bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noncoding elements withinMYCNmRNA are autonomous drivers of oncogenesis in neuroblastoma
Authors: Patel Vishwa , Benhamou Lorraine-Rana E. , Powers John T. 
Published: January 2025

AbstractNeuroblastoma (NB) is a highly metastatic pediatric cancer arising from the neural crest lineage. Genetic amplification of theMYCNproto-oncogene is a defining feature of NB, present in about 20% of all cases. Thelet-7tumor suppressor microRNA targets the 3’ UTR ofMYCNmRNA. We previously demonstrated that the 3’ UTR ofMYCNmRNA acquires the ability to sequesterlet-7inMYCN-amplified (MA) disease, thus inhibiting its function. This work established that a noncoding element within an oncogenic mRNA can contribute independently to disease pathology and genetic patterning. To further investigate the roles of noncoding RNA elements within theMYCNmRNA, we engineered cells expressing eitherMYCN-ORF(MYCN open reading frame only),MYCN-GL(full-length MYCN mRNA from the intact genetic locus), andNull-GL(full-lengthMYCNmRNA variant where EGFP replaces MYCN protein). We observe that all constructs enhance growth compared to controlsin vitroandin vivo. MYCN-GL-expressing cells displayed the most robust growthin vitrodespite containing multiple regulatory RNA elements. Remarkably, theNull-GLconstruct induces cells to grow as fast or faster thanMYCN-ORF-expressing cells. Animal studies further confirmed these observations, where theNull-GL-driven tumors had the highest incidence and lowest latency, followed byMYCN-GLand thenMYCN-ORF. Further, through NGS analysis,let-7, miR-101, andmiR-34atargets are enriched in bothMYCN-GLandNull-GLexpressing cells. Thus, the 3’UTR ofMYCN, which is also targeted by these microRNAs, may interact with them inMYCN-GLandNull-GLcells to deliver a protective effect for the mRNA targets of these microRNAs. We also observed more dynamic differential gene expression in the -GL constructs than in ORF and GFP-expressing cells. In addition,MYCN-GLandNull-GLexpressing cells are similarly enriched in gene ontology pathways for cancer, RNA metabolism, and microRNA processing pathways as compared toORFandGFP. Whole genome sequencing also revealed more similarities in copy number variation inMYCN-GLandNull-GLthan inORFandGFP, suggesting that these constructs may provide selective pressure to favor specific CNV patterns. These observations show that full-lengthMYCNmRNA containing noncoding regulatory elements are more robust drivers of cell growth and oncogenicity than MYCN protein alone and provide insights into the mechanisms of oncogenic contribution. These results open an exciting door for our understanding of NB pathology and genetic patterning and have broad implications for other oncogene-driven cancers.
Wildfire ash impacts to photosynthesis and growth of marine phytoplankton cultures
Authors: Van Houtan Kyle S. , Lambert John , Provatas Anthony A. , Van Houtan Dillon J. , Smith Celia M. 
Published: January 2025

ABSTRACTClimate change includes increasing surface temperatures as well as extreme events—heatwaves, storms, floods, and droughts. In 2020, these factors produced a record 10,000 wildfires that burned 18,000 km2in California USA. Air pollution, including airborne ash, from these fires was a widespread human health hazard. While the ecological effects of wildfires have been extensively documented in terrestrial and freshwater systems, impacts on ocean and coastal ecosystems are largely unexplored. Here, we describe the physical and chemical properties of ash from the CZU Lightning Complex fire and experimentally test its effects on the photosynthesis and growth of four unicellular marine phytoplankton. Sieved air-fall ash was primarily composed of particles 250-500 μm and contained ∼1 ‰ of Fe, Mn, and Ba. Diagnostic indices of polycyclic aromatic hydrocarbons indicated the air-fall ash originated from combusted wood, and the total concentration of the EPA 16 high-priority PAHs exceeded 2.7 ppm. Pulse Amplitude Modulation fluorometry documented various declines in the photosynthetic efficiency of Isochrysis and Dunaliella cultures dosed with ash, and the bulk cellular growth of these cultures was inhibited. While our study demonstrated the impacts of wildfire ash on marine producers, the precise mechanisms are unclear. We provide recommendations for how future studies may further resolve the impacts of ash on phytoplankton productivity, community diversity, and trophic transfer of toxins and describe the long-term impacts of wildfires on coastal marine ecosystems.
The Population Genetics of Biological Noise
Authors: Weinreich Daniel M. , Sgouros Tom , Raynes Yevgeniy , Burtsev Hlib , Chang Edison , Rajakumar Sanyu , Bravo Ignacio G. , Petak Csenge 
Published: January 2025

AbstractNoise is intrinsic to information transmission, and information transmission is intrinsic to life. Critically, while biological noise is random, its amount is in part genetically determined. Here, we explore the population genetics of alleles that heritably influence the amount of noise in any biological mechanism. We argue that biological noise is a doubleedged sword: almost always inducing deleterious phenotypes but also occasionally yielding high fitness outcomes. We further suggest that this implies the existence of an equilibrium amount of noise, at which the advantage of producing additional, rare beneficial phenotypes is balanced by the cost of producing the vastly more common deleterious phenotypes. The location of this equilibrium will reflect the rate at which its environment is changing, the persistence of association between noise-modifying alleles and the phenotypic perturbations they induce, the mode of selection, and the population size. The population genetics of alleles that heritable change mean trait values have been established for nearly a century, but to our knowledge, this is the first general treatment of the evolution of heritable changes in the statistical distribution around that mean. Our framework generalizes modifier theory in the sense used by Altenberg, Feldman and others, and resolves teleological criticisms of the hypothesis that evolvability can evolve via natural selection. We conclude with an outline of open theoretical and empirical questions posed by our framework.
The structure of mitochondrial genomes is associated with geography inArabidopsis thaliana
Authors: Xian Wenfei , Bao Zhigui , Vorbrugg Sebastian , Tao Yueqi , Movilli Andrea , Bezrukov Ilja , Weigel Detlef 
Published: January 2025

AbstractChloroplasts and mitochondria are the primary sites for photosynthesis and respiration, each harboring its own unique genome. Although the organellar genomes are considerably smaller compared to the nuclear genome, they are nonetheless essential for survival of the organism. A common feature of many chloroplast and mitochondrial genomes is the presence of large repeated sequences longer than 1 kb. These can be either in inverted or direct orientation, and recombination between them leads to structural heteroplasmy. To understand the intraspecific evolution of organellar genomes, we assembled chloroplast and mitochondrial genomes of 143A. thalianaaccessions from PacBio HiFi sequencing data. We find large repeats to be associated with heteroplasmy and structural variation. Our extensive genome annotation identifies novel open reading frames (ORFs) in those accessions that lost large repeats, potentially introduced via horizontal gene transfer, illuminating additional paths for diversification of plant organelles. The loss of large repeats correlates with geography and phenotypes, pointing to their adaptive importance. The assembled and annotated organellar genomes constitute a rich source for future functional studies of the interaction between the three genomes of a plant.
Prospective Blinded evaluation of Thermalytix, an artificial intelligence-enhanced breast thermal imaging software, correlated with radiologist-interpreted mammograms: Results of an exploratory study in Zambia
Authors: Mwale Maurice , Nteeni Mutinta S. , Mwaba Peter , Chipamp Mercy N. 
Published: January 2025

AbstractBackgroundWhile mammography is commonly used for breast cancer detection, its widespread implementation in resource-constrained nations is challenging. Artificial intelligence-based Thermalytix is a low-cost, portable, radiation-free, automated test for breast cancer detection in women of all ages. Although used in India, the efficacy of Thermalytix has not been tested in an African population.ObjectivesTo assess the agreement and correlation coefficient of Thermalytix output with radiologist-reported mammography, in a Zambian tertiary care population.MethodologyIn October 2023, 169 women were evaluated with both Thermalytix and standard mammography at Maina Soko Military Hospital at Lusaka. Thermalytix uses advanced machine learning algorithms to interpret breast thermal scans and generates a quantitative score indicating the likelihood of malignancy. All women underwent both tests, with results blinded both ways. Subsequently the Spearman correlation coefficient and level of agreement between Thermalytix output and BIRADs scoring from radiologist-interpreted mammography was calculated.Results144 women with complete data were analysed in this report, with median age of 50 years (53.5% postmenopausal, 65.3% asymptomatic). Six women were assessed as mammography test positive and 138 as mammography negative; in these, the correlation between Thermalytix and mammography using Spearman test of rank correlation was 0.9 [very strong], and using the US FDA recommended test of agreement, positive agreement was obtained in 83.3%.ConclusionDemonstrating a very strong correlation and level of agreement with mammography, along with its good sensitivity, specificity and negative predictive value in previous clinical trials, Thermalytix has the potential to be an additional tool in the early detection of breast cancer in Zambia.
Efficacy of Preemptive Intravenous Ibuprofen and Dexketoprofen on Postoperative Opioid Consumption in Laparoscopic Cholecystectomy: Randomized Controlled Study
Authors: Soyalp Celaleddin , Yayik Ahmet Murat , Öksüz Ersoy , Yüzkat Nurettin 
Published: January 2025

ABSTRACTBackgroundTo compare the effects of preemptive single-dose intravenous (IV) ibuprofen and dexketoprofen on postoperative pain and opioid consumption in patients undergoing laparoscopic cholecystectomy (LCC).MethodsThe study included 90 patients aged 18-65 years with an ASA score of I or II who underwent LCC. Patients were equally divided into three groups: Control Group (Group P), 100 cc 0.9% NaCl was infused intravenously over 30 min, Dexketoprofen Group (Group D), 50 mg dexketoprofen in 100 cc 0.9% NaCl was infused intravenously over 30 min, and Ibuprofen Group (Group I), 800 mg ibuprofen in 100 cc 0.9% NaCl was administered intravenously over 30 min. Visual Analog Scale (VAS) scores and opioid requirement were recorded at 1, 2, 4, 6, 12 and 24 hours postoperatively.ResultsThere was no significant difference between the Dexketoprofen and Ibuprofen groups with regard to VAS scores, whereas VAS scores were higher in the control group than in other groups. In addition, fentanyl consumption was higher in the control group at 0-6 hours and at 24 hours compared to the other two groups.ConclusionPreemptive ibuprofen and dexketoprofen administration showed no significant difference with regard to postoperative pain and opioid consumption, particularly within the first 6 hours after LCC.
Distinct CD8+T-cell types Associated with COVID-19 Severity in Unvaccinated HLA-A2+Patients
Authors: Masuda Kazuya , Iketani Sho , Liu Lihong , Huang Jing , Qiao Yujie , Shah Jayesh , McNairy Meredith L. , Groso Christine , Ricupero Christopher , Loffredo Lucas F. , Wang Qian , Purpura Lawrence , Coelho-dos-Reis Jordana Grazziela Alves , Sheng Zizhang , Yin Michael T , Tsuji Moriya 
Published: January 2025

AbstractAlthough emerging data have revealed the critical role of memory CD8+T cells in preventing and controlling SARS-CoV-2 infection, virus-specific CD8+T-cell responses against SARS-CoV-2 and its memory and innate-like subsets in unvaccinated COVID-19 patients with various disease manifestations in an HLA-restricted fashion remain to be understood. Here, we show the strong association of protective cellular immunity with mild COVID-19 and unique cell types against SARS-CoV-2 virus in an HLA-A2 restricted manner. ELISpot assays reveal that SARS-CoV-2-specific CD8+T-cell responses in mild COVID-19 patients are significantly higher than in severe patients, whereas neutralizing antibody responses against SARS-CoV-2 virus significantly correlate with disease severity. Single-cell analyses of HLA-A2-restricted CD8+T cells, which recognize highly conserved immunodominant SARS-CoV-2-specific epitopes, demonstrate divergent profiles in unvaccinated patients with mild versus severe disease. CD8+T-cell types including cytotoxicKLRB1+CD8αα cells with innate-like T-cell signatures,IFNGhiID3himemory cells andIL7R+proliferative stem cell-like memory cells are preferentially observed in mild COVID-19, whereas distinct terminally-differentiated T-cell subsets are predominantly detected in severe COVID-19: highly activatedFASLhiT-cell subsets and early-terminated or dysfunctionalIL4R+GATA3+stem cell-like memory T-cell subset. In conclusion, our findings suggest that unique and contrasting SARS-CoV-2-specific CD8+T-cell profiles may dictate COVID-19 severity.Abstract FigureGraphical abstract.SARS-CoV-2 epitope-specific CD8+T-cell subtypes associated with mild or severe COVID-19 patients.Potent memory CD8+T-cell subtypes with gene signature in mild COVID-19 patients (upper) and dysfunctional CD8+T-cell subtypes with gene signature in severe COVID-19 patients (lower).
Lower slow wave sleep and rapid eye-movement sleep are associated with brain atrophy of AD-vulnerable regions
Authors: Cho Gawon , Mecca Adam P. , Buxton Orfeu M. , Liu Xiao , Miner Brienne 
Published: January 2025

ABSTRACTStudy objectivesSleep deficiency is associated with Alzheimer’s disease (AD) pathogenesis. We examined the association of sleep architecture with anatomical features observed in AD: (1) atrophy of hippocampus, entorhinal, inferior parietal, parahippocampal, precuneus, and cuneus regions (“AD-vulnerable regions”) and (2) cerebral microbleeds.MethodsIn 271 participants of the Atherosclerosis Risk in the Communities Study, we examined the association of baseline sleep architecture with anatomical features identified on brain MRI 13∼17 years later. Sleep architecture was quantified as the proportion of slow wave sleep (SWS), proportion of rapid eye-movement sleep (REM), and arousals index using polysomnography. Outcomes included (1) volumetric measurements of each AD-vulnerable region and (2) the presence of any cerebral microbleeds (CMBs) and that of lobar CMBs, which are more specifically associated with AD. We analyzed the association of each sleep predictor with each MRI outcome, adjusting for covariates.ResultsHaving less SWS was associated with smaller inferior parietal region (β=−44.19 mm3[95%CI=−76.63,−11.76]) and cuneus (β=−11.99 mm3[−20.93,−3.04]) after covariate adjustment. Having less REM was associated with smaller inferior parietal region (β=−75.52 mm3[−129.34, −21.70]) and precuneus (β=−31.93 mm3[−63.79,−0.07]). After FDR adjustments, lower SWS and REM, respectively, were associated with smaller inferior parietal region. Arousal index was not associated with the volumes of AD-vulnerable regions. None of the sleep architecture variables were associated with CMBs or lobar CMBs.ConclusionsSleep deficiency is associated with the atrophy of the inferior parietal region, which is observed in early AD. Sleep architecture may be a modifiable risk factor for AD.Brief summarya.Current Knowledge/Study Rationale: two sentences summarizing why the study was doneWhile impaired sleep architecture has been associated with Alzheimer’s disease [AD] diagnosis and cognitive decline. To better understand the impact of sleep on AD pathogenesis, this study examined the association of sleep architecture with anatomical features observed in AD, including the atrophy of AD-vulnerable regions and CMBs.b.Study Impact: two sentences summarizing how the study impacts the fieldOur study shows that lower slow wave sleep and rapid eye movement sleep may be precipitating factors of inferior parietal region atrophy, which is associated with AD risk. Importantly, the current study’s findings can help characterize underlying mechanisms of how sleep deficiency, a prevalent disturbance among middle-aged and older adults, may facilitate AD pathogenesis and cognitive impairment.
Hormone gene expression changes in the zebrafish caudal neurosecretory system under acute environmental challenges
Authors: Bichon Bérénice , Alfama Gladys , Gaillard Anne-Laure , Tostivint Hervé , Pézeron Guillaume 
Published: January 2025

AbstractThe caudal neurosecretory system (CNSS) is a neuroendocrine complex, found only in fishes, suggested to be involved in osmoregulation and thermo-adaptation. Although being discovered 70 years ago, the CNSS has been understudied and its physiological significance remains poorly understood. The zebrafish (Danio rerio) is a well-established model organism for functional studies, yet, so far, the role of the CNSS has not really been investigated in this species. In the present study, we attempted to identify environmental factors whose variations induce changes in CNSS activity. Juvenile zebrafish were submitted to acute (2 h, 8 h, and 24 h) pH, salinity, and temperature challenges, and CNSS activity was quantified by measuring the expression levels of peptide hormone-encoding genes using quantitative PCR. Our findings revealed that temperature challenge affected the expression of the largest number of gene, followed by salinity and pH challenges. This suggested that, in the zebrafish, the CNSS is involved in thermo-adaptation and osmoregulation, which is consistent with what has been reported in other species, and showed that the zebrafish is a relevant model to study the function of the CNSS.
Detection of resistance inPhytophthora infestansto the carboxylic acid amide (CAA) fungicides using digital droplet PCR
Authors: Kaur Amanpreet , Mullins Ewen , Kildea Steven 
Published: January 2025

AbstractBackgroundPotato late blight caused byPhytophthora infestansremains the greatest biotic threat to potato production globally. In northern Europe to prevent the disease and associated yield losses fungicides are heavily relied upon, with multiple applications required during the potato growing season. Unfortunately, such intensive fungicide usage has the potential to compromise control efficacy as it puts in place immense selective pressure for the emergence and spread of fungicide resistant strains ofP. infestans. In recent years this scenario has been realised, with the emergence of strains resistant to the carboxylic acid amide (CAA) fungicides. As resistance to the CAA fungicides inP. infestanshas been confirmed to result from changes in the pathogen’s cellulose synthase A3 gene (CesA3), specifically at amino acid position 1105, it opens the possibility to develop molecular tools to rapidly monitor populations of the pathogen for the resistance allele.ResultsUsing the Stilla nacia 3-colour system a droplet digital PCR (ddPCR) was successfully developed to simultaneously detect theP. infestans CesA3gene irrespective of its CAA sensitivity status, and either the CAA wild-type sequence for position 1105 or that conferring the resistant allele G1105S. Using a ‘drop-off’ in ratio of positive droplets for either the wild-type or G1105S alleles relative to those positive for the generalP. infestansCesA3 it was also possible to demonstrate that using the assay other potential alterations known to confer resistance that may occur at this position (e.g. G1105V) can be detected. The assay was validated using multiple sources ofP. infestansDNA, including FTA cards.ConclusionsThe assay developed will allow for the accurate and sensitive detection of CAA resistance conferred by alterations at amino acid position 1105 in the CesA3 gene inP. infestans. The capacity to use the assay with multiple DNA sources and potential to adapt the ‘drop-off’ approach to different ddPCR platforms will ensure its applicability to the widerP. infestanscommunity in monitoring the continued use of CAA-based fungicides forP. infestansmanagement.
Structures of vesicular stomatitis virus glycoprotein G alone and in complex with a neutralizing antibody
Authors: Minoves Marie , Ouldali Malika , Belot Laura , Roche Stéphane , Zakardas Lefteris , Schoehn Guy , Gaudin Yves , Albertini Aurélie 
Published: January 2025

AbstractVSV G mediates viral entryviaendocytosis. In the endosome, G undergoes a pH-dependent conformational change from pre- to post-fusion state, catalyzing membrane fusion. So far, no complete structure of G has been reported. We report cryo-EM structures of G, isolated from virions using detergent, alone and in complex with neutralizing antibody FAb that binds G in all conformations. The post-fusion structure reveals novel details about the organization of the C-terminal part of the ectodomain, showing that it undergoes conformational rearrangement and stabilizes the post-fusion trimer by nesting into a groove between adjacent fusion domains. The fusion loops are visible inside the micelle, which is not the case of the transmembrane domains, suggesting that they are rather mobile. Structures of G-FAb complex show that the epitope belongs to a conserved antigenic site. This work has potential implications for vaccine development and oncolytic virotherapy.
Risk preferences causally rely on parietal magnitude representations: Evidence from combined TMS-fMRI
Authors: de Hollander Gilles , Moisa Marius , Ruff Christian C. 
Published: January 2025

AbstractRisk preferences have traditionally been considered as stable traits that reflect subjective-valuation processes in prefrontal areas. More recently, however, it has been suggested that risk preferences may also be shaped by how choice problems are perceived and processed in perceptual brain regions. Specifically, the acuity of the parietal approximate number system (ANS), which encodes payoff magnitudes for different choice options, has been shown to correlate with both risk preferences and choice consistency. However, this correlational relationship leaves open the question whether parietal magnitude representations in fact causally underlie choice. Here, we provide direct evidence for such a key causal role of parietal magnitude representations in economic choice, using continuous theta-burst transcranial magnetic stimulation (cTBS), combined with functional MRI (fMRI) and numerical population receptive field (nPRF) modeling.Our stimulation protocol targeted numerosity-tuned regions in the right parietal cortex, identified through nPRF modeling of individual fMRI data (n=35; within-subject design). The stimulation successfully perturbed neural processing, as evidenced by decreased amplitude of numerical magnitude-tuned responses and less accurate multivariate decoding of presented magnitudes from unseen data that were not used for model fitting. In line with a perceptual account of risky choice, the reduction in neural information capacity was also reflected in noisier behavioral responses. Moreover, a computational cognitive model fitted to choice behavior revealed that perturbing the ANS specifically increased the noisiness of small-magnitude representations. This perturbation made small magnitudes to be perceived as larger than they actually are, leading to more risk-seeking behavior. Finally, individual estimates of the cTBS effect on cognitive noise correlated with the corresponding decrease in amplitude of numerical magnitude-tuned fMRI responses, further solidifying the role of the parietal ANS in economic choice. In conclusion, our study demonstrates that the precision of parietal magnitude representations causally influences economic decision-making, with noisier encoding promoting biased risk-taking as formalized in recent perceptual models of risky choice.