Hijacking stress response in cancer

July 2, 2013 ? Cancer cells have alteration in metabolic pathways as a result of oncogenes that promote tumor growth. NRF2 (nuclear factor erythroid-derived 2-related factor 2) works as a "master gene" that turns on stress response by increasing numerous antioxidants and pollutant-detoxifying genes to protect the lungs from variety of air pollutants such as diesel exhaust and cigarette smoke. However, researchers at the Johns Hopkins Bloomberg School of Public Health and others have found for the first time that NRF2 signaling also plays a role in the growth of tumor cells by altering metabolic pathways.

The study is published in the July issue of the Journal of Clinical Investigation.

"Previously, we had reported that lung cancer cells, due to mutation in inhibitors of NRF2, hijack the stress response pathway to cause chemoresistance," said Shyam Biswal, PhD, lead investigator of the study and professor in the Department of Environmental Health Sciences at the Bloomberg School of Public Health. "With our latest study, we show how the NRF2 pathway reprograms glucose metabolism, leading to increased energy production and tumor cell proliferation. A better understanding of this process could lead to potential cancer treatments."

The Johns Hopkins study demonstrated an important and previously unrecognized role for the NRF2 transcription factor in regulating cell metabolism. Specifically, NRF2 regulates genes miR-1 and miR-206 to "reprogram" glucose metabolism through PPP (pentose phosphate pathway) and the TCA (tricarboxylic acid) cycle, and fatty acid synthesis. The study demonstrated that these enzyme pathways, working together in specific patterns, stimulated tumor growth. The researchers validated their findings through a series of in vitro experiments and studies involving mice.

"Although Nrf2 has been extensively studied as a target for chemoprevention, recent work from our group and others have highlighted the idea of developing inhibitors of Nrf2 to inhibit cancer " said Anju Singh, PhD, lead author of the study and assistant scientist in the Bloomberg School's Department of Environmental Health Sciences. Using an integrated genomics and 13C-based metabolic flux system wide association analysis, we demonstrate that Nrf2 modulates glucose flux through PPP and TCA cycles in cancer cells. Biswal concludes that "This study reinforces the idea that targeting Nrf2 with small molecule inhibitors will starve the cancer cells by affecting metabolic pathways as well as decrease antioxidants and detoxification genes to intervene in therapeutic resistance." Biswal's group has been working with the National Center for Advancing Translational Sciences at NIH to develop Nrf2 inhibitors for cancer therapy.

"Transcription factor NRF2 regulated miR-1 and miR-206 to drive tumorigenesis" The study involved laboratories from the Johns Hopkins Center for Cancer Research, the National Cancer Institute, the Massachusetts College of Pharmacy, the Dana-Farber Cancer Institute, UCLA and the University of Maryland School of Medicine.

Funding for the research was provided by the National Institutes of Health grant, National Cancer Institute grants RO1 CA140492, P50 CA058184, P30CA006973 and National Institute of Environmental Sciences P30ES03819 and clinical innovator award from the Flight Attendants Medical Research Institute.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/~3/RITaSaY3Apg/130702113443.htm

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Firefox OS hands-on: Alcatel OneTouch Fire and ZTE Open (video)

We've crossed paths with Firefox OS before, but today marks the first time we've played with handsets running the final build of Mozilla's mobile software. The Alcatel OneTouch Fire and ZTE Open you see above are the same hardware we saw at MWC earlier this year -- in fact, the latter just launched in Spain on Telefónica for €69 ($90) contract-free including €30 ($39) of airtime for prepaid customers. We took both phones for a brief spin and immediately noticed a slight improvement in performance. Unfortunately, there's still a significant amount of lag in the UI, especially when scrolling through web pages and navigating the app tray. Websites also take a while to load, even when connecting over Wi-Fi. Then again, what do you expect for €69? Check out the gallery below and hit the break to watch our hands-on video.

Note: the ZTE Open we handled was destined for Movistar (a Telefónica brand) and is launching today for €69 (not €63 as mentioned in our video).

Gallery: Firefox OS hands-on

Filed under: Cellphones, Mobile

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Source: http://www.engadget.com/2013/07/01/firefox-os-hands-on-alcatel-onetouch-fire-and-zte-open-video/?utm_medium=feed&utm_source=Feed_Classic&utm_campaign=Engadget

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Seattle Mariners Fly Gay Pride Flag at Home Game: Inspiring or Inappropriate?

Source: http://www.thehollywoodgossip.com/2013/07/seattle-mariners-fly-gay-pride-flag-at-home-game-inspiring-or-in/

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The Countries Where Edward Snowden Has ... - Business Insider

REUTERS/Bobby Yip

A banner supporting Edward Snowden, a former contractor at the National Security Agency (NSA), is displayed at Hong Kong's financial Central district on June 21, 2013.

The anti-secrecy organization WikiLeaks has submitted 19 additional requests for asylum on behalf of National Security Agency leak source Edward Snowden, the organization announced Monday night.

The 19 requests, which were filed by?WikiLeaks? legal advisor Sarah Harrison at the Russian consulate, come in addition to outstanding requests in Iceland and Ecuador.?

The new requests include what are sure to be some controversial possible destinations ? including Venezuela, China, and Cuba.

Here are the 19 countries:

Republic of Austria, the Plurinational State of Bolivia, the Federative Republic of Brazil, the People?s Republic of China, the Republic of Cuba, the Republic of Finland, the French Republic, the Federal Republic of Germany, the Republic of India, the Italian Republic, the Republic of Ireland, the Kingdom of the Netherlands, the Republic of Nicaragua, the Kingdom of Norway, the Republic of Poland, the Russian Federation, the Kingdom of Spain, the Swiss Confederation and the Bolivarian Republic of Venezuela.

Snowden broke an eight-day silence earlier Monday evening, releasing a statement through WikiLeaks in which he blasted the Obama administration for using "old, bad tools of political aggression" in pursuing him.

Snowden also wrote a letter to Ecuador's President,?Rafael Correa, thanking Correa for helping him travel from Hong Kong to Moscow?and for considering his request for asylum.

Correa brushed back on Snowden's request for asylum over the weekend, when he said he chatted with Vice President Joe Biden about Snowden's request. On Monday, Correa said that Ecuador is not considering Snowden's asylum request and inadvertently helped him travel to Moscow.

Source: http://www.businessinsider.com/the-countries-where-edward-snowden-has-requested-asylum-2013-7

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Mayor's Fourth of July Parade & Picnic

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Source: http://www.publicbroadcasting.net/sdpb/events.eventsmain?action=showEvent&eventID=1390257

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Is that bacteria dead yet? Nano and laser technology packed into small device tests antibiotic treatment in minutes

June 30, 2013 ? Researchers at EPFL have built a matchbox-sized device that can test for the presence of bacteria in a couple of minutes, instead of up to several weeks. A nano-lever vibrates in the presence of bacterial activity, while a laser reads the vibration and translates it into an electrical signal that can be easily read -- the absence of a signal signifies the absence of bacteria. Thanks to this method, it is quick and easy to determine if a bacteria has been effectively treated by an antibiotic, a crucial medical tool especially for resistant strains. Easily used in clinics, it could also prove useful for testing chemotherapy treatment.

The research is published in the latest issue of Nature Nanotechnology.

"This method is fast and accurate. And it can be a precious tool for both doctors looking for the right dosage of antibiotics and for researchers to determine which treatments are the most effective," explains Giovanni Dietler.

Laser and nanotechnology read the bacteria's metabolic activity

It currently takes a long time to measure a bacterial infection's response to antibiotic treatment. Clinicians must culture the bacteria and then observe its growth, sometimes for almost a month, as is the case with tuberculosis, in order to determine if the treatment has been effective.

Thanks to advances in laser and optical technology, the EPFL team of physicists has reduced this time to a couple of minutes. To do so, Giovanni Dietler, Sandor Kasas and Giovanni Longo have exploited the microscopic movements of a bacterium's metabolism.

These vital signs are almost unperceivable. In order to test for them, the researchers place the bacteria on an extremely sensitive measuring device that vibrates a small lever -- only slightly thicker than a strand of hair -- in the presence of certain activity. The lever then vibrates under the metabolic activity of the germs. These infinitely small oscillations, on the order of one millionth of a millimeter, determine the presence or absence of the bacteria.

To measure these vibrations, the researchers project a laser onto the lever. The light is then reflected back and the signal is converted into an electrical current to be interpreted by the clinician or researcher. When the electrical current is a flat line, one knows that the bacteria are all dead; it is as easy to read as an electrocardiogram.

A promising method for cancer treatment

The researchers have miniaturized the tool -- it is currently the size of a matchbox. "By joining our tool with a piezoelectric device instead of a laser, we could further reduce its size to the size of a microchip," says Giovanni Dietler. They could then be combined together to test a series of antibiotics on one strain in only a couple of minutes.

The researchers are currently evaluating the tool's potential in other fields, notably oncology. They are looking into measuring the metabolism of tumor cells that have been exposed to cancer treatment to evaluate the efficiency of the treatment. "If our method also works in this field, we really have a precious tool on our hands that can allow us to develop new treatments and also test both quickly and simply how the patient is reacting to the cancer treatment," says Sandor Kasas.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/top_health/~3/1zTXeSe2UBI/130630145006.htm

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Intergalactic magnifying glasses could help astronomers map galaxy centers

June 30, 2013 ? An international team of astronomers may have found a new way to map quasars, the energetic and luminous central regions often found in distant galaxies. Team leader Prof. Andy Lawrence of the University of Edinburgh presents the new results on Monday 1 July at the RAS National Astronomy Meeting in St Andrews, Scotland.

If a star passes too close to a giant black hole found in the centre of a galaxy, it will be shredded by the strong gravitational field. This produces a flare-up in the brightness of an otherwise normal looking galaxy that then fades over a few months. In a large scale survey using the PanSTARRS telescope on Hawaii, Prof. Lawrence and his team studied millions of galaxies to search for this rare effect. They did find flare-ups but with very different behaviour to the 'star shredding' predictions.

Instead of seeing a fade over months, the objects they found look like 'normal' quasars, regions in the centre of galaxies where material is swirling around a giant black hole in a disk. But the quasars in the survey were not seen a decade ago, so must now be at least ten times brighter than before. Monitoring with the Liverpool Telescope on La Palma showed that they are also changing slowly, fading over a timescale of years rather than months.

The biggest surprise however was that the quasars seemed to be at the wrong distance. Measuring the characteristic shift in lines found in the spectrum of the quasars allows astronomers to measure the speed at which they are moving away from Earth. Knowing the way in which the universe is expanding enables scientists to deduce the distance to each object.

In the new survey, the quasars are typically around 10 billion light years away, whereas the galaxies that host them seem on average to be about 3 billion light years distant. The distances are rough estimates, so it could be that the estimated galaxy distances are completely wrong and that they are actually much further away. The black holes in their centres have then have flared up very dramatically, explaining why they seem so bright. But past studies of thousands of well-known quasars have never shown events on this scale.

If however the estimated galaxy distances are right, then Prof. Lawrence and his team believe they are looking at a distant quasar through a foreground galaxy. Normally this has little effect on the light of the quasar, but if a single star in the foreground galaxy passes exactly in front of the quasar, it can produce a gravitational focusing of the light which makes the background quasar seem temporarily much brighter.

This "microlensing" phenomenon is well known inside our own Galaxy, producing a brightening when one star passes in front of another. (It is for example also now being used to detect exoplanets). Microlensing may also be the cause of low-level "flickering" seen in some quasars. But this is the first time it has been suggested to cause such giant brightening events.

Prof. Lawrence sees real potential in this newly-discovered effect. "This could give us a way to map out the internal structure of quasars in a way that is otherwise impossible, because quasars are so small. As the star moves across the face of the distant quasar, it is like scanning a magnifying glass across it, revealing details that would otherwise simply be impossible to detect."

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/top_technology/~3/dx2MD1m0pB4/130630225229.htm

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