Molecular Characterization of a Novel Big Defensin from Clam Venerupis philippinarum

Antimicrobial peptides (AMPs) are important mediators of the primary defense mechanism against microbial invasion. In the present study, a big defensin was identified from Venerupis philippinarum haemocytes (denoted as VpBD) by RACE and EST approaches. The VpBD cDNA contained an open reading frame (ORF) of 285 bp encoding a polypeptide of 94 amino acids. The deduce amino acid sequence of VpBD shared the common features of big defensin including disulfide array organization and helix structure, indicating that VpBD should be a new member of the big defensin family. The mRNA transcript of VpBD was up-regulated significantly during the first 24 hr after Vibrio anguillarum challenge, which was 7.4-fold increase compared to that of the control group. Then the expression decreased gradually from 24 hr to 96 hr, and the lowest expression level was detected at 96 hr post-infection, which was still 3.9-fold higher than that of control. The mature peptide of VpBD was recombined in Escherichia coli and purified for minimum inhibitory concentration (MIC) determination. The rVpBD displayed broad-spectrum inhibitory activity towards all tested bacteria with the highest activity against Staphyloccocus aureus and Pseudomonas putida. These results indicated that VpBD was involved in the host immune response against bacterial infection and might contribute to the clearance of invading bacteria

Dichloroacetate blocks aerobic glycolytic adaptation to attenuated measles virus and promotes viral replication leading to enhanced oncolysis in glioblastoma

Targeting reprogrammed energy metabolism such as aerobic glycolysis is a potential strategy for cancer treatment. However, tumors exhibiting low-rate glycolysis or metabolic heterogeneity might be resistant to such treatment. We hypothesized that a therapeutic modality that drove cancer cells to high-rate glycolysis might sensitize cancer cells to interference directed against metabolic flux. In this study, we found that attenuated oncolytic measles virus Edmonston strain (MV-Edm) caused glioblastoma cells to shift to high-rate aerobic glycolysis; this adaptation was blocked by dichloroacetate (DCA), an inhibitor of glycolysis, leading to profound cell death of cancer cells but not of normal cells. DCA enhanced viral replication by mitigating mitochondrial antiviral signaling protein (MAVS)-mediated innate immune responses. In a subcutaneous glioblastoma (GBM) xenograft mouse model, low-dose MV-Edm and DCA significantly inhibited tumor growth in vivo. We found that DCA impaired glycolysis (blocking bioenergetic generation) and enhanced viral replication (increasing bioenergetic consumption), which, in combination, accelerated bioenergetic exhaustion leading to necrotic cell death. Taken together, oncolytic MV-Edm sensitized cancer cells to DCA, and in parallel, DCA promoted viral replication, thus, improving oncolysis. This novel therapeutic approach should be readily incorporated into clinical trials

Особенности структуры живого напочвенного покрова и биологической активности лесных почв в условиях урбанизации

Branched octahydro-indenes were first synthesized with methyl isobutyl ketone (MIBK) and methyl benzaldehyde, which can be obtained from lignocellulose. Initially, C-14 oxygenates were prepared by the aldol condensation reaction of MIBK with methyl benzaldehydes. K2CO3/Al2O3 exhibited the highest activity among the studied solid base catalysts. On the basis of the characterizations, the outstanding activity of K2CO3/Al2O3 was comprehended, because this material has a relatively higher surface area and a larger base site concentration. Subsequently, the aldol condensation products were converted to branched octahydro-indene by hydrodeoxygenation over a Pt/C catalyst. This method is also applicable for the manufacture of C-11-C-13 polycycloalkanes with methyl benzaldehyde and other lignocellulosic ketones. According to our measurements, the polycycloalkanes obtained in this work have low freezing points (227.7 similar to 240.0 K) and high densities (0.857 similar to 0.944 g mL(-1)). Consequently, they may potentially be utilized to raise the volumetric heat values and/or the thermal stability of jet fuels

VIBRATION RESPONSE ANALYSIS OF FIVE-DEGREE-FREEDOM VEHICLE WITH STOCHASTIC STRUCTURAL PARAMETERS

In order to study effect that road roughness generated random excitation on the structural parameters of nonlinear vibration response of the vehicle system,random structural parameters of five- degrees-freedom nonlinear vehicle model were established,and the model parameters are considered as random variables,under the premise that between the tire and the body presence nonlinear spring to study the random vibration response of the model under random excitation. Road irregularity is considered to be a white noise process to establish the mechanical model,the nonlinear vehicle system was linearized by the energy difference method,a stationary covariance matrix for the random vibration responses was obtained by solving the Lyapunov equations,and the stable equivalent linear system parameters of vehicle were gained through iteration. The example calculation results show that this method can improve the accuracy and efficiency of computation

The Role of HECT E3 Ubiquitin Ligases in Colorectal Cancer

Colorectal cancer (CRC) is estimated to rank as the second reason for cancer-related deaths, and the prognosis of CRC patients remains unsatisfactory. Numerous studies on gastrointestinal cell biology have shown that the E3 ligase-mediated ubiquitination exerts key functions in the pathogenesis of CRC. The homologous to E6-associated protein C-terminus (HECT) family E3 ligases are a major group of E3 enzymes, featured with the presence of a catalytic HECT domain, which participate in multiple cellular processes; thus, alterations in HECT E3 ligases in function or expression are closely related to the occurrence and development of many human malignancies, including—but not limited to—CRC. In this review, we summarize the potential role of HECT E3 ligases in colorectal carcinogenesis and the related underlying molecular mechanism to expand our understanding of their pathological functions. Exploiting specific inhibitors targeting HECT E3 ligases could be a potential therapeutic strategy for CRC therapy in the future