Mid-June garden: after the rain

Stay hungry, stay foolish and more

If you have never listened to Steve Jobs’ 2005 Stanford Commencement Address, do so. These are 15 minutes of true life lessons, and they do come from the heart. Here is one of the best moments in the speech:

When I was 17, I read a quote that went something like: "If you live each day as if it was your last, some day you'll most certainly be right." It made an impression on me, and since then, for the past 33 years, I have looked in the mirror every morning and asked myself: "If today were the last day of my life, would I want to do what I am about to do today?" And whenever the answer has been "no" for too many days in a row, I know I need to change something.

Are you stuck at doing something that you would not do on your last day of life? 

I am and I have no idea how to get out of the loop.

Diet And Colorectal Cancer: Nucleus To Cell Membrane

Review article:

The International Agency for Research on Cancer recently released an assessment classifying red and processed meat as "carcinogenic to humans" on the basis of the positive association between increased consumption and risk for colorectal cancer. Diet, however, can also decrease the risk for colorectal cancer and be used as a chemopreventive strategy. Bioactive dietary molecules, such as n-3 polyunsaturated fatty acids, curcumin, and fermentable fiber, have been proposed to exert chemoprotective effects, and their molecular mechanisms have been the focus of research in the dietary/chemoprevention field. Using these bioactives as examples, this review surveys the proposed mechanisms by which they exert their effects, from the nucleus to the cellular membrane. In addition, we discuss emerging technologies involving the culturing of colonic organoids to study the physiological effects of dietary bioactives. Finally, we address future challenges to the field regarding the identification of additional molecular mechanisms and other bioactive dietary molecules that can be utilized in our fight to reduce the incidence of colorectal cancer.

Certain bioactive dietary factors have a protective effect against colorectal cancer, and scientists are investigating the cellular mechanisms behind these effects.

Eat your fiber!

Immune Checkpoint Blockade And Treatment For Mismatch Repair Deficient Cancers

At left, a possible mismatch repair cancer showing infiltrating  white blood cells. By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=30309760

Interesting news on the cancer front: tumors exhibiting mismatch repair deficiency, in which DNA repair is aberrant and many mutations occur, produce many mutant proteins.  These can serve as “mutant neoantigens” - in theory recognized by the immune system. However, immune system checkpoint exists in cancer, preventing such recognition.  Therefore, immune therapy that targets and “blockades” such checkpoints, allowing for the recognition of these tumors and their mutant antigens, is a promising therapeutic approach.  The paper shows some positive results for colorectal cancers that are specifically exhibiting the mismatch repair problem.

How to make a team

I would like to share an excellent post on how to make a team:

Steal This: The 90/10 Decision Making Model

According to the post, 90% of the decisions of the team members should be taken on their own - without the permission of the boss. 

How is your team working? 

If you are the boss, have you empowered your team in its decision-taking process? 

If you are a team member, do you have a boss that trusts you?

I am not a boss. And as a "team member", I pass every single decision (or rather, suggestion) through my immediate bosses. Yes, that's right - I have several of them. 

Having multiple bosses hovering above and you not being able to take autonomous decisions are the reasons why things are not done on time in academia. The hands of people who can deliver results are usually tied, and the decision-taking process is muddled.
 
I think that the only decision I can take at my job is when I can visit the ladies' room. 

I did have some creative work done in the lab for the past 10 or more years, but again, even this road is shut down, if one cannot bring funds to support the research.

Man Shall Not Live By Bread Alone

By 3268zauber - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=4298187

Let’s take a look at this article, which I find somewhat misleading.

First, the time periods the bread diets were evaluated were very short. What’s the long term effects of the different diets?  Second, while there may be individual variation in, for example, glycemic response, fact is, your average person is not going to have their metabolic responses to bread types analyzed. You’ll get the most “bang for the buck” with respect to population health providing generally healthy guidelines. Third, whole wheat bread has advantages of white bread with respect to fiber (the long range effects of which on colon cancer risk is going to be measured in years/decades, not a week or two) and vitamin content.

When studies like this are reported without giving all the context, it gives the general public license to gorge on food that is likely not optimal for health - looking forward to an entire lifetime, not just for a week or two.

Now, that doesn’t mean the findings should be ignored.  Maybe white bread isn’t as bad as it has been made at to be – but that needs to be evaluated over a long time frame.  The bottom line though is that whole wheat has a number of advantages for the average person and I don’t see why that should be ignored.  If you are going to eat a certain volume of bread, why not maximize fiber and various micronutrients?

Eat, drink, smoke – no problem

In March this year, there was yet another feast of ignorance, but I could not bring myself to address it until now.

It was reported at that time that “about two-thirds of cancers are caused by random typos in DNA that occur as normal cells make copies of themselves”. 

The report was based upon a "reiterated" research paper by B. Vogelstein.and his mathematician C. Tomasetti. The “finding” supposedly explained why healthy people still get cancer. In other words, no matter how diligently you take care of yourself and how healthy your lifestyle is, you can still develop cancer. 

This part is TRUE. All of us have cells that divide (i.e., replicate), and mistakes are introduced in cells’ DNA during replication. These mistakes may turn out to be mutations that can drive cancer development.

However, the esteemed researchers did not elaborate on the other side of the story: if you do not put any effort into being and staying healthy, if you are obese, physically inactive, smoke and drink, then you do have a HIGHER chance of developing cancer.

The two researchers estimated that 66 percent of mutations in cancers resulted from copying errors (during replication), the rest were due to lifestyle, environmental factors, and inheritance.

What the researchers COULD NOT AND DID NOT estimate was how many replication-introduced DNA errors were eliminated in some people, and therefore, these people NEVER developed cancer. Remember, individuals who lead a healthy lifestyle have also a healthy immune system that eliminates many of the cells with mutations (i.e., DNA errors). Many mutations are also “intercepted” by additional control mechanisms, and the cells can either repair the mistakes in the DNA or kill themselves (i.e., the cells commit to apoptosis).
 
Therefore, a better question that the researchers could have pondered was, why the DNA mistakes are sometimes not “addressed” by the control mechanisms. The esteemed researchers did not discuss that some DNA mistakes are not corrected/addressed by the natural control surveillance mechanisms simply because people have unhealthy lifestyle: eat too much sugar, become overweight/obese, stress out, do not move too much, drink and smoke, etc.

But then isn’t it more interesting to say one side of the story and fatalistically conclude that “most cancers are due to bad luck”?  After all, the words "bad luck" make a much more interesting title.

By the way, the fact that our DNA replication machinery is not perfect has been known for a long time. There is a silver lining to this imperfection – if there were no changes introduced in the DNA, we would not have had evolved from apes to whatever we think we are today.

Here are some comments that appeared after the quoted above article:

“…well that makes us all feel better now we know that its just bad luck”

“…Sounds like the "cancer prevention" industry - which is massive is busy spinning the truth!”

“…Genetics are the key factor. It basically refutes the diet fanatics, and their bleeting about health benefits of certain diets.”
 
The  comments are a prime example of how general public education marches on!

The glory of Spring is in my garden