bluuebunny/crossref_metadata_2025 huggingface dataset:
Thy1transgenic mice expressing the red fluorescent calcium indicator jRGECO1a for neuronal population imagingin vivo
Authors: Dana Hod , Novak Ondrej , Guardado-Montesino Michael , Fransen James W. , Hu Amy , Borghuis Bart G. , Guo Caiying , Kim Douglas S. , Svoboda Karel
Published: March 2018

Calcium imaging is commonly used to measure the neural activity of large groups of neurons in mice. Genetically encoded calcium indicators (GECIs) can be delivered for this purpose using non-invasive genetic methods. Compared to viral gene transfer, transgenic targeting of GECIs provides stable long-term expression and obviates the need for invasive viral injections. Transgenic mice expressing the green GECI GCaMP6 are already widely used. Here we present the generation and characterizarion of transgenic mice expressing the sensitive red GECI jRGECO1a, driven by theThy1promoter. Four transgenic lines with different expression patterns showed sufficiently high expression for cellularin vivoimaging. We used two-photon microscopy to characterize visual responses of individual neurons in the visual cortexin vivo. The signal-to-noise ratio in transgenic mice was comparable to, or better than, for mice transduced with adeno-associated virus. We also show thatThy1-jRGECO1a transgenic mice are useful for transcranial population imaging and functional mapping using widefield fluorescecnce microscopy. We also demonstrate imaging of visual responses in retinal ganglion cells.Thy1-jRGECO1a transgenic mice are therefore a useful addition to the toolbox for imaging activity in intact neural networks.
Assessment of the transmural unipolar electrogram morphology change radius during contact force-guided pulmonary vein isolation using the VISITAG™ Module and CARTOREPLAY™
Authors: Tomlinson David R. , Stevens Kara N. , Streeter Adam J.
Published: March 2018

Aims

To investigate the radius of transmural (TM) ablation effect at the left atrial posterior wall (LAPW) during contact force (CF)-guided pulmonary vein isolation (PVI), using pure R unipolar electrogram (UE) morphology change – a histologically validated marker of radiofrequency (RF)-induced TM atrial ablation.

Methods

Following PVI in 24 consecutive patients (30W, continuous RF), VISITAG™ Module and CARTOREPLAY™ (Biosense Webster Inc.) RF and UE data at left and right-sided LAPW annotated sites 1 and 2 were analysed.

Results

Acutely durable PVI without spontaneous / dormant recovery was achieved following 15s and 10-11s RF, at sites 1 and 2, respectively (p<0.0001). At site 1, RS UE morphology was noted pre-ablation, with RF-induced pure R UE morphology change in 47/48 (98%). Left and right-sided second RF site annotation was at 5.8mm and 5.2mm from site 1 respectively (p=0.64), yet immediate pure R UE morphology was noted in 35/48 (73%). For second-annotated sites, 30 demonstrated inter-ablation site transition time ≤17ms; pure R UE morphology was noted at annotation onset in 22/30 (73%), with overall median time to pure R morphology change significantly shorter than at site 1 – 0.0s, versus 4.1s and 5.3s, for left and right-sided first-annotated LAPW sites, respectively (p<0.0001).

Conclusion

When the first and second-annotated LAPW RF sites were within 7mm, 73% second-annotated sites demonstrated immediate pure R UE morphology change. These analyses support a paradigm of shorter RF duration at immediately adjacent sites during continuous RF application, and may usefully inform the further development of “tailored” approaches towards CF-guided PVI.

What’s known?

The VISITAG™ Module and CARTOREPLAY™ permit investigations into the tissue effects of RF energy deliveryin vivo, via objective annotation methodology and retrospective evaluation of histologically validated unipolar electrogram (UE) criteria for transmural (TM) atrial ablation.

Greater RF energy effect is seen at left compared to right-sided first-annotated left atrial posterior wall (LAPW) sites during pulmonary vein isolation (PVI).

What’s new?

Following ∼15s RF delivery at first-annotated LAPW sites and aiming for ≤6mm inter-ablation site distance during continuous RF delivery, 73% second-annotated sites demonstrated immediate TM UE morphology change.

At second-annotated sites, ∼10s RF resulted in acutely durable PVI in all. Greater left-sided RF energy effect was observed, not explained by differences in RF duration, mean CF or catheter position stability.

The radius of TM RF effect may be determined at the LAPW following CF and VISITAG™ Module-guided PVI.
Mechanistic description of spatial processes using integrative modelling of noise-corrupted imaging data
Authors: Hross Sabrina , Theis Fabian J. , Sixt Michael , Hasenauer Jan
Published: March 2018

Spatial patterns are ubiquitous on the subcellular, cellular and tissue level, and can be studied using imaging techniques such as light and fluorescence microscopy. Imaging data provide quantitative information about biological systems, however, mechanisms causing spatial patterning often remain illusive. In recent years, spatio-temporal mathematical modelling helped to overcome this problem. Yet, outliers and structured noise limit modelling of whole imaging data, and models often consider spatial summary statistics. Here, we introduce an integrated data-driven modelling approach that can cope with measurement artefacts and whole imaging data. Our approach combines mechanistic models of the biological processes with robust statistical models of the measurement process. The parameters of the integrated model are calibrated using a maximum likelihood approach. We used this integrated modelling approach to studyin vivogradients of the chemokine (C-C motif) ligand 21 (CCL21). CCL21 gradients guide dendritic cells and are important in the adaptive immune response. Using artificial data, we verified that the integrated modelling approach provides reliable parameter estimates in the presence of measurement noise and that bias and variance of these estimates are reduced compared to conventional approaches. The application to experimental data allowed the parameterisation and subsequent refinement of the model using additional mechanisms. Among others, model-based hypothesis testing predicted lymphatic vessel dependent concentration of heparan sulfate, the binding partner of CCL21. The selected model provided an accurate description of the experimental data and was partially validated using published data. Our findings demonstrate that integrated statistical modelling of whole imaging data is computationally feasible and can provide novel biological insights.
A Bayesian sequential learning framework to parameterise continuum models of melanoma invasion into human skin
Authors: Browning Alexander P , Haridas Parvathi , Simpson Matthew J
Published: March 2018

We present a novel framework to parameterise a mathematical model of cell invasion that describes how a population of melanoma cells invades into human skin tissue. Using simple experimental data extracted from complex experimental images, we estimate three model parameters:(i) the melanoma cell proliferation rate,λ; (ii) the melanoma cell diffusivity,D; and (iii)δ, a constant that determines the rate that melanoma cells degrade the skin tissue. The Bayesian sequential learning frame-work involves a sequence of increasingly-sophisticated experimental data from:(i) a spatially uniform cell proliferation assay; (ii) a two-dimensional circular barrier assay; and, (iii) a three-dimensional invasion assay. The Bayesian sequential learning approach leads to well-defined parameter estimates. In contrast, taking a naive approach that attempts to estimate all parameters from a single set of images from the same experiment fails to produce meaningful results. Overall our approach to inference is simple-to-implement, computationally efficient, and well-suited for many cell biology phenomena that can be described by low dimensional continuum models using ordinary differential equations and partial differential equations. We anticipate that this Bayesian sequential learning framework will be relevant in other biological contexts where it is challenging to extract detailed, quantitative biological measurements from experimental images and so we must rely on using relatively simple measurements from complex images.
Implementation of CRISPR-Cas13a system in fission yeast and its repurposing for precise RNA editing
Authors: Jing Xinyun , Xie Bingran , Chen Longxian , Zhang Niubing , Jiang Yiyi , Qin Hang , Hao Pei , Yang Sheng , Li Xuan
Published: March 2018

In contrast to genome editing that introduces genetic changes at DNA level, disrupting or editing genes’ transcripts provides a distinctive approach to perturb a genetic system, offering benefits complementary to classic genetic approaches. To develop a new toolset for manipulation of RNA, we first implemented a member of type VI CRISPR systems, Cas13a from Leptotrichia shahii (LshCas13a) in Schizosaccharomyces pombe, an important model organism employed by biologists to study key cellular mechanisms conserved from yeast to humans. While it was shown to knock down targeted endogenous genes’ transcripts, differently from previous studies in E. coli, no collateral cleavage of other non-specific RNA by activated Cas13a-crRNA complex was detected in fission yeast. Second, we engineered a RNA-editing system by tethering an inactive form of LshCas13a (dCas13) to the catalytic domain of human Adenosine Deaminase Act on RNA 2 (hADAR2d), which was shown to be programmable with crRNA to target messenger RNAs and precisely edit specific nucleotide residues. We optimized the system parameters using a dual-florescence reporter and demonstrated its utility in editing of randomly selected endogenous genes’ transcripts. Our engineered RNA-editing system enables a new toolset for transcriptomic manipulation that is widely applicable in basic genetic and biotechnological research.
A constitutively expressed antifungal peptide protectsTenebrio molitorduring a natural infection by the entomopathogenic fungusBeauveria bassiana
Authors: Maistrou Sevasti , Paris Véronique , Jensen Annette B. , Rolff Jens , Meyling Nicolai V. , Zanchi Caroline
Published: March 2018

Antimicrobial peptides have been well studied in the context of bacterial infections. Antifungal peptides have received comparatively less attention. Fungal pathogens of insects and their hosts represent a unique opportunity to study host-pathogen interactions due to the million of years of co-evolution they share. In this study, we investigated role of a constitutively expressed thaumatin-like peptide with antifungal activity expressed by the mealworm beetle Tenebrio molitor, named Tenecin 3, during a natural infection with the entomopathogenic fungus Beauveria bassiana. We monitored the effect of the expression of Tenecin 3 on the survival of infected hosts as well as on the progression of the fungal infection inside the host. Finally, we tested the activity of Tenecin 3 against B. bassiana. These findings could help improving biocontrol strategies and help understanding the evolution of antifungal peptides as a defense mechanism.
Efficient genome editing ofMagnetospirillum magneticumAMB-1 by CRISPR-Cas9 system for analyzing magnetotactic behavior
Authors: Chen Haitao , Zhang Sheng-Da , Chen Linjie , Cai Yao , Zhang Wei-Jia , Song Tao , Wu Long-Fei
Published: March 2018

Magnetotactic bacteria are a diverse group of microorganisms with the ability to use geomagnetic fields for direction sensing. This magnetotactic behavior can help microorganisms move towards favorable habitats for optimal growth and reproduction. Highly efficient genomic editing is very useful for a comprehensive understanding of the magnetotactic mechanism at the molecular level. In this study, we adapted an engineered CRISPR-cas9 system for efficient inactivation of gene in a widely used magnetotactic bacteria model strain,Magnetospirillum magneticumAMB-1. By combining an engineered nuclease-deficient Cas9 and single-guide RNA, a CRISPR interference system was successfully developed to silenceamb0994expression. More importantly, we succeeded in the construction of a singleamb0994gene deletion mutant using CRISPR-Cas9 with approximate 60-fold high efficiency compared to classical homology double-crossing replacement procedure. This mutant synthesized normally the magnetosomes, but reacted quicker and with less time than the wild-type strain to abrupt magnetic field reversals. A dynamics simulation by modelingM. magneticumAMB-1 cell as an ellipsoid showed that the difference of the motions between wild andΔamb0994is due to flagellar influence. The behavior observation being consistent with dynamics simulation indicated that Amb0994 is involved in the cellular response to magnetic torque change via controlling flagella. Besides the contribution to a better understanding of the magnetotaxis mechanism, this study demonstrates the CRISPR system as a useful genetic toolbox for high-efficiency genome editing in magnetotactic bacteria.
Conversion of a soluble protein into a potent chaperonein vivo
Authors: Kwon Soon Bin , Ryu Kisun , Son Ahyun , Jeong Hotcherl , Lim Keo-Heun , Kim Kyun-Hwan , Seong Baik L. , Choi Seong Il
Published: March 2018

Protein-folding assistance and aggregation inhibition by cellular factors are largely understood in the context of molecular chaperones. As an alternative and complementary model, we previously proposed that, in general, soluble cellular macromolecules including chaperones with large excluded volume and surface charges exhibit the intrinsic chaperone activity to prevent aggregation of their connected polypeptides, irrespective of the connection types, and thus to aid productive protein folding. As a proof of concept, we here demonstrated that a model soluble protein with an inactive protease domain robustly exerted chaperone activity toward various proteins harboring a short protease-recognition tag of 7 residues inEscherichia coli. The chaperone activity of this protein was similar or even superior to that of representativeE. colichaperonesin vivo. Furthermore,in vitrorefolding experiments confirmed thein vivoresults. Our findings revealed that a soluble protein exhibits the intrinsic chaperone activity, which is manifested, upon binding to aggregation-prone proteins. This study gives new insights into the ubiquitous chaperoning role of cellular macromolecules in protein-folding assistance and aggregation inhibition underlying the maintenance of protein solubility and proteostasisin vivo.
Synthetic standards combined with error and bias correction improves the accuracy and quantitative resolution of antibody repertoire sequencing in human naïve and memory B cells
Authors: Friedensohn Simon , Lindner John M. , Cornacchione Vanessa , Iazeolla Mariavittoria , Miho Enkelejda , Zingg Andreas , Meng Simon , Traggiai Elisabetta , Reddy Sai T.
Published: March 2018

High-throughput sequencing of immunoglobulin repertoires (Ig-seq) is a powerful method for quantitatively interrogating B cell receptor sequence diversity. When applied to human repertoires, Ig-seq provides insight into fundamental immunological questions, and can be implemented in diagnostic and drug discovery projects. However, a major challenge in Ig-seq is ensuring accuracy, as library preparation protocols and sequencing platforms can introduce substantial errors and bias that compromise immunological interpretation. Here, we have established an approach for performing highly accurate human Ig-seq by combining synthetic standards with a comprehensive error and bias correction pipeline. First, we designed a set of 85 synthetic antibody heavy chain standards (in vitro transcribed RNA) to assess correction workflow fidelity. Next, we adapted a library preparation protocol that incorporates unique molecular identifiers (UIDs) for error and bias correction which, when applied to the synthetic standards, resulted in highly accurate data. Finally, we performed Ig-seq on purified human circulating B cell subsets (naïve and memory), combined with a cellular replicate sampling strategy. This strategy enabled robust and reliable estimation of key repertoire features such as clonotype diversity, germline segment and isotype subclass usage, and somatic hypermutation (SHM). We anticipate that our standards and error and bias correction pipeline will become a valuable tool for researchers to validate and improve accuracy in human Ig-seq studies, thus leading to potentially new insights and applications in human antibody repertoire profiling.
Allosteric receptor modulation of FFA2R turns natural agonists into potent activators of the superoxide generating neutrophil NADPH-oxidase
Authors: Mårtensson Jonas , Holdfeldt André , Sundqvist Martina , Gabl Michael , Björkman Lena , Forsman Huamei , Dahlgren Claes
Published: March 2018

Acetate, agonist for the free fatty acid receptor 2 (FFA2R/GPR43), triggers an increase in the cytosolic concentration of free Ca2+in neutrophils without any assembly of the superoxide generating NADPH-oxidase. We show that the phenylacetamide compound 58 (Cmp58; (S)-2-(4-chlorophenyl)-3,3-dimethyl-N-(5-phenylthiazol-2-yl)butanamide, lacking a direct activating effect on neutrophils, acts as a positive allosteric FFA2R modulator that turns acetate into a potent activating agonist that triggers an assembly of the NADPH-oxidase. The NADPH-oxidase activity could be further increased in neutrophils treated with the pro-inflammatory cytokine TNF. Many neutrophil chemoattractant receptors are stored in secretory organelles but no FFA2R mobilization was induced in neutrophils treated with TNF. The receptor selectivity was demonstrated through the inhibition of the neutrophil response induced by the combined action of acetate and Cmp58 by the FFA2R antagonist CATPB. Allosteric modulators that positively co-operate with natural FFA2R agonists and prime neutrophils in their response to such agonists, may serve as good tools for further unraveling the physiological functions of the FFA2R and its involvement in various diseases. In this study, allosteric modulation of FFA2R is introduced as a novel receptor selective mechanism to prime neutrophils to produce increased amounts of reactive oxygen species.
Better estimation of SNP heritability from summary statistics provides a new understanding of the genetic architecture of complex traits
Authors: Speed Doug , Balding David J
Published: March 2018

LD Score Regression (LDSC) has been widely applied to the results of genome-wide association studies. However, its estimates of SNP heritability are derived from an unrealistic model in which each SNP is expected to contribute equal heritability. As a consequence, LDSC tends to over-estimate confounding bias, under-estimate the total phenotypic variation explained by SNPs, and provide misleading estimates of the heritability enrichment of SNP categories. Therefore, we present SumHer, software for estimating SNP heritability from summary statistics using more realistic heritability models. After demonstrating its superiority over LDSC, we apply SumHer to the results of 24 large-scale association studies (average sample size 121 000). First we show that these studies have tended to substantially over-correct for confounding, and as a result the number of genome-wide significant loci has under-reported by about 20%. Next we estimate enrichment for 24 categories of SNPs defined by functional annotations. A previous study using LDSC reported that conserved regions were 13-fold enriched, and found a further twelve categories with above 2-fold enrichment. By contrast, our analysis using SumHer finds that conserved regions are only 1.6-fold (SD 0.06) enriched, and that no category has enrichment above 1.7-fold. SumHer provides an improved understanding of the genetic architecture of complex traits, which enables more efficient analysis of future genetic data.
Depleting Trim28 in adult mice is well tolerated and reduces levels of α-synuclein and tau
Authors: Rousseaux Maxime W.C. , Revelli Jean-Pierre , Vázquez-Vélez Gabriel E. , Kim Ji-Yoen , Craigen Evelyn , Gonzales Kristyn , Beckinghausen Jaclyn , Zoghbi Huda Y.
Published: March 2018

Alzheimer’s and Parkinson’s disease are late onset neurodegenerative diseases that will require therapy over decades to mitigate the effects of disease-driving proteins such tau and α-synuclein (α-Syn). We recently found that TRIM28 regulates the levels and toxicity of α-Syn and tau (Rousseaux et al., 2016), however, how TRIM28 regulates α-Syn and whether its chronic inhibition later in life is safe remained unknown. Here, we show that TRIM28 mediates the SUMOylation of α-Syn and tau, and that genetic suppression of Trim28 in adult mice is compatible with life. We were surprised to see that mice lacking Trim28 in adulthood do not exhibit behavioral or pathological phenotypes, and importantly, adult reduction of TRIM28 results in a decrease of α-Syn and tau levels. These results suggest that deleterious effects from TRIM28 depletion are limited to development and that its inhibition adulthood provides a potential path for modulating α-Syn and tau levels.
Avian keratin disorder of Alaska black-capped chickadees is associated with Poecivirus infection
Authors: Zylberberg Maxine , Van Hemert Caroline , Handel Colleen M. , DeRisi Joseph L.
Published: March 2018

Background

Avian keratin disorder (AKD) is an epizootic of debilitating beak deformities, first documented in black-capped chickadees (Poecile atricapillus) in Alaska during the late 1990s. Similar deformities have now been recorded in dozens of species of birds across multiple continents. Despite this, the etiology of AKD has remained elusive, making it difficult to assess the impacts of this disease on wild populations. We previously identified an association between infection with a novel picornavirus, Poecivirus, and AKD in a small cohort of black-capped chickadees.

Methods

To test if the association between Poecivirus and AKD holds in a lager study population, we used targeted PCR followed by Sanger sequencing to screen 124 symptomatic and asymptomatic black-capped chickadees for Poecivirus infection. We further compared the efficacy of multiple non-terminal field sampling methods (buccal swabs, cloacal swabs, fecal samples, and blood samples) for Poecivirus screening. Finally, we used both in situ hybridization and a strand-specific expression assay to localize Poecivirus to beak tissue of AKD-positive individuals and to determine if virus is actively replicating in beak tissue.

Results

Poecivirus was detected in 29/29 (100%) individuals with AKD, but only 9/95 (9.5%) asymptomatic individuals with apparently normal beaks (p < 0.0001). We found that cloacal swabs are the most sensitive of these sample types for detecting Poecivirus in birds with AKD, but that buccal swabs should be combined with cloacal swabs in evaluating the infection status of asymptomatic birds. Finally, we used both in situ hybridization and a strand-specific expression assay to localize Poecivirus to beak tissue of AKD-positive individuals and to provide evidence of active viral replication.

Conclusion

The data presented here show a strong, statistically significant relationship between Poecivirus infection and AKD, and provide evidence that Poecivirus is indeed an avian virus, infecting and actively replicating in beak tissue of AKD-affected BCCH. Taken together, these data corroborate and extend the evidence for a potential causal association between Poecivirus and AKD in the black-capped chickadee. Poecivirus continues to warrant further investigation as a candidate agent of AKD.
High-throughput antibody engineering in mammalian cells by CRISPR/Cas9-mediated homology-directed mutagenesis
Authors: Mason Derek M , Weber Cédric R , Parola Cristina , Meng Simon M , Greiff Victor , Kelton William J , Reddy Sai T
Published: March 2018

Antibody engineering is performed to improve therapeutic properties by directed evolution, usually by high-throughput screening of phage or yeast display libraries. Engineering antibodies in mammalian cells offers advantages associated with expression in their final therapeutic format (full-length glycosylated IgG), however, the inability to express large and diverse libraries severely limits their potential throughput. To address this limitation, we have developed homology-directed mutagenesis (HDM), a novel method which extends the concept of CRISPR/Cas9-mediated homology-directed repair (HDR). HDM leverages oligonucleotides with degenerate codons to generate site-directed mutagenesis libraries in mammalian cells. By improving HDM efficiency (>35-fold) and combining mammalian display screening with next-generation sequencing (NGS), we validated this approach can be used for key applications in antibody engineering at high-throughput: rational library construction, novel variant discovery, affinity maturation, and deep mutational scanning (DMS). We anticipate that HDM will be a valuable tool for engineering and optimizing antibodies in mammalian cells, and eventually enable directed evolution of other complex proteins and cellular therapeutics.
Heterogeneity of the Frequency Domain Patterns in Persistent Atrial Fibrillation
Authors: Iravanian Shahriar , Langberg Jonathan J
Published: March 2018

Background

Persistent atrial fibrillation (AF) has remained a challenging clinical problem. The mechanisms of persistent AF are still subject to debate. Both a single mother-rotor with fibrillatory conduction and multiple meandering spiral waves have been proposed to explain persistent AF. Previous frequency domain studies have reported the presence of dominant frequency (DF) gradient (a marker of single mother-rotor) in paroxysmal, but not persistent AF.

Methods and Results

We performed temporally-dense high-resolution frequency domain analysis of 10-40 minutes segments of intracardiac signals recorded in 24 patients undergoing ablation of persistent AF. We observed two predominant patterns. The expected signature of the mother-rotor mechanism was observed in 38% of the patients. The frequency pattern in 54% consisted of two or more distinct frequency peaks with no obvious gradient, which is consistent with multiple separate primary spiral waves in electrophysiologically heterogeneous areas of atria. The average measured number of rotors per case was 1.71 ± 0.32, which provides a lower limit on the actual number of rotors. The single-zone pattern was exclusively seen in patients who were on a membrane-active antiarrhythmic medication at the time of ablation (P < 0.005).

Conclusions

AF is a heterogeneous disorder. High-frequency resolution analysis is a useful tool to detect the underlying mechanisms of AF and to classify it into patterns consistent with a single mother-rotor vs. multiple meandering wavelets.
Managing knowledge through social media
Authors: Crammond Robert , Omeihe Kingsley Obi , Murray Alan , Ledger Kirstin
Published: March 2018

Purpose

The purpose of this paper is to conceptualise social media usage (SMU) as a contributory, knowledge management (KM) tool towards entrepreneurial behaviour amongst small- and medium-sized enterprises (SMEs). Although an underdeveloped concept in entrepreneurship, the conceptual analysis of KM presents evidence which links SMU as complementary to changing KM conventions.

Design/methodology/approach

The pertinent KM and SMU literatures of the SME context were reviewed to form an understanding of this context. Employing a mixed-methods approach, a pragmatic, thematic investigation of SMU-enhanced KM was facilitated.

Findings

Substantial benefits of innovative SMU, as a management tool towards SME entrepreneurialism, were witnessed. SMU enhances the administration of real-time knowledge, encouraging creativity. However, longer-term costs of employing requisite personnel, and anticipated organisational restructuring, present challenges. The paper identifies the potentials of social media technologies in overcoming KM issues. The authors propose a reasoned process model towards entrepreneurial exploitation by acknowledging systematic phases of research, concept, institutionalise, develop, target and assess, referred to as the RCIDTA model.

Practical implications

The authors argue that KM, through social media, facilitates interactions to execute innovative processes within SMEs ever-changing infrastructures. It also informs nascent entrepreneurs, in considering the benefits of systematic KM, and novel SMU, opportunities. The RCIDTA model for SMEs can be utilised in improving knowledge ecosystems of entrepreneurial SMEs, promoting innovation towards sustained organisation growth.

Originality/value

This paper embraces the growing approach of SMEs applying SMU. SMU and its cost efficiency support the start-up activity. This paper highlights central issues concerning the exploitation of sector-specific KM, including organisational strategy, structure, brand formation, fiscal and personnel resource allocation and market share.
Managing paradoxes, dilemmas, and change
Authors: Pauluzzo Rubens , Guarda Marta , De Pretto Laura , Fang Tony
Published: March 2018

Purpose

Drawing on Fang’s (2012) Yin Yang theory of culture while taking up the roadmap proposed by Li (2016) for applying the epistemological system of Yin Yang balancing to complex issues in management research, in general, and to paradoxical issues, in particular, the purpose of this paper is to explore how organizations and individuals in the West can balance cultural paradoxes and manage culture dilemmas through the lens of Yin Yang wisdom.

Design/methodology/approach

The paper is based on a qualitative case study. Data are gathered through interviews, documents, and field observations in four subsidiaries of an Italian insurance multinational corporation and were analyzed according to the three parameters, i.e., situation, context, and time (Fang, 2012).

Findings

The findings show how the integration and learning from seemingly opposite cultures and sets of values lead the organization and individuals to balancing cultural paradox and managing cultural dilemma effectively. With regard to situation, the authors find that both organizations and customers choose the most relevant value(s) to take advantage of specific events or circumstances, and that different value orientations can coexist. As for context, the authors show that organizations can adapt their values either through suppression and/or promotion, which can foster individuals to find new balancing within the paradox. In terms of time, the authors show that the process of learning from other cultures over time can play a role in the shift of people’s and organizations’ choices of attitudes and value orientations.

Originality/value

The paper suggests the relevance and usefulness of adopting Yin Yang wisdom to uncover the dynamic process of cultural learning in Western scenarios.
Minority shareholder participation and earnings management
Authors: Kong Dongming
Published: March 2018

Purpose

The purpose of this paper is to test a catering theory by examining impacts of minority shareholders’ pressures on earnings management (EM), and attempt to answer: what is the role of minority shareholders participation (MSP) in corporate governance? and does MSP serve as an external monitor to managers, or does it put excessive pressure on them?

Design/methodology/approach

Using a novel online voting data set in China’s stock market, the author constructs the measure of MSP, and regress the EM on MSP. To address the endogeneity, the author introduces propensity score matching and difference-in-difference methods, instrumental variables, and Heckman estimation to show that the results are robust to different specifications and alternative measures.

Findings

The author documents that: MSP plays limited role in external monitoring; and firms facing high MSP levels tend to manage earnings more actively. In addition, information asymmetry, proposals’ importance, managerial incentives, and CEO financial expertise significantly affect firms’ catering behaviors.

Originality/value

This paper contributes to different strands of the literature. First, the finding significantly supports the catering hypothesis from a new perspective of EM. Second, the author contributes to a hotly debated issue in corporate governance: whether minority shareholders should be granted increased participation in corporate decisions? The results also provide timely empirical evidence for government regulators who are concerned about the costs and benefits of granting minority shareholders direct control over corporate decisions.
Sustainable institutional entrepreneurship in practice
Authors: Gasbarro Federica , Rizzi Francesco , Frey Marco
Published: March 2018

Purpose

The purpose of this paper is to illustrate how sustainable entrepreneurs (SEs) address the regulative, normative and cultural-cognitive institutional pillars when operating in conservative contexts. It aims to study in depth the use of sustainable innovation (SI) as a means of increasing legitimacy within the institutions, thus triggering an institutional change.

Design/methodology/approach

The paper opted for an exploratory study on the Tuscan geothermal heat pumps market, which presents a promising but still largely unexploited sustainability potential despite its low institutional support, using the open-ended approach of grounded theory. The data include interviews and archive data, such as newspapers, magazines.

Findings

The paper provides empirical insights on how sustainable institutional entrepreneurs (SIEs) have developed innovative business models based on direct relationship with the final customers and strategic partnerships as a means of increasing legitimacy within the normative and cultural-cognitive institutions, and subsequently in the regulative institutions, through: innovative value propositions aimed at changing industry norms and social beliefs; increasing the private benefit of innovative sustainable business models in order to trigger imitation dynamics; inter-sector strategic partnerships sharing the same sustainability objectives; the inclusion of the relevant actors in relation to the social norms and cultural-cognitive barriers in a value proposition. On the basis of these findings a model has been developed.

Research limitations/implications

The study enriches the sustainable entrepreneurship research stream by providing empirical evidence on how SEs foster changes in the three institutional pillars with SI. It also contributes to the institutional entrepreneurship research by extending the results of previous studies regarding institutional tactics.

Practical implications

The paper could help SIEs prioritizing changes in value propositions and strategic partnerships to create market-based coalitions, as a means of institutional legitimization for SI.

Originality/value

The study illustrates the relationship between the sustainable institutional entrepreneurial practices and each institutional pillar, including the cultural-cognitive institutions, which have been neglected in previous research. This allows formulating five key propositions that guide SEs in succeeding as both sustainable and institutional entrepreneurs.
Capital market offenses in Malaysia
Authors: Kan Yoke Yue
Published: March 2018

Purpose

The purpose of this study is to review and evaluate the salient features of stock market manipulation in Malaysia. The research questions used are: Who was involved? How it happened? What were the consequences?

Design/methodology/approach

This study has been conducted using content and thematic analysis. This study includes multiple sources of information to help establish the stylized facts and it uses cases that have been prosecuted in Malaysia for 2005-2015.

Findings

This study presents arguments and empirical data supporting the view that the stock market manipulation was conducted by those in a privileged position and with access to information. Ethical failure, involving greed, self-interest, dishonesty and a preoccupation with a quick profit, could explain why stock market manipulation happened. Manipulation harms legitimate investors, as share prices and earnings of companies are affected.

Practical implications

A better understanding about the prevalence, characteristics and consequences of the market manipulation problems will be useful for stakeholders, investors and policymakers in the financial industry for promoting and maintaining a fair, efficient and transparent stock market.

Originality/value

The originality of this paper lies in examining and presenting interpretations based on contemporary phenomenon within the real-life context of Malaysia. There is little study or literature that focuses on Malaysia, especially in examining stock market manipulation by integrating finance and management perspectives to form a comprehensive understanding of the issue.
Investment decision behaviour of the Malaysian retail investors and fund managers
Authors: Jaiyeoba Haruna Babatunde , Adewale Abideen Adeyemi , Haron Razali , Che Ismail Che Muhamad Hafiz
Published: March 2018

Purpose

This study aims to investigate the Malaysian retail investors and fund managers’ investment decision behaviours. The study offers an important opportunity for understanding the investors’ experiences, how they understand the Malaysian economy and their priorities for company selection. Other main aspects of this study are how investors mitigate the influence of emotions and psychological biases and challenges faced during investment decisions.

Design/methodology/approach

The researchers have mainly adopted an interpretivist approach for the present study. Qualitative data elicited through semi-structured interviews conducted with four retail investors and four fund managers were subjected to qualitative thematic analysis.

Findings

The results reveal that the investment decision processes of fund managers are more comprehensive than those of retail investors. Although both fund managers and retail investors acknowledge the influence of psychological biases on their investment decisions, the former use different and comprehensive approaches to mitigate such influences during investment decisions compared with the latter. Other important findings are how investors understand the Malaysian economy, their priorities for company selection and challenges faced during investment decisions.

Research limitations/implications

The researchers have interviewed eight carefully selected interviewees across retail investors and fund managers divide. Adopting other grouping criteria, focus group discussion with more respondents or adopting a mixed-methods approach may increase our understanding of the investment decision behaviours of Malaysian retail investors and fund managers.

Practical implications

This study could be used as a guide by both retail investors and fund managers when making investment decisions.

Originality/value

This research has included both retail investors and fund managers; it has also increased literature on investment decision and behavioural finance, particularly in the context of Malaysian investors and managers.
Can subaltern professors speak?: examining micro-aggressions and lack of inclusion in the academy
Authors: Orelus Pierre W.
Published: March 2018

Purpose

The purpose of this paper is to highlight various ways in which micro-aggressions and other forms of institutional oppression have affected subaltern professors and students in the academy.

Design/methodology/approach

This qualitative case study draws from testimonios collected from fall 2010 to spring 2016. Six testimonios are incorporated in the study, and they stem from a various set of data. These testimonios show patterns across data set regarding systemic oppression subaltern that professors have experienced in the academy.

Findings

As the findings of this study show, subaltern professors face intersecting forms of discrimination – often race, language, accent, gender, and class based – in predominantly white institutions. Their testimonios unravel the complexity of the professional, academic, and personal lives of these professors highlighting their professional achievements and successes. Their testimonios demonstrate at the same time the ways in which various forms of oppression might have limited their life chances and opportunities.

Research limitations/implications

Suggestions are made as to how social justice educators and policy makers can collectively challenge and eradicate these social wrongs.

Originality/value

This paper is an original take on both micro-aggressions and institutional oppression affecting subaltern professors and students.
A numerical hybrid model for outdoor sound propagation in complex urban environments
Authors: Pasareanu Stephanie M. , Burdisso Ricardo A. , Remillieux Marcel C.
Published: March 2018

Noise mapping in large and dense urban areas is computationally challenging, if not impossible, with the use of conventional numerical techniques. Recently, promising results have shown the potential of energy-based models to compete with conventional numerical techniques. In this paper, a hybrid full-wave/diffusion propagation model is proposed to address some of the flaws of the traditional diffusion model. The full-wave model is used for predicting sound propagation (i) near the source, where interactions between waves are important, and (ii) outside the cluttered environment, where free-field-like conditions apply. The diffusion model is used in regions where diffusion conditions are met.
β-Lactam Combinations with Vancomycin Show Synergistic Activity against Vancomycin-Susceptible Staphylococcus aureus, Vancomycin-Intermediate S. aureus (VISA), and Heterogeneous VISA
Authors: Tran Nikki , Rybak Michael J.
Published: March 2018

Increasing utilization of vancomycin due to the high prevalence of methicillin-resistant
Staphylococcus aureus
(MRSA) infections has led to the emergence of vancomycin-intermediate
S. aureus
(VISA) and heterogeneous VISA (hVISA) strains.
In vitro
data suggest the potential for potent synergy between several beta-lactams and vancomycin. The objective of this study is to evaluate the synergy between beta-lactams and vancomycin against MRSA that is vancomycin susceptible, vancomycin-susceptible
Staphylococcus aureus
(VSSA), hVISA, and VISA. Fifty randomly selected clinical MRSA strains with various susceptibility levels to vancomycin were evaluated for vancomycin alone and vancomycin in combination with various concentrations of cefazolin (CFZ), cefepime (FEP), ceftaroline (CPT), and nafcillin (NAF). The potential for synergy was assessed by 24-h time-kill studies. Beta-lactams reduced vancomycin MIC values against all strains (4- to 16-fold reduction). In time-kill studies against MRSA, CFZ, FEP, CPT, and NAF all demonstrated similar degrees of killing at 24 h, and all showed synergistic activity with vancomycin against VSSA, hVISA, and VISA. Each of these combinations was also superior to any single agent against isolates of all three phenotypes, and each was bactericidal (
P
< 0.001 for all comparisons). All single-agent exposures demonstrated no activity at 24 h. The combination of vancomycin and beta-lactams significantly improved antibacterial activity against VSSA, hVISA, and VISA strains compared to the activity of any agent alone, supporting the potential use of vancomycin–beta-lactam combination therapy in infections caused by MRSA. Further clinical research is warranted to investigate the synergy of vancomycin against these
Staphylococcus
strains.
Esx Paralogs Are Functionally Equivalent to ESX-1 Proteins but Are Dispensable for Virulence in Mycobacterium marinum
Authors: Bosserman Rachel E. , Thompson Cristal Reyna , Nicholson Kathleen R. , Champion Patricia A.
Published: March 2018

Mycobacterium marinum
is a nontuberculous pathogen of poikilothermic fish and an opportunistic human pathogen. Like tuberculous mycobacteria, the
M. marinum
M strain requires the ESX-1 (ESAT-6 system 1) secretion system for virulence in host cells. EsxB and EsxA, two major virulence factors exported by the ESX-1 system, are encoded by the
esxBA
genes within the ESX-1 locus. Deletion of the
esxBA
genes abrogates ESX-1 export and attenuates
M. marinum
in
ex vivo
and
in vivo
models of infection. Interestingly, there are several duplications of the
esxB
and
esxA
genes (
esxB_1
,
esxB_2
,
esxA_1
,
esxA_2
, and
esxA_3
) in the
M. marinum
M genome located outside the ESX-1 locus. We sought to understand if this region, known as ESX-6, contributes to ESX-1-mediated virulence. We found that deletion of the
esxB
_
1
gene alone or the entire ESX-6 locus did not impact ESX-1 export or function, supporting the idea that the
esxBA
genes present at the ESX-1 locus are the primary contributors to ESX-1-mediated virulence. Nevertheless, overexpression of the
esxB_1
locus complemented ESX-1 function in the Δ
esxBA
strain, signifying that the two loci are functionally equivalent. Our findings raise questions about why duplicate versions of the
esxBA
genes are maintained in the
M. marinum
M genome and how these proteins, which are functionally equivalent to virulence factors, contribute to mycobacterial biology.

IMPORTANCE
Mycobacterium tuberculosis
is the causative agent of the human disease tuberculosis (TB). There are 10.4 million cases and 1.7 million TB-associated deaths annually, making TB a leading cause of death globally. Nontuberculous mycobacteria (NTM) cause chronic human infections that are acquired from the environment. Despite differences in disease etiology, both tuberculous and NTM pathogens use the ESX-1 secretion system to cause disease. The nontubercular mycobacterial species,
Mycobacterium marinum
, has additional copies of specific ESX-1 genes. Our findings demonstrate that the duplicated genes do not contribute to virulence but can substitute for virulence factors in
M. marinum
. These findings suggest that the duplicated genes may play a specific role in NTM biology.
In Vitro
Culture of the Insect Endosymbiont
Spiroplasma poulsonii
Highlights Bacterial Genes Involved in Host-Symbiont Interaction
Authors: Masson Florent , Calderon Copete Sandra , Schüpfer Fanny , Garcia-Arraez Gonzalo , Lemaitre Bruno
Published: March 2018

Endosymbiotic bacteria associated with eukaryotic hosts are omnipresent in nature, particularly in insects. Studying the bacterial side of host-symbiont interactions is, however, often limited by the unculturability and genetic intractability of the symbionts.
Spiroplasma poulsonii
is a maternally transmitted bacterial endosymbiont that is naturally associated with several
Drosophila
species.
S. poulsonii
strongly affects its host’s physiology, for example by causing male killing or by protecting it against various parasites. Despite intense work on this model since the 1950s, attempts to cultivate endosymbiotic
Spiroplasma in vitro
have failed so far. Here, we developed a method to sustain the
in vitro
culture of
S. poulsonii
by optimizing a commercially accessible medium. We also provide a complete genome assembly, including the first sequence of a natural plasmid of an endosymbiotic
Spiroplasma
species. Last, by comparing the transcriptome of the
in vitro
culture to the transcriptome of bacteria extracted from the host, we identified genes putatively involved in host-symbiont interactions. This work provides new opportunities to study the physiology of endosymbiotic
Spiroplasma
and paves the way to dissect insect-endosymbiont interactions with two genetically tractable partners.

IMPORTANCE
The discovery of insect bacterial endosymbionts (maternally transmitted bacteria) has revolutionized the study of insects, suggesting novel strategies for their control. Most endosymbionts are strongly dependent on their host to survive, making them uncultivable in artificial systems and genetically intractable.
Spiroplasma poulsonii
is an endosymbiont of
Drosophila
that affects host metabolism, reproduction, and defense against parasites. By providing the first reliable culture medium that allows a long-lasting
in vitro
culture of
Spiroplasma
and by elucidating its complete genome, this work lays the foundation for the development of genetic engineering tools to dissect endosymbiosis with two partners amenable to molecular study. Furthermore, the optimization method that we describe can be used on other yet uncultivable symbionts, opening new technical opportunities in the field of host-microbes interactions.