bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of inflammatory osteoclasts accelerates callus remodeling in osteoporotic fractures by enhancing CGRP+TrkA+ signaling
Authors: Shu Yuexia , Tan Zhenyu , Pan Zhen , Chen Yujie , Wang Jielin , He Jieming , Wang Jia , Wang Yuan 
Published: September 2024

AbstractImpaired callus remodeling significantly contributes to the delayed healing of osteoporotic fractures; however, the underlying mechanisms remain unclear. Sensory neuronal signaling plays a crucial role in bone repair. In this study, we aimed to investigate the pathological mechanisms hindering bone remodeling in osteoporotic fractures, particularly focusing on the role of sensory neuronal signaling. We demonstrate that in ovariectomized (OVX) mice, the loss of CGRP+TrkA+ sensory neuronal signaling during callus remodeling correlates with increased Cx3cr1+iOCs expression within the bone callus. Conditional knockout of Cx3cr1+iOCs restored CGRP+TrkA+ sensory neuronal, enabling normal callus remodeling progression. Mechanistically, we further demonstrate that Cx3cr1+iOCs secrete Sema3A in the osteoporotic fracture repair microenvironment, inhibiting CGRP+TrkA+ sensory neurons’ axonal regeneration and suppressing nerve–bone signaling exchange, thus hindering bone remodeling. Lastly, in human samples, we observed an association between the loss of CGRP+TrkA+ sensory neuronal signaling and increased expression of Cx3cr1+iOCs. In conclusion, enhancing CGRP+TrkA+ sensory nerve signaling by inhibiting Cx3cr1+iOCs activity presents a potential strategy for treating delayed healing in osteoporotic fractures.
PIM1 kinase promotes EMT-associated osimertinib resistance via regulating GSK3β signaling pathway in EGFR-mutant non-small cell lung cancer
Authors: Zhou Jing , Wang Xinyue , Li Zhaona , Wang Fan , Cao Lianjing , Chen Xiuqiong , Huang Dingzhi , Jiang Richeng 
Published: September 2024

AbstractAcquired resistance is inevitable in the treatment of non-small cell lung cancer (NSCLC) with osimertinib, and one of the primary mechanisms responsible for this resistance is the epithelial-mesenchymal transition (EMT). We identify upregulation of the proviral integration site for Moloney murine leukemia virus 1 (PIM1) and functional inactivation of glycogen synthase kinase 3β (GSK3β) as drivers of EMT-associated osimertinib resistance. Upregulation of PIM1 promotes the growth, invasion, and resistance of osimertinib-resistant cells and is significantly correlated with EMT molecules expression. Functionally, PIM1 suppresses the ubiquitin-proteasome degradation of snail family transcriptional repressor 1 (SNAIL) and snail family transcriptional repressor 2 (SLUG) by deactivating GSK3β through phosphorylation. The stability and accumulation of SNAIL and SLUG facilitate EMT and encourage osimertinib resistance. Furthermore, treatment with PIM1 inhibitors prevents EMT progression and re-sensitizes osimertinib-resistant NSCLC cells to osimertinib. PIM1/GSK3β signaling is activated in clinical samples of osimertinib-resistant NSCLC, and dual epidermal growth factor receptor (EGFR)/PIM1 blockade synergistically reverse osimertinib-resistant NSCLC in vivo. These data identify PIM1 as a driver of EMT-associated osimertinib-resistant NSCLC cells and predict that PIM1 inhibitors and osimertinib combination therapy will provide clinical benefit in patients with EGFR-mutant NSCLC.
A decision-making framework to maximise the evolutionary potential of populations - Genetic and genomic insights from the common midwife toad (Alytes obstetricans) at its range limits
Authors: Barratt Christopher D. , Preißler Kathleen , Jennert Pauline R. , Eckhardt Falk , Nadjafzadeh Mirjam , Steinfartz Sebastian 
Published: September 2024

AbstractAnthropogenic habitat modification and climate change are fundamental drivers of biodiversity declines, reducing the evolutionary potential of species, particularly at their distributional limits. Supportive breeding or reintroductions of individuals are often made to replenish declining populations, sometimes informed by genetic analysis. However, most approaches utilised (i.e. single locus markers) do not have the resolution to account for local adaptation to environmental conditions, a crucial aspect to consider when selecting donor and recipient populations. Here, we incorporate genetic (microsatellite) and genome-wide SNP (ddRAD-seq) markers, accounting for both neutral and putative adaptive genetic diversity, to inform the conservation management of the threatened common midwife toad, Alytes obstetricans at the northern and eastern edges of its range in Europe. We find geographically structured populations (n = 4), weak genetic differentiation and fairly consistent levels of genetic diversity across localities (observed heterozygosity and allelic richness). Categorising individuals based on putatively adaptive regions of the genome showed that the majority of localities are not strongly locally adapted. However, several localities present high numbers of private alleles in tandem with local adaptation to warmer conditions and rough topography. Combining genetic diversity and local adaptations with estimates of migration rates, we develop a decision-making framework for selecting donor and recipient populations which maximises the geographic dispersal of neutral and putatively adaptive genetic diversity. Our framework is generally applicable to any species, but especially to amphibians, so armed with this information, conservationists may avoid the reintroduction of unsuitable/maladapted individuals to new sites and increase the evolutionary potential of populations within species.
Fibre-specific mitochondrial protein abundance is linked to resting and post-training mitochondrial content in the muscle of men
Authors: Reisman Elizabeth G. , Botella Javier , Huang Cheng , Schittenhelm Ralf B. , Stroud David A. , Granata Cesare , Chandrasiri Owala S. , Ramm Georg , Oorschot Viola , Caruana Nikeisha J. , Bishop David J. 
Published: September 2024

AbstractAnalyses of mitochondrial adaptations in human skeletal muscle have mostly used whole-muscle samples, where results may be confounded by the presence of a mixture of type I and II muscle fibres. Using our adapted mass spectrometry-based proteomics workflow, we provide insights into fibre-specific mitochondrial differences in the human skeletal muscle of men before and after training. Our findings challenge previous conclusions regarding the extent of fibre-type-specific remodelling of the mitochondrial proteome and suggest that most baseline differences in mitochondrial protein abundances between fibre types reported by us, and others, might be due to differences in total mitochondrial content or a consequence of adaptations to habitual physical activity (or inactivity). Most training-induced changes in different mitochondrial functional groups, in both fibre types, were no longer significant in our study when normalised to changes in markers of mitochondrial content.
Giant impact on early Ganymede and its subsequent reorientation
Authors: Hirata Naoyuki 
Published: September 2024

AbstractGanymede has an ancient impact structure called a furrow system. The furrow system is the largest impact structure in the outer solar system, and the impact should have significantly affected Ganymede’s early history; however, its effects are poorly understood. No attention has been given to the center of the furrow system coinciding with Ganymede's tidal axis, indicating that mass redistribution induced by the furrow-forming impact caused a reorientation (true polar wander) of Ganymede. We propose that the impact ejecta created a mass anomaly that reoriented the impact site toward the tidal axis. We found that an impactor with a radius of 150 km and an incidence angle between 60° and 90° most accurately reproduces the current location of the furrow system. We predict that future explorations would reveal remnant topographic profiles or gravity anomalies associated with the furrow-forming impact and reorientation. Additionally, various possible explanations for the reorientation of Ganymede, such as an impactor-origin mascon beneath the basin or a thickness variation in the lithosphere, should be studied.
Single-strand DNA-binding protein suppresses illegitimate recombination in Escherichia coli, acting in synergy with RecQ helicase
Authors: Feliciello Isidoro , Ljubić Sven , Đermić Edyta , Ivanković Siniša , Zahradka Davor , Đermić Damir 
Published: September 2024

AbstractSingle-strand DNA-binding proteins SSB/RPA are ubiquitous and essential proteins that bind ssDNA in bacteria/eukaryotes and coordinate DNA metabolic processes such as replication, repair, and recombination. SSB protects ssDNA from degradation by nucleases, while also facilitating/regulating the activity of multiple partner proteins involved in DNA processes. Using Spi− assay, which detects aberrantly excised λ prophage from the E. coli chromosome as a measure of illegitimate recombination (IR) occurrence, we have shown that SSB inhibits IR in several DSB resection pathways. The conditional ssb-1 mutation produced a higher IR increase at the nonpermissive temperature than the recQ inactivation. A double ssb-1 recQ mutant had an even higher level of IR, while showing reduced homologous recombination (HR). Remarkably, the ssb gene overexpression complemented recQ deficiency in suppressing IR, indicating that the SSB function is epistatic to RecQ. Overproduced truncated SSBΔC8 protein, which binds to ssDNA, but does not interact with partner proteins, only partially complemented recQ and ssb-1 mutations, while causing an IR increase in otherwise wild-type bacteria, suggesting that ssDNA binding of SSB is required but not sufficient for effective IR inhibition, which rather entails interaction with RecQ and likely some other protein(s). Our results depict SSB as the main genome caretaker in E. coli, which facilitates HR while inhibiting IR. In enabling high-fidelity DSB repair under physiological conditions SSB is assisted by RecQ helicase, whose activity it controls. Conversely, an excess of SSB renders RecQ redundant for IR suppression.
Exploring steric sea level variability in the Eastern Tropical Atlantic Ocean: a three-decade study (1993–2022)
Authors: Ghomsi Franck Eitel Kemgang , Mohamed Bayoumy , Raj Roshin P. , Bonaduce Antonio , Abiodun Babatunde J. , Nagy Hazem , Quartly Graham D. , Johannessen Ola M. 
Published: September 2024

AbstractSea level rise (SLR) poses a significant threat to coastal regions worldwide, particularly affecting over 60 million people living below 10 m above sea level along the African coast. This study analyzes the spatio-temporal trends of sea level anomaly (SLA) and its components (thermosteric, halosteric and ocean mass) in the Eastern Tropical Atlantic Ocean (ETAO) from 1993 to 2022. The SLA trend for the ETAO, derived from satellite altimetry, is 3.52 ± 0.47 mm/year, similar to the global average of 3.56 ± 0.67 mm/year. Of the three upwelling regions, the Gulf of Guinea (GoG) shows the highest regional trend of 3.42 ± 0.12 mm/year. Using the ARMORD3D dataset, a positive thermosteric sea level trend of 0.88 ± 0.04 mm/year is observed, particularly in the equatorial and southern Atlantic regions. The steric component drives the interannual SLA variability, while the ocean mass component dominates the long-term trends, as confirmed by the GRACE and GRACE-FO missions for 2002–2022. For those two decades, the total SLR from altimetry amounts to 3.80 ± 0.8 mm/year, whilst the steric component is reduced to only 0.19 ± 0.05 mm/year, leaving a residual increase in the ETAO of 3.69 ± 0.5 mm/year. The independent mass change from GRACE amounts to 2.78 ± 0.6 mm/year for this region, which just closes the sea level budget within present uncertainty levels. Spatial analysis of the steric components indicates a warming along the equatorial African coast including the GoG and a freshening near Angola. Strong correlations with regional climate factors, particularly the Tropical South Atlantic Index, highlight the influence of persistent climate modes. These findings underscore the urgent need for mitigation and adaptation strategies to SLR in the ETAO, especially for densely populated coastal communities.
Shared genetic architecture between gastro-esophageal reflux disease, asthma, and allergic diseases
Authors: Gong Tong , Kuja-Halkola Ralf , Harder Arvid , Lundholm Cecilia , Smew Awad I. , Lehto Kelli , Andreasson Anna , Lu Yi , Talley Nicholas J. , Pasman Joëlle A. , Almqvist Catarina , Brew Bronwyn K. 
Published: September 2024

AbstractThe aim is to investigate the evidence for shared genetic architecture between each of asthma, allergic rhinitis and eczema with gastro-esophageal reflux disease (GERD). Structural equation models (SEM) and polygenic risk score (PRS) analyses are applied to three Swedish twin cohorts (n = 46,582) and reveal a modest genetic correlation between GERD and asthma of 0.18 and bidirectional PRS and phenotypic associations ranging between OR 1.09-1.14 and no correlations for eczema and allergic rhinitis. Linkage disequilibrium score regression is applied to summary statistics of recently published GERD and asthma/allergic disease genome wide association studies and reveals a genetic correlation of 0.48 for asthma and GERD, and Genomic SEM supports a single latent factor. A gene-/gene-set analysis using MAGMA reveals six pleiotropic genes (two at 12q13.2) associated with asthma and GERD. This study provides evidence that there is a common genetic architecture unique to asthma and GERD that may explain comorbidity and requires further investigation.
Efficacy of a cognitive-behavioral digital therapeutic on psychosocial outcomes in rheumatoid arthritis: randomized controlled trial
Authors: Betz Linda T. , Jacob Gitta A. , Knitza Johannes , Koehm Michaela , Behrens Frank 
Published: September 2024

AbstractCognitive behavioral therapy improves psychosocial outcomes in rheumatoid arthritis (RA), but access is limited. We conducted a randomized controlled trial to evaluate the efficacy of a cognitive-behavioral digital therapeutic, reclarit, on psychosocial outcomes in adult RA patients with impaired health-related quality of life. Participants were randomized to reclarit plus treatment as usual (TAU) or TAU plus educational and informational material (active control). The primary outcome was SF-36 mental (MCS) and physical (PCS) component summary scores at 3 months, with additional assessments at 6 months. reclarit significantly improved SF-36 MCS scores compared to control (mean difference 3.3 [95% CI 0.7, 5.9]; p = 0.014), with high user satisfaction and sustained improvements at 6 months. Depression, anxiety, fatigue, and social/work functioning also improved significantly, while SF-36 PCS, pain, and disability scores did not differ. In conclusion, reclarit offers immediate, effective, evidence-based and personalized psychological support for RA patients.
Abundant mRNA m1A modification in dinoflagellates: a new layer of gene regulation
Authors: Li Chongping , Li Ying , Guo Jia , Wang Yuci , Shi Xiaoyan , Zhang Yangyi , Liang Nan , Ma Honghui , Yuan Jie , Xu Jiawei , Chen Hao 
Published: September 2024

AbstractDinoflagellates, a class of unicellular eukaryotic phytoplankton, exhibit minimal transcriptional regulation, representing a unique model for exploring gene expression. The biosynthesis, distribution, regulation, and function of mRNA N1-methyladenosine (m1A) remain controversial due to its limited presence in typical eukaryotic mRNA. This study provides a comprehensive map of m1A in dinoflagellate mRNA and shows that m1A, rather than N6-methyladenosine (m6A), is the most prevalent internal mRNA modification in various dinoflagellate species, with an asymmetric distribution along mature transcripts. In Amphidinium carterae, we identify 6549 m1A sites characterized by a non-tRNA T-loop-like sequence motif within the transcripts of 3196 genes, many of which are involved in regulating carbon and nitrogen metabolism. Enriched within 3′UTRs, dinoflagellate mRNA m1A levels negatively correlate with translation efficiency. Nitrogen depletion further decreases mRNA m1A levels. Our data suggest that distinctive patterns of m1A modification might influence the expression of metabolism-related genes through translational control.
Rational structure-guided design of a blood stage malaria vaccine immunogen presenting a single epitope from PfRH5
Authors: Harrison Thomas E , Alam Nawsad , Farrell Brendan , Quinkert Doris , Lias Amelia M , King Lloyd D W , Barfod Lea K , Draper Simon J , Campeotto Ivan , Higgins Matthew K 
Published: September 2024

AbstractThere is an urgent need for improved malaria vaccine immunogens. Invasion of erythrocytes by Plasmodium falciparum is essential for its life cycle, preceding symptoms of disease and parasite transmission. Antibodies which target PfRH5 are highly effective at preventing erythrocyte invasion and the most potent growth-inhibitory antibodies bind a single epitope. Here we use structure-guided approaches to design a small synthetic immunogen, RH5-34EM which recapitulates this epitope. Structural biology and biophysics demonstrate that RH5-34EM is correctly folded and binds neutralising monoclonal antibodies with nanomolar affinity. In immunised rats, RH5-34EM induces PfRH5-targeting antibodies that inhibit parasite growth. While PfRH5-specific antibodies were induced at a lower concentration by RH5-34EM than by PfRH5, RH5-34EM induced antibodies that were a thousand-fold more growth-inhibitory as a factor of PfRH5-specific antibody concentration. Finally, we show that priming with RH5-34EM and boosting with PfRH5 achieves the best balance between antibody quality and quantity and induces the most effective growth-inhibitory response. This rationally designed vaccine immunogen is now available for use as part of future malaria vaccines, alone or in combination with other immunogens.
Reanalysis of the Huygens GCMS dataset
Authors: Gautier T. , Serigano J. , Das K. , Coutelier M. , Hörst S. M. , Szopa C. , Vinatier S. , Trainer M. G. 
Published: September 2024

Context. More than 15 years after its landing on the surface of Titan, the data returned by the Huygens probe remain the only available in situ information on Titan’s lower atmosphere and its methane content.
Aims. In this work, we present a reanalysis of the Huygens probe data obtained by the Gas Chromatograph Mass Spectrometer (GCMS) instrument on board Huygens. GCMS measured the atmospheric composition almost continuously during the Huygens probe descent by acquiring mass spectra between 145 km of altitude and Titan’s surface. We first focus on the recollection, reconstruction, and recalibration of the GCMS dataset to facilitate similar future work.
Methods. We then reevaluate the methane vertical profile in Titan’s lower atmosphere by applying novel mass spectra data-treatment methods to this dataset.
Results. In addition to finding a slightly lower methane mixing ratio than those previously reported using GCMS measurements above the Huygens probe landing site, our work has revealed several kilometric to subkilometric-scale oscillations in the methane vertical profile below 30 km of altitude.
Conclusions. We discuss several hypotheses that could explain these features, such as multiple layers of optically thin clouds or local convection cells, and strongly encourage the reanalysis of other Huygens datasets to further investigate these variations in the methane mixing ratio.
The SRG/eROSITA All-Sky Survey: X-ray beacons at late cosmic dawn
Authors: Wolf J. , Salvato M. , Belladitta S. , Arcodia R. , Ciroi S. , Di Mille F. , Sbarrato T. , Buchner J. , Hämmerich S. , Wilms J. , Collmar W. , Dwelly T. , Merloni A. , Urrutia T. , Nandra K. 
Published: September 2024

Context. The Spektrum-Roentgen-Gamma (SRG)/extended Roentgen Survey with an Imaging Telescope Array (eROSITA) All-Sky Survey (eRASS) is expected to contain ∼100 quasars that emitted their light when the universe was less than a billion years old, that is, at z > 5.6. By selection, these quasars populate the bright end of the active galactic nuclei (AGN) X-ray luminosity function, and their space density offers a powerful demographic diagnostic of the parent super-massive black hole (SMBH) population.
Aims. Of the ⪆400 quasars that have been discovered at z > 5.6 to date, less than 15% have been X-ray detected. We present a pilot survey to uncover the elusive X-ray luminous end of the distant quasar population.
Methods. We have designed a quasar selection pipeline based on optical, infrared and X-ray imaging data from DES DR2, VHS DR5, CatWISE2020 and the eRASS (up to its four-pass cumulative version, eRASS:4). The core selection method relies on SED template fitting. We performed optical follow-up spectroscopy with the Magellan/LDSS3 instrument for the redshift confirmation of a subset of candidates. We have further obtained a deeper X-ray image of one of our candidates with Chandra ACIS-S.
Results. We report the discovery of five new quasars in the redshift range 5.6 < z < 6.1. Two of these quasars are detected in eRASS and are, therefore, X-ray ultra-luminous by selection. We also report the detection of these quasars at radio frequencies. The first one is a broad absorption line quasar, which shows significant, order-of-magnitude X-ray dimming over 3.5 years, corresponding to six months in the quasar rest frame. The second X-ray detected quasar is a jetted source with compact morphology. We show that a blazar configuration is likely for this source, making it one of the most distant blazars known to date.
Conclusions. With our pilot study, we demonstrate the power of eROSITA as a discovery machine for luminous quasars in the epoch of reionization. The X-ray emission of the two eROSITA detected quasars are likely to be driven by different high-energetic emission mechanisms, a diversity which we will further explore in a future systematic full-hemisphere survey.