bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternative Wnt-signaling axis leads to a break of oncogene-induced senescence
Authors: Kluge Viola , Kappelmann-Fenzl Melanie , Fischer Stefan , Zimmermann Tom , Pommer Michaela , Kuphal Silke , Bosserhoff Anja-Katrin 
Published: February 2024

AbstractOncogene-induced senescence (OIS) is an important process that suppresses tumor development, but the molecular mechanisms of OIS are still under investigation. It is known that BRAFV600E-mutated melanocytes can overcome OIS and develop melanoma, but the underlying mechanism is largely unknown. Using an established OIS model of primary melanocytes transduced with BRAFV600E, YAP activity was shown to be induced in OIS as well as in melanoma cells compared to that in normal epidermal melanocytes. This led to the assumption that YAP activation itself is not a factor involved in the disruption of OIS. However, its role and interaction partners potentially change. As Wnt molecules are known to be important in melanoma progression, these molecules were the focus of subsequent studies. Interestingly, activation of Wnt signaling using AMBMP resulted in a disruption of OIS in BRAFV600E-transduced melanocytes. Furthermore, depletion of Wnt6, Wnt10b or β-catenin expression in melanoma cells resulted in the induction of senescence. Given that melanoma cells do not exhibit canonical Wnt/β-catenin activity, alternative β-catenin signaling pathways may disrupt OIS. Here, we discovered that β-catenin is an interaction partner of YAP on DNA in melanoma cells. Furthermore, the β-catenin–YAP interaction changed the gene expression pattern from senescence-stabilizing genes to tumor-supportive genes. This switch is caused by transcriptional coactivation via the LEF1/TEAD interaction. The target genes with binding sites for LEF1 and TEAD are involved in rRNA processing and are associated with poor prognosis in melanoma patients. This study revealed that an alternative YAP-Wnt signaling axis is an essential molecular mechanism leading to OIS disruption in melanocytes.
The plasmidome associated with Gram-negative bloodstream infections: A large-scale observational study using complete plasmid assemblies
Authors: Lipworth Samuel , Matlock William , Shaw Liam , Vihta Karina-Doris , Rodger Gillian , Chau Kevin , Barker Leanne , George Sophie , Kavanagh James , Davies Timothy , Vaughan Alison , Andersson Monique , Jeffery Katie , Oakley Sarah , Morgan Marcus , Hopkins Susan , Peto Timothy , Crook Derrick , Walker A. Sarah , Stoesser Nicole 
Published: February 2024

AbstractPlasmids carry genes conferring antimicrobial resistance and other clinically important traits, and contribute to the rapid dissemination of such genes. Previous studies using complete plasmid assemblies, which are essential for reliable inference, have been small and/or limited to plasmids carrying antimicrobial resistance genes (ARGs). In this study, we sequenced 1,880 complete plasmids from 738 isolates from bloodstream infections in Oxfordshire, UK. The bacteria had been originally isolated in 2009 (194 isolates) and 2018 (368 isolates), plus a stratified selection from intervening years (176 isolates). We demonstrate that plasmids are largely, but not entirely, constrained to a single host species, although there is substantial overlap between species of plasmid gene-repertoire. Most ARGs are carried by a relatively small number of plasmid groups with biological features that are predictable. Plasmids carrying ARGs (including those encoding carbapenemases) share a putative ‘backbone’ of core genes with those carrying no such genes. These findings suggest that future surveillance should, in addition to tracking plasmids currently associated with clinically important genes, focus on identifying and monitoring the dissemination of high-risk plasmid groups with the potential to rapidly acquire and disseminate these genes.
Mapping dysfunctional circuits in the frontal cortex using deep brain stimulation
Authors: Hollunder Barbara , Ostrem Jill L. , Sahin Ilkem Aysu , Rajamani Nanditha , Oxenford Simón , Butenko Konstantin , Neudorfer Clemens , Reinhardt Pablo , Zvarova Patricia , Polosan Mircea , Akram Harith , Vissani Matteo , Zhang Chencheng , Sun Bomin , Navratil Pavel , Reich Martin M. , Volkmann Jens , Yeh Fang-Cheng , Baldermann Juan Carlos , Dembek Till A. , Visser-Vandewalle Veerle , Alho Eduardo Joaquim Lopes , Franceschini Paulo Roberto , Nanda Pranav , Finke Carsten , Kühn Andrea A. , Dougherty Darin D. , Richardson R. Mark , Bergman Hagai , DeLong Mahlon R. , Mazzoni Alberto , Romito Luigi M. , Tyagi Himanshu , Zrinzo Ludvic , Joyce Eileen M. , Chabardes Stephan , Starr Philip A. , Li Ningfei , Horn Andreas 
Published: February 2024

AbstractFrontal circuits play a critical role in motor, cognitive and affective processing, and their dysfunction may result in a variety of brain disorders. However, exactly which frontal domains mediate which (dys)functions remains largely elusive. We studied 534 deep brain stimulation electrodes implanted to treat four different brain disorders. By analyzing which connections were modulated for optimal therapeutic response across these disorders, we segregated the frontal cortex into circuits that had become dysfunctional in each of them. Dysfunctional circuits were topographically arranged from occipital to frontal, ranging from interconnections with sensorimotor cortices in dystonia, the primary motor cortex in Tourette’s syndrome, the supplementary motor area in Parkinson’s disease, to ventromedial prefrontal and anterior cingulate cortices in obsessive-compulsive disorder. Our findings highlight the integration of deep brain stimulation with brain connectomics as a powerful tool to explore couplings between brain structure and functional impairments in the human brain.
The CNK–HYP scaffolding complex promotes RAF activation by enhancing KSR–MEK interaction
Authors: Maisonneuve Pierre , Sahmi Malha , Bergeron-Labrecque Fanny , Ma Xianjie Iris , Queguiner Juliette , Arseneault Geneviève , Lefrançois Martin , Kurinov Igor , Fronzes Rémi , Sicheri Frank , Therrien Marc 
Published: February 2024

AbstractThe RAS–MAPK pathway regulates cell proliferation, differentiation and survival, and its dysregulation is associated with cancer development. The pathway minimally comprises the small GTPase RAS and the kinases RAF, MEK and ERK. Activation of RAF by RAS is notoriously intricate and remains only partially understood. There are three RAF isoforms in mammals (ARAF, BRAF and CRAF) and two related pseudokinases (KSR1 and KSR2). RAS-mediated activation of RAF depends on an allosteric mechanism driven by the dimerization of its kinase domain. Recent work on human RAFs showed that MEK binding to KSR1 promotes KSR1–BRAF heterodimerization, which leads to the phosphorylation of free MEK molecules by BRAF. Similar findings were made with the single Drosophila RAF homolog. Here we show that the fly scaffold proteins CNK and HYP stabilize the KSR–MEK interaction, which in turn enhances RAF–KSR heterodimerization and RAF activation. The cryogenic electron microscopy structure of the minimal KSR–MEK–CNK–HYP complex reveals a ring-like arrangement of the CNK–HYP complex allowing CNK to simultaneously engage KSR and MEK, thus stabilizing the binary interaction. Together, these results illuminate how CNK contributes to RAF activation by stimulating the allosteric function of KSR and highlight the diversity of mechanisms impacting RAF dimerization as well as the regulatory potential of the KSR–MEK interaction.
Numerical evaluation of sweeping gas membrane distillation for desalination of water towards water sustainability and environmental protection
Authors: Cao Yan , Taghvaie Nakhjiri Ali , Ghadiri Mahdi 
Published: February 2024

AbstractSweeping gas membrane distillation (SGMD) is considered a membrane distillation configuration. It uses an air stream to collect the water vapour. A 2D mathematical model is prepared in the current study to predict the effect of various operating parameters on the SGMD performance. Also, the temperature distribution in the SGMD was obtained. The effect of air inlet temperature, salt concentration, feed and air flowrate on air and salted solution outlet temperature and vapour flux through the membrane is investigated. There was good agreement between experimental data and modelling outputs. It was found that increase in air inlet temperature from 40 to 72 °C was increased the outlet temperature of air stream and cold solution from 37 to 63 °C and 38 to 65 °C respectively. Furthermore, increase in air inlet temperature led to the enhancement of vapour flux in the membrane distillation. Also, the salt concentration and feed flow rate did not have meaningful influence on the outlet temperatures, however, the flux was increased by increasing feed flowrate.
Machine learning-based disulfidptosis-related lncRNA signature predicts prognosis, immune infiltration and drug sensitivity in hepatocellular carcinoma
Authors: Pu Lei , Sun Yan , Pu Cheng , Zhang Xiaoyan , Wang Dong , Liu Xingning , Guo Pin , Wang Bing , Xue Liang , Sun Peng 
Published: February 2024

AbstractDisulfidptosis a new cell death mode, which can cause the death of Hepatocellular Carcinoma (HCC) cells. However, the significance of disulfidptosis-related Long non-coding RNAs (DRLs) in the prognosis and immunotherapy of HCC remains unclear. Based on The Cancer Genome Atlas (TCGA) database, we used Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression model to construct DRL Prognostic Signature (DRLPS)-based risk scores and performed Gene Expression Omnibus outside validation. Survival analysis was performed and a nomogram was constructed. Moreover, we performed functional enrichment annotation, immune infiltration and drug sensitivity analyses. Five DRLs (AL590705.3, AC072054.1, AC069307.1, AC107959.3 and ZNF232-AS1) were identified to construct prognostic signature. DRLPS-based risk scores exhibited better predictive efficacy of survival than conventional clinical features. The nomogram showed high congruence between the predicted survival and observed survival. Gene set were mainly enriched in cell proliferation, differentiation and growth function related pathways. Immune cell infiltration in the low-risk group was significantly higher than that in the high-risk group. Additionally, the high-risk group exhibited higher sensitivity to Afatinib, Fulvestrant, Gefitinib, Osimertinib, Sapitinib, and Taselisib. In conclusion, our study highlighted the potential utility of the constructed DRLPS in the prognosis prediction of HCC patients, which demonstrated promising clinical application value.
In vitro digestion and colonic fermentation of phenolic compounds and their antioxidant potential in Australian beach-cast seaweeds
Authors: Subbiah Vigasini , Ebrahimi Faezeh , Agar Osman Tuncay , Dunshea Frank R. , Barrow Colin J. , Suleria Hafiz A. R. 
Published: February 2024

AbstractBeach-cast seaweed has recently garnered attention for its nutrient-rich composition, including proteins, carbohydrates, vitamins, minerals, and phytochemicals. This study focuses on the phenolic content and antioxidant potential of five Australian beach-cast seaweed species during in vitro digestion and colonic fermentation. The bioaccessibility of the selected phenolic compounds was estimated and short chain fatty acids (SCFAs) production was determined. Cystophora sp., showed a notable increase in phenolic content (23.1 mg GAE/g) and antioxidant capacity (0.42 mg CE/g) during the intestinal and gastric phases of in vitro digestion. Durvillaea sp. demonstrated a significant release of flavonoids (0.35 mg QE/g), while Phyllosphora comosa released high levels of tannins (0.72 mg CE/g) during the intestinal phase. During colonic fermentation, P. comosa released the highest levels of phenolic compounds (4.3 mg GAE/g) after 2 h, followed by an increase in flavonoids (0.15 mg QE/g), tannins (0.07 mg CE/g), and antioxidant activity (DPPH: 0.12 mg TE/g; FRAP: 0.61 mg TE/g) after 4 h. Moreover, P. comosa released a considerable amount of phenolic compounds during both in vitro digestion and colonic fermentation. All species consistently released phenolic compounds throughout the study. Phloroglucinol, gallic acid, and protocatechuic acid were identified as the most bioaccessible phenolic compounds in all five Australian beach-cast seaweeds in the in vitro digestion. Nevertheless, compound levels declined during the colonic fermentation phase due to decomposition and fermentation by gut microbiota. With regard to SCFAs, P. comosa displayed elevated levels of acetic (0.51 mmol/L) and propionic acid (0.36 mmol/L) at 2 h, while Durvillaea sp. showed increased butyric (0.42 mmol/L) and valeric (0.26 mmol/L) production acid after 8 h. These findings suggest that seaweed such as Cystophora sp., Durvillaea sp., and P. comosa are promising candidates for food fortification or nutraceutical applications, given their rich phenolic content and antioxidant properties that potentially offer gut health benefits.
Metagenomic analysis of the microbial communities and associated network of nitrogen metabolism genes in the Ryukyu limestone aquifer
Authors: Maruyama Rio , Yasumoto Ko , Mizusawa Nanami , Iijima Mariko , Yasumoto-Hirose Mina , Iguchi Akira , Hermawan Oktanius Richard , Hosono Takahiro , Takada Ryogo , Song Ke-Han , Shinjo Ryuichi , Watabe Shugo , Yasumoto Jun 
Published: February 2024

AbstractWhile microbial biogeochemical activities such as those involving denitrification and sulfate reduction have been considered to play important roles in material cycling in various aquatic ecosystems, our current understanding of the microbial community in groundwater ecosystems is remarkably insufficient. To assess the groundwater in the Ryukyu limestone aquifer of Okinawa Island, which is located in the southernmost region of Japan, we performed metagenomic analysis on the microbial communities at the three sites and screened for functional genes associated with nitrogen metabolism. 16S rRNA amplicon analysis showed that bacteria accounted for 94–98% of the microbial communities, which included archaea at all three sites. The bacterial communities associated with nitrogen metabolism shifted by month at each site, indicating that this metabolism was accomplished by the bacterial community as a whole. Interestingly, site 3 contained much higher levels of the denitrification genes such as narG and napA than the other two sites. This site was thought to have undergone denitrification that was driven by high quantities of dissolved organic carbon (DOC). In contrast, site 2 was characterized by a high nitrate-nitrogen (NO3-N) content and a low amount of DOC, and this site yielded a moderate amount of denitrification genes. Site 1 showed markedly low amounts of all nitrogen metabolism genes. Overall, nitrogen metabolism in the Ryukyu limestone aquifer was found to change based on environmental factors.
Deep learning-based, fully automated, pediatric brain segmentation
Authors: Kim Min-Jee , Hong EunPyeong , Yum Mi-Sun , Lee Yun-Jeong , Kim Jinyoung , Ko Tae-Sung 
Published: February 2024

AbstractThe purpose of this study was to demonstrate the performance of a fully automated, deep learning-based brain segmentation (DLS) method in healthy controls and in patients with neurodevelopmental disorders, SCN1A mutation, under eleven. The whole, cortical, and subcortical volumes of previously enrolled 21 participants, under 11 years of age, with a SCN1A mutation, and 42 healthy controls, were obtained using a DLS method, and compared to volumes measured by Freesurfer with manual correction. Additionally, the volumes which were calculated with the DLS method between the patients and the control group. The volumes of total brain gray and white matter using DLS method were consistent with that volume which were measured by Freesurfer with manual correction in healthy controls. Among 68 cortical parcellated volume analysis, the volumes of only 7 areas measured by DLS methods were significantly different from that measured by Freesurfer with manual correction, and the differences decreased with increasing age in the subgroup analysis. The subcortical volume measured by the DLS method was relatively smaller than that of the Freesurfer volume analysis. Further, the DLS method could perfectly detect the reduced volume identified by the Freesurfer software and manual correction in patients with SCN1A mutations, compared with healthy controls. In a pediatric population, this new, fully automated DLS method is compatible with the classic, volumetric analysis with Freesurfer software and manual correction, and it can also well detect brain morphological changes in children with a neurodevelopmental disorder.
Repeated microdoses of LSD do not alter anxiety or boldness in zebrafish
Authors: Hagen Ethan V. , Schalomon Melike , Zhang Yanbo , Hamilton Trevor J. 
Published: February 2024

AbstractThe therapeutic use of lysergic acid diethylamide (LSD) has resurfaced in the last decade, prompting further scientific investigation into its effectiveness in many animal models. Zebrafish (Danio rerio) are a popular model organism in medical sciences and are used to examine the repeated administration of pharmacological compounds. Previous zebrafish research found acute LSD altered behaviour and cortisol levels at high (250 µg/L) but not low (5–100 µg/L) levels. In this study, we used a motion tracking system to record and analyze the movement patterns of zebrafish after acute and repeated 10-day LSD exposure (1.5 µg/L, 15 µg/L, 150 µg/L) and after seven days of withdrawal. The open-field and novel object approach tests were used to examine anxiety-like behaviour, boldness, and locomotion. In the acute experiments we observed a significant decrease in high mobility with 1.5 µg/L, 15 µg/L, and 150 µg/L of LSD compared to the control and a decrease in velocity with 1.5 and 15 µg/L. In repeated experiments, there were no significant differences in the levels of anxiety, boldness, or locomotion between all LSD groups and controls immediately after 10-day treatment or after withdrawal.
Comparative pangenomic analysis of Campylobacter fetus isolated from Spanish bulls and other mammalian species
Authors: Pena-Fernández Nerea , Ocejo Medelin , van der Graaf-van Bloois Linda , Lavín Jose Luís , Kortabarria Nekane , Collantes-Fernández Esther , Hurtado Ana , Aduriz Gorka 
Published: February 2024

AbstractCampylobacter fetuscomprises two closely related mammal-associated subspecies:Campylobacter fetussubsp.fetus(Cff) andCampylobacter fetussubsp.venerealis(Cfv). The latter causes bovine genital campylobacteriosis, a sexually-transmitted disease endemic in Spain that results in significant economic losses in the cattle industry. Here, 33C. fetusSpanish isolates were whole-genome sequenced and compared with 62 publicly availableC. fetusgenomes from other countries. Genome-based taxonomic identification revealed high concordance with in silico PCR, confirming Spanish isolates asCff(n = 4),Cfv(n = 9) andCfvbiovarintermedius(Cfvi, n = 20). MLST analysis assigned the Spanish isolates to 6 STs, including three novel: ST-76 and ST-77 forCfvand ST-78 forCff. Core genome SNP phylogenetic analysis of the 95 genomes identified multiple clusters, revealing associations at subspecies and biovar level between genomes with the same ST and separating theCfvigenomes from Spain and other countries. A genome-wide association study identifiedpqqLas aCfv-specific gene and a potential candidate for more accurate identification methods. Functionality analysis revealed variations in the accessory genome ofC. fetussubspecies and biovars that deserve further studies. These results provide valuable information about the regional variants ofC. fetuspresent in Spain and the genetic diversity and predicted functionality of the different subspecies.
Biomolecular evidence for changing millet reliance in Late Bronze Age central Germany
Authors: Orfanou Eleftheria , Zach Barbara , Rohrlach Adam B. , Schneider Florian N. , Paust Enrico , Lucas Mary , Hermes Taylor , Ilgner Jana , Scott Erin , Ettel Peter , Haak Wolfgang , Spengler Robert , Roberts Patrick 
Published: February 2024

AbstractThe Bronze Age of Central Europe was a period of major social, economic, political and ideological change. The arrival of millet is often seen as part of wider Bronze Age connectivity, yet understanding of the subsistence regimes underpinning this dynamic period remains poor for this region, in large part due to a dominance of cremation funerary rites, which hinder biomolecular studies. Here, we apply stable isotope analysis, radiocarbon dating and archaeobotanical analysis to two Late Bronze Age (LBA) sites, Esperstedt and Kuckenburg, in central Germany, where human remains were inhumed rather than cremated. We find that people buried at these sites did not consume millet before the Middle Bronze Age (MBA) (ca. 1600 BCE). However, by the early LBA (ca. 1300–1050 BCE) people consumed millet, often in substantial quantities. This consumption appears to have subsequently diminished or ceased around 1050–800 BCE, despite charred millet grains still being found in the archaeological deposits from this period. The arrival of millet in this region, followed by a surge in consumption spanning two centuries, indicates a complex interplay of cultural and economic factors, as well as a potential use of millet to buffer changes in aridity in a region increasingly prone to crop failure in the face of climate change today.
A hybrid ResNet-ViT approach to bridge the global and local features for myocardial infarction detection
Authors: Wahid Junaid Abdul , Mingliang Xu , Ayoub Muhammad , Husssain Shabir , Li Lifeng , Shi Lei 
Published: February 2024

AbstractMyocardial infarction (MI) remains a significant contributor to global mortality and morbidity, necessitating accurate and timely diagnosis. Current diagnostic methods encounter challenges in capturing intricate patterns, urging the need for advanced automated approaches to enhance MI detection. In this study, we strive to advance MI detection by proposing a hybrid approach that combines the strengths of ResNet and Vision Transformer (ViT) models, leveraging global and local features for improved accuracy. We introduce a slim-model ViT design with multibranch networks and channel attention mechanisms to enhance patch embedding extraction, addressing ViT’s limitations. By training data through both ResNet and modified ViT models, we incorporate a dual-pathway feature extraction strategy. The fusion of global and local features addresses the challenge of robust feature vector creation. Our approach showcases enhanced learning capabilities through modified ViT architecture and ResNet architecture. The dual-pathway training enriches feature extraction, culminating in a comprehensive feature vector. Preliminary results demonstrate significant potential for accurate detection of MI. Our study introduces a hybrid ResNet-ViT model for advanced MI detection, highlighting the synergy between global and local feature extraction. This approach holds promise for elevating MI classification accuracy, with implications for improved patient care. Further validation and clinical applicability exploration are warranted.