bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wolbachiaand its pWCP plasmid show differential dynamics during the development ofCulexmosquitoes
Authors: Brunner Alice , Gauliard Camille , Tutagata Jordan , Bordenstein Seth , Bordenstein Sarah , Trouche Blandine , Reveillaud Julie 
Published: January 2025

AbstractMosquitoes are major vectors of pathogens such as arboviruses and parasites, causing significant health impacts each year.Wolbachia, an intracellular bacterium widely distributed among arthropods, represents a promising vector control solution. This bacterium can reduce the transmission of dengue, Zika and chikungunya arboviruses and manipulate the reproduction of its host through its prophage WO. Although research on theWolbachiamobilome primarily focuses on WO and the phenotypes it induces, the function ofWolbachiaplasmid pWCP, recently discovered and reported to be strikingly conserved worldwide, remains unknown. In this study, we analyzed the presence and abundance of pWCP as well asWolbachiain two different species ofCulexmosquitoes, one of the most widespread genera in the world and a vector of numerous diseases. We compared relative densities of the bacterium and its mobile genetic element inCulex pipiens molestusandCulex quinquefasciatus, a facultatively autogenous and a anautogenous species, respectively, throughout their development from larval stage L1 to adult individual specimen using quantitative PCR. Our results suggest that 2-5 copies of pWCP occur inWolbachiacells on average, and the plasmid co-replicates withWolbachiacells. Moreover,Wolbachiaand pWCP exhibit differential levels of abundance at specific development stages throughout the mosquito’s life cycle in each species. These findings indicate important, and likely beneficial, roles for the plasmid in the bacterium’s biology in different mosquito species as well as complex interaction dynamics betweenWolbachiaand its host during its life cycle.ImportanceMosquitoes of theCulexgenus are critical vectors for numerous diseases, causing significant public health concerns. The intracellular bacteriumWolbachiahas emerged as a promising vector control solution due to its ability to interfere with pathogen transmission and manipulate mosquito reproduction. However, unlike the extensively studied WO phage, the biological significance and function ofWolbachia’spWCP plasmid, a recently discovered and strikingly conserved mobile genetic element inCulexspecies, remains unknown. This study investigates the developmental dynamics of pWCP andWolbachiain twoCulexmosquito species,Culex pipiens molestusandCulex quinquefasciatusacross their life cycle. In general, the abundance levels ofWolbachiaand the plasmid were found to vary across life stages and differ between the two species. However, a relatively small number of pWCP copies were observed perWolbachiacell, together with a co-replication of the plasmid with the bacterium for most developmental stages. Altogether, these findings suggest a likely beneficial and non-parasitic role for pWCP inWolbachia’s biology, that may contribute to the intricate interactions between the bacterium and its mosquito hosts.
Seagrass arabinogalactan-proteins: Are they important for adaptation to the marine environment?
Authors: Pfeifer Lukas , Johnson Kim L. , Bacic Antony , Reusch Thorsten B. H. , Duarte Carlos M. , Sinclair Elizabeth A. , Classen Birgit 
Published: January 2025

AbstractDuring the late cretaceous period several lineages of angiosperm plants transitioned from land to the sea by successfully adapting to life in salt water, forming the polyphyletic group of seagrasses. Today, four seagrass families inhabit coastal systems and are deeply intertwined with health and welfare of these ecosystems. Adaptation to the ocean environment included changes in the composition of plant cell walls and associated glycoproteins. We have asked the question whether or not there is a convergent and similar arabinogalactan-protein glycan repertoire in all seagrasses, given initial findings of arabinogalactan-proteins with unique features in the well-studied eelgrass,Zostera marina. We isolated and characterized arabinogalactan-proteins from seven species covering the four major seagrass families using carbohydrate analysis and glycan immunoassays, along with a bioinformatic search for relevant gene pathways in newly published seagrass genomes and transcriptomes. Glycan parts of all seagrass arabinogalactan-proteins shared a high proportion of 1,4-linked glucuronic acids and terminal 4-O-methyl glucuronic acid residues. Trait-based dendrograms generated to inform phylogenetic-relatedness showed there was no phylogenetic signal among seagrass families and arabinogalactan-protein features. Transcriptomic datasets fromCymodocea nodosaandThalassia hemprichiigrowing under hypersaline conditions showed an upregulation of enzymes involved in 4O-methylation and glucuronic acid transfer. We therefore conclude that environmental factors, especially salinity with higher monovalent ion concentration, influence seagrass arabinogalactan-proteins structure more intensely than phylogenetic history.
Zero-phase-delay connectivity increases the reliability, concordance with structure, and prognostic ability of functional connectivity metrics
Authors: Mehra Chirag , Beyh Ahmad , Laiou Petroula , Garces Pilar , Murphy Declan , Loth Eva , Dell’Acqua Flavio , Ewen Joshua B , Richardson Mark P , O’Muircheartaigh Jonathan 
Published: January 2025

AbstractZero-phase-delay synchrony between the activity of distant neural populations has been robustly observed. Nevertheless, contemporary electroencephalography and magnetencephalography functional connectivity analyses typically exclude zero-phase-delay functional connections, assuming that they are predominantly artefactual. However, the effects of excluding them on the performance of functional connectivity metrics as potential biomarkers are unknown. Here, we showed that most cortico-cortical functional connections occur with zero- or near-zero phase-delay, even where such connectivity was unlikely to be artefactual. Including, rather than excluding, zero-phase-delay connectivity increased the reliability, concordance with structural connectivity, and predictive validity (for longitudinal changes in cognition) of functional connectivity metrics. We found that excluding zero-phase-delay connections penalised functional connectivity strength between the strongest structurally connected regions: stronger structural connections led to functional connections with phase-delays closer to zero, mediated by a shorter signal propagation time. Our findings challenge generally accepted assumptions that zero-phase-exclusive methods are superior to zero-phase-inclusive methods.
Non-Contrast µCT Analysis of Obese Adipose in Response to Cold-Exposure Reveals Sex-Specific Alterations
Authors: Eades Austin E. , Payne Macy M. , Clark Zachary , Evans Logan , Walsh R. McKinnon , Bye Bailey B. , Rekowski Michaella J. , Morris E. Matthew , Bossmann Stefan H. , VanSaun Michael N. 
Published: January 2025

AbstractIn 2020, it was reported that obesity in the United States had increased by 12% from 1999 to 2018. While exercise and diet are optimal lifestyle modifications to curb obesity, drug-based therapeutics focus on glucagon-like peptide (GLP) modifiers. Alternatively, current research suggests that a specialized type of adipose, called thermogenic adipose, may help protect against obesity. Active thermogenic adipose can metabolize free fatty acids (FFAs) and carbohydrates to carry out non-shivering thermogenesis (NST), potentially providing a method for reducing excess energy stores. While brown adipose tissue (BAT) provides the primary thermogenic response, we hypothesized that exposing diet-induced obese (DIO) mice to colder temperatures would also diminish white adipose tissue (WAT) depots and suppress their inflammatory signature. To measure adipose response to coldin vivo, we applied a non-contrast microCT (µCT) imaging analysis. Male and female mice were housed at thermoneutrality (TN) and fed a Western-style diet (WD)ad libuntil they became obese. Once they reached this stage, the mice were subjected to a thermalshift (TS) and exposed to either room temperature (RT) of 22°C or a colder temperature of 18°C. The adipose response was then assessed in post-exposure tissues by histological analysis, proteomics, and molecular characterization to correlate phenotypic changes with our µCT findings. Results from this analysis revealed a sex-specific response to cold exposure: thermogenic adipose was predominantly formed in the interscapular BAT (iBAT) of male mice, while female mice showed formation in their perigonadal WAT (pgWAT) and iBAT when exposed to 18°C. Furthermore, male mice exhibited a decline in serum glucose levels when subjected to 18°C, which was increased in TS female mice. Serum-free fatty acids (FFAs) were unaffected by either sex across different environmental conditions. Importantly, using a mass-spectrometry-based approach, we detected a reduction in pro-inflammatory cytokines in the conditioned media (CM) of pgWAT and iBAT from TS male mice compared to TN DIO male mice. Overall, our studies demonstrated a new µCT-based analytical method to detect changes in obese adipose tissue and highlighted unique sex-specific responses to environmental exposure. Our findings suggest that thermogenic adipose may offer a promising avenue for combating obesity and reducing its pathologic characteristics.
Morphogen Patterning in Dynamic Tissues
Authors: Plum Alex M. , Serra Mattia 
Published: January 2025

AbstractEmbryogenesis integrates morphogenesis—coordinated cell movements—with morphogen patterning and cell differentiation. While largely studied independently, morphogenesis and patterning often unfold simultaneously in early embryos. Yet, how cell movements affect patterning remains unclear, as most pattern formation models assume static tissues. We address this gap by developing a mathematical framework for morphogen patterning in dynamic tissues, reformulating advection-reaction-diffusion models in cells’ reference frames—the most natural for signal interpretation and fate decisions. This framework (i) elucidates how morphogenesis mediates morphogen transport and compartmentalization: multicellular attractors enhance cell-cell diffusive transport, while repellers act as barriers, affecting cell fate induction and bifurcations. (ii) It formalizes cell-cell signaling ranges in dynamic tissues, deconfounding morphogenetic movements and identifying which cells can communicate. (iii) It provides two nondimensional numbers—typically distinct from the Péclet number—to assess when and where morphogenesis is relevant for patterning. (iv) It elucidates the generative role of cell density dynamics in patterning. We apply this framework to classic patterning models, morphogenetic motifs, and avian gastrulation data. Broadly, our work provides a quantitative perspective to rationalize dynamic tissue patterning in natural and synthetic embryos.
Identification of cutoff value for Homeostatic Model Assessment for insulin resistance (HOMA-IR index) in children at a tertiary care hospital of Bangladesh
Authors: Jahan Ismat , Biswas Dhiraj Chandra , Sharmin Farzana , Parvin Roksana , Rezaul karim Muhammad , begum Suraiya 
Published: January 2025

ABSTRACTObjectiveThe Objective of this study was to find out the optimal cut-off value of HOMA-IR for identification of insulin resistance in Bangladeshi children.Material and MethodsA cross sectional study was conducted at the department of Paediatrics of Bangabandhu Sheikh Mujib Medical University. 613 children aged 6-18years old were investigated for fasting insulin, glucose and lipid profile. HOMA-IR value was calculated from fasting insulin and fasting glucose level. The optimal cut-off value of IR was determined by percentile criteria and metabolic syndrome criteria.ResultsHOMA–IR cutoff value irrespective of age and sex at 85thpercentile ranges between 2.3 to 2.6 and cut off by metabolic syndrome criteria ranges between 2.0 to 2.4 with high sensitivity (93.2%) and specificity (60.1%) while HOMA-IR cut off at 95thpercentile is higher (3.0 to 4.7) than the 85thcentile but at 95thcentile sensitivity (78.6%) and specificity (72.9%) was low. Therefore suggested cut off value of HOMA-IR is 2.4 which is common in both metabolic syndrome criteria and percentile criteria.ConclusionThis study suggests 2.4 as the optimal cut-off point of insulin resistance as because it is supported by both the percentile criteria and metabolic syndrome criteria.
Serum Slit3 is associated with disease activity and interstitial lung disease in rheumatoid arthritis
Authors: Zhang Xuepei , Shi Maohua , Guo Dongmei , Yu Yangtao , Zhang Hongwei , Chen Guoqiang 
Published: January 2025

AbstractRheumatoid arthritis (RA) is a chronic systemic inflammatory disease accompanied by high incidence rate of interstitial lung disease (ILD). Slit guidance ligand 3 (Slit3) which is a member of axon guidance molecule superfamily, mediates a series of biological activities. In this study, we explored the potential clinical significance of Slit3, especially as a serum biomarker for evaluating RA-ILD. Patients diagnosed with RA were recruited between July 2022 to April 2024 from the Department of Rheumatology of Foshan First People’s Hospital. The clinical data were collected from hospital records, serum level of Slit3 was detected by enzyme-linked immunosorbent assay (ELISA). Among 232 recruited patients, RA patients in high Slit3 subgroup were older, showed higher proportion of positive rheumatoid factor (RF) status and anti-cyclic citrullinated peptide antibody (APCA) status, as well as higher levels of ESR, CRP, Disease Activity Score in 28 joints with four variables, including C-reactive protein (DAS28-CRP) or erythrocyte sedimentation rate (DAS28-ESR), Simplified Disease Activity Index (SDAI) and pro-inflammatory cytokine interleukin-6 (IL-6). Notably, Logistic regression analysis showed that elevated serum Slit3 was an independent relevant factor of RA-ILD (OR 1.005 [95% CI 1.002-1.008], P=0.002). Our findings evealed that serum Slit3 was associated with disease activity in RA and may hold promise as a useful serum biomarker and therapeutic target for RA-ILD.
Systemic Metabolic Alterations after Aneurysmal Subarachnoid Hemorrhage: A Plasma Metabolomics Approach
Authors: Yang Bosco Seong Kyu , Savarraj Jude P.J. , Chen Hua , Hinds Sarah N. , Torres Glenda L. , Ryan Alice S. , Atem Folefac D. , Lorenzi Philip L. , Ren Xuefang S. , Badjatia Neeraj , Choi Huimahn A. , Gusdon Aaron M. 
Published: January 2025

AbstractBackgroundAneurysmal subarachnoid hemorrhage (aSAH) causes systemic changes that contribute to delayed cerebral ischemia (DCI) and morbidity. Circulating metabolites reflecting underlying pathophysiological mechanisms warrant investigation as biomarker candidates.MethodsBlood samples, prospectively collected within 24 hours (T1) of admission and 7-days (T2) post ictus, from patients with acute aSAH from two tertiary care centers were retrospectively analyzed. Samples from healthy subjects and patients with non-neurologic critical illness served as controls. A validated external analysis platform was used to perform untargeted metabolomics. Bioinformatics analyses were conducted to identify metabolomic profiles defining each group and delineate metabolic pathways altered in each group. Machine learning (ML) models were developed incorporating key metabolites to improve DCI prediction.ResultsAmong 70 aSAH, 30 healthy control, and 17 sick control subjects, a total of 1,117 metabolites were detected. Groups were matched among key clinical variables. DCI occurred in 36% of aSAH subjects, and poor functional outcome was observed in 70% at discharge. Metabolomic profiles readily discriminated the groups. aSAH subjects demonstrated a robust mobilization of lipid metabolites, with increased levels of free fatty acids (FFAs), mono- and diacylglycerols (MAG, DAG) compared with both control groups. aSAH subjects also had decreased circulating amino acid derived metabolites, consistent with increased catabolism. DCI was associated with increased sphingolipids (sphingosine and sphinganine) and decreased acylcarnitines and S- adenosylhomocysteine at T1. Decreased lysophospholipids and acylcarnitines were associated with poor outcomes. Incorporating metabolites into ML models improved prediction of DCI compared with clinical variables alone.ConclusionsProfound metabolic shifts occur after aSAH with characteristic increases in lipid and decreases in amino acid metabolites. Key lipid metabolites associated with outcomes (sphingolipids, lysophospholipids, and acylcarnitines) provide insight into systemic changes driving secondary complications. These metabolites may also prove to be useful biomarkers to improve prognostication and personalize aSAH care.
Optimizing the Efficacy of Vaccine-Induced Immunotherapy in Melanomas
Authors: Chamseddine Ibrahim , Kambara Manoj , Bhatt Priya , Pilon-Thomas Shari , Rejniak Katarzyna A. 
Published: January 2025

AbstractCancer therapeutic vaccines are used to strengthen a patient’s own immune system by amplifying existing immune responses. Intralesional administration of the bacteria-based emm55 vaccine together with the PD1 checkpoint inhibitor produced a strong anti-tumor effect against the B16 melanoma murine model. However, it is not trivial to design an optimal order and frequency of injections for combination therapies. Here, we developed a coupled ordinary differential equations model calibrated to experimental data and used the mesh adaptive direct search method to optimize the treatment protocols of the emm55 vaccine and anti-PD1 combined therapy. This method determined that early consecutive vaccine injections combined with distributed anti-PD1 injections of decreasing separation time yielded the best tumor size reduction. The optimized protocols led to a twofold decrease in tumor area for the vaccine-alone treatment, and a fourfold decrease for the combined therapy. Our results reveal the tumor subpopulation dynamics in the optimal treatment condition, defining the path for efficacious treatment design. Similar computational frameworks can be applied to other tumors and other combination therapies to generate experimentally testable hypotheses in a fairly unrestricted and inexpensive setting.
Plasma Cell-Free DNA in Acute and Chronic Aortic Syndromes
Authors: Weerakkody Ruwan A , Adamowicz Martyna , Robert Christelle , Pound John , Syed Maaz , Pumpe Caroline , Bilal Alsadeg , Laird Alexander , McLaren Duncan B , Falah Orwa , Tambyraja Andrew L , Reed Matthew J , Newby David E , Aitman Timothy J 
Published: January 2025

AbstractAcute aortic syndromes and other acute aortic events are commonly misdiagnosed and associated with high mortality and morbidity. There is need for a blood-based biomarker to indicate the acutely unstable aorta. Plasma cell-free DNA (cfDNA) is an established diagnostic marker in prenatal testing and cancer. Its use as a potential diagnostic marker in aortic disease remains to be demonstrated.We found that plasma short-fragment (50-700bp) cfDNA concentration is significantly increased in patients with both acute and chronic aortic disease compared with several control groups, and is significantly increased in acute versus chronic aortic disease. Plasma sf-cfDNA may differentiate acute aortic syndromes from other acute presentations of chest pain with good diagnostic accuracy and could prove a significant advance in the management of aortic disease.
A comprehensive benchmark and guide for sequence-function interpretable deep learning models in genomics
Authors: Sun Canzhuang , Sun Yu , Xu Kang , He Zhijie , Li Hao , Li Yaru , Yu Zongyuan , Wang Yuyang , Lin Xuanwei , Xu Xiang , Hu Pengzhen , Bo Xiaochen , Liao Mingzhi , Chen Hebing 
Published: January 2025

AbstractThe development of sequence-based deep learning methods has greatly increased our understanding of how sequence determines function. In parallel, numerous interpretable algorithms have been developed to address complex tasks, such as elucidating sequence regulatory syntax and analyzing non-coding variants from trained models. However, few studies have systematically compared and evaluated the performance and interpretability of these algorithms. Here, we introduce a comprehensive benchmark framework for evaluating sequence-to-function models. We systematically evaluated multiple models and DNA language foundation models using 369 ATAC-seq datasets, employing diverse training strategies and evaluation metrics to uncover their critical strengths and limitations. Our benchmark study highlights that different model architectures and interpretability methods are better suited to specific scenarios. Negative samples derived from naturally inactive regions outperform synthetic sequences, whereas single-cell tasks require specialized models. Additionally, we demonstrate that interpretable sequence-function models can complement traditional sequence alignment methods in studying cross-species enhancer regulatory logic. We also provide a pipeline to help researchers select the optimal sequence-function prediction and interpretability algorithms.
Armadillo Repeat Only Proteins Are Crucial for the Function of Plant CNGC Channels
Authors: Kulich Ivan , Oulehlová Denisa , Vladimirtsev Dmitrii , Zhou Minxia , Lileikyte Edita , Janda Martin , Iakovenko Oksana , Neubergerová Michaela , Studtrucker Tanja , Pleskot Roman , Dietrich Petra , Fendrych Matyáš , Friml Jiří 
Published: January 2025

AbstractPlant cells respond to a wide range of stimuli through intracellular calcium (Ca2+) signaling. Cyclic nucleotide-gated channels (CNGCs) are a major class of plant Ca2+channels, with 20 homologs inArabidopsis. These tetrameric plasma membrane (PM) proteins are activated by diverse stimuli, such as phytohormones, extracellular damage and cell wall integrity signals. Here, we identify a novel class of plant-specific proteins, Armadillo Repeat Only (ARO), as essential regulators of possibly all plant CNGC channels. Abrogation of functional sporophytic AROs results in a phenotypic pattern reminiscent of CNGC dysfunction, including defects in root gravitropism, root hair growth and morphology, stomatal movement, and responses to extracellular ATP and the phytohormone auxin.aro2/3/4mutants are fully resistant to the toxic effects caused by overexpression of CNGCs. AROs colocalize and physically interact with multiple CNGCs and modulate CNGC-dependent currents inXenopusoocytes. Structural modeling suggests that AROs form a tetramer surrounding the CNGC channel. These findings highlight AROs as key plant-specific players in plant CNGC function and Ca2+signaling.