In today’s issue of PNAS, a team made up of University of Chicago and Cornell members have completely rethought the action of robotic gripping. Their “hand” consist of a elastic bag filled with a granular material (I’m guessing something like coffee grounds) that surrounds the object. Once around the object, air is removed from the bag and the material hardens, thus “gripping” the article. The applications are endless.

Check it out:

The Lab of Jan-Ake Gustafsson, University of Houston’s world renowned expert on all things estrogen, recently published a journal article in the prestigious Proceedings of the National Academy of Sciences describing a very interesting link between gallbladder cancer (GBC) and estrogens.

Estrogens (estradiaol, estriol, estrone) are steroid hormones found in both men and women. In women, estrogens are produced mostly by the ovaries and are responsible for female secondary sex characteristics and menstruation. In men they are produced in the testes and regulate sperm growth and in a possible interplay with androgens may drive libido. In both sexes they also found to coordinate the regulation of fat levels, lung health, and fluid balance.

The Estrogens’ link to malicious cell growth is not new for they are long associated with breast, ovary, liver and pancreas cancers. A good example of how estrogen can cause things to go awry is with breast cancer: In healthy female breast tissue high estrogen levels during menstruation cause the propagation of cells that line the milk glands. When estrogen levels fall following the end of menstruation, the cells die and are absorbed by the body. The mechanism by which this happens is this: estrogen molecules in the blood enter a cell and bind to a protein called the Estrogen Receptor (ER) (see, we scientist do sometimes give them obvious names!) and like a switch, ER turns on the genes in charge of cell growth of the milk gland lining.

Since cancer is a disease in which a mutation in cell growth genes causes uncontrolled growth, as shown in the figure above, it is easy to see how in the ~500 times a woman menstruates in her lifetime that one propagated mutation can eventually wreak havoc on those cells.

The gallbladder is a small pear shaped sack located under the liver. The liver creates a digestion aid called bile that is stored and concentrated in the gallbladder. When digesting food, the gallbladder contracts and releases the bile into the intestine to break down fats from your diet. Since fat (think of oil or butter) is not soluble in water, the bile contains special salts and cholesterol derived acids that surround the fat and increases its ability to be absorbed by your body.

GBC is uncommon and has been found to be difficult to diagnose early on due to its overlapping symptoms with other diseases. If GBC is discovered early, drug treatment is pretty much nonexistent and the usual remedy consists of surgery to remove the cancerous gallbladder. In the average 10-15 years it takes to become fully diseased and therefore discovered, the cancer has usually become aggressive and spread to other organs, leaving a rather grim prognosis.

Until now what may be causing GBC was the usual vague cancer causing suspects: could be genetic, could be environmental (pollutants, etc), could be the stars were aligned incorrectly, etc. A review of the literature shows several journal articles reporting a correlation with gallstones and GBC in post-menopausal woman using hormone (i.e. estrogen) replacement therapy as well as women using birth control. It was Gustafsson and his group that finally connected the dots and noticed a critical common ingredient: GBC occurs more frequently in women and therefore estrogen may be playing an important role in the development of GBC.

One of the main proteins responsible for the activation of bile creation is a not too distant relative of the ER called the Liver-X-Receptor (LXR). There are two forms of LXR, named LXR alpha (LXRa) and LXR beta (LXRb). LXRa is found exclusively in the digestive organs (liver, spleen, kidneys, intestines), fat cells, and lungs. In the liver, LXRa is activated by metabolized cholesterol and turns on the genes needed to synthesize bile salts/acids. LXRb is found in all tissues and is involved in regulating fat, sugar and cholesterol levels. A possible association between ER’s and LXR’s is that they both have roles in regulating cholesterol.

When the researchers tested male and female mice lacking LXRa, LXRb or both proteins, they found that the gallbladders of only the female mice missing the LXRb protein were infected, swollen, and pre-cancerous. With this clue Gustaffson’s team figured that since cancer is a metabolic disease where the cells grow uncontrollably, the next logical stones to look under should be the proteins involved with regulation of cell growth. Indeed upon checking, the team found that the pathway involved in cell growth and adhesion to be severely defective in the mice missing LXRb. Finally, they made the LXRb/estrogen/gallbladder cancer connection by testing female mice lacking LXRb and had their ovaries (the main production organ of estrogens in females) removed and sure enough found no evidence of gallbladder precancerous growth.

This is the first time a biochemical association between estrogens and GBC has ever been demonstrated. This is very promising news for those diagnosed with GBC because a new option is to now target LXRb for drug treatment. It will be exciting to see Gustafsson’s team as they determine how estrogens interplay with LXRb and the cell growth proteins.

Atrial fibrillation (AF) effects about 2.2 million Americans. AF is when the upper chambers of the heart shake rapidly instead of pumping, leading to a reduced output of blood moved through the heart. Along with feelings of racing heart and chest pain people who have AF are usually very intolerant of exercise due to a reduced volume of oxygenated blood flowing through their body. This reduced output also creates pools of stagnant blood in the heart chambers that can clot and cause heart attack or stroke. Treatment for AF has been focused on restoring the heart to a normal rhythm, yet did not treat the cause due to little or no details into why the heart behaves this way.

A recent PNAS paper from James Martin, M.D., Ph.D. at The Texas A&M Health Science Center IBT shows that AF could be caused by a gene called Pitx2. Previous research has shown that this gene is involved in coordinating your internal left-right asymmetry during early embryonic stages (i.e. your heart goes on the left side, liver goes on the right, etc.). What the heck is a gene related to internal symmetry got to do with AF? Exactly, what Dr. Martin wanted to know.

The first clue that led Martin and his team to believe Pitx2 may be involved in AF was when they discovered that mice with half a copy of Pitx2 (i.e. only one from the mother and none from the father) had AF, along with racing or arrhythmic hearts. Further experiments indicated that Pitx2 was specifically responsible for turning off the pacemaker gene in the left upper chamber of the heart during embryonic development. With two pacemakers instead of one yelling “beat now!” the upper chambers of the heart simply become confused and they shake like a thirteen year old torn away from his x-box. With this discovery in hand, Martin and his team hope to create a more specific treatment for AF.