Drosophila Argonaute-1 is critical for transcriptional cosuppression and heterochromatin formation

Argonaute-1 (Ago-1) plays a crucial role in gene regulation and genome stability via biogenesis of small non-coding RNAs. Two “Argonaute” family genes, piwi and Ago-2 in Drosophila are involved in multiple silencing mechanisms in the nucleus, transgene cosuppression, long-distant chromosome interaction, nuclear organization and heterochromatin formation. To investigate whether Ago-1 also plays a similar role, we have generated a series of Ago-1 mutations by excising P element, inserted in the Ago-1 promoter (Ago-1k08121). AGO-1 protein is distributed uniformly in the nucleus and cytosol in early embryos but accumulated predominantly in the cytoplasm during the gastrulation stage. Repeat induced silencing produced by the mini-white (mw) array and transcriptional cosuppression of non-homologous transgenes Adh-w/w-Adh was disrupted by Ago-1 mutation. These effects of Ago-1 are distict from its role in microRNA processing because Dicer-1, a critical enzyme for miRNA biogenesis, has no role on the above silencing. Reduction of AGO-1 protein dislodged the POLYCOMB, EZ (enhancer of zeste) and H3me3K27 binding at the cosuppressed Adh-w transgene insertion sites suggesting its role in Polycomb dependent cosuppression. An overall reduction of methylated histone H3me2K9 and H3me3K27 from the polytene nuclei precisely from the mw promoters was also found that leads to concomitant changes in the chromatin structure. These results suggest a prominent role of Ago-1 in chromatin organization and transgene silencing and demonstrate a critical link between transcriptional transgene cosuppression, heterochromatin formation and chromatin organization. We propose Drosophila Ago-1 as a multifunctional RNAi component that interconnects at least two unrelated events, chromatin organization in the nucleus and microRNA processing in the cytoplasm, which may be extended to the other systems

Synthesis, DNA-binding ability and anticancer activity of benzothiazole/benzoxazole–pyrrolo[2,1-c][1,4]benzodiazepine conjugates

A series of benzothiazole and benzoxazole linked pyrrolobenzodiazepine conjugates attached through different alkane or alkylamide spacers was prepared. Their anticancer activity, DNA thermal denaturation studies, restriction endonuclease digestion assay and flow cytometric analysis in human melanoma cell line (A375) were investigated. One of the compounds of the series 17d showed significant anticancer activity with promising DNA-binding ability and apoptosis caused G0/G1 phase arrest at sub-micromolar concentrations. To ascertain the binding mode and understand the structural requirement of DNA binding interaction, molecular docking studies using gold program and more rigorous 2 ns molecular dynamic simulations using Molecular Mechanics-Poisson–Boltzman Surface Area (MM-PBSA) approach including the explicit solvent were carried out. Further, the compound 17d was evaluated for in vivo efficacy studies in human colon cancer HT29 xenograft mice

Understanding the Processes of Online Creative Interaction – Toward a Research Agenda

There is currently a strong belief in Information and Communication Technologies’(ICT) ability to enable innovation. However, there is little knowledge about the creativeprocesses that may occur through the mediation of ICT and consequently lead to innovation.Prior studies have shown that creativity is central when studying innovation and that creativitycan be seen as a social process. Since computers often are used as mediators for humancommunication and as a social tool, ICT harbors a potential to enable the social processes ofcreative interaction. The aim of this paper is therefore to map key concepts and research thatrelate to online creative interactions. Hence, prior research in the IS field regarding creativityis presented, the concepts of computer-mediated communication and creativity are exploredand a possible case to study is suggested. Subsequently, a research agenda is outlined,followed by some methodological considerations and a reflection on the expected knowledgecontribution of the research

Carbazole–pyrrolo[2,1-c][1,4]benzodiazepine conjugates: design, synthesis, and biological evaluation

A series of carbazole–pyrrolobenzodiazepine conjugates (4a–g and 5a–f) have been designed, and synthesized as anticancer agents. These compounds are prepared by linking the C8-position of DC-81 with a carbazole moiety through simple alkane spacers as well as piperazine side-armed alkane spacers in good yields. The DNA binding ability of these conjugates has been determined by thermal denaturation studies and also supported by molecular docking studies. These conjugates showed potent anticancer activity with GI50 ranging from 5.27–0.01 μM. The FACS analysis and BrdU assay of selected conjugates (4c, 4f, 5a and 5f) on MCF-7 cell lines disclosed the increased G1 cell cycle arrest and one of the conjugates 5f has exhibited significant anticancer activity. The analysis of the intrinsic factors involved in causing the G1 arrest in MCF-7 cell lines by 5f conjugate has been demonstrated on the proteins which play a vital role in G1 arrest followed by apoptosis (Cyclin D1, CDK4, c-Jun, JunB, CREB, p53, JNK1/2, procaspase-7, cleaved PARP, pRb, and BAX). Thus, these PBD conjugates (in particular 5f) have promising potency for combating human carcinoma

Chickpea Genomics

As precise phenotyping is essential and the cost of generating phenotyping data at every generation is very expensive, recent advances in genomics technologies and the availability of a wide range of genotyping platforms have made the cost of genotyping much less expensive compared with phenotyping. The recent developments in sequencing technologies have manifold increased the repertoire of various types of markers that are available in chickpea including SSRs, SNPs, DArTs, hundreds of thousands transcript reads and BAC-end sequences saturated genetic maps, QTL maps as well as physical maps, and the sequencing of both kabuli and desi type has greatly helped in using marker-assisted technologies to be applied in plant breeding. Germplasm resequencing for identification of genome-wide SNPs and their subsequent utilization in genomic selection has the potential to break the yield barrier being experienced in chickpea and many other crops. Genomic-assisted breeding for marker-assisted backcrossing (MABC) for introgressing QTL region, marker-assisted recurrent selection, gene pyramiding, marker-assisted selection (MAS), and genomic selection can now be taken up in chickpea. The conventional plant breeding should take these tools to make greater genetic gains, increase selection potential, and have faster breeding cycles so that the genetic improvement gains are increased in chickpea

Chickpea Genomics

As precise phenotyping is essential and the cost of generating phenotyping data at every generation is very expensive, recent advances in genomics technologies and the availability of a wide range of genotyping platforms have made the cost of genotyping much less expensive compared with phenotyping. The recent developments in sequencing technologies have manifold increased the repertoire of various types of markers that are available in chickpea including SSRs, SNPs, DArTs, hundreds of thousands transcript reads and BAC-end sequences saturated genetic maps, QTL maps as well as physical maps, and the sequencing of both kabuli and desi type has greatly helped in using marker-assisted technologies to be applied in plant breeding. Germplasm resequencing for identification of genome-wide SNPs and their subsequent utilization in genomic selection has the potential to break the yield barrier being experienced in chickpea and many other crops. Genomic-assisted breeding for marker-assisted backcrossing (MABC) for introgressing QTL region, marker-assisted recurrent selection, gene pyramiding, marker-assisted selection (MAS), and genomic selection can now be taken up in chickpea. The conventional plant breeding should take these tools to make greater genetic gains, increase selection potential, and have faster breeding cycles so that the genetic improvement gains are increased in chickpea