bluuebunny/crossref_metadata_2025 huggingface dataset:
Fructose-2,6-bisphosphate restores DNA repair activity of PNKP and ameliorates neurodegenerative symptoms in Huntington’s disease
Authors: Chakraborty Anirban , Sreenivasmurthy Sravan Gopalkrishnashetty , Miller Wyatt , Huai Weihan , Biswas Tapan , Mandal Santi Mohan , Boscá Lisardo , Krishnan Balaji , Ghosh Gourisankar , Hazra Tapas
Published: October 2023

Huntington’s disease (HD) and spinocerebellar ataxia type 3 (SCA3) are the two most prevalent polyglutamine (polyQ) neurodegenerative diseases, caused by CAG (encoding glutamine) repeat expansion in the coding region of the huntingtin (HTT) and ataxin-3 (ATXN3) proteins, respectively. We have earlier reported that the activity, but not the protein level, of an essential DNA repair enzyme, polynucleotide kinase 3’-phosphatase (PNKP), is severely abrogated in both HD and SCA3 resulting in accumulation of double-strand breaks in patients’ brain genome. While investigating the mechanistic basis for the loss of PNKP activity and accumulation of DNA double-strand breaks leading to neuronal death, we observed that PNKP interacts with the nuclear isoform of 6-phosphofructo-2-kinase fructose-2,6-bisphosphatase 3 (PFKFB3). Depletion of PFKFB3 markedly abrogates PNKP activity without changing its protein level. Notably, the levels of both PFKFB3 and its product fructose-2,6 bisphosphate (F2,6BP), an allosteric modulator of glycolysis, are significantly lower in the nuclear extracts of post-mortem brain tissues of HD and SCA3 patients. Supplementation of F2,6BP restored PNKP activity in the nuclear extracts of patients’ brain. Moreover, intracellular delivery of F2,6BP restored both the activity of PNKP and the integrity of transcribed genome in neuronal cells derived from striatum of HD mouse. Importantly, supplementing F2,6BP rescued the HD phenotype in Drosophila, suggesting F2,6BP to serve in vivo as a cofactor for the proper functionality of PNKP and thereby, of brain health. Our results thus provide a compelling rationale for exploring the therapeutic use of F2,6BP and structurally related compounds for treating polyQ diseases.

Significance

To unravel the biological basis for the loss of PNKP activity in HD and SCA3, the two most prevalent polyglutamine neurodegenerative disorders, we analyzed PNKP interactome and found that the nuclear isoform of a glycolytic enzyme PFKFB3 associated with PNKP and other repair proteins forming a multiprotein complex. Surprisingly, we found that PFKFB3 and its biosynthetic product, F2,6BP are significantly low in the affected region of patients’ brain. Exogenous addition of F2,6BP restored PNKP activity in patients’ brain nuclear extract. Moreover, supplementing F2,6BP in HD cells and fruit flies restored genome integrity and rescued the disease symptoms. While there is no curative therapy for HD/SCA3, except symptom management, our discovery suggests that F2,6BP supplementation would be a promising therapeutic option.
A fully sequenced collection of homozygous EMS mutants for forward and reverse genetic screens inArabidopsis thaliana
Authors: Carrère Sébastien , Routaboul Jean-Marc , Savourat Pauline , Bellenot Caroline , López Hernán , Monnens Thomas Quiroz , Ricou Anthony , Camilleri Christine , Laufs Patrick , Mercier Raphael , Noël Laurent D.
Published: October 2023

Genetic screens are powerful tools for biological research and are one of the reasons for the success of the thale cressArabidopsis thalianaas a model species. Here, we describe the whole-genome sequencing of 871 Arabidopsis lines from the Homozygous EMS Mutant (HEM) collection as a novel resource for forward and reverse genetics. With an average 576 high-confidence mutations per HEM line, over three independent mutations altering protein sequence are found on average per gene in the collection. Pilot reverse genetics experiments on reproductive, developmental and physiological traits confirmed the efficacy of the tool for identifying both null and knockdown alleles. The possibility of conducting subtle repeated phenotyping of HEM lines and the immediate availability of the mutations will empower forward genetic approaches. The sequence resource is searchable with the ATHEM web interface (https://lipm-browsers.toulouse.inra.fr/pub/ATHEM/), and the biological material is distributed by the Versailles Arabidopsis Stock Center.
The human developing cerebral cortex is characterized by an increased de novo expression of lncRNAs in excitatory neurons
Authors: Morales-Vicente David A. , Tahira Ana C. , Woellner-Santos Daisy , Amaral Murilo S. , Berzoti-Coelho Maria G. , Verjovski-Almeida Sergio
Published: October 2023

Background

Outstanding human cognitive abilities are computed in the cerebral cortex, a mammalian-specific brain region and the place of massive biological innovation. Long noncoding RNAs (lncRNAs) have emerged as gene regulatory elements with higher evolutionary turnover than mRNAs. The many lncRNAs identified in neural tissues make them candidates for molecular sources of cerebral cortex evolution and disease. Here, we characterized the genomic and cellular shifts that occurred during the evolution of the lncRNA repertoire expressed in the developing cerebral cortex of humans and explored their role in the evolution of this brain region.

Results

Using systems biology approaches and comparative transcriptomics, we comprehensively annotated the cortical transcriptomes of humans, macaques, mice, and chickens and classified human cortical lncRNAs into evolutionary groups as a function of their predicted minimal ages. LncRNA evolutionary groups showed differences in expression levels, splicing efficiencies, transposable element contents, genomic distributions, and transcription factor binding to their promoters. Furthermore, older lncRNAs showed preferential expression in germinative zones, outer radial glial cells, and cortical inhibitory neurons. In comparison, younger lncRNAs showed preferential expression in cortical excitatory neurons, belonged to human-specific gene coexpression modules, and were dysregulated in autism spectrum disorder.

Conclusions

These results suggest a shift in the roles of cortical lncRNAs over evolution, highlighting the antique lncRNAs as a source of molecular evolution of conserved developmental programs; conversely, thede novoexpression of primate and human-specific lncRNAs are sources of molecular evolution and dysfunction of cortical excitatory neurons.
Dock1 acts cell-autonomously in Schwann cells to regulate the development, maintenance, and repair of peripheral myelin
Authors: Doan Ryan A. , Monk Kelly R.
Published: October 2023

Schwann cells, the myelinating glia of the peripheral nervous system (PNS), are critical for myelin development, maintenance, and repair. Rac1 is a known regulator of radial sorting, a key step in developmental myelination, and we previously showed in zebrafish that loss of Dock1, a Rac1-specific guanine nucleotide exchange factor, results in delayed peripheral myelination in development. We demonstrate here that Dock1 is necessary for myelin maintenance and remyelination after injury in adult zebrafish. Furthermore, it performs an evolutionary conserved role in mice, acting cell-autonomously in Schwann cells to regulate peripheral myelin development, maintenance, and repair. Additionally, manipulating Rac1 levels in larval zebrafish reveals thatdock1mutants are sensitized to inhibition of Rac1, suggesting an interaction between the two proteins during PNS development. We propose that the interplay between Dock1 and Rac1 signaling in Schwann cells is required to establish, maintain, and facilitate repair and remyelination within the peripheral nervous system.
Sequence-based machine learning reveals 3D genome differences between bonobos and chimpanzees
Authors: Brand Colin M. , Kuang Shuzhen , Gilbertson Erin N. , McArthur Evonne , Pollard Katherine S. , Webster Timothy H. , Capra John A.
Published: October 2023

Phenotypic divergence between closely related species, including bonobos and chimpanzees (genusPan), is largely driven by variation in gene regulation. The 3D structure of the genome mediates gene expression; however, genome folding differences inPanare not well understood. Here, we apply machine learning to predict genome-wide 3D genome contact maps from DNA sequence for 56 bonobos and chimpanzees, encompassing all five extant lineages. We use a pairwise approach to estimate 3D divergence between individuals from the resulting contact maps in 4,420 1 Mb genomic windows. While most pairs were similar,∼17% were predicted to be substantially divergent in genome folding. The most dissimilar maps were largely driven by single individuals with rare variants that pro-duce unique 3D genome folding in a region. We also identified 89 genomic windows where bonobo and chimpanzee contact maps substantially diverged, including several windows harboring genes associated with traits implicated inPanphenotypic divergence. We usedin silicomutagenesis to identify 51 3D-modifying variants in these bonobo-chimpanzee diver-gent windows, finding that 34 or 66.67% induce genome folding changes via CTCF binding motif disruption. Our results reveal 3D genome variation at the population-level and identify genomic regions where changes in 3D folding may contribute to phenotypic differences in our closest living relatives.
How osteons form: A quantitative hypothesis-testing analysis of cortical pore filling and wall asymmetry
Authors: Hegarty-Cremer Solene G. D. , Borggaard Xenia G. , Andreasen Christina M. , van der Eerden Bram C. J. , Simpson Matthew J. , Andersen Thomas L. , Buenzli Pascal R.
Published: October 2023

Osteon morphology provides valuable information about the interplay between different processes involved in bone remodelling. The correct quantitative interpretation of these morphological features is challenging due to the complexity of interactions between osteoblast behaviour, and the evolving geometry of cortical pores during pore closing. We present a combined experimental and mathematical modelling study to provide insights into bone formation mechanisms during cortical bone remodelling based on histological cross-sections of quiescent human osteons and hypothesis-testing analyses. We introduce wall thickness asymmetry as a measure of the local asymmetry of bone formation within an osteon and examine the frequency distribution of wall thickness asymmetry in cortical osteons from human iliac crest bone samples from women 16–78 years old. Our measurements show that most osteons possess some degree of asymmetry, and that the average degree of osteon asymmetry in cortical bone evolves with age. We then propose a comprehensive mathematical model of cortical pore filling that includes osteoblast secretory activity, osteoblast elimination, osteoblast embedment as osteocytes, and osteoblast crowding and redistribution along the bone surface. The mathematical model is first calibrated to symmetric osteon data, and then used to test three mechanisms of asymmetric wall formation against osteon data: (i) delays in the onset of infilling around the cement line; (ii) heterogeneous osteoblastogenesis around the bone perimeter; and (iii) heterogeneous osteoblast secretory rate around the bone perimeter. Our results suggest that wall thickness asymmetry due to off-centred Haversian pores within osteons, and that nonuniform lamellar thicknesses within osteons are important morphological features that can indicate the prevalence of specific asymmetry-generating mechanisms. This has significant implications for the study of disruptions of bone formation as it could indicate what biological bone formation processes may become disrupted with age or disease.
Overcoming antibody-resistant SARS-CoV-2 variants with bispecific antibodies constructed using non-neutralizing antibodies
Authors: Inoue Tetsuya , Yamamoto Yuichiro , Sato Kaoru , Nakamura Yuko , Shimizu Yoshimi , Ogawa Motohiko , Onodera Taishi , Takahashi Yoshimasa , Wakita Takaji , Kaneko Mika K. , Fukasawa Masayoshi , Kato Yukinari , Noguchi Kohji
Published: October 2023

A current challenge is the emergence of SARS-CoV-2 variants, such as BQ.1.1 and XBB.1.5, that can evade immune defenses, thereby limiting antibody drug effectiveness. Emergency-use antibody drugs, including the widely effective bebtelovimab, are losing their benefits. One potential approach to address this issue are bispecific antibodies which combine the targeting abilities of two antibodies with distinct epitopes. We engineered neutralizing bispecific antibodies in the IgG-scFv format from two initially non-neutralizing antibodies, CvMab-6 (which binds to the receptor-binding domain [RBD]) and CvMab-62 (targeting a spike protein S2 subunit epitope adjacent to the known anti-S2 antibody epitope). Furthermore, we created a bispecific antibody by incorporating the scFv of bebtelovimab with our anti-S2 antibody, demonstrating significant restoration of effectiveness against bebtelovimab-resistant BQ.1.1 variants. This study highlights the potential of neutralizing bispecific antibodies, which combine existing less effective anti-RBD antibodies with anti-S2 antibodies, to revive the effectiveness of antibody therapeutics compromised by immune-evading variants.
ER-to-Golgi traffickingviaa dynamic intermediatecis-Golgi tubular network in Arabidopsis
Authors: Fougère Louise , Grison Magali , Laquel Patricia , Montrazi Matheus , Cordelières Fabrice , Fernández-Monreal Mónica , Poujol Christel , Uemura Tomohiro , Nakano Akihiko , Ito Yoko , Boutté Yohann
Published: October 2023

Endoplasmic Reticulum (ER)-to-Golgi trafficking is a central process of the secretory system of eukaryotic cells that ensures proper spatiotemporal sorting of proteins and lipids1–5. However, the nature of the ER-Golgi Intermediate Compartments (ERGIC) and the molecular mechanisms mediating the transition between the ERGIC and the Golgi, as well as the universality of these processes amongst Eukaryotes, remain undiscovered. Here, we took advantage of the plant cell system in which the Golgi is highly dynamic and in close vicinity to the ER6–9. We discovered that the ERGIC is composed from at least two distinct subpopulations ofcis-Golgi. A subpopulation is a reticulated tubulo-vesicular network mostly independent from the Golgi, highly dynamic at the ER-Golgi interface and crossed by ER-induced release of luminal cargos at early stage. Another subpopulation is more stable, cisterna-like and mostly associated to the Golgi. Our results identified that the generation and dynamics of the ER-Golgi intermediate tubulo-vesicular network is regulated by the acyl-chain length of sphingolipids as well as the contacts it establishes with existing Golgi cisternae. Our study is a major twist in the understanding of the Golgi by identifying that the ERGIC in plants is a Golgi-independent highly dynamic tubular network from which arise more stable cisternae-like Golgi structures. This novel model presents a mechanism for early secretory trafficking adapted to respond to developmental and environmental stimuli, including susceptibility or resistance to diseases, autophagy or cell-reprograming.
SART1 localizes to spindle poles forming a SART1 cap and promotes spindle pole assembly
Authors: Yokoyama Hideki , Moreno-Andrés Daniel , Takizawa Kaoru , Chu Zhenzhen , Scheufen Anja , Funabashi Tsumugi , Ma Jian , Antonin Wolfram , Gruss Oliver J. , Haramoto Yoshikazu
Published: October 2023

The nuclear protein SART1 has been associated with pre-mRNA splicing but SART1 RNAi knockdown results also in defects in mitotic progression, centrosome biogenesis and chromosome cohesion. The mitotic roles of SART1 have not been characterized in detail and it remains unclear whether SART1 functions in mitosis directly or indirectly via pre-mRNA splicing. Here, we identify SART1 as a direct, mitosis-specific microtubule-associated protein. SART1 downregulation in human cells leads to spindle assembly defects with reduced microtubule dynamics, lack of end-on attachment, and checkpoint activation, while microtubule dynamics remain unaffected in interphase. SART1 uniquely localizes to the distal surface of mitotic centrosomes along the spindle axis, forming a previously not described structure we refer to as SART1 cap. Immunoprecipitation of SART1 consistently identifies centrosomal proteins as interaction partners. Immunostaining of these shows that SART1 downregulation does not affect centriole duplication and centrosome-accumulation of γ-tubulin but reduces the accumulation of selective pericentriolar material (PCM) proteins like Ninein. Depletion of SART1 from frog egg extracts disrupts spindle pole assembly around sperm nuclei and DNA-coated beads. Spindles formed around DNA-coated beads do not contain centrosomes but still recruits PCM proteins for spindle pole assembly. We finally show that the N-terminus of SART1 is its microtubule-binding region and essential for spindle assembly. Our data unravel a unique localization of SART1 and a novel function to recruit selective PCM proteins for spindle pole assembly in centrosomal and acentrosomal spindle assembly.
The spindle protein CKAP2 regulates microtubule dynamics and ensures faithful chromosome segregation
Authors: Paim Lia Mara Gomes , Lopez-Jauregui Azriel Abraham , McAlear Thomas S. , Bechstedt Susanne
Published: October 2023

Regulation of microtubule dynamics by microtubule-associated proteins (MAPs) is essential for mitotic spindle assembly and chromosome segregation. Altered microtubule dynamics, particularly increased microtubule growth rates, were found to be a contributing factor for the development of chromosomal instability, which potentiates tumorigenesis. The MAP XMAP215/CKAP5 is the only known microtubule growth factor, and whether other MAPs regulate microtubule growth in cells is unclear. Our recentin vitroreconstitution experiments have demonstrated that Cytoskeleton-Associated Protein 2 (CKAP2) increases microtubule nucleation and growth rates, and here we find that CKAP2 is also an essential microtubule growth factor in cells. By applying CRISPR-Cas9 knock-in and knock-out as well as microtubule plus-end tracking live cell imaging, we show that CKAP2 is a mitotic spindle protein that ensures faithful chromosome segregation by regulating microtubule growth. Live cell imaging of endogenously-labelled CKAP2 showed that it localizes to the spindle during mitosis, and rapidly shifts its localization to the chromatin upon mitotic exit before being degraded. Cells lacking CKAP2 display reduced microtubule growth rates and an increased proportion of chromosome segregation errors and aneuploidy that may be a result of an accumulation of kinetochore-microtubule mis-attachments. Microtubule growth rates and chromosome segregation fidelity can be rescued upon CKAP2 expression in knock-out cells, revealing a direct link between CKAP2 expression and microtubule dynamics. Our results unveil a role of CKAP2 in regulating microtubule growth in cells and provide a mechanistic explanation for the oncogenic potential of CKAP2 misregulation.

Significance statement

Cell division is accomplished by the assembly of a mitotic spindle composed of microtubules that segregate the chromosomes. Cells with altered microtubule dynamics frequently mis-segregate chromosomes and develop aneuploidy, which contributes to cancer development. However, how microtubule dynamics are regulated in cells is not entirely understood. Here, using CRISPR-Cas9 genome editing and live cell imaging, we find that the microtubule-associated protein CKAP2 tightly regulates microtubule growth and ensures the proper segregation of chromosomes. Cells lacking CKAP2 develop errors in chromosome segregation and aneuploidy due to a substantial decline in microtubule growth rates. The essential role of CKAP2 in the regulation of microtubule growth provides an explanation for the oncogenic potential of CKAP2 misregulation.

Classification

Biological Sciences – Cell Biology
A time-resolved Förster resonance energy transfer assay to investigate inhibitor binding to ABCG2
Authors: Mitchell-White James I. , Briggs Deborah A. , Mistry Sarah J. , Mbiwan Hannah A , Kellam Barrie , Holliday Nicholas D. , Briddon Stephen J. , Kerr Ian D.
Published: October 2023

The human ATP-binding cassette (ABC) transporter, ABCG2 is responsible for multidrug resistance in some tumours. Detailed knowledge of its activity is crucial for understanding drug transport and resistance in cancer, and has implications for wider pharmacokinetics. The binding of substrates and inhibitors is a key stage in the transport cycle of ABCG2. Here, we describe a novel binding assay using a high affinity fluorescent inhibitor based on Ko143 and time-resolved Förster resonance energy transfer (TR-FRET) to measure saturation binding to ABCG2. This binding is displaced by Ko143 and other known ABCG2 ligands, and is sensitive to the addition of AMP-PNP, a non-hydrolysable ATP analogue. This assay complements the arsenal of methods for determining drug:ABCG2 interactions and has the possibility of being adaptable for other multidrug pumps.

Highlights

ABCG2 is a multidrug pump which moves between states having low or high affinity for substrates and inhibitors

We introduce a time-resolved Förster resonance energy transfer assay to measure interaction of substrates and inhibitors to ABCG2

We confirm that NBD dimerization is associated with a switch from a high to a low affinity site for an ABCG2 inhibitor
Fine-Tuning and Remodelling of Pectins Play a Key Role in the Maintenance of Cell Adhesion
Authors: Grandjean Cyril , Voxeur Aline , Chabout Salem , Jobert François , Gutierrez Laurent , Pelloux Jérôme , Mouille Gregory , Bouton Sophie
Published: October 2023

Plant cell adhesion is essential for development and stress response, mediated by pectin-rich middle lamella deposition between cell walls. However, the precise control mechanism of cell adhesion remains unclear. Thequa2-1andesmd1-1mutants provide a better understanding of this process and suggest a signaling pathway triggering the loss and restoration of adhesion via cell wall modifications. This study attempts to characterize the potential regulatory role of endogenous oligogalacturonides (OGs) and pectin modifications in the control of cell adhesion in Arabidopsis.

From dark-grown hypocotyls, our extraction revealed seven distinct endogenous OGs with varying polymerization and modifications. Abundance variations of OGs were observed among wild type,qua2-1,esmd1-1, andqua2-1/esmd1-1mutants. The structure of homogalacturonans was analyzed by enzymatic fingerprint, in order to identify changes in esterification patterns. Expression analysis of pectin-modifying enzymes showed significant variations inPME,PMEI, andPAEgenes. Gene expressions correlate with homogalacturonans modifications and cell adhesion phenotypes.

This study enhances our understanding of a feedback loop between the endogenous OGs, homogalacturonans esterification fine tuning, and pectin remodeling enzymes expression in controlling cell adhesion.
Illuminating stomatal responses to red light: establishing the role ofCi-dependent vs - independent mechanisms
Authors: Taylor Georgia , Walter Julia , Kromdijk Johannes
Published: October 2023

The stomatal response to red light appears to link stomatal conductance (gs) with photosynthetic rates. Initially, it was suggested that changes in intercellular CO2(Ci) provide the main cue via aCi-dependent response. However, evidence forCi-independent mechanisms suggests an additional, more direct relationship with photosynthesis. While bothCi-dependent and -independent mechanisms clearly function in stomatal red-light responses, little is known regarding their relative contribution. The present study aimed to quantify the relative magnitude ofCi-dependent and - independent mechanisms on the stomatal red-light response, to characterise their interplay and to assess the putative link between plastoquinone (PQ) redox state andCi-independent stomatal responses. Red light response curves measured at a range ofCivalues for wild-typeArabidopsis thaliana(Col-0) and the CO2hyposensitive mutant,ca1ca4, allowed deconvolution ofCi-dependent and -independent pathways. Surprisingly, we observed that both mechanisms contribute equally to stomatal red-light responses, butCi-independent stomatal opening is suppressed at highCi. The present data are also consistent with the involvement of PQ redox in coordinatingCi-independent stomatal movements. Overall, it seems that whileCi-independent mechanisms are distinct from responses toCi,interplay between these two pathways is important to facilitate effective coordination betweengsand photosynthesis.

Highlight

By controlling intercellular CO2(Ci) at a range of values across red-light response curves, we demonstrate independent and interactive roles ofCi-dependent and –independent pathways in coordinating stomatal red-light responses.
A novel pathogenic mutation of MeCP2 impairs chromatin association independent of protein levels
Authors: Zhou Jian , Cattoglio Claudia , Shao Yingyao , Tirumala Harini P. , Vetralla Carlo , Bajikar Sameer S. , Li Yan , Chen Hu , Wang Qi , Wu Zhenyu , Tang Bing , Zahabiyon Mahla , Bajic Aleksandar , Meng Xiangling , Ferrie Jack J. , LaGrone Anel , Zhang Ping , Kim Jean J. , Tang Jianrong , Liu Zhandong , Darzacq Xavier , Heintz Nathaniel , Tjian Robert , Zoghbi Huda Y.
Published: October 2023

Loss-of-function mutations inMECP2cause Rett syndrome (RTT), a severe neurological disorder that mainly affects girls. Mutations inMECP2do occur in males occasionally and typically cause severe encephalopathy and premature lethality. Recently, we identified a missense mutation (c.353G>A, p.Gly118Glu [G118E]), which has never been seen before inMECP2, in a young boy who suffered from progressive motor dysfunction and developmental delay. To determine whether this variant caused the clinical symptoms and study its functional consequences, we established two disease models, including human neurons from patient-derived iPSCs and a knock-in mouse line. G118E mutation partially reduces MeCP2 abundance and its DNA binding, and G118E mice manifest RTT-like symptoms seen in the patient, affirming the pathogenicity of this mutation. Using live-cell and single-molecule imaging, we found that G118E mutation alters MeCP2's chromatin interaction properties in live neurons independently of its effect on protein levels. Here we report the generation and characterization of RTT models of a male hypomorphic variant and reveal new insight into the mechanism by which this pathological mutation affects MeCP2's chromatin dynamics. Our ability to quantify protein dynamics in disease models lays the foundation for harnessing high-resolution single-molecule imaging as the next frontier for developing innovative therapies for RTT and other diseases.
Spectral-brightness optimization of an X-ray free-electron laser by machine-learning-based tuning
Authors: Iwai Eito , Inoue Ichiro , Maesaka Hirokazu , Inagaki Takahiro , Yabashi Makina , Hara Toru , Tanaka Hitoshi
Published: October 2023

A machine-learning-based beam optimizer has been implemented to maximize the spectral brightness of the X-ray free-electron laser (XFEL) pulses of SACLA. A new high-resolution single-shot inline spectrometer capable of resolving features of the order of a few electronvolts was employed to measure and evaluate XFEL pulse spectra. Compared with a simple pulse-energy-based optimization, the spectral width was narrowed by half and the spectral brightness was improved by a factor of 1.7. The optimizer significantly contributes to efficient machine tuning and improvement of XFEL performance at SACLA.
The impact of unanticipated wealth effects on consumption: evidence from Spanish panel data
Authors: Cutanda Antonio , Sanchis Llopis Juan Alberto
Published: October 2023

Purpose

The purpose of this study is to estimate the housing wealth effect on non-durable consumption using data from the Spanish Survey of Household Finances (Encuesta Financiera de las Familias, SHF) for the period 2002–2017.

Design/methodology/approach

The authors aim at identifying the effect of anticipated and unanticipated housing wealth changes on consumption with the sample of homeowners, following Paiella and Pistaferri (2017).

Findings

Results of this study lead us to conclude that there exists a strong housing wealth effect on consumption for the Spanish households.

Originality/value

The authors provide evidence against the permanent income model. They also analyse how the results change with income expectations, age and the household indebtedness rate. Finally, they detect a strong excess sensitivity to income.
Characteristics of business, pleasure, and VFR segments who travel during risky times
Authors: Tasci Asli D.A. , Milman Ady
Published: October 2023

Purpose

This study aims to explore what may have contributed to risk-taking travel behavior during the COVID-19 pandemic and what may be the drivers of satisfaction and intention to travel again. The study compares travelers based on their travel purposes (business, pleasure and visiting friends and relatives [VFR]) and explore the influence of subjective well-being received from their travel activities.

Design/methodology/approach

Data from a structured survey of 323 US residents who traveled during the COVID-19 pandemic were collected on MTurk. Respondents were asked travel behavior questions related to their favorite trips and to rate several multi-item scales measuring the benefits expected and received from their trip, the trip’s contribution to their positive mental and subjective psychological well-being, as well as their satisfaction with the trip and intention to travel in the future. In addition, personality measures focused on risk-taking, thrill-seeking and self-confidence, as well as additional risk-related concepts of optimism bias, probability neglect and proximity to self.

Findings

Data analysis revealed some differences among respondents who traveled for business, pleasure and VFR purposes. Business travelers were more risk takers and thrill seekers; pleasure travelers achieved more well-being benefits from their favorite trips during the pandemic; however, VFR travelers’ satisfaction and intention to go on similar trips were explained more by the benefits they received from their favorite trips.

Originality/value

Although several studies addressed consumers’ travel motivation during the COVID-19 pandemic, there is a lack of empirical research comparing the characteristics of travelers based on their travel purposes, as well as their sociodemographics, personality traits and the expected and perceived well-being benefits from traveling.
Explainable boosted combining global and local feature multivariate regression model for deformation prediction during braced deep excavations
Authors: Zhang Wenchao , Shi Peixin , Wang Zhansheng , Zhao Huajing , Zhou Xiaoqi , Jia Pengjiao
Published: October 2023

Purpose

An accurate prediction of the deformation of retaining structures is critical for ensuring the stability and safety of braced deep excavations, while the high nonlinear and complex nature of the deformation makes the prediction challenging. This paper proposes an explainable boosted combining global and local feature multivariate regression (EB-GLFMR) model with high accuracy, robustness and interpretability to predict the deformation of retaining structures during braced deep excavations.

Design/methodology/approach

During the model development, the time series of deformation data is decomposed using a locally weighted scatterplot smoothing technique into trend and residual terms. The trend terms are analyzed through multiple adaptive spline regressions. The residual terms are reconstructed in phase space to extract both global and local features, which are then fed into a gradient-boosting model for prediction.

Findings

The proposed model outperforms other established approaches in terms of accuracy and robustness, as demonstrated through analyzing two cases of braced deep excavations.

Research limitations/implications

The model is designed for the prediction of the deformation of deep excavations with stepped, chaotic and fluctuating features. Further research needs to be conducted to expand the model applicability to other time series deformation data.

Practical implications

The model provides an efficient, robust and transparent approach to predict deformation during braced deep excavations. It serves as an effective decision support tool for engineers to ensure the stability and safety of deep excavations.

Originality/value

The model captures the global and local features of time series deformation of retaining structures and provides explicit expressions and feature importance for deformation trends and residuals, making it an efficient and transparent approach for deformation prediction.
Literacy instructional coaching practices in writing and writing instruction: an exploration of K–6 teachers' perspectives
Authors: Abbott Jadelyn , Wright Katherine Landau , Carter Hannah
Published: October 2023

Purpose

The purpose of this study was to identify if and how K–6 teachers perceive that their literacy instructional coaches influence their writing teaching.

Design/methodology/approach

The authors employed a parallel convergent mixed-methods design with survey data. The authors used thematic analysis to identify patterns within short-answer responses.

Findings

K–6 teachers receive little literacy coaching specific to writing. However, when they do receive coaching, they believe it benefits their writing instruction. Sustained coaching through the coaching cycle, frequent collaborations, and support with writing instructional resources and strategies were reported as the most influential writing coaching practices.

Research limitations/implications

Sample size was a limitation to this study. Of the 66 participants, 41 (62%) completed the entire survey.

Practical implications

This research provides coaches with valuable insights about coaching practices that teachers find to be the most effective in influencing their writing instruction. The increase in teachers' competence in writing instruction due to coaching provides evidence to administrators and stakeholders that coaching in writing is an area in need of attention.

Originality/value

This study adds to research specific to the coaching of writing within the K–6 context, which currently is sparse.
UnDoing: a research-through-curation project that investigates the reuse of the built environment
Authors: Stone Sally Helen , Sanderson Laura
Published: October 2023

Purpose

This paper considers the exhibition: UnDoing. This research-through-curation project examined interactions within existing spaces and situations. This established links between the selected exhibits, the gallery, the city and with the continuum of the previous exhibition.

Design/methodology/approach

Carefully selected architects, designers and artists were invited to contribute—those who pursued a contextual approach; whose practice explored the way buildings, places and artefacts are reused, reinterpreted and remembered.

Findings

Through the act of curation, this research uncovered a series of different approaches to constructed sites and existing buildings, from layered juxtaposition, the refusal to undo, to interventions of new elements within architectural works.

Research limitations/implications

Curation offered the opportunity to consider works of architecture and of art through the same lens, for direct comparisons to be made and the influence of one upon the other to be comprehended.

Practical implications

The examination processes the architect employs is similar to that of the artist; the development of an understanding of place, and from this synthesis, creative interpretation. However, despite the similarities in the starting position, the elucidation developed by the artist can be vastly different to that of the architect.

Social implications

The juxtaposition and new classifications created by the exhibition encouraged visitors to look at art, architecture and the city in a different way; to grasp the direct link between the different subjects; and the possibilities created.

Originality/value

The two driving factors for UnDoing were places of previous occupation and the city of Manchester. The qualities of surrounding constructed environment combined were combined with attitudes towards existing structures and places.
Palate vs plate: segmenting restaurant consumers through food quality and portion size trade-offs
Authors: Ge Li , Tang Chun-Hung (Hugo) , Behnke Carl , Ghiselli Richard
Published: October 2023

Purpose

This study (1) assessed restaurant consumers' perceived importance of better food quality versus larger portion sizes, (2) classified restaurant consumers into different segments based on their perceived importance of seven food quality attributes (taste, texture, aroma, appearance and the use of natural, local and organic ingredients) relative to portion size and (3) compared the identified market segments.

Design/methodology/approach

An online survey assessed 613 USA adult participants' perceived importance of seven food quality attributes relative to portion size. A K-means cluster analysis classified participants into different segments based on their perceptions.

Findings

Five restaurant consumer segments were identified: sensory-oriented consumers, taste-oriented organic food consumers, local and natural food consumers, quantity-oriented consumers and quality-oriented consumers. In general, quality-oriented consumers were the least likely to visit fast-food restaurants, had the highest average per-meal spending and were the least likely to eat out alone. Local and natural food consumers and taste-oriented organic food consumers had higher total restaurant spending than other groups. Quantity-oriented and sensory-oriented consumers visited fast-food restaurants more often and had lower total restaurant spending and per-meal spending than other groups. Age, sex and income were significantly associated with the segmentation outcomes.

Practical implications

Findings suggest promising opportunities for restaurants to enhance consumer perceptions of value by prioritizing the factors that hold the greatest significance to their target customers.

Originality/value

This study is the first attempt to segment restaurant consumers based on their perceived importance of food quality attributes relative to portion size, effectively identifying five distinct consumer segments.
The relationship between immersive experience and shelf life of mobile apps: an empirical study of a gaming application
Authors: Balapour Ali , Sabherwal Rajiv , Grover Varun
Published: October 2023

Purpose

Mobile apps usually have a short lifespan, and this prevents the majority from surviving long enough to generate revenue for their developers. To address this issue, this study aims to recognize the role of engagement and immersion and develops a cognitive-affective theoretical framework to associate these factors with the lifespan of an app. Moreover, the authors focus on gaming apps because of their dominance on mobile platforms, and because a few of them become lucrative while the majority perish within a few weeks.

Design/methodology/approach

This study uses a longitudinal survey-based approach to collect data on one of the popular gaming apps (Pokémon Go), which received international attention. The design focuses on identifying factors that extend the lifespan of the app and affects users’ decision to continue or stop using the app over time. The authors use the survival analysis and structural equation modeling to analyze the theoretical framework.

Findings

The authors find the centrality of the users’ experience of immersion to extend the mobile app lifespan. Engagement influences immersion and immersion predicts users’ decision to continue or stop using the app. Users’ experience of immersion increases the probability of the apps’ survival by 12%.

Originality/value

To the best of the authors’ knowledge, this is the only study that proposes a theoretical framework, meticulously investigates the factors that can lead to survival of a mobile app and uses longitudinal data for the empirical analysis.
The Governance Role of Minority State Ownership in Non‐state‐owned Enterprises: Evidence from Corporate Fraud in China
Authors: Zhang Liguang , Peng Liao , Liu Xinyu , Zhang Zhe , Wang Yunchen
Published: October 2023

This study attempts to shed new light on how the state as a minority shareholder benefits stakeholders, by investigating its role in deterring corporate fraud in non‐state‐owned enterprises (non‐SOEs). Through an analysis of publicly traded non‐SOEs in China, this study reveals that minority state ownership negatively impacts firm fraud, and the results hold after alternative tests. The identified channels of this association are that minority state ownership mitigates tunnelling, enhances internal control, and alleviates the financial constraints of non‐SOEs. Further analysis shows that this relationship is more pronounced in firms with weaker corporate governance, stronger fraud incentives, and lower levels of political connections. Overall, this study contributes to our understanding of the role of minority state ownership in emerging markets within the context of corporate fraud, highlighting the importance of critically evaluating the effects of government intervention in different contexts.
Impact of obesity and overweight on C‐reactive protein concentrations and disease activity in rheumatoid arthritis: A systematic review and meta‐analysis
Authors: Flores‐Alvarado Diana E. , Esquivel‐Valerio Jorge A. , Vega‐Morales David , Garza‐Cisneros Andrea N. , Balderas‐Palacios Mario A. , Galarza‐Delgado Dionicio A. , Garcia‐Leal Mariana
Published: October 2023

Aim

This study aims to assess the association of obesity and CRP concentrations in adult patients with rheumatoid arthritis (RA), and its influence on measures of disease activity.

Methods

A comprehensive search was performed using Scopus, Web of Science, MEDLINE, and EMBASE, from the time of their inception to November 2021. Observational studies that evaluated the association between CRP concentrations and obesity or overweight in patients with RA were considered eligible. Correlation coefficients were pooled using the inverse variance method, while effect sizes were pre‐calculated for adjusted standardized regression coefficients (β).

Results

A total of 10 studies, which comprised 4024 patients, were included in this systematic review. Individually, most studies report a significant association between CRP concentrations and a higher body mass index or other adiposity measures, but the statistical significance was not sustained when pooling their data together. Through the estimates provided in the present review, it is noted that CRP tends to be more elevated in female patients with RA that have a higher BMI. However, this association is not present in men.

Conclusion

CRP tends to be elevated in female patients with RA that have a higher BMI. Further research is required to assess this possible sex‐related difference and to aid shared decision‐making in order to avoid over‐treatment and increased burden in patients with obesity and RA.

PROSPERO registration number: CRD42022314580.
Clinical applications of calcium silicate‐based materials: a narrative review
Authors: Küçükkaya Eren S
Published: October 2023

Calcium silicate‐based materials are hydrophilic materials with biocompatibility and bioactivity properties. Despite many advantages, they might present some problems related to discolouration, setting time, manipulation and solubility depending on the composition of the product and the type of clinical application. Calcium silicate‐based materials can be evaluated under two types according to their intended use: calcium silicate‐based cements (CSCs) and calcium silicate‐based sealers (CSSs). CSCs can be used in many endodontic procedures including perforation repair, resorption repair, apical barriers, guided endodontic repair, vital pulp treatment, endodontic surgery, root fractures and root canal filling as a core obturation material. CSSs are available for use with gutta‐percha to obturate root canals using cold and warm techniques, including the sealer‐based obturation technique. The purpose of this review is to evaluate the available literature on CSCs and CSSs and to provide up‐to‐date information and recommendations for their clinical applications.
Before and after COVID‐19 pandemic: impact on hepatobiliary and pancreatic surgical services in a Singapore Tertiary Hospital
Authors: Lim Joshua S. H. , Lim Zavier Yongxuan , Teo Zhe Hao Timothy , Wang Bei , Tan Yen Pin , Junnarkar Sameer P. , Low Jee Keem , Huey Cheong Wei Terence , Shelat Vishal
Published: October 2023

Background

Reallocation of healthcare resources to prioritize the COVID‐19 pandemic‐related incremental healthcare needs resulted in longer waiting times for routine elective clinical services.

Aims

We aimed to analyze the effects of the pandemic on the hepatopancreatobiliary (HPB) unit's surgical workload.

Methods

The HPB unit's surgical workload for the months of January‐June from 2019 to 2022 was extracted, retrospectively compared, and analyzed. This study was registered in ClinicalTrials.gov (NCT05572866) and complies with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.

Results

Benign elective surgeries were impacted adversely, with elective gallbladder operations decreasing by 45.2% (146 in 2019 vs 80 in 2020, p = 0.89) before slowly increasing to 120 cases in 2021 and rebounding to 179 cases in 2022 (p = 0.001).

Elective oncology operations paradoxically increased, with liver resections rising by 12.9% (31 in 2019 vs 35 in 2020, p = 0.002) and maintaining 37 cases in 2021 (p = 0.0337) and 34 cases in 2022 (p = 0.69). Elective pancreatic resections increased by 171.4% (7 in 2019 vs 19 in 2020, p < 0.0001) and were maintained at 15 cases in 2021 (p = 0.013) and 18 cases in 2022 (p = 0.022).

The overall emergency workload decreased from 2019 (n = 198) to 2020 (n = 129) to 2021 (n = 122) before recovering to baseline in 2022 (n = 184). The month‐on‐month volume generally showed similar trends compared to the other years except for February 2022 and May 2021.

Conclusion

This audit shows that despite large‐scale disruption of the local healthcare system, essential surgeries can still proceed with careful resource planning by steadfast and vigilant clinical teams.
Solidarity‐based collective action among third parties: The role of emotion regulation and moral outrage
Authors: Green Dorainne J. , Duker Ajua , Onyeador Ivuoma N. , Richeson Jennifer A.
Published: October 2023

Societal injustice can trigger moral outrage, an important predictor of solidarity‐based collective action (CA). The present work investigated whether the impact of emotion regulation strategies on feelings of moral outrage shapes solidarity‐based CA intentions in the context of two recent examples of environmental injustice—water crises of 2015–2016 and 2021 in Flint, Michigan, and Benton Harbor, Michigan. Three studies investigated the effect of engaging in distancing compared with immersion when processing information about the events on feelings of moral outrage among people who did not live in either city. The studies also investigated the downstream effect of moral outrage on people's willingness to engage in CA in solidarity with those affected. Processing the injustice by engaging in distancing compared with immersion resulted in less moral outrage, which reduced interest in engaging in CA. This research highlights the important role of emotion regulation strategies in influencing solidarity‐based collective action among people not directly targeted by an injustice.