bluuebunny/crossref_metadata_2025 huggingface dataset:
Signaling downstream of tumor-stroma interaction regulates mucinous colorectal adenocarcinoma apicobasal polarity
Authors: Pasquier Nicolas , Isomursu Aleksi , Hamidi Hellyeh , Mathieu Jacques R.R. , Härkönen Jouni , Follain Gautier , Desterke Christophe , Fusilier Zoé , Solis Junel , Belaya Irina , Kankaanpää Pasi , Barresi Valeria , Cartry Jérôme , Bedja Sabrina , Jaulin Fanny , Ivaska Johanna
Published: November 2024

Mucinous colorectal carcinoma (MUC CRC) dissemination into the tumor stroma and metastasis to multiple organs, including the peritoneum, is associated with poor prognosis. Disseminating MUC CRCs exhibit either a conventional ‘apical-in’ or an inverted ‘apical-out’ polarity phenotype that influence patient outcome. Identifying the mechanisms controlling MUC CRC polarity is critical to understand disease progression. Here, we analyze patient-derived MUC CRC xenografts, with apical-in or apical-out polarity, ex vivo or within collagen gels to mimic the peritumoral stroma. Single-cell analyses reveal α2β1-integrin as a key collagen-binding receptor in these models. Collagen–α2β1-integrin interaction activates Src and ERK/MAPK signaling and upregulates the expression of SorLA, an endosomal sorting receptor. SorLA supports apical-in polarity and carcinoma-stroma interactions by promoting integrin recycling to the plasma membrane and HER2/HER3 expression through a positive feedback mechanism. Accordingly, we observe positive correlation between HER2, HER3 and SorLA in patient samples with the highest HER2 expression in apical-in-presenting tissues. Treatment of tumor spheres with clinically relevant HER2/HER3-targeting antibodies reverts sphere polarity and impedes collagen remodeling and adhesion to mouse peritoneum. This SorLA—integrin—HER2/HER3 signaling axis may represent a basis for MUC CRC-patient stratification and shed light on other carcinomas with similar apical-out phenotypes.
Assessing the performance of current strain resolution tools on long-read metagenomes
Authors: Afolayan Ayorinde O. , Montaño Stefany Ayala , Akintayo Ifeoluwa J. , Duarte dos Santos Leonardo , Reuter Sandra
Published: November 2024

Recent advances in long-read sequencing-based methods have greatly enhanced genomics and public health applications. However, the challenge of effectively distinguishing strains within microbial communities from clinical samples using these technologies restricts their widespread use. We assessed the strain resolution capabilities of three currently available bioinformatics tools—TRACS, Strainy, and Strainberry—using both mock communities and authentic metagenomic datasets.

Following sample preparation and long-read sequencing using the GridION sequencing platform, raw reads were processed using TRACS, aligning them to a custom reference database, while Strainberry and Strainy mapped reads to metagenome assemblies for strain resolution. Performance on mock microbial community was assessed by comparing predicted microbiota composition to the expected composition, and on both mock and authentic datasets by evaluating strain-resolved genome assemblies. Computational efficiency was measured in terms of task execution time, single-core CPU usage, and physical memory usage.

TRACS demonstrated substantial agreement with the known composition, achieving a median score of 86.7% forEscherichia coli-dominant communities and 94.7% forKlebsiella pneumoniae-dominant communities. Strainberry and Strainy exhibited improved concordance after excluding strains with a genome size below 1 Mb, thus showcasing comparable performance metrics to TRACS. In mock and real metagenomic datasets, TRACS demonstrated the highest haplotype completeness compared to the other two tools, while Strainy demonstrated the highest haplotype accuracy. All tools were able to allocate strains to their respective transmission clusters (< 20 SNPs), albeit with varying degrees of success. Except for single core CPU usage, TRACS outperformed Strainy and Strainberry in terms of speed and computational efficiency.

Our study underscores the utility of TRACS, Strainy, and Strainberry in resolving strains within microbial communities from clinical samples. TRACS stands out for its better haplotype completeness and computational efficiency, suggesting its potential to streamline advanced genomic analyses and public health initiatives.
Aphid effectors suppress plant immunity via recruiting defence proteins to processing bodies
Authors: Liu Qun , Neefjes Anna C. M. , Kobylinska Roksolana , Mugford Sam T. , Marzo Mar , Canham James , Schuster Mariana , van der Hoorn Renier A. L. , Chen Yazhou , Hogenhout Saskia A.
Published: November 2024

Aphids are small insects that have developed specialized mouthparts and effector proteins to establish long-term relationships with plants. The peach-potato aphid,Myzus persicae, is a generalist, feeding on many plant species and capable of transmitting numerous pathogens. This study reveals how host-responsive cathepsins B (CathB) in the oral secretions ofM. persicaefacilitate aphid survival by modulating plant immune responses. Aphid CathB localize to processing bodies (p-bodies) and recruit key immune regulators EDS1, PAD4, and ADR1 to these bodies, suppressing plant defenses. A plant protein, Acd28.9 (Hsp20 family), counteracts this CathB activity and contributes to plant resistance to aphids. These findings highlight a novel role for p-bodies in plant immunity and uncover a plant resistance mechanism to aphid infestation.
BAZ1A, an Imitation Switch (ISWI) protein, interacts and facilitates the recruitment of E2F1 to activate the E2F transcription program
Authors: Prajapati Bidisha , Chowdhury Abhishek , Prasasvi Kaval Reddy , Garg Lakshay , Somasundaram Kumaravel
Published: November 2024

ISWI (ImitationSwitch) family of chromatin remodeling complexes mobilize nucleosomes to regulate DNA-template associated functions. Analysis of glioblastoma (GBM) transcriptome datasets revealed that BAZ1A (BromodomainAdjacent toZinc Finger Domain1A) is a highly expressed ISWI family member. RNAi-based depletion or inhibition by a small molecule inhibited the survival/migration of glioma cells and glioma stem-like cells (GSCs), sensitized glioma cells to Temozolomide but did not affect normal astrocytes. BAZ1A-silencing arrested cells in the G1 phase and induced apoptosis. While GO analysis of BAZ1A regulated transcriptome showed enrichment of “cell cycle” related terms, GSEA showed a depletion of the “HALLMARK_E2F_TARGETS” gene set with the highest significance, indicating a nonfunctional E2F transcription program. BAZ1A silencing and overexpression experiments confirmed the requirement of BAZ1A for the E2F transcription program by identifying E2F1 as the primary target. ChIP experiments revealed that BAZ1A and E2F1 bind to the E2F1 promoter. ChIP-ReChIP demonstrated that BAZ1A-bound chromatin fragments are enriched for E2F1 protein on the E2F1 promoter at specific sites. SMARCA1/5, ATPase subunits of the ISWI family, also exhibited binding to the E2F1 promoter. BAZ1A depletion decreased the DNaseI sensitivity of E2F1 binding regions of the E2F1 promoter. Co-immunoprecipitation experiments revealed an interaction between BAZ1A and E2F1 and the presence of an E2F1-BAZ1A-SMARCA1/5 complex. Finally, BAZ1A silencing inhibited glioma tumor growth in an orthotopic xenograft mouse model. Our results demonstrate that BAZ1A containing ISWI complex recruits E2F1 to activate the E2F transcription program, thus promoting G1-S progression and highlighting BAZ1A as a potential therapeutic target.
Phospholipid Scramblase 1 (PLSCR1) Regulates Interferon-Lambda Receptor 1 (IFN-λR1) and IFN-λ Signaling in Influenza A Virus (IAV) Infection
Authors: Yang Alina X. , Ramos-Rodriguez Lisa , Sorkhdini Parand , Yang Dongqin , Norbrun Carmelissa , Majid Sonoor , Zhang Yong , Holtzman Michael J. , Boyd David F. , Zhou Yang
Published: November 2024

Phospholipid scramblase 1 (PLSCR1) is an antiviral interferon-stimulated gene (ISG) that has several known anti-influenza functions such as interfering with viral nuclear import, regulating toll-like receptor (TLR) 9 and potentiating the expression of other ISGs. However, the exact mechanisms of anti-flu activity of PLSCR1 in relation to its expression compartment and enzymatic activity, and the molecular and cellular mechanisms involved have not been completely explored. Moreover, only limited animal models have been studied to delineate its role at the tissue level in influenza infections. We hypothesize that PLSCR1 protects hosts against IAV infection by regulating type 3 interferon (IFN-λ) signaling pathways. Our results showed that Plscr1 expression was highly induced by IAV infectionin vivoand in epithelial cells treated with IFN-λ. We found thatPlscr1knockout (KO) mice exhibited exacerbated body weight loss, decreased survival rates, heightened viral replication, and increased lung damage. Interestingly, transcriptomic analyses demonstrated that Plscr1 was required for type 3 interferon receptor (Ifn-λr1) expression, and impaired expression of Ifn-λr1 and downstream ISGs may be responsible for delayed viral clearance in Plscr1 KO mice. In addition, Plscr1 interacted with Ifn-λr1 within the epithelial compartment following IAV infection, suggesting Plscr1 may modulate IFN-λ signaling via protein-protein interactions. Finally, single-cell RNA sequencing data indicated thatPlscr1expression was significantly upregulated in ciliated airway epithelial cells in mice following IAV infection. Consistently,Plscr1floxStopFoxj1-Cre+mice with ciliated epithelial cell-specific Plscr1 overexpression showed reduced susceptibility, less inflammation and enhanced Ifn-λr1 expression in IAV infection. Our research will elucidate virus-host interactions and pave the way for the development of novel anti-influenza drugs that target human elements like PLSCR1, thereby mitigating the emergence of drug-resistant IAV strains.
Clinical and Molecular Characterization of Glioma Patients: miR-21 Expression as a Prognostic Biomarker in Tissue and Serum
Authors: Laghari Altaf Ali , Sufiyan Sufiyan , Amin Wajiha , Adnan Umer , Naeem Sana , Abidi Syed Hani , Ilyas Sahar , Uddin Siraj , Bajwa Mohammad Hamza , Enam Syed Ather , Mughal Nouman
Published: November 2024

Background

Glioma remains challenging due to high recurrence rates and resistance to treatment. Diagnosis and follow-up in resource-constrained regions often leads to significant patient attrition. Serum microRNA (miRNA) expression profiles, which have been shown to correlate with tissue expression profiles, are detectable in peripheral blood samples, providing a promising avenue for non-invasive and repeatable liquid biopsies. miR-21 shows promise in many populations; however, there is a dearth of data from our region.

Methodology

We collected 90 tumor tissues, 42 pre- and post-operative serum samples from glioma patients, and included 10 normal tissue adjacent to the tumor (NATs) along with serum samples from 8 healthy individuals and analyzed for miR-21 expression through RT-qPCR. Shapiro Wilk test was applied to calculate data distribution, ANOVA, Fisher’s exact, and Wilcox test, along with pairwise Student’s t-test, were applied to determine the differences in gene expression. The expression level of miR-21 was assessed for correlation with Kaplan-Meier survival curves and different molecular markers (IDH, Ki-67, ATRX and p53). The quantitative hazard ratio was determined using Cox regression analysis.

Results

miR-21 expression in tissue increased with the mean log fold expression 0.101 (median fold = 2.35) in grade 2, 1.00 (median fold = 7.49) in grade 3 and 1.53 (median fold = 26.0) in grade 4 for glioma patients. The expression level showed significant difference between control tissue and grade 4 patients along with significant inter-comparison between grade 1 and grade 4, as well as grade 2 and grade 4.A significant elevated expression of miR-21 has been noticed in patients above 50 years of age. Similarly, in serum samples a significant decline in miR-21 expression was observed in post-operative samples as compared to pre-operative samples mean log fold in grade 2 is 1.30 (11.6-fold), grade 3 is 1.08 (15.3-fold) and grade 4 is 0.749 (13.2-fold). Furthermore, there was positive correlation of miR-21 expression with tumor volume. IDH-wildtype and high Ki-67 expression in gliomas showed significant upregulation of miR-21 compared to IDH-mutant and low Ki-67 respectively. Patients with low miR-21 expression had significantly longer overall survival (OS) than patients with high miR-21 expression. Quantitative hazard analysis indicates that patients in the high expression group have a 3.4 times higher risk of mortality (95% CI: 1.6-7.1), in comparison to patients in the low expression group with AUC of 0.742 (all p <0.05).

Conclusion

This study demonstrates the potential of microRNA 21 as a serum biomarker for early, cost-effective diagnosis of glioma. Furthermore, it may inform the development of targeted treatment strategies for various glioma grades, particularly in our population.
Accelerated growth of the scleractinian coralOrbicella faveolataunder turbid and polluted water conditions
Authors: Lizcano-Sandoval Luis , Marulanda-Gómez Angela , López-Victoria Mateo , Rodriguez-Ramirez Alberto
Published: November 2024

Cartagena Bay, Colombia, experienced historical changes in water quality, mainly due to dredging and channelization of the Canal del Dique, which connects the bay with the Magdalena River. In 1981 the largest dredging events occurred in the Canal del Dique, which negatively affected the water quality in the bay. In this bay, the coral reef of Varadero depicts high coral diversity and large coral colonies, showing apparent signs of a healthy ecosystem, under highly turbid and polluted waters. Here, we evaluated the potential effects of historical water quality changes and environmental variables on the coral skeletal growth ofOrbicella faveolata. We obtained coral growth information from 65 years in the period 1951–2015. Coral skeletal density was 0.73 g cm-3, linear extension 1.02 cm yr-1, and calcification 0.74 g cm-2yr-1. After 1981, significant changes in coral growth and luminescence were found: skeletal density decreased (9.9%), linear extension increased (6.6%), and skeletal luminescence was less intense (1.6%). In overall, Atlantic Multidecadal Oscillation (AMO) data explained changes in skeletal density (8–10%) and linear extension (7–19%). Air temperature explained changes in skeletal luminescence (22–45%). Water flow of the Canal del Dique did not contribute significantly to any coral growth and luminescence variables. The growth ofO. faveolatain Varadero Reef was characterized by low density skeletons and an accelerated linear extension, apparently influenced by the dredging events of 1981. Further research is required to understand coral growth responses and resilience to the conditions of high turbidity, pollution, and low light in Cartagena Bay.
Neural correlates of kinematic features of passive finger movement revealed by univariate and multivariate fMRI analyses
Authors: Pamplona Gustavo S. P. , Sulzer James , Beldzik Ewa , Lambercy Olivier , Ionta Silvio , Gassert Roger , Lewis-Peacock Jarrod
Published: November 2024

Finger movements are associated with a relatively large neural representation. Passive finger movement – which involves refraining from actively performing or resisting movement – is a robust approach to investigate the neural representation of kinesthesia and proprioception in the brain. While some studies have characterized the neural correlates of passive finger movement, they have relied solely on mass univariate analysis, potentially affecting result sensitivity. Additionally, limited consideration has been given to stimulus duration, a factor closely tied to some kinematic features (amplitude and velocity), which recently proposed modeling approaches now take into account. Here, we reanalyzed previously published data using univariate and multivariate analysis to understand how kinesthesia is neurally encoded in neurotypical subjects in two separate experiments. Systematic passive stimulation of the fingers was provided using an MR-compatible robot while functional magnetic resonance imaging data was recorded. Our analyses consisted of univariate and multivariate approaches, conducted separately for each kinematic feature and adjusted for stimulus duration, regardless of whether brain activation scales with it. We provide a detailed mapping of brain areas related to amplitude, velocity, and direction of passive finger movement, including sensorimotor, subcortical, and cerebellar areas. In general, multivariate pattern analysis was more sensitive than the univariate approach in identifying brain regions associated with passive finger movement. Our univariate analysis demonstrated that activity in sensorimotor and subcortical areas was higher for larger amplitudes and slower velocities, which opposes to the original study’s results, likely due to our treatment of stimulus duration as a confounder specified as a parametric modulator. A novel result, we also demonstrated that brain activity in sensorimotor areas was higher for extension compared to flexion of passive finger movement. In terms of kinematic features, a larger neural representation was found for amplitude and direction compared to velocity of passive finger movement. This indicates that kinesthesia and proprioception may be more reliant on displacement than kinematic aspects of passive finger movement. While univariate analyses are limited in addressing spatial heterogeneity and subject-level variability, our multivariate analyses showed increased sensitivity in identifying brain regions encoding passive movement. Our findings may extend the knowledge of how the brain encodes physical movements and may help design neurorehabilitation strategies.
Major changes in gene expression between strains of diapausing and non-diapause spruce budworm despite little evidence of genetic divergence
Authors: van der Burg Karin R. L. , Gauthier Jeff , Roe Amanda D. , Cusson Michel , Boyle Brian , Levesque Roger C. , Marshall Katie E.
Published: November 2024

To survive harsh winter conditions, many insects enter a state of dormancy called diapause which allows them to withstand extreme temperatures and lack of food. When diapause is induced, insects enter a state of arrested development and low metabolic rate. Because diapause and environmental conditions are closely linked, variation within and between species in diapause induction, depth, and duration is extremely common. Studies investigating the genetic underpinnings of diapause tend to focus on either different populations and/or environmental variation, which runs the risk of confounding the genetic signal either due to isolation-by-distance or variation in environmental conditions. We use the eastern spruce budworm (Choristoneura fumiferana) to circumvent these issues and investigate within-population variation in diapause.C. fumiferanausually diapauses as second instar larvae, but a small subset of individuals does not diapause and instead continues through development. This non-diapause phenotype can be selected to create a non-diapause strain. Here, we present a chromosome-level assembly of such a non-diapause strain, and compare it to an earlier published genome assembly of the diapause strain. We did not find evidence of major chromosome rearrangements, indicating that the genetic variation between strains is likely small and multi-genic. Gene expression comparisons between the strains indicate major gene expression changes, where genes associated with glycolysis and environmental signaling processing increase in expression in the diapause strain. Lastly, we found that gene expression diverges halfway through the first instar, and not before, indicating that the signal to induce diapause happens early in the first instar.

Significance statement

The ability to enter diapause is a crucial adaptation for many insects to survive cold winters. The genetic underpinnings of the diapause phenotype has been the target of many investigations. However, many of these studies focus on variation in diapause on between geographic regions or changes in environmental conditions, which can lead to confounding factors. Here, we focus on within-population variation in diapause in the eastern spruce budworm, with two strains established from the same source population that vary in their ability to induce diapause. We present a chromosome level assembly of the non-diapause strain, and report that genetic changes between the diapause and the non-diapause line are likely small and involve multiple loci. Gene expression differences were extensive, and mostly associated with mechanisms to avoid freezing. This work sets the stage to further investigate how minimal genetic changes can lead to large-scale phenotypic changes as impactful as diapause.
The Effect of Human Presence and Activity Type on Innovative Problem-Solving of Urban Eurasian Red Squirrels
Authors: Chow Pizza Ka Yee , Loukola Olli J , Solvi Cwyn
Published: November 2024

Humans impact wildlife positively and negatively, and increasing evidence shows that humans potentially play a major role in shaping cognition in wild animals. Recent evidence suggests, in particular, that the ability to innovate (an important cognitive ability for urban wildlife) can be affected by humans. However, the specific anthropogenic factors associated with shaping animal cognitive performance remain unclear.

Here, across 15 urban areas in Oulu, Finland, we recorded 64 wild Eurasian red squirrels’ interactions with a novel puzzle box (innovative problem-solving) to obtain a highly preferred food, hazelnuts.

We then examined how different levels of human presence nearby, types of activity (walking, dog walking, cycling, and playground activities), and distance to the nearest footpaths influenced squirrels’ innovative problem-solving ability – measured as solving success at the population level and solving latency at the individual level.

At the population level, higher mean human presence nearby significantly decreased the proportion of squirrels that successfully solved the novel food-extraction problem (“innovators”), and greater human presence nearby decreased first-visit solving latency at individual level. Except for cycling, all types of human activities (walking, dog walking, and playground activity) significantly decreased first-visit success rate. Dog walking and playground activity had a greater negative impact on success rate at the population level than walking. Dog walking was the only outstanding factor affecting first-success latency. We also detected interaction effects between the types of human activities and nearest footpath on overall success rate of all innovators.

These results provide evidence for the negative effect of specific human-related factors on squirrels’ innovative problem-solving abilities. These factors may also exert selective pressure, potentially shaping the evolution of wildlife cognition.
De novo identification of protein domains in cryo-electron tomography maps from AlphaFold2 models
Authors: Lu Yi , Chen Guanglin , Sun Fei , Zhu Yun , Zhang Zhiyong
Published: November 2024

In recent years, in situ cryo-electron tomography (cryo-ET) has emerged as a powerful method for visualizing structures of protein complexes within their native cellular environment. However, the resolution of in situ cryo-ET remains lower than that of in vitro cryo-electron microscopy single particle analysis (cryo-EM/SPA). Identifying proteins in a cryo-ET density map is particularly challenging owing to the limited visibility of side chains. To address this issue, we developed DomainSeeker, a tool designed for de novo identification of protein domains in cryo-ET maps of protein complexes. DomainSeeker integrates AlphaFold2-predicted models to partition proteins into domains using predicted aligned errors and a clique-based graph cluttering algorithm, and subsequently fits these domains into segmented density maps. Finally, it uses a two-dimensional scoring metric to identify the most probable domain of each density map. On a test set containing 26 model-based densities segmented from a sperm microtubule doublet map, DomainSeeker efficiently identified nearly all of these domains at both 6.5 Å and 10 Å. On another test set of 20 auto-segmented densities, 17 out of them were also determined. Furthermore, we successfully identified a new protein within an unmodeled region of this map.
A compendium ofbona fidereference markers for genuine plant-derived extracellular vesicles and their degree of phylogenetic conservation
Authors: Rodríguez de Lope Miriam M. , Sánchez-Pajares Ibone R. , Herranz Estela , López-Vázquez Cristina M. , González-Moro Ainara , Rivera-Tenorio Alan , Carlos González-Sanz , Sacristán Soledad , Chicano-Gálvez Eduardo , de la Cuesta Fernando
Published: November 2024

Although the field of plant-derived EVs (PDEVs) is experimenting an exponential growth, rigorous characterization complying with MISEV guidelines has not been yet implemented due to the lack ofbona fidereference markers. In this work, we have paved the way for the standardization of PDEV markers, providing the most profound proteomic data so far from apoplastic washing fluid-derived EVs, a sample enriched in genuine extracellular vesicles from plant tissue, as opposed to methods involving tissue disruption; of two reference plant species:Arabidopsis thaliana(Arath-EVs) andBrassica oleracea(Braol-EVs). Additionally, we have conducted an exhaustive analysis of the proteomic data available so far from genuine EVs from any plant species, evaluating current potential markers, together with those found in our proteomic analyses. Our results provide evidence supporting the potential use of the following families as PDEV markers: fasciclin-like arabinogalactan proteins (FLAs), patellins, germin-like proteins, aquaporins, heat shock 70 proteins, 14-3-3 like proteins, Rab proteins, and vacuolar-type ATPase complex subunits. Next, we analyzed the presence of orthologues and their degree of conservation throughout plant taxa, as well as in 2 reference species from the animal kingdom: human and mouse. Their degree of conservation was compared with that of current EV markers used in animal-derived EVs: CD63, CD81 and CD9. Among the protein families with potential to be used as PDEV markers, 3 were found to be plant-specific: FLAs, patellins and germin-like proteins. Among these, fasciclin-like arabinogalactan (FLA) proteins, in particular FLA1, FLA2 and FLA8, were recurrently identified in EVs from different plant sources showing great abundance and thus arise as a novel family of plant-specific GPI-anchored PDEV markers. Furthermore, FLAs hold promise as ideal PDEV markers since they have orthologues across the different plant subdivisions and display a similar phylogenetic distribution in plants to that of currently used markers in animals.
From high protection to lethal effect: diverse outcomes of immunization against invasive candidiasis with differentCandida albicansextracellular vesicles
Authors: Martínez-López Raquel , Molero Gloria , Parra-Giraldo Claudia , Cabeza Matías , Castejón Guillermo , García-Duran Carmen , Clemente Felipe , Hernáez María Luisa , Gil Concha , Monteoliva Lucía
Published: November 2024

Extracellular vesicles (EVs) fromCandida albicanscan elicit immune responses, positioning them as promising acellular vaccine candidates. We characterized EVs from an avirulentC. albicanscell wall mutant (ecm33Δ) and evaluated their protective potential against invasive candidiasis. EVs from the yeast (YEVs) and hyphal (HEVs) forms of the SC5314 wild-type strain were also tested, yielding high survival rates with SC5314 YEVs (91%) andecm33YEVs immunization (64%). Surprisingly, HEV immunization showed a dual effect, resulting in 36% protection but also causing premature death in some mice. Proteomic analyses revealed distinct profiles among the top 100 proteins in the different EVs which may explain these effects: a shared core of 50 immunogenic proteins such as Pgk1, Cdc19, and Fba1; unique, relevant immunogenic proteins in SC5314 YEVs, and proteins linked to pathogenesis, like Ece1 in SC5314 HEVs. Sera from SC5314 YEVs-immunized mice showed the highest IgG2a titers and moderate IL-17, IFN-γ, and TNF-α levels, indicating the importance of both humoral and cellular responses for protection. These findings highlight the distinct immunogenic properties ofC. albicansEVs, suggesting their potential in acellular vaccine development while emphasizing the need to carefully evaluate pathogenic risks associated with certain EVs.
Glutamic acid-lysine (EK) rich motif of RabD2 self-associates and regulates pathogenesis through multivesicular bodies pathway inE. histolytica
Authors: Navyaka P , Verma Kuldeep
Published: November 2024

Entamoeba histolytica, an enteric pathogen, causes disease by adhering to and destroying the host tissues. The interactions between the parasite and host tissue enable rewiring of the gene expression and global membrane trafficking in the parasite. A fine balance between cargoes/receptors endocytosis and exocytosis is required to establish infection in the host. Multivesicular bodies (MVBs) act as sorting platforms, delivering cargoes/receptors to lysosomes for degradation or secreting their content through plasma membrane fusion. Some of the small GTPases are known to control MVB biogenesis in various organisms. However, the functional contribution of Rab GTPases in MVB biogenesis is poorly studied inE. histolytica. Here, we identified a novel atypical protein RabD2, with an N-terminal glutamic acid-lysine rich motif and a C-terminal conserved Rab domain. Our biochemical and cell biological assays provide evidence that RabD2 self-associates, and this interaction is controlled by the N-terminal EK-rich motif and the GTPase activity mutants (in a nucleotide-specific manner). RabD2 localizes on the surface of MVBs and controls their biogenesis. In line with these findings, overexpression of RabD2 upregulates global ubiquitination, directing the down regulation of the heavy chain of GalNAc lectin, ultimately leading to decreased adherence ofE. histolyticatrophozoites to host cells. Thus, amoebic RabD2 is a new class of Rab protein that forms high-ordered self-association variants and regulates the pathogenicity ofE. histolyticathrough the biogenesis of MVBs.

Author Summary

Amoebiasis is an enteral infection caused byEntamoeba histolyticathat primarily remains asymptomatic but can eventually result in systemic complications like amoebic dysentery, liver abscess, and pulmonary effusions. Recent studies showed thatEntamoebaubiquitin is a robust antigen and linked with the invasive amoebiasis patient samples. Here, we identified a novel RabD2 that self-associates via its glutamic acid-lysine rich motif that causes high ubiquitination levels and biogenesis of multivesicular bodies. We uncovered for the first time that RabD2-mediated ubiquitin-dependent pathway is involved in the down regulation of the notable antigenic marker heavy chain of galactose-N-acetylgalactosamine lectin and thereby controls the parasite adherence to host cells. Further studies on crosstalk between parasite ubiquitination and antigenic receptors downregulation provide insights into how parasites use these strategies to establish the infection in the host intestine.
Expansion of a single Helitron subfamily inHydractinia symbiolongicarpussuggests a shared mechanism of cnidarian chromosomal extension
Authors: Kon Tetsuo , Kon-Nanjo Koto , Simakov Oleg
Published: November 2024

Helitrons are rolling-circle transposons that amplify through rolling-circle replication mechanism. Since Helitrons were relatively recently identified, their impact on genome evolution is still not fully understood. Here, we describe that a single Helitron subfamily specifically accumulates in the subtelomeric regions ofHydractinia symbiolongicarpus, a colonial hydrozoan cnidarian. Based on the sequence divergence, it is suggested that the Helitron subfamily underwent a burst of activity in the species’ recent history. Additionally, there is a IS3EU DNA element accumulation at the putative centromeric regions, as well as minisatellite sequences of approximately 200 bp in length extending from the telomere-side end of the Helitron towards the telomere. Phylogenetic analysis of Helitrons in theH. symbiolongicarpusgenome suggests that the Helitrons underwent local propagation at the subtelomeric regions. The single Helitron subfamily, along with the consecutive minisatellite, accounts for 26.1% of the genome coverage (126 Mb of the 483 Mb genome), which collectively contribute to the genome size increase observed inH. symbiolongicarpuscompared with other cnidarians. Homologous sequences of Helitron inH. symbiolongicarpuswere identified in the genomes of other cnidarians, suggesting that Helitrons in hydractinia were present in at least the common ancestor of Cnidaria. Furthermore, inNematostella vectensis, an anthozoan cnidarian, Helitrons were also accumulated at the subtelomeric regions. All these findings suggest that Helitrons constitute a common cnidarian mechanism of chromosomal extension through local amplification in subtelomeric regions, driving diverse genome expansions within the clade.
Optogenetic and chemical genetic tools for rapid repositioning of vimentin intermediate filaments
Authors: Pasolli Milena , Meiring Joyce C. M. , Conboy James P. , Koenderink Gijsje H. , Akhmanova Anna
Published: November 2024

Intermediate filaments (IFs) are a key component of the cytoskeleton, essential for regulating cell mechanics, maintaining nuclear integrity, positioning organelles, and modulating cell signaling. Unlike actin filaments and microtubules, IFs have slower dynamics, and current insights into IF function primarily come from studies using long-term perturbations, such as protein depletion or mutation. Here, we present tools that allow rapid manipulation of vimentin IFs in the whole cytoplasm or within specific subcellular regions by inducibly coupling them to microtubule motors, either pharmacologically or using light. Perinuclear clustering of vimentin had no strong effect on the actin or microtubule organization, cell spreading, and focal adhesions, but reduced cell stiffness. Mitochondria and endoplasmic reticulum sheets were repositioned together with vimentin, whereas lysosomes were only briefly repositioned and rapidly regained their normal distribution. Keratin was displaced along with vimentin in some cell lines but remained intact in others. Our tools help to study the immediate effects of vimentin perturbation and identify direct links of vimentin to other cellular structures.
mTORC1, the maestro of cell metabolism and growth
Authors: He Long , Cho Sungyun , Blenis John
Published: November 2024

The mechanistic target of rapamycin (mTOR) pathway senses and integrates various environmental and intracellular cues to regulate cell growth and proliferation. As a key conductor of the balance between anabolic and catabolic processes, mTOR complex 1 (mTORC1) orchestrates the symphonic regulation of glycolysis, nucleic acid and lipid metabolism, protein translation and degradation, and gene expression. Dysregulation of the mTOR pathway is linked to numerous human diseases, including cancer, neurodegenerative disorders, obesity, diabetes, and aging. This review provides an in-depth understanding of how nutrients and growth signals are coordinated to influence mTOR signaling and the extensive metabolic rewiring under its command. Additionally, we discuss the use of mTORC1 inhibitors in various aging-associated metabolic diseases and the current and future potential for targeting mTOR in clinical settings. By deciphering the complex landscape of mTORC1 signaling, this review aims to inform novel therapeutic strategies and provide a road map for future research endeavors in this dynamic and rapidly evolving field.
Advancements in prospective single-cell lineage barcoding and their applications in research
Authors: Zhang Xiaoli , Huang Yirui , Yang Yajing , Wang Qi-En , Li Lang
Published: November 2024

Single-cell lineage tracing (scLT) has emerged as a powerful tool, providing unparalleled resolution to investigate cellular dynamics, fate determination, and the underlying molecular mechanisms. This review thoroughly examines the latest prospective lineage DNA barcode tracing technologies. It further highlights pivotal studies that leverage single-cell lentiviral integration barcoding technology to unravel the dynamic nature of cell lineages in both developmental biology and cancer research. Additionally, the review navigates through critical considerations for successful experimental design in lineage tracing and addresses challenges inherent in this field, including technical limitations, complexities in data analysis, and the imperative for standardization. It also outlines current gaps in knowledge and suggests future research directions, contributing to the ongoing advancement of scLT studies.
Plasmon-enhanced Brillouin light scattering spectroscopy for magnetic systems: Theoretical model
Authors: Lozovski Valeri , Chumak Andrii V.
Published: November 2024

Brillouin light scattering (BLS) spectroscopy is an effective method for detecting spin waves in magnetic thin films and nanostructures. While it provides extensive insight into the properties of spin waves, BLS spectroscopy is impeded in many practical cases by the limited range of detectable spin wave wave numbers and its low sensitivity. Here we present a generalized theoretical model describing plasmon-enhanced BLS spectroscopy. Three types of plasmonic nanoparticles in the shape of an ellipsoid of rotation are considered: a single plasmon resonator, a sandwiched plasmonic structure in which two nanoparticles are separated by a dielectric spacer, and an ensemble of metallic nanoparticles on the surface of a magnetic film. The effective susceptibilities for the plasmonic systems at the surface of the magnetic film are calculated using the electrodynamic Green's function method, and the enhancement coefficient is defined. It is analytically shown that the ratio of the plasmon resonator height to its radius plays a key role in the development of plasmon-enhanced BLS spectroscopy. The developed model serves as a basis for the numerical engineering of the optimized plasmon nanoparticle morphology for BLS enhancement.

Published by the American Physical Society
2024
Seeding the decay of the false vacuum
Authors: Canaletti Matteo , Moss Ian G.
Published: November 2024

We present a theory of false vacuum decay induced by spherical nucleation seeds. The type of seed considered has a boundary characterized by surface energy terms. The theory applies to false vacuum decay at zero and finite temperatures. Seeded nucleation may be important for enabling future false vacuum decay experiments on analog systems using Bose Einstein condensates (BEC). We show that our theory of seeded nucleation at finite temperature applied to a potassium BEC in two spatial dimensions agrees with numerical, real-time, simulations.

Published by the American Physical Society
2024
An integrated risk prioritization and determination of activity-wise delay (IRPAD) framework for enhancing schedule management in tunnel projects
Authors: Shelake Abhaysinha Gunvantrao , Gogate Nivedita Gunesh
Published: November 2024

Purpose

This study aims to develop a comprehensive framework for addressing delays in tunnel construction projects by leveraging predictable risk factors. Tunnel projects often encounter scheduling delays due to inherent complexities and uncertainties, necessitating a proactive approach to prevent project underperformance.

Design/methodology/approach

The integrated risk prioritization and determination of activity-wise delay (IRPAD) framework is divided into four phases: identification and prioritization of risk factors, determination of activity-wise risk coefficients using MCDM-based methodology, obtaining the critical risk path, and developing an activity-wise risk matrix. Fault tree analysis (FTA) and event tree analysis (ETA) are employed to determine activity-wise risk coefficients based on expert responses.

Findings

The framework’s applicability in Indian tunnel projects is demonstrated through a real-world case study with 95% validation accuracy. The IRPAD framework enhances the delay analysis process and facilitates the provision of effective activity-wise mitigation measures.

Practical implications

The IRPAD framework predicts delays in infrastructure projects thus enhancing resilience and sustainability, supporting SDGs 9 and 11. It can be applied to a wide range of construction projects to improve project performance.

Originality/value

This research introduces novel concepts such as the three fold activity-wise risk matrix and the critical risk path, contributing to the development of the IRPAD framework for delay reduction. This framework offers valuable insights to practitioners in the construction industry.
Post occupancy evaluation of the relocatable modular construction method for temporary educational facilities
Authors: Nguyen Truong Dang Hoang Nhat , Park Soyeon , Jeong Jinhak , Ahn Yonghan
Published: November 2024

Purpose

This study aims to evaluate user satisfaction and perceptions of the relocatable modular school (RMS) system in South Korea. It seeks to identify key factors for improvement to enhance the performance of this innovative construction method, particularly in the temporary educational sector.

Design/methodology/approach

A comprehensive post occupancy evaluation (POE) was conducted, considering functional spaces, aesthetics, indoor environmental quality and technical aspects. This study also includes a comparative analysis with conventional school buildings to provide insights into the efficiency and potential of RMS.

Findings

Relocatable modular schools can achieve the equivalent quality of building performance and user satisfaction as those built using traditional construction methods. The satisfaction performance of both methods falls within the “satisfied” level, with mean scores ranging from 3.35 to 3.90. Notably, when compared to ES, RMS exhibits a marginally lower satisfaction level in functional performance but a higher satisfaction level in the areas of aesthetics, IEQ and technical performance. Key factors identified for enhancement include optimizing classroom shape, balancing the window-to-wall ratio, enhancing natural ventilation and addressing floor noise and vibration concerns.

Originality/value

This research is pioneering in evaluating user satisfaction and perceptions of RMS in South Korea, a relatively unexplored area. By taking a holistic approach and incorporating comparative analysis with traditional school buildings, the study provides valuable insights into the practical application and potential of modular construction in educational facilities. The results contribute significantly to the advancement of high-performance modular educational buildings, informing practitioners and stakeholders of user demands and guiding future developments in the field.
Does managerial CSR mindset always drive business performance?
Authors: Mensah Henry Kofi , Okyere Gilbert Anyowuo , Mensah Philip Opoku , Ledi Klenam Korbla , Forenten Eric Sie
Published: November 2024

Purpose

This study aims to investigate the relationship between managerial corporate social responsibility (CSR) mindset and business performance in small- and medium-sized enterprises (SMEs), focusing on the mediating role of CSR practices and the moderating influence of institutional forces.

Design/methodology/approach

A structured questionnaire was administered to 221 SME managers. The data was analysed using the Hayes process in SPSS to test the hypothesized relationships.

Findings

This study found that a managerial CSR mindset significantly improves operational and financial business performance. In addition, CSR practices mediate the relationship between managerial CSR mindset and business performance. Furthermore, institutional forces moderate this relationship, highlighting the critical role of external factors in shaping SME performance.

Practical implications

The findings suggest that SME managers should adopt a proactive managerial CSR mindset and integrate CSR into their core strategies to enhance business performance. Moreover, managers must be responsive to institutional forces as they adjust their strategy to meet external pressures to ensure sustainable performance.

Originality/value

This study demonstrates the theoretical explanation of how CSR practices serve as a conduit through which a managerial CSR mindset improves business performance under varying conditions of institutional forces.
Linking workplace spirituality, workplace incivility and employee silence: moderating role of dark triad
Authors: Chouhan Vikram Singh
Published: November 2024

Purpose

This study aimed to observe the effect of workplace spirituality (WPS) on employee silence. In addition, the study investigated the mediating role of workplace incivility on the relationship of WPS with employee silence. We further explored the WPS–workplace incivility link by testing the dark triad as the moderator.

Design/methodology/approach

We collected time-lagged data from 403 employees in the Indian hospitality industry. Statistical Package for Social Sciences (SPSS) and Partial Least Squares - Structural Equation Modeling (PLS-SEM) were used to observe the linkages among the study variables.

Findings

The results revealed that WPS is associated negatively with employee silence. The dark triad moderated the association between WPS and workplace incivility. Workplace incivility significantly mediated the association between WPS and employee silence.

Practical implications

The study findings would help organizations in promoting WPS to alleviate the occurrences of uncivil behavior at work and comprehend the negative consequences of workplace incivility such as employee silence.

Originality/value

To the best of the author’s knowledge, this study is the first of its kind to explore the linkage between WPS and employee silence. The paper makes a significant contribution by analyzing the interactive effect of personal (dark triad), environmental (WPS) and behavioral (workplace incivility) factors on employee silence.
Rethinking the deployment of learning assistants: Changing and reviewing practices
Authors: Vincent Kerry
Published: November 2024

Around the world, the number of learning assistants (LAs) employed in schools has increased dramatically over the last two decades. Underpinned by the global move towards more inclusive education, and consequently an increasingly diverse school population, they now play a key role in supporting learners with additional needs. A number of concerns have been raised in relation to common deployment practices, and the negative impact these have on students and the one‐to‐one support model has come under particular criticism. This article reports the outcome of a decision taken in one school to allocate learning assistants to classes to work alongside teachers rather than using them primarily for one‐to‐one support. In‐depth semi‐structured interviews were used to identify the impact of this change on both teachers and LAs. The research found that class‐based deployment strengthened communication between teacher and LA, enabled more effective collaborative work and resulted in more flexible use of limited LA hours. The article makes a case for the value of reviewing the deployment of LAs and illustrates how and why a change in deployment model can make a noticeable difference to teachers, LAs and the students they support.