Identification of chemical compounds of the pheromone in different ages of female adults of the clearwing moth,Paranthrene diaphana Dalla Torre & Strand

The clearwing moth, Paranthrene diaphana Dalla Torre & Strand (Lep.: Sesiidae) is one of the most destructive pests of willow trees in Tehran province which leads to dieback. In this study, female volatile compounds were identified. For this purpose, female volatile substances were extracted using Solid Phase Micro Extraction and then were identified using Head Space Chromatography method. Female insects were assessed separately at ages of 2–4, 4–6 and 6–8 days of preparation. Among the various compounds identified by GC/MS in the volatile compounds of female insect, 27 compounds were introduced while seven combinations have also been produced and released at all ages of insect which include: Pentadecane, Heptadecane, Dodecane, Tetradecane, Hexadecane, Eicosane and Tridecane. The peak area of curve (log scale) and frequency of these compounds, demonstrate that five combinations including: Tetradecane, Hexadecane, Tridecane, Eicosane and Dodecane are more important. In addition, five compounds including: Octadecane, Palmitic acid (Hexadecanoic acid), 9-Octadecenoic acid, Tricosane and Hexacosane have been released only from fourth to the eighth day of adult life. Therefore, it seems that female sex pheromone is a combination of these 12 compounds.     

Substrate stereo‐specificity in tryptophan dioxygenase and indoleamine 2,3‐dioxygenase

The first and rate‐limiting step of the kynurenine pathway, in which tryptophan (Trp) is converted to N‐formylkynurenine is catalyzed by two heme‐containing proteins, Indoleamine 2,3‐dioxygenase (IDO), and Tryptophan 2,3‐dioxygenase (TDO). In mammals, TDO is found exclusively in liver tissue, IDO is found ubiquitously in all tissues. IDO has become increasingly popular in pharmaceutical research as it was found to be involved in many physiological situations, including immune escape of cancer. More importantly, small‐molecule inhibitors of IDO are currently utilized in cancer therapy. One of the main concerns for the design of human IDO (hIDO) inhibitors is that they should be selective enough to avoid inhibition of TDO. In this work, we have used a combination of classical molecular dynamics (MD) and hybrid quantum‐classical (QM/MM) methodologies to establish the structural basis that determine the differences in (a) the interactions of TDO and IDO with small ligands (CO/O₂) and (b) the substrate stereo‐specificity in hIDO and TDO. Our results indicate that the differences in small ligand bound structures of IDO and TDO arise from slight differences in the structure of the bound substrate complex. The results also show that substrate stereo‐specificity of TDO is achieved by the perfect fit of L ‐Trp, but not D ‐Trp, which exhibits weaker interactions with the protein matrix. For hIDO, the presence of multiple stable binding conformations for L /D ‐Trp reveal the existence of a large and dynamic active site. Taken together, our data allow determination of key interactions useful for the future design of more potent hIDO‐selective inhibitors. Proteins 2010; © 2010 Wiley‐Liss, Inc.     

Novel antigens of CAR T cell therapy: New roads; old destination

Chimeric antigen receptor T cell (CAR-T) therapy has so far proved itself as a reliable therapeutic option for the treatment of relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), diffuse large B-cell lymphoma (DLBCL), multiple myeloma (MM), and mantle cell lymphoma (MCL). However, this picture is not as colorful when it comes to the treatment of solid tumors mainly due to the lack of definitive tumor antigens, as well as the immunosuppressive tumor microenvironments and poor CAR-T infiltration. The recent developments in bioinformatics and cell biology, such as single-cell RNA sequencing, have offered silver linings in the subject of tumor antigen discovery. In the current review, we summarize the development of some CAR-T therapies that target novel tumor antigens, rather than the traditionally CAR-T-targeted ones, and briefly discuss the clinical antitumor achievements of those evaluated in patients, so far. Furthermore, we propose some tumor antigens that might someday be therapeutically beneficial while targeted by CAR-Ts based on the experimental evaluations of their specific monoclonal antibodies.     

A Novel Chromatographic Method for the Preparation of High Density Lipoproteins

High density lipoproteins (HDL) were isolated by a procedure employing polyanion precipitation and column chromatography. The product was free of low density lipoproteins (LDL) but serum albumin (HSA) was still present. The remaining HSA was removed by an immuno-adsorbent column. The HDL isolated by our method was compared to another HDL preparation isolated from the same plasma sample by the combination of ultra centrifugation and gel chromatography.¹ It was found to have approximately the same lipid and protein composition as the HDL isolated by conventional techniques.¹ Minor differences included a higher phospholipid and apoprotein E content and lower triglyceride and ApoC II content of the HDL isolated by column chromatography. The method described here is considerably less tedious than earlier techniques, can be scaled up without substantial increase in labor and results in an approximately 30% higher yield than the method described by Rudel et al.¹