Regulation of p53: a collaboration between Mdm2 and MdmX

p53 plays an important role in the regulation of the cell cycle, DNA repair, and apoptosis and is an attractive cancer therapeutic target. Mdm2 and Mdmx are recognized as the main p53 negative regulators. Although it is still unknown why Mdm2 and Mdmx both are required for p53 degradation, a model has been proposed whereby these two proteins function independent of one another; Mdm2 acts as an E3 ubiquitin ligase that catalyzes the ubiquitination of p53 for degradation, whereas Mdmx inhibits p53 by binding to and masking the transcriptional activation domain of p53, without causing its degradation. However, Mdm2 and Mdmx have been shown to function collaboratively. In fact, recent studies have pointed to a more important role for an Mdm2/Mdmx co-regulatory mechanism for p53 regulation than previously thought. In this review, we summarize current progress in the field about the functional and physical interactions between Mdm2 and Mdmx, their individual and collaborative roles in controlling p53, and inhibitors that target Mdm2 and Mdmx as a novel class of anticancer therapeutics

Temperature-dependent performance of amorphous silicon photovoltaic/thermal systems in the long term operation

The influences of temperature on the performance of amorphous silicon (a-Si) solar cells and photovoltaic (PV) systems are extensively studied in the literature. The benefit from thermal annealing effect at a higher temperature than ambient has been demonstrated, which makes a-Si cells a promising material for photovoltaic/thermal (PV/T) system. However, the temperature-dependent performance of a-Si PV/T system in the long term operation has rarely been reported. The temperature effect will be more complicated than that on a single cell or PV system. Particularly, the exergetic efficiency and mechanical behavior of the PV/T system at different temperatures are unknown. To fill the above knowledge gap, two identical a-Si PV/T systems are developed. One operates at a water inlet temperature of 60 °C with an a-Si cell temperature of up to 70 °C. The other operates at an inlet temperature of 30 °C. Long-term outdoor tests from December 2017 to June 2019 have been conducted. Results indicate that the difference in the electrical efficiency between the two systems is 0.47% in the initial stage, and it gradually narrows to only 0.13% over time. The overall exergy efficiency at 60 °C generally exceeds that at 30 °C, which proves the superiority of the a-Si PV/T operating at medium temperature. Besides, the long-term operation at 60 °C has not led to a lower level of reliability

Feasibility of an innovative amorphous silicon photovoltaic/thermal system for medium temperature applications

Medium temperature photovoltaic/thermal (PV/T) systems have immense potential in the applications of absorption cooling, thermoelectric generation, and organic Rankine cycle power generation, etc. Amorphous silicon (a-Si) cells are promising in such applications regarding the low temperature coefficient, thermal annealing effect, thin film and avoidance of large thermal stress and breakdown at fluctuating temperatures. However, experimental study on the a-Si PV/T system is rarely reported. So far the feasibility of medium temperature PV/T systems using a-Si cells has not been demonstrated. In this study, the design and construction of an innovative a-Si PV/T system of stainless steel substrate are presented. Long-term outdoor performance of the system operating at medium temperature has been monitored in the past 15 months. The average electrical efficiency was 5.65%, 5.41% and 5.30% at the initial, intermediate and final phases of the long-test test, accompanied with a daily average thermal efficiency from about 21% to 31% in the non-heating season. The thermal and electrical performance of the system at 60 °C, 70 °C and 80 °C are also analyzed and compared. Moreover, a distributed parameter model with experimental validation is developed for an inside view of the heat transfer and power generation and to predict the system performance in various conditions. Technically, medium temperature operation has not resulted in interruption or observable deformation of the a-Si PV/T system during the period. The technical and thermodynamic feasibility of the a-Si PV/T system at medium operating temperature is demonstrated by the experimental and simulation results

A Novel Equivalent Continuous Metering Control With a Uniform Switching Strategy for Digital Valve System

Pulse number modulation (PNM) combined with pulse width modulation (PWM) control is an effective solution to improve the resolution of digital valve systems. However, the numerous discrete variables that use parallel on / off valves cause difficult control coordination and uneven switching. To address this issue, this article defines the equivalent spool displacement of the digital flow control unit by the number of PNM-controlled valves and the duty cycle of PWM-controlled valves to replace multiple discrete variables and develops the equivalent continuous metering control method. Furthermore, a uniform switching control strategy is proposed for the PWM-controlled valve using a uniformly distributed permutation for each on / off valve. The proposed control methods are verified by simulation on the built mathematical model of the equal-coded digital valve system. Experimental results for the displacement control of a hydraulic cylinder at 1 rad/s show that the average error of the equivalent continuous metering control is about 0.236 mm and the dispersion index reaches 20%, while the uniform switching control strategy achieves 80% with an average error of 0.215 mm. Simulated and experimental results demonstrate that the equivalent continuous metering control with a uniform switching strategy can almost evenly distribute switching numbers without compromising the accuracy of the displacement control.Peer reviewe

Generation of induced pluripotent stem cell lines from 3 distinct laminopathies bearing heterogeneous mutations in lamin A/C

The term laminopathies defines a group of genetic disorders caused by defects in the nuclear envelope, mostly the lamins. Lamins are the main constituents of the nuclear lamina, a filamentous meshwork associated with the inner nuclear membrane that provides mechanical stability and plays important roles in processes such as transcription, DNA replication and chromatin organization. More than 300 mutations in lamin A/C have been associated with diverse clinical phenotypes, understanding the molecular basis of these diseases may provide a rationale for treating them. Here we describe the generation of induced pluripotent stem cells (iPSCs) from a patient with inherited dilated cardiomiopathy and 2 patients with distinct accelerated forms of aging, atypical Werner syndrome and Hutchinson Gilford progeria, all of which are caused by mutations in lamin A/C. These cell lines were pluripotent and displayed normal nuclear membrane morphology compared to donor fibroblasts. Their differentiated progeny reproduced the disease phenotype, reinforcing the idea that they represent excellent tools for understanding the role of lamin A/C in normal physiology and the clinical diversity associated with these diseases

Recent mixing of<i> Vibrio parahaemolyticus</i> populations

Humans have profoundly affected the ocean environment but little is known about anthropogenic effects on the distribution of microbes. Vibrio parahaemolyticus is found in warm coastal waters and causes gastroenteritis in humans and economically significant disease in shrimps. Based on data from 1103 genomes of environmental and clinical isolates, we show that V. parahaemolyticus is divided into four diverse populations, VppUS1, VppUS2, VppX and VppAsia. The first two are largely restricted to the US and Northern Europe, while the others are found worldwide, with VppAsia making up the great majority of isolates in the seas around Asia. Patterns of diversity within and between the populations are consistent with them having arisen by progressive divergence via genetic drift during geographical isolation. However, we find that there is substantial overlap in their current distribution. These observations can be reconciled without requiring genetic barriers to exchange between populations if long-range dispersal has increased dramatically in the recent past. We found that VppAsia isolates from the US have an average of 1.01% more shared ancestry with VppUS1 and VppUS2 isolates than VppAsia isolates from Asia itself. Based on time calibrated trees of divergence within epidemic lineages, we estimate that recombination affects about 0.017% of the genome per year, implying that the genetic mixture has taken place within the last few decades. These results suggest that human activity, such as shipping, aquatic products trade and increased human migration between continents, are responsible for the change of distribution pattern of this species

Corrigendum to: The TianQin project: current progress on science and technology

In the originally published version, this manuscript included an error related to indicating the corresponding author within the author list. This has now been corrected online to reflect the fact that author Jun Luo is the corresponding author of the article

Establishment of porcine and human expanded potential stem cells.

We recently derived mouse expanded potential stem cells (EPSCs) from individual blastomeres by inhibiting the critical molecular pathways that predispose their differentiation. EPSCs had enriched molecular signatures of blastomeres and possessed developmental potency for all embryonic and extra-embryonic cell lineages. Here, we report the derivation of porcine EPSCs, which express key pluripotency genes, are genetically stable, permit genome editing, differentiate to derivatives of the three germ layers in chimeras and produce primordial germ cell-like cells in vitro. Under similar conditions, human embryonic stem cells and induced pluripotent stem cells can be converted, or somatic cells directly reprogrammed, to EPSCs that display the molecular and functional attributes reminiscent of porcine EPSCs. Importantly, trophoblast stem-cell-like cells can be generated from both human and porcine EPSCs. Our pathway-inhibition paradigm thus opens an avenue for generating mammalian pluripotent stem cells, and EPSCs present a unique cellular platform for translational research in biotechnology and regenerative medicine