Optimal Water Allocation of Surface and Ground Water Resources Under Climate Change with WEAP and IWOA Modeling

Water Resources Management - The water evaluation and planning (WEAP) approach and the invasive weed optimization algorithm (IWOA) are herein employed to determine the optimal operating policies in...     

Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency

Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular stress that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression to late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked to ER stress response; however, most of the evidence has come from studies that correlate the expression of stress markers with poor prognosis or demonstrate proapoptosis by the knockdown of stress-responsive genes. Since ER stress in cancers usually persists and is essentially not induced by genetic manipulations, we used low doses of ER stress inducers at levels that allowed cell adaptation to occur in order to investigate the effect of stress response on chemoresistance. We found that prolonged tolerable ER stress promotes mesenchymal–epithelial transition, slows cell-cycle progression, and delays the S-phase exit. Consequently, cisplatin-induced apoptosis was significantly decreased in stress-adapted cells, implying their acquisition of cisplatin resistance. Molecularly, we found that proliferating cell nuclear antigen (PCNA) ubiquitination and the expression of polymerase η, the main polymerase responsible for translesion synthesis across cisplatin-DNA damage, were up-regulated in ER stress-adaptive cells, and their enhanced cisplatin resistance was abrogated by the knockout of polymerase η. We also found that a fraction of p53 in stress-adapted cells was translocated to the nucleus, and that these cells exhibited a significant decline in the level of cisplatin-DNA damage. Consistently, we showed that the nuclear p53 coincided with strong positivity of glucose-related protein 78 (GRP78) on immunostaining of clinical biopsies, and the cisplatin-based chemotherapy was less effective for patients with high levels of ER stress. Taken together, this study uncovers that adaptation to ER stress enhances DNA repair and damage tolerance, with which stressed cells gain resistance to chemotherapeutics.     

Multifaceted Mechanisms of Action of Metformin Which Have Been Unraveled One after Another in the Long History

While there are various kinds of drugs for type 2 diabetes mellitus at present, in this review article, we focus on metformin which is an insulin sensitizer and is often used as a first-choice drug worldwide. Metformin mainly activates adenosine monophosphate-activated protein kinase (AMPK) in the liver which leads to suppression of fatty acid synthesis and gluconeogenesis. Metformin activates AMPK in skeletal muscle as well, which increases translocation of glucose transporter 4 to the cell membrane and thereby increases glucose uptake. Further, metformin suppresses glucagon signaling in the liver by suppressing adenylate cyclase which leads to suppression of gluconeogenesis. In addition, metformin reduces autophagy failure observed in pancreatic β-cells under diabetic conditions. Furthermore, it is known that metformin alters the gut microbiome and facilitates the transport of glucose from the circulation into excrement. It is also known that metformin reduces food intake and lowers body weight by increasing circulating levels of the peptide hormone growth/differentiation factor 15 (GDF15). Furthermore, much attention has been drawn to the fact that the frequency of various cancers is lower in subjects taking metformin. Metformin suppresses the mechanistic target of rapamycin (mTOR) by activating AMPK in pre-neoplastic cells, which leads to suppression of cell growth and an increase in apoptosis in pre-neoplastic cells. It has been shown recently that metformin consumption potentially influences the mortality in patients with type 2 diabetes mellitus and coronavirus infectious disease (COVID-19). Taken together, metformin is an old drug, but multifaceted mechanisms of action of metformin have been unraveled one after another in its long history.     

Toward optimization of a robust low-cost sulfonated-polyethersulfone containing layered double hydroxide for PEM fuel cells

Polyethersulphone (PES) is an aromatic thermoplastic, at low environmental impact, evaluated in this work as a promising candidate for new polymer electrolytes in the PEMFCs technology. A sulfonation procedure has been tuned in order to graft sulfonic acid groups on the polymer chains (sPES) and to make it hydrophilic. Homogeneous membranes with different polymer's sulfonation degrees (SD%) have demonstrated excellent mechanical properties and very low permeability toward methanol (important in the DMFCs), even if low proton conductivity. Nanocomposite sPES membranes were prepared by dispersion of highly hydrophilic lamellar particles such as layered double hydroxide (LDH) in the polymer. Deep investigations performed by a combination of PFG-NMR, EIS, XRD, DMA, and scanning electron microscopy have evidenced the exfoliation of the lamellae in polymer matrix. However, a certain anisotropy was evidenced both in the morphology and molecular diffusion, favored in the longitudinal direction (parallel to surface), while completely inhibited in the cross-section. This finding is most likely induced by the polymer structure, therefore particular attention must be paid to the choice of the filler and preparation of the composites. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47884.     

The Role of Cell Cycle Regulators in Cell Survival—Dual Functions of Cyclin-Dependent Kinase 20 and p21Cip1/Waf1

The mammalian cell cycle is important in controlling normal cell proliferation and the development of various diseases. Cell cycle checkpoints are well regulated by both activators and inhibitors to avoid cell growth disorder and cancerogenesis. Cyclin dependent kinase 20 (CDK20) and p21^Cip1/Waf1 are widely recognized as key regulators of cell cycle checkpoints controlling cell proliferation/growth and involving in developing multiple cancers. Emerging evidence demonstrates that these two cell cycle regulators also play an essential role in promoting cell survival independent of the cell cycle, particularly in those cells with a limited capability of proliferation, such as cardiomyocytes. These findings bring new insights into understanding cytoprotection in these tissues. Here, we summarize the new progress of the studies on these two molecules in regulating cell cycle/growth, and their new roles in cell survival by inhibiting various cell death mechanisms. We also outline their potential implications in cancerogenesis and protection in heart diseases. This information renews the knowledge in molecular natures and cellular functions of these regulators, leading to a better understanding of the pathogenesis of the associated diseases and the discovery of new therapeutic strategies.     

The World robot summit disaster robotics category – achievements of the 2018 preliminary competition

The World Robot Summit is a robot Olympics and aims to be held in a different country every four years from 2020. The concept of the Plant Disaster Prevention challenge is daily inspections, checks, and emergency response in industrial plants, and in this competition, robots must carry out these types of missions in a mock-up plant. The concept of the Tunnel Disaster Response and Recovery challenge is emergency response to tunnel disasters, and is a simulation competition whereby teams compete to show their ability to deal with disasters, by collecting information and removing debris. The Standard Disaster Robotics challenge assesses, in the form of a contest, the standard performance levels of a robot that are necessary for disaster prevention and emergency response. The World Robot Summit Preliminary Competition was held at Tokyo Big Sight in October 2018, and 36 teams participated in the Disaster Robotics Category. UGVs and UAVs contended the merits of new technology for solving complex problems, using core technologies such as mobility, sensing, recognition, performing operations, human interface, autonomous intelligence etc., as well as system integration and implementation of strategies for completing missions, gaining high-level results.     

Environmental factors and kinetics of microbial degradation of poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) in an aqueous medium

Environmental factors such as oxygen, temperature, and microbial species may have significant effects on decomposition of biodegradable polymers. A representative biodegradable, thermoplastic polymer, poly(3‐hydroxybutyrate‐co‐hydroxyvalerate) (PHBV), was decomposed in an aqueous medium under controlled laboratory conditions by soil microbes for the intrinsic degradation kinetics and the effects of the environmental factors on polymer biodegradation. The amount of proteins, including the PHBV depolymerases, that attached to the polymer surfaces was quite constant during the period of significant mass loss of the polymer specimens. The microbial polymer degradation followed a zero‐order rate model, so the residual mass fraction of PHBV films declined linearly with time. The mixed aerobic microbial organisms from fertile soil showed a higher activity of polymer degradation than an aerobic PHBV‐producing bacterium and the mixed anaerobes in the same soil. The mixed anaerobic microorganisms from barren soil decomposed the polymer at a slower rate than the anaerobes from fertile soil, and this was attributed to fewer microbial cells in the barren soil instead of the difference in the microbial species. The temperature effect on PHBV degradation can be described with an Arrhenius equation, and the activation energy is around 16 kcal/mol. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 205–213, 2003