bluuebunny/crossref_metadata_2025 huggingface dataset:
The glutathione import system satisfies the Staphylococcus aureus nutrient sulfur requirement and promotes interspecies competition
Authors: Lensmire Joshua M. , Wischer Michael R. , Sosinski Lo M. , Ensink Elliot , Dodson Jack P. , Shook John C. , Delekta Phillip C. , Cooper Christopher C. , Havlichek Daniel , Mulks Martha H. , Lunt Sophia Y. , Ravi Janani , Hammer Neal D.
Published: October 2021

Sulfur is an indispensable element for proliferation of bacterial pathogens. Prior studies indicated that the human pathogen, Staphylococcus aureus utilizes glutathione (GSH) as a source of nutrient sulfur; however, mechanisms of GSH acquisition are not defined. Here, we identify a previously uncharacterized five-gene locus comprising a putative ABC-transporter and γ–glutamyl transpeptidase (ggt) that promotes S. aureus proliferation in medium supplemented with either reduced or oxidized GSH (GSSG) as the sole source of nutrient sulfur. Based on these phenotypes, we name this transporter the Glutathione import system (GisABCD). We confirm that Ggt is capable of cleaving GSH and GSSG γ–bonds and that this process is required for their use as nutrient sulfur sources. Additionally, we find that the enzyme is cell associated. Bioinformatic analyses reveal that only Staphylococcus species closely related to S. aureus encode GisABCD-Ggt homologues. Homologues are not detected in Staphylococcus epidermidis. Consequently, we establish that GisABCD-Ggt provides a competitive advantage for S. aureus over S. epidermidis in a GSH-dependent manner. Overall, this study describes the discovery of a nutrient sulfur acquisition system in S. aureus that targets GSH and promotes competition against other staphylococci commonly associated with the human microbiota.
Architecture of the linker-scaffold in the nuclear pore
Authors: Petrovic Stefan , Samanta Dipanjan , Perriches Thibaud , Bley Christopher J. , Thierbach Karsten , Brown Bonnie , Nie Si , Mobbs George W. , Stevens Taylor A. , Liu Xiaoyu , Hoelz André
Published: October 2021

The nuclear pore complex (NPC) is the sole bidirectional gateway for nucleocytoplasmic transport. Despite recent progress in elucidating the arrangement of the structured scaffold building blocks in the NPC symmetric core, their cohesion by multivalent unstructured linker proteins remained elusive. Combining biochemical reconstitution, high resolution structure determination, docking into cryo-electron tomographic reconstructions, and physiological validation, we elucidated the architecture of the entire linker-scaffold, yielding a near-atomic composite structure of the symmetric core accounting for ∼77 MDa of the human NPC. Whereas linkers generally play a rigidifying role, the linker-scaffold of the NPC provides the plasticity and robustness necessary for the reversible constriction and dilation of its central transport channel. Our results complete the structural characterization of the NPC symmetric core, providing a rich foundation for future functional studies.

One sentence summary

An interdisciplinary analysis established the near-atomic molecular architecture and evolutionary conservation of the linker-scaffold of the human nuclear pore complex.
Cyclic uniaxial mechanical load enhances chondrogenesis through entraining the molecular circadian clock
Authors: Vágó Judit , Katona Éva , Takács Roland , Dócs Klaudia , Hajdú Tibor , Kovács Patrik , Zákány Róza , van der Veen Daan R. , Matta Csaba
Published: October 2021

The biomechanical environment plays a key role in regulating cartilage formation, but current understanding of mechanotransduction pathways in chondrogenic cells is incomplete. Amongst the combination of external factors that control chondrogenesis are temporal cues that are governed by the cell-autonomous circadian clock. However, mechanical stimulation has not yet directly been proven to modulate chondrogenesis via entraining the circadian clock in chondroprogenitor cells. The purpose of this study was to establish whether mechanical stimuli entrain the core clock in chondrogenic cells, and whether augmented chondrogenesis caused by mechanical loading was at least partially mediated by the synchronised, rhythmic expression of the core circadian clock genes, chondrogenic transcription factors, and cartilage matrix constituents at both transcript and protein levels. We report here, for the first time, that cyclic uniaxial mechanical load applied for 1 hour for a period of 6 days entrains the molecular clockwork in chondroprogenitor cells during chondrogenesis in limb bud-derived micromass cultures. In addition to the several core clock genes and proteins, the chondrogenic markers SOX9 and ACAN also followed a robust sinusoidal rhythmic expression pattern. These rhythmic conditions significantly enhanced cartilage matrix production and upregulated marker gene expression. The observed chondrogenesis-promoting effect of the mechanical environment was at least partially attributable to its entraining effect on the molecular clockwork, as co-application of the small molecule clock modulator longdaysin attenuated the stimulatory effects of mechanical load. This study suggest that an optimal biomechanical environment enhances tissue homeostasis and histogenesis during chondrogenesis at least partially through entraining the molecular clockwork.
Development of ultrafast camera-based imaging of single fluorescent molecules and live-cell PALM
Authors: Fujiwara Takahiro K. , Takeuchi Shinji , Kalay Ziya , Nagai Yosuke , Tsunoyama Taka A. , Kalkbrenner Thomas , Iwasawa Kokoro , Ritchie Ken P. , Suzuki Kenichi G.N. , Kusumi Akihiro
Published: October 2021

The spatial resolution of fluorescence microscopy has recently been greatly improved. However, its temporal resolution has not been improved much, despite its importance for examining living cells. Here, by developing an ultrafast camera system, we achieved the world’s highest time resolutions for single fluorescent-molecule imaging of 33 (100) µs (multiple single molecules simultaneously) with a single-molecule localization precision of 34 (20) nm for Cy3 (best dye found), and for PALM data acquisition of a view-field of 640×640 pixels at 1 kHz with a single-molecule localization precision of 29 nm for mEos3.2. Both are considered the ultimate rates with available probes. This camera system (1) successfully detected fast hop diffusion of membrane molecules in the plasma membrane, detectable previously only by using less preferable 40-nm gold probes and bright-field microscopy, and (2) enabled PALM imaging of the entire live cell, while revealing meso-scale dynamics and structures, caveolae and paxillin islands in the focal adhesion, proving its usefulness for cell biology research.

An ultrafast camera developed by Fujiwara et al. allows single fluorescent-molecule imaging every 33 μs with a localization precision of 34 nm (every 100 μs; 20 nm), and enables ultrafast PALM imaging of whole live cells.
miRNA mediated downregulation of non-muscle Cyclase associated protein 1 is required for myogenic differentiation
Authors: Singh Anurag Kumar , Rai Amrita , Weber Anja , Posern Guido
Published: October 2021

Myoblast fusion is crucial for the formation, growth and regeneration of healthy skeletal muscle, but the molecular mechanisms that govern fusion and myofiber formation remain poorly understood. Here we report that Cyclase-associated protein 1 (Cap1), a regulator of actin dynamics, plays a critical role in cytoskeletal remodeling during myoblast fusion and formation of myotubes. Cap1 mRNA and protein are expressed in murine C2C12 and human LHCN-M2 myoblasts, but its abundance decreases during myogenic differentiation. Perturbing the temporally controlled expression of Cap1 by overexpression or Crispr-Cas9 mediated knockout impaired actin rearrangement, myoblast alignment, expression of profusion molecules, differentiation into multinucleated myotubes and myosin heavy chain expression. Endogenous Cap1 expression is posttranscriptionally downregulated during differentiation by canonical myomiRs miR-1, miR-133 and miR-206, which have conserved binding sites in the 3’ UTR of the Cap1 mRNA. Deletion of the endogenous 3’ UTR in C2C12 cells phenocopies overexpression of Cap1 by inhibiting myotube formation. Our findings implicate Cap1 and its myomiR-mediated downregulation in the myoblast fusion process and the generation of skeletal muscle.
Chromosome-scale assemblies of Acanthamoeba castellanii genomes provide insights into Legionella pneumophila infection-related chromatin re-organization
Authors: Matthey-Doret Cyril , Colp Morgan J. , Escoll Pedro , Thierry Agnès , Curtis Bruce , Sarrasin Matt , Gray Michael W. , Lang B. Franz , Archibald John M. , Buchrieser Carmen , Koszul Romain
Published: October 2021

The unicellular amoeba Acanthamoeba castellanii is ubiquitous in aquatic environments, where it preys on bacteria. The organism also hosts bacterial endosymbionts, some of which are parasitic, including human pathogens such as Chlamydia and Legionella spp. Here we report complete, high quality genome sequences for two extensively studied A. castellanii strains, Neff and C3. Combining long- and short-read data with Hi-C, we generated near chromosome-level assemblies for both strains with 90% of the genome contained in 29 scaffolds for the Neff strain and 31 for the C3 strain. Comparative genomics revealed strain-specific functional enrichment, most notably genes related to signal transduction in the C3 strain, and to viral replication in Neff. Furthermore, we characterized the spatial organization of the A. castellanii genome and showed that it is reorganized during infection by Legionella pneumophila. Infection-dependent chromatin loops were found to be enriched in genes for signal transduction and phosphorylation processes. In genomic regions where chromatin organization changed during Legionella infection, we found functional enrichment for genes associated with metabolism, organelle assembly, and cytoskeleton organization, suggesting that changes in chromosomal folding are associated with host cell biology during infection.
The Mycobacterium tuberculosis DNA-repair helicase UvrD1 is activated by redox-dependent dimerization via a 2B domain cysteine conserved in other Actinobacteria
Authors: Chadda Ankita , Jensen Drake , Tomko Eric J. , Manzano Ana Ruiz , Nguyen Binh , Lohman Timothy M. , Galburt Eric A.
Published: October 2021

Mycobacterium tuberculosis (Mtb) causes Tuberculosis and, during infection, is exposed to reactive oxygen species (ROS) and reactive nitrogen intermediates (RNI) from the host immune response that can cause DNA damage. UvrD-like proteins are involved in DNA repair and replication and belong to the SF1 family of DNA helicases that use ATP hydrolysis to catalyze DNA unwinding. In Mtb, there are two UvrD-like enzymes where UvrD1 is most closely related to other family members. Previous studies have suggested that UvrD1 is exclusively monomeric, however it is well-known that E. coli UvrD and other UvrD-family members exhibit monomer-dimer equilibria and unwind as dimers in the absence of accessory factors. Here, we reconcile these incongruent studies by showing that Mtb UvrD1 exists in monomer, dimer, and tetramer oligomeric forms where dimerization is regulated by redox potential. We identify a 2B domain cysteine, conserved in many Actinobacteria, that underlies this effect. We also show that UvrD1 DNA unwinding activity correlates specifically with the dimer population and is thus titrated directly via increasing positive (i.e. oxidative) redox potential. Consistent with the regulatory role of the 2B domain and the dimerization-based activation of DNA unwinding in UvrD-family helicases, these results suggest that UvrD1 is activated under oxidizing conditions when it may be needed to respond to DNA damage during infection.
Suitability of GRK antibodies for individual detection and quantification of GRK isoforms in western blots
Authors: Reichel Mona , Weitzel Verena , Klement Laura , Hoffmann Carsten , Drube Julia
Published: October 2021

G protein-coupled receptors (GPCRs) are regulated by GPCR kinases (GRKs) which phosphorylate intracellular domains of the active receptor. This leads to the recruitment of arrestins resulting in desensitization and internalization of the GPCR. Aside from acting on GPCRs, GRKs regulate a variety of membrane, cytosolic, and nuclear proteins not only via phosphorylation but also by acting as scaffold. This multifunctionality is also reflected by their diverse roles in pathological conditions like cancer, influenza infection, malaria, and metabolic disease.

Reliable tools to study GRKs are the key to specify their role in complex cellular signaling networks. Thus, we examined the specificity of eight commercially available antibodies targeting the four ubiquitously expressed GRK2, GRK3, GRK5, and GRK6 in western blot analysis. We thereby identified one antibody that did not recognize its antigen, as well as antibodies that showed unspecific signals or cross reactivity. Thus, we strongly recommend testing any antibody with exogenously expressed proteins to clearly confirm identity of the obtained western blot results.

Utilizing the most suitable antibodies we established the western blot-based, cost-effective, simple tag-guided analysis of relative protein abundance (STARPA). This method allows comparison of protein levels obtained by immunoblotting with different antibodies. Furthermore, we applied STARPA to determine GRK protein levels in five commonly used cell lines revealing differential isoform expression.
RNA compensation: A positive feedback insulation strategy for RNA-based networks
Authors: Liu Baiyang , Samaniego Christian Cuba , Bennett Matthew , Chappell James , Franco Elisa
Published: October 2021

The lack of signalling modularity of biomolecular systems poses major challenges toward engineering complex networks. An important problem is posed by the consumption of signaling molecules upon circuit interconnection, which makes it possible to control a downstream circuit but compromises the performance of the upstream circuit. This issue has been previously addressed with insulation strategies including high-gain negative feedback and phosphorylation-dephosphorylation reaction cycle. In this paper, we focus on RNA-based circuits and propose a new positive-feedback insulation strategy to mitigate signal consumption. An RNA input is added in tandem with transcription output to compensate the RNA consumption, leading to concentration robustness of the input RNA molecule regardless of the amount of downstream modules. We term this strategy RNA compensation, and it can be applied to systems that have a stringent input-output gain, such as Small Transcription Activating RNAs (STARs). Our analysis shows that RNA compensation not only eliminates the signaling consumption in individual STAR-based regulators, but also improves the composability of STAR cascades and the modularity of RNA bistable systems.
PDGFR dimer-specific activation, trafficking and downstream signaling dynamics
Authors: Rogers Madison A. , Fantauzzo Katherine A.
Published: October 2021

Signaling through the platelet-derived growth factor receptors (PDGFRs) plays a critical role in multiple cellular processes during development. The two PDGFRs, PDGFRα and PDGFRβ, dimerize to form homodimers and/or heterodimers. Here, we overcome previous limitations in studying PDGFR dimer-specific dynamics by generating cell lines stably expressing C-terminal fusions of each PDGFR with bimolecular fluorescence complementation (BiFC) fragments corresponding to the N-terminal or C-terminal regions of the Venus fluorescent protein. We find that PDGFRβ receptors homodimerize more quickly than PDGFRα receptors in response to PDGF ligand, with increased levels of autophosphorylation. Further, we demonstrate that PDGFRα homodimers are trafficked and degraded more quickly, while PDGFRβ homodimers are more likely to be recycled back to the cell membrane. We show that PDGFRβ homodimer activation results in a greater amplitude of phospho-ERK1/2 and phospho-AKT signaling, as well as increased proliferation and migration. Collectively, our findings provide significant insight into how biological specificity is introduced to generate unique responses downstream of PDGFR engagement.

The authors utilize a novel bimolecular fluorescence complementation approach to investigate PDGFR homodimer-specific dynamics. They uncover differences in the timing and extent of receptor dimerization, activation and trafficking, which lead to changes in downstream signaling and cellular activity.
Cell wall damage reveals spatial flexibility in peptidoglycan synthesis and a non-redundant role for RodA in mycobacteria
Authors: Melzer Emily S. , Kado Takehiro , García-Heredia Alam , Gupta Kuldeepkumar Ramnaresh , Meniche Xavier , Morita Yasu S. , Sassetti Christopher M. , Rego E. Hesper , Siegrist M. Sloan
Published: October 2021

Cell wall peptidoglycan is a heteropolymeric mesh that protects the bacteria from internal turgor and external insults. In many rod-shaped bacteria, peptidoglycan synthesis for normal growth is achieved by two distinct pathways: the Rod complex, comprised of MreB, RodA and a cognate class B PBP, and the class A PBPs. In contrast to laterally-growing bacteria, pole-growing mycobacteria do not encode an MreB homolog and do not require SEDS protein RodA forin vitrogrowth. However, RodA contributes to survival ofMycobacterium tuberculosisin some infection models, suggesting that the protein could have a stress-dependent role in maintaining cell wall integrity. Under basal conditions, we find here that the subcellular distribution of RodA largely overlaps with that of the aPBP PonA1, and that both RodA and the aPBPs promote polar peptidoglycan assembly. Upon cell wall damage, RodA fortifiesM. smegmatisagainst lysis and, unlike aPBPs, contributes to a shift in peptidoglycan assembly from the poles to the sidewall. Neither RodA nor PonA1 relocalize; instead, the redistribution of nascent cell wall parallels that of peptidoglycan precursor synthase MurG. Our results support a model in which mycobacteria balance polar growth and cell-wide repair via spatial flexibility in precursor synthesis and extracellular insertion.

Importance

Peptidoglycan synthesis is a highly successful target for antibiotics. The pathway has been extensively studied in model organisms under laboratory-optimized conditions. In natural environments, bacteria are frequently under attack. Moreover the vast majority of bacterial species are unlikely to fit a single paradigm because of differences in growth mode and/or envelope structure. Studying cell wall synthesis under non-optimal conditions and in non-standard species may improve our understanding of pathway function and suggest new inhibition strategies.Mycobacterium smegmatis,a relative of several notorious human and animal pathogens, has an unusual polar growth mode and multi-layered envelope. In this work we challengedM. smegmatiswith cell wall-damaging enzymes to characterize the roles of cell wall-building enzymes when the bacterium is under attack.
Expectation violations enhance neuronal encoding of sensory information in mouse primary visual cortex
Authors: Tang Matthew F. , Kheradpezhouh Ehsan , Lee Conrad C.Y. , Dickinson J. Edwin , Mattingley Jason B. , Arabzadeh Ehsan
Published: October 2021

The response of cortical neurons to sensory stimuli is shaped both by past events (adaptation) and the expectation of future events (prediction). Here we employed a visual stimulus paradigm with different levels of predictability to characterise how expectation influences orientation selectivity in the primary visual cortex (V1) of mice. We recorded neuronal activity using two-photon calcium imaging (GCaMP6f) while animals viewed sequences of grating stimuli which either varied randomly in their orientations or rotated predictably with occasional transitions to an unexpected orientation. For single neurons and the population, there was significant enhancement in the gain of orientation-selective responses to unexpected gratings. This gain-enhancement for unexpected stimuli was prominent in both awake and anaesthetised mice. We implemented a computational model to demonstrate how trial-to-trial variability in neuronal responses were best characterised when adaptation and expectation effects were combined.
The future of biomolecular simulation in the pharmaceutical industry: what we can learn from aerodynamics modelling and weather prediction. Part 1. understanding the physical and computational complexity of in silico drug design
Authors: Edwards Tom , Foloppe Nicolas , Harris Sarah Anne , Wells Geoff
Published: October 2021

The predictive power of simulation has become embedded in the infrastructure of modern economies. Computer-aided design is ubiquitous throughout industry. In aeronautical engineering, built infrastructure and materials manufacturing, simulations are routinely used to compute the performance of potential designs before construction. The ability to predict the behaviour of products is a driver of innovation by reducing the cost barrier to new designs, but also because radically novel ideas can be piloted with relatively little risk. Accurate weather forecasting is essential to guide domestic and military flight paths, and therefore the underpinning simulations are critical enough to have implications for national security. However, in the pharmaceutical and biotechnological industries, the application of computer simulations remains limited by the capabilities of the technology with respect to the complexity of molecular biology and human physiology. Over the last 30 years, molecular-modelling tools have gradually gained a degree of acceptance in the pharmaceutical industry. Drug discovery has begun to benefit from physics-based simulations. While such simulations have great potential for improved molecular design, much scepticism remains about their value. The motivations for such reservations in industry and areas where simulations show promise for efficiency gains in preclinical research are discussed. In this, the first of two complementary papers, the scientific and technical progress that needs to be made to improve the predictive power of biomolecular simulations, and how this might be achieved, is firstly discussed (Part 1). In Part 2, the status of computer simulations in pharma is contrasted with aerodynamics modelling and weather forecasting, and comments are made on the cultural changes needed for equivalent computational technologies to become integrated into life-science industries.
The impact of the CEO's financial literacy on family SMEs' growth: the moderating role of generational stage
Authors: Diéguez-Soto Julio , Martínez-Romero María J. , Corten Maarten , Michiels Anneleen
Published: October 2021

Purpose

This study investigates the impact of the CEO's financial literacy on family SMEs' growth, as well as the moderating role of the generational stage on this relationship.

Design/methodology/approach

The study is based on survey data of Spanish private family firms and utilizes a second source of data, the SABI database by Bureau Van Dijk. The authors run ordinary least squares regressions and use both the base and the partition approaches to test the hypotheses.

Findings

The analysis reveals a positive association between the CEO's financial literacy and firm growth. However, this relationship is not uniform across generations. The CEO's financial literacy-firm growth relationship becomes weaker for first- and third or subsequent-generation family firms while becoming stronger for second-generation family firms.

Originality/value

This study adds the financial literacy of the CEO as a novel individual-level determinant of family firm growth. It also shows that CEOs do not always use their financial literacy to its full potential to foster growth. More specifically, the extent to which financial literacy leads to firm growth is found to be conditional on the generational stage of the family SME. The obtained findings are valuable for family SMEs intending to hire a new CEO, encouraging the financial literacy of the current CEO and educating the next generation of family members.
Quiet versus loud luxury: the influence of overt and covert narcissism on young Chinese and US luxury consumers' preferences?
Authors: Jiang Ling , Cui Annie Peng , Shan Juan
Published: October 2021

Purpose

This study examines the impact of narcissism on young luxury consumers' preferences for quiet versus loud luxury products in China and the United States. As young consumers are increasingly becoming the bedrock of global luxury growth, it is imperative for marketing researchers and practitioners to understand the psychological and social needs of these consumers.

Design/methodology/approach

A two-study examination of young Chinese and US luxury consumers suggests that the two types of narcissism influence luxury consumption in different ways. Study 1 is a survey of young Chinese consumers that examines how the impact of narcissism on luxury purchase is mediated by social attitude functions and moderated by social anxiety. Study 2 is an experiment conducted in both the United States and China that establishes the causal relationship between the different types of narcissism and purchase intention toward quiet versus loud luxury products.

Findings

Building on an overarching framework that integrates both the narcissism literature and social attitude function theory, this study shows that overt narcissistic (vs. covert) consumers hold a value-expressive (vs. social-adjustive) attitude toward luxury products, which leads them to prefer quiet (vs. loud) luxury. In addition, higher levels of social anxiety enhance the mediating role of narcissistic consumers' social attitude functions.

Originality/value

This study advances understanding of young Chinese and US luxury consumers' narcissistic consumption patterns by proposing and empirically testing a novel research model that examines the mechanisms by which overt and covert narcissism leads to a different preference of quiet and loud luxury via the routes of different social attitude functions.
The impact of management support on individual learning opportunity and creativity performance in Hong Kong manufacturing companies
Authors: Sun Hongyi , Ali Zulfiqar , Wei Liqun
Published: October 2021

Purpose

The purpose of this study is to explore the relationship and effect of management support on individual creativity performance by focusing on the individual learning opportunity, adaptability to change and learning motivation in Hong Kong manufacturing companies.

Design/methodology/approach

This study is based on survey data collection by using a respondent-driven approach from 266 employees working in Hong Kong-based manufacturing firms. The model and hypotheses were tested by employing variance-based structural equation modeling.

Findings

The findings indicate that management support has a positive effect on individual learning opportunity and creativity performance. Also, a significant positive relationship between individual creativity, performance, individual learning opportunity, adaptability to change, and learning motivation has been yielded. The management support has an overall positive link with all variables directly and indirectly.

Practical implications

Top management can foster employee creativity by supporting and providing learning opportunities and motivating employees to develop adaptive capability at an individual level.

Originality/value

An empirical study of how management support can foster individual creativity performance and individual learning opportunity. This study is one of the first to examine the positive relationship between management support and individual creativity by validating a purposed model, especially in the context of the Hong Kong manufacturing industry.
The hybrid nature of social enterprises how does it affect their revenue sources?
Authors: Searing Elizabeth A.M. , Poledrini Simone , Young Dennis R. , Nyssens Marthe
Published: October 2021

Purpose

This paper aims to examine the applicability of the benefits theory of nonprofit finance to an international sample of social enterprises (SEs).

Design/methodology/approach

This research analyzes the revenue sources of SEs through the lens of benefits theory. In particular, the authors test the links between revenue sources and the character of an enterprise’s mission. This study uses data on 545 SEs collected by the International Comparative Social Enterprise Models project, which was an international collaborative effort of more than 200 researchers. The authors use cross-sectional multivariate regression to identify the factors which influence the revenue portfolios of SEs.

Findings

The findings provide evidence of SE revenue portfolios that are nuanced and complicated. Benefits theory helps to illuminate this nuance. The application of benefits theory to SE goes beyond the traditional characterization of the publicness and privateness of goods and services to include the intended beneficiaries, the nature of benefits they receive and the management practices followed to assure distribution of benefits to intended beneficiary groups. By analyzing the public (and private) goals of SEs, such as employment generation and food security, the authors gain an understanding of what they really do, and hence, how they can be best financed.

Originality/value

This study provides empirical support to the applicability of benefits theory to SEs, which provides both theoretical advancement and practical implications.
Development of empirically-based customer-derived positioning taxonomy for FMCG sector in the Indian emerging market
Authors: Saqib Natasha , Shah Ali M.
Published: October 2021

Purpose

The purpose of this paper is to develop and validate a positioning taxonomy for the FMCG sector in the Indian emerging market, because a review of the literature shows that existing positioning typologies/taxonomies are based on managerial perspectives rather than consumer/customer perceptions and have only been developed for advanced countries. This study helps to solve this problem by creating a positioning taxonomy for emerging markets.

Design/methodology/approach

In three phases, this study uses a systematic procedure for developing and validating a scale. Phase 1 consists of item generation and selection based on a review of the literature, focus group sessions and expert opinion. The second phase entails scale refinement via exploratory factor analysis. Confirmatory factor analysis is used in Phase 3 to establish convergent, discriminant and nomological validity.

Findings

This study’s findings include a consumer-derived taxonomy of positioning strategies that have been tested and validated. There were four distinct positioning strategies that emerged: value for money, being local, premiumization and product attributes.

Research limitations/implications

The main implication of this paper is to support researchers in developing and validating measurement scales. The limitations include target populations, choice of industry and geography and cross-sectional time horizon of this study.

Practical implications

This study’s practical implications are the four positioning strategies that FMCG managers, advertising and marketing experts in the emerging Indian market could adopt to position their fast moving consumer goods (FMCG) products to achieve the overall success of their organizations.

Social implications

Researchers are provided step-by-step guidance on how to develop and validate a measurement scale.

Originality/value

This study adds to the marketing literature by providing both a solid theoretical foundation and a validated instrument for the operationalization of positioning strategies.
Contract‐Based Knowledge Protection and Cooperation Performance: The Effects of Technological Turbulence and Legal System Completeness
Authors: Wang Li , Wang Longwei , Zhang Min
Published: October 2021

This study examines the direct effects of technological turbulence and legal system completeness on contract‐based knowledge protection and the moderating effects of these factors on the relationship between contract‐based knowledge protection and cooperation performance. A conceptual model is developed using the sensemaking perspective. The model is tested using survey data collected from 227 manufacturing firms in China. We find that contract‐based knowledge protection is positively associated with cooperation performance. Technological turbulence and legal system completeness both have significant positive effects on contract‐based knowledge protection. In addition, technological turbulence weakens the positive relationship between contract‐based knowledge protection and cooperation performance, while legal system completeness strengthens the relationship. The findings enrich existing knowledge on how technological and legal environments shape firms’ decisions on knowledge protection in cooperation and moderate its effect on performance outcomes.
Re‐ordering connections: UK healthcare workers' experiences of emotion management during the COVID‐19 pandemic
Authors: Dowrick Anna , Mitchinson Lucy , Hoernke Katarina , Mulcahy Symmons Sophie , Cooper Silvie , Martin Sam , Vanderslott Samantha , Vera San Juan Norha , Vindrola‐Padros Cecilia
Published: October 2021

This paper examines the impact of disruptions to the organisation and delivery of healthcare services and efforts to re‐order care through emotion management during the COVID‐19 pandemic in the UK. Framing care as an affective practice, studying healthcare workers' (HCWs) experiences enables better understanding of how interactions between staff, patients and families changed as a result of the pandemic. Using a rapid qualitative research methodology, we conducted interviews with frontline HCWs in two London hospitals during the peak of the first wave of the pandemic and sourced public accounts of HCWs' experiences of the pandemic from social media (YouTube and Twitter). We conducted framework analysis to identify key factors disrupting caring interactions. Fear of infection and the barriers of physical distancing acted to separate staff from patients and families, requiring new affective practices to repair connections. Witnessing suffering was distressing for staff, and providing a ‘good death’ for patients and communicating care to families was harder. In addition to caring for patients and families, HCWs cared for each other. Infection control measures were important for limiting the spread of COVID‐19 but disrupted connections that were integral to care, generating new work to re‐order interactions.
Pre‐hospital intraosseous use in children: Indications and success rate
Authors: Ting Amy , Smith Karen , Wilson Catherine L , Babl Franz E , Hopper Sandy M
Published: October 2021

Objective

Intraosseous (IO) needle insertion is an effective method to obtain circulatory access in unwell children.

Methods

We conducted a 12‐month retrospective record review of children aged less than 18 years who had a recorded IO attempt by Ambulance Victoria paramedics.

Results

Sixty‐five children underwent IO attempt during pre‐hospital care, 60 had IO outcome recorded and were included. 58/60 (96.7%) children had IO successfully placed, 35 were aged <5 years. Cardiorespiratory arrest (39/58, 67.2%) and status epilepticus (11/58, 19%) were the most common indications.

Conclusion

While IO placement is uncommonly performed pre‐hospital, in critical situations there is a high success rate.
Detecting seasonal episodic‐like spatio‐temporal memory patterns using animal movement modelling
Authors: Thompson Peter R. , Derocher Andrew E. , Edwards Mark A. , Lewis Mark A.
Published: October 2021

Spatial memory plays a role in the way animals perceive their environments, resulting in memory‐informed movement patterns that are observable to ecologists. Developing mathematical techniques to understand how animals use memory in their environments allows for an increased understanding of animal cognition.

Here we describe a model that accounts for the memory of seasonal or ephemeral qualities of an animal's environment. The model captures multiple behaviours at once by allowing for resource selection in the present time as well as long‐distance navigations to previously visited locations within an animal's home range.

We performed a set of analyses on simulated data to test our model, determining that it can provide informative results from as little as 1 year of discrete‐time location data. We also show that the accuracy of model selection and parameter estimation increases with more location data.

This model has potential to identify a specific mechanism in which animals use memory to optimize their foraging, by revisiting temporally and predictably variable resources at consistent time‐lags.
Age‐dependent integrity of the meiotic spindle assembly checkpoint in females requires Aurora kinase B
Authors: Blengini Cecilia S. , Nguyen Alexandra L. , Aboelenain Mansour , Schindler Karen
Published: October 2021

A hallmark of advanced maternal age is a significant increase in meiotic chromosome segregation errors, resulting in early miscarriages and congenital disorders. These errors most frequently occur during meiosis I (MI). The spindle assembly checkpoint (SAC) prevents chromosome segregation errors by arresting the cell cycle until proper chromosome alignment is achieved. Unlike in mitosis, the SAC in oocytes is desensitized, allowing chromosome segregation in the presence of improperly aligned chromosomes. Whether SAC integrity further deteriorates with advancing maternal age, and if this decline contributes to increased segregation errors remains a fundamental question. In somatic cells, activation of the SAC depends upon Aurora kinase B (AURKB), which functions to monitor kinetochore–microtubule attachments and recruit SAC regulator proteins. In mice, oocyte‐specific deletion of AURKB (Aurkb cKO) results in an increased production of aneuploid metaphase II‐arrested eggs and premature age‐related infertility. Here, we aimed to understand the cause of the short reproductive lifespan and hypothesized that SAC integrity was compromised. In comparing oocytes from young and sexually mature Aurkb cKO females, we found that SAC integrity becomes compromised rapidly with maternal age. We show that the increased desensitization of the SAC is driven by reduced expression of MAD2, ZW10 and Securin proteins, key contributors to the SAC response pathway. The reduced expression of these proteins is the result of altered protein homeostasis, likely caused by the accumulation of reactive oxygen species. Taken together, our results demonstrate a novel function for AURKB in preserving the female reproductive lifespan possibly by protecting oocytes from oxidative stress.
A trans‐omic Mendelian randomization study of parental lifespan uncovers novel aging biology and therapeutic candidates for chronic diseases
Authors: Perrot Nicolas , Pelletier William , Bourgault Jérôme , Couture Christian , Li Zhonglin , Mitchell Patricia L. , Ghodsian Nooshin , Bossé Yohan , Thériault Sébastien , Mathieu Patrick , Arsenault Benoit J.
Published: October 2021

The study of parental lifespan has emerged as an innovative tool to advance aging biology and our understanding of the genetic architecture of human longevity and aging‐associated diseases. Here, we leveraged summary statistics of a genome‐wide association study including over one million parental lifespans to identify genetically regulated genes from the Genotype‐Tissue Expression project. Through a combination of multi‐tissue transcriptome‐wide association analyses and genetic colocalization, we identified novel genes that may be associated with parental lifespan. Mendelian randomization (MR) analyses also identified circulating proteins and metabolites causally associated with parental lifespan and chronic diseases offering new drug repositioning opportunities such as those targeting apolipoprotein‐B‐containing lipoproteins. Liver expression of HP, the gene encoding haptoglobin, and plasma haptoglobin levels were causally linked with parental lifespan. Phenome‐wide MR analyses were used to map genetically regulated genes, proteins and metabolites with other human traits as well as the disease‐related phenome in the FinnGen cohorts (n = 135,638). Altogether, this study identified new candidate genes, circulating proteins and metabolites that may influence human aging as well as potential therapeutic targets for chronic diseases that warrant further investigation.
Innate immune remodeling by short‐term intensive fasting
Authors: Qian Jiawei , Fang Yixuan , Yuan Na , Gao Xueqin , Lv Yaqi , Zhao Chen , Zhang Suping , Li Quan , Li Lei , Xu Li , Wei Wen , Wang Jianrong
Published: October 2021

Previous studies have shown that long‐term light or moderate fasting such as intermittent fasting can improve health and prolong lifespan. However, in humans short‐term intensive fasting, a complete water‐only fasting has little been studied. Here, we used multi‐omics tools to evaluate the impact of short‐term intensive fasting on immune function by comparison of the CD45+ leukocytes from the fasting subjects before and after 72‐h fasting. Transcriptomic and proteomic profiling of CD45+ leukocytes revealed extensive expression changes, marked by higher gene upregulation than downregulation after fasting. Functional enrichment of differentially expressed genes and proteins exposed several pathways critical to metabolic and immune cell functions. Specifically, short‐term intensive fasting enhanced autophagy levels through upregulation of key members involved in the upstream signals and within the autophagy machinery, whereas apoptosis was reduced by down‐turning of apoptotic gene expression, thereby increasing the leukocyte viability. When focusing on specific leukocyte populations, peripheral neutrophils are noticeably increased by short‐term intensive fasting. Finally, proteomic analysis of leukocytes showed that short‐term intensive fasting not only increased neutrophil degranulation, but also increased cytokine secretion. Our results suggest that short‐term intensive fasting boost immune function, in particular innate immune function, at least in part by remodeling leukocytes expression profile.
Property, Personhood, and Police: The Making of Race and Space through Nuisance Law
Authors: Graziani Terra , Montano Joel , Roy Ananya , Stephens Pamela
Published: October 2021

This essay is concerned with public nuisance law as a space‐making project, decisively shaping property relations through speculative policing. With a focus on the Citywide Nuisance Abatement Program (CNAP) in Los Angeles, we show how the transformation of “gang‐controlled” neighbourhoods anticipates capital investment through the reformation of property. We situate the contemporary reanimation of public nuisance law in the socio‐spatial histories of racial capitalism, including colonial dispossession, the control of free and fugitive Black people, and formations of counter‐insurgency such as community policing. In doing so, we draw attention to the lawlessness of the law, which in the case of CNAP is apparent not only in its legal hybridity but also in its preemptive logics of surveillance, criminalisation and banishment that target racial others.
Predicting landscape‐scale biodiversity recovery by natural tropical forest regrowth
Authors: Prieto Pablo V. , Bukoski Jacob J. , Barros Felipe S. M. , Beyer Hawthorne L. , Iribarrem Alvaro , Brancalion Pedro H. S. , Chazdon Robin L. , Lindenmayer David B. , Strassburg Bernardo B. N. , Guariguata Manuel R. , Crouzeilles Renato
Published: October 2021

Natural forest regrowth is a cost‐effective, nature‐based solution for biodiversity recovery, yet different socioenvironmental factors can lead to variable outcomes. A critical knowledge gap in forest restoration planning is how to predict where natural forest regrowth is likely to lead to high levels of biodiversity recovery, which is an indicator of conservation value and the potential provisioning of diverse ecosystem services. We sought to predict and map landscape‐scale recovery of species richness and total abundance of vertebrates, invertebrates, and plants in tropical and subtropical second‐growth forests to inform spatial restoration planning. First, we conducted a global meta‐analysis to quantify the extent to which recovery of species richness and total abundance in second‐growth forests deviated from biodiversity values in reference old‐growth forests in the same landscape. Second, we employed a machine‐learning algorithm and a comprehensive set of socioenvironmental factors to spatially predict landscape‐scale deviation and map it. Models explained on average 34% of observed variance in recovery (range 9–51%). Landscape‐scale biodiversity recovery in second‐growth forests was spatially predicted based on socioenvironmental landscape factors (human demography, land use and cover, anthropogenic and natural disturbance, ecosystem productivity, and topography and soil chemistry); was significantly higher for species richness than for total abundance for vertebrates (median range‐adjusted predicted deviation 0.09 vs. 0.34) and invertebrates (0.2 vs. 0.35) but not for plants (which showed a similar recovery for both metrics [0.24 vs. 0.25]); and was positively correlated for total abundance of plant and vertebrate species (Pearson r = 0.45, p = 0.001). Our approach can help identify tropical and subtropical forest landscapes with high potential for biodiversity recovery through natural forest regrowth.
Post‐release comparisons of amphibian growth reveal challenges with sperm cryopreservation as a conservation tool
Authors: Poo Sinlan , Bogisich Allison , Mack Mariah , Lynn Bryan K. , Devan‐Song Anne
Published: October 2021

Conservation translocation using captive‐bred individuals has become increasingly important for species restoration. Despite advancements in technologies for captive‐breeding, such as gamete cryopreservation, it remains largely unknown if these artificially‐produced offspring can be used to establish a viable wild population. Using an amphibian species with a stable conservation status (Anaxyrus fowleri), we measured the post‐release growth and survivorship of offspring produced from frozen/thawed sperm and projected fecundity and population differences. Cryo‐derived tadpoles and post‐metamorphic toadlets were smaller than their natural counterparts. Model projections show that early‐life differences in growth can scale up to substantial differences in final life fecundity and population trends. Our findings call for greater attention towards the differences between captive‐bred and cryo‐derived individuals compared to their natural counterparts, and the need for more investment into developing cryopreservation technologies that are viable at the population level for conservation translocation.