by the recruiting ANTAR proteins to select transcripts; regulating them via translational repression. By overlapping with ORF start sites, these RNAs provide mechanisms by which even leader-less transcripts are regulated. In mycobacteria, transcripts marked by ANTAR-target RNAs are few but encode important redox enzymes especially involved in lipid metabolism. Notably, the cellular response to ANTAR-regulation is hierarchical, wherein immediate metabolic changes induced by ANTAR-RNA binding are amplified through a global transcriptomic response. This includes several genes from oxidative/reductive pathways; ultimately switching cells towards reductive metabolism. This discovery of ANTAR-target RNAs and associated regulation places RNAs as crucial players in controlling metabolic flexibility of mycobacteria, proposing a prominent role for ANTAR regulation across actinobacteria.
ADrosophilaInsulator Interacting Protein Suppresses Enhancer-Blocking Function and Modulates Replication Timing
Authors: Stow Emily C. , An Ran , Schoborg Todd A. , Davenport Nastasya M. , Simmons James R. , Labrador Mariano 
Published: June 2019

AbstractInsulators play important roles in genome structure and function inDrosophilaand mammals. More than six different insulator proteins are required inDrosophilafor normal genome function, whereas CTCF is the only identified protein contributing to insulator function in mammals. Interactions between a DNA binding insulator protein and its interacting partner proteins define the properties of each insulator site. The different roles of insulator protein partners in theDrosophilagenome and how they confer functional specificity remain poorly understood. Functional analysis of insulator partner proteins inDrosophilais necessary to understand how genomes are compartmentalized and the roles that different insulators play in genome function. InDrosophila, the Suppressor of Hairy wing [Su(Hw)] insulator is targeted to the nuclear lamina, preferentially localizes at euchromatin/heterochromatin boundaries, and is associated with theGypsyretrotransposon. The properties that the insulator confers to these sites rely on the ability of the Su(Hw) protein to bind the DNA at specific sites and interact with Mod(mdg4)-67.2 and CP190 partner proteins. HP1 and insulator partner protein 1 (HIPP1) is a recently identified partner of Su(Hw), but how HIPP1 contributes to the function of Su(Hw) insulators has not yet been elucidated. Here, we find that mutations in the HIPP1 crotonase-like domain have no impact on the function of Su(Hw) enhancer-blocking activity but do exhibit an impaired ability to repair double-strand breaks. Additionally, we find that the overexpression of each HIPP1 and Su(Hw) causes defects in cell proliferation by limiting the progression of DNA replication. We also find that HIPP1 overexpression suppresses the Su(Hw) insulator enhancer-blocking function.
Combined EGFR and ROCK inhibition in TNBC leads to cell death via impaired autophagic flux
Authors: Rontogianni Stamatia , Iskit Sedef , van Doorn Sander , Peeper Daniel S. , Altelaar A. F. Maarten 
Published: June 2019

AbstractTriple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with very limited therapeutic options. We have recently shown that the combined inhibition of EGFR and ROCK in TNBC cells results in cell death, however, the underlying mechanisms remain unclear. To investigate this, here we applied a mass spectrometry-based proteomic approach to identify proteins altered upon single and combination treatments. Our proteomic data revealed autophagy as the major molecular mechanism implicated in the cells’ response to combinatorial treatment. In particular, we here show that EGFR inhibition by gefitinib treatment alone induces autophagy, a cellular recycling process that acts as a cytoprotective response for TNBC cells. However, combined inhibition of EGFR and ROCK leads to autophagy blockade and accumulation of autophagic vacuoles. Our data show impaired autophagosome clearance as a cause of antitumor activity. We propose that the inhibition of the autophagic flux upon combinatorial treatment is attributed to the major cytoskeletal changes induced upon ROCK inhibition, given the essential role the cytoskeleton plays throughout the various steps of the autophagy process.
Electron microscopy characterization of minerals formed in vitro by human bone cells and vascular smooth muscle cells
Authors: Tsolaki Elena , Didierlaurent Louis , Müller Eike , Rottmar Markus , Latif Najma , Chester Adrian H. , Herrmann Inge K. , Bertazzo Sergio 
Published: June 2019

AbstractSoft tissue mineralization has been found to be a major component of diseases such as aortic valve stenosis and rheumatic heart disease. Cardiovascular mineralization has been suggested to follow mechanisms similar to those of bone formation with several cell culture models been developed over the years to provide mechanistic insights. These cell models have been characterized by a wide range of biochemical and molecular methods, which identified the presence of osteogenic markers and bone-like cells. However, there is a surprisingly small number of studies where the mineral formed in these cell culture models has been characterized by physico-chemical methods, and even fewer studies have compared this mineral to the one produced by bone cells in cultures. Here we investigated the morphology and composition of the minerals formed in cell cultures of vascular smooth muscle cells and bone cells. Electron microscopy and traditional cell mineralization assays were applied, revealing that vascular cells are indeed able to form calcified nodules of elemental composition similar to bone, however with different morphology. Comparison of morphologies of the two minerals to that found in cardiovascular tissue shows that some of tissue calcification resembles the calcified fibers produced by bone cells in vitro. These results suggest that the characterization of the mineral is of utmost importance and its morphology and chemical properties can contribute an important piece of information in the comprehensive analysis of soft tissue mineralization mechanisms, both in in vitro cell culture as well as in clinical samples.
Challenges and changes in Indian rural credit market: a review
Authors: Ray Sougata 
Published: June 2019

Purpose
Post-independence, the rural credit market in India has undergone significant structural changes in order to enhance the availability and efficient use of credit. The purpose of this paper is to understand the challenges and changes in the Indian rural credit market in the post-independence period.

Design/methodology/approach
Using data from the All India Debt and Investment Survey conducted by the National Sample Survey Organisation of the Government of India from 1971–1972 to 2012 and Reserve Bank of India in 1951–1952 and 1961–1962, the study focuses on three important aspect of rural credit market, i.e. the availability, sources and uses of credit. The analysis is based on both the national and state level data and uses the decadal growth rates to explain the changes in the rural credit market.

Findings
Availability of credit, in terms of volume and number of households indebted, has increased substantially. However, the sharp rise in outstanding debt is a matter of concern. The share of credit from institutional agencies has seen a continuous decline post liberalisation. The non-institutional agencies, particularly the professional moneylenders, continue to be the most preferred sources of credit owing to their flexible nature of operation. Interesting, microfinance has emerged as a major source of credit particularly for the poor rural households. The rise in credit usage for non-income generating activities amongst poor households is another important concern.

Originality/value
The study highlights some of the most important features and characteristics associated with the Indian rural credit market. An understanding of these issues would provide valuable insight for shaping the future policy responses.
Meshfree algorithms based on radial basis functions for numerical simulation and to capture shocks behavior of Burgers’ type problems
Authors: Jiwari Ram , Kumar Sanjay , Mittal R.C. 
Published: June 2019

PurposeThe purpose of this paper is to develop two meshfree algorithms based on multiquadric radial basis functions (RBFs) and differential quadrature (DQ) technique for numerical simulation and to capture the shocks behavior of Burgers’ type problems.Design/methodology/approachThe algorithms convert the problems into a system of ordinary differential equations which are solved by the Runge–Kutta method.FindingsTwo meshfree algorithms are developed and their stability is discussed. Numerical experiment is done to check the efficiency of the algorithms, and some shock behaviors of the problems are presented. The proposed algorithms are found to be accurate, simple and fast.Originality/valueThe present algorithms LRBF-DQM and GRBF-DQM are based on radial basis functions, which are new for Burgers’ type problems. It is concluded from the numerical experiments that LRBF-DQM is better than GRBF-DQM. The algorithms give better results than available literature.
Developing a knowledge-based safety culture instrument for construction industry
Authors: M.D. Deepak , Mahesh Gangadhar 
Published: June 2019

Purpose
Harnessing the power of knowledge management is important for minimizing accidents occurring at construction projects. Yet, knowledge management is a neglected dimension when developing safety culture in the construction industry. Therefore, the purpose of this paper is to develop a knowledge-based safety culture questionnaire and examine its validity and reliability in the Indian context.

Design/methodology/approach
A questionnaire survey was formulated after identifying 69 influencing factors from a thorough literature review. In total, 210 valid responses were obtained from key stakeholders operating in Indian construction industry. Reliability and validity of the measurement scale were examined by factor analysis and inter-item correlation test. Comparison of knowledge-based safety culture scores across several demographic profiles of the respondents was utilized for testing discriminant validity.

Findings
Results suggest that the new instrument appears to be a reliable, valid and sensitive instrument that will contribute in examining the effect of key factors that influence the importance of the knowledge dimension toward developing safety culture in the construction industry.

Originality/value
The measurement tool developed in this study focuses on considering the importance of knowledge management in enhancing safety culture of the construction industry. This instrument can be utilized to compare the level of safety culture among key stakeholders of construction projects. This paper can contribute to the promotion of safety theory in Indian construction industry and provide practical implications for construction enterprises when they engage in improving safety conditions in their organizations.
Effects of information sources for new customers and suppliers on the immediate innovation output of firms
Authors: Medhi Pankaj Kumar , Jain Palakh , Jain Tinu 
Published: June 2019

Purpose
The purpose of this paper is to propose a typology of the information sources for new customers or suppliers on the basis of their existing relational linkage with the acquiring firm and to further explore whether various types of information sources for new customers and suppliers have any differential effect on a firm’s immediate innovation output.

Design/methodology/approach
The research sample was taken from the data collected by WB enterprise surveys (2005). The WB enterprise survey is considerably comprehensive for firm-level data. Relevant questions for the study were extracted from the survey. Simultaneously, EFA, CFA and SEM using AMOS 6.0 was run for the analysis.

Findings
The findings confirm that sources for a new customer and supplier with a strong relational aspect have a significant positive effect on a firm’s innovation output in the immediately following period.

Research limitations/implications
The research acknowledges the need to measure the effect of new supplier/customer on innovation depending on the type of information sources separately for product and process innovation as one of the major limitations.

Practical implications
This research can help managers obtain information of holistic and critical nature to incorporate in decision making for improving firm performance in innovation.

Originality/value
Customers and suppliers are well-established external sources of innovation ideas and information. But to what extant new customers or suppliers may be effective resources for innovation may depend largely on the sources through which they themselves are acquired by a firm, which is relatively unexplored. This study addresses the gap is the first of its kind to explore the role of the sources of information for new customer/supplier on a firm’s innovation output in the immediately following period.
The finance of innovation in Africa
Authors: Ayalew Misraku Molla , Xianzhi Zhang , Hailu Demis Hailegebreal 
Published: June 2019

Purpose
The purpose of this paper is to investigate how firms in developing countries finance innovation. Notably, the study seeks to investigate whether innovative firms exhibit financing patterns different from those of non-innovative ones. It also examines the effect of financing sources on firm’s probability to innovate.

Design/methodology/approach
The study utilizes firm-level data from the World Bank Enterprise Survey. From 28 African countries, 11,173 firms have been included in the sample. A statistical t-test is used for two independent samples and logistic regression models.

Findings
The results show that innovative firms, specifically innovative small- and medium-size firms exhibit financing patterns different from non-innovative peers. Further analysis indicates that there is no statistically significant difference between the financing patterns of innovative and non-innovative large firms. In Africa, innovation is mostly financed using internal sources and bank finance. Equity finance and bank finance have shown a higher effect followed by internal finance, finance from non-bank financial institutions and trade credit finance on firms’ probability to innovate.

Practical implications
The management of innovative firms should reduce dependency on short-term and retained earning financing and increase the use of long-term instruments improve innovation performance.

Social implications
A pending policy task for African leaders is to design and evaluate reforms to create a strong financial sector that willing to support the innovation process.

Originality/value
This study contributes to the existent literature on finance of innovation by examining how firms finance innovation activities in developing countries. This study provides evidence on how innovative firms exhibit financing patterns different from non-innovative ones from developing countries.
The allure of celebrities: unpacking their polysemic consumer appeal
Authors: Wohlfeil Markus , Patterson Anthony , Gould Stephen J. 
Published: June 2019

Purpose
This paper aims to explain a celebrity’s deep resonance with consumers by unpacking the individual constituents of a celebrity’s polysemic appeal. While celebrities are traditionally theorised as unidimensional semiotic receptacles of cultural meaning, the authors conceptualise them here instead as human beings/performers with a multi-constitutional, polysemic consumer appeal.

Design/methodology/approach
Supporting evidence is drawn from autoethnographic data collected over a total period of 25 months and structured through a hermeneutic analysis.

Findings
In rehumanising the celebrity, the study finds that each celebrity offers the individual consumer a unique and very personal parasocial appeal as the performer, the private person behind the public performer, the tangible manifestation of either through products and the social link to other consumers. The stronger these constituents, individually or symbiotically, appeal to the consumer’s personal desires, the more s/he feels emotionally attached to this particular celebrity.

Research limitations/implications
Although using autoethnography means that the breadth of collected data is limited, the depth of insight this approach garners sufficiently unpacks the polysemic appeal of celebrities to consumers.

Practical implications
The findings encourage talent agents, publicists and marketing managers to reconsider underlying assumptions in their talent management and/or celebrity endorsement practices.

Originality/value
While prior research on celebrity appeal has tended to enshrine celebrities in a “dehumanised” structuralist semiosis, which erases the very idea of individualised consumer meanings, this paper reveals the multi-constitutional polysemy of any particular celebrity’s personal appeal as a performer and human being to any particular consumer.
The interplay between market intelligence activities and sales strategy as drivers of performance in foreign markets
Authors: Katsikea Evangelia , Theodosiou Marios , Makri Katerina 
Published: June 2019

Purpose
Exporting is a popular foreign market entry mode, especially among small- and medium-sized enterprises (SMEs). The success of SME exporters depends on their ability to establish and maintain profitable long-term relationships with foreign customers. This study aims to propose that the development of an effective export sales strategy can contribute greatly toward this aim. The study also demonstrates that export market intelligence generation and export market intelligence dissemination activities are important drivers of export sales strategy. Export sales strategy comprises three dimensions, which are expected to have a positive influence on export performance.

Design/methodology/approach
The study uses survey data obtained from 168 exporting firms based in Greece, to test a set of research hypotheses. Structural equation modeling procedures are used.

Findings
Findings indicate that export market intelligence generation and dissemination activities support and facilitate the development of effective export sales strategies, tailored to serve individual foreign accounts. Furthermore, all strategic dimensions of export sales strategy demonstrate significant positive effects on export performance.

Research limitations/implications
The research underlines the importance of incorporating export sales strategy in studies that aim to investigate the drivers of export performance.

Practical implications
The findings also indicate that exporting firms must actively engage in market intelligence activities to reinforce their strategic decision-making process.

Originality/value
The study emphasizes the crucial importance of export sales strategy in achieving superior export performance. The study provides a theory-driven conceptualization and operationalization of export sales strategy and offers an empirical assessment of a comprehensive model that includes the key antecedents and performance outcomes of export sales strategy.
Signaling effects and the role of culture: movies in international auxiliary channels
Authors: Sinha Ashish , Gu Haodong , Kim Namwoon , Emile Renu 
Published: June 2019

Purpose
Given the high uncertainty in the quality perception of experiential products, manufacturers use signals to influence consumers’ decisions. In the movie industry, literature shows that performance of the main channel (e.g. cinema) strongly influences the performance of auxiliary channels (e.g. DVDs). The success of a movie in the home country is also to be resonated by its good performance in host countries. However, the cultural contingency of these success-breeds-success (SBS) effects has not been examined. This paper aims to test the influence of cultural values on the SBS effects across channels and countries.

Design/methodology/approach
Borrowing concepts from the signaling literature and analyzing DVD sales data from six international markets using a multilevel mixed-effects model, the study finds that culture plays a significant role to influence both SBS effects.

Findings
In countries with low power distance, short-term orientation and high indulgence, consumers who purchase from auxiliary channels are more likely to be influenced by the box office performance of movies. Meanwhile, cultural distance between the home and host nations significantly decreases the cross-national SBS effect.

Research limitations/implications
The findings are likely to be generalized to online auxiliary channels of movies, but empirical testing is required to ensure that no major adaptation is required in the process. Future research can also extend the framework of this paper to include more countries into the analysis and investigate cultural variables beyond Hofstede’s dimensions.

Practical implications
This paper suggests that the SBS effects may vary across nations. When managers plan for the sequential distributions of experiential products, the cultural values of target markets should be considered to decrease the uncertainty in sales prediction.

Originality/value
This paper contributes to the existing literature by investigating the international auxiliary channels of movies and incorporating cultural values into the framework of sequential distributions. To the best of the authors’ knowledge, this study is the first to test the links between the main and auxiliary channels from an international marketing perspective.