Saturday, April 27, 2024

6211 - Saturday jokes


A drunk guy walking the streets goes up to a cop.
He says, “Hey man, someone stole my car”.
Cop asks, “Well where did you last see it?”
Guy staggeringly holds up his keys and says, “On the end of these here keys”.
Cop says, “Well I dunno, sounds like you’re gonna have to go downtown to the precinct and file a report”.
Drunk guy starts walking away towards the precinct, and the cop hollers, “Before you go downtown, you may wanna zip up your fly!”
Guy looks down at his fly and moans, “Aw man, they got my girl too!”


When I was younger I trained as an ice cream man.
I went to sundae school.
It was a Rocky Road.


Ejaculate - What a Yorkshire person says to Jack when he's not on time.


My friend went skydiving wearing a regular backpack instead of a parachute. 
He won’t make that mistake again.


I was sued for sexual harassment.
I asked my lawyer if she could get me off.


Met this girl online yesterday. She's so into me.
She wants to know the name of my first pet, my mom's maiden name, and where I was born.


Orchestras are just 1800s cover bands.


Why is everyone at the gym asking me why I'm sitting still on the stationary bike? 
I'm going downhill, dude, mind your business.


I’m just laying here in bed, listening to the Doors and thinking to myself I really should oil those hinges.


My neighbor just yelled at her kids so loud that even I brushed my teeth and went to bed.


I’ve nearly finished my diploma in sandwich making.
I've got my final eggs ham tomorrow.


A man was mending his roof, when suddenly an elderly messy man showed up on his lawn, yelling to him "Sir, would you get down please".
The man, not wanting to have to climb down and up the ladder again, yelled back, "What's the matter, sir?
The old man replied, "Just get down here first!" The man thought for a second, and being the polite man he is, climbed down the ladder
The old guy, "Can you please spare me some money?
The man, after thinking for some moment, said, "Come with me.
He climbed up the ladder, with the old man following him. 
When both of them were up on the roof, the man said to the old man, "No."


A beautiful woman went up to the bar in a quiet rural pub. She gestured alluringly to the bartender who approached her immediately.
The woman seductively signaled that he should bring his face closer to hers. As he did, she gently caressed his full beard.
"Are you the manager?" she asked, softly stroking his face with both hands. "Actually, no," he replied. "Can you get him for me? I need to speak to him," she said, running her hands beyond his beard and into his hair.
"I'm afraid I can't," breathed the bartender. "Is there anything I can do?" "Yes. I need for you to give him a message," she continued, running her forefinger across the bartender's lip and slyly popping a couple of her fingers into his mouth and allowing him to suck them gently.
"What should I tell him?" the flustered bartender managed to stammer.
"Tell him," she whispered, "There's no toilet paper, hand soap, or paper towels in the lady's room.


A Scotsman, an Englishman, and an Irishman walk into a bar Sitting in a bar the Scotsman says, “As good as this bar is, I still prefer the pubs back home. In Glasgow, there’s a wee place. The landlord goes out of his way for the locals. When you buy four drinks, he’ll buy the fifth drink.” “Well,” said the Englishman, “At my local in London, the barman will buy you your third drink after you buy the first two.” “Ahhh, dat’s nothin’,” said the Irishman, “back home in my favorite pub, the moment you set foot in the place, they’ll buy you a drink, then another, all the drinks you like, actually. Then, when you’ve had enough drinks, they’ll take you upstairs and see that you get laid, all on the house!” The Englishman and Scotsman were suspicious of the claims. The Irishman swore every word was true. Then the Englishman asked, “Did this actually happen to you?” “Not to me, personally, no,” admitted the Irishman, “but it did happen to me sister quite a few times.”


I went to a costume party and the host immediately started to pick on me.
"What's your costume?" he asked.
"A harp."
"You're too small to be a harp," he told me.
I was indignant. "Are you calling me a lyre?"


I was at the same party! Saw a bloke wearing a bandana with a lady strapped to his back. He said he was a ninja turtle. ‘What’s the lady doing on your back?’ I asked. ‘It’s Michelle’ he replied.


A young woman goes to confess her sins...
“Forgive me, Father, for I have sinned.”
“What have you done?” asks the priest?
“I have sinned by being vain. Every morning I look in the mirror and think to myself, I am such a beautiful woman. Any man would be lucky to have me.”
“That’s not a sin,” says the priest.
“Really?”
“No. It’s a mistake”.


Bill and Bob, two young guys, were sitting outside a clinic.
Bill happened to be crying very loudly.
"Why are you crying?" Bob asked.
"I came here for a blood test," sobbed Bill.
"So? Are you afraid?"
"No. For the blood test, they cut my finger."
As Bob heard this, he immediately began crying profusely.
Astonished, Bill stopped his tears and asked Bob, "Why are you crying now?"
To which Bob replied, "I came for a urine test!"


“What day is it today?” 
”Just look at the date on the newspaper you have!”
"This is yesterday's newspaper!"


I asked a magic 8-ball if I would ever get better in social situations. 
Not only did it not answer me, but I got yelled at and hit with a pool stick.


Friday, April 26, 2024

6210 - Doggy 19



This incredible human being brings his 19 year old dog to the lake everyday, to give him couple hours of sleep and sweet dreams. Shep can not sleep - he suffers from chronic arthritis. The joints hurt so much that the animal could barely pull on its hind legs.
To save the animal from its torments, veterinarians offer to give it a lethal injection. However, the owner
he can not do that to his friend who saved him from suicide in the past.
And now, to ease the pain of his four-legged friend, the man carries him to the lake and holds him in his arms for several hours so that he can sleep.
Words cannot express this. When you give love, it comes back to you ten times over.
"I want people to remember that when they see these shots," said Shep's owner, John Enger.


Thursday, April 25, 2024

6209 - Thursday trees


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Wednesday, April 24, 2024

6208 - Alzheimer’s, Parkinson’s, and Lewy body dementia


Make it BIG!


DNA damage secondary to radiation, chemical agents, or accumulation of reactive oxygen species (ROS) is the main cause of cellular senescence-inducing stress. Proliferation-induced telomere shortening can also activate the DNA damage response, which in turn leads to activation of the p53–p21 pathway, inhibition of cyclin-dependent kinase (CDK)–cyclin complexes, and formation of the DREAM complex, which represses cell-cycle genes, leading to cell-cycle arrest and senescence. 

Activated p21 can also induce further ROS production, forming a vicious circle. In addition, impaired mitophagy can lead to mitochondrial dysfunction and excessive ROS production. ROS can induce senescence independently of the DNA damage response by activating the p16–RB pathway via activation of ERK, which inhibits BMI1 and thereby enables activation of p16, and by activating p38MAPK signaling, which upregulates ETS2 and in turn activates p16, and by inhibiting NAD+, which leads to reduced expression of sirtuin 1 and activation of FOXO3, which activates p53. 

P16 inhibits the formation of CDK4/6–cyclin D complexes and thereby promotes formation of the RB–2F complex, which inhibits the transcription of cell-cycle genes. Oncogene activation can activate the p53–p21 pathway not only via the DNA damage response, but also via the ARF–MDM2 signaling. In addition, oncogene activation can activate the p16–RB pathway via p38MAPK signaling. Loss of tumor suppressor genes induces senescence via Akt–mTOR signaling, which activates p53. 

Other factors that regulate the p53–p21 pathway include α-Klotho, MBP1 and p300. Epigenetic alterations such as methylation (Me) and acetylation (Ac) can induce senescence through the p16–RB pathway. NF-κB signaling regulates the senescence-associated secretory phenotype (SASP) and together with the transcription factor C/EBPβ, co-activates promoters of SASP genes, such as those that encode pro-inflammatory cytokines. 

The DNA damage response protein ATM together with NEMO activates the NF-κB–C/EBPβ signaling pathway. ROS can activate the SASP not only by promoting nuclear translocation of NEMO and activation of ATM, but also by inhibiting sirtuin 1 and activating p38MAPK and TGFβ, which in turn activate NF-κB. Heat shock, metabolic disorders, mechanical damage, and endoplasmic reticulum (ER) stress can also activate the NF-κB–C/EBPβ pathway via p38MAPK signaling. 

Cytoplasmic DNA accumulation can trigger aberrant activation of cGAS-STING cytoplasmic DNA sensors and promote the SASP via activation of NF-κB. Impairment of autophagy hampers degradation of the transcription factor GATA4, which activates NF-κB and leads to initiation of the SASP. Notably, oncogenic Ras can activate C/EBPβ via ERK–p90 signaling and histone epigenetic changes can regulate the SASP independently of the NF-κB–C/EBPβ pathway. 

ARF, ADP-ribosylation factor; BMI1, B lymphoma Mo-MLV insertion region 1 homolog; cGAS, cyclic GMP–AMP synthase; CHK, checkpoint kinase; ERK, extracellular regulated protein kinases; ETS2, E26 transformation-specific proto-oncogene 2; E2F, early 2 factor; FOXO3, forkhead box protein O3; IKK, IκB kinase; MDM, mouse double minute 2; MSK, mitogen- and stress-activated protein kinase; NEMO, NF-κB essential modulator; STING, stimulator of interferon genes.




I highlighted the words that I thought needed more explanation.

Why did I post this? I liked the picture. 


Tuesday, April 23, 2024

6207 - GUITAR INTROS




This is 14 minutes long. If you have time, try to listen without looking at the screen and see how many you recognize. He puts the name of the song on the screen for all 80. Listen again and see how many you got right. I recognized about 60 of the 80 but only knew the names of about 45 of them.