Phylogeny,biogeography and divergence times of Astragalus section Incani DC. (Fabaceae) inferred from nrDNA ITS and plastid rpl32‐trnL(UAG) sequences

Astragalus sect. Incani, one of the most species‐rich sections of Astragalus with ca 140 species, is well known for its taxonomic complexity resulting from overlapping morphological characters and high phenotypic plasticity. Its main centers of diversity are in Iran and Turkey with about 120 species. Using nrDNA ITS and plastid rpl32‐trnL_(UAG) markers, we reconstructed the phylogeny of members of the section by means of maximum parsimony, maximum likelihood, Bayesian, Beast and S‐DIVA analyses. This is the first comprehensive work on the section Incani covering its full geographic range. All members of the section (including A. subsecundus) except A. platyphyllus formed a well‐supported clade (Incani s.s.). Within the section, two major groups with different geographic distribution were detected. One group includes nine examined species restricted to eastern Iran and Central Asia and the other group comprises a majority of the species from west and northwestern Iran, Turkey and southern Europe. The Divergence time analysis suggests that Incani s.s. originated in the late Pliocene and a majority of the speciation events dates to the last 1–1.5 Myr. This indicates that the recent diversification of Incani s.s. coincided with climatic changes during the Pliocene and Pleistocene and was followed by complex biogeographical processes in which dispersal have been vital for shaping the current distribution pattern . The S‐DIVA suggested a predominantly east–west route of dispersal from an origin in the east, and a major phylogenetic split between eastern and western lineages. However, the geographical distribution of A. monspessulanus/A. incanus and A. ackerbergensis/A. gueldenstaedtiae does not correspond to their phylogenetic positions. The former species are restricted to southern Europe/North Africa, but belong in two distinct subclades. The latter, restricted to northeastern Iran are phylogenetically close to species of western and northwestern Iran and Turkey. Astragalus sykesiae is resurrected as a distinct species separated from a broadly defined A. mercklinii.     

Structure and conformational changes in the C-terminal domain of the beta2-adrenoceptor: insights from fluorescence resonance energy transfer studies

The C terminus of the beta(2)-adrenoceptor (AR) interacts with G protein-coupled receptor kinases and arrestins in an agonist-dependent manner, suggesting that conformational changes induced by ligands in the transmembrane domains are transmitted to the C terminus. We used fluorescence resonance energy transfer (FRET) to examine ligand-induced structural changes in the distance between two positions on the beta(2)-AR C terminus and cysteine 265 (Cys-265) at the cytoplasmic end of transmembrane domain 6. The donor fluorophore FlAsH (Fluorescein Arsenical Helix binder) was attached to a CCPGCC motif introduced at position 351-356 in the proximal C terminus or at the distal C terminus. An acceptor fluorophore, Alexa Fluor 568, was attached to Cys-265. FRET analyses revealed that the average distances between Cys-265 and the proximal and distal FlAsH sites were 57 and 62A(,) respectively. These relatively large distances suggest that the C terminus is in an extended, relatively unstructured conformation. Nevertheless, we observed ligand-specific changes in FRET. All ligands induced an increase in FRET between the proximal C-terminal FlAsH site and Cys-265. Ligands that have been shown to induce arrestin-dependent ERK activation, including the catecholamine agonists and the inverse agonist ICI118551, led to a decrease in FRET between the distal FlAsH site and Cys-265, whereas other ligands had no effect or induced a small increase in FRET. Taken together the results provide new insight into the structure of the C terminus of the beta(2)-AR as well as ligand-induced conformational changes that may be relevant to arrestin-dependent regulation and signaling.     

Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) improved osteogenic differentiation of the human induced pluripotent stem cells while considered as an artificial extracellular matrix

Cocell polymers can be the best implants for replacing bone defects in patients. The pluripotent stem cells produced from the patient and the nanofibrous polymeric scaffold that can be completely degraded in the body and its produced monomers could be also usable are the best options for this implant. In this study, electrospun poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofibers were fabricated and characterized and then osteogenic differentiation of the human-induced pluripotent stem cells (iPSCs) was investigated while cultured on PHBV scaffold. MTT results showed that cultured iPSCs on PHBV proliferation were increased compared to those cultured on tissue culture polystyrene (TCPS) as the control. Alkaline phosphatase (ALP) activity and calcium content were also significantly increased in iPSCs cultured on PHBV compared to the cultured on TCPS under osteogenic medium. Gene expression evaluation demonstrated that Runx2, collagen type I, ALP, osteonectin, and osteocalcin were upregulated in iPSCs cultured on PHBV scaffold in comparison with those cultured on TCPS for 2 weeks. Western blot analysis have shown that osteocalcin and osteopontin expression as two major osteogenic markers were increased in iPSCs cultured on PHBV scaffold. According to the results, nanofiber-based PHBV has a promising potential to increase osteogenic differentiation of the stem cells and iPSCs-PHBV as a cell-co-polymer construct demonstrated that has a great efficiency for use as a bone tissue engineered bioimplant.     

An investigation on Lecanicillium muscarium as a biocontrol agent of stem borer pests of Rosa damascena in Kerman Province of Iran

The Rosa damascena has organic production and this plant is the most important economic crop in Kerman province. Roses have been used since the earliest times in rituals, cosmetics, perfumes, medicines and aromatherapy. The rose stem sawfly (Hartigia trimaculata) and rose stem girdler (Agrilus aurichalceus) are new and major pests of R. damascena in the Lalehzar region of Kerman province. These pests cause severe damage to plants by feeding stems and new management strategies for their control are continually being investigated. To investigate appropriate biological control agent in the region during 2005–2007, 184 isolates of fungi were collected from these pests. Isolation of fungi was achieved using standard methods. In this study, H. trimaculata and A. aurichalceus from R. damascena for the first time were recorded in Iran. Lecnicillium muscarium from H. trimaculata, L. muscarium from A. aurichalceus, Acremonium kiliense from H. trimaculata, and A. egyptiacum from A. aurichalceus have for the first time been recorded, and L. muscarium has been introduced as a suitable biological agent for control of these pests.     

Fungi associated with boll and lint rot of cotton in Southern Khorasan province of Iran

During surveys of cotton fields since 2009 in the Southern Khorasan province of Iran, symptomatic samples with lint and boll rot disease signs were collected and cultured on potato dextrose, malt extract agar and PARPH media. Several fungal isolates were obtained and identified. Among them, we found Penicillium expansum which to our knowledge is reported as a new pathogen of cotton worldwide; Fusarium semitectum and Nigrospora oryzae (associated to mite Siteroptes sp.) were also recorded as lint or boll rot pathogens for the first time from Iran. Disease symptoms and fungal characteristics of Exserohilum rostratum, which has been reported briefly as a new causal agent of boll and lint rot disease, are illustrated and presented. In addition, Aspergillus niger and Rhizopus spp. were also isolated frequently from lint parts of cotton prior to harvesting. There was a positive correlation between disease occurrence and spiny cotton bollworm damage. The pathogenicity test was characterised by inoculating the attached and detached bolls of cotton plants.     

Pyrrolidine and piperidine analogues of SC-57461A as potent,orally active inhibitors of leukotriene A(4) hydrolase

The synthesis and biological evaluation of a series of functionalized pyrrolidine- and piperidine-containing analogues of our lead LTA(4) hydrolase inhibitor, SC-57461A, is described. A number of compounds showed excellent potency in our in vitro screens and several demonstrated good oral activity in a mouse ex vivo assay. These efforts led to the identification of SC-56938 (14) as a potent, orally active inhibitor of LTA(4) hydrolase.     

Comparison of human-induced pluripotent stem cells and mesenchymal stem cell differentiation potential to insulin producing cells in 2D and 3D culture systems in vitro

Diabetes is one of the most common diseases in the world that is chronic, progressive, and costly, and causes many complications. Common drug therapies are not able to cure it, and pancreas transplantation is not responsive to the high number of patients. The production of the insulin producing cells (IPCs) from the stem cells in the laboratory and their transplantation to the patient's body is one of the most promising new approaches. In this study, the differentiation potential of the induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) into IPCs was compared to each other while cultured on poly(lactic-co-glycolic) acid (PLGA)/polyethylene glycol (PEG) nanofibrous scaffold as a 3D substrate and tissue culture polystyrene (TCPS) as a 2D substrate. Although the expression level of the insulin, Glut2 and pdx-1 genes in stem cells cultured on 3D substrate was significantly higher than the stem cells cultured on 2D substrate, the highest expression level of these genes was detected in the iPSCs cultured on PLGA-PEG. Insulin and C-peptide secretions from differentiated cells were also investigated and the results showed that secretions in cultured iPSCs on the PLGA-PEG were significantly higher than cultured iPSCs on the TCPS and cultured MSCs on both PLGA-PEG and TCPS. In addition, insulin protein was also expressed in the cultured iPSCs on the PLGA-PEG significantly higher than cultured MSCs on the PLGA-PEG. It can be concluded that differentiation potential of iPSCs into IPCs is significantly higher than human MSCs at both 2D and 3D culture systems.