bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship of glutamate and glutamine and metabolic profiling in focal epilepsy using 7T CRT-FID-MRSI
Authors: Chambers Stefanie , Lazen Philipp , Shayeste Haniye , Tomschik Matthias , Wais Jonathan , Hingerl Lukas , Strasser Bernhard , Haider Lukas , Traub-Weidinger Tatjana , Baumgartner Christoph , Koren Johannes , Mayer Florian , Feucht Martha , Dorfer Christian , Pataraia Ekaterina , Bogner Wolfgang , Trattnig Siegfried , Kasprian Gregor , Rössler Karl , Hangel Gilbert 
Published: February 2025

AbstractApproximately one-third of people with epilepsy (PWE) remain drug-resistant. In these cases, surgical resection of the epileptogenic zone may significantly reduce or eliminate seizures. Surgery necessitates precise delineation of the epileptogenic zone which proves especially challenging in the 20% of PWE that remain MRI-negative. To this end, the purpose of this study was to analyze the feasibility and robustness of ultra-high-field MRSI in identifying and characterizing pathologies in focal epilepsy. In addition, the relationship of glutamate and glutamine was evaluated in the epileptogenic zone (EZ)Fifty-six people with focal epilepsy were prospectively measured using 7T concentric ring trajectory direct acquisition of free-induction-decay MRSI which generated whole-brain metabolic maps with an isotropic resolution of 3.4mm3. After exclusion criteria were applied, we assessed metabolite ratios in 29 lesional- and MRI-negative PWE.In the lesional group, metabolic alterations in the suspected EZ were present in 86.7% of maps normalized to NAA, whereas this was reduced to 80% in creatine ratios. Metabolites with the highest stability in the lesional group included myo-inositol and choline, increased in 92.3%. In MRI-negative patients, changes were heterogeneous and less circumscribed, with a detection rate of 57.1%. We also observed a tendency towards an inverse relationship of glutamate to glutamine in the EZ, with relative increases of glutamine in PWE with lower seizure frequencies, contrasting relative glutamate increases in higher seizure frequencies.Our preliminary analysis suggests that 7T CRT-FID MRSI shows promise not only in identifying metabolic alterations in focal epilepsy but may also provide insights into disease pathomechanisms.
Comparative pangenome and mobilome analysis of clostridial species clusters reveals different levels of host adaptation and novel conserved biosynthetic potential
Authors: De Vrieze Lucas , Aerts Jan , Masschelein Joleen 
Published: February 2025

AbstractBackgroundThe classClostridiacomprises a diverse and industrially relevant group of anaerobes, ranging from free-living soil inhabitants to beneficial human gut symbionts. Analysing their genomic history and ecological adaptation dynamics beyond the species level allows us to gain deeper insights into their evolutionary traits and understand the impact of host adaptation on their innate functional capabilities.ResultsWe constructed pangenomes and built core genome phylogenies for four ecologically distinct clostridial species clusters (rRNA clusters I, IV, XIVa and XIVb), analysing 492 clostridial genomes in total. All pangenomes were functionally annotated and fitted into a genomic divergence rate model, revealing a striking contrast in metabolic versatility and evolutionary dynamics among the host-associated clusters, IV and XIVa. Based on these findings, we hypothesized that cluster XIVa species are in the earlier stages of a host adaptation process compared to their cluster IV relatives. Targeted follow-up analyses confirmed this and yielded two additional key findings. First, cluster XIVa species are comparably less dependent on their host metabolically, and possess a more extensive secondary metabolism than anticipated for a host-associated clade. Second, a remarkable conservation of ranthipeptide biosynthetic gene clusters reveals underexplored biosynthetic potential with significant evolutionary advantages.ConclusionsThese results show that comparing genomic patterns beyond the species level can uncover distinct ecological trends, such as host and niche adaptation, across entire species groups. Understanding these trends provides valuable insights into the metabolic versatility and biosynthetic potential of these groups.
3BTRON: A Blood-Brain Barrier Recognition Network
Authors: Fletcher-Lloyd Nan , Bravo-Ferrer Isabel , Gaasdal-Bech Katrine , Díaz Castro Blanca , Barnaghi Payam 
Published: February 2025

AbstractThe blood-brain barrier (BBB) plays a crucial role in maintaining brain homeostasis. During ageing, the BBB undergoes structural alterations. Electron microscopy (EM) is the gold standard for studying the structural alterations of the brain vasculature. However, analysis of EM images is time-intensive and can be prone to selection bias, limiting our understanding of the structural effect of ageing on the BBB. Here, we introduce 3BTRON, a deep learning framework for the automated analysis of the BBB architecture (the morphology, structure, and texture of its various components) in EM images. Using age as a readout, we trained and validated our model on a unique dataset (n = 359). We show that the proposed model could confidently identify the BBB architecture of aged mouse brains from young mouse brains across three different brain regions, achieving a sensitivity of 77.8% and specificity of 80.0% post-stratification when predicting on unseen data. Additionally, feature importance methods revealed the spatial features of each image that contributed most to the predictions. These findings demonstrate a new data-driven approach to analysing age-related changes in the architecture of the BBB.
Facial video photoplethysmography for measuring average and instantaneous heart rate: a pilot validation study
Authors: Pstras Leszek , Okupnik Tymoteusz , Ponikowska Beata , Paleczny Bartlomiej 
Published: February 2025

ABSTRACTIntroductionVideo photoplethysmography (vPPG) is a contactless optical technique of recording blood pulsations in the skin vasculature using a digital camera, which is increasingly used to measure or estimate various physiological parameters. Here, we evaluate the accuracy of heart rate (HR) measurements performed using facial vPPG technology Shen.AI Vitals and a smartphone camera.MethodsWe studied 35 healthy volunteers in a sitting position (median age 25 years, 17 females). Video recordings of participants’ faces were obtained using the front camera of a smartphone mounted on a tripod. In parallel, a 1-lead chest electrocardiogram (ECG) was recorded to obtain reference HR values (average value from the entire 60-second measurement and multiple values averaged over 10-second or 4-second periods during the measurement).ResultsThe mean absolute errors were 0.1, 0.2, and 0.4 beats per minute (bpm) for HR averaged over 60-second, 10-second, and 4-second periods, respectively. The errors did not exceed 1 bpm in 100.0%, 99.8%, and 94.5% of cases, respectively. Regardless of the HR averaging time, the correlation between the vPPG-based and reference values was very strong (r > 0.99, P < 0.001).ConclusionsIn predominantly young, white, sitting subjects, the tested vPPG technology provided highly accurate HR values, both when averaging over 60 seconds as well as in the case of short-term averages over 10 seconds or instantaneous HR values averaged over 4 seconds. The results should be confirmed in a larger study with greater diversity in age, skin tone, and lighting conditions.
A subset of conserved phagocytic genes are likely used for the intracellular theft of cnidarian stinging organelles in nudibranch gastropods
Authors: Goodheart Jessica A. , Fiorenza Rose , Rio Robin , Lopez-Anido Rebecca N. , Martin Noah J. , Herrlinger Timothy J. , Tarvin Rebecca D. , Lyons Deirdre C. 
Published: February 2025

AbstractBackgroundPhagocytosis is a universal physiological process in eukaryotes with many important biological functions. In nudibranch gastropods, a novel form of phagocytosis called nematocyst sequestration is specialized for the uptake of venomous stinging organelles stolen from their cnidarian prey. This process is highly selective. Here we use the emerging model nudibranch speciesBerghia stephanieaeandHermissenda opalescensto identify genes enriched within the body regions where nematocyst sequestration occurs, and investigate how the expression profile of phagocytosis, immune, and digestive genes differs between nematocyst sequestering regions relative to those where other phagocytic functions occur.ResultsWe identified 166 genes with significantly higher expression in sequestering regions inB. stephanieae, including genes associated with development, membrane transport, and metabolism. Of these, 41 overlap with transcripts upregulated inH. opalescenssequestering tissues. Using Hybridization Chain Reactionin situs, we show that at least two of these genes were localized to sequestering cells inB. stephanieae, including a putative C-type lectin receptor and a collagen. Genes annotated with phagocytosis, digestion, or immunity GO terms were often expressed in both sequestering and non-sequestering tissues, suggesting that they may also play a role in sequestration processes.ConclusionOur results suggest that phagocytosis genes likely play a role in the sequestration phenotype, and that a small subset of genes (e.g., collagen) may play unique functions yet to be uncovered. However, we also show that genes categorized in GO terms related to endocytosis, immunity, and digestion show a clear decrease in overall expression in sequestering tissues. This study lays the foundation for further inquiry into mechanisms of organelle sequestration in nudibranchs and other organisms.
Hip stabilization in an australopithecine-like hip: the influence of shape on muscle activation
Authors: Kramer Patricia Ann , Sylvester Adam D. 
Published: February 2025

AbstractHip stabilization through muscular activation of the gluteals is a key feature of hominin walking, but the role of pelvic shape on muscular activation remains uncertain. Coupled with this is the uncertainty regarding whether or not the kinematics and kinetics of modern humans are appropriate proxies for the patterns in extinct hominins. In this work we treat modern human kinematics and kinetics as a null hypothesis by applying them to musculoskeletal models with modern human-like and australopithecine-like hips and examine the resulting joint reaction and muscle forces. We test the prediction that the hip functional complex that includes biacetabular breadth, femoral neck length, and iliac blade flare produces hip abductor muscle activations and hip joint reactions that are similar in the modern human- and australopithecine-like forms.Using previously developed musculoskeletal models that approximate gluteus maximus with twelve muscle elements, gluteus medius with twelve, and gluteus minimus with three, we calculated joint reaction and muscle forces using inverse dynamics analyses and a muscle redundancy algorithm. We used data from ten individuals who walked at their normal velocity. We found that the shape of the australopithecine-like pelvis produces absolutely higher muscle activations in gluteus medius and gluteus minimus, but lower muscle activations across a long period of stance in gluteus maximus compared to the modern human-like pelvis when kinematics and size are held constant. Hip joint reaction forces are similarly heterogeneous: the australopithecine-like hip exhibits lower forces in the direction of travel but higher in the vertical. These results suggest that, while the australopithecine-like pelvis is compatible with human walking patterns, influences on pelvic shape other than accommodating muscle and joint reaction forces during walking are present.
H2S is a potential universal reducing agent for Prx6-type peroxiredoxins
Authors: Lang Lukas , Leiskau Laura , Thullen Lea , Deponte Marcel 
Published: February 2025

AbstractThe absence of a universal reducing agent distinguishes the Prx6-type subfamily of peroxiredoxins from the structurally similar Prx1-type subfamily. A likely explanation for the lack of reactivity of Prx6-type enzymes with common reducing agents is that a Prx6-specific histidyl residue at the bottom of the active-site pocket traps the oxidized enzyme with a potentially hypervalent cysteinyl sulfur atom in an inaccessible fully-folded protein conformation. Here, we analyzed the reduction of oxidized PfPrx6 from the human malaria parasitePlasmodium falciparumand human PrxVI by the hydrosulfide ion, HS−, as the smallest possible sulfur-containing universal electron donor using stopped-flow kinetic measurements. We show that HS−rapidly reacts with oxidized wild-type PfPrx6 or human PrxVI (but not the histidyl mutant PfPrx6H39Y) with a second-order rate constant of >108M−1s−1at pH 7.4. The potential protein-persulfide species of PfPrx6 is neither reduced by thioredoxin nor glutaredoxin and glutathione, but further reacts with an excess of HS−with a second-order rate constant of 6.3×103M−1s−1, yielding the reduced enzyme. In summary, we identified HS−as a highly reactive, potential universal electron donor for Prx6-type enzymes in eukaryotes, bacteria, and archaea. Our study marks the starting point for the characterization of the complex reduction pathway of Prx6-type enzymes with potential implications for H2S detoxification, redox signaling, and iron-sulfur metabolism.
Construction of a register-based severity index for anorexia nervosa in Denmark: Association with overall and cause-specific mortality
Authors: Larsen Janne Tidselbak , Chatwin Hannah , Zhang Ziping , Clausen Loa , Bulik Cynthia Marie , Thornton Laura Marie , Micali Nadia , Petersen Liselotte Vogdrup , Yilmaz Zeynep 
Published: February 2025

AbstractBackgroundConsidering the high likelihood of chronicity, it is imperative to understand the risk factors and outcomes associated with severe anorexia nervosa (AN), for which Danish registers provide a unique opportunity. We developed a measure of AN severity adapted from clinical literature for use in register-based research.MethodsThe study population included all Danish individuals born between 1963 and 2007 who were diagnosed with AN from 1969 to 2013. Using register data, we constructed the Anorexia Nervosa Register-based Severity Index (AN-RSI), incorporating early or late illness onset, number of inpatient admissions and outpatient treatments, cumulative treatment length, and illness duration, each weighted based on clinical importance. Associations between AN-RSI scores, evaluated five years after first AN diagnosis, and mortality were estimated using survival analysis.ResultsAmong 9,167 individuals diagnosed with AN, 132 died during follow-up: 17 from AN; 30 from suicide; and 85 from other causes. Higher AN-RSI scores were associated with increased rates of mortality from AN, somatic anorexia diagnosis, suicide, alcohol-related causes, and any cause. AN cases who scored in the top 20% of AN-RSI had especially high mortality rates. Furthermore, severe AN cases were also more likely to be in treatment in the next five years after severity was established.ConclusionsAN-RSI effectively captures mortality and long-term treatment in the absence of detailed patient records and is associated with later mortality in AN patients. AN-RSI could serve as a tool to examine epidemiological and genetic risk factors associated with AN course and outcomes.
Structural and Thermodynamic Impact of Oncogenic Mutations on the Nucleosome Core Particle
Authors: Onyema Augustine C. , DiForte Christopher , Patel Rutika , Poget Sébastien F. , Loverde Sharon M. 
Published: February 2025

AbstractThe nucleosome core particle (NCP) is essential for chromatin structure and function, serving as the fundamental unit of eukaryotic chromatin. Oncogenic mutations in core histones disrupt chromatin dynamics, altering DNA repair and transcription processes. Here, we investigate the molecular consequences of two mutations—H2BE76K and H4R92T—using 36 µs of all-atom molecular dynamics simulations and experimental biophysical assays. These mutations destabilize the H2B-H4 interface by disrupting critical salt bridges and hydrogen bonds, reducing binding free energy at this interface. Principal component analysis reveals altered helix conformations and increased interhelical distances in mutant systems. Thermal stability assays (TSA) and differential scanning calorimetry (DSC) confirm that these mutations lower the dimer dissociation temperature and reduce enthalpy compared to the wild type. Taken together, our results elucidate how these mutations compromise nucleosome stability and propose mechanisms through which they could modulate chromatin accessibility and gene dysregulation in cancer.Statement of SignificanceThe nucleosome is the essential packaging unit of DNA. ‘Oncohistones’ which are histone mutations that are associated with cancer, are known to compromise the stability of the nucleosome and affect nucleosome sliding. Here we perform long-time molecular dynamics simulations of two buried histone core mutations, demonstrating that these mutations reduce the stability of the histone core at the H2B-H4 interface. Next, we demonstrate that these same mutations lower the dimer dissociation temperature and shift the nucleosome dissociation pathway.
DDX5 and DDX17 RNA helicases regulate hepatitis B virus RNA splicing
Authors: Giraud Guillaume , Grand Xavier , Huchon Pélagie , Rodà Mélanie , Diederichs Audrey , Chapus Fleur , De Nicola Francesca , Parent Romain , Rivoire Michel , Bourgeois Cyril F. , Zoulim Fabien , Testoni Barbara 
Published: February 2025

ABSTRACTChronic HBV infection remains a major health burden worldwide and is the main driver of severe liver diseases. Liver pathogenesis is associated with the increased proportion of HBV spliced variants that encode viral proteins involved in liver disease progression. However, how HBV RNA splicing is regulated is poorly understood. Here, we focused on DDX5 and DDX17 RNA helicases, known to regulate HBV RNA metabolism and alternative splicing of host genes. By performing 5’RACE-PCR combined with single molecule sequencing, we demonstrated that silencing both proteins increased the usage of a specific splicing donor site and the expression of the derived HBV spliced variants. Polysome fractionation highlighted the ability of these RNA species to encode new viral proteins potentially contributing to liver pathogenesis. Overall, our data established DDX5 and DDX17 helicases as master regulators of HBV RNA metabolism, by fine-tuning viral splicing, which is linked to HBV-induced liver pathogenesis and disease progression.
Viral-mediated delivery of morphogenic regulators enables leaf transformation inSorghum bicolor(L.)
Authors: Butler Nathaniel M. , Carlson Aidan T. , Starker Colby , Voytas Daniel F. 
Published: February 2025

SummaryRecent advancements in monocot transformation, using leaf tissue as explant material, have expanded the number of grass species capable of transgenesis. However, the complexity of vectors and reliance on inducible excision of essential morphogenic regulators have so far limited widespread application. Plant RNA viruses, such as Foxtail Mosaic Virus (FoMV), present a unique opportunity to express morphogenic regulator genes, such asBabyboom(Bbm),Wuschel2(Wus2),Wuschel-like homeobox protein 2a(Wox2a), and the GROWTH-REGULATING FACTOR 4 (GRF4) GRF-INTERACTING FACTOR 1 (GIF1) fusion protein transiently in leaf explant tissues. Furthermore, altruistic delivery of conventional and viral vectors could provide opportunities to simplify vectors used for leaf transformation— facilitating vector optimization and reducing reliance on morphogenic regulator gene integration. In this study, both viral and conventional T-DNA vectors were tested for their ability to promote the formation of embryonic calli, a critical step in leaf transformation protocols, usingSorghum bicolorleaf explants. Although conventional leaf transformation vectors yielded viable embryonic calli (43.2 ± 2.9%: GRF4-GIF1, 50.2± 3%:Bbm/Wus2), altruistic conventional vectors employing the GRF4-GIF1 morphogenic regulator resulted in improved efficiencies (61.3 ± 4.7%). Altruistic delivery was further enhanced with the use of viral vectors employing both GRF4-GIF1 andBbm/Wus2regulators, resulting in 75.1 ± 2.3% and 79.2 ± 2.5% embryonic calli formation, respectively. Embryonic calli generated from both conventional and viral vectors produced shoots expressing fluorescent reporters, which were confirmed using molecular analysis. This work provides an important proof-of-concept for use of both altruistic vectors and viral-expressed morphogenic regulators for improving plant transformation.
Maternal age and genome-wide failure of meiotic recombination are associated with triploid conceptions in humans
Authors: Picchetta Ludovica , Ottolini Christian Simon , Tao Xin , Zhan Yiping , Jobanputra Vaidehi , Marin Vallejo Carlos , Mulas Francesca , Paraboschi Elvezia Maria , Escribá Pérez Maria José , Molinaro Thomas , Whitehead Christine , Gill Pavan , Mounts Emily , Babariya Dhruti , Rienzi Laura Francesca , Ubaldi Filippo Maria , Garcia-Velasco Juan Antonio , Pellicer Antonio , Carmi Shai , Hoffmann Eva R , Capalbo Antonio 
Published: February 2025

AbstractTriploid and haploid conceptions are not viable and are a common occurrence in humans, where they account for 10% of all pregnancy losses. Despite the parent-of-origin being important in the etiology of the pregnancy, our knowledge of their causes is limited, especially at the point of conception. Using a dataset of 96,660 biopsies and a validation dataset of 44,324 from human blastocysts embryos generated by intra-cytoplasmic sperm injection (ICSI), we estimate that 1.1% of human conceptions (n=1,063) contain extra or missing chromosome sets in zygotes. We identify a maternal age effect, with a 1.059 per year increased risk in triploidy/haploidy (p=0.0008). In 0.03% of couples, we identified three or more triploid/haploid embryos, suggesting a personal risk effect (p=0.03). Genotype analysis of 55 triploid embryo biopsies and their parents show that one third of maternal triploid conceptions originate in meiosis I and two thirds in meiosis II. Seven of these embryos are inferred to have entirely failed to initiate meiotic recombination genome-wide, suggesting that human oocytes with pervasive meiotic recombination failure that are formed during fetal development are capable of ovulation in adult life. Finally, we identify a new type of genome-wide maternal isodiploidy (two maternal chromosome sets) in 0.05% of embryos (41 of 74,009). Collectively, our findings shed light on the biology of meiosis and the formation of human oocytes with the number of chromosome sets.