#MHC variability

[biology-geology-beaches-india]

TSRNOSS, p371.

[brianedner]

SVTFOE oneshot part 6

Lekmet should have been the 2.17.2 episode

Marco and Star stood with Jackie kneeling in front of an old dog lying in a bed.

“Hay there Max. How are you doing today?”

The dog slightly lifted his head a looked at her, his tail wagged after seeing her. He then licked her face.

“Hahaha, glad to hear it. I brought a few people to see you.” She then gestured to the two people with her. “My boyfriend Marco and our friend Star. Can you say hello?”

Max turned to look at them and barked at them. Jackie then backed up and let Marco kneel in front of Max and began to pet him. “Hi there. Jackie told me about you. She said you have been with the family for as long as she can remember.” Max began to lick Marco’s hand then. “Well, you did a great job raising her.”

He then stood up and let Star take his place.

“Hi there Max. I am Star, a magical princess from another dimension. I got a treat for you.”

She then reached into her bag and pulled out a bone.

“My dad eats a lot of meat, and I got a bone from him after he was done with dinner for you.”

Max then started to happily chew on the bone, making Star smile at him.

“You like that bone, don’t you Max?”

She kept smiling at him as she stood up but then began to frown as she turned to look at Jackie.

“Are you sure you have to put him down?”

Jackie frowned at that before turning to look at the dog. “He is an old dog. The vets say that he has several chronic, uncurable, and painful health issues that are cropping up. It would be better to give him a peaceful end than force him to live through them just because we don’t want to say goodbye.”

Star looked downcast at that before her eyes lit up. Marco looked at her with a worried expression.

“Uh, Star? What are you thinking?”

“What if I can get the issues cured?”

Jackie and Marco shared a look before turning back to her.

“Are you thinking of using your wand?”

She just shook her head at that. “After giving Marco a tentacle arm that tried to take over his body? No way am I taking that risk again. I am going to call Mom and ask if she knows any. If that doesn't work, there is a member of the MHC that is in charge of healing magic that could help out.”

Star then turned to leave the house as Marco put a hand on her shoulder. “Star, sometimes things just end, and there is we can do but accept it.”

She paused and let Marco’s head rest on her shoulder for a bit. “Maybe.” She then brushed the hand off. “But this isn’t one of those times.”

She then left the house with Jackie and Marco looking at her with a worried look as she left. Marco then turned to look at Jackie who just held up a hand before he could say anything.

“Don’t worry about any boyfriend duties to help me with my grief. Go after Star and make sure she doesn’t do anything too bad, ok?”

He just sighed in relief and ran after her.

Star’s room

“Call mom.”

Moon appeared in the mirror with a worried look on her face.

“What happened? Are you ok? Is Ludo back?”

Star held up her hands as she looked at her in shock.

“Whoa, there mom. Nothing anywhere near that level Mom. A friend's dog is just suffering from several health issues and I wanted to know if you knew healing spells I could use.”

Moon’s face quickly shifted to relief before settling on downcast. “Unfortunately, Star, healing magic is one of those types of magic that requires you to know multiple variables. What kind of issues are we talking about?”

Marco then walked up next to Star. “Arthritis and other general side effects of getting old.

Moon just sighed at that. “I was afraid of that. Old age is one of those things that magic can’t fix, only soothe. I know a few spells that will make his time left more barrable, but you might want to seriously consider putting him down.”

Star stamped her foot at that. “No! I refuse to accept that there is nothing I can do to help my friend in her time of need!”

“Star-“

“End Call.”

The mirror turned cut from Moon and became a mirror again.

“Call Lekmet.”

Marco tried again to put a hand on her shoulder in a show of support, but Star just waved him off. “I am fine Marco. I just need to fix this.”

The mirror then turned to a picture of a goat man with batwings standing in a hospital.

“Yes Star, what is it?” he then turned to look at Marco. “Hello, Marco.”

Marco just blinked at that. “How did you know who I am?”

He just chuckled. “I am in charge of the magic of life, death, and rebirth. I know everyone’s names. Also, Heckapoo and Omnitraxus Prime are my siblings. Both of them have talked about both of you recently.”

Star just smiled at that. “Sounds great. Now, can you teach me some healing spells? I have a friend whose dog is about to be put down due to how sick he is and I want to save him.”

Lekmet turned to look at Marco who was giving Star a worried look. “The dog is old, that is why he is being put down.”

Lekmet just sighed at that before pulling out a pair of scissors and making a portal to his side, making one appear next to Star and Marco before he hung up.

Star and Marco just turned to look at the portal before he walked in.

“I think the best way to teach you based on what Glosseryck told me about you would be a field trip. Does that sound ok?”

Star smiled and gave him a thumbs-up. “Sounds great!”

Marco shot him a worried look, but Lekmet just shot him a smile and summoned a cue card where Star couldn’t see it.

Trust me, I am going to teach her about how death and endings are just a part of life.

Marco just sighed and stepped forward. “Should I come too?”

He looked at him with a puzzled look before nodding. “Sure, it might make the lesson work better.” He then snapped his fingers and made them all transparent.

“Woah” exclaimed Star, wiggling her hands in front of her as she examined them. She then tried to pass them through each other to see if they were intangible, which they were. She then grew a massive smile. “Cool!”

Lekmet just chuckled at that. “Yes, it is cool. Now, let's get a move on. We will be making 3 stops.”

Scene Change

Between one second and the next, they were in a hospital room at the side of a bald man with a breathing tube in his nose with a woman holding his hand. There were also some nurses around fiddling with some equipment attached to him

“Is he ok?”

Lekmet just smiled. “He is receiving treatment for cancer, but he is responding positively and they just did surgery to remove a tumor.”

He then turned to Star. “For your first lesson, let's start with revealing his physical health aura.”

Star shot him a confused look. “His what?”

Lekmet then turned to look at the man and waved his hand. The woman holding the man's hand suddenly turned into what was best described as an Aurora Borealis in human form.

“This is her physical health aura. Think of each color as a gage for each aspect of his health. The brighter one is, the healthier that part of him is. If you want to use magic to help someone’s health, then you use this first to figure out what is wrong in the first place.”

He then waved his hand again, making the woman’s aura disappear. “There are other versions of the spell that focus on different parts of the person's physical, mental, emotional, spiritual, and other types of health.”

He then turned back towards Star. “To make it appear around the man, point the wand at him and say ‘aura of physical health.’ Don’t worry about them seeing it. the only ones that can see the aura are those that cast the spell, are naturally able to see them, or those under a spell to let them see them.”

Star then did as he asked, making another brilliant cascade of lights appear.

Marco then turned to look at Lekmet. “Did it work?”

“Yes, it did. Now Star, can you tell me what you see that is different from the lights of the women you saw earlier?”

Star just kept staring at the lights in front of her for several seconds before responding.

“some of the colors are dimmer than hers were, and the overall things are dimmer than hers were.”

Lekmet just nodded. “Advanced healing magic like what you want to learn involves looking at these colors and trying to increase the brightness of them without dimming any of the others. Simpler spells for things like healing cuts and mending bones also need this to a degree, but not as much.

“For now, let's point at him and say “Healer Helper.”

Star did as he asked, causing one of the colors, a dark blue, to be outlined. It was also the dimmest of the colors there.

“Healer Helper shows you which color is the dimmest, and warns you when the other colors are getting dimmer. After you identify the color you want to brighten with the second spell, point your wand at the person and say ‘physical illumination’ before saying the exact kind of color you want to increase the brightness of.”

Marco then raised his hand. “I am an artist’s son, so how specific do we have to be when saying the color name?”

Lekmet then reached into his robes and pulled out a large book before opening it up and showing a page with the color specified as Cerulean Blue and what its intensity meant in multiple different auras.

Stat just looked at the book like it would bite her. “Please tell me I don’t need to memorize this.”

Lekmet just laughed. “Don’t worry, there is a copy in the Butterfly Royal Library for you to reference when you want to do this kind of magic. For now, let's just heal this man.”

Star then pointed her wand at him before Lekmet put his hand on her arm. “When the Healer Helper spell tells you to stop, stop the healing spell. If a color gets too bright, it can make the other colors dimmer and cause other health issues.”

Star nodded before turning to the man. “Physical Illumination Cerulean Blue.”

The specified light then began to slightly brighten as Star kept the wand pointed at him. His monitors began to perk up, as well as the man himself.

“Stop Healing”

Star cut off the light in shock from the warning sound coming from the aura, leaving the light of the man double the brightness it was before, but still below what the woman’s was.

Lekmet was just grinning at Star’s reaction. “I love seeing a healer's first reaction to the Healers Helper warning.”

Star and Marco both shot him dirty looks before Star asked a question. “Why couldn't I make it go brighter?”

“Like I said, if the light got too bright, then his other lights would become too dim. With the poor shape he was in from the cancer and treatments, he could only take so much before your healing could kill him.”

He then examined the other colors intently. “It takes a lot of experience to know how bright you can make a color without affecting the others, which is why I had you cast that helper spell earlier.”

Star looked slightly disappointed but was relieved when the Nurses gave each other hopeful and happy expressions on the readouts.

“But he will get better, right?”

Lekmet nodded. “You did all you could with magic here. Now, we have another stop to make.”

Scene change

The group then appeared in front of an old man in a nursing home sitting in a chair and reading a book.

“Let me guess, use the aura spell and helper spell before increasing the color of the brightnesses again?”

Lekmet just nodded. Star then did the mentioned spells but was surprised by the results.

The man's aura was very dim, and the helper spell was instead highlighting one of the brighter colors.

“Um, Lekmet? Did I do something wrong with either of the spells?”

Lekmet just shook his head. “No Star, this man is in such bad condition that there is nothing magic can do to help him be better without causing further complications in other areas. The color your helper is highlighting is already being posted by the pain medication he is on, which is why it is already so high.”

Star just looked shocked at that. “What! But this is magic! How can it not be able to do anything for him?”

Lekmet just sighed. “Star, if there is anything the multiple disasters you and Marco have been involved with over the past months should have taught you, it is that magic can’t solve all your problems. Sometimes there is nothing you can do to help someone.”

Star looked downcast at that, but then Marco held her hand in support. “Hay Star, don’t worry. Just because you can’t make him better doesn’t mean you can’t make him more comfortable. I think your magic can help him with his pain better than the medication can, and with fewer side effects as well.”

Lekmet nodded at that. “Exactly Marco. That is what the helper spell is showing.”

Star looked up at Lekmet with a depressed look before casting the ‘physical illumination’ spell. The light’s illumination level didn’t change, but the spell kept going for a few seconds.

“Ok, I am sure something is going on now.”

“The spell is just purging the medication from his system and simulating the effects. Give it time and cut it off when the warn-“

“Stop Healing”

Star jumped again, almost dropping her wand. Luckily she held onto it and was able to stop the spell.

The light intensity hadn't changed at all despite the spell being cast, but a few of the other lights got a little brighter.

“See? He might not notice it now, but if you give him some time he will notice and be able to enjoy his life a little better than before.”

Star lit up at that and then noticed that another light was highlighted and pointed to it.

“Sometimes you can increase multiple lights in a single healing session. Go ahead, keep doing this until the helper stops telling you to heal things.”

Star did that, increasing a few other colors before it stopped highlighting colors to heal.

“Now, we have one last stop to make. And this time, we will be visible and tangible.”

Scene Change

The last stop was Jackie’s house, causing Jackie to almost drop her plate when the three popped into existence in front of her.

“WHAT THE? Oh, it's you two. Who’s the friend.”

Lekmet held out his hand. “Hello Jackie, I am Lekmet, the MHC member in charge of the magic of life, death, and rebirth. I was just showing Star how to cast healing spells and she was about to try on Max, with your permission of course.”

Jackie scrunched up her face in worry. “What would this entail?”

Star then turned towards Marco and cast the ‘physical aura’ and ‘helper’ spell on Marco before buffing the lowest color for a few seconds and stopping when the warning went off.

“That is exactly what would happen to Max. Ok?”

Marco shot Star an annoyed look at being used as a guinea pig without being asked but nodded to Jackie all the same.

“Ok then, but please don’t hurt him, or turn him into a monster, or worse.”

Star nodded before casting the two spells on Max.

His aura was like that of the old man, with the same color highlighted but a lot dimmer.

Star increased the brightness of it until the warning went off, then increased a few others a little before the helper spell gave an all-clear. She then turned to look at Jackie.

“Ok, that’s the most I can do.” She then turned to look at Lekmet. “Can you do anything else to help him?”

He shook his head. “Sorry, anything else I would be willing to contribute would only be slightly better than what you did.”

“What do you mean by ‘willing to contribute?’”

Lekmet looked at Marco before sighing.

“I have powerful healing abilities that can restore people to their prime, but it is a finite resource tied to my life force. After I use it all up, I would die”

Everyone in the room looked at him in shock. Star was the first to find her voice. “But the MHC is immortal! You guys can’t die!”

He chuckled at that. “You are right, just because I die doesn’t mean I die. Think of me like the phoenix with a bit of ‘The Doctor’ mixed in. I die and am then reborn from the ashes as a baby with my powers at their peak. I can recall memories of my past lives with a lot of effort, but for all intents and purposes, I die and am replaced by a new person with their personality.”

The group didn’t stop looking at him in shock after hearing this. It was Marco this time that asked the question. “How much time do you have left”

He just shrugged. “Depends on how much I have to heal. I am at 12% now, and healing Max back to full would drop me to 10%. As nice a dog as he is, turbulent things are going on and I need to conserve my healing for any massive battles or world-shattering events. I also don’t want to leave the MHC down a member until I get out of diapers.”

He then put a hand on Jackie’s shoulder. “I might not be willing to completely heal him, but I can help him die peacefully. I have several spells that can painlessly let you pass over to the afterlife while seeing visions that make you happy.”

“I’ll have to talk to my parents about that, but we might just take you up on that.”

He nodded and looked to Star, who was walking out the front door and sat on the front stairs. He walked over and sat next to her.

“How are you doing Star.”

‘Sigh.’ “I just thought I could prevent Jackie from losing her dog like I lost-“ she then froze up before continuing. “-something I cared about.”

Lekmet sighed at that. “Star, sometimes things just end, and there is we can do but accept it.”

“Marco already said that.”

He just laughed at that. “Maybe, but did he continue? Endings aren’t always a bad thing. Sure it stinks when the amusement park closes and you have to go home, but all that means is that you can go to the local playground with your friends and hang out with them. Summer ending is always sad, but it means you get to spend time doing things in school you enjoy.”

He then put an arm around Star. “It might stink that someone you love isn’t around anymore, but that doesn’t mean you lost them forever. As long as you remember them and keep them in your heart, they are never gone. There are whole holidays that revolve around this idea.”

Star smiled at that. “Thanks, Lekmet.”

“No problem Star.” He then stood up. “If you have time tomorrow, I can show you a few more healing spells for things like broken bones, burns, and other things.”

She smiled at that. “I would love that.”

Wow, this got away from me. Anyway, I decided to give Lekmet a dedicated episode so we can get to know him and feel the pain when he dies. As Pair of Ramblers (https://www.youtube.com/@pairoframblers3497/videos) said, it’s hard to feel sad about someone dying if you don’t know them. In the show he was just a goat man that Rhomulus cared about that just hung around and healed people before dying. With this, we can care about his death.

The “he dies a bit every time he uses his power” is something the Wiki said was in the “Star and Marco Guide”, but I didn’t see it in either of my copies. I decided to keep it because the idea of the representation in charge of life and death going through a phoenix-style rebirth with a Doctor Who regeneration added was too good an idea to pass up.

As for the healing spell, the only one we see in SVTFOE is the one that turns your arm into a tentacle that tries to take you over. The healing system I put here is a little rough, but I like the idea of manipulating the colors of the aura to affect different parts of physical health. Things like mending broken bones and burns would be the kind of things that have their own simpler spells to cast because of how common they are, but the more complicated it gets, the more you have to manipulate the colors. I might put a more complete version of this out later.

I decided for my New Year's Resolution to do one fanfic chapter a week for all of 2024. Who knows how long I will be able to keep this up, but next week's fanfic chapter is up on my Patreon. This is also being posted on Fanfic.com, AO3, and Tumbler.

Patreon: patreon.com/user?u=10132890

Fanfic.com: https://www.fanfiction.net/s/14051718/1/luz-appreciation-week-2022-from-1228248

AO3: https://archiveofourown.org/works/52823413/chapters/133608991

Tumbler: https://www.tumblr.com/blog/brianedner

I am also doing fanfic info dumps, think wiki articles that go one episode at a time with some compilations at the end on certain topics that are sorted by episode.

Fanfic info dumps here: https://www.deviantart.com/1228248/gallery

[nursingwriter]

Transplant Medicine The Major Histocompatibility Complex (MHC) contains over 128 functional genes. This is the densest part of the human genome and is responsible for most autoimmune diseases. This region also determines vaccine responsiveness, adverse drug reactions, disease progression and transplant rejection. The MHC genes are multigenic with a high degree of allelic polymorphism. There are over 7,500 different alleles and over 5,458 expressed MHC antigens currently known. (DeFranco, Locksley & Robertson, 2007). Genomic evolution and HLA screening have been extremely profitable to Transplant Medicine. A brief analysis of MHC variability reveals two classes of antigens belonging to this complex; class I (A, B, and C) and II (DR, DQ, and DP). Both classes of molecules are expressed in a co-dominant fashion. These molecules are designed to recognize antigens that are foreign to the body and present them to the T cells. (Janeway, Travers & Walport, 2001) The co-dominant mode of inheritance of MHC genes assures that each individual will have a distinct antigen on their cell surface. This forms the basis of graft rejection. Once a foreign antigen enters the human body, activation, proliferation and differentiation of lymphocytes into effector cells continues until the foreign antigen is eliminated, after which the immune system returns to its quiescent state and an immunologic memory is generated. (Janeway, Travers & Walport, 2001) Tissue typing to match HLA antigens is an important step before transplantation. In general, the larger the number of matched MHC alleles between the donor and the recipient, greater are the chances of graft survival. However, routine HLA typing focuses only on HLA-A, B and DR antigens because these are the only loci that appear to predict the likelihood of graft rejection. (Janeway, Travers & Walport, 2001) The extreme polymorphism of the MHC genes poses several challenges in recognizing the perfect donor, thus complicating HLA typing. The HLA nomenclature differs with the type of typing method used. Refinement of the serological typing of HLA antigens through the years has led to the identification of additional gene loci, which were previously thought to yield one antigen. For example, the B. 60 and B. 61 antigen were previously thought to be one antigen, the B. 40, based on their common ability to bind to a shared public epitope. Moreover, serology does not recognize heterogeneity of HLA antigens, as confirmed by DNA sequencing. Thus serological nomenclature is not representative of the true heterogeneity of the HLA system. HLA typing through this method may lead to a greater risk of graft rejection. (Badders, Houp, Sholander, Leffell & Zachary, 2010) Further more, three different nomenclatures exist for defining HLA antigens. It is important to be able to appreciate the differences of each molecular typing nomenclature and to know which system is being used in the laboratory. Failure to do so may result in missed recognition of a donor specific antibody. (Badders et al., 2010) Apart from the likelihood of graft rejection, recipients are faced with several challenges, such as prolonged waiting times and donor shortage, especially for sensitized individuals since they have additional immunological barriers. From 2000-2008, a total of 243,662 candidates were on the waiting list for kidney transplantation, with only 62,622 available donors in the United States. The broadly sensitized patients have average waiting times twice that of un-sensitized patients. It has been observed that the proportion of patients that are broadly sensitized have been increasing through the years. (Reinsmoen, Lai, Vo & Jordan, 2012) Sensitization to HLA antigens occurs through exposures from blood and platelet transfusions, pregnancy and previous transplants. Examining the sera of patients against cells from a panel of HLA typed donors can identify sensitized individuals. The results are used to calculate panel reactive antibodies (PRA) or the percentage of population that the anti-human antibody, present in the blood, reacts with. Sensitized individuals have a higher PRA and are less likely to receive organ transplants due to an increased risk for immediate graft rejection. (Reinsmoen et al., 2012) Calculated PRA and virtual cross-match have proven to be an important means to identify compatible donors for sensitized patients. The histocompatibiilty and immunogenetic laboratories use strategies to identify unacceptable HLA antigens for each prospective donor. These antigens are then registered on the database so that individuals expressing these antigens are not considered as compatible donors for a given patient. The computer then performs a virtual cross-match with the registered donors against every blood group-eligible patient on the transplant list. (Reinsmoen et al., 2012) In a study by Appel et al. (2006), virtual crossmatch increased the donor pool for sensitized patients waiting for lung transplants, thus decreasing the average waiting time and death for such patients. The study also concluded that virtual crossmatch eliminates the need for pre-transplant crossmatch and is an effective approach for thoracic organ transplantation. There are now a range of techniques available for the detection and definition of HLA specific antibodies and to interpret the results from the various assays. Special considerations need to be made for broadly sensitized patients due to certain factors that decrease test accuracy. For example, prozoning effects cause a significant underestimation of donor specific antibody. To eliminate the prozoning effect, the patient's serum should be diluted which will reveal the masked antibodies in the patient's serum. (Reinsmoen et al., 2012) Extensive research in the field of immunology and transplant medicine has led to a better prediction of donor compatibility. Recent advancements in this field are majorly focused on desensitization and improving transplant options for broadly sensitized patients. REFERENCES: Appel J.Z., Hartwig M.G., Cantu E., Palmer S.M., Reinsmoen N.L., Davis R.D. (2006). Role of flow cytometry to define unacceptable HLA antigens in lung transplant recipients with HLA-specific antibodies.Transplantation 81(7),1049-1057. Badders J.L., Houp J.A., Sholander J.T., Leffell M.S., Zachary A.A. (2010). Considerations in interpreting solid phase antibody data. Hum Immunol 71(1),S18. DeFranco, A.L., Locksley, R.M., & Robertson, M. (2007). Immunity: The immune response in infectious and inflammatory disease. (1st ed.). United Kingdom: Oxford University Press. Retrieved from http://www.biomedcentral.com/content/pdf/nsp-mhcpolymorphism.pdf Janeway, C.J., Travers, P., & Walport, M. (2001).Immunobiology: The immune system in health and disease.. (5th ed.). New York: Garland Science. Retrieved from 63/http://www.ncbi.nlm.nih.gov/books/NBK271 Reinsmoen, N., Lai, C., Vo, A., & Jordan, S.C. (2012, October 5). Evolving paradigms for desensitization in managing broadly hla sensitized transplant candidates. Retrieved from http://www.discoverymedicine.com/Nancy-Reinsmoen/2012/04/17/evolving-paradigms-for-desensitization-in-managing-broadly-hla-sensitized-transplant-candidates/ Read the full article

[thebrokencrescent-blog]

📆 03 Jan 2020 📰 Identification of antigens presented by MHC for vaccines against tuberculosis 🗞 npj Vaccines

Mycobacterium tuberculosis (M.tb) is responsible for more deaths globally than any other pathogen. The only available vaccine, bacillus Calmette-Guérin (BCG), has variable efficacy throughout the world. A more effective vaccine is urgently needed. The immune response against tuberculosis relies, at least in part, on CD4+ T cells. Protective vaccines require the induction of antigen-specific CD4+ T cells via mycobacterial peptides presented by MHC class-II in infected macrophages. In order to identify mycobacterial antigens bound to MHC, we have immunoprecipitated MHC class-I and class-II complexes from THP-1 macrophages infected with BCG, purified MHC class-I and MHC class-II peptides and analysed them by liquid chromatography tandem mass spectrometry.

We have successfully identified 94 mycobacterial peptides presented by MHC-II and 43 presented by MHC-I, from 76 and 41 antigens, respectively. These antigens were found to be highly expressed in infected macrophages. Gene ontology analysis suggests most of these antigens are associated with membranes and involved in lipid biosynthesis and transport.

The sequences of selected peptides were confirmed by spectral match validation and immunogenicity evaluated by IFN-gamma ELISpot against peripheral blood mononuclear cell from volunteers vaccinated with BCG, M.tb latently infected subjects or patients with tuberculosis disease.

Three antigens were expressed in viral vectors, and evaluated as vaccine candidates alone or in combination in a murine aerosol M.tb challenge model. When delivered in combination, the three candidate vaccines conferred significant protection in the lungs and spleen compared with BCG alone, demonstrating proof-of-concept for this unbiased approach to identifying new candidate antigens.

[annamariyam]

Principles Of Mental Health counselling With Counselor

Notwithstanding a lot of research about center qualities of equipped as well as compelling authority (e.g., cooperation, inspiration, maintaining ability), few research perceives how key principles/techniques for mental health counselling Dubai (MHC) can display insights about able initiative. There are numerous MHC thoughts and strategies (see Sun, 2013) that are important to initiative, four of which are talked about underneath: 

Initial, two key parts of MHC forms comprise of evaluation and intervention. For instance, powerful interventions or choices and activities result from precisely assessing the truth about customers and the internal and outside interacting factors (e.g., the customer's objective conduct, therapeutic conditions, cognizance, inspiration, feelings, and mentalities, history of indications and past interventions, the social, family and ecological variables, interpersonal injury, financial status, work or training, abilities, and stressors, and additionally the constructive elements or nonattendance of the dysfunctions). 

Thus, able pioneers ground their planning, basic leadership, objective setting, desires, and activities on fastidiously and precisely assessing the truth of individuals and settings, including needs, limits, circumstances, rivalries, snags and facilitating factors, as opposed to on starry-eyed thinking or whimsical wants, as well as blind certainty. Second, one of the ordinary interventions in MHC involves case administration by identifying and coordinating accessible administrations/assets for the customers. Moreover, skilled pioneers perceive that providing and allocating assets, including work force, space, time, cash, device, innovation, and different exercises in help of colleagues are fundamental for attaining objectives, goals and desires. 

Third, powerful professionals or advisors in MHC are completely mindful that their master status in the settings is insufficient for generating changes in customer conditions. It is their capacity to comprehend the customer's needs, to involve them in basic leadership, and to engage them with assets that create the coveted changes. Similarly, influential pioneers comprehend that their situation of specialist does not outfit them with the energy of influence, despite the fact that they appear to control reward and discipline for the subordinates. Power originates from empowering the general population by understanding their worries and points of view, recognizing and meeting their requirements and creating chances to understand their maximum capacity, and from a common vision, joint effort, and trust. 

Fourth, equipped specialists or advisors assume liability for the disappointment in reaching treatment objectives, learning from their mix-ups or misconceptions, and not casting fault on individuals who require help. Similarly, able pioneers concede their errors and assume liability for poor execution in the association or organization. In the meantime, they value the individuals' endeavors and comprehend that achievement originates from the joint endeavors, vision, limit, inspiration of the group, of which the pioneer is just a part. 

Then again, incompetent or inadequate pioneers ordinarily show a few or the greater part of the qualities contradictory to those MHC principles, including: 

1. Their objectives and desires depend on pie in the sky thinking or on orders from a higher expert, instead of on assessing the truth of the necessities, individuals, settings, circumstances, and different conditions. 

2. Unconscious that achieving objectives and desires involves identifying and providing assets for the individuals. 

3. Have the figment or false conviction that by delivering orders, using risk or intimidation, the intended outcomes will happen. 

4. Take credits for others' accomplishments while blaming others for the self's incompetence or disappointments. 

Choice to Divorce 

It is extremely normal for individuals on their approach to separation to attempt a round or two of marriage counselling Dubai. Numerous individuals don't think that they have sufficiently attempted to spare the marriage unless they have endeavored marriage counselling without achievement particle saving the marriage. What this post talks about is the utilization of marriage counselling after one of the gatherings has settled on the choice that the marriage is finished. Think about the following situation: 

"Marie and Don have been hitched fifteen years and despondently wedded for five. Marie, similar to such a significant number of other divorcing ladies, has become dynamically baffled with the absence of intimate association or correspondence amongst her and Don. On various events she has begged Don to go to counselling with her however he has dependably won't, insisting that they co0uld work it out themselves. So Marie has been in individual treatment for a long time and has finally chosen that there is nothing left in the marriage. She has told Don and he was stunned. He doesn't need the separation and now begs her to attempt marriage counselling. Be that as it may, now she feels that it is past the point of no return." 

This is an exceptionally basic situation and it can take a few ways. To start with, Marie, the initiator of the separation may consent to have a go at counselling. She has no expectation of fixing the marriage and in reality needs out as fast as would be prudent. Be that as it may, she consents to this false endeavor at what Don views as a conceivable compromise to "demonstrate" to Don that the marriage is lethally injured and can't survive. She seeks that if Don sees this after himself he will be more inclined to work with her toward an agreeable separation. She likewise subtly trusts that if Deon comes apart she will have the capacity to stop him with the advisor who will enable him to get past the procedure. Some of the time things go as Marie arranged and Don comes to concur with her that they would be in an ideal situation separated But now and then the technique reverse discharges.

Counselling In Dubai, Occupational Therapy Dubai, Clinical Psychologist Dubai, Special Needs Center In Dubai, Lady Psychiatrist In Dubai

[coolmedthingstoknow]

Tuning the Immune System into a One Size Fits All Cancer Killing Solution

While immunotherapy has made incredible leaps in the past decade (watch the video here for a better background - note some proteins have interchangeable names), a reliable cure or treatment remains elusive today. However, exciting new research, published in the Nature Journal in March of last year, has revealed what looks like a possible one size fits all solution with the discovery of novel cancer targeting T-cell. These unconventional MAIT cells have a unique way of binding to the cell that does not use the normal HLA system with CD4 and C8, instead using a MHC – class 1 related protein MR1. This new way of interacting with the cell has been seen to have genes that are coded modularly. This type of protein assembly is not new and is seen within voltage gated potassium channels in the brain but allows the MR1 receptor to have a variation in the final structure. The variability opens the possibility for the protein to change what proteins it binds to and, as a result, change signaling.

 Researchers at the Cardiff university school of medicine were able to identify one of these pathways that does not react to antigens from bacteria, but instead recognizes self-antigens resulting in a cytotoxic response to a wide variety of cancer cells. With their initial trials in vitro, the team was able to clone a certain T cell population that they saw react to cancer cells. The big thing being that these cancer cells were from a different donor with a unique HLA protein. When these cells were cloned and introduced to eight different types of cancer, a strong immune response was recorded within days for all samples.

 Labeled MC.7.G5, the lab sought to find out how these new T cells operated. With Crisper-Cas9, a gene editing technology that uses the Cas9 protein to unravel and identify gene sequences in DNA, they discovered the MR1 protein to be the main point of interaction. To confirm this finding, they utilized CRISPR again to perform a “knockout mutation” which involved the Cas9 protein removing one base pair in the DNA to prevent the cell from making the MR1 protein. The result was the new T cell completely ignoring the cancer it once attacked. When moving in the opposite direction, MC.7.G5 produced an even stronger response which confirmed the importance of the interaction.

 Unfortunately, the team could not completely lock down how exactly the interaction was happening. To get a picture of the structure of MR1, stains were introduced that would bind with and highlight certain structures in organic molecules. After staining failed, CRISPR was revisited and know mutations were inserted into the gene sequence to try to alter the protein. If there was a change in the immune response after one of these mutations, then the scientists would know they had changed the active site of the protein and could figure out where it was. However, even these mutations came up empty. The team could have just tried to crystalize the whole structure. Yet the crystallization process is incredibly difficult, and without even knowing what interactions are taking place, there was a risk the right protein could be missed entirely.

 Unable to pinpoint the mechanism, the team moved on to focus more on possible interactions with healthy cells. If MC.7.G5 was attacked when a normal cell was inflamed or damaged, using it in humans could prove deadly to the patient. When placed into a mix of healthy, cancerous, and cancer cells with the MR1 protein removed, the new T cell still managed to kill more that 95% of the tumor with MR1 intact. To look at cells under stress, the tube was bathed with hydrogen peroxide – a chemical that is known to split cell membranes and kill cells. Damaged cells in these conditions were again ignored by the T cell. Furthermore, MC.7.G5 would not interact with non-cancerous cells even when healthy cells over expressed MR1. leading to believe that there is some specific property that is needed for an immune response tied to cancer. This could be the variability brought on by the modular structure of the protein. It could also be different co-stimulators or cytokines working to regulate activity.

 What’s also so exciting about the new MR1 protein is its monomorphic properties. This means the protein does not change from human to human. Crisper sequencing also saw the presence of a Beta2M complex which forms combines with MR1 to stabilize and unify the presenting antigen making MR1 a very reliable pathway for this T cell to invoke a response. MR1 is so stable, that it’s detected cross species giving rise to questions that this protein could be an important evolutionary advantage and not just a random mutation. This discovery also clears the way for easy research and development for future treatments and allowed the researchers to test their newfound T cell in mice.

 Leukemia was picked as the trial cancer in the test mice and survival was assessed by monitoring body weight. After the mice lost 15% of body weight, they were put down and their bone marrow was looked at. Two weeks after the cancer and novel T cells were introduced, the mice had a shockingly low percentage of cancerous cells while the control mice had tumors that had taken over most of their bone marrow. Unfortunately, even with low variability, the sample size of mice was very small. Nevertheless, the study was able to translate very promising results from the lab bench to an organism giving high hopes for future experiments.

 It’s easy to get excited about what this means for future cancer treatments. The discovery of an immune cell that can selectively destroy a wide variety of tumors with great precision would erase the need for surgery, radiation or the need to tailor treatments bringing costs down. A cell like this could even be used in the development of a vaccine in the future. However, the work is far from over. The selectivity of the immune response to cancer cells suggests that there is a protein that helps to only identify the desired cells. Once the mechanism is mapped and the protein structure emerges, there is real potential that drugs could be developed to work without the need of a MC.7.G5. injection. An inorganic solution means cancer could one day be cured by an over-the-counter pressed pill prescribed over the phone. The cure for cancer, which seemed so out of reach just a couple years ago, now seems to be right around the corner. I personally can’t wait.

 Original Paper

Crowther, Michael D., et al. “Author Correction: Genome-Wide CRISPR–cas9 Screening Reveals Ubiquitous T Cell Cancer Targeting via the Monomorphic MHC Class I-Related Protein MR1.” Nature Immunology, vol. 21, no. 6, 2020, pp. 695–695., https://doi.org/10.1038/s41590-020-0640-6.

[copperbaker39]

The Sarm Holy Bible.

Ostarine

Content

Kate Somerville Peptide K8 Power Lotion.

Production Of Bioactive Peptides By Lactobacillus Species: From Gene To Application.

Peptides Established Of 12 ₤ 220.

What Are Sarms?

Vip Whatsapp Team For Inner Promotions And Sarms Online Forum.

The partner or combining particle may be carbohydrate or non-carbohydrate in nature. If the outcome of UCPCR runs out maintaining with various other scientific finding then we would certainly recommend duplicating the test particularly if it is suddenly reduced. People tipping out boric acid preservative from urine collection tube, in an example taking greater than 3 days to reach the laboratory can lead to unnaturally low outcomes. A control experiment is one that is treated in the same way as an actual experiment, however is not exposed to the speculative agent. There are two kinds of controls for experiments, positive and also unfavorable controls.

Nate Diaz tested positive for trace amounts of a SARM, not suspended for UFC 244 - Bloody Elbow

Nate Diaz tested positive for trace amounts of a SARM, not suspended for UFC 244.

Posted: Fri, 25 Oct 2019 07:00:00 GMT [source]

It is a weird kind of glycosidic bond in which the sugar moiety is attached straight to the carbon atom of the other molecule. It is formed as a result of the response between the carbonyl team of a sugar particle and an alkyl substance like methane and so on . This bond is developed as a result of a response between the carbonyl team of a carbohydrate or its derivate and also a hydroxyl team of a few other substance. The carbonyl group of carb might be a part of an aldehydic group or a ketonic group. A molecule of water is released in this procedure, making it an irreparable reaction. It is a main bond or a covalent bond that offers to connect carbohydrates to other groups or particles.

Kate Somerville Peptide K8 Power Cream.

This slide collection is appropriate as an intro to the subject of peptide ligands. When the charge is related to the electrodes, the various amino acid will certainly move at different speeds to the corresponding electrode. The rate at which they move as well as to which electrode they take a trip to is recorded as well as compared on the glass substrate. Series of bands are developed from their motions which are called Electropherograms. Electropherograms are lines that are created from the motion of the healthy proteins to the electrodes. is the molecular mass of the neutral N-terminal group, is the molecular mass of the neutral C-terminal team, is molecular mass of the neutral amino acid deposits. To acquire m/z values, add or deduct protons as required to get the required charge as well as divide by the variety of fees.

The types of piece ions observed in an MS/MS spectrum rely on lots of variables consisting of main sequence, the quantity of inner power, exactly how the power was introduced, cost state, etc . The approved nomenclature for fragment ions was very first suggested by Roepstorff and Fohlman, as well as consequently modified by Johnson et. Along with the structural characterisation of healthy proteins the center also provides high-throughput protein-ligand testing. Commonly, 10-20μM of protein is required with a 100-fold excess of ligand Using automation multitudes of compounds can be swiftly screened. Hits can be further verified making use of protein-detect methods (1H-15N or 1H-13C HSQC).

Manufacturing Of Bioactive Peptides By Lactobacillus Varieties: From Genetics To Application.

A positive control experiment is one that uses a representative understood to generate a measurable and well recognized effect on the system. In contrast, an adverse control experiment is one that makes use of the same treatments as the real experiment, however has no additional treatment or utilizes an agent that is anticipated to be inactive. Kathy Taylor-Brewin of Biography Active Elegance is a specialist in peptide skin care, distributing the Hydropeptide array in the UK.

To obtain a2-, subtract 2 protons from the Mr worth for an as well as divide by 2. The structures showed above recommend ions with a single positive charge. Mascot likewise consists of assistance for adverse ions, as well as the unfavorable ion types are the same as positive, however with one proton per fee deducted instead of included. We welcomefeedbackconcerning any kind of added ion types that must be taken into consideration. One of the most bountiful fragment ion types observed in MALDI-TOF PSD are a, b, and also y. If accident gas is made use of, after that the ranges look like high energy CID.

Peptides Established Of 12 ₤ 220.

" Hydropeptide integrates each classification of peptide in its VLR technology," comments April Zangl, Chief Executive Officer of Hydropeptide. " VLR technology is made to improve peptide efficiency optimising anti-ageing results. Comparable to a lock as well as secret, peptides call for a certain range, concentration degree and repetition for noticeable age opposing outcomes. N-terminal professional B-type natriuretic peptide (NT-proBNP) is a non-active peptide released along with the active peptide hormone BNP when the wall surfaces of the heart are extended or there is pressure overload on the heart e.g. by liquid overload. BNP then acts upon the kidneys triggering fluid as well as sodium loss in the pee as well as moderate vasodilation so launching the pressure.

Furthermore, more studies are needed in connection with the possible use of collagen supplements in skin problem like eczema. As a matter of fact, collagen is thought to compose around 75% of our skin's completely dry weight. Kind I collagen is crucial for skin flexibility as well as stamina, and a loss of collagen in the skin, which happens naturally with aging, can result in wrinkles. Hydrophobic interactions are important in maintaining the tertiary and also quaternary structure of healthy proteins. The variety of hydrogen bonds formed by an electronegative atom depends upon the variety of totally free electrons present in its outer covering. Oxygen has two cost-free electrons and thus can create 2 hydrogen bonds while nitrogen forms just one hydrogen bond because of one free electron.

What Are Sarms?

Glycosidic bond undertakes deterioration in a process called glycolysis. It is a hydrolytic process in which a water molecule is utilized to break the glycosidic bond as well as release the carb and various other residues. The substances with S-glycosidic bonds are called S-glycosides as an example Sinigrin. It is a harmful compound found in some plants like seed of black mustard etc . In this sort of glycosidic bond, the sugar residue is affixed to the sulfur group of the non-carbohydrate compound. It is developed when the carbonyl team of sugar reacts with the thiol (- SH) group of the other compound.

What is Ostarine used for?

Ostarine is used by mouth to improve athletic performance and for involuntary weight loss in people who are very ill, also known as cachexia or wasting syndrome.

There are no well-known medication interactions and we do not yet recognize what the most effective dose of collagen is. Research studies have used everyday doses of in between 1-- 10 g collagen hydrolysate as well as 0.1-- 10 mg of chicken or bovine kind II collagen. It's been recommended that taking collagen hydrolysate can enhance the signs and symptoms of osteo arthritis by promoting your body's manufacturing of joint collagen. Rather than MHC course I, MHC course II particles do not dissociate at the plasma membrane. The systems that manage MHC course II deterioration have not been developed yet, however MHC class II molecules can be ubiquitinised and then internalised in an endocytic pathway.

Vip Whatsapp Group For Inner Promos And Also Sarms Forum.

Austria bpc157 how does it work of basic NMR ranges extracts from a couple of mins to 3/4 days for every experiment. A complete collection of experiments for protein structure decision typically takes concerning 7-14 days. When it comes to reasonably small healthy proteins, current innovative multidimensional information acquisition plans have been successfully used to decrease speculative acquisition time by approximately an order of magnitude or more. There was no evidence of increased side-effects in individuals taking kind II collagen, although trials did report individuals withdrawing due to the fact that they thought the collagen had not been improving their symptoms. Although individuals in both groups enhanced in the kind II collagen and also methotrexate test, the methotrexate individuals revealed the best enhancement.

Is SARMs considered natural?

Short for selective androgen receptor modulators, SARMs are synthetic drugs designed to have effects similar to those of testosterone. SARMs are still in the research and testing stages for various medical conditions but have not been approved yet for any other use.

It can form extra phosphodiester bonds at both ends due to having a complimentary hydroxyl team at the 3' end as well as a complimentary phosphate group at the 5' end. The ester affiliation is a really high-energy bond launching a remarkable amount of power upon hydrolysis. Like the remainder of the bonds talked about previously, it is additionally damaged down by incorporating a water particle.

Fragments will only be spotted if they carry at least one charge. If this cost is kept on the N incurable piece, the ion is classified as either a, b or c. If the charge is retained on the C terminal, the ion kind is eitherx, y or z.

Hormone or peptideMajor cells places in the gutPrincipal recognized actionsGastrointestinal peptides, their website of expression as well as significant functions. The gastrointestinal hormones make up a team of hormones secreted by enteroendocrine cells in the tummy, pancreatic, and also tiny intestine. This team of hormones regulate different functions of the digestion organs. This 60-slide slide collection available from Slideshare.net gives a great introduction of endogenous peptides and also choose instances of useful drugs. Medications reviewed consist of those that imitate the impacts of endogenous peptides and also those that are villains.

All ion collection can be come with by composition dependent satellites as a result of loss of ammonia or water. Collision induced dissociation of ions at keV energies can generates extra ion types because of side chain bosoms,. Keep in mind that these frameworks include a single charge carrying proton. In electrospray ionisation, tryptic peptides usually lug 2 or even more fees, to make sure that piece ions may carry more than one proton.

Cardarine is a pharmaceutical grade PPAR agonist which has some extremely useful effects for professional athletes.

Because some SARMs are best for bulking as well as others are shown to be specifically efficient for cutting, they're sometimes combined, or stacked, in research studies.

These manufactured SARM-derived metabolites can conveniently be utilized as reference standards for routine mass spectrometry-based doping control analysis of at the very least three generally used performance-enhancing drugs to unambigously recognize misbehavior.

RAD 140 SARM-- a SARM with effective anabolic impacts for improving muscle development, as well as appealing benefits for your mind.

We have actually made a team where sarms users can share their progress, experiences as well as to talk with each various other concerning their cycles and also progress.

view site will be noticeably lowered which means you can boost the intensity and period of your exercises.

An ester bond is formed when a molecule having the carboxylic group responds with an additional molecule having a hydroxyl group. The carboxylic group loses its hydrogen as well as oxygen while the alcohol loses hydrogen of its hydroxyl group. Consequently, a water molecule is released, and the two carbons are linked using an oxygen bridge creating a -COC- link.

[batphone2]

Are Sarms Anabolic Steroids, Are Sarms Anabolic Steroids

Mhc Class Ii Restricted Recognition Of Fmdv Peptides By Bovine T Cells

Content

Dear Daniela: What Do Peptides Do For Skin.

Natural Solvent Nano Ltration In The Peptide Industry.

S23 Sarm Sarms S.

Survival Of Eggshell Peptides Over Numerous Years In Africa Is Because Of Mineral Binding.

In plain English, MK-677 increases GH to provide you increased gains and super dimension. Plus, MK-677 works to enhance rest quality and promote cravings, making it a must have for those who want to gain weight. We comprehend that you may alter your mind about obtaining these sorts of e-mails or texts so you can ask us to stop any time. Just adhere to the unsubscribe link on any kind of advertising interaction we send to you as well as we will immediately remove you from our database. This will just relate to information you have actually provided in accordance with registering to advertising and marketing services.

Ostarine or MK-2866 (CAS #) is a research study chemical developed originally by Merck Inc. as well as now possessed by GTx Inc

. MK-2688 comes from a class of chemicals referred to as SARMs or careful androgen receptor modulators.

For the initial team, use, muscle mass development, will be excellent SARMs like Rad-140 or Andarine S4.

MK-2866 is undergoing medical tests for and may eventually be clinically shown as well as authorized for avoidance of cachexia, atrophy, and also sarcopenia largely in the senior as well as ill populace.

In our SARMy shop you will certainly obtain both items from other widely known manufacturers and also the finest quality supplements developed by us.

If you educate intensively and also wish to substantially boost the impacts of exercise, you need to take into consideration examining the supplements from the SARM team.

Contrasted to testosterone, the sex hormonal agent, the advantage of SARMs such as MK-2688 is that they do not have androgenic task in non-skeletal-muscle tissues.

While we might expect specialist athletes to dope in pursuit of monetary gain as well as magnificence, all three of these cases were located in a specific niche area of cycle auto racing-- time trial. Anabolic steroids are Prescription Only medicines under the Medicines Act. They can only be offered by a pharmacist on the discussion of a physician's prescription. Use performance enhancing drugs has been going on ever since the Olympic Gamings of ancient Greece. Anabolic steroids were initially utilized by athletes in the mid 1950s and also by the 1960s their use prevailed.

Dear Daniela: What Do Peptides Provide For Skin.

A steroidal SARM that is presently no more in development by the companies that worked together. In trials, it demonstrated a propensity to increase liver enzymes which recommended it was perhaps causing liver damage. I found it was the only SARM to increase water retention significantly. Ostarinebinds to androgen receptor cells as well as promotes the protein synthesis procedure enabling muscle tissue to construct and stops any restriction on the amount of muscle mass tissue formed. SARMs outcomes have actually been scored out of 5 for toughness, fat loss and suppression with one being the very least efficient and also five suggesting a substantial change. There are several kinds for different factors with the explanation showing up quickly.

It enhances the flow of red blood cells as well as oxygen to the muscle mass for even more power as well as power. Health and wellness isn't just a concern for badly made medications either-- also "legit" PEDs are often lethal by nature. Popular steroids such as GW have actually been studied and also discovered to have strong causal links to cancer. Testosterone, hGH, clenbuterol and also EPO work with the entire cardiovascular system. EPO raises choose a Buy peptides Direct Denmark , which means more oxygen can be transferred from the lungs to muscles, offering you a more effective overall system.

Natural Solvent Nano Ltration In The Peptide Industry.

Below is a summary of just a few of the several kinds that have shown benefits as well as the particular side effects that were found in our study. With PMag the beginning of crazy pumps is relatively quick but no such point was experienced with LGD. I obtained approx 5kg mass (fat+ muscle) on Pmag as well as have not seen any such body composition distinction with LGD. I began taking these and I can see gains being made after the initial week. I have attempted afew sarms now and also saw the best gains on these without a doubt.

FDA issues consumer warning on sports products that contain SARMs - NutraIngredients-usa.com

FDA issues consumer warning on sports products that contain SARMs.

Posted: Wed, 08 Nov 2017 08:00:00 GMT [source]

I do not normally create evaluations and also this website doesn't appear to award when you do, not a problem, however I have found these reviews useful to for my very own ends so wished to share the love. Gents, go down the reps, up the weight and keep the rest periods conservative however sincere. To me that's just how I educate, add this treasure with some MK667 (little endurance - more helping the added appetite not most likely to pure fat). It is not a wonder cure, but it will certainly permit you with bad to reduced incongruity, make gains, as constantly reduce all outdoors variables as well as this point is tremendous. Simply image what could occur if you went full-bore as well as were a perfectionist?

S23 Sarm Sarms S.

Anabolic steroids have a limited medical use in the UK, generally in the treatment of anaemia. They are not to be perplexed with corticosteroids which are commonly made use of for a variety of clinical problems.

How long does Ostarine stay in your system?

However, the study demonstrated that a single oral dose of as little as 1 μg can be detected for up to 9 (5) days by monitoring ostarine (glucuronide), and hydroxylated metabolites (especially M1a) appear to offer a considerably shorter detection window.

Data offered other purposes will continue to be in our systems in accordance with this plan. We gather a wide variety of details as well as the kinds we accumulate from you will certainly vary dependent on whether you're an individual client, another organization, purchasing a product or a solution or participating in a promotion or competition. Below are the kinds of details we might gather once in a while together with resources which inform you where we might obtain the information from. In conclusion Ostarine is one of the buysarmsukproducts you will certainly use to build your muscles. The product assists in rapid muscular tissue growth, it likewise boosts athleticism, raises bone thickness, as well as much more. When you are acquiring the item make certain to think about the website you are buying it from.

Survival Of Eggshell Peptides Over Numerous Years In Africa Results From Mineral Binding.

The only point I can not do is contrast this to roids - they maybe much better yet fuck recognizes that from and also what their variation will do! , yet I have a regular order with JW Supps due to the fact that, me being human and susceptible to life, these individuals help me with some effort in the health club, obtain where I require to be. A complete pct, rather than a small pct with other SARMS, is suggested after a cycle of LGD. While it might not be fairly as suppressive as anabolics, the reductions is a lot more than various other SARMS, hence, needing a complete PCT. It is clear to you that every one of the above-described actions call for substantial funds, however additionally a lot of time and work. Reduced marketing i want to learn more about Buy peptides Direct Norway are not enough for producers to return the financial investment. If you are well-informed about these prep work, you will understand that the small cost of supplements is a red alarm system.

Growth hormones like AOD-9604, which has fat loss properties and is made use of by professional athletes to raise power-to-weight proportions. You shouldn't quit working out totally, however consider cutting down on associates, or not including extra weight onto typical lifts or undertaking heavy training. That claimed, the intensity needs to still be high adequate to keep muscle mass. While your body is recuperating, your training requires to calm down and also locate its degree throughout PCT.

Dietary Supplements.

Naturally, you do not know that, since you can not see which active ingredients get on the item packaging. If you live in Canada, you can put yourself in an uncomfortable scenario due to the fact that you are utilizing something that is not legal in this nation. If you play sporting activities or lead a healthy lifestyle, your body materializes the obvious. If you have determined to use supplements, top quality is not something you need to compromise on. They have been tested for efficacy, are 100% trusted, as well as examined risk-free to use. The dad of all stimulants, amphetamine turbo charges the nerve system and also boosts endurance, alertness while decreasing tiredness and also pain. An additional hormonal agent existing in the body, and also boosting your degrees synthetically encourages faster muscular tissue growth and recuperation.

CRN helps to shine light on SARMs epidemic - NutraIngredients-usa.com

CRN helps to shine light on SARMs epidemic.

Posted: Fri, 16 Mar 2018 07:00:00 GMT [source]

Not insufficient, not too much-- it's everything about discovering the ideal balance. Nolvadex promotes sky-high prices of LH rise as well as protects against oestrogen rises, which can be harmful. Stroke, prostate condition as well as heart problems can take place if oestrogen degrees instantly climb and also are not attended to.

Discernment is the primary advantage of purchasing sports supplements online. Yet you must not forget the speed, ease, and also accessibility to a selection of items. As for SARMs, you can order them from both Canadian and foreign web sites. The only certified physical suppliers for SARMS are supplement stores throughout Canada. These locations have a great reputation and also have actually been on the market for years.

What is SARMs rad140?

SARMs. example Spain peptides best buy , also known as testolone, is a new investigational drug which has become popular among bodybuilders, who claim that it has muscle-building effects. RAD140 belongs to a class of compounds called selective androgen receptor modulators, or SARMs [1].

Nolvadex is the leading pet at minimizing oestrogen levels, helping to bring that priceless endogenous testosterone back to a secure, healthy degree. Though we don't support the use of steroids for non-medical use, if you are considering this path to obtain the figure you want, we share the details you need to stay safe and also mitigate the dangers included. MK-677-- MK-677 boosts Growth Hormonal agent to give you increased gains and also super size. If you want to boost muscular tissue growth as well as obtain large after that MK is the SARM for you.

Ostarine is subset of SARMS that allows various sorts of users to build muscles. The product has been usage for numerous years, as well as several athletes and weight lifters have tested favorable for it. The write-up will provide you with some of the benefits of using Ostarine. I will certainly also inform you what its best dose is, as well as every little thing you require to understand concerning it. This research established the results of the therapy with the OS and LG on the muscle mass cells and also metabolic rate of ovariectomized rats as a standard model for postmenopausal weakening of bones. Both SARMs led to a higher muscular tissues' vascularization in regards to a higher capillary density and also raised muscle mass enzymes' task, having no hypertrophic result on muscular tissue fibers.

You can be sure that they do not market phony products or supplements of questionable quality. Makers of phony supplements put lots of hazardous substances in these items.

[malaria-mankind-blog]

Malaria and Mankind: Host-Parasite Coevolution and Public Health

Introduction

Malaria is a disease that is caused by species of Plasmodium in humans, and as a parasite, it has coevolved with the hominid immune system since before Homo sapiens became a species. The Plasmodium genus is largely made up of parasites that specialize in feeding on birds and mammals, and the Plasmodium species that infect modern humans are ovale, malariae, falciparum, vivax, and more recently, Plasmodium knowlesi (Ollomo et. al, 2009). The disease that results from these parasites kills around half a million people a year, most of whom are on the African continent (WHO, 2006). The parasitic coevolution of the Plasmodium genus and humans, as well as their phylogenetic predecessors, is an essential aspect of understanding the modern malarial disease process and how to reduce Plasmodium case count and mortality rate; knowing how the Plasmodium parasite has undergone natural selection for virulence and contagion to combat the human immune system can offer insight into the current state of the disease. The coevolution of malaria and its host can also provide insight into the development of human immune responses, such as in the case of sickle cell trait, and the evolution of drug-resistance.

Figure 1: phylogeny of Plasmodium species featuring the recent development of human virulence in P. knowlesi. Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680981/

 Malaria Today

Malaria’s current disease process revolves around vector transmission and development of schizonts; infected liver cells in which immature trophozoites (protozoa) feed and eventually rupture through the cell membrane. Figure 2 demonstrates the lifecycle of the Plasmodium protozoan when infecting a human host.

Figure 2: life cycle of malarial parasites in human hosts and mosquito vectors. Via the Center for Disease Control; https://www.cdc.gov/malaria/about/biology/index.html

For the host, the erythrocytic stages of this cycle result in the symptoms most associated with malarial infection; anemia, high fever, shaking chills, muscle aches, vomiting, and bloody stool can all be traced back to the destruction of erythrocyte membranes and schizont development.

Western medical practices, epidemiological research, and effected populations have found treatments and prevention methods to reduce the spread and mortality rate of malaria; currently, Artemisinin is a common antimalarial medication, and prevention methods largely focus on vector control. In this case, the vector of the malarial parasite is another parasite; female Anopheles mosquitoes (WHO, 2016). Mosquitoes are present throughout most tropical and temperate climates, especially areas with high precipitation. Mosquitoes breed in standing water and feed by extracting blood from their animal hosts by injecting a needle-like organ, called a proboscis, into a blood vessel and storing extracted blood in their gut. Mosquitoes consume multiple blood-meals a day, and when they feed on a malaria-infected person, if the malarial protozoa have entered the erythrocytic stage, the mosquito can carry the protozoa present in the red blood cells to their next host. From there, the newly introduced Plasmodium will incubate and reproduce in the liver, eventually spreading to the hemoglobin and beginning the cycle of infection again when the host is parasitized by a mosquito. Controlling vector transmission is the most accessible form of preventing malaria in most communities; DEET spray, mosquito nets, and clearing standing water have proven to be effective preventative measures against these vectors.

Host-Parasite Coevolution and Medicine

Like bacterial infection, malarial parasites have a fast generation time and are selectively pressured by the human immune system (Hill, 1997). This selective pressure combined with the development of drug-resistant malaria produces a complex problem for modern medicine, but the selective pressures that have influenced the evolution of the malarial parasite can also provide insight into how to develop a vaccine and treatment. Antimalarial medication was originally administered in the form of quinine, followed, but not entirely replaced by, many other medications up to the most recently used artemisinin, and the malarial parasite has developed, in many cases, resistance to these drugs except for artemisinin (WHO, 2003). The influence of natural selection in the development of resistance in malarial protozoa can be seen in the speed at which medications become obsolete in treatment; the first case of quinine resistance was recorded in 1910, and since then six different drugs have been rendered obsolete by Plasmodium and its evolution. Currently, medical treatments rely on artemisinin combined with a partner antimalarial drug.

The development of drug resistance in the malarial parasite makes understanding the host-parasite coevolution between it and hominids that much more paramount. Plasmodium species have highly variable protein-producing genes that can counteract the human immune system and have been selectively pressured over coevolutionary time to do so (Evans & Wellems, 2002). The erythrocytic stage is the most difficult stage of the parasite’s development for the human immune system to respond to because the parasite resides within red blood cells; although with other diseases the immune system can distinguish between infected and normal cells, malaria’s selected-for ability to disguise its chemical signal from the immune response makes it very difficult for the immune system to find and eliminate infected cells. The P. falciparum species of malaria produces a circumsporozite protein (i.e. PfEMP1) to enter and eventually destroy the cell membrane from within. This protein has a high genetic variance; it has multiple forms that each require a specific response from the immune system to combat, and the generation time of P. falciparum is low enough that new effective forms of the TH2R and TH3R genes that produce the circumsporozite proteins are quickly selected for, often outpacing the immune response of the host. In the liver, where the parasite first develops and reproduces, P. falciparum has been selectively pressured by the human immune system to suppress the chemical signals associated with protein development and release, subverting immune detection and avoiding killing lysis by cytotoxic lymphocytes in the organ (Hill et. al., 1997).

Outside of sickle-cell trait, occurrences of human resistance to malaria shed a relatively dim light on the genetic influences on immune system efficacy, as humans as well have a deeply complex and variable genetic code relevant to the immune system. Twin studies and other observational studies have been performed and found connections between the genes that control vitamin D incorporation and malarial resistance, as well as more specific genes that effect lymphocyte efficacy such as major histocompatibility complex (MHC) and human leucocyte antigen (HLA) genes (Hill et. al., 1997). These genes determine the efficacy of lymphocytes and other immune-responses, and therefore are a selective pressure on the TH2R and TH3R genes that produce cell-membrane destroying circumsporozite proteins in the malarial parasite. These genes have undergone mutual selective pressure since their respective species began interacting and are an important focal point in researching vaccines and human resistance to the malarial parasite as well as their evolutionary development.

My Opinion

Research into the genetic influences and interactions between the malarial parasite and the human host could lead to the development of vaccines (for malaria there are very few) and a deeper understanding of human susceptibility to malaria. The circumsporozite proteins produced by the TH2R and TH3R genes have been considered in the Hill study as potential sources of a vaccine, as providing a nonvirulent copy of the protein to the immune system could provide lymphocytes in the liver and other immune responses a chance to recognize the normally difficult-to-detect chemical signals released from the parasite during schizont development and cell membrane rupture. The well-known example of sickle-cell trait as a defense against malaria represents the medical potential of research into the MHC and HLA genes; sickle-cell creates an environment physically uninhabitable for malarial parasites but poses a double-edge in its homozygous form of sickle-cell anemia. This trait’s dimorphism poses a health risk, but the MHC and HLA genes haven’t been found to create autoimmune issues. Researching the MHC, HLA, TH2R, and TH3R genes as well as their interactions over generational time using archaeological evidence and long-term observational studies of malaria-exposed populations would result in a greater understanding of the host-parasite coevolution and therefore potentially provide an opportunity to develop a widely available vaccine, and an opportunity to calculate and prepare for susceptibility to malaria in different populations.

Bibliography

1.  Allison, A. C. “GENETIC FACTORS IN RESISTANCE TO MALARIA.” The New York Academy of Sciences, John Wiley & Sons, Ltd (10.1111), 15 Dec. 2006, nyaspubs.onlinelibrary.wiley.com/doi/epdf/10.1111/j.1749-6632.1961.tb31102.x.

2. G., Andrew, and Thomas E. “Coevolutionary Genetics of Plasmodium Malaria Parasites and Their Human Hosts 1.” OUP Academic, Oxford University Press, 1 Apr. 2002, academic.oup.com/icb/article/42/2/401/652729.

3. Hill, Adrian V.S. et. al., “Genetic Analysis of Host-Parasite Coevolution in Human Malaria.” Royalsocietypublishing.org, 1997, royalsocietypublishing.org/doi/pdf/10.1098/rstb.1997.0116.

4. Mahanta, Anusree et al. “Integrative Approaches to Understand the Mastery in Manipulation of Host Cytokine Networks by Protozoan Parasites with Emphasis on Plasmodium and Leishmania Species.” Frontiers in immunology vol. 9 296. 23 Feb. 2018, doi:10.3389/fimmu.2018.00296

5. Ollomo, Benjamin, et al. “A New Malaria Agent in African Hominids.” PLoS Pathogens, Public Library of Science, May 2009, www.ncbi.nlm.nih.gov/pmc/articles/PMC2680981/.

6. V., Christopher. “Evolution of Drug-Resistant Malaria.” OUP Academic, Oxford University Press, 1 Apr. 2009, academic.oup.com/trstmh/article-abstract/103/Supplement_1/S11/1908160.

7. “Why Is It Important to Combine Malaria Drugs?” World Health Organization, World Health Organization, 15 Mar. 2012, www.who.int/features/qa/33/en/.

8. “Do All Mosquitoes Transmit Malaria?” World Health Organization, World Health Organization, 19 Apr. 2016, www.who.int/features/qa/10/en/.

9. History of Antimalarials | Medicines for Malaria Venture, www.mmv.org/malaria-medicines/history-antimalarials?gclid=CjwKCAiA27LvBRB0EiwAPc8XWQAMdrQrGPS_zT9H2wuebWyeuqFsb452jyqkrKe6nVaNJFgnC3D_6hoCIKQQAvD_BwE.

[nursingwriter]

Transplant Medicine The Major Histocompatibility Complex (MHC) contains over 128 functional genes. This is the densest part of the human genome and is responsible for most autoimmune diseases. This region also determines vaccine responsiveness, adverse drug reactions, disease progression and transplant rejection. The MHC genes are multigenic with a high degree of allelic polymorphism. There are over 7,500 different alleles and over 5,458 expressed MHC antigens currently known. (DeFranco, Locksley & Robertson, 2007). Genomic evolution and HLA screening have been extremely profitable to Transplant Medicine. A brief analysis of MHC variability reveals two classes of antigens belonging to this complex; class I (A, B, and C) and II (DR, DQ, and DP). Both classes of molecules are expressed in a co-dominant fashion. These molecules are designed to recognize antigens that are foreign to the body and present them to the T cells. (Janeway, Travers & Walport, 2001) The co-dominant mode of inheritance of MHC genes assures that each individual will have a distinct antigen on their cell surface. This forms the basis of graft rejection. Once a foreign antigen enters the human body, activation, proliferation and differentiation of lymphocytes into effector cells continues until the foreign antigen is eliminated, after which the immune system returns to its quiescent state and an immunologic memory is generated. (Janeway, Travers & Walport, 2001) Tissue typing to match HLA antigens is an important step before transplantation. In general, the larger the number of matched MHC alleles between the donor and the recipient, greater are the chances of graft survival. However, routine HLA typing focuses only on HLA-A, B and DR antigens because these are the only loci that appear to predict the likelihood of graft rejection. (Janeway, Travers & Walport, 2001) The extreme polymorphism of the MHC genes poses several challenges in recognizing the perfect donor, thus complicating HLA typing. The HLA nomenclature differs with the type of typing method used. Refinement of the serological typing of HLA antigens through the years has led to the identification of additional gene loci, which were previously thought to yield one antigen. For example, the B. 60 and B. 61 antigen were previously thought to be one antigen, the B. 40, based on their common ability to bind to a shared public epitope. Moreover, serology does not recognize heterogeneity of HLA antigens, as confirmed by DNA sequencing. Thus serological nomenclature is not representative of the true heterogeneity of the HLA system. HLA typing through this method may lead to a greater risk of graft rejection. (Badders, Houp, Sholander, Leffell & Zachary, 2010) Further more, three different nomenclatures exist for defining HLA antigens. It is important to be able to appreciate the differences of each molecular typing nomenclature and to know which system is being used in the laboratory. Failure to do so may result in missed recognition of a donor specific antibody. (Badders et al., 2010) Apart from the likelihood of graft rejection, recipients are faced with several challenges, such as prolonged waiting times and donor shortage, especially for sensitized individuals since they have additional immunological barriers. From 2000-2008, a total of 243,662 candidates were on the waiting list for kidney transplantation, with only 62,622 available donors in the United States. The broadly sensitized patients have average waiting times twice that of un-sensitized patients. It has been observed that the proportion of patients that are broadly sensitized have been increasing through the years. (Reinsmoen, Lai, Vo & Jordan, 2012) Sensitization to HLA antigens occurs through exposures from blood and platelet transfusions, pregnancy and previous transplants. Examining the sera of patients against cells from a panel of HLA typed donors can identify sensitized individuals. The results are used to calculate panel reactive antibodies (PRA) or the percentage of population that the anti-human antibody, present in the blood, reacts with. Sensitized individuals have a higher PRA and are less likely to receive organ transplants due to an increased risk for immediate graft rejection. (Reinsmoen et al., 2012) Calculated PRA and virtual cross-match have proven to be an important means to identify compatible donors for sensitized patients. The histocompatibiilty and immunogenetic laboratories use strategies to identify unacceptable HLA antigens for each prospective donor. These antigens are then registered on the database so that individuals expressing these antigens are not considered as compatible donors for a given patient. The computer then performs a virtual cross-match with the registered donors against every blood group-eligible patient on the transplant list. (Reinsmoen et al., 2012) In a study by Appel et al. (2006), virtual crossmatch increased the donor pool for sensitized patients waiting for lung transplants, thus decreasing the average waiting time and death for such patients. The study also concluded that virtual crossmatch eliminates the need for pre-transplant crossmatch and is an effective approach for thoracic organ transplantation. There are now a range of techniques available for the detection and definition of HLA specific antibodies and to interpret the results from the various assays. Special considerations need to be made for broadly sensitized patients due to certain factors that decrease test accuracy. For example, prozoning effects cause a significant underestimation of donor specific antibody. To eliminate the prozoning effect, the patient's serum should be diluted which will reveal the masked antibodies in the patient's serum. (Reinsmoen et al., 2012) Extensive research in the field of immunology and transplant medicine has led to a better prediction of donor compatibility. Recent advancements in this field are majorly focused on desensitization and improving transplant options for broadly sensitized patients. REFERENCES: Appel J.Z., Hartwig M.G., Cantu E., Palmer S.M., Reinsmoen N.L., Davis R.D. (2006). Role of flow cytometry to define unacceptable HLA antigens in lung transplant recipients with HLA-specific antibodies.Transplantation 81(7),1049-1057. Badders J.L., Houp J.A., Sholander J.T., Leffell M.S., Zachary A.A. (2010). Considerations in interpreting solid phase antibody data. Hum Immunol 71(1),S18. DeFranco, A.L., Locksley, R.M., & Robertson, M. (2007). Immunity: The immune response in infectious and inflammatory disease. (1st ed.). United Kingdom: Oxford University Press. Retrieved from http://www.biomedcentral.com/content/pdf/nsp-mhcpolymorphism.pdf Janeway, C.J., Travers, P., & Walport, M. (2001).Immunobiology: The immune system in health and disease.. (5th ed.). New York: Garland Science. Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK27163/ Reinsmoen, N., Lai, C., Vo, A., & Jordan, S.C. (2012, October 5). Evolving paradigms for desensitization in managing broadly hla sensitized transplant candidates. Retrieved from http://www.discoverymedicine.com/Nancy-Reinsmoen/2012/04/17/evolving-paradigms-for-desensitization-in-managing-broadly-hla-sensitized-transplant-candidates/ Read the full article

[jess-the-vampire]

I guess we know how Mina was able to transform Sebastian, the MHC went “LOL we got u” and pulled some strings. I guess the last remaining question with them is what magic were they tracking in “DC-700X”? Pretty much everyone is ruled out by now, and if it were a thing wouldn’t that have delayed their plans? Because it’s an unaccounted for variable? Unless of course there ISN’T any “extremely powerful magic” being used in the monster temple, and it was to make Star further distrust Eclipsa

you mean Junkin Janna

but yeah, either we have to assume they were lying, or there was an actual thing happening there and it comes into play later

[stassendesigns]

In Makanshokus au who do you think would take the throne of mewni? I know I can’t straight up ask since they won’t respond but I wanna chat

Mmmm well anon, I think that Lilith would be the next one to be Queen, even after Bella’s true identity will be found out.

Lilith is the first and only child of the union of Tom and Star, the royal couple of Mewni. Tom and Star got together (with a push from the MHC) in order to solidify the union between two kingdoms as well as to help the monster/mewman racism (?) , as well as marrying two royals together instead of Star marrying a commoner (as if I remember correctly in Makanshoku’s AU, Marco’s status as a commoner (non-royal) is a worse variable for a next gen child to have instead of a next gen with monster/demon genetics). But Lilith is the child of the union between two kingdoms, and therefore as to not upset or violate the treaty between the Lucitors (monsters/demons) and the Butterflys (Mewmans) the legitimate child would sit on the throne, not someone who is technically illegitimate/a bastard (Bella). Although, people with anti monster/demon propaganda would probably rally behind Bella cause racism might be worse than classism?

Take for example in the A Song Of Ice And Fire series, Robert’s next in line was Joffery as he was the oldest trueborn (legal) male. Robert had a ton of children older than Joffery (Mya, Gendry and Bella to name a few) but Joffery was the next in line, bypassing is older “half” siblings as he was legitimate. This is put in place as to honour the union between the two houses and I think this would also apply to Bella’s situation (and if I remember correctly, Star and Marco weren’t married before, but even if they were, my original point/comparison still stands)

Then again, it is an Alternative Universe created by Makanshoku, and honestly anything goes, they can put Bella in Mewni and Lilith in the Underworld, Lilith in Mewni and Bella just stays by her side, anything goes because it is their AU. Heck, its possible that neither Lilith or Bella end up on the throne

[cancerbiophd]

Hey Julia (im also Julia!) :) i’m a grad student and i have a project in immunology right now and i have to present a paper (as u do) in a 40 min presentation but the paper is only 8 pages long... any advice on how to stretch it? i already tried adding to the introduction but it’s just about cytomegalovirus and MHC I retention there’s not THAT much to talk about 🙈 i’ve never seen anyone present a paper (they never did that in my lab) so i’m kinda lost

Hi Julia! Hi Twin!!!

I think we can totally make your 8 page long paper into a 40 min presentation! Here’s how I would structure it (and feel free to ignore any points you’ve already done/don’t want to do. I’m just gonna give my take, in the hopes that something will jump out as doable for you!)

I. Title of presentation = Title of journal article, with authors and institution. I usually just screenshot the title page and put that in. Don’t forget your name + date somewhere too!

II. Outline of your presentation. It’s a nice roadmap (and will take a few seconds to go through) Something like this:

Introduction

Hypothesis/Question

Methods

Figures

Authors’ Conclusions

Authors’ Discussion

Follow-up Thoughts

III. Introduction - sounds like you have this all set up! Just make sure it’s told in a way that leads the audience directly to the hypothesis. Like, to the point where the audience pretty much comes up with the same hypothesis as the authors.

IV. Hypothesis or Main Question

V. Methods - if there are any methods that are novel, or “out of the ordinary” of what the immunobio world is used to, describe it here using schematics and figures and just make it as clear as possible. This is also a great place to show any experimental timelines (eg. treatment schedules) or just the general flow of experiments. 

VI. Figures! Show each figure one at a time, either using animations or by putting them on different slides. Accompany each figure (or set of figures) with: 

The question the authors were trying to answer

The method they used to answer it

And a thorough description of the figure, including what each axis, symbol, color, line, statistic, etc represents. Be sure to have the key or legend if available. Describe the controls, and then the different variables. Basically you want to be able to walk everyone through the figure as if no one has read the paper (and if it’s anything like my journal clubs, 80% of the students haven’t read the paper lol). I personally like to use animations to show one thing at a time, starting with the controls. 

Follow with a slide showing the question again, and then the answer. It’s a nice summary to keep the audience on track. 

Other notes:

You can dilute these descriptions for later figures if the same things are shown of course (like if there are 4 sub-figures with the same axes, you don’t have to describe it 4 times)

Also make sure the figures are as crisp as possible. Nothin worse than staring at deep fried jpegs

Figures should take up the bulk of your presentation, so probably 15-20 min. 

VII. Authors’ Conclusions - “Based off these data, the authors concluded…” Be sure to use either bullet points or a schematic that ties all the findings together (a picture is worth a thousand words!)

VIII. Authors’ Discussions - What do the authors think their results and conclusions mean for the field or science as a whole? What do they plan to do next? Do they mention any study limitations?

IX. Follow-up Thoughts - This is where you get to flex your critical thinking muscles. Basically, what are your thoughts about the paper? Do you agree with the authors’ conclusions and discussion? Did you have an issue with a method or result? What could the authors shown more of to bolster their conclusion? You can also open the discussion up to the audience (and be sure to leave at least 5 min for this!). What did everyone else think of the paper?  

So! Doable? I think that’ll definitely use 40 min (or at least 35 min, since you want to leave room at the end for questions/comments). Also keep in mind that sometimes people will ask questions during the presentation to ask for clarification, so factor in at least 3-5 min for that. 

Hope this helps! Best of luck! You got this, Twin! 

[biomedres]

Journals on Medical Research - BJSTR Journal

Conformational Changes of Vitamin D Receptor as a Potential Cause of Multiple Sclerosis by Miskic B* in Biomedical Journal of Scientific & Technical Research https://biomedres.us/fulltexts/BJSTR.MS.ID.002426.php Multiple sclerosis (MS) is an autoimmune inflammatory disorder of unknown etiology affecting central nervous system (CNS)characterized by demyelination and variable degrees of axonal loss [1]. The etiology of MS is still unknown; however, it is believed to be caused by combination of immune dysregulation, genetic and environmental factors [2]. Recent studies have revealed severeal genes as risk factors including MHC HLA DR15/DQ6 allele being the strongest one, alleles of interleukin-2 receptor alpha gene (IL2RA) and interleukin-7 receptor alpha gene (IL7RA) have also been identified [3]. The pathogenesis of MS includes immune attack against CNS antigens through activation of CD4+ myelin-reactive T cells and a possible contribution by B cells [4]. Furthermore, there are some environmental factors related to increased risk of developing MS like Epstein-Barr virus (EBV) infection and vitamin D deficiency [5,6,7]. Prevalence of MS is increased in geographic areas further away from the equator [8]. This could be related to reduced sun exposure leading to vitamin D deficiency as a possible contributing factor [6,7].Also, studies have shown that higher levels of vitamin D could be protective in certain patient populations [9,10]. Recently, there is a growing number of studies showing how vitmin D deficiency is related to MS development. Approximately one billion people worldwide have vitamin D deficiency or insufficiency [11]. Vitamin D is a fat-soluble vitamin existing in two forms – ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) which is more bioactive than vitamin D2. It can be consumed in food or synthesised in skin by sun exposure [12]. The vitamin D binding protein transports vitamin D3 to the liver where it is hydroxylated, this process results in the formation of 25-hydroxyvitamin D3 (25(OH)D3), the 25(OH)D3 metabolite is also hydroxylated by renal CYP27B1 to 1,25-dihydroxyvitamin D [1,25(OH)2D; calcitriol], the most bioactive vitamin D metabolite [13-15]. When calcitriol binds to the vitamin D receptor (VDR),it forms a nuclear heterodimer with the retinoid X receptor so this complex binds to genomic vitamin D response elements and downregulates expression of a variety of genes [16]. For more articles on Journals on Medical Research please click here bjstr Follow on Twitter : https://twitter.com/Biomedres01 Follow on Blogger : https://biomedres01.blogspot.com/ Like Our Pins On : https://www.pinterest.com/biomedres/

[justslowdown]

i’d like to upload entire textbook chapters and link to every study i’ve read on this but i don’t have time and yall don’t have the patience. i’ll focus on the role of genetic diversity in canine immune response, since i put my foot in my mouth earlier, but there’s plenty of more general links at the end.

wish i could go into what i’ve read over the years regarding livestock and endangered species (the body of research is MUCH larger) but this is already gonna be too long **EDIT** ok i added a couple since this got notes! 

to sum up earlier events: i don’t think it’s absurd that i was interested in an observation that tightly inbred dogs were more likely to die from distemper than crossbred ones back in the day  ¯\_(ツ)_/¯ but i should’ve been clearer about why i found it fascinating.

“To select against one gene, we remove a dog from the breeding population, and all of the good genes it might have go with it. You don't notice losing the immune system genes; they don't produce a coat color, or prick ears, or a better topline that you can see and evaluate. You will only preserve the genes of the immune system if you are preserving genetic diversity in general, by using a breed-wide strategy of genetic management” an entry level ICB article about immune system health and inbreeding

tons of articles and studies after the cut, mostly focused on haplotype diversity. some info on the effects of inbreeding depression on litter size, longevity, as well as info on hybrid vigor, population genetics and inherited disorders in dogs. to round it out there’s now articles and research on conservation biology and livestock breeding.

as i said in another post, this is settled science. still, many dog breeders justify half-sibling and even father-daughter pairings, or repeated linebreeding over generations which leads to the equivalent of sibling pairings, etc, by saying they “know their lines” and that linebreeding will “bring out the best and the worst.” it does a hell of a lot more than that.

 playing with genetics without fully understanding them could prove catastrophic for future generations of dogs (and already has for plenty of breeds). we can’t see the forest for the trees. “perfect” conformation and show ribbons aren’t worth it (besides, perfection is impossible! only breeding the best of the best won’t lead to perfect dogs, it will lead to unhealthy ones with drastically limited gene pools) (“bettering the breed” is 100% subjective)

onto links... “The practice of inbreeding to improve breed traits has inadvertently led to a reduction of MHC diversity within the individual breeds” here’s an article on MHC haplotypes and the role of genetic diversity in immune function, specifically about collies

“There is a large degree of inter-breed variability, but often limited intra-breed diversity, of DLA haplotypes”

yet a diverse combination of these haplotypes (different from each parent) is necessary for robust immune function...

“DLA haplotypes: STR loci linked to the DLA class I and II genes were used to identify genetic differences in regions regulating immune responses and self/non-self recognition. Problems with self/non-self recognition, along with non-genetic factors in the environment, are responsible for autoimmune disease” from here

study indicating that immune function is linked to DLA/MHC haplotypes in dogs. and another.

“There have been many studies of MHC in wild and/or endangered animal populations [blogger note: most dog breeds would be considered endangered due to effective population size] and there is evidence that a certain minimum number of different haplotypes may be necessary for long term survival. If only a few MHC haplotypes exist in a breed or species, the risk of the entire population being wiped out by a new disease is probably very high” this article which is actually about poodles

not specific to immune health but good info nonetheless:

an opinion piece by Terrierman though imo it focuses too much on deletrious genes and not on the finer aspects. good crash course though

this ICB article on hybrid vigor is good.

actually a lot of ICB articles apply here...

why dog breeders need to understand population genetics

this one focuses on inherited disorders

data on the effects of inbreeding on lifespan and litter size compiled here

a compilation of studies from a controversial “dog health activist” Jemima Harrison (Pedigree Dogs Exposed, which is a lil fearmonger-y but great documentary nonetheless)

“The litter size decreased and the percentage of puppies born dead increased with increasing inbreeding coefficients of the puppies, dams and sires” study here

“The least inbred group survive, on average, 14 years -- approximately 4 years longer than the most highly inbred” genetic diversity/inbreeding and longevity in poodles

“Unfortunately, we cannot breed animals based on a single gene - the genes come as a package. We may inbreed and rigorously remove pups with PRA or even their parents and littermates from the breeding pool. But remember inbreeding tends to make all genes more homozygous. In at least one breed, an effort to remove the PRA-causing gene resulted in the surfacing of a completely different and previously unsuspected health problem. It is easier and faster to lose genes (sometimes very desirable genes) from the breeding pool when inbreeding is practiced than when a more open breeding system is used” great article, mostly about COI, but touches on disease expression and the importance of genetic diversity in wildlife conservation breeding programs

not dogs, but a genetic diversity crisis is happening in cheetahs and it’s affecting immune systems. how many dog breeds have gone through genetic bottlenecks just like the cheetah? “A lack of genetic variation causes the cheetahs' immune systems to fail, as indicated by their bodies' failure to reject the skin grafts traded surgically among captive cheetahs in the second phase of the study. A virus that caused feline infectious peritonitis at the Wildlife Safari a few years ago almost wiped out the cheetahs there, and it is feared that if a foreign virus got into Africa, cheetahs could not cope”

**EDIT** and here’s some more on conservation and livestock bc i can’t help myself!

“High levels of inbreeding can result in reduced genetic variation, low reproductive performance and increased cub mortality, as well as reduced immune competence” inbreeding depression in lions

inbred wolf population collapses

conservation genetics

“In general, inbreeding results in an overall lowering in performance: vigor, disease resistance, reproductive efficiency, and survivability. It also increases the frequency of abnormalities” article on breeding strategies in sheep

similar conclusion as the sheep article above but an actual study, focused on dairy goats

[scriptgenetics]

So I'm working on a dystopian-esque story in which spouses are assigned by the government based on matches that would produce ideal offspring. The idea is to "perfect" humanity, and use this process to ereadicat disease. What are somethings that might go wrong with this as far as genetic mutations go or in general? Also, can you recommend a few research sources? What testing would be needed to determine matches? I need all the help I can get! Thanks so much!

Hi there!

There are a few questions you have going on here, and I’m going to answer them in order of shortest to longest answer, and in a way that lets them build on each other. At the end, I’ll include some extra resources and reading you could do to help round out what I’ve said here.

The testing could be done in a couple of different ways- either you could sequence every single person in the population, or you could genotype them, using a functional set of specific markers. I’m going to guess that if the government in your story is going through the effort of basically implementing a mandatory, population wide eugenics program, they are probably going to go for the “sequence” option. It’s the more expensive and in-depth of the two, but is also going to give you full-genome wide information, rather than just looking at a selected subset. The disadvantage of sequencing is that you are going to get EVERYTHING, which can be more information than you need or are looking for. Genotyping can be set up to only look at the functional parts, rather than all of the non-coding parts of the DNA.

So we’ve sequenced everyone, and now we know about all of their genetics, so the next step is pairing everyone up. You said that the primary goal is to eradicate disease, which you could do a certain extent with genetics, but not all the way. You would be able to select matches that would prevent hereditary diseases in your population, but that won’t stop people from getting the common cold! There are very few genetic diseases that are dominant traits, which helps us out here. What you would be able to do is match carriers of these diseases with non-carriers, and that would take away the possibility of their children having that disease (although the children may still be carriers themselves). The next step that could be taken once you have pools of people that can be matched is try and introduce as much heterozygosity, or hybrid vigour, into your population as possible. Genetic variability is your friend, and ensuring that the population crosses are as different as possible means that the children of those populations will be more fit for any environment, and also ensure that they create continuously unique populations. Generally speaking, in the world of genetics, having a very flat population with few differences is bad, because it means if the environment changes, there is no variable group that can deal with that change. Different is good!

So how could this all go horribly wrong? Well, mutagenesis is a strong influencer in genetics. Spontaneous mutations crop up from normal DNA replication and environmental influences regularly. As a general rule, they aren’t harmful- that’s part of the reason we have so much non-coding DNA. If something happens in those regions it’s much less likely to have a negative effect than a mutation in a coding region. But, things happen, and sometimes a mutation occurs in a coding region, leading to a new trait/disease.

For your recommended reading, I would look into both the Wikipedia articles on “heterozygote advantage” and “loss of heterozygosity”. I think they give a good overview of why you want genetically diverse populations.

Here is a link to one of my favourite studies where they had women smell the body odour of different men and rate their preferences. What they found is the women preferred men who were heterozygous on three MHC loci, which has been related to enhancing the rate of disease resistance. It’s an interesting study, and I think relevant to your story. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1689917/pdf/10380676.pdf

I hope this helps, and if you want more info on any part of this, just send me another ask!