#ATGs

[sunlightlion]

Hey I'm making a terrible mistake and working on a ttrpg based around squad warfare where you step into the shoes of Captains, Generals and Lord's of men. Oh also some armored guys.

[decadentkingdomdefendor]

Molecular Mechanisms of Fasting-Induced Autophagy

Introduction: Autophagy is the process of cellular constituents degradation and recycling that is very essential for maintaining cellular homeostasis. It degrades and recycles damaged or redundant cellular constituents that favor survival under stress conditions. Of all the potent inducers of autophagy, fasting has been related to the activation of only a few signaling pathways for an efficient process. A few studies have been conducted in order to identify the molecular mechanisms governing fasting-induced autophagy, and a number of significant factors controlling this process are identified.

1. The mTOR Pathway: Central Regulator of Autophagy

The mechanistic target of rapamycin or mTOR is a serine/threonine kinase which plays an important role in regulating autophagy based on the nutrient availability. Optimal nutrient-rich conditions activate mTOR and subsequently the phosphorylation and inactivation of key proteins associated with autophagy, such as unc-51 like autophagy activating kinase1. Fasting conditions put the active nutrient sensing mechanisms in an inactive state at low levels of mTOR activity. As mTOR shuts off, it removes the inhibition that it had placed on autophagy, and now the ULK1 complex, one of the first steps toward the induction process of autophagy, is allowed to turn on. READ ALSO: PLAY SAFE AND HEALTHY DIWALI.

2. AMP-Activated Protein Kinase Pathway: This too is a major player of the process in starvation. AMPK acts as a sensor of cellular energy, and low energy elicits a response by inducing autophagy. It increases further with fasting as the ATP concentration decreases. Activation, by this mechanism, causes the phosphorylation of several targets which promote autophagy. Another very essential function of AMPK is the inhibition of the activity of mTORC1 which in turn increases autophagy. The activity of ULK1 is enhanced through direct phosphorylation by AMPK which facilitates initiation of autophagy.

3. Sirtuins: NAD+-Dependent Regulators: A family of NAD+-dependent deacetylases, known as Sirtuins, has been characterized to play central roles in controlling autophagy. Interestingly, a greater level of SIRT1 is induced from higher NAD+ levels that have been regarded as a secondary response from reduced food intake during fasting conditions. Through this, autophagy may therefore be induced by deacetylation and activation of other proteins important for the pathway including the ULK1 complex, and transcription factor FOXO upon activation of SIRT1. In addition, SIRT1 also promotes the activity of AMPK for further enhancement of its effect in promoting autophagy. Sirtuins associate with other pathways of signaling, which coordinate a cellular response during fasting and stimulate survival.

4. FOXO Transcription Factors: The association of FOXO transcription factors with the regulation of the cell to upregulate genes for response to stress-related problems includes the induction of autophagy among several others. Enhancement of SIRT1 activity following fasting is translocated into the nucleus as an act that permits the deacetylation, hence the activation, of FOXO factors. The FOXO transcription factors can directly activate the autophagy-related genes such as ATGs that encode the proteins involved in the formation of the autophagosome, the structure that actualizes waste sequestration in a cell. Activation of these genes places FOXO in a very central position concerning the induction of autophagy during starvation by nutrients.

5. Autophagy-Related Genes (ATGs): In aggregate, the overall machinery of autophagy will be a collection of genes, known as the ATGs which is divided among others into five: ATG1, ATG5, ATG7, ATG12, among many others. Coordination activities of these proteins equates into the autophagosomes. Upon starvation, the activity of ATGs are regulated by the upstream signaling pathways containing some among them such as mTOR, AMPK and Sirtuins. For example, starvation causes the dephosphorylation of ULK1 that activates this complex but allows it to bind and associate with ATG13 and FIP200; these further lead to autophagosomal formation. These autophagic structures end up fusing with lysosomes, and their contents are degraded and components recycled into the pool recycled.

6. Lysosomal pathway: final stage of autophagy: This is because the autophagosome fuses to a lysosome, which encompasses all the lysosomal hydrolases to degrade its contents. Lysosomal pathways control fasting-induced autophagy for this reason: there exists an increased and active population of lysosomes during fasting. Their process is regulated by such signaling pathways as mTORC1 and TFEB. TFEB is the master regulator for lysosome biogenesis and autophagy, and fasting induces its nuclear translocation and thereafter activates the expression of both lysosome and autophagy genes.

Conclusion: The fasting-induced autophagy is a multi-signaling pathway and process of molecular players. Quite a few factors are involved in this, including the mTOR pathway, AMPK, sirtuins, FOXO transcription factors, and the set of autophagy-related genes or ATGs. This coordination of molecular players allows cells to respond to fasting stress efficiently, increasing survival and cellular renewal. The clarification of these molecular pathways is fundamental to the development of therapeutic strategies that target autophagy in diseases like cancer, neurodegenerative disorders, and metabolic diseases.

[haridraws]

snippet of something from patreon

[shihlun]

Hôjin Hashiura

- Mitsugetsu / Honeymoon

1984

[llitchilitchi]

the thing about researching anything about ancient Macedon and/or Alexander the Great is the frequent mentions of the Companions Cavalry and my Skyrim-pilled brain always interprets it as the werewolf mercenaries so.

AU where the Companions are a werewolf army, featuring a young Aleko

[goldenpinof]

[official-die-hauptstadt]

[chickenkurage]

In another life...? (ATG Highschool AU)

Alan (President of the Literature Club)

DJ (Vice-President of the Literature Club)

Mary "Satin" (President of the Fencing Club)

"In another world where Alan, DJ and Mary are friends and they we're never a victim of society........."

About this...AU?

Alan had many male suitors because many students thought he was a girl, while Mary attracted many women due to her position as the fencing club president and her charming smile. As for DJ, he had no romantic prospects. In short, he had no "bitches" nor "hoes"

Mary will never be called Satin.

In this AU, Mary and DJ are childhood friends and had collectively decided to befriend and bother Alan every day until eventually he joined them, and they became a trio.

Mary is able to express more emotions because of DJ, she grew into a person who likes to smile and make people laugh.

In a sleepover, Mary and DJ always sandwich Alan in the bed, and in the end, Alan gets no sleep at all because he's squished between the two of them.

Alan has more than one koala who likes to hug him (*whisper* DJ and Mary)

Koala number one: Mary, Koala number two: DJ and the tree branch: Alan

ATG Highschool AU? Want more? If you want to set yourself free from the cage of sadness.

Also! Do you guys also want us to create a happy AU of CS AU? Just like ATG's *wink* - S

[just-a-drawing-bean]

A Dazzling Game of Uno

Short drabble about Sun, Moon, and Razzle in an enthralling game of Uno below the cut.

Word count: 1,380

“Uno”

Razzle leans back in his chair, folding one pair of arms behind his head, the other pair resting on the round table in front of him, clasped atop his last remaining card. Groans broke out from the two bots surrounding him as they stared at the blue four sitting on the pile of cards.

“There’s no way you can be this good at Uno. You must be cheating.” Grumbles Moon while throwing his few remaining cards face down in frustration. He looks off to the side, frowning while ignoring Razzle’s smug grin.

Sun slouches forward in accepted defeat, rays flaring slightly as he adds on, “Yeah! This is the fourth time in a row.” 

“Now, now.” Razzle’s soothing voice cuts through the whines of the celestial pair, “You would accuse me of cheating in my own casino?” He quirks an eyebrow at the two then gives a slight chuckle. “And at Uno much less. Now, I'm not one to cheat but I’d certainly never do so in my favorite game.” Sun groans lightly in frustration, running his hand over his face and rays while Moon only crosses his arms and narrows his eyes. 

Razzle leans in slightly, uncrossing the arms behind his head to prop his faceplate on his hands. His grin stretching wider by the second. He waits a beat before speaking, squinting his eyes playfully, he taunts. “Look boys, I haven't won yet. Sunshine, it's your turn.” 

Eager to get the crushing defeat over with, Sun haphazardly lays down a card at random, a green four. Suddenly Moon perks up the slightest amount before smoothing his expression back to the disgruntled look he wore seconds before. Nonchalantly he places a green card on the top of the deck while making direct eye contact with his ever-so-slightly taller brother. 

“Skip.” 

Razzle tilts his head in response, unbothered. “Prolonging your loss, Moonlight?” He looks over at their solar brother, “Well, It's back to you Sunshine. I hope you’ve still got some fire in you, It would only be fitting.” Sun rolls his eyes at Razzle’s tease, instead focusing on the cards he has and the cards he hopes Moon has. 

Typically, counting cards would be a sin in gambling, but this was a friendly match between brothers. All of them have perfect memory, as animatronics, so they let themselves indulge in card counting. This time. Sun runs the calculations, the possibilities of what his brothers’ cards could be, and hopes that he can set Moon up in a way to foil Razzle. Even if he doesn't win, at least he can have the satisfaction of knocking his youngest brother down a peg. 

Hoping that luck was in his favor, Sun places a wild card and calls the color red. He knows Moon has a red, but it is uncertain what Razzle’s last card is. Even knowing the cards in play can't guarantee the final color. All attention falls on Moon. He silently thanks his solar counterpart for setting him up. Moon holds his last three remaining cards up as if contemplating a move he already has planned before placing down a red reverse. Two sets of optics flick to the solar animatronic. Sun straightens his back and gives a sneaky grin, his rays turning slowly. With a quick flick of his wrist, He deposits a yellow reverse card on the top of the stack. 

“Having fun ping-ponging your turns?” Razzle asks, amusement coloring his voice. He rhythmically taps his fingers on the table and then shifts his piercing gaze to Moon. “Let's hope you have something more interesting up your sleeve, hm?” Moon lets out a soft chuckle, shuffling his two remaining cards idly in his hand before replying, “Nah, I don't have any other fancy tricks, just wishing on a miracle.” 

Moon plucks one of his cards and gingerly places it. A red zero. He cooly looks up at his brother, anticipating a defeat, but hoping for a win.

“Uno.”

Razzle lets his gaze slowly travel over his two brothers. His grin doesn't falter. He doesn't need to look at his card to know it's a winning card. He simply tilts his head and flicks his rays in a circle before reaching out to grab a new card from the deck. “Well,” Razzle cooly directs towards Sun. “It's your move.”

“OH! OH!” Sun exclaims excitedly, his eyes opening fully and brightening. “Oh Moon, we’ve got him!” He shakes his hands around lightly and his rays spin with vigor. Moon looks over at Sun and his grin quirks up a bit at the edges, assured in his victory. His raspy voice drifts out, “Hold on there Sunny, it's still your turn. I haven’t won yet.” Sun quickly calms his composure and settles on a passive grin. 

Taking a deep synthetic breath, Sun trilled, “Ok, ok! I'm calm. Oh, I hope this card works for you.” 

Pretending to pick at his fingers, Moon nonchalantly replied. “Whatever card will do, Sunny, as long as there's no negative effect.”

Razzle glanced over at Moon, voice box crackling to life. “You better not be going out on a plus four. That's against the rules you know.” The two bots held each other’s gaze for a beat before Moon casually leaned back in his chair, red eyes gleaming with amusement. He replied, “I’m well aware of the rules, Razz. Don't get your wires in a twist.”  

Razzle let out a short chuckle and shook his head lightly, turning back to Sun, waiting for the next play. Both his sets of rays slightly pulling in and out in a lethargic pulsing pattern. Sun gave a bright energetic smile that only he could give before vigorously slapping a red nine down. “Ok!” He proclaimed, “Moony it's up to you!” Moon took his time drawing out his well-earned victory. He sat up in his chair and swept imaginary dust off his ruffled baby blue button-up. 

Turning first towards his bright older brother, he saw Sun swaying in excitement as he anticipated Moon to win in this brotherly game of Uno. Moon felt a fond wave of affection for the one who had been with him all his life and gave him a confident grin before turning towards his younger brother. Razzle might be hard to read while in the middle of a game, but Moon knew him well enough to see the love and pride hidden in his seemingly unbothered expression. He was proud of them, not just about the game, but for how far the three of them had made it, together.

Moon gently reached towards his final card and flipped it over revealing a wild card. He placed it on Sun’s red nine and stated. “I win.” 

Sun immediately stood up and rejoiced, “FINALLY! Oh thank goodness Moony, you did it!” he turned towards his youngest brother adding on, “Razzie you know I love you, but it certainly is disheartening to lose so many games in a row.” He playfully narrowed his eyes at that. “Of course, you wouldn't know that, you hardly lose for long.” Sun began to tut at him while playfully shaking his finger. Razzle stood up as well, the rounds of games ending for the night. He chuckled lightly and replied, “You’d certainly be correct on that, so let us end the night on a high for you two.” Crossing his lower set of arms while the upper rest on his hips he gave a genuine smile and tilted his head towards his darker brother.

“Moonshine.” He praised, “Good game.”  

“A good game indeed.” Came the low-toned reply.

Moon was enjoying his victory, a smug grin plastered on his face, foot tapping to some unseen song, arms crossed in triumph. Razzle hadnt seen him look so pleased in quite a while. Building up to Moon’s win had definitely made it all the sweeter. And golden Sun, he was just as ecstatic as if he himself had won, not their lunar brother. His rays spun wildly and his eyes shone with excitement. Sun could hardly contain his joy as his body shook and swayed. He’d throw any game if it meant they were happy.

“Come on then,” He announced while turning to leave the private room, “ We’ve got a casino to run.”

[kindaasrikal]

The tragic existence of the Ninja and co having faces that look so much like another’s, knowing that the face in the mirror is one that mimics a mothers and a fathers, even if they wish despite for it not too.

How did Harumi feel after her parents died and the last thing she had of them is her own face?

How did Pixal feel not knowing of shes simply a copy of someone long gone, or if this face is her own to bear?

How did Arin feel knowing that the only reason he remembers how his parents look like is because of a reflection?

How does Sora feel looking at a face that should be her own, yet all she sees is the faces of those who hurt her most?

How does Wydlfyre feel not knowing of her face look more like her mothers or fathers, questioning why is doesn’t look like Heatwave’s or Caregivers, and wondering why she wished it looked more like Kai’s?

This is part two!

First post :D

Did Cyrus Borg ever look at Pixal when he first designed her, and wondered if that would be how his daughter could’ve looked like? Did he ever question and wonder why he made Pixal look the way he did, despite knowing the answer deep down inside of him?

Did Wydlfyre look at other dragons and realised how similar they looked to their parents? How they had their father’s eyes, or mother’s tail? Did she ever question Heatwave-her father- or the caregiver robot -her mother- as to why she did not have her father’s long fangs or her mother’s sleek skin? When she was finally told they were not biologically family (yet in their hearts they always will be), did she ever sit and wonder whose face matches hers?

When the merge happened and she heard Arin wish for his parents, the ninja wondering where their parents are, Sora in grief of her own, did she ever sit in front of a mirror and tried to pick apart which part would belong to whom? Would her eyes be fierce like her mother’s, or would they be as determined as her father’s? Would her hair be as vibrant as her father’s bold locks, and would her mother bear the mark from birth like she has? Would she wish to have a smile as caring as Kai’s, like how she wishes to have Heatwaves warmth and Caregivers security?

Did Arin ever stare at his face in hope he would be able to fool himself into thinking he was looking at his mother’s instead? Or did he once realise that the only reason he even remembered how his own parents looked like was by his own face? Did he ever feel pain by looking more like his mother than his father? Or would he focus too much in his fathers features when it was his mothers face he last saw? How many times did he cry as a lost child wondering when the next time he sees his parents it won’t be through a mirror?

Did Sora ever wish to scratch off the features that made her look so much like her own parents? Her mothers eyes that seemed to bore into her own and her fathers frown that mimicked hers perfectly? Did she ever cry in gratitude over her pink hair, yet feel loss at how much she never fit in even with her own family? How many times did she cry when she thought she was acting too much like her mother, or her father? That her face warped into expressions that she remembered so clearly on their own faces?

How many times did she catch her self smiling, and loving and fond look in her eyes when she looked at people she cared about, only to realise that she barely ever saw this look on her own parents? That the reason her heart ached, was because the only way she ever will see such a look pointed at her from their own faces was with her own?

How long did Harumi sit staring her face to ensure she never forget the look of her parents? How many times did she move her face to mimic the same ones of terror and fear and acceptance that she last saw on her parent’s face? On their funeral, how many times was she told she looked exactly like her parents? That they must’ve been proud to have such a beautiful daughter? Did she cry, when she wished she looked just as beautiful as her mother once did? Or did her anger at the world climb higher when strangers would say she looks so much like her mother, the queen, despite being adopted? Did she ever scratch at her face, trying to change it, hoping to pull her eyes out when told they look so much like the kings, and not her father’s?

Did they ever wish that their face were their own, and not a sick reminder of what they once had?

Bah since some (haha, one of you actually) of you wanted the dragons rising characters, i did that and slapped you with Harumi too cause shes just tragic.

[slowlystupendousdelusion]

Okay so in an attempt to focus on the positives, here are some bullet points of what I remember from the Greg Doran & David Tennant Shakespeare talk the other week.

Touchstone was DT's first Shakespeare part and As You Like It was the Shakespeare play he first remembers being interested in as there was a tour of it that went to his school.

A licence was needed to be able to use André Tchaikowsky's skull for Hamlet as he had died within the last 100 years old. DT dropped it during dress rehearsal the first time they used it and a bit broke off. Luckily they were able to fix it as it was a cheek(?) bit that had fallen out and could be put back in.

DT did a fair impression of both Sir Ian McKellen and (I think?) Al Pacino (I think this was in reference to 'Looking for Richard'??)

DT felt a lot of pressure in relation to Hamlet to the point that he was curled up in the foetal position before going on and had to be talked out of it by the speech assistant

They hold 'gyms' during the rehearsal period where they go through the play line by line to make sure everyone understands what they're saying. They might have discussions about it if there's not consensus.

GD thinks Love's Labour's Won (the lost play) is Much Ado About Nothing. DT countered this (to much laughter) with the plot of DW S3 Ep2. There was clearly a large Whovian contingent in attendance.

I've mentioned this elsewhere but they talked about other productions of Macbeth and GD mentioned one he'd seen with the following joke in the Porter scene: "Knock knock" "Who's there?" "Tom" "Tom who?" "Tomorrow and tomorrow and tomorrow" DT said he wouldn't tell Jatinder or he'd use it that evening

DT's least favourite Shakespeare is The Taming of the Shrew, I think GD demurred on this. Both said favourite is always the one you're currently working on. So Macbeth atm.

The talked about intervals and how Shakespeare didn't really have them - the crowd would be standing and some scenes were built in as a break. Some plays lose momentum if an interval is place in (Macbeth was cited). It can be a bit of a challenge choosing where to place one and they mentioned how in their Vers of Hamlet they put the interval mid-line to shake up expectations etc.

They talked a bit about iambic pentameter and how it's not as important as purists might have you believe. Shakespeare started having thoughts cross lines as he got older - perhaps to help the actors?

They talked about the challenges of such well-known plays and creating suspense etc. Some of the lines are problematic and how as a director, you're not an academic so if it doesn't work you can cut them!

DT mentioned Iago (among others) as a character he still wanted to play [🙏🙏🙏pls & ty]

One of the questions was about how his Shakespeare performances informed his part in Rivals. The response was that Jilly Cooper and Shakespeare actually have a lot in common in that they understand how humans act and wouldn't shy away from bawdiness etc.

They did mention Richard III a fair amount but the specifics aren't coming to mind

They talked about reviews and how you can dismiss the bad ones but if you do that then you can't really take only the good ones to heart. My friend noted that this topic was the only time GD looked slightly uncomfortable during the talk but I can't say I noticed that.

I didn't actually write notes at the time so I'm sure I missed a bunch, but my other take away from this was how charismatic and naturally funny DT came across.

[haridraws]

small drawing of a bit of marsh I got excited about

[shihlun]

Hôjin Hashiura

- Mitsugetsu / Honeymoon

1984

[llitchilitchi]

osha-noncompliant blowjobs

[usaac-official]

Silver Queen, the personal B-17 transport of General LeMay, and a C-47 of the 27th Air Transport Group at RAF Heston, 1944

[chickenkurage]

The Alan Whump Whump Week!

Now that Fashion Week has come to an end, let us thank JM again. We will be having an Alan Whump Whump Week, where all my Alan's gets whumped to the hell and back. The prompts are shown but what would not be shown is what AU gets that prompt! So, it's all a surprise <//3. So, are you guys ready for your favorite Alan AU to get whumped? :DDD

To answer some of your questions...

Where will the Whump Whump Week be posted? - It will be posted on our tumblr! This will be under Tumblr Only Fics

Is this AA exclusive? - Nope, the whumping will happen in their own universes, the Alan's will not be interacting with each other on this one

Is this an event that happens every day or do you post erratically? - I might post two in one day, who knows...

Starting Date: December 27, 2024