Molecule Drives Aggressive Breast Cancer

 — Recent studies by researchers at Thomas Jefferson University's Kimmel Cancer Center have shown a gene known to coordinate initial development of the eye (EYA1) is a powerful breast tumor promoter in mice. The gene EYA1 was also shown to be overexpressed in a genetic breast cancer subtype called luminal B.

The scientists found that excess activity of this gene -- EYA1 -- also enhances development of breast cancer stem cells that promote resistance to cancer therapy, recurrence, and poor survival.

Because EYA1 is an enzyme, the scientists are now working to identify a natural compound that could shut down EYA1 activity, says Richard Pestell, M.D., Ph.D., Director of Kimmel Cancer Center.

"It was known that EYA1 is over-expressed in some breast cancers, but no one knew what that meant," he says. "Our studies have shown the enzyme drives luminal B breast tumor growth in animals and the enzyme activity is required for tumor growth."

In a mouse model of aggressive breast cancer, the research team targeted a single amino acid on the EYA1 phosphatase activity. They found that inactivating the phosphatase activity of EYA1 stopped aggressive human tumors from growing.

"We are excited about the potential of drug treatment, because it is much easier to develop a drug that targets a phosphatase enzyme like EYA1, than it is to target a gene directly," he says.

Tracing how EYA1 leads to poor outcomes

The study, which was published in the May 1 issue of Cancer Research, examined 2,154 breast cancer samples for the presence of EYA1. The researchers then linked those findings to patient outcomes. They found a direct relationship between increased level of EYA1 and cyclin D1 to poor survival.

They then chose one form of breast cancer -- luminal B -- and traced the bimolecular pathway of how EYA1 with cyclin D1 increases cancer aggressiveness. Luminal B breast cancer, one of five different breast cancer subtypes, is a hormone receptor-positive form that accounts for about 20 percent of human breast cancer. It is more aggressive than luminal A tumors, a hormone receptor-positive cancer that is the most common form of breast cancer.

Their work delineated a string of genes and proteins that are affected by EYA1, and they also discovered that EYA1 pushes an increase in formation of mammospheres, which are a measure of breast cancer stem cells.

"Within every breast cancer are breast cancer stem cells, which give rise to anti-cancer therapy resistance, recurrence and metastases," Dr. Pestell says. "We demonstrated in laboratory experiments that EYA1 expression increase the number of mammospheres and other markers of breast cancer stem cells."

"As the EYA1 phosphatase activity drove breast cancer stem cell expansion, this activity may contribute to worse survival," he says.

AMAZING!!!!!!!! ISN'T IT??!!!

Babies Can Read Each Other’s Moods, Study Finds

 — Although it may seem difficult for adults to understand what an infant is feeling, a new study from Brigham Young University finds that it's so easy a baby could do it.

Psychology professor Ross Flom's study, published in the academic journalInfancy, shows that infants can recognize each other's emotions by five months of age. This study comes on the heels of other significant research by Flom on infants' ability to understand the moods of dogs, monkeys and classical music.

Research shows that babies can understand each others emotional signals at five months of age. These baby boys are cousins - the one on the left is four months old and the one on the right is five months. (Credit: Image courtesy of Brigham Young University)

"Newborns can't verbalize to their mom or dad that they are hungry or tired, so the first way they communicate is through affect or emotion," says Flom. "Thus it is not surprising that in early development, infants learn to discriminate changes in affect."

Infants can match emotion in adults at seven months and familiar adults at six months. In order to test infant's perception of their peer's emotions, Flom and his team of researchers tested a baby's ability to match emotional infant vocalizations with a paired infant facial expression.

"We found that 5 month old infants can match their peer's positive and negative vocalizations with the appropriate facial expression," says Flom. "This is the first study to show a matching ability with an infant this young. They are exposed to affect in a peer's voice and face which is likely more familiar to them because it's how they themselves convey or communicate positive and negative emotions."

In the study, infants were seated in front of two monitors. One of the monitors displayed video of a happy, smiling baby while the other monitor displayed video of a second sad, frowning baby. When audio was played of a third happy baby, the infant participating in the study looked longer to the video of the baby with positive facial expressions. The infant also was able to match negative vocalizations with video of the sad frowning baby. The audio recordings were from a third baby and not in sync with the lip movements of the babies in either video.

"These findings add to our understanding of early infant development by reiterating the fact that babies are highly sensitive to and comprehend some level of emotion," says Flom. "Babies learn more in their first 2 1/2 years of life than they do the rest of their lifespan, making it critical to examine how and what young infants learn and how this helps them learn other things."

Flom co-authored the study of 40 infants from Utah and Florida with Professor Lorraine Bahrick from Florida International University.

Flom's next step in studying infant perception is to run the experiments with a twist: test whether babies could do this at even younger ages if instead they were watching and hearing clips of themselves.

Brain's 'Garbage Truck' May Hold Key to Treating Alzheimer's and Other Disorders

 — In a perspective piece appearing today in the journal Science, researchers at University of Rochester Medical Center (URMC) point to a newly discovered system by which the brain removes waste as a potentially powerful new tool to treat neurological disorders like Alzheimer's disease. In fact, scientists believe that some of these conditions may arise when the system is not doing its job properly.

"Essentially all neurodegenerative diseases are associated with the accumulation of cellular waste products," said Maiken Nedergaard, M.D., D.M.Sc., co-director of the URMC Center for Translational Neuromedicine and author of the article. "Understanding and ultimately discovering how to modulate the brain's system for removing toxic waste could point to new ways to treat these diseases."

Scientists point to a newly discovered system by which the brain removes waste as a potentially powerful new tool to treat neurological disorders like Alzheimer's disease. In fact, scientists believe that some of these conditions may arise when the system is not doing its job properly. (Credit: © James Steidl / Fotolia)

The body defends the brain like a fortress and rings it with a complex system of gateways that control which molecules can enter and exit. While this "blood-brain barrier" was first described in the late 1800s, scientists are only now just beginning to understand the dynamics of how these mechanisms function. In fact, the complex network of waste removal, which researchers have dubbed the glymphatic system, was only first disclosed by URMC scientists last August in the journal Science Translational Medicine.

The removal of waste is an essential biological function and the lymphatic system -- a circulatory network of organs and vessels -- performs this task in most of the body. However, the lymphatic system does not extend to the brain and, consequently, researchers have never fully understood what the brain does its own waste. Some scientists have even speculated that these byproducts of cellular function where somehow being "recycled" by the brain's cells.

One of the reasons why the glymphatic system had long eluded comprehension is that it cannot be detected in samples of brain tissue. The key to discovering and understanding the system was the advent of a new imaging technology called two-photon microscopy which enables scientists to peer deep within the living brain. Using this technology on mice, whose brains are remarkably similar to humans, Nedergaard and her colleagues were able to observe and document what amounts to an extensive, and heretofore unknown, plumbing system responsible for flushing waste from throughout the brain.

The brain is surrounded by a membrane called the arachnoid and bathed in cerebral spinal fluid (CSF). CSF flows into the interior of the brain through the same pathways as the arteries that carry blood. This parallel system is akin to a donut shaped pipe within a pipe, with the inner ring carrying blood and the outer ring carrying CSF. The CSF is draw into brain tissue via a system of conduits that are controlled by a type support cells in the brain known as glia, in this case astrocytes. The term glymphatic was coined by combining the words glia and lymphatic.

The CSF is flushed through the brain tissue at a high speed sweeping excess proteins and other waste along with it. The fluid and waste are exchanged with a similar system that parallels veins which carries the waste out of the brain and down the spine where it is eventually transferred to the lymphatic system and from there to the liver, where it is ultimately broken down.

While the discovery of the glymphatic system solved a mystery that had long baffled the scientific community, understanding how the brain removes waste -- both effectively and what happens when this system breaks down -- has significant implications for the treatment of neurological disorders.

One of the hallmarks of Alzheimer's disease is the accumulation in the brain of the protein beta amyloid. In fact, over time these proteins amass with such density that they can be observed as plaques on scans of the brain. Understanding what role the glymphatic system plays in the brain's inability to break down and remove beta amyloid could point the way to new treatments. Specifically, whether certainly key 'players' in the glymphatic system, such as astrocytes, can be manipulated to ramp up the removal of waste.

"The idea that 'dirty brain' diseases like Alzheimer may result from a slowing down of the glymphatic system as we age is a completely new way to think about neurological disorders," said Nedergaard. "It also presents us with a new set of targets to potentially increase the efficiency of glymphatic clearance and, ultimately, change the course of these conditions."

                                                     courtesy:science daily

ECG: left vs. right bundle block
"WiLLiaMMaRRoW":
W pattern in V1-V2 and M pattern in V3-V6 is Left bundle block.
M pattern in V1-V2 and W in V3-V6 is Right bundle block.
Note: consider bundle branch blocks when QRS complex is wide.

Spleen: dimensions, weight, surface anatomy
"1,3,5,7,9,11":
Spleen dimensions are 1 inch x 3 inches x 5 inches.
Weight is 7 ounces.
It underlies ribs 9 through 11.

Depressed ST-segment: causes
DEPRESSED ST:
Drooping valve (MVP)
Enlargement of LV with strain
Potassium loss (hypokalemia)
Reciprocal ST- depression (in I/W AMI)
Embolism in lungs (pulmonary embolism)
Subendocardial ischemia
Subendocardial infarct
Encephalon haemorrhage (intracranial haemorrhage)
Dilated cardiomyopathy
Shock
Toxicity of digitalis, quinidine

mnemonic

Median nerve: hand muscles innervated
"The LOAF muscles":
Lumbricals 1 and 2
Opponens pollicis
Abductor pollicis brevis
Flexor pollicis brevis
Alternatively: LLOAF, with 2 L's, to recall there's 2 lumbricals.
To remember that these are the Median nerve muscles, think "Meat LOAF".