For anyone who has dreamed of living on a working French wine estate, surrounded by authentic 19th-century architecture wrapped in the finest of modern touches, these luxury chateau residences make an unmatched living experience.
Rising from an 1890-era estate originally designed by architect Louis-Michel Garros will be 36 singular homes in original period character buildings, including the Ch?teau, the Winery, the Blacksmith?s House and the Distillery. Buyers may select from spacious 2-bedroom apartments up to 4-bedroom houses.
The interior design of the French chateau residences will take its cues from the estate?s heritage, a story of grace, beauty and refinement in a country setting. A wealth of period features will marry the traditional and the contemporary.
The properties are sold furnished to the last detail ? from linen to artworks, high spec entertainment systems to chic French tableware. Founding owners will also be able to customise their homes in consultation with both the architect and interior designer. Living areas are generously proportioned and most of the properties feature private terrace and garden and some come with a private pool.
Owners will also share in the excellent Languedoc wines produced from the refurbished winery, with an estimated 20 cases a year assigned to each property. Watch the vineyards come to life every spring, observe their progress and thrill in the harvest and production.
Estate amenities include a salon/lounge, brasserie, community pool, boules area, clay tennis court and terrace that overlooks the vineyards. Concierge services include everything from chauffeurs to chefs.
The incredible 10-acre estate is located in the South of France, with eight international airports within two hours, close to B?ziers, P?zenas and Montpellier, as well as the Mediterranean?s incomparable beaches. Paris and Lyon are easily reached by autoroute and TGV, with Barcelona soon to be added to the high-speed rail route.
Nearby is fishing of all descriptions, as well as amazing farmers? markets, vineyards to explore and fine dining opportunities.
Languedoc is a place of the quintessential Mediterranean climate, basking in sunshine 300 days a year, with short, mild winters and seemingly endless summers.
Now is the time to invest in this Languedoc chateau and vineyard property, with prices one-quarter less than comparable properties on the C?te d?Azur. A key point of difference compared to other newly built developments in France, is that this vineyard chateau estate is designed and built for buyers, offering buyers absolute freedom to use their vacation homes whenever and as often as they wish without any restrictions. The fine property is fully-managed including letting and concierge services, ensuring that owners? investment is well looked after and professionally marketed to maximize rental revenue and property values.
The company behind the development has a superb track record and was behind a recent project which has been widely recognized as the most successful restoration project in the South of France for many years Buyers may also be assured that France?s well-developed property market is well regulated and this development has been approved by major lenders.
A CHANGE management specialist has warned that the Channel Islands governments and businesses need to embrace change because it will be forced upon them from external sources.
Eliot Lincoln, managing director of Greenlight, a company with offices in Jersey and Guernsey, told the Chamber of Commerce monthly lunch that while change was always crucial for business, it was particularly so in the current economic and political environment.
?There is massive scrutiny about what we do and how we do it,? he said.
?Offshore jurisdictions are under attack, especially from the US, and it is easy to see why when the US is struggling with such levels of debt.?
Mr Lincoln, pictured, said that the controversy over comedian Jimmy Carr?s tax avoidance dealings with a Jersey-based scheme had also shifted opinion ?from what?s legally right to what?s morally right?.
To read Guernsey Press stories in full, click here for subscription details. Individual editions are now available online.
SOUTH BEND, Ind. (AP) ? Everett Golson is out for at least the fall semester at Notre Dame, saying he has been suspended by the university for what he called poor academic judgment.
"I take full responsibility for my poor choices and will do all that is asked of me to regain the trust of my family, friends, teammates, coaches and the entire Notre Dame community," he wrote in a letter released Sunday by the university.
Golson was officially no longer enrolled at Notre Dame as of Friday, university spokesman Dennis Brown said Saturday night.
Golson helped the Irish go 12-0 during the regular season last year, regain the No. 1 ranking for the first time in nearly two decades and get to the national title game against Alabama in January. Coach Brian Kelly was counting on him to play an even bigger role in 2013 after his play steadily improved throughout last season.
Golson did not specify what he did to get suspended, and wrote that he understands his integrity could be in question.
"But I want to reassure my supporters that through this experience I will return a better student athlete as well as a better individual," he said.
He said he chose to attend Notre Dame because of its mission to develop him both on and off the field.
"My parents and the community I grew up in have instilled values in me that have and will continue to allow me to be successful in the future. There have been many lessons learned as I worked to become the starting quarterback at Notre Dame and each was a result of Coach Kelly's belief in me as an athlete and a person," he wrote.
He also thanked the university for the opportunity it already has given him and the opportunity to retain his eligibility in January.
"At this point, I understand how my integrity could be in question but I want to reassure my supporters that through this experience I will return a better student athlete as well as a better individual," Golson said. "Lastly, I want to thank the University of Notre Dame for the opportunity already granted and also the opportunity going forth to regain my eligibility in the winter of 2014."
Golson did not respond to telephone or text messages left by The Associated Press.
Athletic Director Jack Swarbrick declined to elaborate on Golson's situation earlier in the day. Brown said the university would have nothing to add to Golson's statement.
Golson's abrupt exit leaves the Irish unsettled at a position they were hoping would be a strength in 2013. The most likely replacement is Tommy Rees, the 2011 starter who played key roles in four victories last season when Golson either struggled or was injured.
Golson completed 58.8 percent of his passes last year for 2,405 yards with 12 touchdown passes and six interceptions. He also ran for 298 yards and team-high six touchdowns.
Notre Dame also has Tommy Hendrix, a senior with no starts, and freshman Malik Zaire at quarterback.
So now quarterback is question mark for the Irish and Golson's future with Notre Dame is uncertain.
One thing is clear: The good feelings in South Bend produced by the best Notre Dame football season in more than two decades have been muted by everything that has come after 12-0.
It started with an embarrassing 42-14 loss against Alabama in the BCS title game, when the Crimson Tide scored on their first three possessions and jumped to a 35-0 lead.
That was quickly followed by news Kelly had interviewed for the vacant Philadelphia Eagles job the day after the BCS game.
Then the bizarre.
Part Manti Te'o's inspirational story turned out to be the result of an elaborate hoax. The dead girlfriend that supposedly inspired throughout his Heisman Trophy run did not exist. He had been duped and embarrassed.
Since then, it's been a series of smaller setbacks.
In March, Kelly announced Gunner Kiel, one of the top-rated quarterbacks coming out of high school a year ago, was leaving before even trying to challenge Golson for the starter's job during spring practice. Kiel transferred to Cincinnati.
NCAA rules would permit Kiel to return, but texted "I'm a Bearcat" to The (Cincinnati) Enquirer.
Then came reports that standout defensive lineman Eddie Vanderdoes from Auburn, Calif., a five-star recruit who signed a letter of intent in February with Notre Dame, was having second thoughts about playing for the Irish.
Though none of those problems will affect the Irish this season like not having Golson.
NEWARK, N.J. (AP) ? Julie Hermann is not resigning as Rutgers' incoming athletic director following a report that 16 years ago she humiliated and emotionally abused players while coaching Tennessee's women's volleyball team. And the university is standing behind her.
"I never considered withdrawing because I feel very qualified to lead Rutgers into the future and into the transition into the Big Ten," Hermann said Monday during a conference call in response to a report in the Star-Ledger of Newark. "And I do feel the support of the Rutgers community."
Embattled Rutgers President Robert Barchi said in a statement the university looks forward to her running the athletic department. He added that she was the best of the 63 candidates interviewed for the job of succeeding Tim Pernetti.
"Rutgers was deliberative at every stage of this process," Barchi said. "Over the course of the search, Julie's record established her as a proven leader in athletics administration with a strong commitment to academic success as well as athletic excellence, and a strong commitment to the well-being of student athletes.
Despite the Star-Ledger report, Barchi said Hermann's entire career is stellar and "we remain confident that we have selected an individual who will work in the best interests of all of our student athletes, our athletics teams, and the university."
Speaking to reporters on a conference call, Hermann denied having knowledge of a letter written by the 15 Tennessee players on the volleyball team. She said her former boss never heard of it and she never heard her former players make the allegation. Rutgers officials, however, have talked to her about it in recent days, she said.
Hermann acknowledged she was an intense coach and may have made a few mistakes handling her team. The 49-year-old administrator said she has matured and believes she is qualified to lead the scandal-marred Rutgers athletic program. Her first day on the job is June 17.
It was Hermann's first comments since the Star-Ledger's story Sunday revealed that the Tennessee volleyball team in 1996 sent a letter to the school in which the players said Hermann called them "whores, alcoholics and learning disabled."
In the past two days, state lawmakers have criticized Hermann's hire and Gov. Chris Christie has said he will speak with school officials about the report. Barring a resignation, only the university's board of governors can withdraw Hermann's appointment.
The governor, however, does appoint six of the board's 11 voting members and can wield pressure through a variety of ways, perhaps by threatening to cut school funding or refusing to renominate a board member who doesn't support his view.
With President Barack Obama scheduled to tour the New Jersey shore Tuesday to see the rebuilding that's been done the area after Hurricane Sandy, it is unlikely that Christie will turn his attention to Rutgers until Wednesday.
Hermann believes she can be an effective leader at Rutgers, which in the past two months fired its men's basketball for physical and verbal abuse, forced out its athletic director for his handling of the problem and had several other key officials resign. And after hiring former Scarlet Knights star Eddie Jordan to become the men's basketball coach, the university mistakenly called him a graduate when he had never finished his degree.
"All of my life has prepared me to lead this organization," said Hermann, who would be the first women athletic director at Rutgers and only the third female AD at the 124 schools playing at college football's top tier.
"Whatever mistakes you make as a young person, you've got to learn from them and go and grow," she added. "It is my intent to go to Rutgers with this vast experience of super highs and super lows and lead what I hope is an outstanding team into the Big Ten."
On other issues during a 10-minute call limited to eight questions:
?Hermann said the company that vetted her for Rutgers did ask about a lawsuit filed by one of her assistant coaches over a job termination.
? Hermann believes she can raise funds despite what has happened.
? Hermann denied the name calling, specifically when asked about calling the players "whores."
"That's not part of my vocabulary. ... Here's what I would say. Am I an intense coach? Absolutely an intense coach as many coaches are," she said. "But there is a big canyon between being super intense and abuse, and this was not an abusive environment for these women. Was it challenging? It was incredibly challenging. Was I aware that there were players that were unhappy? I was aware of that at the end of the season and I was unhappy."
BELGRADE, Serbia (AP) ? Serbia held a funeral on Sunday for Yugoslavia's last king, Peter II Karadjordjevic, who had fled the country at the start of World War II and died in the U.S. in 1970.
The former king's remains, and those of his wife, mother and brother, were interred in the family tomb at St. George church in Oplenac, central Serbia, in a ceremony aired live on the state television.
The funeral was attended by top state officials, who described it as an act of reconciliation and unity.
After fleeing Yugoslavia during its Nazi occupation, the former king never returned because Communists took over the country at the end of the war and abolished the monarchy.
He died in exile at the age of 47 and was buried at a Serbian Orthodox Church monastery in Libertyville, Illinois ? the only European monarch laid to rest on U.S. soil.
"We can no longer afford any divisions and injustice," President Tomislav Nikolic said in a speech at Sunday's ceremony.
Peter was born into a royal family, and his godfather was Britain's King George VI, but his life was often tragic and chaotic.
He was only 11 years old when his father, King Alexander I, was assassinated in 1934 in Marseilles, France. For the next six years the boy's powers were in the hands of a three-man regency headed by his uncle, Prince Paul.
In March 1941, Prince Paul was overthrown in a military coup after signing a pact with Germany.
Peter, then 17, was made the king by the Serb anti-fascists. But when Germany invaded Yugoslavia in April 1941, Peter was forced to flee, first to Greece, then to Egypt, then to Britain, where he headed the government-in-exile. He later lived in France and ended up in the U.S.
History books portray him as a figurehead leader and a victim of cunning politicians.
For the next 12 weeks, I am going into self-experimental, bio-hacking guinea pig mode in preparation for?Ironman Canada in Whistler on August 25.
It?s called the ?Great Ketogenic Ironman Experiment?, and in just a moment, I?m going to spill all the beans for you. I?ll show you a sample ketogenic training diet, a sample minimalist training week using time-saving underground training techniques, and reveal the secret weapons I?m going to use to enhance my fat-burning and training results.
But first?why the heck would YOU even want to try a low-carb, ketogenic diet for something like an Ironman triathlon? Or a marathon, Crossfit training routine, hard swim workouts, multi-day cycling stage race, or anything else that is energetically demanding and requires moderate doses of endurance?
There are two main reasons for using a low-carb, ketogenic diet.
1)?Metabolic superiority of using fats as a fuel.
Peter Attia really gets into this in the excellent blog post on ?Ketosis ? Advantaged or Misunderstood State??, in which he explains how being in a ketogenic state vastly enhances your lipolysis (fat burning efficicency), your aerobic capacity and your muscular endurance, including?significant increases in aerobic power and efficiency in several groups of elite athletes (e.g., Olympians) across multiple physical tasks maximally stressing the aerobic system. Go read his post to dig into this stuff.
2) Health and longevity advantages of controlling high blood sugar.
To illustrate these advantages, I scanned and pasted here a compelling image from Life Extension Magazine (I don?t know about you, but I want to be around to see my grandkids, and considering my 23andme.com genetic testing revealed higher risk for Type II Diabetes, I doubt that shoving any more gooey gels and sugar sports drinks into my gaping maw is going to do me any favors).
Finally, I?m not just messing around here and doing this Ironman at a slow, aerobic pace. Instead I?ll be attempting for an Ironman World Championship qualification, and a total time of 9:15-9:45.?We?re talking pain cave stuff here, with lots of hard anaerobic efforts thrown in ? no lolly-gagging ? a hard and heavy swim, 300-400W power efforts on the bike sprinkled throughout a 112 mile ride, all finished off with a 26.2 mile run (marathon) in 3:00-3:15?
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What Is Ketogenesis?
Great question.
Here?s the deal: I?m not even going to?try?to comprehensively explain this when so many other resources already exist. Here are the best 4 resources for you to become a ketogenic ninja:
1) My recent low carb and ketogenesis podcast on Jimmy Moore?s Livin? La Vida Low Carb Show?(in which we also tackle all the questions that are probably going to end up as comments on this post anyways, such as ?Aren?t You Concerned About Your Thyroid? and ?How Does Your Body Make Glucose If You Don?t Eat Carbs?, etc., etc., etc.).
2) Peter Attia?s excellent series on ?Ketosis ? Advantaged or Misunderstood State??. Put on your geeky propellor hat and scientific wading pants and go read it. He?s good.
3) Any of the other podcasts I?ve done with Peter, including:??How To Turn Yourself Into A Fat Burning Machine By Fasting For 24 Hours Then Going Out And Do Monster Workouts Without Bonking? and??Is It Possible To Be Extremely Active and Eat A Low Carbohydrate Diet??.
4) My Low Carbohydrate Diet For Athletes package?(pictured right), which includes a?complete low carb for athletes meal plan with fat adaptation, low carb maintenance, race/event week and race/event day blueprints, my low carb guidebook and 24-7 access to a low carb forum (warning, this program isn?t necessarily ketogenic ? it has carb re-feed days and stuff like that ? but it?s a good resource nonetheless).
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The Great Ketogenic Ironman Experiment Overview
OK, let?s get down to the nuts and bolts. Here?s how this ketogenic protocol is going to go.
I?ll be implementing a 100%?ketogenic diet?(meaning I?m keeping my blood ketones at 1.0 millimolar or higher)?along with?
-weekly?Talking20?blood measurements to make sure I?m not killing myself, and also to get some interesting data on what happens to thyroid, inflammation, testosterone, cortisol, etc. when combining ketogenesis with hard training.
-daily?Metron?breath ketone measurements to make sure I?m keeping my ketones above 1.0 millimolar (whoopee for smart scientific sounding numbers!)
-daily?Sweetbeat?HRV measurements (that?s ?Heart Rate Variability? ? read this for why I do it)?
-Hypoxico?s Intermittent Hypoxic Training protocols?
-Jay Schroeder?s EVOAthlete electrostimulation, isometric and overspeed training protocols?
-All the other ?underground training methods? I outline in this article?
-And a bunch of other secret weapons I?ll tell you about below?
In addition to putting weekly updates on my Facebook page and video updates on my upcoming phone app (launches June 3), I?ll be discussing the results of the experiment at this year?s?Ancestral Health Symposium?during my panel with Jimmy Moore, Robb Wolf, Mark Sisson, and Jamie Scott. And that symposium will be exactly one week before I actually take things into the deep, deep trenches and try to qualify for Kona at Ironman Canada.
Warning: unless you want to seriously ?F-up? your body (e.g. adrenal fatigue, joint damage, metabolic derangement, etc.), I do not recommend you combine ketogenesis or low carb diets with any form of hard or heavy training unless you?re willing to utilize the strategies you?re about to learn. I?m not even 100% sure that with all the ?damage control? I?m personally going to be doing that I will not experience medical issues while doing this experiment. But SOMEBODY has to find out if elite performance and ketogenesis are compatible, so I?m diving in.
Clear? OK, let?s keep going.
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Sample Weekly Ketogenic Ironman Training Diet
Here?s a sample of what I?ll be eating. Basics: 50-100g carbs on an easy day, 100-150 carbs on an average day, 150-200g carbs on a hard and heavy day, along with lots of medium chain triglycerides to keep my body in ketosis. So this isn?t?calorie-restricted ketosis.?It?s high-fat, high-calorie ketosis (that?s Lesson #1 for you to ensure you don?t destroy your metabolism with stuff like this).
-Breakfast: Piping hot cup of ?upgraded??organic, mold-free Upgraded Coffee?blended with unsalted, organic KerryGold butter and?Medium Chain Triglyceride (MCT) oil,?with a touch of?vanilla powder?and Upgraded Chocolate Powder. That?s what I?m calling ?The Bulletproof Triathlete? breakfast, with more details shortly?
-Mid-morning: TianChi with vegetable juice (I prefer my cleansing cocktail of cilantro, parsley, carrot, lemon and ginger juice, with a few pinches of Himalayan Sea Salt). If this takes me out of ketosis, I?ll leave out the carrots. Sorry, Bugs Bunny.
-Lunch: Large kale salad with extra virgin olive oil, avocado, olives, walnuts, sardines and nori OR my world-famous sexy ketogenic smoothie (kale blended with MCT oil, brazil nuts, cinnamon, coconut milk, Upgraded Chocolate Powder, stevia?and an avocado).
-Pre-Workout Snack: Shot of X2Performance?with 2-3oz?MCT oil.
-Dinner: Grass-fed beef, liver, sweetbreads (yes, that would be thyroid gland), wild salmon, etc. with roasted vegetables.
Rrrrrr ? back it up. Liver and sweetbreads? Yes. Here?s the 30 second elevator pitch: your liver needs glucose to convert T4 to T3 so unless you give yourself extra liver support and thyroid support by eating organ meats and sweetbreads, you?ll mess up your thyroid on a diet like this.)*
-Snack: 2-3 tablespoons coconut manna (AKA nectar of the gods)
*Here?s the rest of the reason, taken straight from this Chris Kresser/Chris Masterjohn podcast:
Chris Masterjohn:? Yeah, and I think you highlighted something important there that there are a lot of classic symptoms that go beyond the blood tests, and you know, I think even if you don?t see the changes in T3 and reverse T3, there are other mechanisms.? For example, if you have increased liberation of free fatty acids beyond what you?re able to utilize, there is some evidence that the free fatty acids will accumulate in the nucleus of the cell at a high enough concentration to inhibit thyroid binding to its receptor, and that will cause all of these symptoms of the metabolic effects, including the high cholesterol, but it might not show up as changes in thyroid hormones in the blood.? So, I think if you see those classics symptoms, if you see high cholesterol and low sex hormones, for example, I think those are good clues in addition to T3 and reverse T3 that might signify that an increase in carbohydrate intake might be needed, but I have an anecdote that I think is pretty interesting to share from?Nutrition and Physical Degeneration, Weston Price?s book.
Chris Kresser:? Yeah, let?s hear it.
Chris Masterjohn:? He says:? ?For the Indians of the far North this reinforcement? ? he?s talking about reinforcement of nutrition for pregnancy ? ?was accomplished by supplying special feedings of organs of animals.? Among the Indians in the moose country near the Arctic circle a larger percentage of the children were born in June than in any other month.? This was accomplished, I was told, by both parents eating liberally of the thyroid glands of the male moose as they came down from the high mountain areas for the mating season, at which time the large protuberances carrying the thyroids under the throat were greatly enlarged.?? So, what he?s saying is when the moose were about to reproduce, they naturally went into a kind of hyperthyroid state where their thyroids were enlarged, and the people there would harvest the thyroid glands so that they could reproduce, and as a consequence, most of their children were born nine months after the moose mating season.
Chris Kresser:? Wow.
Chris Masterjohn:? And what the indicates to me is ? I mean, it?s difficult to interpret it because he doesn?t go into great detail, but I think what we might be seeing here is up in the Arctic circle ? and these are the inland people, they?re not seacoast, so they probably don?t have a lot of iodine in the diet, they certainly don?t have a lot of carbohydrate in the diet.? It seems like they, as part of their natural adaptation to their environment, they supplemented with thyroid hormone so that they could convert their cholesterol to sex hormones so that they could increase their fertility, and I think what we?re witnessing is perhaps a natural acknowledgement that under those certain conditions where you have an extremely carbohydrate-restricted diet, you may need supplemental thyroid hormone in order to maintain that fertility.?
There you have it folks. That?s how I?m going to maintain my yummy, fat-fueled, sweetbread-laden fertility. You can check USWellnessMeats if your local organic farm can?t get you sweetbreads and liver.
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Sample Week of Minimalist Ironman Training
Due to time constraints and my desire to avoid chronic cardio overtraining, I?m following a complete 8-10 hour per week minimalist Ironman training protocol, while implementing all the Underground Training Techniques you learn about in?this post?and?this post. This includes extreme isometrics, hypoxic altitude training, overspeed, high intensity intervals, super slow weight training, cold thermogenesis, heat acclimation, greasing the groove, and electrical muscle stimulation.
Here?s a sample week so you can see what this kind of stuff looks like. It may look a little overwhelming at first, but once you establish your daily habits and patterns, it?s pretty easy to fit this stuff in.
Monday:
-60 minutes yoga and meditation.
-Cold thermogenesis (20-30 minute cold soak in 45-55 degree water).
-Full body foam rolling, 10 minutes inversion table,?mobility work?for any neglected areas.
-Stay off feet.
Tuesday :
-5 minutes hot-cold contrast shower.
-Swim 10?100?s using Wetronome to decrease 100m time by 0.2s per week.
-Run ?Hurricane workout?, 10?30 seconds at 10mph and 10% incline.?All performed with deep nasal breathing (I highly recommend BreatheRight strips for doing hard workouts/races with nasal breathing).
-Commute bike to gym and back for workout above (total 30 minutes cycling).
-All day: 5 pull-ups every 1-2 hours, entire work day is at standing workstation.
Wednesday:
-Superslow lifting: 5x 30 seconds up, 30 seconds down full body lift (e.g. Squat, Overhead Press, Seated Row, Back Extension, Pull-Up).?All performed with deep nasal breathing.
-Bike ? 8-10 30 second overspeed efforts of 120-150rpm.?All performed with deep nasal breathing.
-Isoextreme back foot elevated lunge 2 minutes each side, followed by 1 Russian Lunge every 5 seconds for 2 minutes, then repeat for opposite side (performed in sauna). You can find most of these isoextreme exercises on this YouTube Channel.
-All day: 5 pull-ups every 1-2 hours, entire work day is at standing workstation.
Thursday:
-Swim 50?s and 25?s sprints using Finis front mounted swim snorkel with hypoxic CardioCap.
-Litvinov 400m run repeats as 15-30 dumbbell swings or front squats to 400m uphill or flat run. All performed with deep nasal breathing. If tired, no run, but just easy, fun?Elliptigo?on trail.
-Commute bike to gym and back for workout above (total 30 minutes cycling).?All performed with deep nasal breathing.
-All day: 5 pull-ups per 1-2 hours, entire work day is at standing workstation.
Friday:
-10 minutes inversion table.
-30 minutes suspension trainer workout.
-Easy bike to sauna at gym for?5?20 second on, 5 seconds off isoextreme lunges,?5 minute isoextreme wall squat, and standing hamstring folded dollar bill drill 10?30 seconds on/10 second off.?All performed with deep nasal breathing.
-All day: 5 pull-ups per 1-2 hours, entire work day is at standing workstation.
Saturday:
-Electrostimulation 30 minutes quads/hamstrings + 60-90 minute tempo intervals ride using Sufferfest training videos and Hypoxico altitude generator.?
-If time: easy swim drills 30 minutes in cold river (kind of a combined cold thermogenesis with training).
Sunday:
-Run 60-90 minute tempo intervals on treadmill or trail.
And yes, compared to disappearing from my kids, work and social life for a 5 hour bike ride on a Saturday morning, slipping into the garage ?pain cave? for a quick Hypoxico session is far superior.?
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My Ketogenic Secret Weapons
OK, here?s the stuff that I?ll be relying on for the next 12 weeks ? the things that will make your life?far easier, your training way more productive and your body way less likely to get metabolically damaged if you doing low carb triathlon training. I call these my ?Ketogenic Secret Weapons?.
1. Upgraded Bulletproof Coffee
Bulletproof Coffee is?organic, mold-free coffee?blended with organic KerryGold butter and?Medium Chain Triglyceride (MCT) oil?with a touch of?vanilla powder?and chocolate. This stuff keeps me in a ketogenic state with me having to feel like gnawing my arm off in hunger halfway through the morning.
The idea behind?Bulletproof Upgraded Coffee?is that most coffee beans are processed by either leaving them in the sun and elements to wither and dry ? or by pressing them and letting them ferment (spoil) to remove the outer layer of the bean. Both of these techniques produce significant levels of unhealthy mycotoxins.
In contrast, the?Bulletproof Upgraded Coffee?beans are mechanically processed after picking using only clean cold water, which is more expensive, but safer because it significantly reduces harmful molds and bacteria from impacting your health.
The addition of the MCT oil?provides a readily available fuel source brain mitochondria, and may help you to excrete toxins from the brain, while the fat from the butter and the oil improves the ability of mind-stimulating terpenes and caffeine in coffee to enter your brain, along with potent coffee-based anti-inflammatories such as cafestrol and kawehol. And adding?a touch of?vanilla powder?and?Upgraded Chocolate Powder?makes it all the more heavenly.??
Just call it ?The Bulletproof Triathlete? breakfast.
2. Oxaloacetate
If you?re using extreme isometrics or high-intensity interval training and experiencing the massive lactic acid build-up that occurs in the local muscle tissue during a set, then you should know about something called ?oxaloacetate?.
Strap on your geek hat for a second.
Most chemical reactions in your body take place in a series of several steps.?In chemistry, the rate (or velocity) of a reaction with several steps is often determined by the slowest step, which is known as ?rate-limiting step.
A?significant rate limiting step of converting lactic acid into glucose (a really, really efficient way for your body to get glucose for hard efforts) is the conversion of the molecule Nicotinamide?Adenine?Dinucleotide (NAD) into Nicotinamide?Adenine?Dinucleotide Hydrogenase (NADH). So what does this have to do with oxaloacetate? In studies,?acute oxaloacetate exposure enhances resistance to fatigue?by increasing NAD to NADH conversion and allowing lactic acid to get recycled and converted to glucose at a much higher rate (16).
As a matter of fact, along with calorie restriction (which isn?t much fun, really), enhancing your Cori cycle efficiency is also one of the ways that you can significantly increase the enzyme AMPK, which you learned?earlier in this book?can upregulate mitochondrial biogenesis and improve both carbohydrate and fuel utilization.
Basically, this means that you can become a complete lactic acid metabolizing endurance beast if you?take about 100-200mg of oxaloacetate in supplement form 15-30 minutes prior to a workout?that includes either high intensity intervals, super slow training, or isometrics. I?m using the?Upgraded Anti-Aging?formula for this.
3. X2Performance
The main ingredients that?X2Performance?contains that directly help the purposes of ketogenic training are?
-d-Ribose, which allows you to rapidly regenerate ATP, even in the complete absence of carbohydrates (especially important since high intensity training depletes your total adenine dinucleotide pool much faster than long slow distance training, and you need that precious pool to make ATP)?
-Pinitol, which enhances uptake of cellular energy, even in a state of low insulin, which you?ll be in if you?re following a low-carb or ketogenic diet?
-Low doses of caffeine, which enhance free fatty acid utilization?
For anyone who wants to geek out on how loading with d-Ribose also allows you to more easily tap into your body?s own free fatty acids as a fuel, read?neurosurgeon Jack Kruse?s excellent article that reveals the truth about carbohydrates and exercise performance.?I?ll be slamming a shot before my workouts, and also before and during Ironman, and?X2Performance?has offered you the code BENGREENFIELD to get $10 off a case of the stuff in case you want to do that too.
4. UCAN Superstarch
UCAN Superstarch is for anyone who wants unflavored, 100% pure fuel ? in a non-GMO, slow release form for that allows you to use far less carbohydrate and burn significantly more of your own fat as a fuel. SuperStarch causes a very low release of insulin and results in an extremely stable blood sugar profile compared to sugary gels, sports drinks, powders or? energy bars.
This stuff puts your body in the ideal performance state and make you more metabolically efficient, thus allowing you to burn more fat as a fuel. To listen to an excellent interview about how to practically use this, and why burning more fats during exercise is good,?listen to this interview with Peter Attia.
Also, for more scientific information on Superstarch, read:??A Technological Breakthrough in Sports Nutrition Innovation:?a white paper by Professor Jeff Volek, March 2009?...
?or for a less ?sciency? explanation, read?this article that appears in Feb 2012 Men?s Health magazine.
I?ll be using this during a select few long rides and runs, and of course, quite liberally during the race itself.
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How I?ll Be Tracking & Testing
Of course, it wouldn?t be an experiment if I wasn?t gathering data, right? See, I did take a little bit of college at least, even it was in North Idaho.
1. Metron Ketone Breath Testing
That weird tube pictured on the right is a breath ketone monitor. It?s brand new, cutting-edge stuff developed by medical device manufacturer Akers Biosciences to detect levels of acetone in your breath, an indicator that your body is burning fat as its energy source, rather than carbohydrates
A Metron breath ketone monitor
It?s just a simple breath test can be performed anytime, anywhere. You get a measurement in 3 minutes, and ? most importantly ? there?s no blood testing involved. I?ll be doing enough finger-pricking as it is.
This is the same thing my fellow low carb blogger and podcaster Jimmy Moore has been using to test his ketones during his N=1 weight loss experiment, during which he?s lost 78 pounds so far (in one year).
2. Talking20 Blood Testing
In the video?How To Test Your Blood Anytime, Anywhere In The World, you learned about?Talking20, which?is disrupting health as we know it by merging biology with technology to deliver personal health data in a way that I think may actually trigger a personal health revolution.
Here?s how it works:
You send in a few drops of blood on one of their kits, and you?ve opened the gateway to everything happening inside you,?anytime you want it.??Talking20?is using mass spectrometry to analyze its blood samples, the same technology used by NASA and the Environmental Protection Agency use to conduct their studies of very small samples taken from all over on (and off) the planet. So you can?run 100?s of blood tests off a single, convenient drop of your dried blood.
I think this stuff is going to literally blow the roof off personal biohacking and the ability to peer into your personal health and performance in real time as you test anytime, anywhere in the world. For the purposes of the Great Ketogenic Ironman Experiment, it?s going to allow me to test every week without driving to the lab and giving oodles of blood.
If you want to try it, you can get your blood tested by Talking20 in the USA by clicking here or internationally by clicking here.
3. SweetBeatHRV Measurements
In the episode ?Everything You Need To Know About Heart Rate Variability Testing?, I introduced you to a cool little phone app called the Sweetbeat.
Since heart rate variability testing tracks the strength of your nervous system and can be a key sign of overtraining and metabolic distress, this will be a way to track how beat up my body is, and how my nervous system is responding to carbohydrates (or lack thereof, more specifically).
Interestingly, there may also be a correlation between ketogenesis and the ?low frequency? number you get when measuring your HRV. I was alerted to this fact in a recent reader comment (copied and pasted below):
Oh yeah, that?s kinda small, huh?
Here?s the full conversation from the comments section on my What Kind Of Damage Happens To Your Body After You Do A Hard Workout, Triathlon or Marathon?
Tom ? Some days I have a very very high VLF. say up to 80% of the power. Research is unsure what this means but could be related to diet, stress etc. ?I have noted that if I take serial readings across a morning I am fasting, till 12 noon usually, VLF gets steadily higher until I eat. It also seems to be higher when I am ketogenic, so could be of interest to you.?Also, in regards to your Ketogenic experiment, I take my ketone readings with a blood monitor multiple times a day, I have found from my research that I can consume huge amounts of carbs in and around training (mostly in the form of waxy maise starch) and sweet potato, and still be ketongenic (ketones 1.5-2mmol) the next morning. But If I overdo it on protein and fat later on in the evening and eat my last meal later than say 8.30 pm I have no ketones the next day, down to 0.3 or similar. Food for thought?
?The significance of VLF is still up for debate. I?ve read many theories including infection (this one I have noted in myself, I have predicted my last 3 infections with a sudden surge in VLF noted 2-3 days prior to symptoms). Also there is evidence it is linked to energy expenditure, which could be highly linked to the thermogenic and energy burning effects of MCT/ketogenesis. Such as -?http://www.hindawi.com/journals/jnume/2011/715361/abs/??This correlates well with my findings in ketogenesis.
?If that spiel was all greek to you, go listen to this podcast episode on heart rate variability testing (or read the transcript).?Go ahead, just do it. Once you get it through your head, none of this HRV stuff is too scary, and makes intuitive sense.
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How YOU Can Follow & Learn
This is going to be an exciting adventure, and along the way, I?ll be eager to answer all your questions about low carb diets and endurance training, any of my ?weapons? or training and diet methods listed above, and anything else you want to know.
The very best way to follow this entire experiment will be by 1) following the BenGreenfieldFitness Facebook page and 2) grabbing the brand new, free BenGreenfieldFitness phone app, which will be released on June 4 (don?t worry I?ll send out an email about it, so be sure you?re subscribed to my free newsletter). I?ll be releasing photos and updates to the Facebook page?and insider videos and audio updates to the phone app?
?in the meantime, leave your comments, questions and feedback below.
Rachel, left, and Pam Vingsness of Newton, Mass., hug each other after crossing the finish line as runners who were unable to finish the Boston Marathon on April 15 because of the bombings were allowed to finish the last mile of the race in Boston, Saturday, May 25, 2013. (AP Photo/Winslow Townson)
Rachel, left, and Pam Vingsness of Newton, Mass., hug each other after crossing the finish line as runners who were unable to finish the Boston Marathon on April 15 because of the bombings were allowed to finish the last mile of the race in Boston, Saturday, May 25, 2013. (AP Photo/Winslow Townson)
Pam Vingsness, right, comforts her crying mother, Rachel, of Newton, Mass., after they crossed the finish line, as runners who were unable to finish the Boston Marathon on April 15 because of the bombings were allowed to finish the last mile of the race in Boston, Saturday, May 25, 2013. (AP Photo/Winslow Townson)
Runners who were unable to finish the Boston Marathon on April 15 because of the bombings cross the finish line on Boylston Street after the city allowed them to finish the last mile of the race in Boston, Saturday, May 25, 2013. (AP Photo/Winslow Townson)
Nick Pelton, of Florida, hugs his mom, Colleen, after watching runners who were unable to finish the Boston Marathon because of the bombings on April 15, cross the finish line on Boylston Street after the city allowed them to finish the last mile of the race, in Boston, Saturday, May 25, 2013. (AP Photo/Winslow Townson)
Runners who were unable to finish the Boston Marathon on April 15 because of the bombings pass the first bombing site as they head toward the finish line on Boylston Street after the city allowed them to finish the last mile of the race in Boston Saturday, May 25, 2013. (AP Photo/Winslow Townson)
BOSTON (AP) ? Rosy Spraker was only a half-mile from the finish line of her seventh Boston Marathon when the bombs went off. She received her medal later in the mail at her Lorton, Va., home. But she couldn't bring herself to wear it until Saturday, when she and thousands of other athletes joined victims of the blast to run and walk the last mile of the race.
"Now I feel like I've earned my medal," Spraker said, beaming, after she crossed the Boylston Street finish line, encouraged by a cheering crowd. "I wanted to run for the victims, for freedom, to show the world that nothing is going to stop us."
"Somebody that thinks that they're going to stop a marathoner from running doesn't understand the mentality of a marathoner," said her husband, Lesley, after he placed the medal around Spraker's neck.
On April 15, explosions near the finish line killed three people and wounded more than 260.
On Saturday morning, about 3,000 runners and bombing victims gathered in light rain to run the final mile of the world's oldest annual marathon, said Kathleen McGonagle, spokeswoman for those organizing the event known as OneRun.
OneRun honors victims and emergency workers and allows runners to reclaim the final mile, McGonagle said.
"For the runner that didn't get the chance to finish the marathon, this is the chance for them to experience the final mile that was taken away from them," McGonagle said.
For many runners, it was also a chance to heal from the events of that harrowing day.
"It was very emotional to run down this street and see all the people cheering," said OneRun organizer J. Alain Ferry, who was prevented from completing his ninth consecutive Boston Marathon on April 15 and ran the final mile Saturday.
"There were a lot of tears," Ferry said, clutching his 2013 marathon bib, with the number 22084. "And I can feel in my throat that there are going to be more. This was a scab for everyone that just was not healing."
While the event was not a fundraiser, donations from some corporate sponsors covered OneRun operating costs, McGonagle said, and any leftover funds will be sent to a charity set up to benefit bombing victims.
Before the race, the National Anthem was sung by the choir from St. Ann Parish, where 8-year-old victim Martin Richard's family worshipped.
"It was a beautiful thing," said an emotional Steve Poirier, of Chelmsford, who had been running his sixth Boston Marathon when he was turned back last month. "As a runner, you want the chance to finish. Better late than never."
May 24, 2013 ? New research presented today shows that formation of new neurons in the hippocampus -- a brain region known for its importance in learning and remembering -- could cause forgetting of old memories by causing a reorganization of existing brain circuits. Drs. Paul Frankland and Sheena Josselyn, both from the Hospital for Sick Children in Toronto, argue this reorganization could have the positive effect of clearing old memories, reducing interference and thereby increasing capacity for new learning.
These results were presented at the 2013 Canadian Neuroscience Meeting, the annual meeting of the Canadian Association for Neuroscience -- Association Canadienne des Neurosciences (CAN-ACN).
Researchers have long known of the phenomenon of infantile amnesia: This refers to the absence of long-term memory of events occurring within the first 2-3 years of life, and little long-term memories for events occurring until about 7 years of age. Studies have shown that though young children can remember events in the short term, these memories do not persist. This new study by Frankland and Josselyn shows that this amnesia is associated with high levels of new neuron production -- a process called neurogenesis -- in the hippocampus, and that more permanent memory formation is associated with a reduction in neurogenesis.
Dr. Frankland and Dr. Josselyn's approach was to look at retention of memories in young mice in which they suppressed the usual high levels of neurogenesis in the hippocampus (thereby replicating the circuit stability normally observed in adult mice), but also in older mice in which they stimulated increased neurogenesis (thereby replicating the conditions normally seen in younger mice). Dr. Frankland was able to show a causal relationship between a reduction in neurogenesis and increased remembering, and the converse, decreased remembering when neurogenesis increased.
Dr. Frankland concludes: " Why infantile amnesia exists has long been a mystery. We think our new studies begin to explain why we have no memories from our earliest years."
This research was supported by funds from the Canadian Institutes of Health Research and the "Chase an Idea in Paediatric Neuroscience" grant from The Centre for Brain & Behaviour at the Hospital for Sick Children.
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The above story is reprinted from materials provided by Canadian Association for Neuroscience, via EurekAlert!, a service of AAAS.
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Contact: Marcus Neitzert marcus.neitzert@dzne.de 49-228-433-02271 Helmholtz Association of German Research Centres
A new animal model gives insights into mechanisms of Parkinson's disease pathogenesis
This news release is available in German.
In Parkinson's disease, the protein "alpha-synuclein" aggregates and accumulates within neurons. Specific areas of the brain become progressively affected as the disease develops and advances. The mechanism underlying this pathological progression is poorly understood but could result from spreading of the protein (or abnormal forms of it) along nerve projections connecting lower to upper brain regions. Scientists at the German Center for Neurodegenerative Diseases (DZNE) in Bonn have developed a novel experimental model that reproduces for the first time this pattern of alpha-synuclein brain spreading and provides important clues on the mechanisms underlying this pathological process. They triggered the production of human alpha-synuclein in the lower rat brain and were able to trace the spreading of this protein toward higher brain regions. The new experimental paradigm could promote the development of ways to halt or slow down disease development in humans. The research team headed by Prof. Donato Di Monte presents these results in the scientific journal "EMBO Molecular Medicine".
Parkinson's disease is a disorder of the nervous system. It typically manifests itself with motor disturbances, such as an uncontrollable trembling of the limbs, as well as non-motor symptoms, including sleep disorders and depression.
At the present, no cure exists for Parkinson's disease, although symptomatic intervention, including treatment with dopamine agonists, can alleviate patients' motor impairment. Parkinson's is the second most common neurodegenerative disorder, after Alzheimer's disease; it is estimated that 100,000 to 300,000 patients are affected by Parkinson's disease in Germany alone.
In a small percentage of cases, Parkinson's disease is due to genetic abnormalities carried within families. For the vast majority of patients, however, the cause of the disease remains unknown; the development of this sporadic form of the disease is likely promoted by both environmental and genetic risk factors. An intriguing characteristic of the brain of patients with sporadic Parkinson's disease is the progressive accumulation of intraneuronal inclusions that were first described by a German neurologist, Friedrich Lewy, and are therefore called Lewy bodies.
"A major discovery in the late 90's was that Lewy bodies are formed when the protein alpha-synuclein becomes aggregated," says Di Monte. "Since then, it was also found that aggregates of alpha-synuclein are progressively accumulated within the patients' brains during the course of the disease".
Pathology studies from human brains show that the deposits usually start forming in the lower part of the brain, in an area named "medulla oblongata". In subsequent disease stages, alpha-synuclein aggregates are observed in progressively higher (more rostral) brain regions, including the midbrain and cortical areas.
"This spreading appears to follow a typical pattern based on anatomical connections between regions of the brain," says the neuroscientist. "For this reason, it has been hypothesized that alpha-synuclein or abnormal forms of it can be transferred between two interconnected neurons and hence migrate throughout the brain. But until now, there was no way of targeting the medulla oblongata to reproduce this spreading of alpha-synuclein in the laboratory. It is also unclear what conditions could trigger the inter-neuronal passage of the protein or its aggregates. We have now developed a new experimental paradigm which enables investigations on these fundamental issues."
From the neck into the brain
The researchers' concept is based on reproducing alpha-synuclein spreading in rats: for this, they transferred the blueprint of the human form of alpha-synuclein into the rat brain. The blueprint was transported by specifically engineered viral particles that the scientists injected into nerve fibres in the neck of the animals. The genetic code for the protein passed along these fibres into the medulla oblongata, where transfected rat neurons began producing high quantities of human alpha-synuclein.
"We have good reasons to believe that the medulla oblongata is a primary site of early disease development. This is why we wanted to activate production of alpha-synuclein specifically in this part of the brain. The medulla oblongata is difficult to reach via surgical procedures. For this reason, we injected the viral particles into the vagus nerve. This is a long nerve stretching from the abdomen via the neck to the medulla oblongata. The nerve consequently served as an entrance into the brain and, in particular, the medulla oblongata," Di Monte explains.
A migrating protein
The researchers monitored the production and localization of human alpha-synuclein in rats' brains over a period of four and a half months after injection of the viral particles. As predicted, the exogenous protein was synthesized only within neurons of the medulla oblongata connected to the vagus nerve. Starting at two months, however, human alpha-synuclein was observed also in brain areas more and more distant from the medulla oblongata (see figure). Caudo-rostral spreading involved inter-neuronal passage of the protein along specific nerve tracts and was accompanied by morphological alterations (such as swellings) of the neuronal projections taking up human alpha-synuclein.
The study, sponsored in part by the Blanche A. Paul Foundation, bears a number of critical implications. It reproduces a pattern of protein propagation that resembles the progressive spreading of pathological alpha-synuclein in Parkinson's disease. As importantly, the process of protein transmission was triggered by overproduction of alpha-synuclein within a specific brain region.
"Overproduction of alpha-synuclein accompanies a variety of conditions, such as aging, neuronal injury or genetic polymorphisms, that could promote the development of Parkinson's disease." concludes Di Monte. "Thus, our results suggest a mechanistic link between disease risk factors, enhanced levels of alpha-synuclein, spreading of the protein and its pathological accumulation."
Insight into the early stages of Parkinson's
The new model mimics events that likely occur in the early stages of alpha-synuclein pathology in the absence of overt behavioural (in rats) or clinical (in patients) manifestations. "It will therefore become a valuable tool to investigate early mechanisms of disease pathogenesis that could be targeted for therapeutic intervention. Early intervention would have a greater probability to prevent or halt the spreading of pathology and progression of the disease," says Di Monte.
###
The German Center for Neurodegenerative Diseases (DZNE) investigates the causes of diseases of the nervous system and develops strategies for prevention, treatment and care. It is an institution of the Helmholtz Association of German Research Centres with sites in Berlin, Bonn, Dresden, Gttingen, Magdeburg, Munich, Rostock/Greifswald, Tbingen and Witten. Website: http://www.dzne.de/en
Original publication
"Caudo-rostral Brain Spreading of ?-Synuclein through Vagal Connections", Ayse Ulusoy, Raffaella Rusconi, Blanca I. Prez-Revuelta, Ruth E. Musgrove, Michael Helwig, Bettina Winzen-Reichert, Donato A. Di Monte EMBO Molecular Medicine (2013), DOI: 10.1002/emmm.201302475 - http://onlinelibrary.wiley.com/doi/10.1002/emmm.201302475/abstract
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Contact: Marcus Neitzert marcus.neitzert@dzne.de 49-228-433-02271 Helmholtz Association of German Research Centres
A new animal model gives insights into mechanisms of Parkinson's disease pathogenesis
This news release is available in German.
In Parkinson's disease, the protein "alpha-synuclein" aggregates and accumulates within neurons. Specific areas of the brain become progressively affected as the disease develops and advances. The mechanism underlying this pathological progression is poorly understood but could result from spreading of the protein (or abnormal forms of it) along nerve projections connecting lower to upper brain regions. Scientists at the German Center for Neurodegenerative Diseases (DZNE) in Bonn have developed a novel experimental model that reproduces for the first time this pattern of alpha-synuclein brain spreading and provides important clues on the mechanisms underlying this pathological process. They triggered the production of human alpha-synuclein in the lower rat brain and were able to trace the spreading of this protein toward higher brain regions. The new experimental paradigm could promote the development of ways to halt or slow down disease development in humans. The research team headed by Prof. Donato Di Monte presents these results in the scientific journal "EMBO Molecular Medicine".
Parkinson's disease is a disorder of the nervous system. It typically manifests itself with motor disturbances, such as an uncontrollable trembling of the limbs, as well as non-motor symptoms, including sleep disorders and depression.
At the present, no cure exists for Parkinson's disease, although symptomatic intervention, including treatment with dopamine agonists, can alleviate patients' motor impairment. Parkinson's is the second most common neurodegenerative disorder, after Alzheimer's disease; it is estimated that 100,000 to 300,000 patients are affected by Parkinson's disease in Germany alone.
In a small percentage of cases, Parkinson's disease is due to genetic abnormalities carried within families. For the vast majority of patients, however, the cause of the disease remains unknown; the development of this sporadic form of the disease is likely promoted by both environmental and genetic risk factors. An intriguing characteristic of the brain of patients with sporadic Parkinson's disease is the progressive accumulation of intraneuronal inclusions that were first described by a German neurologist, Friedrich Lewy, and are therefore called Lewy bodies.
"A major discovery in the late 90's was that Lewy bodies are formed when the protein alpha-synuclein becomes aggregated," says Di Monte. "Since then, it was also found that aggregates of alpha-synuclein are progressively accumulated within the patients' brains during the course of the disease".
Pathology studies from human brains show that the deposits usually start forming in the lower part of the brain, in an area named "medulla oblongata". In subsequent disease stages, alpha-synuclein aggregates are observed in progressively higher (more rostral) brain regions, including the midbrain and cortical areas.
"This spreading appears to follow a typical pattern based on anatomical connections between regions of the brain," says the neuroscientist. "For this reason, it has been hypothesized that alpha-synuclein or abnormal forms of it can be transferred between two interconnected neurons and hence migrate throughout the brain. But until now, there was no way of targeting the medulla oblongata to reproduce this spreading of alpha-synuclein in the laboratory. It is also unclear what conditions could trigger the inter-neuronal passage of the protein or its aggregates. We have now developed a new experimental paradigm which enables investigations on these fundamental issues."
From the neck into the brain
The researchers' concept is based on reproducing alpha-synuclein spreading in rats: for this, they transferred the blueprint of the human form of alpha-synuclein into the rat brain. The blueprint was transported by specifically engineered viral particles that the scientists injected into nerve fibres in the neck of the animals. The genetic code for the protein passed along these fibres into the medulla oblongata, where transfected rat neurons began producing high quantities of human alpha-synuclein.
"We have good reasons to believe that the medulla oblongata is a primary site of early disease development. This is why we wanted to activate production of alpha-synuclein specifically in this part of the brain. The medulla oblongata is difficult to reach via surgical procedures. For this reason, we injected the viral particles into the vagus nerve. This is a long nerve stretching from the abdomen via the neck to the medulla oblongata. The nerve consequently served as an entrance into the brain and, in particular, the medulla oblongata," Di Monte explains.
A migrating protein
The researchers monitored the production and localization of human alpha-synuclein in rats' brains over a period of four and a half months after injection of the viral particles. As predicted, the exogenous protein was synthesized only within neurons of the medulla oblongata connected to the vagus nerve. Starting at two months, however, human alpha-synuclein was observed also in brain areas more and more distant from the medulla oblongata (see figure). Caudo-rostral spreading involved inter-neuronal passage of the protein along specific nerve tracts and was accompanied by morphological alterations (such as swellings) of the neuronal projections taking up human alpha-synuclein.
The study, sponsored in part by the Blanche A. Paul Foundation, bears a number of critical implications. It reproduces a pattern of protein propagation that resembles the progressive spreading of pathological alpha-synuclein in Parkinson's disease. As importantly, the process of protein transmission was triggered by overproduction of alpha-synuclein within a specific brain region.
"Overproduction of alpha-synuclein accompanies a variety of conditions, such as aging, neuronal injury or genetic polymorphisms, that could promote the development of Parkinson's disease." concludes Di Monte. "Thus, our results suggest a mechanistic link between disease risk factors, enhanced levels of alpha-synuclein, spreading of the protein and its pathological accumulation."
Insight into the early stages of Parkinson's
The new model mimics events that likely occur in the early stages of alpha-synuclein pathology in the absence of overt behavioural (in rats) or clinical (in patients) manifestations. "It will therefore become a valuable tool to investigate early mechanisms of disease pathogenesis that could be targeted for therapeutic intervention. Early intervention would have a greater probability to prevent or halt the spreading of pathology and progression of the disease," says Di Monte.
###
The German Center for Neurodegenerative Diseases (DZNE) investigates the causes of diseases of the nervous system and develops strategies for prevention, treatment and care. It is an institution of the Helmholtz Association of German Research Centres with sites in Berlin, Bonn, Dresden, Gttingen, Magdeburg, Munich, Rostock/Greifswald, Tbingen and Witten. Website: http://www.dzne.de/en
Original publication
"Caudo-rostral Brain Spreading of ?-Synuclein through Vagal Connections", Ayse Ulusoy, Raffaella Rusconi, Blanca I. Prez-Revuelta, Ruth E. Musgrove, Michael Helwig, Bettina Winzen-Reichert, Donato A. Di Monte EMBO Molecular Medicine (2013), DOI: 10.1002/emmm.201302475 - http://onlinelibrary.wiley.com/doi/10.1002/emmm.201302475/abstract
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
When a big funnel of destruction touches down, it puts everything that's about ground in instant trouble. But exactly how much trouble actually depends a lot on construction, and not just things like structural reinforcement: pretty standard, inherent things like the size of the rooms.
3) Any of the other podcasts I?ve done with Peter, including:??How To Turn Yourself Into A Fat Burning Machine By Fasting For 24 Hours Then Going Out And Do Monster Workouts Without Bonking? and??Is It Possible To Be Extremely Active and Eat A Low Carbohydrate Diet??.
Warning: unless you want to seriously ?F-up? your body (e.g. adrenal fatigue, joint damage, metabolic derangement, etc.), I do not recommend you combine ketogenesis or low carb diets with any form of hard or heavy training unless you?re willing to utilize the strategies you?re about to learn. I?m not even 100% sure that with all the ?damage control? I?m personally going to be doing that I will not experience medical issues while doing this experiment. But SOMEBODY has to find out if elite performance and ketogenesis are compatible, so I?m diving in.
Saturday:
1. Upgraded Bulletproof Coffee
2. Oxaloacetate
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Public release date: 24-May-2013
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