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.

6209 - Thursday trees

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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.

https://www.nature.com/articles/s41581-022-00601-z

https://neurosciencenews.com/neuron-aging-alzheimers-25971/ < Where I got the title for the post.

I highlighted the words that I thought needed more explanation.

Why did I post this? I liked the picture. 

6207 - GUITAR INTROS

TOP 80 GREATEST GUITAR INTROS

Paul Davids

Paul Davids

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.

6206 - Long joke Sunday twofer

After having dug to a depth of 10 feet last year outside of Buffalo, New York scientists found traces of copper cable dating back 120 years. 

They came to the conclusion that their ancestors already had a telephone network more than 100 years ago. 

Not to be outdone by the New Yorkers, in the weeks that followed, a Wheeling WV archaeologist dug to a depth of 20 feet somewhere just outside Woodsdale. 

Shortly after, a story in The Intelligencer read, "WV archaeologists, reporting a finding of 200 year old copper cable, have concluded that their ancestors already had an advanced high-tech communications network a hundred years earlier than the New Yorkers. 

One week later, a local newspaper in Barton Ohio reported the following: "After digging down about 30 feet deep in his pasture near the community of Hell’s Kitchen, Pete Riley, a hell of an engineer and a self-taught archaeologist and gynecologist reported that he found absolutely nothing. 

Riley has therefore concluded that 300 years ago, Ohio had already gone wireless."

Once upon a time, in a land far away, a beautiful, independent, self-assured Princess happened upon a frog as she sat, contemplating ecological issues on the shores of an unpolluted pond in a verdant meadow near her castle.

The frog hopped into the Princess's lap and said. "Elegant Lady, I was once a handsome Prince, until an evil witch cast a spell upon me. 

One kiss from you, however, and I will turn back into the dapper, young Prince that I am. Then, my sweet, we can marry and set up housekeeping in your castle with my mother, where you can prepare my meals, clean my clothes, bear my children, and forever feel grateful and happy doing so."

That night, as the Princess dined sumptuously on lightly sauteed frog legs seasoned in a white wine and onion cream sauce, she chuckled and thought to herself, "I don't think so".