bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling wild type and mutant p53 in telomerase-immortalized human cells
Authors: Miciak Jessica J. , Bunz Fred
Published: June 2023

Genetic alterations that change the functions of p53 or other proteins in the p53 pathway contribute to a majority of cancers. Accordingly, many technological approaches and model systems have been employed to dissect the complex phenotypes of this critical tumor suppressor and its mutants. Studies of human p53 are commonly conducted in tumor-derived cell lines that retain wild typeTP53alleles and isogenic derivatives with engineeredTP53alterations. While this genetic approach has provided numerous insights, such studies are bound to paint an incomplete picture of p53 and its many effects on the cell. Given the preponderance of p53 pathway defects in cancer, it is reasonable to assume that cancers that arise without mutations in theTP53coding sequence would very likely harbor other genetic or epigenetic alterations that effect the normal function of this pathway. One possible solution to this conundrum is to study p53 in cells that have been artificially immortalized. Unlike cells derived from tumorsex vivo, cells that have been immortalizedin vitroare not shaped by evolutionary selection during tumorigenesis, and presumably retain many of the normal functions of p53 and other tumor suppressors. We report here a functional characterization of p53 in the immortalized human cell line hTERT-RPE1 and describe the dominant-negative effects of a heterozygous missense p53 A276P mutation that apparently arose during serial culture. Detailed studies of this contact mutant, also found in human tumors, demonstrate the practical utility of this model system for studying the complex phenotypes of human p53.
Pellioditis pelhamin. sp. (Nematoda: Rhabditidae) andPellioditis pellio(Schneider, 1866), earthworm associates from different subclades withinPellioditis(syn.PhasmarhabditisAndrássy, 1976)
Authors: Tandingan De Ley Irma , Kiontke Karin , Bert Wim , Sudhaus Walter , Fitch David H. A.
Published: June 2023

Recently, much attention has been focused on a group of rhabditid nematodes calledPhasmarhabditis, a junior synonym ofPellioditis, as a promising source of biocontrol agents for invasive slugs.Pellioditis pelhamin. sp. was first isolated from earthworms near Pelham Bay Park in Bronx, New York, USA, in 1990 and has been found to be pathogenic to slugs as well as some earthworms. It has also been used in several comparative developmental studies. Here, we provide a description of this species, as well as a redescription of a similar earthworm-associated nematode,Pellioditis pellioSchneider, 1866, re-isolated from the type locality. AlthoughP. pelhamin. sp. andP. pellioare morphologically similar, they are reproductively isolated. Molecular phylogenetic analysis places both species in a clade that includes all species previously described asPhasmarhabditiswhich are associated with gastropods.PhasmarhabditisAndrássy, 1976 is therefore a junior synonym ofPellioditisDougherty, 1953. Also,P. bohemicaNermut’, Půža, Mekete & Mráček, 2017, described to be a facultative parasite of slugs, is found to be a junior synonym ofPellioditis pellio(Schneider, 1866), adding to evidence thatP. pelliois associated with both slugs and earthworms. The earthworm-associated speciesP. pelhamin. sp. andP. pelliorepresent different subclades withinPellioditis, suggesting thatPellioditisspecies in general have a broader host range than just slugs. Because of this, caution is warranted in using these species as biological control agents until more is understood about their ecology.
Enabling Success Through Transformative Practices in STEM: The Effects of Applying an Anti-Deficit Framework to Diversity and Equity Programming
Authors: Duncan D’Anne S , Jackson Jhia LN , Collins Sally , Teherani Arianne
Published: June 2023

Diversity, equity, and inclusion (DEI) programming and literature for historically underrepresented and marginalized students in science, technology, engineering, and mathematics degree programs often focuses on illuminating the challenges they face. The repeated emphasis on negative experiences creates a deficit-focused thread of inquiry that may unintentionally reinscribe persistent disparities and inequities. In this practice brief, we describe the positive effect of adapting anti-deficit framework with social career cognitive theory in developing and evaluating an Initiative for Maximizing Student Development program at a biomedical sciences graduate school, as well as how other institutions can explore, implement, and evaluate transformative DEI practices. In identifying and emphasizing the enablers of success while facilitating structured opportunities for personal and professional identity development, students and program leadership align values and goals to increase academic and scientific development, as well as community and social support.
What is the therapeutic quality of exercise programs in chronic low back pain randomized controlled trials assessed by i-CONTENT tool? A meta research study protocol
Authors: Geraci Ignazio , Bargeri Silvia , Basso Giacomo , Castellini Greta , Chiarotto Alessandro , Gianola Silvia , Ostelo Raymond , Testa Marco , Innocenti Tiziano
Published: June 2023

Background

Exercise therapy is a common intervention recommended for chronic low back pain (cLBP). Although adequate reporting of intervention is crucial to understand and replicate exercise therapy, it does not help clinicians to determine the therapeutic quality. So The international Consensus on Therapeutic Exercise aNd Training (i-CONTENT) tool was developed to assess therapeutic quality of exercise. Therefore, we will assess the therapeutic quality of different exercise interventions by i-CONTENT tool in cLBP RCTs and its inter-rater reliability.

Methods

We will perform a meta-research study, starting from Cochrane review publication “Exercise therapy for chronic low back pain”. We will select a random sample of 100 arms with different type of exercises included (i.e. Core Strengthening, General Strengthening, Stretching, Aerobic exercises, Motor Control, Pilates, McKenzie, Qigong, Yoga, Tai Chi). For each included study’s arm, two pairs of independent reviewers will assess the therapeutic quality of exercises applying the i-CONTENT tool. We will calculate the percentage agreement between raters to assess inter-rater reliability.

Ethics and dissemination

This study does not require an ethics review as we will not collect personal data. The use of the i-CONTENT tool can help assess the therapeutic quality of studies, reducing the risk of ineffective exercise interventions. The study’s results will be published in peer-reviewed journals and presented at national conferences.
What is the forecasted prevalence and incidence of long-term conditions in Wales: a rapid evidence map
Authors: Edwards Deborah , Csontos Judit , Gillen Elizabeth , Hutchinson Grace , Sha’aban Abubakar , Carrier Judith , Lewis Ruth , Edwards Rhiannon Tudor , Davies Jacob , Collins Brendan , Cooper Alison , Edwards Adrian
Published: June 2023

It is becoming apparent that the NHS will face many issues in years to come due to the growth of ageing population in relation to the working age population alongside the increase in multimorbidity and persistent health inequalities, particularly for preventable illness. This has implications to how healthcare and health systems are delivered, and how the NHS will need to adapt to meet the increasing demand that this places on healthcare services.

This rapid evidence map reports forecasted prevalence and incidence data across a range of long -term conditions in Wales to support planning about how best to organise and finance care for the increasing population with long-term conditions over the next 10 years. The findings by conditions include: atrial fibrillation, cancer, cardiovascular diseases, peripheral vascular disease, stroke, dementia, diabetes, heart failure, hypertension, mental illness, and multi-morbidities. Three risk factors for long term conditions were also included, i.e., poor diet/nutrition, obesity, and smoking. The review included evidence from 2012 to March 2023

Implications for policy and practice:

Results show which long-term conditions are projected to increase over 10 years or more. Further preventive interventions through behavioural science approaches, with increased investment, should be considered to mitigate the rising prevalence of several preventable conditions. Smoking, excessive drinking and obesity are candidates for targeted preventive work, especially in areas of deprivation, to lessen health inequalities. Further research is needed for some conditions, and to provide a more comprehensive understanding of the burden of these conditions in Wales. Earlier diagnosis by genetic and genomic technologies and enabling lifestyle changes or by more cost-effective home care could reduce NHS costs of some long-term conditions.
Performance of Risk Models to Predict Mortality Risk for Patients with Heart Failure: Evaluation in an Integrated Health System
Authors: Ahmad Faraz S. , Hu Ted Ling , Adler Eric D. , Petito Lucia C. , Wehbe Ramsey M. , Wilcox Jane E. , Mutharasan R. Kannan , Nardone Beatrice , Tadel Matevz , Greenberg Barry , Yagil Avi , Campagnari Claudio
Published: June 2023

Background

Referral of patients with heart failure (HF) who are at high mortality risk for specialist evaluation is recommended. Yet, most tools for identifying such patients are difficult to implement in electronic health record (EHR) systems.

Objective

To assess the performance and ease of implementation of Machine learning Assessment of RisK and EaRly mortality in Heart Failure (MARKER-HF), a machine-learning model that uses structured data that is readily available in the EHR, and compare it with two commonly-used risk scores: the Seattle Heart Failure Model (SHFM) and Meta-Analysis Global Group in Chronic (MAGGIC) Heart Failure Risk Score.

Design

Retrospective, cohort study

Participants

Data from 6,764 adults with HF were abstracted from EHRs at a large integrated health system from 1/1/10-12/31/19.

Main Measures

One-year survival from time of first cardiology or primary care visit was estimated using MARKER-HF, SHFM and MAGGIC. Discrimination was measured by the area under the receiver operating curve (AUC). Calibration was assessed graphically.

Key Results

Compared to MARKER-HF, both SHFM and MAGGIC required a considerably larger amount of data engineering and imputation to generate risk score estimates. MARKER-HF, SHFM, and MAGGIC exhibited similar discriminations with AUCs of 0.70 (0.69-0.73), 0.71 (0.69-0.72), and 0.71 (95% CI 0.70-0.73) respectively. All three scores showed good calibration across the full risk spectrum.

Conclusions

These findings suggest that MARKER-HF, which uses readily available clinical and lab measurements in the EHR and required less imputation and data engineering than SHFM and MAGGIC, is an easier tool to identify high-risk patients in ambulatory clinics who could benefit from referral to a HF specialist.
Improved Type 2 Diabetes Risk Stratification in the Qatar Biobank Cohort by Ensemble Learning Classifier Incorporating Multi-Trait, Population-Specific, Polygenic Risk Scores
Authors: Ahmed Ikhlak , Ziab Mubarak , Taheri Shahrad , Chagoury Odette , Hussain Sura A. , Lakshmi Jyothi , Bhat Ajaz A. , Fakhro Khalid A. , Al-Shabeeb Akil Ammira S.
Published: June 2023

Background

Type 2 Diabetes (T2D) is a pervasive chronic disease influenced by a complex interplay of environmental and genetic factors. To enhance T2D risk prediction, leveraging genetic information is essential, with polygenic risk scores (PRS) offering a promising tool for assessing individual genetic risk. Our study focuses on the comparison between multi-trait and single-trait PRS models and demonstrates how the incorporation of multi-trait PRS into risk prediction models can significantly augment T2D risk assessment accuracy and effectiveness.

Methods

We conducted genome-wide association studies (GWAS) on 12 distinct T2D-related traits within a cohort of 14,278 individuals, all sequenced under the Qatar Genome Programme (QGP). This in-depth genetic analysis yielded several novel genetic variants associated with T2D, which served as the foundation for constructing multiple weighted PRS models. To assess the cumulative risk from these predictors, we applied machine learning (ML) techniques, which allowed for a thorough risk assessment.

Results

Our research identified genetic variations tied to T2D risk and facilitated the construction of ML models integrating PRS predictors for an exhaustive risk evaluation. The top-performing ML model demonstrated a robust performance with an accuracy of 0.8549, AUC of 0.92, AUC-PR of 0.8522, and an F1 score of 0.757, reflecting its strong capacity to differentiate cases from controls. We are currently working on acquiring independent T2D cohorts to validate the efficacy of our final model.

Conclusion

Our research underscores the potential of PRS models in identifying individuals within the population who are at elevated risk of developing T2D and its associated complications. The use of multi-trait PRS and ML models for risk prediction could inform early interventions, potentially identifying T2D patients who stand to benefit most based on their individual genetic risk profile. This combined approach signifies a stride forward in the field of precision medicine, potentially enhancing T2D risk prediction, prevention, and management.
PINK1 Deficiency Alters Muscle Stem Cell Fate Decision and Muscle Regenerative Capacity
Authors: Cairns George , Thumiah-Mootoo Madhavee , Abassi Mah Rukh , Racine Jeremy , Larionov Nikita , Prola Alexandre , Khacho Mireille , Burelle Yan
Published: June 2023

Maintenance of optimal mitochondrial function plays a crucial role in the regulation of muscle stem cell (MuSC) behavior, but the underlying maintenance mechanisms remain ill defined. In this study, we explored the importance of mitophagy, as a mitochondrial quality control regulator, in MuSCs and the role this process plays in maintaining optimal muscle regenerative capacity. Here we show that MuSCs exhibit dynamic alterations in mitophagy under different physiological myogenic states. In particular, quiescent MuSCs exhibit high levels of PINK1/Parkin-dependent mitophagy, which is rapidly decreased upon transition to an early activation state. Genetic disruption of this pathway usingPink1knockout mice reduced mitophagy in quiescent MuSCs, which was accompanied by increased mitochondrial ROS release and mitochondrial network fragmentation. These abnormalities led to hampered self-renewal of MuSCs which ultimately translated in a progressive loss of muscle regeneration following repetitive injury. However, proliferation and differentiation capacity were unaltered in the absence of PINK1, indicating that altered fate decisions is the main mechanism underlying impaired muscle regeneration. Impaired fate decisions in PINK1 deficient MuSCs could be restored by scavenging excess mitochondrial ROS. Together, these data shed new light on the regulation of mitophagy during MuSC state transitions and position the PINK1-dependent pathway as an important regulator of MuSC mitochondrial properties and fate decisions.
Biomimetic Artificial Bone Marrow Niches for the Scale Up of Hematopoietic Stem Cells
Authors: Bosch-Fortea Minerva , Marciano Daniele , Gautrot Julien E.
Published: June 2023

Hematopoietic stem cell (HSC) transplantation to treat haematological disorders is greatly restricted by poor cell availability.Ex vivoexpansion of HSCs as a strategy to overcome this limitation has shown limited success so far, due to the loss of stem cell properties in culture. Therefore, engineering of culture platforms that mimic the physiological properties of the bone marrow (BM) in a scalable format is an important target to enable the translation of HSC therapies. Here, we report the design of biomimetic BM niches that enable the culture of HSCs in a scalable 3D platform. Beyond cellular and biochemical components (e.g., matrix and growth factors), an important element of the BM microenvironment is its architecture, dense in adipocytes, with relatively limited matrix and anisotropic mechanical properties. To capture this context, we propose the use of bioemulsions1,2in which oil microdroplets and associated mechanical anisotropy recreate important architectural features of the hematopoietic niche. Mesenchymal stem cells (MSCs) grown at the surface of such bioemulsion remodelled this environment, assembling an interstitial matrix mimicking that of the BM microenvironment composition. In addition, MSCs secreted important factors underpinning the crosstalk between stromal cells and HSCs in the native environment. HSCs cultured in the resulting artificial BM niches maintained stemness whilst expanding significantly (> 33-fold compared to HSCs cultured in suspension) and enabling scale up of expansion in conical flask bioreactors, to produce 2M cells in a single batch. This platform therefore harnesses engineered BM microenvironments and the processability of bioemulsions and microdroplet technologies to produce HSCs in a scalable format, for application in cell-based therapies.
Extracellular sodium regulates fibroblast growth factor 23 (FGF23) formation
Authors: Radvanyi Zsuzsa , Yoo Eun Jin , Kandasamy Palanivel , Salas-Bastos Adrian , Monnerat Sophie , Refardt Julie , Christ-Crain Mirjam , Hayashi Himeka , Kondo Yasuhiko , Jantsch Jonathan , Rubio-Aliaga Isabel , Sommer Lukas , Wagner Carsten A. , Hediger Matthias A. , Kwon Hyug Moo , Loffing Johannes , Pathare Ganesh
Published: June 2023

Fibroblast growth factor-23 (FGF23) is a bone-derived hormone that has recently received much attention due to its association with the progression of chronic kidney disease, cardiovascular disease, and associated mortality. Extracellular sodium concentration ([Na+]) plays a significant role in bone metabolism. Hyponatremia (low serum [Na+]) has recently been shown to be independently associated with FGF23 levels in patients with chronic systolic heart failure. However, nothing is known about the direct impact of [Na+] on FGF23 production. Here, we show that an elevated [Na+] (+20 mM) suppressed FGF23 formation, whereas low [Na+] (−20 mM) increased FGF23 synthesis in the osteoblast-like cell line UMR-106. Similar bidirectional changes in FGF23 abundance were observed when osmolality was altered by mannitol but not by urea, suggesting a role of tonicity in FGF23 formation. Moreover, these changes in FGF23 were inversely proportional to the expression of NFAT5 (nuclear factor of activated T cells-5), a transcription factor responsible for tonicity-mediated cellular adaptations. On the other hand, arginine vasopressin (AVP), which is often responsible for hyponatremia, did not affect FGF23 production. Next, comprehensive and unbiased RNA-seq analysis of UMR-106 cells exposed to low vs. high [Na+] revealed several novel genes involved in cellular adaptation to altered tonicity. Additional analysis of cells with Crisp-Cas9 mediated NFAT5 deletion indicated that NFAT5 controls numerous genes associated with FGF23 synthesis, thereby confirming its role in [Na+]-mediated FGF23 regulation. In line with these in vitro observations, we found that human hyponatremia patients have higher FGF23 levels. Our results suggest that [Na+] is a critical regulator of FGF23 synthesis.

SIGNIFICANCE STATEMENT

Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that controls phosphate and vitamin D metabolism. Excess FGF23 is postulated to cause left ventricular hypertrophy, while FGF23 deficiency reduces life span and mimics age-related diseases in mice. FGF23 is also a potential biomarker for chronic kidney disease and cardiovascular disorders, but its role in disease progression is unclear. Therefore, it is important to explore the regulation of FGF23 production, which is incompletely understood. Our paper identifies extracellular-sodium-NFAT5 signaling as a key regulator of FGF23 formation.
Study on Vibrational Behavior of Cytoskeletons Modeled by Cylindrical Tensegrity Structure
Authors: Nouchi Eiji , Oka Tomoteru , Kataoka Noriyuki , Kawano Yoshihisa , Gan Buntara Sthenly
Published: June 2023

The dynamic mechanism of a cellular cytoskeleton is essential for the role of the cell, and its accurate characterization has been a long-standing problem for cell scientists. A cytoskeleton’s vibrations are highly influenced by interactions of filamentous proteins mediated by axial vibration of the stiff microtubules (compressive member) and lateral vibration of F-actin (tensile member). Among various structures in a cell, the cytoplasmic contractile bundles, lamellipodia, and filipodia cells can be modeled by a symmetrical cylinder-shaped self-equilibrium tensegrity structure with different radii at the top and bottom of the cylinder. The truncated conelike cylinder model is made to be small in height compared to both radii. This study investigates the tensegrity self-vibrational behavior of the cellular cytoskeleton to calculate its natural frequencies, composed of the individual vibration of microtubules and F-actins from measured data. The spectral element method is adopted based on the Wittrick–Williams procedure to solve the vibrational behaviors of the cellular cytoskeleton. Various n-polygon cylindrical truncated cone-shaped tensegrity structures to mimic the cellular cytoskeletons are presented to demonstrate the robustness of the present study.
Improving accuracy and precision of heritability estimation in twin studies: Reassessing the measurement error assumption
Authors: Chen Gang , Moraczewski Dustin , Taylor Paul A.
Published: June 2023

In this study, we demonstrate the need for improvement in the conventional ACE model used for estimating heritability when applied to trait data with measurement errors. The critical issue revolves around an assumption concerning measurement errors in twin studies. In cases where traits are measured using samples, data is aggregated during preprocessing, with only a centrality measure (e.g., mean) being used for modeling. Additionally, measurement errors resulting from sampling are assumed to be part of the nonshared environment and are thus overlooked in heritability estimation. Consequently, the presence of intra-individual variability remains concealed. Moreover, recommended sample sizes (e.g., 600 twin pairs) are typically based on the assumption of no measurement errors.

We argue that measurement errors in the form of intra-individual variability are an intrinsic limitation of finite sampling and should not be considered as part of the nonshared environment. Previous studies have shown that the intra-individual variability of psychometric effects is significantly larger than the inter-individual counterpart. Here, to demonstrate the appropriateness and advantages of our hierarchical modeling approach in heritability estimation, we utilize simulations as well as a real dataset from the ABCD (Adolescent Brain Cognitive Development) study. Moreover, we showcase the following analytical insights for data containing non-negligible measurement errors:

The conventional ACE model may underestimate heritability.

A hierarchical model provides a more accurate assessment of heritability.

Large samples, exceeding 100 observations or thousands of twins, may be necessary to reduce ambiguity. In summary, our study sheds light on the impact of measurement errors on heritability estimation and proposes a hierarchical model as a more accurate alternative. These findings have important implications for understanding individual differences and for the design and analysis of twin studies.
Intrarenal myeloid subsets associated with kidney injury are comparable in mice and patients with lupus nephritis
Authors: Hoover Paul J. , Lieb David J. , Kang Joyce , Li Stephen , Peters Michael , Raparia Chirag , Arazi Arnon , Eisenhaure Thomas , Gurajala Saisram S. , Xiao Qian , Mishra Rakesh , Spurrell Max , Menon Rajasree , Kretzler Matthias , Chen Jonathan , Nieman Linda , Sonny Abraham , Demeke Dawit , Hodgin Jeffrey , Guthridge Joel , Fava Andrea , Clancy Robert , Putterman Chaim , Izmirly Peter , Belmont H. Michael , Kalunian Kenneth , Kamen Diane , Wofsy David , Buyon Jill , James Judith A. , Petri Michelle , Diamond Betty , Raychaudhuri Soumya ,   The Kidney Precision Medicine Project,   The Accelerating Medicines Partnership: RA/SLE network, Hacohen Nir , Davidson Anne ,   Co-senior
Published: June 2023

Resident macrophages and infiltrating monocytes in kidneys of patients with lupus nephritis are altered both in frequency and function relative to their counterparts in healthy kidneys. The extent to which mouse models might be useful in developing approaches to target these cells for treating lupus nephritis is poorly understood. Here, we studied four common lupus mouse models that share clinical, serologic, and histopathologic kidney changes with humans. Using single-cell profiling and multiplex spatial imaging to analyze the intrarenal myeloid compartment with the onset of clinical disease in these models, we identified monocyte and macrophage subsets that expand or contract in kidneys with clinical nephritis. A unique subset of classical monocytes expanded with the onset of disease and expressed genes such asCD9, Spp1, Ctsd, Cd63, Apoe,andTrem2that were previously shown to be induced by tissue injury and play a role in inflammation, lipid metabolism and tissue repair in other organs. Resident macrophages transitioned from a pro-inflammatory to a similar injury-associated state with onset of disease. To test whether these findings in mouse models were also observed in humans, we re-analyzed monocytes and macrophages in a single-cell RNAseq dataset of kidney biopsies from 155 patients with lupus nephritis and 30 healthy donors, collected by the NIH AMP RA/SLE consortium. Human monocytes and macrophages showed conserved changes in gene expression programs associated with lupus nephritis disease indices, and localized to similar kidney microenvironments as in mice. By identifying myeloid subsets and disease-associated alterations in biological processes that are conserved across species, we provide a strong rationale for functional studies of these cells and pathways in mice to uncover mechanisms and find targets relevant to human lupus nephritis.

One sentence summary

This study characterizes intrarenal myeloid cells from four lupus mouse models and 155 patients with lupus nephritis using single-cell RNA-seq and imaging, and identifies novel infiltrating and resident myeloid subsets that are conserved between mouse and human lupus nephritis, thus providing a map and strong rationale for functional studies in mice with relevance to human disease.
Manipulation of encapsulated artificial phospholipid membranes using sub-micellar lysolipid concentrations
Authors: Dimitriou Pantelitsa , Li Jin , Jamieson William D. , Schneider Johannes J. , Castell Oliver K. , Barrow David A.
Published: June 2023

Droplet Interface Bilayers (DIBs) constitute a commonly used model of artificial membranes for molecular biology studies with applications in synthetic biology research. However, these model membranes have limited accessibility due to their requirement to be surrounded by an oil environment. Here, we demonstrate in-situ bilayer manipulation of submillimeter, free-standing, encapsulated droplet interface bilayers (eDIBs) in hydrogel capsules formed using dual-material, 3D-printed microfluidic devices. These microfluidic devices required no post-fabrication assembly, nor surface treatment to achieve the high-order emulsification, required for the formation of robust eDIBs. The eDIB capsules were exposed to various concentrations of lysophosphatidylcholine (LPC), in order to investigate the interaction of lysolipids with three-dimensional, encapsulated droplet bilayer networks. Micellar LPC concentrations trigger the bursting of the eDIB droplets, while at concentrations below the critical micelle concentration (CMC), the encapsulated aqueous inner droplet networks endure structural changes, precisely affecting the DIB contact angles and bilayer area. Manipulation of these enclosed, 3D-orchestrated membrane mimics facilitates the exploration of readily accessible compartmentalized artificial cellular machinery. Collectively, the multi-compartmentalized capsules and the lysolipid-mediated membrane modulation, introduce a chemical approach to control the properties and mechanics of artificial cellular membranes, toward responsive soft material developments.
A mitochondrial surveillance mechanism activated bySRSF2mutations in hematologic malignancies
Authors: Liu Xiaolei , Devadiga Sudhish A. , Stanley Robert F. , Morrow Ryan , Janssen Kevin , Quesnel-Vallières Mathieu , Pomp Oz , Moverley Adam A. , Li Chenchen , Skuli Nicolas , Carroll Martin P. , Huang Jian , Wallace Douglas C. , Lynch Kristen W. , Abdel-Wahab Omar , Klein Peter S.
Published: June 2023

Splicing factor mutations are common in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but how they alter cellular functions is unclear. We show that the pathogenicSRSF2P95H/+mutation disrupts the splicing of mitochondrial mRNAs, impairs mitochondrial complex I function, and robustly increases mitophagy. We also identified a mitochondrial surveillance mechanism by which mitochondrial dysfunction modifies splicing of the mitophagy activatorPINK1to remove a poison intron, increasing the stability and abundance ofPINK1mRNA and protein.SRSF2P95H-induced mitochondrial dysfunction increasedPINK1expression through this mechanism, which is essential for survival ofSRSF2P95H/+cells. Inhibition of splicing with a glycogen synthase kinase 3 inhibitor promoted retention of the poison intron, impairing mitophagy and activating apoptosis inSRSF2P95H/+cells. These data reveal a homeostatic mechanism for sensing mitochondrial stress throughPINK1splicing and identify increased mitophagy as a disease marker and a therapeutic vulnerability inSRSF2P95Hmutant MDS and AML.
IRF8 configures enhancer landscape in postnatal microglia and directs microglia specific transcriptional programs
Authors: Saeki Keita , Pan Richard , Lee Eunju , Kurotaki Daisuke , Ozato Keiko
Published: June 2023

Microglia are innate immune cells in the brain. Transcription factor IRF8 is highly expressed in microglia. However, its role in postnatal microglia development is unknown. We demonstrate that IRF8 binds stepwise to enhancer regions of postnatal microglia along with Sall1 and PU.1, reaching a maximum after day 14. IRF8 binding correlated with a stepwise increase in chromatin accessibility, which preceded the initiation of microglia-specific transcriptome. Constitutive and postnatalIrf8deletion led to a loss of microglia identity and gain of disease-associated microglia-like genes. Combined analysis of scRNA-seq and scATAC-seq revealed a correlation between chromatin accessibility and transcriptome at a single-cell level. IRF8 was also required for microglia-specific DNA methylation patterns. Lastly, in the 5xFAD model, constitutive and postnatalIrf8deletion reduced the interaction of microglia with Aβ plaques and the size of plaques, lessening neuronal loss. Together, IRF8 sets the epigenetic landscape, which is required for postnatal microglia gene expression.
A comparison analysis on forward error correction technology: a future perspective for GNSS
Authors: Süzer Ahmet Esat , Oktal Hakan
Published: June 2023

Purpose

The main aim of this study is to elaborately examine the error correction technology for global navigation satellite system (GNSS) navigation messages and to draw a conceptual decision support framework related to the modernization of the GNSS and other systems.

Design/methodology/approach

The extensive simulation model developed in Matrix Laboratory (MATLAB) is used to evaluate the performance of forward error correction (FEC) codes such as Hamming, Bose–Chaudhuri–Hocquenghem, convolutional, turbo, low-density parity check (LDPC) and polar codes under different levels of noise.

Findings

The performance and robustness of the aforementioned algorithms are compared based on the bit length, complexity and execution time of the GNSS navigation message. In terms of bit error rate, LDPC coding exhibits more ability in the robustness of the navigation message, while polar code gives better results according to the execution time.

Practical implications

In view of future new GNSS signals and message design, the findings of this paper may provide significant insight into navigation message modernization and design as an important part of GNSS modernization.

Originality/value

To the best of the authors’ knowledge, this is the first study that conducts a direct comparison of various FEC algorithms on GNSS navigation message performance against noise, taking into consideration turbo and newly developed polar codes.
Design, manufacturing and testing of pull-out and shear-out insert allowable for sandwich applications
Authors: Pelin Cristina-Elisabeta , Axenie Alexandra-Raluca , Gaz Adrian , Pelin George , Stefan Adriana , Moisei Cristian , Arnau Cubillo Albert
Published: June 2023

Purpose

This paper aims to present the procedures necessary to determine the insert allowable for a composite sandwich, considering that the inserts were the most commonly used means to install equipment on the composite structure of Clean Sky 2 (CS2)-RACER compound helicopter.

Design/methodology/approach

The installation of the equipment inside of the airframe shall comply with the certification regulations, especially in relation to the inertial factors. Establishing of the needed number of inserts to fix the equipment is directly linked to the allowable coming from coupon tests. The materials and test procedures to which they were subjected are part of the process qualification used in the development of the CS2-RACER Main Fuselage. The samples were tested in two different static mechanical loadings, consisting of pull-out insert and shear-out insert tests. The mechanical behaviour and failure mechanism of the materials were evaluated using optical and scanning electron microscopy.

Findings

The insert installation on the sandwich structure influences the behaviour and mechanical properties during pull-out and shear-out testing.

Research limitations/implications

The limited data available in standardized documents related to insert testing makes it difficult to compare results with certified baseline values.

Practical implications

To reduce the effort of selecting the optimized insert system, specific parameters are included in analytical pre-sizing, i.e. type of loads, geometry, materials, failure modes, special conditions such as manufacturing and testing.

Originality/value

The results of the study presenting the design, manufacturing and mechanical testing of pull-out and shear-out inserts used in composite materials sandwich-type coupons provide valuable information regarding the insert allowable determination.
Blockchain-enabled supply chain management: integrated impact on firm performance and robustness capabilities
Authors: Aslam Javed , Saleem Aqeela , Kim Yun Bae
Published: June 2023

Purpose

This study aims to proposed that blockchain helps the organization improve supply chain (SC) performance by improving integration, agility and security through real-time information sharing, end-to-end visibility, transparency, data management, immutability, irrevocable information and cyber-security platforms.

Design/methodology/approach

This study has made an initial effort toward proposing a framework that shows the problems and challenges for the O&G SC under its segments (upstream, midstream and downstream) and provides the interlink among blockchain properties for SCM problems. SC managers were selected for survey questionnaires from the Pakistan O&G industries.

Findings

This study analyzes the impact of blockchain-enabled SC on firm performance with an understanding of the SC robustness capabilities as a mediator. The result revealed that the SC manager believes that the blockchain-enabled SC has a positive and significant on firm performance and robustness capabilities.

Research limitations/implications

Blockchain technology is reflected as high-tech to support the firm process, responses and methods. The technology helps eliminate bottlenecks, avoid uncertainties and improve decision-making, leading to improved SC functions. This study guides managers about the potential problems of existing SC and how blockchain solves SC problems more effectively.

Originality/value

The oil and gas (O&G) sectors are neglected by researchers, and there are limited studies on O&G supply chain management (SCM). Additionally, no empirical evidence suggests implementing blockchain for O&G as a solution for potential problems. Furthermore, present the roadmap to other industries those having complex SC networks for the implication of blockchain to improve the SC performance.
The composite approach as a hybrid approach to business process modeling: proposition and empirical evaluation
Authors: Antunes Pedro , A. Pino José , Nkhoma Mathews , Thuan Nguyen Hoang
Published: June 2023

Purpose

Business process modeling faces a difficult balance: on the one hand, organizations seek to enact, control and automate business processes through formal structures (procedures and rules). On the other hand, organizations also seek to embrace flexibility, change, innovation, value orientation, and dynamic capabilities, which require informal structures (unique user experiences). Addressing this difficulty, the authors propose the composite approach, which integrates formal and informal process structures. The composite approach adopts a socio-material conceptual lens, where both material and human agencies are supported.

Design/methodology/approach

The study follows a design science research methodology. An innovative artifact – the composite approach – is introduced. The composite approach is evaluated in an empirical experiment.

Findings

The experimental results show that the composite approach improves model understandability and situation understandability.

Research limitations/implications

This research explores the challenges and opportunities brought by adopting a socio-material conceptual lens to represent business processes.

Originality/value

The study contributes an innovative hybrid approach for modeling business processes, articulating coordination and contextual knowledge. The proposed approach can be used to improve model understandability and situation understandability. The study also extends the socio-material conceptual lens over process modeling with a theoretical framework integrating coordination and contextual knowledge.
Does enterprise social media use in the post-acceptance stage improve employee autonomy? An information processing perspective
Authors: Yin Pengzhen , Wang Wei , Wang Chuang , Liang Liang
Published: June 2023

Purpose

With the prevalence of enterprise social media (ESM), this study examines how the innovative and routine ESM use behaviors in the post-acceptance stage influence the quality and quantity dimensions of information processing (i.e. information equality and information overload), subsequently affecting employee autonomy grounded in the digital information management theoretical (DIMT) framework. This study further explores the moderating effects of communication visibility on the relationships between employee autonomy and each of the two information processing factors.

Design/methodology/approach

The proposed theoretical model was empirically validated using survey data of 266 knowledge workers that use ESM in a hybrid working context.

Findings

The results demonstrate that innovative and routine ESM use have different impacts on the quality and quantity dimensions of information processing, and information equality (quality dimension) improves employee autonomy as expected, but, surprisingly, information overloads (quantity dimension) as well. ESM communication visibility positively moderates the relationship between employee autonomy and each dimension of information processing.

Originality/value

Prior studies on ESM use widely focused on ESM's positive and negative outcomes and the mechanisms from the perspectives of employees' psychological and cognitive reactions. How ESM use behaviors in the post-acceptance stage empower employee autonomy and allow organizations to leverage the organizations' information technology (IT) investments remains unclear. Drawing on the information processing perspective, this study provides a novel angle to examine how to leverage IT values that stem from ESM use by considering the complementary roles of active and passive information processing.
What employees perceive as personal communication: results of a Q study on internal communication
Authors: Stehle Helena
Published: June 2023

Purpose

Engaging with stakeholders in “a personal, intimate way” (Men and Tsai, 2016, p. 932) or “includ[ing] the ‘personal touch’” (Kent and Taylor, 1998, p. 323) is often seen as desirable in internal communication management. While the importance of personal communication is undisputed from the perspectives of internal communication, its communicators, and from internal stakeholders, this is not true when it comes to the dimensions and characteristics that constitute an experience of communication as feeling personal. The present study aims to explore what makes communication personal from the employees' perspective.

Design/methodology/approach

The study used the Q methodology and Q method, thus focusing on an individual's subjective perspective. The Q methodology was implemented in the form of a Q-sort survey exploring the perceptions of 32 German employees (selected from a representative cross-section of 400 employees in Germany, using a balanced-block design to maximize heterogeneity).

Findings

The results show that while direct and dyadic communication is often perceived as personal, many other dimensions and characteristics are also considered “personal” in both the literature and based on stakeholder perceptions. The Q-sort survey revealed four perception types whose perceptions of communication as “personal” vary widely, with all these types rejecting non-human communicators.

Originality/value

This study contributes to the limited understanding of employees' perceptions of internal communication as “personal.” It shows how the Q methodology and Q method—a rarely used perspective—can complement existing theoretical and empirical research on internal communication. For internal communication management, the findings show that a “one-size-fits-all” approach must be questioned and that a communication team's involvement in personal communication can have negative consequences.
Monetary policy and inflation targeting under global uncertainty: a SVAR approach for Tunisia
Authors: Trabelsi Emna , Ben Khaled Asma
Published: June 2023

Purpose

The implementation of monetary policy by the central bank is an ongoing topic of discussion. This paper aims to explore monetary policy transmission shocks in times of uncertainty using the new World uncertainty index (WUI). The authors investigate the impact of crises, wars and pandemic shocks on selected macroeconomic variables.

Design/methodology/approach

The authors use unit root tests, structural vector autoregressive model and the Granger causality test according to Toda–Yamamoto with quarterly data over 1999–2022.

Findings

The results of this study show that in the short run, there is a unidirectional relationship between the money market rate and WUI, while the relationship between the latter and the money supply (M2) is bidirectional. The short-term effect runs from WUI to inflation. In the long run, the variance decomposition shows that global uncertainty explains around 12% of inflation pressures. The uncertainty caused by special events in the world creates positive shocks on inflation in Tunisia, which decreases the ability of the central bank to control inflation.

Research limitations/implications

The results have implications over necessary and urgent actions to be implemented for a progressive economic recovery but point to a necessary transition to an inflation-targeting regime.

Originality/value

Examining monetary policy under uncertainty is a recent phenomenon. The authors purposely use a novel WUI by Ahir et al. (2022) that is unexploited in literature.
Bank risk exposures and bank stability in Africa: the role of regulations in a non-linear model
Authors: Ofori-Sasu Daniel , Mekpor Benjamin , Adu-Darko Eunice , Sarpong-Kumankoma Emmanuel
Published: June 2023

Purpose

This paper aims to examine the interaction effect of regulations (monetary and macro-prudential) in explaining the possible non-linear effect of bank risk exposures (credit risk and insolvency risk) on banking stability in Africa.

Design/methodology/approach

The study uses a two-step system generalized method of moments (GMM) estimator for a data set of banks across 54 African countries over the period 2006–2020.

Findings

The authors find that the relationships between bank credit risk–bank stability and bank insolvency risk–bank stability are non-linear and characterized by the presence of optimal thresholds, which are 5.3456 for credit risk and 2.3643 for insolvency. Contrary to their positive effects below these optimal thresholds, credit risk and insolvency risk become negatively linked to bank stability in Africa. The authors find that macro-prudential action and monetary policy both have a positive and significant relationship with bank stability. The authors provide evidence to support that the marginal effect of excessive credit risk and insolvency risk on bank stability is reduced when interacted with monetary and macro-prudential regulations, and the impact is significant in strong institutional environment.

Research limitations/implications

Future research should extend data to include developing and emerging economies in the world. Also, policymakers, researchers and practitioners should consider different regulatory and institutional frameworks in explaining the relationship between the thresholds of bank risk exposures and bank stability in the world.

Practical implications

Regulatory authorities should have to deeply reform their financial systems, develop risk-based regulatory framework and effective supervision mechanism relating to appropriate techniques that maintain an optimal and desired level of bank risks and risk-taking behaviours required to ensure a stable banking system.

Originality/value

To the best of the authors’ knowledge, this is the first study to examine how different regulatory frameworks shape the non-linear impact of bank risk exposures on bank stability in Africa.
yogaErie: the growth decision
Authors: Warner Al , Harben Christopher
Published: June 2023

Research methodology

This case is based on an existing firm. The names have not been changed, and all data on the firm’s history and opportunities is accurate. Primary data is based on interviews with the owner of the firm. One of the authors is a client of the studio and friend of the owner. The case has been reviewed and approved by Jill Murphey, owner of yogaErie. The purpose of this paper is to introduce students to industry analysis, to entrepreneurial decisions and to issues with organizational growth and change.

Case overview/synopsis

Jill Murphey, owner of Yoga Erie, is considering whether to or how to expand her studio operations into adjacent communities. Her studio has been very successful since she opened in 2009: the studio has been named Erie’s Best for most of the years since then. Classes were filled and students were asking about the prospects of a satellite studio in other parts of the community. Information on the options Murphey was considering are presented as well as Murphey’s motivations in opening her own studio, and the opportunities as well as concerns she faced in the expansion decision.

Complexity academic level

This case was originally targeted toward graduate and undergraduate courses in Strategy because of the industry definition and diversification problems but can also be used in classes on Organizational Change or Entrepreneurship.