Paramount Gold and Silver (?(NYSE:PZG, AMEX:PZG, TSX:PZG) announced drilling results from four additional holes into the growing La Bavisa target on their San Miguel Project in Mexico.
As quoted in the press release:
The La Bavisa target, located 700 meters north of the high-grade Don Ese resource, has been traced on surface for over 2.8 km. To date, a total of eight drill holes have been completed into La Bavisa, defining a mineralized strike of 1.5 km. containing intercepts up to 12.20 meters wide grading 1.22 g/T gold and 255.8 g/T silver (approximately 5.5 g/T of gold equivalent at a conservative silver-to-gold ratio of 60:1). La Bavisa has not yet been incorporated into San Miguel?s resource estimates and therefore is not part of the project?s first Preliminary Economic Assessment scheduled for completion by year-end.
Paramount?s CEO, Christopher Crupi, said:
The Don Ese resource area has emerged as a major target, potentially the most important of the four main mineralized zones on San Miguel. A swarm of higher-grade structures has now been identified at Don Ese and are likely to be exploited together. The reality is that San Miguel continues to grow quickly and we are far from exhausting our list of excellent opportunities for resource expansion. Our challenge is to develop current engineering and economic projections while at the same time undergoing rapid resource expansion.
Denard Span has been linked to the Nationals in trade rumors dating back to mid-2011 and the Twins finally pulled the trigger today, sending the 28-year-old center fielder to Washington for pitching prospect Alex Meyer.
Span fits what the Nationals were looking for both offensively and defensively, as he?s a prototypical leadoff man with good on-base skills and speed who covers plenty of ground in center field. This year he hit .283 with a .342 on-base percentage in 128 games and Span has a career OBP of .357. He?s under team control through 2015 at reasonable prices, making $20.25 million over the three seasons.
Meyer was the Nationals? first-round pick in 2011 out of the University of Kentucky and the 6-foot-9 right-hander with a mid-90s fastball had a strong pro debut this year, throwing 129 innings with a 2.86 ERA and 139/45 K/BB ratio between two levels of Single-A. He?s certainly not MLB-ready yet, but could be ready at some point in 2014 and the Twins have been desperate to find some hard-throwing starters with top-of-the-rotation potential.
Span will take over as the Nationals? center fielder and leadoff man, allowing Bryce Harper to play a corner spot full time and perhaps signaling the end of Adam LaRoche?s time in Washington. Ben Revere will replace Span as the Twins? center fielder and will likely get every chance to become Minnesota?s leadoff man despite a .319 career on-base percentage though age 24.
Note: For my much longer, Twins-centric view of the trade, click here.
Q76. What are the possible ways of data exchange? Ans. (i) Simplex (ii) Half-duplex (iii) Full-duplex.
Q77. What are the types of Transmission media? Ans. Signals are usually transmitted over some transmission media that are broadly classified in to two categories. Guided Media: These are those that provide a conduit from one device to another that include twisted-pair, coaxial cable and fiber-optic cable. A signal traveling along any of these media is directed and is contained by the physical limits of the medium. Twisted-pair and coaxial cable use metallic that accept and transport signals in the form of electrical current. Optical fiber is a glass or plastic cable that accepts and transports signals in the form of light. Unguided Media: This is the wireless media that transport electromagnetic waves without using a physical conductor. Signals are broadcast either through air. This is done through radio communication, satellite communication and cellular telephony.
Q78. Difference between the communication and transmission. Ans. Transmission is a physical movement of information and concern issues like bit polarity, synchronization, clock etc. Communication means the meaning full exchange of information between two communication media.
Q79.The Internet Control Message Protocol occurs at what layer of the seven layer model? Ans. Network
Q80.Which protocol resolves an IP address to a MAC address? Ans. ARP
Q81.MIDI and MPEG are examples of what layer of the OSI seven layer model? Ans. Presentation
Q82.What is the protocol number for UDP? Ans. 17
Q83.Which protocol is used for booting diskless workstations? Ans. RARP
Q84.Which layer is responsible for putting 1s and 0s into a logical group? Ans. Physical
Q85.What does ?P? mean when running a Trace? Ans. Protocol unreachable
Q86.UDP works at which layer of the DOD model? Ans. Host to Host
Q87.What is the default encapsulation of Netware 3.12? Ans. 802.2
Q88.Ping uses which Internet layer protocol? Ans. ICMP
Q89.Which switching technology can reduce the size of a broadcast domain? Ans. VLAN
Q90.What is the first step in data encapsulation? Ans. User information is converted into data.
Q91.What is the protocol number for TCP? Ans. 6
Q92.What do you use the Aux port for? Ans. Modem
Q93.Repeaters work at which layer of the OSI model? Ans. Physical
Q94.WAN stands for which of the following? Ans. Wide Area Network
Q95.What ISDN protocol specifies concepts, terminology, and services? Ans. I
Q96.LAN stands for which of the following? Ans. Local Are Network
Q97.DHCP stands for Ans. Dynamic Host Configuration Protocol
Q98.What does the acronym ARP stand for? Ans. Address Resolution Protocol
Q99.Which layer is responsible for identifying and establishing the availability of the intended communication partner? Ans. Application.
Q100.Which OSI layer provides mechanical, electrical, procedural for activating, maintaining physical link? Ans. Physical.
Related posts:
100 Networking Interview Questions ? Part 3
100 Networking Interview Questions ? Part 1
100 Networking Interview Questions ? Part 2
S1 C2 Communicating over the Network
Interview Questions for System Engineer / Network Engineer
Building upon the work Google began in 2009, YouTube is now extending its automatic captioning reach to six additional languages. Previously, the transcription service was only available to speakers of English, Japanese, Korean and Spanish, but as of today, German, Italian, French, Portuguese, Russian and Dutch have also been added to the fold. Auto-caps, as the company calls it, works by employing the same voice recognition algorithms used within Google Voice, but as anyone familiar with that speech software can attest, it's not always error-free. So, expect some things to be (unintentionally and somewhat amusingly) lost in translation. Speaking of which, with the site's recent inclusion of the search giant's translation software, users will also have the option take their captioned vids and make them readable across a variety of languages. YouTube: building linguistic bridges across the internet's borders.
Not all space tourism is rocket science. A newly successful test of a balloon could allow paying human customers to enjoy stunning Earth views and the weightless astronaut experience by 2014.?
The test balloon carried a humanoid robot up to an altitude of almost 20 miles (32 kilometers) on Nov. 12 ? just a few miles shy of where skydiver Felix Baumgartner leaped from during his "space dive" in October. Startup Zero 2 Infinity wants to eventually offer hours of flight time for space tourists to do whatever they want in a near-space environment.?
"Some people will want to tweet," said Jose Mariano Lopez-Urdiales, founder and CEO of Zero 2 Infinity. "Some will want to put down a carpet and pray to mecca. Some people will want to eat their favorite buffalo wings while they're up there."
Video: Near-space balloon soars in flight test
The Spanish company already has customers on its wait list?who paid an early deposit of almost $13,000 (10,000 euros) as the first installment out of a total ticket price of $143,000 (110,000 euros). It has also attracted funding from the world's second-largest balloon manufacturer, Spain's third-largest bank, and several angel investors by proving its concept step-by-step and by relying on proven helium balloon technologies.?
Flight testing took place at an Air Force base near Virgen del Camino in Spain. But Lopez-Urdiales envisions future flights launching from many other locations in the country.?
The balloon experience? A typical predawn flight would take several hours to reach maximum altitude, so that passengers could enjoy seeing the sun rise against the blackness of space and see the curvature of the planet Earth. Luckily, the balloon would not need to get anywhere near the 62-mile (100 km) altitude that marks the official edge of space for its riders to enjoy stellar views.?
"You would spend two hours at the floating altitude of 36 kilometers (22 miles)," Lopez-Urdiales told TechNewsDaily. "We could do it higher, but it would not make any difference, because you already see the same visual cues at 39 kilometers or even 100 kilometers."?
Getting back down would mean cutting the cord between the balloon and the enclosed passenger capsule. Passengers could experience about 40 to 60 seconds of weightlessness during free fall, before parachutes and a parafoil carried them safely down to Earth.?
The recent test flight gave Zero 2 Infinity its first successful test of a balloon capsule large enough to carry humans, but only if the two people spent the entire trip lying down. An earlier flight test scheduled in May was canceled after?wind gusts damaged the test balloon.?
Robot test pilots? Future versions of the balloons, called "bloons" by the company, would have donut- or bagel-shaped capsules with plenty of standing room for two pilots and four passengers. But the test capsule proved just right for the humanoid robot named Nao ? made by Aldebaran Robotics ? that stands at knee-height compared to adult humans.?
The robot rode as a passive passenger, but could someday become an active pilot that tests the controls and life-support technologies meant for humans.?
"Little by little, we're teaching it how to pilot, but that's at a very early stage," Lopez-Urdiales explained. "The idea in the future is to have?humanoid robots?testing future complex aerospace vehicles."?
The company has almost finished building a bigger test balloon that could comfortably carry two people standing up. That larger balloon could make an attempt at breaking the manned high-altitude balloon record set in the 1960s ? a record that requires the pilot to take off and land in the balloon. (Space diver Baumgartner intentionally disqualified himself by leaping out of his high-flying balloon.)?
The inner journey? But Zero 2 Infinity doesn't just want to make money. Lopez-Urdiales envisions his balloons carrying scientific experiments or scientists high into Earth's atmosphere. His inspiration for creating the startup company came from his dad, an astrophysicist who worked on an experiment that went with the Cassini-Huygens mission to Saturn's moon Titan.?
"I was growing up around balloons, rockets and telescopes," Lopez-Urdiales said. "My dad tested a Huygens scientific instrument on a high-altitude balloon."?
The balloon space tourism's relatively more affordable price tag could also open the eyes of many more people through the "overview effect," Lopez-Urdiales said. Frank White, a communications director at Harvard's Kennedy School of Government, coined the term to describe how astronauts gained a better appreciation of global and environmental issues after seeing the Earth surrounded by the darkness of space.?
"That's probably the biggest benefit?private spaceflight?will offer to civilians and members of the public," Lopez-Urdiales said. "The overview effect is personal experience, but then you share it. I think it goes a much longer way than bragging rights."?
You can follow TechNewsDaily Senior Writer Jeremy Hsu on Twitter. Follow TechNewsDaily on Twitter?, or on?Facebook.
After swiftly selling out on the carrier's website just a few days ago, it seems T-Mobile USA is back with more stock of the desirable LG Nexus 4. As before, the phone is being sold for $199 on a two-year service plan with Tmo.
The LG-made Nexus phone has been quick to sell out via many online retailers, including Google's own Play Devices store. Previously, Google had directed would-be Play Store buyers to T-Mobile, however shortly after that notice went up Tmo's stock was also depleted.
T-Mobile is offering the 16GB version of the Nexus 4, which sold for $350 during the brief time it was available through Google Play.
DOHA, Qatar (AP) ? The U.S. defended its track record on fighting climate change on Monday at U.N. talks, saying it's making "enormous" efforts to slow global warming and help the poor nations most affected by it.
Other countries have accused Washington of hampering the climate talks ever since the Bush administration abandoned the Kyoto Protocol, the 1997 treaty limiting emissions of heat-trapping gases by industrialized countries. As negotiators met for a two-week session in oil and gas-rich Qatar, U.S. delegate Jonathan Pershing suggested America deserves more credit.
"Those who don't follow what the U.S. is doing may not be informed of the scale and extent of the effort, but it's enormous," Pershing said.
He noted that the Obama administration has taken a series of steps, including sharply increasing fuel efficiency standards for cars and trucks, and made good on promises of climate financing for poor countries. A climate bill that would have capped emissions stalled in the Senate.
"It doesn't mean enough is being done," Pershing said. "It's clear the global community, and that includes us, has to do more if we are going to succeed at avoiding the damages projected in a warming world."
The two-decade-old U.N. talks have not fulfilled their main purpose: reducing the greenhouse gas emissions that scientists say are warming the planet.
The goal is to keep the global temperature rise under 2 degrees C (3.6 F), compared to pre-industrial times.
Efforts taken so far to rein in emissions, reduce deforestation and promote clean technology are not getting the job done. A recent projection by the World Bank showed temperatures are expected to increase by up to 4 degrees C (7.2 F) by 2100.
Scientists warn that dangerous warming effects could include flooding of coastal cities and island nations, disruptions to agriculture and drinking water, the spread of diseases and the extinction of species.
Attempts to forge a new climate treaty failed in Copenhagen three years ago, but countries agreed last year to try again, giving themselves a deadline of 2015 to adopt a new pact.
Several issues need to be resolved by then, including how to spread the burden of emissions cuts between rich and poor countries. That's unlikely to be decided in the current talks in the Qatari capital of Doha, where negotiators from nearly 200 countries are focusing on extending the Kyoto Protocol, and trying to raise billions of dollars to help developing countries adapt to a shifting climate.
"We owe it to our people, the global citizenry. We owe it to our children to give them a safer future than what they are currently facing," said South African Foreign Minister Maite Nkoana-Mashabane, who led last year's talks in Durban, South Africa.
The U.N. process is often criticized, even ridiculed, both by climate activists who say the talks are too slow and by those who challenge the scientific near-consensus that the global temperature rise is at least partly caused by human activity, primarily the burning of fossil fuels like coal and oil.
The concentration of greenhouse gases such as carbon dioxide has jumped 20 percent since 2000, according to a U.N. report released last week. The report also showed that there is a growing gap between what governments are doing to curb emissions and what needs to be done to protect the world from potentially dangerous levels of warming.
"Climate change is no longer some distant threat for the future, but is with us today," said Greenpeace climate campaigner Martin Kaiser, who was also at the Doha talks. "At the end of a year that has seen the impacts of climate change devastate homes and families around the world, the need for action is obvious and urgent."
Many scientists say that extreme weather events, such as Hurricane Sandy's onslaught on the U.S. East Coast, will become more frequent as the Earth warms, although it is impossible to attribute individual weather events to climate change.
The Kyoto Protocol is seen as the most important climate agreement reached in the U.N. process so far. It expires this year, so negotiators in Doha will try to extend it as a stopgap measure until a wider deal can be reached.
The problem is that only the European Union and a handful of other countries ? that together are responsible for than 15 percent of global emissions ? are willing to set emissions targets for a second commitment period of Kyoto.
The U.S. rejected the Kyoto accord because it didn't impose binding commitments on major developing countries such as India and China, which is now the world's top carbon emitter.
China and other developing countries want to maintain a clear division, saying climate change is mainly a legacy of Western industrialization and that their own emissions must be allowed to grow as their economies expand, lifting millions of people out of poverty.
That discord scuttled attempts to forge a climate deal in Copenhagen in 2009 and risks a recurrence in Doha, as talks begin on a new global deal that is supposed to be adopted in 2015 and implemented in 2020.
Environmentalists found the choice of Qatar as host of the two-week conference ironic. The tiny Persian Gulf emirate owes its wealth to large deposits of gas and oil, and it emits more greenhouse gases per capita than any other nation.
Qatar has not even announced any climate action in the U.N. process, and former Qatari oil minister Abdullah Bin Hamad al-Attiyah didn't do so when he opened the conference Monday.
"We should not concentrate on the per capita (emissions). We should concentrate on the amount from each country," al-Attiyah told reporters. "I think Qatar is the right place to host" the conference, he said.
___
AP Environment Writer Michael Casey contributed to this report.
?Portrait of a Young Woman? by Picasso. A 1946 signed lithograph of a 1938 work
In times like these where interest rates are next to nought, it is a thankless task trying to accrue interest from money sat in bank accounts.?
Art, like property, has always been highly regarded as a far greater prospect to invest your money in.?Time and again this has been proven in the London Art Market and it is always an eye opener to see which art is going to be suddenly reassessed to become the next big thing.
I can remember when I visited Sotheby?s in 1995 during the last recession, Modern British art was going through the doldrums and the work of several big name artists could be picked up very reasonably at auction. John Bratby (1928-1992) one time Blackheath resident is a case in point. A prolific ?kitchen sink? artist, noted for depicting such humble domestic subjects as well as lavatories, he courted the press in his day and was as notorious a figure in the 50?s as Damien Hirst or Tracey Emin is today. I saw paintings by him sell under the hammer for a few hundred pounds, including a cracking self portrait I wish in hindsight I had bought when I had the opportunity.
Alex C. Koolman, RP, RBA, (1907 ? 1998). Portrait George Harrison 1970
Charles Saatchi then surprised the art world by buying three very large works from the late 50?s by Bratby from a London dealer in 2003 to display in a dedicated room in his then new County Hall Gallery. This caused something of a ripple effect in the revision of Bratby?s reputation and prices, which had taken a knock since the 1960?s invasion of the American Abstract Expressionists and the new wave of British Pop Art.?Now his work can sell for anywhere between five to fifty thousand pounds plus from London dealers.
My experience in dealing in fine art and antiques for over twenty years has led me to some wonderful finds. On leaving school I went into the family business, The Mount Antiques in Whitby, Yorkshire, where I learnt the art of buying from my mother as I accompanied her to auctions and house calls.?She trained as a textile designer and had a great eye for decorative art and antiques, building an international reputation over twenty years for her emporium on the north east coast.?I then went to college to study both art practice and the history of art.
a view from my studio of Hilly Fields, Brockley
When I came to London I joined Harrods Antiques and Fine Art Department for several years and went on to work as an art consultant in contemporary art to GX Gallery in Camberwell. I have continued to exhibit my own work in London and open my studio each year in Brockley since moving there.
Sunday Art Salon is the latest idea in urban leisure art consumption. It places the emphasis on real social networking, as a platform for meeting like minded professionals and collectors looking for unique stylish statement pieces to enhance their living space and for long term investment.
It creates a stimulating, friendly environment for the public and creatives to meet and engage with a wide range of artist practitioners. Guests have the opportunity of purchasing and talking about artwork with the artists and curator in the setting of a private studio with extensive views across Hilly Fields in Brockley.
Following the opening up of south London in 2010 by the extension of the Overground tube, affectionally nicknamed the ?Ginger line?, places like Brockley and Forest Hill are now on the map as areas of artistic enterprises, with Deptford and Peckham as neighbours, it creates part of a new trend of artistic networks where small galleries and open studios are tailoring themselves to a resurgence in community spirit and awareness.
Whilst the artist?s of the Brockley Open Studios have been quietly opening their doors in their leafy Conservation Area one weekend per summer for twenty years, new initiatives like the South London Art Map have a strong online presence which operates as a listings site, promoting exhibitions in art spaces open late on the last Friday of each month. Undoubtedly as part of the recession and in line with the growing number of markets, both farmers food and craft based, the public are enjoying and demanding something of a renaissance in rediscovering small local trade and commercial premises.
Charles Saatchi and Nigella Lawson visit Canvas and Cream
The Canvas & Cream Cafe and Gallery in Forest Hill is a family-run social enterprise where locals got together with friends and family from their neighbourhood to develop this collaborative project. It comprises artists studios, an artists-designed up cycled restaurant/cafe and a dedicated gallery/project space with art workshop.
It was here where artist Raf Zawistowski?s solo debut show was bought outright by Charles Saatchi before the show even opened in April this year. Proving that once Saatchi has dared to brave this far into London?s south east hinterland, sealing his approval by purchasing art, it can truly be said to have ?arrived?.
Raf Zawistowski?s solo debut show was bought outright by Saatchi
The Misty Moon Gallery in Ladywell, previously the Tank Gallery, originally an 17th?century coaching house behind the Ladywell Tavern, is operated by another artists collective and now caters as an accessible platform for the work of local and international artists, as does Cue B Gallery at the rear of the Brockley Mess cafe on Brockley Road.
The White Room SE4, is the new home of modern women?s wear label, NC23 by a local designer keen to encourage networking and collaboration in the boutique/studio/workshop also on Brockley Road. They plan to offer workshops in sewing, pattern cutting, tailoring and drawing, the first of which is Make a Swing Skirt in 3 hours. This couldn?t be more fitting flanked as it is by a resurgence of vintage style coffee shops selling cupcakes in the area.
Not to mention the unique Grade II Listed Rivoli Ballroom next door, regular home of hipster jivers, where Florence + the Machine just played live in her?BBC Radio 2 concert,?while the White Room held its late night opening party.
Sunday Art Salon
Sunday Art Salon launches its first exclusive Winter Collection on Sunday 2nd December 11am ? 3pm with a wonderful array of bold contemporary art and a unique collection of vintage art and collectables, including important portraits of Charles I, George Harrison and a signed portrait print by Picasso. We hope there will be something for everyone. Artwork can be viewed by appointment at other times to suit busy lifestyles.
Sunday Art Salon -?Hilly Fields Studio, 12 Montague Avenue, London SE4 1YP. Sunday 2nd?December 11am ? 3pm. Coffee station and edible art. Further information visit:?www.sundayartsalon.co.uk? or email info@sundayartsalon.co.uk (stairs so with regret no disabled/pushchair access and no stilettos as wooden floors)
Courtney Carbett, 9 from Riverside, pets her African Grey Congo parrot. (Will Lester/Staff Photographer)
POMONA - Bird enthusiasts flocked to the Everybody's Bird Mart on Sunday at Fairplex.
A variety of birds, cages, seed, feeder, vitamins, toys, perches and other means of spoiling pets were available at the 111th event.
"A lot of people see the outside bird as being brown, black or tan," said small business bird owner Elizabeth Shogren, "but then they come here and they don't realize how many different kinds of birds there are and the colors they come in."
Shogren, who is also a member of the Hemet Valley Bird Society, said that while birds can be pets like dogs and cats, they live much longer.
"This miligold macaw can live up to 75 to 80 years," she said. "When I tell people that, they usually say `I'm going to have to will it to somebody."'
In addition to selling birds, Eric Antheunisse, owner of Cedar Hill Birds in Lodi, provided tips for those looking to purchase a feathered-friend.
"There are two types of birds, pet birds and breed birds," said Antheunisse, who is also a professional aviculturist. "Pet birds are tame and are hand-fed birds, and if anyone is selling you a pet bird they should be able to take them out of the cage and put them in your hand."
Breed birds are not tamed, and are not meant to be because they are used only for the purpose of reproducing, he said.
Unlike most pets, birds' reproductive organs are internal, said Antheunisse, who has been breeding birds for 30 years. Birds have to be DNA tested to know the sex.
Some of the prices Sunday ruffled the feathers of a number of people at the bird mart.
There were birds being sold for less than $10, but others cost more than $1,000.
After a decade of not having birds, Zeus Villaflor of Carson decided to buy six parakeets. Each had distinctive colors and each was about 2 inches tall. Villaflor said they're the cheapest of birds, priced at $6 each.
"I didn't want to jump into buying
something expensive or a high-maintenance bird," said Villaflor, 25. "A friend advised me on which type of bird to purchase and these are lovely, easy to take care of and you don't have to pet them all the time."
Villaflor planned to name them once he got home.
Many bird vendors have birds as pets.
Cesar Fabian, owner of Maria and Artemios Birds in Arleta, has an African Grey parrot named Pancho that talks.
Fabian said birds offer companionship.
"He reacts to me and gives me attention - he's my buddy," said Fabian, of San Fernando.
Marta Armas bought three English budgies on Sunday that will join the 35 other birds at her Canyon Country home.
"I have cats, dogs, turtles. I love animals," she said. "And once I bought one bird I kept on buying more."
Reach Canan via email, call her at 909-987-6397 ext. 425, or find her on Twitter @ChinoValleyNow.
Research reveals new understanding of X chromosome inactivationPublic release date: 27-Nov-2012 [ | E-mail | Share ]
Contact: William Davis william_davis@med.unc.edu 919-962-3405 University of North Carolina Health Care
Chapel Hill, NC In a paper published in the Nov. 21 issue of Cell, a team led by Mauro Calabrese, a postdoctoral fellow at the University of North Carolina in the lab of Terry Magnuson, chair of the department of genetics and member of the UNC Lineberger Comprehensive Cancer Center, broadens the understanding of how cells regulate silencing of the X chromosome in a process known as X-inactivation.
"This is a classic example of a basic research discovery. X-inactivation is a flagship model for understanding how non-coding RNAs orchestrate large-scale control of gene expression. In the simplest terms, we are trying to understand how cells regulate expression of their genes. Our findings are relevant across the board -- by understanding how normal cells function we can apply that knowledge to similar situations in the understanding and treatment of disease," said Calabrese.
Proper regulation of the X chromosome plays a crucial role in mammalian development. Females inherit a pair of X chromosomes from their parents, and the process of X-inactivation shuts down one of these two Xs.
"Males have XY. Females have two Xs. One of those Xs needs to get shut off. If it does not, it's not compatible with life. It's how we have evolved to equalize doses between males and females," said Calabrese.
While the manner in which the X chromosome is deactivated has been actively studied for 50 years, the exact mechanisms that regulate the process remain a mystery. Calabrese's research used high-throughput sequencing to determine the location and activity of chromosomes with far greater accuracy than previous research.
"Basically, this is using the sequencing technology as a high resolution microscope," said Calabrese.
Under a microscope, the inactive X chromosome (Xi) appears as a cloud-like structure, because it is covered with a non-coding RNA known as Xist. In the traditional model of X-inactivation, genes located inside the cloud are completely silenced, with 15 percent of the genes from the inactive X chromosomes escaping to become active.
"The prevailing thought was that genes that escaped X inactivation were pulled out of the core and expressed out there," said Calabrese.
The work of Calabrese's team complicates the current model of X-inactivation by finding indications of gene activity inside the Xist cloud and the presence of inactive genes outside the cloud, both of which would not have been thought possible in the prevailing model.
"It's kind of a subtle thing, but mechanistically it is a big difference," said Calabrese.
Inside the Xist cloud, sequencing discovered traces of DNase I sensitivity, a feature usually linked to transcription activity. While other markers associated with transcription were absent, the presence of DNase I sensitivity suggested that the nucleus did recognize the inactive X as usable DNA, but an unknown suppressive mechanism was preventing genes from being activated.
"We were surprised to see that. If they were totally silent, you would expect this to be not there This suggests that transcription factors or other proteins that bind DNA are still accessing the inactive X," said Calabrese.
The other surprising findings involve the 15 percent of "escaper" genes from the inactive X. Calabrese found evidence that active genes were found both inside and outside the Xist cloud, and that silenced genes that lay alongside active genes outside of the Xist cloud remained inactive.
"If X-inactivation was a strict nuclear barrier, then pulling a gene outside the barrier would turn it on, but it has got to be more than that because when an inactivated gene that is beside an escaper is outside this domain, it is still turned off," said Calabrese.
The presence of DNase I sensitivity within the Xist cloud and the finding of inactive genes outside of the cloud suggest that a site-specific mechanism is regulating genes on the chromosome in a more subtle way than the binary "on/off" function posited by the prevailing model. The exact mechanism for this remains unknown. Although Calabrese believes that Xist still plays a role, its exact function and whether other factors influence X-inactivation remain questions for future research.
"We know that Xist is required to turn off the inactive X. We know that. We have no idea how" said Calabrese.
Beyond revising the understanding of how X-inactivation works, Calabrese said that deeper understanding of the function of Xist could reveal more about the role of other non-coding RNAs in cellular development. These RNAs could become useful targets for future therapies and drug development.
"We know that too much expression of the wrong non-coding RNAs can lead to cancer. Also, forced expression of other non-coding RNAs can prevent cancer. Generally, we do not know how these RNAs work," said Calabrese.
###
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Research reveals new understanding of X chromosome inactivationPublic release date: 27-Nov-2012 [ | E-mail | Share ]
Contact: William Davis william_davis@med.unc.edu 919-962-3405 University of North Carolina Health Care
Chapel Hill, NC In a paper published in the Nov. 21 issue of Cell, a team led by Mauro Calabrese, a postdoctoral fellow at the University of North Carolina in the lab of Terry Magnuson, chair of the department of genetics and member of the UNC Lineberger Comprehensive Cancer Center, broadens the understanding of how cells regulate silencing of the X chromosome in a process known as X-inactivation.
"This is a classic example of a basic research discovery. X-inactivation is a flagship model for understanding how non-coding RNAs orchestrate large-scale control of gene expression. In the simplest terms, we are trying to understand how cells regulate expression of their genes. Our findings are relevant across the board -- by understanding how normal cells function we can apply that knowledge to similar situations in the understanding and treatment of disease," said Calabrese.
Proper regulation of the X chromosome plays a crucial role in mammalian development. Females inherit a pair of X chromosomes from their parents, and the process of X-inactivation shuts down one of these two Xs.
"Males have XY. Females have two Xs. One of those Xs needs to get shut off. If it does not, it's not compatible with life. It's how we have evolved to equalize doses between males and females," said Calabrese.
While the manner in which the X chromosome is deactivated has been actively studied for 50 years, the exact mechanisms that regulate the process remain a mystery. Calabrese's research used high-throughput sequencing to determine the location and activity of chromosomes with far greater accuracy than previous research.
"Basically, this is using the sequencing technology as a high resolution microscope," said Calabrese.
Under a microscope, the inactive X chromosome (Xi) appears as a cloud-like structure, because it is covered with a non-coding RNA known as Xist. In the traditional model of X-inactivation, genes located inside the cloud are completely silenced, with 15 percent of the genes from the inactive X chromosomes escaping to become active.
"The prevailing thought was that genes that escaped X inactivation were pulled out of the core and expressed out there," said Calabrese.
The work of Calabrese's team complicates the current model of X-inactivation by finding indications of gene activity inside the Xist cloud and the presence of inactive genes outside the cloud, both of which would not have been thought possible in the prevailing model.
"It's kind of a subtle thing, but mechanistically it is a big difference," said Calabrese.
Inside the Xist cloud, sequencing discovered traces of DNase I sensitivity, a feature usually linked to transcription activity. While other markers associated with transcription were absent, the presence of DNase I sensitivity suggested that the nucleus did recognize the inactive X as usable DNA, but an unknown suppressive mechanism was preventing genes from being activated.
"We were surprised to see that. If they were totally silent, you would expect this to be not there This suggests that transcription factors or other proteins that bind DNA are still accessing the inactive X," said Calabrese.
The other surprising findings involve the 15 percent of "escaper" genes from the inactive X. Calabrese found evidence that active genes were found both inside and outside the Xist cloud, and that silenced genes that lay alongside active genes outside of the Xist cloud remained inactive.
"If X-inactivation was a strict nuclear barrier, then pulling a gene outside the barrier would turn it on, but it has got to be more than that because when an inactivated gene that is beside an escaper is outside this domain, it is still turned off," said Calabrese.
The presence of DNase I sensitivity within the Xist cloud and the finding of inactive genes outside of the cloud suggest that a site-specific mechanism is regulating genes on the chromosome in a more subtle way than the binary "on/off" function posited by the prevailing model. The exact mechanism for this remains unknown. Although Calabrese believes that Xist still plays a role, its exact function and whether other factors influence X-inactivation remain questions for future research.
"We know that Xist is required to turn off the inactive X. We know that. We have no idea how" said Calabrese.
Beyond revising the understanding of how X-inactivation works, Calabrese said that deeper understanding of the function of Xist could reveal more about the role of other non-coding RNAs in cellular development. These RNAs could become useful targets for future therapies and drug development.
"We know that too much expression of the wrong non-coding RNAs can lead to cancer. Also, forced expression of other non-coding RNAs can prevent cancer. Generally, we do not know how these RNAs work," said Calabrese.
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Following the opening up of south London in 2010 by the extension of the Overground tube, affectionally nicknamed the ?Ginger line?, places like Brockley and Forest Hill are now on the map as areas of artistic enterprises, with Deptford and Peckham as neighbours, it creates part of a new trend of artistic networks where small galleries and open studios are tailoring themselves to a resurgence in community spirit and awareness.
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Public release date: 27-Nov-2012
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