bluuebunny/crossref_metadata_2025_split huggingface dataset:
ARID2deficiency promotes tumor progression and is associated with higher sensitivity to PARP inhibition in lung cancer
Authors: Moreno Thaidy , González-Silva Laura , Monterde Beatriz , Betancor-Fernández Isabel , Revilla Carlos , Agraz-Doblas Antonio , Freire Javier , Isidro Pablo , Quevedo Laura , Montes-Moreno Santiago , Cereceda Laura , Astudillo Aurora , Casar Berta , Crespo Piero , Torres Cristina Morales , Scaffidi Paola , Gomez-Roman Javier , Salido Eduardo , Varela Ignacio 
Published: January 2020

ABSTRACTThe survival rate in lung cancer remains stubbornly low and there is an urgent need for the identification of new therapeutic targets. Last decade’s research has evidenced a clear role of chromatin structure in cancer development and several members of the SWI/SNF chromatin remodeling complexes have been described altered in different tumor types. Nevertheless, the precise mechanisms of their impact on cancer progression, as well as the application of this knowledge to cancer patient management are largely unknown.In this study, we have performed targeted sequencing of a cohort of lung cancer patients on genes involved in chromatin structure, as well as functional experiments to identify the molecular mechanisms linking alterations of chromatin remodeling genes and tumor development.We have identified ARID2 production loss in 20% of lung cancer patients. Additionally, we have shown that ARID2-deficiency provokes profound chromatin structural changes, alters the transcriptional programme and impairs DNA repair which bolster the proliferative and metastatic potential of the cells bothin vitroandin vivo. Moreover, we have demonstrated that ARID2 deficiency significantly affects the sensitivity of the cells to PARP inhibition.All these results support thatARID2is abona-fidetumor suppressor gene in lung cancer that might be exploited therapeutically.
Amino-alcohol Bio-conjugate of Naproxen Exhibits Anti-inflammatory Activity through NF-κB Signaling Pathway
Authors: Das Mahua Rani , Banerjee Anindyajit , Sarkar Sourav , Majumder Joydeb , Chakrabarti Saikat , Jana Siddhartha Sankar 
Published: January 2020

AbstractNaproxen sodium (Ns) is a well-known synthetic compound used vastly as a nonsteroidal anti-inflammatory drug (NSAID). Previously, we demonstrated that the hydrogels, made of Ns bio-conjugate (NBC), either with amino alcohol (NBC-1 and 2) or amino acid (NBC-3 and 4), displayed anti-inflammatory properties better than Ns, but the effectiveness was not well explored. Here, we investigated that NBC-2, conjugated with γ-amino alcohol, significantly reduces the expression of pro-inflammatory proteins; such as inducible nitric oxide synthase (iNOS) and cyclooxygenase isoform-2 (COX-2), and the production of pro-inflammatory mediator nitric oxide (NO) in lipopolysaccharide and interferon-γ (LPS/IFN-γ) treated mouse macrophage RAW 264.7 cells, compared with bio-conjugation of β-amino alcohol (NBC-1) or β-amino acid (NBC-3) or α-amino acid NBC (NBC-4). NBC-2 decreases the nuclear localization of transcription factors NF-κB by stabilizing its cytoplasmic functional inhibitor IκBα. Moreover, NBC-2 also displays selective inhibitory effect towards COX-1 enzyme activity as determined by enzymatic assay andin silicomolecular docking analysis. Thus, we suggest that NBC-2 may be used as a self-delivery anti-inflammatory drug as compared with other NBCs.TOC Graphic
Gene size matters: What determines gene length in the human genome?
Authors: Lopes Inês , Altab Gulam , Raina Priyanka , de Magalhães João Pedro 
Published: January 2020

AbstractWhile it is expected for gene length to be influenced by factors such as intron number and evolutionary conservation, we have yet to fully understand the connection between gene length and function in the human genome.In this study, we show that, as expected, there is a strong positive correlation between gene length and the number of SNPs, introns and protein size. Amongst tissue specific genes, we find that the longest genes are expressed in blood vessels, nerve, thyroid, cervix uteri and brain, while the smallest genes are expressed within the pancreas, skin, stomach, vagina and testis. We report, as shown previously, that natural selection suppresses changes for genes with longer lengths and promotes changes for smaller genes. We also observed that longer genes have a significantly higher number of co-expressed genes and protein-protein interactions. In the functional analysis, we show that bigger genes are often associated with neuronal development, while smaller genes tend to play roles in skin development and in the immune system. Furthermore, pathways related to cancer, neurons and heart diseases tend to have longer genes, with smaller genes being present in pathways related to immune response and neurodegenerative diseases.We hypothesise that longer genes tend to be associated with functions that are important early in life, while smaller genes play a role in functions that are important throughout the organisms’ whole life, like the immune system which require fast responses.Author SummaryEven though the human genome has been fully sequenced, we still do not fully grasp all of its nuances. One such nuance is the length of the genes themselves. Why are certain genes longer than others? Is there a common function shared by longer/smaller genes? What exactly makes gene longer? We tried answering these questions using a variety of analysis. We found that, while there was not a particular strong factor in genes that influenced their size, there could be an influence of several gene characteristics in determining the length of a gene. We also found that longer genes are linked with the development of neurons, cancer, heart diseases and muscle cells, while smaller genes seem to be mostly related with the immune system and the development of the skin. This led us to believe that, whether the gene has an important function early in our life, or throughout our whole lives, or even if the function requires a rapid response, that its gene size will be influenced accordingly.
Extensive nuclear gyration and pervasive non-genic transcription during primordial germ cell development in zebrafish
Authors: Redl Stefan , de Jesus Domingues Antonio M. , Möckel Stefanie , Salvenmoser Willi , Mendez-Lago Maria , Ketting René F. 
Published: January 2020

SUMMARYPrimordial germ cells (PGCs) are the precursors of germ cells, which migrate to the genital ridge during early development. Relatively little is known about PGCs after their migration. We studied this post-migratory stage using microscopy and sequencing techniques, and found that many PGC-specific genes, including genes known to induce PGC fate in the mouse, are only activated several days after migration. At this same timepoint, PGC nuclei become extremely gyrated, displaying general opening of chromatin and high levels of transcription. This is accompanied by changes in nuage morphology, expression of large loci, named PERLs, enriched for retro-transposons and piRNAs, and a rise in piRNA biogenesis signatures. Interestingly, no nuclear Piwi protein could be detected at any timepoint, indicating that the zebrafish piRNA pathway is fully cytoplasmic. Our data show that the post-migratory stage of zebrafish PGCs holds many cues to both germ cell fate establishment and piRNA pathway activation.
Longitudinal whole-exome sequencing of cell-free DNA unravels the metastatic evolutionary dynamics of BRCA2-mutated breast cancer
Authors: Hastings R.K , Openshaw M.R , Vazquez M , Moreno-Cardenas AB , Fernandez-Garcia D , Martinson L , Toghill B , Kulbicki K , Primrose L , Guttery D.S , Page K , Richards C , Thomas A , Tabernero J , Coombes R.C , Ahmed S , Toledo R.A , Shaw J.A 
Published: January 2020

AbstractLittle is known about the metastatic evolutionary dynamics of BRCA2-mutated cancers. Here, we applied whole-exome sequencing (WES) of primary tumor (PT), local relapse (LR) and eight serial plasma cfDNA samples collected from disease progression to depict the 12 years evolutionary trajectory of a metastatic BRCA2-mutated breast cancer. While longitudinal WES-cfDNA recapitulated clonal and subclonal mutations and copy number profiles detected in LR, emergence of plasma-exclusive mutations in TSC2 and HDAC9 cancer-related genes and loss of HLA loci as an immune escape mechanism were also detected. Lastly, mutation signature 3, associated with homologous recombination deficiency and response to platinum-based therapy raised profoundly from 19% in PT to 60% in late stage disease. In conclusion, we show for the first time that longitudinal WES-cfDNA enables the evolutionary trajectory of advanced cancer to be uncovered and that increment of MS3 and loss of HLA are key players in this BRCA2-mutated breast metastasis.
The Escherichia coli RnlA–RnlB toxin–antitoxin complex: production, characterization and crystallization
Authors: Garcia-Rodriguez Gabriela , Talavera Perez Ariel , Konijnenberg Albert , Sobott Frank , Michiels Jan , Loris Remy 
Published: January 2020

The Escherichia coli rnlAB operon encodes a toxin–antitoxin module that is involved in protection against infection by bacteriophage T4. The full-length RnlA–RnlB toxin–antitoxin complex as well as the toxin RnlA were purified to homogeneity and crystallized. When the affinity tag is placed on RnlA, RnlB is largely lost during purification and the resulting crystals exclusively comprise RnlA. A homogeneous preparation of RnlA–RnlB containing stoichiometric amounts of both proteins could only be obtained using a His tag placed C-terminal to RnlB. Native mass spectrometry and SAXS indicate a 1:1 stoichiometry for this RnlA–RnlB complex. Crystals of the RnlA–RnlB complex belonged to space group C2, with unit-cell parameters a = 243.32, b = 133.58, c = 55.64 Å, β = 95.11°, and diffracted to 2.6 Å resolution. The presence of both proteins in the crystals was confirmed and the asymmetric unit is likely to contain a heterotetramer with RnlA2:RnlB2 stoichiometry.
The gratifications in the experience of the use of social media and its impact on the purchase and repurchase of products and services
Authors: Santos Corrada Maria , Flecha Jose A. , Lopez Evelyn 
Published: January 2020

Purpose
The purpose of this paper is to examine the use of social media and its impact on information search, communication with a company, and purchase and re-purchases of products and services. Using use and gratification theory as a starting point, it also examines the impact of satisfaction of use of social media in the process of purchasing and re-purchasing products and services.

Design/methodology/approach
An online survey was conducted with 444 participants, and the data were analyzed using the partial least squares structural equation modeling technique to observe the effects between the variables of social media use, search information, communication with the company, purchase, re-purchase and satisfaction of use of social media.

Findings
The results reflect how the use of social media generates significant rewards that significantly impact the search for information and the communication with the company. The data also show how communication with the company has an impact on the purchase and re-purchase of products and services. Finally, it was empirically confirmed that the gratification received by users through social media use impacts satisfaction with social media use.

Originality/value
The results contribute to how social media impacts alternative evaluations through the gratification of user needs, resulting in motives and behaviors leading to the purchase of goods and services, as established by Use and Gratification Theory. In its contributions to the Academy, Use and Gratification Theory (U&G) explains why individuals use and share information using social media. First, it justifies the purchase and re-purchase of products and services due to user satisfaction according to users’ experience using social media. Second, it presents a vision of how the use of social media is a significantly important result in the gratification of consumer needs.
A dynamic approach to brand portfolio audit and brand architecture strategy
Authors: Brandão Amélia , Sousa Jose Carlos C. , Rodrigues Clarinda 
Published: January 2020

Purpose
This paper aims to propose a dynamic and holistic framework that combines the brand portfolio audit with the brand architecture redesign.

Design/methodology/approach
Depicting from an extensive review on the frameworks of brand audit and brand architecture, a dynamic approach to brand portfolio audit and brand architecture strategy was developed, and later applied and tested in three B2B and B2C companies.

Findings
The paper suggests an eight-step framework to guide practitioners when auditing a specific brand portfolio and designing a revised brand architecture strategy. Additionally, a Brand Audit Scorecard was developed to enable and sustain brand portfolio audits, divided into three dimensions (brand equity, brand contribution and strategic options).

Research limitations/implications
Further research should aim at testing the proposed framework in different types of companies and countries.

Originality/value
This paper contributes to the brand audit and brand architecture literature by proposing a holistic framework that is not static.
Organizational antecedents of exploration and exploitation in SMEs
Authors: Berard Celine , Fréchet Marc 
Published: January 2020

PurposeScholars have recognized that formal hierarchical structures and slack resources are at the core of small- and medium-sized enterprises (SMEs) attainment of ambidexterity. Surprisingly, few studies on SMEs have analyzed the extent to which these structural and resource attributes are associated with exploration and exploitation. This study aims to examine how two structural attributes, formalization and structural empowerment, and two resource attributes, financial slack and human resource slack, affect exploration and exploitation in SMEs.Design/methodology/approachData were gathered from a survey administered to the chief executive officers of 522 French SMEs. The research hypotheses were then tested using seemingly unrelated regressions to investigate the contrasts between the two components of ambidexterity.FindingsThe results show that structural empowerment and financial slack may be conducive to exploration and exploitation at the same time. By contrast, formalization and human resource slack impact only one of these two ambidexterity components in significant ways: the former may be a powerful lever for exploitation, while the latter may be a powerful lever for exploration.Originality/valueRelying on a dual structure–resource perspective, this study allows us to discuss the distinct impacts that several organizational antecedents have on exploration and exploitation in the specific context of SMEs. It thus addresses the recent call to identify which antecedents are integrating and which are differentiating to help firms deal with ambidexterity.
Numerical investigation into the stability of earth dam slopes considering the effects of cavities
Authors: Alateya Hawraa , Ahangar Asr Alireza 
Published: January 2020

PurposeThis study is an attempt to estimate the influence of the presence of cavities on the stability of slopes in earth dams under rapid drawdown conditions. The purpose of this paper is to study the influence of different factors, such as the diameter and location of cavities, in addition to their existence effects.Design/methodology/approachA series of finite element simulation models were developed using PLAXIS 2D finite element software to analyse the stability of slopes in earth dams while considering various effects from cavities in the subsoil under rapid drawdown conditions.FindingsThe results indicated that the presence of cavities and an increase in the diameter of cavities decreased the stability of the upstream face dramatically for all examined locations in a horizontal direction; however, this effect was less on the downstream side. The results also showed that variations in the location of cavities in the horizontal direction have a greater effect on the stability than those in the vertical direction. The results revealed that increasing shear strength parameters of embankment does not reduce the influence of cavities on stability when those cavities are in critical locations.Originality/valueA numerical model has been developed to simulate the effects of cavities on the stability of slopes in water-retaining structures/earth dams. The stability of earth dam slopes on upstream and downstream sides under rapid drawdown conditions considering various cavity effects, including their existence, diameter and location, were numerically analysed.
Three-stage quantitative approach of understanding household adaptation decisions in rural Cambodia
Authors: Jiao Xi , Zheng Yuan , Liu Zhen 
Published: January 2020

PurposeA better understanding of the processes that shape households’ adaptation decisions is essential for developing pertinent policies locally, thereby enabling better adaptation across scales and multiple stakeholders. This paper aims to examine the determinants of household decisions to adapt, it is also possible to target factors that facilitate or constrain adaptation. This helps to identify key components of current adaptive capacity, which leads to important insights into households’ competence to adapt in the future.Design/methodology/approachThis paper takes a full-pledged approach examining factors and processes that shape households’ climate adaptation decision-making in rural Cambodia at three levels: adaptation status, adaptation intensity and choices of adaptation strategy. The three-stage analyses are materialized by applying the double hurdle model and multivariate probit model, which provides a potential way to systematically assess household adaptation decision-making in rural settings.FindingsResults show a high level of involvement in adaptation among local households who are facing multiple stressors including climatic risks. The findings suggest that perceived climate change influence households’ decisions in both adaptation status and intensity. Access to financial credit, farmland size, water availability and physical asset holdings are identified as key factors promoting the adoption of more adaptation measures. To facilitate adaptation, collective effort and support at community level is important in providing knowledge based climate information dissemination and early warning systems. Public sector support and development aid programs should focus on positive triggers for targeted community and household adaptation.Originality/valueThe study, to the authors’ best knowledge, is one of the first studies to investigate the determinants of local adaptation decision-making systematically in Cambodia. It also provides a comprehensive approach to improve understanding of adaptation decision-making processes by exploring how various capital assets are associated with different stages of adaptation decisions. The findings contribute to policy implications enlightening adaptation planning at multi-scales with knowledge of key factors, which enhance local adaptive capacity to reduce climate change vulnerability.
Supervisor conflict management climate and emotion recognition skills
Authors: Way Kirsten A. , Jimmieson Nerina J. , Bordia Prashant 
Published: January 2020

PurposeGroups’ perceptions of their supervisors’ conflict management styles (CMSs) can have important implications for well-being. Rather than being examined in isolation, supervisor CMSs need to be considered in the context of supervisors’ emotional ability and the amount of conflict in workgroups. This paper aims to investigate the three-way interactions between group-level perceptions of supervisor CMSs (collaborating, yielding, forcing), supervisor emotion recognition skills and group relationship conflict in predicting collective employee burnout.Design/methodology/approachGroup-level hierarchical multiple regressions were conducted with 972 teaching professionals nested in 109 groups.FindingsThe positive association between supervisor yielding climate and collective employee burnout was evident when supervisor emotion recognition was low but absent when supervisor emotion recognition was high. Groups with high supervisor forcing climate and high supervisor emotion recognition experienced lower group burnout, an effect evident at high but not low relationship conflict.Practical implicationsSupervisors have a critical – and challenging – role to play in managing conflict among group members. The detrimental effects of supervisor yielding and forcing climates on collective employee burnout are moderated by personal (supervisor emotion recognition) and situational (the level of relationship conflict) variables. These findings have practical implications for how supervisors could be trained to handle conflict.Originality/valueThis research challenges traditional notions that supervisor yielding and forcing CMSs are universally detrimental to well-being.
Status differences in interpersonal strain and job resources at work
Authors: Wallace Jean Elizabeth , Buchanan Tom 
Published: January 2020

PurposeThis study aims to explore how status differences relate to strained working relationships with co-workers and clients. Two statuses, gender and occupation, are examined using data from veterinarians and animal health technologists (AHTs). Competing perspectives regarding exposure to stressful relationships and access and effectiveness of work-related resources are considered.Design/methodology/approachAn explanatory sequential mixed-methods design is used that combines quantitative survey data with open-ended qualitative data. The survey data are used to examine how interpersonal strain and access to work-related resources vary by status. The qualitative data are used to illustrate how strain is experienced by these workers and aids in interpreting the quantitative findings.FindingsStatus is linked to interpersonal client strain and access to resources. Challenging work is widely available to all three groups, but is more beneficial in reducing higher status veterinarians’ client strain. Autonomy is a scarce resource for the lowest status group (female AHTs), yet appears effective in reducing co-worker strain for everyone. Unexpectedly, work overload and market concerns appear to aggravate work-related strain and greater numbers of the lowest status group exacerbates interpersonal tensions with clients.Originality/valueThis paper contributes by examining stressful interactions experienced by two occupations who work side-by-side in the same employment settings, but who vary significantly by gender representation and occupational status. The authors argue that in addition to gender and occupational status, the organizational health of employing clinics and the feminization of veterinary practice may offer insights into how status differences are related to interpersonal conflict experienced in these work places.