Immunogenicity of Salmonella enterica serovar Enteritidis virulence protein,InvH, and cross-reactivity of its antisera with Salmonella strains

Acellular vaccines containing bacterial immunodominant components such as surface proteins may be potent alternatives to live attenuated vaccines in order to reduce salmonellosis risk to human health. invH gene, an important part of needle complex in type three secretion system (TTSS) plays important role in efficient bacterial adherence and entry into epithelial cells. In this work we hypothesize that use of a 15 kDa recombinant InvH as Salmonella enterica serovar Enteritidis surface protein could provoke antibody production in mouse and would help us study feasibility of its potential for diagnosis and/or a recombinant vaccine. The purified InvH provoked significant rise of IgG in mice. Active protection induced by immunization with InvH against variable doses of S. enterica serovar Enteritidis, indicated that the immunized mice were completely protected against challenge with 10⁴ LD₅₀. The immunoreaction of sera from immunized mice with other Salmonella strains or cross reaction with sera of Salmonella strains inoculated mice is indicative of possessing by Salmonella strains of the surface protein, InvH, that can be employed in both prophylactic and diagnostic measures against S. enterica. Bacteria free spleen and ileum of the immunized mice in this study indicate that the invH gene affects bacterial invasion. Efficacy of the virulence protein, InvH, in shuttling into host cells in injectisome of S. enterica serovar Enteritidis and inhibition of this phenomenon by active immunization was shown in this study. In conclusion immunization with InvH protein can develop protection against S. enterica serovar Enteritidis infections. InvH in Salmonella strains can be exploited in protective measures as well as a diagnostic tool in Salmonella infections.     

Diurnal patterns of gas‐exchange and metabolic pools in tundra plants during three phases of the arctic growing season

Arctic tundra plant communities are subject to a short growing season that is the primary period in which carbon is sequestered for growth and survival. This period is often characterized by 24‐h photoperiods for several months a year. To compensate for the short growing season tundra plants may extend their carbon uptake capacity on a diurnal basis, but whether this is true remains unknown. Here, we examined in situ diurnal patterns of physiological activity and foliar metabolites during the early, mid, and late growing season in seven arctic species under light‐saturated conditions. We found clear diurnal patterns in photosynthesis and respiration, with midday peaks and midnight lulls indicative of circadian regulation. Diurnal patterns in foliar metabolite concentrations were less distinct between the species and across seasons, suggesting that metabolic pools are likely governed by proximate external factors. This understanding of diurnal physiology will also enhance the parameterization of process‐based models, which will aid in better predicting future carbon dynamics for the tundra. This becomes even more critical considering the rapid changes that are occurring circumpolarly that are altering plant community structure, function, and ultimately regional and global carbon budgets.     

Molecular phylogeny and historical biogeography of the Anatolian lizard Apathya (Squamata,Lacertidae)

Apathya is a lacertid genus occurring mainly in south-east Turkey and its adjacent regions (part of Iran and Iraq). So far two morphological species have been attributed to the genus; A. cappadocica (with five subspecies, A. c. cappadocica, A. c. muhtari, A. c. schmidtlerorum, A. c. urmiana and A. c. wolteri) and A. yassujica. The first species occupies most of the genus’ distribution range, while A. yassujica is endemic of the Zagros Mountains. Here, we explored Apathya’s taxonomy and investigated the evolutionary history of the species by employing phylogenetic and phylogeographic approaches and using both mitochondrial (mtDNA) and nuclear markers. The phylogenetic relationships and the genetic distances retrieved, revealed that Apathya is a highly variable genus, which parallels its high morphological variation. Such levels of morphological and genetic differentiation often exceed those between species of other Lacertini genera that are already treated as full species, suggesting the necessity for a taxonomic revision of Apathya. The phylogeographical scenario emerging from the genetic data suggests that the present distribution of the genus was determined by a combination of dispersal and vicariance events between Anatolia and Southwest Asia dating back to the Miocene and continuing up to the Pleistocene. Key geological events for the understanding of the phylogeography of the genus are the movement of the Arabian plate that led to the configuration of Middle East (orogenesis of the mountain ranges of Turkey and Iran) and the formation of Anatolian Diagonal.     

The role of microRNAs involved in PI3-kinase signaling pathway in colorectal cancer

In recent decades, cancer has been one of the most important concerns of the human community, which affects human life from many different ways, such as breast, lung, colorectal, prostate, and other cancers. Colorectal cancer is one of the most commonly diagnosed cancers in the world that has recently been introduced as the third leading cause of cancer deaths in the world. microRNAs have a very crucial role in tumorgenesis and prevention of cancer, which plays a significant role with influencing various factors through different signaling pathways. Phosphoinositide 3 (PI3)-kinase/AKT is one of the most important signaling pathways involved in the control and growth of tumor in colorectal cancer, through important proteins of this pathway, such as PTEN and AKT, that they can perform specific influence on this process. Our effort in this study is to collect microRNAs that act as tumor suppressors and oncomirs in this cancer through PI3-kinase/AKT signaling pathway.     

Small interfering RNA–mediated gene suppression as a therapeutic intervention in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the lethal and difficult-to-cure cancers worldwide. Owing to the late diagnosis and drug resistance of malignant hepatocytes, treatment of this cancer by conventional chemotherapy agents is challenging, and researchers are seeking new alternative treatment options to overcome therapy resistance in this neoplasm. RNA interference (RNAi) is a potent and specific approach in targeting gene expression and has emerged as a novel therapeutic tool for many diseases, including cancers. Small interfering RNA (siRNA) is a type of RNAi that is produced intracellularly from exogenous synthetic oligonucleotides and can selectively knock down target gene expression in a sequence-specific manner. Various factors play roles in the initiation and progression of HCC and provide multiple candidate targets for siRNA intervention. In addition, due to the liver's unique architecture and availability of some hepatic siRNA delivery methods, this organ has received much more attention as a target tissue for such oligonucleotide action. Recent advances in designing nanoparticle systems for the in vivo delivery of siRNAs have markedly enhanced the potency of siRNA-mediated gene silencing under clinical development for HCC therapy. The utility of siRNAs as anti-HCC agents is the subject of the current review. siRNA-based gene therapies could be one of the main feasible approaches for HCC therapy in the future.     

Circulating myeloid-derived suppressor cells: An independent prognostic factor in patients with breast cancer

Evading immune destruction is a hallmark of cancer. Myeloid-derived suppressor cells (MDSCs), a heterogeneous population of myeloid immune cells, are thought to foster the establishment of an immunosuppressive tumor microenvironment, but it remains unclear how. This study aims to determine the levels of circulating MDSCs and their subpopulations and test their immunosuppressive functions in patients with breast cancer (BC). We analyzed the fractions of MDSCs in freshly isolated peripheral blood mononuclear cells of patients with BC and healthy donors using flow cytometry. Circulating MDSCs were further phenotyped using fluorescently labeled antihuman monoclonal antibodies. Coculture experiments revealed the effects of MDSCs on CD3⁺ T cell response. Moreover, we correlated circulating MDSC levels with clinicopathological features of patients with BC. We show that the fraction of HLA-DR ^– CD33 ⁺ MDSCs in peripheral blood is about 10-fold higher in patients with BC than in healthy control individuals. The levels of all MDSC subpopulations, including monocytic and granulocytic MDSCs, are significantly elevated. Coculture experiments of purified HLA-DR ^– CD33 ⁺ MDSCs and CD3 ⁺ T cells demonstrate that T cell proliferation is more effectively inhibited by BC patient-derived MDSCs than by healthy control MDSCs. Moreover, increased circulating MDSC levels robustly associate with advanced BC stage and positive lymph node status. By being more abundant and more effective T cell suppressors, BC patient-derived circulating MDSCs exert a dual immunosuppressive effect. Our findings pave the way to develop novel diagnostic and immunotherapeutic strategies, aimed at detecting and inhibiting MDSCs in patients with BC.