bluuebunny/crossref_metadata_2025 huggingface dataset:
Spliced peptides and cytokine driven changes in the immunopeptidome of melanoma
Authors: Faridi Pouya , Woods Katherine , Ostrouska Simone , Deceneux Cyril , Aranha Ritchlynn , Duscharla Divya , Wong Stephen Q. , Chen Weisan , Ramarathinam Sri , Lim Kam Sian Terry C.C. , Croft Nathan P. , Li Chen , Ayala Rochelle , Cebon Jonathan , Purcell Anthony W. , Schittenhelm Ralf B. , Behren Andreas
Published: May 2019

Antigen-recognition by CD8+ T cells is governed by the pool of peptide antigens presented on the cell surface in the context of HLA class I complexes. Recent studies have shown not only a high degree of plasticity in the immunopeptidome, but also that a considerable fraction of all presented peptides is generated through proteasome-mediated splicing of non-contiguous regions of proteins to form novel peptide antigens. Here we used high-resolution mass-spectrometry combined with new bioinformatic approaches to characterize the immunopeptidome of melanoma cells in the presence or absence of interferon-γ. In total, we identified more than 60,000 peptides from a single patient derived cell line (LM-MEL-44) and demonstrated that interferon-γ induced marked changes in the peptidome with an overlap of only ∼50% between basal and treated cells. Around 6-8% of the peptides were identified as cis-spliced peptides, and 2213 peptides (1827 linear, 386 cis-spliced peptides) were derived from known melanoma-associated antigens. These peptide antigens were equally distributed between the constitutive and interferon-γ induced peptidome. We next examined additional HLA-matched patient derived cell lines to investigate how frequently these peptides were identified and found that a high proportion of both linear and spliced peptides were conserved between individual patient tumors, drawing on data amassing to over 100,000 peptide sequences from these extended data sets. Moreover, several of these peptides showed in vitro immunogenicity across multiple melanoma patients. These observations highlight the breadth and complexity of the repertoire of immunogenic peptides that can be exploited therapeutically and suggest that spliced peptides are a major new class of tumor antigens.
APOL1 is not expressed in proximal tubules and is not filtered
Authors: Blessing Natalya A. , Wu Zhenzhen , Madhavan Sethu , Shin Myung K. , Hoek Maarten , Sedor John R. , O’Toole John F. , Bruggeman Leslie A.
Published: May 2019

The kidney expression pattern of APOL1 was examined using both protein and mRNAin situmethods onAPOL1bacterial artificial chromosome transgenic mice, with and without proteinuria. APOL1 was detected in podocytes and endothelial cells of the kidney, but was not expressed in tubular epithelia, nor was plasma APOL1 protein filtered and reabsorbed by the proximal tubule. APOL1 expression in podocytes and endothelia should remain the focus for mechanistic studies of APOL1-mediated pathogenesis.
Yeast surface display of full-length human microtubule-associated protein tau
Authors: Wang Shiyao , Cho Yong Ku
Published: May 2019

Microtubule-associated protein tau is an intrinsically-disordered, highly soluble protein found primarily in neurons. Under normal conditions, tau regulates the stability of axonal microtubules and intracellular vesicle transport. However, in patients of neurodegeneration such as Alzheimer’s disease (AD), tau forms neurofibrillary deposits, which correlates well with the disease progression. Identifying molecular signatures in tau, such as post-translational modification, truncation, and conformational change has great potential to detect earliest signs of neurodegeneration, and develop therapeutic strategies. Here we show that full-length human tau, including the longest isoform found in the adult brain can be robustly displayed on the surface of yeastSaccharomyces cerevisiae. Yeast-displayed tau binds to anti-tau antibodies that cover epitopes ranging from the N-terminus to the 4R repeat region. Unlike tau expressed in the yeast cytosol, surface-displayed tau was not phosphorylated at sites found in AD patients (probed by antibodies AT8, AT270, AT180, PHF-1). However, yeast-displayed tau showed clear binding to paired helical filament (PHF) tau conformation-specific antibodies Alz-50, MC-1, and Tau-2. Although the tau possessed a conformation found in PHFs, oligomerization or aggregation into larger filaments were undetected. Taken together, yeast-displayed tau enables robust measurement of protein interactions, and is of particular interest for characterizing conformational change.
Reduced Permeability to Rifampicin by Capsular Thickening as a Mechanism of Antibiotic Persistence inMycobacterium tuberculosis
Authors: Sebastian Jees , Swaminath Sharmada , Ajitkumar Parthasarathi
Published: May 2019

Persisters constitute a subpopulation of bacteria that can tolerate lethal concentrations of antibiotics. Multiple mechanisms have been suggested for bacterial persistence against antibiotics. With mycobacteria being no exception to this behaviour, we had reported thede novoemergence of genetically antibiotic-resistantMycobacterium tuberculosisfrom persister cells upon prolonged exposure to microbicidal concentrations of the anti-tuberculosis drugs, rifampicin and moxifloxacin. Here, we present evidence for reduced permeability to rifampicin as a mechanism for persistence ofMycobacterium tuberculosis in vitro. We observed that rifampicin persistentM. tuberculosiscells developed a thick outer layer (TOL) capsule. The TOL restricted the entry of fluorochrome-conjugated rifampicin, 5-carboxyfluorescein-rifampicin (5-FAM-rifampicin), which retained only 2.5% of its original bactericidal activity, but high levels of permeability, on actively growing mid-log phase cells. Gentle mechanical removal of TOL significantly enhanced 5-FAM-rifampicin entry into the persister cells. The level of 5-FAM-rifampicin in the persister cells was not affected by the pre-incubation of the cells with verapamil, a drug efflux pump inhibitor, ruling out the involvement of efflux pumps in the reduced intracellular concentration of 5-FAM-rifampicin. GC-MS analysis of TOL showed the presence of ∼7-fold, ∼5-fold and ∼2- fold higher levels of α-D-glucopyranoside, 1,2,5-linked-mannitol, and 3,4-linked mannose, respectively, among ∼2-fold higher levels of derivatives of several other types of sugars such as arabinose and galactose. Taken together, the present study reveals that rifampicin-persistentM. tuberculosiscells develop TOL that enables the bacilli to restrict entry of rifampicin and thereby remain tolerant to the antibioticin vitro.
Tmem119-EGFP and Tmem119-CreERT2 transgenic mice for labeling and manipulating microglia
Authors: Kaiser Tobias , Feng Guoping
Published: May 2019

Microglia are specialized brain-resident macrophages with important functions in health and disease. To improve our understanding of these cells, the research community needs genetic tools to identify and control them in a manner that distinguishes them from closely related cell-types. We have targeted the recently discovered microglia-specific Tmem119 gene to generate knock-in mice expressing EGFP (JAX#031823) or CreERT2 (JAX#031820) for the identification and manipulation of microglia, respectively. Genetic characterization of the locus and qPCR-based analysis demonstrate correct positioning of the transgenes and intact expression of endogenous Tmem119 in the knock-in mouse models. Immunofluorescence analysis further shows that parenchymal microglia, but not other brain macrophages, are completely and faithfully labeled in the EGFP-line at different time points of development. Flow cytometry indicates highly selective expression of EGFP in CD11b+CD45lo microglia. Similarly, immunofluorescence and flow cytometry analyses using a Cre-dependent reporter mouse line demonstrate activity of CreERT2 primarily in microglia upon tamoxifen administration with the caveat of activity in leptomeningeal cells. Finally, flow cytometric analyses reveal absence of EGFP expression and minimal activity of CreERT2 in blood monocytes of the Tmem119-EGFP and Tmem119-CreERT2 lines, respectively. These new transgenic lines extend the microglia toolbox by providing the currently most specific genetic labeling and control over these cells in the myeloid compartment of mice.

Visual abstract

Significance statement

Tools that specifically label and manipulate only microglia are currently unavailable, but are critically needed to further our understanding of this cell type. Complementing and significantly extending recently introduced microglia-specific immunostaining methods that have quickly become a new standard in the field, we generated two mouse lines that label and control gene expression in microglia with high specificity and made them publicly available. Using these readily accessible mice, the research community will be able to study microglia biology with improved specificity.
Prostate-Specific Antigen Dynamics Predict Individual Responses to Intermittent Androgen Deprivation
Authors: Brady Renee , Nagy John D. , Gerke Travis A. , Zhang Tian , Wang Andrew Z. , Zhang Jingsong , Gatenby Robert A. , Enderling Heiko
Published: May 2019

Background

Intermittent androgen deprivation therapy (IADT) is an attractive treatment approach for biochemically recurrent prostate cancer (PCa), whereby cycling treatment on and off can reduce cumulative dose, limit toxicities, and delay development of treatment resistance. To optimize treatment within the context of ongoing intratumoral evolution, underlying mechanisms of resistance and actionable biomarkers need to be identified.

Methods

We have developed a quantitative framework to simulate enrichment of prostate cancer stem cell (PCaSC) dynamics during treatment as a plausible mechanism of resistance evolution.

Results

Simulated dynamics of PCaSC and non-stem cancer cells demonstrate that stem cell proliferation patterns correlate with longitudinal serum prostate-specific antigen (PSA) measurements in 70 PCa patients undergoing multiple cycles of IADT. By learning the dynamics from each treatment cycle, individual model simulations predict evolution of resistance in the subsequent IADT cycle with a sensitivity and specificity of 57% and 94%, respectively and an overall accuracy of 90%. Additionally, we evaluated the potential benefit of docetaxel for IADT in biochemically recurrent PCa. Model simulations based on response dynamics from the first IADT cycle identify patients who would or would not benefit from concurrent docetaxel in subsequent cycles.

Conclusion

Our results demonstrate the feasibility and potential value of adaptive clinical trials guided by patient-specific mathematical models of intratumoral evolutionary dynamics continuously updated with each treatment cycle.

Translational Relevance

Compared to continuous androgen deprivation therapy, intermittent androgen deprivation (IADT) has been shown to reduce toxicity and delay time to progression in prostate cancer. While numerous mathematical models have been developed to study the response to both continuous and intermittent androgen deprivation, very few have identified actionable biomarkers of resistance and exploited them to predict how patients will or will not respond to subsequent treatment. Here, we identify prostate-specific antigen (PSA) dynamics as the first such biomarker. Mechanistic mathematical modeling of prostate cancer stem cell dynamics that dictate prostate-specific antigen serum levels predicts individual responses to IADT with 90% overall accuracy and can be used to develop patient-specific adaptive treatment protocols, and potentially identify patients that may benefit from concurrent chemotherapy. Model results demonstrate the feasibility and potential value of adaptive clinical trials guided by patient-specific mathematical models of intratumoral evolutionary dynamics continuously updated with each treatment cycle.
Mammalian NSUN2 introduces 5-methylcytidines into mitochondrial tRNAs
Authors: Shinoda Saori , Kitagawa Sho , Nakagawa Shinichi , Wei Fan-Yan , Tomizawa Kazuhito , Araki Kimi , Araki Masatake , Suzuki Takeo , Suzuki Tsutomu
Published: May 2019

Post-transcriptional modifications in mitochondrial tRNAs (mt-tRNAs) play critical roles in mitochondrial protein synthesis, which produces respiratory chain complexes. In this study, we used mass spectrometric analysis to map 5-methylcytidine (m5C) at positions 48–50 in eight mouse and six human mt-tRNAs. We also confirmed the absence of m5C in mt-tRNAs isolated fromNsun2knockout (KO) mice, as well as fromNSUN2KO human culture cells. In addition, we successfully reconstituted m5C at positions 48–50 of mt-tRNAin vitrowith NSUN2 protein in the presence ofS-adenosylmethionine (SAM). Although NSUN2 is predominantly localized to the nucleus and introduces m5C into cytoplasmic tRNAs and mRNAs, structured illumination microscopy (SIM) clearly revealed NSUN2 foci inside mitochondria. These observations provide novel insights into the role of NSUN2 in the physiology and pathology of mitochondrial functions.
Simulations of particle tracking in the oligociliated mouse node and implications for left-right symmetry breaking mechanics
Authors: Gallagher M.T. , Montenegro-Johnson T.D. , Smith D.J.
Published: May 2019

The concept of internal anatomical asymmetry is familiar; usually in humans the heart is on the left and the liver is on the right, however how does the developing embryo know to produce this consistent laterality? Symmetry breaking initiates with left-right asymmetric cilia-driven fluid mechanics in a small fluid-filled structure called the ventral node in mice. However the question of what converts this flow into left-right asymmetric development remains unanswered. A leading hypotheses is that flow transports morphogen containing vesicles within the node, the absorption of which results in asymmetrical gene expression. To investigate how vesicle transport might result in the situs patterns observed in wildtype and mutant experiments, we extend the open source Stokes flow package, NEAREST, to consider the hydrodynamic and Brownian motion of particles in a mouse model with flow driven by one, two, and 112 beating cilia.Three models for morphogen-containing particle released are simulated to assess their compatibility with observed results in oligociliated and wildtype mouse embryos: uniformly random release, localised cilium stress induced release, and localised release from motile cilia themselves. Only the uniformly random release model appears consistent with the data, with neither localised-release model resulting in significant transport in the oligociliated embryo.
Cortical Foxp2 supports behavioral flexibility and developmental dopamine D1 receptor expression
Authors: Co Marissa , Hickey Stephanie L. , Kulkarni Ashwinikumar , Harper Matthew , Konopka Genevieve
Published: May 2019

Genetic studies have associated FOXP2 variation with speech and language disorders and other neurodevelopmental disorders involving pathology of the cortex. In this brain region, FoxP2 is expressed from development into adulthood, but little is known about its downstream molecular and behavioral functions. Here, we characterized cortex-specific Foxp2 conditional knockout mice and found a major deficit in reversal learning, a form of behavioral flexibility. In contrast, they showed normal activity levels, anxiety, and vocalizations, save for a slight decrease in neonatal call loudness. These behavioral phenotypes were accompanied by decreased cortical dopamine D1 receptor (D1R) expression at neonatal and adult stages, while general cortical development remained unaffected. Finally, using single-cell transcriptomics, we identified at least five excitatory and three inhibitory D1R-expressing cell types in neonatal frontal cortex, and we found changes in D1R cell type composition and gene expression upon cortical Foxp2 deletion. Strikingly, these alterations included non-cell-autonomous changes in upper-layer neurons and interneurons. Together these data support a role for Foxp2 in the development of dopamine-modulated cortical circuits and behaviors relevant to neurodevelopmental disorders.
Bacteria isolated from bengal cat (Felis catus×Prionailurus bengalensis) anal sac secretions produce volatile compounds associated with animal signaling
Authors: Yamaguchi Mei S. , Ganz Holly H. , Cho Adrienne W. , Zaw Thant H. , Jospin Guillaume , McCartney Mitchell M. , Davis Cristina E. , Eisen Jonathan A. , Coil David A.
Published: May 2019

Anal sacs are an important odor producing organ found across the mammalian Order Carnivora. Secretions from the anal sac may be used as chemical signals by animals for behaviors ranging from defense to species recognition to signaling reproductive status. In addition, a recent study suggests that domestic cats utilize short-chain free fatty acids in anal sac secretions for individual recognition. The fermentation hypothesis is the idea that symbiotic microorganisms living in association with animals contribute to odor profiles used in chemical communication and that variation in these chemical signals reflects variation in the microbial community. Here we examine the fermentation hypothesis by characterizing volatile organic compounds (VOC) and bacteria isolated from anal sac secretions collected from a male bengal cat, a cross between a domestic cat and wild leopard cat (Felis catus×Prionailurus bengalensis).

Both left and right anal sacs of a male bengal cat were manually expressed (emptied) and collected. Half of the material was used to culture bacteria or to extract bacterial DNA and other half was used for VOC analysis. DNA was extracted from the anal sac secretions and used for a 16S rRNA gene sequence based characterization of the microbial community. Additionally, some of the material was plated out in order to isolate bacterial colonies. The same three taxa,Bacteroides fragilis,Tessaracoccus, andFinegoldia magnawere abundant in the 16S rRNA gene sequence data and also isolated by culturing. Using Solid Phase Microextraction (SPME) gas chromatography-mass spectrometry (GC-MS), we tentatively identified 52 compounds from bengal cat anal sac secretions and 67 compounds from cultures of the three bacterial isolates chosen for further analysis.. Among 67 compounds tentatively identified from bacteria isolates, 52 were also found in the anal sac secretion.

We show that the bacterial community in the anal sac consists primarily of only a few abundant taxa and that isolates of these taxa produce numerous volatiles that are found in the combined anal sac volatile profile. Many of these volatiles are found in anal sac secretions from other carnivorans, and are also associated with known bacterial biosynthesis pathways. This supports the fermentation hypothesis and the idea that the anal sac is maintained at least in part to house bacteria that produce volatiles for the host.
Uncovering the subtype-specific temporal order of cancer pathway dysregulation
Authors: Khakabmamaghani Sahand , Ding Dujian , Snow Oliver , Ester Martin
Published: May 2019

Cancer is driven by genetic mutations that dysregulate pathways important for proper cell function. Therefore, discovering these cancer pathways and their dysregulation order is key to understanding and treating cancer. However, the heterogeneity of mutations between different individuals makes this challenging and requires that cancer progression is studied in a subtype-specific way. To address this challenge, we provide a mathematical model, called Subtype-specific Pathway Linear Progression Model (SPM), that simultaneously captures cancer subtypes and pathways and order of dysregulation of the pathways within each subtype. Experiments with synthetic data indicate the robustness of SPM to problem specifics including noise compared to an existing method. Moreover, experimental results on glioblastoma multiforme and colorectal adenocarcinoma show the consistency of SPM’s results with the existing knowledge and its superiority to an existing method in certain cases. The implementation of our method is available at https://github.com/Dalton386/SPM.
Prediction of migratory routes of the invasive fall armyworm in eastern China using a trajectory analytical approach
Authors: Li Xi-Jie , Wu Ming-Fei , Ma Jian , Gao Bo-Ya , Wu Qiu-Lin , Chen Ai-Dong , Liu Jie , Jiang Yu-Ying , Zhai Bao-Ping , Early Regan , Chapman Jason W. , Hu Gao
Published: May 2019

BACKGROUND

The fall armyworm (FAW), an invasive pest from the Americas, is rapidly spreading through the Old World, and has recently invaded the Indochinese Peninsula and southern China. In the Americas, FAW migrates from winter-breeding areas in the south into summer-breeding areas throughout North America where it is a major pest of corn. Asian populations are also likely to evolve migrations into the corn-producing regions of eastern China, where they will pose a serious threat to food security.

RESULTS

To evaluate the invasion risk in eastern China, the rate of expansion and future migratory range was modelled by a trajectory simulation approach, combined with flight behaviour and meteorological data. Our results predict that FAW will migrate from its new year-round breeding regions into the two main corn-producing regions of eastern China (the North China and Northeast China Plains), via two pathways. The western pathway originates in Myanmar and Yunnan, and FAW will take four migration steps to reach the North China Plain by July. Migration along the eastern pathway from Indochina and southern China progresses faster, with FAW reaching the North China Plain in three steps by June and reaching the Northeast China Plain in July.

CONCLUSION

Our results indicate that there is a high risk that FAW will invade the major corn-producing areas of eastern China via two migration pathways, and cause significant impacts to agricultural productivity. Information on migration pathways and timings can be used to inform integrated pest management strategies for this emerging pest.
Phenanthrene contamination and ploidy level influence the rhizosphere microbiome of Spartina
Authors: Cavé-Radet Armand , Monard Cécile , El-Amrani Abdelhak , Salmon Armel , Ainouche Malika , Yergeau Étienne
Published: May 2019

Spartina spp. are widely distributed salt marsh plants that have a recent history of hybridization and polyploidization. These evolutionary events have resulted in species with a heightened resilience to hydrocarbon contamination, which could make them an ideal model plant for the phytoremediation/reclamation of contaminated coastal ecosystems. However, it is still unknown if allopolyploidization events also resulted in differences in the plant rhizosphere-associated microbial communities, and if this could improve the plant phytoremediation potential. Here, we grew two parental Spartina species, their hybrid and the resulting allopolyploid in salt marsh sediments that were contaminated or not with phenanthrene, a model tricyclic PAH. The DNA from the rhizosphere soil was extracted and the bacterial 16S rRNA gene and ITS region were amplified and sequenced. Generally, both the presence of phenanthrene and the identity of the plant species had significant influences on the bacterial and fungal community structure, composition and diversity. In particular, the allopolyploid S. anglica, harbored a more diverse bacterial community in its rhizosphere, and relatively higher abundance of various bacterial and fungal taxa. Putative hydrocarbon degraders were significantly more abundant in the rhizosphere soil contaminated with phenanthrene, with the Nocardia genus being significantly more abundant in the rhizosphere of S. anglica. Overall our results are showing that the recent polyploidization events in the Spartina did influence the rhizosphere microbiome, both under normal and contaminated conditions, but more work will be necessary to confirm if these differences result in a higher phytoremediation potential.

Importance

Salt marshes are at the forefront of coastal contamination events caused by marine oil spills. Microbes in these environments play a key role in the natural attenuation of these contamination events, often in association with plant roots. One such plant is the Spartina, which are widely distributed salt marsh plants. Intriguingly, some species of the Spartina show heightened resistance to contamination, which we hypothesized to be due to differences in their microbiota. This was indeed the case, with the most resistant Spartina also showing the most different microbiota. A better understanding of the relationships between the Spartina and their microbiota could improve the coastal oil spill clean-up strategies and provide green alternatives to more traditional physico-chemical approaches.
Models for infantile hypertrophic pyloric stenosis development in patients with esophageal atresia
Authors: ten Kate Chantal A. , Brouwer Rutger W.W. , van Bever Yolande , Martens Vera K. , Brands Tom , van Beelen Nicole W.G. , Brooks Alice S. , Huigh Daphne , Eussen Bert J.F.M.M. , van IJcken Wilfred F.J. , IJsselstijn Hanneke , Tibboel Dick , Wijnen Rene M.H. , de Klein Annelies , Hofstra Robert M.W. , Brosens Erwin
Published: May 2019

Patients born with esophageal atresia (EA) have a 30 times higher prevalence of infantile hypertrophic pyloric stenosis (IHPS). This makes sense from a developmental perspective as both the esophagus and the pyloric sphincter are foregut derived structures. EA and IHPS are variable features in several (monogenetic) syndromes. This, and twin and familial studies, indicates a genetic component for both conditions as single entities. We hypothesized that genetic defects, disturbing foregut morphogenesis, are responsible for this combination of malformations. Non-genetic factors could also contribute, as mice exposed to Adriamycin develop EA andin uterodiethylstilbestrol exposure is associated with EA.

We investigated the copy number profiles and protein coding variants of 15 patients with both EA and IHPS. As all parents were unaffected, we first considered dominant(de novo)or recessive inheritance models but could not identify putatively deleterious mutations or recessive variants. We did identify inherited variants in genes either known to be involved in EA or IHPS or important in foregut morphogenesis in all patients. Unfortunately, variant burden analysis did not show a significant difference with unaffected controls. However, the IHPS associated risk SNP rs1933683 had a significantly higher incidence (OR 3.29, p=0.009).

Although the genetic variation in likely candidate genes as well as the predisposing locus nearBARX1(rs1933683) suggest a genetic component, it does not fully explain the abnormalities seen in these patients. Therefore, we hypothesize that a combination of high impact genetic, mechanical and environmental factors together can shift the balance to abnormal development.

Summary statement

Instead of one affected gene, the higher incidence of IHPS in EA patients is more likely the result of multiple (epi)genetic and environmental factors together shifting the balance to disease development.
ExpressWeb: A Web application for clustering and visualization of expression data
Authors: Savelli Bruno , Picard Sylvain , Roux Christophe , Dunand Christophe
Published: May 2019

The recent explosion of transcriptomics and proteomic data have resulted in vast amounts of datasets without connection and sometime too large to be easily analysed. Integration between datasets and analysis of an extracted datasets are limiting factors which need to be solved in order to make full use of the data and to connect data.

ExpressWeb is an online web tool that combines a Taylor clustering of expressed data sets to extract gene network with gene annotations to visualise the co-expression network. Data sets can become from personal or publically experiments. ExpressWeb allows to easily compute clustering on expression data and provides friendly and useful visualisation tools as heatmaps, graphs and networks, generating output images which can be used for scientific publications.
Investigation of cellular stress response related heat shock proteinhsp70/Hsp70 and multixenobiotic transporterabcb1in Siberian freshwater amphipods upon cadmium exposure
Authors: Protopopova Marina V. , Pavlichenko Vasiliy V. , Luckenbach Till
Published: May 2019

Induction of stress response geneshsp70andabcb1and Hsp70 protein by cadmium chloride (CdCl2) was explored in amphipod species with different stress adaptation strategies from the Lake Baikal area. Based on lethal concentrations (LC) the sensitivities to CdCl2were ranked (24 hr LC50 – mg/L CdCl2):Gammarus lacustris(1.7) <Eulimnogammarus cyaneus(2.9) <E. verrucosus(8.3) <E. vittatus(18.2). Conjugated dienes indicating lipid peroxidation were significantly increased by 5 mg/L CdCl2(24 hr exposure) only inG. lacustrisandE. cyaneus. Upon treatment with 0.54 – 5.8 mg/L CdCl2hsp70transcript levels were more increased in the toxicologically more sensitive species. Relating the exposure concentrations to LCx values revealed that across the species the increases ofhsp70transcript levels were comparatively low (up to 2.6-fold) up to LC50; at higher LCx valueshsp70induction was more pronounced (up to a 9.1-fold by 5 mg/L CdCl2(≙LC70) inE. cyaneus). In contrast,abcb1inductions did not correspond with CdCl2LCx values across species;abcb1induction was highest (4.7-fold) inE. verrucosusby 5.0 mg/L CdCl2(≙LC45, 24 hr exposure). Induction of stress gene responses by lethal CdCl2concentrations indicates that in the amphipods they are rather insensitive.
Xenotransplanted human cortical neurons reveal species-specific development and functional integration into mouse visual circuits
Authors: Linaro Daniele , Vermaercke Ben , Iwata Ryohei , Ramaswamy Arjun , Davis Brittany A. , Boubakar Leila , Libé-Philippot Baptiste , Bilheu Angéline , Bruyne Lore De , Gall David , Conzelmann Klaus , Bonin Vincent , Vanderhaeghen Pierre
Published: May 2019

How neural circuits develop in the human brain has remained almost impossible to study at the neuronal level. Here we investigate human cortical neuron development, plasticity and function, using a mouse/human chimera model in which xenotransplanted human cortical pyramidal neurons integrate as single cells into the mouse cortex. Combined neuronal tracing, electrophysiology, andin vivostructural and functional imaging revealed that the human neurons develop morphologically and functionally following a prolonged developmental timeline, revealing the cell-intrinsic retention of juvenile properties of cortical neurons as an important mechanism underlying human brain neoteny. Following maturation, human neurons transplanted in the visual cortex display tuned responses to visual stimuli that are similar to those of mouse neurons, indicating capacity for physiological synaptic integration of human neurons in mouse cortical circuits. These findings provide new insights into human neuronal development, and open novel experimental avenues for the study of human neuronal function and diseases.

Highlights:

Coordinated morphological and functional maturation of ESC-derived human cortical neurons transplanted in the mouse cortex.

Transplanted neurons display prolonged juvenile features indicative of intrinsic species-specific neoteny.

Transplanted neurons develop elaborate dendritic arbors, stable spine patterns and long-term synaptic plasticity.

In the visual cortex transplanted neurons display tuned visual responses that resemble those of the host cortical neurons.
WWP2 ubiquitylates RNA polymerase II for DNA-PK-dependent transcription arrest and repair at DNA breaks
Authors: Caron Pierre , Pankotai Tibor , Wiegant Wouter W. , Tollenaere Maxim A.X. , Furst Audrey , Bonhomme Celine , Helfricht Angela , de Groot Anton , Pastink Albert , Vertegaal Alfred C.O. , Luijsterburg Martijn S. , Soutoglou Evi , van Attikum Haico
Published: May 2019

DNA double-strand breaks (DSBs) at RNA polymerase II (RNAPII) transcribed genes lead to inhibition of transcription. The DNA-dependent protein kinase (DNA-PK) complex plays a pivotal role in transcription inhibition at DSBs by stimulating proteasome-dependent eviction of RNAPII at these lesions. How DNA-PK triggers RNAPII eviction to inhibit transcription at DSBs remains unclear. Here we show that the HECT E3 ubiquitin ligase WWP2 associates with components of the DNA-PK and RNAPII complexes and is recruited to DSBs at RNAPII transcribed genes. In response to DSBs, WWP2 targets the RNAPII subunit RPB1 for K48-linked ubiquitylation, thereby driving DNA-PK- and proteasome-dependent eviction of RNAPII. The lack of WWP2 or expression of nonubiquitylatable RPB1 abrogates the binding of nonhomologous end joining (NHEJ) factors, including DNA-PK and XRCC4/DNA ligase IV, and impairs DSB repair. These findings suggest that WWP2 operates in a DNA-PK-dependent shutoff circuitry for RNAPII clearance that promotes DSB repair by protecting the NHEJ machinery from collision with the transcription machinery.
ATDC is required for the initiation of KRAS-induced pancreatic tumorigenesis
Authors: Wang Lidong , Yang Huibin , Zamperone Andrea , Diolaiti Daniel , Palmbos Phillip L. , Abel Ethan V. , Purohit Vinee , Dolgalev Igor , Rhim Andrew D. , Ljungman Mats , Hadju Christina H. , Halbrook Christopher J. , Bar-Sagi Dafna , di Magliano Marina Pasca , Crawford Howard C. , Simeone Diane M.
Published: May 2019

Pancreatic adenocarcinoma (PDA) is an aggressive disease driven by oncogenic KRAS and characterized by late diagnosis and therapeutic resistance. Here we show that deletion of the ataxia-telangiectasia group D-complementing (Atdc) gene, whose human homolog is up-regulated in the majority of pancreatic adenocarcinoma, completely prevents PDA development in the context of oncogenic KRAS. ATDC is required for KRAS-driven acinar–ductal metaplasia (ADM) and its progression to pancreatic intraepithelial neoplasia (PanIN). As a result, mice lacking ATDC are protected from developing PDA. Mechanistically, we show ATDC promotes ADM progression to PanIN through activation of β-catenin signaling and subsequent SOX9 up-regulation. These results provide new insight into PDA initiation and reveal ATDC as a potential target for preventing early tumor-initiating events.
Environmental management accounting practices in Australian cotton farming
Authors: Tashakor Shamim , Appuhami Ranjith , Munir Rahat
Published: May 2019

Purpose

The purpose of this paper is to examine the association between the belief-based factors (attitude, subjective norm (SN) and perceived behavioural control (PBC)) and environmental management accounting (EMA) practices.

Design/methodology/approach

Drawing on the theory of planned behaviour (TPB), the study develops a structural model and uses partial least squares (PLS) technique to analyse data collected based on a survey of the Australian cotton farmers.

Findings

The findings indicate that while attitude and PBC significantly influence farmers’ intention to adopt EMA practices, SN has a significant indirect influence on EMA practices through farmers’ attitude and PBC. Further, the study reveals that while the intention of more environmentally friendly farmers is largely influenced by attitude and SN, the intention of less environmentally friendly farmers is primarily driven by PBC.

Practical implications

The study provides important insights into the role of attitude, SN and PBC in motivating farmers towards adopting EMA practices. Such insights could also help farmers in designing effective EMA practices.

Originality/value

This study contributes to very limited EMA literature on TPB by integrating three belief-based factors namely attitude, SN and PBC.
Expansive learning in contemporary construction organisations
Authors: Sackey Enoch , Tuuli Martin , Dainty Andrew
Published: May 2019

Purpose

The evolving roles of BIM and smart building technologies in the design and management of construction projects often present unexpected events and variabilities, which tend to erode professionals’ prior knowledge authority. The purpose of this paper is to explore how construction organisations can deploy knowledge and adapt to the requisite skills in order to make fitting responses to the ever-evolving technological and organisational transformations to address the prevailing construction challenges.

Design/methodology/approach

The paper opted for an abductive research approach that ensures back-and-forth iterative dialogue between the empirical data and an amalgam of the theoretical proposition towards new understanding of the phenomenon under investigation. A multiple case study method was adopted to collate the empirical data from three separate construction organisations as they transitioned into BIM compliant work processes.

Findings

The study has described new processes that not only mediate existing practices but focus on consistently resolving known tensions and contradictions between prior knowledge and the requirement of the changing work situation. The study also illustrates the cognitive synchronisation of the learning approaches within contemporary work organisations that align well with the merits and utilities entrenched within their niche technological choices.

Research limitations/implications

Due to the chosen research methodology, it is acknowledged that future comparative studies using a much larger quantitative data sample to further elucidate the findings of this paper would be an interesting further step.

Originality/value

The study contributes to construction management literature by providing new insights into expansive learning environments capable of addressing cognitive contradictions and ambiguities inherent in the changing contemporary work patterns in the construction context as a consequence of BIM deployment.
An empirical survey of the perceived benefits of executing BIM and sustainability practices in the built environment
Authors: Olawumi Timothy Oluwatosin , Chan Daniel W.M.
Published: May 2019

Purpose

The increasing urbanization of the built environment has bolstered the need to promote green Building Information Modeling (BIM) initiative in new construction projects and the rehabilitation of old premises. This study aims to explore and examine the key benefits of the implementation of BIM and sustainability practices in the built environment.

Design/methodology/approach

The study gathered the worldwide perceptions of 220 survey participants from 21 countries which were analyzed using descriptive and inferential analytical methods. The identified individual benefits of green BIM were further categorized into their underlying clusters using factor analysis.

Findings

The key benefits are related to enhancing project efficiency and productivity, ensuring real-time sustainable design and multi-design alternatives, facilitating the selection of sustainable materials and components, together with reducing material wastage and project’s environmental impact, among others. The study analyzed and compared the perceptions of the diverse groups of the respondents as well.

Practical implications

Effective blueprints and insightful recommendations for enhancing the various stakeholders’ capacities to implement green BIM in their construction projects were put forward to achieve the aim of sustainable smart urbanization.

Originality/value

The study identified salient benefits of the adoption of BIM and sustainability practices. The proper integration of these concepts and the execution of the recommended useful strategies by construction stakeholders, policymakers and local authorities will enable the built environment to reap the gains of its implementation.
Materiality: stakeholder accountability choices in hotels’ sustainability reports
Authors: Guix Mireia , Font Xavier , Bonilla-Priego Maria Jesus
Published: May 2019

Purpose

This paper aims to examine the choices made by the hotel industry about what to include, and who to be accountable to, in their sustainability reports; a process defined as materiality assessment.

Design/methodology/approach

The paper is based on the findings of semi-structured interviews with eight sustainability managers (from eight of the world’s 50 largest hotel groups) to explore their understanding of, and use of, materiality and any barriers to its uptake and eight industry sustainability experts to assess the general industry-wide application of materiality.

Findings

Sustainability managers from large hotel groups are evasive when disclosing their materiality criteria, their decision-making processes and how they aggregate stakeholder feedback; they limit their disclosure to the reporting process. Sustainability managers are disempowered, with limited resources, time, knowledge and skills to apply to materiality assessment. Experts confirm that hotel groups are unsystematic and opaque about their decision-making and how they control their materiality assessments.

Practical implications

Materiality assessment is concealed from the public and may be constructed around business imperatives with high managerial capture. The hospitality industry needs to improve its sustainability reporting by examining how it defines and applies materiality and by addressing the barriers identified, if it is to demonstrate an enduring commitment to sustainability and organisational legitimacy.

Originality/value

This study addresses the limited knowledge of how hotel groups undertake materiality assessments. It identifies gaps in the conception and application of materiality by pinpointing barriers to its uptake and recommending areas in need of further research.
Unlucky for some? Are some hotel rooms and floors really unluckier than others?
Authors: Pratt Stephen , Kwan Pia
Published: May 2019

Purpose

Different cultures believe that some numbers are “lucky” and other numbers are “unlucky”. The purpose of this paper is to determine to what extent hotels follow numerological superstitions in their floor and room numbering, if more accidents or complaints occur on unlucky hotel floors compared to other floors and if more accidents or complaints occur in unlucky hotel rooms compared to other rooms.

Design/methodology/approach

For the first research objective, an audit of hotels in a particular destination, Hong Kong, is taken capturing the number of floors and rooms on each floor and determining if “unlucky” numbers are used. For the second and third objectives, the accident and complaint database of one upscale hotel in Hong Kong across a five-year period is investigated.

Findings

The authors find that hotels do follow superstitious numbering, with “unlucky” numbers not being included in floor or room numbering. Chinese superstition is more likely to be followed than Western superstition. The non-inclusion of “unlucky” numbers is more likely for hotel floors than for hotel rooms. In the case study hotel, they found no significant differences in the number of accidents and complaints between unlucky and other rooms and floors across the five years of analysis.

Originality/value

Superstitions surrounding numbers can affect decisions made by individuals and businesses and can have significant economic consequences. There is little academic research into how the hotel sector is impacted by numerology superstitions.
Signalling IPO quality through female directors
Authors: Badru Bazeet Olayemi , Ahmad-Zaluki Nurwati A. , Wan-Hussin Wan Nordin
Published: May 2019

Purpose

The purpose of this paper is to investigate whether or not the presence of female directors at the time of an initial public offering (IPO) can be considered as a signal of IPO quality.

Design/methodology/approach

A sample of 220 Malaysian IPOs over the period of 2005–2015 was used. This study employed the mean regression technique (ordinary least squares and White’s heteroskedasticity-consistent standard errors) and the median regression technique (quantile regression) to examine the signalling power of female directors on the board at the time of an IPO.

Findings

The results show that the presence and proportion of female directors at the time of the IPO have negative effects on IPO initial returns (IR). The negative effects occur at both the conditional mean and the dispersion of IPO IR. These results are robust to endogeneity bias.

Practical implications

The findings of this study suggest that female directors on the board at the time of an IPO can be considered as a desirable signal of IPO quality. As a result, IPO issuers can consider signalling the quality of their IPOs by having female directors on their boards. Likewise, market participants can use female directors as an instrument to value an IPO.

Originality/value

Studies on the impact of female directors on the board have largely been centred on established companies. Thus, this study contributes to the literature by examining the signalling role of women at the time of an IPO, which is considered as a significant milestone in the lifecycle of a company.
Trade credit, firm profitability, and financial constraints
Authors: Hoang Huan Cong , Xiao Qin , Akbar Saeed
Published: May 2019

Purpose

The purpose of this paper is to investigate the non-linear association between trade credit and profitability of small and medium-sized enterprises (SMEs). Moreover, this paper analyses whether the above relationship varies according to financial constraints of SMEs.

Design/methodology/approach

The authors use panel data methodology to conduct investigations for a sample of 1,509 non-financial listed SMEs from nine countries or territories located in the East Asia and Pacific region, namely, China, Vietnam, Malaysia, Thailand, Japan, South Korea, Taiwan, Singapore and Hong Kong, over the period from 2010 to 2016.

Findings

This study indicates that trade credit receivable (TCR) and trade credit payable (TCP) have an invertedU-shaped relationship with SMEs’ profitability, which implies the existence of an optimal trade credit level that balances between costs and benefits to maximize their profitability. This result suggests that managers should try to keep the level of trade credit investment as close to the optimal point as possible to avoid the case that their profitability reduces when they move away from this point. Moreover, this study also finds that the optimal trade credit level is sensitive to the financial constraints of SMEs. In particular, optimal level of more financially constrained firms is lower than that of less financially constrained firms.

Originality/value

A number of contributions that this study makes to the existing literature are presented as follows. First, the paper takes account of the possible presence of a concave relationship between trade credit and SMEs’ profitability, largely ignored by the existing empirical literature. Second, it demonstrates this association in terms of both aspects of trade credit, including TCR and TCP. Third, the study investigates the effect of the different level of financial constraints faced by SMEs on the relationship between trade credit and their profitability.