Notes

Programs glycemic difference from the assessment involving patients with intracerebral hemorrhage.
Familial hypercholesterolemia (FH) is a monogenic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C). A FH causing genetic variant in LDLR, APOB, or PCSK9 is not identified in 12-60% of clinical FH patients (FH mutation-negative patients). We aimed to assess whether altered DNA methylation might be associated with FH in this latter group.

In this study we included 78 FH mutation-negative patients and 58 FH mutation-positive patients with a pathogenic LDLR variant. All patients were male, not using lipid lowering therapies and had LDL-C levels >6mmol/L and triglyceride levels <3.5mmol/L. DNA methylation was measured with the Infinium Methylation EPIC 850K beadchip assay. Multiple linear regression analyses were used to explore DNA methylation differences between the two groups in genes related to lipid metabolism. A gradient boosting machine learning model was applied to investigate accumulated genome-wide differences between the two groups.

Candidate gene analysis revealed one significantly hypomethylated CpG site in CPT1A (cg00574958) in FH mutation-negative patients, while no differences in methylation in other lipid genes were observed. The machine learning model did distinguish the two groups with a mean Area Under the Curve (AUC)±SD of 0.80±0.17 and provided two CpG sites (cg26426080 and cg11478607) in genes with a possible link to lipid metabolism (PRDM16 and GSTT1).

FH mutation-negative patients are characterized by accumulated genome wide DNA methylation differences, but not by major DNA methylation alterations in known lipid genes compared to FH mutation-positive patients.

ZonMW grant (VIDI no. 016.156.445).
ZonMW grant (VIDI no. 016.156.445).Muscle architecture has a significant influence on the mechanical properties of skeletal muscles. Important parameters include the fascicle length, the angle of pennation, the physiological cross-sectional area (PCSA) as well as aponeurosis and tendon dimensions. During growth, skeletal muscles have to react to an increasing body mass and size demanding adaptations in muscle dimensions. Investigations of muscle architectural changes during growth are sparse, and existing studies often confine their scope to specific parameters or regions of the muscle. 10058F4 For this cross-sectional study, we determined the entire three-dimensional fascicle architecture of rabbit M. soleus via manual digitization. To this end, the investigations covered nine rabbits in the age-range between 29 days and 109 days. Fascicle length, muscle belly length, and aponeurosis length increased by 40%, 107%, and 111%, respectively. As the pennation angle remained almost constant and the contribution of fascicle length growth to muscle belly growth was minor, the increase in muscle mass primarily led to an increase in PCSA (462%), which required a similar increase in aponeurosis area (434%). Results gain new insight into the build-up of rabbit M. soleus and reveal that increases in muscle belly length are primarily connected to increases in aponeurosis length (83%). Contributions from fascicle length increase (17%) only play a minor role.Inactivated H9N2 influenza vaccines required adjuvants to induce strong immune responses to protect poultry from the infections of H9N2 influenza viruses. Recently, positively charged nanoparticles-based adjuvant delivery systems have been extensively investigated as the novel vaccine adjuvant due to the protection antigens and drugs from degradation, promoting antigens and drugs uptake by antigen presenting cells (APCs), and inducing strong humoral and cellular immune responses. In this study, the immunostimulant Angelica sinensis polysaccharide (ASP) was encapsulated into Poly (lactic-co-glycolic acid) PLGA nanoparticles, and the Polyethylenimine (PEI) was coated on the nanoparticles to develop a novel adjuvant (ASP-PLGA-PEI). To further investigate the adjuvant activities of ASP-PLGA-PEI nanoparticles for H9N2 vaccines in chickens and compare the adjuvant activities of nanoparticles adjuvant and conventional adjuvants (Alum and oil-based adjuvant), the H9N2 antigen was incubated with three different adjuvants and then immunized with chickens to evaluate the ability of inducing humoral and cellular immune responses. The results revealed that compared to Alum adjuvant, ASP-PLGA-PEI nanoparticles adjuvant stimulated higher antibody responses, promoted the activation of CD4+ T cells and CD8+ T cells, increased the expression of Th1 cytokines IFN-γ. Compared to oil-based adjuvant (ISA-206), ASP-PLGA-PEI nanoparticles adjuvant induced comparable antibody immune responses at later period after immunization, improved the activation of CD4+ T cells and CD8+ T cells. Therefore, compared to Alum and oil-based adjuvant, the ASP-PLGA-PEI nanoparticles serve as an efficient adjuvant for H9N2 vaccine and have the potential to induce vigorous humoral and cellular immune responses in chickens.Porcine circovirus type 2 (PCV2) infection causes porcine circovirus associated diseases (PCVAD) worldwide. Identification of host factors that interact with viral proteins is a fundamental step to understand the pathogenesis of PCV2. Our previous study reported that ORF5, a newly identified PCV2 viral protein supports PCV2 replication and interacts with multiple host factors. Here, we showed that a host factor YWHAB is an ORF5-interacting protein and plays essential roles during PCV2 infection. By using protein-protein interaction assays, we confirmed that YWHAB directly interacts with PCV2-ORF5 protein. We further showed that YWHAB expression was potently induced upon ORF5 overexpression and PCV2 infection. Remarkably, we found that the YWHAB strongly inhibited PCV2 replication, suggesting its role in defending PCV2 infection. By using the ectopic overexpression and gene knockdown approaches, we revealed that YWHAB inhibits PCV2-induced endoplasmic reticulum stress (ERS), autophagy, reactive oxygen species (ROS) production and apoptosis, suggesting its vital role in alleviating PCV2-induced cellular damage. Together, this study demonstrated that an ORF5-interacting host factor YWHAB affects PCV2 infection and PCV2-induced cellular response, which expands the current understanding of YWHAB biological function and might serves as a new therapeutic target to manage PCV2 infection-associated diseases.
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