Nutrient deprivation induces the Warburg effect through ROS/AMPK-dependent activation of pyruvate dehydrogenase kinase

AbstractThe Warburg effect is known to be crucial for cancer cells to acquire energy. Nutrient deficiencies are an important phenomenon in solid tumors, but the effect on cancer cell metabolism is not yet clear. In this study, we demonstrate that starvation of HeLa cells by incubation with Hank's buffered salt solution (HBSS) induced cell apoptosis, which was accompanied by the induction of reactive oxygen species (ROS) production and AMP-activated protein kinase (AMPK) phosphorylation. Notably, HBSS starvation increased lactate production, cytoplasmic pyruvate content and decreased oxygen consumption, but failed to change the lactate dehydrogenase (LDH) activity or the glucose uptake. We found that HBSS starvation rapidly induced pyruvate dehydrogenase kinase (PDK) activation and pyruvate dehydrogenase (PDH) phosphorylation, both of which were inhibited by compound C (an AMPK inhibitor), NAC (a ROS scavenger), and the dominant negative mutant of AMPK. Our data further revealed the involvement of ROS production in AMPK activation. Moreover, DCA (a PDK inhibitor), NAC, and compound C all significantly decreased HBSS starvation-induced lactate production accompanied by enhancement of HBSS starvation-induced cell apoptosis. Not only in HeLa cells, HBSS-induced lactate production and PDH phosphorylation were also observed in CL1.5, A431 and human umbilical vein endothelial cells. Taken together, we for the first time demonstrated that a low-nutrient condition drives cancer cells to utilize glycolysis to produce ATP, and this increases the Warburg effect through a novel mechanism involving ROS/AMPK-dependent activation of PDK. Such an event contributes to protecting cells from apoptosis upon nutrient deprivation

Will Your Project Get the Green Light? Predicting the Success of Crowdfunding Campaigns

Capital is always essential for a business project over times. After emerging in 2000, crowdfunding gradually becomes one of the most popular fundraising resources. However, the mechanism of crowdfunding significantly differs from traditional capital-collecting approaches. As long as the amount of pledged money reaches the goal in time, the project succeeds, its initiator receives the funds, the platform gains the revenue, and its backers acquire rewards. Reaching the goal by deadline becomes an important issue. The goal of our study is to develop an effective technique for predicting whether a crowdfunding campaign will succeed or fail. On the basis of a dataset collected from Kickstarter, our empirical evaluation results suggest that our proposed technique significantly outperforms the benchmark method. In addition, with the use of time-dependent factors, the prediction accuracy improves from 72.89% at day 0 to 87.13% at the first day and eventually to 89.62% at day 7

Burkitt's Lymphoma Mimicking a Primary Gynecologic Tumor

SummaryObjectiveBurkitt's lymphoma (BL) occurs mostly in children; bilateral ovarian involvement mimicking a gynecologic malignancy in adults is extremely rare. Here, we report a patient with BL mimicking a gynecologic tumorCase ReportA 50-year-old Taiwanese woman presented with the complaint of persistent lower abdominal distension with dull pain, easy satiety, and progressively increasing abdominal girth for 2 weeks. Amenorrhea was also noted for about 2 months, and her review of systems was negative for the common “B” symptoms associated with lymphoma. At our hospital, imaging studies revealed a huge pelvic mass (10.8 ×8.7 cm), suggesting a large subserous myoma or an ovarian tumor. Under the impression of pelvic mass, she underwent exploratory laparotomy. Primary ovarian sex-cord malignancy with cecum involvement was impressed by the primitive intraoperative frozen section report. Subsequently, an optimal cytoreductive operation with right hemicolectomy was performed. However, final histopathologic report was an extranodal multifocal BL.ConclusionAlthough extranodal BL in ovaries is a rare condition, it should be noted in the differential diagnosis of pelvic gynecologic malignancies

Minimizing the Total Service Time of Discrete Dynamic Berth Allocation Problem by an Iterated Greedy Heuristic

Berth allocation is the forefront operation performed when ships arrive at a port and is a critical task in container port optimization. Minimizing the time ships spend at berths constitutes an important objective of berth allocation problems. This study focuses on the discrete dynamic berth allocation problem (discrete DBAP), which aims to minimize total service time, and proposes an iterated greedy (IG) algorithm to solve it. The proposed IG algorithm is tested on three benchmark problem sets. Experimental results show that the proposed IG algorithm can obtain optimal solutions for all test instances of the first and second problem sets and outperforms the best-known solutions for 35 out of 90 test instances of the third problem set

Investigating casino event management integration: The case of East and South Asia casinos

The aim of this study is to investigate the gap of event management in East and South Asia’s casinos throughout the information provided by casinos on their websites. Main objective is to identify the differences and similarities of event holding in East and South Asia’s casinos and suggest future directions for casino managers and event organizers. Four research questions were developed to provide ourselves a goal, as well as to further our understanding of our investigation. There are two steps to structure our study. First is to evaluate the performance of 138 casino’s websites, which were obtained from worldcasinodirectory. com by using a website evaluation tool that we have constructed. In the second step, we conduct a content analysis for the website so we can identify what kind of events are organized in the area on our samples. The data of the content analysis provides a comparison of events in our sampling, such as the event’s size, type, and frequency of holding an event. We believe that our research would contribute to event organizers and large scale corporations to give them an insight on the overall efficiency of websites, as well as the frequency of events around East and South Asian casinos

A putative lytic transglycosylase tightly regulated and critical for the EHEC type three secretion

Open reading frame l0045 in the pathogenic island of enterohemorrhagic Escherichia coli O157:H7 has been predicted to encode a lytic transglycosylase that is homologous to two different gene products encoded by the same bacteria at loci away from the island. To deduce the necessity of the presence in the island, we created an l0045-deleted strain of EHEC and observed that both the level of cytosolic EspA and that of the other type III secreted proteins in the media were affected. In a complementation assay, a low level-expressing L0045 appeared to recover efficiently the type III secretion (TTS). On the other hand, when l0045 was driven to express robustly, the intracellular levels of representative TTS proteins were severely suppressed. This suppression is apparently caused by the protein of L0045 per se since introducing an early translational termination codon abolished the suppression. Intriguingly, the authentic L0045 was hardly detected in all lysates of EHEC differently prepared while the same construct was expectedly expressed in the K-12 strain. A unique network must exist in EHEC to tightly regulate the presence of L0045, and we found that a LEE regulator (GrlA) is critically involved in this regulation

Suppressing Decoherence in Quantum Plasmonic Systems by Spectral Hole Burning Effect

Quantum plasmonic systems suffer from significant decoherence due to the intrinsically large dissipative and radiative dampings. Based on our quantum simulations via a quantum tensor network algorithm, we numerically demonstrate the mitigation of this restrictive drawback by hybridizing a plasmonic nanocavity with an emitter ensemble with inhomogeneously-broadened transition frequencies. By burning two narrow spectral holes in the spectral density of the emitter ensemble, the coherent time of Rabi oscillation for the hybrid system is increased tenfold. With the suppressed decoherence, we move one step further in bringing plasmonic systems into practical quantum applications