Sebacinales are associates of the leafy liverwort Lophozia excisa in the southern maritime Antarctic
The leafy liverwort Lophozia excisa, which is colonised by basidiomycete fungi in other biomes and which evidence suggests may be colonised by mycorrhizal fungi in Antarctica, was sampled from L,onie Island in the southern maritime Antarctic (67A degrees 36′ S, 68A degrees 21′ W). Microscopic examination of plants indicated that fungal hyphae colonised 78% of the rhizoids of the liverwort, apparently by entering the tips of rhizoids prior to growing into their bases, where they formed hyphal coils. Extensive colonisation of stem medullary cells by hyphae was also observed. DNA was extracted from surface-sterilised liverwort tissues and sequenced following nested PCR, using the primer set ITS1F/TW14, followed by a second round of amplification using the ITSSeb3/TW13 primer set. Neighbour-joining analyses showed that the sequences obtained nested in Sebacinales clade B as a 100% supported sister group to Sebacinales sequences from the leafy liverworts Lophozia sudetica, L. incisa and Calypogeia muelleriana sampled from Europe. Direct PCR using the fungal specific primer set ITS1F/ITS4 similarly identified fungi belonging to Sebacinales clade B as the principal colonists of L. excisa tissues. These observations indicate the presence of a second mycothallus in Antarctica and support the previous suggestion that the Sebacinales has a wide geographical distribution.
It has long been known that cancer cells use nutrients differently than normal cells. In recent years, the rapidly re-emerging field of cancer metabolism has shed new light on the ways that cancers use glucose to grow and thrive, demonstrating that manipulation of an enzyme called PKM2 is important to this metabolic process.Now a new study led by a scientific team at Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School (HMS) has uncovered another key mechanism that cancer cells use as part of their survival strategy — and once again it seems that they are using PKM2 to their advantage.Reported in the Nov. 3 express online edition of Science, the new findings show that by keeping PKM2 activity at lower-than-normal levels, cancer cells are able to withstand damage caused by oxidative stress and the generation of potentially toxic reactive oxygen species (ROS). Importantly, the study shows that small-molecule PKM2 activator drugs could be a way to interfere with this process — and thereby disrupt tumor growth.“Many cancer cells take up glucose at higher rates than most normal cells, and then use the sugar in a distinct way to fuel their proliferation,” explains senior author Lewis Cantley, director of the Cancer Center at BIDMC and the William Bosworth Castle Professor of Medicine at HMS. “Several years ago, it was discovered that the M2 form of the pyruvate kinase enzyme [PKM2] plays a key role in this metabolic process. Now, these new findings demonstrate yet another way that cancer cells are able to manipulate PKM2 to their advantage, suggesting that by keeping PKM2 activity low, cancer cells channel incoming glucose to metabolic pathways that generate antioxidants, and thereby survive oxidative stress.”Glycolysis is a multistep process in which glucose is broken down so that cells can make use of the sugar for energy and other essential functions, and the PKM2 enzyme is responsible for the final step of the process. Previous work from the Cantley lab had suggested that inhibition of PKM2 by growth-factor signaling was providing a stall-point in the glycolytic process, functioning like a dam in a river to enable glucose breakdown products to accumulate and eventually spur cancer cell growth.But the investigators thought there might be more to the story.“Growth-factor signaling emerged relatively late in evolution but glycolysis is a highly conserved process and occurs in bacteria much like it occurs in human cells,” says Dimitrios Anastasiou, a research fellow in the Department of Signal Transduction at BIDMC and the Department of Systems Biology at HMS and first author of this new paper. “We were intrigued by the possibility that something other than growth factors might also be influencing the activity of PKM2.”They turned their attention to reactive oxygen species (ROS), chemically reactive molecules that form as a natural byproduct of cell metabolism and can lead to cell damage when not kept under control. “To survive, cancer cells require the ability to squelch potentially toxic ROS molecules, which can arise as a result of both their aberrant metabolism as well as their environment,” explains Anastasiou. “We thought that PKM2 might somehow be playing a supporting role in tamping down ROS.”To test this hypothesis, the scientific team embarked on a series of experiments that showed ROS can inhibit PKM2 activity, and that low PKM2 activity under oxidative stress helps push glucose into pathways that generate antioxidant molecules.“We engineered cells to express a PKM2 mutant that is resistant to ROS-induced inhibition,” says Anastasiou. “This showed us that when challenged by oxidative stress these cells died more readily than cells expressing the wild-type oxidizable version of PKM2. Strikingly, we also observed that oxidation-resistant PKM2 could not efficiently support the ability of human lung-cancer cells to form tumors in mice, but that this defect could be rescued by treating mice with an antioxidant in their water.”The team also collaborated with the National Institutes of Health (NIH) Chemical Genomics Center to identify small-molecule PKM2 activators, drugs that keep PKM2 active and thereby prevent cancer cells from using glucose to grow and survive. Treatment of cancer cells with these activators kept PKM2 activity at high levels even under oxidative stress. It also sensitized cells to oxidant-induced death similar to the oxidation-resistant mutant.“This paper demonstrates that oxidants inhibit PKM2 activity,” says Cantley. “While moderate ROS levels can influence growth signaling and promote proliferation, too much ROS can cause irreversible damage to cells, and lead to their demise. We propose that expression of PKM2 allows cancer cells greater flexibility in manipulating how glucose is metabolized to ensure that ROS concentrations remain low.“Now that we’ve figured out yet another scheme that cancer uses to survive, we might be able to use small-molecule PKM2 activators to prevent cancer from inhibiting the enzyme,” he adds. “Because radiation therapy and some chemotherapeutic agents are believed to kill cancer cells by inducing excess ROS, there is a possibility that PKM2 activators may improve the efficiency of these therapies.”This work was supported by grants from the National Institutes of Health, the Starr Cancer Consortium, the Molecular Libraries Program of the National Institutes of Health Roadmap for Medical Research, and the Intramural Research Program of the National Human Genome Research Institute at the National Institutes of Health.
ANKENY, Iowa (March 20) – The biggest event in dirt track racing and drivers in the premier series for IMCA Late Models enjoy the support of Casey’s General Store again this season. Based in Ankeny, Iowa, third-year marketing partner Casey’s returns as presenting sponsor for the Sept. 7-12 IMCA Speedway Motors Super Nationals, and title sponsor for the redraw at all Deery Brothers Summer Series main events.The Official Convenience Store of IMCA, Casey’s will give a hat and a $20 gift card to eligible heat winners in all divisions during the IMCA Speedway Motors Super Nationals fueled by Casey’s.Both Casey’s and IMCA will donate $10 to Hope for the Warriors on behalf of each heat winner during the week at Boone Speedway. More than $10,000 was donated to Hope For The Warriors in 2013 and 2014. Drivers drawing the pole start for each Deery feature receive $50 gift cards. Drivers with perfect attendance for the entire season also receive $100 gift cards.Super Nationals and Deery competitors are required to display two Casey’s decals on their race car to be eligible. All gift cards are redeemable at any of the 1,865 Casey’s stores located in 14 states. The first Casey’s store opened in Boone in 1968. Casey’s continues to maintain a very visible presence in the hometown of Super Nationals with a store that opened along Highway 30, just across the road from the Boone Speedway grounds. In addition to selling grocery items, bakery goods and gasoline, Casey’s has grown to become the fifth largest pizza chain in the United States with stores in Arkansas, Illinois, Indiana, Iowa, Kansas, Kentucky, Minnesota, Missouri, Nebraska, North Dakota, Oklahoma, South Dakota, Tennessee and Wisconsin.The Casey’s website is www.caseys.com. Information about new promotions is on Facebook. “Casey’s has always been a supporter of racing in general and they’ve been extremely generous and professional to work with the past two seasons,” noted IMCA Marketing Director Kevin Yoder. “Sharing common support for the Hope For The Warriors organization also unites us at the largest dirt track event in the world and that has solidified the bond. We look forward to promoting Casey’s as the Official Convenience Store of IMCA for years to come.”