bluuebunny/crossref_metadata_2025 huggingface dataset:
Airway basal stem cells are necessary for the maintenance of functional intraepithelial airway macrophages
Authors: Kooistra Tristan , Saez Borja , Roche Marly , Egea-Zorrilla Alejandro , Li Dongzhu , Anketell Dilanjan , Nguyen Nhan , Villoria Jorge , Gillis Jacob , Petri Eva , Vera Laura , Blasco-Iturri Zuriñe , Smith Neal P. , Alladina Jehan , Zhang Yanting , Vinarsky Vladimir , Shivaraju Manjunatha , Sheng Susan L. , Gonzalez-Celeiro Meryem , Mou Hongmei , Waghray Avinash , Lin Brian , Paksa Azadeh , Yanger Kilangsungla , Tata Purushotama Rao , Zhao Rui , Causton Benjamin , Zulueta Javier J. , Prosper Felipe , Cho Josalyn L. , Villani Alexandra-Chloe , Haber Adam , Rajagopal Jayaraj , Medoff Benjamin D. , Pardo-Saganta Ana
Published: June 2024

Adult stem cells play a crucial role in tissue homeostasis and repair through multiple mechanisms. In addition to being able to replace aged or damaged cells, stem cells provide signals that contribute to the maintenance and function of neighboring cells. In the lung, airway basal stem cells also produce cytokines and chemokines in response to inhaled irritants, allergens, and pathogens, which affect specific immune cell populations and shape the nature of the immune response. However, direct cell-to-cell signaling through contact between airway basal stem cells and immune cells has not been demonstrated. Recently, a unique population of intraepithelial airway macrophages (IAMs) has been identified in the murine trachea. Here, we demonstrate that IAMs require Notch signaling from airway basal stem cells for maintenance of their differentiated state and function. Furthermore, we demonstrate that Notch signaling between airway basal stem cells and IAMs is required for antigen-induced allergic inflammation only in the trachea where the basal stem cells are located whereas allergic responses in distal lung tissues are preserved consistent with a local circuit linking stem cells to proximate immune cells. Finally, we demonstrate that IAM-like cells are present in human conducting airways and that these cells display Notch activation, mirroring their murine counterparts. Since diverse lung stem cells have recently been identified and localized to specific anatomic niches along the proximodistal axis of the respiratory tree, we hypothesize that the direct functional coupling of local stem cell-mediated regeneration and immune responses permits a compartmentalized inflammatory response.
Characterising cancer cell responses to cyclic hypoxia using mathematical modelling
Authors: Celora Giulia , Nixson Ruby , Pitt-Francis Joe , Maini Philip , Byrne Helen
Published: June 2024

In vivo observations show that oxygen levels in tumours can fluctuate on fast and slow timescales. As a result, cancer cells can be periodically exposed to pathologically low oxygen levels; a phenomenon known as cyclic hypoxia. Yet, little is known about the response and adaptation of cancer cells to cyclic, rather than, constant hypoxia. Further, existing in vitro models of cyclic hypoxia fail to capture the complex and heterogeneous oxygen dynamics of tumours growingin vivo. Mathematical models can help to overcome current experimental limitations and, in so doing, offer new insights into the biology of tumour cyclic hypoxia by predicting cell responses to a wide range of cyclic dynamics. We develop an individual-based model to investigate how cell cycle progression and cell fate determination of cancer cells are altered following exposure to cyclic hypoxia. Our model can simulate standardin vitroexperiments, such as clonogenic assays and cell cycle experiments, allowing for efficient screening of cell responses under a wide range of cyclic hypoxia conditions. Simulation results show that the same cell line can exhibit markedly different responses to cyclic hypoxia depending on the dynamics of the oxygen fluctuations. We also use our model to investigate the impact of changes to cell cycle checkpoint activation and damage repair on cell responses to cyclic hypoxia. Our simulations suggest that cyclic hypoxia can promote heterogeneity in cellular damage repair activity within vascular tumours.
CRISPR screen decodes SWI/SNF chromatin remodeling complex assembly
Authors: Schwaemmle Hanna , Soldati Hadrien , Lykoskoufis Nikolaos M. R. , Docquier Mylène , Hainard Alexandre , Braun Simon M. G.
Published: June 2024

The SWI/SNF (or BAF) complex is an essential chromatin remodeler that regulates DNA accessibility at developmental genes and enhancers. SWI/SNF subunits are among the most frequently mutated genes in cancer and neurodevelopmental disorders. These mutations are often heterozygous loss-of-function alleles, indicating a dosage-sensitive role for SWI/SNF subunits in chromatin regulation. However, the molecular mechanisms that regulate SWI/SNF subunit dosage to ensure proper complex assembly remain largely unexplored. We performed a genome-wide CRISPR KO screen, using epigenome editing in mouse embryonic stem cells, and identifiedMlf2andRbm15as regulators of SWI/SNF complex activity. First, we show that MLF2, a poorly characterized chaperone protein, regulates a subset of SWI/SNF target genes by promoting chromatin remodeling activity. Next, we find that RBM15, part of the m6A RNA methylation writer complex, controls m6A modifications on specific SWI/SNF mRNAs to regulate protein levels of these subunits. Misregulation of m6A methylation causes overexpression of core SWI/SNF subunits leading to the assembly of incomplete complexes lacking the catalytic ATPase/ARP subunits. These data indicate that targeting modulators of SWI/SNF complex assembly may offer a potent therapeutic strategy for diseases associated with impaired chromatin remodeling.
Co-Metabolic Growth and Microbial Diversity: Keys for the depletion of the α, δ, β and γ-HCH isomers
Authors: Bernabei Giacomo , De Simone Giampiero , Becarelli Simone , Di Mambro Riccardo , Gentini Alessandro , Di Gregorio Simona
Published: June 2024

The objective of this study was to select and enhance microbiomes capable of degrading the α, δ, β and γ-HCH isomers. These microbiomes were isolated and enriched from an HCH-contaminated dumpsite in Italy, both in the presence of HCH isomers (1:1:1:1) as the sole carbon sources and under co-metabolic growth conditions in presence of glucose (0.1%). Four microbiomes were assessed for their relevant metabolic capabilities. A quantitative metabarcoding approach was employed to analyze the compositional evolution of the four microbiomes during the enrichment phase and the phase of tsting of the HCH isomers degradation kinetics. The use of a co-metabolic substrate during enrichment process was essential for selecting microbiomes with higher biodiversity. All microbiomes efficiently degraded the α, δ, and γ-HCH isomers. The highest efficiency in the β-HCH degradation capacity was associated to the highest biodiversity of the microbiome, and the involvement ofChryseobacteriumandAsinibacteriumsps. has been proposed for a recorded increment in bacterial load during the HCH degradation process.

Statement of environmental implications

Soil contaminated with hexachlorocyclohexane (HCH), including all four isomers, poses a significant risk to environmental and public health. This study isolates and selects microbiomes capable of degrading HCH, demonstrating their degradation efficiency using GC-MS analysis, and studies the microbial communities through metabarcoding of both the initial soils and the selected microbiomes. The contaminated soil originates from the historically polluted area of Italy known as SIN-Valle del Sacco. Developing and optimizing microbiome selection techniques for application on contaminated sites can significantly enhance soil bioremediation, thereby reducing contamination and protecting the environment.
Sensitive quantification of fibroblast activation protein and high-throughput screening for inhibition by FDA-approved compounds
Authors: Čermáková Kateřina , Šimková Adéla , Wichterle Filip , Kryštůfek Robin , Staňurová Jana , Bušek Petr , Konvalinka Jan , Šácha Pavel
Published: June 2024

Fibroblast activation protein (FAP) has been extensively studied as a cancer biomarker for decades. Recently, small-molecule FAP inhibitors have been widely adopted as a targeting moiety of experimental theranostic radiotracers. Here we present a fast qPCR-based analytical method allowing FAP inhibition screening in a high-throughput regime. In order to identify clinically relevant compounds that might interfere with FAP-targeted approaches, we focused on the library of FDA-approved drugs. Using theDNA-linkedInhibitorAntibodyAssay (DIANA), we tested a library of 2,667 compounds within just few hours and identified numerous FDA-approved drugs as novel FAP inhibitors. Notably, prodrugs of cephalosporin antibiotics, reverse-transcriptase inhibitors, and one elastase inhibitor were the most potent FAP inhibitors in our dataset. In addition, by employing FAP DIANA in quantification mode, we were able to determine FAP concentrations in human plasma samples. Together, our work expands the repertoire of FAP inhibitors, underscores the potential interference of co-administered drugs with FAP-targeting strategies, and presents a sensitive and low-consumption ELISA alternative for FAP quantification with a detection limit of 50 pg/ml.

Graphical abstract
Retinal microglial cells increase expression and release of IL-1β when exposed to ATP
Authors: Campagno Keith E. , Lu Wennan , Sripinun Puttipong , Albalawi Farraj , Cenaj Aurora , Mitchell Claire H.
Published: June 2024

Cytokine IL-1β is an early component of inflammatory cascades, with both priming and activation steps required before IL-1β release. Here, the P2X7 receptor (P2X7R) for ATP was shown to both prime and release IL-1β from retinal microglial cells. Isolated retinal microglial cells increased expression ofIl1bwhen stimulated with endogenous receptor agonist extracellular ATP; ATP also rapidly downregulated expression of microglial markersTmem119andCd206.Changes to all three genes were reduced by specific P2X7R antagonist A839977, implicating the P2X7R. Microglial cells expressed the P2X7R on ramifications and responded to receptor agonist BzATP with robust and rapid rises in intracellular Ca2+. BzATP increased expression of IL-1β protein colocalizing with CX3CR1-GFP in retinal wholemounts consistent with microglial cells. ATP also triggered release of IL-1β from isolated retinal microglia into the bath; release was inhibited by A839977 and induced by BzATP, supporting a role for the P2X7R in release as well as priming. The IL-1β release triggered by ATP was substantially greater from microglial cells compared to astrocytes from the optic nerve head region.Il1bexpression was increased by a transient rise in intraocular pressure andIl1blevels remained elevated 10 days after a single IOP elevation. In summary, this study suggests the P2X7 receptor can both prime IL-1β levels in microglial cells and trigger its release. The P2Y12R was previously identified as a chemoattractant for retinal microglia, suggesting the recruitment of the cells towards the source of released extracellular ATP could position microglia for P2X7R receptor, enabling both priming and release of IL-1β.
Modification of regulatory tyrosines biases human Hsp90α for interaction with cochaperones and clients
Authors: Huo Yuantao , Karnawat Rishabh , Liu Lixia , Knieß Robert A. , Gross Maike , Chen Xuemei , Mayer Matthias P.
Published: June 2024

The highly conserved Hsp90 chaperones control stability and activity of many essential signaling and regulatory proteins including many protein kinases, E3 ligases and transcription factors. Thereby, Hsp90s couple cellular homeostasis of the proteome to cell fate decisions. High-throughput mass spectrometry revealed 178 and 169 posttranslational modifications (PTMs) for human cytosolic Hsp90α and Hsp90β, but for only a few of the modifications the physiological consequences are investigated in some detail. In this study, we explored the suitability of the yeast model system for the identification of key regulatory residues in human Hsp90α. Replacement of three tyrosine residues known to be phosphorylated by phosphomimetic glutamate and by non-phosphorylatable phenylalanine individually and in combination influenced yeast growth and the maturation of 7 different Hsp90 clients in distinct ways. Furthermore, wild-type and mutant Hsp90 differed in their ability to stabilize known clients when expressed in HepG2HSP90AA1−/−cells. The purified mutant proteins differed in their interaction with the cochaperones Aha1, Cdc37, Hop and p23 and in their support of the maturation of glucocorticoid receptor ligand binding domainin vitro.In vivoandin vitrodata correspond well to each other confirming that the yeast system is suitable for the identification of key regulatory sites in human Hsp90s. Our findings indicate that even closely related clients are affected differently by the amino acid replacements in the investigated positions, suggesting that PTMs could bias Hsp90’s client specificity.
Cap-related modifications of RNA regulate binding to IFIT proteins
Authors: Geng Jingping , Chrabaszczewska Magdalena , Kurpiejewski Karol , Stankiewicz-Drogon Anna , Jankowska-Anyszka Marzena , Darzynkiewicz Edward , Grzela Renata
Published: June 2024

All cells in our body are equipped with receptors to recognize pathogens and trigger a rapid defense response. As a result, foreign molecules are blocked and cells are alerted to the danger. Among the many molecules produced in response to viral infection are interferon-induced proteins with tetratricopeptide repeats (IFITs). Their role is to recognize foreign mRNA and eliminate it from the translational pool of transcripts. In the present study, we used biophysical methods to characterize the interactions between IFIT1 protein and its partners IFIT2 and IFIT3. IFIT1 interacts with IFIT3 with nanomolar binding affinity, which did not change significantly in the presence of the preformed IFIT2/3 complex. The interactions between IFIT2 and IFIT3 and IFIT1 and IFIT2 were one order of magnitude weaker. We also present kinetic data of the interactions between the IFIT protein complex and short RNA bearing various modifications at the 5’ end. We show kinetic parameters for interaction between IFIT complex and RNA with m6Ammodification. The results show that the cap adjacent m6Ammodification is a stronger signature than cap1 alone. It blocks the formation of a complex between IFIT proteins and m7Gpppm6Am-RNA much more effectively than other cap modifications. In contrast, m6A in the 5’UTR is not recognized by IFIT proteins and does not contribute to translation repression by IFIT proteins. The data obtained are important for understanding the regulation of expression of genetic information. They indicate that 2’-Oand m6Ammodifications modulate the availability of mRNA molecules for proteins of innate immune response.
Non-Human Recognition of Orthography: How is it implemented and how does it differ from Human orthographic processing
Authors: Gagl Benjamin , Weyers Ivonne , Eisenhauer Susanne , Fiebach Christian J. , Colombo Michael , Scarf Damian , Ziegler Johannes C. , Grainger Jonathan , Güntürkün Onur , Mueller Jutta L.
Published: June 2024

The ability to robustly recognize strings of letters, a cornerstone of reading, was observed in Baboons and Pigeons despite their lack of phonological and semantic knowledge. Here, we apply a comparative modeling approach to investigate the neuro-cognitive basis of Human, Baboon, and Pigeon orthographic decision behavior, addressing whether phylogenetic relatedness entails similar underlying neuro-cognitive phenotypes. We use the highly transparent Speechless Reader Model (SLR), which assumes letter string recognition based on widely accepted computational principles of predictive coding so that orthographic decisions rely on a prediction error signal emerging from multiple, hierarchically ordered representational levels, i.e., low-level visual, letter, or letter sequence representations. We investigate which representations species use during successful orthographic decision-making. We introduce multiple SLR variants, each including one or multiple prediction error representations, and compare the simulations of each SLR variant to the orthographic decisions from individuals of three species after learning letter strings without meaning. Humans predominantly relied on letter-sequence-level representations, resulting in the highest task performance in behavior and model simulations. Baboons also relied on sequence-based representations but in combination with pixel- and letter-level representations. In contrast, all Pigeons relied on pixel-level representations, partly in combination with letter- and letter-sequence-level representations. These findings suggest that orthographic representations utilized in orthographic decisions reflect the phylogenetic distance between species: Humans and Baboons use more similar representations compared to Pigeons. Overall, the description of orthographic decisions based on a small set of representations and computations was highly successful in describing behavior, even for Humans who mastered reading in its entirety.

Significance Statement

Imagine being able to read without ever learning the alphabet. Research has shown that baboons and pigeons can exhibit reading-like behavior, suggesting shared processes across the species involved. To increase our understanding of the similarities and differences between humans and animals in reading-like behavior, we use a computational model to uncover the underlying processes that enable humans, baboons, and pigeons to perform these tasks. We found that humans and baboons rely on similar processes, focusing on information related to letters and letter sequences. In contrast, pigeons rely more heavily on visual cues. This discovery sheds light on the evolution of processes underlying reading and reading-like behavior, indicating that the lower the evolutionary distance between species, the more similar processes are involved.
Adhesive interactions within microbial consortia can be differentiated at the single-cell level through expansion microscopy
Authors: Dong Pu-Ting , Shi Wenyuan , He Xuesong , Borisy Gary G.
Published: June 2024

Significance

A single-cell understanding of microbe-microbe interactions is critical for unraveling the organization and dynamics of microbial communities. Through an unconventional application of expansion microscopy, we oppose the adhesive force holding microbes together by an expansion force pulling them apart, resulting in microbial separation dependent on the strength of microbial adhesion. Our new approach establishes a proof-of-principle for differentiating adhesive interactions within microbial consortia at the single-cell level.

Investigating microbe-microbe interactions at the single-cell level is critical to unraveling the ecology and dynamics of microbial communities. In many situations, microbes assemble themselves into densely packed multi-species biofilms. The density and complexity pose acute difficulties for visualizing individual cells and analyzing their interactions. Here, we address this problem through an unconventional application of expansion microscopy, which allows for the ‘decrowding’ of individual bacterial cells within a multispecies community. Expansion microscopy generally has been carried out under isotropic expansion conditions and used as a resolution-enhancing method. In our variation of expansion microscopy, we carry out expansion under heterotropic conditions; that is, we expand the space between bacterial cells but not the space within individual cells. The separation of individual bacterial cells from each other reflects the competition between the expansion force pulling them apart and the adhesion force holding them together. We employed heterotropic expansion microscopy to study the relative strength of adhesion in model biofilm communities. These included mono and dual-speciesStreptococcusbiofilms, and a three-species synthetic community (Fusobacterium nucleatum,Streptococcus mutans, andStreptococcus sanguinis) under conditions that facilitated interspecies coaggregation. Using adhesion mutants, we investigated the interplay betweenF. nucleatumouter membrane protein RadD and differentStreptococcusspecies. We also examined theSchaalia-TM7epibiont association. Quantitative proximity analysis was used to evaluate the separation of individual microbial members. Our study demonstrates that heterotropic expansion microscopy can ‘decrowd’ dense biofilm communities, improve visualization of individual bacterial members, and enable analysis of microbe-microbe adhesive interactions at the single-cell level.
Genomic evidence ofEscherichia coligut population diversity translocation in leukemia patients
Authors: Marin Julie , Walewski Violaine , Braun Thorsten , Dziri Samira , Magnan Mélanie , Denamur Erick , Carbonnelle Etienne , Bridier-Nahmias Antoine
Published: June 2024

Escherichia coli, a commensal species of the human gut, is an opportunistic pathogen which can reach extra-intestinal compartments, including the bloodstream and the bladder, among others. In non-immunosuppressed patients, purifying or neutral evolution ofE. colipopulations has been reported in the gut. Conversely, it has been suggested that when migrating to extra-intestinal compartments,E. coligenomes undergo diversifying selection as supported by strong evidence for adaptation. The level of genomic polymorphism and the size of the populations translocating from gut to extra-intestinal compartments is largely unknown.

To gain insights in the pathophysiology of these translocations, we investigated the level of polymorphism and the evolutionary forces acting on the genomes of 77E. coliisolated from various compartments in three immunosuppressed patients. Each patient had a unique strain which was a mutator in one case. In all instances, we observed that translocation encompasses the majority of the genomic diversity present in the gut. The same signature of selection, whether purifying or diversifying, and as anticipated, neutral for mutator isolates, was observed in both the gut and bloodstream. Additionally, we found a limited number of non-specific mutations among compartments for non-mutator isolates. In all cases, urine isolates were dominated by neutral selection. These findings indicate that substantial proportions of populations are undergoing translocation and that they present a complex compartment-specific pattern of selection at the patient level.

Importance

It has been suggested that intra and extra-intestinal compartments differentially constrain the evolution ofE. colistrains. Whether host particular conditions, such as immunosuppression, could affect the strain evolutionary trajectories remain understudied. We found that, in immunosuppressed patients, large fractions ofE. coligut populations are translocating with variable modifications of the signature of selection for commensal and pathogenic isolates according to the compartment and/or the patient. Such multiple site sampling should be performed in large cohorts of patients to get a better understanding ofE. coliextra-intestinal diseases.
The Conserved Transcription Factor Krüppel Regulates the Survival and Neurogenesis of Mushroom Body Neuroblasts inDrosophilaAdult Brains
Authors: Man Jin , Shu Xian , Shi Haoer , Xia Xue , Abula Yusanjiang , Kimata Yuu
Published: June 2024

In various metazoans, includingDrosophilaand humans, neural progenitors exit the cell cycle and are eliminated by the end of development, limiting adult neurogenesis. We demonstrate that inDrosophila,the conserved transcription factorKrüppel(Kr) controls neurogenic capacity of a specific subset of neuroblasts that forms the mushroom body (MBNBs), analogous to the mammalian hippocampus. TheIrregular facetmutation, which altersKrexpression, and neuroblast-specific Kr depletion allow MBNBs, but not other neuroblasts, to persist beyond development and generate neurons in adult brains. Persisting MBNBs express Imp, an RNA-binding protein that promotes neuroblast proliferation and survival. Our results underscore a critical role for Kr in the developmental control of a specific progenitor population, uncovering a novel mechanism controlling adult neurogenesis.
Bridging the Sequencing Gap: N501Y SNP RT-qPCR Assay Detects First SARS-CoV-2 Beta Variant in the Philippines
Authors: Bado Samantha Louise P. , Galap Niquitta B. , Manalo Joanna Ina G. , Onza Othoniel Jan T. , Pelingon Mary Rose B. , Parayray Joy Mariette L. , Palciso Justine Mae , Tomas Karen Iana C. , Abulencia Miguel Francisco B. , Polotan Francisco Gerardo M. , Dancel Lei Lanna M. , Nicolasora Amalea Dulcene
Published: June 2024

Whole genome sequencing (WGS) is used extensively in identifying SARS-CoV-2 variants. However, this method requires stringent sample acceptance criteria, long turn-around time (TAT), expensive processing and maintenance costs, and highly skilled staff. Although sequencing offers comprehensive pathogen insights, a cost-effective tool with faster TAT is beneficial in detecting SARS-CoV-2 variants of concern (VOCs). Here, we used a single nucleotide polymorphism (SNP) RT-qPCR assay to detect the N501Y mutation in banked SARS-CoV-2 RNA extracts (N=452) collected from December 2020 to April 2021. Of the SARS-CoV-2 positives (n=367), 22% carried the N501Y mutation and were classified as probable VOCs. This includes a sample that was confirmed to belong to the Beta lineage and was collected earlier than the first reported Beta variant in the country suggesting an earlier emergence of the variant. Validation experiments for the SNP RT-qPCR assay showed a limit of detection (LOD) of 3.01 copies/μL for both N501 and 501Y targets. A 99.35% concordance with partial S gene Sanger sequencing was observed confirming the presence of the N501Y SNP in 83 samples. In conclusion, the optimized SNP RT-qPCR assay serves as an important complementary or alternative tool for detecting probable SARS-CoV-2 variants, ensuring that samples ineligible for WGS are not overlooked. This effectively resolves sequencing gaps, including stringent sample acceptance criteria, extended TAT, and rigorous data analysis. Therefore, embracing this technology provides a rapid, economical, and dependable solution for managing pathogens of public health concern.
Evaluation of population immunity against SARS-CoV-2 variants, EG.5.1, FY.4, BA.2.86, JN.1, and JN.1.4, using samples from two health demographic surveillance systems in Kenya
Authors: Lugano Doreen , Kutima Bernadette , Kimani Makobu , Sigilai Antipa , Gitonga John , Karani Angela , Akech Donald , Karia Boniface , Ziraba Abdhalah K. , Maina Angela , Lambisia Arnold , Omuoyo Donwilliams , Mugo Daisy , Lucinde Ruth , Newman Joseph , Bailey Dalan , Nduati Eunice , Githinji George , Agoti Charles N. , Bejon Philip , Scott J Anthony G , Agweyu Ambrose , Kagucia Wangeci , Warimwe George M , Sande Charles , Ochola-Oyier Lynette I , Nyagwange James
Published: June 2024

Increased immune evasion by emerging and highly mutated SARS-CoV-2 variants is a key challenge to the control of COVID-19. The majority of these mutations mainly target the spike protein, allowing the new variants to escape the immunity previously raised by vaccination and/or infection by earlier variants of SARS-CoV-2. In this study, we investigated the neutralizing capacity of antibodies against emerging variants of interest circulating between May 2023 and March 2024 using sera from representative samples of the Kenyan population. From our genomics data, we identified the most prevalent Kenyan and global variants and performed pseudoviruses neutralization assays with the most recent SARS-CoV-2 variants. Our data show that antibodies from individuals in the general population in Kenya were less effective against the recent prevalent SARS-CoV-2 omicron variants (i.e. EG.5.1, FY.4, BA.2.86, JN.1, and JN.1.4) compared to the ancestral wildtype strain. Although there was increased neutralization following multiple doses of vaccine, antibodies from >40% of the vaccinated individuals did not neutralize the omicron variants, suggesting that individuals were susceptible to infection by these variants.
A proteomic signature of healthspan
Authors: Kuo Chia-Ling , Liu Peiran , Drouard Gabin , Vuoksimaa Eero , Kaprio Jaakko , Ollikainen Miina , Chen Zhiduo , Pilling Luke C. , Atkins Janice L. , Fortinsky Richard H. , Kuchel George A. , Diniz Breno S.
Published: June 2024

The focus of aging research has shifted from increasing lifespan to enhancing healthspan to reduce the time spent living with disability. Despite significant efforts to develop biomarkers of aging, few studies have focused on biomarkers of healthspan. We developed a proteomics-based signature of healthspan (healthspan proteomic score (HPS)) using proteomic data from the Olink Explorer 3072 assay in the UK Biobank Pharma Proteomics Project (53,018 individuals and 2920 proteins). A lower HPS was associated with higher mortality risk and several age-related conditions, such as COPD, diabetes, heart failure, cancer, myocardial infarction, dementia, and stroke. HPS showed superior predictive accuracy for these outcomes compared to other biological age measures. Proteins associated with HPS were enriched in hallmark pathways such as immune response, inflammation, cellular signaling, and metabolic regulation. The external validity was established using the Essential Hypertension Epigenetics study with proteomic data also from the Olink Explorer 3072 and complementary epigenetic data, making it a valuable tool for assessing healthspan and as a potential surrogate marker to complement existing proteomic and epigenetic biological age measures in geroscience-guided studies.

Significance

Despite substantial efforts to develop biomarkers of aging, few studies have focused on biomarkers of healthspan. The challenge lies in the need for long follow-up periods and large sample sizes of healthy individuals to observe aging outcomes. Therefore, developing surrogate biomarkers that can predict healthspan is crucial. We addressed this by developing a proteomics-based signature of healthspan, termed the Healthspan Proteomic Score (HPS), in a healthy cohort. We demonstrated its clinical, predictive, and biological validity in the UK Biobank and Essential Hypertension Epigenetics study, which represents a focused subset of the Finland Twin Cohort. The HPS, serving as a surrogate marker of healthspan, is useful for gauging an individual’s biological health and monitoring the impact of geroscience-guided interventions.
High-resolution cryo-EM structures of a protein pore reveal diverse roles of membrane lipids
Authors: Šolinc Gašper , Srnko Marija , Merzel Franci , Crnković Ana , Kozorog Mirijam , Podobnik Marjetka , Anderluh Gregor
Published: June 2024

The structure and function of membrane proteins depend on their interactions with the lipid molecules that constitute lipid membranes. Actinoporins are a family of α-pore-forming proteins that bind specifically to sphingomyelin-containing lipid membranes, where they oligomerize and form transmembrane pores. The numerous contacts they form with the lipid membrane make them an exemplary object for studying the different roles that lipids play in the structure and function of membrane proteins. Through a comprehensive cryo-electron microscopic analysis of a pore formed by an actinoporin Fav from the coralOrbicella faveolata, we show that the octameric pore interacts with 112 lipids in the upper leaflet of the membrane. The structures of Fav pores formed on different lipid membranes reveal the different roles of lipids and demonstrate that the actinoporin surface is perfectly suited for binding multiple receptor sphingomyelin molecules. When cholesterol is present in the membrane, it forms nanodomains associated with the pore, leading to a tighter arrangement of lipids, which in turn increases the stability of the pores. Atomistic simulations support the structural data, show that the protein-bound lipids are not mobile, and reveal additional effects of the pore on the lipid membrane. Overall, these data reveal a complex network of protein-lipid and lipid-lipid interactions, and an underrated role of lipids in the structure and function of transmembrane protein complexes.
A biosensor-based phage display selection method for automated, high-throughput Nanobody discovery
Authors: De Keyser Phebe , Kalichuk Valentina , Zögg Thomas , Wohlkönig Alexandre , Schenck Stephan , Brunner Janine , Pardon Els , Steyaert Jan
Published: June 2024

Biopanning methods to select target-specific Nanobodies®(Nbs) involve presenting the antigen, immobilized on plastic plates or magnetic beads, to Nb libraries displayed on phage. Most routines are operator-dependent, labor-intensive and often material- and time-consuming. Here we validate an improved panning strategy that uses biosensors to present the antigen to phage-displayed Nbs in a well. The use of automated Octet biolayer interferometry sensors (Sartorius) enables high throughput and precise control over each step. By playing with association and dissociation times and buffer composition, one can efficiently decrease the background of aspecific and low-affinity Nbs, reducing the rounds of panning needed for the enrichment of high-affinity binders. Octet panning also enables the use of unpurified target proteins and unpurified phage from a bacterial culture supernatant. Additionally, downscaling to a 384-well format significantly reduces the amount of protein required. Moreover, enrichment of binders can be quantified by monitoring phage binding to the target by interferometry, omitting additional phage titration steps. Routinely, up to three rounds of Octet panning can be performed in only five days to deliver target-specific binders, ready for screening and characterization using the same Octet instrument.

Graphical abstract
Macroscopic dynamics of ferromagnetic smectic-
A
Authors: Pleiner Harald , Brand Helmut R.
Published: June 2024

We derive the macroscopic dynamic equations for ferromagnetic smectic-A liquid crystals for which the spontaneous magnetization is parallel to the layer normal of the layering. As additional macroscopic variables when compared to simple fluids, we have the layer displacement u, familiar from smectic liquid crystals, and the magnetization density M. We find a number of reversible and dissipative cross-coupling terms to the additional macroscopic variables and discuss possible experiments to detect them. Among other effects, we point out that the velocity of first sound becomes anisotropic due to the influence of the modulus of the magnetization, while the magnitude of the velocity of second sound is modified. As for the static behavior, we find cross-coupling terms between the magnitude of the magnetization, on the one hand, and layer compression as well as osmotic pressure, on the other hand. In addition, we point out that as a dissipative effect, temperature gradients can induce gradients in the magnetization parallel to the layer normal, mediated by layer compressions.

Published by the American Physical Society
2024
Universal Phenomenology at Critical Exceptional Points of Nonequilibrium
O(N)
Models
Authors: Zelle Carl Philipp , Daviet Romain , Rosch Achim , Diehl Sebastian
Published: June 2024

In thermal equilibrium the dynamics of phase transitions is largely controlled by fluctuation-dissipation relations: On the one hand, friction suppresses fluctuations, while on the other hand, the thermal noise is proportional to friction constants. Out of equilibrium, this balance dissolves and one can have situations where friction vanishes due to antidamping in the presence of a finite noise level. We study a wide class of O(N) field theories where this situation is realized at a phase transition, which we identify as a critical exceptional point. In the ordered phase, antidamping induces a continuous limit cycle rotation of the order parameter with an enhanced number of 2N−3 Goldstone modes. Close to the critical exceptional point, however, fluctuations diverge so strongly due to the suppression of friction that in dimensions d<4 they universally either destroy a preexisting static order or give rise to a fluctuation-induced first-order transition. This is demonstrated within a full resummation of loop corrections via Dyson-Schwinger equations for N=2, and a generalization for arbitrary N, which can be solved in the long wavelength limit. We show that in order to realize this physics it is not necessary to drive a system far out of equilibrium: Using the peculiar protection of Goldstone modes, the transition from an xy magnet to a ferrimagnet is governed by an exceptional critical point once weakly perturbed away from thermal equilibrium.

Published by the American Physical Society
2024
The growth of e-learning in the technology industry in Middle Tennessee
Authors: Bilderback Stephanie , Movahed Mohammad , McCarthy Vikkie
Published: June 2024

Purpose

This paper intends to explore the significant growth and multifaceted benefits of e-learning within the technology sector in Middle Tennessee, particularly in the transformative context of the COVID-19 pandemic. It seeks to highlight the fundamental shift from traditional training methods to e-learning modalities and emphasize the potential of e-learning to revolutionize technical skill development and expand learning opportunities in the post-pandemic era.

Design/methodology/approach

The study employs a comprehensive review of existing literature to glean insights into the use and effectiveness of e-learning in the technology industry, particularly within Middle Tennessee. It synthesizes research findings to understand the growing preference for e-learning and online self-directed training as primary methods for technical skill development in the technology sector.

Findings

The literature review reveals a growing trend toward e-learning in the technology industry, driven by its flexibility, accessibility, and ability to rapidly update training materials. E-learning is increasingly integrated into academic programs related to technology, preparing students for the evolving job market. The COVID-19 pandemic has further highlighted the necessity for adaptable and resilient training methods, reinforcing the pivotal role of e-learning in the industry.

Originality/value

This paper contributes to the understanding of the expansion and impact of e-learning in the technology industry in Middle Tennessee, especially in light of the COVID-19 pandemic. It provides valuable insights for organizations and educators on the significance of e-learning in addressing the training needs of the technology workforce and its potential to shape the future of education and skill development in the region.
Exploring emerging technologies: librarians’ awareness, challenges and ethical perspectives in Thai library contexts, with a focus on the metaverse
Authors: A. Subaveerapandiyan , Alam Abid Fakhre , Butdisuwan Sujin , Taj Amreen , Kataria Sanjay
Published: June 2024

Purpose

This study aims to assess the awareness, interest, and challenges faced by Librarians in Thailand regarding Augmented Reality (AR), Virtual Reality (VR), and the Metaverse. Specifically, it investigates librarians' current proficiency levels, interests, perceptions of future impacts, and ethical considerations associated with these emerging technologies in the context of Library and Information Science (LIS).

Design/methodology/approach

A quantitative survey approach was employed, utilising a structured questionnaire distributed to Thai librarians across various library types. The questionnaire aligned with the study objectives and incorporated Likert-scale and multiple-choice questions. The analysis involved descriptive and inferential statistics using SPSS version 29.

Findings

The study reveals varying levels of awareness and competence among librarians in AR, VR, and the Metaverse technologies. While interest levels are high across various aspects of these technologies within LIS, challenges such as cost, expertise, ethics, and infrastructure hinder their integration into library services. Respondents anticipate a moderate to significant impact of the Metaverse on future library services, with concerns and optimism regarding ethical implications and innovative opportunities.

Originality/value

This study contributes to understanding the landscape of emerging technologies within library settings in Thailand, shedding light on librarians' awareness, interest, challenges, and ethical perspectives. The findings underscore the importance of targeted training programmes and strategic planning to facilitate the effective integration of AR, VR, and Metaverse technologies into library services, ensuring ethical considerations are prioritised alongside innovation.
A new two-step iterative technique for efficiently solving absolute value equations
Authors: Gul Nisar , Chen Haibo , Iqbal Javed , Shah Rasool
Published: June 2024

Purpose

This work presents a new two-step iterative technique for solving absolute value equations. The developed technique is valuable and effective for solving the absolute value equation. Various examples are given to demonstrate the accuracy and efficacy of the suggested technique.

Design/methodology/approach

In this paper, we present a new two-step iterative technique for solving absolute value equations. This technique is very straightforward, and due to the simplicity of this approach, it can be used to solve large systems with great effectiveness. Moreover, under certain assumptions, we examine the convergence of the proposed method using various theorems. Numerical outcomes are conducted to present the feasibility of the proposed technique.

Findings

This paper gives numerical experiments on how to solve a system of absolute value equations.

Originality/value

Nowadays, two-step approaches are very popular for solving equations (1). For solving AVEs, Liu in Shams (2021), Ning and Zhou (2015) demonstrated two-step iterative approaches. Moosaei et al. (2015) introduced a novel approach that utilizes a generalized Newton’s approach and Simpson’s rule to solve AVEs. Zainali and Lotfi (2018) presented a two-step Newton technique for AVEs that converges linearly. Feng and Liu (2016) have proposed minimization approaches for AVEs and presented their convergence under specific circumstances. Khan et al. (2023), suggested a nonlinear CSCS-like technique and a Picard-CSCS approach. Based on the benefits and drawbacks of the previously mentioned methods, we will provide a two-step iterative approach to efficiently solve equation (1). The numerical results show that our proposed technique converges rapidly and provides a more accurate solution.
Relationship between intellectual capital and firm performance: evidence from the Indian sugar mill industry
Authors: Sharma Dhanraj , Verma Ruchita , Patil Chidanand , Nayak Jitendra Kumar
Published: June 2024

Purpose

The aim of the study is to examine the influence of Intellectual Capital (IC) and its components on the financial performance of Indian sugar mill companies.

Design/methodology/approach

The present study follows the quantitative research, and uses data from Indian sugar mill companies over the period of recent 10 years. The Modified Value- Added Intellectual Capital (MVAIC) method is employed to evaluate IC. Authors construct panel regression models to test the hypotheses where Return on Equity (RoE) and Return on Asset (RoA) were considered as a representation of financial performance (dependent variable) and IC has been considered as the independent variable along with control variables.

Findings

The findings reveal that IC components show greater explanatory power than aggregate IC and MVAIC has a positive relationship with firm performance. It is evident that Capital Employed Efficiency (CEE) and Relational Capital Efficiency (RCE) have a positive effect on the RoA, while Human Capital Efficiency (HCE) and CEE have a positive impact on RoE. CEE is found to be a highly significant component to explain the financial performance of Indian sugar mill firms.

Practical implications

The study has practical implications for the policymakers for effective utilization of IC resources for worth enhancement which is essential for the improvement of financial performance.

Originality/value

The research extends the literature of IC by linking it to the financial performance of Indian sugar mill industry.
Credit card reward donation with scarcity messages
Authors: Song Chanho , Han Min Chung , Paik Sung-Hee Wendy , Hu Michael Y.
Published: June 2024

Purpose

The purpose of this paper is to investigate the effect of reward redemption programs on donation amount, donation percentage and donation intention in the context of a bank credit card.

Design/methodology/approach

A 2 × 2 × 3 experiment is implemented with 1,070 consumers accessing a national US-based sample with a small compensation. The authors use general linear model to test the proposed hypotheses.

Findings

The findings show the main effects of reward types, limited-time message and value of reward redemptions on the percentage of donations and overall donation intention to charity. The type of reward (cash/points) is found to interact with the limited-time message and with the value of reward redemptions.

Originality/value

No prior studies have addressed the relationship between credit card redemption rewards and scarcity messages in the donation context. The study contributes to the understanding of the effectiveness of credit card redemption rewards with scarcity message in improving a consumer’s donation intention.
How the reviewer’s historical ratings influence the review helpfulness?: focus on the extremity and negativity
Authors: Jang Moonkyoung , Lee Saerom , Baek Hyunmi
Published: June 2024

Purpose

As online reviews have become a potent marketing tool, the underlying motivation has come into question. Focus has shifted towards assessing reviewer credibility before appraising online review credibility. Guided by source credibility theory, this study investigates the effect of reviewers’ historical ratings on review helpfulness to gain insight into the role of reviewer credibility.

Design/methodology/approach

We explore readers’ underlying psychological processes using web data analysis (Study 1) and experiments (Study 2). Study 1 empirically examines the effect of reviewers’ historical ratings on review helpfulness using 100,621 reviews authored by 890 TripAdvisor reviewers. Study 2 involves two experiments with 328 participants to scrutinize the readers’ underlying mechanisms in establishing reviewer credibility, with a specific focus on the effect of reviewers’ historical ratings.

Findings

When a reviewer’s historical ratings are predominantly extreme, readers perceive the reviewer as less credible, leading to decreased helpfulness in reviews authored by that reviewer. Interestingly, high negativity in historical ratings does not have a significant effect on either reviewer credibility or review helpfulness.

Originality/value

This study offers two significant contributions to the existing literature. First, it extends previous research on review helpfulness by incorporating reviewers’ historical rating behavior. This provides a more comprehensive understanding of the factors that influence the perceived usefulness of reviews. Second, it integrates two distinct research methods: TripAdvisor web data analysis and experiments. This methodological synthesis enhances the robustness of the study by offering a more nuanced and well-rounded perspective on the dynamics between reviewers’ historical ratings and perceived helpfulness of reviews.