Generation and Bioenergetic Profiles of Cybrids with East Asian mtDNA Haplogroups

Human mitochondrial DNA (mtDNA) variants and haplogroups may contribute to susceptibility to various diseases and pathological conditions, but the underlying mechanisms are not well understood. To address this issue, we established a cytoplasmic hybrid (cybrid) system to investigate the role of mtDNA haplogroups in human disease; specifically, we examined the effects of East Asian mtDNA genetic backgrounds on oxidative phosphorylation (OxPhos). We found that mtDNA single nucleotide polymorphisms such as m.489T>C, m.10398A>G, m.10400C>T, m.C16223T, and m.T16362C affected mitochondrial function at the level of mtDNA, mtRNA, or the OxPhos complex. Macrohaplogroup M exhibited higher respiratory activity than haplogroup N owing to its higher mtDNA content, mtRNA transcript levels, and complex III abundance. Additionally, haplogroup M had higher reactive oxygen species levels and NAD+/NADH ratios than haplogroup N, suggesting difference in mitonuclear interactions. Notably, subhaplogroups G2, B4, and F1 appeared to contribute significantly to the differences between haplogroups M and N. Thus, our cybrid-based system can provide insight into the mechanistic basis for the role of mtDNA haplogroups in human diseases and the effect of mtDNA variants on mitochondrial OxPhos function. In addition, studies of mitonuclear interaction using this system can reveal predisposition to certain diseases conferred by variations in mtDNA

Immunogenicity and Protective Capacity of Sugar ABC Transporter Substrate-Binding Protein against Streptococcus suis Serotype 2, 7 and 9 Infection in Mice

Background: Streptococcus suis (S. suis) is a Gram-positive bacterium that causes substantial disease in pigs. S. suis is also an emerging zoonoses in humans, primarily in Asia, through the consumption of undercooked pork and the handling of infected pig meat as well as carcasses. The complexity of S. suis epidemiology, characterized by the presence of multiple bacterial serotypes and strains with diverse sequence types, identifies a critical need for a universal vaccine with the ability to confer cross-protective immunity. Highly conserved immunogenic proteins are generally considered good candidate antigens for subunit universal vaccines. Methods: In this study, the cross-protection of the sugar ABC transporter substrate-binding protein (S-ABC), a surface-associated immunogenic protein of S. suis, was examined in mice for evaluation as a universal vaccine candidate. Results: S-ABC was shown to be highly conserved, with 97% amino acid sequence identity across 31 S. suis strains deposited in GenBank. Recombinantly expressed S-ABC (rS-ABC) was recognized via rabbit sera specific to S. suis serotype 2. The immunization of mice with rS-ABC induced antigen-specific antibody responses, as well as IFN-γ and IL-4, in multiple organs, including the lungs. rS-ABC immunization conferred high (87.5% and 100%) protection against challenges with S. suis serotypes 2 and 9, demonstrating high cross-protection against these serotypes. Protection, albeit lower (50%), was also observed in mice challenged with S. suis serotype 7. Conclusions: These data identify S-ABC as a promising antigenic target within a universal subunit vaccine against S. suis

Multi-omics analysis of the biological mechanism of the pathogenesis of non-alcoholic fatty liver disease

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a type of liver metabolic syndrome. Employing multi-omics analyses encompassing the microbiome, metabolome and transcriptome is crucial for comprehensively elucidating the biological processes underlying NAFLD.MethodsHepatic tissue, blood and fecal samples were obtained from 9 NAFLD model mice and 8 normal control mice. Total fecal microbiota DNA was extracted, and 16S rRNA was amplified, to analyze alterations in the gut microbiota (GM) induced by NAFLD. Subsequently, diagnostic strains for NAFLD were screened, and their functional aspects were examined. Differential metabolites and differentially expressed genes were also screened, followed by enrichment analysis. Correlations between the differential microbiota and metabolites, as well as between the DEGs and differential metabolites were studied. A collinear network involving key genes-, microbiota-and metabolites was constructed.ResultsIleibacterium and Ruminococcaceae, both belonging to Firmicutes; Olsenella, Duncaniella and Paramuribaculum from Bacteroidota; and Bifidobacterium, Coriobacteriaceae_UCG_002 and Olsenella from Actinobacteriota were identified as characteristic strains associated with NAFLD. Additionally, differentially expressed metabolites were predominantly enriched in tryptophan, linoleic acid and methylhistidine metabolism pathways. The functions of 2,510 differentially expressed genes were found to be associated with disease occurrence. Furthermore, a network comprising 8 key strains, 14 key genes and 83 key metabolites was constructed.ConclusionThrough this study, we conducted a comprehensive analysis of NAFLD alterations, exploring the gut microbiota, genes and metabolites of the results offer insights into the speculated biological mechanisms underlying NAFLD

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

The Role of Context in Stimulus-Response Binding and Retrieval

Feature binding has been proven to be a common and general mechanism underlying human information processing and action control. There is strong evidence showing that when humans perform a task, stimuli (e.g., the target, the distractor) and responses are bound together into an episodic representation, called an event file or a stimulus-response (S-R) episode, which can be retrieved upon feature repetition. As compared with the target and the distractor, the context (i.e., an additional stimulus presented together with the target and the distractor, but not associated with any response keys throughout the whole course of the task), which is considered as task-irrelevant, did not receive that much attention in previous studies. The current thesis was aimed to provide insights into the different roles the context plays in S-R binding and retrieval. Specifically, in Study One and Two, the role of context as an element that can be integrated into an S-R episode was investigated, with a focus on the saliency and the inter-trial variability of the contextual stimulus. Both properties were found to influence how the context is integrated into an S-R episode. More specifically, results show that both saliency and inter-trial variability determine whether the context is directly bound in a binary fashion with the response, or it enters in to a configural binding together with another stimulus and the response. In Study Three, intrigued by the role of context as an event segmentation factor in the event perception literature, whether the context can demarcate the integration window of an S-R episode was tested. Results provide consistent evidence that sharing a common context leads to a stronger binding between a stimulus and the response, as compared with the condition when these elements are separated by different contexts, thereby suggesting a binding principle of common context. Taken together, the current thesis specifies the role of context in S-R binding and retrieval, and sheds some light on how contextual information influences human behavior

N170 Reveals the Categorical Perception Effect of Emotional Valence

As an important attribute of facial expression, emotional valence has been well explored, but its processing mechanisms remain ambiguous. Investigating the categorical perception (CP) of emotional valence might help uncover the objective basis of the subjective dichotomy of emotional valence and identify the stage at which this processing of valence information might occur. A judgment task was used in the current study with stimuli from the within- or between-category condition, in which participants were required to decide whether two presented faces showed the same emotion. The results of the behavioral experiment revealed a significant CP effect of emotional valence, with faster RTs and greater accuracy for the between- than for the within-category stimuli. In the ERP experiment, the N170 (peaking at approximately 150–170 ms) was found to reflect the CP effect of emotional valence, with a larger amplitude for the within- than for the between-category condition. In contrast, the P1 component (peaking at approximately 100–130 ms) was insensitive to the CP effect of emotional valence. These results reveal the existence of the CP of emotional valence and indicate that the N170 is its earliest electrophysiological index. Therefore, the categorization of emotional valence not only has an objective neural basis but occurs at a relatively early stage of processing

Freezing-Thawing Damage Mechanism of Coal Gangue Concrete Based on Low-Field Nuclear Magnetic Resonance, Scanning Electron Microscopy, and N2 Adsorption

To study waterborne frost heaving failure mechanism of coal gangue ceramsite concrete (CGCC) under freeze-thaw cycles, capillary water absorption test, nonmetallic ultrasonic testing test, low-field nuclear magnetic resonance (LNMR) test, N2 adsorption test, and other tests were used to determine the effect of freeze-thaw cycles on the porosity, relative dynamic elastic modulus (RDM), and capillary adsorption rate of different coal gangue ceramsite (MT) replacement rates (0, 20%, 40%, and 60%). Combining the changes of performance indexes and the changes of micropore structure under freeze-thaw cycles, the freeze-thaw failure mechanism of normal concrete (OC) and CGCC was analyzed. In view of the particularity of MT material, the method based on pore size is put forward to distinguish M pores from T pores, and the reasons for different properties are analyzed from the microperspective. The results show that the freeze-thaw cycle changes the microstructure of coal gangue concrete and has an obvious influence on its properties. And when the replacement rate is 40%, degradation mitigation performance is optimal. Due to the particularity of MT shape, T pores are dominant in coal gangue concrete matrix, which is different from the microstructure of ordinary concrete and can reduce the structural deterioration caused by freeze-thaw. The research results of this paper can provide a reference for the research and application of CGCC in freeze-thaw environment