Prion strain diversity may be greater than previously thought

first_imgCredit: Pixabay, Free-Photos (CC0 Source:https://www.plos.org Prion diseases are transmissible neurodegenerative diseases that affect humans and other animals and are caused by a misfolded form of the prion protein. Currently, effective treatment for prion diseases is not available, and they are inevitably fatal. Prion strains can differ in incubation period and can interfere with each other when present in the same host, in some cases, completely blocking another strain from causing disease. Interference between prion strains is thought to be an important factor affecting the emergence of a dominant strain after interspecies transmission. Previous studies have examined the capacity of strains with long incubation periods to interfere with a short-incubation strains, but until now, it was not known if two strains with long incubation periods could interfere with each other.Related StoriesScreenIn3D receives technology innovation prizeNanoparticles used to deliver CRISPR gene editing tools into the cellTrump administration cracks down on fetal tissue researchIn the new study, Bartz and colleagues show that combinations of prion strains with long incubation periods do not interfere with each other in a test tube or in infected hamsters. Rather, both co-infecting strains amplified independently. The concept that not all prion strain combinations result in interference suggests that strain diversity in naturally infected animals may be greater than previously thought. Overall, this observation changes the paradigm of prion strain interactions, provides further evidence that strains are a dynamic mixture of substrains, and has important implications for interspecies transmission and the emergence of prion strains.“This work provides further evidence that prion strains compete for the template of conversion, PrPC,” says Bartz. “Importantly, we found that when the abundance of PrPC can fully support conversion of both prion strains in the same environment, strain interference does not occur.”center_img Oct 19 2018The first example of prion strains that replicate independently in vitro and in vivo suggests that strain diversity may be greater than previously thought, according to a study published October 18 in the open-access journal PLOS Pathogens by Jason Bartz of Creighton University, and colleagues.last_img read more

New protein target for deadly ovarian cancer

first_imgThe good news about the newly discovered protein is that it can be inhibited, thus inactivating cell processes within ovarian cancer cells to switch them from a constitutively proliferative cell cycle to one which results in senescence, or going to sleep. The key role of the protein was identified on cell culture experiments by researchers at Penn State College of Medicine.The current study focused on teasing out the differences in the metabolism of ovarian cancer cells by comparing them with cells from a normal fallopian tube.The route used to achieve this was quantitative spectrometry, which helped analyze the metabolites produced by various cellular pathways in the two type of tissue. Among the differences, it was revealed that cancer cells utilized glucose, a form of sugar, via the key energy cycle called the citric acid cycle, far more often, as against the more common use of an oxygen-requiring pathway called aerobic glycolysis. This accounts for the presence of a high level of citric acid activity in all high-grade serous ovarian cancer cells.  Related StoriesLiving with advanced breast cancerUsing machine learning algorithm to accurately diagnose breast cancerMother calls for protein shake regulation after daughter diesThis means that many therapies which inhibit the breakdown of glucose (glycolysis) to destroy cancer cells may be quite ineffective. Dahl commented that this could often result, in fact, in the production of toxins that harm normal healthy tissue.Instead, the team in the current study looked at the effects of inhibiting the wildtype or normal form of an enzyme, isocitrate dehydrogenase 1 (IDH 1), which plays a vital part in the citric acid cycle. They selected this protein because it was the only one in this pathway that is expressed at higher levels in both adherent and spheroid tumor cells. Increased activity of this enzyme severely impacts progression-free survival, which is an important outcome measured in assessing the effectiveness of any cancer therapy.Mutants of this protein are common in other tumors, but the wildtype form is typically present in cells within HGSC. The researchers hypothesize that the presence of this enzyme is an important advantage to these cells, and its inhibition is a key step to inducing senescence.The researchers found that suppressing the work of this protein stopped cell division completely by suppressing the activity of multiple other genes, inhibiting vital metabolic pathways. Both adherent cells of the primary tumor, and spheroid cells of secondary HGSC, become senescent when the wildtype IDH 1 enzyme is inhibited. Thus, this could be an excellent way to treat HGSC at all stages. This is an important consideration, as ovarian cancers are rarely diagnosed at early stages.While there are already FDA (US Food and Drug Administration)-approved drugs against one of the mutant forms of this enzyme, the team wondered whether they would work against the wildtype form as well. They found that one did, and this is now a part of their continued research agenda.Aird says, “One of our long-term goals is to try and repurpose this already-approved drug as a treatment for this form of ovarian cancer.” Besides adapting existing drugs against the enzyme to fight this type of cancer, the researchers want to examine the differences in the metabolic functioning of normal and HGSC cells more closely. Another goal is to examine the effectiveness of combining IDH 1 inhibitors with other treatments. Journal reference:Targeting IDH1 as a Prosenescent Therapy in High-grade Serous Ovarian Cancer, Erika S. Dahl, Raquel Buj, Kelly E. Leon, Jordan M. Newell, Yuka Imamura, Benjamin G. Bitler, Nathaniel W. Snyder and Katherine M. Aird, Mol Cancer Res June 17 2019 DOI: 10.1158/1541-7786.MCR-18-1233, http://mcr.aacrjournals.org/content/early/2019/06/17/1541-7786.MCR-18-1233 By Dr. Liji Thomas, MDJul 14 2019A new study shows that targeting a specific protein found within quickly spreading high-grade serous carcinomas (HGSC) of the ovary could help contain these cancers. HGSC is the most common and deadly form of epithelial ovarian cancer, which is itself the deadliest cancer of the female reproductive tract. When HGSC spreads outside the ovaries, within the peritoneal cavity, it forms detached balls called spheroids, which may look and act differently from the adherent cells of the primary tumor.The study is published in the current issue of the journal Molecular Cancer Research. However, as researcher Erika Dahl explains, “A hallmark of cancer cells is that their metabolic processes are often different from normal, healthy cells.”  This is called metabolic reprogramming. As one of the outcomes, study author Katherine Aird says, “Cancer cells can grow forever without stimulus.” 70% of HGSC relapse despite treatment, becoming resistant to chemotherapy, which makes the new discovery a true potential breakthrough in the treatment of this tumor.All life at cellular and organism level depends upon thousands of life processes that provide and degrade a range of chemicals required for proper function of the cells and tissues. These intricately interdependent processes together they make up the body’s metabolism. Cancer cell Illustration. Image Credit: Jovan Vitanovski / Shutterstocklast_img read more

Amazons potential HQ2 sites leaves many cities disappointed

In this Wednesday, Dec. 20, 2017, file photo, a clerk reaches to a shelf to pick an item for a customer order at the Amazon Prime warehouse, in New York. Amazon announced Thursday, Jan. 18, 2018, that it has narrowed down its potential site for a second headquarters in North America to 20 metropolitan areas, mainly on the East Coast. (AP Photo/Mark Lennihan, File) Maybe next time: Cities see failed Amazon bids as trial runs ___DETROIT”We would have loved to have made it into the next round for Amazon’s second headquarters but everyone here is incredibly proud of the proposal we submitted,” Mayor Mike Duggan said. “It showed a clear vision for the future of our city and brought out the very best of our city and our region.”___MEMPHIS, Tennessee”We came together and gave it our best shot,” Mayor Jim Strickland said. “The good news is that this exercise showed us new ways to showcase our city that we are already using to attract other businesses.””Memphis has momentum and other companies have seen and will continue to see our value”The city offered Amazon $60 million in cash incentives.___KANSAS CITY, Missouri”I can understand that some Kansas Citians may be disappointed, but it’s important to remember that as a result of this very collaborative effort, more people today know more great things about Kansas City than they ever did before,” said Mayor Sly James. “Kansas City will continue to develop transformational projects and partnerships that continue the momentum you feel in every block and every neighborhood of this great city. We truly are a city on the rise, and I look forward to our exciting future.”___DELAWAREDelaware’s Gov. John Carney and the state’s congressional delegation said they were “of course” disappointed not to be chosen.”But we used this opportunity to showcase all the options in Delaware not just for Amazon, but for any business looking for a location to set down roots and grow,” they said. “In that respect, Delaware’s effort—which brought together leaders in the public and private sectors to promote our great state—was a resounding success. Going forward, we’ll do everything we can to support Philadelphia’s application, to help bring Amazon to our region.”___NEW HAMPSHIRE”New Hampshire’s groundbreaking proposal to recruit Amazon was the most comprehensive business marketing plan our state has ever produced,” Gov. Chris Sununu said in a statement. “While we always knew that our bid was considered a long shot, we are excited that it is already serving as a template for other businesses that now have New Hampshire on their radar. Our commitment to economic and workforce development is already yielding results. We will never stop emphasizing that New Hampshire is open for business, open for workers, and open for opportunity.” Amazon’s move to whittle its list for a second headquarters leaves more than 200 municipalities disappointed. Here are statements from some of the places that didn’t make the tech giant’s cut to 20 contenders: Explore further Citation: Amazon’s potential HQ2 sites leaves many cities disappointed (2018, January 19) retrieved 18 July 2019 from https://phys.org/news/2018-01-amazon-potential-hq2-sites-cities.html New Hampshire’s Amazon proposal was centered in Londonderry and emphasized the state’s lack of a sales or income tax.___SAN DIEGO”While disappointed San Diego/Chula Vista did not advance, we are not at all surprised,” said Mark Cafferty, president and CEO of the San Diego Regional Economic Development Corp. “We knew that this would be a long shot based on geography and incentive options, but we also know that as a region, San Diego can most definitely compete with others in terms of talent, entrepreneurship, innovation and quality of life.”___NORTHERN CALIFORNIAThe two bids submitted by cities in the San Francisco Bay Area were both rejected by Amazon. Bay Area Council President Jim Wunderman said the decision was disappointing. “We’re not completely surprised by Amazon’s decision,” he said. “The Bay Area is one of the most innovative regions in the world and the huge economic expansion we have witnessed here over the past 10 years has created significant challenges in the form of high housing costs, high cost of living and growing traffic. We are working hard to address these challenges, but we suspect they factored heavily in Amazon’s decision to look elsewhere.”___VIRGINIA BEACH, VIRGINIA”We’re disappointed the City of Virginia Beach was not listed among the top 20 finalists for this project. However, we’re excited the Commonwealth of Virginia is still under consideration,” Virginia Beach Mayor William Sessoms Jr. said. “A project of this magnitude will create many opportunities, and, if Virginia is selected, we expect Virginia Beach and Hampton Roads will benefit.” This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only. © 2018 The Associated Press. All rights reserved. read more