bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-Canonical Binding of a Small Molecule to Sortilin Alters Cellular Trafficking of ApoB and PCSK9 in Liver Derived Cells
Authors: Sparks Robert P. , Arango Andres S. , Aboff Zachary L. , Jenkins Jermaine L. , Guida Wayne C. , Tajkhorshid Emad , Sparks Charles E. , Sparks Janet D. , Fratti Rutilio A.
Published: October 2019

Sortilin regulates hepatic exocytosis and endocytosis of ApoB containing lipoproteins (ApoB-Lp) and mediates the secretion of the subtilase PCSK9. To elucidate connections between these pathways, we previously identified a small molecule (cpd984) that binds to a non-canonical site on Sortilin. In hepatic cells cpd984 augments ApoB-Lp secretion, increases cellular PCSK9 levels, and reduces LDLR expression indicative of reduced secretion of PCSK9. We have shown that insulin-induced ApoB-Lp degradation occurs through Vps34-dependent autophagy. Here we show that the specific Vps34 inhibitor PIK-III enhances ApoB-100 secretion, reducing cellular levels of PCSK9 and Sortilin resulting in reduced LDLR expression, which implicates a role for autophagy in PCSK9 secretion. Results suggest that Sortilin is central to both PCSK9 and ApoB-100 secretion. Finally, we found that cpd984 in yeast blocks CPY secretion while increasing vacuolar homotypic fusion in a Vps10-dependent manner, indicating an evolutionarily conserved mechanism required for lysosomal protease trafficking.
A reciprocal inhibition model of alternations between non-dissociative and dissociative states in patients with PTSD
Authors: Chiba Toshinori , Ide Kentaro , Boku Shuken , Taylor Jessica E. , Toda Hiroyuki , Kanazawa Tetsufumi , Kato Sumie , Horiuchi Yuka , Hishimoto Akitoyo , Maruyama Toru , Yamamoto Taisuke , Shirakawa Miyako , Sora Ichiro , Kawato Mitsuo , Koizumi Ai
Published: October 2019

Objective

Traumatic life-events can leave individuals with contrasting posttraumatic stress disorder (PTSD) symptoms, including re-experiencing and avoidance. Notably, patients with PTSD are known to periodically switch between two opposing attentional biases; namely, toward threat and away from threat. We hypothesized that reciprocal inhibition between the amygdala and ventromedial prefrontal cortex (vmPFC) may induce alternations between these attentional biases, which in turn may contribute to the re-experiencing and avoidance symptoms, respectively.

Methods

To test this reciprocal inhibition model, we performed an experiment to measure the attentional biases of patients with PTSD. We examined the differential relationships between PTSD symptom clusters (re-experiencing/avoidance) and attentional biases (toward/away from threat). Additionally, we performed a meta-regression analysis to examine the role of amygdala reactivity in the imbalance between re-experiencing and avoidance symptoms.

Results

We found that attentional bias toward threat was selectively associated with re-experiencing symptoms whereas attentional bias away from threat was selectively associated with avoidance symptoms. Meta-regression analysis based on twelve participant populations (total N = 316) revealed that left amygdala activity was positively correlated with the severity of re-experiencing symptoms relative to avoidance symptoms.

Conclusions

Our findings support the hypothesis that reciprocal inhibition of common neural circuits may underlie the switch between attentional biases toward and away from threat as well as that between re-experiencing and avoidance symptoms. Re-experiencing and avoidance/emotional numbing are the core symptoms used to distinguish between the non-dissociative and dissociative PTSD subtypes. The reciprocal inhibition mechanism may help elucidate the mechanisms underlying those PTSD subtypes.
Default mode network anatomy and function is linked to pediatric concussion recovery
Authors: Iyer Kartik K. , Zalesky Andrew , Barlow Karen M. , Cocchi Luca
Published: October 2019

Objective

To determine whether anatomical and functional brain features relate to key persistent post-concussion symptoms (PPCS) in children recovering from mild traumatic brain injuries (mTBI), and whether such brain indices can predict individual recovery from PPCS.

Methods

110 children with mixed recovery following mTBI were seen at the concussion clinic at Neurology department Alberta Children’s Hospital. The primary outcome was the Post-Concussion Symptom Inventory (PCSI, parent proxy). Sleep disturbance scores (PCSI sub-domain) and the Neurocognition Index (CNS Vital Signs) were also measured longitudinally. PPCS was assessed at 4 weeks post-injury and 8-10 weeks post-injury. Grey matter volumes were assessed using magnetic resonance imaging (MRI) and voxel-based morphometry. Functional connectivity was estimated using resting-state MRI. Two complementary machine learning methods were used to assess if the combination of grey matter and functional connectivity indices carried meaningful prognostic information.

Results

Higher scores on a composite index of sleep disturbance, including fatigue, were associated with converging decreases in grey matter volume and local functional connectivity in two key nodes of the default mode network: the posterior cingulate cortex and the medial prefrontal cortex. Sleep-related disturbances also significantly correlated with reductions in functional connectivity between these brain regions. The combination of structural and functional brain indices associated to individual variations in the default mode network accurately predicted clinical outcomes at follow-up (area under the curve = 0.86).

Interpretation

These results highlight that the function-structure profile of core default mode regions underpins sleep-related problems following mTBI and carries meaningful prognostic information for pediatric concussion recovery.
A detailed graphical and computational model of the mammalian renal circadian clock
Authors: Ivy Jessica R. , Shih Barbara , Hogenesch John B. , Mullins John J. , Freeman Tom C.
Published: October 2019

Here we describe the construction of a detailed graphical and computational model of the mammalian circadian clock. We use it to simulate the clock activity within the kidney, where it plays a pivotal role in regulating blood pressure. First, we assembled a network-based process diagram, which includes all known components of the clock and the interactions between them. Parameterisation of the model for Petri net-based simulation experiments used mRNA levels in the kidney to define initial conditions. With empirical testing, model parameterisation was further refined such that the simulated activity of core genes closely matched their measured activity. Furthermore, virtual knockout experiments performed on the model were shown to reflect experimental gene knockout data. It also identified points at which canonical clock genes may integrate with downstream genes likely to affect blood pressure and other aspects of kidney function. We believe that the model provides new insights into the complexity and function of this most central of physiological pathways and provides a valuable resource for the research community.
Structural and Dynamic Insights Into α-Synuclein Dimer Conformations
Authors: Zamel Joanna , Chen Jiaxing , Zaer Sofia , Harris Paul David , Drori Paz , Lebendiker Mario , Kalisman Nir , Dokholyan Nikolay V. , Lerner Eitan
Published: October 2019

Parkinson’s disease is associated with the aggregation of the protein α-synuclein. While α-synuclein can exist in multiple oligomeric states, the dimer has been a subject of extensive debates. Here, using an array of biophysical approaches, we demonstrate that α-synucleinin vitroexhibits primarily a monomer-dimer equilibrium in nanomolar concentrations and up to a few micromolars. We then use spatial information from hetero-isotopic cross-linking mass spectrometry experiments as restrains in discrete molecular dynamics simulations to obtain the ensemble structure of dimeric species. Out of eight structural sub-populations of dimers, we identify one that is compact, stable, abundant, and exhibits partially exposed β-sheet structures. This compact dimer is the only one where the hydroxyls of tyrosine 39 are in proximity that may promote dityrosine covalent linkage upon hydroxyl radicalization, which is implicated in α-synuclein amyloid fibrils. We propose that this α-synuclein dimer features etiological relevance to Parkinson’s disease.
CDR3 binding chemistry controls TCR V-domain rotational probability and germline CDR2 scanning of polymorphic MHC
Authors: Murray Joseph S.
Published: October 2019

The mechanism which adapts the T-cell antigen receptor (TCR) within a given major histocompatibility complex (MHC/HLA) genotype is essential for protection against pathogens. Historically attributed to relative affinity, genetically vast TCRs are surprisingly focused towards a micromolar affinity for their respective peptide (p) plus MHC (pMHC) ligands. Thus, the somatic diversity of the TCR with respect to MHC-restriction, and (ultimately) to pathogens, remains enigmatic. Here, we derive a triple integral solution (from fixed geometry) for any given V domain in TCR bound to pMHC. Solved complexes involving HLA-DR and HLA-DQ, where genetic linkage to the TCR is most profound, were examined in detail. Certain V domains displayed rare geometry within this panel—specifying a restricted rotational probability/volumetric density (dV). Remarkably, hydrogen (H) bond charge-relays distinguished these structures from the others; suggesting that CDR3 binding chemistry dictates CDR2 contacts on the opposite MHC-II alpha helix. Together, these data suggest that TCR recapitulate dV and specialise target pMHC recognition.
Patients with different cancer types are stratified by CBC data
Authors: Sadovsky Michael G. , Feller Alena A. , Martynova Elena A. , Chernyaev Denis V. , Semenov Edward V. , Slepov Eugene V. , Zukov Ruslan A.
Published: October 2019

Searching for informative indices indicating cancer type and cause of the disease is of great importance. Here we tried to identify those indices from the data of complete blood analysis, only. We studied the inhomogeneity in the mutual distribution of a number of oncology patients with various types of tumors in the space of qualitative data provided by the complete blood count. The patients with oncology in hematology system were excluded. Ultimate goal is to reveal the relation between such inhomogeneity issues and the cause of a disease. We used the database on complete blood count comprising oncology patients with various causes of tumor development. The analysis has been carried out both by linear (K-means) and non-linear (elastic map technique) methods. No linear clustering has been found. On the contrary, elastic map technique yields stable clustering identifying not less than three clusters, in the set of patients. No relation of those clusters to sex or age of patients has been found. Four indices (namely, BAS, EOS, WBC and IG) exhibit no relation to the cluster structure, while all others do it. Thus, the patients are stratified according to their respond on the stress caused by cancer tumor. The data on complete blood count may be used for preliminary diagnostics of a tumor and its cause, for oncology patients. This type of analysis is cheap, standard and available at any medical organization.
Changes in Extracellular Matrix Gene and Protein Expressions in Human Trabecular Meshwork Cells in Response to Mechanical Fluid Flow Stimulation
Authors: Yoshida Koichi , Kawai Motofumi , Utsunomiya Tsugiaki , Ishibazawa Akihiro , Song Young-Seok , Udo Mariana Sayuri B. , Tasaki Yoshikazu , Yoshida Akitoshi
Published: October 2019

Purpose

To investigate the changes in extracellular matrix (ECM) gene and protein expressions in human trabecular meshwork (HTM) cells in response to mechanical fluid flow stimulation.

Methods

HTM cells were cultured on a glass plate and exposed to shear stress (0, 0.2, and 1.0 dyne/cm2) for 12 hours. Changes in gene expressions were evaluated using microarray analysis. The representative genes related to ECM metabolism underwent real-time reverse-transcriptase polymerase chain reaction. Fibronectin (FN) and collagen (COL) IV levels in the supernatant were evaluated using immunoassays. Rho-associated coiled-coil-containing protein kinase (ROCK) activity also was investigated.

Results

After stimulation, transforming growth factor β2 mRNA levels were significantly (p < 0.01) lower than that of the static control (0 dyne/cm2 for 12 hours). Matrix metalloproteinase 2 mRNA levels were significantly (p < 0.05) higher than the static control. COL type 1 alpha 2 mRNA, COL type 4 alpha 2 mRNA, and COL type 6 alpha 1 mRNA levels were significantly (p < 0.05, < 0.01, and < 0.05, respectively) higher than the static control. The mean ± standard deviation FN levels (ng/mL) in the supernatant after stimulation (0, 0.2, 1.0 dyne/cm2) were 193.7 ± 7.6, 51.5 ± 21.8, and 34.9 ± 23.6, respectively (p < 0.01). The FN and COL IV levels and ROCK activity were significantly (p < 0.01 and < 0.05, respectively) lower than the static control.

Conclusions

Changes in gene and protein expressions related to ECM metabolism occurred in HTM cells after stimulation. Specifically, the suppression of FN and COL IV production might explain the importance of mechanical fluid flow stimulation on maintenance of the normal aqueous humor outflow.
Computational identification of cell-specific variable regions in ChIP-seq data
Authors: Andreani Tommaso , Albrecht Steffen , Fontaine Jean-Fred , Andrade-Navarro Miguel A.
Published: October 2019

Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is used to identify genome-wide DNA regions bound by proteins. Given one ChIP-seq experiment with replicates, binding sites not observed in all the replicates will usually be interpreted as noise and discarded. However, the recent discovery of high-occupancy target (HOT) regions suggests that there are regions where binding of multiple transcription factors can be identified. To investigate ChIP-seq variability, we developed a reproducibility score and a method that identifies cell-specific variable regions in ChIP-seq data by integrating replicated ChIP-seq experiments for multiple protein targets on a particular cell type. Using our method, we found variable regions in human cell lines K562, GM12878, HepG2, MCF-7, and in mouse embryonic stem cells (mESCs). These variable-occupancy target regions (VOTs) are CG dinucleotide rich, and show enrichment at promoters and R-loops. They overlap significantly with HOT regions, but are not blacklisted regions producing non-specific binding ChIP-seq peaks. Furthermore, in mESCs, VOTs are conserved among placental species suggesting that they could have a function important for this taxon. Our method can be useful to point to such regions along the genome in a given cell type of interest, to improve the downstream interpretative analysis before follow up experiments.
Maternal immune activation in rats is associated with a lower number of dopamine receptor 3-expressing granulocytes in the male offspring with no alterations in cocaine reward, resistance to extinction or cue-induced reinstatement
Authors: Santos-Toscano Raquel , Ucha Marcos , Borcel Érika , Ambrosio Emilio , Higuera-Matas Alejandro
Published: October 2019

There is evidence for increased rates of drug use among schizophrenic patients. However, the causality in this relationship remains unclear. In addition, biomarkers of schizophrenia are vital, given the heterogeneous nature of the disorder that can lead to difficulties in the early diagnosis. In the present work, we use a maternal immune activation model to experimentally test whether animals at high risk of developing a schizophrenia-like condition are more prone to acquire cocaine self-administration, show enhanced sensitivity to the reinforcing actions of cocaine or if they are resistant to extinction or vulnerable to relapse. Pregnant rats were injected with lipopolysaccharide (LPS) (2 mg/kg s.c.) or saline every other day during pregnancy, and the offspring was tested for sensorimotor gating (prepulse inhibition –PPI-). After this test, one group of rats was submitted to cocaine self-administration (0.5 mg/kg) under fixed and progressive ratio schedules, dose-response testing, extinction and cue-induced drug-seeking. Another group was sacrificed to study potential biomarkers in the immune blood cells by flow cytometry. While rats born to LPS-treated mothers showed impaired PPI, there were no differences in cocaine self-administration acquisition, responsiveness to dose shifts, extinction or cue-induced reinstatement. Finally, there were fewer DRD3+ granulocytes in the LPS-offspring and an exciting trend for CNR2+ lymphocytes to be more abundant in LPS-exposed rats. Our results indicate that the higher prevalence of cocaine abuse among people with schizophrenia is not due to a pre-existing pathology and suggest that DRD3+ granulocytes and possibly CNR2+ lymphocytes could be potential biomarkers of schizophrenia.
Amino Acid Requirements of the Chinese Hamster Ovary Cell Metabolism during Recombinant Protein Production
Authors: Traustason Bergthor
Published: October 2019

Majority of biopharmaceutical drugs today are produced by Chinese hamster ovary (CHO) cells, which have been the standard industry host for the past decades. To produce and secrete a substantial amount of the target recombinant proteins the CHO cells must be provided with suitable growth conditions and provided with the necessary nutrients. Amino acids play a key role in this as the building blocks of proteins, playing important roles in a large number of metabolic pathways and being important sources of nitrogen as well as carbon under certain conditions. In this study exploratory analysis of the amino acid requirements of CHO cells was carried out using metabolic modelling approaches. Flux balance analysis was employed to evaluate the optimal distribution of fluxes in a genome-scale model of CHO cells to gain information on the cells’ metabolic response in silico.

The results showed that providing non-essential amino acids (NEAAs) has a positive effect on CHO cell biomass production and that cysteine as well as tyrosine play a fundamental role in this. This implies that extracellular provision of NEAAs limits the extent of energy loss in amino acid biosynthetic pathways and renders additional reducing power available for other biological processes. Detailed analysis of the possible secretion and uptake of D-serine in the CHO model was also performed and its influence on the rest of the metabolism mapped out, which revealed results matching various existing literature. This is interesting since no mention of D-serine in regard to CHO cells was found in current literature, as well as the fact that this opens up the possibility of using the model for better understanding of certain disorders in higher up organisms that have been implicated with D-serine, such as motor neuron and cognitive degeneration. Finally, outcome from the model optimisation of different recombinant proteins demonstrated clearly how the difference in protein structure and size can influence the production outcome. These results show that systematic and model-based approaches have great potential for broad de novo exploration as well as being able to handle the cellular burden associated with the production of different types of recombinant protein.
Immuno-moodulin: a new anxiogenic factor produced by autoimmune-prone T cells
Authors: Piras Giuseppa , Rattazzi Lorenza , Paschalidis Nikolaos , Oggero Silvia , Berti Giulio , Ono Masahiro , Bellia Fabio , D’Addario Claudio , Dell’Osso Bernardo , Pariante Carmine Maria , Perretti Mauro , D’Acquisto Fulvio
Published: October 2019

Patients suffering from autoimmune diseases are more susceptible to mental disorders yet, the existence of specific cellular and molecular mechanisms behind the co-morbidity of these pathologies is far from being fully elucidated. By generating transgenic mice overexpressing Annexin-A1 exclusively in T cells to study its impact in models of autoimmune diseases, we made the unpredicted observation of an increased level of anxiety. Gene microarray of Annexin-A1 CD4+T cells identified a novel anxiogenic factor, a small protein of approximately 21kDa encoded by the gene 2610019F03Rik which we named Immuno-moodulin. Neutralizing antibodies against Immuno-moodulin reverted the behavioral phenotype of Annexin-A1 transgenic mice and lowered the basal levels of anxiety in wild type mice; moreover, we also found that patients suffering from obsessive compulsive disorders show high levels of Imoodin their peripheral mononuclear cells. We thus identify this protein as a novel peripheral determinant that modulates anxiety behavior. Therapies targeting Immuno-moodulin may lead to a new type of treatment for mental disorders through regulation of the functions of the immune system, rather than directly acting on the nervous system.
Enzyme-constrained models and omics analysis of Streptomyces coelicolor reveal metabolic changes that enhance heterologous production
Authors: Sulheim Snorre , Kumelj Tjaša , van Dissel Dino , Salehzadeh-Yazdi Ali , Du Chao , van Wezel Gilles P. , Nieselt Kay , Almaas Eivind , Wentzel Alexander , Kerkhoven Eduard J
Published: October 2019

Many biosynthetic gene clusters (BGCs) require heterologous expression to realize their genetic potential, including silent and metagenomic BGCs. Although the engineeredStreptomyces coelicolorM1152 is a widely used host for heterologous expression of BGCs, a systemic understanding of how its genetic modifications affect the metabolism is lacking and limiting further development. We performed a comparative analysis of M1152 and its ancestor M145, connecting information from proteomics, transcriptomics, and cultivation data into a comprehensive picture of the metabolic differences between these strains. Instrumental to this comparison was the application of an improved consensus genome-scale metabolic model (GEM) ofS. coelicolor. Although many metabolic patterns are retained in M1152, we find that this strain suffers from oxidative stress, possibly caused by increased oxidative metabolism. Furthermore, precursor availability is likely not limiting polyketide production, implying that other strategies could be beneficial for further development ofS. coelicolorfor heterologous production of novel compounds.
Plexin-Bs enhance their GAP activity with a novel activation switch loop generating a cooperative enzyme
Authors: Li Zhen-lu , Müller-Greven Jeannine , Kim SoonJeung , Tamagnone Luca , Buck Matthias
Published: October 2019

Plexins receive guidance cues from semaphorin ligands and transmit their signal through the plasma membrane. This family of proteins is unique amongst single-pass transmembrane receptors as their intracellular regions interact directly with several small GTPases, which regulate cytoskeletal dynamics and cell adhesion. Here, we characterize the GTPase Activating Protein (GAP) function of Plexin-B1 and find that a cooperative GAP activity towards the substrate GTPase, Rap1b, is associated with the N-terminal Juxtamembrane region of Plexin-B1. Importantly, we unveil an activation mechanism of Plexin-B1 by identifying a novel functional loop which partially blocks Rap1b entry to the plexin GAP domain. Consistent with the concept of allokairy developed for other systems, Plexin-B activity is increased by an apparent substrate mediated cooperative effect. Simulations and mutagenesis suggest the repositioned JM conformation is stabilized by the new activation switch loop when the active site is occupied, giving rise to faster enzymatic turnover and cooperative behavior. The biological implications, essentially of a threshold behavior for cell migration are discussed.
Vaping nicotine-containing electronic cigarettes produces addiction-like behaviors and cardiopulmonary abnormalities in rats
Authors: Smith Lauren C. , Kallupi Marsida , Tieu Lani , Jaquish Abigail , Barr Jamie , Su Yujuan , Velarde Nathan , Sedighim Sharona , Klodnicki Mike , Carrette Lieselot L. G. , Sun Xin , de Guglielmo Giordano , George Olivier
Published: October 2019

The debate about electronic cigarettes has divided healthcare professionals, policymakers, and communities. Central points of disagreement are whether vaping electronic cigarettes are addictive and whether they produce major pulmonary complications. We developed a novel model of nicotine vapor self-administration in rats and found that rats voluntarily exposed themselves to nicotine vapor to the point of reaching blood nicotine levels that are similar to humans, exhibiting both addiction-like behaviors and cardiopulmonary abnormalities. The smoking cessation drug varenicline decreased electronic cigarette self-administration. These findings confirm the addictive properties and harmful effects of nicotine vapor and identify a potential medication for the treatment of electronic cigarette addiction.

One Sentence Summary

Vaping nicotine-containing electronic cigarettes produces cardiopulmonary abnormalities, nicotine dependence and addiction-like behaviors, which are reduced by the smoking cessation drug varenicline.
Differential sorting behavior for soluble and transmembrane cargoes at the trans-Golgi network in endocrine cells
Authors: Hummer Blake H. , Maslar Drew , Soltero Gutierrez Margarita , de Leeuw Noah F. , Asensio Cedric S.
Published: October 2019

Regulated secretion of neuropeptides and peptide hormones by secretory granules (SGs) is central to physiology. Formation of SGs occurs at the trans-Golgi network (TGN) where their soluble cargo aggregates to form a dense core, but the mechanisms controlling the sorting of regulated secretory cargoes (soluble and transmembrane) away from constitutively secreted proteins remain unclear. Optimizing the use of the retention using selective hooks (RUSH) method in (neuro-)endocrine cells, we now quantify TGN budding kinetics of constitutive and regulated secretory cargoes. We further show that, by monitoring two cargoes simultaneously, it becomes possible to visualize sorting to the constitutive and regulated secretory pathways in real-time. Further analysis of the localization of SG cargoes immediately after budding from the TGN revealed that, surprisingly, the bulk of two studied transmembrane SG cargoes (phogrin and VMAT2) does not sort directly onto SGs during budding, but rather exit the TGN into non-regulated vesicles to get incorporated to SGs at a later step. This differential behavior of soluble and transmembrane cargoes suggests a more complex model of SG biogenesis than anticipated.
Conformational dynamics at microsecond timescale in the RNA-binding regions of dsRNA-binding domains
Authors: Paithankar H , Chugh J
Published: October 2019

Double-stranded RNA-binding domains (dsRBDs) are involved in a variety of biological functions via recognition and processing of dsRNAs. Though the primary substrate of the dsRBDs are dsRNAs with A-form helical geometry; they are known to interact with structurally diverse dsRNAs. Here, we have employed two model dsRBDs – TAR-RNA binding protein and Adenosine deaminase that acts on RNA – to understand the role of intrinsic protein dynamics in RNA binding. We have performed a detailed characterization of the residue-level dynamics by NMR spectroscopy for the two dsRBDs. While the dynamics profiles at the ps-ns timescale of the two dsRBDs were found to be different, a striking similarity was observed in the μs-ms timescale dynamics for both the dsRBDs. Motions at fast μs timescale (kex > 50000 s−1) were found to be present not only in the RNA-binding residues but also in some allosteric residues of the dsRBDs. We propose that this intrinsic μs timescale dynamics observed independently in two distinct dsRBDs allows them to undergo conformational rearrangement that may aid dsRBDs to target substrate dsRNA from the pool of structurally different RNAs in cellular environment.

Statement of Significance

This study reports for the first time the detailed characterization of microsecond timescale dynamics observed in RNA-binding regions of two distinct double-stranded RNA-binding domains (dsRBDs) using NMR relaxation dispersion experiments. dsRBDs have been known to target topologically distinct dsRNAs. However, the mechanistic details of the structural adaptation of proteins is not fully understood. We propose that the presence of such dynamics may have large-scale implications in understanding the RNA recognition mechanisms by the dsRBDs.
DMD-based super-resolution structured illumination microscopy visualizes live cell dynamics at high speed and low cost
Authors: Sandmeyer Alice , Lachetta Mario , Sandmeyer Hauke , Hübner Wolfgang , Huser Thomas , Müller Marcel
Published: October 2019

Structured illumination microscopy (SIM) is among the most widely used super-resolution fluorescence microscopy techniques for visualizing the dynamics of cellular organelles, such as mitochondria, the endoplasmic reticulum, or the cytoskeleton. In its most wide-spread implementation, SIM relies on the creation of an interference pattern at the diffraction limit using the coherent addition of laser beams created by a diffraction pattern.

Spatial light modulators based on liquid crystal displays allow SIM micro-scopes to run at image rates of up to hundreds of super-resolved images per second. Digital micromirror devices are another natural choice for creating interference-based SIM patterns, but are not used to their fullest potential because of the blazed grating effect. This effect arises due to the fixed angles between which the mirrors can be switched, creating a sawtooth arrangement of mirrors and thus leading to a change in the intensity distribution of the diffracted beams. This results in SIM patterns with varying modulation contrast which are prone to reconstruction artifacts.

We have carefully studied the blazed grating effect of DMDs by simulations, varying a range of parameters and compared the simulation results with experiments. This allowed us to identify settings which result in very high modulation contrast across all angles and phases required to generate 2-beam SIM pattern. The use of inexpensive industry-grade CMOS cameras as well as low-cost lasers enabled us to construct a cost-effective, high-speed SIM system. Reconstruction of the super-resolved SIM images is achieved on a recently demonstrated parallel-computing platform, which allowed us to visualize living cells with super-resolution at multiple reconstructed frames per second in real time. We demonstrate the versatility of this new platform by imaging cellular organelle dynamics based on live-cell fluorescent stains as well as with fluorescent protein stained samples.
The maize heterotrimeric G-protein β subunit controls shoot meristem development and immune responses
Authors: Wu Qingyu , Xu Fang , Liu Lei , Char Si Nian , Ding Yezhang , Schmelz Eric , Yang Bing , Jackson David
Published: October 2019

Heterotrimeric G-proteins are important transducers of receptor signaling, functioning in plants with CLAVATA receptors in control of shoot meristem size, and with pathogen associated molecular pattern (PAMP) receptors in basal immunity. However, whether specific members of the heterotrimeric complex potentiate crosstalk between development and defense, and the extent to which these functions are conserved across species, has not been addressed. Here we used CRISPR/Cas9 to knockout the maize Gβ subunit gene, and found that the mutants were lethal, differing from Arabidopsis, where homologous mutants have normal growth and fertility. We show that lethality is not caused by a specific developmental arrest, but by autoimmunity. We used a genetic diversity screen to suppress the lethal gβ phenotype, and also identified a new maize Gβ allele with weak autoimmune responses but strong development phenotypes. Using these tools, we show that Gβ controls meristem size in maize, acting epistatically with Gα, suggesting that Gβ and Gα function in a common signaling complex. Furthermore, we used an association study to show that natural variation in Gβ influences maize kernel row number, an important agronomic trait. Our results demonstrate the dual role of Gβ in immunity and development in a cereal crop, and suggest that it functions in crosstalk between these competing signaling networks. Therefore, modification of Gβ has the potential to optimize the tradeoff between growth and defense signaling to improve agronomic production.

Significance

Cereal crops, such as maize provide our major food and feed. Crop productivity has been significantly improved by selection of favorable architecture and development alleles, however crops are constantly under attack from pathogens, which severely limits yield due to a defense-growth tradeoff. Therefore, it is critical to identify key signaling regulators that control both developmental and immune signaling, to provide basic knowledge to maximize productivity. This work shows that the maize G protein β subunit regulates both meristem development and immune signaling, and suggests that manipulation of this gene has the potential to optimize the tradeoff between yield and disease resistance to improve crop yields.
Textual analysis for China’s financial markets: a review and discussion
Authors: Huang Alan , Wu Wenfeng , Yu Tong
Published: October 2019

Purpose

This is a literature survey paper. The purpose of this paper is to focus on the latest developments in textual analysis on China’s financial markets, highlighting its differences from existing works in the US markets.

Design/methodology/approach

The authors review the literature and carry out an experiment of sentiment analysis based on a small sample of Chinese news articles.

Findings

Based on the experiment of sentiment analysis, there is limited evidence on the association between sentiment and other contemporaneous or future returns.

Originality/value

The supply of financial textual information has grown exponentially in the past decades. Technological advancements in recent years make the programming-based analysis an effective tool to digest such information. The authors highlight the use of credible textual information and discuss directions of research in this important field.
Unleashing the power of salespersons’ implementation intentions through coaching
Authors: Pousa Claudio
Published: October 2019

Purpose

The purpose of the paper is to validate if managers (through the use of managerial coaching) can help subordinates develop implementation intentions to address difficult problems and situations with customers. These implementation intentions take the form of new task strategies and go beyond the automated mechanisms of providing more effort, persisting longer in the pursuit of goals or adapting old strategies to solve new problems.

Design/methodology

We designed a cross-sectional field study with a convenience sample of 184 salespeople from different companies. Respondents provided information concerning the coaching received from their supervisors, the degree to which they were able to develop implementation intentions in future encounters with customers, and sales performance. Data was analyzed using structural equation modeling in AMOS.

Findings

We found that coaching can help salespeople develop better implementation intentions and, thus, be more effective in their interactions with customers, ultimately increasing their sales performance.

Originality

The paper explores the use of coaching to help subordinates develop new task-oriented strategies, using two theoretical frameworks: implementation intentions and goal-setting.
Cultivating voice through hands, heart, and spirit: motivating language’s role in gaining feedback
Authors: Mayfield Milton , Mayfield Jacqueline
Published: October 2019

Purpose

This manuscript presents guidelines for how managers can use communication (motivating language) to increase the feedback they receive from their followers.

Design/methodology/approach

These guidelines were developed from careful analysis of leader motivating language and follower voice literature.

Findings

Analysis results lead research based suggestions for how leaders can increase feedback from followers.

Originality/value

This manuscript will help leaders to increase needed feedback from followers on how to improve and develop organizations.
Scientometric analysis of research on “remotely piloted aircraft”
Authors: Golizadeh Hamed , Hosseini M. Reza , Martek Igor , Edwards David , Gheisari Masoud , Banihashemi Saeed , Zhang Jingxiao
Published: October 2019

Purpose

Remotely piloted aircraft (RPA) systems have emerged as an established tool within the construction industry. Concurrent with this trend has been the rise in research on RPA, establishing this as a new field of study within the construction management domain. What is needed now is an assessment of the current state of research in this emerging discipline – its strengths and weaknesses – by which future research on RPA in construction may be guided. The purpose of this paper is to address this need.

Design/methodology/approach

A total of 59 peer-reviewed journal articles covering RPAs within the construction domain were systematically reviewed using a mixed-methods approach, utilizing qualitative-scientometric analyses techniques.

Findings

The results reveal a field of study in its fledgling stage, with a limited number of experts operating somewhat in isolation, from a limited number of institutions. Key publication outlets are identified, with the main focus of research being in the technical areas of remote sensing, photogrammetry and image processing.

Practical implications

The study benefits researchers and industry practitioners alike. For researchers, the identified gaps reveal areas of high priority in future research. For construction companies, particularly small to medium-sized businesses, the study raises awareness of the latest developments and potential applicability of RPAs in the industry.

Originality/value

The study exposes what is missing from current research: a broader consideration of organizational adjustments needed to accommodate RPA usage, economic analyses and impediments to wider acceptance.
Application of lean manufacturing tools and techniques for waste reduction in Nigerian bricks production process
Authors: Aka Adefemi , Isah Abubakar Danladi , Eze Chukwudum J. , Timileyin Owolabi
Published: October 2019

Purpose

Non-value adding activities or wastes in the lean term have been the major challenge of the construction industry. Numerous studies have been conducted to investigate how such wastes can be reduced so as to improve the performance of the construction industry. However, the aspect of bricks production process (BPP) has not been extensively covered. Therefore, the purpose of this paper is to investigate the application of lean manufacturing concepts in BPP with a view to identifying the various wastes in the practice, the causes of these wastes and how such wastes can be reduced.

Design/methodology/approach

Mixed methods research design was adopted by the researchers where literature review was first conducted to establish the fundamental theories and practice standards of lean manufacturing process. Thereafter, a phenomenological study was carried out in a Shelter Clay and Brick Factory located in Minna, Niger State, Nigeria. The data obtained in the phenomenological study were analyzed through content analysis. These data served as the basis for the validation survey that subsequently followed the phenomenological study.

Findings

The findings in the study show that poor or inadequate supervision is the main factor responsible for wastes such as excessive drying of bricks, overheating of bricks and re-glazing of bricks in Nigerian BPP.

Research limitations/implications

The study focused on the various wastes in Nigerian BPP. It also focused on the various lean tools/techniques that can be adopted to reduce the wastes. Aspects such as the percentage of the wastes and their cost implication on the factory were not covered during the study and could be further investigated by prospective researchers.

Practical implications

The study provides knowledge on how lean thinking can be adopted to reduce wastes in BPP. Such knowledge may be beneficial to the present and prospective bricks producers. This implies that the proposed framework in the study allows producers of bricks to identify gaps in their implementation efforts, focus attention on areas that may require improvements, and access the benefits of lean approach in their factory products. The proposed framework may also be beneficial to the academics.

Originality/value

This paper first gain originality in the study context to propose for a lean framework that can be adopted to reduce wastes in BPP. Furthermore, the paper has not been previously published and all the information obtained from other sources are duly referenced.
Assessing students’ multimodal compositions: an analysis of the literature
Authors: Anderson Kate T. , Kachorsky Dani
Published: October 2019

Purpose

This article presents an analysis of empirical literature on classroom assessment of students’ multimodal compositions to characterize the field and make recommendations for teachers and researchers.

Design/methodology/approach

An interpretive synthesis of the literature related to practices and possibilities for assessing students’ multimodal compositions.

Findings

Findings present three overarching types of studies across the body of literature on assessment of student multimodal compositions: reshaping educational practices, promoting multiliteracies approaches to learning and evaluating students’ understanding and competence. These studies’ recommendations range along a continuum of more to less structural changes to “what counts” in classrooms.

Research limitations/implications

This review only considers studies published in English from 2000to 2019. Future studies could extend these parameters.

Practical implications

This analysis of the literature on assessing student multimodal compositions highlights foundational differences across studies’ purposes and offers guidance for educations seeking to revise their practices, whether their goals are more theoretical/philosophical, oriented toward reshaping classroom practice or focused on ways of measuring student understanding.

Social implications

Rethinking assessment can reshape educational practices to be more equitable, more theoretically commensurate with teachers’ beliefs and/or include more thorough and accurate measures of student understanding. Changes to any or all of these facets of educational practices can lead to continued discussion and change regarding the role of multimodal composition in teaching and learning.

Originality/value

This study fills a gap in the literature by considering what empirical studies suggest about why, how and what to assess with regard to multimodal compositions.
Sport logistics research: reviewing and line marking of a new field
Authors: Herold David M. , Breitbarth Tim , Schulenkorf Nico , Kummer Sebastian
Published: October 2019

Purpose

Although logistics management is a crucial part of local and global sports events, there is no research-driven characterization of “sports logistics management”. The purpose of this paper is to conceptualize a framework that allows for a more structured recognition of logistics in sports, in general, and sport event management, in particular. In addition, we conduct a systematic literature review of sports logistics management and locate opportunities for future research both for sports management and logistics management scholars.

Design/methodology/approach

Guided by Durach et al.’s (2017) systematic literature review approach, we identify key attributes and characteristics of sports logistics management. These are based on studies featuring at least partial aspects of logistics management in sports and sport events, and that were published between 2000 and mid-2019.

Findings

The study reveals that sports logistics management – meaning logistics activities in sports and sport event management – is a heavily under-researched area that provides an abundance of scientific opportunities. Based on the three sport event types of local/regional sport events, major sport events and mega sport events, the authors propose four sports logistics management pillars that are central to the proposed Sport Logistics Framework: venue logistics management, sports equipment logistics management, athletes logistics management, and fan and spectators logistics management.

Practical implications

By providing a conceptual framework for sports logistics, the authors progress towards informing the sport sector on relevant strategic and operational levels of logistics management and set the stage for empirical studies that are likely to advance sport logistics planning and management.

Originality/value

This is the first study that builds on a systematic review of literature specifically focused on the logistics aspect in sports and sport event management. It provides a conceptual framework of sports logistics management and offers an agenda of future research opportunities.
What demographics matter for organisational culture, commitment and identification?
Authors: Volkova Natalia , Chiker Vera
Published: October 2019

Purpose

The purpose of this study to establish what demographic characteristics (gender, generations and organisational tenure) play a role in employee perceptions of organisational culture, commitment and identification in Russian public organisations.

Design/methodology/approach

The data were collected electronically from 248 employees of two public organisations. Three questionnaires were used.

Findings

Organisational tenure plays a central role in the way how employees perceive organisational culture; tenure also shapes the levels of both commitment and identification. The specific finding of Russian settings is that the longer employees work for a company, the lower the levels of psychological attachments they demonstrate, while it is not the case for some existing international results. The other findings correspond with those in international studies, in which women were more psychologically attached to the organisation and showed a higher level of identification and lower rates of negative forms of this concept than men did. The older the employees are, the higher the level of identification they express.

Practical implications

Managers working in Russian settings can struggle with engaging and retaining employees. Understanding the demographic effects can help alleviate these challenges.

Originality/value

Based on empirical findings, this paper contributes to the literature on organisational socialisation by providing evidence of the damaging effects of the length of organisational tenure on psychological attachment to the company (in the form of commitment and identification). Additionally, tenure is the shaping factor of employee perception of organisational culture.