Exposure to Leishmania major modulates the proportion of CD4+ T cells without affecting cellular immune responses

The immune responses of individuals exposed to Leishmania major were evaluated and compared with those of non-exposed volunteers. Forty-one patients with active lesion(s), 43 healed individuals, 15 vaccinees 1 month or 1 year post vaccination, and 15 non-exposed volunteers were studied. Leishmanin skin test (LST) response, proliferative response of lymphocyte (PRL) to L. major antigen, IFN-gamma and IL-4 production, and percentage of L. major-specific CD4+, CD8+ and CD16+/CD56+ cells in peripheral blood mononuclear cells were assessed. Data showed positive LST (>5 mm) in 92% of patients, 98% of healed, and 80% or 43% of vaccinees 1 month and 1 year post vaccination, respectively. Positive PRL (SI>2.5) was displayed in 90%, 84%, 46% and 7% of patients, healed, vaccinated (post 1 year) and non-exposed donors, respectively. The mean +/-S.E. of IFN-gamma was 924 +/- 149, 1,278 +/- 185, 470 +/- 282 or 258 +/- 82 pg/ml in patients, healed cases and vaccinees after 1 month or 1 year, respectively. Positive IFN-gamma responders (>300 pg/ml) were shown in 72% of patients, 81% of healed cases, 31% or 39% of vaccinees and 0% of non-exposed donors. A reduced percentage of CD4+ T-cells and an increased percentage of NK cells were found in exposed individuals compared to non-exposed donors. The data indicated that exposure to L. major modulates the proportion of CD4+ T cells and increases NK cells percentage. However, the cellular immune responses including induction of LST, and IFN-gamma production are increased in exposed individuals.     

Gene delivery in adherent and suspension cells using the combined physical methods

Cytotechnology - Physical methods are widely utilized to deliver nucleic acids into cells such as electro-transfection or heat shock. An efficient gene electro-transfection requires the best...     

Current progress in cancer immunotherapy based on natural killer cells

One of the most common diseases in the present era is cancer. The common treatment methods used to control cancer include surgery, chemotherapy, and radiotherapy. Despite progress in the treatment of cancers, there still is no definite therapeutic approach. Among the currently proposed strategies, immunotherapy is a new approach that can provide better outcomes compared with existing therapies. Employing natural killer (NK) cells is one of the means of immunotherapy. As innate lymphocytes, NK cells are capable of rapidly responding to cancer cells without being sensitized or restricted to the cognate antigen in advance, as compared to T cells that are tumor antigen-specific. Latest insights into the biology of NK cells have clarified the underlying molecular mechanisms of NK cell maturation and differentiation, as well as controlling their effector functions through the investigation of the ligands and receptors engaged in recognizing cancer cells by NK cells. Elucidating the fact that NK cells recognize cancer cells could similarly show the mechanism through which cancer cells possibly avoid NK cell-dependent immune surveillance. Additionally, the expectations for novel immunotherapies by targeting NK cells have increased through the latest clinical outcomes of T–cell-targeted cancer immunotherapy. For this emerging method, researchers are still attempting to develop protocols for conferring the best proliferation and expansion medium, activation pathways, utilization dosage, transferring methods, as well as reducing possible side effects in cancer therapy. This study reviews the NK cells, their proliferation and expansion methods, and their recent applications in cancer immunotherapy.     

Treatment of Lime Witches’ Broom Phytoplasma-Infected Mexican Lime with a Resistance Inducer and Study of its Effect on Systemic Resistance

Journal of Plant Growth Regulation - Destruction caused by plant diseases is terrible. Mexican lime witches' broom (MLWB) is a phytoplasma disease, which has caused considerable damage...     

Novelty is not surprise: Human exploratory and adaptive behavior in sequential decision-making

Classic reinforcement learning (RL) theories cannot explain human behavior in the absence of external reward or when the environment changes. Here, we employ a deep sequential decision-making paradigm with sparse reward and abrupt environmental changes. To explain the behavior of human participants in these environments, we show that RL theories need to include surprise and novelty, each with a distinct role. While novelty drives exploration before the first encounter of a reward, surprise increases the rate of learning of a world-model as well as of model-free action-values. Even though the world-model is available for model-based RL, we find that human decisions are dominated by model-free action choices. The world-model is only marginally used for planning, but it is important to detect surprising events. Our theory predicts human action choices with high probability and allows us to dissociate surprise, novelty, and reward in EEG signals.     

Association of Genetic Structure and Diversity in Iranian Wild Germplasms of Mentha longifolia L. Based on Phenotypical,Biochemical, and Molecular Markers

Mentha longifolia L. is well-known to be one of the most pervasive wild-growing species of the Lamiaceae family, which has extensive beneficial properties in the fields of pharmacology and biological products. In the present study, the correlation between Inter-simple sequence repeat (ISSR) markers and morpho-chemical parameters of twenty different M. longifolia accessions (MLACs) were assessed. The geographic information system (GIS) has been employed to interpret the original habitat of the accessions in Iran. ISSR analysis indicated a remarkable difference in the studied accessions, segregated them into three main groups, constructed by an unweighted pair-group method with arithmetic (UPGMA) and principal coordinate analysis (PCoA). A total of 89 bands were generated by 12 ISSR primers, among which 82 (91.97 %) of them were polymorphic. The cluster analysis based on agro-morphological data scattered MLACs into two main groups. The essential oils (EOs) were analyzed through GC/FID/MS, and four chemotypes were characterized according to the major constituents. Pulegone ranged from 0.17 to 69.50 % was the main oil constituent with the highest content. Also, HPLC-PDA was employed to identify and to quantify the phenolic compounds in the MeOH extracts of MLACs. Heatmap cluster based on phenolic compounds produced three main categories of accessions. The components identified in the extracts were rosmarinic acid, rutin, vanillic acid, ferulic acid, chlorogenic acid, caffeic acid, 3,4-dihydroxybenzoic acid, 2,5-dihydroxybenzoic acid, and p-coumaric acid, which among them rosmarinic acid (RA) varied from 39.16 to 261.55 mg/100 g (DW) as a predominant constituent. Subsequently, multiple regression analyses between ISSR fragments and morpho-chemical data illustrated considerable relationships in the plant materials. The high variation and correlation observed in metabolic and phenotypic traits of MLACs establish an adequate source to conduct reserves conservation programs.     

Adsorption and immobilisation of human insulin on graphene monoxide,silicon carbide and boron nitride nanosheets investigated by molecular dynamics simulation

The adsorption and immobilisation of human insulin onto the bio-compatible nanosheets including graphene monoxide, silicon carbide and boron nitride nanosheets were studied by molecular dynamics simulation at the temperature of 310 K. After equilibration, heating and 100 ns production molecular dynamic runs, it was found that the insulin was adsorbed and immobilised onto the considered surfaces in a native folded state. The structural parameters, including root-mean-square deviation and fluctuation, surface accessible solvent area, radius of gyration (R_g) and the distance between the centre of the mass of immobilised protein and the surface of the considered nanosheets, were measured, analysed and discussed. The energetics of the studied systems such as the interaction energy between protein and nanosheet was also measured and addressed. The discussions were centred on the structural and energetic parameters of the protein and nanosheets, including charge density, hydrophobicity, hydrophilicity and residue polarity. The results also showed that the active site of C-termini of chain B played an important role in the adsorption process and this could be helpful in the protection of insulin in its smart delivery and release applications.     

IL-35, a double-edged sword in cancer

Interleukin 35 (IL-35), a cytokine mainly produced by regulatory T cells (Treg cells), is composed of an Epstein-Barr virus–induced gene 3 β-chain and an IL-12 p35 α-chain. IL-35 causes tumorigenicity in cancer, protects cancer cells against apoptosis, and facilitates cancer progression. However, a few reports have referred to its contradictory roles in cancer prevention. Therefore, the exact purpose of this cytokine in cancer development has become a fundamental question that needs to be answered. In this review, we explain the structure of IL-35 and its receptors and their different signaling pathways. Finally, the function of IL-35 in some cancers and the possible application of this cytokine in approaches for cancer therapy have been discussed.     

Structural stability and endonuclease activity of a PI-SceI GFP-fusion protein

Homing endonucleases are site-specific and rare cutting endonucleases often encoded by intron or intein containing genes. They lead to the rapid spread of the genetic element that hosts them by a process termed 'homing'; and ultimately the allele containing the element will be fixed in the population. PI-SceI, an endonuclease encoded as a protein insert or intein within the yeast V-ATPase catalytic subunit encoding gene (vma1), is among the best characterized homing endonucleases. The structures of the Sce VMA1 intein and of the intein bound to its target site are known. Extensive biochemical studies performed on the PI-SceI enzyme provide information useful to recognize critical amino acids involved in self-splicing and endonuclease functions of the protein. Here we describe an insertion of the Green Fluorescence Protein (GFP) into a loop which is located between the endonuclease and splicing domains of the Sce VMA1 intein. The GFP is functional and the additional GFP domain does not prevent intein excision and endonuclease activity. However, the endonuclease activity of the newly engineered protein was different from the wild-type protein in that it required the presence of Mn(2+) and not Mg(2+) metal cations for activity.