bluuebunny/crossref_metadata_2025_split huggingface dataset:
Equivalence of plasma and serum for clinical measurement of p-tau217: comparative analyses of four blood-based assays
Authors: Chen Yijun , Albert Ally L. , Sehrawat Anuradha , Farinas Marissa , Lopez Oscar L. , Zeng Xuemei , Cohen Ann D. , Karikari Thomas K. 
Published: December 2024

AbstractBackgroundPhosphorylated tau (p-tau) 217 is a promising blood biomarker for Alzheimer’s disease (AD). However, most p-tau217 assays have been validated solely in ethylenediaminetetraacetic acid (EDTA) plasma, leaving the clinical applicability of serum p-tau217 largely unexplored despite serum being a preferred matrix in many clinical laboratories. To address this gap, we compared p-tau217 concentrations and diagnostic performances in matched plasma and serum samples using four research-use-only assays, including three from commercial sources i.e., Lumipulse, ALZpath, NULISA, and one from University of Pittsburgh.MethodsPaired plasma and serum samples were processed from the same venipuncture collection and assessed with the four p-tau217 assays following manufacturer-recommended procedures in two research cohorts (N=84).ResultsPlasma and serum p-tau217 levels varied across assays; the ALZpath, Pittsburgh, and NULISA methods showed significantly lower p-tau217 levels in serum compared with plasma (p<0.0001), while Lumipulse showed higher or non-significant differences in serum. Yet, strong correlations (rho >0.8) were observed between plasma and serum p-tau217 pairs. Both plasma and serum p-tau217 demonstrated strong classification accuracies to differentiate clinical AD from normal controls, with high AUC (up to 0.963) for all methods. The exception was the Pittsburgh assay, where plasma p-tau217 had superior AUC than serum p-tau217 (plasma: 0.912, serum: 0.844). The rest of the assays had equivalent accuracies in both matrices.ConclusionsSerum p-tau217 performs equivalently as plasma p-tau217 for most assessed assays. Serum can therefore be used in place of plasma for p-tau217 assessment for research and clinical purposes.
PHALCON: phylogeny-aware variant calling from large-scale single-cell panel sequencing datasets
Authors: Priya  , Chowdary Sunkara B V , Zafar Hamim 
Published: December 2024

AbstractSingle-cell sequencing (SCS) technologies provide cellular resolution data for inferring variants and reconstructing tumor phylogeny for resolving intra-tumor heterogeneity (ITH), which causes drug resistance and relapse in cancer. Moreover, recently emerged panel sequencing methods can parallely sequence thousands of cells by targeting disease-specific genes. Current variant callers and SCS-specific phylogenetic methods fail to handle such large-scale datasets or address the amplification biases in panel-based sequencing protocols. Here, we present a statistical variant caller, PHAL-CON, which enables scalable mutation detection from large-scale single-cell panel sequencing data by modeling their evolutionary history under a finite-sites model along a clonal phylogeny. PHAL-CON infers the underlying cellular sub-populations based on mutation likelihoods of candidate sites and reconstructs a clonal phylogeny and the most likely mutation history using a likelihood-based probabilistic framework. Using numerous simulated datasets across varied experimental settings, we showed that PHALCON outperforms state-of-the-art methods in terms of variant call-ing accuracy (7.29-51.67% improvement), accuracy of tumor phylogeny inference (410.43-32931.8% improvement) and runtime (40-50×faster). Furthermore, when applied on datasets from triple negative breast cancer patients, PHALCON detected novel somatic mutations with high functional impact in important oncogenes and tumor suppressor genes, and better resolved ITH by identifying rare clones, and elucidating lineages harboring deleterious mutations in key oncogenes and tumor suppressor genes.
A new nanoDSF approach to anti-tubulin compounds screening revealed novel MTAs among approved drugs
Authors: Baksheeva Viktoriia E , La Rocca Romain , Leloup Ludovic , Souberan Aurelie , Bergès Raphael , Allegro Diane , Derviaux Carine , Pasquier Eddy , Roche Philippe , Morelli Xavier , Devred François , Tchoghandjian Aurélie , Tabouret Emeline , Golovin Andrey V , Tsvetkov Philipp O 
Published: December 2024

AbstractMicrotubule Targeting Agents (MTAs) constitute a vital category of tubulin-binding compounds, deployed across anticancer therapies. Despite the array of MTA drugs developed by pharmaceutical entities, the quest for novel efficacious molecules continues unabated. We unveil an innovativein vitroMTA screening methodology employing nano differential scanning fluorimetry (nanoDSF), presenting distinct advantages over known assays. This novel approach not only assesses compound-tubulin binding but also quantitatively analyzes their impact on tubulin polymerization. Proposed nanoDSF assay was rigorously validated using the Prestwick Chemical Library, which encompasses 1,520 approved compounds, successfully identifying all previously known MTAs. Furthermore, this screening has unearthed potential anti-tubulin agents among drugs currently utilized for non-related medical conditions, offering insights into their mechanisms of action in inhibiting cancer cell proliferation and/or inducing cytotoxicity. These discoveries herald new opportunities for drug repositioning involving the newly identified MTAs and substantially streamline the process of screening extensive chemical libraries for MTAs featuring novel chemical structures.
Tertiary and quaternary structure remodeling by occupancy of the substrate binding pocket in a large glutamate dehydrogenase
Authors: Lázaro Melisa , Chamorro Nicolás , López-Alonso Jorge P. , Charro Diego , Rasia Rodolfo M. , Jiménez-Osés Gonzalo , Valle Mikel , Lisa María-Natalia 
Published: December 2024

ABSTRACTGlutamate dehydrogenases (GDHs) catalyze the oxidative deamination of L-glutamate to 2-oxoglutarate using NAD(P)+as a cofactor. The large type of GDHs (L-GDHs) displays a dynamic homotetrameric architecture that alternates between open and closed states. The catalytic mechanism and the role of the large conformational changes of L-GDHs in enzymatic function are unknown. Here, we explore by cryoEM the structure and the conformational space of the mycobacterial L-GDH composed of 180 kDa subunits (mL-GDH180) when incubated with L-glutamate and NAD+. Classification of the heterogeneous population of tetramers into different subsets reveals opening-closing motions and sorting of individual subunits resolves the occupancy of the cofactor and substrate binding pockets. Maps show that ligand binding to the glutamate binding pocket is accompanied by structural changes in a distant region that mediates a novel interaction between the catalytic domains of neighboring subunits in closed tetrameric states. Our findings indicate that the occupancy of the orthosteric site of mL-GDH180is linked to a remodeling of the enzyme tertiary and quaternary structure.
The GPR4 antagonist NE-52-QQ57 increases survival, mitigates the hyperinflammatory response and reduces viral load in SARS-CoV-2-infected K18-hACE2 transgenic mice
Authors: Wu Xin-Jun , Oppelt Karen A. , Fan Ming , Marie Mona A. , Swyers Madison M. , Williams Ashley J. , Lemasson Isabelle M. , Roper Rachel L. , Bolin Paul , Yang Li V. 
Published: December 2024

AbstractCOVID-19 (Coronavirus disease 19) is caused by infection with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in the respiratory system and other organ systems. Tissue injuries resulting from viral infection and host hyperinflammatory responses may lead to moderate to severe pneumonia, systemic complications, and even death. While anti-inflammatory agents have been used to treat patients with severe COVID-19, their therapeutic effects are limited. GPR4 (G protein-coupled receptor 4) is a pro-inflammatory receptor expressed on vascular endothelial cells, regulating leukocyte infiltration and inflammatory responses. In this study, we evaluated the effects of a GPR4 antagonist, NE-52-QQ57, in the SARS-CoV-2-infected K18-hACE2 transgenic mouse model. Our results demonstrated that GPR4 antagonist treatment increased the survival rate in this severe COVID-19 mouse model. The inflammatory response, characterized by proinflammatory cytokines and chemokines, was reduced in the GPR4 antagonist group compared with the vehicle group. Additionally, both SARS-CoV-2 RNA copy numbers and infectious viral titers in the mouse lung were decreased in the GPR4 antagonist group. The percentage of SARS-CoV-2 antigen-positive mouse brains was also decreased in the GPR4 antagonist group compared to the vehicle group. Furthermore, the GPR4 antagonist inhibited SARS-CoV-2 propagation in Vero E6 cells. Together, these results suggest that GPR4 antagonism may be explored as a novel approach for the treatment of COVID-19 and other similar viral diseases.
Targeting primary and metastatic ovarian cancer with a peptide derived from the human NAF-1/CISD2 protein
Authors: Neumann Ehud , Sohn Yang Sung , Karmi Ola , Darash Yahana Merav , Cardenas Alfredo E. , Pikarsky Eli , Elber Ron , Friedler Assaf , Mittler Ron , Nechushtai Rachel 
Published: December 2024

AbstractOvarian cancer is the most fatal cancer of female reproductive organs. Ovarian cancer is typically diagnosed at a late stage, after metastasis occurred, leading to a 5-years relative survival rate of only ∼5%. Here, we demonstrate the anti-ovarian cancer properties of a peptide derived from the human protein CISD2/NAF-1 (3D-NAF-144-67-6K). This peptide selectively permeates the plasma membrane of ovarian cancer SKOV-3 cells without affecting healthy cells. 3D-NAF-144-67-6Ktargets and destroys the cancer cells’ mitochondria which leads to cancer cell death.In vivostudies of mice carrying xenograft tumours of SKOV-3 showed that the peptide significantly decreased the overall size and growth rate of both primary and metastatic ovarian cancer tumours. We further show that 3D-NAF-144-67-6Khas a broad-spectrum anticancer activity targeting leukaemia, brain, and pancreas cancer cells. Our study suggests that 3D-NAF-144-67-6Kcould be used, alone or in drug combinations, to treat ovarian cancer and improve patient survival.
Long-term, cell type-specific effects of prenatal stress on dorsal striatum and relevant behaviors in mice
Authors: Evans Maya M. , Hing Benjamin W. Q. , Weber Matthew A. , Maurer Sara V. , Baig Ahmed I. , Kim Grace S. , Anema Samantha L. , Ellerbroek Rhett M. , Sivakumar Kartik , Michaelson Jacob J. , Narayanan Nandakumar S. , Stevens Hanna E. 
Published: December 2024

AbstractMaternal stress during pregnancy, or prenatal stress, is a risk factor for neurodevelopmental disorders in offspring, including autism spectrum disorder (ASD). In ASD, dorsal striatum displays abnormalities correlating with symptom severity, but there is a gap in knowledge about dorsal striatal cellular and molecular mechanisms that may contribute. Using a mouse model, we investigated how prenatal stress impacted striatal-dependent behavior in adult offspring. We observed enhanced motor learning and earlier response times on an interval timing task, with accompanying changes in time-related medium spiny neuron (MSN) activity. We performed adult dorsal striatal single-cell RNA sequencing following prenatal stress which revealed differentially expressed genes (DEGs) in multiple cell types; downregulated DEGs were enriched for ribosome and translational pathways consistently in MSN subtypes, microglia, and somatostatin neurons. DEGs in MSN subtypes over-represented ASD risk genes and were enriched for synapse-related processes. These results provide insights into striatal alterations relevant to neurodevelopmental disorders.
Vegetative induction increases plant resistance to antagonistic insect frugivores
Authors: Jacobsen Deidra J. , Hewko Carmen D. 
Published: December 2024

AbstractPlant fitness is shaped by interactions with insect mutualists and antagonists. Vegetative (leaf) herbivory often results in increased allocation of resources to defense in order to deter further damage. This allocation to defense can reduce floral or reproductive allocation. Reductions in floral allocation can have negative effects on pollinator attraction and therefore decrease plant fitness. However, defense-induced changes in reproductive tissues may also be protective against antagonistic fruit-feeding insects (frugivores). This may have important implications for plant fitness when plants experience multiple types of insect damage, but the potential protective effect of herbivory against frugivory is not well-understood.In this study, we tested the prediction that herbivory mediates interactions between plants and their antagonistic frugivores. In the greenhouse, we manipulated vegetative induction inPhysalis pubescens(Solanaceae) and measured the effects on plant fitness via changes in floral and fruit allocation, herbivore resistance in the next generation, and deterrence of an antagonistic frugivore (Chloridea virescens(Lepidoptera)).Vegetative induction inP. pubescensenhanced plant resistance toChloridea virescensfrugivores with minimal negative effects on plant reproductive traits. Vegetative induction reducedC. virescenslarval growth rate on fruits.Chloridea virescensalso avoided induced plants for larval fruit feeding and oviposition. While leaf induction reduced flower size, induction did not negatively affect fruit size, seed set, or seed germination. Furthermore, offspring of induced plants showed increased resistance toManduca sextaleaf herbivory. These findings indicate that herbivore-induced resistance may benefit plant fitness when plants are under simultaneous pressure from herbivores and frugivores.
Taylor’s power law rules the dynamics of allele frequencies during viral evolution in response to host changes
Authors: Silva João M. F. , Olmo-Uceda María J. , Morley Valerie J. , Turner Paul E. , Elena Santiago F. 
Published: December 2024

AbstractSudden and gradual changes in host species composition —transitioning from more permissive to less permissive hosts— have been shown to influence viral fitness, virulence, and rates of molecular evolution. In this study, we analyzed the roles of stochasticity and selection using previously published time-series data from evolving populations of Sindbis virus under different rates of host replacement. First, an approximate Markov model within the Wright-Fisher diffusion framework revealed a reduction in effective population size by approximately half in scenarios involving sudden host changes. These scenarios were also associated with fewer and generally weaker beneficial mutations. Second, genetic distance analysis between populations at consecutive time points indicated that populations undergoing gradual host changes evolved steadily until the original host was no longer present. Distances to the ancestral sequence in these cases exhibited occasional leapfrog phenomena, where the rise of certain haplotypes is not predictable based solely on their relatedness to previously dominant ones. In contrast, populations exposed to sudden host changes displayed less stable compositions and diverged from the ancestral sequence at a more constant rate. Third, we observed that allele frequencies distribution followed a power law consistent with Taylor’s law. Both treatments exhibited high levels of allele aggregation with significant fluctuations, where neutral, beneficial, and deleterious alleles could be distinguished by their general behavior and their position on Taylor’s plot. Finally, we found evidence that the host replacement regime influences the temporal distribution of mutations across the genome.
Effects of Forefoot versus Rearfoot Landing on Biomechanical Risk Factors for Lower Limb Injuries and Performance During Stop-Jump Tasks
Authors: Huang Tianchen , He Yuqi , Mao Lizhi , Ruan Mianfang , Takeshita Daisuke 
Published: December 2024

AbstractBackgroundLower limb injuries commonly occur during sudden deceleration movements. Instructing landing with forefoot or rearfoot is hard to answer, especially considering the injury prevention and keep the performance. Therefore, the purpose of this study is to evaluate the effect of the forefoot and rearfoot landing on the biomechanical risk of lower limb injury prevention and performance during the stop-jumping task.MethodTwenty-three male health subjects were recruited for this study. During a stop-jumping task, three-dimensional kinematic and kinetic, and performance data were collected under two conditions: forefoot landing at initial ground contact and rearfoot landing at initial ground contact. Statistical parametric mapping analysis was used to compare the differences between different landing strategies.ResultSignificant differences were found in ankle internal rotation angle and ankle joint moment at foot initial contact with ground between different landing strategies. Landing with forefoot has shorter stance time compared with landing with rearfoot. In the rearfoot strike, posterior ground reaction force (GRF) and GRF inclination angle were smaller than forefoot strike in 0-14% of the stance phase.ConclusionLanding with forefoot may decrease the risk of non-contact anterior cruciate ligament injuries and have an advancement in quick reaction time, as indicated by decreased stance time, but the risk of lateral ankle sprain may increase for the stop-jump task.
Mixed DAMP/MAMP oligosaccharides promote both growth and defense against fungal pathogens of cucumber
Authors: Pring Sreynich , Kato Hiroaki , Taniuchi Keiko , Camagna Maurizio , Saito Makoto , Tanaka Aiko , Merritt Bryn A. , Argüello-Miranda Orlando , Sato Ikuo , Chiba Sotaro , Takemoto Daigo 
Published: December 2024

ABSTRACTPlants recognize a variety of environmental molecules, thereby triggering appropriate responses to biotic or abiotic stresses. Substances containing microbes-associated molecular patterns (MAMPs) and damage-associated molecular patterns (DAMPs) are representative inducers of pathogen resistance and damage repair, thus treatment of healthy plants with such substances can pre-activate plant immunity and cell repair functions. In this study, the effects of DAMP/MAMP oligosaccharides mixture (Oligo-Mix) derived from plant cell wall (cello-oligosaccharide and xylo-oligosaccharide), and fungal cell wall (chitin-oligosaccharide) were examined in cucumber. Treatment of cucumber with Oligo-Mix promoted root germination and plant growth, along with increased chlorophyll contents in the leaves. Oligo-Mix treatment also induced typical defense responses such as MAP kinase activation and callose deposition in leaves. Pretreatment of Oligo-Mix enhanced disease resistance of cucumber leaves against pathogenic fungiPodosphaera xanthii(powdery mildew) andColletotrichum orbiculare(anthracnose). Oligo-Mix treatment increased the induction of hypersensitive cell death around the infection site of pathogens, which inhibited further infection and the conidial formation of pathogens on the cucumber leaves. RNA-seq analysis revealed that Oligo-Mix treatment upregulated genes associated with plant structural reinforcement, responses to abiotic stresses and plant defense. These results suggested that Oligo-Mix has beneficial effects on growth and disease resistance in cucumber, making it a promising biostimulant for agricultural application.
Understanding the mechanisms underlying microbiota variation in wild tick populations
Authors: Noguerales Víctor , de la Fuente José , Díaz-Sánchez Sandra 
Published: December 2024

AbstractTicks are fascinating arthropods that have developed a unique blood-feeding lifestyle, making them intriguing subjects for understanding how they adapt to living with vertebrate hosts, their ability to transmit diseases, and their versatile roles in the ecosystem. Recent research highlights how significantly microbes impact the evolution of ticks, suggesting a genetic link to their hosts. These microbial partnerships are vital in improving tick nutrition, metabolism, reproduction, and overall survival, highlighting their important role as vectors in diverse ecological environments. In this study, we took a close look at the microbial communities present in three wild tick species—Hyalomma lusitanicum,Rhipicephalus sanguineus, andRhipicephalus bursa—collected from several sites across central Spain. Through high-throughput DNA sequencing of the 16S rRNA gene, we discovered a complex and diverse microbiota largely composed of Proteobacteria, Bacteroidota, and Firmicutes. While all species exhibited a shared core microbiota, notable differences in microbial composition and network microbial interactions suggest that each species may be influenced by ecological and evolutionary factors shaping their microbiota. These insights deepen our understanding of the complex relationships between ticks, their microbiota, and the surrounding environment, which can inform better strategies for managing vectors and controlling pathogens.
Long-term homogenization of vascular plant and lichen communities across Fennoscandian heathlands and tundra is connected to the expansion of an allelopathic dwarf shrub
Authors: Maliniemi Tuija , Kiilunen Petteri , Bråthen Kari Anne , Kapfer Jutta , Bockelie Rosendal Torunn , Grytnes John-Arvid , Saccone Patrick , Virtanen Risto 
Published: December 2024

AbstractBoreal and tundra plant communities are expected to change in biodiversity due to increasing global change pressures such as climate warming. One long-term scenario is increasing compositional similarity, i.e., biotic homogenization, which has been relatively little studied in high-latitude plant communities. Here, we study how the composition and diversity of heathland and tundra plant communities have changed in northern Fennoscandia over several decades. In 2013–2023, we resurveyed 275 historic vegetation plots, originally surveyed in 1964–1975, with percentage covers for vascular plant, bryophyte and lichen species. We analyzed temporal changes in community composition and diversity across the study area and in different habitat types, biogeographic zones, and along the continentality-humidity gradient. We found a strong trend across the study area, with plant communities becoming more similar in composition over the decades. The observed homogenization was associated with compositional changes in vascular plant and lichen communities, and in particular with the encroachment of the evergreen dwarf shrubEmpetrum nigrum. In comparison to vascular plants and lichens, the diversity of bryophytes generally remained more stable over time. Our findings suggest that Fennoscandian heathland and tundra vegetation is transforming towards a more homogenous evergreen dwarf shrub dominated system, which may threaten ecosystem multifunctionality. Our results highlight the importance of exploring biodiversity among different metrics and growth forms to understand the overall changes in heathland and tundra biodiversity.