Cyclin G A Regulator of the p53-Mdm2 Network

AbstractA recent study published in the April issue of Molecular Cell has shown that cyclin G, a p53 target, is a regulatory component of the active PP2A holoenzyme, which activates Mdm2 through dephosphorylation. These findings suggest that cyclin G is a key regulator of the p53-Mdm2 network

The Rbm38-p63 feedback loop is critical for tumor suppression and longevity.

The RNA-binding protein Rbm38 is a target of p63 tumor suppressor and can in-turn repress p63 expression via mRNA stability. Thus, Rbm38 and p63 form a negative feedback loop. To investigate the biological significance of the Rbm38-p63 loop in vivo, a cohort of WT, Rbm38-/-, TAp63+/-, and Rbm38-/-;TAp63+/- mice were generated and monitored throughout their lifespan. While mice deficient in Rbm38 or TAp63 alone died mostly from spontaneous tumors, compound Rbm38-/-;TAp63+/- mice had an extended lifespan along with reduced tumor incidence. We also found that loss-of-Rbm38 markedly decreased the percentage of liver steatosis in TAp63+/- mice. Moreover, we found that Rbm38 deficiency extends the lifespan of tumor-free TAp63+/- mice along with reduced expression of senescence-associated biomarkers. Consistent with this, Rbm38-/-;TAp63+/- MEFs were resistant, whereas Rbm38-/- or TAp63+/- MEFs were prone, to cellular senescence. Importantly, we showed that the levels of inflammatory cytokines (IL17D and Tnfsf15) were significantly reduced by Rbm38 deficiency in senescence-resistant Rbm38-/-;TAp63+/- mouse livers and MEFs. Together, our data suggest that Rbm38 and p63 function as intergenic suppressors in aging and tumorigenesis and that the Rbm38-p63 loop may be explored for enhancing longevity and cancer management

DEC1, a Basic Helix-Loop-Helix Transcription Factor and a Novel Target Gene of the p53 Family, Mediates p53-dependent Premature Senescence

Cellular senescence plays an important role in tumor suppression. p53 tumor suppressor has been reported to be crucial in cellular senescence. However, the underlying mechanism is poorly understood. In this regard, a cDNA microarray assay was performed to identify p53 targets involved in senescence. Among the many candidates is DEC1, a basic helix-loop-helix transcription factor that has been recently shown to be up-regulated in K-ras-induced premature senescence. However, it is not clear whether DEC1 is capable of inducing senescence. Here, we found that DEC1 is a novel target gene of the p53 family and mediates p53-dependent premature senescence. Specifically, we showed that DEC1 is induced by the p53 family and DNA damage in a p53-dependent manner. We also found that the p53 family proteins bind to, and activate, the promoter of the DEC1 gene. In addition, we showed that overexpression of DEC1 induces G1 arrest and promotes senescence. Moreover, we found that targeting endogenous DEC1 attenuates p53-mediated premature senescence in response to DNA damage. Furthermore, overexpression of DEC1 induces cellular senescence in p53-knockdown cells, albeit to a lesser extent. Finally, we showed that DEC1-induced senescence is p21-independent. Taken together, our data provided strong evidence that DEC1 is one of the effectors downstream of p53 to promote premature senescence

Fluoroquinolone-mediated inhibition of cell growth, S-G2/M cell cycle arrest, and apoptosis in canine osteosarcoma cell lines.

Despite significant advancements in osteosarcoma research, the overall survival of canine and human osteosarcoma patients has remained essentially static over the past 2 decades. Post-operative limb-spare infection has been associated with improved survival in both species, yet a mechanism for improved survival has not been clearly established. Given that the majority of canine osteosarcoma patients experiencing post-operative infections were treated with fluoroquinolone antibiotics, we hypothesized that fluoroquinolone antibiotics might directly inhibit the survival and proliferation of canine osteosarcoma cells. Ciprofloxacin or enrofloxacin were found to inhibit p21(WAF1) expression resulting in decreased proliferation and increased S-G(2)/M accumulation. Furthermore, fluoroquinolone exposure induced apoptosis of canine osteosarcoma cells as demonstrated by cleavage of caspase-3 and PARP, and activation of caspase-3/7. These results support further studies examining the potential impact of quinolones on survival and proliferation of osteosarcoma

SunSat Design Competition 2014-2015 First Place Winner – Team CAST: Multi-Rotary Joints SPS

Space Power Satellite (SPS) is a huge spacecraft designed to collect solar energy in space for supplying electric power to the electric grid on the ground. The SPS concept was first proposed by Dr. Peter Glaser in 1968. Various studies on SPS in various countries have been produced over the past forty years. Today, there are multiple variations on this early concept, both in innovation and in optimization. Because of the huge size, immense mass and high power of these SPS installations, there are many technological difficulties. Here, a new Multi-Rotary Joints SPS (MR-SPS) concept is proposed. The large solar array is taken apart to illustrate the many small solar sub-arrays, and to show that each solar sub-array has two middle-power rotary joints. The extreme technical difficulty of high-power rotary joints is simplified by many middle-power rotary joints. The single-point failure problem existing in traditional SPS concept is also solved. At the same time, the modular solar arrays can be more easily assembled in GEO where the power can best be generated and continuously transmitted. Based on our new concept, a whole system full-life NPV analysis method has been developed to evaluate the economics. Our primary results show that the investment is near 30 billion US dollars, with development and transportation costs representing the main portions. When the price of power and the development and construction costs are fixed, the cost of capital becomes an important parameter in influencing the NPV. Click here to see the China Academy of Space Technology\u27s (CAST) video: Multi-Rotary Joints SPS - 2015 SunSat Design Competitio

A quantitative review of the effects of Se application on the reduction of Hg concentration in plant: a meta-analysis

Mercury (Hg) is a highly toxic heavy metal entering the human body through the food chain after absorption by plant. Exogenous selenium (Se) has been suggested as a potential solution to reduce Hg concentration in plants. However, the literature does not provide a consistent picture of the performance of Se on the accumulation of Hg in plant. To obtain a more conclusive answer on the interactions of Se and Hg, 1,193 data records were collected from 38 publications for this meta-analysis, and we tested the effects of different factors on Hg accumulation by meta-subgroup analysis and meta-regression model. The results highlighted a significant dose-dependent effect of Se/Hg molar ratio on the reduction of Hg concentration in plants, and the optimum condition for inhibiting Hg accumulation in plants is at a Se/Hg ratio of 1–3. Exogenous Se significantly reduced Hg concentrations in the overall plant species, rice grains, and non-rice species by 24.22%, 25.26%, and 28.04%, respectively. Both Se(IV) and Se(VI) significantly reduced Hg accumulation in plants, but Se(VI) had a stronger inhibiting effect than Se(IV). Se significantly decreased the BAFGrain in rice, which indicated that other physiological processes in rice may be involved in restricting uptake from soil to rice grain. Therefore, Se can effectively reduce Hg accumulation in rice grain, which provides a strategy for effectively alleviating the transfer of Hg to the human body through the food chain

Boosting oxygen evolution over inverse spinel Fe-Co-Mn oxide nanocubes through electronic structure engineering

Fossil fuels are urgent to be replaced with renewable energies to achieve carbon neutrality. Intermittent renewable energies such as solar and wind could be stored in chemical bonds, such as hydrogen and carbon-containing chemicals through water and CO2 electrolyzers respectively. Those two energy systems share a common anodic reaction, the sluggish oxygen evolution reaction (OER), which currently relies on precious noble metals to achieve a reasonable energy conversion efficiency. Herein, tuning the d-band center of Fe-based inverse spinel oxides has been achieved through compositions and morphologies engineering. Ternary Mn0.5Co0.5Fe2O4 nanocubes exhibit oxygen evolution activity superior to the benchmark RuO2. Mössbauer and in-situ infrared spectra combined with density functional theory calculations prove that the optimized d-band center offers a balanced adsorption strength of intermediate *OOH on Mn0.5Co0.5Fe2O4 nanocubes. This work provides a promising approach to the design and synthesis of highly efficient electrocatalysts beyond oxygen evolution.</p

Hatchery-reared enhancement program for silver carp (Hypophthalmichthys molitrix) in the middle Yangtze River: monitoring the effectiveness based on parentage analysis

Introduction A hatchery-reared silver carp (Hypophthalmichthys molitrix) program has been intensively carried out since 2010 to enhance the rapidly declining fisheries production in the middle Yangtze River. However, only a little information regarding the effectiveness of the enhancement program has been reported. In this context, this study investigates on an enhancement program through monitoring the efficacy based on parentage analysis. Methods A total of 1,529 hatchery-reared fish and 869 larvae were sampled from the middle Yangtze River in 2016 and 2017 and were genotyped by thirteen microsatellite loci. Based on the results of parentage analysis the larvae were divided into three populations: (1) larvae population with both parents being hatchery-reared fish (=R), (2) larvae population with only a male or a female parent being hatchery-reared fish (=H), and (3) larvae population with no hatchery-reared fish parent (=W). The following analyses were also carried out: (1) assessing the contribution of hatchery-reared offspring to larval resources, and (2) evaluating the genetic effect of stock enhancement on the wild population. Results In total, 10.37% and 11.56% of larvae were identified as the offspring produced by hatchery-reared fish released in 2016 and 2017, respectively. In 2017, some of the larvae were assigned unambiguously to hatchery-reared fish released in 2016. In terms of the number of offspring produced, the hatchery-reared fish have shown significant variations. No significant differences were found among all the larvae populations concerning genetic parameters for diversity. High levels of genetic diversity of all larvae populations were obtained. Low FSTvalues obtained from pairwise FST analysis, as well as the analysis of molecular variance (AMOVA), revealed high genetic structural similarity among all the larvae populations. The genetic composition of the W larvae population in 2017 was different from that of all other larvae populations (all larvae populations in 2016, and R and H larvae populations in 2017), as demonstrated from the results of STRUCTURE and PCA analyses. Conclusion It was demonstrated that hatchery-reared fish are successful in producing the offspring in the natural environment during multiple years, which might assist in increasing the abundance of larvae. The hatchery-reared fish had variations in terms of the success rates on reproduction. Also, the hatchery-reared enhancement program had no significant effect on the genetic diversity or the genetic structure of wild populations. However, the genetic component of the W larvae population in 2017 was changed as compared to 2016, which was not due to the hatchery-reared enhancement program for silver carp. This could be due to flooding, but the specific causes need further studies. Our results clearly show the necessity to continuously inspect the genetic impact of the enhancement program so that historical information can be utilized for further research