bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning on multiple epigenetic features reveals H3K27Ac as a driver of gene expression prediction across patients with glioblastoma
Authors: Suita Yusuke , Bright Hardy , Pu Yuan , Toruner Merih Deniz , Idehen Jordan , Tapinos Nikos , Singh Ritambhara
Published: June 2024

Cancer cells show remarkable plasticity and can switch lineages in response to the tumor microenvironment. Cellular plasticity drives invasiveness and metastasis and helps cancer cells to evade therapy by developing resistance to radiation and cytotoxic chemotherapy. Increased understanding of cell fate determination through epigenetic reprogramming is critical to discover how cancer cells achieve transcriptomic and phenotypic plasticity.

Glioblastoma is a perfect example of cancer evolution where cells retain an inherent level of plasticity through activation or maintenance of progenitor developmental programs. However, the principles governing epigenetic drivers of cellular plasticity in glioblastoma remain poorly understood. Here, using machine learning (ML) we employ cross-patient prediction of transcript expression using a combination of epigenetic features (ATAC-seq, CTCF ChIP-seq, RNAPII ChIP-seq, H3K27Ac ChIP-seq, and RNA-seq) of glioblastoma stem cells (GSCs). We investigate different ML and deep learning (DL) models for this task and build our final pipeline using XGBoost. The model trained on one patient generalizes to another one suggesting that the epigenetic signals governing gene transcription are consistent across patients even if GSCs can be very different. We demonstrate that H3K27Ac is the epigenetic feature providing the most significant contribution to cross-patient prediction of gene expression. In addition, using H3K27Ac signals from patients-derived GSCs, we can predict gene expression of human neural crest stem cells suggesting a shared developmental epigenetic trajectory between subpopulations of these malignant and benign stem cells.

Our cross-patient ML/DL models determine weighted patterns of influence of epigenetic marks on gene expression across patients with glioblastoma and between GSCs and neural crest stem cells. We propose that broader application of this analysis could reshape our view of glioblastoma tumor evolution and inform the design of new epigenetic targeting therapies.
Intraperitoneal activation of myeloid cells clears ascites and reveals IL27-dependent regression of metastatic ovarian cancer
Authors: Murphy Brennah , Miyamoto Taito , Manning Bryan S. , Mirji Gauri , Ugolini Alessio , Kannan Toshitha , Hamada Kohei , Zhu Yanfang Peipei , Claiborne Daniel T. , Huang Lu , Zhang Rugang , Nefedova Yulia , Kossenkov Andrew , Veglia Filippo , Shinde Rahul , Zhang Nan
Published: June 2024

Patients with metastatic ovarian cancer (OvCa) have a 5-year survival rate of less than 30% due to persisting dissemination of chemoresistant cells in the peritoneal fluid and the immunosuppressive microenvironment in the peritoneal cavity. Here, we report that intraperitoneal administration of β-glucan and IFNγ (BI) induced robust tumor regression in clinically relevant models of metastatic OvCa. BI induced tumor regression by controlling fluid tumor burden and activating localized antitumor immunity. β-glucan alone cleared ascites and eliminated fluid tumor cells by inducing intraperitoneal clotting in the fluid and Dectin-1-Syk-dependent NETosis in the omentum. In omentum tumors, BI expanded a novel subset of immunostimulatory IL27+ macrophages and neutralizing IL27 impaired BI efficacyin vivo. Moreover, BI directly induced IL27 secretion in macrophages where single agent treatment did not. Finally, BI extended mouse survival in a chemoresistant model and significantly improved chemotherapy response in a chemo-sensitive model. In summary, we propose a new therapeutic strategy for the treatment of metastatic OvCa.
The Role of Biopsy Position and Tumor-Associated Macrophages for Predictions on Recurrence of Malignant Gliomas: An In Silico Study
Authors: Shojaee Pejman , Weinholtz Edwin , Schaadt Nadine S. , Hatzikirou Haralampos
Published: June 2024

Predicting the biological behavior and time to recurrence (TTR) of high-grade diffuse gliomas (HGG) after the maximum safe neurosurgical resection and combined radiation and chemotherapy plays a pivotal role in planning the clinical follow-up, the choice of potentially necessary second-line treatment, and the quality of life of patients faced with the diagnosis of a malignant brain tumor. The current standard-of-care (SoC) for HGG includes follow-up neuroradiological imaging to detect recurrence as early as possible and several clinical, neuropathological, and radiological prognostic factors with limited accuracy toward predicting TTR. Herein, using an in-silico analysis, we aim to improve predictive power towards TTR considering the role of (i) prognostically relevant information available by diagnostics used in current SoC, (ii) advanced image-based information that is currently not part of the standard diagnostic workup, such as interface of tumor and normal tissue (edge) features and quantitative data specific for the position of biopsies within the tumor, and (iii) information on tumor-associated macrophages. In particular, we introduce a state-of-the-art spatio-temporal model of tumor-immune interactions, emphasizing the interplay between macrophages and glioma cells. This model serves as a synthetic reality for assessing the predictive value of various features. We generate a cohort of virtual patients based on our mathematical model. Each patient’s dataset includes simulated T1 and FLAIR MRI volumes, and simulated results on macrophage density and proliferative activity either in a specified part of the tumor, namely tumor core or edge (”localized”), or unspecified (”non-localized”). We impose different levels of noise to enhance the realism of our synthetic data. Our findings reveal that macrophage density at the tumor edge contributes to a high predictive value of feature importance for the selected regression model. Moreover, there is a lower MSE and higherR2for the ”localized” biopsy in prediction accuracy toward recurrence post-resection compared with ”non-localized” specimens. In conclusion, the results show us that localized biopsies can bring more information about the tumor behavior, especially at the interface of tumor and normal tissue (Edge).
Network-Based Analysis Identifies Targetable Pathways in Comorbid Type II Diabetes and Neuropsychiatric Disorders
Authors: Onisiforou Anna , Zanos Panos
Published: June 2024

Comorbid diseases complicate patient outcomes and escalate healthcare costs, necessitating a deeper mechanistic understanding. Neuropsychiatric disorders (NPDs) such as Neurotic Disorder, Major Depression, Bipolar Disorder, Anxiety Disorder, and Schizophrenia significantly exacerbate Type 2 Diabetes Mellitus (DM2), often leading to suboptimal treatment outcomes. The neurobiological underpinnings of this comorbidity remain poorly understood. To address this, we developed a novel pathway-based network computational framework that identifies critical common disease mechanisms between DM2 and the five prevalent NPDs. Our approach involves reconstructing an integrated DM2 ∩ NPDs KEGG pathway network and applying two complementary analytical methods, including the “minimum path to comorbidity” method to identify the shortest pathways fostering comorbid development. This analysis uncovered shared pathways like the PI3K-Akt signaling pathway and highlighted key nodes such as calcium signaling, MAPK, estrogen signaling, and apoptosis pathways. The dysregulation of these pathways likely contributes to the development of DM2-NPDs comorbidity. Our model not only elucidates the intricate molecular interactions driving this comorbidity but also identifies promising therapeutic targets, paving the way for innovative treatment strategies. This framework can be adapted to study other complex comorbid conditions, offering broad implications for improving patient care.
Adaptive Container Service: a New Paradigm for Robust and Optimized Bioinformatics Workflow Deployment in the Cloud
Authors: Kang Kevin , Wo Jinwen , Jiang Jon , Wang Zhong
Published: June 2024

We propose Adaptive Container Service (ACS), a new paradigm for deploying bioinformatics workflows in cloud computing environments. By encapsulating the entire workflow within a single virtual container, combined with automatic workflow checkpointing and dynamic migration to appropriately scaled containers, ACS-based deployment demonstrates several key advantages over alternative strategies: it enables optimal resource provision to any workflow that comprise of multiple applications with diverse computing needs; it provides protection against application-agnostic out-of-memory (OOM) errors or spot instance interruptions; and it reduces efforts required for workflow development, optimization, and management because it runs workflows with minimal or no code modifications. Proof-of-concept experiments show that ACS avoided both under- and over-provisioning in monolithic single-container deployment. Despite being deployed as a single container, it achieved comparable resource utilization efficiency as optimized Nextflow-managed, multi-modular workflows. Analysis of over 18,000 workflow runs demonstrated that ACS can effectively reduce workflow failures by two-thirds. These findings suggest that ACS frees developers from navigating the complexity of deploying robust workflows and rightsizing compute resources in the cloud, leading to significant reduction in workflow development time and savings in cloud computing costs.
Medulloblastoma Spatial Transcriptomics Reveals Tumor Microenvironment Heterogeneity with High-Density Progenitor Cell Regions Correlating with High-Risk Disease
Authors: Chien Franklin , Michaud Marina E. , Bakhtiari Mojtaba , Schroff Chanel , Snuderl Matija , Velazquez Vega Jose E. , MacDonald Tobey J. , Bhasin Manoj K.
Published: June 2024

The tumor microenvironment (TME) of medulloblastoma (MB) influences progression and therapy response, presenting a promising target for therapeutic advances. Prior single-cell analyses have characterized the cellular components of the TME but lack spatial context. To address this, we performed spatial transcriptomic sequencing on sixteen pediatric MB samples obtained at diagnosis, including two matched diagnosis-relapse pairs. Our analyses revealed inter- and intra-tumoral heterogeneity within the TME, comprised of tumor-associated astrocytes (TAAs), macrophages (TAMs), stromal components, and distinct subpopulations of MB cells at different stages of neuronal differentiation and cell cycle progression. We identified dense regions of quiescent progenitor-like MB cells enriched in patients with high-risk (HR) features and an increase in TAAs, TAMs, and dysregulated vascular endothelium following relapse. Our study presents novel insights into the spatial architecture and cellular landscape of the medulloblastoma TME, highlighting spatial patterns linked to HR features and relapse, which may serve as potential therapeutic targets.
Bee microbiomes in a changing climate: investigating the effects of temperature on solitary bee life history and health
Authors: Crowley Bailey L. , Schaeffer Robert N.
Published: June 2024

Climate change is rapidly warming thermal environments, an important abiotic stimulus governing bee development and species interactions. Increasing evidence suggests that solitary bees rely upon pollen provision microbes for successful development. The effects of heat stress on provision microbiota and resulting consequences for larval health and development, however, remain to be examined. We performed anin vitrostudy to investigate the effects of thermal environment on provision microbiome composition and measured fitness outcomes forOsmia lignarialarvae. Elevated temperatures moderately increased the mean rank relative abundance ofArsenophonus, a putative son-killing symbiont. While pollen sterilization removedArsenophonusfrom microbe-rich provisions, larval survivorship did not significantly differ between bees reared on microbe-rich and sterile diets. In contrast to previous research in solitary bees, larvae reared on sterile provisions weighed more and had higher total fat contents, with temperature moderating the degree of difference. As anticipated, we observed a negative relationship between the duration of larval development and temperature. Our results indicated that an intact provision microbiota may not always improve bee fitness, and that bee-microbe interactions during larval development may contribute to the size-shrinking effect observed for cavity-nesting bees under warming conditions.
In silico generation and augmentation of regulatory variants from massively parallel reporter assay using conditional variational autoencoder
Authors: Jin Weijia , Xia Yi , Thela Sai Ritesh , Liu Yunlong , Chen Li
Published: June 2024

Predicting the functional consequences of genetic variants in non-coding regions is a challenging problem. Massively parallel reporter assays (MPRAs), which are anin vitrohigh-throughput method, can simultaneously test thousands of variants by evaluating the existence of allele specific regulatory activity. Nevertheless, the identified labelled variants by MPRAs, which shows differential allelic regulatory effects on the gene expression are usually limited to the scale of hundreds, limiting their potential to be used as the training set for achieving a robust genome-wide prediction. To address the limitation, we propose a deep generative model, MpraVAE, toin silicogenerate and augment the training sample size of labelled variants. By benchmarking on several MPRA datasets, we demonstrate that MpraVAE significantly improves the prediction performance for MPRA regulatory variants compared to the baseline method, conventional data augmentation approaches as well as existing variant scoring methods. Taking autoimmune diseases as one example, we apply MpraVAE to perform a genome-wide prediction of regulatory variants and find that predicted regulatory variants are more enriched than background variants in enhancers, active histone marks, open chromatin regions in immune-related cell types, and chromatin states associated with promoter, enhancer activity and binding sites of cMyC and Pol II that regulate gene expression. Importantly, predicted regulatory variants are found to link immune-related genes by leveraging chromatin loop and accessible chromatin, demonstrating the importance of MpraVAE in genetic and gene discovery for complex traits.
A large-scale optogenetic neurophysiology platform for improving accessibility in NHP behavioral experiments
Authors: Griggs Devon J. , Bloch Julien , Stanis Noah , Zhou Jasmine , Fisher Shawn , Jahanian Hesamoddin , Yazdan-Shahmorad Azadeh
Published: June 2024

Optogenetics has been a powerful scientific tool for two decades, yet its integration with non-human primate (NHP) electrophysiology has been limited due to several technical challenges. These include a lack of electrode arrays capable of supporting large-scale and long-term optical access, inaccessible viral vector delivery methods for transfection of large regions of cortex, a paucity of hardware designed for large-scale patterned cortical illumination, and inflexible designs for multi-modal experimentation. To address these gaps, we introduce a highly accessible platform integrating optogenetics and electrophysiology for behavioral and neural modulation with neurophysiological recording in NHPs. We employed this platform in two rhesus macaques and showcased its capability of optogenetically disrupting reaches, while simultaneously monitoring ongoing electrocorticography activity underlying the stimulation-induced behavioral changes. The platform exhibits long-term stability and functionality, thereby facilitating large-scale electrophysiology, optical imaging, and optogenetics over months, which is crucial for translationally relevant multi-modal studies of neurological and neuropsychiatric disorders.

Graphical Abstract
Exploration and exploitation are flexibly balanced during local search in flies
Authors: Goldschmidt Dennis , Guo Yipei , Chitnis Shivam S , Christoforou Christina , Turner-Evans Dan , Ribeiro Carlos , Hermundstad Ann M , Jayaraman Vivek , Haberkern Hannah
Published: June 2024

After finding food, a foraging animal must decide whether to continue feeding, or to explore the environment for potentially better options. One strategy to negotiate this tradeoff is to perform local searches around the food but repeatedly return to feed. We studied this behavior in flies and used genetic tools to uncover the underlying mechanisms. Over time, flies gradually expand their search, shifting from primarily exploiting food sources to exploring the environment, a change that is likely driven by increases in satiety. We found that flies’ search patterns preserve these dynamics even as the overall scale of the search is modulated by starvation-induced changes in metabolic state. In contrast, search induced by optogenetic activation of sugar sensing neurons does not show these dynamics. We asked what navigational strategies underlie local search. Using a generative model, we found that a change in locomotor pattern after food consumption could account for repeated returns to the food, but failed to capture relatively direct, long return trajectories. Alternative strategies, such as path integration or sensory taxis could allow flies to return from larger distances. We tested this by individually silencing the fly’s head direction system, olfaction and hygrosensation, and found that the only substantial effect was from perturbing hygrosensation, which reduced the number of long exploratory trips. Our study illustrates that local search is composed of multiple behavioral features that evolve over time based on both internal and external factors, providing a path towards uncovering the underlying neural mechanisms.
Stabilization of GTSE1 by cyclin D1-CDK4/6-mediated phosphorylation promotes cell proliferation: relevance in cancer prognosis
Authors: García-Vázquez Nelson , González-Robles Tania J. , Lane Ethan , Spasskaya Daria , Zhang Qingyue , Kerzhnerman Marc , Jeong YeonTae , Collu Marta , Simoneschi Daniele , Ruggles Kelly V. , Rona Gergely , Kaisari Sharon , Pagano Michele
Published: June 2024

In healthy cells, cyclin D1 is expressed during the G1 phase of the cell cycle, where it activates CDK4 and CDK6. Its dysregulation is a well-established oncogenic driver in numerous human cancers. The cancer-related function of cyclin D1 has been primarily studied by focusing on the phosphorylation of the retinoblastoma (RB) gene product. Here, using an integrative approach combining bioinformatic analyses and biochemical experiments, we show that GTSE1 (G-Two and S phases expressed protein 1), a protein positively regulating cell cycle progression, is a previously unrecognized substrate of cyclin D1-CDK4/6 in tumor cells overexpressing cyclin D1 during G1 and subsequent phases. The phosphorylation of GTSE1 mediated by cyclin D1-CDK4/6 inhibits GTSE1 degradation, leading to high levels of GTSE1 across all cell cycle phases. Functionally, the phosphorylation of GTSE1 promotes cellular proliferation and is associated with poor prognosis within a pan-cancer cohort. Our findings provide insights into cyclin D1’s role in cell cycle control and oncogenesis beyond RB phosphorylation.
Strong, but not weak, noise correlations are beneficial for population coding
Authors: Mahuas Gabriel , Buffet Thomas , Marre Olivier , Ferrari Ulisse , Mora Thierry
Published: June 2024

Neural correlations play a critical role in sensory information coding. They are of two kinds: signal correlations, when neurons have overlapping sensitivities, and noise correlations from network effects and shared noise. It is commonly thought that stimulus and noise correlations should have opposite signs to improve coding. However, experiments from early sensory systems and cortex typically show the opposite effect, with many pairs of neurons showing both types of correlations to be positive and large. Here, we develop a theory of information coding by correlated neurons which resolves this paradox. We show that noise correlations are always beneficial if they are strong enough. Extensive tests on retinal recordings under different visual stimuli confirm our predictions. Finally, using neuronal recordings and modeling, we show that for high dimensional stimuli noise correlation benefits the encoding of fine-grained details of visual stimuli, at the expense of large-scale features, which are already well encoded.
Nanopore Direct RNA Sequencing Reveals Virus-Induced Changes in the Transcriptional Landscape in Human Bronchial Epithelial Cells
Authors: Wang Dongyu , Booth J. Leland , Wu Wenxin , Kiger Nicholas , Lettow Matthew , Bates Averi , Pan Chongle , Metcalf Jordan , Schroeder Susan J.
Published: June 2024

Direct RNA nanopore sequencing reveals changes in gene expression, polyadenylation, splicing, m6A methylation, and pseudouridylation in response to influenza virus exposure in primary human bronchial epithelial cells. This study focuses on the epitranscriptomic profile of genes in the host immune response. In addition to polyadenylated noncoding RNA, we purified and sequenced nonpolyadenylated noncoding RNA and observed changes in expression, N6-methyl-adenosine (m6A), and pseudouridylation (Ψ) in these novel RNA. Two recently discovered lincRNA with roles in immune response,ChaserrandLEADR, became highly methylated in response to influenza exposure. Several H/ACA type snoRNAs that guide pseudouridylation are decreased in expression in response to influenza, and there is a corresponding decrease in the pseudouridylation of two novel lncRNA. Thus, novel epitranscriptomic changes revealed by direct RNA sequencing with nanopore technology provides unique insights into the host epitranscriptomic changes in epithelial gene networks that respond to influenza virus infection.
Natural variation in seed coat color in lettuce and wildLactucaspecies
Authors: Mehrem Sarah L. , Van den Ackerveken Guido , Snoek Basten L.
Published: June 2024

Seed coat color is a well described trait in lettuce (Lactuca sativa), varying from black to pale white pigmentation. In this study, we delve into seed coat color variation of several species within theLactucagenus, encompassingL. sativaand 15 wild varieties, offering broader insights into the diversity of this trait. To capture seed coat color quantitatively, we use grey pixel values from publicly available images, enabling us to measure seed coat color as a continuous trait across the genus. Darker seed coats predominate within theLactucagenus, withL. sativadisplaying a distinctive bimodal distribution of black and white seed coats.Lactuca virosaexhibits the darkest seed coat coloration and less variation, whileLactuca salignaandLactuca serrioladisplay lighter shades and greater variability. To identify the polymorphic loci underlying the observed variation we performed GWAS on seed coat color in bothL. sativaandL. serriola. ForL. sativa, we confirmed the one known major QTL linked to black and white seed coat color, which we reproduce in two independent, published genotype collections (n=129, n=138). Within the same locus, we identify additional candidate genes associated with seed coat color. ForL. serriola, GWAS yielded several minor QTLs linked to seed coat color, harboring candidate genes predicted to be part of the anthocyanin pathway. These findings highlight the phenotypic diversity present within the broaderLactucagenus and provide insights into the genetic mechanisms governing seed coat coloration in both cultivated lettuce and its wild relatives.
TOMM40 regulates hepatocellular and plasma lipid metabolism via an LXR-dependent pathway
Authors: Yang Neil V , Chao Justin Y , Garton Kelly A , Tran Tommy , King Sarah , Orr Joseph , Oei Jacob H , Crawford Alexandra , Kang Misun , Zalpuri Reena , Jorgens Danielle , Konchadi Pranav , Chorba John S , Theusch Elizabeth , Krauss Ronald M
Published: June 2024

The gene encoding TOMM40 (Transporter of Outer Mitochondrial Membrane 40) is adjacent to that encoding APOE, which has a central role in lipid and lipoprotein metabolism. Human genetic variants nearAPOEandTOMM40are strongly associated with plasma lipid levels, but a specific role for TOMM40 in lipid metabolism has not been established. Investigating this, we show that suppression ofTOMM40in human hepatoma cells upregulates expression ofAPOEandLDLRin part via activation of LXRB (NR1H2) by oxysterols, with consequent increased uptake of VLDL and LDL. This is in part due to disruption of mitochondria-endoplasmic reticulum contact sites, with resulting accrual of reactive oxygen species and non-enzymatically derived oxysterols. WithTOMM40knockdown, cellular triglyceride and lipid droplet content are increased, effects attributable in part to receptor-mediated VLDL uptake, since lipid staining is significantly reduced by concomitant suppression of eitherLDLRorAPOE. In contrast, cellular cholesterol content is reduced due to LXRB-mediated upregulation of the ABCA1 transporter as well as increased production and secretion of oxysterol-derived cholic acid. Consistent with the findings in hepatoma cells,in vivoknockdown ofTOMM40in mice results in significant reductions of plasma triglyceride and cholesterol concentrations, reduced hepatic cholesterol and increased triglyceride content, and accumulation of lipid droplets leading to development of steatosis. These findings demonstrate a role for TOMM40 in regulating hepatic lipid and plasma lipoprotein levels and identify mechanisms linking mitochondrial function with lipid metabolism.

GRAPHICAL ABSTRACT
Cyanobacteria form a procarboxysome-like structure in response to high CO2
Authors: Huffine Clair A. , Fontana Catherine , Avramov Anton , Sempeck Colin , Cameron Jeffrey C.
Published: June 2024

Fixing 25% of CO2globally, cyanobacteria are integral to climate change efforts. The cyanobacterial CO2concentrating mechanism (CCM) features the carboxysome, a bacterial microcompartment which houses their CO2fixing machinery. The proteinaceous shell of the carboxysome restricts diffusion of CO2, both inward and outward. While necessary for CCM function in air (0.04% CO2), when grown in high CO2levels (3% CO2) representative of early earth, the shell would harmfully limit CO2fixation. To understand how carboxysomes change form and function in response to increased CO2conditions, we used a Grx1-roGFP2 redox sensor and single cell timelapse fluorescence microscopy to track subcellular redox states ofSynechococcussp. PCC 7002 grown in air or 3% CO2. Comparing different levels of compartmentalization, we targeted the cytosol, a shell-less carboxysomal assembly intermediate called the procarboxysome, and the carboxysome. The carboxysome redox state was dynamic and, under 3% CO2, procarboxysome-like structures formed and mirrored cytosolic redox states, indicating that a more permeable shell architecture may be favorable when [CO2] is high. This work represents a step in understanding how cyanobacteria respond to changing CO2concentrations and the selective forces driving carboxysome evolution.
Identification of key residues inBacillus subtilisgerminant receptor protein GerAB involved in spore water uptake
Authors: Chen Longjiao , Beekhuis Houdijn , van den Bosch Christina , Vinay Gianni , Korza George , Vreede Jocelyne , Setlow Peter , Brul Stanley
Published: June 2024

Some species in the Bacillales andClostridialesbacterial orders form spores in unfavorable environments. These spores are metabolically dormant, and resistant to harsh conditions. However, upon triggering by a variety of small molecule nutrients, termed germinants, spores may germinate, increasing their core water content from 25%-45% in spores to ~80% in growing cells, thus restoring rapid metabolism and leading to outgrowth and then vegetative growth. Recent structural modeling and mutagenesis studies showed that a subunit of the prototypicalBacillus subtilisspore germinant receptor (GR) GerA, the integral inner membrane (IM) protein GerAB, is involved in spore germination initiated by L-alanine. Notably, a previous molecular simulation study showed the formation of a putative water channel in GerAB. In the current study we employed Steered Molecular Dynamics (SMD) simulations to force a single water molecule through GerAB. Examining the simulations revealed three key amino acid residues, Y97, L199 and F342, that interfere with water passage. These three residues were altered to alanine, followed by assays of germination. In the Y97A, L199A, F342A single mutants and the Y97A, L199A and F342A triple mutant (triA), all four types of mutant spores barely responded to L-alanine, while wild type spores germinated almost 100% under the same conditions. Y97A spores expressed the GerAA protein as determined by western blot analysis, corroborating the presence of the GerA GR in this mutant. However, for the other three mutants, the existence of GerA receptor in the spore could not be confirmed. In conclusion, Y97 plays a key role in GerAB mediated germination and suggests that GerAB indeed facilitates water passage and further indicating that water passage through GerAB is a crucial event inB. subtilisspore germination.
EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases
Authors: Nandi Ipsita , Ramachandran Rachana Pattani , Shalev Deborah E. , Schneidman-Duhovny Dina , Shtuhin-Rahav Raisa , Melamed-Book Naomi , Rosenshine Ilan , Aroeti Benjamin
Published: June 2024

EnteropathogenicE. coli(EPEC) is a Gram-negative bacterial pathogen that causes persistent diarrhea. Upon attachment to the apical plasma membrane of the intestinal epithelium, the pathogen translocates virulent proteins called effectors into the infected cells. These effectors hijack numerous host processes for the pathogen’s benefit. Therefore, studying the mechanisms underlying their action is crucial for a better understanding of the disease. We show that translocated EspH interacts with multiple host Rab GTPases. AlphaFold predictions and site-directed mutagenesis identified glutamic acid and lysine at positions 37 and 41 as Rab interacting residues. Mutating these sites abolished the EspH ability to inhibit the Akt and mTORC1 signaling, lysosomal exocytosis, and bacterial invasion. Knocking out the endogenous Rab8a gene expression highlighted the involvement of Rab8a in Akt/mTORC1 signaling and lysosomal exocytosis. A phosphoinositide binding domain with a critical tyrosine was identified in EspH. Mutating the tyrosine abolished the localization of EspH at infection sites and its capacity to interact with Rabs. Our data suggest novel EspH-dependent mechanisms that elicit immune signaling and membrane trafficking during EPEC infection.
The mediating role of employer attractiveness and prestige on the relationship between green recruitment and job pursuit intention in Ghana
Authors: Damoah Obi Berko Obeng
Published: June 2024

Purpose

Whilst organisations' responses to implementing sustainability principles have been influenced significantly by external pressures (e.g. competitor action, regulator influences), researchers are turning attention to the influence of internal stakeholders (staff members) and external stakeholders (e.g. prospective applicants) on an organisation's sustainability motivations. This study aimed to assess the relationship between green recruitment practices and job pursuit intention and the role of organisational attractiveness and prestige among prospective employees.

Design/methodology/approach

The study uses the cross-sectional survey; a sample of 215 students are used to validate the five (5) hypotheses developed from the literature review. To achieve a more plausible regression parameter estimates, the structural equation modelling is the main analytical technique used to analyse the hypotheses.

Findings

The results show that there is a positive effect of green recruitment on organisational attractiveness, organisational prestige, and job pursuit intention. Similarly, organisational attractiveness and organisational prestige serially mediated the relationship between green recruitment and job pursuit intentions.

Originality/value

This study is an addition to the literature on the soft green human resource management practices, specifically green recruitment from the perspective of potential job applicants. In addition, the study uses data from a new and under-researched geographical context, Ghana to contribute and shed light on the topic. Critically, research on sustainable human resource management has been shown to be very limited from the Africa's context. Consequently, the present evidence from the Ghana's perspective responds to the call.
Impact of environmental awareness and knowledge on purchase intention of an eco-friendly hotel: mediating role of habits and attitudes
Authors: Tavitiyaman Pimtong , Zhang Xinyan , Chan Hiu Man
Published: June 2024

Purpose

This study explored the impact of environmental awareness, knowledge, habits, attitudes, subjective norms and perceived behavioural control on purchase intention towards an eco-friendly hotel from a hotel guest perspective. The mediating role of habits and attitudes in the relationships was also examined.

Design/methodology/approach

Anchored on an extended theory of planned behaviour (TPB) model, the study employed a quantitative method through a self-administered questionnaire. Convenience and snowball sampling approaches were used to select 241 respondents. Structural equation modelling was adopted to examine relationships between constructs.

Findings

Results showed that hotel guests’ perceived environmental awareness positively influences their habits and that environmental knowledge positively affects their attitudes. Hotel guests’ habits, attitudes and perceived behavioural control also influence their purchase intention towards an eco-friendly hotel. In addition, habits and attitudes have a mediating effect on the relationship between environmental awareness and knowledge and purchase intention.

Practical implications

Hotel operators should implement marketing campaigns to arouse hotel guests’ eco-friendly habits and attitudes by promoting environmental awareness and knowledge such as energy saving initiatives and green activities, which can increase their purchase intention.

Originality/value

The findings extend the current hospitality and tourism literature advocating for the mediating role of habits and attitudes with the consequence of environmental awareness and knowledge about purchase intention. Moreover, this study increases the original TPB’s predictive power in the context of eco-friendly hotels by adding complementary constructs.
Copper resistance in the cold: Genome analysis and characterisation of a PIB‐1 ATPase in Bizionia argentinensis
Authors: Burgardt Noelia I. , Melian Noelia A. , González Flecha F. Luis
Published: June 2024

Copper homeostasis is a fundamental process in organisms, characterised by unique pathways that have evolved to meet specific needs while preserving core resistance mechanisms. While these systems are well‐documented in model bacteria, information on copper resistance in species adapted to cold environments is scarce. This study investigates the potential genes related to copper homeostasis in the genome of Bizionia argentinensis (JUB59‐T), a psychrotolerant bacterium isolated from Antarctic seawater. We identified several genes encoding proteins analogous to those crucial for copper homeostasis, including three sequences of copper‐transport P1B‐type ATPases. One of these, referred to as BaCopA1, was chosen for cloning and expression in Saccharomyces cerevisiae. BaCopA1 was successfully integrated into yeast membranes and subsequently extracted with detergent. The purified BaCopA1 demonstrated the ability to catalyse ATP hydrolysis at low temperatures. Structural models of various BaCopA1 conformations were generated and compared with mesophilic and thermophilic homologous structures. The significant conservation of critical residues and structural similarity among these proteins suggest a shared reaction mechanism for copper transport. This study is the first to report a psychrotolerant P1B‐ATPase that has been expressed and purified in a functional form.
Single‐cell RNA sequencing elucidated the landscape of breast cancer brain metastases and identified ILF2 as a potential therapeutic target
Authors: Xie Jindong , Yang Anli , Liu Qianwen , Deng Xinpei , Lv Guangzhao , Ou Xueqi , Zheng Shaoquan , Situ Min‐Yi , Yu Yang , Liang Jie‐Ying , Zou Yutian , Tang Hailin , Zhao Zijin , Lin Fuhua , Liu Wei , Xiao Weikai
Published: June 2024

Distant metastasis remains the primary cause of morbidity in patients with breast cancer. Hence, the development of more efficacious strategies and the exploration of potential targets for patients with metastatic breast cancer are urgently needed. The data of six patients with breast cancer brain metastases (BCBrM) from two centres were collected, and a comprehensive landscape of the entire tumour ecosystem was generated through the utilisation of single‐cell RNA sequencing. We utilised the Monocle2 and CellChat algorithms to investigate the interrelationships among each subcluster. In addition, multiple signatures were collected to evaluate key components of the subclusters through multi‐omics methodologies. Finally, we elucidated common expression programs of malignant cells, and experiments were conducted in vitro and in vivo to determine the functions of interleukin enhancer‐binding factor 2 (ILF2), which is a key gene in the metastasis module, in BCBrM progression. We found that subclusters in each major cell type exhibited diverse characteristics. Besides, our study indicated that ILF2 was specifically associated with BCBrM, and experimental validations further demonstrated that ILF2 deficiency hindered BCBrM progression. Our study offers novel perspectives on the heterogeneity of BCBrM and suggests that ILF2 could serve as a promising biomarker or therapeutic target for BCBrM.
An experimental test of intra‐ and inter‐specific competition between invasive western mosquitofish (Gambusia affinis) and native plains topminnow (Fundulus sciadicus)
Authors: Lewis Samuel T. , Salerno Jonathan D. , Sanderson John S. , Kanno Yoichiro
Published: June 2024

Invasive species are a major threat to freshwater conservation. The coexistence of species in invaded habitats depends on the relative strength of intra‐ versus inter‐specific competition, where inter‐specific competition from invasive to native species is often stronger than intra‐specific competition, jeopardising their coexistence.

In this study, we conducted a laboratory experiment to test for the relative strength of interference competition between native plains topminnow (Fundulus sciadicus) and invasive western mosquitofish (Gambusia affinis) at three experimental temperatures. Intra‐ and inter‐specific competition was quantified using an isodar approach, which assumes that animals are ideally distributed to maximise their fitness. Thus, their distributions measure the quality and quantity of habitat patches. This was supplemented by behavioural observations of intra‐ and inter‐specific competition.

Contrary to our predictions, we did not find evidence that competition was asymmetrical from the invasive mosquitofish to the native plains topminnow. Instead, more individuals occupied their shared preferred habitat (a slow‐moving pool) in sympatry compared to allopatry, and the isodar analysis demonstrated that intra‐specific interference competition was significantly stronger than inter‐specific competition at all temperature levels. Behavioural observations corroborated this analysis of habitat selection that aggression was most frequent among plains topminnow in sympatry.

This study shows that the widely perceived aggression of adults might not be the only key mechanism of global invasion success by mosquitofish. Other ecological traits, such as rapid reproduction, environmental tolerance, and interactions with early life stages of native species, might also be responsible for their invasion success. Additional investigations are warranted to determine whether their invasions directly affect native species or they invade degraded ecosystems opportunistically.
Epidermolysis Bullosa in Spain: A Qualitative Analysis of Its Social Impact on Families With Diagnosed Minors
Authors: Martínez‐Ripoll Juan Manuel , García‐Domingo Marta , de la Fuente Robles Yolanda María
Published: June 2024

Background

Epidermolysis bullosa (EB) comprises a group of rare types of genodermatoses characterized by extreme mucocutaneous fragility, leading to blistering and/or erosions, even with minimal trauma. Continuous care through wound management is an integral part of daily life for the families and individuals affected. The aim of this study was to assess the social reality and impacts on families of having minor members diagnosed with EB in Spain.

Methods

A qualitative methodology was employed, utilizing four focus groups entailing participation by 24 parents (19 mothers and five fathers) of minors diagnosed with EB in Spain.

Results

Negative impacts on the family nucleus were evident in four priority areas of analysis: sociorelational, economic‐labour, physical and psychoemotional, with significant differences observed based on the severity of the symptoms.

Conclusion

Impacts on the family nucleus are noticeable from birth, influencing all other daily life routines and complicating family planning and organization. There is an imperative need to enhance the availability of sociohealth resources and to adopt an interdisciplinary approach to address their biopsychosocial needs.

Patient or Public Contribution

The active participation of relatives of minors diagnosed with Epidermolysis Bullosa (EB) is invaluable to sociohealth professionals, legislators and researchers. A team member conducts their professional activities at DEBRA España (national patient association dedicated to enhancing the quality of life for individuals with EB and their families), actively engaging in all study phases.
Corrosion behavior of TiN monolayer and CrN/TiN multilayer coatings: Impact of immersion time and saline solution type
Authors: Fazel Zahra Andalibi , Elmkhah Hassan , Molaei Maryam , Riahi‐Noori Nastaran , Fattah‐alhosseini Arash
Published: June 2024

The corrosion behavior of the TiN monolayer and CrN/TiN multilayer coatings deposited via cathodic arc evaporation physical vapor deposition (CAE‐PVD) on the Ti–6Al–4V substrates were evaluated in Ringer's and Hank's physiological saline electrolytes. XRD (x‐ray diffractometry) and scanning electron microscopy (SEM) analysis were used to characterize the coatings. The corrosion behavior of coatings was assessed by impedance spectroscopy and potentiodynamic polarization techniques. The results showed that the corrosion resistance of coatings was increased in the order of TiN‐Ringer's < TiN‐Hank's < CrN/TiN‐Ringer's < CrN/TiN‐Hank's. Therefore, it can be concluded that the CrN/TiN coating, due to having a large number of interfaces and a smoother surface with fewer macroparticles and pinholes, is more efficient in raising the corrosion resistance properties of titanium than TiN monolayer coating. Moreover, it was observed that Ringer's solution is a more severe environment than Hank's solution. Both coatings, because of the precipitation of a protective corrosion products layer on their surface, showed an enhancement in corrosion resistance with increasing the immersion time from 1 to 14 days in Hank's. The results suggest TiN monolayer and CrN/TiN multilayer coatings as promising candidates for biomedical applications.
Investigation of sintering properties and behavior of sericite ceramifying powder under low temperature
Authors: He Shengkai , Sun Qing , Shen Jiapei , Zhang Jian , Sheng Jiawei
Published: June 2024

Polymer–ceramic composites are widely used in refractory cables. The ceramic fillers provide high temperature and fire resistance, while the polymer matrix provides flexibility and improved electrical insulation. The properties of the polymer–ceramic composites are determined by the ceramization‐forming properties of the corresponding ceramifying powders. Properties such as shrinkage, density, and porosity were characterized to compare the effects of different contents of glass powder. The sintering activation energy was calculated using the logarithmic relationship between shrinkage and holding time. The microstructure, cross‐section, and crystalline phases were investigated by scanning electron microscopy (SEM) and X‐ray diffraction analysis (XRD) to explore the ceramization process of sericite ceramifying powder. The ceramization process of ceramifying powder is proposed. The results show that during low‐temperature sintering, the glass powder and muscovite phases melt and partially transform into α‐quartz and albite low during cooling down.
Bioactive lipid‐enriched concentrates from squid discards by one‐step and two‐step extractions with non‐halogenated solvents
Authors: Paz David , Trigo Marcos , Martínez Sidonia , Aubourg Santiago P.
Published: June 2024

This study focused on the preparation of lipid concentrates with high contents of bioactive molecules. Different one‐step and two‐step extractions with non‐halogenated solvents (hexane, HX; isopropanol, IP) were carried out on Patagonian squid (Doryteuthis gahi) discards. As a first step, HX extractions (one, two or three times) were carried out. The resulting substrates were extracted with IP (two, three or four times). Analysis of lipid extracts included total lipid, phospholipid (PL) and tocopherol values, and fatty acid (FA) profile. HX extractions led to remarkable α‐ and γ‐tocopherol values (ca. 1400 and 23 mg kg−1 lipids, respectively); no effect (P > 0.05) of the number of HX extractions was observed. IP extracts provided high PL values (383–501 mg kg−1 lipids); the highest average values were detected with four IP extractions after three HX extractions. Values obtained for tocopherols and PLs were higher (P < 0.05) than those obtained by employing the conventional (chloroform/methanol, 1:1) lipid extraction (ca. 496 and 11 mg kg−1 lipids and 400 g kg−1 lipids, respectively). Range values detected for eicosapentaenoic and docosahexaenoic acid values and the ω3/ω6 FA ratio were similar to those obtained by the conventional procedure. A valuable procedure is proposed for obtaining PL‐ and tocopherol‐enriched concentrates from marine waste with non‐halogenated solvents.
Variation among clones of Myzus persicae and Myzus nicotianae in the transmission of a poorly and a highly aphid‐transmissible isolate of potato leafroll luteovirus (PLRV)
Authors: Bourdin D , Rouzé J. , Tanguy S. , Robert Y.
Published: June 2024

Fifteen clones of Myzus persicae (Mp) and two of Myzus nicotianae (Mn) were used to assess the aphid transmission of two isolates of PLRV characterized as highly (HAT) and poorly (PAT) transmissible. Experiments conducted tinder controlled conditions showed that the HAT isolate was very efficiently transmitted by all the clones tested. In contrast, an important aphid clonal effect was observed with the PAT isolate, with mean transmission rates by 15 clones being low (0‐26%) and by the two others much higher (57 and 71%). Transmission values for each clone were shown to be stable over time and independent of the kind of source plant used for acquisition, either infected Physalis floridana plants propagated by cuttings or grown from seedlings previously inoculated by aphids. These results lead to the conclusion that poor transmissibility cannot be related to intrinsic properties of either the viral particles or the aphid clones on their own: the transmission process and its specificity depend on interactions between both parameters.