bluuebunny/crossref_metadata_2025 huggingface dataset:
Charting cortical-layer specific area boundaries using Gibbs’ ringing attenuated T1w/T2w-FLAIR myelin MRI
Authors: Autio Joonas A. , Uematsu Akiko , Ikeda Takuro , Ose Takayuki , Hou Yujie , Magrou Loïc , Kimura Ikko , Ohno Masahiro , Murata Katsutoshi , Coalson Tim , Kennedy Henry , Glasser Matthew F. , Van Essen David C. , Hayashi Takuya
Published: September 2024

Cortical areas have traditionally been defined by their distinctive layer cyto- and/or myelo- architecture using postmortem histology. Recent studies have delineated many areas by measuring overall cortical myelin content and its spatial gradients using the T1w/T2w ratio MRI in living primates, including humans. While T1w/T2w studies of areal transitions might benefit from using the layer profile of this myelin-related contrast, a significant confound is Gibbs’ ringing artefact, which produces signal fluctuations resembling cortical layers. Here, we address these issues with a novel approach using cortical layer thickness-adjusted T1w/T2w-FLAIR imaging, which effectively cancels out Gibbs’ ringing artefacts while enhancing intra-cortical myelin contrast. Whole-brain MRI measures were mapped onto twelve equivolumetric layers, and layer-specific sharp myeloarchitectonic transitions were identified using spatial gradients resulting in a putative 182 area/subarea partition of the macaque cerebral cortex. The myelin maps exhibit notably high homology with those in humans, suggesting cortical myelin shares a similar developmental program across species. Comparison with histological Gallyas myelin stains explains over 80% of the variance in the laminar T1w/T2w-FLAIR profiles, substantiating the validity of the method. Altogether, our approach provides a novel, noninvasive means for precision mapping layer myeloarchitecture in the primate cerebral cortex, advancing the pioneering work of classical neuroanatomists.
Pexidartinib plus FLT3-directed CAR-Macrophage for the treatment of FLT3-ITD-mutated acute myeloid leukemia in preclinical model
Authors: Chen Fan , Lv Min-Hong , Li Chun-Wei , Zhang Yi-Qiong , Wei Ze-Xiao , Yuan Zhi , Cao Jian-Yong , Yang Xinming , Xu Jing-Bo , Wang Li , He Bai-Liang
Published: September 2024

Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Internal tandem duplication of FMS-like tyrosine kinase 3 (FLT3-ITD) mutations occur in about 25%-30% of AML cases and are associated with adverse prognosis. Recent advances indicate that M2-like leukemia-associated macrophages (M2-LAM) are highly infiltrated in the bone marrow of FLT3-ITD+ AML patients; however, the underlying mechanisms and therapeutic implications are still elusive. Herein, we reveal that conditioned medium from FLT3-ITD+ MOLM-13 AML cells polarized M2-LAM and impaired their phagocytic activities. Unexpectedly, co-culture of M2-LAM protected MOLM-13 cells from the treatment of FLT3 inhibitor quizartinib by activating their FLT3 signaling pathway. Pharmaceutically, FLT3/CSF1R dual inhibitor pexidartinb effectively suppressed M2-LAM, reduced leukemic burden, and prolonged the survival of MOLM-13-xenografted mice. To enhance the phagocytic activities of macrophages, FLT3-directed chimeric antigen receptor-engineered macrophages (FLT3L-CAR-Macrophage) were generated using FLT3 ligand (FLT3L) as the recognizing domain of CAR. Transfection of THP-1 monocytic cells-or umbilical cord blood mononuclear cells-derived macrophages with FLT3L-CAR-encoding mRNA enhanced their phagocytic activities to MOLM-13 cells in vitro. Consistently, FLT3L-CAR-Macrophage differentiated from FLT3L-CAR-expressing THP-1 cells effectively phagocytosed MOLM-13 cells in vitro, reduced leukemic burden and prolonged the survival of MOLM-13-xenografted mice. Importantly, treatment of pexidartinib resulted in upregulation and surface localization of FLT3-ITD protein in MOLM-13 cells, sensitized MOLM-13 cells to the treatment of FLT3L-CAR-Macrophage in vitro, and synergized with FLT3L-CAR-Macrophage to further reduce leukemic burden in MOLM-13-xenografted mice. Together, our data indicate that pexidartinib plus FLT3L-CAR-Macrophage could be a promising therapeutic strategy for the treatment of FLT3-ITD+ AML in preclinical model which warrants further investigation.

Graphical Abstract

Pexidartinib plus FLT3L-CAR-Mφ for the treatment of FLT3-ITD+ AML in preclinical model. Pexidartinib suppressed AML growth, reduced M2-LAM, increased FLT3 surface expression and synergized with FLT3L-CAR-Mφ to target FLT3-ITD+ AML in vitro and in vivo.
Insertion of fluorescent proteins near the plug domain of MotB generates functional stator complex
Authors: Gurung Jyoti P , Ridone Pietro , Biquet-Bisquert Anaïs , Bryant Gary , Pedaci Francesco , Nord Ashley L. , Baker Matthew AB
Published: September 2024

Many bacteria swim by the rotation of the bacterial flagellar motor (BFM). The BFM is powered by proton translocation across the inner membrane through the hetero-heptameric MotA5MotB2protein complex. Two periplasmic domains of MotB are critical in activating BFM rotation: (1) the peptidoglycan binding (PGB) domain that anchors MotB in the peptidoglycan layer and (2) the plug domain that modulates the proton flow. Existing cytoplasmic fluorescent probes have been shown to negatively affect motor rotation and switching. Here we inserted a fluorescent probe in the periplasm near the plug of MotB in an attempt to circumvent issues with cytoplasmic probes and for possible use in observing the mechanism of plug-based regulation of proton flow. We inserted green fluorescent protein (GFP) and iLOV, a fluorescent version of the light-oxygen-voltage (LOV) domain, in four periplasmic locations in MotB. Insertions near the plug retained motility but showed limited fluorescence for both fluorophores. Additional short, flexible glycine-serine (GS) linkers improved motility but did not improve brightness. Further optimization is necessary to improve the fluorescence of these periplasmic probes.
A framework for gene representation on spatial transcriptomics
Authors: Cao Shenghao , Yuan Ye
Published: September 2024

Recent foundation models for single-cell transcriptomics data generate informative, context-aware gene representations. The spatially resolved transcriptomics data offer extra positional insights, yet corresponding gene representation methods that integrate both intracellular and spatial context are still lacking. Here, we introduce a gene representation framework tailored for spatial transcriptomics data. It incorporates ligand genes within the spatial niche into the transformer encoder of single-cell transcriptomics. We further propose a biased cross-attention method to enable the framework to do learning with single-cell resolution on low-resolution, whole-transcriptome Visium data. We implemented our framework on a hybrid Visium dataset derived from two human tissue types with distinct developmental and disease states, and tested on various downstream applications. Compared with the latest foundation model for single-cell transcriptomics, our spatially informed gene representations could identify cell groups and gene functions more accurately, and could predict the perturbation effects of cell-cell ligand-receptor interactions on downstream targets.
Plasmid conjugation drives within-patient plasmid diversity
Authors: Grayson Fan , Loman Leo , Nonnenmacher Toby , Pople Diane , Pollard Jack , Williams David , Patel Bharat , Hounsome Luke , Hopkins Katie L , Robotham Julie , Ledda Alice
Published: September 2024

Plasmids are well known vehicles of antimicrobial resistance (AMR) genes dissemination. Through conjugation, plasmid–encoded AMR genes are spread among neighbouring bacteria, irrespective of their strain or even their species. This process is very concerning from a public health perspective, as plasmid-borne AMR gene outbreaks are often not confined to single species or strains and are therefore more difficult to be fully uncovered. At the moment, the impact of plasmid conjugation on within-patient plasmid diversity is not well understood. In this work we will tackle the role of conjugation on within-patient plasmid diversity using a dataset of carbapenemase-producingEnterobacterales(CPEs). The dataset of 256 sequences from 115 patients was sampled across England over 30 months. Each patient has more than one sequence, with at least one sequence carrying an OXA-48 gene, a well-known plasmid-borne carbapenemase-encoding gene. If more than one sequence carries the OXA-48 gene, they are carried on different bacterial hosts. Using a hybridde novo-on-reference assembly pipeline, we were able to reconstruct the full OXA-48 plasmid from short read sequencing data for 232 of the 256 sequences. Of the 115 patients, 83 (72%) of patients had an identical OXA-48 plasmid in two or more sequences. Only 2 patients carried very different (>200 SNPs) alleles of the OXA-48 plasmid, probably from separate acquisitions. Our study shows that when more than one bacterial host carrying an OXA-48 plasmid is found in a patient, it is most likely that the same plasmid has been shared via conjugation. The event of separate acquisition of different plasmids in different bacterial hosts is highly unlikely in our dataset.

Data Statement

We use data provided by Hopkins et al 2022 [16]. The data can be accessed from the National Center for Biotechnology Information (NCBI) and can be found at Bioproject Accession no. PRJNA788733. None of the data used was synthetically generated.

Impact Statement

Conjugative plasmids are well known vessels of horizontal gene transfer, with a prominent role in the spread of antimicrobial resistance genes among different bacterial species or strains. At the epidemiological level, conjugation combined with sequencing a single colony per patient, results in plasmids outbreaks carrying antimicrobial resistance genes being found in different bacterial species and strains in different patients, potentially eluding surveillance protocols based on same bacterium/same resistance scheme. In this study we analyse within-patient plasmid diversity in a dataset with more than one sequence per patient. Only two patients show clear genomic signs of separate plasmids acquisition, while 83 patients share identical plasmids in different bacterial hosts. This points out to a very strong role of plasmid conjugation in shaping within-patient plasmid diversity.
Ancient origin and high diversity of zymocin-like killer toxins in the budding yeast subphylum
Authors: Heneghan Padraic G. , Salzberg Letal I. , Cinnéide Eoin Ó , Dewald Jan A. , Weinberg Christina E. , Wolfe Kenneth H.
Published: September 2024

Zymocin is a well-characterized killer toxin secreted by some strains of the yeastKluyveromyces lactis. It acts by cleaving a specific tRNA in sensitive recipient cells. Zymocin is encoded by a killer plasmid or virus-like element (VLE), which is a linear DNA molecule located in the cytosol. We hypothesized that a tRNA-cleaving toxin similar to zymocin may have caused the three parallel changes to the nuclear genetic code that occurred during yeast evolution, in which the codon CUG became translated as Ser or Ala instead of Leu. However, zymocin-like toxins are rare – both among species, and among strains within a species – and only four toxins of this type have previously been discovered. Here, we identified 45 new zymocin-like toxin genes in Saccharomycotina, the budding yeast subphylum, using a novel bioinformatics strategy, and verified that many of them are toxic toS. cerevisiaewhen expressed. Some of the new toxin genes are located on cytosolic VLEs, whereas others are on VLE-derived DNA integrated into the nuclear genome. The toxins are extraordinarily diverse in sequence and show evidence of positive selection. Toxin genes were found in five taxonomic orders of budding yeasts, including two of the three orders that reassigned CUG codons, indicating that VLEs have been parasites of yeast species for at least 300 million years and that their existence pre-dates the genetic code changes.
Cannabis Expression Atlas: a comprehensive resource for integrative analysis ofCannabis sativaL. gene expression
Authors: Barbosa-Xavier Kevelin , Pedrosa-Silva Francisnei , Almeida-Silva Fabricio , Venancio Thiago M.
Published: September 2024

Cannabis sativaL., a plant originating from Central Asia, is a versatile crop with applications spanning textiles, construction, pharmaceuticals, and food products. This study aimed to compile and analyze publicly available Cannabis RNA-Seq data and develop an integrated database tool to help advance Cannabis research in various topics such as fiber production, cannabinoid biosynthesis, sex determination, and plant development. We identified 515 publicly available RNA-Seq samples that, after stringent quality control, resulted in a high-quality dataset of 394 samples. Utilizing the Jamaican Lion genome as reference, we constructed a comprehensive database and developed the Cannabis Expression Atlas (https://cannatlas.venanciogroup.uenf.br/), a web application for visualization of gene expression, annotation, and functional classification. Key findings include the quantification of 27,640 Cannabis genes and their classification into seven expression categories: not-expressed, low-expressed, housekeeping, tissue-specific, group-enriched, mixed, and expressed-in-all tissues. The study revealed substantial variability and coherence in gene expression across different tissues and chemotypes. We found 2,382 tissue-specific genes, including 177 transcription factors.. The Cannabis Expression Atlas constitutes a valuable tool for exploring gene expression patterns and offers insights into Cannabis biology, supporting research in plant breeding, genetic engineering, biochemistry, and functional genomics.
Terrestrial herbivory drives adaptive evolution in an aquatic community via indirect effects
Authors: Schäfer Martin , Malacrinò Antonino , Walcher Christoph , Spaak Piet , Sárazová Marie Serwaty- , Käser Silvana , Bulas Thea , Dambone-Bösch Christine , Dexter Eric , Hottinger Jürgen , Böttner Laura , Vorburger Christoph , Ebert Dieter , Xu Shuqing
Published: September 2024

Indirect ecological effects, which occur when the impact of one species on another is mediated by a third species or the shared environment, are ubiquitous in nature. Given the complexity of natural systems, indirect ecological effects were thought to be important in driving eco-evolutionary processes across community boundaries. However, we know remarkably little about such effects. Here we show that indirect effects of terrestrial insect (aphids) herbivory on macrophytes (duckweed) drives adaptive evolution of water fleas (Daphnia) in large outdoor aquatic mesocosms. Aphid herbivory reduced macrophyte growth and increased the abundance of phytoplankton, which in turn increased the abundance ofDaphnia. Whole genome pool sequencing and phenotypic assays revealed an impact on the genetic compositions of theDaphniapopulations and transplant experiments indicated that these evolutionary changes were adaptive. Furthermore, these changes in the aquatic community altered the interactions of the aphids and the macrophytes. These results demonstrate that indirect ecological effects can shape eco-evolutionary interactions between different communities.
TMED9 coordinates the clearance of misfolded GPI-anchored proteins out of the endoplasmic reticulum and into the Golgi
Authors: Ronzier Elsa , Satpute-Krishnan Prasanna
Published: September 2024

The p24-family member, TMED9, has recently emerged as a player in secretory pathway protein quality control (PQC) that influences the trafficking and degradation of misfolded proteins. Here we show that TMED9 plays a central role in the PQC of GPI-anchored proteins (GPI-APs). Typically, upon release from the endoplasmic reticulum (ER)-resident chaperone calnexin, misfolded GPI-APs traffic to the Golgi by an ER-export pathway called Rapid ER stress-induced Export (RESET). From the Golgi, they access the plasma membrane where they are rapidly internalized for lysosomal degradation. We used biochemical and imaging approaches in cultured cells to demonstrate that at steady-state, the majority of misfolded GPI-APs reside in the ER in association with calnexin and TMED9. During RESET, they dissociate from calnexin and increase their association with TMED9. Inhibition of TMED9’s function through siRNA-induced depletion or chemical inhibitor, BRD4780, blocked ER-export of misfolded GPI-APs. By contrast, TMED9-inhibition did not prevent ER-export of wild type GPI-APs, indicating a specific role for TMED9 in GPI-AP PQC. Intriguingly, we discovered that acute treatment with BRD4780 induced a shift in TMED9 localization away from the ER to the downstream Golgi cisternae and blocked the RESET pathway. Upon removal of BRD4780 following acute treatment, TMED9 regained access to the ER where TMED9 was able to associate with the RESET substrate and restore the RESET pathway. These results suggest that TMED9 plays a requisite role in RESET by capturing misfolded GPI-APs that are released by calnexin within the ER and conveying them to the Golgi.
Mapping the landscape of social behavior
Authors: Klibaite Ugne , Li Tianqing , Aldarondo Diego , Akoad Jumana F. , Ölveczky Bence P. , Dunn Timothy W.
Published: September 2024

Social interaction is integral to animal behavior. However, we lack tools to describe it with quantitative rigor, limiting our understanding of its principles and neuropsychiatric disorders, like autism, that perturb it. Here, we present a technique for high-resolution 3D tracking of postural dynamics and social touch in freely interacting animals, solving the challenging subject occlusion and part assignment problems using 3D geometric reasoning, graph neural networks, and semi-supervised learning. We collected over 140 million 3D postures in interacting rodents, featuring new monogenic autism rat lines lacking reports of social behavioral phenotypes. Using a novel multi-scale embedding approach, we identified a rich landscape of stereotyped actions, interactions, synchrony, and body contact. This enhanced phenotyping revealed a spectrum of changes in autism models and in response to amphetamine that were inaccessible to conventional measurements. Our framework and large library of interactions will greatly facilitate studies of social behaviors and their neurobiological underpinnings.
Mycobacterium tuberculosisovercomes phosphate starvation by extensively remodelling its lipidome with phosphorus-free lipids
Authors: Gray Robert M. , Hunt Debbie M. , dos Santos Mariana S. , Liu Jiuyu , Agapova Aleksandra , Rodgers Angela , Garza-Garcia Acely , Macrae James , Gutierrez Maximiliano G. , Lee Richard E. , de Carvalho Luiz Pedro S.
Published: September 2024

Tuberculosis (TB) is the biggest cause of death from infectious disease worldwide [1–4]. The causative agent,Mycobacterium tuberculosis(Mtb), possesses a complex cell envelope that determines many of the key physiologic and virulence properties that facilitate infection, which comprises multiple classes of unique lipids [5–7]. The macrophage phagosome is a key reservoir of infection in pulmonary TB and multiple studies have shown that inorganic phosphate (Pi) is limiting in this environment [8–11]. The ability of Mtb to sense and respond to phosphate starvation is required for virulence in animal models and replication in human macrophages in vitro [12–14]. Here, we show that during Pi restriction the Mtb lipidome is markedly remodelled such that phospholipids are replaced with multiple classes of phosphorus-free lipids, some of which have not been documented before. Further, we discover that Mtb can metabolise phospholipid polar heads derived from host pulmonary surfactant as an alternative phosphate source, which sustains cell division for several generations during Pi restriction. These dual manipulations of phospholipid metabolism provide Mtb with an escape from phosphate restriction specific to the infection of alveolar macrophages, one of the earliest steps in establishing pulmonary tuberculosis. The changes in envelope lipidome remodelling, akin to that observed in some marine and terrestrial bacteria [15–20] suggests that standard Mtb culture conditions that use media with high concentrations of Pi do not reflect the physiologic environment during infection, thereby potentially undermining vaccine and drug development for tuberculosis. Moreover, the distinct Mtb phosphate-free lipids and the metabolic pathways that generate them could provide new antibiotic targets.
The oneirogen hypothesis: modeling the hallucinatory effects of classical psychedelics in terms of replay-dependent plasticity mechanisms
Authors: Bredenberg Colin , Normandin Fabrice , Richards Blake , Lajoie Guillaume
Published: September 2024

Classical psychedelics induce complex visual hallucinations in humans, generating percepts that are co-herent at a low level, but which have surreal, dream-like qualities at a high level. While there are many hypotheses as to how classical psychedelics could induce these effects, there are no concrete mechanistic models that capture the variety of observed effects in humans, while remaining consistent with the known pharmacological effects of classical psychedelics on neural circuits. In this work, we propose the “oneirogen hypothesis”, which posits that the perceptual effects of classical psychedelics are a result of their pharmacological actions inducing neural activity states that truly are more similar to dream-like states. We simulate classical psychedelics’ effects via manipulating neural network models trained on perceptual tasks with the Wake-Sleep algorithm. This established machine learning algorithm leverages two activity phases, a perceptual phase (wake) where sensory inputs are encoded, and a generative phase (dream) where the network internally generates activity consistent with stimulus-evoked responses. We simulate the action of psychedelics by partially shifting the model to the ‘Sleep’ state, which entails a greater influence of top-down connections, in line with the impact of psychedelics on apical dendrites. The effects resulting from this manipulation capture a number of experimentally observed phenomena including the emergence of hallucinations, increases in stimulus-conditioned variability, and large increases in synaptic plasticity. We further provide a number of testable predictions which could be used to validate or invalidate our oneirogen hypothesis.
Zebrafish glial-vascular interactions progressively expand over the course of brain development
Authors: Gall Lewis G. , Stains Courtney M. , Freitas-Andrade Moises , Jia Bill Z. , Patel Nishi , Megason Sean G. , Lacoste Baptiste , O’Brown Natasha M.
Published: September 2024

Glial-vascular interactions are critical for the formation and maintenance of brain blood vessels and the blood-brain barrier (BBB) in mammals, but their role in zebrafish is not well understood. Our previous work has detailed the timeline of BBB functional maturation in zebrafish, revealing a conserved mechanism of BBB induction through the suppression of endothelial transcytosis. Yet, as opposed to extensive research on glial-vascular interactions in rodents, such interactions remain largely overlooked in the zebrafish model system. Here, we focus on glial-vascular development in the zebrafish brain, leveraging three glial gene promoters:gfap(glial fibrillary acidic protein),glast(an astrocyte-specific glutamate transporter), andglastini(a new, shortened, equally effective version of the Glast promoter). Using these glial promoters, sparse labeling revealed fewer glial-vascular interactions during early larval stages, with both glial coverage and contact area increasing as the zebrafish brain matured. We then generated stable transgenic lines for both the Glast and Glastini promoters and observed similar increases in glial coverage during larval development, starting at ∼30% coverage at 3 days post-fertilization (dpf) and peaking at ∼60% at 10 dpf. Ultrastructural assessment of glial-vascular interactions using electron microscopy (EM) confirmed a progressive increase in glial coverage over larval development, with maximal coverage reaching ∼70% in adult zebrafish, significantly lower than the nearly 100% coverage observed in mammals. Finally, immunogold-EM labeling confirmed that cells identified as glia in aforementioned morphological analyses were indeed Glast-positive. Taken together, our results identify the temporal profile of glial-vascular maturation in the zebrafish brain.
Comparative tissue-specific transcriptomics reveal the genetic bases underlying evolutionary convergence of seed shattering in two independently evolved weedy rice lineages
Authors: Li Xiang , Caicedo Ana L.
Published: September 2024

The repeated evolution of high seed shattering during multiple independent de-domestications of cultivated Asian rice (Oryza sativa) into weedy rice is a prime example of convergent evolution. Weedy rice populations converge in histological features of the abscission zone (AZ), a crucial structure for seed abscission, while ancestral cultivated rice populations exhibit varied AZ morphology and levels of shattering. However, the genetic bases of these phenotypic patterns remain unclear. We examined the expression profiles of the AZ region and its surrounding tissues at three developmental stages in two low-shattering cultivars ofausandtemperate japonicadomesticated varieties and in two genotypes of their derived high-shattering weed groups, Blackhull Awned (BHA) and Spanish Weedy Rice (SWR), respectively. Consistent with the greater alteration of AZ morphology during the de-domestication of SWR than BHA, fewer genes exhibited a comparable AZ-region exclusive expression pattern between weed and crop in thejaponicalineage than inauslineage. Transcription factors related to the repression of lignin and secondary cell deposition, such as,OsWRKY102andOsXND-1-like, along with certain known shattering genes involved in AZ formation, likely played a role in maintaining AZ region identity in both lineages. Meanwhile, most genes exhibiting AZ-region exclusive expression patterns do not overlap between the two lineages and the genes exhibiting differential expression in the AZ region between weed and crop across the two lineages are enriched for different gene ontology terms. Our findings suggest genetic flexibility in shaping AZ morphology, while genetic constraints on AZ identity determination in these two lineages.

Significance statement

Exploring the extent of genetic convergence that underlies the morphological convergence - specifically, the recurrent evolution of complete abscission zones in independently evolved weedy rice populations originating from different cultivated rice populations with varying degrees of disrupted abscission zones - can improve our understanding not only of the genetic mechanisms behind convergent evolution, but also of the genetics underlying the agriculturally importance trait of seed shattering.
Ancient environmental DNA indicates limited human impact on marine biodiversity in pre-industrial Iceland
Authors: Holman Luke E. , Arfaoui Emilia M. R. , Pedersen Lene Bruhn , Farnsworth Wesley R , Ascough Phillipa , Butler Paul , Guðmundsdóttir Esther R. , Reynolds David J. , Trofimova Tamara , Wilkin Jack T. R. , Carøe Christian , Frøslev Tobias Guldberg , Harrison Ramona , Gopalakrishnan Shyam , Pedersen Mikkel Winther , Scourse James , Bohmann Kristine
Published: September 2024

Human activities are affecting marine biodiversity globally by accelerating extinction rates, altering ecosystem conditions, and changing community structures. These changes can only be understood through establishing the ecosystem state prior to significant anthropogenic impact, and by disentangling the anthropogenic effect from natural climatic changes. Here, we reconstruct marine biodiversity in Iceland across three millennia (1315 BCE-1785 CE), encompassing periods of climatic fluctuation and human settlement, to explore the comparative effect of natural and anthropogenic forces on marine biodiversity. We performed 18S metabarcoding of ancient environmental DNA from two sediment cores collected from northern Icelandic shelf seas, integrating local climatic records, population estimates and zooarchaeological remains from published sources to estimate the influence of climatic and anthropogenic impacts. Against the backdrop of increasing human populations and marine exploitation, we observe no large-scale taxonomic shifts or anthropogenic biodiversity changes across the period. In contrast, we found a positive correlation between herring (Clupea harengus) detection rates and proxy-reconstructed sea surface temperature, suggesting a role for climate in shaping marine biodiversity. Overall, our data suggest that despite impacts on terrestrial ecosystems and the development of a substantial export fishery across the study period, Icelandic society may have had a limited effect on marine biodiversity.
Interaction between histone residue H3K56 and mismatch repair protein MutSβ drives CAG repeat expansion
Authors: Guo Jinzhen , Yang Wei , Li Guo-Min
Published: September 2024

DNA repair protein MutSβ promotes CAG•CTG repeat expansions, which cause ∼20 untreatable neurodegenerative disorders including Huntington’s disease (HD). However, how MutSβ is recruited onto chromatin to enable repeat expansion is unknown. Here, we show that H3K56 interacts with MutSβ and brings it to chromatin. The H3K56-MutSβ interaction is regulated by H3K56 acetylation (H3K56ac) conditions, with acetylation inhibiting but deacetylation facilitating MutSβ chromatin recruitment. Blocking the H3K56-MutSβ interaction by either disrupting the MutSβ aromatic packet or increasing the H3K56ac level by removing histone deacetylases stabilizes CAG repeats, while depleting histone acetyltransferase p300/CBP promotes the H3K56-MutSβ interaction and CAG•CTG repeat instability, including expansion of CAG repeats of the huntingtin gene. Therefore, our study suggests a novel mechanism, by which MutSβ induces triplet repeat expansion, and new strategies of blocking the H3K56-MutSβ interaction to prevent HD and other triplet repeat expansion-caused disorders.
Radical Protein Footprinting in Mammalian Whole Blood
Authors: Tobin Lyle , Misra Sandeep K. , Luo Haolin , Jones Lisa M. , Sharp Joshua S.
Published: September 2024

Hydroxyl Radical Protein Footprinting (HRPF) is a powerful method to probe the solvent-accessible surface area of proteins. It is mostly used to study the higher-order structure of proteins, as well as protein-protein and protein-carbohydrate interactions. Hydroxyl radicals are generated by the photolysis of hydrogen peroxide and these radicals modify the surface amino acids. Bottom-up proteomics is then applied and peptide oxidation is calculated and correlated with solvent accessibility. It is mainly performedin vitro; however, it has been recently used in living systems, including live cells, live nematodes, and 3D cell cultures. Mammalian tissues are still out of reach as they absorb UV strongly, hindering radical generation. Here, we describe the first example of RPF in mammalian stabilized whole blood. Using photoactivation of persulfate with a commercially available FOX Photolysis System modified for sample handling and inline mixing, we demonstrate the first labeling of proteins in whole blood. We demonstrate that the RPF protocol does not alter the blood cell gross morphology outside of a moderate hypertonicity equivalent to sodium chloride exposure prior to labeling. We detail an improved quenching protocol to limit background labeling in persulfate RPF. We describe the labeling of the top ten most abundant proteins in the blood. We demonstrate the equivalence ofex vivolabeling in whole blood with labeling of the same structurein vitrousing hemoglobin as a test system. Overall, these results now open the possibility of performing RPF-based structural proteomics in pre-clinical models and using readily available clinical samples.
The effect of meta-commerce consumption value on consumer satisfaction and continuous usage intention: the moderating roles of meta-verse involvement and consumer competency
Authors: Kim Nayeon , Kim Woo-Hyuk
Published: September 2024

Purpose

The purpose of this study is to investigate the relationships between Meta-commerce consumption value, consumer satisfaction and continuous usage intention in light of the moderating effects of involvement and consumer competency.

Design/methodology/approach

A survey for hypothesis testing was conducted targeting 200 domestic consumers in South Korea aged 19 years and above with experience in Meta-commerce. In order to examine the data, we used exploratory factor analysis (EFA), confirmatory factor analysis (CFA) and structural equation modeling using SPSS and AMOS.

Findings

The paper discovered that Meta-commerce consumption value affects consumer satisfaction and continuous usage intention. Specifically, the extrinsic value and the epistemic value of Meta-commerce have a positively significant effect on satisfaction. Additionally, the hedonic value of Meta-commerce has a positively significant effect on continuous usage intention. It also presented the differences in influence between low-involvement/high-involvement groups and low-competency/high-competency groups and examined consumer perceptions in detail.

Originality/value

The paper discovered that Meta-commerce consumption value affects consumer satisfaction and continuous usage intention. Specifically, the extrinsic value and the epistemic value of Meta-commerce have a positively significant effect on satisfaction. Additionally, the hedonic value of Meta-commerce has a positively significant effect on continuous usage intention. It also presented the differences in influence between low-involvement/high-involvement groups and low-competency/high-competency groups and examined consumer perceptions in detail.
Fermentation dynamics, physicochemical and sensory characteristics of Malaysian traditional rice wines
Authors: Koay Meiwei , Fan Hui Yin , Wong Clemente Michael Vui Ling
Published: September 2024

Purpose

Malaysian rice wines (tapai) manufactured in small-scale industries are usually formulated based on personal experiences under minimally controlled conditions for generations, especially in Sabah, one of the East Malaysian states. However, the quality and safety of rice wines were receiving increased attention to ensure better quality control, particularly those produced on an industrial scale. Therefore, this research aims to determine the fermentation dynamics and consumers’ acceptance of Malaysian rice wines produced using different sasad (a local term for starter culture from Sabah).

Design/methodology/approach

The physicochemical [total soluble solids (TSS), alcohol content, total titratable acidity (TTA) and pH] and microbiological [total yeast and mould count (TYMC) and total lactic acid bacteria (LAB) count] changes in Malaysian rice wines were determined to better understand the fermentation process for future process optimisation. Additionally, sensory evaluations were conducted to determine the consumers’ preferences for the rice wines.

Findings

The overall fermentation dynamics of rice wines exhibited similar trends with slight variations between the samples, demonstrating the effect of microbial compositions of sasad on the quality of final rice wines. Additionally, consumer acceptance tests showed that rice wines with darker shades of yellow and a stronger alcoholic aroma were preferable.

Originality/value

This is the first research that provides important insights into both the fermentation dynamics and consumers’ acceptance of Malaysian traditional rice wines, enriching the rice wine literature from the academic perspective and contributing to the production of safe and high-quality rice wines.
How has scientific performance of distinguished young scholars in China changed compared to their early careers?
Authors: Niu Lihui , Si Xiangyun , Ma Feicheng
Published: September 2024

Purpose

This paper aims to conduct a comparative analysis of the scientific performance of distinguished young scholars in China during the pre-award and early stages of their research careers, aiming to provide insights into their growth pattern.

Design/methodology/approach

Spearman correlation was used to analyse the correlation between various academic ages and awarding age of the distinguished young scholars. The Wilcoxon matched pairs test was used to analyse variations in their scientific performance across different research stages.

Findings

The findings showed that: a) early successful research experiences significantly impact their emergence as outstanding scientists. While a low correlation exists between publication ages and awards, perseverance proves crucial for later-stage academic achievements; b) productivity increases before awards, with notable variations between first-author and non-first-authored publications; c) collaboration intensifies before awards, particularly in non-first author roles. However, discipline-specific variations highlight the importance of smaller teams and first-author roles, especially in the early career stage; d) the correlation between collaboration and productivity depends on research roles, emphasizing the evolving nature of collaboration dynamics as scholars progress in their careers.

Originality/value

This study could offer a reference for formulating well-founded talent training programs and reward mechanisms.
Report on culture towards critical rapport: basis for cautious, conscious and careful contemporary cultural studies and literacy
Authors: Servaña Alvin
Published: September 2024

Purpose

This paper offers a critical exegesis of popular culture and its intersections with the other cultural expressions in the contemporary Philippine scene. As a distinct Reformed-Evangelical critique, the paper hopes to shed light on the areas of popular culture that are often assumed rather than discussed; affirmed but not analysed.

Design/methodology/approach

Although the following exposition is readily and arguably Western by orientation, most especially on the (post)modern mood in the space it belongs, as hegemonised by Anglo-American discourse, most of the concepts that this paper tackles are definitely universal and principled in praxes. The persuasion is that these criticisms will cover even the Filipino sub-/culture and sensibility in its attempt to exegete culture ontologically and contemplate on the phenomenon of popular culture at the very least. In that case, everyone who reads and specialises in cultural hermeneutics is thereby urged to offer a conscious understanding, comprehension and correspondence on the aforementioned particular aspects, albeit not everyone in the masses can readily grasp what this paper intends to build its discourse on. In carrying out this cultural exegetical task, certain markers and indicators will be used as halters, so to defamiliarise one’s attention on matters that may have immediate correspondence to the Filipino culture in its contemporary scene/sense, be it urban, suburban or rural depending on the spatial location of the readers as they interact with this treatise. As a whole, this paper endeavours to mould and uphold one’s glocal consciousness, distinctions, and differentiations in the assessment of culture, popular culture and popular culture in the Philippines vis-a-vis or vs other factors of this shared reality, sub-/culture and literacy and their probable popular culture counterparts elsewhere in the signifying and significant human experiences, challenges and perspectives.

Findings

The paper finds out that without a critico-practical approach to the implications of popular culture, it will be an insidious challenge to anyone who wishes to coexist with it, most especially the subcultural expressions of certain communities.

Originality/value

The paper possesses novelty in its being an intersection of cultural studies, criticism, theology and philosophy as basis for interpretation of certain socio-cultural phenomena in the contemporary urban space.
Memory response in quasi-static thermoelastic stress in a rod due to distributed time-dependent heat sources
Authors: Balwir Apeksha , Kamdi Dilip , Varghese Vinod
Published: September 2024

Purpose

To find the quasi-static thermoelastic stress and displacement, the proposed model looks at how the microstructures interact with each other and how the temperature changes inside a rod. It uses the fractional-order dual-phase-lag (FODPL) theory to derive analytical solutions for one-dimensional problems in nonsimple media within the MDD framework. The dimensionless equations are used to analyze a finite rod experiencing the heat sources continuously distributed over a finite portion of the rod which vary with time according to the ramp-type function with other sectional heat supplies kept at zero temperature. The study introduces a technique using integral transforms for exact solutions in the Laplace transform domain for different kernel functions.

Design/methodology/approach

A novel mathematical model incorporating dual-phase-lags, two-temperatures and Riesz space-fractional operators via memory-dependent derivatives has been established to analyze the effects of thermal stress and displacement in a finite rod. The model takes into account the continuous distribution of heat sources over a finite portion of the rod and their time variation according to the ramp-type function. It incorporates the finite Riesz fractional derivative in two-temperature thermoelasticity with dual-phase-lags via memory effect, and its solution is obtained using Laplace transform with respect to time and sine-Fourier transform with respect to spatial coordinates defined over finite domains.

Findings

In memory-dependent derivatives, thermal field variables are strongly influenced by the phase-lag heat flux and temperature gradient. The non-Fourier effects of memory-dependent derivatives substantially impact the distribution and history of the thermal field response, and energy dissipation may result in a reduction in temperature without heat transfer. The temperature, displacement and stress profile exhibit a reduced magnitude with the MDD effect compared to when the memory effect is absent (without MDD). To advance future research, a new categorization system for materials based on memory-dependent derivative parameters, in accordance with the principles of two-temperature thermoelasticity theory, must be constructed.

Research limitations/implications

The one-dimensional assumption introduces limitations. For example, local heating of a one-dimensional plate will not extend radially, and heating one side will not heat the surrounding sides. Furthermore, while estimating heat transfer, object shape limits may apply.

Originality/value

This paper aims to revise the classical Fourier law of heat conduction and develop analytical solutions for one-dimensional problems using fractional-order dual-phase-lag (FODPL) theory in nonsimple media in the context of MDD.
Research on the monitoring system for induced voltage and ground current of 27.5 kV cable sheath in railways
Authors: Zhang Zehui , Huang Qian , Li Lewen , Li Dan , Luo Xueping , Zeng Xiaohong
Published: September 2024

Purpose

The purpose of this study is to address the deficiency in safety monitoring technology for 27.5 kV high-voltage cables within the railway traction power supply by analyzing the grounding methods employed in high-speed railways and developing an effective monitoring solution.

Design/methodology/approach

Through establishing a mathematical model of induced potential in the cable sheath and analyzing its influencing factors, the principle of grounding current monitoring is proposed. Furthermore, the accuracy of data collection and alarm function of the monitoring equipment were verified through laboratory simulation experiments. Finally, through practical application in the traction substation of the railway bureau on site, a large amount of data were collected to verify the stability and reliability of the monitoring system in actual environments.

Findings

The experimental results show that the designed monitoring system can effectively monitor the grounding current of high-voltage cables and respond promptly to changes in cable insulation status. The system performs excellently in terms of data collection accuracy, real-time performance and reliability of alarm functions. In addition, the on-site trial results further confirm the accuracy and reliability of the monitoring system in practical applications, providing strong technical support for the safe operation of high-speed railway traction power supply systems.

Originality/value

This study innovatively develops a 27.5kV high-voltage cable grounding current monitoring system, which provides a new technical means for evaluating the insulation status of cables by accurately measuring the grounding current. The design, experimental verification and application of this system in high-speed railway traction power supply systems have demonstrated significant academic value and practical significance, contributing innovative solutions to the field of railway power supply safety monitoring.
Multisystemic therapy for young people involved in or at risk of child criminal exploitation: Young people and Caregivers' perspectives
Authors: Fox Simone , Wake Holly , Glorney Emily
Published: September 2024

Child criminal exploitation is a form of child abuse, linked to youth gang involvement and with long‐lasting serious consequences for communities. Multisystemic therapy (MST) is a systemic intervention for antisocial behaviour with an extensive evidence base but there is limited research focussing on gang involved or criminally exploited young people. Through semi‐structured interviews, this study qualitatively explored young people at risk of exploitation (n = 4) and their caregivers (n = 6) experience of MST across three sites in England. Four themes emerged through thematic analysis: changes experienced; improved caregiver‐young person relationship; facilitators of change; and barriers to change. The process of MST facilitated behaviour change and supported development of support networks for caregivers and engagement with prosocial young peers. Barriers to change included young people's association with negative adults and frequent peer relationship changes. Further exploration of the complex associations between negative adults and young people at risk of exploitation is recommended.