Podcasts about Laminin

In the podcast episode "Rhythms That Restore," Host Cherisse Hixson shares her transformative experiences from a recent trip of a lifetime to Italy's Amalfi Coast.  She reflects on the beauty and insights gained, emphasizing the importance of being present and appreciating creation.  Cherisse discusses the significance of bravery, courage, community, and faith, drawing from personal anecdotes and Ephesians 3:14-20.  She recounts challenging yet rewarding experiences, like a hike in the rain and learning about the resilience of local women who formed and built the Amalfi Coast.  Cherisse encourages listeners to embrace discomfort, seek beauty, and trust in God's plan that is so much sweeter than our own, encouraging listeners to lean into the discomfort to discover all that lays ahead of them in the unknown. --------------------------------------------------------------------------------------------------- Tools and Resources Ephesians 3:14-20: "00:06:06" Emily Ozier Artist: "00:14:30" @emyoartwork @TravelwithEmyo @Welcome_Wanderers  Wren Robbins Podcast Coach: "00:13:30" Brené Brown's Work: "00:22:28" Laminin:- cell that holds all things together in our body "00:26:30" Colossians 1:17: "00:26:30" Ephesians 2:10: "00:34:59" Lemon Grove Tour in Amalfi: "00:48:19" "Vivo Per Lei:" by Andrea Bocelli: "00:49:22" Instagram @RhythmsThatRestorePodcast: "00:54:08" Questions for Reflection What restores me?: "00:50:41" What brings you joy?: "00:51:46" What is forming you?: "00:52:56" Notable Quotes Ephesians 3:20: "00:52:56" --------------------------------------------------------------------------------------------- Connect with Cherisse & Join our Podcast Community  Join our "Rhythms that Restore" Community: Click below and pull up a chair with us and walk through life IN COMMUNITY and beside others who are learning and putting these new Rhythms in place. Click: https://www.facebook.com/groups/339272845793051/ -------------------------------------- Follow "Rhythms that Restore Podcast" on Instagram: https://www.instagram.com/rhythmsthatrestorepodcast?igsh=Z3lmY2UzcXZzMTlq&utm_source=qr -------------------------------------------- Tune In- Subscribe, Rate, and Share: If you found value in this episode, be be sure to subscribe, rate, and share with "Rhythms that Restore" Podcast with a friend who can be encouraged through the message. Help us share this incredible transformative message of Gods word through the beautiful act of "ceasing to strive" and learning to "simply BE". ------------------------------------ Connect more with me on Instagram, Facebook and Email: Lets Chat: cherissehixson@hotmail.com  Facebook: Cherisse Mathias Hixson  DM on Instagram: @cherissehixson01  https://www.instagram.com/cherissehixson01?igsh=dDY4ZWNrcWowb2Vx&utm_source=qr

In this episode of "Rhythms That Restore," host Cherisse explores the word "ATTUNE" for Fall and How we can Attune our Hearts for the Rhythms of the Season. She reflects on the beauty and transformation of the season, emphasizing the importance of personal growth and soul care. Drawing inspiration from a recent women's retreat and Joanna Gaines' Magnolia Magazine. Cherisse encourages listeners to pause, reflect, and adjust their patterns and know their values they want to hold close to their heart.  She shares lessons on the significance of silence and scripture, urging listeners to embrace stillness and find peace in their relationship with God during this seasonal shift. ------------------------------------------------------------------------------------------- **Introduction to the Episode (00:00:02)**   Cherisse welcomes listeners to "Rhythms That Restore" and introduces the theme of the episode. **Embracing Fall (00:00:28)**   Cherisse shares her excitement for fall and the beauty of the changing season. **The Importance of Gathering (00:02:39)**   Cherisse discusses her love for gathering people and how it connects friends. **Reflections from the Women's Retreat (00:03:46)**   Insights from a women's retreat, emphasizing the importance of caring for our soul. **Summer Soul Care Series (00:04:56)**   Cherisse encourages listeners to revisit her summer series on soul care and its significance. **Join the Podcast Community (00:06:03)**   Invitation to join the Rhythms That Restore podcast community for support and connection. **The Concept of 'Attune' (00:07:56)**   Cherisse introduces the concept of attuning our hearts to the rhythms of fall. **The Process of Settling (00:09:12)**   Discussion on the importance of allowing our souls to settle and find peace. **Understanding 'Attune' (00:10:14)**   Cherisse explains the meaning of attuning as making receptive and finding harmony. **Scriptural Insights (00:11:25)**   Cherisse shares relevant scriptures that encourage attuning our hearts to God. **Prayer and Reflection (00:13:47)**   A prayer for listeners to attune their hearts and find peace in God's presence. **Finding the Source of Wisdom (00:14:45)**   Exploration of God as the source of all power, love, and wisdom. **The Science of Laminin (00:16:12)**   Cherisse discusses the protein laminin and its significance in holding things together. **Joanna Gaines' Wisdom (00:17:49)**   Cherisse shares insights from Joanna Gaines about the richness of the fall season. **Patterns and Values (00:19:06)**   Encouragement to reflect on personal patterns and values as summer transitions to fall. **Tuning Practices (00:21:09)**   Cherisse discusses fine-tuning personal practices and values as we transition into fall. **Non-Negotiable Values (00:22:20)**   She shares a friend's five essential values for navigating new seasons, emphasizing faith, family, and friendships. **Quieting the Noise (00:23:27)**   Cherisse highlights the importance of reducing distractions to fully embrace the richness of the fall season. **The Power of Silence (00:24:26)**   She explores the benefits of quiet moments for mental clarity, creativity, and emotional processing. **Regrowing Our Brains (00:26:59)**   Cherisse explains how silence can stimulate brain growth and improve decision-making and emotional health. **Practicing Silence (00:28:16)**   Listeners are encouraged to set aside time for silence and reflection in their daily routines. **Savoring Stillness (00:30:26)**   Cherisse invites listeners to affirm their needs and find peace in stillness through Psalm 23. **Embracing Boredom (00:35:31)**   She discusses the potential benefits of boredom and the value of allowing space for contemplation.  **Journey of Restoration (00:37:13)**   Cherisse closes by encouraging listeners to embrace their true selves and find peace in their daily lives. ---------------------------------------------------------------------------- Connect with Cherisse online Instagram @cherissehixson01 & @RhythmsThatRestorePodcast Email: Cherissehixson@hotmail.com  Rate, Review and Share the Show with a friend  If you found value in this episode leave a 5 star review and tell us what you loved, share the show with a friend and help others find us on the podcast platform. 

Dr. Dallas Willard wrote "The most important thing in your life is not what you do; it's who you become." According to Jesus' own word, the only way that truly happens is when we are born from above. Jesus did not mean some kind of ephemeral, philosophical, state of mind, he meant that we need to be supernaturally reborn through the Spirit, empowered by his sacrificial, vicarious death and resurrection. This is the Gospel he, himself, prescribed. But that presupposes that life is precious - not just to the individual, but to the One who started it all. The sad fact of the matter is that neo-darwinianism, based solely on naturalist phenomenon, will always render one towards nihilism: nothing matters. That is the opposite of good news. Who can - literally - live with that? In this fourth installment of The Fourth Word, Rick discusses the topic of the specialness, holiness, and consequence of life that began with God. You are not an accident or an abberation: you are prized and preferred by Majesty and are uniquely designed and lovingly created for His purpose! Don't forget to check out the special links below!

Romans 1:20 For since the creation of the world God's invisible qualities—his eternal power and divine nature—have been clearly seen, being understood from what has been made, so that people are without excuse. I am FINISHED with EXCUSES. Pictures-excuses You can make EXCUSES or you can make PROGRESS but you can't make both. We are finished with excuses because: The ANGER of God is SERIOUS.  Romans1:18 The wrath of God is being revealed from heaven against all the godlessness and wickedness of people, who suppress the truth by their wickedness You will never be able to understand how GOOD the GOOD news is, if you don't understand how BAD the BAD news is. HUMAN anger: emotional response that is irrational, uncontrolled, and cruel. GOD'S anger: righteous opposition to evil and those who choose it  The opposite of anger isn't LOVE, it's PASSIVITY. Romans 1:21-25 For although they knew God, they neither glorified him as God nor gave thanks to him, but their thinking became futile and their foolish hearts were darkened. Although they claimed to be wise, they became fools and exchanged the glory of the immortal God for images made to look like a mortal human being and birds and animals and reptiles. Therefore God gave them over in the sinful desires of their hearts to sexual impurity for the degrading of their bodies with one another. They exchanged the truth about God for a lie, and worshiped and served created things rather than the Creator—who is forever praised. Amen. God's anger/ judgment is shown in:  Deceived hearts Depraved minds Unnatural desires Acceptance of sin Romans 1:32 Although they know God's righteous decree that those who do such things deserve death, they not only continue to do these very things but also approve of those who practice them. The CREATION of God is SIGNIFICANT. Romans 1:20 For since the creation of the world God's invisible qualities—his eternal power and divine nature—have been clearly seen Picture of galaxy. Picture of cross-galaxy.   photo Laminin-molecules photo 2-laminin-actual The CREATION declares there is a CREATOR. The SACRIFICE of Jesus was SUFFICIENT. Romans 2:1 You, therefore, have no excuse, you who pass judgment on someone else, for at whatever point you judge another, you are condemning yourself, because you who pass judgment do the same things. Romans 2:5-6 But because of your stubbornness and your unrepentant heart, you are storing up wrath against yourself for the day of God's wrath, when his righteous judgment will be revealed. God “will repay each person according to what they have done.” Romans 3:23-25 for all have sinned and fall short of the glory of God, and all are justified freely by his grace through the redemption that came by Christ Jesus. God presented Christ as a sacrifice of atonement, through the shedding of his blood—to be received by faith. Jesus took what I deserved, so that I could get what HE deserved.  --- Send in a voice message: https://podcasters.spotify.com/pod/show/coastalchurch/message

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.27.538597v1?rss=1 Authors: Rotty, J., Stinson, M., Laurenson, A. Abstract: Macrophages are indispensable for proper immune surveillance and inflammatory regulation. They also exhibit dramatic phenotypic plasticity and are highly responsive to their local microenvironment, which includes the extracellular matrix (ECM). The present work demonstrates that two fibrous ECM glycoproteins, fibronectin (FN) and laminin (LAM), elicit distinct morphological and migratory responses to macrophages in 2D environments. Laminin 111 inhibits macrophage cell spreading, but drives them to migrate rapidly and less persistently compared to cells on fibronectin. Differential integrin engagement and ROCK/myosin II organization helps explain why macrophages alter their morphology and migration character on these two ECM components. The present study also demonstrates that laminin 111 exerts a suppressive effect toward fibronectin, as macrophages plated on a LAM/FN mixture adopt a morphology and migratory character almost identical to LAM alone. This suggests that distinct responses can be initiated in the cell downstream of receptor-ECM engagement, and that one component of the microenvironment may affect the ability to sense another. Overall, macrophages appear intrinsically poised to rapidly switch between distinct migratory modes based on their ECM environments. The role of ECM composition in dictating motile and inflammatory responses in 3D and in vivo contexts warrants further study. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Laminin is a protein that holds life together. Pastor Chuck Layne discusses God's creation, the sanctity of human life, and how a cross shaped protein is important to life! Colossians 1:15-23 

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.15.507987v1?rss=1 Authors: Nishimura, K., Yang, S., Lee, K., Asgrimsdottir, E. S., Nikouei, K., Paslawski, W., Gnodde, S., Lyu, G., Hu, L., Salto, C., Svenningsson, P., Hjerling-Leffler, J., Linnarsson, S., Arenas, E. Abstract: Stem cell technologies provide new opportunities for modeling cells in the healthy and diseased states and for regenerative medicine. In both cases developmental knowledge as well as the quality and molecular properties of the cells are essential for their future application. In this study we identify developmental factors important for the differentiation of human embryonic stem cells (hESCs) into midbrain dopaminergic (mDA) neurons. We found that Laminin-511, and dual canonical and non-canonical WNT activation followed by GSK3b inhibition plus FGF8b, improved midbrain patterning. In addition, mDA neurogenesis and differentiation was enhanced by activation of liver X receptors and inhibition of fibroblast growth factor signaling. Moreover, single-cell RNA-sequencing analysis revealed a developmental dynamics similar to that of the endogenous human ventral midbrain and the emergence of high quality molecularly-defined midbrain cell types, including mDA neurons that become functional. Thus, our study identifies novel factors important for human midbrain development and opens the door for a future application of molecularly-defined hESC-derived midbrain cell types in Parkinsons disease. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

* Woke by Warming: Having trouble getting to sleep lately? Forget the one million and six reasons we know may interfere with sleep… Perhaps it's all that Climate Change going around…  *At the Cross:  Fred Williams and co-host Doug McBurney continue their discussion of laminin, (and whether or not it resembles the shape of the cross, and what we should or shouldn't say about it anyway).  *Information Miss? Pastor Keith Giles might not want to be called a pastor, but he certainly behaves like one. And he might not appreciate being criticized for mis-stating Louie Giglio's take on laminin either. Hear the fallout and the dustup surrounding this minor controversy, and more.  *A Little Bit About Laminin: Fred Williams discusses an article from the Journal Cell Adhesion & Migration to help us better understand the little he knows, (and it turns out to be the little anyone really knows) about the sophisticated properties, interactions and behavior of laminin!  *And Little Bit More: Fred looks at research from over 5 years ago into the treatment of muscular dystrophy, and how laminin, combined with genetic therapies are helping unlock mysteries that may lead us to a cure!  *No More Butterfly Boys? Hear how laminins played an important role in the treatment of a then seven-year-old boy named Patrick who was suffering from an often-fatal skin condition called Junctional Epidermolysis Bullosa, and how doctors were able to replace most of his diseased skin! That work continues to produce promising treatments, and what some are already calling a cure, to the Glory of our Creator!

* Woke by Warming: Having trouble getting to sleep lately? Forget the one million and six reasons we know may interfere with sleep… Perhaps it's all that Climate Change going around…  *At the Cross:  Fred Williams and co-host Doug McBurney continue their discussion of laminin, (and whether or not it resembles the shape of the cross, and what we should or shouldn't say about it anyway).  *Information Miss? Pastor Keith Giles might not want to be called a pastor, but he certainly behaves like one. And he might not appreciate being criticized for mis-stating Louie Giglio's take on laminin either. Hear the fallout and the dustup surrounding this minor controversy, and more.  *A Little Bit About Laminin: Fred Williams discusses an article from the Journal Cell Adhesion & Migration to help us better understand the little he knows, (and it turns out to be the little anyone really knows) about the sophisticated properties, interactions and behavior of laminin!  *And Little Bit More: Fred looks at research from over 5 years ago into the treatment of muscular dystrophy, and how laminin, combined with genetic therapies are helping unlock mysteries that may lead us to a cure!  *No More Butterfly Boys? Hear how laminins played an important role in the treatment of a then seven-year-old boy named Patrick who was suffering from an often-fatal skin condition called Junctional Epidermolysis Bullosa, and how doctors were able to replace most of his diseased skin! That work continues to produce promising treatments, and what some are already calling a cure, to the Glory of our Creator!

The RAYID MODEL is about permanent research of the Divine Design for the Human Soul. All the contents are shared as gifts. You can find other Rayid materials or support the continuation of the gifts worldwide through: https://linklist.bio/rayidinternational Link to Youtube video: https://youtu.be/YGPlzHWD-QA

The RAYID MODEL is about permanent research of the Divine Design for the Human Soul. All the contents are shared as gifts. You can find other Rayid materials or support the continuation of the gifts worldwide through: https://linklist.bio/rayidinternational Link to Youtube video: https://youtu.be/v926fUjARAI

Insights from my CLUBHOUSE room: WONDERFULLY MADE MONDAYS. Monday Sept 20th 2021 I talked about one of the most wonderful love letters that God wrote in your DNA code, inside you, in the form of a really cool protein molecule: Laminin This protein inside you is responsible for so much going right in your body and in this episdoe we go into how it represents all that Jesus did for us, for any of you that missed that clubhouse talk I hosted last Monday and didn't get to see the way that protein is shaped it looks exactly like a three strand cross. Learn more at: https://anagaeta.com/laminin-gods-love-letter-inside-you/ --- Send in a voice message: https://podcasters.spotify.com/pod/show/ana-e-gaeta/message

A few articles in each issue are chosen by the EIC for their interest. The issue highlights include: laminin-521 –a novel GBM autoantigen, iron biomarkers & mortality in nondialysis kidney disease, & disparities among hemodialysis patients with COVID-19.

Laminin is a protein that holds our bodies together and a protein that resembles the Cross of Christ. 

The term Shekinah Glory comes from the Hebrew language, meaning the presence of God dwelling on Earth, and many believe that this pillar of light, which guided the Israelites throughout their journey in the desert, was an example of God's Shekinah glory and this type of light. However, it's not a type of light that we are familiar with here on Earth. And so just as sound has its own frequencies, light also has various frequencies of waves that can be measured. But Shekinah Glory light doesn't appear to follow any laws of light that we know of on this Earth, and so it's different. It's brilliant, yet not blinding, and science has not been able to define this type of light. Dr. Paula shares with listeners her experience with what she believes was Shekinah Glory during a near-death experience, along with an amazing discovery about "light" in the form of Laminin, embedded into the very structure of the cells in our bodies.

Gem Of the Day (G.O.D.) about who and what holds the body together... --- Support this podcast: https://anchor.fm/anthonyblackmon/support

Sultry Sounds Sessions is a podcast show showcasing the latest mixes from DJ's and Producers from around the globe in the house music scene. we hope to bring you exciting content that will keep you coming back for more Todays feature is none other than the formidable force that is @lamininmusicsa Bringing us a deep and dub techno mix with house infusions , taking us on their rendition of absolute bliss to follow our whereabouts checkout www.sultrysounds.info and join the movement Links to all socials and streaming platforms available below www.mixcloud.com/LamininMusic/ @lamininmusicsa www.facebook.com/lamininmusicSA www.instagram.com/lamininmusicsa_official/ https://www.youtube.com/channel/UC0-h36031T_U-0QKIlucesQ https://twitter.com/laminin_music https://music.apple.com/za/artist/laminin-music/1148949579 https://open.spotify.com/artist/4p30OBnZP3NpQFpEhQXl4Z https://ra.co/dj/lamininmusic like , share and comment. ENJOY Tracklist 1) Vandal M - Surrounded By Groove (Original Mix) 2) Laminin Music - Zongo the Tamagotchi (Original Mix) 3) Random Fact - Questions (Original Mix) 4) Sean Munnick - Week N Chill (Original Mix) 5) Laminin Music - Stimulant of Choice (Original Mix) 6) Bongani Zulu - Mouth of the Whale (Laminin Music Remix) 7) LUC - It’s Complicated (Original Mix) 8) Luc Angenehm - Anabel (Original Mix) 9) Keegs Bantom & D’Phault - Anomalistic (Original Mix) 10) Filter (ZA) - Tribulation (Original Mix) 11) Bongani Zulu - Desolate (Original Mix

Welcome to this episode of Sho’kwani as we unpack the concept of Trust. It’s worth noting that— TRUST is sanctifying and conscious awakening— it’s the “Laminin” that holds all social interactions... But don’t get it twisted— trusting is RISKY business! Nevertheless, as a principle it has the power to maintain the “integrity” of all longstanding RELATIONS.

Welcome to this episode of Sho’kwani as we unpack the concept of Trust. It’s worth noting that— TRUST is sanctifying and conscious awakening— it’s the “Laminin” that holds all social interactions... But don’t get it twisted— trusting is RISKY business! Nevertheless, as a principle it has the power to maintain the “integrity” of all longstanding RELATIONS.

Welcome to this episode of Sho’kwani as we unpack the concept of Trust. It’s worth noting that— TRUST is sanctifying and conscious awakening— it’s the “Laminin” that holds all social interactions... But don’t get it twisted— trusting is RISKY business! Nevertheless, as a principle it has the power to maintain the “integrity” of all longstanding RELATIONS.

Paul discusses our spiritual DNA and the DNA protein Laminin. See omnystudio.com/policies/listener for privacy information.

Missy Robertson continually sets a prime example of humility and consistent faith in her public and personal life. We first came to know Missy and the important role she plays in the Robertson family in their family reality show, Duck Dynasty. Duck Dynasty broke several ratings records on A&E and on cable television during their successful run that finished in 2017. Despite the increased publicity on her family, company and personal life, she has managed to become a strong voice for morality and virtue both locally and globally. Missy now spends a large amount of her time volunteering to give back to her community. She is heavily involved in missionary work, both domestically and internationally. In October 2015, she authored a book entitled, “Blessed, Blessed...Blessed“ chronicling her family’s journey of raising a child born with a cleft lip and palate. In early 2014, she co-authored The Women of Duck Commander with Miss Kay, and her sisters-in-law, in which they shared never-before-told stories about the Robertson family. In April 2016 Missy launched a new jewelry line, Laminin by Missy Robertson, providing jobs for women in the West Monroe area who are in need of work. This serves as a ministry to women coming out of hard situations and in need of assistance of finding a way to break into the workforce coming out of sex trafficking, homelessness, and struggling single mothers. Say it Forward with Missy Robertson.

Sultry Sounds Sessions is a podcast show showcasing the latest mixes from DJ's and Producers on the house music scene. This mix is brought to you by Laminin Music bringing you a variation of minimal and dub tech with a bodacious tracklist too. to checkout all things Laminin Music follow them on the socials & soundcloud @lamininmusicsa like , share and comment. check www.sultrysounds.info for all things music ENJOY

Missy Robertson of "Duck Dynasty" and founder of a jewelry line, Laminin by Missy Robertson, joins me to discuss motherhood, faith, and running a business that helps struggling women by giving them a second chance. Learn more about your ad choices. Visit megaphone.fm/adchoices

Shannon Bream, host of FOX News @ Night on the FOX News Channel returns with a new "Livin' the Bream" podcast. This week, Shannon sat down with Missy Robertson, of Duck Dynasty fame. Missy discusses how her faith lead her to open her new jewelry business Laminin, a company that helps local women and previously incarcerated people. Follow Shannon on Twitter: @ShannonBream

Leroux Cilliers, Solutions Director at Laminin sits down with Michael Tanner, Corporate Development VP at M-Files to discuss information management and Laminin's role as a business consultancy providing data and business intelligence solutions to the global marketplace. They talk about the MFSQL Connector that Laminin has developed to connect SQL applications and M-Files, unlocking tremendous potential for businesses to connect SQL-based applications to M-Files and develop a 360-degree view of all business information across all systems, in context. Visit M-Files: http://www.m-files.com Visit Laminin: https://lamininsolutions.com/   Subscribe to the Information Innovation Podcast Stitcher iTunes Google Play iHeartRadio Spotify Soundcloud

When Missy Robertson started her jewelry company, Laminin, she thought it would turn out one way. But God had other plans. Every woman Missy has hired has dealt with addiction issues, but God is moving mightily. Listen to the podcast with host Jessilyn Lancaster to hear how God is working in these precious lives.

On the 50th episode of Multi-Racial Sessions Kamanda handles the A-SIDE while guests Laminin Music are on the B-SIDE. A-SIDE Tracklist by Kamanda: 1. Hiroyuki Kajino Yuichiro Kotani - Playground 1(Original Mix) 2. Elias Dore - Ayasa (Original Mix) 3. Shunus - Knockin(Original Mix) 4. Makebo - Sunland(Original Mix) 5. Rodaq - Picus (Original Mix) 6. Kuriose Naturale - Massiv Passiv(Original Mix) 7.Suulo vs. Curl - City Of Belem(Original Mix) 8.ManQ- Voices(Original Mix) 9. Arthus - Chapa(Original Mix) Contact us: www.multi-racial.co.za @multiracialrec on all social media platforms @KamandaTsiane on instagram @KamandaT on twitter @lamininmusicsa on instagram

One of the most important missions to Missy Robertson and her family has been to work selflessly to help others find faith and inner joy through charity. Missy has established Laminin House to provide jobs for women in the West Monroe area with a desire for community in a supportive work environment. Each piece of jewelry is inspired by southern femininity and a love for the outdoors. It is individually crafted by women in need of a new purpose, including those rescued from sex trafficking, homelessness and addiction. Laminin exists to equip, empower, and enrich the lives of the women it employs while bringing a reminder of God's creations to the marketplace. For show notes & resources visit the episode webpage below or click here. Want more information on #BoutiqueChat? Visit www.theboutiquehub.com/boutiquechat ***Facebook: @boutiquehubashleyInstagram: @boutiquehubbusiness & @ajalderson Join our community of retailers, brands, influencers, service providers and insiders: www.theboutiquehub.com/join  

Joy and Purpose for the Journey || Allie interviews Missy Robertson, author of Blessed, Blessed…Blessed and co-author of The Women of Duck Commander with Miss Kay and her sisters-in-law. She is one of the stars of the hit reality TV show Duck Dynasty. In 2016, Missy launched a jewelry line, Laminin which provides jobs for women in the West Monroe area who are in need of work. Missy offers encouragement... Read More

Missy Robertson speaks to another Laminin woman with an incredible story of redemption. Charlie was a straight A student, but soon the lure of drugs became too much for her, beginning a downward spiral that goes far beyond what most people would ever dream of experiencing. Charlie decided that since she was "going to hell anyway" she was going to go there full speed. How God worked in her life to turn things around is nothing short of a miracle.

You need to prioritize. If you can't get to everything or do everything, that's okay. Julie Chen Girl Scout Convention in Columbus Goodale Park and Victorian Village Stacie Simpson of the Silver and Gold podcast Chelsea Clinton Barbara Bush Pierce Sophia Dominguez-Heithoff Kathy Rodriquez Caly Bevier: cancer survivor and now a performer who has been on America’s Got Talent Brooke Yoakam: Gift Pocket app Alyssa Mastromonaco’s book ‘Who Thought This Was a Good Idea?” http://amzn.to/2g7LeJE Sheila Walsh, “The Shelter of God’s Promises” http://amzn.to/2ybQC4x https://en.wikipedia.org/wiki/Laminin Oktoberfest in Lacrosse chocolate soda with chocolate ice cream Find us on social media! Facebook fb.me/sensorystrides Twitter @sensorystrides We are a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for us to earn fees by linking to Amazon.com and affiliated sites.

The fall is the reason for the flood.Check our the protein molecule LAMININ for a picture of how our cells hold together.

Luke 9:23 And he said to all, “If anyone would come after me, let him deny himself and take up his cross daily and follow me. For whoever would save his life will lose it, but whoever loses his life for my sake will save it. For what does it profit a man if he gains the whole world and loses or forfeits himself? The daily life of the cross is about having an understanding of the vertical and horizontal dimensions of the cross of Jesus, and finding God's presence in the very centre of the cross in our lives. The vertical dimension is the ‘being' dimension of our life in the cross, and the horizontal dimension is the ‘doing' dimension of our life in the cross. We find ourselves in the very centre if we practice being still enough to connect to both at the one time. The horizontal ‘doing' is always moving through time across our vertical ‘being'. Colossians 1:16 All things were created through Him and for Him. He was before all else began and it is his power that holds everything together. He is the Head of the body, his Church--which he began; and he is the Leader of all those who arise from the dead, so that he is first in everything; for God wanted all of himself to be in his Son. It was through what his Son did that God cleared a path for everything to come to him--all things in heaven and on earth--for Christ's death on the cross has made God one together with us all. The Laminin molecule has proteins that form a cross, giving a structure that can bind to other cell membrane . The three shorter arms are particularly good at binding to other laminin molecules, which allows them to form sheets. The long arm is capable of binding to cells, which helps anchor organized tissue cells to the membrane.      

Recorded earlier - 7/4/16 In this episode of The Willie Robertson Podcast, Willie is joined by his sister-in-law Missy who has an amazing jewelry line called Laminin. Not only is the jewelry beautiful and unique, but the story behind the company is as well. Missy joined forces with Project 41, a Christian non-profit that rescues women and children from sex trafficking, to provide women of West Monroe, Louisiana with meaningful employment. During the podcast, Missy introduces Brandy and Lara, two women who share their heartbreaking stories and how working at Laminin gave them purpose. And be sure to check out some of Missy's beautiful jewelry at laminindesigns.com.

Listen to learn more...

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Ever hear about the protein known as Laminin? If not, listen to this podcast. What you are about to hear will truly amaze you.

Today we will see how Jesus really holds us together. See below sermon player for link to todays video. Thank You!

Today we will see how Jesus really holds us together. See below sermon player for link to todays video. Thank You!

Eine zunehmende Zahl von Daten aus der Fachliteratur weist immer deutlicher darauf hin, dass Tumor- und Stammzellen trotz aller funktionellen Unterschiede, wie beispielsweise der Destruktion von gesundem Gewebe bzw. Regeneration von zerstörtem Gewebe, offensichtlich wesentliche Gemeinsamkeiten aufzeigen, insbesondere hinsichtlich der molekularen Mechanismen, die z.B. den zellulären Prozessen Differenzierung/Transformation, Zellalterung, Apoptose und Migration/Invasion zugrunde liegen. Im Gegensatz zur Situation bei Tumorzellen ist die Rolle lysosomaler Cysteinproteasen in humanen mesenchymalen Stammzellen (hMSC) bei diesen Prozessen jedoch noch weitgehend unbekannt und sollte daher im Rahmen dieser Arbeit genauer definiert werden. So konnten wir erstmals nachweisen, dass lysosomale Cysteinproteasen sowohl in hMSC exprimiert als auch während deren Kultivierung sezerniert werden. Von den elf bekannten humanen lysosomalen Cystein¬proteasen (Cathepsine) wurden vor allem Cathepsin B und Cathepsin K durch extrazelluläre Matrix (EZM)-Proteine, insbesondere durch Vitronektin, in ihrer Expression beeinflusst und zeigten eine kontinuierliche Erhöhung der Expression im Verlauf von 21 Tagen. Eine vermehrte Sekretion nach Vitronektinstimulation wurde proteinche-misch bei Cathepsin B und X nachgewiesen. Im Gegensatz dazu hatten Stimulationen mit Kollagen I und Laminin keinen signifikanten Einfluss auf die Expression bzw. Freisetzung dieser Proteasen. Weitere Untersuchungen ergaben, dass das Adhäsions-/Migrationsverhalten der hMSC durch EZM-Proteine vor allem über deren Wechselwirkung mit Adhäsionsmolekülen (Integrinen) beeinflusst wird. Zudem kann auch Procathepsin X in Abhängigkeit von Integrin αvβ3 an hMSC binden. Durch die Interaktionen der hMSC mit EZM-Proteinen sowie mit Procathepsin X wird eine Reihe von Signaltransduktionswegen, darunter der ERK-Signalweg, aktiviert. In Transmigrationsversuchen mit Cathepsin X-defizienten hMSC wurde zudem nachgewiesen, dass Procathepsin X – im Gegensatz zur Konstellation bei Tumorzellen – keine bedeutende Rolle bei der Migration der hMSC spielt. Es kann daher davon ausgegangen werden, dass gegen dieses Enzym gerichtete Tumortherapiestrategien nur geringe (oder gar keine) Auswirkungen auf Stammzell-Mobilisation/Migration haben. Die im Rahmen dieser Arbeit erhobenen in vitro-Daten zeigen somit neue Erkenntnisse bezüglich der Regulation lysosomaler Cysteinproteasen durch extrazelluläre Matrixproteine in hMSC und stellen daher eine gute Basis für weitere in vitro- bzw. auch in vivo-Evaluierungen dar.

Sat, 1 Jan 2011 12:00:00 +0100 https://epub.ub.uni-muenchen.de/16881/1/10_1159_000322842.pdf Hertl, M.; Zgazarova, S.; Niedermeier, A.; Jedlickova, H. ddc:610,

Microtubules align along the apical-basal axis of epithelial cells with their plus ends pointing to the basal side. Hotta et al. reveal how signals from the extracellular matrix establish this arrangement by recruiting the microtubule-anchoring factors LL5s to the basal cell cortex. This biosights episode presents the paper by Hotta et al. from the May 31, 2010 issue of The Journal of Cell Biology, and includes an interview with senior author Yuko Mimori-Kiyosue. Produced by Caitlin Sedwick and Ben Short.   Subscribe to biosights via iTunes or RSS View biosights archive The Rockefeller University Press biosights@rockefeller.edu

Fri, 15 May 2009 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/13091/ https://edoc.ub.uni-muenchen.de/13091/1/Pflanz_Heike.pdf Pflanz, Heike ddc:540, ddc:500, Fakultät für

Wed, 16 Jul 2008 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/8800/ https://edoc.ub.uni-muenchen.de/8800/1/Zuber_Chantal.pdf Zuber, Chantal

Das Vulvakarzinom und seine Vorstufen sind seltene Krankheitsbilder. Die operative Therapie ist Methode der Wahl beim Vulvakarzinom. Sie ist allerdings mit hohen postoperativen Komplikationen und psychosexuellen Problemen belastet. Probleme bei der Behandlung von vulvären intraepithelialen Neoplasien stellen vor allem die hohe Rezidivrate und das Risiko einer Karzinomentstehung dar. So ist es sowohl für die Therapie des Vulvakarzinoms als auch seiner Vorstufen wünschenswert, verlässliche Parameter zu finden, die eine Aussage über den wahrscheinlichen Verlauf der Krankheit erlauben und damit auch eine individualisierte, risikoadaptierte Therapie ermöglichen können. In der vorliegenden Arbeit sollten neben klinischen und histologischen Merkmalen insbesondere der immunhistologische Nachweis der laminin-5-gamma-2 Kette im Hinblick auf die Prognose der vulvären intraepithelialen Neoplasie (VIN III) und des Plattenepithelkarzinoms der Vulva untersucht werden. Der immunhistochemische Nachweis der laminin-5-gamma-2 Kette wurde gewählt, da für diesen Marker bisher keine Ergebnisse an tumorösen Veränderungen der Vulva vorliegen. Die laminin-5-gamma-2 Kette wird von invasiv wachsenden Zellen unterschiedlicher Tumoren im Zytoplasma exprimiert (Adenokarzinome des Dickdarms, des Magens und der Brust sowie Plattenepithelkarzinome der Zervix und der Mundhöhle). Dabei konnte ein Zusammenhang zwischen einer Überexprimierung der laminin-5-gamma-2 Kette und geringer Gewebedifferenzierung, größerer Tiefeninfiltration, dem Auftreten von Metastasen und einer schlechteren Überlebensprognose nachgewiesen werden. Folgende Fragestellungen sollten bei den Patientinnen mit VIN beurteilt werden: 1. Sind die bekannten histologischen Parameter mit dem Auftreten von Rezidiven assoziiert? 2. Ist der immunhistologische Marker laminin-5-gamma-2 mit den bekannten histologischen Parametern assoziiert? 3. Ist der immunhistologische Marker laminin-5-gamma-2 mit dem Auftreten von Rezidiven assoziiert? 4. Kann mit der immunhistologischen Anfärbung der laminin-5-gamma-2 Kette die frühe Invasivität nachgewiesen werden? Folgende Fragestellungen sollten bei Patientinnen mit Plattenepithelkarzinom der Vulva bearbeitet werden: 1. Sind die bekannten histologischen Parameter mit dem Lymphknotenbefall, dem Auftreten von Rezidiven und dem Gesamtüberleben assoziiert? 2. Ist der immunhistologische Marker laminin-5-gamma-2 mit den bekannten histologischen Parametern assoziiert? 3. Ist der immunhistologische Marker laminin-5-gamma-2 mit dem Lymphknotenbefall, dem Auftreten von Rezidiven und dem Gesamtüberleben assoziiert? Nach einem festgelegten Merkmalkatalog wurden die anamnestischen und therapeutischen Daten aus den Krankenunteralgen der Patientinnen entnommen. Die histologischen Parameter wurden anhand von Hämatoxylin-Eosin gefärbten Großflächenschnitten erhoben. Für den immunhistologischen Nachweis der laminin-5-gamma-2 Kette wurden die Gewebeblöcke herausgesucht, um neue Schnitte anzufertigen, die mit Hilfe der Avidin-Biotin-Komplex-Methode (ABC) und 3,3-Diaminobenzidintetrahydrochlorid (DAB) gefärbt wurden. Die Auswertung erfolgte semiquantitativ mit Abschätzung des Anteils der gefärbten Zellen an der Gesamtzahl der Tumorzellen in Prozent. Die statistische Analyse erfolgte univariat durch Prüfung auf Signifikanz mit dem χ2-Tests oder – wenn erforderlich – mit dem exakten Test nach Fisher. Die Überlebenskurven (rezidivfreies Überleben, Gesamtüberleben) wurden nach der Kaplan-Meier-Methode errechnet und mit dem Log-Rank-Test auf signifikante Unterschiede geprüft. Ein derartiger Unterschied wurde bei p-Werten kleiner 0,05 angenommen. Die retrospektive Studie umfasste zwei Patientengruppen: • 88 Patientinnen mit VIN aus der Zeit von 1991 bis 2002 • 155 Patientinnen mit Plattenepithelkarzinom der Vulva von 1987 bis 2002 Alle Patientinnen wurden im angegebenen Zeitraum an der I. Frauenklinik der Universität München, Maistraße, behandelt. Für die Patientinnen mit VIN zeigte nur das histologische Merkmal „Entfernung in sano / non in sano“ einen statistisch auffälligen Unterschied im rezidivfreien Überleben. Alle anderen histologischen Merkmale, einschließlich des immunhistologischen Nachweises der laminin-5-gamma-2 Expression, zeigten keinen Zusammenhang mit der Häufigkeit von Rezidiven. Bei den Patientinnen mit Plattenepithelkarzinom der Vulva korrelierten folgende histologischen Merkmale statistisch auffällig mit Nachweis von inguinalen Lymphknotenmetastasen: Infiltrationstiefe, Anzahl der Mitosen, Differenzierungsgrad, Lymphangiosis carcinomatosa und lokales Tumorstadium (pT). Der immunhistologische Nachweis der laminin-5-gamma-2 Kette zeigte hingegen keine Assoziation zur lymphatischen Metastasierung. Das lokale Tumorstadium (pT) und die Entfernung in sano zeigten eine statistisch auffällige Korrelation mit der Rezidivhäufigkeit: 100% Rezidive bei pT3 versus 34% bei pT1 und pT2. 60% Rezidive bei Entfernung non in sano versus 31% bei Entfernung in sano. Neben diesen beiden Merkmalen zeigten auch die Infiltrationstiefe und der Nachweis von inguinalen Metastasen einen statistisch auffälligen Unterschied im rezidivfreien Überleben. Karzinome, die laminin-5-gamma-2 exprimierten, zeigten sowohl häufiger Rezidive als auch eine kürzere mittlere rezidivfreie Zeit. Ein statistisch auffälliger Unterschied im Gesamtüberleben ließ sich in Abhängigkeit von folgenden histologischen Merkmalen nachweisen: Infiltrationstiefe, Grading, Lymphangiosis und Hämangiosis carcinomatosa, lokales Tumorstadium (pT), inguinaler Lymphknotenstatus sowie Karzinomentfernung im Gesunden. Patientinnen, deren Karzinome laminin-5-gamma-2 exprimierten, hatten ein deutlich schlechteres Gesamtüberleben gegenüber Patientinnen, deren Karzinome keine Expression aufwiesen (5-Jahresüberlebensrate 97% versus 68%). Weiter konnten folgende Ergebnisse beobachtet werden: Laminin-5-gamma-2 war vor allem in Tumorzellen an der Tumor-Stroma-Grenze positiv nachweisbar. Karzinome mit ungünstigen histologischen Parametern (Infiltrationstiefe > 1mm, G2 oder G3, Lymphangiosis und Hämangiosis carcinomatosa) zeigten häufiger positive Ergebnisse für die laminin-5-gamma-2 Färbung. Rezidive traten häufiger bei laminin-5-gamma-2 exprimierenden Tumoren auf. Die Überlebenszeit war kürzer bei Patientinnen, deren Vulvakarzinom laminin-5-gamma-2 exprimieren. Aus diesen zunächst univariat gewonnenen Ergebnissen lassen sich folgende vorläufige Schlüsse ziehen: 1. der Nachweis der laminin-5-gamma-2 Kette hat für die Prognose der vulvären intraepithelialen Neoplasie keine Bedeutung. 2. Die Expression der laminin-5-gamma-2 Kette scheint mit einem aggressiveren Tumortyp und damit einer schlechteren Prognose des Vulvakarzinoms verbunden zu sein. Das Ziel der vorliegenden Arbeit war zu überprüfen, welche Bedeutung die immunhistologische Darstellung der laminin-5-gamma-2 Kette in der Prognose der vulvären intraepithelialen Neoplasie und des Vulvakarzinoms hat. Auf Grund der hier gewonnenen univariaten Ergebnisse scheinen weitere Untersuchungen mit multivariater Analyse und an größeren Patientenkollektiven sicher sinnvoll. So könnte in Zukunft vielleicht die immunhistologische Färbung mit dem laminin-5-gamma-2 Antikörper zusammen mit histologischen Untersuchungen eine genauere Einschätzung der Prognose erlauben und zur individuellen, tumoradaptierten Therapie beitragen.

Prion diseases are a group of rare, fatal neurodegenerative diseases, also known as transmissible spongiform encephalopathies (TSEs), that affect both animals and humans and include bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep, chronic wasting disease in deer and elk and Creutzfeldt-Jakob disease (CJD) in humans. TSEs are usually rapidly progressive and clinical symptoms comprise dementia and loss of movement coordination. A common hallmark of TSEs is the accumulation of an abnormal isoform (PrPSc) of the host-encoded prion protein (PrPc) in the brains of affected animals and humans. PrPc is a highly conserved cell surface sialoglycoprotein that is expressed in several cell types, mainly neuronal cells, but its normal physiological function is still not known. However, PrPc is elementary for the acquisition and the replication of prion diseases. Several inhibitors of the PrPSc formation have been reported, but none of them showed great potency in an in vivo application. Thus, the identification of the 37kDa/67kDa laminin receptor (LRP/LR) as the cell surface receptor for prions opened a new direction for the development of a TSE therapy. Currently, no treatment to slow down or stop the disease process in humans with any form of CJD is established. However, several strategies have been investigated to find an anti-prion treatment including development of a vaccination therapy and screening for potent chemical compounds. In scrapie-infected neuronal cells, which represent a widely used and well characterized in vitro model for transmissible spongiform encephalopathies, the accumulation of PrPSc has been prevented by transfection of (i) antisense LRP RNA, (ii) small interfering RNAs targeting the LRP mRNA and (iii) incubation with the polyclonal anti-LRP antibody W3. Furthermore, the knock down of surface LRP/LR resulted in a reduction of the cellular PrP levels, suggesting an interference with the PrP internalization process. Thus, LRP/LR is required for the PrPSc propagation in vitro and involved in the PrPc metabolism.Due to the existence of several LR genes, a major step to investigate the role of the 37kDa/67kDa laminin receptor in scrapie pathogenesis in vivo is the generation of transgenic mice exhibiting a lower level of LRP/LR. Hemizygous transgenic mice that express LRP/LR antisense RNA under the control of the neuron-specific enolase (NSE) promoter were generated and showed a reduced LRP/LR protein level in the cerebellum and the hippocampus. Intracerebral inoculation of these transgenic mice with the scrapie agent will show, whether the accumulation of pathogenic PrPSc in the brain is delayed or prevented due to a reduced LRP/LR level. A further therapeutic anti-prion approach is given by LRP/LR deletion mutants that can be secreted to the cell culture medium and might act as decoys. Previously, it has been demonstrated that a transmembrane deletion mutant is able to prevent PrPc binding and internalization. In vitro studies using an N-terminally truncated LRP mutant, representing the extracellular domain of LRP/LR (LRP102-295::FLAG), revealed a reduced binding of (i) recombinant cellular PrP to mouse neuroblastoma cells, (ii) infectious moPrP 27-30 to BHK21 cells and (iii) interfered with the PrPSc propagation in chronically scrapie-infected mouse neuroblastoma cells. Furthermore, a cell free binding assay demonstrated the direct binding of the LRP102-295::FLAG mutant to both PrPc and PrPSc. These results together with the finding that that endogenous LRP levels remain unaffected by the expression of the mutant indicate that the secreted LRP102-295::FLAG mutant may act in a trans-dominant negative manner as a decoy by trapping PrP molecules. To investigate the therapeutic potential of the LRP102-295::FLAG decoy mutant in vivo transgenic mice were generated ectopically expressing LRP102-295::FLAG in the brain. Animals showed no phenotype and transgene expression was detected in cortical and cerebellar brain regions. An intracerebral prion inoculation of these mice will prove whether the expression of the LRP102-295::FLAG mutant can impair the PrPSc accumulation in the brain and can thus, act as a alternative therapeutic tool in prion diseases. The recent finding that experimental introduction of RNA can be used to interfere with the function of an endogenous gene (RNA interference) provided another tool for the development of gene-specific therapeutics. In order to evaluate a gene transfer therapeutic TSE strategy, human immunodeficiency virus (HIV)-derived vectors that express short hairpin RNA (shRNA) directed against the LRP mRNA were used. Following integration of LRP-shRNA-expressing lentiviral vectors into the genome of neuronal cells efficient LRP/LR downregulation was observed. In scrapie infected neuronal cells, downregulation of the LRP gene expression resulted in a diminishment of PrPSc propagation, providing a further therapeutic strategy in the development of a TSE treatment.

Prions are unconventional pathogens that cause transmissible spongiform encephalopathies (TSEs). According to the "protein only" hypothesis, prions consist of an infectious protein that is capable of converting a normal host protein termed PrPc into a protease resistant form termed PrPSc. PrPSc is poorly degraded by the host and accumulates in the CNS. Normal biological functions of PrPc and mechanisms involved in neurodegeneration remain obscure. During the past two decades, considerable efforts have been made to elucidate prion diseases and in particular to identify PrP interactors for a better understanding in prion biology. A major break-through was the identification of the 37 kDa laminin receptor (LRP), which represents the precursor of the human 67 kDa high-affinity laminin receptor (LR), as the cell surface receptor for the cellular prion protein. We investigated the role of LRP/LR in the propagation of PrPSc in chronically infected cells by different approaches. Three strategies resulted in downregulation or blocking of LRP and prevented PrPSc accumulation in different scrapie infected neuronal cell lines (i) transfection with an antisense LRP RNA expression plasmid (ii) transfection with small interfering (siRNAs) specific for the LRP mRNA and (iii) incubation with the polyclonal anti-LRP antibody, W3. We observed that the treatment with W3 abolished PrPSc deposition and reduced PrPc levels after one week of incubation. PrPSc did not reappear in cells being cultured for 14 additional days without therapeutic antibody treatment. Taken together, these results indicate that LRP is not only required for PrPc metabolism under non-pathological conditions but also has a pivotal role in prion propagation in a cell culture model. LRP/LR appears then to be a promising potential target for the development of therapeutics for the treatment of prion disease. Due to these encouraging cell culture data, we decided to select single chain antibodies (scFv) encompassing a suitable format for therapy. ScFvs are composed of variable parts of heavy and light chains of an immunoglobulin that are connected by a peptidic linker. The antibodies were screened on recombinant GST::LRP employing a phage display strategy. Two scFvs termed N3 and S18 were screened and selected by ELISA. Both antibodies were further characterized by western blotting and FACS analysis: both N3 and S18 specifically recognized mouseLRP and humanLRP overexpressed in mammalian cells under denaturating conditions (western blot) and under native conditions at the cell surface (FACS). Epitope mapping revealed that as expected both scFvs are directed against the extracellular part of LRP: S18 and N3 recognized amino acid residues 225-233 and 273-278, respectively. The ability of N3 and S18 to interfere with LRP/PrP interaction was tested by pull-down assays. In contrast to the control scFv C9 directed against the pre-S1 coat-protein of hepatitis B virus, both anti-LRP scFvs were able to block the specific LRP/PrP binding. In order to investigate a potential curing effect of scFv S18 in vivo, this scFv was tested in a scrapie mouse model by passive immunization. The application of S18 by intra-peritoneal injection was able to reduce PrPSc deposition in the spleen in comparison to mice injected with PBS or C9. However the survival times of S18 treated animals was not increased. Anti-LRP scFv S18 seems to contribute to block prion propagation in the periphery but it is likely that this effect was not enough strong to have an impact on the CNS invasion. Thus, we hypothesized that a strategy targeting directly the brain should be more effective. In this context, an approach based on the expression of single chain antibodies as secretory molecules in the brain via an adeno-associated virus (AAV) vector was initiated. To assure secretion of the scFv expressed in mammalian cells, a signal sequence was fused to the scFvs. Tranfection experiments demonstrated that neuronal cells were able to express and secrete high quantities of both scFvs. Furthermore, the generated scFvs were still functional as shown by western blotting. To find the appropriate AAV serotype for scFv expression, neuronal cells were transduced with varying serotypes carrying a GFP. AAV serotype 2 was chosen due to (i) its good transduction performance in two neuronal cell lines and (ii) the possibility of its purification by affinity chromatography. The sequences encoding for the scFvs N3, S18 and C9 have been cloned in an AAV-based vector. The AAV system was also able to drive high expression of scFvs into the supernatant by transfection or transduction. rAAV-scFv particles were produced and purifed for further stereotaxic injections into mice. Although the investigation of this therapeutic strategy is still in progress in a murine scrapie model, we already proved that a single injection of rAAV led to the expression of scFvs into the brain of mice 30 days post injection. This study represents the first gene therapeutic approach for the treatment of prion diseases.

Unzureichende Möglichkeiten in Diagnose und Behandlung von epithelialen Ovartumoren führen zu einer niedrigen Überlebensrate der Patientinnen. Die molekularen Zusammenhänge, die der Progression dieser Krankheit zugrunde liegen, sind noch weitgehend unbekannt und erschweren Verbesserungen in der Früherkennung und Therapie. In der vorliegenden Arbeit wurden mit Hilfe der Affymetrix Genchip-Technologie die Genexpressionsprofile von elf Ovartumor-Zelllinien mit denen von zwei IOSE-Zelllinien, die aus normalen Epithelzellen des Ovars etabliert wurden, verglichen. So sollten Gene identifiziert werden, welche die Tumorzellen von den normalen Zellen unterscheiden und eventuell als diagnostischer Marker oder als Zielgen für therapeutische Zwecke dienen können. Mit besonderem Augenmerk auf Transmembran- bzw. sezernierte Proteine wurden zunächst 21 bzw. sieben Gene in den beiden Gruppen identifiziert, deren Überexpression in Karzinomen des Ovars zum ersten Mal ermittelt wurde. Die Ergebnisse der Affymetrix-Analyse wurden mittels RT-PCR in sieben ausgewählten Genen bestätigt. Die Expressionsanalysen von drei ausgewählten Genen, NMU, JAG2 und L1CAM, wurden auf Ovartumor-Gewebeproben ausgeweitet und eine mögliche Rolle in der Tumorgenese des Ovarkarzinoms diskutiert. Da für L1CAM spezifische Antikörper zur Verfügung standen, konnte gezeigt werden, dass die Abundanz der L1CAM-mRNA mit der Protein-Abundanz korrelierte und die Lokalisierung in der Zelle wie erwartet in der Plasmamembran erfolgte. Die Expression von L1CAM konnte immunhistochemisch in Paraffinschnitten von Ovarkarzinomen nachgewiesen werden. Zu einem geringeren Prozentsatz konnte das Zelladhäsionsmolekül auch in Borderline-Tumoren, die in der Regel durch eine gute Prognose gekennzeichnet sind, und Fibromen identifiziert werden. In malignen Ovartumoren nicht epithelialer Herkunft konnte keine L1CAM-Expression festgestellt werden. Zeitgleich wurde die Überexpression von L1CAM in Ovarkarzinomen beschrieben und das Molekül als prognostischer Marker in Karzinomen des Ovars, Uterus und des Endometriums identifiziert. Durch funktionelle Analysen sollte die Funktion von L1CAM in Ovartumorzellen untersucht werden. Bei der Klonierung von L1CAM wurde festgestellt, dass aus den verwendeten Ovartumor-Zelllinien nur eine Isoform des Gens isoliert werden konnte, in der die Exons 2 und 27 deletiert sind. In stabilen L1CAMΔ2,27-Transfektanten konnte gezeigt werden, das die Expression dieser Isoform zu erhöhter Adhäsion an Laminin im Vergleich zu Vektor-Transfektanten führt. Die Invasionsfähigkeit der Transfektanten wurde durch die ektopische L1CAMΔ2,27-Expression nicht verändert. Zusammenfassend wurden in dieser Arbeit unter der Verwendung der Genchip-Technologie die zwei potenziellen Markergene NMU und JAG2 identifiziert, die in weiteren Analysen auf ihre Bedeutung in Ovarkarzinomen untersucht werden müssen. L1CAM wurde in immunhistochemischen Studien als Marker identifiziert, dessen prognostischer Wert in Zukunft die Diagnose und Therapie dieser aggressiven Erkrankung verbessern könnte. Zudem bieten die vielfältigen Funktionen von L1CAM Möglichkeiten bei der therapeutischen Intervention durch monoklonale Antikörper, die durch die Expression einer Spleißvariante in Ovartumorzellen spezifiziert werden könnte.

In der vorliegenden Arbeit wurden 45 Nebenhoden von klinisch gesunden Katern im Alter zwischen fünf Monaten und zehn Jahren im Hinblick auf Morphologie, Ultrastruktur und Histochemie untersucht. Es wurden zehn verschiedene immunhistologische Reaktionen auf verschiedene Proteine bzw. Hormonrezeptoren durchgeführt. Der Nebenhoden des Katers entspricht in seinem anatomischen Aufbau dem anderer Tierarten. Durch das Auftreten verschiedener Zellarten, unterschiedlicher Epithelhöhe und der Länge des Zellbesatzes sowie Form und Lage des Nukleus kann der Epididymidis des Katers in fünf verschieden Segmente unterteilt werden. Die Ductuli efferentes bilden mit Segment 1 und 2 den Nebenhodenkopf, Segment 3 und 4 entsprechen dem Corpus epididymidis und der Nebenhodenschwanz besteht aus Segment 5. Die Ductuli efferentes besitzen zilienbesetzte und zilienlose Zellen, die in verschiedenen Färbungen und immunhistologischen Reaktionen auch unterscheiden. Das Epithel des Ductus epididymidis des Katers besteht aus Hauptzellen, Basalzellen und Lymphozyten, sowie Apikalzellen in Segment 2 und 5. Neben den genannten Zellarten bzw. ihrer Kerne oder des Zytoplasmas wurden bei den immunhistologischen Reaktionen Spermien, luminale Epithelzellen, Muskulatur, Gefäße und die Basallamina beurteilt. VEGF (“Vascular endothelial growth factor“) ist immunhistochemisch nur schwach nachweisbar, dafür zeigt sich der VEGF-Rezeptor deutlich positiv, vor allem in den Zellkernen der Hauptzellen von Nebenhodenkopf und –schwanz. GHR (“Growth hormone receptor“) reagiert in Kernen der Hauptzellen und Apikalzellen des gesamten Nebenhodens, sowie deren Zytoplasma. Außerdem ist es in den Gefäßen und der Muskulatur nachweisbar. Vimentin kommt im Zytoplasma der Ductuli efferentes sowie in Muskulatur, Interstitium, Gefäßen und Basallamina des Ductus epididymidis vor. Cytokeratin färbt das Zytoplasma der Ductuli efferentes und der Hauptzellen in Segment 1 und 5 an. Laminin kommt vorwiegend in der Muskulatur, den Gefäßen und der Basallamina, in geringer Menge auch im Zytoplasma der Hauptzellen vor. a-SMA (“Smooth muscle actin“) zeigt sich ausschließlich in den glatten Muskelzellen der Ductuli efferentes, des Nebenhodenganges und der Gefäße, ohne regionale Unterschiede. Androgen-Rezeptor ist in den Kernen aller Hauptzellen, vorwiegend aber von Segment 1 bis 4 sowie im Interstitium nachweisbar. Östrogen-Rezeptor a reagiert dagegen nur in den Kerne der Ductuli efferentes und färbt in Segment 4 und 5 den Zellbesatz und die Spermien an. Progesteron-Rezeptor reagiert im gesamten Nebenhodengang positiv im Interstitium, den Gefäßen und den luminalen Spermien. Außerdem färbt es den Zellbesatz von Segment 2 bis 5 an.

Prionen Erkrankungen sind neurodegenerative Erkrankungen, bei denen die abnormale Form (PrPSc) des zellulären Prion Proteins (PrPC) eine entscheidente Rolle spielt. PrPSc lagert sich im Gehirn von Menschen und verschiedenen Säugetieren zu langen Ketten, sogenanntem Amyloid, zusammen und bildet amyloide Plaques. Dies führt letzendlich zum Tod des Individuums. Die Pathogenese und die zelluläre Funktion des Prion Proteins ist jedoch noch nicht vollständigig verstanden. Es wird vermutet, daß PrPC, sowie PrPSc mit verschieden Makromolekülen interagieren. In dieser Dissertation wird die Interaktion des 37-kDa/67-kDa Laminin-Rezeptor (LRP/LR) mit dem Prion Protein beleuchtet. Dabei konnte gezeigt werden, das beide Proteine an der Zelloberfläche von neuronalen Zellen interagieren und daß LRP/LR für die Internalisierung von rekombinantem PrPC notwending ist. Diese Internalisierung ist ein aktiver, rezeptorvermittelter Prozess. Darüberhinaus konnte gezeigt werden, daß LRP/LR notwendig für die Propagation des abnormalen Prion Proteins, PrPSc, in scrapie-infizierten neuronalen Zellen ist. Scrapie-infizierte neuronale Zellen stellen ein Modellsystem für PrPSc-Infektionen dar. Verschiedene Isoformen von LRP/LR aus Mäusehirn sind identifiziert worden und binden PrPC in overlay-assays. Damit konnte eine Interaktion aller Isoformen mit dem Prion Protein gezeigt werden. PrPC konnte in großen Mengen in der Hefe Pichia pastoris hergestellt werden. Dabei wurde sowohl eine monomere Form, als auch ein kovalent verknüpftes Dimer des Proteins von der Hefe produziert. Beide Proteine wurden biochemisch charakterisiert und stellen ein Substrat für Kristallisations- und Funktionsstudien dar.

The influence of estrogen-like substances on the gonadal development in frogs (Rana temporaria and Xenopus laevis). Ultrastructural and immunohistochemical investiga-tions on the gonads of frogs (Rana temporaria). The aim of the present thesis was the investigation and assessment of the estrogen pollu-tion of a river in South-Germany above and below a sewage plant outlet and its possible effects on the gonadal development in amphibians. In an exposure experiment with differ-ent sewage dilutions the effect on the indigenous gras frog (Rana temporaria) were com-pared with the effects on the African claw frog (Xenopus laevis). Because of the lack of relevant data in current literature it was necessary to first collect some basic data on light microscopy, ultrastructure and immunohistochemistry with reference to frogs. Furthermore the sexual differentiation of two populations of different origin were compared histologically. Characterisation of the gonads The ovaries of Xenopus laevis displayed a garland-like structure in contrast to the compact ovaries of Rana temporaria. The ovaries of both frog species were surrounded by an epi-thelium and filled with germ cells which enclosed an ovarian cavity. The oogonies were mainly found in the peripheral parts of the organ. The oocytes were characterised by a big and irregularly shaped cell nucleolus with peripherally located nucleoli. They were sur-rounded by a thin one-layered follicular epithelium. Electron microscopical examination of the ovaries of Rana temporaria showed elongated tubular mitochondria in the cytoplasm which were found exclusively in oocytes. Some of the mitochondria from subadult frogs contained yolk crystals. Additionally an accumulation of electron-tight Granule was found just below the plasma membrane, which could be a preliminary stage of the cortical granule. The testis of the frogs were enveloped by an epithelium and a tunica albuginea which al-ready showed a tubular structure. The testis from Rana temporaria and the Xenopus laevis differed in their developmental stages. The testis of juvenile Rana temporaria contained only germ cells whereas the testis of some Xenopus laevis already contained spermato-cytes and spermatozoa. The spermatocysts, characteristic of frog testis, could be seen in conjunction with the appearance of spermatocytes only. By using light microscopy two different types of germ cells in both frog species could be distinguished which probably were primary and secondary germ cells. By electron microscopical investigation of the testis of Rana temporaria the somatic cells could, on the basis of location and morphology, be differentiated in two types. The somatic cells of the first type were located inside the Tubuli seminiferi and have probably the same function as the Sertoli cells of mammals. The cells of the second type, the Leydig cells or interstitial cells, were located outside the Tubuli and were characterized by granular vesicle in the cytoplasm. With view to the sexual differentiation of Rana temporaria a comparative histological inves-tigation of the gonads of juvenile and subadult frogs of a native midland population and a high alpine population was performed. The midland population proved to be a sexually semi-differentiated species since apart from clearly male or female animals it also com-prises intersex individuals in different stages of the transformation process. The genotypi-cally male animals developed female gonads in the first place which secondly converted into testis during a hermaphrodite stage. The transformation process from female into male gonads was, on the basis of morphological criteria, classified into three stages. The highal-pin population on the other hand proved to be a sexually differentiated race. By using the Avidin-Biotin-Complex-Technique five different antibodies were tested on the gonadal tissue of juvenile and subadult Rana temporaria. The test for Laminin, a non-collagen glycoprotein, which is part of the basal membrane in mammals, resulted in a posi-tive reaction. It seems therefore that similar to Laminin in mammals a glycoprotein plays an important part in the basal membrane of frogs. α-Actin, a fibrous protein of the smooth muscles, which was detected in the Theca externa of the layer of follicle cells in different species, could be established in the blood vessel wall only and not in the layer of follicle cells. Furthermore the occurrence of a Zona pellucida by using antibodies against the por-cine glycoprotein ZP3 was investigated. The ovum including the surrounding layer of follicle cells showed a negative reaction which however did not implicitly exclude the occurrence of a glycoprotein layer with a different antigenicity. Until now the existence of a glycoprotein layer in anurans, in connection with microscopical anatomy of ovaries in Rana temporaria or other species of frogs has not been mentioned in references. The examination of the go-nadal tissue as to the occurrence of ACE (Angiotensin Converting Enzymes) turned out negative as well. Example of application With the exception of a temporarily higher concentration of alkylphenol in the beginning of the exposure, the chemical analyses revealed a relatively low degree of pollution with alcyl-phenols and steroids. The results were comparable to other results of German rivers and stayed well below other European comparative data. According to the results of this study the current level of pollution of the experimental water with estrogens does not endanger the amphibian population. The examination did not reveal any influence of the sewage on the embryonal and larval development. Furthermore, the histological investigation of the gonads in exposed and unexposed frogs with reference to the gonadal sexual differentia-tion as well as the sex ratios did not reveal significant changes. There was no correlation as to the frequency of the occurrence of intersex in the groups of exposed and unexposed frogs, neither of Xenopus laevis nor of Rana temporaria. Only the transformation process from ovaries to testis of the sexually semi-differentiated species of Rana temporaria was slowed down in the group of exposed animals in contrast to unexposed animals. The rea-son for this phenomenon could be the inhibitive influence of the low-level but more continu-ous estrogen pollution in sewage than in river water. Conversely, a link between the accel-eration of the transformation process within the group of unexposed animals and the tem-porarily higher alkylphenol level in the beginning of the exposure cannot completely be ruled out. According to references alkylphenol can cause an increase of testosterone. The semiquantitative RT-PCR detecting Vitellogenin-mRNA carried out by the Institute of Freshwater Ecology and Inland Fisheries in Berlin showed a minor increase in females of Xenopus laevis which were exposed to sewage in the ration of a 2:1 dilution in contrast to the unexposed animals. Taking into account the synergistic effects of estrogens, the in-crease could be attributed to the higher estrogen pollution of the sewage. The histopa-thological analysis for the detection of toxical effects of the sewage as well as other poten-tial influential factors provided no hints as to a possibly toxical influence of the sewage.

Die extrazelluläre Matrix umgibt Zellen, stabilisiert Gewebe und reguliert Zellfunktionen. Bestandteile der ECM transduzieren Signale durch Zellmembranrezeptoren, sog. Integrine. Integrine vermitteln Änderungen der Zellmorphologie, Proliferation, Differenzierung und Apoptose in Zellen. Die Frage ob die ECM eine wichtige Rolle in der Physiologie und Tumorgenese der Hypophyse spielt, ist immer noch offen. In der vorliegenden Arbeit wurden zum ersten Mal die regulatorischen Möglichkeiten der ECM in der Hypophyse dargestellt. Es wurde der Einfluß der extrazellulären Matrix auf das Wachstum und die Zytokinsekretion von follikulostellaren Zellen, sowie Hormonsekretion, Proliferation und Signaltransduktion in kortikotropen Zellen untersucht. Desweiteren werden in dieser Arbeit Änderungen der Expression von Laminin, als auch deren mögliche funktionale Konsequenzen innerhalb der Prolaktinomgenese demonstriert. In der follikulostellaren Zellinie TtT-GF konnte gezeigt werden, daß Fibronektin und Kollagen I die Zellproliferation stimulieren. Simultan führte nur Kollagen I zu einer Erhöhung der Interleukin-6 Sekretion, welches ein bekannter Wachstumsfaktor für follikulostellare Zellen ist. Die signifikante Hemmung der Proliferation von FS-Zellen bei Kombination von Kollagen I mit einem anti-IL6-Antikörper läßt darauf schließen, daß Kollagen I die Proliferation und Zytokinsekretion von follikulostellaren Zellen reguliert. Die Fibronektin vermittelte Proliferationsteigerung scheint dagegen einem anderen Mechanismus zugrunde zu liegen. In der kortikotropen Tumorzellinie AtT-20 konnte nachgewiesen werden, daß die ACTH Sekretion durch Fibronektin, Laminin und Kollagen I inhibiert wird. Ein Reporterkonstrukt bestehend aus dem POMC Promoter und Luciferasegen zeigte ähnliche Ergebnisse, was auf eine Hemmung der ACTH Sekretion bereits auf Ebene der POMC-Transkription schließen läßt. Im Gegensatz dazu konnte keine signifikante Veränderung der ACTH Sekretion in normalen Hypophysenzellen festgestellt werden. AtT-20 Zellproliferation wurde durch Kollagen IV und Fibronektin stimuliert, wogegen Kollagen I und Laminin zu einer Inhibition führten. Parallel dazu fand eine Veränderung der Zellform statt. Ein möglicher integrinvermittelter Signalweg umfasst die Aktivierung von Rac, einer kleinen GTPase, mit der konsekutiven Produktion von reaktiven Sauerstoffradikalen (ROS) und einer runden Zellform. Es konnte gezeigt werden, daß eine Inhibition der AtT-20 Proliferation durch Laminin mit einer signifikanten Erhöhung der reaktiven Sauerstoffradikalen und einer runden Zellform einhergeht. Dieser Effekt war mit NAcetylcystein (NAC), einem ROS-Antagonisten, umkehrbar und am ehesten Rac vermittelt. Unter Kollagen IV fand ebenfalls eine Inhibition des Zellwachstums statt. AtT-20 Zellen nahmen auch hier eine runde Zellform an und produzierten, wenn auch weniger stark als Laminin und Kollagen I, ROS. Dieser Effekt war jedoch nicht durch NAC umkehrbar. Kollagen I führte dagegen zu einer Steigerung der Proliferation und ROS-Produktion, sowie zu ausgebreiteten als auch runden Zellen. Diese z.T. gegensätzlichen durch Kollagen I+IV vermittelten Effekte könnten durch simultane Aktivierung alternativer Mechanismen, wie z.B. eine integrinbedingte Aktivierung als auch Hemmung von Rezeptoren für Wachstumsfaktoren, verursacht sein. Ein weiterer, oft mit Fibronektin assoziierter Signalweg, beinhaltet die integrinvermittelte Aktivierung von Rho, einer weiteren kleinen GTPase. Die fehlende ROS Erhöhung, der Einsatz eines β1-integrin stimulierenden Antikörpers, sowie die integrinunabhängige Stimulation von Rho durch Lysophosphatidatsäure läßt auf eine Rho assoziierte Proliferationserhöhung in AtT-20 Zellen durch Fibronektin schließen. In GH3 Zellen führte Laminin zu einer Abnahme der Prolaktinsekretion und zur Inhibition der Proliferation. Im Gegensatz dazu konnten keine Veränderungen der Prolaktinsekretion in normalen Rattenhypophysenzellen beobachtet werden. Übereinstimmend zeigte sich im Dopamin2 Rezeptor defizienten Mausprolaktinom, einem Knock-Out in vivo Modell für spontane Prolaktinomentwicklung, und humanen Prolaktinom eine bereits sehr frühe Abnahme der Lamininexpression. Diese Hemmung der Lamininexpression während der Prolaktinomgenese könnte einen weiteren Faktor für erhöhte Hormonproduktion und Zellproliferation in Prolaktinomen darstellen. Die hier erstmalig beschriebenen Auswirkungen der extrazellulären Matrix auf Hypophysenzellproliferation und -hormonsekretion verdeutlichen die wichtige, aber wenig erforschte Rolle der ECM in der Hypophyse. Diese Resultate sind nicht nur neue Ansatzpunkte der Hypophysenphysiologie und -pathophysiologie, sondern lassen auch die Weitläufigkeit der unterschiedlichen regulativen Systeme innerhalb der Hypophyse erkennen.

Prions have been extensively studied since they represent a new class of infectious agents in which a protein, PrPSc (prion scrapie), appears to be the sole component of the infectious particle. They are responsible for transmissible spongiform encephalopathies (TSEs), which affect both, humans and animals. Human prion diseases occur in infectious, sporadic or genetic forms. The "protein only" hypothesis argues that the key event in the pathogenesis represents the conversion of the normal host protein, PrPc, into its pathogenic isoform PrPSc. Prion diseases have been associated with the accumulation of this abnormally folded protein and its neurotoxic effects. However, it is not known if PrPc loss of function is an important factor since the normal biological function of PrPc, a cell surface-anchored glycoprotein predominantly expressed in neuronal cells, and the cellular processes in which this protein is involved remain obscure. Recently, the human 37 kDa laminin receptor precursor (LRP), which represents the precursor of the human 67 kDa high-affinity laminin receptor (LR), was identified as a binding partner for the cellular prion protein in a yeast two-hybrid screen. In order to characterize the possible role of LRP/LR as a cell surface receptor for PrPc, cell culture studies were performed to investigate the cellular localization of PrP and LRP/LR and to analyse the binding and internalization behaviour of PrP depending on the presence of LRP/LR on the cell surface of neuronal and non-neuronal cells. Immunofluorescence analysis of non-permeabilized murine neuroblastoma cells demonstrated that PrP and LRP/LR co-localize on the surface of these cells. In addition, baby hamster kidney (BHK) cells transfected with recombinant Semlik-Forest virus RNAs overexpressed human PrP and human LRP at their cell surface, the latter one orientated as a type II transmembrane protein with its C-terminus outside and its N-terminus inside the cell. Co-localization of both proteins was observed on BHK cells co-transfected with LRP and PrP encoding recombinant SFV RNAs. Cell binding and internalization assays with recombinant human PrP demonstrated the LRP/LR-dependent binding and endocytosis of externally added human PrP. An increased, dose-dependent cell binding of recombinant PrP was demonstrated by BHK cells overexpressing full-length human LRP on their cell surface. Trypsin treatment of the cell surface revealed the LRP dependent internalization of GST-tagged and untagged, glycosylated PrP. In contrast to wild-type LRP, the expression of an LRP mutant lacking its transmembrane domain led to the secretion of this mutant from transfected BHK cells and totally abolished the binding and internalization of exogenous, recombinant PrP. This LRP mutant could function as a decoy recetor in therapy of TSEs. The strict LRP/LR specificity of the PrP binding to neuronal cells was verified by testing the displacement capacity of a series of different antibodies in the LRP-PrP binding reaction. Only LRP and PrP specific antibodies were able to block totally the binding of human GST-fused PrP to N2a and NT2 cells whereas various control antibodies used for competition showed no effect. Mapping analyses in the yeast two-hybrid system and cell-binding assays identified direct and heparan sulfate proteoglycan (HSPG)-dependent interaction sites mediating the binding of cellular PrP to the 37-kDa/67-kDa LRP/LR. The relationship between the 37-kDa LRP and the 67-kDa high-affinity LR is unknown so far. Both forms were observed in plasma membrane fractions of N2a cells. We conclude from these data that the 37-kDa/67-kDa laminin receptor acts as the main cell surface receptor for PrP. High-level expression and purification of recombinant, glycosylated prion proteins in mammalian cells is essential for a better understanding of the physiological function of PrPc and biochemical processes responsible for prion diseases. Due to the presence of important organelles, membranes and other cellular cofactors which are necessary for the correct processing, trafficking and localization of prion proteins mammalian cell culture systems such as the Semliki-Forest virus (SFV) system allow the synthesis and characterization of wild-type as well as mutant PrP to get a better insight into the biology of these proteins. Therefore, the SFV system was used to generate recombinant highly glycosylated human wild-type and human disease-associated mutant prion proteins as well as FLAG-tagged human and bovine PrP in cultured BHK cells. Both mutated variants, which are related to the human prion diseases fatal familial insomnia (FFI) and Creutzfeldt-Jakob disease (CJD) reveal proteinase K (PK) resistance, one of the most typical biochemical properties characteristic for the infectious scrapie isoform of the prion protein. The subcellular location of both PrP mutants at the cell surface and in intracellular compartments of transfected BHK cells was similar to that of wild-type PrP without any significant differences regarding the cellular distribution and expression level. In addition, FLAG-tagged prion proteins were expressed with high efficiency in BHK cells showing the typical glycosylation pattern allowing the rapid and simple purification via anti-FLAG antibody chromatography. PrP dimers could play an essential role in the PrPc to PrPSc conversion process and might be involved in PrP interspecies transmission. Recently, crystallization of the prion protein in a dimeric form was reported. Size exclusion chromatography showed that native soluble homogeneous FLAG tagged prion proteins from hamster, man and cattle expressed in the baculovirus system were predominantly dimeric. The PrP/PrP interaction was confirmed in rec. SFV-RNA transfected BHK cells co-expressing FLAG and oligohistidine tagged human PrP. The yeast two-hybrid system identified the octarepeat region and the C-terminal structured domain (aa90-aa230) of PrP as PrP/PrP interaction domains. The identification of the 37-kDa/67-kDa laminin receptor as the receptor for the cellular prion protein might represent an important step for a better understanding of the molecular biology of prion diseases and might lead to the development of powerful therapeutics such as LRP/LR specific antibodies for the treatment of these unconventional diseases.

Fibronectin, collagen type III, laminin, and cytokeratin 5 were visualized in normal skin and in skin showing early or advanced signs of autolytic decomposition to prove whether the immunohistochemical analysis of these antigens can provide useful information for an age-estimation of skin wounds obtained from putrified corpses. In cases with early signs of decomposition (visible course of veins, greenish discoloration) and without microscopic alterations like relaxation of the epidermal cell layers or destruction of the blood vessel structures, the staining pattern was identical to that found in normal, non-putrefied skin. In skin already showing microscopic alteration of the tissue structure, fibronectin and collagen type III could not be localized unambiguously. The distribution of laminin and cytokeratin 5, however, was well preserved. In advanced putrefied skin no reliable staining results could be obtained for fibronectin, collagen type III, and laminin. Even though cytokeratin 5 was still detectable in remnants of decomposition-resistant skin appendages, no information useful for an age-estimation of skin wounds can be obtained due to the autolytic detachment of the epidermal layers.