bluuebunny/crossref_metadata_2025 huggingface dataset:
New tyrosinases with a broad spectrum of action against contaminants of emerging concern: Insights fromin silicoanalyses
Authors: Senra Marcus V. X. , Fonseca Ana Lúcia
Published: July 2020

Tyrosinases (EC 1.14.18.1) are type-3 copper metalloenzymes with strong oxidative capacities and low allosteric selectivity to phenolic and non-phenolic aromatic compounds that have been used as biosensors and biocatalysts to mitigate the impacts of environmental contaminants over aquatic ecosystems. However, the widespread use of these polyphenol oxidases is limited by elevated production costs and restricted knowledge on their spectrum of action. Here, six tyrosinase homologs were identified and characterized from the genomes of 4 widespread freshwater ciliates using bioinformatics. Binding energies between 3D models of these homologs and ~1000 contaminants of emerging concern (CECs), including fine chemicals, pharmaceuticals, personal care products, illicit drugs, natural toxins, and pesticides were estimated through virtual screening, suggesting their spectrum of action and potential uses in environmental biotechnology might be considerably broader than previously thought. Moreover, considering that many ciliates, including those caring tyrosinase genes within their genomes are fast-growing unicellular microeukaryotes that can be efficiently culturable at large-scales underin vitroconditions, should be regarded as potential low-cost sources for the production of relevant biotechnological molecules.
Ad26-vector based COVID-19 vaccine encoding a prefusion stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses
Authors: Bos Rinke , Rutten Lucy , van der Lubbe Joan E.M. , Bakkers Mark J.G. , Hardenberg Gijs , Wegmann Frank , Zuijdgeest David , de Wilde Adriaan H. , Koornneef Annemart , Verwilligen Annemiek , van Manen Danielle , Kwaks Ted , Vogels Ronald , Dalebout Tim J. , Myeni Sebenzile K. , Kikkert Marjolein , Snijder Eric J. , Li Zhenfeng , Barouch Dan H. , Vellinga Jort , Langedijk Johannes P.M. , Zahn Roland C. , Custers Jerome , Schuitemaker Hanneke
Published: July 2020

Development of effective preventative interventions against SARS-CoV-2, the etiologic agent of COVID-19 is urgently needed. The viral surface spike (S) protein of SARS-CoV-2 is a key target for prophylactic measures as it is critical for the viral replication cycle and the primary target of neutralizing antibodies. We evaluated design elements previously shown for other coronavirus S protein-based vaccines to be successful, e.g. prefusion-stabilizing substitutions and heterologous signal peptides, for selection of a S-based SARS-CoV-2 vaccine candidate. In vitro characterization demonstrated that the introduction of stabilizing substitutions (i.e., furin cleavage site mutations and two consecutive prolines in the hinge region of S1) increased the ratio of neutralizing versus non-neutralizing antibody binding, suggestive for a prefusion conformation of the S protein. Furthermore, the wild type signal peptide was best suited for the correct cleavage needed for a natively-folded protein. These observations translated into superior immunogenicity in mice where the Ad26 vector encoding for a membrane-bound stabilized S protein with a wild type signal peptide elicited potent neutralizing humoral immunity and cellular immunity that was polarized towards Th1 IFN-γ. This optimized Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in a phase I clinical trial (ClinicalTrials.gov Identifier: NCT04436276).
Systemic sterile induced-co-expression of IL-12 and IL-18 drives IFN-γ-dependent activation of microglia and recruitment of MHC-II-expressing inflammatory monocytes into the brain
Authors: Gaviglio Emilia A. , Peralta Ramos Javier M. , Arroyo Daniela S. , Bussi Claudio , Iribarren Pablo , Rodriguez-Galan Maria C.
Published: July 2020

The development of neuroinflammation, as well as the progression of several neurodegenerative diseases, has been associated with the activation and mobilization of the peripheral immune system due to systemic inflammation. However, the mechanism by which this occurs remains unclear. Herein, we addressed the effect of systemic, endotoxin-free induced-co-expression of IL-12 and IL-18 in the establishment of a novel cytokine-mediated model of neuroinflammation. Following peripheral hydrodynamic shear of IL-12 plus IL-18 cDNAs in C57BL/6 mice, we induced systemic and persistent level of IL-12, which in turn promoted the elevation of circulating pro-inflammatory cytokines TNF-α and IFN-γ, accompanied with splenomegaly. Moreover, even though we identified an increased gene expression of both TNF-α and IFN-γ in the brain, only TNF-α was shown to be dispensable, revealing an IFN-γ-dependent activation of microglia and the recruitment of leukocytes, particularly of highly activated inflammatory monocytes. Taken together, our results argue for a systemic cytokine-mediated establishment and development of neuroinflammation, having identified IFN-γ as a potential target for immunotherapy.
Epigenetic age-predictions in mice using pyrosequencing, droplet digital PCR or barcoded bisulfite amplicon sequencing
Authors: Han Yang , Nikolić Miloš , Gobs Michael , Franzen Julia , de Haan Gerald , Geiger Hartmut , Wagner Wolfgang
Published: July 2020

Age-associated DNA methylation reflects aspects of biological aging - therefore epigenetic clocks for mice can help to elucidate the impact of treatments or genetic background on the aging process in this model organism. Initially, age-predictors for mice were trained on genome-wide DNA methylation profiles, whereas we have recently described a targeted assay based on pyrosequencing of DNA methylation at only three CG dinucleotides (CpGs). Here, we have re-evaluated pyrosequencing approaches in comparison to droplet digital PCR (ddPCR) and barcoded bisulfite amplicon sequencing (BBA-seq). At individual CpGs the correlation of DNA methylation with chronological age was slightly higher for pyrosequencing and ddPCR as compared to BBA-seq. On the other hand, BBA-seq revealed that neighboring CpGs tend to be stochastically modified in murine age-associated regions. Furthermore, the binary sequel of methylated and non-methylated CpGs in individual reads can be used for single-read predictions, which may reflect heterogeneity in epigenetic aging. In comparison to C57BL/6 mice the epigenetic age-predictions using BBA-seq were also accelerated in the shorter-lived DBA/2 mice, and in C57BL/6 mice with a lifespan quantitative trait locus of DBA/2 mice. Taken together, we describe further optimized and alternative targeted methods to determine epigenetic clocks in mice.
Overexpression of key sterol pathway enzymes in two model marine diatoms alters sterol profiles inPhaeodactylum tricornutum
Authors: Jaramillo-Madrid Ana Cristina , Abbriano Raffaela , Ashworth Justin , Fabris Michele , Ralph Peter J.
Published: July 2020

Sterols are a class of triterpenoid molecules with diverse functional roles in eukaryotic cells, including intracellular signaling and regulation of cell membrane fluidity. Diatoms are a dominant eukaryotic phytoplankton group that produce a wide diversity of sterol compounds. The enzymes 3-hydroxy-3-methyl glutaryl CoA reductase (HMGR) and squalene epoxidase (SQE) have been reported to be rate-limiting steps in sterol biosynthesis in other model eukaryotes; however, the extent to which these enzymes regulate triterpenoid production in diatoms is not known. To probe the role of these two metabolic nodes in the regulation of sterol metabolic flux in diatoms, we independently over-expressed two versions of the nativeHMGRand a conventional, heterologous SQE gene in the diatomsThalassiosira pseudonanaandPhaeodactylum tricornutum. Overexpression of these key enzymes resulted in significant differential accumulation of downstream sterol pathway intermediates inP. tricornutum. HMGR-mVenus overexpression resulted in the accumulation of squalene, cycloartenol, and obtusifoliol, while cycloartenol and obtusifoliol accumulated in response to heterologous NoSQE-mVenus overexpression. In addition, accumulation of the end-point sterol 24-methylenecholesta-5,24(24’)-dien-3β-ol was observed in allP. tricornutumoverexpression lines, and campesterol increased 3-fold inP. tricornutumlines expressing NoSQE-mVenus. Minor differences in end-point sterol composition were also found inT. pseudonana, but no accumulation of sterol pathway intermediates was observed. Despite the successful manipulation of pathway intermediates and individual sterols inP. tricornutum, total sterol levels did not change significantly in transformed lines, suggesting the existence of tight pathway regulation to maintain total sterol content.
Base-edited CAR T Cells for combinational therapy against T cell malignancies
Authors: Georgiadis Christos , Rasaiyaah Jane , Gkazi Soragia Athina , Preece Roland , Etuk Aniekan , Christi Abraham , Qasim Waseem
Published: July 2020

Targeting T cell malignancies using chimeric antigen receptor (CAR) T cells is hindered by ‘T v T’ fratricide against shared antigens such as CD3 and CD7. Genome-editing can overcome such hurdles through targeted disruption of problematic shared antigens. Base editing offers the possibility of seamless disruption of gene expression through the creation of stop codons or elimination of splice donor or acceptor sites. We describe the generation of fratricide resistant, T cells by orderly removal of shared antigens such as TCR/CD3 and CD7 ahead of lentiviral mediated expression of CARs specific for CD3 or CD7. Molecular interrogation of base edited cells confirmed virtual elimination of chromosomal translocation events detected in conventional Cas9 treated cells. Interestingly, co-culture of 3CAR and 7CAR cells resulted in ‘self-enrichment’ yielding populations that were 99.6% TCR-/CD3/-CD7-. 3CAR or 7CAR cells were able to exert specific cytotoxicity against their relevant target antigen in leukaemia lines with defined CD3 and/or CD7 expression as well as primary T-ALL cells. Co-cultured 3CAR/7CAR cells exhibited the highest level of cytotoxicity against T-ALL targets expressing both targetin vitroand anin vivohuman:murine chimeric model. While APOBEC editors can reportedly exhibit guide-independent deamination of both DNA and RNA, we found no evidence of promiscuous base conversion activity affecting CAR antigen specific binding regions which may otherwise redirect T cell specificity. Combinational infusion of fratricide resistant anti-T CAR T cells may enable enhanced molecular remission ahead of allogeneic haematopoietic stem cell transplantation for T cell malignancies.
The ectomycorrhizal community of urban linden trees in Gdańsk, Poland
Authors: Olchowik Jacek , Suchocka Marzena , Jankowski Paweł , Malewski Tadeusz , Hilszczańska Dorota
Published: July 2020

The linden tree (Tiliaspp.) is a popular tree for landscaping and urban environments in central and northwest European countries, and it is one of the most popular in cities in Poland. Ectomycorrhizal fungi form a symbiosis with many urban tree species and protect the host plant from heavy metals and against salinity. The aim of this study was to characterize the ECM fungal community of urban linden trees along the tree damage gradient. The study was performed on two homogeneous sites located in the centre of the city of Gdańsk, in northern Poland. The vitality assessment of urban linden trees was made according to Roloff’s classification. Tree damage classes were related to soil characteristics using principal component analysis. The five ectomycorrhizal fungal species were shared among all four tree damage classes, andCenococcum geophilumwas found to be the most abundant and frequent ectomycorrhizal fungal species in each class. Park soil had significantly lower pH and Na, Cl and Pb content than street soils. Our knowledge of ectomycorrhizal communities in urban areas is still limited, and these findings provide new insights into ectomycorrhizal distribution patterns in urban areas.
Repurposing Novobiocin for activity against latency associatedMycobacterium tuberculosisdrug target nicotinate-nucleotide adenylyltransferase (Rv2421c)
Authors: Cloete Ruben , Shahbaaz Mohd , Grobbelaar Melanie , Sampson Samantha L. , Christoffels Alan
Published: July 2020

Nicotinamide-nucleotide adenylyl transferase (Rv2421c) was selected as a potential drug target, because it has been shown,in vitro, to be essential forMycobacterium tuberculosisgrowth. It is conserved between mycobacterium species, is up-regulated during dormancy, has a known 3D crystal structure and has no known human homologs. A model of Rv2421c in complex with nicotinic acid adenine dinucleotide and magnesium ion was constructed and subject to virtual ligand screening against the Prestwick Chemical Library and the ZINC database, which yielded 155 potential hit molecules. 3D-QSAR studies of the 155 drug molecules indicated five compounds with similar inhibitory efficiencies compared to known inhibitors of Rv2421c. Molecular docking validation and molecular dynamics simulation analysis of the top five compounds indicated that the identified inhibitor molecules bind to Rv2421c with comparable efficiency as the substrate DND. Subsequentin vitrotesting of the five compounds identified Novobiocin sodium salt with activity againstMycobacterium tuberculosisat 50 μM, 25μM and weakly at 10μM concentrations. Although, Novobiocin salt targetsMycobacterium tuberculosisDNA gyrase B our studies suggest that it has the potential to be repurposed to inhibit Rv2421c. Subsequentin silicostructural analysis of known Novobiocin sodium salt derivatives against Rv2421c suggest promising alternatives for the treatment ofMycobacterium tuberculosis.

Author Summary

Rv2421c has been shown to be essential forMycobacterium tuberculosisgrowth, shares no homology to known proteins in the human host, is conserved between various Mycobacterium species, is up-regulated during the non-replicative metabolic growth phase, making it an attractive drug target. It has a known 3D structure which has been exploited to screen for putative compounds within the Prestwick chemical library and ZINC database, resulting in the successful identification of 155 candidate compounds. Thereafter 3D-QSAR, molecular docking and molecular dynamics simulation studies were used to prioritize five potential compounds. Of the five compounds testedin vitro, only one, a Novobiocin disodium salt, showed activity againstMycobacterium tuberculosisat 50, 25 and weakly at 10 μM concentrations. Novobiocin is known to targetMycobacterium tuberculosisDNA gyrase B, but emerging resistance stimulated us to seek derivatives to target Rv2421c as alternatives for the treatment ofMycobacterium tuberculosis. Docking studies supported the higher binding affinities of Novobiocin derivatives to Rv2421c compared to DNA gyrase B. Future studies will involve testing these Novobiocin derivatives for activity againstMycobacterium tuberculosis.
Acrylamide Inhibits Vaccinia Virus Through Vimentin-independent Anti-Viral Granule Formation
Authors: Wood Jennifer J , White Ian J , Mercer Jason
Published: July 2020

The replication and assembly of vaccinia virus (VACV), the prototypic poxvirus, occurs exclusively in the cytoplasm of host cells. While the role of cellular cytoskeletal components in these processes remains poorly understood, vimentin - a type III intermediate filament - has been shown to associate with viral replication sites and to be incorporated into mature VACV virions. Here we employed chemical and genetic approaches to further investigate the role of vimentin during the VACV lifecycle. The collapse of vimentin filaments, using acrylamide, was found to inhibit VACV infection at the level of genome replication, intermediate- and late- gene expression. However, we found that CRISPR-mediated knockout of vimentin did not impact VACV replication. Combining these tools, we demonstrate that acrylamide treatment results in the formation of antiviral granules (AVGs) known to mediate translational inhibition of many viruses. We conclude that vimentin is dispensable for poxvirus replication and assembly and that acrylamide, as a potent inducer of AVGs during VACV infection, serves to bolster cell’s antiviral response to poxvirus infection.

Summary Statement

Acrylamide inhibits poxvirus replication by inducing anti-viral granules and blocking translation. This inhibition is independent of the effect of acrylamide on vimentin filaments which were found to be dispensable for viral replication and assembly.
EdiTyper: a high-throughput tool for analysis of targeted sequencing data from genome editing experiments
Authors: Yahi Alexandre , Hoffman Paul , Brandt Margot , Mohammadi Pejman , Tatonetti Nicholas P. , Lappalainen Tuuli
Published: July 2020

Genome editing experiments are generating an increasing amount of targeted sequencing data with specific mutational patterns indicating the success of the experiments and genotypes of clonal cell lines. We present EdiTyper, a high-throughput command line tool specifically designed for analysis of sequencing data from polyclonal and monoclonal cell populations from CRISPR gene editing. It requires simple inputs of sequencing data and reference sequences, and provides comprehensive outputs including summary statistics, plots, and SAM/BAM alignments. Analysis of simulated data showed that EdiTyper is highly accurate for detection of both single nucleotide mutations and indels, robust to sequencing errors, as well as fast and scalable to large experimental batches. EdiTyper is available in github (https://github.com/LappalainenLab/edityper) under the MIT license.
Differential BUM-HMM: a robust statistical modelling approach for detecting RNA flexibility changes in high-throughput structure probing data
Authors: Marangio Paolo , Law Ka Ying Toby , Sanguinetti Guido , Granneman Sander
Published: July 2020

Combining RNA structure probing with high-throughput sequencing technologies has greatly enhanced our ability to analyze RNA structure at transcriptome scale. However, the high level of noise and variability encountered in these data call for the development of computational tools that robustly extract RNA structural information. Here we present diffBUM-HMM, a noise-aware model that enables accurate detection of RNA flexibility and conformational changes from high-throughput RNA structure-probing data. DiffBUM-HMM is compatible with a wide variety of high-throughput RNA structure probing data, taking into consideration biological variation, sequence coverage and sequence representation biases. We demonstrate that, compared to the existing approaches, diffBUM-HMM displays higher sensitivity while calling virtually no false positives. DiffBUM-HMM analysis ofex vivoandin vivoXist SHAPE-MaP data detected many more RNA structural differences, involving mostly single-stranded nucleotides located at or near protein-binding sites. Collectively, our analyses demonstrate the value of diffBUM-HMM for quantitatively detecting RNA structural changes and reinforce the notion that RNA structure probing is a very powerful tool for identifying protein-binding sites.
Nanopore sequencing reveals full-length Tropomyosin 1 isoforms and their regulation by RNA binding proteins during rat heart development
Authors: Cao Jun , Routh Andrew L. , Kuyumcu-Martinez Muge N.
Published: July 2020

Alternative splicing (AS) contributes to the diversity of the proteome by producing multiple isoforms from a single gene. Although short-read RNA sequencing methods have been the gold standard for determining AS patterns of genes, they have a difficulty in defining full length mRNA isoforms assembled using different exon combinations. Tropomyosin 1 (TPM1) is an actin binding protein required for cytoskeletal functions in non-muscle cells and for contraction in muscle cells.Tpm1undergoes AS regulation to generate muscle versus non-muscle TPM1 protein isoforms with distinct physiological functions. It is unclear which full lengthTpm1isoforms are produced via AS and how they are regulated during heart development. To address these, we utilized nanopore long-read cDNA sequencing without gene-specific PCR amplification. In rat hearts, we identified full lengthTpm1isoforms composed of distinct exons with specific exon linkages. We showed thatTpm1undergoes AS transitions during embryonic heart development such that muscle-specific exons are connected together generating predominantly muscle specificTpm1isoforms in adult hearts. We found that the RNA binding protein RBFOX2 controls AS of ratTpm1exon 6a, which is important for cooperative actin binding. Furthermore, RBFOX2 regulatesTpm1AS of exon 6a antagonistically to the RNA binding protein PTBP1. In sum, we defined full lengthTpm1isoforms with different exon combinations that are tightly regulated during cardiac development and provided insights into regulation ofTpm1AS by RNA binding proteins. Our results demonstrate that nanopore sequencing is an excellent tool to determine fulllength AS variants of muscle enriched genes.
Quantitative sub-cellular acyl-CoA analysis reveals distinct nuclear regulation
Authors: Trefely Sophie , Huber Katharina , Liu Joyce , Noji Michael , Stransky Stephanie , Singh Jay , Doan Mary T. , Lovell Claudia D. , von Krusenstiern Eliana , Jiang Helen , Bostwick Anna , Pepper Hannah L. , Izzo Luke , Zhao Steven , Xu Jimmy P. , Bedi Kenneth C. , Eduardo Rame J. , Bogner-Strauss Juliane G. , Mesaros Clementina , Sidoli Simone , Wellen Kathryn E. , Snyder Nathaniel W.
Published: July 2020

Quantitative sub-cellular metabolomic measurements can yield crucial insights into the roles of metabolites in cellular processes, but are subject to multiple confounding factors. We developedStableIsotopeLabeling ofEssential nutrients in cellCulture –Sub-cellularFractionation (SILEC-SF), which uses isotope labeled internal standard controls that are present throughout fractionation and processing to quantify acyl-Coenzyme A thioesters in sub-cellular compartments by liquid chromatography-mass spectrometry. We tested SILEC-SF in a range of sample types and examined the compartmentalized responses to oxygen tension, cellular differentiation, and nutrient availability. Application of SILEC-SF to the challenging analysis of the nuclear compartment revealed a nuclear acyl-CoA profile distinct from that of the cytosol, with notable nuclear enrichment of propionyl-CoA. Using isotope tracing we identified the branched chain amino acid (BCAA) isoleucine as a major metabolic source of nuclear propionyl-CoA and histone propionylation, thus revealing a new mechanism of crosstalk between metabolism and the epigenome.
Adaptation of spontaneous activity in the developing visual cortex
Authors: Wosniack Marina E. , Kirchner Jan H. , Chao Ling-Ya , Zabouri Nawal , Lohmann Christian , Gjorgjieva Julijana
Published: July 2020

Spontaneous activity drives the establishment of appropriate connectivity in different circuits during brain development. In the mouse primary visual cortex, two distinct patterns of spontaneous activity occur before vision onset: local low-synchronicity events originating in the retina, and global high-synchronicity events originating in the cortex. We sought to determine the contribution of these activity patterns to jointly organize network connectivity through different activity-dependent plasticity rules. We found that local events shape cortical input selectivity and topography, while global events have a homeostatic role regulating connection strength. To generate robust selectivity, we predicted that global events should adapt their amplitude to the history of preceding cortical activation, and confirmed by analyzingin vivospontaneous cortical activity. This adaptation led to the sparsification of spontaneous activity on a slower timescale during development, demonstrating the remarkable capacity of the developing sensory cortex to acquire sensitivity to visual inputs after eye-opening.
Genetically-encoded fluorescent biosensor for rapid detection of protein expression
Authors: Eason Matthew G. , Pandelieva Antonia T. , Mayer Marc M. , Khan Safwat T. , Garcia Hernan G. , Chica Roberto A.
Published: July 2020

Fluorescent proteins are widely used as fusion tags to detect protein expressionin vivo. To become fluorescent, these proteins must undergo chromophore maturation, a slow process with a half-time of 5 to >30 min that causes delays in real-time detection of protein expression. Here, we engineer a genetically-encoded fluorescent biosensor to enable detection of protein expression within seconds in live cells. This sensor for transiently-expressed proteins (STEP) is based on a fully matured but dim green fluorescent protein in which pre-existing fluorescence increases 11-foldin vivofollowing the specific and rapid binding of a protein tag (Kd120 nM,kon1.7 × 105M−1s−1). In liveE. colicells, our STEP biosensor enables detection of protein expression twice as fast as the use of standard fluorescent protein fusions. Our biosensor opens the door to the real-time study of short-timescale processes in research model animals with high spatiotemporal resolution.
The mode of expression divergence inDrosophilafat body is infection-specific
Authors: Ramirez-Corona Bryan A. , Fruth Stephanie , Ofoegbu Oluchi , Wunderlich Zeba
Published: July 2020

Transcription is controlled by the interactions ofcis-acting DNA elements with diffusibletrans-acting factors. Changes incisortransfactors can drive expression divergence within and between species, and the relative prevalence of each can reveal the evolutionary history and pressures that drive expression variation. Previous work delineating the mode of expression divergence in animals has largely used whole body expression measurements in a single condition. Sincecis-acting elements often drive expression in a subset of cell types or conditions, these measurements may not capture the complete contribution ofcis-acting changes. Here, we quantify the mode of expression divergence in theDrosophilafat body, the primary immune organ, in several conditions. We performed allele-specific expression analysis using two geographically distinct lines ofD. melanogasterand their F1 hybrids. We measured expression in the absence of infection and in separate infections with Gram-negativeS. marcescensor Gram-positiveE. faecalisbacteria, which trigger the two primary signaling pathways in theDrosophilainnate immune response. The mode of expression divergence strongly depends on the condition, withtrans-acting effects dominating in response to Gram-positive infection andcis-acting effects dominating in Gram-negative and pre-infection conditions. Expression divergence in several receptor proteins may underlie the infection-specifictranseffects. Before infection, when the fat body has a metabolic role, there are many compensatory effects, changes incisandtransthat counteract each other to maintain expression levels. This work demonstrates that within a single tissue, the mode of expression divergence varies between conditions and suggests that these differences reflect the diverse evolutionary histories of host-pathogen interactions.
Generation of an Unbiased Interactome for the Tetratricopeptide Repeat Domain of O-GlcNAc Transferase Indicates a Role for the Enzyme in Intellectual Disability
Authors: Stephen Hannah M. , Praissman Jeremy L. , Wells Lance
Published: July 2020

The O-GIcNAc transferase (OGT) is localized to the nucleus and cytoplasm where it regulates nucleocytoplasmic proteins by modifying serine and threonine residues with a non-extended monosaccharide, β-N-Acetyl-Glucosamine (O-GlcNAc). With thousands of known O-GlcNAc modified proteins but only one OGT encoded in the mammalian genome, a prevailing question is how OGT selects its substrates. Prior work has indicated that the N-terminal tetratricopeptide repeat (TPR) domain of OGT, rather than its C-terminal catalytic domain, is responsible for subcellular targeting and substrate selection. An additional impetus for exploring the OGT TPR domain interactome is the fact that missense mutations inOGTassociated with X-linked intellectual disability (XLID) are primarily localized to the TPR domain without substantial impact on activity or stability of the enzyme. Therefore, we adapted the BioID labeling method to identify interactors of a TPR-BirA* fusion protein in HeLa cells. We identified 115 high confidence interactors representing both known and novel O-GlcNAc modified proteins and OGT interactors. The TPR interactors are highly enriched in processes in which OGT has a known role (e.g. chromatin remodeling, cellular survival of heat stress, circadian rhythm), as well as processes i n which OGT has yet to be implicated (e.g. pre-mRNA processing). Importantly, the identified TPR interactors are involved in several disease states but most notably are highly enriched in pathologies featuring intellectual disability. These proteins represent candidate interactors that may underlie the mechanism by which mutations inOGTlead to XLID. Furthermore, the identified interactors provide additional evidence of the importance of the TPR domain for OGT targeting and/or substrate selection. Thus, this defined interactome for the TPR domain of OGT serves as a jumping off point for future research exploring the role of OGT, the TPR domain, and its protein interactors in multiple cellular processes and disease mechanisms, including intellectual disability.
The analysis of emission values from commercial flights at Dalaman international airport Turkey
Authors: Kafali Hasim , Altuntas Onder
Published: July 2020

Purpose

This study aims to present atmospheric emissions (NOx, CO and HC) of commercial flights at Dalaman Airport for the years between 2016 and 2018.

Design/methodology/approach

Growing up, the potential for domestic and international airports will cause an increase in air transportation. Increasing demand for air transportation will cause adverse environmental impacts as well as positive economic contributions. Finding negative environmental effects and searching for solutions is an essential first step.

Findings

Emissions were calculated under three different groups (as daily, number of flights and per passenger). The maximum CO emission calculated was 1031.71 kg/day in August 2018, 41.55 g/pax. in October 2016 and 6909.27 g/flight in August 2018. The maximum HC emission calculated was 117.22 kg/day in August 2018, 4.78 g/pax. in May 2018 and 796.47 g/flight in May 2018. The maximum NOx emission calculated was 148.63 kg/day in August 2018, 6.04 g/pax. in October 2017 and 995.34 g/flight in August 2018.

Practical implications

The current study intends to show how can emission results differ under three different units.

Originality/value

The originality is the using of the real-time values for all calculations. The value of this study is to be key study for future applications of emission calculation methodologies.
The enhancement of the prescribed track for unmanned air vehicles
Authors: Usanmaz Oznur , Karaderili Murat , Sahin Ozlem , Savaş Tamer
Published: July 2020

Purpose

Unmanned aerial vehicles (UAVs) are more affected by adverse wind conditions in especially landing. Therefore, they need to change the runway in use. In case of this change, to eliminate the uncertain maneuvers, there is a need for a special prescribed track. The purpose of this study is the construction of a prescribed track at a single runway to provide a facility to change the runway in use.

Design/methodology/approach

Two forms of prescribed tracks, as standard and alternate, were constructed for UAVs by taking into consideration the key parameters to design flight procedures. Both tracks were assessed in a real-time simulation method. Moreover, unmanned vehicle simulation was used for a validation process.

Findings

According to the real-time simulation results, 8.14 NM and 6.64 NM of flight distance and 5.43 min and 4.43 min of flight time for the standard and alternate prescribed tracks were found, respectively. The obtained results were in favor of the alternate prescribed track. Furthermore, the prescribed track was assessed and validated in both air traffic control and UAV simulations. The feedback of pilots and controllers was very positive for a prescribed track, as it provided them with foresight and time to take care in any situations.

Practical implications

The prescribed track in this paper may be applied by airspace designers and UAV users to perform safe and efficient landing in adverse wind conditions.

Originality/value

In this study, a prescribed track was constructed for UAVs. Quantitative results were achieved using a real-time simulation method in terms of flight distance and flight time. Additionally, validation of the prescribed track was achieved by unmanned air vehicle simulation.
Supply chain channel conflict coordination with consumer network acceptance
Authors: Liu Yong , Liu Zhi-yang , Li Jiao
Published: July 2020

Purpose

The purpose of this paper is an attempt to design a proper incentive coordination mechanism to deal with the channel conflicts between the traditional sales and online direct sales.

Design/methodology/approach

With respect to the problems of channel conflicts between the traditional sales and online direct sales, to optimize the sale system and get more profits, considering the influences of consumer network acceptance, the authors establish demand and profit function based on consumer's utility, respectively. What's more, we exploit the game theory to analyze the optional decisions of the supply chain under the incentive coordination condition and no incentive coordination condition, and then we discuss the supply chain's optimal pricing, demand, profit and compensation incentive levels with the different effect of consumer network acceptance.

Findings

The level of compensation incentive provided by the manufacturer is influenced by consumer network acceptance and product cost. The lower the consumer network acceptance, the better the compensation incentive coordination effect of manufacturers. Manufacturers, wholesalers, retailers and consumers are all important players in real supply chain relationships. When a manufacturer exists as a dominant role, it should pay full attention to the impact of consumer behavior on supply chain decisions.

Practical implications

The research can clarify the influence and mechanism of consumer behavior on supply chain channel conflict coordination, and deal with channel conflicts.

Originality/value

The proposed incentive coordination can effectively realize supply chain channel conflict resolution, and provide decision-making ideas and methods for manufacturers to develop the supply chain management of online direct sales channels.
Review of construction journals on causes of project cost overruns
Authors: Durdyev Serdar
Published: July 2020

Purpose

The study investigates the causes of project cost overruns (COs) that have been reported in the construction-management-related articles since 1985.

Design/methodology/approach

To achieve the aim and provide recommendations to avoid project COs, 48 selected journal articles were reviewed and assessed with regard to the countries, institutions and researchers that have contributed to the subject.

Findings

The review of the articles shows that the subject has attracted a considerable attention from the researchers worldwide. However, the problem mainly occurred in developing countries and the researchers drew the attention on the resource-related, economic/financial as well as political problems. While 79 causes of COs were identified, the top ten causes of project COs, which have received the highest number of citations by the reviewed articles, were presented and discussed. These causes are: design problems and incomplete design, inaccurate estimation, poor planning, weather, poor communication, stakeholder's skill, experience and competence, financial problems/poor financial management, price fluctuations, contract management issues and ground/soil conditions.

Research limitations/implications

The study findings have several implications, which are not only for the academic world, but also for the construction front line. For scholars, the study provides a list of project COs that the researchers in the area could benefit for their future studies. The industry practitioners could find ways to improve project cost performance by giving attention to the causative factors that are significantly affecting construction projects and investing their resources and efforts towards the most occurred ones.

Originality/value

Thus, this study provides insight into the research output on the subject and a checklist of COs, which is believed to provide a better understanding of significant areas requiring attention where steps should be taken to minimize or control factors causing COs in construction projects.
Evolutionary resilience in the housing sector: requirements proposal
Authors: Bigolin Morgane , Bussular Camilla Zanon , Silva Filho Luiz Carlos Pinto
Published: July 2020

Purpose

This paper aims to discuss how to apply the evolutionary resilience theory in the housing sector, aiming to develop an alternative resilience framework for planning social housing programmes.

Design/methodology/approach

Based on the literature review, it was developed a theoretical framework for building evolutionary resilience. Based on this framework, the outline for the empirical research was specified through interviews with 21 multidisciplinary experts. The statements of these experts were examined through content analysis, as a means to assign a set of requirements for resilient buildings.

Findings

The analysis showed that the holistic framework based on evolutionary resilience could constitute a comprehensive and innovative resilience approach. The main contribution of the set of requirements was to adapt theoretical concepts by proposing operational surrogates, enabling such knowledge to be more applicable to devising resilience to the housing sector.

Originality/value

Resilience is establishing itself as one of the top agendas on the built environment. The construction sector, however, has yet to embrace the concept and little research has been conducted on a practical approach to assess the building’s resilience. This paper presents a list of practical requirements showing that the housing sector must to build differently to have a resilient future.
Oil-food price dynamics in an oil-dependent emerging economy
Authors: Adeosun Opeoluwa Adeniyi , Olayeni Olaolu Richard , Ayodele Olumide Steven
Published: July 2020

Purpose

This paper aims to examine the transmission from oil price to local food price returns in Nigeria from January 1995 to May 2019.

Design/methodology/approach

To circumvent erratic behaviours and account for possibilities of noises at the edge of the wavelet signals, the paper combines wavelet and Markov-switching techniques to determine the significance and magnitude of oil–food price dynamics across different time scales.

Findings

It is shown that oil to food price pass-through changed across frequencies. Notably, results reveal a swift pass-through which signals the dominance of the direct effect of oil price shocks on food prices with evidence of weak spillover in the short term. The medium- and long-term horizons witness the dominance of the indirect effect of oil price shocks with much sluggish transmission to food prices; the highest significant pass-through of about 4% are also observed when the oil price is denominated in the naira–USD exchange rate.

Originality/value

The study improves understanding of the relationship between oil price shocks and domestic food price returns. It shapes policy prescription on appropriate inflation targeting strategies of monetary authorities.
Decision-making framework for using ambient assisted living
Authors: Alsulami Majid H. , Alsaqer Mohammed S. , Atkins Anthony S.
Published: July 2020

Purpose

Technology plays an important role in assisting elderly people to live independently, longer and improve their quality of life and health, in supporting their daily activities, etc. The ageing population becomes a global phenomenon. The population of Saudi Arabia continues to age (>60 years of age) currently (5%) compared to other group ages. In 2050, it will increase rapidly to 20.9% of the Saudi population. The current research aims at examining the barriers that health-care providers in the Kingdom of Saudi Arabia are experiencing in the adoption of ambient assisted living (AAL) technologies among the elderly. The study aims to identify a challenging issue with the increasing the number of elderly among the population in the country, which has highlighted the need to use AAL technology to improve the quality of life among the elderly.

Design/methodology/approach

This study involved a community of practice (CoP) study as a method of data collection where data collected were presented and discussed in line with the existing literature review findings.

Findings

In total, 14 factors were identified in this study and discussed in the context of Saudi Arabia, which resulted in developing a decision-making framework for using AAL by health-care providers. Those factors are essential in boosting the usage of technology in improving elderly health in Saudi Arabia.

Research limitations/implications

This study includes implications for developing a decision-making framework for using AAL.

Social implications

This study clarifies that technology can connect elderly people with society.

Originality/value

In total, 14 factors were identified in this study and discussed in the context of Saudi Arabia.
Semantic assessment of smart healthcare ontology
Authors: Tiwari Sanju , Abraham Ajith
Published: July 2020

Purpose

Health-care ontologies and their terminologies play a vital role in knowledge representation and data integration for health information. In health-care systems, Internet of Technology (IoT) technologies provide data exchange among various entities and ontologies offer a formal description to present the knowledge of health-care domains. These ontologies are advised to assure the quality of their adoption and applicability in the real world.

Design/methodology/approach

Ontology assessment is an integral part of ontology construction and maintenance. It is always performed to identify inconsistencies and modeling errors by the experts during the ontology development. A smart health-care ontology (SHCO) has been designed to deal with health-care information and IoT devices. In this paper, an integrated approach has been proposed to assess the SHCO on different assessment tools such as Themis, Test-Driven Development (TDD)onto, Protégé and OOPs! Several test cases are framed to assess the ontology on these tools, in this research, Themis and TDDonto tools provide the verification for the test cases while Protégé and OOPs! provides validation of modeled knowledge in the ontology.

Findings

As of the best knowledge, no other study has been presented earlier to conduct the integrated assessment on different tools. All test cases are successfully analyzed on these tools and results are drawn and compared with other ontologies.

Originality/value

The developed ontology is analyzed on different verification and validation tools to assure the quality of ontologies.
Deformation mechanism and tribological behavior of hydrogen-free carburized layer on Ti-6Al-4V alloy
Authors: Tian Tian , Zhao Ruibo , Wei Dongbo , Yang Kai , Zhang Pingze
Published: July 2020

Purpose

The purpose of this paper is to expound the relationship among microstructure, mechanical property, tribological behavior and deformation mechanism of carburized layer deposited on Ti-6Al-4V alloy by double-glow plasma hydrogen-free carburizing surface technology.

Design/methodology/approach

Morphologies and phase compositions of the carburized layer were observed by scanning electron microscope and X-ray diffraction. The micro-hardness tests were used to evaluate the surface and cross-sectional hardness of carburized layer. The reciprocating friction and wear experiments under various load conditions were implemented to investigate the tribological behavior of carburized layer. Moreover, scratch test with ramped loading pattern was carried out to illuminate the deformation mechanism of carburized layer.

Findings

Compared to substrate, the hardness of surface improved to ∼1,100 HV0.1, while the hardness profile of carburized layer presented gradual decrease from ∼1,100 to ∼300 HV0.1 within the distance of the total carburizing-affected region about 30 µm. The coefficient of friction, wear rate and wear morphology of carburized layer were analyzed. Scratch test indicated that the deformation process of carburized layer could be classified into three mechanisms (elastic, changing elastic–plastic and stable elastic–plastic mechanisms), and the deformation transition of the carburizing-affected region was from changing elastic–plastic to elastic mechanisms. Both the elastic and changing elastic–plastic mechanisms are conducive to the wearing course.

Originality/value

Using this technology, hydrogen embrittlement was avoided and wear resistance property of titanium alloy was greatly improved. Simultaneously, the constitutive relation during the whole loading process was deduced in terms of scratch approach, and the deformation mechanism of carburized layer was discussed from a novel viewpoint.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-11-2019-0489/
Systemic preconditions and ontological modeling for peri-urban communities
Authors: Nousala Susu , Galindo Kim Blanca , Romero David , Feng Xin , Aibeo Pedro
Published: July 2020

Purpose

This research presents an ontological model, to communicate the impact of dynamic preconditions for peri-urban communities. As such, this paper approaches perturbation communities as social-complex-adaptive-systems.

Design/methodology/approach

Previous assessment of dynamic preconditions have typically been based on top-down approaches. Through the lens of social-complex-adaptive and systemic design approaches (requiring a range of different disciplines), this work focuses on providing a broader view towards periurban research. The methodological approach involved academic literature, fieldwork observations, in-depth discussions with community, government, experts and research groups, focusing on a region called “Xochimilco” on the outskirts of Mexico City, a unique pre-Hispanic, Aztec ecosystem. This evolving man made agricultural/ecological structure of island plots, still provides environmental services to Mexico City. This region provides the basis of the research and subsequent ontological model. Ontology, in this instance, refers to the nature of being within a range of constraining dynamic forces relating to resilient behaviors of the current Xochimilco perturbation ecosystem.

Findings

Xochimilco can be considered as a longitudinal phenomenon that contributed to the understanding of observable resilient and precondition elements between the past and present of a living complex-adaptive-system.

Practical implications

The research has provided a better understanding of community resilience through preconditions, contributing towards preparation of environmental change and future urbanization. To this end, the research focused on visualizing key dynamics elements for communities attempting to absorb new urban conditions (being continuously pushed into it).

Originality/value

The outcomes of this research have provided specific systemic, bottom up approaches with ontological modeling to assist with visualizing and understanding intangible dynamic conditions that impact high complex areas of perturbation regions.