Continuation of mTORC1 p2: Mast cells.... p1 --> Link
2. Overview and activation of MCs
Although the role of MCs is overlooked compared with microglia, MCs remain an important factor in the immune signaling pathway (29). MCs, the effector cells of the innate immune system, are derived from hematopoietic stem cells and multifunctional antigen-presenting cells and have a pivotal role in immunoglobulin type E (IgE)-associated allergic and inflammation-associated diseases (35). Despite their low numbers in most organs, MCs are present in both healthy and disease states. MCs are the first line of defense against invading pathogens and are distributed in almost all organs and vascularized tissues (36). Blood MCs express CD34 and contain cytoplasmic granules filled with heparin and histamine, the latter of which is released after binding to IgE. Unlike other myeloid-derived cells, tissue MCs have a hematopoietic developmental lineage (37,38). During MC development, immature lineage progenitors enter the circulation and are recruited to peripheral tissues by endothelial cells, regulating the appearance of granules with proteases (37,38). Human MCs may be classified into mucosal and connective tissue types according to the type of proteases present in their cytoplasmic granules; the mucosal type contains tryptase, whereas the connective tissue type contains both tryptase and chymase (39). MCs act as first responders and environmental βsensorsβ to interact with other cellular elements involved in physiological and immune responses, promoting the neuroinflammation process (40). MCs are present in various areas of the brain and meninges. Although less distributed in the brain, they are generally found in the subthalamic nucleus, choroid plexus and the parenchyma of the hypothalamic region (41). The pathogenic roles of MCs were indicated to extend from allergic disease to autoimmune diseases and carcinogenesis (42-47).
The most common way through which MCs perform their function is degranulation. The activation of the inflammatory process results in a rapid release of MC granules into the interstitium. MC granules contain pre-formed and newly synthesized reactive chemicals known as MC mediators. These mediators include histamine, tryptase, chymase, interleukin families, tumor necrosis factor-Ξ± (TNF-Ξ±), serotonin, heparin, proteoglycans, vascular endothelial growth factor (VEGF), prosta
... keep reading on reddit β‘I don't want to step on anybody's toes here, but the amount of non-dad jokes here in this subreddit really annoys me. First of all, dad jokes CAN be NSFW, it clearly says so in the sub rules. Secondly, it doesn't automatically make it a dad joke if it's from a conversation between you and your child. Most importantly, the jokes that your CHILDREN tell YOU are not dad jokes. The point of a dad joke is that it's so cheesy only a dad who's trying to be funny would make such a joke. That's it. They are stupid plays on words, lame puns and so on. There has to be a clever pun or wordplay for it to be considered a dad joke.
Again, to all the fellow dads, I apologise if I'm sounding too harsh. But I just needed to get it off my chest.
Two main active ingredients, hypericin and hyperforin.
What hypericin does:
- Stimulates capillary blood flow.
- Weak MAO-A and B inhibitor at high levels, not possible to obtain through normal doses.
- Has affinity for Ο receptors
- Receptor antagonist at adenosine, benzodiazepine, GABA-A and B and inositol triphosphate.
- Decreased the release of corticotropin-releasing hormone in the paraventricular nucleus of hypothalamus ( in vitro), and decreased plasma levels of adrenocorticotropic hormone and corticosterone (in vitro).
- Along with flavonoids modulate the HPA function. Major depression has elevated ACTH and cortisol.
What hyperforin does:
- Potent reuptake inhibitor of serotonin, dopamine, noradrenaline, GABA and L-glutamate.
- Increases the number of 5-HT receptors.
The general consensus states that it is effective treatment of mild to moderate depression. However, this is applicable to standardised extracts.
For more details: Medical attributes of st John's Wort
For reference the extract used:
LI 160: contain 0.3% hypericin derivatives, hyperforin 1%-4%.
Ze 117: is a 50% ethanolic extract with an herb-to-extract ratio of between 4:1 and 7:1; hyperforin 0.8% - 3.8%.
WS 5570 is an 80% ethanolic extract of SJW with a plant-to-extract ratio of between 3:1 and 3:1-7:1; 5-6% hyperforin and 0.12-0.28% hypericin.
STEI 300: contains 0.2-0.3% hypericin and pseudohypericin, and 2-3% hyperforin.
Galanin neurons "By tracing the long axon fibers of this pool of neurons they found that they extend out from neurons in the hub region of the hypothalamus, the team closely investigated the function and anatomy of four of the 20 pools they had found. One set of axons projected to the periacqueductal gray in the midbrain, an area involved in motor behaviors. Manipulating that pool of neurons affected grooming behavior, although not the parentsβ retrieval of pups. A pool in the ventral tegmental area (VTA), a reward-related region, controlled the motivation to engage in parenting tasks. When the VTA neurons were stimulated, both male and female mice worked harder to cross barriers placed between them and their pups. A third projection to the medial amygdala (MeA), a locus for emotion, inhibited competing social interactions with other adults such as male aggression against other males. The fourth projection led to the paraventricular hypothalamic nucleus, a key area for neuroendocrine control. This area modulated parenting-related hormones such as oxytocin, vasopressin and corticotropin-releasing hormone."
Other researchers have also performed blood transfusions between pregnant dams and virgin mice. The transfused virgin mice stopped their avoidance of mouse pups and began grooming behaviors.
Others have found that virgin female rats avoid or attack pups, but postpartum dams will press a lever more than 100 times per hour to have a pup delivered into their nest box with each press.
It is interesting to think where this discovery might be therapeutically applicable?
[https://www.nature.com/articles/s41586-018-0027-0.epdf?sharing_token=C1yuxHNnQora3ZlL2E89ONRgN0jAjWel9jnR3ZoTv0OCwg_t4gDmPeD0aWQSJwh3bV3ab-DAhVHmBkuuQ7jAMO5P99cB4XrK9vRWHoFZdXh5eHyfRBraxWOvUkj6RqqAygGk4jvv1-0kYXY2bw9Vffx4UM2Ln2X0sCfRFTuaso5N1SzXmSLzcvOuOKQa5fhK6WDAKsUyaG8w5ghLpRs_YSdzJGQGCHDqIwZLxwKnyWNnMXasK66xdE4q7O2DHx_PRvEw4pSp4YYe0DkRZaE3KcgsSD0Pm1H0wABDTEl0-IwBnTBDD222lTz8NmGw2sqK6TIDDTzFWxEZiDD_oLsB0g%3D%3D&tracking_referrer=www.scientificamerican.com](https://www.nature.com/articles/s41586-018-0027-0.epdf?sharing_token=C1yuxHNnQora3ZlL2E89ONRgN0jAjWel9jnR3ZoTv0OCwg_t4gDmPeD0aWQSJwh3bV3ab-DAhVHmBkuuQ7jAMO5P99cB4XrK9vRWHoFZdXh5eHyfRBraxWOvUkj6RqqAygGk4jvv1-0kYXY2bw9Vffx4UM2Ln2X0sCfRFTuaso5N1SzXmSLzcvOuOKQa5fhK6WDAKsUyaG8w5ghLpRs_YSdzJGQGCHDqIwZLxwKnyWNnMXasK66xdE4q7O2DHx_PRvEw4pSp4YYe0DkRZaE3KcgsSD0Pm1H0wABDTEl0-IwBnTBDD222lTz8NmGw2sqK6TIDDTzFWxEZiDD_oLsB0g%3D%3D&trackin
... keep reading on reddit β‘Do your worst!
I'm surprised it hasn't decade.
For context I'm a Refuse Driver (Garbage man) & today I was on food waste. After I'd tipped I was checking the wagon for any defects when I spotted a lone pea balanced on the lifts.
I said "hey look, an escaPEA"
No one near me but it didn't half make me laugh for a good hour or so!
Edit: I can't believe how much this has blown up. Thank you everyone I've had a blast reading through the replies π
It really does, I swear!
Theyβre on standbi
Pilot on me!!
Nothing, he was gladiator.
Dad jokes are supposed to be jokes you can tell a kid and they will understand it and find it funny.
This sub is mostly just NSFW puns now.
If it needs a NSFW tag it's not a dad joke. There should just be a NSFW puns subreddit for that.
Edit* I'm not replying any longer and turning off notifications but to all those that say "no one cares", there sure are a lot of you arguing about it. Maybe I'm wrong but you people don't need to be rude about it. If you really don't care, don't comment.
When I got home, they were still there.
What did 0 say to 8 ?
" Nice Belt "
So What did 3 say to 8 ?
" Hey, you two stop making out "
I won't be doing that today!
[Removed]
This morning, my 4 year old daughter.
Daughter: I'm hungry
Me: nerves building, smile widening
Me: Hi hungry, I'm dad.
She had no idea what was going on but I finally did it.
Thank you all for listening.
You take away their little brooms
There hasn't been a post all year!
This is my opinion but I think it makes the most sense out of anything anyone has put forth about this "condition."
First and foremost "adrenal fatigue" is a thing and it's not in your head. Most people want to relate adrenal fatigue to high or low cortisol, or other adrenal hormones. There are anomalies detected in salvia tests and blood work related to cortisol and other adrenal hormones, but this is not the root cause.
When someone develops adrenal fatigue, there always seems to be a stressor of sorts. This could be anything, but I believe it triggers unchecked systemic inflammation, and this affects the brain and specifically paraventricular nucleus which controls the downstream cascade of many hormones including adrenal hormones. This has been pointed out by doctors before, however I think adrenal fatigue and chronic fatigue are close cousins. They may even overlap.
At the same time, systemic inflammation could cause a higher release of cortisol to fight the inflammation. Inflammation is mainly caused by your immune system, and one of cortisol's jobs is to low inflammation. In this case we may see higher or lower cortisol levels depending on how much inflammation is occurring and how it may create a negative feed back loop with the PVN (which could also cause lower cortisol levels.
This inflammation may take a few paths. 1. It could trigger or exacerbate a new or existing auto immune condition such as lupus. You can do a blood test for autoimmune conditions such as ANA and it could come back negative but you may still have it based on symptoms, most of which simply present as persistent fatigue, like "adrenal fatigue." So it's possible to have an autoimmune condition with only symptoms of fatigue, while having negative blood tests (you are seronegative). In this case cortisol would tend to be lower, allowing inflammation to run rampant and allow for the perfect environment for autoimmunity.
- The inflammation causes higher levels of cortisol which depresses the immune system, and paradoxically you still have high levels of inflammation but at the same time this high cortisol environment allows for viral reactivation of something like EBV, or HHV6. The virus is the responsible for keeping you in this state.
In the end, no matter the trigger, you have created a complex situation that may not only be resolved with rest, especially if it persists beyond 6 months. The reason rest may help for the more mild cases of "adrenal f
... keep reading on reddit β‘
Why
