The role of Pro-P5C Cycle in chs mutants of Arabidopsis under cold stress

Proline metabolism is implicated in plant responses to abiotic stresses, including the chilling stress. During proline catabolism, the two-step oxidation of proline is performed by the continuous actions of proline dehydrogenase (ProDH), which produces Δ¹-pyrroline-5-carboxylate (P5C), and P5C dehydrogenase (P5CDH), which oxidizes P5C to glutamate. The Arabidopsis thaliana chilling mutants chs1 and chs2 are sensitive to chilling temperatures of 13–18°C. For a better understanding of Arabidopsis responses to chilling stress, 4-week-old wild-type (WT) and chs1 and chs2 lines, with three plants in each group, were subjected to chilling stress (13°C), cold stress (4°C), or remained under normal conditions (23°C); and several factors including the expression of ProDH2 and P5CDH genes, POX (peroxidase) and SOD (superoxide dismutase) activities, as well as MDA and proline contents were examined. Our results showed an increase in the proline content in all lines under chilling conditions. In addition, a greater expression of ProDH2 and a lower expression of P5CDH were observed, leading us to speculate a greater breakdown of proline into P5C and a consequent overproduction of ROS in the ETC cycle. The higher POX and SOD activities and a higher MDA content in chs mutants at 13°C are in line with this speculation. Finally, cold-treated plants (4°C) only showed an increase in proline levels.     

Enhanced Specificity of Minimally Modified Anti-c-myc Oligonucleotides

Abstract

The sequence-specificity of antisense oligonucleotides (ODN) against c-myc mRNA was tested by Northern blot analysis. Rat smooth muscle cells were treated with antisense or control ODN against c-myc modified by the “minimal protection strategy”. At 0.3 μM concentration the ODN show a very specific reduction in c-myc mRNA levels. Use of the “minimal protection strategy” minimizes nonspecific effects as observed for all-phosphorothioate ODN containing four consecutive guanine residues.     

When to estimate sex ratio in natural populations of insects? A study on sex ratio variations of gall midges within a generation

Precise estimation of arthropods' sex ratio is an important issue in a wide range of ecological studies and biological control programs. Although, in many cases changes in arthropods' sex ratio may be under the control of parents or some symbiotic microorganisms, biased sex ratios in some other species are caused by some extrinsic factors, neglect of which may lead to under/overestimation of true sex ratio. In this paper, we pursued those factors that cause false estimation of sex ratio in insects' species. We studied the predatory gall midge, Aphidoletes aphidimyza Rondani (Diptera: Cecidomyiidae), an important biological control agent of aphids, that shows protandry (i.e. early male emergence), differential lifespan of sexes, and differential distribution of sexes across habitat. Ten populations of A. aphidimyza were released separately in transparent cages and their sex ratio variations were recorded every 12 hours. The primary sex ratio in this species seems to be slightly male‐biased (52.41% males), however early emergence of males biases the sex ratio up to 72% males in a few hours after emergence. Shortly after the emergence of females, the sex ratio reaches its primary situation, but as a result of male‐biased mortality after mating, the proportion of females increases gradually to 97% by the fourth and fifth days after emergence. These results explicitly suggest that direct estimation of sex ratio in natural populations may be affected by some secondary factors such as differential mortality of sexes, protandry, and differential distribution of males and females over time and/or across habitat.     

λ Phage Nanobioparticle Expressing Apoptin Efficiently Suppress Human Breast Carcinoma Tumor Growth In Vivo

Using phages is a novel field of cancer therapy and phage nanobioparticles (NBPs) such as λ phage could be modified to deliver and express genetic cassettes into eukaryotic cells safely in contrast with animal viruses. Apoptin, a protein from chicken anemia virus (CAV) has the ability to specifically induce apoptosis only in carcinoma cells. We presented a safe method of breast tumor therapy via the apoptin expressing λ NBPs. Here, we constructed a λ ZAP-CMV-apoptin recombinant NBP and investigated the effectiveness of its apoptotic activity on BT-474, MDA-MB-361, SKBR-3, UACC-812 and ZR-75 cell lines that over-expressing her-2 marker. Apoptosis was evaluated via annexin-V fluorescent iso-thiocyanate/propidium iodide staining, flow-cytometric method and TUNEL assay. Transfection with NBPs carrying λ ZAP-CMV-apoptin significantly inhibited growth of all the breast carcinoma cell lines in vitro. Also nude mice model implanted BT-474 human breast tumor was successfully responded to the systemic and local injection of untargeted recombinant λ NBPs. The results presented here reveal important features of recombinant λ nanobioparticles to serve as safe delivery and expression platform for human cancer therapy.     

Pomalidomide Shows Significant Therapeutic Activity against CNS Lymphoma with a Major Impact on the Tumor Microenvironment in Murine Models

Primary CNS lymphoma carries a poor prognosis. Novel therapeutic agents are urgently needed. Pomalidomide (POM) is a novel immunomodulatory drug with anti-lymphoma activity. CNS pharmacokinetic analysis was performed in rats to assess the CNS penetration of POM. Preclinical evaluation of POM was performed in two murine models to assess its therapeutic activity against CNS lymphoma. The impact of POM on the CNS lymphoma immune microenvironment was evaluated by immunohistochemistry and immunofluorescence. In vitro cell culture experiments were carried out to further investigate the impact of POM on the biology of macrophages. POM crosses the blood brain barrier with CNS penetration of ~ 39%. Preclinical evaluations showed that it had significant therapeutic activity against CNS lymphoma with significant reduction in tumor growth rate and prolongation of survival, that it had a major impact on the tumor microenvironment with an increase in macrophages and natural killer cells, and that it decreased M2-polarized tumor-associated macrophages and increased M1-polarized macrophages when macrophages were evaluated based on polarization status. In vitro studies using various macrophage models showed that POM converted the polarization status of IL4-stimulated macrophages from M2 to M1, that M2 to M1 conversion by POM in the polarization status of lymphoma-associated macrophages is dependent on the presence of NK cells, that POM induced M2 to M1 conversion in the polarization of macrophages by inactivating STAT6 signaling and activating STAT1 signaling, and that POM functionally increased the phagocytic activity of macrophages. Based on our findings, POM is a promising therapeutic agent for CNS lymphoma with excellent CNS penetration, significant preclinical therapeutic activity, and a major impact on the tumor microenvironment. It can induce significant biological changes in tumor-associated macrophages, which likely play a major role in its therapeutic activity against CNS lymphoma. POM should be further evaluated in clinical trials.     

Family Ismaridae Thomson (Hymenoptera,Diaprioidea), new to fauna of Iran

Occurrence of the family Ismaridae Thomson is recorded for the first time from Iran, represented by a single species, Ismarus rugulosus Förster, 1850. A series of diagnostic characters and morphometric ratios for this species is presented, as well as a distribution map throughout the Holarctic region.