bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of elevation and microclimatic temperatures on butterfly-flower interaction networks in a Mediterranean mountain range
Authors: Alamo Mario , Álvarez Hugo Alejandro , Mingarro Mario , Wilson Robert J. 
Published: January 2025

ABSTRACTResearching the properties of mutualistic networks over environmental gradients is a promising but underexplored means to test how global change can affect ecosystem assembly and functioning. We examined how elevation and microclimate influenced butterfly-flower interaction networks at the hottest time of year in a Mediterranean mountain range.Throughout July 2023, we recorded weekly butterfly-flower interaction networks from 36 transects in nine sites, across an 800 m elevation gradient in the Sierra de Guadarrama (Central Spain). We quantified the connectance, nestedness, modularity and robustness to species loss of networks, and related these descriptors using Generalized Additive Mixed Models to elevation, microclimate temperature (modelled using Microclima), date and time of day.The networks were dominated at all sites by one or two abundant butterfly and flower species, but these varied with elevation. Butterfly networks were more robust to plant species loss at higher elevations, where communities showed increased linkage density. Butterfly-plant networks became less nested at higher microclimatic temperatures in July. Network properties also varied through the day, with connectance decreasing markedly from morning to afternoon.In the Mediterranean mountains studied, summer butterfly-flower interaction networks were more resilient to disturbance at high elevations and in cooler microclimates. Nectar availability could become an important limiting factor for insects in a warming climate, and understanding the mechanisms influencing the properties of flower visitor networks is therefore likely to become increasingly important for adapting the conservation of insects to climate change.
Generation of a T cell receptor, cytokine and cell repertoire synovial fluid atlas to define commonalities and dissimilarities between arthritic diseases through systems immunology approaches
Authors: Ha My K. , Deuren Vincent Van , de Carvalho Fraga Carlos Alberto , Hotterbeekx An , Dehoorne Joke , Renson Thomas , Geens Elke , Aerts Nicolaas , Heusdens Christiaan , Kuznetsova Maria , Mechelen Margot Van , Bulcke Michaël Vanden , Hoffman Ilse , Wittoek Ruth , Wachter Eva De , Andrzejewski Aurelie , Bartholomeus Esther , de Vrij Nick , Suls Arvid , Lion Eva , Vanhee Stijn , Adriaensen Wim , Mullan Kerry , Nakaya Helder , Kumar-Singh Samir , Laukens Kris , Joos Rik , Meysman Pieter , Ogunjimi Benson 
Published: January 2025

ABSTRACTAlthough different chronic arthritic diseases are defined by clinical factors like gender, psoriasis and auto-antibodies, the biology of inflamed joints while comparing the different diseases remains neglected. Here, after curating an inflamed joint derived T-cell receptor (TCR) database, our new TRIASSIC tool identified 66303 significantly convergent TCR clonotypes. Clustering TCR clonotypes showed that synovial fluid convergence clusters (SFCCs) characterized HLA-B27+ mediated diseases (spondyloarthritis, SpA, and enthesitis-related juvenile idiopathic arthritis, JIA-ERA), Lyme arthritis and oligoarticular JIA. Single-cell transcriptomics and bulk proteomics showed upregulated interferon type I and II and TNF-α pathways in oJIA. Adult and juvenile psoriatic arthritis, (JIA-)PsA, was characterized by upregulated HSP expression in monocytes and TXNIP in T-cells. We discovered an abundance of CCL5 expressing CD8+ T-cells in SF from HLA-B27+ JIA-ERA and SpA patients. JIA-ERA patients showed upregulation of CD74 and LGALS1 in Th1 and Th17 cells and IGHV7-4.1 in B-cells. oJIA patients shared a TRBV28 RG-motif on CXCL13 producing helper T-cells. Rheumatoid arthritis and (JIA-)PsA patients carried EBV-reactive cytotoxic CD8+ T-cells. Annexin signalling was shown to be important in the intercellular communication for all arthritis groups. Collectively, our work showed that chronic arthritis is characterized by both disease-specific and broadly shared mechanisms.
Larger larval sea lamprey (Petromyzon marinus)have longer survival times when exposed to the lampricide 3-trifluoromethyl-4-nitrophenol
Authors: Nalesnik Allison M. , Martin Emily L. , Kovacs Ian S. , Johnson Connor S. , Carroll Emma I. , Jubar Aaron , Hemstrom William , Wilkie Michael P. , Dunlop Erin S. , Sepulveda Maria S. , Johnson Nicholas S. , Christie Mark R. 
Published: January 2025

AbstractInvasive sea lamprey (Petromyzon marinus) in the Laurentian Great Lakes have negatively impacted ecological and economically important fishes for nearly a century. To mitigate these negative effects, the lampricide 3-trifluoromethyl-4-nitrophenol (TFM) is applied annually to Great Lakes tributaries to kill larval lampreys before they become juveniles, out-migrate to the lakes, and parasitize other fishes. It has been hypothesized that larval size (e.g., mass, length, condition) may affect survival time in response to TFM. To test this hypothesis, we conducted an experiment with 8,611 larvae across four temporal replicates, in which TFM concentrations like those used in present-day stream treatments were applied for up to 18 hours. We found a significant, positive correlation between the total length and mass of larval sea lamprey and their survival times to TFM. Specifically, there was a 4.56 minute increase in survival time for each one centimeter increase in total length after accounting for the effect of mass. We also identified a phenotypic trade-off where the survival time of heavier larvae decreased with an increase in total length and vice versa. The changes in total length and mass of larval sea lamprey stored in ethanol for four months was also quantified. The observation that five larvae survived well past the 12-hour time window of a typical TFM field treatment highlights the need for continuous monitoring and the development of new control strategies to ensure the continued effective management of this invasive species.
Recurrent oncogenic ZC3H18 mutations stabilize endogenous retroviral RNA
Authors: Tanu Tanzina , Cox Anna M. , Karlow Jennifer , Sharma Priyanka , He Xueyang , Wu Constance , Babu Swathy , Brown Jared , Brown Kevin M. , Chanock Stephen J. , Liu David , Zhang Tongwu , Burns Kathleen H. , Boutz Paul L. , Insco Megan L. 
Published: January 2025

AbstractEndogenous retroviral (ERV) RNA is highly expressed in cancer, although the molecular causes and consequences remain unknown. We found that ZC3H18 (Z18), a component of multiple nuclear RNA surveillance complexes, has recurrent truncating mutations in cancer. We show that Z18truncmutations are oncogenic and that Z18 plays an evolutionarily conserved role in nuclear RNA surveillance of ERV RNA. In zebrafish, Z18truncexpedited melanoma onset and promoted a specific accumulation of ERV RNA. Z18 mutant human cell lines from the Cancer Cell Line Encyclopedia also expressed higher levels of ERV RNA. In engineered human melanoma cells, Z18truncenhanced ERV RNA accumulation more than loss of one Z18 copy, indicating dominant negative activity. Z18truncdirectly bound and stabilized ERV RNA. Notably, expression of ERV RNA was sufficient to expedite oncogenesis in a zebrafish model, which is the first evidence of which we are aware that ERV transcripts can play a functional role in cancer. Our work illuminates a mechanism for elevated ERV transcripts in cancer and supports that aberrant RNA accumulation is broadly oncogenic.
A genealogy-based approach for revealing ancestry-specific structures in admixed populations
Authors: Tang Ji , Chiang Charleston W. K. 
Published: January 2025

AbstractElucidating ancestry-specific structures in admixed populations is crucial for comprehending population history and mitigating confounding effects in genome-wide association studies. Existing methods for elucidating the ancestry-specific structures generally rely on frequency-based estimates of genetic relationship matrix (GRM) among admixed individuals after masking segments from ancestry components not being targeted for investigation. However, these approaches disregard linkage information between markers, potentially limiting their resolution in revealing structure within an ancestry component. We introduce ancestry-specific expected GRM (as-eGRM), a novel framework for elucidating the relatedness within ancestry components between admixed individuals. The key design of as-eGRM consists of defining ancestry-specific pairwise relatedness between individuals based on genealogical trees encoded in the Ancestral Recombination Graph (ARG) and local ancestry calls and computing the expectation of the ancestry-specific relatedness across the genome. Comprehensive evaluations using both simulated stepping-stone models of population structure and empirical datasets based on three-way admixed Latino cohorts showed that analysis based on as-eGRM robustly outperforms existing methods in revealing the structure in admixed populations with diverse demographic histories. Taken together, as-eGRM has the promise to better reveal the fine-scale structure within an ancestry component of admixed individuals, which can help improve the robustness and interpretation of findings from association studies of disease or complex traits for these understudied populations.
Overexpression of the MADS-box geneCRM3in the fernCeratopteris richardiiaffects sporophyte development
Authors: Schulz Robin , Theißen Günter 
Published: January 2025

AbstractMADS-box genes encode MADS-domain transcription factors that play important roles in the development and evolution of land plants. Especially well-characterized is their role as organ identity genes during flower development of angiosperms. Even though the first MADS-box genes have been molecularly cloned from ferns almost 30 years ago, little is known about their function, mainly due to a lack of mutants. Also their quite broad expression domain, often comprising both the gametophytic and the sporophytic phase of the life cycle of ferns, provide few specific clues concerning gene function. However, as sister group of seed plants monilophytes (ferns and their allies such as horsetails) are of great interest in many attempts to understand both MADS-box gene and land plant evolution. Here we report, to the best of our knowledge, the first mutant phenotype based on transgenic overexpression of a fern MADS-box gene. Transgenic plants of the fern model systemCeratopteris richardiioverexpressing the MIKCC-type MADS-box geneCRM3under control of the Cauliflower Mosaic Virus (CaMV) 35S promoter show a significant reduction of the length of sporophylls. This finding reveals that overexpression ofCRM3affects sporophyll development inC. richardii, possibly by inhibiting cell proliferation or elongation.
Psychometric and biomedical outcomes of glycated haemoglobin target-setting in adults with type 1 and type 2 diabetes: A mixed-methods parallel-group randomised feasibility study
Authors: Westall Samuel J , Watmough Simon , Narayanan Ram Prakash , Irving Greg , Hardy Kevin 
Published: January 2025

AbstractBackgroundGlycated haemoglobin (HbA1c) targets are commonly used to guide patient management in diabetes to reduce future risk of diabetes complications, but little is known of the psychological impact of HbA1ctarget-setting. We explored the feasibility of undertaking a conclusive study evaluating the impact of setting explicit HbA1ctargets in adults with diabetes.MethodsA randomised, mixed-methods study design was used to quantitatively and qualitatively evaluate the psychometric and biomedical impact of intensified or relaxed glycaemic targets in adults with diabetes. Alongside baseline measurement of HbA1c, blood pressure and body mass index, patients completed baseline validated psychometric questionnaires (EuroQoL-5D-5L, Problem Areas In Diabetes, Summary of Diabetes Self-Care Activities, Well-Being Quetionnaire-12, Diabetes Empowerment Scale-Long Form) and were randomised 1:1. Participants in group A received explicit HbA1ctarget intervention targets 5 mmol/mol above current HbA1c. Participants in group B received explicit HbA1ctargets 5 mmol/mol below current HbA1c. Rates of eligibility, recruitment, retention and questionnaire response were recorded. Outcomes were re-measured 3-months post-intervention. Patients and healthcare professionals attended semi-structured interviews for qualitative evaluation.ResultsFifty participants were recruited. Withdrawal rate was 34% (n=17). Endpoint evaluation revealed no significant between-group differences in patient-reported outcome measures or HbA1clevels. Overall, levels of distress (-4.4, p=.009), self-efficacy (.25 [.09–.41], p=.004) and subsequent HbA1creadings (-2.8 [-5.0–-.7], p=.012) improved, with non-significant changes seen in health-related quality of life, wellbeing, and self-care. Patients and healthcare professional interviews demonstrated study acceptability alongside specific motivators (e.g., target achievability, hypoglycaemia avoidance) and demotivators (e.g., lack of understanding, lack of target achievability) for striving to reach glycaemic targets. Combined qualitative data from patient and healthcare professional interviews and quantitative study aspects triangulated, enhancing data trustworthiness, and informing future hypotheses and methodologies.DiscussionThis mixed-methods study demonstrates feasibility and provides a novel insight into the psychological implications of HbA1ctarget-setting.Trial registrationThe study is registered with the ISRCTN (registration number:12461724; date registered: 11thJune 2021).
Anticancer synthetic arylsulfonamides with Wnt1-modulating activity
Authors: Gutti Mihira , Luo Jennifer , Sharma Vihaan , Lee Emilia , Desarkar Arshia , Raval Rushika , Soedarmono Augustus , Zhu Joy , Njoo Edward 
Published: January 2025

AbstractDysregulation of the Wnt1/β-catenin signaling pathway has been demonstrated to be a driving factor in the propagation of several human cancers. Previous studies have discovered methyl 3-{[(4-methylphenyl)sulfonyl]amino}benzoate (MSAB) as a selective inhibitor of the Wnt1/β-catenin signaling pathway, which putatively functions through direct engagement of β-catenin. To understand how changes to the identity and position of the methyl ester affect thein vitropotency of this compound in Wnt1-driven mammalian cell lines, we prepared and evaluated three analogs of MSAB with 3- and 4-substituted methyl and ethyl esters. In MTT assays, analogs with methyl esters showed significantly more activity than their ethyl ester counterparts and both 4-substituted esters exhibited significantly attenuated antiproliferative activity, with MSAB exhibiting dose-dependent activity across cancerous cell lines. Further analysis by flow cytometry reveals low-Annexin V signal, suggesting that these compounds do not function via a pro-apoptotic pathway. Additionally, through a TCF/LEF-activated luciferase reporter cell assay, we observe that the 4-substituted methyl ester analogous to MSAB exhibits slightly diminished Wnt1-inhibitory activity, while 3- and 4-substituted ethyl esters exhibit minimal Wnt1-inhibitory activity. This difference in potency with a simple ester substitution might be attributed to several factors that ultimately drive antiproliferative activity, prompting the investigation of other potential substituents to further investigate the structure-activity relationship of these compounds as Wnt1-based antiproliferative agents.
BicD and MAP7 collaborate to activate homodimericDrosophilakinesin-1 by complementary mechanisms
Authors: Ali M Yusuf , Lu Hailong , Fagnant Patricia M. , Macfarlane Jill E. , Trybus Kathleen M. 
Published: January 2025

AbstractThe folded auto-inhibited state of kinesin-1 is stabilized by multiple weak interactions and binds weakly to microtubules. Here we investigate the extent to which homodimericDrosophilakinesin-1 lacking light chains is activated by the dynein activating adaptorDrosophilaBicD. We show that one or two kinesins can bind to the central region of BicD (CC2), a region distinct from that which binds dynein-dynactin (CC1) and cargo-adaptor proteins (CC3). Kinesin light chain significantly reduces the amount of kinesin bound to BicD and thus regulates this interaction. Binding of kinesin to BicD increases the number of motors bound to the microtubule, the fraction moving processively and the run length, suggesting that BicD relieves kinesin auto-inhibition. In contrast, microtubule-associated protein 7 (MAP7) has minimal impact on the percentage of motors moving processively but enhances both kinesin-1 recruitment to microtubules and run length. BicD relieves auto-inhibition of kinesin, while MAP7 enables activated motors to engage productively with microtubules. When BicD and MAP7 are combined, the most robust activation of kinesin-1 occurs, highlighting the crosstalk between adaptors and microtubule associated proteins in regulating transport. These observations imply that when both dynein and kinesin-1 are simultaneously bound to BicD, the direction the complex moves on MTs will be influenced by MAP7 and the number of bound kinesins.
FGFR1 inhibition improves therapy efficacy and prevents metabolic adaptation associated with temozolomide resistance in glioblastoma
Authors: Zarzuela Laura , López-Cepero Ignacio G. , Rattigan Kevin M. , Sánchez-Escabias Elena , Morillo-Huesca Macarena , Reina-Bando Ana , Oltra Sara S. , Sierra-Párraga Jesús M. , Ceballos-Chávez María , Capilla-González Vivian , Moreno-Bueno Gema , Murdoch Piedad del Socorro , Reyes José C. , Helgason G. Vignir , Tomé Mercedes , Durán Raúl V. 
Published: January 2025

ABSTRACTRecurrent therapy resistance is a major limitation in clinical efficacy and for the outcome of glioblastoma (GBM) patients, positioning GBM among the tumor types with the poorest survival outcomes. In this work, we dissected resistance mechanisms in GBM, which resulted in the identification of FGFR1 pathway as a major regulator of the signaling and metabolic rewiring associated with temozolomide (TMZ) resistance in GBM. Hence, we described a mechanism of resistance that operates at two major levels. First, a p53-mediated regulation of cell cycle inducing cell cycle arrest to allow DNA repair in response to TMZ. And second, a complete metabolic rewiring promoting lipid catabolism and preventing lipid peroxidation. Both the p53-mediated response and the metabolic adaptation are controlled by FGFR1, as inhibition of the FGFR1 pathway completely abolishes this signaling and metabolic reprograming, restoring sensitivity to TMZ. Our results also indicated a correlation of FGFR1 levels with poor prognosis in GBM patients, and validated the treatment of TMZ in combination with FGFR1 inhibitors as an efficient strategy to induce tumor cell death in pre-clinical animal models. This data position the receptor FGFR1 as a very promising candidate for evaluation in future clinical approaches to limit the development of therapy resistance to TMZ in GBM patients.
Biosynthesis and Bioactivity of Anti-Inflammatory Triterpenoids inCalendula officinalis(pot marigold)
Authors: Golubova D , Salmon M , Su H , Tansley C , Kaithakottil GG , Linsmith G , Schudoma S , Swarbreck D , O’Connell MA , Patron NJ 
Published: January 2025

AbstractPlants have been central to traditional medicine for millennia, yet the precise metabolites responsible for their therapeutic properties often remain unidentified. Moreover, the low natural abundance and structural complexity of bioactive molecules can hinder their accessibility and chemical synthesis. Here, we investigate the widely reported anti-inflammatory properties ofCalendula officinalis(pot marigold), an ancient medicinal herb. We confirm C16-hydroxylated triterpenoids as key contributors to the anti-inflammatory activity ofC. officinalisfloral extracts and uncover a novel mechanism by which they act in modulating interleukin 6 release. Through biosynthetic pathway elucidation, we demonstrate that the oxidosqualene synthase catalysing the first committed step emerged early in Asteraceae evolution and identify residues governing product specificity. Further, we functionally characterise cytochrome P450s and acyltransferases responsible for downstream modifications. By reconstructing the complete biosynthetic pathway in the heterologous plant chassisNicotiana benthamiana, we provide a platform for production of the anti-inflammatory components. Our work highlights how integrated studies of bioactivity and biosynthesis can unlock the therapeutic potential of medicinal plants.
Secreted small RNAs ofNaegleria fowleriare biomarkers for diagnosis of primary amoebic meningoencephalitis
Authors: Russell A. Cassiopeia , Dainis Joseph , Alexander Jose , Ali Ibne Karim M. , Kyle Dennis E. 
Published: January 2025

AbstractRapid and accurate diagnostics are needed to effectively detect and treat primary amoebic meningoencephalitis (PAM) caused byNaegleria fowleri(Nf). Delayed diagnosis and similarities to other causes of meningitis contribute to a case mortality rate of >97%. Thus, there is an unmet medical need for a non-invasive liquid biopsy diagnostic method. We sequencedNfextracellular vesicles (EVs) and identified microRNAs, tRNAs and other small RNAs inNf-EVs. From these data we selected two prevalent small RNAs as biomarker candidates. We developed an RT-qPCR assay and both small RNAs were detected inNf-EVs and amoeba-conditioned media. In the mouse model of PAM both small RNA biomarkers were detected in 100% of mouse plasma samples at the end-stage of infection. Notably, smallRNA-1 was detected in the urine of infected mice at timepoints as early as 24h post infection (18/23 mice) and in the plasma as early as 60h post infection (8/8 mice). Additionally, smallRNA-1 was detected in 100% (n=6) of CSF samples from human PAM cases, and in whole blood samples, but not in human plasma from PAM cases. In this study, we discovered small RNAs as biomarkers ofNfinfection, one which can be detected reliably in CSF, urine, and whole blood. The RT-qPCR assay is a highly sensitive diagnostic assay that can be conducted in ∼3h after receipt of liquid biopsy. The data suggest detection of smallRNA-1 biomarker could provide earlier diagnosis of PAM and be used to monitor biomass of amoebae during treatment.One Sentence SummarySmall RNAs ofNaegleria fowlerican be detected in liquid biopsies and serve as early diagnostic biomarkers of primary amoebic meningoencephalitis.