https://doi.org/10.1371/journal.pcbi.1009259

Bistability in fatty-acid oxidation resulting from substrate inhibition

Abstract

In this study we demonstrated through analytic considerations and numerical studies that the mitochondrial fatty-acid β-oxidation can exhibit bistable-hysteresis behavior. In an experimentally validated computational model we identified a specific region in the parameter space in which two distinct stable and one unstable steady state could be attained with different fluxes. The two stable states were referred to as low-flux (disease) and high-flux (healthy) state. By a modular kinetic approach we traced the origin and causes of the bistability back to the distributive kinetics and the conservation of CoA, in particular in the last rounds of the β-oxidation. We then extended the model to investigate various interventions that may confer health benefits by activating the pathway, including (i) activation of the last enzyme MCKAT via its endogenous regulator p46-SHC protein, (ii) addition of a thioesterase (an acyl-CoA hydrolysing enzyme) as a safety valve, and (iii) concomitant activation of a number of upstream and downstream enzymes by short-chain fatty-acids (SCFA), metabolites that are produced from nutritional fibers in the gut. A high concentration of SCFAs, thioesterase activity, and inhibition of the p46Shc protein led to a disappearance of the bistability, leaving only the high-flux state. A better understanding of the switch behavior of the mitochondrial fatty-acid oxidation process between a low- and a high-flux state may lead to dietary and pharmacological intervention in the treatment or prevention of obesity and or non-alcoholic fatty-liver disease. Author summary: Obesity is a complex disease which is still poorly understood at the systemic level. Impaired capacity in fat oxidation may contribute to the development of obesity. In this manuscript using a detailed mitochondrial fatty acid oxidation computational model, we demonstrate that the oxidation of fat can exhibit bistability and hysteresis, implying that there is a risk that the pathway gets trapped in a stable state with low activity. We also identify the cause of bistability in the metabolic network and analyse which clinically relevant factors shift the pathway between the high-flux, healthy and low-flux, diseased state.

Authors:

Joseph Blommer, Megan C. Fischer, Athena R. Olszewski, Rebeccah

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.

https://doi.org/10.1371/journal.ppat.1009495

Fatty acid oxidation participates in resistance to nutrient-depleted environments in the insect stages of Trypanosoma cruzi

Abstract

Trypanosoma cruzi, the parasite causing Chagas disease, is a digenetic flagellated protist that infects mammals (including humans) and reduviid insect vectors. Therefore, T. cruzi must colonize different niches in order to complete its life cycle in both hosts. This fact determines the need of adaptations to face challenging environmental cues. The primary environmental challenge, particularly in the insect stages, is poor nutrient availability. In this regard, it is well known that T. cruzi has a flexible metabolism able to rapidly switch from carbohydrates (mainly glucose) to amino acids (mostly proline) consumption. Also established has been the capability of T. cruzi to use glucose and amino acids to support the differentiation process occurring in the insect, from replicative non-infective epimastigotes to non-replicative infective metacyclic trypomastigotes. However, little is known about the possibilities of using externally available and internally stored fatty acids as resources to survive in nutrient-poor environments, and to sustain metacyclogenesis. In this study, we revisit the metabolic fate of fatty acid breakdown in T. cruzi. Herein, we show that during parasite proliferation, the glucose concentration in the medium can regulate the fatty acid metabolism. At the stationary phase, the parasites fully oxidize fatty acids. [U-14C]-palmitate can be taken up from the medium, leading to CO2 production. Additionally, we show that electrons are fed directly to oxidative phosphorylation, and acetyl-CoA is supplied to the tricarboxylic acid (TCA) cycle, which can be used to feed anabolic pathways such as the de novo biosynthesis of fatty acids. Finally, we show as well that the inhibition of fatty acids mobilization into the mitochondrion diminishes the survival to severe starvation, and impairs metacyclogenesis. Author summary: Trypanosoma cruzi is a protist parasite with a life cycle involving two types of hosts, a vertebrate one (which includes humans, causing Chagas disease) and an invertebrate one (kissing bugs, which vectorize the infection among mammals). In both hosts, the parasite faces environmental challenges such as sudden changes in the metabolic composition of the medium in which they develop, sever

Alot of great jokes get posted here! However just because you have a joke, doesn't mean it's a dad joke.

THIS IS NOT ABOUT NSFW, THIS IS ABOUT LONG JOKES, BLONDE JOKES, SEXUAL JOKES, KNOCK KNOCK JOKES, POLITICAL JOKES, ETC BEING POSTED IN A DAD JOKE SUB

Try telling these sexual jokes that get posted here, to your kid and see how your spouse likes it.. if that goes well, Try telling one of your friends kid about your sex life being like Coca cola, first it was normal, than light and now zero , and see if the parents are OK with you telling their kid the "dad joke"

I'm not even referencing the NSFW, I'm saying Dad jokes are corny, and sometimes painful, not sexual

So check out r/jokes for all types of jokes

r/unclejokes for dirty jokes

r/3amjokes for real weird and alot of OC

r/cleandadjokes If your really sick of seeing not dad jokes in r/dadjokes

Punchline !

Edit: this is not a post about NSFW , This is about jokes, knock knock jokes, blonde jokes, political jokes etc being posted in a dad joke sub

Edit 2: don't touch the thermostat

Do your worst!

They were cooked in Greece.

I'm surprised it hasn't decade.

Don't you know a good pun is its own reword?

Two muffins are in an oven, one muffin looks at the other and says "is it just me, or is it hot in here?"

Then the other muffin says "AHH, TALKING MUFFIN!!!"

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 😂

It really does, I swear!

And now I’m cannelloni

Because she wanted to see the task manager.

But that’s comparing apples to oranges

Ants don’t even have the concept fathers, let alone a good dad joke. Keep r/ants out of my r/dadjokes.

But no, seriously. I understand rule 7 is great to have intelligent discussion, but sometimes it feels like 1 in 10 posts here is someone getting upset about the jokes on this sub. Let the mods deal with it, they regulate the sub.

And boy are my arms legs.

Heard they've been doing some shady business.

but then I remembered it was ground this morning.

Edit: Thank you guys for the awards, they're much nicer than the cardboard sleeve I've been using and reassures me that my jokes aren't stale

Edit 2: I have already been made aware that Men In Black 3 has told a version of this joke before. If the joke is not new to you, please enjoy any of the single origin puns in the comments

aaron abbey abbie abby abdul abe abel abigail abraham abram ada adah adalberto adaline adam adan addie adela adelaida adelaide adele adelia adelina adeline adell adella adelle adena adina adolfo adolph adria adrian adriana adriane adrianna adrianne adrien adriene adrienne afton agatha agnes agnus agripina agueda agustin agustina ahmad ahmed ai aida aide aiko aileen ailene aimee aisha aja akiko akilah al alaina alaine alan alana alane alanna alayna alba albert alberta albertha albertina albertine alberto albina alda alden aldo alease alec alecia aleen aleida aleisha alejandra alejandrina alejandro alena alene alesha aleshia alesia alessandra aleta aletha alethea alethia alex alexa alexander alexandra alexandria alexia alexis alfonso alfonzo alfred alfreda alfredia alfredo ali alia alica alice alicia alida alina aline alisa alise alisha alishia alisia alison alissa alita alix aliza alla allan alleen allegra allen allena allene allie alline allison allyn allyson alma almeda almeta alona alonso alonzo alpha alphonse alphonso alta altagracia altha althea alton alva alvaro alvera alverta alvin alvina alyce alycia alysa alyse alysha alysia alyson alyssa amada amado amal amalia amanda amber amberly ambrose amee amelia america ami amie amiee amina amira ammie amos amparo amy an ana anabel analisa anamaria anastacia anastasia andera anderson andra andre andrea andreas andree andres andrew andria andy anette angel angela angele angelena angeles angelia angelic angelica angelika angelina angeline angelique angelita angella angelo angelyn angie angila angla angle anglea anh anibal anika anisa anisha anissa anita anitra anja anjanette anjelica ann anna annabel annabell annabelle annalee annalisa annamae annamaria annamarie anne anneliese annelle annemarie annett annetta annette annice annie annika annis annita annmarie anthony antione antionette antoine antoinette anton antone antonetta antonette antonia antonietta antonina antonio antony antwan anya apolonia april apryl ara araceli aracelis aracely arcelia archie ardath ardelia ardell ardella ardelle arden ardis ardith aretha argelia argentina ariana ariane arianna arianne arica arie ariel arielle arla arlean arleen arlen arlena arlene arletha arletta arlette arlie arlinda arline arlyne armand armanda armandina armando armida arminda arnetta arnette arnita arnold arnoldo arnulfo aron arron art arthur artie arturo arvilla asa asha ashanti ashely ashlea ashlee ashleigh ashley ashli ashlie ashly ashlyn ashton asia asley a

BamBOO!

They’re on standbi

A play on words.

My daughter, Chewbecca, not so much.

Pilot on me!!

Christopher Walken

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.

Or would that be too forward thinking?

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 "

Hindus, on the other hand, never had any beef.

I won't be doing that today!

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.

https://doi.org/10.1371/journal.pone.0248482

Enteral nutrition modulation with n-3 PUFAs directs microbiome and lipid metabolism in mice

Abstract

Nutritional support using exclusive enteral nutrition (EEN) has been studied as primary therapy for the management of liver diseases, Crohn’s disease, and cancers. EEN can also increase the number of beneficial microbiotas in the gut, improve bile acid and lipid metabolism, and decrease the number of harmful dietary micro-particles, possibly by influencing disease occurrence and increasing immunity. This study investigated the effects of EEN-n-3 polyunsaturated fatty acids (3PUFAs) (EEN-3PUFAs) on the gut microbiome, intestinal barrier, and lipid or bile acid metabolism in mice. Metagenomic sequencing technology was used to analyze the effects of EEN-3PUFAs on the composition of gut microbiome signatures. The contents of short-chain fatty acids (SCFAs) and bile acids in the feces and liver of the mice were assayed by gas chromatography and ultra-high-pressure liquid chromatography/high-resolution tandem mass spectrometry, respectively. The levels of lipopolysaccharide (LPS) and D-lactic acid in the blood were used to assess intestinal permeability. The results indicated that EEN-3PUFAs could improve the composition of gut microbiome signatures and increase the abundance of Barnesiella and Lactobacillus (genus), Porphyromonadaceae, and Bacteroidia (species), and Bacteroidetes (phylum) after EEN-3PUFAs initiation. In addition, EEN-3PUFAs induced the formation of SCFAs (mainly including acetic acid, propionic acid, and butyric acid) and increased the intestinal wall compared to the control group. In conclusion, EEN-3PUFAs modulate the alterations in gut microbiome signatures, enhanced intestinal barrier, and regulated the fatty acid composition and lipid metabolism shifts and the putative mechanisms underlying these effects.

Authors:

Joseph Blommer, Megan C. Fischer, Athena R. Olszewski, Rebeccah J. Katzenberger, Barry Ganetzky, David A. Wassarman, William H. Hoffman, Stephen A. Whelan, Norman Lee, Roaya S. Alqurashi, Audrey S. Yee, Taylor Malone, Sumaiah Alrubiaan, Mary W. Tam, Kai Wang, Rozena R. Nandedwalla, Wesley Field, Dalal Alkhelb, Katherine S. Given, Raghib Siddiqui, James D. Baleja, K. Eric Paulson, Amy S. Yee, Irene Tosi, Tatiana Art, François Boemer, Dominique-Marie Votion, Michael S. Davis, Hyun Sang Kim, Eun Tae Kim, Jun Sik Eom, You