Dynamics of Vesicle Formation from Lipid Droplet: Mechanism and Controllability

A coarse-grained model developed by Marrink et al. [J. Phys. Chem. B 111, 7812 (2007)] is applied to investigate vesiculation of lipid [dipalmitoylphosphatidylcholine (DPPC)] droplets in water. Three kinds of morphologies of micelles are found with increasing lipid droplet size. When the initial lipid droplet is smaller, the equilibrium structure of the droplet is a spherical micelle. When the initial lipid droplet is larger, the lipid ball starts to transform into a disk micelle or vesicle. The mechanism of vesicle formation from a lipid ball is analyzed from the self-assembly of DPPC on the molecular level, and the morphological transition from disk to vesicle with increasing droplet size is demonstrated. Importantly, we discover that the transition point is not very sharp, and for a fixed-size lipid ball, the disk and vesicle appear with certain probabilities. The splitting phenomenon, i.e., the formation of a disk/vesicle structure from a lipid droplet, is explained by applying a hybrid model of the Helfrich membrane theory. The elastic module of the DPPC bilayer and the smallest size of a lipid droplet for certain formation of a vesicle are successfully predicted.Comment: 22 pages, 11 figures Submitted to J. Chem. Phy

Loss of ATF3 exacerbates liver damage through the activation of mTOR/p70S6K/ HIF-1α signaling pathway in liver inflammatory injury.

Activating transcription factor 3 (ATF3) is a stress-induced transcription factor that plays important roles in regulating immune and metabolic homeostasis. Activation of the mechanistic target of rapamycin (mTOR) and hypoxia-inducible factor (HIF) transcription factors are crucial for the regulation of immune cell function. Here, we investigated the mechanism by which the ATF3/mTOR/HIF-1 axis regulates immune responses in a liver ischemia/reperfusion injury (IRI) model. Deletion of ATF3 exacerbated liver damage, as evidenced by increased levels of serum ALT, intrahepatic macrophage/neutrophil trafficking, hepatocellular apoptosis, and the upregulation of pro-inflammatory mediators. ATF3 deficiency promoted mTOR and p70S6K phosphorylation, activated high mobility group box 1 (HMGB1) and TLR4, inhibited prolyl-hydroxylase 1 (PHD1), and increased HIF-1α activity, leading to Foxp3 downregulation and RORγt and IL-17A upregulation in IRI livers. Blocking mTOR or p70S6K in ATF3 knockout (KO) mice or bone marrow-derived macrophages (BMMs) downregulated HMGB1, TLR4, and HIF-1α and upregulated PHD1, increasing Foxp3 and decreasing IL-17A levels in vitro. Silencing of HIF-1α in ATF3 KO mice ameliorated IRI-induced liver damage in parallel with the downregulation of IL-17A in ATF3-deficient mice. These findings demonstrated that ATF3 deficiency activated mTOR/p70S6K/HIF-1α signaling, which was crucial for the modulation of TLR4-driven inflammatory responses and T cell development. The present study provides potential therapeutic targets for the treatment of liver IRI followed by liver transplantation

Hepatitis B virus inhibition in mice by lentiviral vector mediated short hairpin RNA

<p>Abstract</p> <p>Background</p> <p>Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma. The major challenges for current therapies are the low efficacy of current drugs and the occurrence of drug resistant HBV mutations. RNA interference (RNAi) of virus-specific genes offers the possibility of developing a new anti-HBV therapy. Recent reports have shown that lentiviral vectors based on HIV-1 are promising gene delivery vehicles due to their ability to integrate transgenes into non-dividing cells. Herein, a lentivirus-based RNAi system was developed to drive expression and delivery of HBV-specific short hairpin RNA (shRNA) in a mouse model for HBV replication.</p> <p>Methods</p> <p>Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in the sera of the mice were analyzed by quantitative sandwich enzyme linked immunosorbent assay (ELISA) technique, hepatitis B core antigen (HBcAg) and HBsAg in the livers of the mice were detected by immunohistochemical assay, HBV DNA and HBV mRNA were measured by fluorogenic quantitative polymerase chain reaction (FQ-PCR) and quantitative real-time PCR respectively.</p> <p>Results</p> <p>Co-injection of HBV plasmids together with the lentivirus targeting HBV shRNA induced an RNAi response. Secreted HBsAg was reduced by 89% in mouse serum, and HBeAg was also significantly inhibited, immunohistochemical detection of HBcAg or HBsAg in the liver tissues also revealed substantial reduction. Lentiviral mediated shRNA caused a significant suppression in the levels of viral mRNA and DNA synthesis compared to the control group.</p> <p>Conclusion</p> <p>Lentivirus-based RNAi can be used to suppress HBV replication in vivo, it might become a potential therapeutic strategy for treating HBV and other viral infections.</p

Phase transition of a single star polymer: a Wang-Landau sampling study

Star polymer is a typical nonlinear macromolecule possessing special thermodynamic behaviors for the existence of a jointing point. The thermodynamic transitions of a single star polymer are systematically studied with bond fluctuation model using Wang-Landau sampling technique. A new analysis method applying the shape factor is proposed to determine coil-globule (CG) and liquid-crystal (LC) transitions, which shows higher efficiency and precision than canonical specific heat function. It is found that the LC transition of star polymer at lower temperature obeys the identical scaling law as linear polymer. With the increase of the arm density of star polymer, however, the CG transition point, corresponding to {\theta} temperature, shifts towards the LC transition and the reason comes from the high density arms of star polymer, which requires the lower temperature for attracting force to overcome the volume excluding effects of chain. This work clearly demonstrates that the distinction of linear and star polymers in structures only affects CG transition and has no influence on LC transition.Comment: 30 pages, 10 figures, submit to JC

Wearable cardiorespiratory monitoring with stretchable elastomer optical fiber.

peer reviewedThis work presents a stretchable elastomer optical fiber sensor incorporated into a belt for respiratory rate (RR) and heart rate (HR) monitoring. Different materials and shapes of prototypes designed were tested in terms of performance and the best choice was identified. The optimal sensor was tested by 10 volunteers to evaluate the performance. The proposed elastomer optical fiber sensor can achieve simultaneous measurement of RR and HR in different body positions, and also ballistocardiography (BCG) signal measurement in the lying position. The sensor has good accuracy and stability, with maximum errors of 1 bpm and 3 bpm for RR and HR, respectively, and average weighted mean absolute percentage error (MAPE) of 5.25% and root mean square error (RMSE) of 1.28 bpm. Moreover, the results of the Bland-Altman method showed good agreement of the sensor with manual counting of RR and with electrocardiogram (ECG) measurements of HR

Rapamycin Regulates iTreg Function through CD39 and Runx1 Pathways

It has been shown that rapamycin is able to significantly increase the expression of FoxP3 and suppress activity in induced Treg (iTreg) cells in vivo and in vitro. CD39 is a newly determined Treg marker that relates to cell suppression. Runx1, a regulator of FoxP3, controls the expression of adenosine deaminase (ADA) gene, which is found recently in the downstream of CD39 pathway in trophoblast cells. Whether rapamycin would influence CD39 pathway and regulate the expression of Runx1 remains to be determined. The addition of rapamycin to human CD4(+) naïve cells in the presence of IL-2, TGF-β promotes the expression of FoxP3. In this paper, we found that CD39 positively correlated with the FoxP3 expression in iTreg cells. Rapamycin induced iTreg cells showed a stronger CD39/Runx1 expression with the enhanced suppressive function. These data suggested that CD39 expression was involved in iTreg generation and the enhanced suppressive ability of rapamycin induced Treg was partly due to Runx1 pathway. We conclude that rapamycin favors CD39/Runx1 expression in human iTreg and provides a novel insight into the mechanisms of iTreg generation enhanced by rapamycin