Functional and biological properties of the nuclear receptor coregulator PELP1/MNAR

Proline-, glutamic acid-, and leucine-rich protein (PELP)1, also known as modulator of nongenomic actions of the estrogen receptor (MNAR), is a novel nuclear receptor coregulator with a multitude of functions. PELP1/MNAR serves as a scaffolding protein that couples various signaling complexes with nuclear receptors and participates in genomic and nongenomic functions. Recent data suggest that PELP1/MNAR expression is deregulated in several cancers, including breast, endometrial, prostate, and ovarian cancer, and that PELP1/MNAR interacts with several oncogenes. In this review, we summarize the emerging biological properties and functions of PELP1/MNAR

Complete genome sequence of sixteen plant growth promoting Streptomyces strains

The genome sequences of 16 Streptomyces strains, showing potential for plant growth-promotion (PGP) activities in rice, sorghum, chickpea and pigeonpea, isolated from herbal vermicompost, have been decoded. The genome assemblies of the 16 Streptomyces strains ranged from 6.8 Mb to 8.31 Mb, with a GC content of 72 to 73%. The extent of sequence similarity (in terms of shared ortholog) in 16 Streptomyces strains showed 70 to 85% common genes to the closest publicly available Streptomyces genomes. It was possible to identify ~1,850 molecular functions across these 16 strains, of which close to 50% were conserved across the genomes of Streptomyces strains, whereas, ~10% were strain specific and the rest were present in various combinations. Genome assemblies of the 16 Streptomyces strains have also provided genes involved in key pathways related to PGP and biocontrol traits such as siderophores, auxin, hydrocyanic acid, chitinase and cellulase. Further, the genome assemblies provided better understanding of genetic similarity among target strains and with the publically available Streptomyces strains

Regulation of rDNA Transcription by Proto-Oncogene PELP1

Proline-, glutamic acid-, and leucine-rich protein (PELP1) is a novel nuclear receptor coregulator with a multitude of functions. PELP1 serves as a scaffolding protein that couples various signaling complexes with nuclear receptors and participates as a transcriptional coregulator. Recent data suggest that PELP1 expression is deregulated in hormonal cancers, and that PELP1 functions as a proto-oncogene; however, the mechanism by which PELP1 promotes oncogenesis remains elusive.Using pharmacological inhibitors, confocal microscopy and biochemical assays, we demonstrated that PELP1 is localized in the nucleolus and that PELP1 is associated with the active ribosomal RNA transcription. Cell synchronization studies showed that PELP1 nucleolar localization varies and the greatest amount of nucleolar localization was observed during S and G2 phases. Using pharmacological compounds and CDK site mutants of PELP1, we found that CDK's activity plays an important role on PELP1 nucleolar localization. Depletion of PELP1 by siRNA decreased the expression of pre-rRNA. Reporter gene assays using ribosomal DNA (pHrD) luc-reporter revealed that PELP1WT but not PELP1MT enhanced the expression of reporter. Deletion of nucleolar domains abolished PELP1-mediated activation of the pHrD reporter. ChIP analysis revealed that PELP1 is recruited to the promoter regions of rDNA and is needed for optimal transcription of ribosomal RNA.Collectively, our results suggest that proto-oncogene PELP1 plays a vital role in rDNA transcription. PELP1 modulation of rRNA transcription, a key step in ribosomal biogenesis may have implications in PELP1-mediated oncogenic functions

Plant growth-promoting traits of Streptomyces with biocontrol potential isolated from herbal vermicompost

Three strains of Streptomyces (CAI-21, CAI-26 and MMA-32) were earlier reported by us as having potential for biocontrol of charcoal rot of sorghum, caused by Macrophomina phaseolina (Tassi) Goid., and plant growth promotion (PGP) of the plant. In the present investigation, the three Streptomyces were characterised for their physiological traits (tolerance of salinity, temperature, pH and resistance to antibiotics) and further evaluated in the field for their PGP of rice, grown by a system of rice intensification methods. All three Streptomyces were able to grow in NaCl concentrations of up to 12% (except MMA-32), at pH values between 5 and 13 and temperatures between 20 and 40°C. They were highly resistant to ampicillin and trimethoprim (>800 ppm), sensitive to chloramphenicol, kanamycin and nalidixic acid (50–100 ppm) and highly sensitive to streptomycin and tetracycline (5–25 ppm). When evaluated for their PGP activity on seedlings of rice, % germination and shoot and root lengths were significantly enhanced over the control. In the field, the Streptomyces strains significantly enhanced the panicle length, filled grain numbers and weight, panicle weight, 1000 seed weight, tiller numbers, total dry matter, root length (39–65%), root volume (13–30%), root dry weight (16–24%), grain yield (9–11%) and stover yield (11–22%) over the control. In the rhizosphere soil (0–15 cm from root) at harvest, the population of actinomycetes was significantly enhanced as was microbial biomass carbon (27–83%) and nitrogen (24–43%), dehydrogenase activity (34–152%), available P (13–34%) and N (30–53%) and % organic carbon (26–28%). This study further confirms that the selected Streptomyces have PGP properties

ANTI-INFLAMMATORY ACTIVITY OF ALSTONIA SCHOLARIS IN ALBINO RATS

Evaluation of anti-inflammatory activities along with the phytochemical screening of hot methanolic extract of A. scholaris stem bark (ASE) in albino rats was undertaken. The preliminary phytochemical screening of the plant revealed the presence of tannins, alkaloids, saponins, phystosterols, phenolic compounds, glycoside and flavonoids. Oral LD50 of ASE by limit test was found to be above 2000 mg/kg. Two dose level of 200 (1/10 LD50) and 400 mg/kg (1/5 LD50) were selected for studying the anti -inflammatory activity of ASE using the carrageenan - induced acute paw oedema model in rats. The extract showed significant (p < 0.01) dose dependent reduction in rat paw oedema. The percentages of inhibition of oedema were 42.55 and 53.19 with 200 and 400 mg/kg, p.o. doses of ASE, respectively, as compared to control. The anti-inflammatory action of ASE can be attributed to its flavonoid contents, which are known to act through inhibition of prostaglandin biosynthesis

Evaluation of Streptomyces spp. for their plant-growth-promotion traits in rice

Five strains of Streptomyces (CAI-17, CAI-68, CAI-78, KAI-26, and KAI-27) were previously reported to have potential for charcoal rot control and plant growth promotion (PGP) in sorghum. In this study, those 5 Streptomyces strains were characterized for their enzymatic activities and evaluated for their PGP capabilities on rice. All the Streptomyces strains were able to produce lipase and β-1,3-glucanase; grew in NaCl (up to 8%), at pH 5–13, and at temperatures 20–40 °C; and were resistant to ampicillin, sensitive to nalidixic acid, and highly sensitive to chloramphenicol, kanamycin, streptomycin, and tetracycline. They were highly tolerant to the fungicide bavistin but were highly sensitive to benlate, benomyl, and radonil. When evaluated on rice in the field, Streptomyces significantly enhanced tiller and panicle numbers, stover and grain yields, dry matter, root length, volume and dry weight, compared with the control. In the rhizosphere at harvest, microbial biomass carbon and nitrogen, dehydrogenase activity, total nitrogen, available phosphorus, and % organic carbon were also found significantly higher in Streptomyces-treated plots than in the control plots. This study further confirms that the selected Streptomyces have PGP activities

Characterization of a pathogenic variant in the ABCD1 gene through protein molecular modeling

Background. The ATP-binding cassette, subfamily D, member 1 (ABCD1) protein is a peroxisomal half-transporter that allows for very long chain fatty acid (VLCFA) degradation. Pathogenic variants of ABCD1 cause VLCFAs to build up in various tissues and bodily fluids, resulting in a disorder called X-linked adrenoleukodystrophy (X-ALD). This disorder is most commonly marked by adrenocortical insufficiency and high VLCFA concentration, and has varying levels of neurological involvement depending on phenotype. For example, the Addison-only form of X-ALD has no neurological impact, while the cerebral form of X-ALD often causes severe sensory loss, motor function impairment, cognitive decline, and death. Methods. A newly characterized and suspected pathogenic variant in ABCD1 was analyzed using our protein informatics platform (PIP). Personalized protein-level molecular studies were completed on genetic testing data, complementing the analysis and clinical study. Results. A case of adult onset adrenomyeloneuropathy (AMN) and a novel ABCD1 variant are presented. The unique ABCD1 protein is discussed, and the proband’s case is compared to existing reports of AMN. Conclusions. Data fusion from multiple sources was combined in a comprehensive approach yielding an enriched assessment of the patient’s disease and prognosis. Molecular modeling was performed on the variant to better characterize its clinical significance and confirm pathogenicity

Insecticidal activity of a novel fatty acid amide derivative from Streptomyces species against Helicoverpa armigera

Helicoverpa armigera, an important pest causes serious damage to grain legumes. The main objective of this study was to isolate and identify the metabolite against H. armigera from a previously characterised Streptomyces sp. CAI-155. The culture filtrate of CAI- 155 was extracted using Diaion HP-20 and the active fractions were fractionated on Silica and C18 column chromatography. The C18 active fraction was further fractionated on Silica gel 60 F254 thin layer chromatography (TLC). The most active fraction (Rf 0.64) purified from TLC led to the identification of a novel metabolite N-(1-(2,2-dimethyl- 5-undecyl-1,3-dioxolan-4-yl)-2-hydroxyethyl)stearamide by spectral studies. The purified metabolite showed 70–78% mortality in 2nd instar H. armigera by diet impregnation assay, detached leaf assay and greenhouse assay. The LD50 and LD90 values of the purified metabolite were 627 and 2276 ppm, respectively. Hence, this novel metabolite can be exploited for pest management in future

p21-activated kinase signaling in breast cancer

The p21-activated kinases signal through a number of cellular pathways fundamental to growth, differentiation and apoptosis. A wealth of information has accumulated at an impressive pace in the recent past, both with regard to previously identified targets for p21-activated kinases that regulate the actin cytoskeleton and cellular stress pathways and with regard to newly identified targets and their role in cancer. Emerging data also provide new clues towards a previously unappreciated link between these various cellular processes. The present review attempts to provide a quick tutorial to the reader about the evolving significance of p21-activated kinases and small GTPases in breast cancer, using information from mouse models, tissue culture studies, and human materials