bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of insect odorant receptor trafficking and functional expression via transient transfection in HEK293 cells
Authors: Miazzi Fabio , Hoyer Carolin , Sachse Silke , Knaden Markus , Wicher Dieter , Hansson Bill S. , Lavista-Llanos Sofia
Published: June 2019

Insect odorant receptors show a limited functional expression in various heterologous expression systems including insect and mammalian cells. This may be in part due to the absence of key components driving the release of these proteins from the endoplasmic reticulum and directing them to the plasma membrane. In order to mitigate this problem we took advantage of small export signals within the human HCN1 and Rhodopsin that have been shown to promote protein release from the endoplasmic reticulum and the trafficking of post-Golgi vesicles, respectively. Moreover, we designed a new vector based on a bidirectional expression cassette to drive the functional expression of the insect odorant receptor co-receptor (Orco) and an odor-binding odorant receptor, simultaneously. We show that this new method can be used to reliably express insect odorant receptors in HEK293 cells via transient transfection and that is highly suitable for downstream applications using automated and high-throughput imaging platforms.
The organizer of chromatin topology RIF1 ensures cellular resilience to DNA replication stress
Authors: Ribeyre Cyril , Lebdy Rana , Patouillard Julie , Larroque Marion , Abou-Merhi Raghida , Larroque Christian , Constantinou Angelos
Published: June 2019

Eukaryotic genomes are duplicated from thousands of replication origins that fire sequentially forming a defined spatiotemporal pattern of replication clusters. The temporal order of DNA replication is determined by chromatin architecture and, more specifically, by chromatin contacts that are stabilized by RIF1. Here we show that RIF1 localizes in close proximity to newly synthesized DNA. In cells exposed to the DNA replication inhibitor aphidicolin, suppression of RIF1 markedly decreased the efficacy of protein isolation on nascent DNA (iPOND), suggesting that the iPOND procedure is biased by chromatin topology. RIF1 was required to limit the accumulation of DNA lesions induced by aphidicolin treatment and promoted the recruitment of cohesins in the vicinity of nascent DNA. Collectively, the data suggest that the stabilization of chromatin topology by RIF1 limits replication-associated genomic instability.
Coordination between stochastic and deterministic specification in the Drosophila visual system
Authors: Courgeon Maximilien , Desplan Claude
Published: June 2019

Many sensory systems use stochastic fate specification to increase their repertoire of neuronal types. How these stochastic decisions are coordinated with the development of their target post-synaptic neurons in processing centers is not understood. In the Drosophila visual system, two subtypes of the UV-sensitive R7 color photoreceptors called yR7 and pR7 are stochastically specified in the retina. In contrast, the target neurons of photoreceptors in the optic lobes are specified through a highly deterministic program. Here, we identify subtypes of the main postsynaptic target of R7, the Dm8 neurons, that are each specific to the different subtypes of R7s. We show that during development the different Dm8 subtypes are produced in excess by distinct neuronal progenitors, independently from R7 subtype specification. Following matching with their respective R7 target, supernumerary Dm8s are eliminated by apoptosis. We show that the two interacting cell adhesion molecules Dpr11, expressed in yR7s, and its partner DIPγ, expressed in yDm8s, are essential for the matching of the synaptic pair. Loss of either molecule leads to the death of yDm8s or their mis-pairing with the wrong pR7 subtype. We also show that competitive interactions between Dm8 subtypes regulate both cell survival and targeting. These mechanisms allow the qualitative and quantitative matching of R7 subtypes with their target in the brain and thus permit the stochastic choice made in R7 to propagate to the deterministically specified downstream circuit to support color vision.
Toxoplasma gondiibradyzoites induce transcriptional changes to host cells and prevent IFNγ-mediated cell death
Authors: Seizova Simona , Garnham Alexandra L , Coffey Michael J , Whitehead Lachlan W , Rogers Kelly L , Tonkin Christopher J
Published: June 2019

Toxoplasma gondii, the causative agent of toxoplasmosis, lies dormant for life and is a reservoir for disease reactivation, causing blindness, encephalitis and congenital birth defects. Acute-stage tachyzoites extensively manipulate their host cell by exporting a repertoire of proteins across the parasitophorous vacuolar membrane (PVM). This interferes with the hosts transcriptional program, allowing for persistence during immune attack. It is unknown how bradyzoites persist and what role host manipulation plays in latency. Here we show that bradyzoite-containing host cells have a unique transcriptional landscape when compared to tachyzoite infection. We demonstrate that many of these changes are dependent parasite protein export. Furthermore, we show that bradyzoite effector proteins protect host cell’s from IFNγ-mediated cell death, thus highlighting the functional importance of host manipulation. Together, our work provides the first understanding of howToxoplasmasets up latency to persist in its host.
Tomato yellow leaf curl virus V2 protein plays a critical role in the nuclear export of V1 protein and viral systemic infection
Authors: Zhao Wenhao , Ji Yinghua , Wu Shuhua , Barton Elizabeth , Fan Yongjian , Wang Xiaofeng , Zhou Yijun
Published: June 2019

Geminiviruses are an important group of circular, single-stranded DNA viruses that cause devastating diseases in crops. Geminiviruses replicate their genomic DNA in the nucleus. The newly-synthesized viral DNA is subsequently transported to the cytoplasm, moved to adjacent cells through plasmodesmata with the help of viral movement proteins, and, ultimately, moved long-distance to establish systemic infection. Thus, the nucleocytoplasmic transportation is crucial for a successful infection by geminiviruses. For Tomato yellow leaf curl virus (TYLCV), the V1 protein is known to bind and shuttle viral genomic DNA, but the role of V2 protein in this process is still unclear. Here, we report that the nucleus-localized V1 protein dramatically decreases when co-expressed with V2 protein, and that V2-facilitated nuclear export of V1 protein depends on host exportin-α and a specific V1-V2 interaction. Chemical inhibition of exportin-α or a substitutions at cysteine 85 of V2 protein, which abolishes the V1-V2 interaction, blocks the promoted redistribution of V1 protein to the perinuclear region and the cytoplasm. When the V2C85S mutation is incorporated into a TYLCV infectious clone, the TYLCV-C85S causes delayed onset of very mild symptoms compared to wild-type TYLCV, indicating that the V1-V2 interaction and, thus, V2-mediated nuclear export of V1 protein is crucial for viral spread and systemic infection. Our data point to a critical role of the V2 protein in promoting the nuclear export of the V1 protein, likely by promoting V1-mediated nucleocytoplasmic transportation of TYLCV genomic DNA, and in turn, promoting viral systemic infection.

Author summary

As both replication and the transcription of geminiviruses occur in the nucleus, transportation of the viral genomic DNA into and out of the nucleus of the infected cells is essential for a successful infection cycle. However, the nuclear export of geminiviruses is still little known and even less is known about the process for monopartite geminiviruses. We use TYLCV, a typical monopartite begomovirus in the family Geminiviridae, to examine the nucleocytoplasmic transportation. In this study, we found TYLCV V2 is able to redistribute the nucleus-localized V1 protein to the perinuclear region. Moreover, the nuclear export of V1 protein is dependent on the V1-V2 interaction and host exportin-α. Blocking the V1-V2 interaction impeded the V2-mediated V1 protein redistribution and decrease TYLCV infection efficiency with delayed and mild symptoms. This report shows us a new explanation for the role of V2 in the nuclear export of V1 protein and TYLCV viral systemic infection.
Low oxygen enhances trophoblast column growth by potentiating the extravillous lineage and promoting LOX activity
Authors: Treissman Jenna , Yuan Victor , Baltayeva Jennet , Le Hoa T. , Castellana Barbara , Robinson Wendy P. , Beristain Alexander G.
Published: June 2019

Early placental development and the establishment of the invasive trophoblast lineage take place within a low oxygen environment. However, conflicting and inconsistent findings have obscured the role of oxygen in regulating invasive trophoblast differentiation. In this study, the effect of hypoxic, normoxic, and atmospheric oxygen on invasive extravillous pathway progression was examined using a human placental explant model. Here, we show that exposure to low oxygen enhances extravillous column outgrowth and promotes the expression of genes that align with extravillous trophoblast (EVT) lineage commitment. By contrast, super-physiological atmospheric levels of oxygen promote trophoblast proliferation while simultaneously stalling EVT progression. Low oxygen-induced EVT differentiation coincided with elevated transcriptomic levels of lysyl oxidase (LOX) in trophoblast anchoring columns, where functional experiments established a role for LOX activity in promoting EVT column outgrowth. The findings of this work support a role for low oxygen in potentiating the differentiation of trophoblasts along the extravillous pathway. Additionally, these findings generate insight into new molecular processes controlled by oxygen during early placental development.

Summary Statement

Low oxygen promotes extravillous trophoblast differentiation
A Protein Engineering Approach for Uncovering Cryptic Ubiquitin-binding Sites: from a Ubiquitin-Variant Inhibitor of APC/C to K48 Chain Binding
Authors: Watson Edmond R. , Grace Christy R. R. , Zhang Wei , Miller Darcie J. , Davidson Iain F. , Prabu J. Rajan , Yu Shanshan , Bolhuis Derek L. , Kulko Elizaveta T. , Vollrath Ronnald , Haselbach David , Stark Holger , Peters Jan-Michael , Brown Nicholas G. , Sidhu Sachdev S. , Schulman Brenda A.
Published: June 2019

Ubiquitin-mediated proteolysis is a fundamental mechanism used by eukaryotic cells to maintain homeostasis and protein quality, and to control timing in biological processes. Two essential aspects of ubiquitin regulation are conjugation through E1-E2-E3 enzymatic cascades, and recognition by ubiquitin-binding domains. An emerging theme in the ubiquitin field is that these two properties are often amalgamated in conjugation enzymes. In addition to covalent thioester linkage to ubiquitin’s C-terminus for ubiquitin transfer reactions, conjugation enzymes often bind non-covalently and weakly to ubiquitin at “exosites”. However, identification of such sites is typically empirical and particularly challenging in large molecular machines. Here, studying the 1.2 MDa E3 ligase Anaphase-Promoting Complex/Cyclosome (APC/C), which controls cell division and many aspects of neurobiology, we discover a method for identifying unexpected ubiquitin-binding sites. Using a panel of ubiquitin variants (UbVs) we identify a protein-based inhibitor that blocks ubiquitin ligation to APC/C substrates in vitro and ex vivo. Biochemistry, NMR, and cryo EM structurally define the UbV interaction, explain its inhibitory activity through binding the surface on the APC2 subunit that recruits the E2 enzyme UBE2C, and ultimately reveal that this APC2 surface is also a ubiquitin-binding exosite with preference for K48-linked chains. The results provide a new tool for probing APC/C activity, have implications for the coordination of K48-linked Ub chain binding by APC/C with the multistep process of substrate polyubiquitylation, and demonstrate the power of UbV technology for identifying cryptic ubiquitin binding sites within large multiprotein complexes.

SIGNIFICANCE STATEMENT

Ubiquitin-mediated interactions influence numerous biological processes. These are often transient or a part of multivalent interactions. Therefore, unmasking these interactions remains a significant challenge for large, complicated enzymes such as the Anaphase-Promoting Complex/Cyclosome (APC/C), a multisubunit RING E3 ubiquitin (Ub) ligase. APC/C activity regulates numerous facets of biology by targeting key regulatory proteins for Ub-mediated degradation. Using a series of Ub variants (UbVs), we identified a new Ub-binding site on the APC/C that preferentially binds to K48-linked Ub chains. More broadly, we demonstrate a workflow that can be exploited to uncover Ub-binding sites within ubiquitylation machinery and other associated regulatory proteins to interrogate the complexity of the Ub code in biology.
Chemical precision glyco-mutagenesis by glycosyltransferase engineering in living cells
Authors: Schumann Benjamin , Malaker Stacy A. , Wisnovsky Simon P. , Debets Marjoke F. , Agbay Anthony J. , Fernandez Daniel , Wagner Lauren J. S. , Lin Liang , Choi Junwon , Fox Douglas M. , Peh Jessie , Gray Melissa A. , Pedram Kayvon , Kohler Jennifer J. , Mrksich Milan , Bertozzi Carolyn R.
Published: June 2019

Studying posttranslational modifications classically relies on experimental strategies that oversimplify the complex biosynthetic machineries of living cells. Protein glycosylation contributes to essential biological processes, but correlating glycan structure, underlying protein and disease-relevant biosynthetic regulation is currently elusive. Here, we engineer living cells to tag glycans with editable chemical functionalities while providing information on biosynthesis, physiological context and glycan fine structure. We introduce a non-natural substrate biosynthetic pathway and use engineered glycosyltransferases to incorporate chemically tagged sugars into the cell surface glycome of the living cell. We apply the strategy to a particularly redundant yet disease-relevant human glycosyltransferase family, the polypeptideN-acetylgalactosaminyl transferases. This approach bestows a gain-of-function modification on cells where the products of individual glycosyltransferases can be selectively characterized or manipulated at will.
Host circadian rhythms are disrupted during malaria infection in parasite genotype-specific manners
Authors: Prior Kimberley F. , O’Donnell Aidan J. , Rund Samuel S. C. , Savill Nicholas J. , van der Veen Daan R. , Reece Sarah E.
Published: June 2019

Infection can dramatically alter behavioural and physiological traits as hosts become sick and subsequently return to health. Such “sickness behaviours” include disrupted circadian rhythms in both locomotor activity and body temperature. Host sickness behaviours vary in pathogen species-specific manners but the influence of pathogen intraspecific variation is rarely studied. We examine how infection with the murine malaria parasite, Plasmodium chabaudi, shapes sickness in terms of parasite genotype-specific effects on host circadian rhythms. We reveal that circadian rhythms in host locomotor activity patterns and body temperature become differentially disrupted and in parasite genotype-specific manners. Locomotor activity and body temperature in combination provide more sensitive measures of health than commonly used virulence metrics for malaria (e.g. anaemia). Moreover, patterns of host disruption cannot be explained simply by variation in replication rate across parasite genotypes or the severity of anaemia each parasite genotype causes. It is well known that disruption to circadian rhythms is associated with non-infectious diseases, including cancer, type 2 diabetes, and obesity. Our results reveal that disruption of host circadian rhythms is a genetically variable virulence trait of pathogens with implications for host health and disease tolerance.
Familiarity increases processing speed in the visual system
Authors: Manahova Mariya E. , Spaak Eelke , de Lange Floris P.
Published: June 2019

Familiarity with a stimulus leads to an attenuated neural response to the stimulus. Alongside this attenuation, recent studies have also observed a truncation of stimulus-evoked activity for familiar visual input. One proposed function of this truncation is to rapidly put neurons in a state of readiness to respond to new input. Here, we examined this hypothesis by presenting human participants with target stimuli that were embedded in rapid streams of familiar or novel distractor stimuli at different speeds of presentation, while recording brain activity using magnetoencephalography (MEG) and measuring behavioral performance. We investigated the temporal and spatial dynamics of signal truncation and whether this phenomenon bears relationship to participants’ ability to categorize target items within a visual stream. Behaviorally, target categorization performance was markedly better when the target was embedded within familiar distractors, and this benefit became more pronounced with increasing speed of presentation. Familiar distractors showed a truncation of neural activity in the visual system, and this truncation was strongest for the fastest presentation speeds. Moreover, neural processing of the target was stronger when it was preceded by familiar distractors. Taken together, these findings suggest that truncation of neural responses for familiar items may result in stronger processing of relevant target information, resulting in superior perceptual performance.

Significance statement

The visual response to familiar input is attenuated more rapidly than for novel input. Here we find that this truncation of the neural response for familiar input is strongest for very fast image presentations. We also find a tentative function for this truncation: the neural response to a target image that is embedded within distractors is much greater when the distractors are familiar than when they are novel. Similarly, target categorization performance is much better when the target is embedded within familiar distractors, and this advantage is most obvious for very fast image presentations. This suggests that neural truncation helps to rapidly put neurons in a state of readiness to respond to new input.
Multifaceted genome-wide study identifies novel regulatory loci for body mass index in Indians
Authors: Giri Anil K , Prasad Gauri , Bandesh Khushdeep , Parekatt Vaisak , Mahajan Anubha , Banerjee Priyanka , Kauser Yasmeen , Chakraborty Shraddha , Rajashekar Donaka ,   INDICO, Sharma Abhay , Mathur Sandeep Kumar , Basu Analabha , McCarthy Mark I , Tandon Nikhil , Bharadwaj Dwaipayan
Published: June 2019

Obesity, a risk factor for various human diseases originates through complex interactions between genes and prevailing environment that varies across populations. Indians exhibit a unique obesity phenotype likely attributed by specific gene pool and environmental factors. Here, we present genome-wide association study (GWAS) of 7,259 Indians to understand the genetic architecture of body mass index (BMI) in the population. Our study revealed novel association of variants in BAI3 (rs6913677) and SLC22A11 (rs2078267) at GWAS significance, and of ZNF45 (rs8100011) with near GWAS significance. As genetic loci may dictate the phenotype through modulation of epigenetic processes, we overlapped discovered genetic signatures with DNA methylation patterns of 236 Indian individuals, and analyzed expression of the candidate genes using publicly available data. The variants in BAI3 and SLC22A11 were found to dictate methylation patterns at unique CpGs harboring critical cis- regulatory elements. Further, BAI3, SLC22A11 and ZNF45 variants were found to overlie repressive chromatin, active enhancer, and active chromatin regions, in that order, in human subcutaneous adipose tissue in ENCODE database. Besides, the identified genomic regions represented potential binding sites for key transcription factors implicated in obesity and/or metabolic disorders. Interestingly, rs8100011 (ZNF45) acted as a robust cis-expression quantitative trait locus (cis-eQTL) in subcutaneous adipose tissue in GTEx portal, and ZNF45 gene expression showed an inverse correlation with BMI in skeletal muscle of Indian subjects. Further, gene-based GWAS analysis revealed CPS1 and UPP2 as additional leads regulating BMI in Indians. Our study decodes potential genomic mechanisms underlying obesity phenotype in Indians.
Evolution of C4 photosynthesis predicted by constraint-based modelling
Authors: Blätke Mary-Ann , Bräutigam Andrea
Published: June 2019

Constraint-based modelling (CBM) is a powerful tool for the analysis of evolutionary trajectories. Evolution, especially evolution in the distant past, is not easily accessible to laboratory experimentation. Modelling can provide a window into evolutionary processes by allowing the examination of selective pressures which lead to particular optimal solutions in the model. To study the evolution of C4 photosynthesis from a ground state of C3 photosynthesis, we initially construct a C3 model. After duplication into two cells to reflect typical C4 leaf architecture, we allow the model to predict the optimal metabolic solution under various conditions. The model thus identifies resource limitation in conjunction with high photorespiratory flux as a selective pressure relevant to the evolution of C4. It also predicts that light availability and distribution play a role in guiding the evolutionary choice of possible decarboxylation enzymes. The data shows evolutionary CBM in eukaryotes predicts molecular evolution with precision.
Effect of sampling frequency on fractal fluctuations during treadmill walking
Authors: Marmelat Vivien , Duncan Austin , Meltz Shane
Published: June 2019

The temporal dynamics of stride-to-stride fluctuations in steady-state walking reveal important information about locomotor control and can be quantified using so-called fractal analyses, notably the detrended fluctuation analysis (DFA). Gait dynamics are often collected during treadmill walking using 3-D motion capture to identify gait events from kinematic data. The sampling frequency of motion capture systems may impact the precision of event detection and consequently impact the quantification of stride-to-stride variability. This study aimed i) to determine if collecting multiple walking trials with different sampling frequency affects DFA values of spatiotemporal parameters during treadmill walking, and ii) to determine the reliability of DFA values across downsampled conditions. Seventeen healthy young adults walked on a treadmill while their gait dynamics was captured using different sampling frequency (60, 120 and 240 Hz) in each condition. We also compared data from the highest sampling frequency to downsampled versions of itself. We applied DFA to the following time series: step length, time and speed, and stride length, time and speed. Reliability between experimental conditions and between downsampled conditions were measured with 1) intraclass correlation estimates and their 95% confident intervals, calculated based on a single-measurement, absolute-agreement, two-way mixed-effects model (ICC 3,1), and 2) Bland-Altman bias and limits of agreement. Both analyses revealed a poor reliability of DFA results between conditions using different sampling frequencies, but a relatively good reliability between original and downsampled spatiotemporal variables. Collectively, our results suggest that using sampling frequencies of 120 Hz or 240 Hz provide similar results, but that using 60 Hz may alter DFA values. We recommend that gait kinematics should be collected at around 120 Hz, which provides a compromise between event detection accuracy and processing time.
The role of transporters and synaptic cleft morphology in glutamate and GABA homeostasis and their effect on neuronal function
Authors: Ullah Ghanim
Published: June 2019

The spatiotemporal dynamics of glutamate and gama-aminobutyric acide (GABA) in the synaptic cleft plays a key role in the signal integration in the brain. Since there is no extracellular metabolism of glutamate and GABA, cellular uptake through transporters and diffusion to extracellular space (ECS) regulates the concentration of both neurotransmitters in the cleft. We use the most up to date information about the transporters and synaptic cleft to model the homeostasis of both glutamate and GABA. We show that the models can be used to investigate the role played by different isoforms of transporters, uptake by different neuronal compartments or glia cells, and key parameters determining the morphology of synaptic cleft in the neurotransmitter concentration in the cleft and ECS, and how they shape synaptic responses through postsynaptic receptors. We demonstrate the utility of our models by application to simple neuronal networks and showing that varying the neurotransmitter uptake capacity and synaptic cleft parameters within experimentally observed range can lead to significant changes in neuronal behavior such as the transition of the network between gamma and beta rhythms. The modular form of the models allows easy extension in the future and integration with other computational models of normal and pathological neuronal functions.
A reduced Gompertz model for predicting tumor age using a population approach
Authors: Vaghi C. , Rodallec A. , Fanciullino R. , Ciccolini J. , Mochel J. , Mastri M. , Poignard C. , Ebos J. ML , Benzekry S.
Published: June 2019

Tumor growth curves are classically modeled by ordinary differential equations. In analyzing the Gompertz model several studies have reported a striking correlation between the two parameters of the model.

We analyzed tumor growth kinetics within the statistical framework of nonlinear mixed-effects (population approach). This allowed for the simultaneous modeling of tumor dynamics and interanimal variability. Experimental data comprised three animal models of breast and lung cancers, with 843 measurements in 94 animals. Candidate models of tumor growth included the Exponential, Logistic and Gompertz. The Exponential and – more notably – Logistic models failed to describe the experimental data whereas the Gompertz model generated very good fits. The population-level correlation between the Gompertz parameters was further confirmed in our analysis (R2> 0.96 in all groups). Combining this structural correlation with rigorous population parameter estimation, we propose a novel reduced Gompertz function consisting of a single individual parameter. Leveraging the population approach using bayesian inference, we estimated the time of tumor initiation using three late measurement timepoints. The reduced Gompertz model was found to exhibit the best results, with drastic improvements when using bayesian inference as compared to likelihood maximization alone, for both accuracy and precision. Specifically, mean accuracy was 12.1% versus 74.1% and mean precision was 15.2 days versus 186 days, for the breast cancer cell line.

These results offer promising clinical perspectives for the personalized prediction of tumor age from limited data at diagnosis. In turn, such predictions could be helpful for assessing the extent of invisible metastasis at the time of diagnosis.

Author summary

Mathematical models for tumor growth kinetics have been widely used since several decades but mostly fitted to individual or average growth curves. Here we compared three classical models (Exponential, Logistic and Gompertz) using a population approach, which accounts for inter-animal variability. The Exponential and the Logistic models failed to fit the experimental data while the Gompertz model showed excellent descriptive power. Moreover, the strong correlation between the two parameters of the Gompertz equation motivated a simplification of the model, the reduced Gompertz model, with a single individual parameter and equal descriptive power. Combining the mixed-effects approach with Bayesian inference, we predicted the age of individual tumors with only few late measurements. Thanks to its simplicity, the reduced Gompertz model showed superior predictive power. Although our method remains to be extended to clinical data, these results are promising for the personalized estimation of the age of a tumor from limited measurements at diagnosis. Such predictions could contribute to the development of computational models for metastasis.
Phylogenetic correlations can suffice to infer protein partners from sequences
Authors: Marmier Guillaume , Weigt Martin , Bitbol Anne-Florence
Published: June 2019

Determining which proteins interact together is crucial to a systems-level understanding of the cell. Recently, algorithms based on Direct Coupling Analysis (DCA) pairwise maximum-entropy models have allowed to identify interaction partners among the paralogs of ubiquitous prokaryotic proteins families, starting from sequence data alone. Since DCA allows to infer the three-dimensional structure of protein complexes, its success in predicting protein-protein interactions could be mainly based on contacting residues coevolving to remain physicochemically complementary. However, interacting proteins often possess similar evolutionary histories, which also gives rise to correlations among their sequences. What is the role of purely phylogenetic correlations in the performance of DCA-based methods to infer interaction partners? To address this question, we employ controlled synthetic data that only involves phylogeny and no interactions or contacts. We find that DCA accurately identifies the pairs of synthetic sequences that only share evolutionary history. It performs as well as methods explicitly based on sequence similarity, and even slightly better with large and accurate training sets. We further demonstrate the ability of these various methods to correctly predict pairings among actual paralogous proteins with genome proximity but no known direct physical interaction, which illustrates the importance of phylogenetic correlations in real data. However, for actually interacting and strongly coevolving proteins, DCA and mutual information outperform sequence similarity.

Author summary

Many biologically important protein-protein interactions are conserved over evolutionary time scales. This leads to two different signals that can be used to computationally predict interactions between protein families and to identify specific interaction partners. First, the shared evolutionary history leads to highly similar phylogenetic relationships between interacting proteins of the two families. Second, the need to keep the interaction surfaces of partner proteins biophysically compatible causes a correlated amino-acid usage of interface residues. Employing simulated data, we show that the shared history alone can be used to detect partner proteins. Similar accuracies are achieved by algorithms comparing phylogenetic relationships and by coevolutionary methods based on Direct Coupling Analysis, which are a priori designed to detect the second type of signal. Using real sequence data, we show that in cases with shared evolutionary but without known physical interactions, both methods work with similar accuracy, while for physically interacting systems, methods based on correlated amino-acid usage outperform purely phylogenetic ones.
Shining light on cysteine modification: connecting protein conformational dynamics to catalysis and regulation
Authors: van den Bedem Henry , Wilson Mark A
Published: June 2019

Cysteine is a rare but functionally important amino acid that is often subject to covalent modification. Cysteine oxidation plays an important role in many human disease processes, and basal levels of cysteine oxidation are required for proper cellular function. Because reactive cysteine residues are typically ionized to the thiolate anion (Cys-S−), their formation of a covalent bond alters the electrostatic and steric environment of the active site. X-ray-induced photo-oxidation to sulfenic acids (Cys-SOH) can recapitulate some aspects of the changes that occur under physiological conditions. Here we propose how site-specific cysteine photo-oxidation can be used to interrogate ensuing changes in protein structure and dynamics at atomic resolution. Although this powerful approach can connect cysteine covalent modification to global protein conformational changes and function, careful biochemical validation must accompany all such studies to exclude misleading artifacts. New types of X-ray crystallography experiments and powerful computational methods are creating new opportunities to connect conformational dynamics to catalysis for the large class of systems that use covalently modified cysteine residues for catalysis or regulation.
Effects of primary school’s physical environment on children’s spatial perception and behavior
Authors: Türel Ahmet , Ayşe Gür Elmira
Published: June 2019

Purpose

The relationship between the child and his/her physical environment is an area of interaction that includes social, psychological and cultural factors along with the spatial experience, perception and behavior of the child. This study is based on the effects of spatial perception and behavior of the child within the physical environment of primary schools. In this direction, the purpose of this paper is to investigate how spatial and physical characteristics of primary school typologies affect the spatial perception and behavior of the child. Also, the parameters affecting spatial perception and behavior are examined.

Design/methodology/approach

The question to be investigated is how the spatial and physical characteristics of the school’s physical environment affect the child’s spatial perception and behavior in primary schools with different typologies. Within this scope, Istanbul’s Kagithane region is selected as a case study. Schools are chosen for their similar spatial and dimensional features and similar socio-economic environment. The methodology of the study consists of a literature review, an observational study carried out to discover the interaction between the child and his/her school building and the analysis of the student’s cognitive maps. These maps were evaluated according to topological, projective, metric and imaginative parameters.

Findings

The results show spatial organization and physical characteristics of primary school buildings with a structure that allows for change and transformation, and contributes to the physical and cognitive development of children.

Originality/value

This study will provide an opportunity to develop the design of future primary school buildings that can support the spatial perception and spatial experiences of the children.
A parallel high-order compressible flows solver with domain decomposition method in the generalized curvilinear coordinates system
Authors: Piquet Arthur , Zebiri Boubakr , Hadjadj Abdellah , Safdari Shadloo Mostafa
Published: June 2019

Purpose

This paper aims to present the development of a highly parallel finite-difference computational fluid dynamics code in generalized curvilinear coordinates system. The objectives are to handle internal and external flows in fairly complex geometries including shock waves, compressible turbulence and heat transfer.

Design/methodology/approach

The code is equipped with high-order discretization schemes to improve the computational accuracy of the solution algorithm. Besides, a new method to deal with the geometrical singularities, so-called domain decomposition method (DDM), is implemented. The DDM consists of using two different meshes communicating with each other, where the base mesh is Cartesian and the overlapped one a hollow cylinder.

Findings

The robustness of the present implemented code is appraised through several numerical test cases including a vortex advection, supersonic compressible flow over a cylinder, Poiseuille flow, turbulent channel and pipe flows. The results obtained here are in an excellent agreement when compared to the experimental data and the previous direct numerical simulation (DNS). As for the DDM strategy, it was successful as simulation time is clearly decreased and the connection between the two subdomains does not create spurious oscillations.

Originality/value

In sum, the developed solver was capable of solving, accurately and with high-precision, two- and three-dimensional compressible flows including fairly complex geometries. It is noted that the data provided by the DNS of supersonic pipe flows are not abundant in the literature and therefore will be available online for the community.
Teaching performance assessments in the USA and Australia
Authors: Charteris Jennifer
Published: June 2019

Purpose

Teaching performance assessments (TPAs) have developed in the USA and Australia as a “bar exam” for the profession and are used means to assure that graduates are classroom ready. The purpose of this paper is to outline how these assessments have been implemented in teacher education in the USA and Australian contexts. The edTPA is embroiled in controversy in the USA and there are important lessons from the related research literature that could inform the how other countries engage with TPAs in pre-service teacher education.

Design/methodology/approach

This conceptual paper outlines how Australia has introduced TPAs in initial teacher education (ITE) through policy borrowing from the USA. The paper synthesises critiques of the edTPA (USA) from research literature and considers the implications of TPAs in the Australian context.

Findings

The TPA impacts the focus of pre-service teacher practicum teaching, and pedagogy and curriculum in ITE education. The TPA could be used to mobilise detrimental accountability mechanisms. With the outsourcing of assessment to edu-business, Pearson Education, teacher education institutions in the USA have a sense that they have lost control over determining which students are credentialed to teach. Although pre-service teacher assessment is still administered and assessed by ITE institutions in Australia, there is a concern that could change. It is argued that educators, administrators and policy makers should avoid moves to outsource TPAs in Australia.

Originality/value

Because it is in its infancy, there is a little robust research into the implication of introducing teacher performance assessments into the Australian teacher education context.
Estimation of expected years of life lost for patients with ischemic stroke and intracerebral hemorrhage
Authors: Butsing Nipaporn , Tipayamongkholgul Mathuros , Ratanakorn Disya
Published: June 2019

Purpose

The purpose of this paper is to estimate the mean life expectancy (LE) and the expected years of life lost (EYLL) for ischemic stroke and intracerebral hemorrhage.

Design/methodology/approach

This retrospective cohort study included 5,210 patients with a diagnosis of first ischemic stroke or intracerebral hemorrhage between 2005 and 2013 from Ramathibodi Hospital, Bangkok, Thailand. The survival of each case was followed until December 31, 2016. A semiparametric extrapolation method was applied to estimate the lifetime survival function relative to an age and sex-matched reference population.

Findings

Of 5,210 patients, 74.2 percent experienced ischemic stroke. About 54.3 percent were men. Mean age at diagnosis was 64.3 years. The mean LE was 12.5 years for ischemic stroke and 12.0 years for intracerebral hemorrhage. The EYLL among patients with intracerebral hemorrhage was significantly higher than among those with ischemic stroke (10.1 vs 5.7). Women were expected to lose more LE than men for both types of stroke (p-value<0.05), while younger aged patients were expected to lose more years of life than older ones.

Originality/value

This study fulfilled an identified need to estimate LE and EYLL among patients with ischemic stroke and intracerebral hemorrhage.
Is there still a gender effect on CEO compensation?
Authors: Leszczynska Dorota , Chandon Jean-Louis
Published: June 2019

Purpose

Do female CEOs face a compensation gap? The purpose of this paper is to examine whether gender affects the total compensation of today’s CEOs, and whether it moderates ten factors influencing their total compensation.

Design/methodology/approach

Taking the 54 female CEOs cited in the US 2014 Fortune’s 1000 report, a matched sample of male CEOs was selected, matched according to the crosstab of age by education and by the sizes of the companies directed by these female CEOs.

Findings

Using four years’ worth of Fortune reports, between 2013 and 2016, this matched sample indicates that female CEOs are not discriminated against in terms of total compensation. However, eight factors do show a significant effect on total compensation. Using moderation analysis, the present study reveals how gender interacts with company size, sector, membership of outside boards and nature of previous experience.

Research limitations/implications

This paper addresses an important and under-researched gap, with contradictory findings in the existing literature, by compiling and testing the characteristics of male and female CEOs which are not cited in Fortune 1000 reports.

Originality/value

Arguably, this is therefore one of the first papers to study gender differences in total compensation among Fortune 1000 CEOs using a matched sample technique, based on a larger number of female CEOs and a larger number of years than any previous research.
Thermal creep of shear tab connection assemblies under transient-state temperatures of fire
Authors: Al Khatib Karim , Hantouche Elie , Morovat Mohammed Ali
Published: June 2019

Purpose

This study aims to investigate the thermal creep behavior of steel frame assemblies with shear tab connections subjected to transient-state fire temperatures. Different key parameters are investigated to study their effect on the global response of the steel frames in fire.

Design/methodology/approach

Finite element (FE) models of connection assemblies are first analyzed using Abaqus under transient-state temperature conditions and validated against experimental work available in the literature. Upon acquiring the validated conditions, parametric studies are carried out to study the effect of key geometric and heating parameters on the overall response of the frame assembly to fire temperatures. Thermal creep material is also incorporated in the analyses through a user-defined subroutine, and a comparison between including and excluding creep material is illustrated to show the effect of thermal creep on the structural behavior.

Findings

The results reported herein indicate that having a rigid column increases the thermal-induced axial forces, thus increasing the development of thermal creep strains. Slow heating rates can cause axial stress relaxation in the restrained beam and increase the mid-span deflection and consequently the development of beam catenary action. The results also show that reaching higher initial cooling temperatures and having longer cooling phase durations result in more tensile forces at the end of the cooling phase.

Originality/value

Previous studies were limited to isolated steel connections under steady-state conditions. This study investigates the creep behavior of shear tab connection assemblies under transient-state conditions of fire when creep effects are explicitly considered. This can provide a rational and realistic assessment of the steel behavior in fire events.
Workplace learning in crowdwork
Authors: Margaryan Anoush
Published: June 2019

Purpose

This paper aims to explore workplace learning practices within two types of crowdwork – microwork and online freelancing. Specifically, the paper scopes and compares the use of workplace learning activities (WLAs) and self-regulatory learning (SRL) strategies undertaken by microworkers (MWs) and online freelancers (OFs). We hypothesised that there may be quantitative differences in the use of WLAs and SRL strategies within these two types of crowdwork, because of the underpinning differences in the complexity of tasks and skill requirements.

Design/methodology/approach

To test this hypothesis, a questionnaire survey was carried out among crowdworkers from two crowdwork platforms – Figure Eight (microwork) and Upwork (online freelancing). Chi-square test was used to compare WLAs and SRL strategies among OFs and MWs.

Findings

Both groups use many WLAs and SRL strategies. Several significant differences were identified between the groups. In particular, moderate and moderately strong associations were uncovered, whereby OFs were more likely to report (i) undertaking free online courses/tutorials and (ii) learning by receiving feedback. In addition, significant but weak or very weak associations were identified, namely, OFs were more likely to learn by (i) collaborating with others, (ii) self-study of literature and (iii) making notes when learning. In contrast, MWs were more likely to write reflective notes on learning after the completion of work tasks, although this association was very weak.

Originality/value

The paper contributes empirical evidence in an under-researched area – workplace learning practices in crowdwork. Crowdwork is increasingly taken up across developed and developing countries. Therefore, it is important to understand the learning potential of this form of work and where the gaps and issues might be. Better understanding of crowdworkers’ learning practices could help platform providers and policymakers to shape the design of crowdwork in ways that could be beneficial to all stakeholders.
How would the managementof human behavior variables influence customer-oriented management?
Authors: Valenzuela-Fernández Leslier M. , Arroyo-Cañada Francisco-Javier , Villegas Pinuer Francisco Javier
Published: June 2019

Purpose

Salesperson’s actions are critical in helping the firm develop customer value orientation and long-term relationship with profitable customers to achieve sustainable sales growth and profitability over time. The purpose of this paper is to examine the salespeople and service executives’ perceptions about the relevance of some human resource management variables and employees’ attitudes as key factors to develop a company’s customer value orientation. The authors tested whether the perceptions of role ambiguity, incentives policy and provided training (PT) had an impact on job involvement (JI), job satisfaction (JS), and consequently, on customer value orientation.

Design/methodology/approach

Research design was nested with data from 327 executives from medium and upper positions in Chilean companies.

Findings

The results show that while the perception of role ambiguity had an indirect negative impact on customer value orientation through JI, perception of PT level had a direct impact over and above the other variables.

Research limitations/implications

JS and JI are attitudinal variables, which companies try to encourage in their employees through different human resources, practices. Incentives and training are ways to develop favorable employees’ attitudes and improve their customer value orientation. With the research, companies could invest their resources in better and more effective practices to generate favorable attitudes toward customer value orientation.

Originality/value

Through structural equation modeling, the model shows the relevance in the perception of sales executives about the relationship of employees’ JI and customer value orientation. This commands to open the view of the customer value orientation management to include other attitudinal variables as JI.