Androgen Receptor Drives Cellular Senescence

The accepted androgen receptor (AR) role is to promote proliferation and survival of prostate epithelium and thus prostate cancer progression. While growth-inhibitory, tumor-suppressive AR effects have also been documented, the underlying mechanisms are poorly understood. Here, we for the first time link AR anti-cancer action with cell senescence in vitro and in vivo. First, AR-driven senescence was p53-independent. Instead, AR induced p21, which subsequently reduced ΔN isoform of p63. Second, AR activation increased reactive oxygen species (ROS) and thereby suppressed Rb phosphorylation. Both pathways were critical for senescence as was proven by p21 and Rb knock-down and by quenching ROS with N-Acetyl cysteine and p63 silencing also mimicked AR-induced senescence. The two pathways engaged in a cross-talk, likely via PML tumor suppressor, whose localization to senescence-associated chromatin foci was increased by AR activation. All these pathways contributed to growth arrest, which resolved in senescence due to concomitant lack of p53 and high mTOR activity. This is the first demonstration of senescence response caused by a nuclear hormone receptor

Heart Transplantation as a Treatment Method for Refractory Heart Failure due to Post-myocarditis Dilated Cardiomyopathy: a Clinical Case

Background. Implementation of mechanical circulatory support and heart transplantation technologies in paediatric clinical practice is changing approaches of diagnostics and treatment of heart failure (HF) in children. The experience of carrying out such operations in Russian Federation is extremely limited until recently due to absence of legal mechanisms of people declaration of intention recording about postmortal use of organs for transplantation.Clinical Case Description. The rare clinical case of drug-refractory (cardiotonic agents and cardioverter defibrillator implantation) chronic cardiac failure caused by post-myocarditis dilated cardiomyopathy (DCM) which demanded heart transplantation. Postoperative course, specific and non-specific complications, diagnostics and correction approaches are described.Conclusion. In the absence of proper analysis of non-specific slight symptoms myocarditis can progress to DCM and be complicated by development of refractory HF. The only method of sustaining child’s life in such case is heart transplantation which is connected with high risk of numerous and life-threatening complications

Cyanobacterial Root Associations of Leafless Epiphytic Orchids

The leafless orchids are rare epiphytic plants with extremely reduced leaves, and their aerial roots adopted for photosynthesis. The beneficial plant–microbial interactions contribute significantly to host nutrition, fitness, and growth. However, there are no data available on the bacterial associations, inhabiting leafless orchids. Here, we describe the diversity of cyanobacteria, which colonize the roots of greenhouse Microcoelia moreauae and Chiloschista parishii. The biodiversity and structure of the cyanobacterial community were analyzed using a complex approach, comprising traditional cultivable techniques, denaturing gradient gel electrophoresis (DGGE), and phylogenetic analysis, as well as the light and scanning electron microscopy (SEM). A wide diversity of associated bacteria colonize the root surface, forming massive biofilms on the aerial roots. The dominant populations of filamentous nitrogen-fixing cyanobacteria belonged to the orders Oscillatoriales, Synechococcales, and Nostocales. The composition of the cyanobacterial community varied, depending on the nitrogen supply. Two major groups prevailed under nitrogen-limiting conditions, belonging to Leptolyngbya sp. and Komarekiella sp. The latter was characterized by DGGE profiling and sequencing, as well as by its distinctive features of morphological plasticity. The leading role of these phototrophophic and diazotrophic cyanobacteria is discussed in terms of the epiphytic lifestyle of the leafless orchids