bluuebunny/crossref_metadata_2025 huggingface dataset:
A Neural Circuit Model of Proprioceptive Feedback from Muscles Recruited during an Isometric Knee Extension
Authors: York Gareth , Osborne Hugh , Sriya Piyanee , Astill Sarah , de Kamps Marc , Chakrabarty Samit
Published: October 2019

The influence of proprioceptive feedback on muscle activity during isometric tasks is the subject of conflicting studies. To better understand the relationship, we performed an isometric knee extension task experiment at four pre-set angles of the knee, recording from five muscles, and for two different hip positions. We applied muscle synergy analysis using NMF on the sEMG recordings to identify structure in the data which changed with internal knee angle, suggesting a link between proprioception and muscle activity. We hypothesised that such patterns in the data arise from the way proprioceptive and cortical signals are integrated in neural circuits of the spinal cord. Using the MIIND neural simulation platform, we developed a computational model based on current understanding of spinal circuits with an adjustable proprioceptive input. The model produces the same synergy patterns as observed in the experimental data indicating that such synergies are indeed encoded in the neural connectivity of the spinal cord and modulated by the proprioceptive input. When matching the proprioceptive input to the knee angles of the experiment, the model predicts the need for three distinct inputs: two to control the normal reciprocity between the agonist and antagonist muscles, and an additional to match the non-linear trend towards the limit of extension. Finally, we discuss the risks of using NMF for synergy analysis and demonstrate how to increase confidence in its results. Future modelling of human motor outputs should include interneuronal spinal circuits such as this to distinguish the modulatory role of supraspinal and peripheral afferent inputs to the spinal cord, during both passive and dynamic tasks.

Significance statement

Sensory feedback from muscles has a significant role in motor control, but its role in tasks where limbs are held in a fixed position is disputed, because the effect is reduced when muscles are not stretched. Here, we first identified patterns of muscle activity during such tasks which changed with different leg positions. We developed a computational spinal motor circuit model with adjustable muscle stretch input, which reproduced the same patterns of activity as observed experimentally. The model predicts three distinct muscle stretch signals required to produce the activity patterns for all leg positions. Because the connections in the model are based on well known spinal circuits, it is likely the observed activity patterns are generated in the spinal cord.
Champagne: Whole-genome phylogenomic character matrix method places Myomorpha basal in Rodentia
Authors: Schull James Kusik , Turakhia Yatish , Dally William J. , Bejerano Gill
Published: October 2019

We present Champagne, a whole-genome method for generating character matrices for phylogenomic analysis using large genomic events that, by rigorously picking orthologous genes and locating large, virtually homoplasy-free insertion and deletion events, delivers a character matrix that outperforms existing morphological and nucleotide-based matrices on both established phylogenies, and difficult-to-resolve nodes in the mammalian tree. Champagne harbors distinct theoretical advantages, and can easily be run on any clade of related species, of the many currently being sequenced. Champagne considerably improves the retention index in the parsimony analysis of a number of widely established topologies, observes incomplete lineage sorting (ILS) at the root of Paenungulata, finds little evidence for human-chimp-gorilla ILS, and most surprisingly, offers convincing evidence for a reconsideration of squirrel’s position in the rodent tree.
DNA demethylation is a driver for chick retina regeneration
Authors: Luz-Madrigal Agustín , Grajales-Esquivel Erika , Tangeman Jared , Kosse Sarah , Liu Lin , Wang Kai , Fausey Andrew , Liang Chun , Tsonis Panagiotis A. , Rio-Tsonis Katia Del
Published: October 2019

Background

A promising avenue toward human retina regeneration lies in identifying the factors that promote cellular reprogramming to retinal neurons in organisms able to undergo retina regeneration. The embryonic chick can regenerate a complete neural retina, after retinectomy, via retinal pigment epithelium (RPE) reprogramming in the presence of FGF2. Cellular reprogramming resets the epigenetic landscape to drive shifts in transcriptional programs and cell identity. Here, we systematically analyzed the reprogramming competent chick RPE prior to injury, and during different stages of reprogramming. We examined the dynamic changes in the levels and distribution of histone marks and DNA modifications, as well as conducted a comprehensive analysis of the DNA methylome during this process.

Results

In addition to changes in the expression of genes associated with epigenetic modifications during RPE reprogramming, we observed dynamic changes in histone marks and intermediates of the process of DNA demethylation. At early times after injury, H3K27me3 and 5mC repression marks decreased while 5caC and the H3K4me3 activation mark increased, suggesting genome-wide changes in the bivalent chromatin, impaired DNA methylation, and active DNA demethylation in the chromatin reconfiguration of reprogramming RPE. Comprehensive analysis of the methylome by whole-genome bisulfite sequencing (WGBS) confirmed extensive rearrangements of DNA methylation patterns including differentially methylated regions (DMRs) found at promoters of genes associated with chromatin organization and fibroblast growth factor production. In contrast, genes associated with early RPE reprogramming are hypomethylated in the intact RPE and remain hypomethylated during the process. During the generation of a neuroepithelium (NE) at later stages of reprogramming, decreased levels of H3K27me3, 5mC, and 5hmC coincide with elevated levels of H3K27Ac and 5caC, indicating an active demethylation process and genome-wide changes in the active regulatory landscape. Finally, we identify Tet methylcytosine dioxygenase 3 (TET3) as an important factor for DNA demethylation and retina regeneration in the embryonic chick, capable of reprogramming RPE in the absence of exogenous FGF2.

Conclusion

Our results demonstrated that injury signals early in RPE reprogramming trigger genome-wide dynamic changes in chromatin, including bivalent chromatin and DNA methylation. In the presence of FGF2 these dynamic modifications are further sustained in the commitment to form a new retina. We identify DNA demethylation as a key process driving the process of RPE reprogramming and identified TET3 as a factor able to reprogram RPE in absence of FGF2. Our findings reveal active DNA demethylation as an important process that may be applied to remove the epigenetic barriers in order to regenerate retina in mammals.
Polymorphisms inBrucellaCarbonic anhydrase II mediate CO2dependence and fitnessin vivo
Authors: García-Lobo JM , Ortiz Y , González-Riancho C , Seoane A , Arellano-Reynoso B , Sangari FJ
Published: October 2019

SomeBrucellaisolates are known to require an increased concentration of CO2for growth, especially in the case of primary cultures obtained directly from infected animals. Moreover, the differentBrucellaspecies and biovars show a characteristic pattern of CO2requirement, and this trait has been included among the routine typing tests used for species and biovar differentiation. By comparing the differences in gene content among different CO2-dependent and CO2-independentBrucellastrains we have confirmed that carbonic anhydrase II (CA II), is the enzyme responsible for this phenotype in all theBrucellastrains tested.Brucellaspecies contain two carbonic anhydrases of the β family, CA I and CA II; genetic polymorphisms exist for both of them in different isolates, but only those putatively affecting the activity of CA II correlate with the CO2requirement of the corresponding isolate. Analysis of these polymorphisms does not allow the determination of CA I functionality, while the polymorphisms in CA II consist of small deletions that cause a frameshift that changes the C-terminus of the protein, probably affecting its dimerization status, essential for the activity.

CO2-independent mutants arise easilyin vitro, although with a low frequency ranging from 10−6to 10−10depending on the strain. These mutants carry compensatory mutations that produce a full length CA II. At the same time, no change was observed in the sequence coding for CA I. A competitive index assay designed to evaluate the fitness of a CO2-dependent strain compared to its corresponding CO2-independent strain revealed that while there is no significant difference when the bacteria are grown in culture plates, growthin vivoin a mouse model of infection provides a significant advantage to the CO2-dependent strain. This could explain why someBrucellaisolates are CO2-dependent in primary isolation. The polymorphism described here also allows thein silicodetermination of the CO2requirement status of anyBrucellastrain.
A novel major output target for pheromone-sensitive projection neurons in male moths
Authors: Chu Xi , Heinze Stanley , Ian Elena , Berg Bente G.
Published: October 2019

The male-specific macroglomerular complex (MGC) in the moth antennal lobe contains circuitry dedicated to pheromone processing. Output neurons from this region project along three parallel pathways, the medial, mediolateral, and lateral tracts. The MGC-neurons of the lateral tract are least described and their functional significance is unknown. We used mass-staining, calcium imaging, and intracellular recording/staining to characterize the morphological and physiological properties of these neurons in Helicoverpa armigera. All lateral-tract MGC neurons targeted the column, a small region within the superior intermediate neuropil. We identified this region as the major converging site for lateral-tract neurons responsive to pheromones and plant-odors. The lateral-tract MGC-neurons consistently responded with a faster onset than the well-described medial-tract neurons. Different from the medial-tract MGC neurons encoding odor quality important for signal identification, those in the lateral tract seem to convey a robust and rapid, but fixed signal – potentially important for fast control of hard-wired behavior.
Impaired renal gluconeogenesis is a major determinant of acute kidney injury associated mortality
Authors: Legouis David , Ricksten Sven-Erick , Faivre Anna , Gariani Karim , Galichon Pierre , Berchtold Lena , Feraille Eric , Koppitch Kari , Hertig Alexandre , Martin Pierre-Yves , Naesens Maarten , Pugin Jérôme , McMahon Andrew P , Cippà Pietro E , de Seigneux Sophie
Published: October 2019

Nature letter

Acute Kidney Injury (AKI) is strongly associated with adverse outcome and mortality independently of the cause of renal damage1-3. The mechanisms determining the deleterious systemic effects of AKI are poorly understood and specific interventions, including optimization of renal replacement therapy, had a marginal effect on AKI-associated mortality in clinical trials4-8. The kidney contributes to up to 40% of systemic glucose production by gluconeogenesis during fasting and stress conditions, mainly synthesized from lactate in the proximal tubule9-12, rendering this organ a major systemic lactate disposal13. Whether kidney gluconeogenesis is impaired during AKI and how this might influence systemic metabolism remains unknown. Here we demonstrate that glucose production and lactate clearance are impaired during human AKI using renal arteriovenous catheterization in patients. Using single cell transcriptomics in mice and RNA sequencing in human biopsies, we show that glycolytic and gluconeogenetic pathways are modified during AKI in the proximal tubule specifically, explaining the metabolic alterations. We further demonstrate that impaired renal gluconeogenesis and lactate clearance during AKI are major determinants of systemic glucose and lactate levels in critically ill patients. Most importantly, altered glucose metabolism in AKI emerged as a major determinant of AKI-associated mortality. Thiamine supplementation restored renal glucose metabolism and substantially reduced AKI-associated mortality in intensive care patients. This study highlights an unappreciated systemic role of renal glucose and lactate metabolism in stress conditions, delineates general mechanisms explaining AKI-associated mortality and introduces a potential therapeutic intervention for a highly prevalent clinical condition with limited therapeutic options.
Drug Combination Antagonism and Single Agent Dominance Result from Differences in Death Activation Kinetics
Authors: Richards Ryan , Schwartz Hannah R. , Stewart Mariah S. , Cruz-Gordillo Peter , Honeywell Megan E. , Joyce Anna J. , Landry Benjamin D. , Lee Michael J.
Published: October 2019

Therapeutic regimens for cancer generally involve drugs used in combinations. Most prior work has focused on identifying and understanding synergistic drug-drug interactions; however, understanding sources of antagonistic interactions remains an important and understudied issue. To enrich for antagonistic interactions and reveal common features of these drug combinations, we screened all pairwise combinations of drugs characterized as canonical activators of different forms of regulated cell death. We find that this network is strongly enriched for antagonistic interactions, and in particular, enriched for an extreme form of antagonism, which we call “single agent dominance”. Single agent dominance refers to antagonisms in which a two drug combination phenocopies one of the two agents. We find that dominance results from differences in the cell death onset time, with dominant drugs inducing death earlier and at faster rates than their suppressed counterparts. Finally, we explored the mechanisms by which parthanatotic agents dominate apoptotic agents, finding that dominance in this scenario is caused by mutually exclusive and conflicting use of PARP1. Taken together, our study reveals death activation kinetics as a predictive feature of antagonism, due to inhibitory crosstalk between cell death pathways.
Targeting endogenous K-RAS for degradation through the affinity-directed protein missile system
Authors: Röth Sascha , Macartney Thomas J. , Konopacka Agnieszka , Queisser Markus A. , Sapkota Gopal P.
Published: October 2019

For over three decades,K-RAShas been known as the holy grail of cancer targets, one of the most frequently mutated oncogenes in cancer. Because the development of conventional small molecule K-RAS inhibitors has been extremely challenging, K-RAS has been dubbed as an undruggable target, and only recently a mutation specific inhibitor has reached clinical trials. Targeted protein degradation has emerged as a new modality in drug discovery to tackle undruggable targets. However, no degrader for K-RAS has been described thus far. Our laboratory has developed an Affinity-directed PROtein Missile (AdPROM) system for targeted proteolysis of endogenous proteins through the ubiquitin proteasome system. Here, we show that we can achieve degradation of endogenous K-RAS and H-RAS in different cell lines in a targeted manner using our AdPROM system. Our findings imply that endogenous RAS proteins can be targeted for proteolysis, thereby offering tantalising possibilities for an alternative therapeutic approach to these so-called undruggable targets in cancer.
Cryo-electron microscopy structure of a nucleosome-bound SWI/SNF chromatin remodeling complex
Authors: Han Yan , Reyes Alexis A , Malik Sara , He Yuan
Published: October 2019

The multi-subunit chromatin remodeling complex SWI/SNF1–3 is highly conserved from yeast to humans and plays critical roles in various cellular processes including transcription and DNA damage repair4, 5. It uses the energy from ATP hydrolysis to remodel chromatin structure by sliding and evicting the histone octamer6–10, creating DNA regions that become accessible to other essential protein complexes. However, our mechanistic understanding of the chromatin remodeling activity is largely hindered by the lack of a high-resolution structure of any complex from this family. Here we report the first structure of SWI/SNF from the yeast S. cerevisiae bound to a nucleosome at near atomic resolution determined by cryo-electron microscopy (cryo-EM). In the structure, the Arp module is sandwiched between the ATPase and the Body module of the complex, with the Snf2 HSA domain connecting all modules. The HSA domain also extends into the Body and anchors at the opposite side of the complex. The Body contains an assembly scaffold composed of conserved subunits Snf12 (SMARCD/BAF60), Snf5 (SMARCB1/BAF47/ INI1) and an asymmetric dimer of Swi3 (SMARCC/BAF155/170). Another conserved subunit Swi1 (ARID1/BAF250) folds into an Armadillo (ARM) repeat domain that resides in the core of the SWI/SNF Body, acting as a molecular hub. In addition to the interaction between Snf2 and the nucleosome, we also observed interactions between the conserved Snf5 subunit and the histones at the acidic patch, which could serve as an anchor point during active DNA translocation. Our structure allows us to map and rationalize a subset of cancer-related mutations in the human SWI/SNF complex and propose a model of how SWI/SNF recognizes and remodels the +1 nucleosome to generate nucleosome-depleted regions during gene activation11–13.
Dynamic interactions and intracellular fate of label-free, thin graphene oxide sheets within mammalian cells: role of lateral sheet size
Authors: Chen Yingxian , Rivers-Auty Jack , Crică Livia Elena , Barr Katie , Rosano Vinicio , Arranz Adrian Esteban , Loret Thomas , Spiller David , Bussy Cyrill , Kostarelos Kostas , Vranic Sandra
Published: October 2019

Graphene oxide (GO) holds great potential for biomedical applications, however fundamental understanding of the way it interacts with biological systems is still lacking even though it is essential for successful clinical translation. In this study, we exploit intrinsic fluorescent properties of thin GO sheets to establish the relationship between lateral dimensions of the material, its cellular uptake mechanisms and intracellular fate over time. Label-free GO with distinct lateral dimensions, small (s-GO) and ultra-small (us-GO) were thoroughly characterised both in water and in biologically relevant cell culture medium. Interactions of the material with a range of non-phagocytic mammalian cell lines (BEAS-2B, NIH/3T3, HaCaT, 293T) were studied using a combination of complementary analytical techniques (confocal microscopy, flow cytometry and TEM). The uptake mechanism was initially interrogated using a range of pharmaceutical inhibitors and validated using polystyrene beads of different diameters (0.1 and 1 μm). Subsequently, RNA-Seq was used to follow the changes in the uptake mechanism used to internalize s-GO flakes over time. Regardless of lateral dimensions, both types of GO were found to interact with the plasma membrane and to be internalized by a panel of cell lines studied. However, s-GO was internalized mainly via macropinocytosis while us-GO was mainly internalized via clathrin- and caveolae-mediated endocytosis. Importantly, we report the shift from macropinocytosis to clathrin-dependent endocytosis in the uptake of s-GO at 24 h, mediated by upregulation of mTORC1/2 pathway. Finally, we show that both s-GO and us-GO terminate in lysosomal compartments for up to 48 h. Our results offer an insight into the mechanism of interaction of GO with non-phagocytic cell lines over time that can be exploited for the design of biomedically-applicable 2D transport systems.
Classification of platelet aggregates by agonist type
Authors: Zhou Yuqi , Yasumoto Atsushi , Lei Cheng , Huang Chun-Jung , Kobayashi Hirofumi , Wu Yunzhao , Yan Sheng , Sun Chia-Wei , Yatomi Yutaka , Goda Keisuke
Published: October 2019

Platelets are anucleate cells in blood whose principal function is to stop bleeding by forming aggregates for hemostatic reactions. In addition to their participation in physiological hemostasis, platelet aggregates are also involved in pathological thrombosis and play an important role in inflammation, atherosclerosis, and cancer metastasis. The aggregation of platelets is elicited by various agonists, but these platelet aggregates have long been considered indistinguishable and impossible to classify. Here we present an intelligent method for classifying them by agonist type. It is based on a convolutional neural network trained by high-throughput imaging flow cytometry of blood cells to identify and differentiate subtle yet appreciable morphological features of platelet aggregates activated by different types of agonists. The method is a powerful tool for studying the underlying mechanism of platelet aggregation and is expected to open a window on an entirely new class of clinical diagnostics, pharmacometrics, and therapeutics.
A memory of RPS25 loss drives resistance phenotypes
Authors: Johnson Alex G. , Flynn Ryan A. , Lapointe Christopher P. , Ooi Yaw Shin , Zhao Michael L. , Richards Christopher M. , Qiao Wenjie , Yamada Shizuka B. , Couthouis Julien , Gitler Aaron D. , Carette Jan E. , Puglisi Joseph D.
Published: October 2019

In order to maintain cellular protein homeostasis, ribosomes are safeguarded against dysregulation by myriad processes. Many cell types can nonetheless withstand genetic lesions of certain ribosomal protein genes, some of which are linked to diverse cellular phenotypes and human disease. However, the direct and indirect consequences from sustained alterations in ribosomal protein levels are poorly understood. To address this knowledge gap, we studied in vitro and cellular consequences that follow genetic knockout of the ribosomal proteins RPS25 or RACK1 in a human cell line, as both proteins are implicated in direct translational control. Prompted by the unexpected detection of an off-target ribosome alteration in the RPS25 knockout, we closely interrogated cellular phenotypes. We found that multiple RPS25 knockout clones display viral- and toxin-resistance phenotypes that cannot be rescued by functional cDNA expression, suggesting that RPS25 loss elicits a cell state transition. We characterized this state and found that it underlies pleiotropic phenotypes and has a common rewiring of gene expression. Rescuing RPS25 expression by genomic locus repair failed to correct for the phenotypic and expression hysteresis. Our findings illustrate how the elasticity of cells to a ribosome perturbation can drive specific phenotypic outcomes that are indirectly linked to translation.
In vivo imaging defines vascular interplay in the development of lymphocytic leukemia in zebrafish models
Authors: Revskoy Sergei , Blair Margaret E. , Powell Shaw M. , Hausman Elizabeth S. , Blackburn Jessica S.
Published: October 2019

The vascular microenvironment at the primary tumor site is represented by functionally diverse types of vessels that contribute to metabolic supply, trafficking/dissemination of tumor cells, and delivery of chemotherapeutics. However, the role of leukemia-associated vascular networks in leukemia progression remains poorly understood. We utilized a MYC-induced T cell leukemia model in zebrafish to assess the involvement of vascular endothelial growth factor A-dependent (VEGFR2+), VEGFA-independent vasculature (VEGFR2-), and lymphatics in the initial stages of leukemia cell dissemination using intravital microscopy. Leukemogenesis underwent sequential progression, from initial successive emigration of single leukemic cells from the thymus towards the kidney marrow, followed by collective migration in a dorsal-lateral direction with scattered migration from the ventral thymus towards the aortic arches, before streaming towards the rostral kidney area. Trafficking appeared independent of VEGFR2+ vasculature but was closely associated with VEGFR2-microvessels, and, interestingly, leukemic cells did not utilize lymphatics during initial dissemination. Overall, leukemic cells appeared to utilize the same routes as normal T cell progenitors during development but in a reverse order, and primarily recruited VEGFR2-microvessels during the initial stages of progression. Ultimately, interfering with leukemia cell migration by targeting vascular networks may represent a new therapeutic strategy to control leukemia progression.
Spatiotemporal control of gene expression boundaries using a feedforward loop
Authors: Bandodkar Prasad U. , Asafen Hadel Al , Reeves Gregory T.
Published: October 2019

A feed forward loop (FFL) is commonly observed in several biological networks. The FFL network motif has been mostly been studied with respect to variation of the input signal in time, with only a few studies of FFL activity in a spatially distributed system such as morphogen-mediated tissue patterning. However, most morphogen gradients also evolve in time. We studied the spatiotemporal behavior of a coherent FFL in two contexts: (1) a generic, oscillating morphogen gradient and (2) the dorsal-ventral patterning of the earlyDrosophilaembryo by a gradient of the NF-κB homolog Dorsal with its early target Twist. In both models, we found features in the dynamics of the intermediate node – phase difference and noise filtering – that were largely independent of the parameterization of the models, and thus were functions of the structure of the FFL itself. In the Dorsal gradient model, we also found that the dynamics of Dorsal require maternal pioneering factor Zelda for proper target gene expression.
Exosomes transmit retroelement RNAs to drive inflammation and immunosuppression in Ewing Sarcoma
Authors: Evdokimova Valentina , Ruzanov Peter , Gassmann Hendrik , Zaidi Syed H. , Peltekova Vanya , Heisler Lawrence E. , McPherson John D. , Orlic-Milacic Marija , Specht Katja , Steiger Katja , Schober Sebastian J. , Thiel Uwe , McKee Trevor D. , Zaidi Mark , Spring Christopher M. , Lapouble Eve , Delattre Olivier , Burdach Stefan , Stein Lincoln D. , Sorensen Poul H.
Published: October 2019

Ewing sarcoma (EwS) is an aggressive childhood malignancy with a high propensity for metastasis. By analyzing cohorts of patients and age-matched healthy donors, we establish that EwS metastatic progression is accompanied by elevated plasma levels of multiple proinflammatory cytokines, interferons and extracellular vesicles (EVs). The latter were enriched with transcripts derived from LINE, SINE and ERV retroelements and from locus-specific pericentromeric regions, including HSAT2. We show that some of these RNAs, including HSAT2 and HERV-K, are selectively transmitted in EwS EVs and taken up by stromal fibroblasts and peripheral blood CD33+ myeloid cells and CD8+ T-cells, inducing immune exhaustion, immunosuppressive phenotypes and proinflammatory responses. Moreover, EwS EV-derived repeat RNAs were propagated and serially transmitted in recipient cell EVs, reminiscent of viral infection. As such, this study uncovers a novel mechanism driving cancer-associated inflammation, immunosuppression and metastatic progression.
Identification of peptides interfering the lrrk2/pp1 interaction
Authors: Dong Chang Zhi , Bruzzoni-Giovanell Heriberto , Yu Yanhua , Dorgham Karim , Parizot Christophe , Zini Jean Marc , Tuffery Pierre , Rebollo Angelita
Published: October 2019

Serine/threonine phosphatases are responsible for counteracting the effect of the protein kinases implicated in the development of several pathologies. Here we identified by PEP-scan approach the sequence of a fragment of LRRK2, a Parkinson’s disease associated protein, interacting with the phosphatase PP1. The fragment, that is located in a LRRK2 domain of undefined function, was associated in N-terminal to an optimized cell penetrating peptide in order to study their in vitro and in vivo biological activity. From this original sequence, we developed and studied five interfering peptides (IPs) and identified two peptides able to disrupt the LRRK2/PP1 interaction by in vitro competition in anti-LRRK2 immunoprecipitates. Using FITC-labelled peptides, we confirmed the internalization of the peptides in cell lines as well as in and primary human normal and pathological cells. Finally, we have confirmed by ELISA test the association of Mut3DPT-LRRK2-Long and Mut3DPT-LRRK2-Short peptides to purified PP1 protein in a selective manner. The shortest peptides, MuteDPT-LRRK2-5 to 8 with either N or C-terminal deletions are not able neither disrupt the association LRRK2/PP1 nor to associate to purified PP1 protein. The peptides Mut3DPT-LRRK2-Long and Mut3DPT-LRRK2-Short may be new tools to study the role of LRRK2/PP1 interaction in normal and pathological conditions.
Performance of agricultural cooperative banks in Japan
Authors: Harimaya Kozo , Kagitani Koichi
Published: October 2019

Purpose

The purpose of this paper is to investigate the efficiency of the banking business of Japan’s agricultural cooperatives (JAs), which depend heavily on financial business with non-farmers, contradictory to cooperative principles.

Design/methodology/approach

The authors construct a panel data set over 2005–2016 from the financial statements of JAs’ prefectural-level federations and use the input distance stochastic frontier model with a time-variant inefficiency effect for analysis. Both the flow and stock measures of the banking output are used in identical models and the efficiency results are compared. The authors also investigate the determinants of efficiency by using the Tobit and ordinary least squares regression models.

Findings

There is strong evidence of significant prefectural differences in efficiency values. The ratio of lending to non-members to total loans is positively related to efficiency. In contrast, the higher reliance on a central organization and credit business leads to lower efficiency.

Research limitations/implications

Apart from banking, JAs provide mutual insurance business services. As the authors investigate only the efficiency of JAs’ banking business in this study, it would be necessary to investigate the efficiency of their insurance business as well when evaluating JAs’ overall financial business.

Originality/value

There are few studies that investigate the efficiency of JAs’ banking business and its determinants, although significant attention has been paid to their excessive dependence on the financial business.
The effects of intangible assets on firm performance
Authors: Ferdaous Jannatul , Rahman Mohammad Mizanur
Published: October 2019

Purpose

Using the resource-based view and knowledge-based view as theoretical backdrop, the purpose of this paper is to explore the relationship between intangible assets and firm performance.

Design/methodology/approach

The firms’ audited annual reports were collected during the period of 2007–2017 from 49 listed manufacturing firms of four industries in DSE, Bangladesh. This inductive research uses panel data (fixed-effect) estimation technique for balanced panel data to measure, describe, and analyze the firm performance.

Findings

After controlling some specific variables, the results reveal mixed behavioral effects of intangible assets on firm performance. Even if intangible assets trigger a significant rise in the firms’ EPS (a measure of financial performance), the firms cannot maximize shareholders’ wealth due to their poor performance in the stock market of Bangladesh.

Practical implications

The proposed models could be important tools for managers to integrate intangible assets in their decision process. The proposed models could also be important tools for investors to select their portfolios that have a track record for continuous investment in intangible assets in an efficient and sustainable way.

Originality/value

Intangible assets are largely absent from the firms’ balance sheet. Consequently, previous empirical research works struggled to measure and quantify the effects of intangible assets on firm performance. The study fills that gap in the understanding of intangible assets’ nature, measurement method, and their effects on firm performance.
Performance analysis of differential spin hall effect (DSHE)-MRAM-based logic gates
Authors: Tankwal Piyush , Nehra Vikas , Prajapati Sanjay , Kaushik Brajesh Kumar
Published: October 2019

Purpose

The purpose of this paper is to analyze and compare the characteristics of hybrid conventional complementary metal oxide semiconductor/magnetic tunnel junction (CMOS/MTJ) logic gates based on spin transfer torque (STT) and differential spin Hall effect (DSHE) magnetic random access memory (MRAM).

Design/methodology/approach

Spintronics technology can be used as an alternative to CMOS technology as it is having comparatively low power dissipation, non-volatility, high density and high endurance. MTJ is the basic spin based device that stores data in form of electron spin instead of charge. Two mechanisms, namely, STT and SHE, are used to switch the magnetization of MTJ.

Findings

It is observed that the power consumption in DSHE based logic gates is 95.6% less than the STT based gates. DSHE-based write circuit consumes only 5.28 fJ energy per bit.

Originality/value

This paper describes how the DSHE-MRAM is more effective for implementing logic circuits in comparison to STT-MRAM.
“Everybody needs everyone”: a case study of workplace learning after a downsize
Authors: Miller Sarah M. , Kim JungHwan , Lim Doo Hun
Published: October 2019

Purpose

This study aims to explore how employees’ emotions after downsizing impact their learning that they partook in after the downsizing event.

Design/methodology/approach

The methodological approach was a qualitative case study. Nine employees, considered layoff survivors in a downsized organization, participated in semi-structured interviews. For data analysis, authors performed an initial, focused and axial coding.

Findings

The findings highlight three themes: “resilience,” “loyalty” and “moral support.” These themes show the empathy that layoff survivors experienced and the impact the layoff had on their commitment to the organization, as well as the social learning that occurred after downsizing.

Practical implications

Downsized organizations need to consider the emotions of employees who survive layoffs and how layoffs impact their behavior at work, particularly their learning behavior. Organizations need to understand how to positively impact layoff survivors’ emotions to influence the survivors’ willingness to learn and implement the changes within the organization. Providing outlets for survivors to network within the company, as well as meaningful opportunities, is one of the few ways of addressing employees’ emotions and ensuring they will be encouraged to change with the organization.

Originality/value

Research that explores how emotions resulting from an organizational downsize impact employees’ learning is minimal. Although much of the downsizing research does explore layoff survivors’ experiences after a downsizing, it does not address the emotional factors or the learning experiences. This study seeks to fill this gap.
A neuroscientific perspective of a mixed-use lifestyle center
Authors: Rosenbaum Mark Scott , Ramirez German Contreras
Published: October 2019

Purpose

This paper aims to explore consumers’ cognitive responses to the presence of other people in a planned lifestyle center. The featured lifestyle center contains shopping, lodging, dining and retail options in an open-air setting full of natural elements. This work helps explain the affinity of consumers to lifestyle centers and shows marketing researchers and practitioners how to use neuroscience hardware and software in service design research.

Design/methodology/approach

The study draws on social impact theory to show how the social presence of others in a lifestyle center influences six different cognitive responses. The authors evaluate consumers’ cognitive responses by using the Emotiv EPOC+ headset to obtain electroencephalogram recordings. To interpret these recordings, they use EmotivPro software, which provides readings on six emotional states, including excitement, interest, stress, engagement, attention and relaxation.

Findings

The data obtained from mall shoppers reveal that the presence of other people in a lifestyle center evokes high levels of interest and excitement and encourages relaxation.

Research limitations/implications

The paper shows marketers how to use neural data to obtain insights into consumers’ cognitive responses to stimuli by using Emotiv headsets and software.

Practical implications

The results show the importance of social elements in encouraging customers to approach and spend time in lifestyle centers.

Originality/value

The paper is one of the first to explore consumers’ responses to strangers in shared settings using neuroscience.
A systematic review of the servant leadership literature in management and hospitality
Authors: Bavik Ali
Published: October 2019

Purpose

The purpose of this study is two-fold. First, it systematically reviews and synthesizes research on servant leadership in management and hospitality management literature. Second, by reviewing and comparing the characteristics of the hospitality industry and servant leadership attributes, this study provides insights concerning the conceptualizations and theorization of servant leadership in hospitality management and discusses future research directions.

Design/methodology/approach

The current study reviewed 106 articles published during the period of 1970 to 2018 in hospitality management and broader management literature.

Findings

The characteristics of the hospitality industry and servant leadership attributes were found to be mutually inclusive, both consisting qualities such as trust, integrity, honesty, care, servant behavior, listening and community focus.

Practical implications

Scholars should concentrate on exploring what makes servant leaders unique in the hospitality industry.

Originality/value

The study reviews the hospitality characteristics, and servant leadership attributes offer new research avenues.
Blockchain: a paradigm shift in business practices
Authors: Kizildag Murat , Dogru Tarik , Zhang Tingting (Christina) , Mody Makarand Amrish , Altin Mehmet , Ozturk Ahmet Bulent , Ozdemir Ozgur
Published: October 2019

Purpose

The purpose of this paper is to introduce and explore blockchain technology and its potential implementation to hospitality and tourism firms’ wide range of business operations and transactions from a technological and functional point of view. This study’s central interest is to produce novel and rigorous in-depth-review analysis and foundations for a broad discussion and outlook on the potential applications of blockchain technology benefiting hospitality and tourism research, as well as the industry as a whole.

Design/methodology/approach

This study identifies and proposes several potential areas of the adoption and implementation of blockchain technology to the hospitality and tourism industry, including payment and cryptocurrencies, tracking and service customization, the disintermediation of hospitality and tourism, innovative loyalty programs, smart contracts, integrated property management systems, verified rating and review systems, collaborative initiatives and due diligence and smart tourism, each of which represents fertile avenues for future research.

Findings

This paper provides extensive critical discussions, reviews and answers to a fundamental question: “What critical functions of Blockchain mechanisms can be implemented to the existing core operational (i.e. booking and reservation systems, guest management, etc.) and business functions (i.e. loyalty/reward programs, agent transactions, etc.) of hospitality and tourism companies?”.

Research limitations/implications

Future studies should specifically delve further into various angles of this “BizTech” environment based not only on business operations and competition but also on vendor and customer collaboration.

Practical implications

This study intends to serve as a guidance for future research, facilitate knowledge accumulation and create a new understanding and awareness in both practice and academia. One of the most important applications of blockchain in this industry would be that pertaining to direct booking, online reservation systems (i.e. airlines and online travel agencies) and check-in/out with digital identities. With industry-wide blockchain adoption, guests’ personal information can be digitally validated, saved and secured as previously established cryptographically secured codes verify one’s identity without disclosing essential personal information.

Originality/value

It is obvious that the hospitality and tourism industry needs urgent technological transformation, industrial innovations and new growth avenues such as the adoption of blockchain technology and systems to maintain its global market share in the future. Therefore, the implementation of blockchain systems can promote the formation of multi-center (i.e. guest operations and customer service), weakly intermediated (i.e. loyalty programs and/or review and rating systems) areas in this industry.
SME employee performance appraisal formalization and trust in leadership change
Authors: Belsito Carrie Anne , Reutzel Christopher Ray
Published: October 2019

Purpose

This study aims to examine the influence of employee performance appraisal (PA) formalization on changes to one component of the employee–leadership social exchange relationship within the context of small and medium-sized enterprises (SMEs). Specifically, it builds upon extant research on human resource management within SMEs, performance appraisals and social exchange theory to consider the role of performance appraisal formalization in effecting change in the level of trust employees have in their leaders.

Design/methodology/approach

To test study hypotheses, this study analyzes responses to two survey waves completed by employees of a US-based SME operating within the commercial construction industry. This SME formalized the PA process in between the administration of the first and second surveys. Study data were analyzed using hierarchical ordinary least squares regression.

Findings

The results of this study suggest that the formalization of PA has a positive effect on change in trust in leadership (TIL). Study results also suggest that employee perceptions of PA utility, procedural justice and satisfaction with the PA process are positively related to changes in TIL. This study also found that the effects of employee perceptions of PA utility and procedural justice on changes in TIL are mediated by employee satisfaction with the PA process.

Research limitations/implications

As a consequence of study design, the results found in this study may be limited with respect to their external validity. Researchers and practitioners are encouraged to use caution before generalizing study findings to other contexts.

Practical implications

This study suggests that PA formalization represents a means of increasing employee trust. Moreover, study results suggest that SME leaders hoping to increase employee TIL should be thoughtful about how they implement the PA process, paying particular attention to the usefulness of the feedback they provide and ensuring that the process of PA is viewed as being fair by employees. In doing so, SME leaders will enhance their employees’ satisfaction with the PA process, thereby increasing the trust they place in SME leadership.

Originality/value

This study extends research by considering the consequences of PA formalization with respect to changes in SME employee TIL. In doing so, this study heeds calls for additional research on the consequences of PA within SMEs, as well as sheds light on how PA formalization shapes the relationship between SME employees and leaders.
The importance of Interactive Network Branding for business relationship development: insights from emerging markets
Authors: Koporcic Nikolina , Ivanova-Gongne Maria
Published: October 2019

Purpose

This paper aims to clarify the meaning of Interactive Network Branding (INB) and demonstrate its importance for business relationship development, within a cross-cultural context of emerging markets (EM). More specifically, it integrates the idea of INB through its three branding dimensions into the first three relationship development stages introduced in the seminal article by Ford (1980). By bringing INB into relationship development, and by considering its embeddedness in a cultural context, the study extends current understanding of business relationships in connection to corporate branding.

Design/methodology/approach

The study is empirical and explorative. To reach the research aims, the authors apply a qualitative approach and present findings from four business relationships in two EM contexts, namely, the Croatian and Russian markets. Ten interviews have been undertaken, and the analysis was conducted by applying sensemaking and narrative approaches.

Findings

Findings show the influence of INB dimensions on three stages of business relationship development. In both EMs, the external dimension is found to be dominant for the pre-relationship stage while the internal dimension for the early stage. At the same time, mutual INB dimension, which is built on interpersonal interactions, is influencing each stage to a certain manner, while being a dominant dimension in the development stage. Also, the role of each dimension in a specific stage of relationship development is conditioned by the cultural context in which business relationships are embedded.

Research limitations/implications

Based on the chosen qualitative research approach and focus on two countries, the findings might lack generalizability. Thus, future research is needed to observe business relationship development through INB dimensions in different cultural environments.

Practical implications

This paper provides a new perspective for managers on coping with the development of business relationships and branding in the EM context.

Originality/value

This is the first attempt to study business relationship development through branding perspective in general and INB perspective in particular. It builds a deeper understanding of identity, reputation and mutual INB dimension and their manifestation and influence on each relationship stage. In addition, the study has a cultural context, which makes it one of the rare cross-cultural studies related to branding in business marketing research.