bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of non-contact infrared thermometers for COVID-19 fever screening in healthcare workers: A prospective observational study in a tertiary care hospital
Authors: Kumar D. Suresh , Ratheesh R. , Poojadharshini M. , Kalyani P. , Pooja S.
Published: December 2023

Background

In the fight against COVID-19, efficient fever screening was essential to curb transmission. Fever served as a cardinal symptom, aiding early and timely identification of fever among healthcare workers (HCWs) was crucial. While non-contact infrared thermometers (NCITs) offered non-invasive screening, existing data gaps were present. This study aimed to assess the NCIT effectiveness in HCW fever screening by comparing results with serology and RT-PCR tests, ascertaining their utility in healthcare settings for COVID-19 detection.

Methods

This prospective observational study was conducted at a dedicated COVID-19 tertiary care hospital with 250 beds in South India. The study population comprised 736 healthcare workers (HCWs) working in the hospital, and the study was carried out between April 2020 and December 2020. Daily fever screening using non-contact infrared thermometers (NCITs) was performed on all HCWs upon their entry to the hospital. Additionally, serological tests were offered to all HCWs starting from November 2020 to assess prior COVID-19 infection exposure. COVID-19 admissions were closely monitored during the study period to identify hospitalized HCWs with symptoms who subsequently tested positive for COVID-19 using RT-PCR.

Results

In this study cohort of 736 HCWs, 44,836 NCIT screenings revealed no fever cases. The serological analysis identified prior COVID-19 exposure in 229 HCWs. McNemar’s test (χ2= 26.27, p < 0.05) emphasized discordance between NCIT and serology. ROC analysis yielded an AUC of 0.500, indicating NCIT’s challenge in distinguishing febrile cases. Additionally, 68 symptomatic HCWs tested COVID-19 positive through RT-PCR, highlighting the role of complementary diagnostics.

Conclusion

The failure of NCIT to identify fever cases in our study highlights the importance of incorporating supplementary screening methods and comprehensive strategies in future pandemic preparedness.
Whole genome and transcriptome sequencing in neuromuscular disorders: a diagnostic and health economic analysis
Authors: Yang Ziying , Yang Xiaoru , Chen Yunmei , Wang Zhonghua , Fu Xiangke , Song Lijie , Yang Xunzhe , Peng Zhiyu , Dai Yi
Published: December 2023

Background

A considerable number of patients suffering from neuromuscular disorders (NMD) are unable to receive an accurate diagnosis through initial genetic testing. It is imperative to develop a cost-effective diagnostic strategy that incorporates appropriate multi-omics techniques.

Methods

This study included 33 NMD patients with negative results from whole-exome sequencing (WES). Whole-genome sequencing (WGS) and RNA sequencing (RNA-seq) were performed concurrently to evaluate clinical utility. Additionally, eight diagnostic pathways were compared in terms of diagnostic rate, turnaround time, and cost.

Results

Our implementation of parallel WGS and RNA-seq testing successfully validated the clinical utility of this strategy in the cohort of 33 NMD patients initially yielding negative results from WES. The combined utilization of both methods resulted in an additional diagnosis for 42% (15/33) of the patients, with WGS contributing to 36% and RNA-seq contributing to 6% of the diagnoses. The Integration of alternative splicing results derived from RNA-seq data into variant filtering significantly reduced the number of rare intronic variants requiring interpretation and provided compelling evidence to support the classification of variant pathogenicity based on functional impact. Our comprehensive analysis, comparing eight different diagnostic pathways, revealed the cost-effectiveness of parallel WGS and RNA-seq testing as a diagnostic approach for patients. Moreover, the analysis of rare genomic findings within our cases showcased their potential to inform patient care, aid treatment decisions, and expand the range of NMD mutations in diagnosing rare NMD cases.

Conclusion

The integration of parallel WGS and RNA-seq testing represents a transformative diagnostic approach for NMD patients. The cost-effectiveness of this approach, coupled with its ability to improve diagnostic yield and interpretation efficiency, makes it a highly recommended strategy for clinical implementation to enhance the management and care of NMD patients.
Alterations in gamma frequency oscillations correlate with cortical tau deposition in Alzheimer’s disease
Authors: Nencha Umberto , Rigoni Isotta , Ribaldi Federica , Altomare Daniele , Seeck Margitta , Garibotto Valentina , Vulliémoz Serge , Frisoni Giovanni B.
Published: December 2023

We assessed the relationship of gamma oscillations with tau deposition in Alzheimer’s disease (AD) and other cognitive diseases, as both are altered during the disease course and relate to neurodegeneration. We retrospectively analyzed data from 7 AD, tau positive patients and 9 tau negative patients, that underwent amyloid PET, and cerebral tau PET and EEG within 12 months. Relative gamma power was higher in tau positive (AD) patients than in tau negative patients (p<.05) and tau burden was associated with a linear increase in gamma power (p<.001), while no association was present with amyloid-β burden. Thus, increase in the gamma power might represent a novel biomarker for tau driven neurodegeneration.
Deep immune profiling of chronic rhinosinusitis in allergic and non-allergic cohorts using mass cytometry
Authors: Kidane Fana Alem , Müller Lena , Rocha-Hasler Marianne , Tu Aldine , Stanek Victoria , Campion Nicholas , Bartosik Tina , Zghaebi Mohammed , Stoshikj Slagjana , Gompelmann Daniela , Spittler Andreas , Idzko Marco , Schneider Sven , Eckl-Dorna Julia
Published: December 2023

Background

Chronic rhinosinusitis (CRS) is characterized by persistent nasal and paranasal sinus mucosa inflammation. It comprises two phenotypes, namely CRS with nasal polyps (CRSwNP) and without (CRSsNP). CRSwNP can be associated with asthma and hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) in a syndrome known as NSAID-exacerbated respiratory disease (N-ERD). Furthermore, CRS frequently intertwines with respiratory allergies.

Objective

This study investigated the phenotypic characteristics of peripheral blood mononuclear cells (PBMCs) within cohorts of CRS patients, additionally examining the influence of comorbid respiratory allergies on these parameters.

Methods

24 participants were grouped into controls, CRSsNP, CRSwNP, and N-ERD (n=6/group), with half of the patients in each group having respiratory allergies. Levels of cytokines were quantified in nasal secretions and sera. The abundance and phenotypic features of immune cells in PBMCs were evaluated through mass cytometry and clustering methods.

Results

N-ERD patients showed heightened type 2 nasal cytokine levels. Mass cytometry analysis revealed increased activated naive B cell levels in CRSwNP and N-ERD, while resting naive B cells were higher in CRSsNP. Th2a cell levels did not differ between CRS subtypes but were significantly elevated in allergic subjects. In CRSwNP and N-ERD patients, naive B cells had a lower CXCR5 and higher CD45RA expression, while NK cells displayed reduced CD56 levels.

Conclusions

There are distinct immunological features in PBMCs of CRS phenotypes and allergy, characterized by elevated resting naive B cells in CRSsNP, increased activated naive B cells in CRSwNP and N-ERD, and higher Th2a cell levels in allergic subjects.

Capsule summary

This study examines immunological profiles in different phenotypes of CRS with and without comorbid allergy patients, highlighting immune cell intricacies in CRS subtypes and immune differences in CRS and respiratory allergy.
Role of the metallo-reductase FADING and vacuolinos in anthocyanin degradation in flowers and fruits
Authors: Passeri Valentina , Li Shuangjiang , Strazzer Pamela , i Calvó’ Enric Martínez , Senden Esther , Guzzo Flavia , Commisso Mauro , Spelt Cornelis , Vandenbussche Michiel , Bliek Mattijs , Verweij Walter , Koes Ronald , Quattrocchio Francesca M.
Published: December 2023

Anthocyanins are vacuolar pigments that confer red-violet colors to plant tissues. Pigmentation patterns result from spatio-temporally regulated anthocyanin synthesis and degradation. Mutational inactivation of a conserved MYB-bHLH-WDrepeat-WRKY transcriptional complex (MBWW) causes degradation of anthocyanins and ‘fading’ of flower color via a pathway that involvesFADING (FA). Here we show thatFAencodes a vacuolar membrane Fe-reductase-oxidase that promotes anthocyanin degradation. In wild type petals anthocyanins in the central vacuole (CV) are stable, because FA-GFP is upheld in small vacuoles (vacuolinos) and kept away from the CV, indicating that vacuolinos act as gatekeepers in protein trafficking. In cells lacking vacuolinos, includingmbww-mutant petals, FA-GFP reaches the CV and triggers anthocyanin degradation. Virus-induced gene silencing (VIGS) of an FA-homolog in pepper fruits prevented the “fading” of anthocyanins during fruit maturation. These findings provide new insights to breed ornamental and food crops with increased anthocyanin-content and enhanced nutritional value of edible parts.
Maximizing glycoproteomics results through an integrated PASEF workflow
Authors: Baerenfaenger Melissa , Post Merel A , Zijlstra Fokje , van Gool Alain J , Lefeber Dirk J , Wessels Hans JCT
Published: December 2023

Glycoproteins play important roles in numerous physiological processes and are often implicated in disease. Analysis of site-specific protein glycobiology through glycoproteomics is evolving rapidly in recent years thanks to hardware and software innovations. Particularly, the introduction of Parallel Accumulation Serial Fragmentation (PASEF) on hybrid trapped ion mobility time-of-flight mass spectrometry instruments combined deep proteome sequencing with separation of (near-)isobaric precursor ions or converging isotope envelopes through ion mobility separation. However, reported use of PASEF in integrated glycoproteomics workflows to comprehensively capture the glycoproteome is still limited. To this end, we developed an integrated methodology using the timsTOF Pro 2 to enhance N-glycopeptide identifications in complex mixtures. We systematically optimized the ion optics tuning, collision energies, mobility isolation width and the use of do-pant-enriched nitrogen gas (DEN). Thus, we obtained a marked increase in unique glycopeptide identification rates compared to standard proteomics settings showcasing our results on a large set of glycopeptides. With short liquid chromatography gradients of 30 minutes, we increased the number of unique N-glycopeptide identifications in human plasma samples from around 100 identifications under standard proteomics condition to up to 1500 with our optimized glycoproteomics approach, highlighting the need for tailored optimizations to obtain comprehensive data.

Abstract Figure
UnveilingCryptosporidium parvumSporozoite-Derived Extracellular Vesicles: Profiling, Origin, and Protein Composition
Authors: Bertuccini Lucia , Boussadia Zaira , Salzano Anna Maria , Vanni Ilaria , Passerò Ilaria , Nocita Emanuela , Scaloni Andrea , Sanchez Massimo , Sargiacomo Massimo , Fiani Maria Luisa , Tosini Fabio
Published: December 2023

Cryptosporidium parvumis a common cause of a zoonotic disease and a main cause of diarrhea in newborns around the world. Effective drugs or vaccines are still lacking. Oocyst is the infective form of the parasite; after the ingestion the oocyst excysts and releases four sporozoites into the intestine that rapidly attack the enterocytes. The membrane protein CpRom1 is a large rhomboid protease that is expressed by sporozoites and recognized as antigen by the host immune system. In this study, we observed the release of CpRom1 with extracellular vesicles (EVs) not previously described. To investigate this phenomenon, we isolated and resolved EVs from the excystation medium by differential ultracentrifugation. By fluorescence flow cytometry and transmission electron microscopy (TEM), we identified two types of sporozoite-derived vesicles: large extracellular vesicles (LEVs) and small extracellular vesicles (SEVs), having different a mean size of 150 nm and 60 nm, respectively. Immunodetection experiments proved the occurrence of CpRom1 and the Golgi protein CpGRASP in LEVs, while immune-electron microscopy experiments demonstrated localization of CpRom1 on LEVs surface.

TEM and scanning electron microscopy (SEM) showed the generation of LEVs by budding of the outer membrane of sporozoites; conversely, the origin of SEVs remained uncertain.

Differences between LEVs and SEVs were observed for protein composition as proved by the corresponding electrophoretic profiles. Indeed, a dedicated proteomic analysis identified 5 proteins unique to LEVs composition and 16 proteins unique to SEVs. Overall, 60 proteins were identified in the proteome of both types of vesicles and most of these proteins (48 in number) were already identified in the molecular cargo of extracellular vesicles from other organisms. Noteworthy, we identified 12 proteins unique toCryptosporidiumspp. that had never been associated with EVs. This last group included the immunodominant parasite antigen glycoprotein GP60, which is one of the most abundant proteins in both LEVs and SEVs.
Structure and methyl-lysine binding selectivity of the HUSH complex subunit MPP8
Authors: Nikolopoulos Nikos , Oda Shun-ichiro , Prigozhin Daniil M. , Modis Yorgo
Published: December 2023

The Human Silencing Hub (HUSH) guards the genome from the pathogenic effects of retroelement expression. Composed of MPP8, TASOR, and Periphilin-1, HUSH recognizes actively transcribed retrotransposed sequences by the presence of long (>1.5-kb) nascent transcripts without introns. HUSH recruits effectors that alter chromatin structure, degrade transcripts, and deposit transcriptionally repressive epigenetic marks. Here, we report the crystal structure of the C-terminal domain (CTD) of MPP8 necessary for HUSH activity. The MPP8 CTD consists of five ankyrin repeats followed by a domain with structural homology to the PINIT domains of Siz/PIAS-family SUMO E3 ligases. AlphaFold-Multimer modeling predicts that the MPP8 CTD forms extended interaction interfaces with a SPOC domain and a domain with a novel fold in TASOR. The MPP8 chromodomain, known to bind the repressive mark H3K9me3, binds with similar or higher affinity to sequences in the H3K9 methyltransferase subunits SETDB1, ATF7IP, G9a, and GLP. Hence, MPP8 promotes heterochromatinization by recruiting H3K9 methyltransferases. Our work identifies novel structural elements in MPP8 required for HUSH complex assembly and silencing, thereby fulfilling vital functions in controlling retrotransposons.
Shared features of blastula and neural crest stem cells evolved at the base of vertebrates
Authors: York Joshua R. , Rao Anjali , Huber Paul B. , Schock Elizabeth N. , Montequin Andrew , Rigney Sara , LaBonne Carole
Published: December 2023

The neural crest is vertebrate-specific stem cell population that helped drive the origin and evolution of the vertebrate clade. A distinguishing feature of these stem cells is their multi-germ layer potential, which has drawn developmental and evolutionary parallels to another stem cell population—pluripotent embryonic stem cells (animal pole cells or ES cells) of the vertebrate blastula. Here, we investigate the evolutionary origins of neural crest potential by comparing neural crest and pluripotency gene regulatory networks (GRNs) in both jawed (Xenopus) and jawless (lamprey) vertebrates. Through comparative gene expression analysis and transcriptomics, we reveal an ancient evolutionary origin of shared regulatory factors between neural crest and pluripotency GRNs that dates back to the last common ancestor of extant vertebrates. Focusing on the key pluripotency factorpou5(formerly oct4), we show that the lamprey genome encodes apou5ortholog that is expressed in animal pole cells, as in jawed vertebrates, but is absent from the neural crest. However, gain-of-function experiments show that both lamprey andXenopus pou5enhance neural crest formation, suggesting thatpou5was lost from the neural crest of jawless vertebrates. Finally, we show thatpou5is required for neural crest specification in jawed vertebrates and that it acquired novel neural crest-enhancing activity after evolving from an ancestralpou3-like clade that lacks this functionality. We propose that a pluripotency-neural crest GRN was assembled in stem vertebrates and that the multi-germ layer potential of the neural crest evolved by deploying this regulatory program.
WITHDRAWN: (CA)noligonucleotides correct RNA mis-splicing in TDP-43 pathology
Authors: Wang Congwei , Terrigno Marco , Joenson Lars , Li Meiling , Schröter Manuel , Nordbo Bettina , Chyzynska Katarzyna , Weile Christian , Bastien Jessica , Mogensen Marianne B. , Seidel Antonia S. , Hagedorn Peter H. , Jagasia Ravi , Vikesaa Jonas
Published: December 2023

Withdrawal Statement

The authors have withdrawn their manuscript owing to not all authors having approved the manuscript. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Deep super-resolution imaging of thick tissue using structured illumination with adaptive optics
Authors: Wang Jingyu , Stoychev Danail , Phillips Mick , Pinto David Miguel Susano , Parton Richard M. , Hall Nick , Titlow Josh , Faria Ana Rita , Wincott Matthew , Gala Dalia , Gerondopoulos Andreas , Irani Niloufer , Dobbie Ian , Schermelleh Lothar , Booth Martin , Davis Ilan
Published: December 2023

3D structured illumination microscopy (3D-SIM) doubles the resolution of fluorescence imaging in lateral and axial directions and increases contrast in both fixed and live specimens. However, 3D-SIM has so far not been widely applied to imaging deep in thick tissues due to its sensitivity to specimen-induced aberrations, making the method difficult to apply beyond 10 µm in depth. Furthermore, 3D-SIM has not been available in an upright configuration, limiting its use for live imaging while manipulating the specimen, for example with electrophysiology. Here, we have overcome these barriers by developing a novel upright 3D-SIM system (termed Deep3DSIM) that incorporates adaptive optics (AO) for aberration correction and remote focusing, reducing artefacts, and removing the need to move the specimen or objective. Both these advantages are equally applicable to inverted 3D-SIM microscopes. We demonstrate high-quality 3D-SIM imaging up to 130 µm into complex tissue and live sample manipulation, including human cells andDrosophilalarval brains and embryos.
Porcine sapovirus protease controls the innate immune response and targets TBK1
Authors: Georgana Iliana , Hosmillo Myra , Jahun Aminu S. , Emmott Edward , Sorgeloos Frederic , Cho Kyoung-Oh , Goodfellow Ian G.
Published: December 2023

Human sapoviruses (HuSaVs) and noroviruses are considered the leading cause of acute gastroenteritis worldwide. While extensive research has focused on noroviruses, our understanding of sapoviruses (SaVs) and their interactions with the host’s immune response remains limited. HuSaVs have been challenging to propagate in vitro, making the porcine sapovirus (PSaV) Cowden strain a valuable model for studying SaV pathogenesis. In this study we show, for the first time, that PSaV Cowden strain has mechanisms to evade the host’s innate immune response. The virus 3C-like protease (NS6) inhibits type I IFN production by targeting TBK1. Catalytically active NS6, both during ectopic expression and during PSaV infection, targets TBK1 which is then led for rapid degradation by the proteasome. Moreover, deletion of TBK1 from porcine cells led to a significant increase in PSaV titres, emphasizing its role in regulating PSaV infection. Additionally, we successfully established PSaV infection in IPEC-J2 cells, an enterocytic cell line originating from the jejunum of a neonatal piglet. Overall, this study provides novel insights into PSaV evasion strategies, opening the way for future investigations for SaV-host interactions, and enabling the use of a new cell line model for PSaV research.
DHCR24-mediated sterol homeostasis during spermatogenesis is required for sperm mitochondrial sheath formation and impacts male fertility over time
Authors: Relovska Sona , Wang Huafeng , Zhang Xinbo , Fernández-Tussy Pablo , Jeong Kyung Jo , Choi Jungmin , Suárez Yajaira , McDonald Jeffrey G. , Fernández-Hernando Carlos , Chung Jean-Ju
Published: December 2023

Desmosterol and cholesterol are essential lipid components of the sperm plasma membrane. Cholesterol efflux is required for capacitation, a process through which sperm acquire fertilizing ability. In this study, using a transgenic mouse model overexpressing 24-dehydrocholesterol reductase (DHCR24), an enzyme in the sterol biosynthesis pathway responsible for the conversion of desmosterol to cholesterol, we show that disruption of sterol homeostasis during spermatogenesis led to defective sperm morphology characterized by incomplete mitochondrial packing in the midpiece, reduced sperm count and motility, and a decline in male fertility with increasing paternal age, without changes in body fat composition. Sperm depleted of desmosterol exhibit inefficiency in the acrosome reaction, metabolic dysfunction, and an inability to fertilize the egg. These findings provide molecular insights into sterol homeostasis for sperm capacitation and its impact on male fertility.
mDia2 is an important mediator of MRTF-A-dependent regulation of breast cancer cell migration
Authors: Eder Ian , Yu Virginia , Antonello Jacob , Chen Fangyuan , Gau David , Chawla Pooja , Joy Marion , Lucas Peter , Boone David , Lee Adrian V. , Roy Partha
Published: December 2023

Dysregulated actin cytoskeleton gives rise to aberrant cell motility and metastatic spread of tumor cells. This study evaluates the effect of overexpression of wild-type vs functional mutants of MRTF-A on migration and invasion of breast cancer (BC) cells. Our studies indicate that SRF’s interaction is critical for MRTF-A-induced promotion of both 2D and 3D cell migration, while the SAP-domain function is important selectively for 3D cell migration. Increased MRTF-A activity is associated with more effective membrane protrusion, a phenotype that is attributed predominantly to SRF’s interaction of MRTF. We demonstrate formin-family protein mDia2 as an important mediator of MRTF-stimulated actin polymerization at the leading edge and cell migration. Multiplexed quantitative immunohistochemistry and transcriptome analyses of clinical BC specimens further demonstrate a positive correlation between nuclear localization of MRTF with malignant traits of cancer cells and enrichment of MRTF-SRF gene signature in pair-matched distant metastases vs primary tumors. In conclusion, this study establishes a novel mechanism of MRTF-dependent regulation of cell migration and provides evidence for the association between MRTF activity and increased malignancy in human breast cancer, justifying future development of a specific small molecule inhibitor of the MRTF-SRF transcriptional complex as a potential therapeutic agent in breast cancer.

SIGNIFICANCE

Actin cytoskeletal dysregulation gives rise to metastatic dissemination of cancer cells. This study mechanistically investigates the impact of specific functional disruption of MRTF (a transcriptional co-factor of SRF) on breast cancer cell migration.

This study establishes a novel mechanism linking mDia2 to MRTF-dependent regulation of cell migration and provides clinical evidence for the association between MRTF activity and increased malignancy in human breast cancer.

Findings from these studies justify future exploration of specific small molecule inhibitor of the MRTF-SRF transcriptional complex as a potential therapeutic agent in breast cancer.
Intracellular pH modulates vimentin remodeling in response to oxidants
Authors: Martínez Alma E. , González-Jiménez Patricia , Vidal-Verdú Cristina , Pajares María A. , Pérez-Sala Dolores
Published: December 2023

The intermediate filament protein vimentin plays key roles in the integration of cytoskeletal functions with impact on essential cellular processes including migration, mitosis and autophagy. Moreover, vimentin is involved in pathological processes such as cancer, fibrosis and interaction with pathogens. The vimentin network is finely tuned by posttranslational modifications, among which, those affecting its single cysteine residue (C328) play a critical role not only in vimentin function, but also in its interplay with actin. Interestingly, C328 exhibits a low pKa, which favors the presence of the thiol group in the thiolate form, and therefore its reactivity, at physiological pH. Therefore, C328 reactivity and modifications could be modulated by pH fluctuations in the physiological range. Here we show that indeed, vimentin cysteine oxidation and alkylation, and the subsequent vimentin remodeling, can be modulated as a function of pH, in vitro and in cells. Lowering intracellular pH by several means renders vimentin unresponsive to disruption by oxidants, whereas provoking an intracellular alkalinization exerts a sensitizing effect. The protective effect of low pH appears selective for vimentin since it does not preclude oxidant-elicited disruption of actin or tubulin structures. Importantly, a C328A vimentin mutant is resistant to disruption by oxidants under all pH conditions, highlighting the role of the thiol group at this position in the pH-dependent modulation of vimentin susceptibility to oxidants. Taken together, these results put forward intracellular pH as a key factor modulating redox-dependent vimentin remodeling.
Lamin B Receptor Upregulation in Metastatic Melanoma Causes Cholesterol-Mediated Nuclear Envelope Fragility
Authors: Baird Michelle A. , Fischer Robert S. , Jewett Cayla E. , Malide Daniela , Cartagena-Rivera Alexander X. , Waterman Clare M.
Published: December 2023

Metastatic cancer cells migrate through regions of tissue confinement, causing nuclear envelope (NE) rupture and heritable DNA damage. We discovered that cells from multiple cancers have increased NE fragility in confinement and transcriptional upregulation of nuclear genes compared to benign counterparts. A bioinformatic-driven siRNA screen revealed that lamin B receptor (LBR) upregulation correlates with melanoma progression and NE fragility. Increased LBR cholesterol synthase activity causes accumulation of cholesterol in the NE, which is necessary and sufficient for nuclear deformability and NE rupture in cells confinedin vitroand is associated with NE rupture in invasive cells migrating out of tumor organoids and tumorsin vivo.Thus, LBR upregulation causes excess NE cholesterol, driving nuclear fragility in confined migrating melanoma cells, establishing a direct role for nuclear membrane lipid composition in metastatic cancers.
The Reelin Receptor ApoER2 is a Cargo for the Adaptor Protein Complex AP-4: Implications for Hereditary Spastic Paraplegia
Authors: Caracci Mario O. , Pizarro Héctor , Alarcón-Godoy Carlos , Fuentealba Luz M. , Farfán Pamela , Pace Raffaella De , Santibañez Natacha , Cavieres Viviana A. , Pástor Tammy P. , Bonifacino Juan S. , Mardones Gonzalo A. , Marzolo María-Paz
Published: December 2023

Adaptor protein complex 4 (AP-4) is a heterotetrameric complex that promotes protein export from thetrans-Golgi network. Mutations in each of the AP-4 subunits cause a complicated form of Hereditary Spastic Paraplegia (HSP). Herein, we report that ApoER2, a receptor in the Reelin signaling pathway, is a cargo of the AP-4 complex. We identify the motif ISSF/Y within the ApoER2 cytosolic domain as necessary for interaction with the canonical signal-binding pocket of the µ4 (AP4M1) subunit of AP-4.AP4E1-knock-out (KO) HeLa cells and hippocampal neurons fromAp4e1-KO mice display increased Golgi localization of ApoER2. Furthermore, hippocampal neurons fromAp4e1-KO mice andAP4M1-KO human iPSC-derived cortical i3Neurons exhibit reduced ApoER2 protein expression. Analyses of biosynthetic transport of ApoER2 reveal differential post-Golgi trafficking of the receptor, with lower axonal distribution in KO compared to wild-type neurons, indicating a role of AP-4 and the ISSF/Y motif in the axonal localization of ApoER2. Finally, analyses of Reelin signaling in mouse hippocampal and human cortical KO neurons show that AP4 deficiency causes no changes in Reelin-dependent activation of the AKT pathway and only mild changes in Reelin-induced dendritic arborization, but reduces Reelin-induced ERK phosphorylation, CREB activation, and Golgi deployment. Altogether, this work establishes ApoER2 as a novel cargo of the AP-4 complex, suggesting that defects in the trafficking of this receptor and in the Reelin signaling pathway could contribute to the pathogenesis of HSP caused by mutations in AP-4 subunits.
Nerve Growth Factor Receptor Limits Inflammation to Promote Remodeling and Repair of Osteoarthritic Joints
Authors: Zhao Lan , Lai Yumei , Jiao Hongli , Huang Jian
Published: December 2023

Osteoarthritis (OA) is a painful, incurable disease affecting over 500 million people. The need for relieving OA pain is paramount but inadequately addressed, partly due to limited understandings of how pain signaling regulates non-neural tissues. Here we report that nerve growth factor receptor (NGFR) is upregulated in skeletal cells during OA and plays an essential role in the remodeling and repair of osteoarthritic joints. Specifically, NGFR is expressed in osteochondral cells but not in skeletal progenitor cells and induced by TNFα to attenuate NF-κB activation, maintaining proper BMP-SMAD1 signaling and suppressing RANKL expression. NGFR deficiency hyper-activates NF-κB in murine osteoarthritic joints, which impairs bone formation and enhances bone resorption as exemplified by a reduction in subchondral bone and osteophytes. In human OA cartilage, NGFR is also negatively associated with NF-κB activation. Together, this study uncovers a role of NGFR in limiting inflammation for repair of diseased skeletal tissues.
Crystal structure and Hirshfeld surface analysis of 3-benzyl-2-[bis(1H-pyrrol-2-yl)methyl]thiophene
Authors: Sadikhova Nurlana D. , Atioğlu Zeliha , Guliyeva Narmina A. , Shelukho Evgeniya R. , Polyanskaya Darya K. , Khrustalev Victor N. , Akkurt Mehmet , Bhattarai Ajaya
Published: December 2023

In the title compound, C20H18N2S, the asymmetric unit comprises two similar molecules (A and B). In molecule A, the central thiophene ring makes dihedral angles of 89.96 (12) and 57.39 (13)° with the 1H-pyrrole rings, which are bent at 83.22 (14)° relative to each other, and makes an angle of 85.98 (11)° with the phenyl ring. In molecule B, the corresponding dihedral angles are 89.49 (13), 54.64 (12)°, 83.62 (14)° and 85.67 (11)°, respectively. In the crystal, molecular pairs are bonded to each other by N—H...N interactions. N—H...π and C—H...π interactions further connect the molecules, forming a three-dimensional network. A Hirshfeld surface analysis indicates that H...H (57.1% for molecule A; 57.3% for molecule B), C...H/H...C (30.7% for molecules A and B) and S...H/H...S (6.2% for molecule A; 6.4% for molecule B) interactions are the most important contributors to the crystal packing.
Toward digitalization strategic perspective in the European food industry: non-linear nexuses analysis
Authors: Alnoor Alhamzah , Atiyah Abbas Gatea , Abbas Sammar
Published: December 2023

Purpose

Organizations deal with digital technologies to achieve their strategic goals. The shift toward digitization is a major challenge because it requires companies to create a digital outlook that influences organizational design. As a result, investigation of institutional theory and entrepreneurial orientation theory in the European food industry has become the focus of research in recent times.

Design/methodology/approach

To this end, data were collected from 83 companies related to the food industry in the European context. By applying a hybrid phase of the partial least squares structural equation modeling (PLS-SEM) and artificial neural network (ANN) methods, this study captured the causal–non-linear relationships among the study constructs.

Findings

The findings revealed that the variables of institutional theory and entrepreneurial orientation theory affect the adoption of the digital strategy. There is also a dual interaction role for e-business capabilities and digital transformation. The results of non-linear relationships confirmed that digital strategy adoption is highly influenced by digital transformation, followed by risk-taking, digital leadership, e-business capabilities, organizational agility, proactiveness and innovativeness.

Research limitations/implications

The authors provided significant implications for practitioners and academics about the most influential determinants of digital strategy – businesses must move swiftly toward digitization across its various units to achieve their objectives. An organization’s leadership must realize that equipping the employees with necessary skills is the first step toward digitalization.

Originality/value

The current study underscores the digital strategy, which is usually an overlooked area of investigation, in the food industry. The study identifies some important predictors of digital strategy adoption with the interaction’s role of digital transformation and e-business capabilities. Such relationships have been rarely discussed. In addition, the adoption of a hybrid SEM-AAN approach makes the study an original one.
Challenges of the MSE sector in the digital economy in Poland and Ukraine: comparative and statistical analysis
Authors: Remlein Marzena , Chugaievska Svitlana , Dehnel Grażyna , Romanchuk Kateryna
Published: December 2023

Purpose

The authors aimed to examine how the level of digitalization in Poland and Ukraine affects the contribution of small and medium-sized enterprises (SMEs) to the countries’ gross domestic product (GDP).

Design/methodology/approach

The study involved a comparative analysis and statistical modeling of the impact of key economic factors on the contribution of SMEs to Poland’s and Ukraine’s GDP in the 2010–2020 period. The authors used principles of the theory of economic growth and calculated the coefficient of digital competitiveness as a composite indicator consisting of a number of global indices.

Findings

The study revealed significant differences between both countries, which can be attributed to a higher level of digitalization in Polish SMEs. The authors used the Polish experience to recommend how to reform Ukraine’s digital economy in postwar recovery.

Originality/value

The contribution of SMEs to Poland’s GDP is higher than that of Ukraine’s because of the higher entrepreneurship rate in the Polish micro and small enterprises (MSEs) sector. The authors found that a unit change in the integrated coefficient of digital competitiveness is related to the greatest change in the contribution of SMEs to the country’s GDP when the other factors in the model equation remain fixed.
Motivating, developing and retaining talent through job enrichment: an exploration of “side-of-desk” projects in a corporate environment
Authors: Thomas Carla , Rowe Lisa , Moore Neil
Published: December 2023

Purpose

Global talent shortages, new skill demand and rising numbers of unfilled posts are fuelling an increasingly challenging job market, exacerbated by economic uncertainty and transformational digital change. Seeking creative solutions in response, the authors examine talent management’s (TM) theoretical and conceptual foundations, specifically the identification and selection of talent and TM programme design to explore the challenges and benefits of side-of-desk projects as interventions.

Design/methodology/approach

Taking an inductive qualitative approach, questionnaires, focus groups and semi-structured interviews gathered data from three employee groups in a UK digital communications organisation.

Findings

The authors reveal inconsistencies in the definition and selection of talent, highlighting programme quality challenges to expose a direct correlation between participant experience and motivation and retention, along with the longer-term challenges of balancing talented human capital, shareholder expectations and sustainable workforce resourcing.

Originality/value

The authors' research extends existing knowledge concerning the effect of organisational culture, context and workforce demands upon TM programmes, providing theoretical and practical implications for leaders and policymakers in designing enrichment activities to motivate, develop and retain talent. The authors make recommendations to inform the future design of TM programmes, revealing new opportunities to develop hidden talent and presenting a realistic and sustainable toolkit for future practice in the form of an organisational logic model.
Irish apprenticeships in financial services: negotiating gender and navigating social justice
Authors: Sheerin Corina , Brittain Jonathan
Published: December 2023

Purpose

Set within the context of International Financial Services (IFS), this research aims to considers the demographic profile of IFS apprenticeship candidates in relation to gender equality and social mobility in Ireland. This study also offers valuable insights as to the gendered nature of these “new” apprenticeships and examine whether these programmes provide opportunities for social mobility.

Design/methodology/approach

Implementing a quantitative approach, underpinned by a positivist stance, this study analyses Irish national apprenticeship data relating to IFS programmes (n = 1118). Non-parametric tests were applied in the analysis of the gender dimension, while to analyse social mobility, the socio-economic status and spatial profile of candidates were compiled and analysed using the Pobal HP Deprivation Index (SA).

Findings

The findings revealed more women are undertaking non-traditional apprenticeship programmes as compared with traditional craft apprenticeships. Within the IFS context, while female participation was seen to be growing, gender divergence was observed in terms of programme level, with a greater number of men, as compared with women, engaging in higher-level degree apprenticeship programmes. The findings also show that IFS apprentices are primarily from socio-economic areas that are above average. This trend indicates a distinctive candidate who is more aligned with the sectoral profile of IFS than that of traditional apprenticeship programmes. Such findings reveal that the “widening participation” aim of IFS apprenticeships is not yet fully realised with issues of gender inequality and social mobility persistent within the wider IFS sector.

Originality/value

This study provides an important dimension to both academic and practitioner literature concerning apprenticeships. To date, there has been a proliferation of publications concerning the beneficial impact of skills and vocational-led apprenticeships. However, limited attention has been directed to non-traditional apprenticeships and even less still within the setting of IFS. This research initiates the process of addressing that gap within an Irish context. This study also adds to the existing apprenticeship discourse regarding issues of gender and social mobility by examining the gendered nature of IFS apprenticeships and well as assessing whether these apprenticeships aid social mobility.
Exporting is a team sport: the link between management training and performance in SMEs
Authors: Idris Bochra , Saridakis George , Georgellis Yannis , Lai Yanqing , Johnstone Stewart
Published: December 2023

Purpose

This paper examines how soft skills training for owner-managers affects the financial performance of exporting small and medium-sized enterprises (SMEs). Furthermore, the authors examine the differential influence of specific owner-manager skills, such as “team working skills”, “technical skills” and “leadership skills”, on performance.

Design/methodology/approach

The paper utilises the Longitudinal Small Business Survey, which is a nationally representative employer dataset of UK SMEs with up to 249 employees, including those with no employees. The dataset contains information on firms' turnover, export status of goods or services and training provision for employees or owner-managers.

Findings

The results suggest that owner-manager's training has a positive effect on turnover in non-exporting firms. Moreover, a combination of soft and hard skills is associated with higher turnover in exporting firms. Amongst the specific skills of owner-managers, training on “team working” has the most significant impact on exporting SMEs' performance.

Practical implications

The authors' findings imply that managerial training to develop soft skills such as leadership, decision-making and communication is a worthwhile investment. The knowledge that owner-managers acquire through soft and hard skills training enables them to develop essential internationalisation competencies. Moreover, the authors demonstrate that teamwork is a significant predictor of performance.

Originality/value

The authors contribute to the literature by examining the role of owner-managers' training in shaping internal systems, structure, processes and internationalisation strategies, thus affecting SMEs performance. The authors' also provide a nuanced analysis of how various types of soft and hard skills underpin the successful implementation of internationalisation initiatives.
Digital investment, intellectual capital and enterprise value: evidence from China
Authors: Bai Fuping , Shang Mengting , Huang Yujie , Liu Donghui
Published: December 2023

Purpose

Based on resource-based theory and intellectual capital theory, this paper aims to investigate the impact of digital investment on enterprise value and the mediating role of intellectual capital. Additionally, it explores the heterogeneous impacts of digital investment on enterprise value and intellectual capital.

Design/methodology/approach

The study utilizes a sample of listed companies in Chinese A-shares from 2013 to 2020. The entropy-weighted method is applied to measure digital investment from two dimensions: scale and increment. Finally, the research hypotheses are tested through multiple regression analysis.

Findings

The empirical results demonstrate that digital investment significantly and positively impacts enterprise value. From the channel mechanism test, digital investment can enhance enterprise value by influencing intellectual capital through human, structural and relational capital. Of these, the mediating effect of human capital is the most significant. Moreover, the impacts of digital investment on enterprise value and intellectual capital are related to the industry sectors. In the agricultural sector, digital investment has adverse effects. In the industrial and service sectors, digital investment promotes intellectual capital and enterprise value. However, in the service sector, the impact on relational capital is not significant, and the mediating effect of relational capital does not hold.

Research limitations/implications

This research has a limited potential for generalization due to the lack of standard measurement models for the exploration of digital investment.

Practical implications

The research findings are valuable for assessing the economic effects of digital investment comprehensively and providing essential information for policy formulation and strategy implementation.

Originality/value

This study represents the first attempt to evaluate the relationship between digital investment and enterprise value using the entropy-weighted method. In addition, this study investigates the mediating role of intellectual capital.
Job happiness: influence of work flexibility through work-life balance and gender moderation
Authors: Hernández Martínez Luz Esmeralda , Chunga-Liu Zeidy Edith
Published: December 2023

Purpose

This research aims to determine the influence that work flexibility (WF) has on the happiness of workers through the work and personal life balance, work-life balance (WLB), as a mediating variable, as well as the moderating role of gender between WLB and job happiness (JH). A structural model that describes the interactions between these study variables is proposed.

Design/methodology/approach

A quantitative approach was used. The data were collected by non-probabilistic sampling, surveying 200 mid-level employees in small and medium industrial enterprises (industrial SMEs). The proposed hypotheses were analyzed and tested using partial least squares structural equation modeling.

Findings

The results confirmed the hypotheses presented. In the relation of WLB and JH, positive work-family and family-work interactions would result in a greater increase in JH in the women group compared to men, and special characteristics were found in the variables in the Mexican context.

Practical implications

This study will provide information to those responsible for the human resources departments of companies to design and implement good practices in which importance can be given to labor agreements involving WF and the implementation of WLB policies differentiated by gender to generate happiness at work.

Originality/value

The JH construct proposed by Fisher (2010) was applied, and its relationship with WF and WLB in a post-pandemic context was studied. The research applied to supervisors and area managers of industrial SMEs reflects the importance of considering the balance between their life and work to achieve JH, understanding it as job satisfaction and more commitment to work, in addition to considering the differences by gender.
The effect of women’s entrepreneurship on corporate social responsibility
Authors: Prialé María Angela , Dávalos Jorge E. , Daza Brian , Ninahuanca E. Frances
Published: December 2023

Purpose

The purpose of this paper is to identify the causal (not correlational) effect of women’s entrepreneurship on corporate social responsibility (CSR) practices in Latin America.

Design/methodology/approach

This study builds on a hitherto unexploited sparse data set on Latin American B Corporations to identify the causal relationship of interest and on a (synthetic) instrumental variable method.

Findings

The results confirm that women’s entrepreneurship has a positive causal effect on social responsibility. This study finds that an increase of 1% in the proportion of women entrepreneurs leads to an increase of 0.5 in the B Impact Assessment score, the CSR indicator.

Originality/value

This study contributes to the literature by providing robust statistical evidence of a causal relationship between women entrepreneurs and social responsibility practices in the Latin American context. This research captures the multidimensional nature of social responsibility by using a comprehensive and vast metric of CSR obtained from the data of the B Impact Assessment tool. This study illustrates how machine learning methods can be used to address the lack of structure of the Latin American B Impact Assessment data.
Knowledge in the public realm – the educative agent
Authors: Charman Karen
Published: December 2023

Purpose

The purpose of the project was to intervene in a deficit reading of communities. This article engages public pedagogy in a way that suggests a new approach to the field. To this end, both the terms public and pedagogy are interrogated.

Design/methodology/approach

The approach in this paper is an analysis of a qualitative research project: the knowledge project and pop-up school. The theoretical framework used to undertake the analysis of this project is Hannah Arendt's conceptualisation of the public realm and Michele Foucault's use of parrhesia (the truth teller), alongside Foucault's work on power.

Findings

This article offers a whole new subject position that of the educative agent. Further, this article suggests that the educative agent takes a carriage of knowledge and therefore enacts authority.

Originality/value

This article is an original theoretical engagement with knowledge, authority and power.