搜索结果：Biophysics reports

Despite previous reports of hippocampal alterations in breast cancer patients, the structural evolution of hippocampal subfields in relationship with memory remains to be characterized in this population. We aimed to measure hippocampal subfield volumes and their links with memory performances before and after chemotherapy in breast cancer patients compared to healthy controls. Forty-two middle aged women were evaluated, including 19 patients assessed before (T1), one-month (T2) and one-year (T3) after chemotherapy, and 23 controls assessed at T1 and T3. Using high-resolution MRI, hippocampal subfields were automatically segmented. Derived volumetric measures were compared between groups at T1 and T3 and within the patient group (T1, T2, T3). Both encoding and retrieval memory performances were measured using a dedicated task. At T1 and globally (i.e., T1 and T3 together), patients showed lower retrieval performance and larger subiculum and whole hippocampal volumes compared to controls. Volumes of the whole hippocampus and of the Cornu Ammonis (CA) 4-Dentate gyrus increased over time in controls. Longitudinal comparisons within the patients' group did not yield significant changes. Volumes were negatively associated with age in controls, and positively with education level in patients. Our results highlight structural differences in the subiculum and whole hippocampus of breast cancer patients both post-surgery and over the adjuvant treatment course. These modifications may reflect a combination of cancer-related and early perioperative factors, while the lack of subsequent longitudinal changes in patients prevents conclusions regarding the specific impact of chemotherapy. Additional studies with larger sample sizes will be of help to further our findings.

Advanced practice (AP) is a common role expansion strategy for radiographers, involving autonomous clinical activities such as reporting that extend beyond technical tasks. Its benefits on medical imaging efficacy and service continuity were documented. This study aims to investigate radiographers' opinions on AP implementation in Morocco. A cross-sectional study was conducted using an online questionnaire. A random sample of 120 radiographers was drawn from the national Moroccan Association of Radiographers' professional database (N = 605). The questionnaire investigated opinions about prerequisites, competency areas, barriers to implementation, and perceived impacts of AP. Likert scales measured current AP activities, beliefs, and support for AP, with higher scores indicating greater frequency. The response rate was 90.8% (n = 109/120). The findings indicate that radiographers perceived AP regulatory reform (59.6%) as the main prerequisite and the lack of a legal framework as the main barrier. (64.2%). The most expected AP benefit is improved quality of care (74.3%). Most radiographers supported AP, and those working in the public sector showed stronger support (p = 0.037). However, participation in advanced activities is limited, with higher involvement in protocol selection (mean score = 2.8) than in reporting (mean score = 1.2) or communicating diagnostic results (mean score = 1.3). This study provides the first national evidence on Moroccan radiographers' perceptions of AP, highlighting strong belief in its value alongside significant perceived systemic barriers. Results provide a foundation for shaping future policy, education, and workforce planning. Some radiographers take on advanced roles, such as choosing imaging approaches or writing reports, where they work more independently to support patient care. This study used an online survey to ask radiographers in Morocco about their views on introducing advanced practice and how often they take part in these activities. This study found strong support for advanced practice and hope for better care, but also concern about missing laws and limited chances to use advanced skills. This matters because these insights can help leaders plan training, rules, and roles that support safe and effective care.

Transcription factors (TFs) efficiently locate their target DNA sequences by combining three-dimensional diffusion and one-dimensional sliding on nonspecific DNA. To balance rapid sliding with strong specific binding, TFs were proposed to switch between search and recognition conformations. For Escherichia coli lac repressor (LacI), the folding of the hinge helices has been implicated in the conformational switch. Here, we tested how mutations in the hinge region impact the search speed and binding stability. Based on molecular dynamics simulations, we selected two LacI mutants favoring either search or recognition conformation. We measured the binding kinetics of the mutants both in vitro on DNA microarrays with 2479 different Lac operators and in vivo via single-molecule experiments. We identified a mutation that enhances the specificity but reduces binding strength globally, and another mutation that makes the operator binding stronger but also reduces the specificity. However, the altered specificity impacts the search time less than expected. Instead, the major effect was impaired dissociation in response to Isopropyl β-D-1-thiogalactopyranoside (IPTG) induction for the strongly binding mutant. Together with earlier reports of affinity-inducibility trade-offs in LacI, our data support the model in which the trade-off is between binding stability and inducibility rather than between speed and binding stability.

Phytoecdysteroids have garnered increasing interest due to their broad biological and pharmacological properties. The present study reports on the development and validation of a reliable liquid chromatography-mass spectrometry method for the detection and quantification of 20-hydroxyecdysone, turkesterone, and ponasterone. The optimized procedure improved ionization efficiency and chromatographic resolution through gradient elution using 0.1% formic acid in water and acetonitrile. Data acquisition in selective ion monitoring modes ensured high analytical precision, reproducibility, and sensitivity. The method demonstrated excellent linearity, accuracy, repeatability, and low detection limits, making it suitable for routine phytochemical and quality control applications. Application of the method to extracts from nutrient-rich superfoods, including kaniwa, spinach, quinoa, and asparagus, confirmed these plants as natural sources of phytoecdysteroids. Additionally, thirteen commercially available dietary supplements labeled as containing extracts of Rhaponticum carthamoides, Cyanotis arachnoidea, Ajuga turkestanica, or ecdysteroids were analyzed. Several products standardized to 80-95% ecdysterone contained substantially lower amounts than declared, with measured 20-hydroxyecdysone levels ranging from below the limit of detection to approximately 50 mg per capsule, whereas some non-standardized products exhibited moderate to high levels, reaching up to approximately 105 mg per capsule. Variability in turkesterone content was also observed among products marketed as standardized extracts. The method provides a simple, reliable, and accessible approach for the quantitative analysis of major phytoecdysteroids in complex plant matrices and dietary supplements. Its implementation may support phytochemical research, routine quality control, and anti-doping monitoring of ecdysteroid-containing products.

There have been several attempts to develop machine learning (ML) models to identify human infecting viruses from their genomic sequences, with varying degrees of success. Direct comparison between models is problematic, because these models are typically trained and evaluated on different datasets with alternative data splitting schemes, features, and model performance metrics. In this paper we present a standardized dataset of mammal infecting and non-infecting viral pathogens, refined from the previous work of Mollentze et al. to include the latest literature evidence, roughly doubling the number of curated host-virus records available to the community, and new host target labels, primate and mammal. The new host labels were included for several reasons, including previous reports that classification performance is better at broader taxonomic ranks and the idea that there may be more data for primate infection that might serve as a suitable proxy for zoonotic potential and avoidance of false positives for human infection due to absence of evidence. On this dataset, we report the performance of eight machine learning models for predicting mammal-infecting viruses from their genomic sequences. We find that randomly assigning cases in our improved dataset to training/testing sets, when compared to the original assignments into training/testing in Mollentze et al., increases the overall average ROC AUC of prediction of human infection from 0.663 ± 0.070 to 0.784 ± 0.013, consistent with the reduction in phylogenetic distance between train and test sets (relative entropy change from 3.00 to 0.08). The broadest host category of mammal infection can be predicted most reliably at 0.850 ± 0.020. We share our improved dataset and code to enable standardized comparisons of machine learning methods to predict human host infections. Overall, we have presented preliminary evidence that classification of virus host infection is more tractable at higher taxonomic ranks, that unsurprisingly reducing the phylogenetic distance between training and test sets can improve predictive performance, that peptide kmer features appear to be harmful to out of sample model performance, and we are left with the question of whether models for virus host prediction can reasonably be expected to perform well in out of sample scenarios given the likelihood that viruses do not share a common ancestor. Consistent with this concern, when the data is resampled such that there is no overlap between viral families in training and test sets (relative entropy > 24), models perform no better than random chance at prediction of human infection regardless of whether kmers are included (ROC AUC 0.50 ± 0.08) or not (ROC AUC 0.50 ± 0.04).

Molecular dynamics (MD) simulations provide detailed, time-resolved insight into molecular motion. Advances in hardware and software now make very large systems accessible, increasing the need for efficient tools to analyze the resulting trajectories. We introduce mdxplain, a high-level Python API that facilitates the creation of scalable, streamlined, and reusable analysis pipelines for large MD datasets with only a few lines of code. A unified object exposes all functionality, combining typical MD featurization and MD metrics with dimensionality reduction, clustering and feature selection via decision trees, supporting expert and non-expert users in identifying structural patterns and explain the dynamic behavior of their systems. Leveraging metadata annotations for trajectory- and residue-selection, mdxplain can handle multiple topologies in a single execution and uses optimized memory handling to process large datasets (millions of frames) efficiently. Its reports include distributional and time-series plots, representative conformations and decision trees combined with optional 3D visualization via PyMOL and NGLView. Pipelines can be exported at all time, bundling all relevant data for sharing and reuse, ensuring reproducibility and FAIR compliance. The Python API, together with documentation, examples, and tutorials is available on github.com/maximilian-salomon/mdxplain and on mdxplain.de.

Phage display of macrocyclic peptide libraries has proven highly effective for ligand discovery, yet the impact of target immobilization and structural integrity on selection outcomes has not been systematically examined. Using the ZNRF3 ectodomain as a model, we incorporated p-azidophenylalanine (AzF) at three phenylalanine residues with distinct solvent exposures (F217, F85, F156) to enable selective perturbation of the protein's structure via site-specific strain-promoted azide-alkyne cycloaddition (SPAAC) immobilization. Biochemical evaluation of the mutants confirmed efficient conjugation and structural disruption of the protein, with the F156AzF mutant displaying the most significant reduction in activity. Phage selections using a CX12C macrocyclic library demonstrated that enrichment efficiency and sequence diversity correlated with structural preservation: F217AzF and F85AzF yielded robust and overlapping peptide pools, while F156AzF produced few and modestly enriched sequences. Biophysical characterization of top hits indicated that peptides derived from structurally intact immobilizations were most likely to bind wild-type ZNRF3, with the highest-affinity ligand, 85-2 (KD = 124 nM), emerging from the shared pool. This work reports a technique to selectively disrupt protein domains during phage selections, while also demonstrating that the structural integrity of immobilized targets is a primary determinant of phage display success. Not only does the necessity to maintain structural integrity influence sequence composition and affinities of peptides toward native protein targets, but also the overall enrichment efficiency of the selection itself. While disruptive immobilization may still yield useful ligands, strategies that preserve native folds enhance phage enrichment and maximize the identification of biologically relevant binders.

Anecdotal reports about smokers with low SARS-CoV-2 infection rates prompted a search for nicotine and its pyrolysis products as SARS-CoV-2 main protease (MPro) inhibitors. From this search, 3-vinylpyridine was discovered as a weak binder for the MPro S1 subsite and was used subsequently as a de novo starting point for covalent inhibitor design that quickly yielded a highly potent inhibitor, SR-A-174, with an IC50 value of 60 nM. Representing a novel class of MPro inhibitors, SR-A-174 features an N,N-diaryl-α,α-dichloroacetamide scaffold that facilitated rapid exploration of alternative covalent warheads and various N-substituents, leading to the identification of multiple inhibitors with potent antiviral activity. Eight such MPro inhibitor structures were determined, all demonstrating covalent binding to catalytic Cys145 of MPro. In six determined structures, binding is dominated by the covalent bond plus van der Waals contacts, which contrasts with the extensive hydrogen bond networks formed with peptidomimetic inhibitors such as nirmatrelvir. Strikingly, two N,N-diaryl-α,α-dichloroacetamide inhibitors exhibit an unprecedented dual covalent modification mode of the catalytic dyad, forming bonds to both Cys145 and His41 with a concomitant loss of both chlorides and displacing the inhibitors from the S1 subsite. This dyad-targeting reactivity suggests a novel route for bioconjugation of both cysteine and histidine.

Genetically encoded voltage indicators (GEVIs) enable cell‑type-specific optical readout of membrane potential, but two‑photon (2P) spike detection has been hampered by low signal‑to‑noise and ultrafast off‑kinetics, restricting use to specialized microscopes. We introduce FORCE1s, a green, positive‑going GEVI engineered to make robust 2P voltage imaging broadly accessible. FORCE1s brightens from a dark baseline during depolarization, reports spikes with ~100% ΔF / F in awake mice, and displays repolarization kinetics that are tuned for reliable spike detection at sub‑kilohertz frame rates. As a result, FORCE1s supports spike‑resolved multi‑cell recordings on standard resonant-scanning microscopes, and further scales to larger fields of view and neuron counts on advanced modalities. FORCE1s also enables multiplexed voltage-neurotransmitter imaging and extended recordings in freely moving mice using a compact, affordable MEMS‑based 2P miniscope. Together, these advances establish FORCE1s as a community‑ready tool that democratizes deep‑tissue voltage imaging across platforms and experimental contexts.

Due to the rising incidence of skin diseases, the World Health Organization has emphasized the need for improved prevention and treatment strategies. The search for new compounds active against skin lesions and pathologies has attracted significant attention. This work reports the synthesis, analytical, spectroscopic, and electrochemical characterization of four copper(II)-tripeptide complexes using Gly-Gly-Ile (GGI), Ala-Ala-Ala (AAA), Phe-Gly-Gly (FGG), and Val-Tyr-Val (VYV) as ligands. Results show that GGI, AAA, and FGG monodeprotonate and coordinate to copper(II) through the aminic N and the adjacent carbonyl O, following a 1:2 metal-to-ligand stoichiometry. VYV doubly deprotonates and forms a 1:1 complex with the tripeptide coordinated through the aminic N atom a deprotonated amidic N and a carbonyl O. Aqueous solution studies confirm that the tripeptide stays coordinated in the major species in solution. Complexes are redox active in the biologically relevant window, with CuVYV presenting the most accessible Cu(III)/Cu(II) transition. The ability to promote wound healing was assessed through a scratch wound healing assay. CuAAA and CuVYV are promising inducers of wound healing by promoting migration in MRC-5 cells. Cytotoxicity assays confirm that the compounds are not cytotoxic at the doses used for wound repair, making CuAAA and CuVYV interesting candidates for further studies.

Apolipoprotein epsilon (APOE) is a small molecular protein that regulates lipid and lipoprotein homeostasis. Several reports demonstrated that apolipoprotein epsilon-4 allele (APOE4) expression significantly increases the genetic risk of Alzheimer's disease (AD) and chronic kidney disease. However, there is inconsistent evidence of the association of AD with dietary habits, especially salt intake. Therefore, we hypothesized that high dietary salt intake would exacerbate cognitive decline in mice expressing the human APOE4 allele. We used human APOE (APOE4 and APOE3) knock-in mice to test this hypothesis. Young adult male and female mice aged 5-7 months old (n = 18 in each group) were fed a 4% NaCl (high-salt) or a 0.1% NaCl (low-salt) diet for 4 weeks. Metabolic cage studies were used to assess 24 h measurements of food and water intake, and urine output. Spatial memory and learning were determined using the Barnes maze test. Both the APOE3 and APOE4 mice on a low-salt diet had significantly decreased urinary volume, and female mice had lower body weight. The APOE4 mice on the low-salt diet (0.1%) performed significantly better on the 72 h probe test as compared to the APOE4 mice on 4% salt diet. The results demonstrate an association among dietary salt, memory, and APOE4 genotype.

TRIM21 is a multifunctional E3 ubiquitin ligase and intracellular antibody receptor, yet its role during viral infection remains unclear, with reports describing both antiviral and proviral activities. Here, we show that TRIM21 regulates influenza infection in an expression-dependent manner by functioning as a molecular rheostat rather than a binary restriction factor. This graded activity of TRIM21, which leads to both suppression and promotion of influenza replication, couples linkage-specific ubiquitination of viral nucleoprotein with modulation of innate immune signaling. Additionally, loss of TRIM21 unmasks a compensatory antiviral program centered on PRKDC, which is a ubiquitination target of TRIM21. This positions PRKDC as a latent restriction factor selectively engaged when primary TRIM21 control is lost. Together, these findings reveal a hierarchical and plastic antiviral network in which TRIM21 sets an adjustable threshold for host defense while restraining secondary restriction pathways. This framework highlights the sophisticated layers of regulation of the host ubiquitin-mediated antiviral immunity.

Platelet aggregation at sites of vascular injury is essential for hemostasis. However, the mechanisms that prevent excessive clot growth are not fully understood. In the prevailing "core and shell" model, based largely on small vessel injury studies, a central core of highly activated platelets is surrounded by a limited signal intensity shell of less activated, minimally degranulated platelets. Recent reports, especially in mouse models of profuse bleeding, suggest thrombus architecture and platelet activation states are more heterogeneous than the binary core and shell model proposes. Here, we performed high-resolution morphometric mapping of individual platelet activation states in mouse jugular vein and femoral artery puncture wound thrombi, using serial block face scanning electron microscopy and wide-area transmission electron microscopy. Manually annotated images were analyzed at multiple time points, revealing initial, 1-minute, near-complete intermixing of platelet activation states with no distinct core of highly activated platelets. At 5 minutes, highly activated, degranulated platelets became concentrated along the interior surfaces of vaulted thrombus structures. At 20 minutes, platelet numbers decreased and distinct clustering of degranulated, highly activated platelets was observed within central portions of the intravascular platelet-rich crown, limiting their access to the circulation. Deletion of the α-granule vesicle-soluble N-ethylmaleimide-sensitive factor attachment protein receptor, vesicle associated membrane protein 8, increased both the frequency and clustering of highly activated platelets. Similar patterns were observed in femoral artery wounds. We conclude that thrombus organization is more complex than previously recognized and provide evidence that progressive structural changes help limit procoagulant surface exposure and thrombus growth during hemostasis after puncture wounding.

This Letter reports the first measurement of photonuclear D^{0} meson production in ultraperipheral heavy ion collisions. The study is performed using lead-lead collision data, with an integrated luminosity of 1.34  nb^{-1}, collected by the CMS experiment at a nucleon-nucleon center-of-mass energy of 5.36 TeV. Photonuclear events, where one of the colliding nuclei breaks up and the other remains intact, are selected based on breakup neutron emissions and by requiring no particle activity in a large rapidity interval in the direction of the photon-emitting nucleus. The D^{0} mesons are reconstructed via the D^{0}→K^{-}π^{+} decay channel, with the cross section measured as a function of D^{0} meson transverse momentum and rapidity. The results are compared with next-to-leading-order perturbative QCD calculations that employ recent parametrizations of the lead nuclear parton distribution functions, as well as with predictions based on the color glass condensate framework. This measurement is the first photonuclear collision study characterizing parton distribution functions of lead nuclei for parton fractional momenta x (relative to the nucleon) ranging approximately from a few 10^{-4} to 10^{-2} for different hard energy scale Q^{2} selections.

Photosynthesis constantly adapts to fluctuating light and temperature. Under high light, non-photochemical quenching (NPQ) protects the photosynthetic machinery by dissipating excess excitation energy as heat. With rising global temperatures and more frequent heat events, understanding how photosynthesis responds to combined light and temperature stress is critical. In vascular plants, NPQ is regulated by the protonation of Photosystem II subunit S (PsbS) and the enzymatic formation of zeaxanthin, but it remains unclear how temperature influences the complete NPQ response and the roles of these molecular components. Here, we analyzed NPQ in Arabidopsis thaliana WT and mutant genotypes affecting PsbS, zeaxanthin, or thylakoid membrane fluidity: npq1 (no zeaxanthin), npq2 (constitutive zeaxanthin), npq4 (no PsbS), PsbS-OE (overexpressed PsbS), and fad7fad8 (more rigid membranes). Plants were acclimated to 10 °C, 20 °C, 30 °C, or 40 °C for 30 min before measuring NPQ induction and relaxation. NPQ kinetics generally accelerated with increasing temperature, enabling faster responses to fluctuating light, and more absorbed energy was allocated to photochemistry rather than dissipation. Our results suggest that the concentration of PsbS is important to regulate this balance between photochemistry and NPQ. Full NPQ development and its temperature dependence required both PsbS and zeaxanthin. Arrhenius analysis of the NPQ induction and relaxation rates revealed that NPQ induction could be hindered by a rigid thylakoid membrane. These results demonstrate that NPQ is modulated by temperature, highlighting the importance of considering thermal effects on photoprotection when predicting plant performance under future climates.

Ferroptosis is a new form of cell death driven by iron-dependent lipid peroxidation. Thus, it is closely related to the lipid and iron metabolism. Accumulating evidence has suggested mitochondria, the center of cell metabolism, are important regulators of ferroptosis. This is not surprising as mitochondria are also the center for lipid metabolism and iron metabolism, as well as redox balance. As the essential way of mitochondrial quality control, mitophagy may alleviate ferroptosis. On the other hand, the digestion of iron-rich mitochondria may provide ample sources for the activation of ferroptosis. This review describes these new findings about the interplay of mitophagy and ferroptosis and demonstrates the dual role of mitophagy in ferroptosis.

T cell receptors (TCRs) can recognize peptides presented by major histocompatibility complex (MHC) molecules, referred to as HLA in humans, which enables the targeted eradication of tumor cells expressing specific antigens. In recent years, TCR-engineered T cell (TCR-T) cell therapy has demonstrated substantial advancements in clinical trials targeting solid tumors. Notably, in August 2024, the U.S. FDA approved the first TCR-T drug for the treatment of advanced synovial sarcoma, representing a pivotal milestone in the field. For the development of TCR-T therapy, identifying tumor-associated antigen epitopes and high-functional TCRs are critical. Here, we present a comprehensive protocol outlining the process of identification of immunogenic epitopes and the efficient screening of antigen-specific TCRs from HLA transgenic mice. Additionally, the protocol encompasses methodologies for TCR-T cell preparation and their functional evaluation in vitro. These approaches provide a robust framework for advancing the development of tumor-specific TCRs and fostering the clinical translation of TCR-T therapies.

The m5C modification is one of the widely occurring modifications on RNA. In recent years, m5C modification on RNA has increasingly become a focal point in cancer research. Nevertheless, investigating scientific and quantitative research on the publication trends in this field can help us understand the research background and emerging hotspots, providing insights for targeting RNA m5C sites in cancer therapy. Co-occurrence analyses and visualizations, including authorship, keywords, genes and diseases, were performed using VOSviewer. CiteSpace was used to identify bursting institutions, keywords and references. R packages, including clusterProfiler, enrichplot and ggplot2, were used to visualize the enrichment results of GO and KEGG. The top contributors to this field were the United States and China, and the journals with the most publications were Frontiers in Genetics and Frontiers in Oncology. The most common keyword was "m5C methylation" and the most related genes were "NSUN2", "AKT1" and "METTL3". This study conducted a bibliometric analysis covering the development process of RNA m5C modification in cancer progression, identifying the countries, institutions, authors, journals, and publications in this field. Additionally, we found that the genes most closely associated with m5C are likely to play a significant role in the process of viral oncogenesis. These findings provide a comprehensive overview of RNA m5C modification during cancer research and insights into RNA m5C-tageted cancer therapy.

Common variable immunodeficiency disorder (CVID) is the most prevalent primary immunodeficiency in adults. Pathogenic mutations of the TNFRSF13B gene were identified in CVID patients and associated with autoimmunity and lymphoproliferation. A study on Swedish children unaffected by CVID has shown that rare variants in the TNFRSF13B gene increase the risk of asthma. To the best of our knowledge, asthma has not been reported in CVID patients with TNFRSF13B gene mutations. We described a patient suffering from asthma and CVID with a heterozygous mutation in the TNFRSF13B gene. According to our findings and previous studies, mutations in the TNFRSF13B gene seem to be possibly associated with the occurrence of asthma in CVID patients.