The neural representation of body part concepts.

Neuropsychological and neuroimaging studies provide evidence for a degree of category-related organization of conceptual knowledge in the brain. Some of this evidence indicates that body part concepts are distinctly represented from other categories; yet, the neural correlates and mechanisms underlying these dissociations are unclear. We expand on the limited prior data by measuring functional magnetic resonance imaging responses induced by body part words and performing a series of analyses investigating the cortical representation of this semantic category. Across voxel-level contrasts, pattern classification, representational similarity analysis, and vertex-wise encoding analyses, we find converging evidence that the posterior middle temporal gyrus, the supramarginal gyrus, and the ventral premotor cortex in the left hemisphere play important roles in the preferential representation of this category compared to other concrete objects.

Palmitoylation is required for Sept8-204 and Sept5 to form vesicle-like structure and colocalize with synaptophysin.

Sept8 is a vesicle associated protein and there are two typical transcriptional variants (Sept8-204 and Sept8-201) expressed in mice brain. Interestingly, the coexpression of Sept8-204/Sept5 induces the formation of small sized vesicle-like structure, while that of the Sept8-201/Sept5 produces large puncta. Sept8 is previously shown to be palmitoylated. Here it was further revealed that protein palmitoylation is required for Sept8-204/Sept5 to maintain small sized vesicle-like structure and colocalize with synaptophysin, since either the expression of nonpalmitoylated Sept8-204 mutant (Sept8-204-3CA) or inhibiting Sept8-204 palmitoylation by 2-BP with Sept5 produces large puncta, which barely colocalizes with synaptophysin (SYP). Moreover, it was shown that the dynamic palmitoylation of Sept8-204 is controlled by ZDHHC17 and PPT1, loss of ZDHHC17 decreases Sept8-204 palmitoylation and induces large puncta, while loss of PPT1 increases Sept8-204 palmitoylation and induces small sized vesicle-like structure. Together, these findings suggest that palmitoylation is essential for the maintenance of the small sized vesicle-like structure for Sept8-204/Sept5, and may hint their important roles in synaptic functions.

VMP1: a multifaceted regulator of cellular homeostasis with implications in disease pathology.

Vacuole membrane protein 1 (VMP1) is an integral membrane protein that plays a pivotal role in cellular processes, particularly in the regulation of autophagy. Autophagy, a self-degradative mechanism, is essential for maintaining cellular homeostasis by degradation and recycling damaged organelles and proteins. VMP1 involved in the autophagic processes include the formation of autophagosomes and the subsequent fusion with lysosomes. Moreover, VMP1 modulates endoplasmic reticulum (ER) calcium levels, which is significant for various cellular functions, including protein folding and cellular signaling. Recent studies have also linked VMP1 to the cellular response against viral infections and lipid droplet (LD). Dysregulation of VMP1 has been observed in several pathological conditions, including neurodegenerative diseases such as Parkinson's disease (PD), pancreatitis, hepatitis, and tumorogenesis, underscoring its potential as a therapeutic target. This review aims to provide an overview of VMP1's multifaceted roles and its implications in disease pathology.

Correction: Enhancing Specific-Antibody Production to the ragB Vaccine with GITRL That Expand Tfh, IFN-γ+ T Cells and Attenuates Porphyromonas gingivalis Infection in Mice.

[This corrects the article DOI: 10.1371/journal.pone.0059604.].

Serum metabolomics analysis of patients with chronic obstructive pulmonary disease and 'frequent exacerbator' phenotype.

Chronic obstructive pulmonary disease (COPD) exacerbations accelerate loss of lung function and increased mortality. The complex nature of COPD presents challenges in accurately predicting and understanding frequent exacerbations. The present study aimed to assess the metabolic characteristics of the frequent exacerbation of COPD (COPD­FE) phenotype, identify potential metabolic biomarkers associated with COPD­FE risk and evaluate the underlying pathogenic mechanisms. An internal cohort of 30 stable patients with COPD was recruited. A widely targeted metabolomics approach was used to detect and compare serum metabolite expression profiles between patients with COPD­FE and patients with non­frequent exacerbation of COPD (COPD­NE). Bioinformatics analysis was used for pathway enrichment analysis of the identified metabolites. Spearman's correlation analysis assessed the associations between metabolites and clinical indicators, while receiver operating characteristic (ROC) analysis evaluated the ability of metabolites to distinguish between two groups. An external cohort of 20 patients with COPD validated findings from the internal cohort. Out of the 484 detected metabolites, 25 exhibited significant differences between COPD­FE and COPD­NE. Metabolomic analysis revealed differences in lipid, energy, amino acid and immunity pathways. Spearman's correlation analysis demonstrated associations between metabolites and clinical indicators of acute exacerbation risk. ROC analysis demonstrated that the area under the curve (AUC) values for D­fructose 1,6­bisphosphate (AUC=0.871), arginine (AUC=0.836), L­2­hydroxyglutarate (L­2HG; AUC=0.849), diacylglycerol (DG) (16:0/20:5) (AUC=0.827), DG (16:0/20:4) (AUC=0.818) and carnitine­C18:2 (AUC=0.804) were >0.8, highlighting their discriminative capacity between the two groups. External validation results demonstrated that DG (16:0/20:5), DG (16:0/20:4), carnitine­C18:2 and L­2HG were significantly different between patients with COPD­FE and those with COPD­NE. In conclusion, the present study offers insights into early identification, mechanistic understanding and personalized management of the COPD­FE phenotype.

Interhemispheric Connectivity of the Human Temporal Lobes.

Much is known regarding the major white matter pathways connecting the right and left temporal lobes, which project through the posterior corpus callosum, the anterior commissure, and the dorsal hippocampal commissure. However, details about the spatial location of these tracts are unclear, including their exact course and proximity to cortical and subcortical structures, the spatial relations between corpus callosum and anterior commissure projections, and the caudal extent of transcallosal connections within the splenium. We present an atlas of these tracts derived from high angular resolution diffusion tractography maps, providing improved visualization of the spatial relationships of these tracts. The data show several new details, including branching of the transcallosal pathway into medial and lateral divisions, projections of the transcallosal pathway into the external capsule and claustrum, complex patterns of overlap and interdigitation of the transcallosal and anterior commissure tracts, distinct dorsal and ventral regions of the splenium with high tract densities, and absence of temporal lobe projections in the caudal third of the splenium. Intersection of individual tract probability maps with individual cortical surfaces were used to identify likely regions with relatively higher cortical termination densities. These data should be useful for planning surgical approaches involving the temporal lobe and for developing functional-anatomical models of processes that depend on interhemispheric temporal lobe integration, including speech perception, semantic memory, and social cognition. Highlights: Interhemispheric connections of the human temporal lobes were visualized using high angular resolution diffusion tensor imaging tractography.Results are displayed on serial orthogonal sections to reveal detailed spatial relationships.Corpus callosum projections through the splenium form distinct dorsal and ventral bundles and are absent from the caudal splenium.The transcallosal pathway consists of distinct medial and lateral divisions.The results reveal projections to the external capsule and claustrum not previously described.Transcallosal and anterior commissural pathways show complex patterns of overlap and interdigitation.Surface mapping revealed areas with relatively high density of projections to the cortical surface.

Pathogenicity and virulence of O'nyong-nyong virus: A less studied Togaviridae with pandemic potential.

O'nyong-nyong virus (ONNV) is a neglected mosquito-borne alphavirus belonging to the Togaviridae family. ONNV is known to be responsible for sporadic outbreaks of acute febrile disease and polyarthralgia in Africa. As climate change increases the geographical range of known and potential new vectors, recent data indicate a possibility for ONNV to spread outside of the African continent and grow into a greater public health concern. In this review, we summarise the current knowledge on ONNV epidemiology, host-pathogen interactions, vector-virus responses, and insights into possible avenues to control risk of further epidemics. In this review, the limited ONNV literature is compared and correlated to other findings on mainly Old World alphaviruses. We highlight and discuss studies that investigate viral and host factors that determine viral-vector specificity, along with important mechanisms that determine severity and disease outcome of ONNV infection.

Tripeptidyl peptidase II coordinates the homeostasis of calcium and lipids in the central nervous system and its depletion causes presenile dementia in female mice through calcium/lipid dyshomeostasis-induced autophagic degradation of CYP19A1.

Rationale: Tripeptidyl peptidase II (TPP2) has been proven to be related to human immune and neurological diseases. It is generally considered as a cytosolic protein which forms the largest known protease complex in eukaryotic cells to operate mostly downstream of proteasomes for degradation of longer peptides. However, this canonical function of TPP2 cannot explain its role in a wide variety of biological and pathogenic processes. The mechanistic interrelationships and hierarchical order of these processes have yet to be clarified. Methods: Animals, cells, plasmids, and viruses established and/or used in this study include: TPP2 knockout mouse line, TPP2 conditional knockout mouse lines (different neural cell type oriented), TRE-TPP2 knockin mouse line on the C57BL/6 background; 293T cells with depletion of TPP2, ATF6, IRE1, PERK, SYVN1, UCHL1, ATG5, CEPT1, or CCTα, respectively; 293T cells stably expressing TPP2, TPP2 S449A, TPP2 S449T, or CCTα-KDEL proteins on the TPP2-depleted background; Plasmids for eukaryotic transient expression of rat CYP19A1-Flag, CYP19A1 S118A-Flag, CYP19A1 S118D-Flag, Sac I ML GFP Strand 11 Long, OMMGFP 1-10, G-CEPIA1er, GCAMP2, CEPIA3mt, ACC-GFP, or SERCA1-GFP; AAV2 carrying the expression cassette of mouse CYP19A1-3 X Flag-T2A-ZsGreen. Techniques used in this study include: Flow cytometry, Immunofluorescence (IF) staining, Immunohistochemical (IHC) staining, Luxol fast blue (LFB) staining, ß-galactosidase staining, Lipid droplet (LD) staining, Calcium (Ca2+) staining, Stimulated emission depletion (STED) imaging, Transmission electron microscopic imaging, Two-photon imaging, Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end Labeling (TUNEL) assay, Bromodeoxyuridine (BrdU) assay, Enzymatic activity assay, Proximity ligation assay (PLA), In vivo electrophysiological recording, Long-term potentiation (LTP) recording, Split-GFP-based mitochondria-associated membrane (MAM) detection, Immunoprecipitation (IP), Cellular fractionation, In situ hybridization, Semi-quantitative RT-PCR, Immunoblot, Mass spectrometry-based lipidomics, metabolomics, proteomics, Primary hippocampal neuron culture and Morris water maze (MWM) test. Results: We found that TPP2, independent of its enzymatic activity, plays a crucial role in maintaining the homeostasis of intracellular Ca2+ and phosphatidylcholine (PC) in the central nervous system (CNS) of mice. In consistence with the critical importance of Ca2+ and PC in the CNS, TPP2 gene ablation causes presenile dementia in female mice, which is closely associated with Ca2+/PC dysregulation-induced endoplasmic reticulum (ER) stress, abnormal autophagic degradation of CYP19A1 (aromatase), and estrogen depletion. This work therefore uncovers a new role of TPP2 in lipogenesis and neurosteroidogenesis which is tightly related to cognitive function of adult female mice. Conclusion: Our study reveals a crucial role of TPP2 in controlling homeostasis of Ca2+ and lipids in CNS, and its deficiency causes sexual dimorphism in dementia. Thus, this study is not only of great significance for elucidating the pathogenesis of dementia and its futural treatment, but also for interpreting the role of TPP2 in other systems and their related disorders.

Efficacy and safety of Qingfei Huatan formula in the treatment of acute exacerbation of chronic obstructive pulmonary disease: A multi-centre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD), a common respiratory disease, can be effectively treated by traditional Chinese medicine (TCM). Qingfei Huatan, a TCM formula, has been reported to effectively alleviate the clinical symptoms of COPD patients. However, there is a lack of multi-centre, randomised, double-blind, controlled clinical trials documenting the clinical efficacy and safety of this formula in the treatment of acute exacerbation of COPD (AECOPD). OBJECTIVE: This study evaluated the efficacy and safety of Qingfei Huatan formula in the treatment of AECOPD, thereby providing high-quality clinical evidence. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 276 patients with AECOPD were included in this multi-centre, randomised, double-blind, placebo-controlled trial and were randomised into treatment and control groups at a ratio of 1:1. Patients in the treatment and control groups took Qingfei Huatan granules or simulated Qingfei Huatan granules twice a day, for 14 days, in addition to Western medicine treatment. All patients were followed up for 3 months. MAIN OUTCOME MEASURES: The primary outcome was time taken to symptom stabilisation. The secondary outcomes included duration of antibiotic use, clinical symptom and sign score, TCM syndrome score, dyspnoea score, and quality of life (QOL) score. Meanwhile, the safety of the formula was assessed through routine urine and stool tests, electrocardiograms, liver and kidney function tests, and the observation of adverse events throughout the trial. RESULTS: The time taken for effective stabilisation (P < 0.05) and obvious stabilisation (P < 0.01), and the duration of antibiotic use (P < 0.05) were significantly shorter in the treatment group than in the control group. On days 6, 9, 12 and 14 of treatment, clinical symptom and sign score decreased in both groups, particularly in the treatment group (P < 0.01). On days 9, 12 and 14 of treatment, the TCM syndrome scores of both groups were reduced (P < 0.01), with more significant reductions in the treatment group. At 3 months after the end of treatment, the treatment group continued to have lower clinical symptom and sign score and TCM syndrome score than the control group (P < 0.01). On days 6, 9, 12 and 14 of treatment, dyspnoea and QOL scores were markedly reduced in the two groups (P < 0.05 and P < 0.01, respectively), especially in the treatment group. At 3 months after the end of treatment, dyspnoea and QOL scores were lower in the treatment group than those in the control group (P < 0.01). No serious adverse events were observed in either group. CONCLUSION: The Qingfei Huatan formula can effectively shorten the duration of AECOPD and antibiotic use, significantly relieve clinical symptoms, and increase QOL for AECOPD patients, with a favourable safety profile. These results suggest that this formula can be used as a complementary treatment for AECOPD patients. TRIAL REGISTRATION: The protocol was registered at the Chinese Clinical Trial Registry (ChiCTR1900026576). Please cite this article as: Zhu HZ, Li CY, Liu LJ, Tong JB, Lan ZH, Tian SG, Li Q, Tong XL, Wu JF, Zhu ZG, Li SY, Li JS. Efficacy and safety of Qingfei Huatan formula in the treatment of acute exacerbation of chronic obstructive pulmonary disease: A multi-centre, randomised, double-blind, placebo-controlled trial. J Integr Med. 2024; Epub ahead of print.