bluuebunny/crossref_metadata_2025 huggingface dataset:
The oncometabolite D-2-hydroxyglutarate promotes DNA hypermethylation at lineage-specific enhancers controlling microglial activation in IDHmutgliomas
Authors: Laurenge Alice , Pugliese Pietro , Richard Quentin , Mathon Bertrand , Jouannet Stéphanie , Hayat Yvette , Scuderi Sarah , Capelle Laurent , Marijon Pauline , Labreche Karim , Alentorn Agustí , Verreault Maïté , Idbaih Ahmed , Birzu Cristina , Huillard Emmanuelle , Pottier Nina , Desmons Aurore , Fayache Inès , Kaas Garrett A. , Kingsley Philip J. , Marnett Lawrence J. , Duplus Eric , El-Habr Elias , Salas Lucas A. , Mokhtari Karima , Tran Suzanne , Touat Mehdi , Bielle Franck , Suvà Mario L. , Iavarone Antonio , Ceccarelli Michele , Mallat Michel , Sanson Marc , Castro-Vega Luis Jaime
Published: August 2024

Tumor-associated macrophages and microglia (TAMs) are highly abundant myeloid cells in gliomas, with their phenotypes and immune responses shaped by ontogeny and microenvironment. TAMs display distinctive transcriptional programs based on the IDH status of tumors, yet the underlying signaling mechanisms remain largely unknown. Herein, we uncover that CD11B+ myeloid cells in human IDH-mutant gliomas exhibit DNA hypermethylation, predominantly at distal enhancers. This hypermethylation impairs the binding of core transcription factors that govern microglial responses, resulting in reduced expression of inflammatory and glycolytic metabolism programs. Prolonged exposure of human primary microglia to D-2-hydroxyglutarate (D-2HG) inhibits TET-mediated demethylation at lineage-specific enhancers, evidenced by elevated 5mC/5hmC ratios near binding motifs. D-2HG-treated microglia showed reduced proinflammatory capacity and enhanced oxidative phosphorylation, consistent with the remodeled enhancer landscape. Conversely, depletion of D-2HG following treatment of a glioma patient with an IDH-mutant inhibitor unleashed microglial reactivity, as assessed by snRNA-seq. Our findings provide a mechanistic rationale for the hyporesponsive state of microglia in IDH-mutant gliomas and support the concept that oncometabolites may disrupt the function of immune cells residing in the tumor microenvironment.
The selective culture and enrichment of major rumen bacteria on three distinct anaerobic culture media
Authors: Buckner Alice M. , Glendinning Laura , Palma Hidalgo Juan M. , van Munster Jolanda M. , Stevens Mark , Watson Mick , Newbold C. Jamie
Published: August 2024

Ruminants play an important part in global food security, but also emit methane which contributes to global warming. Microbes in the rumen strongly influence the energy retention efficiency from the host’s plant-based diet and produce methane as a by-product. While thousands of novel microbial genomes have been assembled from metagenome sequence data, their culturability is ill-defined. Here different media were used to isolate microbes from rumen fluid. 34 genera were grown, and the majority belonged to the phylumBacillota(75.28% ± 6.34),Bacteroidota(19.99% ± 4.85),Pseudomonadota(2.46% ± 2.01), andActinomycetota(2.09% ± 1.07). The most abundant genera wereSelenomonas(28.08% ± 11.71),Streptococcus(22.67% ± 6.06),Prevotella(18.71% ± 4.02), and unclassifiedLachnospiraceae(11.50% ± 2.54). When comparing the mean relative abundance of these genera between media, 31 were significantly enriched on at least one medium. The composition of the source rumen fluid was vastly different to those cultured.Bacteroidota(52.53% ± 5.10) predominated, with byBacillota(41.00% ± 3.96), the archaealEuryarchaeota(5.12% ± 1.94),Pseudomonadota(1.22% ± 0.78), andActinomycetota(0.12% ± 0.08) comprising the rest. The most abundant genera werePrevotella(29.13% ± 4.16),Butyrivibrio(18.21% ± 2.08),Succiniclasticum(15.57% ± 5.03), unclassifiedBacteroidetes(13.91% ± 1.67), and unclassifiedPrevotellaceae(9.50% ± 2.01). These data further emphasise the importance of using defined media to selectively enrich for different microbial taxa. This is essential to understand the complex workings of the rumen microbes to enhance digestion efficiency and reduce the loss of energy as methane.
Spatio-temporal variability of airborne viruses over sub-Antarctic South Georgia: Effects of sampling device and proximity of the ocean
Authors: Das Ritam , Malard Lucie , Pearce David A. , Rahlff Janina
Published: August 2024

Studying airborne viral diversity in pristine, remote environments like the sub-Antarctic island South Georgia provides crucial insights into viral ecology and their role in sustaining unique ecosystems. Viruses influence microbial dynamics and nutrient cycles, which are vital for ecological balance and long-term ecosystem sustainability. We explored the community composition of airborne viral operational taxonomic units (vOTUs) of two sites in South Georgia, using various sampling devices and viral metagenomics. The Coriolis µ device (wet collection) was the most effective, yielding 30 viral scaffolds. Two-thirds of the scaffolds were from sea-level samples, indicating that location impacts viral diversity. Protein-based clustering of 39 vOTUs revealed similarities of 15 with known marine viruses, suggesting oceanic influence on the island’s airborne viral community. Genes related to UV damage protection and photosynthesis from two airborne vOTUs were widely distributed in the major oceans, emphasizing the potential resilience in changing climates. Host predictions indicated associations with bacterial genera likeRickettsia,Myroides, and Bacteroidota. Some vOTUs matched viruses from extremophiles, indicating adaptations to harsh environments. This study provides a baseline for understanding the complexity and sustainability of airborne viral communities in remote ecosystems, underscoring the need for continued monitoring in the face of environmental change.

Sustainability Statement

Antarctic microbes have potentially unique adaptations to extreme cold and harsh conditions. Viruses that infect these microbes may play a pivotal role in shaping these adaptations and thus understanding virus-host interactions is vital for preserving the unique microbial biodiversity of Antarctica. Moreover, investigating the dynamics of viral aerosolization in and around Antarctica is important for understanding the global dispersal of viruses and their potential impacts on distant ecosystems. Monitoring microbial viruses in Antarctica is essential for tracking community changes over time. Since Antarctica is often considered one of the last pristine environments on Earth, understanding the role of microbial viruses is relevant for developing conservation strategies to protect this ecosystem from potential anthropogenic impacts, including unintentional introduction of foreign microorganisms and viruses. Our research aligns with Sustainable Development Goals Life below water (SDG14) and Life on land (SDG15).
Individual Differences in the Correspondence Between Psychological and Physiological Stress Indicators
Authors: Hilger Kirsten , Talić Irma , Renner Karl-Heinz
Published: August 2024

Stress threatens physical and mental health. Reactions to acute stress comprise multiple levels, including negative thoughts, bodily symptoms and behaviors. Individuals differ in their reaction to acute stress, and importantly, also in the extent to which these levels align, with a closer correspondence between psychological and physiological stress indicators being beneficial for mental health and well-being. This preregistered study investigates such individual differences systematically by inducing psychological (social-evaluative) and physiological (cold water) stress with the Maastricht Acute Stress Test (MAST) in 149 healthy adults. Participants indicated the extent to which they perceived to be stressed and four physiological stress indicators (blood pressure, heart rate, salivary cortisol, alpha-amylase) were measured. Finally, multiple personality traits were assessed as potential moderators, including the Big Five, trait anxiety, and general cognitive ability. In line with previous research, psychological and physiological stress indicators were only weakly correlated. However, considering individual differences in personality, revealed especially conscientiousness and openness as potential moderators of the correspondence between psychological and physiological stress indicators. We propose individual differences in interoceptive abilities as another critical moderator, which deserves further investigation, and discuss how future research on individual differences in psycho-physiological correspondence can contribute to further our understanding of mental and physical diseases.

Impact Statement

Stress has substantially increased over the last decade. A missing correspondence between self-reported stress and physiological stress measures has been related to mental illnesses and lower well-being. In revealing that specific personality traits might act as potential moderators of the psycho-physiological correspondence, our research complements recent prospects towards personalized medicine and offers starting points for the development of individualized psychological interventions and prevention programs.
Identification and structural characterization of a novel acetyl xylan esterase fromAspergillus oryzae
Authors: Yamada Chihaya , Kato Tomoe , Shiono Yoshihito , Koseki Takuya , Fushinobu Shinya
Published: August 2024

Acetyl xylan esterase plays a crucial role in the degradation of xylan, the major plant hemicellulose, by liberating acetic acid from the backbone polysaccharides. Acetyl xylan esterase B fromAspergillus oryzae, designatedAoAXEB, was biochemically and structurally investigated. TheAoAXEB-encoding gene with a native signal peptide was successfully expressed inPichia pastorisas an active extracellular protein. The purified recombinant protein had pH and temperature optima of 8.0 and 30 °C, respectively, and was stable up to 35°C. The optimal substrate for hydrolysis by purified recombinantAoAXEB among a panel of α-naphthyl esters was α-naphthyl acetate. RecombinantAoAXEB catalyzes the release of acetic acid from wheat arabinoxylan. The release of acetic acid from wheat arabinoxylan increases synergistically with xylanase addition. No activity was detected using the methyl esters of ferulic,p-coumaric, caffeic, or sinapic acids. The crystal structures ofAoAXEB in the apo and succinate complexes were determined at resolutions of 1.75 and 1.90 Å, respectively. AlthoughAoAXEB has been classified in the Esterase_phb family in the ESTerases and alpha/beta-Hydrolase Enzymes and Relatives (ESTHER) database, its structural features partly resemble those of ferulic acid esterase in the FaeC family. Phylogenetic analysis also indicated thatAoAXEB is located between the clades of the two families. Docking analysis provided a plausible binding mode for xylotriose substrates acetylated at the 2- or 3-hydroxy position. This study expands the repertoire of side chain-degrading enzymes required for complete plant biomass degradation.
Paracrine rescue of MYR1-deficientToxoplasma gondiimutants reveals limitations of pooledin vivoCRISPR screens
Authors: Torelli Francesca , da Fonseca Diogo M. , Butterworth Simon , Young Joanna C. , Treeck Moritz
Published: August 2024

Toxoplasma gondiiis an intracellular parasite that subverts host cell functions via secreted virulence factors. Up to 70% of parasite-controlled changes in the host transcriptome rely on the MYR1 protein, which is required for the translocation of secreted proteins into the host cell. Mice infected with MYR1 knock-out (KO) strains survive infection, supporting a paramount function of MYR1-dependent secreted proteins inToxoplasmavirulence and proliferation. However, we have previously shown that MYR1 mutants have no growth defect in pooledin vivoCRISPR-Cas9 screens in mice, suggesting that the presence of parasites that are wild-type at themyr1locus in pooled screens can rescue the phenotype. Here, we demonstrate that MYR1 is not required for the survival in IFN-γ-activated murine macrophages, and that parasites lacking MYR1 are able to expand during the onset of infection. While ΔMYR1 parasites have restricted growth in single-strain murine infections, we show that the phenotype is rescued by co-infection with wild-type (WT) parasitesin vivo, independent of host functional adaptive immunity or key pro-inflammatory cytokines. These data show that the major function of MYR1-dependent secreted proteins is not to protect the parasite from clearance within infected cells. Instead, MYR-dependent proteins generate a permissive niche in a paracrine manner, which rescues ΔMYR1 parasites within a pool of CRISPR mutants in mice. Our results highlight an important limitation of otherwise powerfulin vivoCRISPR screens and point towards key functions for MYR1-dependentToxoplasma-host interactions beyond the infected cell.

SIGNIFICANCE STATEMENT

Pooled CRISPR screens are powerful tools to interrogate gene function in a high-throughput manner. Genes conferring fitness advantages or disadvantages upon disruption can be identified by sequencing. However, inToxoplasma gondiipooled CRISPR screens in mice, fitness defects for some selected mutants drastically diverge from those observed in single-strain infections. Here, we show that a growth defect of a singleToxoplasmagene deletion mutant is rescued if co-infected with wildtype parasites. These results shine light onToxoplasma’s ability to subvert the host response beyond the infected cell, and highlight an important limitation of pooled CRISPR screens in mice. This limitation is probably encountered in CRISPR screens in general where paracrine effects occur.
BGC Atlas: A Web Resource for Exploring the Global Chemical Diversity Encoded in Bacterial Genomes
Authors: Bağcı Caner , Nuhamunada Matin , Goyat Hemant , Ladanyi Casimir , Sehnal Ludek , Blin Kai , Kautsar Satria A. , Tagirdzhanov Azat , Gurevich Alexey , Mantri Shrikant , von Mering Christian , Udwary Daniel , Medema Marnix H. , Weber Tilmann , Ziemert Nadine
Published: August 2024

Secondary metabolites are compounds not essential for an organism’s development, but provide significant ecological and physiological benefits. These compounds have applications in medicine, biotechnology, and agriculture. Their production is encoded in biosynthetic gene clusters (BGCs), groups of genes collectively directing their biosynthesis. The advent of metagenomics has allowed researchers to study BGCs directly from environmental samples, identifying numerous previously unknown BGCs encoding unprecedented chemistry. Here, we present the BGC Atlas (https://bgc-atlas.cs.uni-tuebingen.de), a web resource that facilitates the exploration and analysis of BGC diversity in metagenomes. The BGC Atlas identifies and clusters BGCs from publicly available datasets, offering a centralized database and a web interface for metadata-aware exploration of BGCs and gene cluster families (GCFs). We analyzed over 35,000 datasets from MGnify, identifying nearly 1.8 million BGCs, which were clustered into GCFs. The analysis showed that ribosomally synthesized and post-translationally modified peptides (RiPPs) are the most abundant compound class, with most GCFs exhibiting high environmental specificity. We believe that our tool will enable researchers to easily explore and analyze the BGC diversity in environmental samples, significantly enhancing our understanding of bacterial secondary metabolites, and promote the identification of ecological and evolutionary factors shaping the biosynthetic potential of microbial communities.
Structural basis for the strict substrate specificity of β-D-galactofuranosidase fromStreptomycessp. JHA19
Authors: Fujio Noriki , Yamada Chihaya , Kashima Toma , Matsunaga Emiko , Nash Robert J. , Takegawa Kaoru , Fushinobu Shinya
Published: August 2024

D-Galactofuranose (Galf) is widely distributed in polysaccharides and glycoconjugates of bacteria, filamentous fungi, and protozoa. The biosynthetic and degradation pathways of Galfin pathogens have attracted attention as potential targets for drug development. β-D-Galactofuranosidase (Galf-ase) releases Galffrom the non-reducing ends of glycans. Galf-ase activity is often exhibited by α-L-arabinofuranosidases, which hydrolyze a similar substrate. Several Galf-specific Galf-ases that cleave only Galfand not L-arabinofuranose (Araf) have recently been identified in the glycoside hydrolase (GH) families 2, 5, and 43. However, the structural basis of how they discriminate the substrates is unknown. ORF1110, belonging to GH2, is the first identified Galf-specific Galf-ase isolated fromStreptomycessp. JHA19. Here, we solved the crystal structure of ORF1110 in complex with a mechanism-based potent inhibitor, D-iminogalactitol (Ki= 65 μM). ORF1110 binds to the C5-C6 hydroxy groups of D-iminogalactitol with an extensive and integral hydrogen bond network. This result suggests that in the case of Araf, which lacks the C6 hydroxymethyl group, this network is not formed. The domain structure of ORF1110 is similar to that of β-glucuronidases and β-galactosidases, which belong to the same GH2 family and hydrolyze pyranose substrates. However, their active site structures were completely different. A predicted structure of the C-terminal Abf domain of ORF1110 was very similar to the carbohydrate-binding module family 42, which binds Araf, and pockets that may bind Galfwere present.
Properties and predictive potential of the pre-ictal oscillatory dynamics in an ex vivo model of epileptiform activity in the different hippocampal subregions
Authors: Vagiaki Lida-Evmorfia , Xydias Dionysis , Kefalogianni Maria , Psilodimitrakopoulos Sotiris , Stratakis Emmanuel , Sidiropoulou Kyriaki
Published: August 2024

Neuronal oscillatory activity facilitates the transmission of information between neurons. However, abnormally synchronous neuronal activity results in the emergence of seizure-like activity (SLA). The hippocampus (HPC) is a brain area highly susceptible to SLA. The mechanisms leading to SLA are not yet well understood, although changes in neuronal oscillations have been suggested to exist in the time period before SLA onset. Anti-epileptic drugs, such as diazepam (DZP), a GABAA receptor agonist, and carbamazepine (CBZ), a sodium channel blocker, have significant anti-convulsant properties. However, their role in modulating the oscillatory activity within HPC subregions remains unclear. In our study, we used a high [K+] (HK+) artificial cerebrospinal fluid (aCSF) solution to induce SLA in mouse HPC slices, which was detected using spontaneous local field potential (LFP) recordings. SLA activity was recorded in the three HPC subregions, namely CA1, CA3 and the dentate gyrus (DG). LFP analysis in the pre-ictal period revealed significant changes in the oscillatory activity compared to the absence of SLA and to ictal events. A classification algorithm revealed that the oscillatory dynamics, particularly in the CA1 subregion, can predict the emergence of an ictal event with high accuracy. Furthermore, we detected differential DZP and CBZ-induced changes in the oscillatory activity in the CA1, CA3 and DG. Imaging of neuronal activation in the ex vivo model of SLA, using the Fos protein as an activity marker, also revealed a subregion-dependent differential modulation following DZP and CBZ perfusion, which resembled the pattern of oscillatory activity changes. Therefore, the oscillatory dynamics could serve a potential electrophysiological biomarker for predicting seizure activity and are differentially modulated by anti-epileptic drugs.
Significant and persistent carryover effects in Scots pine
Authors: Perry Annika , Beaton Joan K. , Stockan Jenni A. , Iason Glenn R. , Cottrell Joan E. , Cavers Stephen
Published: August 2024

After tracking Scots pine plants from germination to 15 years old, through contrasting early life environments, we observed significant and persistent carryover effects. Groups of plants from common genetic backgrounds were raised in distinct nursery environments, and growth and phenology traits were measured repeatedly once trees had established in their field sites. Growth and phenology differences were evident for 10 and 6 years post-transplantation to the field, respectively. There was a clear interaction between site of origin and carryover effect, indicating that local adaptation also played a role. Given the increasing rate of tree planting initiatives being undertaken around the world in the name of the climate and biodiversity crises, and the strong dependence on those initiatives of nursery-grown plants, our finding of strong carryover effects of the early life environment has significant implications.
Selective enrichment of specific bacterial taxa in downy mildew-affected spinach: Comparative analysis in laboratory and field conditions
Authors: Goossens Pim , Baremans Kim , Alderkamp Marrit , Boshoven Jordi C. , van den Ackerveken Guido , Berendsen Roeland L.
Published: August 2024

Plants host diverse microbial communities that can be influenced by their hosts to mitigate biotic stress. Previous research demonstrated that distinct laboratory cultures ofHyaloperonospora arabidopsidis(Hpa) onArabidopsis thaliana, consistently harbor nearly identical bacteria. In this study, we analyzed the bacterial phyllosphere communities of laboratory-grown spinach plants infected by the downy mildew pathogenPeronospora effusa(Pe). Using 16S amplicon sequencing, we identified 14 Amplicon Sequence Variants (ASVs), with diverse taxonomies, that were enriched in at least 3 out of 5 investigated Pe cultures. This small set of 14 ASVs occupied on average 6.9% of the total bacterial communities in healthy spinach plants, and 43.1% in Pe-inoculated plants. A specificRhodococcusand aPaenarthrobacterASV were particularly prevalent and abundant. To validate these findings outside of the laboratory, we planted a susceptible variety of spinach in 4 agricultural fields and sampled leaves from Pe-infected plants in 2 fields where this pathogen naturally occurred. Comparative microbiome analysis of diseased and healthy plants revealed significant enrichment of 16 and 31 ASVs in these 2 fields, respectively. Among these, thePaenarthrobacterASV was enriched in one field and theRhodococcusASV in the other field, suggesting that disease-associated microbiota that are abundantly detected in Pe laboratory cultures are also associated with Pe-infected field plants. Additionally, we observed an overlap of ASVs that were associated with both Pe and Hpa, indicating that similar bacteria are linked to downy mildew disease across different hosts.
Rhamnose Polysaccharide-Decorated Outer Membrane Vesicles as a Vaccine Candidate Targeting Group A Streptococcus fromStreptococcus pyogenesandStreptococcus dysgalactiaesubsp.equisimilis
Authors: Ajay Castro Sowmya , Thomson Sarah , Shaw Helen Alexandra , Zorzoli Azul , Meyer Benjamin H , Reglinski Mark , Dorfmueller Helge C.
Published: August 2024

Group A Streptococcus (Strep A) cause a wide range of human-exclusive infections, annually killing more than 500,000 people. Antibiotic resistance incidence of invasive Strep A tripled in the past decade and emphasises the need to develop a universal Strep A vaccine. In this study, we developed recombinant rhamnose polysaccharides (RhaPS), a validated universal Strep A vaccine candidate, presented onE. coliouter membrane vesicles (OMVs). We investigated OMV-RhaPS for their immunogenicity in the mouse and rabbit models. Through flow cytometry, ELISA, Luminex assays, and immunofluorescence microscopy, we demonstrated that RhaPS-specific antibodies recognise Strep A strains via the Group A Carbohydrate (GAC) inS. pyogenesand the newly emergedS. dysgalactiaesubsp.equisimilis. Elevated IL-17a levels from RhaPS-OMV-immunised splenocytes indicate the RhaPS-specific stimulation of long-term memory immune cells. We are the first to report the efficacy and potency of recombinant produced RhaPS inducing humoral-mediated immune responses and triggering antibodies that recognise Strep A bacteria.
SpatialLeiden - Spatially-aware Leiden clustering
Authors: Müller-Bötticher Niklas , Sahay Shashwat , Eils Roland , Ishaque Naveed
Published: August 2024

Clustering can identify the natural structure that is inherent to measured data. For single-cell omics, clustering finds cells with similar molecular phenotype after which cell types are annotated. Leiden clustering is the algorithm of choice in the single-cell community. However, in the field of spatial omics, Leiden has been considered a non-spatial clustering method. Here, we show that by integrating spatial embeddings Leiden clustering is rendered into a computationally highly performant, spatially aware clustering method that compares well with state-of-the art clustering methods.
Expanding the biotechnological scope of metabolic sensors through computation-aided designs
Authors: Orsi Enrico , Schulz-Mirbach Helena , Cotton Charles A. R. , Satanowski Ari , Petri Henrik M. , Arnold Susanne L. , Grabarczyk Natalia , Verbakel Rutger , Jensen Karsten S. , Donati Stefano , Paczia Nicole , Glatter Timo , Küffner Andreas M. , Chotel Tanguy , Schillmüller Farah , De Maria Alberto , He Hai , Lindner Steffen N. , Noor Elad , Bar-Even Arren , Erb Tobias J. , Nikel Pablo I.
Published: August 2024

Metabolic sensors are microbial strains modified so that biomass formation correlates with the availability of specific metabolites. These sensors are essential for bioengineering (e.g. in growth-coupled designs) but creating them is often a time-consuming and low-throughput process that can potentially be streamlined byin silicoanalysis. Here, we present the systematic workflow of designing, implementing, and testing versatileEscherichia colimetabolic sensor strains. Glyoxylate, a key metabolite in (synthetic) CO2fixation and carbon-conserving pathways, served as the test molecule. Through iterative screening of a compact metabolic model, we identified non-trivial growth-coupled designs that resulted in six metabolic sensors with a wide sensitivity range for glyoxylate, spanning three orders of magnitude in detected concentrations. We further adapted theseE. colistrains for sensing glycolate and demonstrated their utility in both pathway engineering (testing a key metabolic moduleviaglyoxylate) and applications in environmental monitoring (quantifying glycolate produced by photosynthetic microalgae). The versatility and ease of implementation of this workflow make it suitable for designing and building multiple metabolic sensors for diverse biotechnological applications.

Teaser

A streamlined workflow enables the rapid design of versatileE. colimetabolic sensors for detecting key metabolites in bioengineering and monitoring.
The knockdown of the snoRNA-jouvence blocks the cell proliferation and leads to cell death of human primary cancerous glioblastoma cells
Authors: Jaque-Cabrera Lola , Buggiani Julia , Bignon Jérôme , Daira Patricia , Bernoud-Hubac Nathalie , Martin Jean-René
Published: August 2024

Cancer research aims to identify new therapeutic targets and provide patients with more effective therapies that generate fewer deleterious side effects. Previous studies have demonstrated the role of small nucleolar RNAs (snoRNAs) in many physiological and pathological cellular processes, including cancers. SnoRNAs are a group of non-coding RNAs involved in different post-transcriptional modifications of ribosomal RNAs. Recently, we have identified a new snoRNA, namedjouvence(snoRNA-jou) in humans. Here, we characterize the effect of the knockdown of the snoRNA-jouvence by sh-lentivirus on human primary glioblastoma cells. The sh-lentivirus induces a significant decrease of cell proliferation, proportional to the amount of lentivirus used. For example, with a MOI-20, a decrease of more than 50% is observed after only 72 hours, and even up to 80% after 10 days. Moreover, a EdU proliferative test confirms this decrease in cell proliferation, while a TUNEL test reveals the presence of apoptotic cells. A RNA-Seq analysis, validated by RT-qPCR, reveals that the snoRNA-jou knockdown induces a significant deregulation of several key genes involved in the cell cycle regulation, such as cyclins B1, A2 and p21, indicating a cell cycle blockage. Altogether, these results allow hypothesising that the knockdown of the snoRNA-jouvence could potentially be use as a new anti-cancer treatment (sno-Therapy).
Moult cycle and setal development of the Atlantic ditch shrimpPalaemon variansLeach, 1814 (Decapoda: Caridea: Palaemonidae)
Authors: Kim Kenneth , Antcliffe Jonathan , Daley Allison C. , Robinson-Rechavi Marc
Published: August 2024

The Atlantic ditch shrimpPalaemon variansLeach, 1814 is a common estuarine and brackish water species on Northern Atlantic coasts.Palaemon variansis an appealing model organism for studying arthropod developmental processes, such as moulting (ecdysis). Detailed morphological information on its moult cycle is still lacking, hence we have characterised the changes in the setal features corresponding to the moult stages ofP. variansgrown under laboratory conditions. The stages of the moult cycle were differentiated and described using microscopic analysis of the setae in the uropods ofP. variansbased on Drach’s classification system. Moult stages were defined as early and late post-moult (A and B), inter-moult (C), early-, mid- and late pre-moult (D0, D1,and D2), as well as ecdysis stage (E), the actual shedding of the exuvia. Average moult cycle duration was 8.7 days, where pre-moult accounted for the longest duration of 4.4 days on average. This study provides a morphological reference for determining the moult stage ofP. varianswithout the use of invasive techniques, and thus it is well suited for repetitive observations of an individual to track the entire moulting process.
Assessing male reproductive investment in Papaveraceae using flow cytometry reveals lineage-specific trajectories to pollen-to-ovule ratio reduction
Authors: de Vos Jurriaan M. , Woudstra Yannick , Leitch Ilia J. , Hidalgo Oriane
Published: August 2024

Male reproductive investment, in particular pollen production, is a crucial and ecologically relevant component of a plant’s phenotype and reproductive success. Its evolutionary trajectory, however, remains understudied, partly due to a lack of convenient methods to assess it. We developed a protocol for pollen quantification by flow cytometry and applied it to 107 flowers from 38 Papaveraceae species differing widely in floral traits (e.g., floral symmetry, stamen number), pollination syndromes (e.g., wind and insect pollination) and reproductive systems (e.g., degree of autogamy). We phylogenetically tested whether pollen number evolved in association with ovule, carpel, stamen and flower numbers per inflorescence, and if there were interacting effects between floral symmetry and/or self-compatibility with pollen and ovule production.

Compared to manual counts, results using flow cytometry were similar, but much faster to obtain and more precise. Pollen and ovule numbers per flower varied > 39,000x and > 550x, respectively, among species. Pollen production correlated positively with ovule, carpel and stamen numbers. Lineage-specific trajectories to pollen-to-ovule ratio reduction (to values < 300) are observed. One involved increased female investment in ruderal species belonging to the subfamily Papaveroideae, while the other occurs through decreased male investment and is associated with the evolution of floral traits towards greater specialisation. The impact of reproductive systems on male and female investment is limited to ovule production in non-actinomorphic flowers.

Taken together, these results revealed that the evolutionary associations between reproductive systems, floral traits, and pollen and ovule production are lineage-specific. Given the profound contrasts at the subfamily level of Papaveraceae, broader surveys across the diversity of flowering plants are clearly needed to better understand factors driving the evolution of reproductive investment. Such studies will certainly be facilitated by our new high-throughput pollen counting method outlined here.
DNA Base Pair Polarities of Pyrimidine(s)-Purine(s) (Pyu) dsDNA induce stronger Hybridization and unique DNA Conformation compared to Purine(s)-Pyrimidine(s) (Puy) dsDNA
Authors: Lee Suk Keun , Lee Dae Gwan , Kim Yeon Sook
Published: August 2024

The present study introduces a concept of DNA base pair polarity in double-stranded DNA (dsDNA), which has led the serial investigation of hydrogen bonding magnetic resonance-based gene regulation. DNA base pair polarity is characterized by hydrogen bonding between electrostatically positive purine and negative pyrimidine, exerting the stabilization and organization of dsDNA. Comparison of DNA hybridization potential between Pyu (pyrimidine(s)-purine(s)) and Puy (purine(s)-pyrimidine(s)) oligo-dsDNAs in EtBr intercalated electrophoresis showed that Pyu ds(nTnA) (n=3, 4,5,6,7,8,10,12) and ds(nCnA) (n=7,8,10,12) exhibit stronger hybridization than Puy ds(nAnT) and ds(nAnC), respectively. In the HPLC for DNA conformation change in 0.1M NaCl solution, Pyu oligo-dsDNA tended to have a larger peak area than Puy oligo-dsDNA, indicating that the former had a more extended and organized DNA conformation than the latter. FT-IR results showed that Pyu ds3T3A, ds3C3G, dsCTCGAG, and dsTCTAGA showed higher IR absorbance at 3400-3200 cm-1than Puy ds3A3T, ds3G3C, dsGAGCTC, and dsAGATCT, respectively, indicating Pyu oligo-dsDNAs have increased N-H stretching in hybridization than Puy oligo-dsDNAs.In vitroRNA transcription from template plasmid DNAs inserted with six segments of Pyu ds6(TCTGA) and positive ds14(GA) produced more RNA than those with seven segments of palindromic Pyu ds(CATG) and negative ds14(CT), respectively, indicating the former plays a stimulating role for RNA transcription while the latter plays an inhibitory role. When comparing PCR primers between Pyu ds12/n(nCnA) and Puy ds12/n(nAnC) (n=1,2,3,4,6,12), Pyu primers can easily hybridize on template DNA and subsequently produce abundant DNA compared to Puy primers. The data suggest that Pyu oligo-dsDNAs hybridize strongly and form distinctive conformation, thereby stimulating RNA transcription more than Puy oligo-dsDNAs. Since Pyu oligo-dsDNA appears to preserve DNA signal and conformation relevant to DNA function more efficiently than Puy dsDNA, it is proposed that the entire DNA code can be divided into Pyu dsDNAs with unique DNA base pair polarities.
Growth patterns of theoretical bite force and jaw musculature in southern sea otters (Enhydra lutris nereis)
Authors: Law Chris J.
Published: August 2024

The transition from milk to solid food requires drastic changes in the morphology of the feeding apparatus and its performance. As durophagous mammals, southern sea otters exhibit significant ontogenetic changes in cranial and mandibular morphology to presumably enable them to feed on a variety of hard-shelled invertebrate prey. Juvenile sea otters begin feeding independently by 6 –8 months of age, but how quickly they reach sufficient maturity in biting performances remains unknown. Here, I found that theoretical bite force of southern sea otters does not reach full maturation until during the adult stage at 3.6 and 5.0 years of age in females and males, respectively. The slow maturation of biting performance can be directly attributed to the slow growth and development of the cranium and the primary jaw adductor muscle (i.e., the temporalis) and may ultimately impact the survival of newly weaned juveniles by limiting their ability to process certain hard-shelled prey. Alterative foraging behaviors such as tool use, however, may mitigate the disadvantages of delayed maturation of biting performance. In analyses of sexual dimorphism, I found that female otters reached bite force maturation earlier whereas male otters exhibit initial rapid growth in bite force–to quickly reach sufficient biting performances needed to process prey early in life–followed by a slower growth phase towards bite force maturation that coincides with sexual maturity. This biphasic growth in bite force suggests that male to male competition for resources and mates exhibits strong selection in the growth and development of skull form and function in male otters. Overall, this study demonstrates how the analysis of anatomical data can provide insight on the foraging ecologies and life histories of sea otters across ontogeny.
Identification of an intrinsically disordered region (IDR) in arginyltransferase 1 (ATE1)
Authors: Cartwright Misti , Parakra Rinky , Oduwole Ayomide , Zhang Fangliang , Deredge Daniel J. , Smith Aaron T.
Published: August 2024

Arginyltransferase 1 (ATE1) catalyzes arginylation, an important post-translational modification (PTM) in eukaryotes that plays a critical role in cellular homeostasis. The disruption of ATE1 function is implicated in mammalian neurodegenerative disorders and cardiovascular maldevelopment, while post-translational arginylation has also been linked to the activities of several important human viruses such as SARS-CoV-2 and HIV. Despite the known significance of ATE1 in mammalian cellular function, past biophysical studies of this enzyme have mainly focused on yeast ATE1, leaving the mechanism of arginylation in mammalian cells unclear. In this study, we sought to structurally and biophysically characterize mouse (Mus musculus) ATE1. Using size-exclusion chromatography (SEC), small angle X-ray scattering (SAXS), and hydrogen deuterium exchange mass spectrometry (HDX-MS), assisted by AlphaFold modeling, we found that mouse ATE1 is structurally more complex than yeast ATE1. Importantly, our data indicate the existence of an intrinsically disordered region (IDR) in all mouse ATE1 splice variants. However, comparative HDX-MS analyses show that yeast ATE1 does not have such an IDR, consistent with prior X-ray, cryo-EM, and SAXS analyses. Furthermore, bioinformatics approaches reveal that mammalian ATE1 sequences, as well as in a large majority of other eukaryotes, contain an IDR-like sequence positioned in proximity to the ATE1 GNAT active-site fold. Computational analysis suggests that the IDR likely facilitates the formation of the complex between ATE1 and tRNAArg, adding a new complexity to ATE1 structure and providing new insights for future studies of ATE1 functions.

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High-resolution structures of the UapA purine transporter reveal unprecedented aspects of the elevator-type transport mechanism
Authors: Broutzakis George , Pyrris Yiannis , Akrani Ifigeneia , Neuhaus Alexander , Mikros Emmanuel , Diallinas George , Gatsogiannis Christos
Published: August 2024

UapA is an extensively studied elevator-type purine transporter from the model fungusAspergillus nidulans. Determination of a 3.6Å inward-facing crystal structure lacking the cytoplasmic N-and C-tails, molecular dynamics (MD), and functional studies have led to speculative models of its transport mechanism and determination of substrate specificity. Here, we report full-length cryo-EM structures of UapA in new inward-facing apo- and substrate-loaded conformations at 2.05-3.5 Å in detergent and lipid nanodiscs. The structures reveal in an unprecedented level of detail the role of water molecules and lipids in substrate binding, specificity, dimerization, and activity, rationalizing accumulated functional data. Unexpectedly, the N-tail is structured and interacts with both the core and scaffold domains. This finding, combined with mutational and functional studies and MD, points out how N-tail interactions couple proper subcellular trafficking and transport activity by wrapping UapA in a conformation necessary for ER-exit and but also critical for elevator-type conformational changes associated with substrate translocation once UapA has integrated into the plasma membrane. Our study provides detailed insights into important aspects of the elevator-type transport mechanism and opens novel issues on how the evolution of extended cytosolic tails in eukaryotic transporters, apparently needed for subcellular trafficking, might have been integrated into the transport mechanism.
Analysis and control of an active balance tail for the tilting dual-rotor UAV
Authors: Xu Yurui , Gao Liang , Liu Benshan , Zhang Junming , Zhu Yanhe , Zhao Jie , Li Liyi
Published: August 2024

Purpose

Compared to quad-rotor unmanned aerial vehicle (UAV), the tilting dual-rotor UAV is more prone to instability during exercises and disturbances. The purpose of this paper is using an active balance tail to enhance the hovering stability and motion smoothness of tilting dual-rotor UAV.

Design/methodology/approach

A balance tail is proposed and integrated into the tilting dual-rotor UAV to enhance hovering stability and motion smoothness. By strategically moving, the balance tail generates additional force and moment, which can promote the rapid stability of the UAV. Subsequently, the control strategy of the UAV is designed, and the influence of the swing of the balance tail at different installation positions with different masses on the dual-rotor UAV is analyzed through simulation. The accompany motion law and the active control, which is based on cascade Proportion Integration Differentiation (PID) control to enhance the hovering stability and motion smoothness of the UAV, are proposed.

Findings

The results demonstrate that active control has obvious adjustment effectiveness when the UAV moves to the target position or makes an emergency stop compared with the results of balance tail no swing and accompany motion.

Practical implications

The balance tail offers a straightforward means to enhance the motion smoothness of tilting dual-rotor UAV, rendering it safer and more reliable for practical applications.

Originality/value

The novelty of this works comes from the application of an active balance tail to improve the stability and motion smoothness of dual-rotor UAV.
Stigma toward individuals with intellectual disabilities and severe mental disorders: analysis of postgraduate university students’ perceptions
Authors: Moraleda Ruano Alvaro , Galán-Casado Diego
Published: August 2024

Purpose

The purpose of this study is to delve into societal stigma surrounding severe mental disorders and intellectual disabilities, emphasizing gender differences and students’ proximity influence.

Design/methodology/approach

Involving 572 Spanish master’s students, this nonexperimental study categorizes participants based on contact frequency, using Goratu and CAEE questionnaires to measure stigma.

Findings

Gender-based stigma differences are absent; however, increased contact correlates with lower stigma levels. Notably, greater closeness is associated with more positive attitudes toward intellectual disability, resulting in diminished stigma toward severe mental disorders.

Practical implications

This research sheds light on the pervasive stigma faced by individuals with intellectual disabilities and severe mental disorders among postgraduate university students. Notably, the recognition of widespread stigma among individuals with higher education highlights a more significant societal problem. The findings underscore the urgent need for targeted interventions, especially in higher education contexts, to enhance understanding and reduce societal bias.

Social implications

By identifying factors influencing stigma and emphasizing the importance of contact in fostering empathy, the study lays the groundwork for informed socioeducational strategies. These strategies have the potential to promote inclusivity, challenge stereotypes and contribute to the well-being and social integration of those affected by intellectual disabilities and severe mental disorders.

Originality/value

The findings highlight the efficacy of direct contact in reducing stigma and underscore the necessity for nuanced understanding. The study suggests fostering positive attitudes through increased contact can combat prejudice and promote social inclusion. Nevertheless, further research is crucial to explore factors influencing stigma reduction and design comprehensive socioeducational interventions addressing diverse cultural proficiencies. This study contributes valuable insights for mitigating stigma, fostering inclusivity and informing future interventions.
The effects of high-performance work systems on the creativity of a faculty member: a moderated mediated analysis
Authors: Alsafadi Yousef , Al-Okaily Manaf , Al-Okaily Aws , Shiyyab Fadi Shehab
Published: August 2024

Purpose

This paper aims to examine the main factors by which the high-performance work system (HPWS) influences the creativity of faculty members in Jordanian institutions. This work seeks to examine the factors that may influence the relationship between entrepreneurial orientation and faculty members’ creativity. The current study also seeks to fill the gaps and differences in the literature that addressed the subject of the study.

Design/methodology/approach

To achieve the main goal, the sample included 230 faculty members working in Jordanian universities in Jordan. After examination and scrutiny, it was found that 11 questionnaires were not suitable for analysis to take appropriate samples, 219 questionnaires were included in the survey.

Findings

The results of the paper showed that HPWS improves the entrepreneurial orientation, which in turn improves the creativity of the faculty member. Moreover, the results indicate that entrepreneurship education positively modifies the relationship between the entrepreneurial orientation and creativity of a faculty member.

Originality/value

The results of this study contribute to universities that seek to improve the creativity of their faculty members needing to apply the pioneering approach in the course of the educational process and create innovative creative ideas, and this in turn needs to be implemented HPWS. In addition, universities need to encourage and promote entrepreneurial education, moving away from traditional education. Lastly, this study is considered as one of the recent studies that dealt with a sample of faculty members and their creativity and linked it with HPWS. By developing new educational technologies and methods, the efficiency of knowledge transfer can be improved and access to high-quality education can be enhanced for all.
Three-dimensional scanning measurement and characterization of air gap entrapped on air ventilation garments with different fabrics and clothing sizes
Authors: Wang Wanwan , Zhao Mengmeng
Published: August 2024

Purpose

The purpose of this paper is to determine the effect of clothing fabrics, sizes and air ventilation rate on the volume and thickness of the air gap under the air ventilation garments (AVGs).

Design/methodology/approach

The geometric models of the human body and clothing were obtained by using a 3D body scanner. Then the distribution of the volume and thickness of the air gap for four clothing fabrics and three air ventilation rates (0L/S, 12L/S and 20L/S) were calculated by Geomagic software. Finally, a more suitable fabric was selected from the analysis to compare the distribution of the air gap entrapped for four clothing sizes (S, M, L and XL) and the three air ventilation rates.

Findings

The results show that the influence of air ventilation rate on the air gap volume and thickness is more obvious than that of the clothing fabrics and sizes. The higher is the air ventilation rate, the thicker is the air gap entrapped, and more evenly distributed is the air gap. It can be seen that the thickness of the air gap in the chest does not change significantly with the changes of the air ventilation rates, clothing fabrics and sizes, while the air gap in the waist is affected significantly.

Originality/value

This research provides a better understanding of the distribution of the air gap entrapped in ventilated garments, which can help in designing the optimal air gap dimensions and thus provide a basis and a reference for the design of the AVGs.