ORIGINS

I copy below a lecture I gave in my undergraduate course on Molecular Parasitology. Of course this has nothing to do with Parasitology, but I like to think about these things and I thought that the students might also. I told the students that this was not going to be on the exam and to close their notebooks but to open their minds.

ORIGINS

Origin of the Universe

The End of the Beginning?

Alzheimer’s Disease (AD) represents 70% of all dementia cases and dementia is the fifth biggest cause of death world-wide.The cause of this disease is unknown and there is no therapy. The universal presence of β-amyloid peptide in plaques and over-expression of mutated versions of the microtubule-associated protein, tau, in “tangles” in the brain were proposed as the possible causes of AD more than 25 years ago. However, the failure rate of the 123 drugs developed to affect amyloid formation of brain plaques in humans has been a disappointing 99%! And recently a study of the brains of eight “superagers” who lived until their 90’s with excellent memory and cognition even though both plaques and tangles were present in brain tissue appears to be a possible counter argument against the amyloid/tau hypothesis.

A recent article in the New Scientist journal entitled “We may finally know what causes Alzheimer’s – and how to stop it” reviews an intriguing and fairly compelling alternative hypothesis, that the presence of bacteria in the brain coming from gum infections with the common gum bacterium, Porphyromonas gingivalis, represents the primary cause of the dementia and the formation of plaques and tangles  is a secondary event. The classic proof that a microbe causes a specific pure culture disease involves four postulates first proposed by Robert Koch in 1884:  The bacteria must be present in every case of the disease. The bacteria must be isolated from the host with the disease and grown in pure culture. And finally, the specific disease must be reproduced when the bacterium is inoculated into a healthy susceptible host.  These postulates have been confirmed in the case of the bacterial hypothesis for Alzheimers: It was found that P. gingivalis invades and inflames brain regions affected in Alzheimers; that gum infections can worsen symptoms in mice genetically engineered to have Alzheimers and can cause Alzheimers-like brain inflammation, neural damage and amyloid plaques in healthy mice.  P. gingivalis is known to secrete two toxic enzymes called gingipains. These were found in 99% of 54 human Alzheimers brain samples from the hippocampus (The region for memory), and also in the cerebral cortex in three Alzheimers brains. Normal brains sometimes had P. gingivalis and gingipains, but at low levels.

Chronic periodontitis shows a correlation with dementia. It is thought that P. gingivalis can invade white blood cells and cells lining blood vessels and could invade the brain in that way. Invasion might also occur by way of cranial nerves near the mouth. The mechanism for P. gingivalis brain infections to cause dementia could be by triggering the release of amyloid, or it may directly damage the brain, e.g. through inflammation.

The bacterial hypothesis does not eliminate a role for genetics. I copy below from the New Scientist article: "The biggest genetic risk factor for Alzheimer’s is a variant of the gene that makes the ApoE immune protein. Last year, a team in Sweden found that the gingipains released by P. gingivalis break up the ApoE protein into fragments, cleaving it at the site of a particular amino acid within the protein, and that these fragments may harm nerves. The ApoE4 variant of this protein contains more of this amino acid, suggesting that the reason people who make this variant are at a higher risk of developing Alzheimer’s may be because harmful levels of ApoE protein fragments build up more quickly in their brains than in those of other people."

If this hypothesis proves correct, it could rapidly lead to effective treatments, such as by preventing gum disease, or blocking gingipains with specific drugs. Initial results in mice studies were very promising.

-- Now please excuse me, I must go brush my teeth.

Comments:

• Takuji Kasamatsu The evidence for the alternative thinking seems strong - is the sample size in humans substantial?

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  Larry Simpson The role of the human microbiome (your gut bacteria) in health and disease is getting stronger. "The iconic case is stomach ulcers, once thought to be caused by stress or excess acid, and treated with acid-lowering medications. Then Australian doctor Barry Marshall showed that a stomach bacterium called Helicobacter pylori was behind them, a feat that won him a Nobel prize."

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  Larry Simpson The bacterial hypothesis does not eliminate a role for genetics. I copy below: "The biggest genetic risk factor for Alzheimer’s is a variant of the gene that makes the ApoE immune protein. Last year, a team in Sweden found that the gingipains released…See More

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    Dan Ray Hmm Are there people who lack the ApoE4 protein?

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  Paula Vandever MacRae Interesting that our microbiology may be the key to so many things. Thank God for basic science research.

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  Michele Klingbeil I think the NEXT BIG thing will be Oral and Nasal cavity microbiome studies to truly understand the mechanisms in which microbes promote the "healthy" environment of those niches. Maybe we can even figure out a way to keep inhaled viruses at bay. I LOVE MICROBIOLOGY!

Blue Ice from the Sky

Larry Simpson

January 14 at 7:54 PM · 

Blue Ice
Gag me with a spoon - I just read this in a local blurb:
.......while most airline sewage is disposed of properly these days, there have been reports of it being felt by residents. Below is a link to one such report : https://slate.com/…/long-island-couple-pelted-with-poo-wher…

It made me think of once when I was flying cross country. I had just purchased a new expensive trifocal eye glasses and it was not very tight and when I was using the bathroom, it fell into the toilet. I had an existential moral decision to make whether I should quickly stick my hand into the swirling blue liquid and save my glasses, but I rapidly thought better of this. But I did ask the Stewardess to ask the pilot to contact the unfortunate house into which blue ice fell from his airplane during a landing to see if they saw my glasses when it melted.

Oh well, nothing asked, nothing achieved.

I told you so

I hate to say "I told you so" but here it goes. I copy below a posting I did last February which seems to have been further proved by the FBI investigation:

Trump is a Traitor to the United States

This is a powerful statement and should be backed up by evidence.

For some time Trump has treated Russia and in particular Putin with kid gloves. He has claimed that the Mueller investigation is a hoax devised by the Democratic Party. And he also claims, usually multiple times in the same statement, that neither he nor his campaign has committed collusion with the Russians. Today Trump's statement that there is no collusion has been proved false by the new indictments by Mueller of multiple Russians who actually set up shop in the United States, impersonated American citizens and rented space on servers. They opened accounts in banks and in PayPal to pay people to unknowingly do work for them. They had a budget from Russia of around $1,000,000 per month.

Recently Trump refused to enable a new Russian sanctions law that was overwhelmingly passed in both houses. This is illegal since he is required by law to implement this law. He has also refused to the present day to do anything to prevent the Russians from repeating an attack on the 2018 midterm elections, a cyber attack which the heads of the Intelligence Agencies say is ongoing. This in itself is treasonous behavior and may actually be the most significant damage Trump is doing to our country.

Yet another problem is that Trump had people at the White House such as his Private Secretary, Rob Porter, who was not given high level security clearances due to domestic violence and still saw every top secret classified paper that went to Trump's desk, including the daily intelligence briefings. How do we know that Porter was not blackmailed and gave national secrets to the Russians? His son in law, Jared Kushner, also was not given a high level security clearance but nevertheless had access to many top secret material due to his portfolios given by Trump. How do we know what happened? But in any case, Trump himself gave top secret materials to the Russians in the Oval Office when he told them that he fired Comey to stop the investigation of his possible collusion with the Russians.

As for why has Trump acted like this, one need only look at the Steele Dossier. There are reports of witnesses in the hotel who corroborate Steele's most salacious reporting. One witness was an American who claimed to have seen an argument with hotel security over whether the prostitutes would be allowed up to Trump's suite. In addition, the BBC Correspondent, Paul Wood, wrote that he heard about additional compromising material from two sources. And claims of the existence of more video tapes showing even more extreme behavior have been circulating. Trump's behavior could very well be one reason for blackmail by Russia. Another reason could be the likely Russian Oligarch money laundering that Trump and his family appear to have engaged in.

It looks like the Russians were able to essentially take over the US government by engineering the election of Trump as President and blackmailing him to behave as they wish. Trump is a traitor and the continued presence of Trump as President is a true national security problem for our country.

Now is the Time

The Trump government shutdown has reached very dangerous unprecedented territory. Almost all Homeland Security agencies, including the FBI, the Coast Guard, the TSA, Immigration, FEMA, Secret Service, National Security Agency, etc., are affected and will begin losing their irreplaceable people as the Shutdown continues beyond the second missing paycheck. This cannot continue without danger to the security of our country. 

The FBI Counter Intelligence Office suggested strongly that Trump has been compromised by the Russians for whatever reason such as money laundering or some yet unknown activity. In fact, the evidence that Trump is essentially an agent of the Russian government is overwhelming and it appears that Putin has finally asked his agent to cause serious damage to our country by irreversibly shutting down the most important agencies based on a fake demand of building a wall, which he had promised Mexico will pay for, to solve a non-existent immigration problem on the US-Mexican border. It would be nice to be able to wait for the final Mueller report but by then it may be too late.

Think about it. If Trump is actually a Russian agent, what would be the best way to end investigations and damage the FBI ? It would be exactly what he is doing.

I propose that the US begin the process to remove Trump as President by impeachment or the 25th amendment. Now is the time!

Just Saying

Over 800,000 Federal workers suffered through the longest government shutdown ever due to the orange monster himself lying that there is an emergency at the Southern border and wanting 5.7 billion dollars to begin making his wall (that he had claimed  many times would be paid by Mexico.) Last  Friday  I realized that  the best way to end the shutdown immediately is for all TSA workers and Air Controllers to call in sick. This will stop all air traffic in the US immediately and I am sure that the Republican Senators and the great orange moron in the White House will bring a rapid stop to the shutdown without ransom having to be paid for his proposed Medieval border wall.

1/24/2018
Turns out that nothing so drastic as I suggested had to be done - The system is collapsing on its own. I hope someone in the White House reads this news flash to Trump (since he himself does not read):

https://www.cnn.com/…/air-traffic-controller-sho…/index.html

And of course Trump's pathetic spokeswoman, Sarah Sanders - who looks like she definitely had a problem with her breakfast  (below) - says in panic mode to Democrats: "Sit down at the table. Let's negotiate". 

I truly hope that the Dems wait for Trump to declare a victory and stop the shutdown. 

Well he did shout it down for 3 weeks but mentioned yesterday that  he plans to do another shutdown if the Dems do not give him his money for his verdamded wall.  We will see.

Change is Coming – Whether you Like it or Not

A letter to the Editor of The New Scientist from a Blaise Bullimore in the UK states in much more compelling language what I have been thinking and saying for several  years now.  The best way to see this is to copy her letter below (with some revisions).

“I agree wholeheartedly with your exhortation not to blow the chance to save our climate. But barring a major miracle, it is game over: not for saving the planet itself of course – ….., it will survive in some state or other- but for saving a planet fit for supporting humanity and a good slice of other life forms. The necessary time scales for the essential, tough actions you describe …leave no room for optimism. Let's set aside for a moment the likes of Trump and the commitment to exponential growth in the current economic model (Full disclosure: I never articulated this compelling idea. Thanks, Blaise). ….. At 65, I will be spared the worst of the impacts of climate change. The fate of everyone under the age of, say, 45  terrifies me, though. Speaking on behalf of her generation at last month’s climate summit in Poland, 15 -rear old Greta Thunberg said “We have not come here to beg the world leaders to care for our future. They have ignored  us in the past and they will ignore us again. We have come  here to let them know that change is coming whether they like it or not.””