bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of a Western Diet High in Phosphate on the CKD-MBD in an Alport Syndrome Model
Authors: Williams Matthew J. , Patel Hiral M. , Halling Carley B. , Hruska Keith A. 
Published: January 2025

AbstractBackgroundChronic kidney disease – mineral bone disorder (CKD-MBD) is a syndrome that begins early in CKD, contributes to CKD-associated mortality, and includes components of FGF23 elevation, αklotho deficiency, CKD-stimulated vascular disease, and renal osteodystrophy. Hyperphosphatemia, occurring in later stages of CKD, is also driven by mechanisms of CKD-MBD, and has been shown to stimulate vascular calcification. In a mouse model of Alport CKD that is resistant to vascular calcification, we examine the effects of a high-phosphate Western-type diet on the CKD-MBD, and test whether the diet promotes induction of vascular calcification.MethodsAn X-linked Col4a5 deficient murine homolog of Alport Syndrome (CKD) and wild type (WT) littermates were fed an animal protein 1.2% high phosphate diet or a standard vegetable protein diet. At disease progression equivalent to CKD stage 4-5, we examined kidney histology for fibrosis, blood for BUN (marker of CKD), and markers of CKD-MBD disease progression, kidney tissue for klotho production, and aorta histology and tissue mRNA and protein analysis for vascular calcification.ResultsThe Western high Pi diet produced hyperphosphatemia in the CKD animals compared to WT and increased plasma PTH (1880 from 110 pg / ml), FGF23 c-term (670 from 120 pg / ml), and FGF23 intact (3780 from 280 pg / ml), and reduced kidney klotho mRNA and protein (57-67% reduction) (all p < 0.01). Referenced against the CKD animals fed vegetable-based diet, the Western high phosphate-fed CKD animals showed higher levels of plasma PTH and FGF23s. In the wild-type control mice with normal renal function, Western diet produced increased PTH, intact FGF23, and reduced renal klotho (all p <0.01). Vascular smooth muscle transdifferentiation and vascular calcification was not induced by Western high phosphate diet in this model of CKD.ConclusionsOur results show that a Western-style high-phosphate diet advances elements of the CKD-MBD. Renal klotho, FGF23 and PTH are affected by diet even with normal kidney function, suggesting a need for early intervention in the management of phosphate homeostasis as a component of CKD therapy. Additionally, CKD, klotho, and FGF23 all are associated with early aging. Therefore, our findings suggest that a Western high Pi diet accelerates aging and would contribute to the systemic complications of CKD – cardiac disease, osteodystrophy, and vascular disease.
CYP722A1-driven 16-hydroxylation of carlactonoic acid regulates the floral transition in Arabidopsis
Authors: Kuno Masaki , Miyamoto Ayumi , Takano Hinako , Homma Masato , Shiotani Nanami , Uchida Kiyono , Takikawa Hirosato , Nakajima Masatoshi , Mizutani Masaharu , Wakabayashi Takatoshi , Sugimoto Yukihiro 
Published: January 2025

AbstractStrigolactones (SLs) are multifunctional plant hormones and rhizosphere signals with diverse structures, broadly categorized as canonical or noncanonical SLs. InArabidopsis thaliana, SL biosynthesis mutants exhibit increased shoot branching and early flowering, underscoring their roles in developmental regulation. Shoot branching inhibition in Arabidopsis depends on the methylation of carlactonoic acid (CLA), a key intermediate classified as a noncanonical SL, catalyzed by CLA methyltransferase (CLAMT). Canonical SLs primarily function as rhizosphere signals, with their biosynthesis in dicots mediated by CYP722C enzymes. It is hypothesized that Arabidopsis does not produce canonical SL because of the lack of theCYP722Cgenes in its genome. Instead, Arabidopsis possesses CYP722A1, a member of the previously uncharacterized CYP722A subfamily, distinct from the CYP722C subfamily.This study demonstrates that Arabidopsiscyp722a1mutants exhibit an earlier floral transition without excessive shoot branching. Biochemical analysis revealed that CYP722A1 catalyzes the hydroxylation of CLA to produce 16-hydroxy-CLA (16-HO-CLA), which is subsequently methylated by CLAMT to form 16-HO-MeCLA. 16-HO-CLA and 16-HO-MeCLA were detected in the wild-type; however, these compounds were absent inmax1-4mutant, which is deficient in CLA synthesis, and incyp722a1mutant. These findings indicate the presence of CYP722A1-dependent 16-hydroxylation activity of CLA in Arabidopsis. Moreover, they suggest that hydroxylated CLA specifically regulates floral transition, distinct from branching inhibition. By identifying CYP722A1 as a regulator of floral transition, which is the distinct role of the CYP722A subfamily, this work provides insights into the adaptation of SL structures for specialized biological functions in plant development.
Macrophages restrict tumor permissiveness to immune infiltration by controlling local collagen topography through a Tcf4-Collagen3 fibrotic axis
Authors: Fusilier Zoé , Simon Franck , Calvente Isabel , Crestey Lou , Clément Alexandra , Mathieu Mathilde , Jean-Marie Roude , Piastra-Facon Florence , George Clément Jeyani , Lumineau Enola , Tonani Mattia , Manriquez Valeria , Lacerda Livia , de Villemagne Perrine , Piaggio Eliane , Semetey Vincent , Coscoy Sylvie , Martini Emanuele , Scita Giorgio , Gelly Jean-Christophe , Ivaska Johanna , Isambert Hervé , Goudot Christel , Pierobon Paolo , Lennon-Duménil Ana-Maria , Moreau Hélène D. 
Published: January 2025

AbstractDuring tumorigenesis, the extracellular matrix (ECM), which constitutes the structural scaffold of tissues, is profoundly remodeled. While the impact of such remodeling on tumor growth and invasion has been extensively investigated, much less is known on the consequences of ECM remodeling on tumor infiltration by immune cells. By combining tissue imaging and machine-learning, we here show that the localization of T lymphocytes and neutrophils, which orchestrate antitumor immune responses, can be predicted by defined topographical features of fibrillar collagen networks. We further show that these collagen topographies result from the activation of a fibrotic pathway controlled by the transcription factor Tcf4 upon depletion of tumor-associated macrophages at late tumor stages. This pathway promotes the deposition of collagen 3 by both tumor and stromal cells, resulting in intermingled collagen networks that favor intra-tumoral T cell and neutrophil localization. Importantly, analysis of human colorectal cancer public bulk RNAseq databases showed a strong correlation betweenTcf4andcollagen 3, as well as between the expression of these genes and tumor infiltration by T lymphocytes and neutrophils, attesting the clinical relevance of our findings. This study highlights the key structural role of macrophages on the tumor extracellular matrix and identifies collagen network topographies as a major regulator of tumor infiltration by immune cells.
Future heatwave conditions inhibit CO2-induced stomatal closure in wheat
Authors: Caine Robert S. , Khan Muhammad S. , Shan Yixiang , Osborne Colin P. , Croft Holly L. 
Published: January 2025

AbstractRising atmospheric CO2concentrations are driving ongoing climatic changes, leading to agricultural crops increasingly experiencing extreme weather events1. Stomata serve as gatekeepers on plant leaves, regulating both CO2capture for photosynthesis and the concomitant release of water. At higher CO2concentrations or higher vapour pressure deficit (VPD), stomatal pores narrow, reducing stomatal conductance to water vapour (gsw) and transpiration (E)2–6. Increasing temperatures and/or nitrogen fertilisation promote an opposite stomatal response, enhancinggswandE7,8. With atmospheric CO2concentration, temperature and VPD predicted to rise throughout this century1, it is unclear how crops will modify stomatal gaseous exchanges, particularly under differing N-fertilisation regimes. Here, we show in wheat (Triticum aestivum), that elevated CO2does not reducegsworEduring heatwaves when VPD is high, instead plant water usage increases. High-VPD heatwave events also impact stomatal responsiveness to N-fertiliser application, prompting significantly higher gas exchange contributions from abaxial leaf surfaces, irrespective of CO2growth conditions. Dynamic stomatal responsiveness to light and high CO2are also attenuated during heatwaves in a CO2-independent manner. Taken together, our data suggests that future wheat crops will use significantly more water during heatwaves than might be expected, which has substantial implications for future global food security.
Preserved suppressive function despite loss of Foxp3: insights into the identity of regulatory T cells
Authors: Luckerbauer B , Villarino AV , Laurence A , Hirahara K , Sciume G , Mikami Y , Shih HY , Sun HW , Tosevska A , Brinkmann M , Brooks SR , Scheffel J , Meylan F , Afzali B , Bonelli M 
Published: January 2025

AbstractRegulatory T (Treg) cells are essential for maintaining immune homeostasis, with Foxp3 acting as the master transcription factor governing their differentiation and function. The acquisition of effector signatures in Treg cells is closely tied to the surrounding tissue-specific immune environment and typically occurs alongside Foxp3 expression. In this study, we investigated the transcriptomic and functional consequences of Treg-mediated regulation in a Th2-driven disease setting. The application of bothin vitrosystems andin vivodisease models allowed us to mimic Th2-mediated environments.We could demonstrate Th2-driven loss of Foxp3 expression in Treg cellsin vitroandin vivo. Transcriptomic analysis revealed a maintained Treg signature despite the loss of active Foxp3 expression. Functional characterization of Tregs bothin vitroandin vivouncovered a preserved suppressive capacity even in the absence of Foxp3.Our findings unveil that, despite loss of Foxp3, a preserved Treg signature remains intact enabling the regulation of Th2-mediated diseases. The persistence of this regulatory transcriptome highlights the importance for developing Treg-cell therapy strategies in cancer and autoimmune diseases independent of Foxp3 expression.
Voluntary Running Sustains the Correction of Inflammation-Related Gene Expression Conferred by AAV Gene Therapy in Mdx Mice
Authors: Yuan Claire , Hamm Shelby E. , Mack David L. , Dupont Jean-Baptiste , Grange Robert W. 
Published: January 2025

ABSTRACTDuchenne Muscular Dystrophy is a fatal disease characterized by persistent skeletal muscle degeneration, inflammation, and fibrosis. Gene therapy using an adeno-associated virus derived vector and a microdystrophin transgene is currently under investigation in patients but the impact of physical activity on long-term therapeutic outcome remains poorly understood. Recently, we reported 21-weeks of voluntary wheel running complemented the positive endurance and muscle function outcomes of gene therapy in mdx mice. In the present study, we performed a transcriptomic analysis of the gene expression changes associated with functional recovery in the diaphragm. RNA-Sequencing and bioinformatic analysis revealed 2881 dysregulated genes in untreated and unexercised mdx mice including inflammatory and fibrotic signaling pathways frequently affected in Duchenne Muscular Dystrophy patients. Among the dysregulated genes, 774 were rescued towards WT after adeno-associated virus microdystrophin injection. Importantly, 93% of the rescued genes were maintained by voluntary running, which indicates that physical exercise has no significant impact on the outcome of gene therapy in the mdx diaphragm. Our study provides vital information that could help guide DMD patient follow-up protocols after treatment with gene therapy.
Super-omics and PCAS reveal rheumatoid arthritis as a tumor-like disease
Authors: Xiao Lanlan , Aishan Nadire , Ju Siwei , Zhao Fengchao , Ouyang Xiaoxi , Chen Dazhi , Chen Weiqian , Xie Jie , Zhu Danhua , Zhang Junchi , Sun Lingyun , Li Yimin , Zhou Dan , Hu Qingqing , Wu Jinzhi , Meng Qingna , Zhou Jichun , Xu Danyi , Yu Jingyi , Liang Junyu , Cai Yangjun , Zhang Minmin , He Yanlin , Sun Zeyu , Wang Linbo , Lin Jin , Ji Feiyang 
Published: January 2025

SUMMARYRheumatoid arthritis (RA) is a debilitating systemic autoimmune disorder that significantly impairs quality of life. To elucidate the molecular alterations in RA progression, we performed comprehensive super-omics analyses on synovial tissues from patients with joint trauma, arthritis, and RA. These analyses included transcriptomics, proteomics, metabolomics, microbiomics, and fourteen PTMs (phosphorylation, acetylation, lactylation, O-GlcNAc glycosylation, arginine monomethylation, lysine monomethylation, lysine dimethylation, lysine trimethylation, succinylation, malonylation, glutarylation, tyrosine nitration, N-glycosylation, and O-glycosylation). Additionally, we developed a protein-centered association study (PCAS) method to integrate these complex datasets. Using this approach, we identified key proteins, such as STK17B, and its interactors, which may be crucial in RA pathogenesis. Tumor-like features, including aberrant angiogenesis and epithelial-mesenchymal transition, were observed in RA, alongside the potential involvement of oncogenes and tumor suppressor genes. Finally, we constructed a molecular interaction blueprint of RA, providing a comprehensive framework for advancing RA pathogenesis, diagnosis, and therapy.
Functional effects of deforestation on stream ecosystems in Madagascar based on growth and production of mayflies (Ephemeroptera)
Authors: Oliarinony Ranalison , Sartori Michel 
Published: January 2025

AbstractThe effects of deforestation on species richness and abundance of tropical freshwater organisms are increasingly well documented, but corresponding effects on functional properties of ecosystems, such as productivity and growth, are largely unknown. Here we investigated the biomass production and growth of eight species of mayflies (Ephemeroptera) in streams of eastern Madagascar. We compared three study sites in primary tropical forest with three in degraded open canopy area (savoka). All species were asynchronous and aseasonal. Seven species were multivoltine (3-4 generations per year) and one was semi-voltine. Biomass production of the most abundant species was 4-5 times greater insavokathan in forest, and standing biomass: productivity (P/B) was always higher insavoka. This production shift was mainly caused by the twoXyrodromeusspecies, both of which feed on periphytic algae that are more abundant in an open canopy. Surprisingly,Xyrodromeusfemales emerged more rapidly and were larger in size insavokathan in forest. Our results clearly indicate that deforestation in tropical Madagascar leads not only to a shift in mayfly community composition, but perhaps more importantly to functional changes in the ecosystem, namely standing biomass, annual production, and female size at maturity.
Interrupting T cell memory ameliorates exaggerated metabolic response to weight cycling
Authors: Garcia Jamie N. , Cottam Matthew A. , Rodriguez Alec S. , Hussein Agha Anwar F. , Winn Nathan C. , Hasty Alyssa H. 
Published: January 2025

SummaryPeople frequently experience cycles of weight gain and loss. This weight cycling has been demonstrated, in humans and animal models, to increase cardiometabolic disease and disrupt glucose homeostasis. Obesity itself — and to an even greater extent weight regain — causes adipose tissue inflammation, resulting in metabolic dysfunction. Studies show that even after weight loss, increased numbers of lipid associated macrophages and memory T cells persist in adipose tissue and become more inflammatory upon weight regain. These findings suggest that the immune system retains a "memory" of obesity, which may contribute to the elevated inflammation and metabolic dysfunction associated with weight cycling. Here, we show that blocking the CD70-CD27 axis, critical for formation of immunological memory, decreases the number of memory T cells and reduces T cell clonality within adipose tissue after weight loss and weight cycling. Furthermore, while mice with impaired ability to create obesogenic immune memory have similar metabolic responses as wildtype mice to stable obesity, they are protected from the worsened glucose tolerance associated with weight cycling. Our data are the first to target metabolic consequences of weight cycling through an immunomodulatory mechanism. Thus, we propose a new avenue of therapeutic intervention by which targeting memory T cells can be leveraged to minimize the adverse consequences of weight cycling. These findings are particularly timely given the increasing use of efficacious weight loss drugs, which will likely lead to more instances of human weight cycling.
No effect of education on Telomere Length: a natural experiment in aging individuals
Authors: Judd Nicholas , Kievit Rogier 
Published: January 2025

AbstractTelomere length is increasingly used as a proxy for an ‘aging exposome’ – an index of non-genetic environmental (and behavioral) exposures that an individual encounters, leading to differences in rates of aging. One of the largest associations with telomere length is schooling, leading to the suggestion of long-lasting protective effects of (additional) education. However, for ethical and practical reasons, education cannot generally be randomized, precluding an understanding of the causal effect of education on health outcomes. Here, we leverage a well-established policy change in the UK to test whether an additional year of education caused differences in telomere length decades later. Employing a fuzzy regression discontinuity design, we find no effect of education on telomere length in the UK BioBank across multiple analytic frameworks (continuity, local randomization & Bayesian approaches) and a series of robustness tests, such as increasing the analysis window around the cutoff, and changing the prior, similarly find no effect of an additional year of education on telomere length. This robust finding contrasts the prevailing ‘aging exposome account’ of telomere length and offers a cautionary note in attributing causal power to environmental factors based on observational differences.
Epigenetic mechanisms regulating CD8+ T cell senescence in aging humans
Authors: Turano Paolo S. , Akbulut Elizabeth , Dewald Hannah K. , Vasilopoulos Themistoklis , Fitzgerald-Bocarsly Patricia , Herbig Utz , Martínez-Zamudio Ricardo Iván 
Published: January 2025

ABSTRACTAging leads to the decline of immunity, rendering the elderly susceptible to infection and disease. In the CD8+ T cell compartment, aging leads to a substantial increase of cells with high levels of senescence-associated ß-galactosidase activity (SA-ßGal) and other senescence characteristics, including a pro-inflammatory transcriptome and impaired proliferative potential. Using senescent cell isolation coupled with multiomic profiling, here we characterized the epigenetic mechanisms regulating CD8+ T cell senescence in a cohort of younger and older donors. High levels of SA-ßGal activity defined changes to global transcriptomes and chromatin accessibility landscapes, with a minor effect of age. Widespread enhancer remodeling was required for the repression of functional CD8+ T cell genes and upregulation of inflammatory and secretory pathway genes. Mechanistically, the senescence program in CD8+ T cells was controlled by chromatin state-specific transcription factor (TF) networks whose composition was largely insensitive to donor age. Pharmacological inhibition of TF network nodes AP1, KLF5, and RUNX2 modulated the transcriptional output, demonstrating the feasibility of TF network perturbation as an approach to modulate CD8+ T cell senescence. Further, CD8+ T cell senescence gene signatures faithfully predicted refractoriness to chimeric antigen receptor (CAR) T-cell therapy in a cohort of diffuse large B cell lymphomas and were highly enriched in the transcriptomes of peripheral CD8+ T cells of individuals with active systemic lupus erythematosus. Collectively, our findings demonstrate the potential of multiomic profiling in identifying key regulators of senescence across cell types and suggest a critical role of senescent CD8+ T cells in disease progression.
Mammal niches are not conserved over continental scales
Authors: Goldstein Benjamin R. , Pacifici Krishna , Jensen Alex J. , Reich Brian J. , Cove Michael V. , McShea William J. , Rooney Brigit , Kierepka Elizabeth M. , Roberts Rachel A. , Kays Roland 
Published: January 2025

Summary paragraphThe niche conservatism hypothesis states that a species’ relationships to habitat and climate conditions are maintained across space and time1–6. Niche stationarity is assumed when ecologists estimate species’ habitat needs or transfer findings across geographic regions7,8. Recent studies show that some species’ associations with climate and habitat vary spatially, contradicting the niche conservatism hypothesis9–18. The sources of this nonstationarity are unknown and potential mechanisms remain untested. Here we show that the environmental niches of 36 common North American mammals vary spatially across dimensions of human influence, climate, and landscape. Spatial variation is not explained by known genetic subspecies lineages. Instead, niches vary at a relatively fine spatial scale consistent with adaptations by animals to local conditions, which may be explained by genetic or behavioral changes or by unmodeled interactions with unobserved variables. Spatially varying ecology means that static niche models are not appropriate at large scales and extrapolating species’ niches to novel contexts may be impossible19. This complicates management decisions based on transferring findings across space and projecting species’ current environmental associations to responses to future change, but may provide optimism if nonstationarity represents potential for rapid evolutionary rescue.
First occurrence of Ranavirus in Scandinavian peninsula
Authors: Thumsová B , Chondrelli N , Valdés AE , Eghbal R , Höglund J , Laurila A , Bosch J , Cortázar-Chinarro M 
Published: January 2025

AbstractEmerging infectious diseases (EIDs) pose a major threat to global amphibian populations, contributing to widespread mortality and species extinctions. Among EIDs, those caused by fungal infection pathogensBatrachochytrium dendrobatidis(Bd) andB. salamandrivorans(Bsal), and viral infections of the genus Ranavirus (Rv), represent the most significant threats to amphibian biodiversity. Here, we test for occurrence ofRvinfection in three different locations in southeastern Sweden. Using a quantitative PCR (qPCR) assay, complemented by a secondary PCR-based validation method targeting the viral major capsid protein gene (MCP) and additional five partial sequences, we detectedRvinfection in two of three locations and in five out of 43 individuals tested. This is the first confirmed record ofRvoccurrence reported at such high latitudes in north Europe and the first one from Scandinavian peninsula, contributing important insights into infection prevalence in northern amphibian populations. These findings establish a basis for further research for the conservation of these vulnerable populations.