bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune chromatin reader SP140 regulates microbiota and risk for inflammatory bowel disease
Authors: Fraschilla Isabella , Amatullah Hajera , Rahman Raza-Ur , Jeffrey Kate L.
Published: March 2022

Inflammatory bowel disease (IBD) is driven by host genetics and environmental factors, including commensal microorganisms. Epigenetics facilitate integration of environmental cues for transcriptional output. However, evidence of epigenetic dysregulation directly causing host-commensal dysbiosis and IBD is lacking. Speckled Protein 140 (SP140) is an immune-restricted chromatin ‘reader’ with homology to Autoimmune Regulator (AIRE). SP140 mutations associate with three immune diseases: Crohn’s disease (CD), multiple sclerosis (MS) and chronic lymphocytic leukemia (CLL), but disease-causing mechanisms remain undefined. Here we identify a critical immune-intrinsic role for SP140 in preventing expansion of inflammatory Proteobacteria, including Helicobacter in mice and Enterobacteriaceae in humans. Mice harboring altered microbiota due to hematopoietic Sp140 deficiency exhibited severe colitis which was transmissible upon co-housing and ameliorated with antibiotics. SP140 was critical for calibration of macrophage microbicidal responses required for normal host-commensal crosstalk and elimination of invasive pathogens. Mutations within this epigenetic reader may constitute a predisposing event in human diseases provoked by the microbiome, such as IBD and MS.
3’UTR-directed, kinase proximal mRNA decay inhibits C/EBPβ phosphorylation/activation to suppress senescence in tumor cells
Authors: Salotti Jacqueline , Asif Nida , Basu Srikanta , Das Aniruddha , Yang Mei , Karim Baktiar , Saylor Karen , Martin Nancy , Scheiblin David A. , Misra Sweta , Luke Brian T. , Andresson Thorkell , Lockett Stephen , Tessarollo Lino , Johnson Peter F.
Published: March 2022

C/EBPβ is a potent regulator of oncogene-induced senescence (OIS) and the SASP. C/EBPβ is post-translationally activated in OIS cells by the effector kinases ERK1/2 and CK2. However, in tumor cells C/EBPβ activation is suppressed by its 3’UTR. 3′UTR regulation of protein activity (UPA) requires a G/U-rich element (GRE) and its cognate binding protein, HuR. These components segregateCEBPBtranscripts away from a perinuclear compartment harboring ERK1/2 and CK2, restricting C/EBPβ from its activating kinases. We report here that the mRNA decay proteins UPF1 and Staufen1/2 are essential UPA factors enriched within the perinuclear cytoplasm. STAU1/2 and UPF1 overlap with CK2 on perinuclear signaling endosomes where they promote localizedCEBPBmRNA decay. UPF1 or STAU1/2 depletion in tumor cells increasedCEBPBtranscripts adjacent to CK2 foci, coinciding with C/EBPβ activation and senescence. The GRE and an adjacent STAU binding site independently suppress C/EBPβ-mediated senescence, while a distinct 3’UTR region inhibits its SASP-inducing activity.KrasG12D-driven lung tumors in mice carrying aCebpbGRE deletion rarely progressed to malignant adenocarcinomas, demonstrating the importance of UPA to enable tumor progressionin vivo. Thus, kinase-proximal mRNA decay is a novel mechanism that inhibits C/EBPβ activation in tumor cells to facilitate senescence bypass.
Holobiont transcriptomes for the critically endangered staghorn coral (Acropora cervicornis) from two environmentally distinct sites on Turneffe Atoll, Belize
Authors: Lesneski Kathryn C. , Labadorf Adam T , Lord Karina Scavo , Agus Filisia , Finnerty John R.
Published: March 2022

Historically, staghorn coral (Acropora cervicornis) was a preeminent reef-builder in the Caribbean and Tropical Western Atlantic, where it constructed extensive thickets at 5-20 m depth that supported diverse ecosystems and provided coastal populations with food, storm protection, and income from tourism. In recent decades, A. cervicornis declined precipitously, up to 97% in some localities. To reverse its decline, widespread efforts are underway to characterize the phenotypic and genetic diversity of persisting populations with the goal of restoring them to historical levels by out-planting nursery grown specimens. To support this target, we developed transcriptomes for two A. cervicornis populations located in Turneffe Atoll Marine Reserve, Belize. These populations experience significantly different temperatures, light levels and water currents, and they harbor individuals that differ in key phenotypes. Because differentiating the gene activity of diverse taxa—i.e., coral host, algal photosymbiont, plus associated eukaryotes, bacteria, archaea, and viruses— is critical to understanding the function of the coral holobiont, we developed a pipeline for parsing transcripts by taxon. Separate transcriptomes for each population contain complete representatives for >96% of 978 conserved metazoan single copy orthologs. The taxonomic breakdown of transcripts differed between sites, with more bacterial transcripts recovered from Calabash Caye and more symbiont transcripts from Blackbird Caye. The assembled transcriptomes will facilitate gene expression studies and in silico cloning from this endangered coral.
The growth rate of DNA condensate droplets increases with the size of participating subunits
Authors: Agarwal Siddharth , Osmanovic Dino , Klocke Melissa A. , Franco Elisa
Published: March 2022

Liquid–liquid phase separation (LLPS) is a common phenomenon underlying the formation of dynamic membraneless organelles in biological cells, which are emerging as major players in controlling cellular functions and health. The bottom-up synthesis of biomolecular liquid systems with simple constituents, like nucleic acids and peptides, is useful to understand LLPS in nature as well as to develop programmable means to build new amorphous materials with properties matching or surpassing those observed in natural condensates. In particular, understanding which parameters determine condensate growth kinetics is essential for the synthesis of condensates with the capacity for active, dynamic behaviors. Here we use DNA nanotechnology to study artificial liquid condensates through programmable star-shaped subunits, focusing on the effects of changing subunit size. First, we show that LLPS is achieved in a six-fold range of subunit size. Second, we demonstrate that the rate of growth of condensate droplets scales with subunit size. Our investigation is supported by a general model that describes how coarsening and coalescence are expected to scale with subunit size under ideal assumptions. Beyond suggesting a route toward achieving control of LLPS kinetics via design of subunit size in synthetic liquids, our work suggests that particle size may be a key parameter in biological condensation processes.
Risk reporting: do country-level institutional forces really matter?
Authors: Serrasqueiro Rogério , Oliveira Jonas
Published: March 2022

Purpose

The study aims to analyse annual reports of the non-financial European firms listed at the EURO STOXX 50 index over the period of 2007 and 2011.

Design/methodology/approach

This study intends to address two main issues: to what extent the country-level institutional forces compel (directly) firm's risk reporting (RR) behaviour and in which way these country-level institutional forces moderate the relationship between RR and firm-level characteristics.

Findings

Main findings indicate that, during this period, the European listed companies disclosed more risk information on a voluntary basis (such as operational and strategic risks) and with better informative content (more forward-looking and focused on positive news). Consistent with institutional theory, findings confirm that the country-level institutional forces explain variations on RR. Additionally, it also indicates that the relationship between RR and leveraged firms is weaker among countries with stronger institutional forces. These findings have several implications for investors and regulators in Europe basically in helping achieve efficiency in investment decisions and to stimulate further efforts to improve RR regulations.

Originality/value

This study makes two major contributions. First, it extends Elshandidy'set al.(2015) work by using other country-level institutional forces that capture the efficacy of corporate boards, the protection of minority shareholders' interests, country's level of democracy, law enforcement mechanisms and press freedom. Second, it uses firms that are considered as a blue-chip representation of super-sector leaders in the Eurozone (but from different institutional contexts). This research setting can be more insightful in shedding some light towards our understanding on how these leading firms can promote innovative and high quality level of RR and how country-level driving forces influence these variables.
Role of National Digital Library of India (NDLI) for facilitating open access resources (OARs): an investigation on COVID-19 research repository
Authors: Singh Sonam
Published: March 2022

Purpose

This paper aims to proffer a glimpse of diverse e-resources and materials accumulated by National Digital Library of India (NDLI) for facilitating open access resources (OARs) during the difficult times of global pandemic. Out of all the resources, an attempt has been made to place a focus on COVID-19 research repository maintained at NDLI platform to facilitate related research activities for envisaging experiments by scientists and researchers.

Design/methodology/approach

The study is based on COVID-19 research repository assimilated by NDLI, and a detailed investigative research has been made about various resources and materials available for research community. The official website of NDLI (direct link of NDLI website: https://ndl.iitkgp.ac.in/) has been referred for collection of requisite data for study. The collected information has been presented through eight tables, two charts and two figures, which have further been analyzed and interpreted to attain the objectives.

Findings

The brief examples in this paper indicates that a wealth of OARs related to COVID-19 such as scholarly communications, data sets, documents and videos and journals and conferences, etc. are available for access and research by scientists and researchers to expand their research during and also beyond this global crisis. Social distancing has forced academics to displace to online platform from physical deliverables. Institutions are forced to adopt new technologies for delivering education in online mode such as online teaching, online access of educational resources, online conferences, webinars and a host of such related activities. NDLI has been instrumental in this journey by accumulating providing research materials through its platform.

Originality/value

In addition to the blended learning process, this paper provides a structured overview about COVID-19 research repository facilitated by NDLI to provide access about related research activities by scientists and researchers. This investigative research on NDLI platform has been done originally by the author with a sacrosanct aim to help serious academia and has a high referral value for the scientific, technocratic and realistic researchers with deep thrust on availability of all materials under one roof, i.e. NDLI.
Consumers' intention toward buying ethically produced products in Bangladesh
Authors: Ho Yi-Hui , Alam Syed Shah , Ahsan Mst. Nilufar , Lin Chieh-Yu
Published: March 2022

Purpose

While many companies begin to promote ethically produced products, much remains to be known about consumers' buying intention toward these products. This paper attempts to integrate the theory of planned behavior and the Hunt–Vitell theory of marketing ethics to explore the buying intention toward ethically produced food products in a developing economy.

Design/methodology/approach

Data were collected through a questionnaire survey in Bangladesh. Structural equation modeling technique was used to test the research model.

Findings

Research findings showed that deontological evaluation and teleological evaluation have significantly positive effects on perceived behavioral control and subjective norm. Perceived behavioral control, subjective norm, attitude, hedonic and utilitarian value have significantly positive effects on buying intention toward ethically produced foods.

Originality/value

The results are practically and theoretically meaningful because the integrated model holds well explanatory power to predict consumers' intention toward buying ethical foods and thereby understand consumers' ethical decision-makings.
The benefits of nature-based therapy for the individual and the environment: an integrative review
Authors: Bonham-Corcoran Meabh , Armstrong Alexandra , O’Briain Amy , Cassidy Amy , Turner Niall
Published: March 2022

Purpose

This review aims to identify the commonly used nature-based therapies, the cohorts that benefit from these interventions, and the potential environmental impact of nature-based therapies.

Design/methodology/approach

An integrative review methodology was taken. The literature was analysed and synthesised through thematic analysis.

Findings

Three themes emerged from the analysis: categories of nature-based therapies; benefits of nature-based therapies; and the gains from nature-based therapies are not universal. Evidence of physiological, psychological, social, vocational and quality of life benefits from participation in nature-based therapies was evident in the literature. However, there was insufficient empirical evidence of the benefits for the environment.

Practical implications

Occupational therapists assist populations across the life course. Consequentially, they can be found working in a diverse range of clinical contexts. This review asserts that nature-based therapies could be a positive addition in many of these contexts. Further, while engagement in activities in natural environments is frequently used by occupational therapists practicing within institution environments, there is evidence to support its use in community service models and potentially in public health strategies.

Originality/value

This integrative review brings together evidence on a diverse range of nature-based therapies, cohorts, associated benefits and factors that influence these. The lack of empirical evidence on the benefits of nature-based therapies for the environment is acknowledged as a gap in the literature
Influence of quality management and allied certifications on consumers
Authors: Yadav Neeraj , Heriyati Pantri , Kumar Harsh , Tamara Dewi
Published: March 2022

Purpose

The perception of consumers towards the products or services that are provided by organisations that are certified to various international quality management and allied standards, such as the standards developed by the International Organization for Standardization, has not been extensively researched. Available research is limited to few standards. It is not comprehensively explored if consumers view certified products, services or organisations favourably in each case. This study aims to explore inclination of three consumer categories i.e. retail consumers, business consumers and subject expert consumers towards 11 international management system standards.

Design/methodology/approach

A survey is carried out among 229 consumers of different types in different countries. Total 11 quality management and allied standards are studied. Similarities and differences among different consumer groups towards these 11 standards are analysed using Chi-square test.

Findings

The study shows that although all consumer categories perceive products, services, and organisations certified to international management system standards favourably, the inclination towards certification is greater among developing economies than in developed economies. It is also proven that all standards are not equally popular among consumers. The brand name of a certification agency is found not influencing consumer’s preference towards certification.

Originality/value

The study is unique in three ways. First, it comprehensively analyses multiple quality management and allied standards from consumers’ point of view. Similarities and differences among retail consumers, business consumers and subject experts are researched, which was not attempted previously and thus it shows a novel approach. Second, no other study has analysed so many standards together. Third, differences in perception of consumers towards international standards between developing and developed nations are compared, which was not available earlier for all the 11 standards.
Shopping app features: influencing the download and use intention
Authors: Sinemus Kathrin , Zielke Stephan
Published: March 2022

Purpose

Shopping apps are a highly relevant channel and an increasingly important part of omni-channel retailing, as they strengthen the customer relationship. This study analyses the possibilities available to retailers to encourage consumers to download a shopping app and use it in the long-term.

Design/methodology/approach

The study uses a scenario-based online experiment with a 2 × 2 × 2 between-subjects design and data from 332 participants. A second online experiment with a 2 × 3 between-subjects design and data from 200 participants supplements the main experiment. The data obtained from these experiments were analysed using M/ANCOVA and PROCESS.

Findings

Findings suggest that a rebate (monetary incentive) increases the download intention. Online and in-store app features (non-monetary incentives) do also have positive impacts on the use intention, though the in-store feature only works when it is offered in combination with the online feature. The relationships are mediated by the perceived usefulness of the shopping app. Moreover, the non-monetary features interact with the channel preference of the consumers, who react more positively towards features offered in a non-preferred channel. A supplementary study supports this finding.

Originality/value

This research is novel as it analyses the impact of monetary (rebate) and non-monetary (online and in-store features) incentives on both the download and use intention of a shopping app separately. Further, it contributes to research on the topic by examining which features consumers perceive as useful. Finally, the study considers the omni-channel environment regarding consumers’ channel preference.
How do actors coordinate for value creation? A signaling and screening perspective on resource integration
Authors: Dehling Sebastian , Edvardsson Bo , Tronvoll Bård
Published: March 2022

Purpose

Although service research typically asserts that institutions coordinate actors’ value creation processes, institutions and resources are not necessarily transparent, aligned, or pre-existing. This paper aims to develop a more granular perspective on how actors coordinate for value.

Design/methodology/approach

Drawing on the established concepts of signaling and screening theory, this paper adopts a service marketing perspective to explore how independent heterogeneous actors coordinate for value creation at the individual level. Illustrative cases of corporate startup collaborations are presented in support of the proposed conceptual framework.

Findings

Actors share and acquire information through signaling and screening activities in a coordinative dialogue with other actors. These resource integration activities (for resource creation and matching) affect actors’ valuations and future actions.

Originality/value

The one-sided explanations of coordination in the existing literature reflect the dominance of the institutional theory. By contrast, the proposed agency-oriented perspective based on the integration of signaling and screening functions offers a more granular conceptualization of the resource integration process. As well as capturing how actors use coordinating dialogue to match resources and institutions, this account also shows that matching is a core element of resource integration rather than an antecedent. The findings indicate paths for future research that focus on the actor.
Metaverse: the future of immersive training
Authors: Upadhyay Ashwani Kumar , Khandelwal Komal
Published: March 2022

Purpose

This paper aims to review and explore the adoption of Metaverse as a training ecosystem. The paper focuses on the current debate on the relevance of Metaverse for training.

Design/methodology/approach

This paper reviews the recent articles and interviews and then critically discusses the future of training in Metaverse.

Findings

Recent reports, studies and developments show that immersive training holds much potential. The future for training in Metaverse seems to be bright with benefits for both employers and employees.

Originality/value

This viewpoint paper is easy to read and comprehensive.
Employee financial health comes to the fore after COVID
Authors: Jackson Paul
Published: March 2022

Purpose

This paper aims to discuss employee financial health post COVID.

Design/methodology/approach

The following article outlines different schemes that can be used to improve employee financial health.

Findings

Analysis of the transactional data that open banking provides gives employers unprecedented capabilities to finally measure the improvement they make on the financial health of its workforce.

Originality/value

This paper provides insight into how financial wellbeing tools can improve the financial health of employees post COVID.
Properties of mortar made with bottom ash and silica fume as sustainable construction materials
Authors: Saleh Fadillawaty , Gunawan Muhammad Adhi , Yolanda Tri Ismarani , Monika Fanny , Prayuda Hakas , Cahyati Martyana Dwi , Pratama Muhammad Mirza Abdillah
Published: March 2022

Purpose

This study aims to investigate the properties of mortar made from a bottom ash substitute as a sustainable construction material. It is believed that the use of cement in concrete construction contributes to the release of carbon dioxide into the atmosphere, which has been a consistent increase in recent years. The utilization of bottom ash waste is expected to reduce pollution associated with cement production.

Design/methodology/approach

Bottom ash is used as replacement materials for cement and fine aggregate in the manufacture of mortar. Bottom ash substituted for cement of 10%, 20% and 30% of the total weight of the binder, whereas bottom ash substituted for the fine aggregate of 30%, 40% and 50% of the total weight of the sand. Binder properties were determined using scanning electron microscopy and energy dispersive X-ray. Meanwhile, the fresh properties (slump flow) and hardened properties were determined (compressive strength and mass density). In the hardened properties test, two types of curing were used: water and sealed curing.

Findings

The compressive strength of mortar decreased as the amount of bottom ash as cement replacement. However, the compressive strength increased when bottom ash was used as aggregate replacement. Additionally, bottom ash was sufficient as a substitute for fine aggregate than as a substitute for cement.

Originality/value

This research presents test results that are more straightforward to apply in the construction site.
Reducing Nav1.6 expression attenuates the pathogenesis of Alzheimer's disease by suppressing BACE1 transcription
Authors: Yuan De‐Juan , Yang Guang , Wu Wei , Li Qi‐Fa , Xu De‐en , Ntim Michael , Jiang Chun‐Yan , Liu Ji‐Chuan , Zhang Yue , Wang Ying‐Zi , Zhu Dan‐Dan , Kundu Supratik , Li Ai‐Ping , Xiao Zhi‐Cheng , Ma Quan‐Hong , Li Shao
Published: March 2022

Aberrant increases in neuronal network excitability may contribute to cognitive deficits in Alzheimer's disease (AD). However, the mechanisms underlying hyperexcitability of neurons are not fully understood. Voltage‐gated sodium channels (VGSC or Nav), which are involved in the formation of excitable cell's action potential and can directly influence the excitability of neural networks, have been implicated in AD‐related abnormal neuronal hyperactivity and higher incidence of spontaneous non‐convulsive seizures. Here, we have shown that the reduction of VGSC α‐subunit Nav1.6 (by injecting adeno‐associated virus (AAV) with short hairpin RNA (shRNA) into the hippocampus) rescues cognitive impairments and attenuates synaptic deficits in APP/PS1 transgenic mice. Concurrently, amyloid plaques in the hippocampus and levels of soluble Aβ are significantly reduced. Interfering with Nav1.6 reduces the transcription level of β‐site APP‐cleaving enzyme 1 (BACE1), which is Aβ‐dependent. In the presence of Aβ oligomers, knockdown of Nav1.6 reduces intracellular calcium overload by suppressing reverse sodium–calcium exchange channel, consequently increasing inactive NFAT1 (the nuclear factor of activated T cells) levels and thus reducing BACE1 transcription. This mechanism leads to a reduction in the levels of Aβ in APP/PS1 transgenic mice, alleviates synaptic loss, improves learning and memory disorders in APP/PS1 mice after downregulating Nav1.6 in the hippocampus. Our study offers a new potential therapeutic strategy to counteract hippocampal hyperexcitability and subsequently rescue cognitive deficits in AD by selective blockade of Nav1.6 overexpression and/or hyperactivity.
Confidential enquiry into maternal deaths in the Netherlands, 2006–2018
Authors: Kallianidis Athanasios F. , Schutte Joke M. , Schuringa Louise E. M. , Beenakkers Ingrid C. M. , Bloemenkamp Kitty W. M. , Braams‐Lisman Babette A. M. , Cornette Jerome , Kuppens Simone M. , Rietveld Anna L. , Schaap Timme , Stekelenburg Jelle , Zwart Joost J. , van den Akker Thomas
Published: March 2022

Introduction

To calculate the maternal mortality ratio (MMR) for 2006–2018 in the Netherlands and compare this with 1993–2005, and to describe women’s characteristics, causes of death and improvable factors.

Material and Methods

We performed a nationwide, cohort study of all maternal deaths between January 1, 2006 and December 31, 2018 reported to the Audit Committee Maternal Mortality and Morbidity. Main outcome measures were the national MMR and causes of death.

Results

Overall MMR was 6.2 per 100 000 live births, a decrease from 12.1 in 1993–2005 (risk ratio [RR] 0.5). Women with a non‐western ethnic background had an increased MMR compared with Dutch women (MMR 6.5 vs. 5.0, RR 1.3). The MMR was increased among women with a background from Surinam/Dutch Antilles (MMR 14.7, RR 2.9). Half of all women had an uncomplicated medical history (79/161, 49.1%). Of 171 pregnancy‐related deaths within 1 year postpartum, 102 (60%) had a direct and 69 (40%) an indirect cause of death. Leading causes within 42 days postpartum were cardiac disease (n = 21, 14.9%), hypertensive disorders (n = 20, 14.2%) and thrombosis (n = 19, 13.5%). Up to 1 year postpartum, the most common cause of death was cardiac disease (n = 32, 18.7%). Improvable care factors were identified in 76 (47.5%) of all deaths.

Conclusions

Maternal mortality halved in 2006–2018 compared with 1993–2005. Cardiac disease became the main cause. In almost half of all deaths, improvable factors were identified and women with a background from Surinam/Dutch Antilles had a threefold increased risk of death compared with Dutch women without a background of migration.
Air versus fluorinated gas tamponades in pars plana vitrectomy treatment for primary rhegmatogenous retinal detachment
Authors: Govers Birgit Marlies , Lamers Martijn P.M. , Klevering B. Jeroen , Keijser Sander
Published: March 2022

Purpose

To compare the treatment success of air with fluorinated gas (20% SF6 or 14% C3F8) tamponade in pars plana vitrectomy for primary rhegmatogenous retinal detachment.

Methods

A retrospective cohort study comprised of 1023 consecutive primary retinal detachment cases between 2014 and 2020. We employed a univariate multivariable binary logistic regression model.

Results

We used intraocular gas tamponades in 872 cases with PVR grade B or lower: air tamponade was used in 414 eyes and 458 eyes were treated with a type of fluorinated gas tamponade. There was no significant difference in the type of tamponade with regard to the re‐detachment rate (95% CI −1.0% and 4.1%). Additionally, also in the subgroup of rhegmatogenous retinal detachments with inferior located retinal defects we found no significant difference between the two types of tamponade (p = 0.54 Fisher's exact). The multivariable model, which included tamponade, PVR grade, a retinal detachment involving the 6 o'clock position and age as covariates, also showed no significant effect of tamponade choice on treatment success (OR 0.5, 95% 0.2–1.0, p = 0.10).

Conclusion

We found no difference in treatment success with air tamponade versus fluorinated gas tamponades in the repair of primary retinal detachments, this also includes inferiorly located retinal tears and detachments.
Residency time of agonists does not affect the stability of GPCR–arrestin complexes
Authors: Mösslein Nadja , Pohle Lisa‐Marie Geertje , Fuss Anneke , Bünemann Moritz , Krasel Cornelius
Published: March 2022

Background and Purpose

The interaction of arrestins with G‐protein coupled receptors (GPCRs) desensitizes agonist‐dependent receptor responses and often leads to receptor internalization. GPCRs that internalize without arrestin have been classified as “class A” GPCRs whereas “class B” GPCRs co‐internalize with arrestin into endosomes. The interaction of arrestins with GPCRs requires both agonist activation and receptor phosphorylation. Here, we ask the question whether agonists with very slow off‐rates can cause the formation of particularly stable receptor–arrestin complexes.

Experimental Approach

The stability of GPCR–arrestin‐3 complexes at two class A GPCRs, the β2‐adrenoceptor and the μ opioid receptor, was assessed using two different techniques, fluorescence resonance energy transfer (FRET) and fluorescence recovery after photobleaching (FRAP) employing several ligands with very different off‐rates. Arrestin trafficking was determined by confocal microscopy.

Key Results

Upon agonist washout, GPCR–arrestin‐3 complexes showed markedly different dissociation rates in single‐cell FRET experiments. In FRAP experiments, however, all full agonists led to the formation of receptor–arrestin complexes of identical stability whereas the complex between the μ receptor and arrestin‐3 induced by the partial agonist morphine was less stable. Agonists with very slow off‐rates could not mediate the co‐internalization of arrestin‐3 with class A GPCRs into endosomes.

Conclusions and Implications

Agonist off‐rates do not affect the stability of GPCR–arrestin complexes but phosphorylation patterns do.

Our results imply that orthosteric agonists are not able to pharmacologically convert class A into class B GPCRs.
Transition Motion Synthesis for Object Interaction based on Learning Transition Strategies
Authors: Hwang Jaepyung , Park Gangrae , Kwon Taesoo , Ishii Shin
Published: March 2022

In this study, we focus on developing a motion synthesis framework that generates a natural transition motion between two different behaviours to interact with a moving object. Specifically, the proposed framework generates the transition motion, bridging from a locomotive behaviour to an object interaction behaviour. And, the transition motion should adapt to the spatio‐temporal variation of the target object in an online manner, so as to naturally connect the behaviours. To solve this issue, we propose a framework that combines a regression model and a transition motion planner. The neural network‐based regression model estimates the reference transition strategy to guide the reference pattern of the transitioning, adapted to the varying situation. The transition motion planner reconstructs the transition motion based on the reference pattern while considering dynamic constraints that avoid the footskate and interaction constraints. The proposed framework is validated to synthesize various transition motions while adapting to the spatio‐temporal variation of the object by using object grasping motion, and athletic motions in soccer.
Activation of P2X4 receptor exacerbates acute brain injury after intracerebral hemorrhage
Authors: Wu Si‐Ting , Han Jin‐Rui , Yao Nan , Li Yu‐Lin , Zhang Fang , Shi Yao , Shi Fu‐Dong , Li Zhi‐Guo
Published: March 2022

Introduction

Intracerebral hemorrhage (ICH) accounts for 10%–15% of all strokes and culminates in high mortality and disability. After ICH, brain injury is initiated by the mass effect of hematoma, followed by secondary cytotoxic injury from dying brain cells, hematoma disintegration, and cascading brain immune response. However, the molecular mechanism of secondary cytotoxic brain injury in ICH is not completely understood. The sensitive purinergic receptor, P2X4 receptor (P2X4R), was known to recognize extracellular free ATP released by dying cells during tissue injury.

Aims

In this study, we aim to understand the role of P2X4R in acute brain injury triggered by ICH.

Results

In this study, we found that the sensitive purinergic receptor, P2X4R, was upregulated in the brain of patients with ICH as well as in a mouse model of ICH induced by collagenase injection. P2X4R blockage with the specific inhibitor 5‐BDBD attenuated brain injury in ICH mice by significantly reducing brain edema, blood–brain barrier leakage, neural death, and ultimately acute neurodeficits. Further study indicated that the protective effect of P2X4R inhibition is related to decreased pro‐inflammatory activity of microglia and recruitment of peripheral immune cells into the hemorrhagic brain.

Conclusions

These results suggest that the P2X4 receptor is activated by ICH stimuli which worsen brain injury following ICH.
Dnmt1 is required for the development of auditory organs via cell cycle arrest and Fgf signalling
Authors: Tang Dongmei , Zheng Shimei , Zheng Zhiwei , Liu Chang , Zhang Jiner , Yan Renchun , Wu Cheng , Zuo Na , Wu Lijuan , Xu Hongfei , Liu Shaofeng , He Yingzi
Published: March 2022

Objectives

To explore the role of DNA methyltransferase 1 (DNMT1) in the development of auditory system using zebrafish as experimental model.

Methods

Morpholino oligonucleotide was used to induce Dnmt1 deficiency. RNA sequencing, in situ hybridization (ISH), whole genomic bisulfide sequencing (WGBS) and immunostaining were used to investigate the morphologic alterations and mechanisms.

Results

We found that downregulation of Dnmt1 induced decreased number of neuromasts and repressed cell proliferation of primordium in the developing posterior lateral line system of zebrafish. The ISH data uncovered that Fgf signalling pathway was inhibited and the expression of chemokine memberscxcr4b,cxcr7bandcxcl12awere interfered, whilelef1expression was increased after inhibiting Dnmt1. Additionally, Dnmt1 downregulation led to malformed otoliths and deformed semicircular canals, and hair cell differentiation in utricle and saccule was inhibited severely. The in situ staining of otic placode markerspax2/5andfgf 3/8/10was decreased when Dnmt1 downregulated. The WGBS analysis demonstrated that the global methylation status was markedly downregulated, and cell cycle genes were among those most differently expressed between Dnmt1 morphants and the controls. Further ISH analysis confirmed the findings by RNA‐seq and WGBS assay thatcdkn1aandtp53were both upregulated after knockdown of Dnmt1.

Conclusion

Our results revealed that Dnmt1 is essential for the development of zebrafish auditory organ through regulating cell cycle genes together with Wnt and Fgf signalling pathways.
Neurostimulation in people with drug‐resistant epilepsy: Systematic review and meta‐analysis from the ILAE Surgical Therapies Commission
Authors: Touma Lahoud , Dansereau Bénédicte , Chan Alvin Y. , Jetté Nathalie , Kwon Churl‐Su , Braun Kees P. J. , Friedman Daniel , Jehi Lara , Rolston John D. , Vadera Sumeet , Wong‐Kisiel Lily C. , Englot Dario J. , Keezer Mark R.
Published: March 2022

Objective

Summarize the current evidence on efficacy and tolerability of vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS) through a systematic review and meta‐analysis.

Methods

We followed the Preferred Reporting Items of Systematic reviews and Meta‐Analyses reporting standards and searched Ovid Medline, Ovid Embase, and the Cochrane Central Register of Controlled Trials. We included published randomized controlled trials (RCTs) and their corresponding open‐label extension studies, as well as prospective case series, with ≥20 participants (excluding studies limited to children). Our primary outcome was the mean (or median, when unavailable) percentage decrease in frequency, as compared to baseline, of all epileptic seizures at last follow‐up. Secondary outcomes included the proportion of treatment responders and proportion with seizure freedom.

Results

We identified 30 eligible studies, six of which were RCTs. At long‐term follow‐up (mean 1.3 years), five observational studies for VNS reported a pooled mean percentage decrease in seizure frequency of 34.7% (95% confidence interval [CI]: −5.1, 74.5). In the open‐label extension studies for RNS, the median seizure reduction was 53%, 66%, and 75% at 2, 5, and 9 years of follow‐up, respectively. For DBS, the median reduction was 56%, 65%, and 75% at 2, 5, and 7 years, respectively. The proportion of individuals with seizure freedom at last follow‐up increased significantly over time for DBS and RNS, whereas a positive trend was observed for VNS. Quality of life was improved in all modalities. The most common complications included hoarseness, and cough and throat pain for VNS and implant site pain, headache, and dysesthesia for DBS and RNS.

Significance

Neurostimulation modalities are an effective treatment option for drug‐resistant epilepsy, with improving outcomes over time and few major complications. Seizure‐reduction rates among the three therapies were similar during the initial blinded phase. Recent long‐term follow‐up studies are encouraging for RNS and DBS but are lacking for VNS.
Effects of nucleos(t)ide analogs on hepatitis B surface antigen reduction with interferon‐lambda 3 induction in chronic hepatitis B patients
Authors: Umemura Machiko , Ogawa Koji , Morikawa Kenichi , Kubo Akinori , Tokuchi Yoshimasa , Yamada Ren , Kitagataya Takashi , Shigesawa Taku , Shimazaki Tomoe , Kimura Megumi , Suzuki Kazuharu , Nakamura Akihisa , Ohara Masatsugu , Kawagishi Naoki , Izumi Takaaki , Nakai Masato , Sho Takuya , Suda Goki , Natsuizaka Mitsuteru , Ono Kota , Murata Kazumoto , Sugiyama Masaya , Mizokami Masashi , Sakamoto Naoya
Published: March 2022

Background & Aims

Benefits of nucleos(t)ide analogs (NAs) on hepatitis B surface antigen (HBsAg) reduction and interferon‐lambda3 (IFN‐λ3) induction are still not known. This study aimed to investigate the effects of NAs on HBsAg reduction and association with serum IFN‐λ3 levels in chronic hepatitis B (CHB) patients.

Methods

A total of 91 patients [51 treated with nucleoside analog entecavir hydrate (ETV) and 40 treated with nucleotide analog adefovir dipivoxil (ADV) or tenofovir disoproxil fumarate (TDF)] with clinically evident CHB (chronic hepatitis, 57; liver cirrhosis, 34) were enrolled in this study. Serum IFN‐λ3 levels among patients receiving ETV and ADV/TDF were measured before the initiation of therapy and 1, 3, and 5 years post‐therapy.

Results

The change (mean ± standard deviation) in serum HBsAg levels from baseline to year five was −0.38 ± 0.46 and −0.84 ± 0.64 log10 IU/ml in ETV and ADV/TDF groups, respectively (p = 0.0004). Higher serum IFN‐λ3 levels were observed in ADV/TDF group compared with ETV group during treatment (p < 0.001). Serum IFN‐λ3 levels showed negative correlation with HBsAg reduction in ADV/TDF group (r = −0.386, p = 0.038) at week 48. Nucleotide analogs (ADV/TDF) treatment has associated factors with −0.3 log HBsAg decline at 1 year, −0.5 log HBsAg decline at 3 years, and −0.8 log HBsAg decline at 5 years after NAs treatment on multivariate analysis.

Conclusions

Nucleotide analog (ADV/TDF) treatment reduced HBsAg levels greater compared with nucleoside analog (ETV) in parallel with IFN‐λ3 induction.
Santonian‐Campaniandinoflagellate cyst biostratigraphy and paleoenvironment of theKrishna‐GodavariBasin, India
Authors: Mishra Ashish K. , Singh Arun Deo , Prasad Vandana
Published: March 2022

The present study deals with the biostratigraphic framework of Late Cretaceous sediments of the subsurface Well (DNG) “A” (2085–1840 m depth) from the Raghavapuram/Chintalapalli Shale of the Krishna‐Godavari Basin and analyzed the palynological assemblage. The recorded palynological assemblage is dominated by marker dinoflagellate cyst viz.Areoligera coronata, Areoligera senonensis, Heterosphaeridium spinaconjunctum, Nelsoniella aceras, Nelsoniella semireticulata, Odontochitina porifera, Xenascus ceratioides, andXenascus gochtiispecies. The last occurrence (LO) of significant species of dinoflagellate cysts is considered for the biostratigraphic establishment. On the basis of dinoflagellate cyst biostratigraphy, the examined sequences correspond to the Santonian‐Campanian age. The dominance of gonyaulacoid dinoflagellate cysts is interpreted in terms of sea‐level fluctuation and other paleoenvironmental signals through this biostratigraphic establishment. The recorded dinoflagellate cysts indicate the outer neritic, cool depositional environment. The sea‐level rise, recorded in our study is linked with the transgressive phase during the Late Cretaceous (Santonian‐Campanian) period.
Vesicoureteral reflux treatment following kidney transplantation potentially prevents graft function deterioration and allows long‐term graft survival
Authors: Hirose Takayuki , Hotta Kiyohiko , Harada Hiroshi , Tanabe Tatsu , Sasaki Hajime , Shinohara Nobuo
Published: March 2022

Objectives

The impact of vesicoureteral reflux post‐kidney transplantation on graft survival remains unclear, and guidelines on appropriate vesicoureteral reflux management post‐kidney transplantation are lacking. For this reason, we conducted a retrospective study on the impact of vesicoureteral reflux and its treatment on graft survival.

Methods

We evaluated 347 consecutive kidney transplantation recipients, who also underwent a ureteroneocystostomy, between 1996 and 2012.

Results

Vesicoureteral reflux was diagnosed in 55 cases (15.9%), with a median post‐kidney transplantation duration of 50 months (range 0–172 months). Among these, 22 were monitored, 17 underwent transurethral collagen injections, and 16 received a ureteroneocystostomy. The 10‐year graft survival rate was significantly lower in recipients with vesicoureteral reflux (68.9%) than in those without vesicoureteral reflux (84.4%) (P = 0.0165). Moreover, among the vesicoureteral reflux recipients, the 10‐year graft survival rate was significantly higher in those whose vesicoureteral reflux was cured (80.1%) than in those whose vesicoureteral reflux persisted (53.6%) (P = 0.0062). Multivariate analysis showed that vesicoureteral reflux was significantly associated with both overall and death‐censored graft loss (odds ratio 3.737 and 3.685; P = 0.0015 and P = 0.0052, respectively). Lastly, the incidence of interstitial fibrosis and tubular atrophy was higher in recipients with vesicoureteral reflux than in those without vesicoureteral reflux (P = 0.0009).

Conclusions

Post‐kidney transplantation vesicoureteral reflux has a negative impact on long‐term graft survival, and that treatment prevents graft deterioration. From the perspective of maintaining long‐term graft function in kidney recipients, vesicoureteral reflux may be one of the most important complications to be addressed.
Frailty in chronic kidney disease: challenges in nephrology practice. A review of current literature
Authors: Kennard Alice , Glasgow Nicholas , Rainsford Suzanne , Talaulikar Girish
Published: March 2022

Frailty is a multidimensional clinical syndrome characterised by low physical activity, reduced strength, accumulation of multi‐organ deficits, decreased physiological reserve and vulnerability to stressors. Frailty pathogenesis and ‘inflammageing’ is augmented by uraemia, leading to a high prevalence of frailty potentially contributing to adverse outcomes in patients with advanced chronic kidney disease (CKD), including end‐stage kidney disease (ESKD). The presence of frailty is a stronger predictor of CKD outcomes than estimated glomerular filtration rate and more aligned with dialysis outcomes than age. Frailty assessment should form part of routine assessment of patients with CKD and inform key medical transitions. Frailty screening and interventions in CKD/ESKD should be a research priority.
Host range and virulence diversity of Pectobacterium carotovorum subsp. brasiliense strain RDKLR infecting radish in India, and development of a LAMP-based diagnostics
Authors: Chandrashekar Byalahalli Subramani , PrasannaKumar Mothukapalli Krishnareddy , Parivallal Perumal Buela , Pramesh Devanna , Banakar Sahana Nagaraj , Patil Swathi Shivanagouda , Mahesh Hirehally Basavarajegowda
Published: March 2022

Aim

This work aimed at determining the pathogenicity, molecular characterization, host range and rapid detection of Pectobacterium carotovorum subsp. brasiliense (Pcb) causing soft rot disease in radish.

Methods and Results

The four isolated isolates were inoculated to radish, typical soft rot symptoms were observed and Koch’s postulates were proved. The most virulent strain RDKLR was morphologically and biochemically distinct. Pcb showed a positive potato soft rot test and elicited hypersensitivity response on Nicotiana tobaccum. The genes Pel2 and pmrA were used for subspecies characterization of Pcb. It has a wide host range and infection was observed on slices of carrot, tomato, radish, potato, cauliflower, cabbage, chilli, knol-khol, bell pepper and cucumber. Infectivity was also seen in seedlings under glasshouse conditions. Pcb produced cell wall degrading enzymes in semi-quantification assay and is a strong biofilm producer. The LAMP technique was standardized to help rapid detection and take prophylactic measures to manage the disease.

Conclusion

This work reports Pcb as a new soft rot causing organism of radish in India. Pcb is highly virulent with a broad host range. The LAMP technique helps in rapid detection.

Significance and impact of the study

Pcb-induced soft rot causes significant yield loss, decreased market value, damage in transit, storage and the market. Disease characterization and early identification aid in disease management and prevention in the field.
Antrodia camphorata polysaccharide improves inflammatory response in liver injury via the ROS/TLR4/NF‐κB signal
Authors: Yang Yi , Han Chenyang , Sheng Yongjia , Wang Jin , Li Wenyan , Zhou Xiaohong , Ruan Shuiliang
Published: March 2022

Antrodia Camphorata Polysaccharide (ACP) refers to a kind of polysaccharide extracted from the natural porous fungus Antrodia camphorata. This study investigated the mechanism of action of ACP in protecting the liver. The results showed that ACP suppressed the LPS‐induced KC cell activation, reduced the expression of inflammatory factors, increased the SOD level and suppressed ROS expression. In addition, N‐acetylcysteine (NAC) was adopted for pre‐treatment to suppress ROS. The results indicated that NAC synergistically exerted its effect with ACP, suggesting that ACP played its role through suppressing ROS. Further detection revealed that ACP activated the Nrf2 signal. It was discovered in the mouse model that, ACP effectively improved liver injury in mice, decreased ALT and AST levels, and suppressed the expression of inflammatory factors. This study suggests that ACP can exert its effect against oxidative stress via the Nrf2‐ARE signalling, which further improves the production of ROS and the activation of TLR4‐NF‐κB signalling, and protects the liver against liver injury.