Tell me more about prions!!

Small regions within prion proteins regulate their ability to cross species barriers

Researchers have known for decades that certain neurodegenerative diseases, such as mad cow disease or its human equivalent, Cruetzfeldt-Jakob disease, result from a kind of infectious protein called a prion. Remarkably, in recent years researchers also have discovered non-pathogenic prions that play beneficial roles in biology, and prions even may act as essential elements in learning and memory.

But although prions have received a great deal of scrutiny, scientists still don't understand many of the most fundamental mechanisms of how prions form, replicate and cross from one species to another.

Now, through studying non-toxic yeast prions, scientists at Whitehead Institute have discovered small but critical regions within prions that determine much of their behavior.

"These findings provide a new framework for us to begin exploring properties of prion biology that, up until now, have proven difficult to investigate," says Whitehead Member and MIT Professor of Biology Susan Lindquist, senior author on the paper, published in Nature.

Proteins are the cell's workhorses, and they need to fold into complex and precise shapes to do their jobs. Prions are proteins that start out normally, but then at some point misfold - rather like an origami swan that comes out looking and acting instead like a vulture.

But prions have another characteristic that enables them to wreak havoc. They recruit other, properly folded proteins into misforming along with them, a process Lindquist calls a "conformational cascade." In many organisms, this conformational cascade creates long fibers called amyloids. (The brains of animals that have died from prion infections are literally packed with amyloid clumps.)

In order to glean insights into the mechanics that enable amyloid formation, Peter Tessier, a postdoctoral scientist in Lindquist's lab, used peptide arrays - glass slides covered with thousands of tiny protein fragments. Traditionally, these arrays are used for finding binding sites within well-behaved proteins. Here, Tessier designed the arrays so that he could observe protein folding and amyloid formation in real time.

Tessier covered the array with peptides from baker's yeast and then added prion protein to the array, also from the same yeast species. He found that a small cluster of peptides recruited the prion proteins to misfold into an amyloid structure. This region of the protein, which Tessier called a "recognition element," constitutes about 10 percent of the prion. Tessier repeated this experiment with peptides and a prion taken from pathogenic fungi. The results were the same.
While this prion is a laboratory construct not found in nature, these findings provide researchers with a new way to approach old questions, such as why some prion diseases can jump from one species to another but others can't. Tessier and Lindquist say it is likely that natural prions contain more than one recognition element, and recognition elements can slide into a neighboring region. Many external factors can determine which recognition element is activated, in turn influencing the downstream behavior of the prion.
FINDINGS

Scientists at Whitehead Institute have found that small regions within prion proteins are responsible for their infectious properties. Moreover, these regions regulate the ability of prions to cross species barriers.

RELEVANCE

Prions are highly robust and infectious proteins, most notable for their central role in bovine spongiform encephalopathy, commonly called mad cow disease. But very little is known about how prions form aggregates of malformed proteins that ultimately result in disease. This study provides initial insights into how prions recruit and distort healthy neighboring proteins.

"These findings are remarkable for two reasons," says Lindquist, who is also an investigator for Howard Hughes Medical Institute. "For one thing, this is the first time that these peptide arrays have been used to study protein folding. We've taken this platform to a whole new level. Also, we've seen just one small part of this prion inducing proteins to fold. This is an entirely new concept."

Earlier research from the Lindquist lab, published in Nature in 2005, identified the amino acid regions where prions connect with one another to form amyloids. Those interaction regions turn out to be the same regions Tessier identified as recognition elements - further confirmation that these regions are key to prion activity.

Tessier and his colleagues plan to further investigate this process in mammalian prions, such as those responsible for mad cow and Cruetzfeldt-Jakob diseases, as well as in other non-prion proteins that can also form amyloid structures.

Source: http://www.medicalnewstoday.com/articles/70530.php

Wow...what a run!!!

I had a hard time getting up this morning and I was yawning the entire way as I drove to my running route. However, as soon as I started and my blood starting moving I felt great. I ran along the Mississippi River and it was such a beautiful day! It was steamy out, but the path was shady for the most part and there was a little of a breeze. I listened to praise music the whole time and prayed that God would give me strength and energy to finish the 14 miles. If you know the cities you'll understand how long of a run I did. I started out on Frankline Ave and ran several miles into the Fort Snelling National Park. It was quite a hefty run, but I could've definitely gone further. There was a strange thing that happened towards the end of the run when I ran across the Franklin bridge. There were all these cop cars blocking the street and lots of people stopped to gawk. Everybody was looking over the bridge and I couldn't really pick out what they were looking at...I sure didn't see anything. However, I saw that the cop was standing by a pair of sandals and I came to the conclusion that somebody must've jumped off the bridge. I did ask a spectator, but she didn't seem to know much. What a crazy thing to do, but please pray for this person that he or she makes it out ok.

Also, once again I'm going to ask for your prayers for me as I start my first official week as a kindergarten Spanish Immersion teacher for Minnetonka. There is so much to learn and so much to do. Eventhough I'm very excited to start, it is all very overwhelming and suffocating at times. Please pray that I stay calm and centered through it all.

One last thing. Please let me know if you are interested in purchasing a t-shirt and what you would like it to say (loved one or father, walk or run). I need to get a rough guestimate for an order in asap. Thanks so much!

Much love,
Lacy

New life...

Uncle Ray went home peacefully early Friday morning. I'm glad that I went to go visit him when I did. It kind of feels like he was waiting for me, just like my dad waited for him. I didn't think it would all happen this fast, but I couldn't be happier for him that he is finally free. Please continue to pray for Uncle Ray's family. I know that they will really miss his heartwarming presence, I know I will.

Also, please send some prayers out there tomorrow morning for me because I will be running 14 miles. I have never ran more than 13 miles so I'm a little bit nervous that it will all go ok. I had such a great run last weekend...I just pray that God confirms to me that I can do this. I'm going to go to bed pretty soon here so that I will be all rested up. Wish me luck!

One more thing, I need to know if any of you out there would be interested in purchasing a shirt and if you want, you can order it with "Loved one" instead of "father" and you can even replace "run" with "walk". Please shoot me an email and let me know. I don't know of the exact price yet, but the cost will include for the shirt, printing, for Holli and a little donation to my dad's account. It will most likely be more than $20 I'm thinking. I just need to know how many are interested so I can place an order and they can give me a bulk price.

Check out this Fox 9 News Story. It is frustrating how much CJD goes misdiagnosed and incorrectly reported. Even though only 8 have passed away in Minnesota from CJD....I'm pretty sure the actual number is much higher. It is here and we need to know more!
Misdiagnosis: CJD

Last Edited: Thursday, 14 Sep 2006, 3:13 PM CDT
Created: Wednesday, 13 Sep 2006, 5:17 PM CDT

AP

FOX 9 -- Her daughter say their mother sparkled in her golden years, but when Shirly Rassieur turned 68 -- it was like someone flipped a switch.

She lost the ability to walk and talk. Suddenly, she couldn’t figure out how to work the thermostat.

The doctors diagnosed Shirly with Alzheimer’s, even though some of the symptoms didn’t fit. Shirly didn’t just slip away -- her decline was abrupt and brutal.

When she dies in July of last year, her daughters demanded an autopsy.

They found their mother dies from Creutzfeldt-Jakob Didease, or CJD -- often referred to as a human form of mad cow disease.

Like British mad cow disease, which is transmitted through contaminated meat, the disease is caused by the same microscopic and indestructible protein.

No one knows what causes cases of CJD in the U.S., which afflict about one in a million.

The Minnesota Health Department has been tracking CJD deaths since 1991. Last year eight people died from the disease, but the health department bases that number on death certificates.

Shirly Rassieur’s death certificate still says Alzheimer’s -- her doctor refuses to change it.

It’s a disease that stole the sparkle from the woman they love, and her daughters can’t help wondering how many other cases may be misdiagnosed.

Source: www.myfoxtwincities.com/myfox/pages/Home/Detail;jsessionid=60D2D47D0B02B08E3FD1CD1EAF6614F9?contentId=876930&version=1&locale=EN-US&layoutCode=TSTY&pageId=1.1.1&sflg=1

No vacation for me....bummers!!

I found out last night that my new teacher orientation actually started today!! I was thinking that the ball started rolling on Friday, but I was wrong and boy am I glad I realized that. After my last night class, I headed out to sing karoake with my good friend Tracee. It was a night to celebrate not only because I successfully finished my two summer courses, but also because it was Tracee's birthday. I sang "Can't fight the moonlight" and "Let's hear it for the boy". I had a lot of fun singing the second song and I plan to sing it to my future husband one day. If that ever happens...hehe!

It was an early night though, because I had to be in Minnetonka for training at 9:30am. It was a good first day and I learned a lot of beneficial information, but at the same time everything I have to do and know is so overwhelming. Please pray for me! Tomorrow will be an even longer day...I have to be there from 8am-4pm oofta! Anyway, after my training was over, I picked up my grandma Hladky to go out to lunch and visit my great uncle Ray who is in the hospital.

Just a little bit about Uncle Ray. He is truly an amazing man. He took care of my dad and his siblings a lot when they were young. My dad often talked about Uncle Ray and how much he loved him. He saw him like a second dad. Uncle Ray is over 90 years old and even though he has an ailing heart, it couldn't be more full of love. When my dad was in hospice care, Uncle Ray found a way to make it all the way up to St. Cloud to visit him. It was after his visit that my dad went to be with the Lord. He was waiting for Uncle Ray! I actually wasn't in the room when my dad passed. I knew I wouldn't be able to take it so I had been outside, walking by the river and listening to praise music on my ipod. When I walked back into the hospital, it was the first time that my heart didn't race thinking that someone was going to tell me that my dad passed. He went at the one moment when I didn't expect it. So it came as a shock when Uncle Ray who came walking towards me to give me a hug and let me know that my dad has been freed. It was truly a special moment. That just goes to show how special my great Uncle Ray is.

Anyway, Uncle Ray is currently in hospice care at methodist hospital and preparing to make his way to heaven. He has had complications from the heart meds that he has been taking for many years and they are causing him to blead internally. His body can't recover not only because of his age, but because he doesn't want to fight for life. He wants more than ever to go home! I felt a huge peace come over me as I sat by his side, holding his hand and saying prayers for his comfort and peace. Even though he couldn't verbally respond, I knew he could hear me by the squeeze of his hand. It does all kind of seem eary that he is in a similar end of life situation as my dad and around the same time, but it also couldn't feel more right. The more that I see my loved ones pass away, the more I adjust to the reality of death and it not being all that scary. This may be wierd for some of you that I say this, but witnessing the passing of life is a relief. We are here temporarily, it is just a passing ground to our eternal home of everlasting life in heaven. Why is death viewed with such darkness? It is unfortunate for us who are left behind, but I couldn't be happier for Uncle Ray that he will make his journey to live in complete happiness. He definitely deserves it!

I ask for your prayers for my great Unlce Ray and his family. May that feel God's love comfort their aching hearts at this time. May his peace warm them from head to toe.

As for my training today, I went rollerblading for 2 hours. I got sprinkled on here and there, but it was very refreshing. My legs were sore and I could feel a blister coming on strong, but I kept on truckin'. I knew that this workout will be nothing compared to Sunday when I have to run 14 miles. Please keep me in your prayers that all goes well. This will be the most that I have ever ran at 1 time. Thank you for your continued thoughts and prayers. Remember...don't stop spreading the word.

Much love,
Lacy

Angry survivors pursue CJD mystery, seek government support, research

These stories took the words right out of my mouth!!

Please take a look...
www.pvc.maricopa.edu/puma/may05/cjd_schwan.html

Here I go again....

Yesterday was my first day of vacation and I was planning to do my blog post in the evening and then things got really hectic. I ended up going over to my sister's house so that I could watch my nephew. They are both very sick with ear infections and chest colds. My sister and I commented how it is so hard to see someone who is so young and so helpless be sick. However, I reminded her that dad was in a very similar position, but worse. We must be thankful that it is only a cold and it too shall pass.

I thought that I might not get a chance to run today, because it started to poor when I headed for home. However, God cleared the sky and provided for another great run for me. I felt so good running today...I definitely was going at a faster pace. I even decided to run on the bike path around Lake Harriet so that I could get in a little bit more distance. However, I got a few nasty stares from bike riders and even one was so gutsy to tell me, "wrong trail". I just kept on going, but there was something inside of me that wanted to see that woman again and say, "By the way, I know I'm on the wrong trail..I'm just going for more distance." Oh well...I don't need to explain myself to her. Anyway, that was kind of upsetting, but I just kept on going and praising God for the health He has given me to run. I feel so blessed. I once again saw those people practicing a play outside and a part of me wanted to stop and watch, but that probably wasn't necessary. Another interesting, but amazing run! Thanks God!

I ask for your prayers for my sister and my little nephew. May God restore them back to health so that they may live out their every day for him. Please also pray for me that God continues to bless me with good health to successfully complete this marathon for Him and for my dad.

Much love,
Lacy

8th week of training finished with success!!

I said so many prayers Friday night that God would give me the strength and energy to have a better 12 mile run than last weekend. He never proves me wrong! It was absolutely amazing! I woke up at 7:30am and got myself ready mentally and physically for the run. It was a beautiful morning and the birds were chirping like crazy. During the whole run I felt so good...it was like I was flying on cloud 9. I was truckin'! The hardcore runners definitely come out in the morning. I saw so many people in running gear and most of them have to be training for the marathon. So I ran around Lake Harriet first, then Lake Calhoun and last Lake of the Isles. There were these two girls that came running quickly up behind me as I started around Lake Calhoun and then they passed me. Well, for some reason something came over me and I kept up with them and even ended up passing them. I decided to go the opposite way than usual around Lake of the Isles and I actually met up with them again at about the half way point. Then, as I reached Lake Calhoun and stopped for a drink and headed on my way soon the same two girls came flying up behind me. They were sprinting and I was like wow...I'm not going to win this one. However, they finished about 50 meters ahead and headed for home. As they turned around, I said "good job girls" and they said the same to me. I thank them for helping me keep up the pace. However, I still kept on going to finish the last lag of the run around Lake Harriet. As I was running up the hill that way, I passed this older man and he said "I'll race you". I looked at him and smiled and started to book it. He definitely kept up good pace, but I beat him to the top! He was probably about 60 years old so he definitely did a good job. I hope I'm able to run like that at his age. Anyway, he asked me if how far of a run I was going for and asked if I was running the marathon. When he heard my answer he said, "keep up the good work". At that moment, I thanked my dad because I saw that as him speaking through that man to tell me that he proud of me. It was definitely a good run!
However, I didn't stop when I finally got home. I actually cleaned the house for several hours for our party. Yeah..it was a long day, but a fun day. Our housewarming party was a blast! I talked to a lot of people about the marathon and about my dad and many were very interested. I never stop spreading the word. Please do the same! Thank you to all who came!
So today I just have been taking it easy and being a couch potato. I haven't done that in a long time and it definitely feels good. I like being lazy from time to time! He he! I hope you all were able to rest today as well. May God bless you!
Much love,
Lacy