bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic morphine induces adaptations in opioid receptor signaling in a thalamo-cortico-striatal circuit that are projection-dependent, sex-specific and regulated by mu opioid receptor phosphorylation
Authors: Jaeckel Elizabeth R. , Arias-Hervert Erwin R. , Perez-Medina Alberto L. , Herrera Yoani N. , Schulz Stefan , Birdsong William T.
Published: February 2023

Chronic opioid exposure induces tolerance to the pain-relieving effects of opioids but sensitization to some other effects. While the occurrence of these adaptations is well-understood, the underlying cellular mechanisms are less clear. This study aimed to determine how chronic treatment with morphine, a prototypical opioid agonist, induced adaptations to subsequent morphine signaling in different subcellular contexts. Opioids acutely inhibit glutamatergic transmission from medial thalamic (MThal) inputs to the dorsomedial striatum (DMS) and anterior cingulate cortex (ACC) via activity at μ-opioid receptors (MORs). MORs are present in somatic and presynaptic compartments of MThal neurons terminating in both the DMS and ACC. We investigated the effects of chronic morphine treatment on subsequent morphine signaling at MThal-DMS synapses, MThal-ACC synapses, and MThal cell bodies in male and female mice. Surprisingly, chronic morphine treatment increased subsequent morphine inhibition of MThal-DMS synaptic transmission (morphine facilitation), but decreased subsequent morphine inhibition of transmission at MThal-ACC synapses (morphine tolerance) in a sex-specific manner; these adaptations were present in male but not female mice. Additionally, these adaptations were not observed in knockin mice expressing phosphorylation-deficient MORs, suggesting a role of MOR phosphorylation in mediating both facilitation and tolerance to morphine within this circuit. The results of this study suggest that the effects of chronic morphine exposure are not ubiquitous; rather adaptations in MOR function may be determined by multiple factors such as subcellular receptor distribution, influence of local circuitry and sex.
Motor “laziness” constrains fixation selection in real-world tasks
Authors: Burlingham Charlie S. , Sendhilnathan Naveen , Komogortsev Oleg , Murdison T. Scott , Proulx Michael J.
Published: February 2023

Abstract

People coordinate their eye, head, and body movements to gather information from a dynamic environment while maximizing reward and minimizing biomechanical and energetic costs. Such natural behavior is not possible in a laboratory setting where the head and body are usually restrained and the tasks and stimuli used often lack ecological validity. Therefore, it’s unclear to what extent principles of fixation selection derived from lab studies, such as inhibition-of-return (IOR), apply in a real-world setting. To address this gap, participants performed nine real-world tasks, including driving, grocery shopping, and building a lego set, while wearing a mobile eye tracker (169 recordings; 26.6 hours). Surprisingly, spatial and temporal IOR were absent in all tasks. Instead, participants most often returned to what they just viewed, and saccade latencies were shorter preceding return than forward saccades. We hypothesized that participants minimize the time their eyes spend in an eccentric position to conserve eye and head motor effort. Correspondingly, we observed center biases in the distributions of fixation location and duration, relative to the head’s orientation. A model that generates scanpaths by randomly sampling these distributions reproduced the spatial and temporal return phenomena seen in the data, including distinct 3-fixation sequences for forward versus return saccades. The amount of the orbit used in each task traded off with fixation duration, as if both incur costs in the same space. Conservation of effort (“laziness”) explains all these behaviors, demonstrating that motor costs shape how people extract and act on relevant visual information from the environment.

Significance Statement

Humans display remarkably precise yet flexible control of eye and body movements, allowing for a wide range of activities. However, most studies of gaze behavior use the same setup: a head-restrained participant views small images on a computer. Such lab studies find that people avoid looking at the same thing twice, and hesitate in cases when they do. We had people perform nine everyday activities while wearing glasses with embedded eye tracking, and surprisingly found that they did the opposite, often returning to what they just viewed and expediting these “return” eye movements over others. A tendency to keep the eyes centered in the head, which we speculate helps to conserve motor effort, explained these behaviors for all tasks.
Botulinum neurotoxin A modulates the axonal release of pathological tau in hippocampal neurons
Authors: Panzi Chiara , Surana Sunaina , De La-Rocque Samantha , Moretto Edoardo , Lazo Oscar Marcelo , Schiavo Giampietro
Published: February 2023

Pathological tau aggregates propagate across functionally connected neuronal networks in human neurodegenerative pathologies, such as Alzheimer’s disease. However, the mechanism underlying this process is poorly understood. Several studies have showed that tau release is dependent on neuronal activity and that pathological tau is found in the extracellular space in free form, as well as in the lumen of extracellular vesicles. We recently showed that metabotropic glutamate receptor activity and the SNAP25 integrity modulate the release of pathological tau from human and mouse synaptosomes. Here, we have leveraged botulinum neurotoxins (BoNTs), which impair neurotransmitter release by cleaving specific synaptic SNARE proteins, to dissect molecular mechanisms related to tau release at synapses. In particular, we have tested the effect of botulinum neurotoxin A (BoNT/A) on the synaptic release of tau in primary mouse neurons. Hippocampal neurons were grown in microfluidic chambers and transduced with lentiviruses expressing human tau (hTau). We found that neuronal stimulation significantly increases the release of mutant hTau, whereas wild-type hTau is unaffected. Importantly, BoNT/A blocks mutant hTau release, indicating that this process is modulated by SNAP25 in intact neurons. These results suggest that BoNTs are potent tools to study the spreading of pathological proteins in neurodegenerative diseases and will play a central role in identifying novel molecular targets for the development of therapeutic interventions to treat tauopathies.
Role of maternal, fetal and placental histopathology factors in the pathogenesis of retinopathy of prematurity
Authors: Kaur Tarandeep , Sharma Neha , Jakati Saumya , Bagga Nitasha , Mitra Sanchita , Bhargavi K Katamtreddy , Jalali Subhadra , Kaur Inderjeet
Published: February 2023

Purpose

To investigate if maternal, fetal and placental vascular and/or molecular changes predict the risk for retinopathy of prematurity in preterm infants.

Methodology

The postnatal and antenatal data and placental histopathological changes; H&E staining of placental sections and molecular findings; gene expression analysis by qRT-PCR and protein expression by IHC at the maternal-fetal interface were collected from 20 placental samples and categorized into 3 groups: full-term (n=10), preterm without ROP (n=7) and preterm with ROP (n=6).

Results

The correlation analysis indicated significant association of increased monocytes (p=0.042), fetal growth retardation (p=0.000), apnoeic spell (p=0.033), ventilation (p=0.009), length in hospital stay (p=0.001) and decreased RBC (p=0.02), Hb (p=0.048), PCV (p=0.010), gestational age (p=0.003), birth weight (p=0.000) with increased risk of ROP. Along with these factors, placental weight(p=0.001), diameter (p=0.019), Tenny-Parker changes (p=0.025), alternating area of small and short hyper mature villi (p=0.033) are also found to be significant determinants of the disease. Gene expression analysis revealed significant increase in hypoxia (HIF-1gene expression; p=0.007) and non-significant increase in the pro-inflammatory markerIL-6. The protein expression also showed the significantly increased activation of complement pathway (CFH) and NF- ΚB at maternal-fetal interface.

Conclusions

Our preliminary results support the changes in the maternal-fetal factors, placental histopathology and molecular alterations related to hypoxia, inflammation and complement activation at maternal-fetal interface in preterm with ROP placentas. These changes have the potential to predict the risk of the disease but the results are required to be further validated in larger cohort.
Redefinition of archetypal phytoplankton-associated bacteria taxa based on globally distributed dinoflagellates and diatoms
Authors: Yang Xiaoyu , Cai Guanjing , Cai Runlin , Gu Haifeng , Chen Yuerong , Xie Jianmin , Hu Zhong , Wang Hui
Published: February 2023

Bacteria colonizing in the phycosphere formed by phytoplankton exudates play important roles in marine ecosystems, yet their taxonomy is poorly defined. Here, we customized the analytical approaches for the microalga-attached microbiotas from 110 diatom and 86 dinoflagellate samples to reveal key bacterial players and their ecological significance in the phycosphere. The results demonstrated a co-occurrence of host-specificity and conservation of phytoplankton-associated bacterial communities, defined 8 diatom- and 23 dinoflagellate-affiliated characteristic genera, as well as identifying 14 core genera prevalent with phytoplankton populations. Further classification of these 14 core genera into three tiers showed their distinct ecological features regarding occupancy, connectivity and community-stabilizing, whilst also matching their inherent metabolic properties. Our study redefines the archetypal phytoplankton-associated bacteria taxa more specifically up to the genus level, highlighting the significance of rarely noticed bacteria in the phycosphere, which is invaluable when selecting target bacteria for studying phytoplankton-bacteria interactions.
Judging the difficulty of perceptual decisions
Authors: Löffler Anne , Zylberberg Ariel , Shadlen Michael N. , Wolpert Daniel M.
Published: February 2023

Deciding how difficult it is going to be to perform a task allows us to choose between tasks, allocate appropriate resources, and predict future performance. To be useful for planning, difficulty judgments should not require completion of the task. Here we examine the processes underlying difficulty judgments in a perceptual decision making task. Participants viewed two patches of dynamic random dots, which were colored blue or yellow stochastically on each appearance. Stimulus coherence (the probability,pblue, of a dot being blue) varied across trials and patches thus establishing difficulty, |pblue− 0.5|. Participants were asked to indicate for which patch it would be easier to decide the dominant color. Accuracy in difficulty decisions improved with the difference in the stimulus difficulties, whereas the reaction times were not determined solely by this quantity. For example, when the patches shared the same difficulty, reaction times were shorter for easier stimuli. A comparison of several models of difficulty judgment suggested that participants compare the absolute accumulated evidence from each stimulus and terminate their decision when they differed by a set amount. The model predicts that when the dominant color of each stimulus is known, reaction times should depend only on the difference in difficulty, which we confirm empirically. We also show that this model is preferred to one that compares the confidence one would have in making each decision. The results extend evidence accumulation models, used to explain choice, reaction time and confidence to prospective judgments of difficulty.
IL-6 SIGNALING EXACERBATES HALLMARKS OF CHRONIC TENDON DISEASE BY STIMULATING REPARATIVE FIBROBLASTS
Authors: Stauber Tino , Moschini Greta , Hussien Amro A. , Jaeger Patrick K. , De Bock Katrien , Snedeker Jess G.
Published: February 2023

Tendinopathies are debilitating diseases currently increasing in prevalence and associated costs. There is a need to deepen our understanding of the underlying cell signaling pathways to unlock effective treatments. In this work, we screen cell signaling pathways in human tendinopathies and find positively enriched IL-6/JAK/STAT signaling alongside signatures of cell populations typically activated by IL-6 in other tissues. In human tendinopathic tendons, we also confirm the strong presence and co-localization of IL-6, IL6R, and CD90, an established marker of reparative fibroblasts. To dissect the underlying causalities, we combine IL-6 knock-out mice with an explant-based assembloid model of tendon damage to successfully connect IL-6 signaling to reparative fibroblast activation and recruitment. Vice versa, we show that these reparative fibroblasts promote the development of tendinopathy hallmarks in the damaged explant upon IL-6 activation. We conclude that IL-6 activates tendon fibroblast populations which then initiate and deteriorate tendinopathy hallmarks.
CK1δ homeostasis by activity-dependent shuttling and degradation of orphan kinase
Authors: Serrano Fidel E. , Marzoll Daniela , Ruppert Bianca , Diernfellner Axel C. R. , Brunner Michael
Published: February 2023

Casein kinase 1δ (CK1δ) is a simple monomeric enzyme involved in the regulation of a variety of functions, including signal transduction, the circadian clock, and the cell cycle. Although CK1δ is targeted by the ubiquitin ligase APC/CCdh1is not understood how CK1δ expression is regulated to support its multiple functions. Here, we show that kinase activity controls CK1δ homeostasis by coordinating two competing processes: export from the nucleus to ensure distribution of CK1δ between its assembly partners, and proteasomal degradation of unassembled CK1δ in the nucleus to keep the amount of active, potentially deleterious orphan kinase low. During mitosis, CK1δ is released from centrosomes and stabilized by (auto)phosphorylation to preserve it for the subsequent G1 phase.

Teaser

Competitive nuclear export and nuclear degradation of active CK1δ ensure efficient partner interaction and keep unassembled kinase levels low.
An allele-resolved nanopore-guided tour of the human placental methylome
Authors: Kindlova Michaela , Byrne Hannah , Kubler Jade M , Steane Sarah E , Whyte Jessica M , Borg Danielle J , Clifton Vicki L , Ewing Adam D
Published: February 2023

The placenta is a temporary organ present during pregnancy that is responsible for coordinating all aspects of pregnancy between the mother and fetus. It has a distinct epigenetic, transcriptomic, and mutational landscape with low levels of methylation, high numbers of transcribed loci, and a high mutational burden relative to somatic tissues. We present this landscape through the application of nanopore sequencing technology to provide a more comprehensive picture of female placental genomics and methylomics along with integrated haplotype-resolved transcriptomic analyses across eight trios. Whole genome sequencing of trios allows robust phasing, permitting comprehensive genome-wide investigation of parent-of-origin methylation and transcription. This enhanced view facilitates identifications of many new differentially methylated regions (DMRs), both conserved and differing between individuals, as well as novel imprinted genes including ILDR2 and RASA1 which are potentially important for healthy placental and fetal development.
Complex waste stream valorisation through combined enzymatic hydrolysis and catabolic assimilation byPseudomonas putida
Authors: Alvarez-Gonzalez Guadalupe , Chacόn Micaela , Berepiki Adokiye , Fisher Karl , Gosalvitr Piya , Cuéllar-Franca Rosa , Dixon Neil
Published: February 2023

The use of biomass and organic waste as a feedstock for the production of fuels, chemicals and materials offers great potential to support the transition to net-zero and circular economic models. However, such renewable feedstocks are often complex, highly heterogeneous, and subject to geographical and seasonal variability, creating supply-chain inconsistency that impedes adoption. Towards addressing these challenges, the development of engineered microorganisms equipped with the ability to flexibly utilise complex, heterogenous substrate compositions for growth and bio-production would be greatly enabling. Here we show through careful strain selection and metabolic engineering, that Pseudomonas putida can be employed to permit efficient co-utilisation of highly heterogeneous substrate compositions derived from hydrolysed mixed municipal-like waste fractions, with remarkable resilience to compositional variability. To further illustrate this, one pot enzymatic pre-treatments of the five most abundant, hydrolytically labile, mixed waste feedstocks was performed – including food, plastic, organic, paper and cardboard, and textiles – for growth and synthesis of exemplar bio-products by engineered P. putida. Finally, prospective life cycle assessment and life cycle costing illustrated the climate change and economic advantage, respectively, of using the waste-derived feedstock for biomanufacturing compared to conventional waste treatment options. This work demonstrates the potential for expanding the treatment strategies for mixed municipal waste to include engineered microbial bio-production platforms that can accommodate variability in feedstock inputs to synthesise a range of chemical and material outputs.
Phosphoproteomics of cellular mechanosensing reveals NFATC4 as a regulator of myofibroblast activity
Authors: Mattner Laura F. , Zeng Zhen , Mayr Christoph H. , Ansari Meshal , Wei Xin , Asgharpour Sara , Wasik Anita A. , Kneidinger Nikolaus , Stoleriu Mircea-Gabriel , Behr Jürgen , Polleux Julien , Yildirim Ali Önder , Burgstaller Gerald , Mann Matthias , Schiller Herbert B.
Published: February 2023

Feedback connections between tissue stiffness and cellular contractile forces can instruct cell identity and activity via a process referred to as mechanosensing. Specific phosphoproteome changes during mechanosensing are poorly characterized. In this work, we chart the global phosphoproteome dynamics of primary human lung fibroblasts sensing the stiffness of injury relevant fibronectin coated Poly(dimethylsiloxane) substrates. We discovered a key signaling threshold at a Young’s modulus of eight kPa stiffness, above which cells activated a large number of pathways including RhoA, CK2A1, PKA, AMPK, AKT1, and Hippo-YAP1/TAZ mediated signaling. Time-resolved phosphoproteomics of cell spreading on stiff substrates revealed the temporal dynamics of these stiffness-sensitive signaling pathways. ECM substrate stiffness above eight kPA induced fibroblast contractility, cytoskeletal rearrangements, ECM secretion, and a fibroblast to myofibroblast transition. Our data indicate that phosphorylation of the transcriptional regulator NFATC4 at S213/S217 enhances myofibroblast activity, which is the key hallmark of fibrotic diseases. NFATC4 knock down cells display reduced stiffness induced collagen secretion, cell contractility, nuclear deformation and invasion, suggesting NFATC4 as a novel target for antifibrotic therapy.

Synopsis

How tissue stiffness regulates identity and activity of tissue fibroblasts is unclear. Mass spectrometry based analysis of tissue stiffness dependent phosphoproteome changes reveals how primary lung fibroblasts sense the mechanical properties of their environment and identifies NFATC4 as a novel regulator of the stiffness dependent transition of fibroblasts to ECM secreting myofibroblasts.

Mass spectrometry analysis reveals the signaling landscape of fibroblast mechanosensing

Time-resolved phosphoproteomic analysis of cell spreading on fibronectin

NFATC4 regulates myofibroblast collagen secretion, cell contractility and invasion
Cooperative super-enhancer inactivation caused by heterozygous loss of CREBBP and KMT2D skews B cell fate decisions and yields T cell-depleted lymphomas
Authors: Li Jie , Chin Christopher R. , Ying Hsia-Yuan , Meydan Cem , Teater Matthew R. , Xia Min , Farinha Pedro , Takata Katsuyoshi , Chu Chi-Shuen , Rivas Martin A. , Chadburn Amy , Steidl Christian , Scott David W. , Roeder Robert G. , Mason Christopher E. , Béguelin Wendy , Melnick Ari M.
Published: February 2023

Mutations affecting enhancer chromatin regulatorsCREBBPandKMT2Dare highly co-occurrent in germinal center (GC)-derived lymphomas and other tumors, even though regulating similar pathways. Herein, we report that combined haploinsufficiency ofCrebbpandKmt2d(C+K) indeed accelerated lymphomagenesis. C+K haploinsufficiency induced GC hyperplasia by altering cell fate decisions, skewing B cells away from memory and plasma cell differentiation. C+K deficiency particularly impaired enhancer activation for immune synapse genes involved in exiting the GC reaction. This effect was especially severe at super-enhancers for immunoregulatory and differentiation genes. Mechanistically, CREBBP and KMT2D formed a complex, were highly co-localized on chromatin, and were required for each-other’s stable recruitment to enhancers. Notably, C+K lymphomas in mice and humans manifested significantly reduced CD8+T-cell abundance. Hence, deficiency of C+K cooperatively induced an immune evasive phenotype due at least in part to failure to activate key immune synapse super-enhancers, associated with altered immune cell fate decisions.

SIGNIFICANCE

Although CREBBP and KMT2D have similar enhancer regulatory functions, they are paradoxically co-mutated in lymphomas. We show that their combined loss causes specific disruption of super-enhancers driving immune synapse genes. Importantly, this leads to reduction of CD8 cells in lymphomas, linking super-enhancer function to immune surveillance, with implications for immunotherapy resistance.
Hemodynamics in Patients with Aortic Coarctation: A Comparison ofin vivo4D-Flow MRI and FSI Simulation
Authors: Nair Priya J. , Pfaller Martin R. , Dual Seraina A. , Loecher Michael , McElhinney Doff B. , Ennis Daniel B. , Marsden Alison L.
Published: February 2023

The analysis of quantitative hemodynamics provides information for the diagnosis and treatment planning in patients with aortic coarctation (CoA). Patient-specific computational fluid dynamics (CFD) simulations reveal detailed hemodynamic information, but their agreement with the clinical standard 4D-Flow magnetic resonance imaging (MRI) needs to be characterized. This work directly comparesin vivoCFD fluid-structure interaction (FSI) simulations against 4D-Flow MRI in patients with CoA (N=5). 4D-Flow MRI-derived flow waveforms and cuff blood pressure measurements were used to tune the boundary conditions for the FSI simulations. Flow rates from 4D-Flow MRI and FSI were compared at cross-sections in the ascending aorta (AAo), CoA and descending aorta (DAo). Qualitative comparisons showed an overall agreement of flow patterns in the aorta between the two methods. TheR2values for the flow waveforms in the AAo, CoA, and DAo were 0.97, 0.84 and 0.81 respectively, representing a strong correlation between 4DFlow MRI measurements and FSI results. This work characterizes the use of patient-specific FSI simulations in quantifying and analyzing CoA hemodynamics to inform CoA treatment planning.
Lifelong molecular consequences of high Glucocorticoids exposure during development
Authors: Choi Min-Kyeung , Cook Alex , Mungikar Kanak , Eachus Helen , Tochwin Anna , Linke Matthias , Gerber Susanne , Ryu Soojin
Published: February 2023

Early life stress (ELS) is one of the strongest risk factors for developing psychiatric disorders in humans. As conserved key stress hormones of vertebrates, glucocorticoids (GCs) are thought to play an important role in mediating the effects of ELS exposure in shaping adult phenotypes. In this process, early exposure to high level of GCs may induce molecular changes that alter developmental trajectory of an animal and primes differential adult responses. However, comprehensive characterization of identities of molecules that are targeted by developmental GC exposure is currently lacking. In our study, we describe lifelong molecular consequences of high level of developmental GC exposure using an optogenetic zebrafish model. First, we developed a new double-hit stress model using zebrafish by combining exposure to a high endogenous GC level during development and acute adulthood stress exposure. Our results establish that similar to ELS-exposed humans and rodents, developmental GC exposed zebrafish model shows altered behavior and stress hypersensitivity in adulthood. Second, we generated time-series gene expression profiles of the brains in larvae, in adult, and upon stress exposure to identify molecular alterations induced by high developmental GC exposure at different developmental stages. Third, we identify a set of GC-primed genes that show altered expression upon acute stress exposure only in animals exposed to a high developmental GC. Interestingly, our datasets of GC primed genes are enriched in risk factors identified for human psychiatric disorders. Lastly, we identify potential epigenetic regulatory elements and associated post-transcriptional modifications following high developmental GC exposure. Thus, we present a translationally relevant zebrafish model for studying stress hypersensitivity and alteration of behavior induced by exposure to elevated GC levels during development. Our study provides comprehensive datasets delineating potential molecular targets underlying the impact of developmental high GC exposure on adult responses.
In vivoevaluation of the effect of sickle cell hemoglobin S, C and therapeutic transfusion on erythrocyte metabolism and cardiorenal dysfunction
Authors: D’Alessandro Angelo , Nouraie S. Mehdi , Zhang Yingze , Cendali Francesca , Gamboni Fabia , Reisz Julie A. , Zhang Xu , Bartsch Kyle W. , Galbraith Matthew D. , Gordeuk Victor R. , Gladwin Mark T
Published: February 2023

Despite a wealth of exploratory plasma metabolomics studies in sickle cell disease (SCD), no study to date has evaluate a large and well phenotyped cohort to compare the primary erythrocyte metabolome of hemoglobin SS, SC and transfused AA red blood cells (RBCs)in vivo. The current study evaluates the RBC metabolome of 587 subjects with sickle cell sickle cell disease (SCD) from the WALK-PHaSST clinical cohort. The set includes hemoglobin SS, hemoglobin SC SCD patients, with variable levels of HbA related to RBC transfusion events, and HbF related to hydroxyurea therapy. Here we explore the modulating effects of genotype, age, sex, severity of hemolysis, and hydroxyurea and transfusion therapy on sickle RBC metabolism. Data - collated in an online portal – show that the Hb SS genotype is associated with significant alterations of RBC acylcarnitines, pyruvate, sphingosine 1-phosphate, creatinine, kynurenine and urate metabolism. Surprisingly, the RBC metabolism of SC RBCs is dramatically different from SS, with all glycolytic intermediates significantly elevated in SS RBCs, with the exception of pyruvate. This result suggests a metabolic blockade at the ATP-generating phosphoenolpyruvate to pyruvate step of glycolysis, which is catalyzed by redox-sensitive pyruvate kinase. Increasing in vivo concentrations of HbA improved glycolytic flux and normalized the HbS erythrocyte metabolome. An unexpectedly limited metabolic effect of hydroxyurea and HbF was observed, possibly related to the modest induction of HbF in this cohort. The metabolic signature of HbS RBCs correlated with the degree of steady state hemolytic anemia, cardiovascular and renal dysfunction and mortality.

Key points

In vivo dysregulation of RBC metabolism by HbS is evaluated by metabolic profiling of 587 patients with variable HbA, HbC and HbF levels;

RBC acyl-carnitines, urate, pyruvate metabolism, S1P, kynurenine relate to hemolysis and cardiorenal dysfunction, respond to transfusion;
Threshold inclusion size triggers conversion of huntingtin to prion-like state that is reversible in newly born cells
Authors: Asgarkhani Leila , Khandakar Ibrahim , Pakan Rachel , Swayne Theresa C. , Emtage Lesley
Published: February 2023

Aggregation of mutant Huntingtin protein (mHtt) leads to neuronal cell death and human disease. We investigated the effect of inclusion formation on yeast cells. Previous work indicates that mHtt protein moves both in and out of inclusions, potentially undergoing refolding in the inclusion. However, the sustained influx of unfolded protein into an inclusion leads to a dramatic change from a phase-separated body to an irregular, less soluble form at a threshold inclusion size. Altered morphology was associated with a prion-like seeding that accelerated inclusion growth despite loss of soluble cytoplasmic protein. The structural change abolished exchange of material between the inclusion and the cytosol and resulted in early cell death. Affected cells continued to divide occasionally, giving rise to daughters with a similar phenotype. Most newly born cells were able to reverse the prion-like aggregation, restoring both soluble cytoplasmic protein and a normal inclusion structure.
Nuclear Myosin 1 regulates platelet activation and immune response in mice
Authors: Venit Tomas , Percipalle Piergiorgio
Published: February 2023

Cellular differentiation involves a complex series of events associated with change in cellular shape, function and proliferative capacity. This process is mostly regulated by specific expression of multiple genes which guide the cell through the differentiation process but also ensure proper function of terminal cell types. Over the last decade, the role of cellular metabolism on maintaining pluripotency of stem cells and subsequent differentiation is getting more attention as there is a direct link between the metabolic status of cells and their differentiation potential. We have recently shown that deletion of Nuclear Myosin 1 (NM1) leads to a molecular switch from oxidative phosphorylation to glycolysis and subsequent tumorigenesis in mice. In the present study, we explored the role of NM1 during differentiation of hematopoietic progenitor stem cells to terminal blood and bone marrow stromal cells. Remarkably, we found that NM1 deletion leads to differential expression of genes associated with platelet activation, immune system response and osteoclast differentiation with glycolysis-dependent processes being upregulated while oxidative phosphorylation-dependent processes being generally suppressed in bone marrow tissue isolated from NM1 knock-out mice. The study provides novel insights into the underlying mechanisms of hematopoietic differentiation and suggests that NM1 is a potential therapeutic target for blood-related disorders.
Coopetition configuration and performance of international joint ventures for high-speed rail projects
Authors: Niu Yanliang , Li Huimin , Luo Xiaowei , Deng Xiaopeng
Published: February 2023

Purpose

Members in the international joint ventures (IJVs) for high-speed rail (HSR) projects usually engage in coopetition interactions to create common benefits (CB) and simultaneously safeguard private benefits (PB). Previous studies of coopetition and performance using variance-based methods usually ignore the combinational influence of diverse coopetition constructs on performance, which can be effectively compensated by adopting a configuration perspective. Therefore, this research aims to ascertain various combinations of three coopetition constructs (coopetition relationship, coopetition capability and coopetition strategy) that lead to high IJVs’ performance through a configuration approach.

Design/methodology/approach

First, the research framework of coopetition configuration was established, and the key constructs were operationalized, which were validated by expert interviews. Then the information on 12 HSR IJVs was collected and quantified through nine rounds of interviews and a questionnaire survey. Later, the fuzzy-set qualitative comparative analysis (fsQCA) was applied to explore what coopetition configurations benefit the CB or PB achievement.

Findings

Configuration results indicate that six coopetition configurations lead to CB outcome and seven configurations lead to PB outcome. Based on the results, coopetition contexts are divided into four categories: firm-based coopetition, project-based coopetition, firm-project-based coopetition and none-based coopetition. Then, a selection scheme for coopetition strategies in various contexts has been developed. The results also show that the core conditions mostly appear in the coopetition relationships and coopetition strategies dimensions, and the optimal coopetition strategies vary in different contexts.

Originality/value

This study enhances the theoretical understanding of coopetition in HSR IJVs and assists relative HSR industrialists, as well as the mega infrastructure project managers, in IJVs’ implementation. The configuration perspective of this paper also contributes to a systemic and holistic view of coopetition in HSR IJVs.
Green human resource management: the role of positive levers of control and environmental performance measures in managing performance
Authors: Baird Kevin , Tung Amy
Published: February 2023

Purpose

This study focuses on the role of green human resource management (GHRM) practices through providing an empirical insight into the mediating role of the use of environmental performance measures (EPMs) in the association between Simons’ (1995) positive levers of control (beliefs and the interactive use of controls) with environmental and organisational performance.

Design/methodology/approach

A survey questionnaire was distributed to 577 chief financial officers within Australian manufacturing organisations who were randomly chosen from the OneSource online database.

Findings

The use of operational EPMs is found to mediate the association between the use of the positive levers of control with two of the four dimensions of environmental performance (resource usage and stakeholder interaction), and non-financial performance (through stakeholder interaction). In addition, the use of management EPMs mediates the association between the use of the positive levers of control with the regulatory compliance dimension of environmental performance. The findings highlight the importance of GHRM practices, in particular, the need for managers to focus on the positive levers of control and using operational EPMs and management EPMs to a greater extent.

Originality/value

The study contributes to the limited empirical research examining GHRM practices, highlighting the importance of EPMs and integrating such measures with internal control mechanisms, specifically beliefs and the interactive use of controls.
Organizational values in support of leadership styles fostering organizational resilience: a process perspective
Authors: Tvedt Ida Marie , Tommelein Iris D. , Klakegg Ole Jonny , Wong John-Michael
Published: February 2023

Purpose

The purpose of this paper is to describe how resilience unfolded in a project-based organization with the support of organizational values through changing leadership styles. The rapidly announced restrictions on businesses during the coronavirus disease 2019 (COVID-19) provided an opportunity to observe and study resilience unfold.

Design/methodology/approach

The process-perspective case study approach of a structural and civil engineering design firm in San Francisco, California, USA, integrates interviews, observations, document analysis and information tracking via email and Microsoft Teams. The researchers adopted a leadership perspective, where the units of analysis are the internal management and the employees' behaviors.

Findings

In the case examined, the capability represented in the organizational values influenced the choice of situation-appropriate leadership styles to support employees. The values of relationship, passion and trust influenced the dominant choice of a transformational style, where stability and excellence facilitate a transactional style – all equally important for the balance and resilience of the project-based organization.

Originality/value

This study demonstrated that when organizational values support leaders in cultivating a learning environment, those values provide stability for leaders to promote resilience. To the best of the researchers' knowledge, no previous work described how situational-, transformational- and transactional-leadership styles evolve in response to a crisis and together facilitate organizational resilience.
Relationship between unemployment and policy uncertainty in Nigeria: ARDL evidence from 1990 to 2020
Authors: Zaria Yusuf Bala , Tuyon Jasman
Published: February 2023

Purpose

Apart from providing theoretical clarity, the present research aims to validate empirically that the EPU will be adversely affecting these key macroeconomic variables and that managing EPU matters for economic policymaking in Nigeria.

Design/methodology/approach

A dynamic autoregressive distributed lag regression model is employed to analyse the relationship from 1990 to 2020. Based on the theory of multiplier effect, the analysis could examine the positive and negative changes in policy uncertainty, as well as the reliability in macroeconomic activities such as unemployment, infrastructure development and foreign direct investment inflows.

Findings

The findings revealed EPU is cointegrated with the key economic variables in focus. Further, the negative impact of EPU on corporate investment in FDI and positive impact of EPU on unemployment confirm for both short and long-run. However, the impact of EPU on government investment in infrastructure development is found to be positive which does not confirm the expected hypothesis.

Practical implications

Dynamic relationship between policy uncertainty and macroeconomic activities in Nigeria seems to exist. Taking risky decisions has impact and causing a high unemployment rate, poor infrastructural development and lower foreign direct investment inflows in the country.

Originality/value

Policy uncertainty in Nigeria is determining. Despite that, very little research found that rising uncertainty issues may significantly affect unemployment, investment in infrastructure and foreign direct investment inflows adversely. Therefore, policy uncertainty is an open space for economic activities to thrive in Nigeria, especially unemployment.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/IJSE-08-2022-0555
A proposal of conceptual model for Brazilian popular music
Authors: Padron Marcos Fragomeni , Cruz Fernando William , Silva Juliana Rocha De Faria , Smiraglia Richard P.
Published: February 2023

Purpose

The term “Brazilian popular music” refers to a varied repertoire of musical styles with a strong connection to local culture. The initiatives of representation of this domain of interest occur through adaptations of generic models and strategies coming from contexts and musical styles that differ from the essential characteristics of the national music. The purpose of this paper is to present a characterization of Brazilian popular music as a conceptual model which supports the communication and analysis of this domain and serves as a reference ontology for various applications in the field of Information Science and others.

Design/methodology/approach

To achieve the purpose, a mapping about Brazilian popular music was done from a literature review and a data collection with expert users, based on domain analysis theory. From this characterization, the conceptual model was built using an Ontology Engineering approach. To facilitate understanding, the results were described using a more user-friendly notation.

Findings

The paper presents a conceptual model as a first semantic reference on Brazilian popular music that serves (1) to better understand, communicate and analyze the domain of Brazilian popular music and, (2) to supply some semantic aspects not covered by the adaptations that have been proposed on the literature for musical representation.

Originality/value

The paper adds a new perspective to the understanding of Brazilian popular music and open opportunity to explore other repertoires about popular music.
Integrated care systems and equity: prospects and plans
Authors: Goddard Maria
Published: February 2023

Purpose

Policies on integrated care have waxed and waned over time in the English health and care sectors, culminating in the creation of 42 integrated care systems (ICSs) which were confirmed in law in July 2022. One of the four fundamental purposes of ICSs is to tackle health inequalities. This paper reports on the content of the overarching ICS plans in order to explore how they focus on health inequalities and the strategies they intend to employ to make progress. It explores how the integrated approach of ICSs may help to facilitate progress on equity.

Design/methodology/approach

The analysis is based on a sample of 23 ICS strategic plans using a framework to extract relevant information on health inequalities.

Findings

The place-based nature of ICSs and the focus on working across traditional health and care boundaries with non-health partners gives the potential for them to tackle not only the inequalities in access to healthcare services, but also to address health behaviours and the wider social determinants of health inequalities. The plans reveal a commitment to addressing all three of these issues, although there is variation in their approach to tackling the wider social determinants of health and inequalities.

Originality/value

This study adds to our knowledge of the strategic importance assigned by the new ICSs to tackling health inequalities and illustrates the ways in which features of integrated care can facilitate progress in an area of prime importance to society.
Immersive virtual reality training for excavation safety and hazard identification
Authors: Feng Zhenan , Lovreglio Ruggiero , Yiu Tak Wing , Acosta Dwayne Mark , Sun Banghao , Li Nan
Published: February 2023

Purpose

In the construction sector, site excavation is one of the most dangerous and challenging activities. Proper training can be an effective way to mitigate excavation hazards. Virtual reality (VR) has been used as an effective training tool to enhance safety performance in various industries. However, little attention has been paid to the potential of this technology for construction excavation safety training.

Design/methodology/approach

This study proposes an immersive VR training system for excavation safety and hazard identification. The proposed VR training system was compared with a health and safety manual via a controlled experiment.

Findings

Results based on scores obtained immediately after training indicate that VR training significantly enhanced practical performance, knowledge acquisition and self-efficacy. Results also show that knowledge was retained four weeks after training. In addition, VR training outperformed health and safety manuals regarding knowledge retention.

Originality/value

This study measures the practical performance to evaluate the effectiveness of the proposed VR training system. Also, this study compares the VR training system with a traditional training method by measuring knowledge acquisition and retention. The results demonstrate the potential of VR as a training tool for excavation safety and hazards.
Responses of bud banks and shoot density to experimental drought along an aridity gradient in temperate grasslands
Authors: Qian Jianqiang , Zhang Zhiming , Dong Yawei , Ma Qun , Yu Qiang , Zhu Jinlei , Zuo Xiaoan , Broderick Caitlin M. , Collins Scott L. , Han Xingguo , Luo Wentao
Published: February 2023

Climate change is expected to increase the magnitude and frequency of extreme drought in most grassland ecosystems. Exploring the responses of below‐ground bud banks and their relationships with above‐ground plant structure and drought is need to explain how climate change will impact grassland ecosystems. However, studies on the response of community‐scale bud and shoot densities to experimental drought along an aridity gradient are rare.

We experimentally removed 66% of growing season precipitation for 4 years in three temperate grasslands that spanned an aridity gradient in northern China. We quantified the legacy effects of drought on grass, forb and total community below‐ground bud density, above‐ground shoot density and the ratio of bud to shoot density 1 year following treatment.

Below‐ground bud density was lowest at the highest aridity site for the entire community, while above‐ground shoot density was highest at the medium aridity site. Below‐ground bud and above‐ground shoot densities were the lowest at the high aridity site for grasses but the highest for forbs at this site. Bud:shoot ratios decreased with increasing aridity for grasses, yet remained constant for forbs along the aridity gradient. Below‐ground bud density in drought plots remained lower than controls a year following drought at each site. Experimental drought did not alter the below‐ground bud bank for grasses but decreased forb bud banks across sites. Experimental drought had little legacy effects on above‐ground shoot density and bud:shoot ratios for grasses, forbs and the total community at each site.

Our results suggest that grass and forb bud banks can differ in their responses to both multi‐year drought along an aridity gradient, and that bud limitation for shoot generation may increase as grasslands get drier. Bud bank responses to climate will impact plant community functioning and resilience. Thus, incorporating bud bank dynamics will improve projections of grassland ecosystems under future climate change.

Read the free Plain Language Summary for this article on the Journal blog.
CircADSS contributes to hepatocellular carcinoma development by regulating miR‐431‐5p/TOP2A
Authors: Gong Jianzhuang , Du Chenxu , Sun Nai , Xiao Xingguo , Wu Huili
Published: February 2023

CircRNAs participated in regulating hepatocellular carcinoma (HCC), and the regulation function of circRNA adenylosuccinate synthase (circADSS) on HCC development is not clear. RT‐qPCR and western blot were performed to detect RNA expression. Cell proliferation was analysed by CCK‐8 and EdU assay. Cell cycle distribution was analysed by flow cytometry assay. Cell migration and invasion were measured by transwell assay. Mechanism assays were employed to examine the interaction between miR‐431‐5p and circADSS, or TOP2A. Xenograft mouse model was constructed for in vivo assay. CircADSS and TOP2A expression were boosted, while miR‐431‐5p was limited in tumour tissues and cells. CircADSS silencing decreased HCC cell proliferation, cell cycle progression, migration, invasion, as well as EMT. MiR‐431‐5p inhibitors or ectopic TOP2A expression could restore the effect of circADSS knockdown on HCC progression. There was target relationship between miR‐431‐5p and circADSS, or TOP2A. Knockdown of circADSS suppressed tumour growth in vivo. CircADSS could regulate HCC cell malignancy by miR‐431‐5p/TOP2A axis.