Neuropilin-2 regulates androgen-receptor transcriptional activity in advanced prostate cancer

Aberrant transcriptional activity of androgen receptor (AR) is one of the dominant mechanisms for developing of castration-resistant prostate cancer (CRPC). Analyzing AR-transcriptional complex related to CRPC is therefore important towards understanding the mechanism of therapy-resistance. While studying its mechanism, we observed that a transmembrane protein called neuropilin-2 (NRP2) plays a contributory role in forming a novel AR-transcriptional complex containing nuclear pore proteins. Using immunogold electron microscopy, high-resolution confocal microscopy, chromatin immunoprecipitation, proteomics, and other biochemical techniques, we delineated the molecular mechanism of how a specific splice variant of NRP2 becomes sumoylated upon ligand stimulation and translocates to the inner nuclear membrane. This splice variant of NRP2 then stabilizes the complex between AR and nuclear pore proteins to promote CRPC specific gene expression. Both full-length and splice variants of AR have been identified in this specific transcriptional complex. In vitro cell line-based assays indicated that depletion of NRP2 not only destabilizes the AR-nuclear pore protein interaction but also inhibits the transcriptional activities of AR. Using an in vivo bone metastasis model, we showed that the inhibition of NRP2 led to the sensitization of CRPC cells toward established anti-AR therapies such as enzalutamide. Overall, our finding emphasize the importance of combinatorial inhibition of NRP2 and AR as an effective therapeutic strategy against treatment refractory prostate cancer

Impact of N fertilization on C balance and soil quality in maize-dhaincha cropping sequence

Excess N fertilization to achieve high crop yield is a grand old practice in developing countries. However, inorganic nutrient sources considerably replenish soil organic C (SOC). In the present study, we applied six different levels of N keeping P and K constant for maize, grown under maize (Zea mays) - dhaincha (Sesbania aculeata) cropping sequence. We recorded high crop yield, profuse root biomass and SOC stock with increasing N fertilization. Moreover, water holding capacity, microbial biomass carbon and particulate organic carbon improved significantly with increasing levels of N. Conversely, bulk density, mineral associated organic carbon and pH decreased with increasing application of inorganic N. Furthermore, a significant positive correlation was recorded between root biomass and soil organic carbon. A study of the sensitivity index showed particulate organic carbon and microbial biomass carbon to be good indicators of nutrient management practices. Dhaincha cultivation accelerated C and N mineralization in soil, which is reflected in increased biomass and crop yield. Hence, we conclude that inorganic N fertilization rate (7280 kg ha-1) in maize-dhaincha cropping sequence successfully maintains the SOC balance and optimize N stock in soil

Nature of Sexual Dysfunctions in Major Depressive Disorder and its Impact on Quality of Life

Background: Adequate sexual expression is an essential part of many human relationships, and may enhance quality of life and provide a sense of physical, psychological, and social well-being. Epidemiological and clinical studies show that depression is associated with impairments of sexual function and satisfaction, even in untreated patients. Most antidepressant drugs have adverse effects on sexual function, but accurate identification of the incidence of treatment-emergent dysfunction has proved troublesome. However, few investigators have reported the base rate for disturbances in sexual desire, arousal, and orgasm or ejaculation in patients with major depressive disorder (MDD) prior to antidepressant treatment. The purpose of this study is to define the frequency of sexual dysfunction (SD) in 60 patients with MDD and examine the relationship between SD and quality of life enjoyment and satisfaction variables. Materials and Methods: A consecutive series of 24 male and 36 female MDD patients diagnosed by SCID-DSM IV assessment completed a series of psychometric measures including a Sexual Function Questionnaire-Arizona Sexual Experience Scale (ASEX) which asked about change in sexual interest and function as well as quality of life of life enjoyment using QLESQ-SF. Results: Over 33.33% of men and 42% of women reported decreased sexual interest. Reduced levels of arousal were more common in both men and women (8-22%) than ejaculatory or orgasm difficulties (11-16%). In women, SDs were more than males. Quality of life was more impaired in sample with SDs than those without dysfunction showing significant impact of SD on quality of life. Limitation and Conclusion: Although limited by a relatively small sample of drug-free patients with MDD, and by the absence of a non-depressed comparison sample, these results emphasize the importance of factors beyond specific drug effects in the assessment of SD in drug naive-depressed patients