A combined in silico approaches of 2D-QSAR, molecular docking, molecular dynamics and ADMET prediction of anti-cancer inhibitor activity for actinonin derivatives.

Inhibition of human mitochondrial peptide deformylase (HsPDF) plays a major role in reducing growth, proliferation, and cellular cancer survival. In this work, a series of 32 actinonin derivatives for HsPDF (PDB: 3G5K) inhibitor's anticancer activity was computationally analyzed for the first time, using an in silico study considering 2D-QSAR modeling, and molecular docking studies, and validated by molecular dynamics and ADMET properties. The results of multilinear regression (MLR) and artificial neural networks (ANN) statistical analysis reveal a good correlation between pIC50 activity and the seven (7) descriptors. The developed models were highly significant with cross-validation, the Y-randomization test and their applicability range. In addition, all considered data sets show that the AC30 compound, exhibits the best binding affinity (docking score = -212.074 kcal/mol and H-bonding energy = -15.879 kcal/mol). Furthermore, molecular dynamics simulations were performed at 500 ns, confirming the stability of the studied complexes under physiological conditions and validating the molecular docking results. Five selected actinonin derivatives (AC1, AC8, AC15, AC18 and AC30), exhibiting best docking score, were rationalized as potential leads for HsPDF inhibition, in well agreement with experimental outcomes. Furthermore, based on the in silico study, new six molecules (AC32, AC33, AC34, AC35, AC36 and AC37) were suggested as HsPDF inhibition candidates, which would be combined with in-vitro and in-vivo studies to perspective validation of their anticancer activity. Indeed, the ADMET predictions indicate that these six new ligands have demonstrated a fairly good drug-likeness profile.

Impact of Two Strains of Rhizobium leguminosarum on the Adaptation to Terminal Water Deficit of Two Cultivars Vicia faba.

Drought stress has become one of the most uncontrolled and unpredictable constraints on crop production. The purpose of this study was to evaluate the impacts of two different Rhizobium leguminosarum strains on terminal drought tolerance induction in two faba bean genotypes cultivated in Algeria, Aquadulce and Maltais. To this end, we measured physiological parameters-osmoprotectants accumulation, oxidative stress markers and enzyme activities-to assess the effect of R. leguminosarum inoculation on V. faba under terminal water deficiency conditions in greenhouse trials. Upregulation of anti-oxidative mechanisms and production of compatible solutes were found differentially activated according to Rhizobium strain. Drought stress resilience of the Maltais variety was improved using the local Rhizobium strain OL13 compared to the common strain 3841. Symbiosis with OL13 strain leads in particular to a much better production of proline and soluble sugar in nodules but also in roots and leaves of Maltais plant. Even if additional work is still necessary to decipher the mechanism by which a Rhizobium strain can affect the accumulation of osmoprotectants or cellular redox status in all the plants, inoculation with selected Rhizobium could be a promising strategy for improving water stress management in the forthcoming era of climate change.

Arabidopsis Growth-Promotion and Root Architecture Responses to the Beneficial Rhizobacterium Phyllobacterium brassicacearum Strain STM196 Are Independent of the Nitrate Assimilatory Pathway.

Phyllobacterium brassicacearum STM196, a plant growth-promoting rhizobacterium isolated from roots of oilseed rape, stimulates Arabidopsis growth. We have previously shown that the NRT2.5 and NRT2.6 genes are required for this growth promotion response. Since these genes are members of the NRT2 family of nitrate transporters, the nitrogen assimilatory pathway could be involved in growth promotion by STM196. We address this hypothesis using two nitrate reductase mutants, G5 deleted in the major nitrate reductase gene NIA2 and G'4-3 altered in both NIA1 and NIA2 genes. Both mutants had a reduced growth rate and STM196 failed to increase their biomass production on a medium containing NO3- as the sole nitrogen source. However, they both displayed similar growth promotion by STM196 when grown on an NH4+ medium. STM196 was able to stimulate lateral roots development of the mutants under both nutrition conditions. Altogether, our results indicate that the nitrate assimilatory metabolism is not a primary target of STM196 interaction and is not involved in the root developmental response. The NIA1 transcript level was reduced in the shoots of nrt2.5 and nrt2.6 mutants suggesting a role for this nitrate reductase isoform independently from its role in nitrate assimilation.

Therapeutic and diagnostic relevance of Crispr technology.

CRISPR is a family of DNA repeats providing immunity against viral and plasmid invading DNA in bacteria and archaea. The system consist of an endonuclease Cas, guided by a RNA sequence, able to cleave the DNA double strand at a specific site. The discovery of Crispr function in 2007 has revolutionized genetic engineering by giving to the world the most powerful and precise tool for targeted genome editing. The aim of this review is to synthesize the current knowledge on Crispr/cas system and its application in biomedical field. In particular, we focus on the relevance of this new tool in progressing our comprehension for biological mechanisms and improving our ability to treat and prevent genetic diseases, to control microbial virulence and to generate animal models for basic and clinical research. We discuss also the ethical issues that may prevent the application of Crispr technology in living beings.

In vitro screening of durum wheat against water-stress mediated through polyethylene glycol.

Three durum wheat (Triticum durum Desf.) genotypes with three levels of drought tolerance were screened in order to evaluate their response to water stress at callus induction and plant regeneration levels. Significant differences were observed among the genotypes, and polyethylene glycol (PEG) levels used, and their interactions were however, significant for all the studied characters. Increase in PEG concentration increased the time required for callus initiation and reduced the number of calli frequency of embryogenic structures and number of plants regenerated, showing the adverse effect of PEG on the somatic embryogenesis developmental., under in vitro conditions tested, and Djenah Khetifa was the most tolerant genotype, followed by Oued Zenati and Waha. This pattern was per their drought tolerance behavior under field conditions. Principal component analysis (PCA) showed that 95.56% of the total variation was explained by the first two principal components. Biplot analysis allowed the stress-tolerant genotype to be distinguished from the two less tolerant genotypes. Time required for callus initiation was strongly negatively correlated with all other studied traits. These traits can be recommended as suitable selection criteria for screening drought-tolerant genotypes. The selected cells and plants will provide a tool for determining the mechanisms involved in tolerance to water stress.

Genotypic and symbiotic diversity of Rhizobium populations associated with cultivated lentil and pea in sub-humid and semi-arid regions of Eastern Algeria.

The genetic structure of rhizobia nodulating pea and lentil in Algeria, Northern Africa was determined. A total of 237 isolates were obtained from root nodules collected on lentil (Lens culinaris), proteaginous and forage pea (Pisum sativum) growing in two eco-climatic zones, sub-humid and semi-arid, in Eastern Algeria. They were characterised by PCR-restriction fragment length polymorphism (RFLP) of the 16S-23S rRNA intergenic region (IGS), and the nodD-F symbiotic region. The combination of these haplotypes allowed the isolates to be clustered into 26 distinct genotypes, and all isolates were classified as Rhizobium leguminosarum. Symbiotic marker variation (nodD-F) was low but with the predominance of one nod haplotype (g), which had been recovered previously at a high frequency in Europe. Sequence analysis of the IGS further confirmed its high variability in the studied strains. An AMOVA analysis showed highly significant differentiation in the IGS haplotype distribution between populations from both eco-climatic zones. This differentiation was reflected by differences in dominant genotype frequencies. Conversely, no host plant effect was detected. The nodD gene sequence-based phylogeny suggested that symbiotic gene diversity in pea and lentil nodulating rhizobial populations in Algeria was low compared to that reported elsewhere in the world.

Localization of the Bacillus subtilis beta-propeller phytase transcripts in nodulated roots of Phaseolus vulgaris supplied with phytate.

Soil organic phosphorus (Po) such as phytate, which comprises up to 80 % of total Po, must be hydrolyzed by specific enzymes called phytases to be used by plants. In contrast to plants, bacteria, such as Bacillus subtilis, have the ability to use phytate as the sole source of P due to the excretion of a beta-propeller phytase (BPP). In order to assess whether the B. subtilis BPP could make P available from phytate for the benefit of a nodulated legume, the P-sensitive recombinant inbred line RIL147 of Phaseolus vulgaris was grown under hydroaeroponic conditions with either 12.5 µM phytate (C6H18O24P6) or 75 µmol Pi (K2HPO4), and inoculated with Rhizobium tropici CIAT899 alone, or co-inoculated with both B. subtilis DSM 10 and CIAT899. The in situ RT-PCR of BPP genes displayed the most intense fluorescent BPP signal on root tips. Some BPP signal was found inside the root cortex and the endorhizosphere of the root tip, suggesting endophytic bacteria expressing BPP. However, the co-inoculation with B. subtilis was associated with a decrease in plant P content, nodulation and the subsequent plant growth. Such a competitive effect of B. subtilis on P acquisition from phytate in symbiotic nitrogen fixation might be circumvented if the rate of inoculation were reasoned in order to avoid the inhibition of nodulation by excess B. subtilis proliferation. It is concluded that B. subtilis BPP gene is expressed in P. vulgaris rhizosphere.

The NRT2.5 and NRT2.6 genes are involved in growth promotion of Arabidopsis by the plant growth-promoting rhizobacterium (PGPR) strain Phyllobacterium brassicacearum STM196.

The Phyllobacterium brassicacearum STM196 strain stimulates Arabidopsis thaliana growth and antagonizes high nitrate inhibition of lateral root development. A previous study identified two STM196-responsive genes, NRT2.5 and NRT2.6 (Mantelin et al., 2006, Planta 223: 591-603). We investigated the role of NRT2.5 and NRT2.6 in the plant response to STM196 using single and double Arabidopsis mutants. The single mutants were also crossed with an nrt2.1 mutant, lacking the major nitrate root transporter, to distinguish the effects of NRT2.5 and NRT2.6 from potential indirect effects of nitrate pools. The nrt2.5 and nrt2.6 mutations abolished the plant growth and root system architecture responses to STM196. The determination of nitrate content revealed that NRT2.5 and NRT2.6 do not play an important role in nitrate distribution between plant organs. Conversely, NRT2.5 and NRT2.6 appeared to play a role in the plant response independent of nitrate uptake. Using a nitrate reductase mutant, it was confirmed that the NRT2.5/NRT2.6-dependent plant signalling pathway is independent of nitrate-dependent regulation of root development. Our findings demonstrate that NRT2.5 and NRT2.6, which are preferentially expressed in leaves, play an essential role in plant growth promotion by the rhizospheric bacterium STM196.