Biotic Stress Alleviation in Plant Using Rhizobacteria: An Overview of Mechanism of Action, Antimicrobial Compounds Production, (Nano) Formulations and Employment Methods.

The biotic stress induced by phytopathogens causes a significant loss to several crops in terms of yield and quality. Biotic stress may disrupt phenotypic characteristics and alter metabolic pathways in plants. Sustainable approaches like the employment of rhizobacteria control phytopathogens and diseases thereof through production of antimicrobial compounds and boosting plant defense systems.

AKIRIN2 controls the nuclear import of proteasomes in vertebrates.

Protein expression and turnover are controlled through a complex interplay of transcriptional, post-transcriptional and post-translational mechanisms to enable spatial and temporal regulation of cellular processes. To systematically elucidate such gene regulatory networks, we developed a CRISPR screening assay based on time-controlled Cas9 mutagenesis, intracellular immunostaining and fluorescence-activated cell sorting that enables the identification of regulatory factors independent of their effects on cellular fitness. We pioneered this approach by systematically probing the regulation of the transcription factor MYC, a master regulator of cell growth.

Apelin inhibition prevents resistance and metastasis associated with anti-angiogenic therapy.

Angiogenesis is a hallmark of cancer, promoting growth and metastasis. Anti-angiogenic treatment has limited efficacy due to therapy-induced blood vessel alterations, often followed by local hypoxia, tumor adaptation, progression, and metastasis. It is therefore paramount to overcome therapy-induced resistance.

SWI/SNF regulates a transcriptional program that induces senescence to prevent liver cancer.

Oncogene-induced senescence (OIS) is a potent tumor suppressor mechanism. To identify senescence regulators relevant to cancer, we screened an shRNA library targeting genes deleted in hepatocellular carcinoma (HCC). Here, we describe how knockdown of the SWI/SNF component ARID1B prevents OIS and cooperates with RAS to induce liver tumors.

Transcriptional plasticity promotes primary and acquired resistance to BET inhibition.

Following the discovery of BRD4 as a non-oncogene addiction target in acute myeloid leukaemia (AML), bromodomain and extra terminal protein (BET) inhibitors are being explored as a promising therapeutic avenue in numerous cancers. While clinical trials have reported single-agent activity in advanced haematological malignancies, mechanisms determining the response to BET inhibition remain poorly understood. To identify factors involved in primary and acquired BET resistance in leukaemia, here we perform a chromatin-focused RNAi screen in a sensitive MLL-AF9;Nras(G12D)-driven AML mouse model, and investigate dynamic transcriptional profiles in sensitive and resistant mouse and human leukaemias.

Kidins220/ARMS associates with B-Raf and the TCR, promoting sustained Erk signaling in T cells.

The activation kinetics of MAPK Erk are critical for T cell development and activation. In particular, sustained Erk signaling is required for T cell activation and effector functions, such as IL-2 production. Although Raf-1 triggers transient Erk activation, B-Raf is implicated in sustained Erk signaling after TCR stimulation.

Semi-automatic determination of cell surface areas used in systems biology.

Quantitative biology requires high precision measurement of cellular parameters such as surface areas or volumes. Here, we have developed an integrated approach in which the data from 3D confocal microscopy and 2D high-resolution transmission electron microscopy were combined. The volumes and diameters of the cells within one population were automatically measured from the confocal data sets.

Quantitative analysis of protein phosphorylations and interactions by multi-colour IP-FCM as an input for kinetic modelling of signalling networks.

Background: To understand complex biological signalling mechanisms, mathematical modelling of signal transduction pathways has been applied successfully in last few years. However, precise quantitative measurements of signal transduction events such as activation-dependent phosphorylation of proteins, remains one bottleneck to this success.

Methodology/principal Findings: We use multi-colour immunoprecipitation measured by flow cytometry (IP-FCM) for studying signal transduction events to unrivalled precision.

Calorie restriction up-regulates iron and copper transport genes in Saccharomyces cerevisiae.

Calorie restriction (CR) is a non genetic intervention, known to confer longevity benefits across the various phyla from unicellular yeast to mammals. CR also invokes homeostatic responses similar to stress, however the sequence of molecular events leading to longevity is still illusive. In this study, we analysed the whole genome gene expression profile in response to CR, mutations mimicking CR, heat shock and H(2)O(2) from a gene ontology perspective.

Pre-clustered TCR complexes.

The T-cell antigen receptor (TCR) is a multisubunit transmembrane complex that mediates the antigen-specific activation of T cells. Using a variety of techniques, several research groups have shown that TCRs are at least partially pre-clustered before antigen binding. These new findings are contradictory to the "classical" view, according to which TCRs are randomly distributed on the cell surface and only associate upon antigen binding.

Detection of phosphorylated T and B cell antigen receptor species by Phos-tag SDS- and Blue Native-PAGE.

Detection of phospho-proteins and differently phosphorylated forms of the same protein are important in understanding cell behaviour. One novel method is Phos-tag SDS-PAGE. A dinuclear Mn(2+) complex that binds to phosphate groups (the Phos-tag) is covalently attached to the polyacrylamide gel matrix.

Models of antigen receptor activation in the design of vaccines.

Vaccination techniques have developed rapidly over the last several decades from the immunization with live attenuated pathogens to the use of peptide and DNA subunit vaccines, from the use of classical adjuvants to cell-directed delivery. Vaccination techiques are also under investigation for the treatment of tumors and autoimmune diseases. However, profound knowledge of activation mechanisms of the immune cells on a molecular level is prerequisite for a better understanding of the immune response, and for the development of effective immunomodulatory tools.

A novel range based QSAR study of human neuropeptide Y (NPY) Y5 receptor inhibitors.

A conventional QSAR study has been carried out using thermodynamic and other descriptors, on a set of arylsulfonamidomethylcyclohexyl derivatives as antagonists of potential obesity drug target human neuropeptide Y Y5 receptor. In addition, a novel range based method was applied to obtain a QSAR model so that the information contained in the compounds for which an approximate value instead of exact value of inhibitory activity was available could be included in the model. Analysis of models suggests that range based model is better in screening biologically active compounds from chemical library.

Quantitative structure activity relationship studies of aryl heterocycle-based thrombin inhibitors.

A quantitative structure activity relationship (QSAR) analysis has been performed on a data set of 42 aryl heterocycle-based thrombin inhibitors. Several types of descriptors including topological, spatial, thermodynamic, information content and E-state indices were used to derive a quantitative relationship between the anti thrombin activity and structural properties. Genetic algorithm based genetic function approximation method of variable selection was used to generate the model.