Hitting 'reset' in protein synthesis restores myelination: Suggests new treatment for misfolded protein diseases such as Alzheimer's

Apr. 26, 2013 ? A potential new treatment strategy for patients with Charcot-Marie-Tooth disease is on the horizon, thanks to research by neuroscientists now at the University at Buffalo's Hunter James Kelly Research Institute and their colleagues in Italy and England.

The institute is the research arm of the Hunter's Hope Foundation, established in 1997 by Jim Kelly, Buffalo Bills Hall of Fame quarterback, and his wife, Jill, after their infant son Hunter was diagnosed with Krabbe Leukodystrophy, an inherited fatal disorder of the nervous system. Hunter died in 2005 at the age of eight. The institute conducts research on myelin and its related diseases with the goal of developing new ways of understanding and treating conditions such as Krabbe disease and other leukodystrophies.

Charcot-Marie-Tooth or CMT disease, which affects the peripheral nerves, is among the most common of hereditary neurological disorders; it is a disease of myelin and it results from misfolded proteins in cells that produce myelin.

The new findings sere published online earlier this month in The Journal of Experimental Medicine.

They may have relevance for other diseases that result from misfolded proteins, including Alzheimer's disease, Parkinson's, multiple sclerosis, Type 1 diabetes, cancer and mad cow disease.

The paper shows that missteps in translational homeostasis, the process of regulating new protein production so that cells maintain a precise balance between lipids and proteins, may be how some genetic mutations in CMT cause neuropathy.

CMT neuropathies are common, hereditary and progressive; in severe cases, patients end up in wheelchairs. These diseases significantly affect quality of life but not longevity, taking a major toll on patients, families and society, the researchers note.

"It's possible that our finding could lead to the development of an effective treatment not just for CMT neuropathies but also for other diseases related to misfolded proteins," says Lawrence Wrabetz, MD, director of the institute and professor of neurology and biochemistry in UB's School of Medicine and Biomedical Sciences and senior author on the paper. Maurizio D'Antonio, of the Division of Genetics and Cell Biology of the San Raffaele Scientific Institute in Milan is first author; Wrabetz did most of this research while he was at San Raffaele, prior to coming to UB.

The research finding centers around the synthesis of misfolded proteins in Schwann cells, which make myelin in nerves. Myelin is the crucial fatty material that wraps the axons of neurons and allows them to signal effectively. Many CMT neuropathies are associated with mutations in a gene known as P0, which glues the wraps of myelin together. Wrabetz has previously shown in experiments with transgenic mice that those mutations cause the myelin to break down, which in turn, causes degeneration of peripheral nerves and wasting of muscles.

When cells recognize that the misfolded proteins are being synthesized, cells respond by severely reducing protein production in an effort to correct the problem, Wrabetz explains. The cells commence protein synthesis again when a protein called Gadd34 gets involved.

"After cells have reacted to, and corrected, misfolding of proteins, the job of Gadd34 is to turn protein synthesis back on," says Wrabetz. "What we have shown is that once Gadd34 is turned back on, it activates synthesis of proteins at a level that's too high -- that's what causes more problems in myelination.

"We have provided proof of principle that Gadd34 causes a problem with translational homeostasis and that's what causes some neuropathies," says Wrabetz. "We've shown that if we just reduce Gadd34, we actually get better myelination. So, leaving protein synthesis turned partially off is better than turning it back on, completely."

In both cultures and a transgenic mouse model of CMT neuropathies, the researchers improved myelin by reducing Gadd34 with salubrinal, a small molecule research drug. While salubrinal is not appropriate for human use, Wrabetz and colleagues at UB and elsewhere are working to develop derivatives that are appropriate.

"If we can demonstrate that a new version of this molecule is safe and effective, then it could be part of a new therapeutic strategy for CMT and possibly other misfolded protein diseases as well," says Wrabetz.

And while CMT is the focus of this particular research, the work is helping scientists at the Hunter James Kelly Research Institute enrich their understanding of myelin disorders in general.

"What we learn in one disease, such as CMT, may inform how we think about toxins for others, such as Krabbe's," Wrabetz says. "We'd like to build a foundation and answer basic questions about where and when toxicity in diseases begin."

The misfolded protein diseases are an interesting and challenging group of diseases to study, he continues. "CMT, for example, is caused by mutations in more than 40 different genes," he says. "When there are so many different genes involved and so many different mechanisms, you have to find a unifying mechanism: this problem of Gadd34 turning protein synthesis on at too high a level could be one unifying mechanism. The hope is that this proof of principle applies to more than just CMT and may lead to improved treatments for Alzheimer's, Parkinson's, Type 1 diabetes and the other diseases caused by misfolded proteins."

Co-authors with D'Antonio and Wrabetz are M. Laura Feltri, MD, professor of neurology and biochemistry at UB and a researcher with UB's Hunter James Kelly Research Institute at the NYS Center of Excellence in Bioinformatics and Life Sciences; Nicolo Musner, Cristina Scapin Daniela Ungaro and Ubaldo Del Carro from the San Raffaele Scientific Institute and David Ron of Cambridge and the National Institute for Health Research Cambridge Biomedical Research Centre.

Funding was provided by the National Institutes of Health, the European Community and an award to D'Antonio from the Italian Ministry of Health.

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Story Source:

The above story is reprinted from materials provided by University at Buffalo. The original article was written by Ellen Goldbaum.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Journal Reference:

1. M. D'Antonio, N. Musner, C. Scapin, D. Ungaro, U. Del Carro, D. Ron, M. L. Feltri, L. Wrabetz. Resetting translational homeostasis restores myelination in Charcot-Marie-Tooth disease type 1B mice. Journal of Experimental Medicine, 2013; 210 (4): 821 DOI: 10.1084/jem.20122005

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/~3/_o1zELs2WuM/130426135037.htm

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Asia stocks waver amid drop in Japan CPI

BANGKOK (AP) ? Asian stock markets wavered Friday despite better-than-expected U.S. employment data after Japan faced an unwelcome drop in consumer prices.

Wall Street closed higher Thursday after the U.S. government reported the number of Americans seeking jobless benefits dropped last week by 16,000, suggesting that companies are cutting fewer jobs and that the U.S. may be headed for an uptick in job growth. Analysts said that solid U.S. corporate earnings also helped to lift the market mood.

But the Nikkei 225 in Tokyo slipped from a five-year high after Japan's consumer price index fell 0.9 percent in March from a year earlier. The result flies in the face of efforts by Prime Minister Shinzo Abe, who took office in December vowing to reverse a long bout of deflation, or falling prices, which has crippled economic growth.

The Nikkei, which in the morning hit its highest intraday level in five years at 13,983.87, fell into negative territory before edging up marginally to 13,934.69. Later in the day, attention will turn to a meeting by the Bank of Japan, which will issue an updated inflation outlook.

Also Friday, the U.S. Commerce Department will release economic growth figures for the first three months of 2013.

"A solid GDP figure out of the US should give markets a boost," said Daniel Martin of Capital Economics in Singapore. He said he expected the data to show that the world's No. 1 economy grew at an annual rate of 3.2 percent. That would be a sharp improvement from the anemic 0.4 percent growth rate reported for the final quarter of the year.

Elsewhere, Hong Kong's Hang Seng rose 1 percent to 22,613.83. Australia's S&P/ASX 200 slipped marginally to 5,101.10. South Korea's Kospi fell 0.3 percent at 1,946.98. Benchmarks in Singapore and Taiwan rose while those in mainland China and India fell.

In Britain, meanwhile, growth figures released Thursday came as a surprise relief to analysts who predicted that the U.K. would sink into its third recession in five years. Instead, GDP for the first quarter of 2013 grew 0.3 percent compared with the previous quarter.

Wall Street posted modest gains Wednesday on the heels of a U.S. Labor Department report showing the number of Americans seeking unemployment benefits fell last week to a seasonally adjusted 339,000, the second-fewest in more than five years. The drop suggests that layoffs have declined and that job growth may pick up from last month's sluggish pace.

Among companies reporting earnings, children's clothing maker Carter's, motorcycle maker Harley-Davidson and cruise line Royal Caribbean all reported higher profit and revenue, as did 3M, the maker of Scotch tape and construction equipment.

The Dow Jones industrial average rose 0.2 percent to 14,700.80. The Standard & Poor's 500 rose 0.4 percent to 1,585.16. The Nasdaq composite index gained 0.6 percent, to 3,289.99

Benchmark oil for June delivery was down 55 cents to $93.08 per barrel in electronic trading on the New York Mercantile Exchange. The contract rose $2.21 to close at $93.64 on the Nymex on Thursday.

In currencies, the euro rose to $1.3038 from $1.3002 late Thursday in New York. The dollar fell to 98.81 yen from 99.31 yen.

Source: http://news.yahoo.com/asia-stocks-waver-amid-drop-japan-cpi-051453836--finance.html

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Competing pathways affect early differentiation of higher brain structures

Apr. 25, 2013 ? Sand-dwelling and rock-dwelling cichlids living in East Africa's Lake Malawi share a nearly identical genome, but have very different personalities. The territorial rock-dwellers live in communities where social interactions are important, while the sand-dwellers are itinerant and less aggressive.

Those behavioral differences likely arise from a complex region of the brain known as the telencephalon, which governs communication, emotion, movement and memory in vertebrates -- including humans, where a major portion of the telencephalon is known as the cerebral cortex. A study published this week in the journal Nature Communications shows how the strength and timing of competing molecular signals during brain development has generated natural and presumably adaptive differences in the telencephalon much earlier than scientists had previously believed.

In the study, researchers first identified key differences in gene expression between rock- and sand-dweller brains during development, and then used small molecules to manipulate developmental pathways to mimic natural diversity.

"We have shown that the evolutionary changes in the brains of these fishes occur really early in development," said Todd Streelman, an associate professor in the School of Biology and the Petit Institute for Bioengineering and Biosciences at the Georgia Institute of Technology. "It's generally been thought that early development of the brain must be strongly buffered against change. Our data suggest that rock-dweller brains differ from sand-dweller brains -- before there is a brain."

For humans, the research could lead scientists to look for subtle changes in brain structures earlier in the development process. This could provide a better understanding of how disorders such as autism and schizophrenia could arise during very early brain development.

The research was supported by the National Science Foundation and published online April 23 by the journal.

"We want to understand how the telencephalon evolves by looking at genetics and developmental pathways in closely-related species from natural populations," said Jonathan Sylvester, a postdoctoral researcher in the Georgia Tech School of Biology and lead author of the paper. "Adult cichlids have a tremendous amount of variation within the telencephalon, and we investigated the timing and cause of these differences. Unlike many previous studies in laboratory model organisms that focus on large, qualitative effects from knocking out single genes, we demonstrated that brain diversity evolves through quantitative tuning of multiple pathways."

In examining the fish from embryos to adulthood, the researchers found that the mbuna, or rock-dwellers, tended to exhibit a larger ventral portion of the telencephalon, called the subpallium -- while the sand-dwellers tended to have a larger version of the dorsal structure known as the pallium. These structures seem to have evolved differently over time to meet the behavioral and ecological needs of the fishes. The team showed that early variation in the activity of developmental signals expressed as complementary dorsal-ventral gradients, known technically as "Wingless" and "Hedgehog," are involved in creating those differences during the neural plate stage, as a single sheet of neural tissue folds to form the neural tube.

To specifically manipulate those two pathways, Sylvester removed clutches of between 20 and 40 eggs from brooding female cichlids, which normally incubate fertilized eggs in their mouths. At about 36 to 48 hours after fertilization, groups of eggs were exposed to small-molecule chemicals that either strengthened or weakened the Hedgehog signal, or strengthened or weakened the Wingless signal. The chemical treatment came while the structures that would become the brain were little more than a sheet of cells. After treatment, water containing the chemicals was replaced with fresh water, and the embryos were allowed to continue their development.

"We were able to artificially manipulate these pathways in a way that we think evolution might have worked to shift the process of rock-dweller telencephalon development to sand-dweller development, and vice-versa. Treatment with small molecules allows us incredible temporal and dose precision in manipulating natural development," Sylvester explained. "We then followed the development of the embryos until we were able to measure the anatomical structures -- the size of the pallium and subpallium -- to see that we had transformed one to the other."

The two different brain regions, the dorsal pallium and ventral subpallium, give rise to excitatory and inhibitory neurons in the forebrain. Altering the relative sizes of these regions might change the balance between these neuronal types, ultimately producing behavioral changes in the adult fish.

"Evolution has fine-tuned some of these developmental mechanisms to produce diversity," Streelman said. "In this study, we have figured out which ones."

The researchers studied six different species of East African cichlids, and also worked with collaborators at King's College in London to apply similar techniques in the zebrafish.

As a next step, the researchers would like to follow the embryos through to adulthood to see if the changes seen in embryonic and juvenile brain structures actually do change behavior of adults. It's possible, said Streelman, that later developmental events could compensate for the early differences.

The results could be of interest to scientists investigating human neurological disorders that result from an imbalance between excitatory and inhibitory neurons. Those disorders include autism and schizophrenia. "We think it is particularly interesting that there may be some adaptive variation in the natural proportions of excitatory versus inhibitory neurons in the species we study, correlated with their natural behavioral differences," said Streelman.

In addition to the researchers already mentioned, the study included undergraduate coauthors Constance Rich and Chuyong Yi from Georgia Tech, and Joao Peres and Corinne Houart from King's College in London. Rich is presently in the neuroscience PhD program at the University of Cambridge.

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The above story is reprinted from materials provided by Georgia Institute of Technology, via Newswise.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Journal Reference:

1. J B. Sylvester, C A. Rich, C Yi, J N. Peres, C Houart, J T. Streelman. Competing signals drive telencephalon diversity. Nature Communications, 2013; 4: 1745 DOI: 10.1038/ncomms2753

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/top_environment/~3/I3zAKn_ACS0/130426115636.htm

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CA-BUSINESS Summary

TSX clocks sixth day of gains on U.S. data, Potash results

TORONTO (Reuters) - Canada's main stock index advanced for a sixth straight session on Thursday, helped by resources sectors as U.S. economic data and a stronger-than-expected earnings performance from fertilizer producer Potash Corp buoyed sentiment. Investors were encouraged by data showing the number of Americans filing new claims for unemployment benefits fell last week, offering reassurance that the bottom is not falling out of the U.S. labor market.

Yahoo Chairman Fred Amoroso resigns

(Reuters) - Yahoo Inc Chairman Fred Amoroso is resigning effective immediately, the struggling Internet company announced on Thursday. Amoroso will be replaced in the chairman role by director Maynard Webb Jr. on an interim basis until the company's annual shareholder meeting on June 25.

Amazon growth slows, while profit margins expand

SAN FRANCISCO (Reuters) - Amazon.com Inc's revenue growth slowed in the first quarter as the world's largest Internet retail struggled overseas, but margins jumped on lower shipping expenses and the expansion of more profitable new businesses. Amazon shares fell 1.9 percent to $269.43 in after-hours trading on Thursday following the results.

Starbucks raises outlook but shares fall

(Reuters) - Starbucks Corp reported higher quarterly profit on Thursday that matched Wall Street estimates and it raised its full-year earnings forecast. The world's biggest coffee chain cited increased sales in the United States, its top market, despite an industry-wide spending downturn in February due to a U.S. payroll tax increase that lowered take-home pay.

BOJ stands pat, to face credibility test with new forecasts

TOKYO (Reuters) - The Bank of Japan will probably project on Friday that it will meet its 2 percent inflation target in two years due to its massive stimulus plan, a forecast analysts say may be too optimistic and which could put its credibility on the line. In a reminder of how ambitious and stiff the target is, data on Friday showed core consumer prices marked their fifth straight month of annual declines in March even as the yen's recent falls pushed up import costs.

Samsung Electronics profit jumps ahead of Galaxy S4 debut

SEOUL (Reuters) - Samsung Electronics Co Ltd reported on Friday its sixth straight quarter of profit growth ahead of the debut of its latest Galaxy smartphone, the South Korean IT giant's biggest assault on rival Apple Inc yet. By launching the Galaxy S4 in the United States on Saturday, Samsung is taking aim at Apple's home market at a time when the iPhone maker appears to have hit a snag. Earlier this week, Apple reported its first profit decline in more than a decade and indicated no major product releases until the fall.

Monte Paschi committed to avoid state becoming majority shareholder: CEO

MILAN (Reuters) - Italy's Banca Monte dei Paschi di Siena is committed to avoiding the state becoming a majority shareholder in the bank, chief executive Fabrizio Viola said on Friday. "One thing is having the state as minority shareholder another is imagining the majority becomes public: this latter is a scenario certainly possible but the bank is committed to avoid it," Fabrizio Viola said in an interview in Il Sole 24 Ore.

Asian shares rise on U.S. data, regional earnings eyed

TOKYO (Reuters) - Asian shares rose on Friday, tracking global equities higher after upbeat U.S. labor market data, while the dollar eased slightly on currency markets that were otherwise watching for the strength of signals coming from a Bank of Japan policy review. In the share markets, investors turned attention toward regional corporate earnings to assess the outlook for growth.

New York drops damages claim in suit against ex-AIG chief

NEW YORK (Reuters) - New York's attorney general is dropping a claim for damages in a high-profile civil lawsuit accusing the former chief executive of American International Group Inc , Maurice "Hank" Greenberg, of defrauding investors, according to a letter sent by the attorney general's office on Thursday. The 2005 lawsuit filed by then-Attorney General Eliot Spitzer against Greenberg and former AIG chief financial officer Howard Smith sought as much as $6 billion in damages.

U.S. seizes on ruling to boost Wells Fargo mortgage fraud case

NEW YORK (Reuters) - The Justice Department has promptly capitalized on a court victory to bolster a case before another federal judge, citing a ruling on Wednesday that endorsed the agency's use of a little known financial fraud law to prosecute bank actions during the financial crisis. In a letter made public on Thursday, the agency told District Judge Jesse Furman on Wednesday that the ruling is one reason why its mortgage-fraud case against Wells Fargo & Co should not be dismissed.

Source: http://news.yahoo.com/ca-business-summary-004019720--finance.html

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Novelist Banks "stunned" by fan support over terminal cancer

By Li-mei Hoang

LONDON (Reuters) - Scottish author Iain Banks, who announced this month he was suffering from terminal cancer, said he was "stunned" by the messages of support he has received from his fans.

The "Wasp Factory" author said he was deeply flattered and touched by all the responses left on the website Banksophilia, which was set up by his friend Martin Belk.

"Good grief! - what an outpouring of love, affection and respect. I honestly had no idea," he wrote.

"Discovering the sheer extent and depth of the feelings people have expressed on the message board over the past two weeks has been truly astounding," he added.

Banks, 59, said his problems came to light after a visit to his doctor about a sore back. Tests revealed he was not only suffering from jaundice but also cancer in his gall bladder.

He announced his illness on his website on April 3, before he canceled all future public engagements.

The author, who also writes science fiction under the name of Iain M Banks, said that as a late-stage gall bladder cancer patient he is only expected to live for a few months.

Banks has returned to Britain after a short honeymoon with his wife Adele in Paris and Venice to continue working on his new book "The Quarry."

Born in Fife, Banks studied at Stirling University before publishing "The Wasp Factory", his first novel, in 1984.

In 2008, he was named one of the 50 greatest British writers since 1945 in a list compiled by the Times newspaper.

Banks said he would be looking "seriously" at the medical advice and suggestions made by his fans and would continue to post the occasional update for as long as he is able.

"I feel treasured, I feel loved ... and I can't deny I've been made to feel very special indeed," he added.

(Editing by Paul Casciato)

Source: http://news.yahoo.com/novelist-banks-stunned-fan-support-over-terminal-cancer-114755776.html

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Family upset over Air Force officer's transfer

PHOENIX (AP) ? The Air Force's decision to transfer a lieutenant colonel to a Tucson military base after his sexual assault conviction was overturned by a commander has outraged the family of the woman who made the allegations, adding to the growing criticism of the military justice system.

The family says Lt. Col. James Wilkerson' transfer of to Davis-Monthan Air Force Base on the southern edge of Tucson is upsetting because roughly half the woman's family lives there. They're planning a protest Thursday outside the base.

The news comes amid a congressional uproar over the Wilkerson case, and follows heavy criticism of the military's handling of another case involving sex-crime allegations in California.

"They could send him to a number of places," said Stephen Hanks, an orthopedic surgeon in Tucson who is the brother of Wilkerson's accuser. "Why send him to a place where her family lives? It makes no sense."

The woman, a civilian employee who works with service members, accused Wilkerson of sexually assaulting her after a party at his house. Wilkerson and his wife denied the charges but said the woman stayed at their house that night.

A military jury in November convicted Wilkerson, a former inspector general at Aviano Air Base in Italy, of aggravated sexual assault and other charges. He was sentenced to one year in prison and dismissal from the service.

But a commander overturned the verdict and dismissed the charges, saying he found Wilkerson and his wife more believable than the alleged victim. Wilkerson already has reported for duty in southern Arizona, where he will work as a safety officer for the 12th Air Force.

Air Force spokesman Lt. Col. Brett Ashworth said military officials wouldn't have known about the woman's family in Tucson when Wilkerson's transfer was decided.

"His assignment was based on his qualifications and the needs of the Air Force," Ashworth said.

Wilkerson declined an interview request from The Associated Press.

The decision by Lt. Gen. Craig Franklin, commander of the 3rd Air Force at Ramstein Air Base in Germany, to overturn the verdict has been criticized by congressional leaders and advocates for confronting the problem of sexual assaults in the military.

The move led the Defense Department to propose that commanders be largely stripped of their ability to reverse criminal convictions of service members.

Under military law, a commander who convenes a court martial is known as the convening authority and has the discretion to reduce or set aside guilty verdicts and sentences, or to reverse a jury's verdict.

Protect Our Defenders, which advocates for military members who have been sexually assaulted, is calling for Defense Secretary Chuck Hagel to fire Franklin. The group's president, Nancy Parrish, said the Wilkerson case demonstrates that the military justice system needs to be changed.

Commanders who have broad authority in letting cases go forward face a conflict of interest, Parrish said.

"They are incentivized to sweep these cases under the rug. A commander's career is on the chopping block if a rape happens under his or her watch," said Parrish, whose group is pressing the Defense Department on behalf of Wilkerson's accuser.

The military justice system also came under heavy criticism in February, after a former soldier killed two police officers in California.

Records show the Army commander of the former soldier, Jeremy Goulet, allowed Goulet to resign from the military instead of facing a court-martial when he was twice accused of rape. The Army said a lack of evidence prevented it from prosecuting Goulet on charges dating back to 2006.

Critics say Goulet's case is as an example of what can go wrong when military cases are dropped.

Goulet shot and killed two detectives when they went to his house to question him about allegations that he was sexually inappropriate with a former co-worker. Goulet died in the Feb. 26 shootout with police in Santa Cruz, Calif.

Ashworth declined to comment on the group's call for Franklin to be fired. Franklin declined an interview request from the AP.

In a letter to a Pentagon official that surfaced earlier this month, Franklin said a combination of details led to his decision, including that the victim turned down offers to be driven home from the party, didn't accurately describe the house layout and gave a version of events that he didn't find credible. He said Wilkerson was a doting father with a good career, and it would be "incongruent" for him to leave his wife in bed, go downstairs and assault a sleeping woman he'd met earlier that evening.

Protect Our Defenders issued a response to Franklin's letter Tuesday, saying Franklin's account of the woman's options for rides home was inaccurate, Franklin showed blind loyalty toward the accused officer, and that the jury found the woman's story credible.

Source: http://news.yahoo.com/family-upset-over-air-force-officers-transfer-080951538.html

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The South African Safari Experience

The South African safari is a definitive safari experience like no other. Canopies of ancient trees, a landscape largely untouched by humans and witnessing wildlife in the wild changes the outlook of tourists for life. There are hundreds of game reserves and national parks in South Africa. There are safaris that claim to be truly South African, but the true South African Safari can only be experienced in a few gems of game reserves.

One of the gems of game reserves is the safari lodge located in Ulusaba private game reserve. The tree-house style rooms allow guests to live right on the reserve. Tourists can experience wildlife while being within the walls of the room. Picture windows and a porch make for a living experience like no other. Bordering the enormous Kruger National Park, tourists are bound to see herds of animals go past their rooms every day of their stay. Owned by Sir Richard Branson, the game reserve delivers on luxury as well as an authentic South African safari experience.

The Thanda private game reserve is also another safari that positively portrays South Africa. Recipient of many travel awards such as the World travel award for being a leading South Africa safari lodge and a leading luxury South Africa safari lodge, the game reserve lives up to the expectations. Located in Northern KwaZulu Natal, the game reserve is home to the big five. The big five is a terminology to the animals most regularly spotted on safaris. The elephant, the lion, the buffalo, the rhino and the leopard are what is popularly called the big five. Comprising of 7800 hectares of nearly untouched land, the game reserve is truly a South Africa safari lodge. The lodge comprises of only nine luxury villas set in the heart of the bush land. The numbers are a clue to the privacy and utter luxury that the lodge is capable of. Each of the nine villas are equipped with private infinity pools, viewing deck, lounge, fireplace, thatched outdoor bed area and indoor and outdoor showers.

The Ivory Lodge located within Lion Sands private game reserve like the afore mentioned game reserves makes for a South Africa safari experience that fulfills the expectations attached to the term South Africa safari. The lodge has won many international travel awards owing to the ultra-luxurious private villas it houses. Awe-inspiring views of the Sabie river, heated swimming pools and an eye for privacy throughout the reserve make it a lodge that delivers on luxury while being nestled in the lap of nature.

Source: http://www.articlesnatch.com/Article/The-South-African-Safari-Experience/4571294

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