bluuebunny/crossref_metadata_2025 huggingface dataset:
Layered dynamic regulation for improving metabolic pathway productivity in
Escherichia coli
Authors: Doong Stephanie J. , Gupta Apoorv , Prather Kristala L. J.
Published: March 2018

Significance

Optimization of the engineered pathway for production of D-glucaric acid, a precursor to nylons and detergents, requires strategies that manage pathway competition with glycolysis as well as the stability and activity of the rate-controlling enzyme. To address both of these challenges, two orthogonal, autonomous, and tunable dynamic regulation strategies were layered to produce the highest reported glucaric acid titers in
Escherichia coli
K-12 strains. The implementation of two regulatory circuits harnesses synthetic biology tools to program and optimize cellular behavior and demonstrates the power of multiplexed dynamic control for strain optimization.
Exploring modular allostery via interchangeable regulatory domains
Authors: Fan Yifei , Cross Penelope J. , Jameson Geoffrey B. , Parker Emily J.
Published: March 2018

Significance

Protein functions are often evolved from recombination of a limited suite of protein folds. Engineering desired function into proteins via manipulation of the genes, mimicking natural evolutionary processes, represents a promising approach to synthesizing useful molecular tools. Allosteric proteins play important roles in many biological processes, often as regulatory switches or metabolic checkpoints. In this study, analysis of two natural allosteric proteins from different organisms revealed comparable yet distinct regulatory mechanisms via conformation rearrangement. Interchanging gene segments encoding for the nonhomologous regulatory elements of the two proteins results in new functional proteins with switched regulatory behavior. This modular approach represents a step toward a general scheme for construction of functional changes in proteins.
Single-molecule analysis of phospholipid scrambling by TMEM16F
Authors: Watanabe Rikiya , Sakuragi Takaharu , Noji Hiroyuki , Nagata Shigekazu
Published: March 2018

Significance

Membrane proteins that translocate various compounds across biological membranes play important roles in maintaining intracellular homeostasis in cells. Scramblases are membrane proteins that translocate phospholipids between the inner and outer leaflets of the plasma membrane. However, the mechanisms through which these scramblases translocate phospholipids carrying a hydrophilic residue across the hydrophobic membranes are still unclear. Here, we developed a microsystem containing lipid-bilayer membrane arrays with asymmetrically distributed fluorescent phospholipids. Using this system, we measured phospholipid transport mediated by the TMEM16F scramblase at the single-molecule level, thereby enabling characterization of the biophysical features of phospholipid transport.
Chirality-controlled spontaneous twisting of crystals due to thermal topochemical reaction
Authors: Rai Rishika , Krishnan Baiju P. , Sureshan Kana M.
Published: March 2018

Significance

Recently many crystals have been reported to show various mechanical responses when triggered by stimuli (heat, light, and pressure). Such properties are attributed to polymorphic transitions, conformational changes, packing changes, isomerizations, or chemical reactions inside the crystal and the consequent strain developed between parent and daughter phases. The role of molecular chirality in such macroscopic phenomena is yet to be established. In the present study we found that crystals of dipeptide LL undergo right-handed twisting and those of its enantiomer, dipeptide DD, undergo left-handed twisting upon heat-induced topochemical azide–alkyne cycloaddition. This study provides clear evidence for the role of molecular chirality in controlling the direction of macroscopic twisting of crystals.
N-terminal arginylation generates a bimodal degron that modulates autophagic proteolysis
Authors: Yoo Young Dong , Mun Su Ran , Ji Chang Hoon , Sung Ki Woon , Kang Keum Young , Heo Ah Jung , Lee Su Hyun , An Jee Young , Hwang Joonsung , Xie Xiang-Qun , Ciechanover Aaron , Kim Bo Yeon , Kwon Yong Tae
Published: March 2018

Significance

Conjugation of the amino acid
l
-arginine (
l
-Arg) to the protein N termini is a universal posttranslational modification in eukaryotes, yet its functions remain poorly understood. Previous studies showed that the N-terminal Arg of arginylated substrates is bound by N-recognins to induce substrate ubiquitination and proteasomal degradation via the N-end rule pathway of the ubiquitin (Ub)-proteasome system (UPS). Here, we show that the same Nt-Arg residues of arginylated proteins modulate proteolytic flux via macroautophagy when misfolded proteins accumulate beyond the UPS’s capacity. Their Nt-Arg residues bind and allosterically activate the autophagic adaptor p62/STQSM/Sequestosome-1, facilitating cargo collection and lysosomal degradation. Our results suggest that the Nt-Arg proteome of arginylated proteins contributes to reprogramming global proteolytic flux when the UPS is in trouble.
Guanidinium export is the primal function of SMR family transporters
Authors: Kermani Ali A. , Macdonald Christian B. , Gundepudi Roja , Stockbridge Randy B.
Published: March 2018

Significance

The small multidrug resistance (SMR family) was named for its founding member, a promiscuous exporter of antibiotics and antiseptics, and has become an important model system in membrane protein mechanism and evolution. But most members of this family do not share drug export activity, and their function has been enigmatic. Here we show that the SMR family is mostly comprised of proteins that export guanidinium ion, a small, cationic metabolic byproduct. In addition to opening up an unusual bacterial physiology for further exploration, this work provides a comprehensive view of the SMR family and provides critical context to understand the evolution and mechanism of the multidrug transporters.
Allostery revealed within lipid binding events to membrane proteins
Authors: Patrick John W. , Boone Christopher D. , Liu Wen , Conover Gloria M. , Liu Yang , Cong Xiao , Laganowsky Arthur
Published: March 2018

Significance

The diverse environment of cellular membranes presents unique challenges in deciphering the roles that lipids play in modulating membrane protein structure and function. Here, we developed a native mass spectrometry approach to monitor binding of different lipid types to membrane proteins. We discovered that specific lipid−protein interactions can allosterically modulate the binding of lipids of different types. We also determined the structure of AmtB bound to cardiolipin, and mutation of residues involved in binding this lipid abolishes the observed allosteric effect. Our findings are of particular significance as they contribute to our general knowledge of how lipids modulate protein structure and function and how membrane proteins may recruit, through allostery, their own lipid microenvironment.
Cyclin-dependent kinase activity is required for type I interferon production
Authors: Cingöz Oya , Goff Stephen P.
Published: March 2018

Significance

Innate immune responses are the first line of defense against pathogens. Upon sensing a pathogen, cells produce IFNs: signaling molecules that activate a diverse array of genes involved in antiviral immunity. Cyclin-dependent kinases (CDKs) are enzymes involved in cell cycle progression and transcription. We discovered that CDKs are essential for IFN production following nucleic acid sensing and virus infection. Depletion of CDK activity results in a block to the translation of IFN mRNA into protein, even though the mRNA levels remain unchanged. This block is specific for IFN, as the translation of other mRNAs proceeds normally. Our results establish a previously unknown and critical requirement for CDKs for IFN production in the response against pathogens.
BEST1
gene therapy corrects a diffuse retina-wide microdetachment modulated by light exposure
Authors: Guziewicz Karina E. , Cideciyan Artur V. , Beltran William A. , Komáromy András M. , Dufour Valerie L. , Swider Malgorzata , Iwabe Simone , Sumaroka Alexander , Kendrick Brian T. , Ruthel Gordon , Chiodo Vince A. , Héon Elise , Hauswirth William W. , Jacobson Samuel G. , Aguirre Gustavo D.
Published: March 2018

Significance

One of the most common forms of monogenic macular degeneration worldwide is caused by dominant or recessive bestrophinopathies associated with mutations in the
BEST1
gene. Disease expression is known to start with a retina-wide electrophysiological defect leading to localized vitelliform and atrophic lesions and vision loss. To develop lasting therapies for this incurable disease, there is a need for greater understanding of the early pathophysiology before lesion formation. Here we find that the loss of retinal pigment epithelium apical microvilli and resulting microdetachment of the retina represent the earliest features of canine bestrophinopathies. We show that retinal light exposure expands, and dark adaptation contracts, the microdetachments. Subretinal adeno-associated virus-based gene therapy corrects both the vitelliform lesions and the light-modulated microdetachments.
Molecular mechanism of ATP versus GTP selectivity of adenylate kinase
Authors: Rogne Per , Rosselin Marie , Grundström Christin , Hedberg Christian , Sauer Uwe H. , Wolf-Watz Magnus
Published: March 2018

Significance

As a prerequisite for life, enzymes enhance the rate constants of chemical reactions that otherwise would be orders-of-magnitude too slow. One of the challenges facing enzymes is recognition of correct substrates in the complex and multifaceted cellular environment. This is especially true when distinction must be made between substrates that have similar chemical structures. Here we have discovered an elegant solution to the problem of distinguishing between the correct substrate ATP over the incorrect, but related substrate GTP by the enzyme adenylate kinase. We have found that binding of GTP arrests the enzyme in a catalytically incompetent and open structural state, whereas it is known that binding of ATP activates the enzyme by promoting a large conformational change.
hnRNP R and its main interactor, the noncoding RNA 7SK, coregulate the axonal transcriptome of motoneurons
Authors: Briese Michael , Saal-Bauernschubert Lena , Ji Changhe , Moradi Mehri , Ghanawi Hanaa , Uhl Michael , Appenzeller Silke , Backofen Rolf , Sendtner Michael
Published: March 2018

Significance

Neurons are highly polarized cells. RNA-binding proteins contribute to this polarization by generating diverse subcellular transcriptomes. The RNA-binding protein hnRNP R is essential for axon growth in motoneurons. This study reports the RNA interactome for hnRNP R. The main interacting RNA of hnRNP R was the noncoding RNA 7SK. Depletion of 7SK from primary motoneurons disturbed axon growth. This effect was dependent on the interaction of 7SK with hnRNP R. Both hnRNP R and 7SK localize to axons. Loss of 7SK led to a similar depletion of axonal transcripts as loss of hnRNP R. Our data suggest that 7SK, in addition to its role in transcriptional regulation, acts in concert with hnRNP R to sort specific transcripts into axons.
Stable iridium dinuclear heterogeneous catalysts supported on metal-oxide substrate for solar water oxidation
Authors: Zhao Yanyan , Yang Ke R. , Wang Zechao , Yan Xingxu , Cao Sufeng , Ye Yifan , Dong Qi , Zhang Xizi , Thorne James E. , Jin Lei , Materna Kelly L. , Trimpalis Antonios , Bai Hongye , Fakra Sirine C. , Zhong Xiaoyan , Wang Peng , Pan Xiaoqing , Guo Jinghua , Flytzani-Stephanopoulos Maria , Brudvig Gary W. , Batista Victor S. , Wang Dunwei
Published: March 2018

Significance

While research on single-atom catalysts (SACs) is arguably mature, rare work has been done on atomically dispersed catalyst featuring two atoms. We synthesized Ir dinuclear heterogeneous catalyst in a facile photochemical way. It exhibits outstanding stability and high activity toward water oxidation. The significance of this work can also be appreciated from the catalysis perspective. A grand challenge in heterogeneous catalysis is how to understand the detailed mechanisms at the molecular level, because the most active heterogeneous catalysts are often poorly defined in their atomic structures. Our finding is built upon recent advances aimed at studying SACs but takes a crucial step forward. It provides a material platform to study reactions that would require more than one active site.
Surface chemical heterogeneity modulates silica surface hydration
Authors: Schrader Alex M. , Monroe Jacob I. , Sheil Ryan , Dobbs Howard A. , Keller Timothy J. , Li Yuanxin , Jain Sheetal , Shell M. Scott , Israelachvili Jacob N. , Han Songi
Published: March 2018

Significance

Silica, conventionally known as “glass,” is a universally used material in catalysis, nanofabrication, and many other applications, but details of its surface chemistry and interactions with water are notoriously complicated and unclear––partially due to its tunable surface chemistry. We utilize this tunable surface chemistry of silica to reveal properties of surface-bound water that impact surface reactions, adhesion, and colloidal interactions. Using a combination of surface forces, hydration dynamics, and simulation techniques, we show that surface silanol groups stabilize the surface water layer, and also that variations/fluctuations are more pronounced at intermediate silanol densities on the surface. This work provides insight into fundamental interactions of water with chemically heterogeneous surfaces.
Mechanism of the G-protein mimetic nanobody binding to a muscarinic G-protein-coupled receptor
Authors: Miao Yinglong , McCammon J. Andrew
Published: March 2018

Significance

Protein–protein interactions are important in cellular signaling. However, they have presented a challenge for molecular dynamics (MD) simulations, due to increased system complexity and slowly evolving dynamics. In particular, binding of the medically important G-protein-coupled receptors (GPCRs) with intracellular signaling proteins has not been simulated with MD to date. In this study, we performed long-timescale enhanced MD simulations using the Gaussian accelerated MD (GaMD) method on the M
2
muscarinic GPCR. The simulations revealed pathways and important low-energy intermediate states of the G-protein mimetic nanobody binding to the M
2
receptor. Our simulation results are consistent with experimental data and provide important insights into the GPCR–nanobody binding mechanism. GaMD is thus applicable to enhanced simulations of protein–protein interactions.
Category genesis in Chitimacha
Authors: Hieber Daniel W.
Published: March 2018

The genesis of new lexical categories poses a challenge to theories of diachronic change: If there are no pre-existing words in the class to analogize to, how does the category arise? This paper shows that a constructional approach to category change successfully accounts for the genesis of a diverse class of preverbs in Chitimacha, an isolate of the U.S. Southeast linguistic area. It is shown that what enabled the creation of the preverb category was schematization across a variety of forms with similar properties, namely, a preverbal syntactic position and a directional semantics. Category genesis can therefore be viewed as simply a special case of constructionalization wherein schematization plays a crucial role.
Derivation without category change
Authors: Norde Muriel , Morris Caroline
Published: March 2018

Dutch derivational morphology is rich in intensifying prefixoids, i.e. morphemes that occur as independent lexemes but have an intensifying meaning when bound to adjectives or adverbs. A specific variant of these are diminutive prefixoid constructions such as bloedjeserieus (blood-dim-serious) ‘very serious’ or kletsjenat (splash-dim-wet) ‘very wet’. Unlike the regular derivational diminutive however, the diminutive morpheme lacks the ability to change category when added to a prefixoid, and its primary function is a pragmatic one of either emphasis or downtoning. In this paper, we will discuss the formal and semantic-pragmatic properties of the diminutive prefixoid construction, based on an empirical study into its synchronic distribution, as well as explore how prefixoid constructions may be organised in a constructional network.
Why would anyone take long?
Authors: Denison David
Published: March 2018

I review the word classes proposed for long in such idiosyncratic English usages as I won’t be/take long, all night long. Although adverb fits most of the contentious data best, sometimes the word class is underdetermined. I suggest that long exhibits adjective ~ adverb underspecification from Old and Middle English onwards and can also be a semi-grammatical, decategorialised word. We need not assume that every word in every grammatical sentence must belong to one and only one word class (Denison, 2013). At the phrasal level the distribution is less anomalous and correlates with semantic and pragmatic features. Accordingly, it is sensible to describe the history of such usages in Construction Grammar terms. Recent Danish developments make an intriguing comparison.
The emergence of a new adverbial downtoner
Authors: Van Goethem Kristel , Vanderbauwhede Gudrun , De Smet Hendrik
Published: March 2018

The English expression far from, denoting spatial or metaphorical distance, has developed into an adverbial downtoner (De Smet, 2012). In this corpus-based study, our first purpose is to analyze to which degree the Dutch counterparts of the English [far from X] construction, that is [ver van X] and [verre van X], have also developed into downtoners. We show that synchronically ver van mostly has a spatial or metaphorical meaning, while verre van is generally used as an adverbial downtoner. As a second objective, we explore the diachronic pathways taken by both constructions and argue that the category change undergone by [verre van X] is part of a true constructionalization process, while [ver van X] has been affected by minor constructional changes only.
Evaluative morphology in German, Dutch and Swedish
Authors: Battefeld Malte , Leuschner Torsten , Rawoens Gudrun
Published: March 2018

The separation or ‘debonding’ of prefixoids in informal language use in Germanic and the question whether spelling reflects re-categorization of such compound members as adjectives have recently been attracting increased attention among linguists. This contribution focuses on category changes involving lexical items with an evaluative function, both bound (prefixoids, loan prefixes) and unbound (bare nouns), that give rise to defective adjectives in German, Dutch and Swedish. This occurs via two loci of change: the non-head position in nominal and adjectival compounds and the predicative position in sentence constructions. The diverse items serving as ‘evaluatives’ are unified by one abstract schema for ‘evaluative compounds’ across these languages which is paradigmatically related to other, free uses of such items.
Constructional change on the contentful-procedural gradient
Authors: Koutsoukos Nikos
Published: March 2018

This chapter focuses on a rather neglected type of morphological change, that is, the change from derivation to inflection. Contrary to the assumption that derivational patterns usually do not develop any further, this analysis proposes that some derivational constructions may change by acquiring a more functional status, which is characteristic of inflectional categories. Based on the distinction between contentful and procedural constructions, as proposed by Traugott & Trousdale (2013), the emergence of the new constructions can be conceived of as a gradual shift on the contentful-procedural gradient. The argumentation is based on examination of the ‑idz(o) constructions in Griko, a Greek-based dialect spoken in South Italy.
Structure and strength of sub-100 nm lamellar structures in cold-drawn pearlitic steel wire
Authors: Zhang Xiaodan , Hansen Niels , Godfrey Andrew , Huang Xiaoxu
Published: March 2018

Pearlitic steel wire, with a representative sub-100 nm lamellar structure, is the strongest mass-produced steel with an excellent combination of formability and strength. This overview summarises investigations of cold-drawn pearlitic steel wire in the last decades, covering the microstructural evolution and strengthening mechanisms. Based on quantitative structural parameters, this overview covers a quantitative and extensive analysis of structure–strength relationships. By focusing on the structure, challenges and future strategy are outlined to further improve the mechanical behaviour and performance of pearlitic steel wire to widen its use in society.

This is part of a thematic issue on Pearlitic Steel Wires.
Novel effect of α-lactalbumin on the yohimbine-induced hot flush increase of the tail skin temperature in ovariectomized rats
Authors: Uchida Masayuki , Kobayashi Orie
Published: March 2018

5-Hydroxytryptamine (5-HT) and noradrenaline have been thought to play important roles in the mechanism of hot flush. Then, to clarify the relation between serotonergic and adrenergic nervous systems on the mechanism of hot flush, the effect of paroxetine, 5-HT reuptake inhibitor (SSRI) was evaluated on the yohimbine-induced hot flush increase of tail skin temperature in ovariectomized female rats. Yohimbine (adrenaline α2 antagonist) significantly increased the tail skin temperature in course of time. Clonidine (adrenaline α2 agonist) significantly attenuated this effect. Paroxetine also significantly inhibited the increase of tail skin temperature by yohimbine. α-Lactalbumin having SSRI activity in vitro study also significantly inhibited the increase of tail skin temperature, but not significantly decreased the initial temperature. This difference may explain the different mechanism between paroxetine (SSRI) and α-lactalbumin, suggesting new mechanism of hot flush.
VASP regulates leukocyte infiltration, polarization, and vascular repair after ischemia
Authors: Laban Hebatullah , Weigert Andreas , Zink Joana , Elgheznawy Amro , Schürmann Christoph , Günther Lea , Abdel Malik Randa , Bothur Sabrina , Wingert Susanne , Bremer Rolf , Rieger Michael A. , Brüne Bernhard , Brandes Ralf P. , Fleming Ingrid , Benz Peter M.
Published: March 2018

In ischemic vascular diseases, leukocyte recruitment and polarization are crucial for revascularization and tissue repair. We investigated the role of vasodilator-stimulated phosphoprotein (VASP) in vascular repair. After hindlimb ischemia induction, blood flow recovery, angiogenesis, arteriogenesis, and leukocyte infiltration into ischemic muscles in VASP−/− mice were accelerated. VASP deficiency also elevated the polarization of the macrophages through increased signal transducer and activator of transcription (STAT) signaling, which augmented the release of chemokines, cytokines, and growth factors to promote leukocyte recruitment and vascular repair. Importantly, VASP deletion in bone marrow–derived cells was sufficient to mimic the increased blood flow recovery of global VASP−/− mice. In chemotaxis experiments, VASP−/− neutrophils/monocytes were significantly more responsive to M1-related chemokines than wild-type controls. Mechanistically, VASP formed complexes with the chemokine receptor CCR2 and β-arrestin-2, and CCR2 receptor internalization was significantly reduced in VASP−/− leukocytes. Our data indicate that VASP is a major regulator of leukocyte recruitment and polarization in postischemic revascularization and support a novel role of VASP in chemokine receptor trafficking.
TAK1ng control: TAK1 restrains NLRP3 activation
Authors: Mangan Matthew Stephen , Latz Eicke
Published: March 2018

In this issue of JEM, Malireddi et al. (https://doi.org/10.1084/jem.20171922) demonstrate that macrophage-specific loss of TAK1 causes spontaneous NLRP3 inflammasome activation, driven by unregulated TNF secretion and signaling. This has implications for therapeutically targeting TAK1, enhancing its potential function as an anticancer drug treatment.
Mammals: A Very Short Introduction
Authors: Kemp T. S.
Published: March 2018

Mammals: A Very Short Introduction explores the nature, evolutionary history, and modern diversity of mammals. From a little shrew-like, nocturnal, insect-eating ancestor living 200 million years ago (mya), mammals have evolved into a huge variety of different kinds of animals. This VSI explains how it is endothermy—‘warm-bloodedness’—enabling high levels of activity and the relatively large brain associated with complex, adaptable behaviour that epitomizes mammals. It describes their remarkable fossil record, revealing how and when the mammals gained their characteristics, and the tortuous course of their evolution. It reveals the adaptations mammals evolved to suit their varied modes of life, including those of mainly arboreal primates culminating in Homo sapiens.
Genome Annotation Generator: a simple tool for generating and correcting WGS annotation tables for NCBI submission
Authors: Geib Scott M , Hall Brian , Derego Theodore , Bremer Forest T , Cannoles Kyle , Sim Sheina B
Published: March 2018

Background

One of the most overlooked, yet critical, components of a whole genome sequencing (WGS) project is the submission and curation of the data to a genomic repository, most commonly the National Center for Biotechnology Information (NCBI). While large genome centers or genome groups have developed software tools for post-annotation assembly filtering, annotation, and conversion into the NCBI's annotation table format, these tools typically require back-end setup and connection to an Structured Query Language (SQL) database and/or some knowledge of programming (Perl, Python) to implement. With WGS becoming commonplace, genome sequencing projects are moving away from the genome centers and into the ecology or biology lab, where fewer resources are present to support the process of genome assembly curation. To fill this gap, we developed software to assess, filter, and transfer annotation and convert a draft genome assembly and annotation set into the NCBI annotation table (.tbl) format, facilitating submission to the NCBI Genome Assembly database. This software has no dependencies, is compatible across platforms, and utilizes a simple command to perform a variety of simple and complex post-analysis, pre-NCBI submission WGS project tasks.

Findings

The Genome Annotation Generator is a consistent and user-friendly bioinformatics tool that can be used to generate a .tbl file that is consistent with the NCBI submission pipeline

Conclusions

The Genome Annotation Generator achieves the goal of providing a publicly available tool that will facilitate the submission of annotated genome assemblies to the NCBI. It is useful for any individual researcher or research group that wishes to submit a genome assembly of their study system to the NCBI.
Defective gene expression of the membrane complement inhibitor CD46 in patients with progressive immunoglobulin A nephropathy
Authors: Coppo Rosanna , Peruzzi Licia , Loiacono Elisa , Bergallo Massimilano , Krutova Alexandra , Russo Maria Luisa , Cocchi Enrico , Amore Alessandro , Lundberg Sigrid , Maixnerova Dita , Tesar Vladimir , Perkowska-Ptasińska Agnieszka , Durlik Magdalena , Goumenos Dimitris , Gerolymos Miltiadis , Galesic Kresimir , Toric Luka , Papagianni Aikaterini , Stangou Maria , Mizerska-Wasia Membek Malgorzata , Gesualdo Loreto , Montemurno Eustacchio , Benozzi Luisa , Cusinato Stefano , Hryszko Tomasz , Klinger Marian , Kamińska Dorota , Krajewska Magdalena ,   VALIGA Study Group of the ERA-EDTA Immunonephrology Working Group
Published: March 2018

Background

Complement is thought to play a role in immunoglobulin A nephropathy (IgAN), though the activating mechanisms are unknown. This study focused on the gene expression of CD46 and CD55, two key molecules for regulating C3 convertase activity of lectin and alternative complement pathways at a cellular level.

Methods

The transcriptional expression in peripheral white blood cells (WBCs) of CD46 and CD55 was investigated in 157 patients enrolled by the Validation of the Oxford Classification of IgAN group, looking for correlations with clinical and pathology features and estimated glomerular filtration rate (eGFR) modifications from renal biopsy to sampling. Patients had a previous median follow-up of 6.4 (interquartile range 2.8–10.7) years and were divided into progressors and non-progressors according to the median value of their velocity of loss of renal function per year (−0.41 mL/min/1.73 m2/year).

Results

CD46 and CD55 messenger RNA (mRNA) expression in WBCs was not correlated with eGFR values or proteinuria at sampling. CD46 mRNA was significantly correlated with eGFR decline rate as a continuous outcome variable (P = 0.014). A significant difference was found in CD46 gene expression between progressors and non-progressors (P = 0.013). CD46 and CD55 mRNA levels were significantly correlated (P < 0.01), although no difference between progressors and non-progressors was found for CD55 mRNA values. The prediction of progression was increased when CD46 and CD55 mRNA expressions were added to clinical data at renal biopsy (eGFR, proteinuria and mean arterial blood pressure) and Oxford MEST-C (mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, presence of any crescents) score.

Conclusions

Patients with progressive IgAN showed lower expression of mRNA encoding for the complement inhibitory protein CD46, which may implicate a defective regulation of C3 convertase with uncontrolled complement activation.
Data-driven analysis of biomedical literature suggests broad-spectrum benevolence of culinary herbs and spices
Authors: N K Rakhi , Tuwani Rudraksh , Mukherjee Jagriti , Bagler Ganesh
Published: March 2018

Spices and herbs are key dietary ingredients used across cultures worldwide. Beyond their use as flavoring and coloring agents, the popularity of these aromatic plant products in culinary preparations has been attributed to their antimicrobial properties. Last few decades have witnessed an exponential growth of biomedical literature investigating the impact of spices and herbs on health, presenting an opportunity to mine for patterns from empirical evidence. Systematic investigation of empirical evidence to enumerate the health consequences of culinary herbs and spices can provide valuable insights into their therapeutic utility. We implemented a text mining protocol to assess the health impact of spices by assimilating, both, their positive and negative effects. We conclude that spices show broad-spectrum benevolence across a range of disease categories in contrast to negative effects that are comparatively narrow-spectrum. We also implement a strategy for disease-specific culinary recommendations of spices based on their therapeutic tradeoff against adverse effects. Further by integrating spice-phytochemical-disease associations, we identify bioactive spice phytochemicals potentially involved in their therapeutic effects. Our study provides a systems perspective on health effects of culinary spices and herbs with applications for dietary recommendations as well as identification of phytochemicals potentially involved in underlying molecular mechanisms.
Bistable emergence of oscillations in structured cell populations
Authors: Martinez-Corral Rosa , Liu Jintao , Suel Gurol , Garcia-Ojalvo Jordi
Published: March 2018

Biofilm communities ofBacillus subtilisbacteria have recently been shown to exhibit collective growth-rate oscillations mediated by electrochemical signaling to cope with nutrient starvation. These oscillations emerge once the colony reaches a large enough number of cells. However, it remains unclear whether the amplitude of the oscillations, and thus their effectiveness, builds up over time gradually, or if they can emerge instantly with a non-zero amplitude. Here we address this question by combining microfluidics-based time-lapse microscopy experiments with a minimal theoretical description of the system in the form of a delay-differential equation model. Analytical and numerical methods reveal that oscillations arise through a subcritical Hopf bifurcation, which enables instant high amplitude oscillations. Consequently, the model predicts a bistable regime where an oscillating and a non-oscillating attractor coexist in phase space. We experimentally validate this prediction by showing that oscillations can be triggered by perturbing the media conditions, provided the biofilm size lies within an appropriate range. The model also predicts that the minimum size at which oscillations start decreases with stress, a fact that we also verify experimentally. Taken together, our results show that collective oscillations in cell populations can emerge suddenly with non-zero amplitude via a discontinuous transition.
Central dogma rates and the trade-off between precision and economy
Authors: Hausser Jean , Mayo Avi , Alon Uri
Published: March 2018

Steady-state protein abundance is set by four rates: transcription, translation, mRNA decay and protein decay. A given protein abundance can be obtained from infinitely many combinations of these rates. This raises the question of whether the natural rates for each gene result from historical accidents, or are there rules that give certain combinations a selective advantage? We address this question using high-throughput measurements in rapidly growing cells from diverse organisms to find that about half of the rate combinations do not exist: genes that combine high transcription with low translation are strongly depleted. This depletion is due to a trade-off between precision and economy: high transcription decreases stochastic fluctuations but increases transcription costs. Our theory quantitatively explains which rate combinations are missing, and predicts the curvature of the fitness function for each gene. It may guide the design of gene circuits with desired expression levels and noise.
Democratisation or individualisation? On the distribution of food consumption
Authors: Necula Raluca Alexandra , Mann Stefan
Published: March 2018

Purpose

While economists are increasingly acknowledging the importance of distributional issues, the distribution of the consumption of food items has largely been neglected. The purpose of this paper is to demonstrate that important insights can be obtained by analysing the distribution of consumption of food products within society.

Design/methodology/approach

This study was conducted by analysing food consumption in two very different countries: Romania, a middle-income country and Switzerland, one of the most prosperous countries in the world. In order to test the formulated hypotheses, consumption per capita was calculated, as a base for the calculation of the Gini coefficient of consumption for each product. A mixed effect model was applied for total food and for meat, computing the predictors for the variable “consumption distribution”.

Findings

Using the Gini coefficients of food and drink item consumption by Romanian and Swiss households, the authors tested the hypothesis that in prosperous middle-income countries the homogeneity of food consumption is growing over time as a sign of consumption democratisation, whereas in high-income countries a growing degree of individualisation is leading to decreasing homogeneity. For meat, the bifurcation of consumption patterns between vegetarians and hedonists leads to a growing Gini coefficient over time for both countries. The analysis controls for factors such as the products’ importance in the diet and their price.

Originality/value

The paper approaches a new subject and raises a new research question that may be relevant for structural issues of contemporary society. Both the comparative analysis of food distribution in two different societies and their dynamics is a novelty.
Pilot study on food sharing and social media in Italy
Authors: D’Ambrosi Lucia
Published: March 2018

Purpose

The purpose of this paper is to gauge consumer attitudes to food sharing practices in Italy and to assess the support that digital technologies can offer in to promote more responsible consumption.

Design/methodology/approach

The methodology involves a web-based survey through using specialized online platforms (e.g. websites; Facebook groups; and Facebook pages), which provide content on sustainable and responsible consumption and crowd funding campaigns.

Findings

The research highlights the increasingly aware and attentive consumer attitudes towards collaborative economic practices compared to the past. In Italy, however, digital platforms for exchanging surplus food or goods are still poorly used. In fact, there is still a lack of knowledge, largely conditioned by recent experienced with some apps and by the poor development of this type of market.

Research limitations/implications

The research is a pilot of a small-scale study protocol conducted in January 2017 to ascertain the suitability of a wider project on social food sharing practices and environmental sustainability, by determining its feasibility or obtaining information for identification of the key indicators and analysis of the dimensions of the final study.

Originality/value

The research produces first empirical results that may provide new information, related to the role of digital media, on consumption habits.
Perceived quality and intention to revisit coffee concept shops in Malaysia
Authors: Ting Hiram , Lau Wee Ming , Cheah Jun-Hwa , Yacob Yusman , Memon Mumtaz Ali , Lau Evan
Published: March 2018

Purpose

The purpose of this paper is to examine the effect of perceived quality on intention to revisit coffee concept shops among regular and irregular consumers. Specifically, the framework developed by Pine and Gilmore (2000) is adopted to look into the effect of product, service and experience qualities on intention to revisit.

Design/methodology/approach

The explanatory sequential mixed-methods design was used to articulate the intention of consumers to revisit coffee concept shops. A preliminary study was conducted to define regular and irregular consumers. Self-administered questionnaire was first administered before using interview to elicit more insights and triangulate the findings.

Findings

The combination of both quantitative and qualitative findings show that the experiences of regular consumers at coffee concept shops include personal routine activities, while the experiences of irregular customers are composed of occasions with specific and collective purposes. While the intention to revisit of the former is related to the product and service quality, the intention of the latter is largely affected by its service and experience quality.

Originality/value

Given the rapid rise of coffee concept shops in the developing markets, the use of a mixed-methods design provides more insights into the intention to revisit of the regular and irregular consumers. It underscores the importance for the organisations to know what really matters to the diverse consumers.
Exploring loyalty to specialty foods among tourists and residents
Authors: Suhartanto Dwi , Chen Brendan T. , Mohi Zurinawati , Sosianika Adila
Published: March 2018

Purpose

The purpose of this paper is to examine a specialty food loyalty model which includes perceived quality, satisfaction, and motivation, and to assess the model’s applicability in two distinct groups of customers: tourists and residents.

Design/methodology/approach

Data were collected from 455 specialty food customers in Bandung, Indonesia. Variance-based structural equation modeling (partial least squares (PLS)) was used to examine the relationship between the drivers (perceived quality, satisfaction and motivation) and loyalty according to the data presented by tourists and residents.

Findings

This study indicates that the perception of quality is an important factor affecting tourists’ and residents’ satisfaction with, and loyalty to, a product. Furthermore, this study suggests that motivation factors are important for tourists and residents in regard to developing loyalty to specialty foods.

Practical implications

This study provides a venue for retail managers and producers to improve their business performance by developing specialty foods of high quality. To improve their quality, this research suggests that managers and retailers focus on innovation based on exotic and unique traditional food reflecting the richness of local culture. To ensure their loyalty, customers of specialty foods need to be motivated by internal and external factors.

Originality/value

This study is one of the first to examine the formation of specialty food loyalty in two distinct groups of customers: tourists and residents.
Organic food online shopping in Poland
Authors: Bryła Paweł
Published: March 2018

Purpose

The purpose of this paper is to analyse selected characteristics, attitudes and opinions of organic food e-consumers (online shoppers) in Poland.

Design/methodology/approach

A survey was conducted among 1,000 inhabitants of Poland aged 15-65. The sample resembled the general population, regarding: age, sex, education and the size of the city of origin. In total, 63 respondents reported buying organic food online. This segment was compared with the rest of the sample with the use of two-tailed t-tests. A logistic regression model was applied to identify the determinants of organic food online shopping in Poland.

Findings

In a logistic regression model, age, income, willingness to pay (WTP) a premium price for organic food, importance attached to product appearance and to quality signs turned out to be statistically significant determinants of online shopping behaviour for organic food in Poland. Higher income, importance attached to quality signs and higher WTP increase the likelihood of being an organic e-consumer, while higher age and importance attached to product appearance decrease it.

Research limitations/implications

First, some determinants of organic online shopping have been identified. Second, this study has provided some frameworks to analyse organic food selection motives, barriers to the development of the market, food authenticity assessment criteria, distribution channels, and product characteristics.

Practical implications

The findings may be useful for the industry due to the identification of the role of quality signs in online food purchases and of the importance of selected organic food consumption motives.

Originality/value

To the best of the author’s knowledge, this is the first study of organic food online shopping in Poland.
Strategic human resource management: a power based critique
Authors: Das Roshni , Kodwani Amitabh Deo
Published: March 2018

Purpose

By undertaking a detailed review of the Strategic Human Resource Management (SHRM) discourse, the purpose of this paper is to uncover and explicate the power differentials embedded in the social structure of organizations and suggests ways to reconcile them.

Design/methodology/approach

Methods used are thematic review, content analysis, and inductive theorizing, with Foucault’s archaeological and genealogical analysis style as the overarching framework.

Findings

At the methodological level, the authors demonstrate the application of Foucault’s twin methods: archaeological and genealogical analysis. At the substantive level, the authors have two contributions. First, the authors critique and analyze the various themes of power that emerge from the SHRM discourse as well as the hybridized overlaps of SHRM with other organization studies topics of interest such as organizational learning, network studies, control and postmodernism. Second, the authors propose a “Power” theory based nomothetic, typological synthesis for crafting the business-facing human resource (HR) function. The power lens manifests as the meta-theory to guide a much required streamlining of constructs and “value laden” synthesis of the literature.

Research limitations/implications

The potential of critical theory in crafting situated and context-sensitive research propositions is demonstrated.

Practical implications

Organizational strategists and HR managers can utilize the proposed typology to better understand their current ideological positions and decide future aspired images.

Originality/value

This is a conversation between two paradigms, SHRM and power theory, that are epistemologically at two opposite poles.
Importance-performance analysis (IPA) for testing – and calibration – laboratories in India
Authors: Karthiyayini Nagarajan , Rajendran C. , Kumaravel Munusamy
Published: March 2018

Purpose

The purpose of this paper is to formulate the strategy for improving the laboratory practices to enhance customer satisfaction by analyzing the performance of critical factors of IS/ISO/IEC 17025 (2005) laboratory accreditation and the importance attached by the quality/technical managers in the accredited Indian testing/calibration laboratories.

Design/methodology/approach

The perceptions of the critical factors of laboratory accreditation and the importance attached by the quality/technical managers in their organizations have been collected and analyzed to develop an importance-performance analysis (IPA) model to enhance the customer satisfaction.

Findings

Findings report that the performance of the critical factors and the importance assigned to them are not the same. There exist gaps between the performance and importance which need to be measured and analyzed by the management to strive toward continual improvement to enhance the customer satisfaction through the accredited testing and calibration services.

Research limitations/implications

This study is restricted to 54 responses out of 150 which were sent (i.e. about 36 percent response rate) to capture the perspectives of the quality/technical managers.

Practical implications

This study would enable the accredited laboratories to analyze the gap in performance and the importance assigned to critical factors through the feedback from the quality/technical managers. By analyzing the strengths and weaknesses in the accredited testing/calibration laboratories, managerial decisions and strategic plans can be proposed to gain greater insights into benchmarking improvement of the laboratory quality management system with the existing resources to strive toward customer satisfaction.

Originality/value

This paper proposes IPA as a tool to assess the gap between the importance and performance of critical factors of accredited testing and calibration laboratories in India.
User experience sharing
Authors: Chen Tom , Drennan Judy , Andrews Lynda , Hollebeek Linda D.
Published: March 2018

Purpose

This paper aims to propose user experience sharing (UES) as a customer-based initiation of value co-creation pertaining to service provision, which represents customers’ level of effort made for the direct benefit of others in their service network. The authors propose and empirically examine a user experience sharing model (UESM) that explicates customer-to-customer (C2C) UES and its impacts on firm-desired customer-based outcomes in online communities.

Design/methodology/Approach

Based on an extensive review, the authors conceptualize UES and UESM. By using online survey data collected from mobile app users in organic online communities, the authors performed structural equation modeling analyses by using AMOS 24.

Findings

The results support the proposed UESM, showing that C2C UES acts as a key driver of both firm-desired customer efforts and customer insights. The results also confirmed that service-dominant (S-D) logic-informed motivational drivers exert a significant impact on C2C UES. Importantly, C2C UES mediates the relationship between S-D logic-informed motivational drivers and firm-desired customer-based outcomes.

Originality/value

This study offers a pioneering attempt to develop an overarching concept, UES, which reflects customers’ initiation of value co-creation, and to empirically examine C2C UES. The empirical evidence supports the key contention that firms should proactively facilitate C2C UES.