bluuebunny/crossref_metadata_2025_split huggingface dataset:
βIV spectrin abundancy, cellular distribution and sensitivity to AKT/GSK3 regulation in schizophrenia
Authors: Di Re Jessica , Marini Michela , Hussain Syed Ibrar , Singh Aditya K. , Venkatesh Akshaya , Alshammari Musaad A. , Alshammari Tahani K. , Hamoud Abdul-Rizaq Ali , Imami Ali Sajid , Haghighijoo Zahra , Fularcyzk Nickolas , Stertz Laura , Hawes Derek , Mosebarger Angela , Jernigan Jordan , Chaljub Claire , Nehme Ralda , Walss-Bass Consuelo , Schulmann Anton , Vawter Marquis P. , McCullumsmith Robert , Damoiseaux Robert D. , Limon Agenor , Labate Demetrio , Wells Michael F. , Laezza Fernanda 
Published: February 2025

Abstract
Schizophrenia (SCZ) is a complex psychiatric disorder with unclear biological mechanisms. Spectrins, cytoskeletal proteins linked to neurodevelopmental disorders, are regulated by the AKT/GSK3 pathway, which is implicated in SCZ. However, the impact of SCZ-related dysregulation of this pathway on spectrin expression and distribution remains unexplored. Here, we show that βIV spectrin protein levels were reduced in neurons of the dorsolateral prefrontal cortex in SCZ postmortem samples compared to healthy control (HC) from the Human Brain Collection Core (HBCC). To investigate potential links between βIV spectrin and the AKT/GSK3 pathway, we analyzed the PsychEncode dataset, revealing elevated SPTBN4 and AKT2 mRNA levels with correlated gene transcription in both HCs and individuals with SCZ. Next, computational tools were employed to identify potential AKT and GSK3 phosphorylation sites on βIV spectrin, and two GSK3 sites were validated through in vitro assays. To assess whether βIV spectrin distribution and sensitivity to AKT/GSK3 are altered in SCZ, we used iPSC-derived neurons from two independent cohorts of patients with significantly increased familial genetic risk for the disorder. Alteration in βIV spectrin levels and sensitivity to AKT/GSK3 inhibitors were consistently observed across both cohorts. Importantly, a Random Forest classifier applied to βIV spectrin imaging achieved up to 98% accuracy in classifying cells by diagnosis in postmortem samples, and by diagnosis or diagnosis × perturbation in iPSC samples. These findings reveal altered βIV spectrin levels and AKT/GSK3 sensitivity in SCZ, identifying βIV spectrin image-based endophenotypes as robust, generalizable predictive biomarkers of SCZ, with the potential for scalable clinical applications.
Five millennia of mitonuclear discordance in Atlantic bluefin tuna identified using ancient DNA
Authors: Eriksen Emma Falkeid , Andrews Adam Jon , Nielsen Svein Vatsvåg , Persson Per , Malca Estrella , Onar Vedat , Aniceti Veronica , Piquès Gäel , Piattoni Federica , Fontani Francesco , Wiech Martin , Ferter Keno , Kersten Oliver , Ferrari Giada , Cariani Alessia , Tinti Fausto , Cilli Elisabetta , Atmore Lane M. , Star Bastiaan 
Published: February 2025

Abstract
Mitonuclear discordance between species is readily documented in marine fishes. Such discordance may either be the result of past natural phenomena or the result of recent introgression from previously seperated species after shifts in their spatial distributions. Using ancient DNA spanning five millennia, we here investigate the long-term presence of Pacific bluefin tuna (Thunnus orientalis) and albacore (Thunnus alalunga) -like mitochondrial (MT) genomes in Atlantic bluefin tuna (Thunnus thynnus), a species with extensive exploitation history and observed shifts in abundance and age structure. Comparing ancient (n = 130) and modern (n = 78) Atlantic bluefin MT genomes from most of its range, we detect no significant spatial or temporal population structure, which implies ongoing gene flow between populations and large effective population sizes over millennia. Moreover, we identify discordant MT haplotypes in ancient specimens up to 5000 years old and find that the frequency of these haplotypes has remained similar through time. We therefore conclude that MT discordance in the Atlantic bluefin tuna is not driven by recent introgression. Our observations provide oldest example of directly observed MT discordance in the marine environment, highlighting the utility of ancient DNA to obtain insights in the long-term persistence of such phenomena.
ATG8ylation of vacuolar membrane protects plants against cell wall damage
Authors: Julian Jose , Gao Peng , Del Chiaro Alessia , Carlos De La Concepcion Juan , Armengot Laia , Somssich Marc , Duverge Heloise , Clavel Marion , Grujic Nenad , Kobylinska Roksolana , Polivka Ingo , Besten Maarten , Andersen Tonni Grube , Dank Christian , Korbei Barbara , Bachmair Andreas , Coll Nuria S. , Minina Elena A. , Sprakel Joris , Dagdas Yasin 
Published: February 2025

Abstract
Vacuoles are essential for cellular metabolism and growth and the maintenance of internal turgor pressure. They sequester lytic enzymes, ions and secondary metabolites that, if leaked into the cytosol, could lead to cell death. Despite their pivotal roles, quality control pathways that safeguard vacuolar integrity have remained elusive in plants. Here we describe a conserved vacuolar quality control pathway that is activated upon cell wall damage in a turgor-pressure-dependent manner. Cell wall perturbations induce a distinct modification—ATG8ylation—on the vacuolar membrane (tonoplast) that is regulated by the V-ATPase and ATG8 conjugation machinery. Genetic disruption of tonoplast ATG8ylation impairs vacuolar integrity, leading to cell death. Together, our findings reveal a homeostatic pathway that preserves vacuolar integrity upon cell wall damage.
Macroevolution along developmental lines of least resistance in fly wings
Authors: Rohner Patrick T. , Berger David 
Published: February 2025

Abstract
Evolutionary change requires genetic variation, and a reigning paradigm in biology is that rates of microevolution can be predicted from estimates of available genetic variation within populations. However, the accuracy of such predictions should decay on longer evolutionary timescales, as the influence of genetic constraints diminishes. Here we show that intrinsic developmental variability and standing genetic variation in wing shape in two distantly related flies, Drosophila melanogaster and Sepsis punctum, are aligned and predict deep divergence in the dipteran phylogeny, spanning >900 taxa and 185 million years. This alignment cannot be easily explained by constraint hypotheses unless most of the quantified standing genetic variation is associated with deleterious side effects and is effectively unusable for evolution. However, phenotyping of 71 genetic lines of S. punctum revealed no covariation between wing shape and fitness, lending no support to this hypothesis. We also find little evidence for genetic constraints on the pace of wing shape evolution along the dipteran phylogeny. Instead, correlational selection related to allometric scaling, simultaneously shaping developmental variability and deep divergence in fly wings, emerges as a potential explanation for the observed alignment. This suggests that pervasive natural selection has the potential to shape developmental architectures of some morphological characters such that their intrinsic variability predicts their long-term evolution.
Telemedicine-supported lifestyle intervention for glycemic control in patients with CHD and T2DM: multicenter, randomized controlled trial
Authors: Mueller Stephan , Dinges Sophia M. T. , Gass Felix , Fegers-Wustrow Isabel , Treitschke Julian , von Korn Pia , Boscheri Alessandra , Krotz Janosch , Freigang Felix , Dubois Clara , Winzer Ephraim B. , Linke Axel , Edelmann Frank , Feuerstein Anna , Wolfram Oliver , Schäfer Kerstin , Verket Marlo , Wolfarth Bernd , Dörr Marcus , Wachter Rolf , Hackenberg Björn , Rust Sarah , Nebling Thomas , Amelung Volker , Halle Martin 
Published: February 2025

Abstract
Patients with coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM) have a substantially increased risk for major cardiovascular events and mortality. Increasing physical activity and improving a healthy diet may effectively reduce cardiovascular risk factors; however, the effects are often transient. In a multicenter, 1:1 randomized controlled trial including 502 patients with combined CHD and T2DM (68 ± 8 years; 84% men), we assessed the effects of a home-based telemedicine-supported lifestyle intervention (exercise training, nutritional recommendations and health literacy training) with regular individualized feedback versus usual care. The study met its primary endpoint of reduced glycated hemoglobin after 6 months in favor of the lifestyle intervention group (mean between-group difference in the complete-case analysis (n = 197 and n = 193), −0.13% (95% confidence interval, −0.25 to −0.01), P = 0.04). When individualized feedback and health literacy training were discontinued after 6 months (while other telemedicine tools were maintained), no statistically significant between-group differences were observed at 12 months. At 12 months, 31 patients (6.2%) had a major adverse cardiovascular event (lifestyle intervention, n = 20 (8.0%); usual care, n = 11 (4.4%); P = 0.15), with the main reason being hospitalization for angina or revascularization (lifestyle intervention, n = 15; usual care, n = 8). There were five deaths (lifestyle intervention, n = 2; usual care, n = 3), none of which were categorized as related to the intervention. However, three events that resulted in hospitalization were categorized as potentially related to the intervention (decompensation of heart failure, vertebral disc prolapse and inguinal hernia). In conclusion, a home-based lifestyle intervention with telemedicine support showed modest effects in patients with CHD and T2DM. ClinicalTrials.gov registration: NCT03835923.
Metal oxides carbon xerogel nanocomposite for methanol oxidation fuel cell
Authors: Mohamed Fatma , Shaban Mohamed , Salem Omnia M. 
Published: February 2025

Abstract
The primary requirement for electrode materials in direct methanol fuel cells (DMFC) is efficient electrocatalyst that exhibit high tolerance to methanol oxidation, excellent stability, and reasonable cost. The combination of distinct active materials with distinctive architectures may facilitate the attainment of this objective. The present study included the preparation of a Carbon Xerogel Doped with various metal oxides derived from Banana peels. The nanocomposites were thoroughly examined utilizing several characterization modalities including XRD, FTIR, and SEM. The electrocatalytic performance of Carbon xerogel doped with Iron (Fe3O4/CX), carbon xerogel doped with magnesium (MgO/CX), and carbon xerogel doped with Copper (CuO/CX) about the Methanol Oxidation Reaction (MOR) was investigated using electrochemical methods such as cyclic voltammetry, impedance spectroscopy, and chronoamperometry. The results showed that the Fe3O4/CX, MgO/CX, and CuO/CX are effective electrocatalysts with an onset potential of around 1.00 V and current densities of approximately 42.98 mA cm − 2, 28.2784 mA.cm − 2, and 6.60698 mA.cm − 2, respectively, in the optimized electrolyte for methanol oxidation. The stability of Fe3O4/CX, MgO/CX, and CuO/CX electrodes was examined using chronoamperometry and the Cyclic Stability method. The results revealed that the (Fe3O4/CX) electrode exhibited outstanding stability throughout the whole 60-minute chronoamperometry Technique and demonstrated great stability for 100 cycles in the Cyclic Stability technique. The remarkable electrochemical activity and stability may be attributed to the synergistic effect of Fe3O4/CX, which provided sufficient active sites for methanol electro-oxidation and reduced the equivalent series resistance, as shown by the electrochemical impedance spectroscopy analysis. This work used environmentally friendly materials, which presents a novel opportunity to enhance the efficiency of methanol oxidation via the utilization of affordable catalysts. This study of the theoretical technique methods for establishing the route of methanol decomposition, and systematizes their confirmation with experimental data, within the methodological framework.
Multiscale correlations between joint and tissue-specific biomechanics and anatomy in postmortem ovine stifles
Authors: Chatterjee Aritra , Davis Zachary Robert , Lescun Timothy , Chan Deva D. 
Published: February 2025

Abstract
Joint stability depends on various properties that include the bone anatomy, joint capsule geometry and stiffness, and soft tissues within. The multiscale biomechanical relationships between the whole joint and individual tissues are useful in estimating the physiological condition of the knee. To better understand these relationships, we evaluated multiple structural and mechanical parameters in healthy ovine stifles, specifically joint laxity, joint morphology, individual tissue T

2

*
relaxation and mechanical properties of ligaments (ACL, PCL, MCL, LCL), patellar tendon, menisci, and cartilage. By combining mechanical testing at two length scales and magnetic resonance imaging (MRI) scans, we quantify the strength of correlation coefficients between measured metrics, among joint size, whole joint and individual tissue properties. We observe positive correlations between joint laxity forces and the inter-epicondylar distance. Further, the viscoelastic properties of the tendons and ligaments correlate positively with joint laxity forces; however, no such correlations were observed for the cartilage and menisci. We also found weak inverse correlation between tissue viscoelasticity and T

2

*
for MCL; and positive correlations for cartilage and menisci, LCL and PCL respectively. These results provide useful insights into the role of individual tissues that are crucial in measuring whole joint responses as key indicators of knee health.
Towards autonomous robotic THz-based in vivo skin sensing: the PicoBot
Authors: Dogra Anubhav , Jones Dominic , Hernandez Serrano Arturo Ignacio , Chakraborty Shruti , Young Jacob Joshua , Page Benjamin George , Hardwicke Joseph , Valdastri Pietro , Pickwell-MacPherson Emma 
Published: February 2025

Abstract
Terahertz (THz) light has the unique properties of being very sensitive to water, non-ionizing, and having sub-millimeter depth resolution, making it suitable for medical imaging. Skin conditions including eczema, psoriasis and skin cancer affect a high percentage of the population and we have been developing a THz probe to help with their diagnosis, treatment and management. Our in vivo studies have been using a handheld THz probe, but this has been prone to positional errors through sensorimotor perturbations and tremors, giving spatially imprecise measurements and significant variations in contact pressure. As the operator tires through extended device use, these errors are further exacerbated. A robotic system is therefore needed to tune the critical parameters and achieve accurate and repeatable measurements of skin. This paper proposes an autonomous robotic THz acquisition system, the PicoBot, designed for non-invasive diagnosis of healthy and diseased skin conditions, based on hydration levels in the skin. The PicoBot can 3D scan and segment out the region of interest on the skin’s surface, precisely position (± 0.5/1 mm/degrees) the probe normal to the surface, and apply a desired amount of force (± 0.1N) to maintain firm contact for the required 60 s during THz data acquisition. The robotic automation improves the stability of the acquired THz signals, reducing the standard deviation of amplitude fluctuations by over a factor of four at 1 THz compared to hand-held mode. We show THz results for skin measurements of volunteers with healthy and dry skin conditions on various parts of the body such as the volar forearm, forehead, cheeks, and hands. The tests conducted validate the preclinical feasibility of the concept along with the robustness and advantages of using the PicoBot, compared to a manual measurement setup.
Searching for the cellular underpinnings of the selective vulnerability to tauopathic insults in Alzheimer’s disease
Authors: Torok Justin , Maia Pedro D. , Anand Chaitali , Raj Ashish 
Published: February 2025

Abstract
Neurodegenerative diseases such as Alzheimer’s disease exhibit pathological changes in the brain that proceed in a stereotyped and regionally specific fashion. However, the cellular underpinnings of regional vulnerability are poorly understood, in part because whole-brain maps of a comprehensive collection of cell types have been inaccessible. Here, we deployed a recent cell-type mapping pipeline, Matrix Inversion and Subset Selection (MISS), to determine the brain-wide distributions of pan-hippocampal and neocortical cells in the mouse, and then used these maps to identify general principles of cell-type-based selective vulnerability in PS19 mouse models. We found that hippocampal glutamatergic neurons as a whole were significantly positively associated with regional tau deposition, suggesting vulnerability, while cortical glutamatergic and GABAergic neurons were negatively associated. We also identified oligodendrocytes as the single-most strongly negatively associated cell type. Further, cell-type distributions were more predictive of end-time-point tau pathology than AD-risk-gene expression. Using gene ontology analysis, we found that the genes that are directly correlated to tau pathology are functionally distinct from those that constitutively embody the vulnerable cells. In short, we have elucidated cell-type correlates of tau deposition across mouse models of tauopathy, advancing our understanding of selective cellular vulnerability at a whole-brain level.
Congenital Ataxia with Progressive Cerebellar Atrophy, Camptodactyly, and Hypertrichosis: A Novel Recognizable Phenotype for NALCN Heterozygous Variants
Authors: Sartorelli Jacopo , Travaglini Lorena , Garone Giacomo , Dentici Maria L. , Sinibaldi Lorenzo , Digilio Maria C. , Novelli Antonio , Agolini Emanuele , D'Amico Adele , Bertini Enrico , Nicita Francesco 
Published: February 2025

Abstract
Background Non-selective sodium leak channel (NALCN) protein encoded by the NALCN gene is of key importance for neuronal cell excitability. Previous reports showed that biallelic NALCN pathogenic variants cause infantile hypotonia with psychomotor retardation and characteristic facies 1 (IHPRF1) while monoallelic variants lead to congenital contractures of the limbs and face, hypotonia, and developmental delay (CLIFAHDD). In our work, we aimed to expand the heterozygous NALCN-related clinical spectrum, presenting two affected individuals and a literature review.
Methods We describe two new unrelated subjects harboring monoallelic NALCN pathogenic variants identified through clinical exome sequencing and review the current literature of other heterozygous NALCN patients.
Results The c.3542G > A (p.Arg1181Gln) and the novel c.3423C > A (p.Phe1141Leu) heterozygous missense variants were disclosed in two subjects manifesting a similar phenotype characterized by congenital ataxia with progressive cerebellar atrophy, camptodactyly, and hypertrichosis of the arms (CAPCACH). Other NALCN subjects with overlapping features have already been reported. A combination of these clinical and neuroimaging findings suggests the definition of the new CAPCACH phenotype.
Conclusion We expand the heterozygous NALCN-related clinical spectrum from the more severe CLIFFAHDD to the milder CAPCACH phenotype. These conditions should be considered in the differential diagnosis of syndromic congenital ataxias, and the presence of camptodactyly and/or hypertrichosis may represent peculiar diagnostic clues.
Auditory pathway abnormalities in Parkinson's disease
Authors: Souza Rafaela Valiengo de , Silva Liliane Aparecida Fagundes , Matas Carla Gentile 
Published: February 2025

Abstract
Background Parkinson's disease (PD) is a degenerative, progressive, chronic disease that mainly affects the central nervous system, caused by dopamine deficiency. One of the ways to evaluate the central nervous system is with auditory evoked potentials (AEP).
Objective To characterize the audiometric responses, and the auditory brainstem response (ABR), and cortical auditory evoked potentials (CAEP) in individuals with PD.
Methods Thirty-two patients aged between 40 and 81 of both sexes were assessed, 16 with PD (study group [SG]) and 16 without PD (control group [CG]) matched for sex and age. The subjects were assessed using pure tone audiometry, ABR with click stimuli, and CAEP using the oddball paradigm with tone burst and speech stimuli. The results were compared between the groups using a repeated measures analysis of variance (ANOVA) test.
Results In pure-tone audiometry, significantly higher hearing thresholds were found in the SG at 6 and 8 kHz. For the ABR, no differences were observed between groups. The CAEP analysis did not find statistical differences in the latencies between the groups, however, the SG presented smaller amplitudes of P1-N1, P2-N2, and N2-P3 than the CG.
Conclusion The results of this study showed a significantly higher threshold in higher frequencies in PD. Although no differences were observed at the brainstem level, the decrease in amplitude of all components in patients with PD in the CAEP suggests a deficit in both automatic and attentional cortical processing of acoustic stimuli.