Biomarkers for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. The HCC diagnosis is usually achieved by biomarkers, which can also help in prognosis prediction. Furthermore, it might represent certain therapeutic interventions through some combinations of biomarkers. Here, we review on our current understanding of HCC biomarkers

THE BALANCE AMONG QUALITY, SCALE AND EFFECTIVENESS AN EMPIRICAL STUDY ON SCALE EFFECT IN TEACHING VENUES AT PREFECTURE AND CITY LEVEL OF RADIO & TV UNIVERSITIES IN CHINA

Teaching venues are playing an important role in the filed of open and distance education (ODL). In China's ODL system over 70% enrolled students are from Radio and TV Universities (RTVUs). Many off-campus teaching venues of e-colleges in 67 conventional universities have been established in RTVUs at prefecture and city level. In this article, the authors have done a direct survey on the data of distance education cost over the past consecutive 4 years in 21 RTVUs at prefecture and city level from 3 provinces (Xinjiang, Hunan and Fujian) in China's western, central and eastern areas, and empirically studied the scale effect in teaching venues at prefecture and city level under the hypothesis condition-teaching effect of ODL and conventional education is the same. The study result illustrates that the average student cost of RTVUs at prefecture and city level demonstrates a scale economy feature, that is, with the expansion of enrolled students scale, there is a fall in the average student cost. The study indicates large differences between average student variable cost and average student cost, which shows a possible average cost reduction in RTVUs at prefecture and city level. In terms of geographical and economic differences, some imbalances of development have been found among RTVUs at prefecture and city level. A quadratic form regression model has been established for doing this research in the perspective of education economics. The results of the regression show that the optimal enrolled student number of RTVUs nationwide at prefecture and city level is around 7,800. For provinces, the most optimal enrolled student numbers are as follows: 9,100 for Fujian, 3,800 for Hunan, and 2,200 for Xianjiang, which can serve as the reference for expanding scale economy in ODL. The research finding also indicate the changes in student average cost resulting from the changes in scale, the problem of determining investment direction. It is suggested that more input which benefit the quality improvement of distance education should be made

The glutathione peroxidase Gpx4 prevents lipid peroxidation and ferroptosis to sustain Treg cell activation and suppression of antitumor immunity

T regulatory (Treg) cells are crucial to maintain immune tolerance and repress antitumor immunity, but the mechanisms governing their cellular redox homeostasis remain elusive. We report that glutathione peroxidase 4 (Gpx4) prevents Treg cells from lipid peroxidation and ferroptosis in regulating immune homeostasis and antitumor immunity. Treg-specific deletion of Gpx4 impairs immune homeostasis without substantially affecting survival of Treg cells at steady state. Loss of Gpx4 results in excessive accumulation of lipid peroxides and ferroptosis of Treg cells upon T cell receptor (TCR)/CD28 co-stimulation. Neutralization of lipid peroxides and blockade of iron availability rescue ferroptosis of Gpx4-deficient Treg cells. Moreover, Gpx4-deficient Treg cells elevate generation of mitochondrial superoxide and production of interleukin-1β (IL-1β) that facilitates T helper 17 (TH17) responses. Furthermore, Treg-specific ablation of Gpx4 represses tumor growth and concomitantly potentiates antitumor immunity. Our studies establish a crucial role for Gpx4 in protecting activated Treg cells from lipid peroxidation and ferroptosis and offer a potential therapeutic strategy to improve cancer treatment

Host Langerin (CD207) is a receptor for Yersinia pestis phagocytosis and promotes dissemination

Yersinia pestis is a Gram-negative bacterium that causes plague. After Y. pestis overcomes the skin barrier, it encounters antigen-presenting cells (APCs), such as Langerhans and dendritic cells. They transport the bacteria from the skin to the lymph nodes. However, the molecular mechanisms involved in bacterial transmission are unclear. Langerhans cells (LCs) express Langerin (CD207), a calcium-dependent (C-type) lectin. Furthermore, Y. pestis possesses exposed core oligosaccharides. In this study, we show that Y. pestis invades LCs and Langerin-expressing transfectants. However, when the bacterial core oligosaccharides are shielded or truncated, Y. pestis propensity to invade Langerhans and Langerin-expressing cells decreases. Moreover, the interaction of Y. pestis with Langerin-expressing transfectants is inhibited by purified Langerin, a DC-SIGN (DC-specific intercellular adhesion molecule 3 grabbing nonintegrin)-like molecule, an anti-CD207 antibody, purified core oligosaccharides and several oligosaccharides. Furthermore, covering core oligosaccharides reduces the mortality associated with murine infection by adversely affecting the transmission of Y. pestis to lymph nodes. These results demonstrate that direct interaction of core oligosaccharides with Langerin facilitates the invasion of LCs by Y. pestis. Therefore, Langerin-mediated binding of Y. pestis to APCs may promote its dissemination and infection.Peer reviewe

Proximity of Transmembrane Segments 5 and 8 of the Glutamate Transporter GLT-1 Inferred from Paired Cysteine Mutagenesis

BACKGROUND: GLT-1 is a glial glutamate transporter which maintains low synaptic concentrations of the excitatory neurotransmitter enabling efficient synaptic transmission. Based on the crystal structure of the bacterial homologue Glt(Ph), it has been proposed that the reentrant loop HP2, which connects transmembrane domains (TM) 7 and 8, moves to open and close access to the binding pocket from the extracellular medium. However the conformation change between TM5 and TM8 during the transport cycle is not clear yet. We used paired cysteine mutagenesis in conjunction with treatments with Copper(II)(1,10-Phenanthroline)(3) (CuPh), to verify the predicted proximity of residues located at these structural elements of GLT-1. METHODOLOGY/PRINCIPAL FINDINGS: To assess the proximity of transmembrane domain (TM) 5 relative to TM8 during transport by the glial glutamate transporter GLT-1/EAAT2, cysteine pairs were introduced at the extracellular ends of these structural elements. A complete inhibition of transport by Copper(II)(1,10-Phenanthroline)(3) is observed in the double mutants I295C/I463C and G297C/I463C, but not in the corresponding single mutants. Glutamate and potassium, both expected to increase the proportion of inward-facing transporters, significantly protected against the inhibition of transport activity of I295C/I463C and G297C/I463C by CuPh. Transport by the double mutants I295C/I463C and G297C/I463C also was inhibited by Cd(2+). CONCLUSIONS/SIGNIFICANCE: Our results suggest that TM5 (Ile-295, Gly-297) is in close proximity to TM8 (Ile-463) in the mammalian transporter, and that the spatial relationship between these domains is altered during the transport cycle

Beyond static detectors: a Bayesian approach to fusing long-term motion with appearance for robust people detection in highly cluttered scenes

In this work we present a framework for robust people detection in highly cluttered scenes with low resolution image sequences. Our model utilises both human appearance and their long-term motion information through a fusion formulated in a Bayesian framework. In particular, people appearance is modeled by histograms of oriented gradients. Motion information is computed via an improved background modeling by spatial motion constrains. Experiments demonstrate that our method reduces significantly the false positive rate compared to that of a state of the art human detector under very challenging conditions.

The Accessibility in the External Part of the TM5 of the Glutamate Transporter EAAT1 Is Conformationally Sensitive during the Transport Cycle. PLoS One 2012

Background: Excitatory amino acid transporter 1 (EAAT1) is a glutamate transporter which is a key element in the termination of the synaptic actions of glutamate. It serves to keep the extracellular glutamate concentration below neurotoxic level. However the functional significance and the change of accessibility of residues in transmembrane domain (TM) 5 of the EAAT1 are not clear yet. Methodology/Principal Findings: We used cysteine mutagenesis with treatments with membrane-impermeable sulfhydryl reagent MTSET [(2-trimethylammonium) methanethiosulfonate] to investigate the change of accessibility of TM5. Cysteine mutants were introduced from position 291 to 300 of the cysteine-less version of EAAT1. We checked the activity and kinetic parameters of the mutants before and after treatments with MTSET, furthermore we analyzed the effect of the substrate and blocker on the inhibition of the cysteine mutants by MTSET. Inhibition of transport by MTSET was observed in the mutants L296C, I297C and G299C, while the activity of K300C got higher after exposure to MTSET. Vmax of L296C and G299C got lower while that of K300C got higher after treated by MTSET. The L296C, G299C, K300C single cysteine mutants showed a conformationally sensitive reactivity pattern. The sensitivity of L296C to MTSET was potentiated by glutamate and TBOA,but the sensitivity of G299C to MTSET was potentiated only by TBOA. Conclusions/Significance: All these facts suggest that the accessibility of some positions of the external part of the TM5 i