bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid Adaptation of Cellular Metabolic Rate to the MicroRNA Complements of Mammals and its Relevance to the Evolution of Endothermy
Authors: Fromm Bastian , Sorger Thomas
Published: November 2022

The metabolic efficiency of mammalian cells depends on attenuation of intrinsic translation noise by microRNAs. We devised a metric of cellular metabolic rate (cMR),rMR/Mexpoptimally fit to the number of microRNA families (miRNA.Fam), that is robust to variation in mass and sensitive to body temperature, consistent with the Heat Dissipation Limit Theory of Speakman and Król (2010)1. UsingmiRNA.Famas predictor, an Ornstein-Uhlenbeck process of stabilizing selection, with an adaptive shift at the divergence of Boreoeutheria, accounted for 95% of the variation incMRacross mammals. Branchwise rates of evolution ofcMR,miRNA.Famand body temperature concurrently increased 6- to 7-fold at the divergence of Boreoeutheria, independent of mass. CellularMRvariation across placental mammals was also predicted by the sum of model conserved microRNA-target interactions, revealing an unexpected degree of integration of the microRNA-target apparatus into the energy economy of the mammalian cell.
Why Does Synergistic Activation of WASP, but Not N-WASP, by Cdc42 and PIP2Require Cdc42 Prenylation?
Authors: Dey Souvik , Zhou Huan-Xiang
Published: November 2022

Human WASP and N-WASP are homologous proteins that require the binding of multiple regulators, including the acidic lipid PIP2and the small GTPase Cdc42, to relieve autoinhibition before they can stimulate the initiation of actin polymerization. Autoinhibition involves intramolecular binding of the C-terminal acidic and central motifs to an upstream basic region and GTPase binding domain. Little is known about how a single intrinsically disordered protein, WASP or N-WASP, binds multiple regulators to achieve full activation. Here we used molecular dynamics simulations to characterize the binding of WASP and N-WASP with PIP2and Cdc42. In the absence of Cdc42, both WASP and N-WASP strongly associate with PIP2-containing membranes, through their basic region and also possibly through a tail portion of the N-terminal WH1 domain. The basic region also participates in Cdc42 binding, especially for WASP; consequently Cdc42 binding significantly compromises the ability of the basic region in WASP, but not N-WASP, to bind PIP2. PIP2binding to the WASP basic region is restored only when Cdc42 is prenylated at the C-terminus and tethered to the membrane. This distinction in the activation of WASP and N-WASP may contribute to their different functional roles.
Identification of novel proteins regulating lipid droplet biogenesis by reverse genetics
Authors: Mamun Md. Abdulla Al , Reza M. Abu , Islam Md Sayeedul
Published: November 2022

Lipid droplets (LDs) are storage organelles for neutral lipids. Our knowledge about fungal LD biogenesis is limited to budding yeast. Moreover, the regulation of LD in multinucleated filamentous fungi with considerable metabolic activity is unknown. Here, 19 LD-associated proteins were identified inAspergillus oryzaeusing colocalization screening of a previously established Enhanced green fluorescent protein (EGFP) fusion proteins library. Following a functional screening, 12 candidates have been identified as lipid droplet regulating (LDR) proteins, the loss of which resulted in aberrant LD biogenesis. Four LDR proteins localize to LD via the putative amphipathic helices (AHs), as demonstrated with bioinformatics, targeted mutagenesis, and imaging. Further analysis revealed that LdrA with Opi1 domain is essential for cytoplasmic and nuclear LD biogenesis via this novel AH. Phylogenetic analysis demonstrated the pattern of their evolution, which was predominantly based-on gene duplication. Our study provides substantial molecular and evolutionary insights into LD biogenesis and creates a breakthrough in using reverse genetics for identifying LD-regulating proteins.
Measuring cell-to-cell expression variability in single-cell RNA-sequencing data: a comparative analysis and applications to B cell ageing
Authors: Zheng Huiwen , Vijg Jan , Fard Atefeh Taherian , Mar Jessica Cara
Published: November 2022

Background

Single-cell RNA-sequencing (scRNA-seq) technologies enable the capture of gene expression heterogeneity and consequently cell-to-cell variability at the cell type level. Although different methods have been proposed to quantify cell-to-cell variability, it is unclear what the optimal statistical approach is, especially in light of challenging data structures that are unique to scRNA-seq data like zero inflation.

Results

In this study, we conducted a systematic evaluation of cell-to-cell gene expression variability using 14 different variability metrics that are commonly applied to transcriptomic data. Performance was evaluated with respect to data-specific features like sparsity and sequencing platform, biological properties like gene length, and the ability to recapitulate true levels of variability based on simulation and known biological gene sets like ribosomal genes and stably expressed genes. scran had the strongest all-round performance, and this metric was then applied to investigate the changes in cell-to-cell variability that occur during ageing. Studying ageing showcases the value of cell-to-cell variability as it is a genetically-regulated program that is influenced by stochastic processes.scRNA-seq datasets from hematopoietic stem cells (HSCs) and B lymphocytes and other cell types from this differentiation lineage were used with scran to identify the genes with consistent patterns of variable and stable expression profiles during differentiation. Furthermore, to understand the regulatory relationship for genes that were differentially-variable in their expression between young and old mice, we constructed networks using transcription factors and their known targets for HSC and B lymphocyte cells. Comparisons of these networks identified a shared TFSfpi1that although was seen to increase in gene expression variability in old mice versus young in both cell types, the corresponding targets were distinct and their gene expression variability had different directions between cell types.

Conclusions

Through these analyses, we highlight the importance of capturing cell-to-cell gene expression variability in a complex biological process like differentiation and ageing, and emphasise the value and specificity of interpreting these findings at the level of individual cell types.
A novel TGF-β-responsive enhancer regulates SRC expression and epithelial–mesenchymal transition-associated cell migration
Authors: Noshita Soshi , Kubo Yuki , Kajiwara Kentaro , Okuzaki Daisuke , Nada Shigeyuki , Okada Masato
Published: November 2022

The non-receptor tyrosine kinase SRC is overexpressed and/or hyperactivated in various human cancers, and facilitates cancer progression by promoting invasion and metastasis. However, the mechanisms underlying SRC upregulation are poorly understood. In this study, we demonstrated that transforming growth factor-β (TGF-β) induces SRC expression at the transcriptional level by activating a novel intragenic SRC enhancer. In the human breast epithelial cell line MCF10A, TGF-β1 stimulation upregulated theSRC1Apromoter, resulting in increased SRC mRNA and protein levels. Chromatin immunoprecipitation (ChIP)-sequencing analysis revealed that SMAD complex is recruited to three enhancer regions ~15 kb upstream and downstream of theSRCpromoter, and one of them is capable of activating theSRCpromoter in response to TGF-β. In addition, JUN, which is a member of the activator protein (AP)-1 family, also localizes to the enhancer and regulates TGF-β-induced SRC expression. Furthermore, the total amount of active SRC also increased, coinciding with the TGF-β-induced SRC expression. In TGF-β-induced epithelial–mesenchymal transition (EMT), TGF-β-induced SRC upregulation plays a crucial role in EMT-associated cell migration by activating the SRC/focal adhesion kinase (FAK) circuit. Overall, these results suggest that TGF-β-induced SRC upregulation promotes cancer cell invasion and metastasis in a subset of human malignancies.
Exploring the role of learner characteristics in learners' learning environment preferences
Authors: Chaw Lee Yen , Tang Chun Meng
Published: November 2022

Purpose

This study intends to examine whether the reasons learners like or dislike a learning environment can help explain the differences in the characteristics of the learner and whether learner characteristics can influence a learner's preference for a learning environment.

Design/methodology/approach

This study adopted an exploratory sequential mixed methods research design. The study first conducted focus groups with university students to uncover their learner characteristics by examining the reasons they liked or disliked a learning environment. This was followed by a questionnaire survey to explore how these learner characteristics influenced learner inclination for a learning environment. The survey data were analysed using exploratory and confirmatory factor analysis (partial least squares structural equation modelling).

Findings

The findings showed that two types of learner characteristics, i.e. online learner characteristics and classroom learner characteristics, significantly affected learner inclination for a learning environment. Analyses also indicated that learner demographics had no major moderating effect between learner characteristics and learner inclination for a learning environment.

Practical implications

The findings can be useful for education institutions, learning designers and academics to design engaging learning activities to better support different learning needs.

Originality/value

This study makes a novel attempt to distinguish learner characteristics based on the reasons learners like or dislike a learning environment and establishes that individual learners' characteristics play a role in influencing their preference for a specific learning environment.
Trade protection and firm innovation in China
Authors: Huang Tao
Published: November 2022

Purpose

The author investigates the effect of trade protection on domestic firm innovation in China and explores the channel through which trade protection affects corporate innovation.

Design/methodology/approach

Using a sample of Chinese A-share manufacturing companies from 2003 to 2019, the author starts with a univariate analysis by examining the innovation output after trade protection for all samples. The author uses the natural logarithm of one plus the number of trade protection cases received by the industry to which the firm belongs in a particular year to proxy for trade protection.

Findings

The author finds that trade protection significantly encourages firms’ patent application, particularly substantive patents, which is stronger in non-state-owned enterprises. Moreover, the mitigation of financial constraint is plausible channel that allows trade protection to promote innovation.

Practical implications

For practitioners, they should seize the dividends of national policies. In the process of implementing trade protection, they should concentrate on improving their innovation level and enhancing their core competitiveness. When they are not subject to trade protection, they can also make profits and develop in the long run.

Social implications

For policy makers, in the early stage of industry development, trade protection can be used to ease the companies’ financing constraints and improve the companies’ profits, which will help them concentrate their efforts, promote innovation and further develop. However, in the mid-term development of the industry, policy makers should reduce trade protection. Through the entry of foreign capital, companies face increased competition, which can enhance the companies’ motivation for long-term development.

Originality/value

Overall, this paper sheds light on the real effects of trade protection and the determinants of innovation. First, the paper sheds light on the impact of international trade on firms’ innovation. Second, this study also contributes to the emerging literature on the effect of trade policy uncertainty on financial constraint. Third, the paper adds to the stream of literature on the drivers of innovation.
The role of openness and cultural intelligence in students' intention to study abroad
Authors: Butkovic Ana , Brkovic Irma , Buretic Ines
Published: November 2022

Purpose

Higher education performance is boosted through cross-border cooperation and increased transnational mobility of students. In addition, exchange students have better employability skills after staying abroad compared to the students' peers. A number of studies have investigated factors that determine whether a student studies abroad. In this study, the authors focused on the role of personality trait openness to experience and cultural intelligence (CI) in explaining Croatian students' experience with and/or intention to travel abroad for studying purposes.

Design/methodology/approach

The authors analyzed results from 482 students (M = 22.61, standard deviation (SD) = 2.24, 66% female), of whom 35% reported that they studied abroad or intended to study abroad. They filled in The Cultural Intelligence Scale and openness facets items from the International Personality Item Pool (IPIP-300) questionnaire.

Findings

The authors conducted a hierarchical binary logistic regression analysis and found that students who were younger, had higher adventurousness and higher motivational CI were more likely to study abroad. Results of the mediation analysis showed that the association between openness to experience facet adventurousness and intention to study abroad was partially mediated by the motivational aspect of CI.

Originality/value

This study contributes to the better understanding of complex interrelations between personality traits and CI in the context of higher education internationalization processes. This study offers unique insight into the mediating role CI has in the association between personality and mobility behavior.
Unfolding design and technology for superior sales growth under moderating effect of technological environment
Authors: Parkhi Shilpa , Karande Kiran , Barge Prashant , Belal H.M. , Foropon Cyril R.H.
Published: November 2022

Purpose

Firms use design capability across the globe to compete and increase sales, e.g. Apple. However, the payoff from design know-how has been overlooked thus far. Academic research lags in this space despite the intersection of sales, technology and design in practice. This paper provides researchers and managers with implications of the interplay between design capability and technological market conditions to enhance a firm's sales.

Design/methodology/approach

Firms' capability design, and sales impact have been studied in this paper across different technological market conditions. Primary technological conditions of the industry under which firms operate are captured, which are technological intensity (TI), technological competitive intensity (TCI) and technological maturity (TM). Their interplay has been studied using panel data analysis, examining fixed and random effects.

Findings

Design is an important, interesting and non-imitable capacity that yields positive firm execution results. It provides an urgent differentiator and improves deal development. This study found that all four hypotheses are generally supported. The main finding is that, provided underlying technology is good, design significantly improves sales, but design alone cannot substitute for poor technology.

Practical implications

The results of this study link the three technological environment conditions, namely, TI, TCI and TM with sales growth. The authors find that design can and does add to superior performance, provided technological excellence exists prior. But, in the absence of good technology, design alone will hinder performance.

Originality/value

This paper examines the effect of firm design capability on sales growth. The paper finds a positive moderating effect of TCI and TM but a negative moderating effect of TI. The researchers believe these aspects of the design have not been studied before.
Tertiary education for all and wage inequality: policy insights from quantile regression
Authors: Andini Corrado
Published: November 2022

Purpose

The aim is to assess how a policy of tertiary education for all affects the shape of the unconditional earnings distribution.

Design/methodology/approach

The paper discusses the quantile-regression literature looking at the link between education and wage inequality, also proving new evidence based on unconditional quantile regressions.

Findings

The findings support the idea that a policy of tertiary education for all increases the overall level of wage inequality.

Research limitations/implications

The research has implications for public policy and administration. Among the limitations, the paper does not deal with distributional aspects related to other outcomes (e.g. health outcomes) of the policy of interest.

Practical implications

The analysis highlights a series of potential government interventions aimed at reducing the wage-inequality externalities of the policy of interest.

Social implications

A policy of tertiary education for all, by itself, is not useful to fight wage inequality.

Originality/value

This paper belongs to the small group of studies using unconditional quantile regressions to study the link between education and wage inequality. It is the first study specifically looking at the distributional effects of a policy of tertiary education for all.
Analyzing the legal environment for public procurement as a demand-side innovation policy measure
Authors: Foss Maria Carolina , Bonacelli Maria Beatriz M.
Published: November 2022

Purpose

This paper aims to analyze Brazil’s legal and institutional arrangements for the design, implementation and accountability of public procurement for innovation (PPI) and to investigate how this apparatus has been adjusted, modified and even replaced to enable its use in innovation policies.

Design/methodology/approach

It is a descriptive analysis of the legal framework for PPI in Brazil supplemented with case reports of ongoing PPI contracts.

Findings

Despite the significant advances in the PPI legal framework in Brazil, this instrument’s implementation is still limited. A disconnection between PPI and innovation policy goals and legal-institutional constraints are reasonable answers to this problem.

Social implications

Law is closely related to the design, implementation and control of public policy tools. However, there is still a tine understanding of how the legal framework can corroborate or constrain new mechanisms to state purchase power, such as PPI.

Originality/value

Public procurement is the most crucial tool of demand-side policies for innovation, and it is implemented according to the legal framework in each country. This paper adds to the law and innovation research agenda, providing an overview of the Brazilian PPI legal framework and how it is going so far.
Managers’ strategies in handling the COVID-19 pandemic in Norwegian nursing homes and homecare services
Authors: Ree Eline , Wiig Siri , Seljemo Camilla , Wibe Torunn , Lyng Hilda Bø
Published: November 2022

Purpose

This study aims to explore nursing home and home care managers’ strategies in handling the COVID-19 pandemic.

Design/methodology/approach

This study has a qualitative design with semistructured individual interviews conducted digitally by videophone (Zoom). Eight managers from nursing homes and five managers from home care services located in a large urban municipality in eastern Norway participated. Systematic text condensation methodology was used for the analysis.

Findings

The managers used several strategies to handle challenges related to the COVID-19 pandemic, including being proactive and thinking ahead in terms of possible scenarios that might occur, continuously training of staff in new procedures and routines and systematic information sharing at all levels, as well as providing different ways of disseminating information for staff, service users and next-of-kins. To handle staffing challenges, managers used strategies such as hiring short-term staff that were temporary laid off from other industries and bringing in students.

Originality/value

The COVID-19 pandemic heavily affected health-care systems worldwide, which has led to many health-care studies. The situation in nursing homes and home care services, which were strongly impacted by the pandemic and in charge of a vulnerable group of people, has not yet received enough attention in research. This study, therefore, seeks to contribute to this research gap by investigating how managers in nursing homes and home care services used different strategies to handle the COVID-19 pandemic.
Time‐resolved single virus tracking and spectral imaging to understand HIV‐1 entry and fusion
Authors: Padilla‐Parra Sergi
Published: November 2022

Single Virus Tracking (SVT) is a key technique to understand how individual viral particles evolve during the infection cycle. In the case of the human immunodeficiency virus (HIV‐1), this technology, which can be employed using a simple and affordable wide‐field microscope, has proven to be very useful in the first steps of infection, such as the kinetics of the fusion reaction or the point of fusion within live cells. Here, we describe how SVT in combination with other spectral imaging approaches is a powerful technique to illuminate crucial mechanistic aspects of the HIV‐1 fusion reaction. We also stress the role of our laboratory in elucidating a few mechanistic aspects of retroviral fusion employing SVT such as: (i) the role of dynamin, (ii) how metabolism modulates membrane composition and cholesterol and its impact in fusion, (iii) the importance of envelope glycoprotein (Env) intra‐ and inter‐molecular dynamics for neutralization, or (iv) the time‐resolved fusion stoichiometry in three characteristic steps for the HIV‐1 prefusion step. These observations constitute a good testimony of the complexity of retroviral fusion and show the strength of SVT when applied to live cells and combined with quantitative spectral approaches. Finally, we propose several crucial remaining questions around HIV‐1 fusion and how the combined use of these technologies, always in live cells, will be able to shed light into the intricacies of arguably the most important step of the HIV‐1 infection cycle.
Unusual mitochondrial tRNA rearrangements in stingless bee Tetragonula pagdeni and phylogenetic analysis
Authors: Wang Cheng‐Ye , Yang Pan‐Li , Zhao Min , Xu Huan‐Li , Liu Li‐Ning , Feng Ying , Wang Shi‐Jie
Published: November 2022

Tetragonula pagdeni (Hymenoptera: Meliponini) is a widely distributed and economically important stingless bee. The taxonomic status and evolution of this species have not been fully understood. We sequenced the mitogenome of T. pagdeni and analyzed its characteristics including gene rearrangements in present work, which will provide help for better protection and utilization of this germplasm resource. The mitochondrial genome sequence was obtained by establishing library and high‐throughput sequencing. Using all protein coding sequences joined, the phylogenetic analysis demonstrated that T. pagdeni has the closest kinship with Lepidotrigona species, and then has a second closest kinship with the Melipona stingless bees. All the stingless bee species (Meliponini) analyzed formed a single clade, and among them the T. pagdeni mitogenome exhibited the highest gene rearrangement score, suggesting this species has an overactive evolutionary history. Especially, an unusual tRNA‐Gly translocation was observed in T. pagdeni mitogenome, which broke the super‐conserved atp8‐atp6‐cox3‐G block in Hymenoptera mitogenomes. The translocated tRNA‐Gly moved to a position next to the D‐loop control region, and whether this translocation has a functional effect to the widely distributed T. pagdeni need further exploration. The variations of gene positions in mitogenome could also provide useful information to clarify the phylogenetic relations in Meliponini.
Raynaud's phenomenon associated with calcitonin gene‐related peptide receptor antagonists case report
Authors: Bedrin Kate , Ailani Jessica , Dougherty Carrie
Published: November 2022

Background

Calcitonin gene‐related peptide (CGRP) is a potent vasodilator that regulates the cerebrovascular and peripheral circulation. A new class of migraine therapies decreases CGRP through various mechanisms. One unknown off‐target effect is the impact decreasing CGRP will have on the peripheral circulation. The following cases report new onset Raynaud's phenomenon (RP) following the use of CGRP receptor antagonists (−gepants) for both the acute and preventive treatment of migraine. These cases describe the development of RP in two individuals after using each of the currently available gepant medications. To our knowledge these are the first cases reported of RP associated with the use of gepants. RP has previously been reported in association with monoclonal antibodies to the CGRP ligand and CGRP receptor indicated in the prevention of migraine.

Case presentation

One case involved oral CGRP receptor antagonists for acute treatment inducing RP. In this case, rimegepant and ubrogepant used separately for different migraine attacks each led to RP in the digits. The other case involved oral CGRP receptor antagonist, atogepant, used as a preventive treatment and induced RP in the digits. This patient had a prior history of areolar tissue RP while breastfeeding, but never in her fingers. In both cases, the offending medications were discontinued, and the patients reported no further episodes of RP.

Conclusion

Two cases are reported of people with migraine with new onset digital RP while taking CGRP receptor antagonists (rimegepant, ubrogepant, atogepant) for acute and preventive treatment.
Investigating potential ferroptosis‐related differentially expressed genes of UVB‐induced skin photodamage
Authors: Deng Li , Li Yi , Wu Qian , Zeng QianWen , He Yuanmin , Chen AiJun
Published: November 2022

Objectives

Ultraviolet B (UVB) is one of the most dangerous insults for skin, which can cause skin sunburn, pigment disease, photoaging, and photocarcinogenesis. This study aimed to identify pathogenic genes related to ferroptosis in the skin of humans after UVB radiation.

Methods

The gene expression profiles (GSE41078, GSE54413) were downloaded from the Gene Expression Omnibus (GEO) database, and the ferroptosis‐related genes (FRGs) were downloaded from the Genecards database. To identify the differentially expressed genes (DEGs) and obtain differentially expressed FRGs by intersecting DEGs with FRGs. To identify the functional annotation and potential pathways by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Differentially expressed FRGs‐associated protein–protein interaction network (PPI) was performed by STRING database and Cytoscape software.

Results

A total of 628 co‐expressed DEGs of the two profiles (GSE41078 and GSE54413) were identified, including 371 upregulated and 257 downregulated DEGs. A total of 32 differentially expressed FRGs were identified. The results of GO analyses showed that, in the biological processes, UVB had a great influence on the response to oxidative stress; in the molecular functions, UVB had a great influence on antioxidant activity; in the cellular components, UVB had a great influence on endocytic vesicle lumen. The key pathways of differentially expressed FRGs were identified by KEGG analyses. The most significant 12 central node genes were identified by PPI network.

Conclusion

We identified differentially expressed FRGs candidate genes and pathways in UVB‐induced skin photodamage, which could contribute to the development of new therapeutic targets for skin photodamage.
Preferential binding effect of cocoa powder on fried donuts through the electrostatic coating method
Authors: Murid Misbah , Khan Muhammad Kashif Iqbal , Maan Abid Aslam , Asif Muhammad , Sablani Shyam S.
Published: November 2022

Donuts are the snack food which are coated with powdered seasonings to increase flavour and shelf life. In this regard, electrostatic coating is being developed for efficient coating method and to overcome uneven coating and dust production. During electrostatic coating, charged powder particles produce even coating on target surface. Electrostatic coating of cocoa powder was carried out at high voltage (0–20 kV) and the results were compared to manually coated fried donuts. Cocoa powder particles had irregular polygonal and polyhedral shapes with an average particle diameter (18.12 ± 0.91 μm). The values of adhesion, dust reduction and transfer efficiency were higher at 15 kV and lower values at 0 kV. Coated sample at 15 kV showed the lowest change in weight loss (05.99%) during the storage. Due to an even coating of cocoa powder at 15 kV, donuts exhibited pleasant taste, uniform and dark brown colour. While, shelf life of coated donuts at 15 kV lasts up to 29 days as compared to other samples. It can be concluded from the results that the electrostatic coating of donuts with cocoa powder was best at 15 kV with higher transfer efficiency, adhesion and consumer acceptability.
Exploration of the efficacy of anti‐immunoglobulin E monoclonal antibodies in the treatment of allergic asthma
Authors: Qian Xue‐Jiao , Hu Xiao‐Tian , Jiang Ping
Published: November 2022

The present study aims to evaluate the efficacy of an anti‐immunoglobulin E monoclonal antibody (omalizumab) in the treatment of allergic asthma (AS). A total of 34 patients with moderate‐to‐severe bronchial asthma admitted to the Respiratory Department of Tianjin First Central Hospital between September 2019 and September 2021 were enrolled in this study. The patients were treated with omalizumab in addition to conventional inhaled corticosteroids + long‐acting β2 agonist treatment. The therapeutic effects before and after the addition of omalizumab were compared. The lung function indicators (ratio of the forced expiratory volume [FEV] in the first second to the forced vital capacity, FEV in the first second, forced expiratory flow [FEF] at 50% of vital capacity, FEF at 75% of vital capacity, and maximum mid‐expiratory flow), fractionated exhaled nitric oxide values, asthma control test scores, rhinoconjunctivitis quality of life questionnaire scores, and urticaria control test scores were significantly different after 4 months of the regular administration of omalizumab (p < 0.05) compared with before administration. The use of omalizumab had a significant efficacy in the treatment of patients with AS, and the effects were obvious in the subgroups of patients with a combination of AS and atopic dermatitis, chronic urticaria, and allergic rhinitis. These results indicate that the treatment is worthy of clinical promotion.
Aquatics for epileptic children
Authors: Pearn John
Published: November 2022

Epileptic children should have a lifestyle which is fulfilled, safe, and as near to normal as possible. There Is controversy about allowing epileptic children full access to aquatic play and sports. The Brisbane Drowning Study, and a study from Hawaii have shown that fatal drowning of epileptic children is rare if the child's epilepsy Is controlled, and the child is closely supervised by a custodian who knows the child has epilepsy. Adequate blood levels of anticonvulsant drugs may be a further requirement. The bath tub is a special risk for epileptic children, and certain safety procedures should be followed. Hyperventilation is of particular risk to epileptic children and its dangers should be emphasised.
An outline of the management and prognosis of Duchenne muscular dystrophy in Western Australia
Authors: Miller Geoffrey , Dunn Norma
Published: November 2022

The management of Duchenne muscular dystrophy is a difficult subject with various approaches taken by different centres throughout the world. In a centre for handicapped children in Western Australia a centre‐based programme of active management has been practised by a multidisciplinary team over the past twenty years (1961‐1981). To analyse its efficacy the records of 46 boys were examined for length of assisted ambulation, and the ages at which the onset of scoliosis and death occurred. Longevity and assisted ambulation is greater than generally reported and the attitude of boys in their twenties who have experienced the programme is favourabie. its success is dependent on ali the staff invoived providing motivation, counseliing and anticipatory guidance.
Real‐world assessment of SmartExam, a novel FibroScan computational method: A retrospective single‐center cohort study
Authors: Nogami Asako , Iwaki Michihiro , Kobayashi Takashi , Honda Yasushi , Ogawa Yuji , Imajo Kento , Higurashi Takuma , Hosono Kunihiro , Kirikoshi Hiroyuki , Saito Satoru , Nakajima Atsushi , Yoneda Masato
Published: November 2022

Background and Aim

SmartExam is a novel computational method compatible with FibroScan that uses a software called SmartDepth and continuous controlled attenuation parameter measurements to evaluate liver fibrosis and steatosis. This retrospective study compared the diagnostic accuracy of conventional and SmartExam‐equipped FibroScan for liver stiffness measurement (LSM).

Methods

The liver stiffness and the associated controlled attenuation parameters of 167 patients were measured using conventional and SmartExam‐Equipped FibroScan as well as reference methods like magnetic resonance elastography (MRE) and magnetic resonance imaging‐based proton density fat fraction (MRI‐PDFF) measurements to assess its diagnostic performance. M or XL probes were selected based on the probe‐to‐liver capsule distance for all FibroScan examinations.

Results

The liver stiffness and controlled attenuation parameter (CAP) correlation coefficients calculated from conventional and SmartExam‐equipped FibroScan were 0.97 and 0.82, respectively. Using MRE/MRI‐PDFF as a reference and the DeLong test for analysis, LSM and the area under the receiver operating characteristic curve for CAP measured by conventional and SmartExam‐equipped FibroScan showed no significant difference. However, the SmartExam‐equipped FibroScan measurement (33.6 s) took 1.4 times longer than conventional FibroScan (23.2 s).

Conclusions

SmartExam has a high diagnostic performance comparable with that of conventional FibroScan. Because the results of the conventional and SmartExam‐equipped FibroScan were strongly correlated, it can be considered useful for assessing the fibrosis stage and steatosis grade of the liver in clinical practice, with less variability but little longer measurement time compared with the conventional FibroScan.
Characterization of huntingtin interactomes and their dynamic responses in living cells by proximity proteomics
Authors: Xu Hongyuan , Bensalel Johanna , Raju Sunil , Capobianco Enrico , Lu Michael L. , Wei Jianning
Published: November 2022

Huntingtin (Htt) is a large protein without clearly defined molecular functions. Mutation in this protein causes Huntington's disease (HD), a fatal inherited neurodegenerative disorder. Identification of Htt‐interacting proteins by the traditional approaches including yeast two‐hybrid systems and affinity purifications has greatly facilitated the understanding of Htt function. However, these methods eliminated the intracellular spatial information of the Htt interactome during sample preparations. Moreover, the temporal changes of the Htt interactome in response to acute cellular stresses cannot be easily resolved with these approaches. Ascorbate peroxidase (APEX2)‐based proximity labeling has been used to spatiotemporally investigate protein–protein interactions in living cells. In this study, we generated stable human SH‐SY5Y cell lines expressing full‐length Htt23Q and Htt145Q with N‐terminus tagged Flag‐APEX2 to quantitatively map the spatiotemporal changes of Htt interactome to a mild acute proteotoxic stress. Our data revealed that normal and mutant Htt (muHtt) are associated with distinct intracellular microenvironments. Specifically, mutant Htt is preferentially associated with intermediate filaments and myosin complexes. Furthermore, the dynamic changes of Htt interactomes in response to stress are different between normal and mutant Htt. Vimentin is identified as one of the most significant proteins that preferentially interacts with muHtt in situ. Further functional studies demonstrated that mutant Htt affects the vimentin's function of regulating proteostasis in healthy and HD human neural stem cells. Taken together, our data offer important insights into the molecular functions of normal and mutant Htt by providing a list of Htt‐interacting proteins in their natural cellular context for further studies in different HD models.

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Emergency Department‐Attended Injuries Resulting from School‐Based Violence in Baltimore Adolescents, 2019‐2020
Authors: Walter Creason , Miller Mattea , Jones Vanya , Ryan Leticia Manning
Published: November 2022

BACKGROUND

Our objective is to describe violence‐related injuries to early adolescents that occurred at school, resulting in emergency department (ED) evaluation.

METHODS

This retrospective cohort study at an urban academic pediatric ED in Baltimore, MD, identified patients 10‐15 years old who presented with an injury from intentional, interpersonal violence that occurred at school between January 2019‐December 2020. Descriptive statistics were used to summarize patient and event characteristics.

RESULTS

Of 819 youth 10‐15 years of age evaluated for a violence‐related injury, school was the location in 115 cases (14.0%). All events occurred prior to the statewide stay at home order (March 30, 2020). School‐injured youth had a mean age of 12.7 ± 1.7 years and were predominantly male (64.3%). Of the 115 cases, 75 (65.2%) involved an altercation with a peer, 26 (22.6%) involved a teacher or school staff, 6 (5.2%) involved a family member, 1 (0.9%) involved police, 6 (5.2%) involved an unknown party, and 1 (0.9%) involved an unrelated but known adult. All injured youth were discharged from the ED.

CONCLUSIONS

School‐based violence is a well‐recognized cause of traumatic injuries to adolescents and may involve peers, teachers, or school staff.
Disentangling the genetic consequences of demographic change
Authors: Kreiner Julia M. , Booker Tom R.
Published: November 2022

Quantifying the impact of human activity on the capacity of populations to persist is paramount to conservation biology, as numerous species and populations have already been driven to or beyond the brink of extinction. Those populations that persist are often a sobering example of the evolutionary power of human‐disturbance, such as the loss of tusks in African elephants resulting from ivory harvesting (Campbell‐Staton et al., 2021) and rapid life‐history evolution in northern Atlantic cod in response to fisheries (Olsen et al., 2004). These evolutionary responses reflect a delicate interplay between demographic and selective processes (e.g., evolutionary rescue: Bell & Gonzalez, 2009; Gomulkiewicz & Holt, 1995), both of which can modify genetic variation for fitness. While quantifying fitness remains a difficult challenge, generalizable insights into the evolutionary consequences of population collapse can be provided in systems with independent demographic shifts in response to human activity. Unfortunately, such was the case for sea otter populations across its range in the 18th and 19th centuries, where the fur‐trade had catastrophic, range‐wide effects on sea otter (Enhydra lutris) populations. In a From the Cover article in this issue of Molecular Ecology, Beichman et al. (2022) combine a population genomic spatiotemporal data set and theoretical simulations not only to quantify past demographic change in response to sea otter exploitation, but also to understand the consequences of population collapse on species persistence.
Activated fibroblasts induce immune escape of TSCC through CCL25/AKT pathway
Authors: Li Yiting , Lin Ken , Ren Xiaobin , Xu Jianguo , Yuan Haiming , Bian Li , He Yongwen
Published: November 2022

Objectives

Accumulating evidence suggests that activated fibroblasts are the key cells in the T‐cell response to tumor immunosuppression. We attempted to investigate the effect of activated fibroblasts on PD‐L1 expression and the related immune escape mechanism in tongue squamous cell carcinoma.

Methods

Western blotting, qPCR, and other techniques were used to study the expression of PD‐L1 in tongue squamous cell carcinoma cells and the nude mouse model of transplanted tumors in vivo; clinical tissue samples were verified. In addition, we established a direct coculture model of T cells and tongue squamous cell carcinoma cells explore the mechanisms of immune escape.

Results

We found that PDGF‐BB induces fibroblast activation by facilitating the oversecretion of chemokine CCL25. Further analysis showed that CCL25 derived from activated fibroblasts activated the Akt signaling pathway to promote PD‐L1 expression. The activated fibroblasts inhibited T‐cell IFN‐γ secretion through the CCL25/Akt/PD‐L1 pathway, which indirectly inhibited T‐cell proliferation.

Conclusion

Activated fibroblasts can induce the high expression of PD‐L1 in the oral and tongue squamous cell carcinoma cell line Cal‐27 via the CCL25/CCR9/p‐Akt axis, to significantly inhibit the proliferation and IFN‐γ secretion of T cells and promote the immune escape of tongue squamous cell carcinoma cells.
Submergence tolerance in immature stages of the stalk‐eyed fly Sphyracephala detrahens (Diptera: Diopsidae)
Authors: Kudo Ayumi
Published: November 2022

Sphyracephala detrahens (Walker, 1860) (Diptera: Diopsidae) inhabits the riparian zones of streams and rivers. Because of the limited dispersal ability of S. detrahens during egg, larval, and pupal stages, immature individuals are at risk of being submerged by floodwater after heavy rain. In this study, I evaluated the submergence tolerances of immatures of S. detrahens by comparing them to immatures of Drosophila melanogaster, which also feed on rotten fruits but are not restricted to the riparian zone. The results showed that S. detrahens eggs were susceptible to desiccation, but more than 80% of eggs hatched after full submergence. Later instar larvae were more resistant to full submergence than earlier instar larvae. The duration of submergence causing 50% pupation (PD50) in the first, second, and third‐instar larvae of S. detrahens were 15.88, 58.46, and 91.74 h, respectively. The PD50 of the third‐instar larvae of D. melanogaster was 20.01 h. Third‐instar S. detrahens larvae continued to develop in water for a longer duration than D. melanogaster larvae of the same instar. In the pupal stages, late pupae tended to remain afloat longer than early pupae. The duration of submergence causing 50% emergence (ED50) of adults from early and late pupae were 40.70 and 104.74 h, respectively. In the larval and pupal stages, individuals in the later developmental phases tended to be more tolerant to full submergence. The submergence tolerance of the immature stages of S. detrahens may reflect adaptation to an environment with fluctuating water levels.
Efficient Photoreactivation of Solar UV‐InjuredMetarhizium robertsii by Rad1 and Rad10 Linked to DNA Photorepair‐Required Proteins
Authors: Zhang Yi‐Lu , Peng Han , Ying Sheng‐Hua , Feng Ming‐Guang
Published: November 2022

Nucleotide excision repair (NER) of ultraviolet (UV)‐induced DNA lesions known as cyclobutane pyrimidine dimer (CPD) and (6–4)‐pyrimidine‐pyrimidone (6‐4PP) photoproducts depends on the activities of multiple anti‐UV radiation (RAD) proteins in budding yeast. However, NER remains poorly known in filamentous fungi, whose DNA lesions are photorepaired by one or two photolyases, namely CPD‐specific Phr1 and/or 6‐4PP‐specific Phr2. Previously, the white collar proteins WC1 and WC2 were proven to regulate expressions of phr2 and phr1 and photorepair 6‐4PP and CDP DNA lesions, respectively, in Metarhizium robertsii, a filamentous entomopathogenic‐phytoendophytic fungus. We report here high activities of orthologous Rad1 and Rad10 in 5‐h photoreactivation of UVB‐injured or UVB‐inactivated conidia but a severely compromised capability of their reactivating those conidia via 24‐h dark incubation in M. robertsii. The null mutants of rad1 and rad10 were much more compromised in conidial UVB resistance and photoreactivation capability than the previous null mutants of phr1, phr2, wc1 and wc2. Multiple protein–protein (Rad1‐Rad10, Rad1‐WC2, Rad10‐Phr1, WC1‐Phr1/2 and WC2‐Phr1/2) interactions detected suggest direct/indirect links of Rad1 and Rad10 to Phr1/2 and WC1/2 and an importance of the links for their photoreactivation activities. Conclusively, Rad1 and Rad10 photoreactivate UVB‐impaired M. robertsii through their interactions with the DNA photorepair‐required proteins.
Intraspecific variation in morphology of spiny pollen grains along an altitudinal gradient in an insect‐pollinated shrub
Authors: Hasegawa T. M. , Itagaki T. , Sakai S.
Published: November 2022

Intraspecific variations in pollen morphological traits are poorly studied. Interspecific variations are often associated with pollination systems and pollinator types. Altitudinal environmental changes, which can influence local pollinator assemblages, provide opportunities to explore differentiation in pollen traits of a single species over short distances. The aim of this study is to examine intraspecific variations in pollen traits of an insect‐pollinated shrub, Weigela hortensis (Caprifoliaceae), along an altitudinal gradient.

Pollen spine phenotypes (length, number and density), pollen diameter, lipid mass (pollenkitt) around pollen grains, pollen production per flower and pollinator assemblages were compared at four sites at different altitudes.

Spine length and the spine length/diameter ratio of pollen grains were greater at higher altitudes but not correlated with flower or plant size. Spine number and density increased as flower size increased, and pollen lipid mass decreased as plant size increased. Bees were the predominant pollinators at low‐altitude sites whereas flies, specifically Oligoneura spp. (Acroceridae), increased in relative abundance with increasing altitude.

The results of this study suggest that the increase in spine length with altitude was the result of selection favouring longer spines at higher‐altitude sites and/or shorter spines at lower‐altitude sites. The altitudinal variation in selection pressure on spine length could reflect changes in local pollinator assemblages with altitude.
Behavioral consequences of intergroup sensitivity
Authors: Thürmer J. Lukas , McCrea Sean M.
Published: November 2022

Communication of criticism between groups is important to productive societal discourse, but may serve to inflame conflict. The defensive rejection of intergroup, relative to intragroup, criticism (intergroup sensitivity effect [ISE]) may contribute to such divides. The ISE has been observed in self‐report measures, but such measures are weak and biased predictors of actual (divisive) behavior. We review recent research demonstrating that the ISE does have costly behavioral consequences. We next consider the debate concerning whether the ISE reflects defense of a valued social identity or enforcement of a conversational norm. We therefore review recent evidence for an ISE among individuals lacking identification with the target of the criticism. Third, we examine how the ISE may affect a variety of behaviors relevant to societal divisions, including political reconciliation, environmental sustainability, and vaccination. Lastly, we outline future research that can clarify the underlying mechanisms of the ISE and promote conciliatory intergroup behavior.