Autoantibodies against eukaryotic translation elongation factor 1 delta in two patients with autoimmune cerebellar ataxia

BackgroundAutoantibodies are useful biomarkers for the early detection and diagnosis of autoimmune cerebellar ataxia (ACA).ObjectiveTo identify novel autoantibody candidates in ACA patients.MethodsPatients with cerebellar ataxia of unknown cause were recruited from July 2018 to February 2023. Anti-neural autoantibodies in patient samples were detected by tissue-based indirect immunofluorescence assay (TBA) on rat cerebellum sections. TBA-positive samples were further screened for well-established anti-neural autoantibodies using commercial kits. Tissue-immunoprecipitation (TIP) and subsequent mass spectrometric (MS) analysis were used to explore the target antigens of autoantibodies in samples that were TBA-positive but negative for known autoantibodies. The specific binding between autoantibodies and the identified target antigen was confirmed by neutralization experiments, recombinant cell-based indirect immunofluorescence assay (CBA), and western blotting experiments.ResultsThe eukaryotic translation elongation factor 1 delta (EEF1D) protein was identified as a target antigen of autoantibodies in samples from a 43-year-old female ACA patient, while the specific binding of autoantibodies and EEF1D was confirmed by subsequent experiments. A second anti-EEF1D autoantibody-positive ACA patient, a 59-year-old female, was detected in simultaneous screening. The main clinical manifestations in each of the two patients were cerebellar syndrome, such as unsteady walking and limb ataxia. Both patients received immunotherapy, including corticosteroids, intravenous immunoglobulin, and mycophenolate mofetil. Their outcomes provided evidence to support the effectiveness of immunotherapy, but the cerebellar atrophy that occurred before treatment may be irreversible.ConclusionIn the current study, we identified anti-EEF1D autoantibody as a novel autoantibody candidate in ACA. Its pathological roles and diagnostic value need to be further verified in larger-scale studies

A comprehensive review of computation-based metal-binding prediction approaches at the residue level

Clear evidence has shown that metal ions strongly connect and delicately tune the dynamic homeostasis in living bodies. They have been proved to be associated with protein structure, stability, regulation, and function. Even small changes in the concentration of metal ions can shift their effects from natural beneficial functions to harmful. This leads to degenerative diseases, malignant tumors, and cancers. Accurate characterizations and predictions of metalloproteins at the residue level promise informative clues to the investigation of intrinsic mechanisms of protein-metal ion interactions. Compared to biophysical or biochemical wet-lab technologies, computational methods provide open web interfaces of high-resolution databases and high-throughput predictors for efficient investigation of metal-binding residues. This review surveys and details 18 public databases of metal-protein binding. We collect a comprehensive set of 44 computation-based methods and classify them into four categories, namely, learning-, docking-, template-, and meta-based methods. We analyze the benchmark datasets, assessment criteria, feature construction, and algorithms. We also compare several methods on two benchmark testing datasets and include a discussion about currently publicly available predictive tools. Finally, we summarize the challenges and underlying limitations of the current studies and propose several prospective directions concerning the future development of the related databases and methods

The Combination of Molecular Adjuvant CCL35.2 and DNA Vaccine Significantly Enhances the Immune Protection of Carassius auratus gibelio against CyHV-2 Infection

Cyprinid herpesvirus 2 (CyHV-2) infection results in huge economic losses in gibel carp (Carassius auratus gibelio) industry. In this study, we first constructed recombinant plasmids pcORF25 and pcCCL35.2 as DNA vaccine and molecular adjuvant against CyHV-2, respectively, and confirmed that both recombinant plasmids could be effectively expressed in vitro and in vivo. Then, the vaccination and infection experiments (n = 50) were set as seven groups. The survival rate (70%) in ORF25/CCL35.2 group was highest. The highest specific antibody levels were found in ORF25/CCL35.2 group in major immune tissues by qRT-PCR, and confirmed in serum by ELISA assay, antibody neutralization titer, and serum incubation-infection experiments. Three crucial innate immune indices, namely C3 content, lysozyme, and total superoxide dismutase (TSOD) activities, were highest in ORF25/CCL35.2 group in serum. pcORF25/pcCCL35.2 can effectively up-regulate mRNA expressions of some important immune genes (IL-1β, IL-2, IFN-γ2, and viperin), and significantly suppress CyHV-2 replication in head kidney and spleen tissues. The minimal tissue lesions can be seen in ORF25/CCL35.2 group in gill, spleen, and trunk kidney tissues by histopathological examination. The results indicated that the combination of DNA vaccine pcORF25 and molecular adjuvant pcCCL35.2 is an effective method against CyHV-2 infection, suggesting a feasible strategy for the control of fish viral diseases

Research on Users’ Exercise Behaviors of Online Exercise Community Based on Social Capital Theory

Online exercise communities play an important role in their users’ self-health management. The willingness of users to interact and create user-generated content in online communities reflects the vitality of the online exercise community and the positive impact it has on offline users’ health performance. Therefore, based on social capital theory, we study the relationship between three types of social capital and users’ offline exercise behaviors and add off-topics in the community in the model. We select the KEEP health community user group as the research setting and conduct the regression analysis. The results show that owned centrality and reciprocity have a significant positive relationship with users’ exercise behaviors; accessed centrality and trust have a significant negative relationship with users’ exercise behaviors; and common topics and off-topics show a partly significant correlation. As a moderating variable, off-topics have a negative moderating effect on owned centrality and betweenness centrality, but a positive moderating effect on reciprocity and trust among group members. The results enrich and expand social capital theory, deepen the research on users’ exercise behaviors in the online exercise community, and provide a good reference for online exercise community management

Analysis on Pigment and Photosynthetic Characteristics of Leaves of New Strain of Rehmannia glutinosa

Through the analysis on the leaf color and photosynthetic characteristics of new strains and main cultivars of Rehmannia glutinosa, it is expected to provide theoretical basis for breeding of new varieties. Chlorophyll, anthocyanin, and net photosynthetic rate (Pn), stomatal conductance (Cond), transpiration rate (Tr), and intercellular CO2 concentration (Ci) in 8 varieties of Rehmannia glutinosa were measured by spectrophotometer and LI-6400XT Portable Photosynthesis System. The results showed that the chlorophyll content of Huaidijin 8 (2.84 mg/g), Huaidi 81 (2.71 mg/g), Huaidi 85-5 (2.69 mg/g), Jinjiu (2.66 mg/g) and Huaidi 83 (2.63 mg/g) was higher; the anthocyanin content of Jinjiu (0.169) and Huaidijin 8 (0.165) was higher, while the anthocyanin content Huaidi 83(0.060) was the lowest; Pn of Huaidi 81 [2.41 μmol/(m2·s)], Huaidi 83 [2.37 μmol/(m2·s)] and Huaidijin 8 [2.25 μmol/(m2·s)] was higher, and the anthocyanin content was positively correlated with Pn, while the anthocyanin content was negatively correlated with Pn; Huaidijin 8 and Huaidi 83 showed dominant advantages in single plant fresh weight, indicator component, and resistance over the main cultivars. This indicates that the new variety Huaidijin 8 and Huaidi 83 have excellent comprehensive traits and can be properly popularized

2-Amino-5-methylpyridinium nitrate

In the title salt, C6H9N2+·NO3−, the 2-amino-5-methylpyridinium cation and the nitrate anion are cyclically linked through pyridinium and amine N—H...O hydrogen bonds [graph set R43(12)]. These units are extended into a zigzag chain structure lying parallel to the a axis, through a second cyclic R22(8) association involving amine N—H...O and aromatic C—H...O hydrogen bonds to nitrate O-atom acceptors

The Circular RNA Profiles of Colorectal Tumor Metastatic Cells

Circular RNAs (circRNAs) have been reported that can be used as biomarkers for colorectal cancers (CRC) and other types of tumors. However, a limited number of studies have been performed investigating the potential role of circRNAs in tumor metastasis. Here, we examined the circRNAs in two CRC cell lines (a primary tumor cell SW480 and its metastasis cell SW620), and found a large set of circRNA (2,919 ncDECs) with significantly differential expression patterns relative to normal cells (NCM460). In addition, we uncovered a set of 623 pmDECs that differ between the primary CRC cells and its metastasis cells. Both differentially expressed circRNA (DEC) sets contain many previously unknown putative CRC-related circRNAs, thereby providing many new circRNAs as candidate biomarkers for CRC development and metastasis. These studies are the first large-scale identification of metastasis-related circRNAs for CRC and provide valuable candidate biomarkers for diagnostic and a starting point for additional investigations of CRC metastasis

Protective Effect of Lycium ruthenicum Murr. Against Radiation Injury in Mice

The protective effect of Lycium ruthenicum Murr. against radiation injury was examined in mice. Kunming mice were randomly divided into a control group, model group, positive drug group and L. ruthenicum high dose (8 g/kg), L. ruthenicum middle dose (4 g/kg), L. ruthenicum low dose (2 g/kg) treatment groups, for which doses were administered the third day, seventh day and 14th day after irradiation. L. ruthenicum extract was administered orally to the mice in the three treatment groups and normal saline was administered orally to the mice in the control group and model group for 14 days. The positive group was treated with amifostine (WR-2721) at 30 min before irradiation. Except for the control group, the groups of mice received a 5 Gy quantity of X-radiation evenly over their whole body at one time. Body weight, hemogram, thymus and spleen index, DNA, caspase-3, caspase-6, and P53 contents were observed at the third day, seventh day, and 14th day after irradiation. L. ruthenicum could significantly increase the total red blood cell count, hemoglobin count and DNA contents (p < 0.05). The spleen index recovered significantly by the third day and 14th day after irradiation (p < 0.05). L. ruthenicum low dose group showed a significant reduction in caspase-3 and caspase-6 of serum in mice at the third day, seventh day, and 14th day after irradiation and L. ruthenicum middle dose group experienced a reduction in caspase-6 of serum in mice by the seventh day after irradiation. L. ruthenicum could decrease the expression of P53. The results showed that L. ruthenicum had protective effects against radiation injury in mice