Alzheimer’s disease (AD) steals memories and disrupts lives of 5.4 million Americans (according to Alzheimer’s Foundation statistics) and 26.6 million people worldwide. Moreover AD is predicted to affect 1 in 85 people globally by 2050! AD still cannot be cured and is degenerative, so the sufferer relies on others for assistance, placing a great burden on the caregiver, who are mostly spouses or close relatives.

Now a new study conducted by a group Harvard, Boston University, The University of Alberta, The University of Arizona, and The Chopra Foundation ascribe AD memory loss to disruption of microtubules by zinc imbalance (March 23 issue of the journal PLoS One).

AD brains have two types of lesions: beta-amyloid plaques outside neurons, and neurofibrillary tangles within them. The known AD genes implicate plaques, but AD symptoms correlate more closely with tangles, comprised of “tau” protein, that are normally adhered to microtubules. So AD might be the result of the building up of beta-amyloid proteins, which convert into plaques within the brain. Excess beta-amyloid plaques induce tangles, disrupt microtubules (MTs), and cause memory loss, even with normal synaptic function. But how does it work?

The new twist is that Beta-amyloid plaques outside neurons themselves aren’t destructive directly, but lead to lower zinc levels within neurons. Zinc stabilizes many protein complexes, including MTs, polymers of tubulin. MTs regulate synapses, and play recently-revealed key roles in memory encoding in neurons.

In the present study, Craddock et al: 1) identified specific zinc binding sites to tubulin promoting side-to-side tubulin interactions which are crucial to MT polymer structure; 2) used kinetic analysis to show how extra-neuronal zinc sequestration reduces intra-neuronal zinc available to tubulin, leading to MT destabilization and tangles; and, 3) presented metallomic imaging mass spectrometry (MIMS) of AD model mice, revealing abnormal zinc distribution in critical brain regions (see featured image).

This view of AD can lead to new therapies based on stabilizing MTs. This can be achieved by normalizing intra-neuronal zinc levels, using zinc ionophore drugs such as PBT2, or promoting MT self-assembly and stability by other drugs and transcranial therapies, e.g. ultrasound at MT resonant frequencies in megahertz.

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Citation and further reading:

Craddock TJA, Tuszynski JA, Chopra D, Casey N, Goldstein LE, Hameroff SR, Tanzi RE (2012) The Zinc Dyshomeostasis Hypothesis of Alzheimer’s Disease. PLoS ONE 7(3): e33552. doi:10.1371/journal.pone.0033552

Brookmeyer R, Johnson E, Ziegler-Graham K, MH Arrighi. Forecasting the global burden of Alzheimer’s disease.

Prana Biotechnology

Some students I was teaching thought that this might be possible: to engineer the insulin-producing cells with a correctly functioning gene, a type of gene therapy.  While this has been a goal for researchers, and they have successfully made insulin-producing cells in the lab from embryonic stem cells, they are not appropriate for transplant because they do not release the insulin in response to glucose levels.  Plus, the immune system might still recognize these cells as foreign and destroy them.

So a new study is looking at transforming cells of the gut that don’t have a specific job yet.  These cells receive signals throughout the life of an individual to become many different types of cells that are used for normal gut function.  So could they engineer these cells to receive the signals to become insulin-producing cells?  Also, would the cells only release the insulin in response to blood glucose levels?

Two Columbia University researchers have started finding possible answers to these questions.  Once they turned off a gene that normally plays a key role in the fate of a cell, insulin-producing cells were generated.  Having cells in the gut that make insulin can be dangerous if they did not release insulin in response to blood glucose levels, but these “new” gut cells have glucose-sensing receptors to allow them to do just that. Another remarkable feature was that the gene could be turned off either early on in development, or later on in adulthood, so it wouldn’t matter how old the patient was.

The next step is to take the research that has been done on mice so far, and see if they can mimic this in humans with the use of a drug or chemical.  This method will also need to prove to be safe and more effective than current methods of treatment, not just to avoid the burden of daily injections.

While most students don’t fully grasp this idea, there are a few examples we can use that can help to explain this.  I have always used examples of giraffes and the development of long necks, or antibiotic resistance in bacteria, but these seem to be a bit out of the realm of many 5^th grade students.  So what better example than ourselves!

During another lesson, I introduced the development of lactase persistence, or having the ability to drink and eat dairy products past infancy.  Digesting the sugar in milk (lactose) is dependent on whether or not the cells of your small intestine are producing the enzyme lactase.  Lactase is responsible for breaking lactose into smaller components that then get absorbed into the bloodstream.  For mammals that get milk from mother early in life, this enzyme is essential.  Would a mutation in the DNA that would allow a cell to continue to make lactase past infancy be beneficial?  It all depends on which population of humans you ask.

If it is a population of humans that began drinking the milk of other animals after the development of agriculture, like those of Northern European descent, it would be selected for.  These populations now show the highest frequency of lactase persistence among all human populations.  If dairy was not a part of your diet after infancy, this mutation wouldn’t be considered beneficial and would not have been selected for, such as in African, Asian and South American populations.

So, when teaching evolution and the changes that we see in species over time, it is nice to be able to give an example that we can see in humans.  Using an example that is a recent development in humans over the last 10,000 years, may help students to understand this concept better, and apply it across any species.

This may help to answer many questions.  How can we have so many different types of cells and they all carry the same genetic information?  How is it possible for one identical twin to develop cancer while the other does not?  Can we use this control of the gene expression to help cells that may have lost their way?

It is amazing to think that just about all of the cells of the human body has the same DNA.  The full genetic profile with all of the instructions on how to make a human is in almost every cell.  When most students come through the DNA Learning Center, many of them think that there is different DNA inside of these cells.  That red blood cells have different DNA than bone cells and nerve cells.  One way this is done is through the interaction of small methyl groups (-CH₃) that get added to the DNA molecule, which can help to silence a gene that is not needed in some type of cell or at some point of development.  This is a epigenetic “tag” because there is no change to the sequence of DNA, it is just whether or not there is access to the DNA.  The methyl groups that get added make the cell unable to activate that gene.

This addition of methyl groups, called methylation, also can change throughout the course of our life.  So as we get older the interaction of these groups with our DNA can change.  So even with identical twins, who are born with the same DNA, their epigenetic “tags” can vary and occur independent of one another.  And even more, certain lifestyle choices and experiences throughout the life of a person can change the epigenetic profile of an individual.  And then this gets passed on to our children.  So even what a mother eats while pregnant can affect the tags that get passed to their child.  This ultimately will affect the expression of genes in the child.

And now we are using this information to help treat disease, such as cancer.  So if a gene is turned on that shouldn’t be, could we add methyl groups to that section of the DNA to turn it off?  This has started being used as a new therapy for the treatment for certain cancers.

This has recently been reported for patients with Hemophilia B.  Hemophilia B, also known as Christmas disease, is due to a deficiency of the clotting factor IX (FIX).  The first reported case of Hemophilia B due to a decrease in FIX was in 1952, and was called “Christmas Disease” after the first patient diagnosed was named Stephen Christmas.  Without this clotting factor, the blood does not form clots and results in severe bleeding episodes, especially in the joints and muscles.

Bettert reatment for this disorder began back in the 1960’s where they would inject FIX concentrates into the blood of patients with hemophilia B.  This increased the average age of death of 24 to a median lifespan of 63 years of age.  So with the success of the protein therapy, why try to fix the genes?  With each treatment costing $150,000 to $300,000, a patient needing clotting factors for hemophilia could incur a lifetime cost of $20 million.

So there needs to be a way that a patient can have a more effective treatment option that will cost less.  This new treatment option offers some hope.  Using a new virus for the administration of the gene, patients have seen an increased production of FIX protein for longer periods of time, and were able to stop or decrease the amount of concentrate injections they would need.  With one injection of the virus only costing about $30,000, dramatic cost savings have already been seen.  While this does offer new hope for the treatment of clotting disorders, follow-up with a larger number of patients and for longer periods of time will be needed to fully weigh the benefits and risks of this technique.  Once this has been done, hopefully we will see gene therapy used more in practice and maybe even for more than just clotting disorders.

Ponder, Katherine P.  Merry Christmas for Patients with Hemophilia B. The New England Journal of Medicine 10.1056; December 10, 2011.  Nathwani A.C., Tuddenham E.G.D., Rangarajan S., et al.

When we think of a detective the first thing that comes to mind is an investigator, either a member of a police agency or a private entity.  However there are unique detectives within the multifaceted arena of medicine.  All though we might already think of most doctors as detectives there are special doctors, units, working at the National Institute of Health’s (NIH) undiagnosed disease program.  Doctors such as William A. Gahl at the NIH are disease detectives that try to elucidate the causes and genetic basis involved in the hundreds of unsolved and mysterious diseases that arise each year.  Dr. Gahl who was interviewed for an article in scientific American explained that his group has accepted 400 out of 1700 special cases of unsolved disease.  The selection process of these cases is tough, determining which cases are new diseases and if there is a possibility of determining the genetic and biochemical basis of the disease.   As each case is worked mutations are identified that are associated with each disease.  But Dr. Gahl States that this is only the beginning of the puzzle.  The challenge becomes to identify the genetics with the pathology.

Dr. Gahls’ group has been working on a case in which a patient has endured pain for approximately twenty years and muscles of their legs have turned as hard as bricks limiting mobility.  It was determined that the patient had a rare condition in which their blood vessels bore a thick coat of calcium that restricted blood flow.  One of the first steps taken in the study was to examine the parents of the patient.  The parents after examination were healthy, which lead the group to believe that the patients’ disposition might be due to a recessive mutation.  Meaning that each parent had only one copy of a unique mutation but upon having children probability lead to the patient receiving two copies of the mutation.  After an in depth study Dr. Gahls’ group identified the location of the mutation and the error prone gene associated.  The gene that was identified is NT5E.  NT5E is involved in the production of the nucleoside adenosine (which is involved in a number of biochemical processes).  To examine this gene closely doctors cultured the patients skin cells and inserted the normal gene of NT5E and even introduced adenosine alone into the cells and miraculously they observed a reduction in calcification.  Through this analysis a better understanding of adenosine in the regulation of calcium has been brought to light.  However Dr. Gahl explains that there are a number of reasons why patients cannot just receive adenosine, but there is a class of osteoporosis drugs that pose as good candidates for treatment and they are waiting to see how these drugs perform.

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For most of the year, deciduous trees are green because of chlorophyll in the chloroplasts.  This pigment helps harness energy from the sun to fuel photosynthesis, or food production.  In the fall, days become shorter and sunlight more sparse, so plants begin to prepare for the winter – a period during which they rely on stored nutrients.   Nutrients are stored and superfluous leaves are shed , but before that, the chlorophyll begins to disappear, revealing other pigments such as yellow and orange that weren’t visible before.  Sometimes during this process, new pigments (such as reds) are produced as well.

This is controlled by up to 35 genes that can turn on and off in response to the reduction of sunlight hours.  It is a great example of the interaction between an organism’s DNA and its environment, a phenomenon many people are unaware of.  The traits and characteristics of all living things are the result of a combination of its genetic makeup and its physical and chemical surroundings.  To learn more about this type of interaction, go to chapter 35, “DNA responds to signals from outside the cell.”

Many hours of belly laughs later and I began to feel rather guilty. How terrible it must be to labor through life as Super Mann. How the schoolyard must cackle when Garage Empty is called back to class. For children with truly awful names, life is undeniably tough. Sherwood and Rayback found that these kids are more likely to require psychiatric care and to perform poorly at school. But then again, if you’re called Warren Peace, what kind of parents did you have to begin with?

Even for the majority of us not saddled with monickers such as Infinity Hubbard and Hugh Jass, names can go some way toward determining future success in life. One particularly intriguing set of analyses was conducted by Leif Nelson at UCSD and Joseph Simmons at Yale University. The authors found that individuals with the letter ‘A’ or ‘B’ in theirs initials are more likely to achieve higher grades and attend higher-ranked universities than those with ‘C’ or ‘D’ initials. Similarly, baseball players whose names begin with the strikeout-signifying letter ‘K’ tend to strike out more often. Nelson and Jackson contend that this represents an unconscious drive to produce “name-resembling performance”. Although this particular suggestion may be hard to swallow, one should not ignore the presence of name-letter effects in many walks of life.

For example, if I am called Lawrence, I am more likely to move to Los Angeles for the simple reason that our names both begin with ‘L’. If I am called Doris, I am more likely to move to Denver. This is known as “implicit egotism” and has been observed in career choice (people named Dennis or Denise are overrepresented among dentists) and choice of partner (people tend to marry those whose first or last names resemble their own). Whatever the reason, there does seem to be more to a name than meets the eye.

For many, this type of social science research only serves to fuel skepticism of the field in general. That said, the impact of broader cultural factors on cognition and cognitive decisions is undeniable. G2C Online is all about how different levels of understanding synchronize to produce human behavior – about how experiences can alter gene expression and neural connections. We receive all our experiences through the filter of culture and history and it would be foolish to underestimate them. That said, I won’t be rushing out to name my first son Aaron Aardvark.

Scientists have used genome-wide studies to define a relationship between body mass index and polymorphisms in the FTO gene (Fat Mass and Obesity Associated Gene). Recently, insights into the function of the gene has revealed some very interesting data that gives rise to optimism. Fischer et al. (2009) have shown that mice who do not have the FTO gene product are capable of decreasing fat tissue. In addition they have shown that down-regulation of the FTO gene seems to provide protection against calorie-induced obesity. These findings verify the importance of the FTO gene for the regulation of body weight. The results of this research will become very important for the development of new ways to treat obesity.

Reference: Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Bruning JC, Ruther U: Inactivation of the Fto gene protects from obesity. Nature 2009, 458(7240):894-898.

Once upon a time, in a forest with leaves and soil on the ground, there is a family of rabbits. Many animals live in this forest, including several predators for the rabbits. The mom and dad are both brown rabbits and most of their rabbit children are also brown. One of the children was born with all white fur due to a mutation in the gene for fur color. The mutation was a random mutation that occurred in the egg cell before conception even occurred. In their current environment, which of rabbits will be more likely to survive (brown or white)?

The brown rabbits are more likely to survive because they can blend in with their environment. If a predator walks by they will probably see the white rabbit before the brown ones. Unfortunately this means the white rabbit has a greater chance of dying early.

The question that stirs up confusion is: Can an organism change in response to their environment?

I would first answer this by saying that the cells of an organism can respond to changes in their environment. In fact, this flexibility allows organisms to live. Does this mean that the white rabbit will adapt to its environment and become brown? No.

Adaptation in relation to evolution refers to the population as a whole. If a member of the population has a trait that provides an advantage for survival, it is likely that the trait will be passed on to future generations. Eventually, the trait can be seen in greater numbers and even throughout the population.

Although an organism may produce different proteins under different conditions, the DNA of the individual organism will not change because there is a need for a different trait.