bluuebunny/crossref_metadata_2025 huggingface dataset:
Australia’s Environment and Its Management
Authors: Rutherfurd I.D.
Published: July 2018

The Southern Hemisphere island continent of Australia (7 million km2) is old, flat, stable, and dry, with a high proportion of endemic biota. The environment of Australia is fundamentally shaped by its age, its aridity and interannual climate variability, and the role of fire. These help to explain the continent’s characteristic ecology, animals, and evergreen vegetation. Fire has also been the main tool used by indigenous populations to substantially alter the landscape in their 50,000 years of occupation. In just 200 years, a relatively small population of European colonizers (by world standards) has even more effectively transformed the environment of Australia through mining, land use change, invasive plants and animals, exploitation of water resources, and water quality degradation. Very high endemism is matched by some of the world’s highest rates of extinctions of plants and animals. Although human populations are clustered in capital cities, and on the coast, particular pressure has come on three globally notable environments: the Great Barrier Reef, Northern Australia, and the Great Artesian Basin. Parallel with destruction has been preservation, and Australia has a long history of environmental protection. Nearly 12 percent of the continent is in protected areas, including Australia’s sixteen UNESCO World Heritage Areas. There are also some globally notable developments in environmental management, including the burgeoning role of indigenous groups in managing over 30 percent of the continent, and radical water management in response to overexploitation of water resources. In the early 21st century, climate change influences every aspect of Australia’s environment. Australia also has seven external territories (including 42 percent of Antarctica) that are also of great environmental importance but are not covered in this review.
Environmental Sociology
Authors: Knight Kyle W.
Published: July 2018

Having emerged in the 1970s as public awareness of and concern for environmental problems increased, environmental sociology’s main goal is to understand the interconnections between human societies and the natural (or biophysical) environment. Environmental sociology has been described as comprising four major areas of research. First, environmental sociologists study the social causes of environmental problems. Along these lines, scholars have developed an array of theoretical frameworks to explain how various social factors, including demographic, social, cultural, political, economic, and technological dynamics, generate environmental impacts and problems, and they have conducted many empirical studies on a wide range of environmental indicators to assess hypotheses derived from these theories. Second, environmental sociology is concerned with how the natural environment influences and impacts society. Early environmental sociologists strongly emphasized the dependence of human societies on the natural environment and stressed that the field should consider how the environment shapes society in addition to how society impacts the environment. Research in this area tackles issues such as the social consequences of natural disasters and the inequitable distribution of environmental hazards along racial and socioeconomic lines. Third, environmental sociology examines social reactions and responses to environmental threats and problems. Research in this area focuses on understanding patterns and trends in environmental attitudes and behaviors (e.g., recycling) as well as various aspects of the environmental movement. Fourth, environmental sociologists are concerned with understanding social processes and dynamics that could advance environmental reform and sustainability. In general, environmental sociology has tended to focus more on explaining how society causes environmental problems while paying less attention to potential solutions, but a shift has taken place in recent decades. The development, discussion, and empirical assessment of theories of environmental reform, analyses of potential solutions to environmental crises, and drafting of conceptual frameworks for sustainability have become important foci of scholarly activity in environmental sociology. Another major area of research, one that cuts across the preceding four, is the human dimensions of global climate change, which has become one of the main substantive issues studied by environmental sociologists. In this article, important scholarly works in each of these five areas are highlighted and briefly discussed, along with a selection of the most relevant textbooks, handbooks and collections, encyclopedia and review articles that provide general overviews of the field, and academic journals that publish environmental sociology research.
The Unequal Treaties and the Treaty Ports
Authors: Wang Dong
Published: July 2018

The “unequal treaties” and the treaty ports are two intricately linked elements of modern China’s experience with the world from 1843 to 1943 and beyond. The legal framework of treaty ports was rooted and developed in a series of documents signed between China and foreign countries that are considered by the Chinese to be unfair treaties. Although the definition and exact number of the “unequal treaties” are subject to fierce debate, it is generally agreed that a total of at least fourteen countries concluded unequal treaties with China, and that there were forty-eight treaty ports under a binding international treaty, except for three self-opened ports—Sandu Ao (Santuao), Yueyang (Yochow), and Qinhuangdao (Chinwangtao)—that were voluntarily opened by a Qing imperial decree in 1898 under the same trade regulations as the treaty ports. Among the nineteen Chinese provinces, by the early 20th century only Shanxi, Shaanxi, Gansu, Henan, and Guizhou had no treaty ports. Not necessarily located on the coast or near navigable water, the treaty ports were the “ports of entry,” but also something more. In historiographical terms, the treaty ports have been variously characterized as sites of paramount importance, as centers of controversy, and as a significant dimension of the encounter between China and the world. During the first half of the 20th century, the foreign presence and establishment served as the “port of entry” to the study of modern China for two generations of Western scholars, epitomized by Hosea Ballou Morse and John King Fairbank. From the 1980s on, social, cultural, and bottom-up approaches took the China history field by storm, in tandem with the master narrative of nation-states and transnationalism through nation-states. In the Chinese-speaking world, scholarly interest in the history of treaty ports is no match, to say the least, for research into issues surrounding the unequal treaties. China’s recent rise, especially the prosperity of former treaty port areas since the late 1970s, has prompted reconsideration of whether the Western presence did indeed matter in modern China. There is still a considerable hiatus to be covered regarding the interplay between bilateral and transnational aspects of the treaties and the ports. This article intends to further the study of the many dimensions of the treaties and treaty ports phenomena as viewed from the development of the main historical paradigms of Anglophone and Chinese research and the major source collections in Chinese, English, and Japanese.
Anti-Japanese War
Authors: Rose Caroline
Published: July 2018

The Anti-Japanese War 抗日战争 (kangRi zhanzheng), or the Chinese People’s War of Resistance Against Japan 中国人民抗日战争 (Zhongguo renmin kangRi zhanzheng), dates from July 1937 to 1945 (or in some interpretations the war dates from the so-called Manchurian Incident of 18 September 1931) and was the most bitter and destructive war the region had experienced. Millions of Chinese soldiers and civilians were killed or injured during the Japanese invasion and occupation, and millions more became refugees for the duration of the conflict. The failure to fully reconcile the legacy of the war has led to ongoing tensions and diplomatic wrangles between China and Japan over different interpretations of the past and continues to de-stabilize East Asia. The subject of the Anti-Japanese War has long been the focus of academic attention but has benefited in particular in the last two decades from the opening of archives, declassification of documents, and publication of memoirs, letters, and diaries: this, in turn, has produced a much richer understanding of an increasingly wider spectrum of topics including the role of women, cities at war, visual and popular cultural studies, among others. Despite the depth and breadth of scholarly engagement with the topic, the Anti-Japanese War continues to be a contested and sometimes emotive field of study (particularly in relation to war responsibility and the difficulties surrounding reconciliation), and the field would benefit from further collaborative efforts to address some of these issues.
Proteomics of Bulked Rachides Combined with Documented QTL Uncovers Genotype Nonspecific Players of the Fusarium Head Blight Responses in Wheat
Authors: Liu Jiajun , Li Lei , Foroud Nora A. , Gong Xuan , Li Changcheng , Li Tao
Published: July 2018

Fusarium head blight (FHB) is a destructive disease of wheat that reduces yield and grain quality. High-throughput proteomic techniques have been used to identify a wide range of candidate proteins involved in host resistance. The majority of the published works on the proteomics of the wheat response to Fusarium graminearum infection are case specific. In the current study, a high-throughput quantitative label-free strategy was employed on bulked rachides of F. graminearum-infected wheat collected from multiple genotypes. Differentially accumulated proteins among the following four pools were identified: mock-inoculated FHB-resistant accessions (RM), mock-inoculated FHB-susceptible accessions (SM), F. graminearum-inoculated FHB-resistant accessions (RFg), and F. graminearum-inoculated FHB-susceptible accessions (SFg). Four pairs of comparisons were made: RFg versus RM, SFg versus SM, RM versus SM, and RFg versus SFg. Proteins were projected onto the consensus intervals of previously reported quantitative trait loci in the FHB-resistant pool by blasting against the Chinese Spring reference sequences. In addition to proteins previously reported in the host response to Fusarium spp., new candidates have emerged in association with resistance or susceptibility, including a group 3 late embryogenesis abundant as a resistance-related protein and a purple acid phosphatase as a susceptibility protein. The protein atlas presented here provides new perspectives on the interaction between F. graminearum and wheat.
Cdk5‐mediated phosphorylation regulates phosphatidylinositol 4‐phosphate 5‐kinase type I γ 90 activity and cell invasion
Authors: Li Liqing , Kołodziej Tomasz , Jafari Naser , Chen Jing , Zhu Haining , Rajfur Zenon , Huang Cai
Published: July 2018

Phosphatidylinositol 4‐phosphate 5‐kinase type I γ (PIPKIγ90) regulates cell migration, invasion, and metastasis. However, it is unknown how cellular signals regulate those processes. Here, we show that cyclin‐dependent kinase 5 (Cdk5), a protein kinase that regulates cell migration and invasion, phosphorylates PIPKIγ90 at S453, and that Cdk5‐mediated PIPKIγ90 phosphorylation is essential for cell invasion. Moreover, Cdk5‐mediated phosphorylation down‐regulates the activity of PIPKIγ90 and the secretion of fibronectin, an extracellular matrix protein that regulates cell migration and invasion. Furthermore, inhibition of PIPKIγ activity with the chemical inhibitor UNC3230 suppresses fibronectin secretion in a dose‐dependent manner, whereas depletion of Cdk5 enhances fibronectin secretion. With total internal reflection fluorescence microscopy, we found that secreted fibronectin appears as round dots, which colocalize with Tks5 and CD9 but not with Zyxin. These data suggest that Cdk5‐mediated PIPKIγ90 phosphorylation regulates cell invasion by controlling PIPKIγ90 activity and fibronectin secretion.—Li, L., Kotodziej, T., Jafari, N., Chen, J., Zhu, H., Rajfur, Z., Huang, C. Cdk5‐mediated phosphorylation regulates phosphatidylinositol 4‐phosphate 5‐kinase type I γ 90 activity and cell invasion. FASEB J. 33, 631–642 (2019). www.fasebj.org
RYBP modulates stability and function of Ring1B through targeting UBE3A
Authors: Li Meng , Zhang Shiqiang , Zhao Wen , Hou Congcong , Ma Xiaoli , Li Xuekun , Huang Bingren , Chen Hong , Chen Deng
Published: July 2018

Ring1 and yin yang 1–binding protein (RYBP) are central components of noncanonical polycomb‐repressive complex 1 (nc‐PRC1), which represses target gene expression and is required for normal organismal development. However, the molecular function of RYBP in this complex is obscure. In this study, we showed that RYBP inhibits the polyubiquitination‐mediated proteasomal degradation of RingIB independently of its ubiquitin (Ub)‐protein isopeptide ligase (E3) ligase activity, leading to its stabilization and increased catalytic activity toward monoubiquitination of histone H2A at lysine 119. Mechanistic dissection further disclosed that RYBP directly binds to ubiquitin protein ligase E3A (UBE3A) to promote its ubiquitination and proteasomal degradation in an autoubiquitination‐independent manner. The resultant reduction of UBE3A protein level alleviates its effect on ubiquitination‐mediated degradation of Ring1B, therefore resulting in increased stability and enhanced transcriptional repressor activity on its target genes. Thus, our current findings lay a foundation for understanding how RYBP functions in nc‐PRC1 complexes, which is involved in development, stem cell maintenance, and carcinogenesis.—Li, M., Zhang, S., Zhao, W., Hou, C., Ma, X., Li, X., Huang, B., Chen, H., Chen, D. RYBP modulates stability and function of Ring1B through targeting UBE3A. FASEB J. 33, 683–695 (2019). www.fasebj.org
Integrative and conjugative elements and their hosts: composition, distribution, and organization
Authors: Cury Jean , Touchon Marie , Rocha Eduardo P. C.
Published: July 2018

Conjugation of single-stranded DNA drives horizontal gene transfer between bacteria and was widely studied in conjugative plasmids. The organization and function of integrative and conjugative elements (ICE), even if they are more abundant, was only studied in a few model systems. Comparative genomics of ICE has been precluded by the difficulty in finding and delimiting these elements. Here, we present the results of a method that circumvents these problems by requiring only the identification of the conjugation genes and the species’ pan-genome. We delimited 200 ICEs and this allowed the first large-scale characterization of these elements. We quantified the presence in ICEs of a wide set of functions associated with the biology of mobile genetic elements, including some that are typically associated with plasmids, such as partition and replication. Protein sequence similarity networks and phylogenetic analyses show that ICEs are modular and that their gene repertoires can be grouped in function of their conjugation types, even if integrases were shown to be paraphyletic relative to the latter. We show that there are general trends in the functional organization of genes within ICEs and of ICEs within the bacterial chromosome paving the way for future functional and evolutionary analyses.
Seasonal occurrence of diamondback moths Plutella xylostella and their parasitoid wasps Cotesia vestalis in greenhouses and their surrounding areas
Authors: Abe Junichiro , Uefune Masayoshi , Yoneya Kinuyo , Shiojiri Kaori , Takabayashi Junji
Published: July 2018

We observed the seasonal occurrence of diamondback moth (DBM) larvae, Plutella xylostella (Lepidoptera: Plutellidae), and their native parasitoid wasps, Cotesia vestalis (Hymenoptera: Braconidae), on mizuna plants, Brassica rapa var. laciniifolia (Brassicales: Brassicaceae), in three commercial greenhouses and on wild cruciferous weeds, Rorippa indica (Brassicales: Brassicaceae), in the surrounding area in the Miyama countryside in Kyoto, Japan. The occurrences of DBM larvae in greenhouses followed their occurrence in the surrounding area: however, some occurrences of DBM in greenhouses took place when the DBM population in the surrounding was rather low. This suggests that the occurrence of DBM in greenhouses cannot always be explained by its seasonal occurrence in the surrounding areas. The occurrence of C. vestalis followed that of DBM larvae in mizuna greenhouses and in the surrounding areas. No C. vestalis were recorded in greenhouses when DBM was not present. Cotesia vestalis females preferred volatiles emitted from DBM-infested mizuna plants to those from uninfested conspecifics under laboratory conditions. Natural HIPVs (herbivory-induced plant volatiles) emitted from DBM-infested mizuna plants in greenhouses probably attracted C. vestalis from the surrounding area to cause their co-occurrence.
Structure of the ciliary axoneme at nanometer resolution reconstructed by TYGRESS
Authors: Song Kangkang , Shang Zhiguo , Fu Xiaofeng , Lou Xiaochu , Grigorieff Nikolaus , Nicastro Daniela
Published: July 2018

The resolution of subtomogram averages calculated from cryo-electron tomograms (cryo-ET) of crowded cellular environments is often limited due to signal loss in, and misalignment of the subtomograms. In contrast, single-particle cryo-electron microcopy (SP-cryo-EM) routinely reaches near-atomic resolution of isolated complexes. We developed a novel hybrid-method called “TomographY-Guided 3DREconstruction ofSubcellularStructures” (TYGRESS) that combines cryo-ET with SP-cryo-EM to achieve close-to-nanometer resolution of complexes inside crowded environments. Using TYGRESS, we determined the native 3D structures of the intact ciliary axoneme with up to 12 Å resolution. These results reveal many structures and details that were not visible by cryo-ET. TYGRESS is generally applicable to cellular complexes that are amenable to subtomogram averaging, bringing us a step closer to (pseudo-)atomic models of cells.

One Sentence Summary

A hybrid cryo-electron microscopy method reveals subcellular structures at unprecedented resolution.
The Effect of Phylogenetic Uncertainty and Imputation on EDGE Scores
Authors: Weedop K. Bodie , Mooers Arne Ø. , Tucker Caroline M. , Pearse William D.
Published: July 2018

Faced with the challenge of saving as much diversity as possible given financial and time constraints, conservation biologists are increasingly prioritizing species on the basis of their overall contribution to evolutionary diversity. Metrics such as EDGE (Evolutionary Distinct and Globally Endangered) have been used to set such evolutionarily-based conservation priorities for a number of taxa, such as mammals, birds, corals, amphibians, and sharks. Each application of EDGE has required some form of correction to account for species whose position within the tree of life are unknown. Perhaps the most advanced of these corrections is phylogenetic imputation, but to date there has been no systematic assessment of both the sensitivity of EDGE scores to a phylogeny missing species, and the impact of using imputation to correct for species missing from the tree. Here we perform such an assessment, by simulating phylogenies, removing some species to make the phylogeny incomplete, imputating the position of those species, and measuring (1) how robust ED scores are for the species that are not removed and (2) how accurate the ED scores are for those removed and then imputed. We find that the EDGE ranking for species on a tree is remarkably robust to missing species from that tree, but that phylogenetic imputation for missing species, while unbiased, does not accurately reconstruct species’ evolutionary distinctiveness. On the basis of these results, we provide clear guidance for EDGE scoring in the face of phylogenetic uncertainty.
A natural killer cell gene signature predicts melanoma patient survival
Authors: Cursons Joseph , Souza-Fonseca-Guimaraes Fernando , Anderson Ashley , Foroutan Momeneh , Hediyeh-Zadeh Soroor , Behren Andreas , Huntington Nicholas D. , Davis Melissa J
Published: July 2018

Animal models have demonstrated that natural killer (NK) cells can limit the metastatic dissemination of tumors, however their ability to combat established human tumors has been difficult to investigate.

A number of computational methods have been developed for the deconvolution of immune cell types within solid tumors. We have taken the NK cell gene signatures from several tools, then curated and expanded this list using recent reports from the literature. Using a gene set scoring method to investigate RNA-seq data from The Cancer Genome Atlas (TCGA) we show that patients with metastatic cutaneous melanoma have an improved survival rate if their tumor shows evidence of greater NK cell infiltration. Furthermore, these survival effects are enhanced in tumors which have a higher expression of NK cell stimuli such as IL-15, suggesting NK cells are part of a coordinated immune response within these patients. Using this signature we then examine transcriptomic data to identify tumor and stromal components which may influence the penetrance of NK cells into solid tumors.

These data support a role for NK cells in the regulation of human tumors and highlight potential survival effects associated with increased NK cell activity. Furthermore, our computational analysis identifies a number of potential targets which may help to unleash the anti-tumor potential of NK cells as we enter the age of immunotherapy.
LDpred-funct: incorporating functional priors improves polygenic prediction accuracy in UK Biobank and 23andMe data sets
Authors: Márquez-Luna Carla , Gazal Steven , Loh Po-Ru , Kim Samuel S. , Furlotte Nicholas , Auton Adam ,   23andMe Research Team, Price Alkes L.
Published: July 2018

Genetic variants in functional regions of the genome are enriched for complex trait heritability. Here, we introduce a new method for polygenic prediction, LDpred-funct, that leverages trait-specific functional priors to increase prediction accuracy. We fit priors using the recently developed baseline-LD model, which includes coding, conserved, regulatory and LD-related annotations. We analytically estimate posterior mean causal effect sizes and then use cross-validation to regularize these estimates, improving prediction accuracy for sparse architectures. LDpred-funct attained higher prediction accuracy than other polygenic prediction methods in simulations using real genotypes. We applied LDpred-funct to predict 21 highly heritable traits in the UK Biobank. We used association statistics from British-ancestry samples as training data (avgN=373K) and samples of other European ancestries as validation data (avgN=22K), to minimize confounding. LDpred-funct attained a +4.6% relative improvement in average prediction accuracy (avg predictionR2=0.144; highestR2=0.413 for height) compared to SBayesR (the best method that does not incorporate functional information). For height, meta-analyzing training data from UK Biobank and 23andMe cohorts (totalN=1107K; higher heritability in UK Biobank cohort) increased predictionR2to 0.431. Our results show that incorporating functional priors improves polygenic prediction accuracy, consistent with the functional architecture of complex traits.
Costimulation through TLR2 drives polyfunctional CD8+T cell responses
Authors: Salerno Fiamma , Freen-van Heeren Julian J. , Guislain Aurelie , Nicolet Benoit P. , Wolkers Monika C.
Published: July 2018

Optimal T cell activation requires antigen recognition through the T cell receptor (TCR), engagement of costimulatory molecules, and cytokines. T cells can also directly recognize danger signals through the expression of toll-like receptors (TLRs). Whether TLR ligands have the capacity to provide costimulatory signals and enhance antigen-driven T cell activation is not well understood. Here, we show that TLR2 and TLR7 ligands potently lower the antigen threshold for cytokine production in T cells. To investigate how TLR triggering supports cytokine production, we adapted the protocol for flow cytometry-based fluorescencein situhybridization (Flow-FISH) to mouse T cells. The simultaneous detection of cytokine mRNA and protein with single-cell resolution revealed that TLR triggering primarily drivesde novomRNA transcription.IfngmRNA stabilization only occurs when the TCR is engaged. TLR2, but not TLR7-mediated costimulation, can enhance mRNA stability at low antigen levels. Importantly, TLR2 costimulation increases the percentage of polyfunctional T cells, a hallmark of potent T cell responses. In conclusion, TLR-mediated costimulation effectively potentiates T cell effector function to suboptimal antigen levels.
A new actin depolymerase: a Myosin 1 motor
Authors: Pernier Julien , Kusters Remy , Bousquet Hugo , Lagny Thibaut , Morchain Antoine , Joanny Jean-François , Bassereau Patricia , Coudrier Evelyne
Published: July 2018

The regulation of actin dynamics is essential for various cellular processes. Former evidence suggests a correlation between the function of non-conventional myosin motors and actin dynamics. We investigate the contribution of myosin1b to actin dynamics using sliding motility assays. We observe that sliding on myosin1b immobilized or bound to a fluid bilayer enhances actin depolymerization at the barbed end, while sliding on myosin II, although 5 times faster, has no effect. This work reveals a non-conventional myosin motor as a new type of depolymerase and points to its singular interactions with the actin barbed end.
Combinatorial Genetic Control of Rpd3S through histone H3K4 and H3K36 Methylation in Budding Yeast
Authors: Lee Kwan Yin , Ranger Mathieu , Meneghini Marc D.
Published: July 2018

Much of euchromatin regulation occurs through reversible methylation of histone H3 lysine-4 and lysine-36 (H3K4me and H3K36me). Using the budding yeast Saccharomyces cerevisiae, we previously found that levels of H3K4me modulated temperature sensitive alleles of the transcriptional elongation complex Spt6-Spn1 through an unknown H3K4me effector pathway. Here we identify the Rpd3S histone deacetylase complex as the H3K4me effector underlying these Spt6-Spn1 genetic interactions. Exploiting these Spt6-Spn1 genetic interactions, we show that H3K4me and H3K36me collaboratively impact Rpd3S function in an opposing manner. H3K36me is deposited by the histone methyltransferase Set2 and is known to promote Rpd3S function at RNA PolII transcribed open reading frames. Using genetic epistasis experiments, we find that mutations perturbing the Set2-H3K36me-Rpd3S pathway suppress the growth defects caused by temperature sensitive alleles of SPT6 and SPN1, illuminating that this pathway antagonizes Spt6-Spn1. Using these sensitive genetic assays, we also identify a role for H3K4me in antagonizing Rpd3S that functions through the Rpd3S subunit Rco1, which is known to bind H3 N-terminal tails in a manner that is prevented by H3K4me. Further genetic experiments reveal that the H3K4 and H3K36 demethylases JHD2 and RPH1 mediate this combinatorial control of Rpd3S. Finally, our studies also show that the Rpd3L complex, which acts at promoter-proximal regions of PolII transcribed genes, counters Rpd3S for genetic modulation of Spt6-Spn1, and that these two Rpd3 complexes balance the activities of each other. Our findings present the first evidence that H3K4me and H3K36me act combinatorially to control Rpd3S.
Extracellular matrix regulates morphogenesis and function of ciliated sensory organs inCaenorhabditis elegans
Authors: De Vore Deanna M. , Knobel Karla M. , Nguyen Ken C.Q. , Hall David H. , Barr Maureen M.
Published: July 2018

Cilia and extracellular vesicles (EVs) are signaling organelles that play important roles in human health and disease. InC. elegansand mammals, the Autosomal Dominant Polycystic Kidney Disease (ADPKD) gene products polycystin-1 and polycystin-2 localize to both cilia and EVs, act in the same genetic pathway, and function in a sensory capacity, suggesting ancient conservation. Hence, the nematode offers an excellent system in which to address central questions regarding the biology of cilia, EVs, and the polycystins. We discovered an unexpected role of themec-1, mec-5, andmec-9genes encoding extracellular matrix (ECM) components. We determined that these ECM encoding genes regulate polycystin localization and function, ciliary EV release, cilia length, dendritic morphology, and neuron-glia interactions. Abnormal ECM and fibrosis are observed in ciliopathies such as ADPKD, nephronophthisis, and Bardet-Biedl Syndrome. Our studies reveal multifaceted roles for ECM proteins in the ciliated nervous system of the worm and provide a powerful newin vivomodel to study the relationship between ECM, the polycystins, and ciliopathies.
Epigenetic silencing of miRNA-338-5p and miRNA-421 drives SPINK1-positive prostate cancer
Authors: Bhatia Vipul , Yadav Anjali , Tiwari Ritika , Nigam Shivansh , Goel Sakshi , Carskadon Shannon , Gupta Nilesh , Goel Apul , Palanisamy Nallasivam , Ateeq Bushra
Published: July 2018

Purpose

Serine Peptidase Inhibitor, Kazal type-1 (SPINK1) overexpression defines the second most recurrent and aggressive prostate cancer (PCa) subtype. However, the underlying molecular mechanism and pathobiology of SPINK1 in PCa remains largely unknown.

Experimental Design

MicroRNA-prediction tools were employed to examine theSPINK1-3’UTR for miRNAs binding. Luciferase reporter assays were performed to confirm theSPINK1-3’UTR binding of shortlisted miR-338-5p/miR-421. Further, miR-338-5p/-421 overexpressing cancer cells (SPINK1-positive) were evaluated for oncogenic properties using cell-based functional assays and mice xenograft model. Global gene expression profiling was performed to unravel the biological pathways altered by miR-338-5p/-421. Immunohistochemistry and RNAin-situhybridization was carried-out on PCa patients’ tissue microarray for SPINK1 andEZH2expression respectively. Chromatin immunoprecipitation assay was performed to examine EZH2 occupancy on the miR-338-5p/-421 regulatory regions. Bisulfite sequencing and methylated DNA-immunoprecipitation was performed on PCa cell lines and patients’ specimens.

Results

We established a critical role of miRNA-338-5p/-421 in post-transcriptional regulation ofSPINK1. Ectopic expression of miRNA-338-5p/-421 in SPINK1-positive PCa cells abrogate oncogenic properties including cell-cycle progression, stemness and drug resistance, and show reduced tumor burden and distant metastases in mice model. Importantly, we show SPINK1-positive PCa patients exhibit increased EZH2 expression, suggesting its role in miRNA-338-5p/-421 epigenetic silencing. Furthermore, presence of CpG dinucleotide DNA methylation marks on the regulatory regions of miR-338-5p/-421 in SPINK1-positive PCa cells and patients’ specimens confirms epigenetic silencing.

Conclusion

Our findings revealed that miRNA-338-5p/-421 are epigenetically silenced in SPINK1-positive PCa, while restoring the expression of these miRNAs using epigenetic drugs or synthetic mimics could abrogate SPINK1-mediated oncogenesis.

TRANSLATIONAL IMPACT

We establish a regulatory model involving the functional interplay between SPINK1, miRNA-338-5p/miRNA-421 and EZH2, thereby, revealing hitherto unknown mechanism of SPINK1 up-regulation in SPINK1-positive subtype. Our findings provide a strong rationale for the development of potential therapeutic strategies for SPINK1-positive malignancies. We demonstrate that restoring miRNA-338-5p/miRNA-421 expression using epigenetic drugs including DNMTs inhibitors in combination with HDACs or HKMTs inhibitors or miRNA synthetic mimics in SPINK1-positive prostate cancer abrogate SPINK1-mediated oncogenicity. The major findings of this study will not only advance the prostate cancer field, but will also be valuable for treatment and disease management of other SPINK1-positive malignancies.
Cellular acidosis triggers MondoA transcriptional activity by driving mitochondrial ATP production
Authors: Wilde Blake R. , Ye Zhizhou , Ayer Donald E.
Published: July 2018

MondoA and its transcriptional target thioredoxin-interacting protein (TXNIP) constitute a regulatory loop that senses glycolytic flux and controls glucose availability. Cellular stress also triggers MondoA activity and TXNIP expression. To understand how MondoA integrates glucose and stress signals, we studied its activation by acidosis. We found that acidosis drives mitochondrial ATP (mtATP) synthesis. The subsequent export of mtATP from mitochondria via adenine-nucleotide transporter and voltage-dependent anion channel, and the enzymatic activity of mitochondria-bound hexokinase results in the production of glucose-6-phosphate (G6P), a known activator of MondoA transcriptional activity. MondoA localizes to the outer-mitochondrial membrane (OMM), and in response to G6P, shuttles to the nucleus and activates transcription. Our data suggests that MondoA is a required feature of a glucose- and mtATP-dependent, OMM-localized signaling center. We propose MondoA functions as a coincidence detector and its ability to sense glucose and cellular stress is coupled to the concerted production of G6P.
Developmental Regulation of an Organelle Tether Coordinates Mitochondrial Remodeling in Meiosis
Authors: Sawyer Eric M. , Joshi Pallavi R. , Berchowitz Luke E. , Ünal Elçin
Published: July 2018

Cellular differentiation involves remodeling cellular architecture to transform one cell type to another. By investigating mitochondrial dynamics during meiotic differentiation in budding yeast, we sought to understand how organelle morphogenesis is developmentally controlled in a system where regulators of differentiation as well as organelle architecture are known, but the interface between them remains unexplored. We found that mitochondria abruptly detach from the cell cortex shortly before segregating into gametes. Mitochondrial detachment is enabled by the programmed destruction of themitochondria-endoplasmic reticulum-cortexanchor (MECA), an organelle tether that forms contact sites between mitochondria and the plasma membrane. MECA regulation is governed by a meiotic transcription factor, Ndt80, which promotes the activation of a conserved kinase, Ime2. We found that MECA undergoes Ime2-dependent phosphorylation. Furthermore, Ime2 promotes MECA degradation in a temporally controlled manner. Our study defines a key mechanism that coordinates mitochondrial morphogenesis with the landmark events of meiosis and demonstrates that cells can developmentally regulate tethering to induce organelle remodeling.
High-density HNIW/TNT cocrystal synthesized using a green chemical method
Authors: Liu Yan , An Chongwei , Luo Jin , Wang Jingyu
Published: July 2018

The main challenge for achieving better energetic materials is to increase their density. In this paper, cocrystals of HNIW (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane, often referred to as CL-20) with TNT (2,4,6-trinitrotoluene) were synthesized using ethanol in a green chemical method. The cocrystal was formulated as C13H11N15O18 and possesses a higher density (1.934 g cm−3) than published previously (1.846 g cm−3). This high-density cocrystal possesses a new structure, which can be substantiated by the different types of hydrogen bonds. The predominant driving forces that connect HNIW with TNT in the new cocrystal were studied at ambient conditions using single-crystal X-ray diffraction, powder X-ray diffraction, Fourier transform–infrared spectroscopy and Raman spectroscopy. The results reveal that the structure of the new HNIW/TNT cocrystals consists of three one-dimensional hydrogen-bonded chains exploiting the familiar HNIW–TNT multi-component supramolecular structure, in which two hydrogen-bonded chains are between —NO2 (HNIW) and —CH (TNT), and one hydrogen-bonded chain is between —CH (HNIW) and —NO2 (TNT). The changes to the electron binding energy and type of element in the new cocrystal were traced using X-ray photoelectron spectroscopy. Meanwhile, the physicochemical characteristics alter after cocrystallization due to the hydrogen bonding. It was found that the new HNIW/TNT cocrystal is more thermodynamically stable than HNIW. Thermodynamic aspects of new cocrystal decomposition are investigated in order to explain this observation. The detonation velocity of new HNIW/TNT cocrystals is 8631 m s−1, close to that of HNIW, whereas the mechanical sensitivity is lower than HNIW.
Crystal structure of a mononuclear copper(II) complex with 2-methoxy-N,N-bis(quinolin-2-ylmethyl)ethylamine (DQMEA)
Authors: Frey Steven T. , Li Jason , Kaur Manpreet , Jasinski Jerry P.
Published: July 2018

Structural characterization of the compound [Cu(C2H3N)(C23H23N3O)](ClO4)2] or [Cu(C2H3N)(DQMEA)](ClO4)2] [DQMEA = 2-methoxy-N,N-bis(quinolin-2-ylmethyl)ethylamine] {systematic name: (acetonitrile)[2-methoxy-N,N-bis(quinolin-2-ylmethyl)ethylamine]copper(II) diperchlorate} by single-crystal X-ray diffraction reveals a complex cation with a tetradentate coordination of the DQMEA ligand along with monodentate coordination of a CH3CN ligand to a single CuII center, with two perchlorate anions providing charge balance. The CuII center has a distorted square-pyramidal geometry in which the nitrogen atoms of the DQMEA and CH3CN ligands occupy the equatorial positions, while the oxygen atom of the DQMEA ligand resides in the axial position with an elongated Cu—O bond. The quinoline ring systems are nearly co-planar in the structure, while the linear CH3CN ligand is tilted significantly below this plane, and the central nitrogen of DQMEA is above it. Within the complex, weak C—H...N hydrogen bonding takes place between the nitrogen of CH3CN and a neighboring quinolyl group. The perchlorate ions are disordered within the structure, but undergo a number of weak intermolecular C—H...O hydrogen-bonding interactions. Additional weak π-stacking interactions between the quinolyl groups of neighboring complexes further stabilize the crystal packing.
The 11 commandments of publishing
Authors: De Lange Paul , Daff Lyn , Jackling Beverley
Published: July 2018

Purpose

Publishing in scholarly journals is a practical necessity for academics. Put simply, this reality can be described as “publish or perish”. To be treated as a serious contender for tenure and promotion, scholarly research and activities directed towards publication are necessary aspects of faculty life. The purpose of this paper is to provide insights into “dealing” with the editorial review process of publishing from the perspective of a relatively new author.

Design/methodology/approach

Using the lens of Q and R theory, a case study approach combined with critical reflection provides a documented tour to enable other authors to enhance their understanding of the publication process through including references to associated reviews and correspondence with a journal editor. The review extracts from the editor and authors’ responses are discussed within the context of a theoretical schema and timeline.

Findings

Drawing from the theoretical schema, the paper identifies 11 lessons learned along the way to publishing, and these are summarised as the 11 commandments of publishing.

Research limitations/implications

Utilisation of the Q and R theory can assist researchers as they reflect on how to maximise their publication outcomes.

Practical implications

The 11 commandments provide a practical approach for those wanting to improve their understanding and likelihood of publishing success.

Originality/value

The originality of this paper is that it considers the publication process from a novice author who subsequently draws on the knowledge of more experienced co-authors. The findings are based on a theoretical schema that is transferable and able to be adopted by others to guide publication outcomes.
Determinants of women representation on corporate boards: evidence from Australia
Authors: Ahmed Ammad , Higgs Helen , Ng Chew , Delaney Deborah Anne
Published: July 2018

Purpose

This paper aims to investigate the determinants of women representation on Australian corporate boards under the ASX’s “if not, why not” corporate governance framework. It further aims to improve the study of Geiger and Marlin (2012) by using a theoretically sound two-limit Tobit model to examine the determinants.

Design/methodology/approach

This study uses the two-limit Tobit model to examine the determinants of women representation on ASX 500 boards. This approach is used due to the censored nature of the dependent variable.

Findings

This study finds that the two-limit Tobit model is an appropriate methodology to accommodate the censored dependent variable. It further finds that firm size, women as chair of boards, corporate governance index, Global Reporting Initiative signatory, debt ratio, average board age, BIG4 auditors, chief executive officer tenure and shareholder concentration are major determinants of women on boards.

Research limitations/implications

The use of only ASX 500 companies and the sample years (2011-2014) may limit the generalisation of the findings.

Originality/value

This is the first extensive longitudinal Australian study to examine the drivers of women representation on corporate boards. It is also the first of its kind to use the two-limit Tobit model to consider these determinants.
How to regain public trust in audit firms? The case of the Financial Reporting Council
Authors: Eldaly Mohamed Khaled , Abdel-Kader Magdy
Published: July 2018

Purpose

This study aims to provide a better understanding of the role of the Financial Reporting Council (FRC), as the unified regulator of the audit profession in the UK, in restoring public trust in audit profession in the UK. It further analyses the views of partners in the Big 4 audit firms on this role.

Design/methodology/approach

The research data were gathered by conducting 17 semi-structured interviews with the top management of FRC’s members and executive partners of the Big 4 firms in the UK. The interviews were complemented by analysing data available on the web pages of the Big 4 firms and published reports related to the FRC’s projects.

Findings

This study identified three main strategies followed by the FRC to promote the trust and enhance the choice of auditors in the UK audit market. These strategies are improving the audit quality, increasing the transparency of the big audit firms and reducing the barriers to compete in the big audit market.

Practical implications

An analysis of the FRC’s efforts may help auditors to identify what they are expected to do to improve the reliability of information provided in the capital market. Audit committees can get a better understanding of the criteria that they need to improve the process of auditors’ choice. Auditors will also better understand how and why current audit regulations have been issued. This may improve their satisfaction with regulations and standards, and their efficient implementation. Furthermore, it is believed that audit regulators need to get feedback additional to the formal feedback they receive to improve their performance and current regulations.

Originality/value

This paper contributes to the literature by discussing the auditors’ criticism to the Audit Inspection Unit’s inspectors and the way the inspectors defend themselves. The findings suggest that partners of the Big 4 believe that the FRC’s projects effectively participate in improving the audit quality, as well as providing wider information about the audit firms to the public. However, different actions need to be taken to enhance the choice of auditors and increase the number of big audit firms that compete in the market.
Corporate governance and carbon transparency: Australian experience
Authors: Elsayih Jibriel , Tang Qingliang , Lan Yi-Chen
Published: July 2018

Purpose

The purpose of this paper is to explore the association between corporate governance (CG) mechanisms and the extensiveness of carbon disclosure.

Design/methodology/approach

This paper uses Ordinary Least Squares (OLS) regression model with data from 2009 to 2012 for largest Australian companies that voluntarily disclose their information to the carbon disclosure project.

Findings

The authors find that board independence, board diversity and managerial ownership are significantly correlated with the degree of carbon transparency, while the existence of environmental committee is not.

Practical implications

The findings of this paper should be useful for government and capital market regulators who concern the quality of CG and carbon actions. First, the evidence in this paper suggests that current CG practice that emphasize board diversity and independence seems encouraging an environment friendly decision and adopt carbon reduction initiatives. Second, however, the current version of CG codes need more stress on none financial goals that should help corporate executives to balance value enhancement vis-à-vis ecosystem protection. Finally, another implication for policy-makers is CG should be re-structured so as to motivate firms to pursue long-term sustainable development instead of taking short-sight view of firm performance.

Originality/value

This paper contributes in the increasing body of literature indicating that CG encourages a proactive corporate strategy in general and carbon disclosure in particular. The authors add new empirical evidence which has policy implication that CG should be improved so as to encourage executives to engage in more sustainable development and stakeholder long-term value protection.
Improving public sector service delivery: a developing economy experience
Authors: Adaku Ebenezer , Amoako-Gyampah Kwasi , Lomotey Seth Nii Anang , Amoatey Charles Teye , Famiyeh Samuel
Published: July 2018

Purpose

The Pension Trust Company (PTC) in Ghana is the sole agency responsible for the management of the first-tier pension scheme as well as processing of claims submitted by beneficiaries for this scheme. The claim processing system at PTC was wrought with significant delays resulting in severe customer dissatisfaction and hardship to retirees. Hence, a new system – Age 54+ project – was developed to address the problems related to claims processing. The purpose of this paper is to report on the efficiency gains from the new claim processing system implemented at PTC and to use the philosophies behind the lean operations concept to explain the results.

Design/methodology/approach

Data for this study were obtained from the benefits system of PTC for the period 2009–2013. The data consist of a series of benefits processing time for two groups of 56,000 claimants – those cleared under the Age 54+ project and those cleared under the old processing system. The processes of the two claim processing systems were analysed and their processing times compared.

Findings

The new system – Age 54+ – decreased the average processing time for new claims by 20 per cent. The new system is a simple approach which is driven by a “Let’s Start in Time” idea.

Originality/value

The operations management literature suggests that process redesign approaches and the implementation of continuous improvement techniques represent mechanisms for achieving performance improvements at governmental agencies. This study shows and discusses the redesign of a social security scheme process using a lean operation concept of waste elimination method and application of kanban to deliver performance improvement.