bluuebunny/crossref_metadata_2025 huggingface dataset:
A primitive type of renin-expressing lymphocyte protects the organism against infections
Authors: Belyea Brian C. , Santiago Araceli E. , Vasconez Wilson A. , Nagalakshmi Vidya K. , Mehalic Theodore C. , Sequeira-Lopez Maria Luisa S. , Ariel Gomez R.
Published: September 2019

The hormone renin plays a crucial role in the regulation of blood pressure and fluid-electrolyte homeostasis. Normally, renin is synthesized by juxtaglomerular (JG) cells, a specialized group of myoepithelial cells located near the entrance to the kidney glomeruli. In response to low blood pressure and/or a decrease in extracellular fluid volume (as it occurs during dehydration, hypotension, or septic shock) JG cells respond by releasing renin to the circulation to reestablish homeostasis. Interestingly, renin-expressing cells also exist outside of the kidney, where their function has remained a mystery. We discovered a unique type of renin-expressing B-1 lymphocytes that may have unrecognized roles in defending the organism against infections. These cells synthesize and release renin, entrap and phagocyte bacteria and control bacterial growth. The ability of renin-bearing lymphocytes to control infections – which is enhanced by the presence of renin – adds a novel, previously unsuspected dimension to the defense role of renin-expressing cells, linking the endocrine control of circulatory homeostasis with the immune control of infections to ensure survival.
Non-enzymatic primer extension with strand displacement
Authors: Zhou Lijun , Kim Seohyun Chris , Ho Katherine H. , O’Flaherty Derek K. , Giurgiu Constantin , Wright Tom H. , Szostak Jack W.
Published: September 2019

Non-enzymatic RNA self-replication is integral to the ‘RNA World’ hypothesis. Despite considerable progress in non-enzymatic template copying, true replication remains challenging due to the difficulty of separating the strands of the product duplex. Here, we report a prebiotically plausible solution to this problem in which short ‘invader’ oligonucleotides unwind an RNA duplex through a toehold/branch migration mechanism, allowing non-enzymatic primer extension on a template that was previously occupied by its complementary strand. Kinetic studies of single-step reactions suggest that following invader binding, branch migration results in a 2:3 partition of the template between open and closed states. Finally, we demonstrate continued primer extension with strand displacement by employing activated 3′-aminonucleotides, a more reactive proxy for ribonucleotides. Our study suggests that complete cycles of non-enzymatic replication of the primordial genetic material may have been catalyzed by short RNA oligonucleotides.
Mechanical Roles of Vinculin/β-catenin interaction in Adherens Junction
Authors: Bertocchi Cristina , Ravasio Andrea , Ong Hui Ting , Toyama Yusuke , Kanchanawong Pakorn
Published: September 2019

Mechanical force transmission through the adherens junctions (AJs) are highly regulated processes essential for multicellular organization of tissues. AJ proteins such as E-cadherin, α-catenin, and vinculin have been shown to be sensing or bearing mechanical forces being transmitted between the actin cytoskeleton and the intercellular contacts. However, the molecular organization and connectivity of these components remains not well understood. Using a super-resolution microscopy approach, we report that vinculin, once activated, could form a direct structural connection with β-catenin, which can bypass α-catenin, one of the main mechanotransducers in AJs. Direct vinculin/β-catenin interaction is capable of supporting mechanical tension and contributes to the stabilization of the cadherin-catenin complexes. These findings suggest a multi-step model for the force-dependent reinforcement of AJs whereby α-catenin may serve as the initial catalytic activator of vinculin, followed by vinculin translocation to form a direct link between E-cadherin-bound β-catenin and the actin cytoskeleton.
Temporal complexity of fMRI is reproducible and correlates with higher order cognition
Authors: Omidvarnia Amir , Zalesky Andrew , Mansour Sina , Van De Ville Dimitri , Jackson Graeme D. , Pedersen Mangor
Published: September 2019

It has been hypothesized that resting state networks (RSNs) likely display unique temporal complexity fingerprints, quantified by their multi-scale entropy patterns [1]. This is a hypothesis with a potential capacity for developing digital biomarkers of normal brain function, as well as pathological brain dysfunction. Nevertheless, a limitation of [1] was that resting state functional magnetic resonance imaging (rsfMRI) data from only 20 healthy individuals was used for the analysis. To validate this hypothesis in a larger cohort, we used rsfMRI datasets of 1000 healthy young adults from the Human Connectome Project (HCP), aged 22-35, each with four 14.4-minute rsfMRI recordings and parcellated into 379 brain regions. We quantified multi-scale entropy of rsfMRI time series averaged at different cortical and sub-cortical regions. We performed effect-size analysis on the data in 8 RSNs. Given that the morphology of multi-scale entropy is affected by the choice of its tolerance parameter (r) and embedding dimension (m), we repeated the analyses at multiple values ofrandmincluding the values used in [1]. Our results reinforced high temporal complexity in the default mode and frontoparietal networks. Lowest temporal complexity was observed in the sub-cortical areas and limbic system. We investigated the effect of temporal resolution (determined by the repetition timeTR) after downsampling of rsfMRI time series at two rates. At a low temporal resolution, we observed increased entropy and variance across datasets. Test-retest analysis showed that findings were likely reproducible across individuals over four rsfMRI runs, especially when the tolerance parameterris equal to 0.5. A strong relationship was observed between temporal complexity of RSNs and fluid intelligence (people’s capacity to reason and think flexibly) through step-wise regression analysis suggesting that complex dynamics of the human brain is an important attribute of high-level brain function. Finally, the results confirmed that the relationship between functional brain connectivity strengths and rsfMRI temporal complexity changes over time scales, likely due to the regulation of neural synchrony at local and global network levels.
Avoiding pitfalls: Trace conditioning and rapid aversive learning during route navigation in desert ants
Authors: Wystrach Antoine , Buehlmann Cornelia , Schwarz Sebastian , Cheng Ken , Graham Paul
Published: September 2019

The ability of bees and ants to learn long visually guided routes in complex environments is perhaps one of the most spectacular pieces of evidence for the impressive power of their small brains. While flying bees can visit flowers in an optimised sequence over kilometres, walking ants can precisely recapitulate routes of up to a hundred metres in complex environments. It is clear that route following depends largely on learnt visual information and we have good idea how views can guide individuals along them, however little is known about the mechanisms that control route learning and development. Here we show that ants in natural environments can actively learn a route detour to avoid a pit trap and that this depends on a process analogous to aversive trace conditioning. Views experienced before falling into the trap become associated with the ensuing negative outcome and thus trigger salutary turns on the subsequent trip. This drives the ants to orient away from the goal direction and avoid the trap. If the pit is avoided, the novel views experienced during the detour become positively reinforced and the new route crystallises. We discuss how such an interplay between appetitive and aversive memories might be implemented in insect neural circuitry.
The impact of Relative Language Distance on Bilingual Language Control – a functional imaging study
Authors: Ramanujan Keerthi
Published: September 2019

Cross-linguistic activation is unavoidable in bilinguals and they require language control to manage it. In this study, it is posited that Relative Language Distance (RLD; the extent of lexical feature-similarity between bilinguals’ languages) can affect the extent of cross-linguistic activation and hence influence bilingual language control. This was investigated via an er-fMRI word-translation task on three similar bilingual groups but with varying RLDs: Dutch-English (low-RLD), Hindi-English (intermediate-RLD) and Cantonese-English (high-RLD). Cross-linguistic conflict and the degree of conflict monitoring/control necessary to manage it were expected to increase with decreasing RLD across groups and be appropriately reflected in the activity of conflict monitoring/control neural regions, such as the ACC (anterior cingulate cortex). Analysis revealed a significantly differential ACC response across the groups, reflecting its adaptation to differential conflict monitoring/control demands generated by RLD. The findings provide emerging evidence for RLD as a dimension of bilingualism impacting bilingual language control processes and neurobiology.
Patterns of smallpox mortality in London, England, over three centuries
Authors: Krylova Olga , Earn David J.D.
Published: September 2019

Smallpox is unique among infectious diseases in the degree to which it devasted human populations, its long history of control interventions, and the fact that it has been successfully eradicated. Mortality from smallpox in London, England, was carefully documented, weekly, for nearly 300 years, providing a rare and valuable source for the study of ecology and evolution of infectious disease. We describe and analyze smallpox mortality in London from 1664 to 1930. We digitized the weekly records published in the London Bills of Mortality and the Registrar General’s Weekly Returns. We annotated the resulting time series with a sequence of historical events that appear to have influenced smallpox dynamics in London. We present a spectral analysis that reveals how periodicities in smallpox dynamics changed over decades and centuries, and how these changes were related to control interventions and public health policy changes. We also examine how the seasonality of smallpox epidemics changed from the 17th to 20th centuries in London.
Functional interactions between post-translationally modified amino acids of methyl-coenzyme M reductase inMethanosarcina acetivorans
Authors: Nayak Dipti D , Liu Andi , Agrawal Neha , Rodriguez-Carerro Roy , Dong Shi-Hui , Mitchell Doug A , Nair Satish K , Metcalf William W
Published: September 2019

Methyl-coenzyme M reductase (MCR) plays an important role in mediating global levels of methane by catalyzing a reversible reaction that leads to the production or consumption of this potent greenhouse gas in methanogenic and methanotrophic archaea. In methanogenic archaea, the alpha subunit of MCR (McrA) typically contains four to six post-translationally modified amino acids near the active site. Recent studies have identified genes that install two of these modifications (thioglycine and 5-(S)-methylarginine), yet little is known about the installation and function of the remaining post-translationally modified residues. Here, we providein vivoevidence that a dedicated SAM-dependent methyltransferase encoded by a gene we designatedmcmAis responsible for formation ofS-methylcysteine inMethanosarcina acetivoransMcrA. Phenotypic analysis of mutants incapable of cysteine methylation suggests that theS-methylcysteine residue plays an important role in adaptation to a mesophilic lifestyle. To examine the interactions between theS-methylcysteine residue and the previously characterized thioglycine, 5-(S)-methylarginine modifications, we generatedM. acetivoransmutants lacking the three known modification genes in all possible combinations. Phenotypic analyses revealed complex, physiologically relevant interactions between the modified residues, which alter the thermal stability of MCR in a combinatorial fashion that is not readily predictable from the phenotypes of single mutants. Surprisingly, high-resolution crystal structures of the various unmodified MCRs were indistinguishable from the fully modified enzyme, suggesting that interactions between the post-translationally modified residues do not exert a major influence on the physical structure of the enzyme, but rather serve to fine-tune the activity and efficiency of MCR.
Molecular mechanisms of fentanyl mediated β-arrestin biased signaling
Authors: Waal Parker W. de , Shi Jingjing , You Erli , Wang Xiaoxi , Melcher Karsten , Jiang Yi , Xu H. Eric , Dickson Bradley M.
Published: September 2019

The development of novel analgesics with improved safety profiles to combat the opioid epidemic represents a central question to G protein coupled receptor structural biology and pharmacology: What chemical features dictate G protein or β-arrestin signaling? Here we use adaptively biased molecular dynamics simulations to determine how fentanyl, a potent β-arrestin biased agonist, activates the μ-opioid receptor (μOR). The resulting fentanyl-bound pose provides rational insight into a wealth of historical structure-activity-relationship on its chemical scaffold. We found that fentanyl and the synthetic opioid peptide DAMGO require M153 to induce β-arrestin coupling, while M153 was dispensable for G protein coupling. We propose and validate a mechanism where the n-aniline ring of fentanyl mediates μOR β-arrestin through a novel M153 “microswitch” by synthesizing fentanyl-based derivatives that exhibit complete, clinically desirable, G protein biased coupling. Together, these results provide molecular insight into fentanyl mediated β-arrestin biased signaling and a rational framework for further optimization of fentanyl-based analgesics with improved safety profiles.

Author Summary

The global opioid crisis has drawn significant attention to the risks associated with over-use of synthetic opioids. Despite the public attention, and perhaps in-line with the profit-based incentives of the pharmaceutical industry, there is no public structure of mu-opioid receptor bound to fentanyl or fentayl derivatives. A publicly available structure of the complex would allow open-source development of safer painkillers and synthetic antagonists. Current overdose antidotes, antagonists, require natural products in their synthesis which persists a sizable barrier to market and develop better antidotes. In this work we use advance molecular dynamics techniques to obtain the bound geometry of mu-opioid receptor with fentanyl (and derivatives). Based on our in-silico structure, we synthesized and tested novel compounds to validate our predicted structure. Herein we report the bound state of several dangerous fentanyl derivatives and introduce new derivatives with signaling profiles that may lead to lower risk of respiratory depression.
Sexual dichromatism in the neotropical genus Mannophryne (Anura: Aromobatidae)
Authors: Greener Mark S. , Hutton Emily , Pollock Christopher J. , Wilson Annabeth , Lam Chun Yin , Nokhbatolfoghahai Mohsen , Jowers Michael J. , Downie J. Roger
Published: September 2019

Recent reviews on sexual dichromatism in frogs included Mannophryne trinitatis as the only example they could find of dynamic dichromatism (males turn black when calling) within the family Aromobatidae and found no example of ontogenetic dichromatism in this group. We demonstrate ontogenetic dichromatism in M. trinitatis by rearing post-metamorphic froglets to near maturity: the throats of all individuals started as grey coloured; at around seven weeks, the throat became pale yellow in some, and more strongly yellow as development proceeded; the throats of adults are grey in males and variably bright yellow in females, backed by a dark collar. We demonstrated the degree of throat colour variability by analysing a large sample of females. The red: green (R:G) ratio ranged from ~1.1 to 1.4, reflecting variation from yellow to yellow/orange, and there was also variation in the tone and width of the dark collar, and in the extent to which the yellow colouration occurred posterior to the collar. Female M. trinitatis are known to be territorial in behaviour. We show a positive relationship between throat colour (R:G ratio) and escape performance, as a proxy for quality. Our field observations on Tobago’s M. olmonae showed variability in female throat colour and confirmed that males in this species also turn black when calling. Our literature review of the 20 Mannophryne species so far named showed that all females have yellow throats with dark collars, and that male colour change to black when calling has been reported in eight species; in the remaining 12 species, descriptions of males calling are usually lacking so far. We predict that both dynamic and ontogenetic sexual dichromatism are universal in this genus and provide discussion of the ecological role of dichromatism in this genus of predominantly diurnal, non-toxic frogs, with strong paternal care of offspring.
Seminal quality and global proteomic analysis of spermatozoa from captive Amazon squirrel monkeys (Saimiri collinsiOsgood, 1916) during the dry and rainy seasons
Authors: Leão Danuza Leite , Domingues Sheyla Farhayldes Souza , da Cunha Sousa Patrícia , Sampaio Wlaisa Vasconcelos , Vasconcelos Fábio Roger , Moura Arlindo Alencar , dos Santos Regiane Rodrigues , Skaugen Morten , Oskam Irma Caroline
Published: September 2019

The squirrel monkey (Saimiri collinsi), a Neotropical primate endemic to the Amazon in Brazil, is used as a biological model for reproductive research on the genusSaimiri. Although this animal is known to exhibit reproductive seasonality, nothing is known about the differences in its seminal quality, sperm protein composition, or sperm protein profile between the breeding (dry) and non-breeding (rainy) seasons. Thus, the aims of this study were to evaluate the quality ofS. collinsisemen during the dry and rainy seasons and to describe the global sperm proteomics and expression variations in the sperm proteins during the two seasons. Aside from the pH, there was no difference in the seminal quality between the dry and rainy seasons. The study approach based on bottom-up proteomics allowed the identification of 2343 proteins present in the sperm samples throughout these two seasons. Of the 79 proteins that were differentially expressed between the two seasons, 39 proteins that were related to spermatogenesis, sperm motility, capacitation, fecundation, and defense systems against oxidative stress were upregulated in the dry season. Knowledge on the sperm proteins provides crucial information for elucidating the underlying mechanisms associated with sperm functionality. Thus, our results help to advance our understanding of the reproductive physiology ofS. collinsi, providing valuable information for the improvement of protocols used in assisted reproduction techniques for the conservation of endangeredSaimirispecies.
P16methylation increases the sensitivity of cancer cells to the CDK4/6 inhibitor palbociclib
Authors: Li Paiyun , Zhang Xuehong , Gu Liankun , Zhou Jing , Deng Dajun
Published: September 2019

TheP16(CDKN2Aink4a) gene is an endogenous CDK4/6 inhibitor. Palbociclib (PD0332991) is an anti-CDK4/6 chemical for cancer treatment.P16is most frequently inactivated by copy number deletion and DNA methylation in cancers. It is well known that cancer cells withP16deletion are more sensitive to palbociclib than those without. However, whetherP16methylation is related to palbociclib sensitivity is not known. By analyzing public pharmacogenomic datasets, we found that the IC50 of palbociclib in cancer cell lines (n=522) was positively correlated with both theP16expression level andP16gene copy number. Our experimental results further showed that cancer cell lines withP16methylation were more sensitive to palbociclib than those without. To determine whetherP16methylation directly increased the sensitivity of cancer cells to palbociclib, we inducedP16methylation in the lung cancer cell lines H661 and HCC827 and the gastric cancer cell line BGC823 via an engineeredP16-specific DNA methyltransferase (P16-Dnmt) and found that the sensitivity of these cells to palbociclib was significantly increased. The survival rate of P16-Dnmt cells was significantly lower than that of vector control cells 48 hrs post treatment with palbociclib (10 μM). Notably, palbociclib treatment also selectively inhibited the proliferation of theP16-methylated subpopulation of P16-Dnmt cells, further indicating thatP16methylation can increase the sensitivity of cells to this CDK4/6 inhibitor. These results were confirmed in an animal experiment. In conclusion, inactivation of theP16gene by DNA methylation can increase the sensitivity of cancer cells to palbociclib.
Can the response of above- and below-ground traits to overgrazing vary between annual and perennial species?
Authors: Zhang Hui , Long Wenxing
Published: September 2019

Understanding functional traits that capture species response to grazing is crucial for uncovering mechanisms underlying the grazing-induced alterations in vegetation composition. Currently, the majority of studies ignore the effects of life form on the response of above- and below-ground traits to grazing. In this study we quantified i) whether below-ground traits exhibit similar response to overgrazing as do above-ground traits; and ii) whether the response of above- and below-ground traits to overgrazing varied with life form (annual versus perennial species). To testify the generality of these two questions, we compared common grassland species between an undisturbed and an over grazed meadow at each of four elevations ranging from 3000m to 3600m on the Qinghai Tibetan Plateau. We found both above-ground and below-ground traits exhibited similar resource conservationvs. resource acquisition trade-off for responding to overgrazing. Moreover, perennial species but not annual species determine the response of above- and below-ground traits to overgrazing. This work bridges the gap in the literature for the influence of land-use (in the absence and presence of overgrazing) and life forms (annual and perennial species) on species-specific response at both above-, and below-ground level.
The MEK1/2 pathway as a therapeutic target in high-grade serous ovarian carcinoma
Authors: Chesnokov Mikhail , Khan Imran , Park Yeonjung , Ezel Jessica , Mehta Geeta , Yousif Abdelrahman , Hong Linda J. , Buckanovich Ronald J. , Chefetz Ilana
Published: September 2019

Rationale

High-grade serous ovarian carcinoma (HGSOC) is the deadliest of gynecological cancers due to high rate of recurrence and acquired chemoresistance. Mutation and activation of the RAS/MAPK pathway has been linked to cancer cell proliferation and therapeutic resistance in numerous cancers. While RAS mutations are not commonly observed in HGSOC, less is known about downstream pathway activation. We therefore sought to investigate the role of MEK1/2 signaling in ovarian cancer.

Methods

MEK1/2 pathway activity was evaluated in clinical HGSOC tissue samples and ovarian cancer cell lines by using tissue microarray-based immunohistochemistry, immunoblotting, and RT-qPCR. OVCAR8 and PEO4 HGSOC cell lines were used to assess the effect of MEK1/2 inhibition on cell viability, proliferation rate, and stem-like characteristics. Xenografts were used in mice to investigate the effect of MEK1/2 inhibition on tumor growth in vivo. A drug washout experimental model was used to study the lasting effects of MEK1/2 inhibition therapy.

Results

MEK1/2 signaling is active in a majority of HGSOC tissue samples and cell lines. MEK1/2 is further stimulated by cisplatin treatment, suggesting that MEK1/2 activation may play a role in chemotherapy resistance. The MEK1/2 inhibitor, trametinib, drastically inhibits MEK1/2 downstream signaling activity, causes prominent cell cycle arrest in the G1/0-phase in cell cultures, and reduces the rate of tumor growth in vivo, but does not induce cell death. Cells treated with trametinib display a high CD133+ fraction and increased expression of stemness-associated genes. Transient trametinib treatment causes long-term increases in a high ALDH1 activity subpopulation of cells that possess the capability of surviving and growing in non-adherent conditions.

Conclusions

MEK1/2 inhibition in HGSOC cells efficiently inhibits proliferation and tumor growth and therefore may be a promising approach to suppress ovarian cancer cell growth. MEK1/2 inhibition promotes stem-like properties, thus suggesting a possible mechanism of resistance and that a combination with CSC-targeting drugs should be considered.
Dietary Induction and Modulation of Ferroptosis in Caenorhabditis elegans
Authors: Perez Marcos A. , Magtanong Leslie , Dixon Scott J. , Watts Jennifer L.
Published: September 2019

Ferroptosis is an iron-dependent form of regulated cell death associated with oxidized polyunsaturated phospholipids. Understanding the role of this process in vivo has been slowed by the lack of readily accessible model systems. Exposing the nematode Caenorhabditis elegans to the polyunsaturated fatty acid dihomogamma-linolenic acid (DGLA; 20:3n-6) causes germ cell death and sterility that is largely independent of the canonical apoptosis pathway. Here we demonstrate that DGLA-induced germ cell death is modulated by small molecule ferroptosis inhibitors, genetic manipulation of ferritin, NADPH oxidase, and glutathione peroxidases, and by dietary co-supplementation with oleic acid. Thus, DGLA-induced germ cell death in C. elegans is highly analogous to ferroptosis in mammalian cells. DGLA can also induce ferroptosis in human cells, further highlighting this omega-6 PUFA as a metabolic instigator of ferroptosis. Together, these results establish C. elegans as a powerful animal model to study the induction and modulation of ferroptosis by dietary fats.

Highlights

- Dietary dihomogamma-linolenic acid (DGLA)-induced germ cell death in C. elegans is alleviated by small molecule antioxidants and iron chelators

- Dietary and endogenous oleic acid protects from DGLA-induced ferroptosis

- Ether-lipid deficiency increases sensitivity to DGLA-induced ferroptosis

- DGLA specifically induces ferroptosis in human cancer cells
17α Estradiol promotes plasticity of spared inputs in the adult amblyopic visual cortex
Authors: Sengupta Deepali C. , Lantz Crystal L. , Rumi M.A. Karim , Quinlan Elizabeth M.
Published: September 2019

The promotion of structural and functional plasticity by estrogens is a promising therapy to enhance central nervous system function in the aged. However, how the sensitivity to estrogens is regulated across brain regions, age and experience is poorly understood. To ask if estradiol treatment impacts structural and functional plasticity in sensory cortices, we examined the acute effect of 17α Estradiol in adult Long Evans (LE) rats following chronic monocular deprivation, a manipulation that reduces the strength and selectivity of deprived eye vision. Chronic monocular deprivation decreased thalamic input from the deprived eye to the binocular visual cortex and accelerated short-term depression of the deprived eye pathway, without changing the total density of excitatory synapses. Importantly, we found that the classical estrogen receptors ERα and ERβ are robustly expressed in the adult visual cortex, and that a single dose of 17α Estradiol increased the size of excitatory postsynaptic densities, reduced the expression of parvalbumin and decreased the integrity of the extracellular matrix. Furthermore, 17α Estradiol enhanced experience-dependent plasticity in the amblyopic visual cortex, and promoted response potentiation of the pathway served by the non-deprived eye. The promotion of plasticity at synapses serving the non-deprived eye may reflect selectivity for synapses with an initially low probability of neurotransmitter release, and may inform applications to remap spared inputs around a scotoma or a cortical infarct
Sequence determinants of polyadenylation-mediated regulation
Authors: Vainberg Slutskin Ilya , Weinberger Adina , Segal Eran
Published: September 2019

The cleavage and polyadenylation reaction is a crucial step in transcription termination and pre-mRNA maturation in human cells. Despite extensive research, the encoding of polyadenylation-mediated regulation of gene expression within the DNA sequence is not well understood. Here, we utilized a massively parallel reporter assay to inspect the effect of over 12,000 rationally designed polyadenylation sequences (PASs) on reporter gene expression and cleavage efficiency. We find that the PAS sequence can modulate gene expression by over five orders of magnitude. By using a uniquely designed scanning mutagenesis data set, we gain mechanistic insight into various modes of action by which the cleavage efficiency affects the sensitivity or robustness of the PAS to mutation. Furthermore, we employ motif discovery to identify both known and novel sequence motifs associated with PAS-mediated regulation. By leveraging the large scale of our data, we train a deep learning model for the highly accurate prediction of RNA levels from DNA sequence alone (R = 0.83). Moreover, we devise unique approaches for predicting exact cleavage sites for our reporter constructs and for endogenous transcripts. Taken together, our results expand our understanding of PAS-mediated regulation, and provide an unprecedented resource for analyzing and predicting PAS for regulatory genomics applications.
Entrepreneurial learning in China’s low-end mobile phone market
Authors: Yu Fu Lai Tony , Kwan Diana S.
Published: September 2019

Purpose

The purpose of this paper is to explain the miraculous rise of the mobile phone industry in China in particular and China’s impressive industrial growth in recent decades in general.

Design/methodology/approach

This paper uses qualitative or story-telling approach for empirical analysis. Specifically, it uses case studies to illustrate the authors’ arguments.

Findings

Utilizing the theory of imitative strategies of latecomer firms and I.M. Kirzner’s concept of entrepreneurial alertness, this paper argues that adaptive entrepreneurs in China’s phone industry survive by being alert to profit opportunities, flexible and adaptable to the changing environments. With limited resources and low technological capabilities at the beginning, Chinese phone makers conduct replication via reverse engineering. Through entrepreneurial learning and imitation, they are able to make indigenous or incremental innovation. The modified models with functions compatible to different groups of consumers and sold at low prices are able to penetrate the low-end markets in the Third World nations.

Practical implications

The authors’ explanation on the success of China’s mobile phone industry sheds light on broader China’s industrial growth as a result of economic reform.

Originality/value

Most studies on China’s mobile phone industry focus on technological analysis, without acknowledging the role of entrepreneurship. This study fills the gap.
The effects of audit client tenure, audit lag, opinion shopping, liquidity ratio, and leverage to the going concern audit opinion
Authors: Simamora Rahmat Akbar , Hendarjatno Hendarjatno
Published: September 2019

Purpose

The going concern audit opinion is an audit opinion issued by an auditor to evaluate the company’s ability in maintaining the business continuity. The purpose of this paper is to discover the effects of audit client tenure, audit lag, opinion shopping, liquidity ratio and leverage on the going concern audit opinion.

Design/methodology/approach

The study used secondary data obtained from financial reports and independent audit reports published by Indonesian Stock Exchange (ISE) as well as Indonesian Capital Market Directory. Besides, the population of the study included manufacturing companies registered in ISE from 2009 to 2013. Further, the present study applied purposive sampling technique which resulted in 16 companies used as the sample of the study. Then the hypothesis was examined by applying logistic regression.

Findings

Results of the hypothesis examination indicated that the variables of opinion shopping and leverage affected the going concern audit opinion, whereas the variables of audit client tenure, audit lag and liquidity ratio did not affect the going concern audit opinion.

Originality/value

Results of the hypothesis examination indicated that the variables of opinion shopping and leverage affected the going concern audit opinion, whereas the variables of audit client tenure, audit lag and liquidity ratio did not affect the going concern audit opinion.
Financial statements disclosure on Indonesian local government websites
Authors: Nor Wahyudin , Hudaya Muhammad , Novriyandana Rifqi
Published: September 2019

Purpose

The purpose of this paper is to examine the extent to which audit opinion, audit findings, follow-up audit recommendations, level of education, level of welfare and heads of local governments’ commitment influence the disclosure of financial statements on the official website of local government.

Design/methodology/approach

The data of this research comprise 68 financial statements during the period 2015–2016 collected from 34 local governments across Indonesia by employing the census method. The data then are analyzed using logistic regression.

Findings

The results of this study show that audit opinion has a positive significant influence on the disclosure of financial statements on local government websites in Indonesia, while the audit findings, follow-up audit recommendations, level of education, level of welfare and heads of local governments’ commitment have no significant influences on the disclosure of financial statements local governments’ websites across Indonesia.

Originality/value

The study contributes to the public sector accounting research by enhancing our understanding to the disclosure of financial statements on local government websites.
Effect of country image and materialism on the quality evaluation of Korean products
Authors: Jin Byoungho Ellie , Kim Naeun Lauren , Yang Heesoon , Jung Minji
Published: September 2019

Purpose

It is critical to understand how global consumers evaluate the quality of Asian products while marketing Asian products in the global marketplaces. The purpose of this paper is to examine the impact of Korea’s macro and micro country image and global consumers’ materialism level on the quality evaluation of Korean cosmetics among consumers in four countries.

Design/methodology/approach

Data from 900 participants were collected from consumers aged 20 or older living in economically developed countries (the USA and France) and economically developing countries (China and Vietnam) via professional online survey firms. Multiple regression analyses were used to analyze the data.

Findings

Along with the direct effect of macro and micro country image and materialism on product quality evaluation, a moderating effect of materialism and the respective country was discovered. Subsequently, the effect of macro country image on quality evaluation was found to be only significant in the USA and France and not in China and Vietnam. In contrast, the impact of micro country image was robust across all four countries. Furthermore, the effect of materialism on product quality was significant only in Vietnam. This implies that materialistic consumers in emerging markets might have favorable perceptions regarding the quality of Korean cosmetics.

Originality/value

This study advances country image research by providing new theoretical and managerial implications for countries whose image is less distinctive with respect to the effective marketing of products by the destination countries’ development status and consumers’ familiarity.
Revisiting the role of professionals in designing buildings with low embodied and operational energy
Authors: Tennakoon G.A. , Waidyasekara Anuradha , Ekanayake B.J.
Published: September 2019

Purpose

Many studies have focused on embodied energy (EE) and operational energy (OE), but a shortage of studies on decision making, which involves several decision makers whose decisions can affect the energy performance of buildings, is evident. From the stages of the project life cycle, the design stage is identified as the ideal stage for integrating energy efficiency into buildings. Therefore, the purpose of this paper is to revisit the role of professionals in designing energy-conscious buildings with low EE and OE.

Design/methodology/approach

This study administered a qualitative approach. Data were collected through semi-structured interviews only with 12 experts, due to the lack of expertise in the subject matter. The data were analyzed using manual content analysis.

Findings

The outcomes revealed the necessity to revisit the role of construction professionals in terms of adopting energy-efficient building design concepts from the project outset. The roles of the key professional groups (i.e. architects, structural engineers, services engineers and quantity surveyors) were identified through this research. Common issues in designing energy-efficient buildings and the means of addressing such problems were outlined.

Originality/value

This study contributes to the knowledge by revisiting the roles of construction professionals and proposing how they could leverage their strengths to play the important role and contribute collectively to design buildings with both low OE and EE.
A systematic review of the applications of multi-criteria decision-making methods in site selection problems
Authors: Yap Jeremy Yee Li , Ho Chiung Chiung , Ting Choo-Yee
Published: September 2019

Purpose

The purpose of this paper is to perform a systematic review on the application of different multi-criteria decision-making (MCDM) methods in solving the site selection problem across multiple problem domains. The domains are energy generation, logistics, public services and retail facilities. This study aims to answer the following research questions: Which evaluating criteria were used for each site selection problem domain? Which MCDM methods were frequently applied in a particular site selection problem domain?

Design/methodology/approach

The goals of the systematic review were to identify the evaluating criteria as well as the MCDM method used for each problem domain. A total of 81 recent papers (2014–2018) including 32 papers published in conference proceedings and 49 journal articles from various databases including IEEE Xplore, PubMed, Springer, Taylor and Francis as well as ScienceDirect were evaluated.

Findings

This study has shown that site selection for energy generation facilities is the most active site selection problem domain, and that the analytic hierarchy process (AHP) method is the most commonly used MCDM method for site selection. For energy generation, the criteria which were most used were geographical elements, land use, cost and environmental impact. For logistics, frequently used criteria were geographical elements and distance, while for public services population density, supply and demand, geographical layout and cost were the criteria most used. Criteria useful for retail facilities were the size (space) of the store, demographics of the site, the site characteristics and rental of the site (cost).

Research limitations/implications

This study is limited to reviewing papers which were published in the years 2014–2018 only, and only covers the domains of energy generation, logistics, public services and retail facilities.

Practical implications

MCDM is a viable tool to be used for solving the site selection problem across the domains of energy generation, logistics, public services and retail facilities. The usage of MCDM continues to be relevant as a complement to machine learning, even as data originating from embedded IoT devices in built environments becomes increasingly Big Data like.

Originality/value

Previous systematic review studies for MDCM and built environments have either focused on studying the MCDM techniques itself, or have focused on the application of MCDM for site selection in a single problem domain. In this study, a critical review of MCDM techniques used for site selection as well as the critical criteria used during the MCDM process of site selection was performed on four different built environment domains.
MyCREST embedded framework for enhancing the adoption of green office building development in Sarawak
Authors: Ohueri Chukwuka Christian , Enegbuma Wallace Imoudu , Habil Hadina
Published: September 2019

Purpose

Green building development practices reduce carbon footprint and promote sustainability in the built environment. To foster green building construction in Malaysia, several strategies and sustainability metrics like the Malaysian Carbon Reduction and Environmental Sustainability Tool (MyCREST) have been established. Yet, the implementation of green office building development in Sarawak still remains low. Therefore, the purpose of this paper is to develop MyCREST Embedded Framework (MEF) for enhancing the adoption of green office building construction in Sarawak.

Design/methodology/approach

To achieve the research aim, document analysis of the overarching MyCREST Reference Guide was conducted. Then, questionnaire was used to survey 120 green construction professionals in Kuching, the capital of Sarawak. Afterwards, data from the questionnaire was analyzed using Statistical Package for Social Science software version 22. As a result, the significant strategies for enhancing the adoption of green office building construction in Sarawak were identified, and ranked hierarchically using the Relative Importance Index.

Findings

The established significant strategies include: government policies and incentives, sustainable technological practices, defined process for executing green building projects and adequate information for the public. Moreover, this study recommends MyCREST as the suitable Green Building Assessment Tool for developing green office buildings in Sarawak due to its integration of carbon reduction strategies with sustainability indicators.

Research limitations/implications

This study is limited to Kuching; hence future study should be extended to other cities in Sarawak.

Originality/value

Based on the findings, the MEF is developed to enlighten the industry practitioners on the approaches that will elevate green office building development in Sarawak.
Sociodemographic characteristics and dietary patterns in cardiometabolic risk subjects
Authors: Silveira Brenda Kelly Souza , Novaes Juliana Farias de , Vieira Sarah Aparecida , Rocha Daniela Mayumi Usuda Prado , Leal Arieta Carla Gualandi , Hermsdorff Helen Hermana Miranda
Published: September 2019

Purpose

The purpose of this paper is to examine the associations of dietary patterns with sociodemographic and lifestyle characteristics in a cardiometabolic risk population.

Design/methodology/approach

In this cross-sectional study data from 295 (n=123 men/172 women, 42±16 years) participants in a Cardiovascular Health Care Program were included. After a 24-hour recall interview the dietary patterns were determined using principal component analysis. Sociodemographic, clinical and lifestyle data were collected by medical records.

Findings

Subjects with diabetes and hypertension had a higher adherence in the “traditional” pattern (rice, beans, tubers, oils and meats). Poisson regression models showed that male subjects with low schooling and smokers had greater adherence to the “traditional” pattern. Also, students, women, and those with higher schooling and sleeping =7 h/night showed higher adherence to healthy patterns (whole grains, nuts, fruits and dairy). Women, young adults and those with higher schooling and fewer sleep hours had greater adherence to healthy dietary patterns. Those with low schooling and unhealthy lifestyle showed more adherence to the “traditional” pattern.

Social implications

The results indicate the importance to personalized nutritional therapy and education against cardiometabolic risk, considering the dietary patterns specific to each population.

Originality/value

Socioeconomic and lifestyle characteristics can influence dietary patterns and this is one of the few studies that investigated this relationship performing principal component analysis.
New patterns in wine consumption: the wine by the glass trend
Authors: Acuti Diletta , Mazzoli Valentina , Grazzini Laura , Rinaldi Rinaldo
Published: September 2019

Purpose

The purpose of this paper is to advance the understanding of wine by the glass (WBG) consumption as a new growing trend in wine consumption. To this end, the roles of risk perception, wine involvement and variety seeking are investigated in determining WBG purchase intentions.

Design/methodology/approach

Two studies based on a scenario-based survey have been conducted. In Study 1 (n=248), the relationship between WBG risk perception and WBG purchase intention mediated by variety seeking is tested. In Study 2 (n=200), the relationship between wine involvement and WBG purchase intention with the mediating role of variety seeking is analysed.

Findings

Results show that variety seeking plays a key role in determining WBG purchase intentions considering both WBG perceived risk and wine involvement as independent variables.

Research limitations/implications

The study advances the literature on WBG consumption by enclosing the psychological mechanism (i.e. variety seeking) behind consumers’ WBG purchase intentions. The main limitation of this study lies in it being conducted in a single country (i.e. Italy).

Practical implications

This paper provides useful guidelines for wine managers. Specifically, variety seeking can attract consumers in new wine-consuming places based on a rich assortment. Moreover, it can present a challenge to wine producers in creating brand loyalty.

Originality/value

Although WBG is a growing trend in wine consumption, empirical studies are still scant and a deeper comprehension of its antecedents and consequences is needed. By showing variety seeking as the mechanism behind WBG consumption, this study offers a new theoretical explanation of this phenomenon.