Regulation of AR mRNA translation in response to acute AR pathway inhibition

We report a new mechanism of androgen receptor (AR) mRNA regulation and cytoprotection in response to AR pathway inhibition (ARPI) stress in prostate cancer (PCA). AR mRNA translation is coordinately regulated by RNA binding proteins, YTHDF3 and G3BP1. Under ambient conditions m6A-modified AR mRNA is bound by YTHDF3 and translationally stimulated, while m6A-unmodified AR mRNA is bound by G3BP1 and translationally repressed. When AR-regulated PCA cell lines are subjected to ARPI stress, m6A-modified AR mRNA is recruited from actively translating polysomes (PSs) to RNA-protein stress granules (SGs), leading to reduced AR mRNA translation. After ARPI stress, m6A-modified AR mRNA liquid–liquid phase separated with YTHDF3, while m6A-unmodified AR mRNA phase separated with G3BP1. Accordingly, these AR mRNA messages form two distinct YTHDF3-enriched or G3BP1-enriched clusters in SGs. ARPI-induced SG formation is cell-protective, which when blocked by YTHDF3 or G3BP1 silencing increases PCA cell death in response to ARPI stress. Interestingly, AR mRNA silencing also delays ARPI stress-induced SG formation, highlighting its supportive role in triggering this stress response. Our results define a new mechanism for stress adaptive cell survival after ARPI stress involving SG-regulated translation of AR mRNA, mediated by m6A RNA modification and their respective regulatory proteins.     

Cellular Response to Substrate Rigidity Is Governed by Either Stress or Strain

Cells sense the rigidity of their substrate; however, little is known about the physical variables that determine their response to this rigidity. Here, we report traction stress measurements carried out using fibroblasts on polyacrylamide gels with Young’s moduli ranging from 6 to 110 kPa. We prepared the substrates by employing a modified method that involves N-acryloyl-6-aminocaproic acid (ACA). ACA allows for covalent binding between proteins and elastomers and thus introduces a more stable immobilization of collagen onto the substrate when compared to the conventional method of using sulfo-succinimidyl-6-(4-azido-2-nitrophenyl-amino) hexanoate (sulfo-SANPAH). Cells remove extracellular matrix proteins off the surface of gels coated using sulfo-SANPAH, which corresponds to lower values of traction stress and substrate deformation compared to gels coated using ACA. On soft ACA gels (Young’s modulus <20 kPa), cell-exerted substrate deformation remains constant, independent of the substrate Young’s modulus. In contrast, on stiff substrates (Young’s modulus >20 kPa), traction stress plateaus at a limiting value and the substrate deformation decreases with increasing substrate rigidity. Sustained substrate strain on soft substrates and sustained traction stress on stiff substrates suggest these may be factors governing cellular responses to substrate rigidity.     

Synthesis and in vitro study of 14-aryl-14H-dibenzo[a.j]xanthenes as cytotoxic agents

A simple and expedient method for the synthesis of a series of 14-aryl-14H-dibenzo[a.j]xanthenes is described through a one-pot condensation of β-naphthol with aryl aldehydes catalysed by TaCl₅ under solvent-free conventional heating. The major advantages of the present method are: high yields, less reaction time, solvent-free condition and easy purification of the products. The synthesized 14-aryl-14H-dibenzo[a.j]xanthenes were evaluated against a panel of six human cancer lines of different tissues. Synthesized compound 3o showed IC₅₀ of 37.9 and 41.3 μM against Colo-205 and 502713, respectively, whereas 3g showed IC₅₀ of 41.9 μM against Colo-205.     

Microbial production of 1,3-propanediol: Recent developments and emerging opportunities

1,3-Propanediol, a valuable bifunctional molecule, can be produced from renewable resources using microorganisms. It has several promising properties for many synthetic reactions, particularly for polymer and cosmetic industries. By virtue of being a natural product, relevant biochemical pathways can be harnessed into fermentation processes to produce 1,3-propanediol. Various strategies for the microbial production of 1,3-propanediol are reviewed and compared in this article with their promises and constraints. Furthermore, genetic and metabolic engineering could significantly improve product yields and overcome the limitations of fermentation technology. Present review gives an overview on 1,3-propanediol production by wild and recombinant strains. It also attempts to encompass the various issues concerned in utilization of crude glycerol for 1,3-propanediol production, with particular emphasis laid on biodiesel industries. This review also summarizes the present state of strategies studied for the downstream processing and purification of biologically produced 1,3-propanediol. The future prospect of 1,3-propanediol and its potential as a major bulk chemical are discussed under the light of the current research.     

Discrimination with a Mixture Population

The regions of classification when one of the populations is a mixture of two or more multivariate normal populations are found to be defined by the functions of the linear discriminant functions used for discriminating between the components of the mixture population and the other multivariate normal population.     

In vivo, testosterone propionate induced aberrations in Notopterus notopterus

Germ cell chromosomes of N. notopterus responded ot the higher doses of testosterone propionate peculiarly. Emergence of anomalies like agglutination at terminal ends, clumping and precocious despiralization was evident. The stickiness, breaks, laggard and a few achromatic lesions also appeared. Effect up to 72 hrs stages was evincible and varying occurrences of chromosomal irregularities.