Immune Defect As A Cause Of Alzheimer's Disease

An interesting hypothesis, abstract:

Inflammation is an immune activity designed to protect the host from pathogens and noxious agents. In its low-intensity form, presence of an inflammatory process must be inferred from appropriate biomarkers. Occult neuroinflammation is not just secondary to Alzheimer's disease (AD) but may contribute to its pathogenesis and promote its progression. A leaky blood-brain barrier (BBB) has been observed in early AD and may play a role in its initiation and development. Studies of the temporal evolution of AD's biomarkers have shown that, in AD, the brain's amyloid burden correlates poorly with cognitive decline. In contrast, cognitive deficits in AD correlate well with synapse loss. Oligomeric forms of amyloid-beta (oAβs) can be synaptotoxic and evidence of their deposition inside synaptic terminals of cognition-associated neurons explains early memory loss in AD better than formation of extracellular Aβ plaques. Among innate immune cells that reside in the brain, microglia sense danger signals represented by proteins like oAβ and become activated by neuronal damage such as that caused by bacterial endotoxins. The resulting reactive microgliosis has been implicated in generating the chronic form of microglial activation believed to promote AD's development. Genome-wide association studies (GWASs) have yielded data from patients with sporadic AD indicating that its causes include genetic variation in the innate immune system. Recent preclinical studies have reported that β-hydroxybutyrate (βOHB) may protect the brain from the adverse effects of both the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome and the deacetylation of histone. Consequently, there is an urgent need for clinical investigations designed to test whether an orally administered βOHB preparation, such as a ketone ester, can have a similar beneficial effect in human subjects.

Immune problems and inflammation may be at the heart of many chronic disorders.  Hopefully, β-hydroxybutyrate  will be helpful.  Doing everything possible to improve immune function and reduce (unnecessary) inflammation may be helpful as well.

Flex your financial muscle

I have previously written about financial independence because it is my goal.  

I have always been thrifty; yet, in my early years no one told me that I could be more financially disciplined and more purposeful with my money. These days, however, I look around my house and instead of stuff, I see money I could have invested. I see days of freedom I would never recover.

How am I going to get rid of all the material junk? This is another question that frightens me. One day, I would like all my belongings to fit in two suitcases. And then a reasonable bank account would propel me into my adventure.

Luckily, some young people today are well aware of what they can achieve financially and how they can achieve it. Some of them even preach it online (see below)! Therefore, my child does not have to follow the road of extreme slavery that describes my everyday life.

For the past three or four years, I have listened to various podcasts on early retirement and financial independence; however, with time, these became a bit repetitive and boring.

Eventually, I switched to videos on investing. At this point, I do not need the impetus that is constantly drummed up in podcasts. All I need is to know more about the tools and the detailed implementation of a successful personal financial plan.

Here are some of the useful (and entertaining) video resources I have found in the past months:

Personal finances, taxes, investing: Money and Life TV with Mike the CPA

Investing, dividends, passive income: Joseph Carlson 

Investing, real estate, practical advice: Graham Stephan

Investing, passive income: Andrei Jikh

If you have kids, let them watch Graham Stephan and Adrei Jikh. After all, peer-to-peer advice is ranked higher than parent-to-child! 

I wish you profitable watching!

Epigenomics And Cancer Heterogeneity

There can be considerable heterogeneity in cancers, and this can contribute to progression and resistance to therapy.  This heterogeneity can arise not only from DNA sequence changes (i.e., mutation) but also from epigenetic changes - changes in the modifications of chromosomes - on a single cell level, making one cell different than another with respect to gene expression, even if the gene sequences remain the same.  A paper of interest, abstract:

Cell-to-cell heterogeneity is a major driver of cancer evolution, progression, and emergence of drug resistance. Epigenomic variation at the single-cell level can rapidly create cancer heterogeneity but is difficult to detect and assess functionally.

RESULTS: We develop a strategy to bridge the gap between measurement and function in single-cell epigenomics. Using single-cell chromatin accessibility and RNA-seq data in K562 leukemic cells, we identify the cell surface marker CD24 as co-varying with chromatin accessibility changes linked to GATA transcription factors in single cells. Fluorescence-activated cell sorting of CD24 high versus low cells prospectively isolated GATA1 and GATA2 high versus low cells. GATA high versus low cells express differential gene regulatory networks, differential sensitivity to the drug imatinib mesylate, and differential self-renewal capacity. Lineage tracing experiments show that GATA/CD24hi cells have the capability to rapidly reconstitute the heterogeneity within the entire starting population, suggesting that GATA expression levels drive a phenotypically relevant source of epigenomic plasticity.
CONCLUSION: Single-cell chromatin accessibility can guide prospective characterization of cancer heterogeneity. Epigenomic subpopulations in cancer impact drug sensitivity and the clonal dynamics of cancer evolution.

Identifying these epigenetic changes can be the first step in developing novel approaches to reverse the changes and/or target those cells containing such changes, for therapeutic benefit.

Corn muffins and brownie muffins

The perfect breakfast would meet your savory and sweet cravings without any guilt. Therefore, the perfect breakfast comes into the shape of a corn muffin and a brownie muffin!

The corn muffins below can be enriched by adding some pumpkin or sunflower seeds and flaxseed. 

The added sugar in the brownie muffins comes only from the chocolate chips. These muffins are also rich in fiber; therefore, the sugar spike would be lower after indulging a muffin.


Corn muffins (12 muffins)
 
Ingredients:
1 cup cornmeal
1 cup whole-wheat flour
1tsp salt
1 tsp baking powder
2 tsp baking soda
2 eggs
1 cup whole milk yogurt (plain)
½ cup water
1 cup corn kernels (canned)
¼ cup olive oil
1Tbsp hot pepper flakes (optional)
seeds (optional)
 
Directions:
Preheat the oven to 375°F. Stir together the dry ingredients (flour, cornmeal, salt, baking soda and baking powder, the pepper flakes). In another bowl, combine the three lightly beaten eggs, yogurt, water, oil, and corn kernels. Add the dry ingredients and stir gently. Distribute the dough into an oiled12-muffin pan. Bake for 25 minutes or until golden-brown.

Brownie muffins (12 muffins)

Ingredients:
3-4 ripe bananas (mashed)
4 oz (113 g) of unsweetened applesauce
1 Tbsp vanilla essence
3 eggs (lightly beaten)
1 cup whole-wheat flour
½ cup cocoa powder
2 tsp baking soda
3/4 cup semi-sweet chocolate chips
1 cup walnuts, chopped
 
Directions:
Preheat the oven to 375°F. Oil a muffin pan. Combine the mashed bananas, apple sauce, vanilla and eggs. Add the pre-mixed flour, cocoa powder, and baking soda. Stir to incorporate all. Add the chocolate chips and walnuts, distribute into the 12 slots of the muffin pan. Bake for 25-30 minutes.

Mushroom and pepper soup

Soups are the best nourishment for cold, winter days. At this time of the year, my dinners frequently consist of a bowl of warm soup, a boiled egg and a piece of fruit.
Below is the recipe for a mushroom soup. This could be served with a bit of lemon juice.
Mushroom and pepper soup

Ingredients: 
5-6 cups mushrooms, diced
1 medium size onion, diced
1 medium size red sweet pepper, diced
½ cup bulgur wheat
2-3 medium size potatoes, cut into big chinks
1 tsp turmeric
¼ tsp black pepper
salt to taste
1-2 Tbsp cooking oil
Directions:
Add oil to the soup pot and saute the onion for five minutes. Add the mushrooms and potatoes, continue cooking with a closed lid. Once the liquid of the mushrooms decreases, add some water to keep the potato chinks under the water surface. Once the potatoes are soft, mash them and add water to the desired final volume (I usually add 12 cups of warmed up water). Bring to boil and add the diced pepper. Once the pepper is cooked, add the bulgur, all spices and stop the heat. Cover the pot again and keep the lid on for one hour before serving.