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Posts Tagged ‘Biology’

Our headline is not in the least bit misleading. Stick around for an intriguing tale from the annals of modern medicine.

Michael LeBalanc, 40, was an healthy man who fainted one day. He began to get weaker and weaker as time passed and occasionally blacked out. It became obvious to doctors that something was wrong with his heart and they theorized that a virus may have caused his heart to weaken. One potential cause of a heart attack is a malfunctioning sinoatrial node, the heart’s natural pacemaker.

Brief biology lesson: The sinoatrial node is a clump of cells in the right atrium of the heart which generate the impulse controlling the heartbeat. Interestingly, these cells in the sinoatrial node are modified version of cardiac myocytes (human muscle cells), yet they do not contract.

Mr. LeBlanc had an internal pacemaker implanted which would give his heart a brief jolt to correct any abnormality in its rhythm, thereby preventing a heart attack. That type of pacemaker is formally called an Implantable Cardioverter Defibrillator (ICD). Dr. Helen, a Knoxville based psychologist, suffered a heart attack at the tender age of 37 and an ICD is responsible for keeping her alive today. However, her heart problem was not properly diagnosed right away:

Despite the fact that I was short of breath and shaking like a leaf, the doctor decided I was allergic to something in the gym and gave me a shot of benadryl. Actually, I later learned that shortness of breath and a sense of impending doom or death were signs (especially in women) of heart problems. I felt ok once I left the hospital and even for a week or two later. I was on vacation in Charleston, South Carolina when I again got short of breath and could not walk. I was so dizzy, scared and light-headed that I spent the day in bed until finally that night, I went to an emergency room.

There is a whole lot more to the story, so go read the whole thing. Fortunately, it has a happy ending and is a strong endorsement for the effectiveness of ICDs.

Unfortunately for Mr. LeBlanc, his ICD was working a little too well because his heart was deteriorating too quickly:

To keep me going, I qualified for a defibrillator, which basically shocked me if my heart rhythm started to get worse,” Mr. LeBlanc said. “But as I got sicker, the defibrillator kept going off, and it was awful.”

Even with the defibrillator, Mr. LeBlanc suffered a heart attack in April, followed by a stroke in July. Luckily, he was able to get to an emergency room before the stroke did too much damage.

Since Mr. LeBlanc was in otherwise good health and relatively young, UT Southwestern Medical Center in Texas decided he would be a great candidate for the newest generation of implantable heart saving devices, the Left-Ventricular Assist Device (LVAD).

“Mr. LeBlanc has cardiomyopathy, which causes the heart to dilate. The muscle becomes weaker, and it can’t pump efficiently,” said Dr. Dan Meyer, professor of cardiovascular and thoracic surgery at UT Southwestern and Mr. LeBlanc’s surgeon. “UT Southwestern has always had a presence in studying new mechanical assist devices, so we were honored to be only one of two sites in the state selected to implant the HeartWare LVAD as part of a national clinical trial.”

The pump is designed to rest inside the patient’s chest. A small cable attached to the device exits the body and connects to an externally worn controller. The controller is powered by a battery pack. The HeartWare LVAD has only one moving part, which contributes to its diminutive size. The lack of mechanical bearings is expected to lead both to longer-term device reliability and to a reduced risk of physical damage to blood cells as they pass through the pump, said Dr. Meyer, also director of the mechanical support program at UT Southwestern.

“The size of the device means the incision is also smaller. The entire implantation surgery takes about four hours,” Dr. Meyer said. “Mr. LeBlanc is a really great patient. He’s otherwise very healthy, and we believe he will do very well with the LVAD until he can get a new heart.”

Ok, as promised, here is where the story takes a left turn into “unusual land”:

He’s still adjusting to some of the stranger side effects of his new device, including no pulse. The LVAD keeps blood moving continually with no pulsation, so he no longer has a palpable heart beat or traditionally measurable blood pressure.

Think of all the mischief you could get into with an LVAD. Apparently, the infamous castle of Vlad the Impaler (the inspiration for Bram Stoker’s Dracula) is up for sale. With the right outfit and a bit of makeup you could show up and simply claim ownership.

Habsburg: I own it.

You: No, I do.

Habsburg: Not unless you’re some kind of vampire.

You: Check my pulse.

Habsburg: AAAAAAAAAAAAAAAAAHHHHHHHHHH!!!!

Habsburg: ::: runs away :::


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Gene therapy has been successfully used to restore vision in patients suffering from a rare genetic disorder. The nature of this disorder means that the therapy is much more successful in children than adults.

Leber’s congenital amaurosis (LCA) causes sight to deteriorate beginning at birth and and resulting in complete blindness before the age of forty.

Children born with one form, LCA2, have defects in a gene called RPE65 that helps the retina’s light-sensing cells make rhodopsin, a pigment needed to absorb light. Without rhodopsin, the photoreceptor cells gradually die.

Gene therapy works by using a modified virus as a delivery system to get specific genes into specific areas. (Take a look at our article Is Chronic Fatigue Syndrome Caused By A Virus? for some background about how viruses work explained in plain English). Researchers first tested the therapy on dogs and found they could partially restore sight by using a virus loaded with the RPE65 gene. Then the researchers conducted a limited study on six young adult humans, which also resulted in sight improvements.

But the Penn researchers knew from their studies in animals that children should improve even more because they have more intact retinal tissue than adults do. Today in an online paper in The Lancet, their team and collaborators in Europe report full study results for three of the adults they treated earlier and nine more patients, including four children ages 8 to 11. The children gained more light sensitivity than the adults did–their light sensitivity increased as much as four orders of magnitude, versus one–and they made far fewer mistakes in an obstacle course.

This is one of those good news/bad news stories.

The bad news:

  • Older individuals with this disorder have lost more tissue, and therefore the therapy can be significantly less effective.
  • This therapy only applies to blindness caused by a specific defective gene, and will not benefit someone suffering from any other type of blindness.

Now, the good news:

  • Gene therapy sounds great in theory but has had few successes in real life applications. The success of this study will serve as boost to continue research into gene therapy.
  • Other vision diseases are caused by genetic defects. In the near future it may be possible to do a simple blood test to determine which defective gene a child has and then apply the appropriate therapy to prevent a loss of vision from occurring in the first place.

There is a lot of excitement in the air because of the successful results. Take a look here to see a video of one of the patients, Cory Haas, breezing through an obstacle course a mere three months after therapy.

The LCA2 trials are a rare success for the field of gene therapy, which has also cured children with the immune disorder known as bubble boy disease. And they should pave the way for treating more vision disorders. “It’s an incredible launching pad to be able to target other diseases,” says Penn gene therapy researcher Jean Bennett, who led the study.

Showing that the LCA2 gene therapy treatment works best in children is “a big step” for inherited blindness, says geneticist Frans Cremers of Radboud University Nijmegen Medical Center in the Netherlands, who wrote an accompanying commentary in The Lancet. He notes that eight other vision diseases, including retinitis pigmentosa, have now been treated in mice and are ready to be tested in people. The challenge, he says, will be to expand genetic testing of people with blindness so as to find enough eligible patients for clinical trials of these rare disorders.

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Eva Redei, the David Lawrence Stein Professor of Psychiatry at Northwestern’s Feinberg School has published new research which explains why antidepressants don’t work for so many people.

There are two prevailing theories about the causes of depression. One is that depression can be caused by stressful life events and the second is that depression results from an imbalance in neurotransmitters. However, medications based on those theories are treating effects, not causes.

Most animal models that are used by scientists to test antidepressants are based on the hypothesis that stress causes depression. “They stress the animals and look at their behavior,” she said. “Then they manipulate the animals’ behavior with drugs and say, ‘OK, these are going to be good anti-depressants.’ But they are not treating depression; they are treating stress.”

That is one key reason why current antidepressants aren’t doing a great job, Redei noted. She is now looking at the genes that differ in the depressed rat to narrow down targets for drug development.

She said another reason current antidepressants are often ineffective is that they aim to boost neurotransmitters based on the popular molecular explanation of depression, which is that it’s the result of decreased levels of the neurotransmitters serotonin, norepinephrine and dopamine. But that’s wrong, Redei said.

Redei examined the genes involved in both stress and depression. Of the 254 genes related to stress and the 1275 genes related to depression there is an overlap of only 5 genes.

“This overlap is insignificant, a very small percentage,” Redei said. “This finding is clear evidence that at least in an animal model, chronic stress does not cause the same molecular changes as depression does.”

If current medications are only treating effects then research should be focused on finding and treating the causes.

In the second part of the study, Redei found strong indications that depression actually begins further up in the chain of events in the brain. The biochemical events that ultimately result in depression actually start in the development and functioning of neurons.

“The medications have been focusing on the effect, not the cause,” she said. “That’s why it takes so long for them to work and why they aren’t effective for so many people.”

Her animal model of depression did not show dramatic differences in the levels of genes controlling neurotransmitters functions. “If depression was related to neurotransmitter activity, we would have seen that,” she said.

Unfortunately, although we now know those theories are wrong, we still do not have a theory that is right.

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A major question rested heavily on the minds of certain people in the scientific community: can you taste carbonation?

One way to answer that question would be to consume a carbonated beverage in an environment which prevents the bubbles from bursting.

Ryba added that the taste of carbonation is quite deceptive. “When people drink soft drinks, they think that they are detecting the bubbles bursting on their tongue,” he said. “But if you drink a carbonated drink in a pressure chamber, which prevents the bubbles from bursting, it turns out the sensation is actually the same. What people taste when they detect the fizz and tingle on their tongue is a combination of the activation of the taste receptor and the somatosensory cells. That’s what gives carbonation its characteristic sensation.”

Perhaps some of you are interested in a little bit of history. What on Earth prompted people to indulge in fizzy beverages? Hint: it predates Coca-Cola.

In 1767, chemist Joseph Priestley stood in his laboratory one day with an idea to help English mariners stay healthy on long ocean voyages. He infused water with carbon dioxide to create an effervescent liquid that mimicked the finest mineral waters consumed at European health spas. Priestley’s man-made tonic, which he urged his benefactors to test aboard His Majesty’s ships, never prevented a scurvy outbreak. But, as the decades passed, his carbonated water became popular in cities and towns for its enjoyable taste and later as the main ingredient of sodas, sparkling wines, and all variety of carbonated drinks.

Other research has been conducted on our sense of taste for sweet, sour, salty, bitter and savory. Jayaram Chandrashekar, Ph.D., David Yarmolinsky Ph.D. and Lars von Buchholtz, Ph.D. teamed up to find the source responsible for detecting the taste of carbonation.

Here is the science of what they found:

Carbonic anhydrase 4, or CA-IV, is one of a family of enzymes that catalyzes the conversion carbon dioxide to carbonic acid, which rapidly ionizes to release a proton (acid ion) and a bicarbonate ion (weak base). By so doing, carbonic anhydrases help to provide cells and tissues with a buffer that helps prevent excessive changes in pH, a measure of acidity.

The scientists found that if they eliminated CA-IV from the sour-sensing cells or inhibited the enzyme’s activity, they severely reduced a mouse’s sense of taste for carbon dioxide. Thus CA-IV activity provides the primary signal detected by the taste system. As CA-IV is expressed on the surface of sour cells, Chandrashekar and co-workers concluded that the enzyme is ideally poised to generate an acid stimulus for detection by these cells when presented with carbon dioxide.

They worked with mice, which have a sense of taste similar to human. The question remains, why do mammals taste carbonation at all?

The scientists are still not sure if carbon dioxide detection itself serves an important role or is just a consequence of the presence of CA-IV on the surface of the sour cells, where it may be located to help maintain the pH balance in taste buds. As Ryba says, “That question remains very much open and is a good one to pursue in the future.”

Thanks to their hard work you can rest assured it is not merely your imagination.

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Carl Zimmer has a new brief article up discussing an interesting point which was raised during his research for On The Origin Of Eukaryotes.

No living eukaryote, whether animal, plant, fungus, or protozoan, has completely lost its mitochondria since that symbiotic milestone some 2 billion years ago. It wasn’t the only time that two species merged, however. Plants, for example, descend from algae that engulfed a species of photosynthesizing bacteria. Many protozoans have swallowed up photosynthetic partners as well.

Absorbing an external organism through a cellular membrane and safely enclosing it in a bubble takes complex molecular machinery. One theory is that such a system evolved in eukaryotes, not prokaryotes, which gave them an advantage in integrating mitochondria.

But today, there’s a provocative new alternative to consider. Maybe a lot of today’s prokaryotes are also the result of an ancient merger. The idea comes from James Lake of the University of California, Los Angeles, a veteran researcher on the early history of life. In my essay, I describe how Lake first proposed in the early 1980s that the host cell that gave rise to eukaryotes belonged to a lineage of prokaryotes he dubbed eocytes. Now, a quarter of a century later, new studies on genomes are strongly supporting his eocyte hypothesis.

It is still not clear how prokaryotes handled fusion, but there is evidence that it happened. The double membrane of gram negative bacteria seem to be one indication of a bacteria swallowing another at some point in the ancient past.

It will be interesting to see if Lake’s new hypothesis fares as well as his eocyte hypothesis is doing. If he’s right, this symbiosis had an impact on the history of life on par with the origin of eukaryotes. Gram-negative bacteria were the first photosynthesizers, for example, and were then swallowed up by the ancestors of plants. And the same lineage also gave rise to the bacteria that became our own mitochondria. Our cells, in other words, are not just microbes within microbes; they are microbes within microbes within microbes: a true Russian doll of evolution.

Carl Zimmer is the author of Evolution: The Triumph of an Idea and Parasite Rex : Inside the Bizarre World of Nature’s Most Dangerous Creatures among others. We highly recommend these books.

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Offensive Defense

The world of insects can get pretty strange when it comes to the various exotic ways of survival and procreation for these tiny terrorists. For example, Aphidius ervi, a wasp, injects its eggs directly into aphids. When the eggs hatch, the larvae eat the aphid from the inside out.

Acyrthosiphon pisum, the pea aphid, has an unusual defense mechanism against this attack. Some aphids are infected with the Hamiltonella defensa bacteria and with the APSE (A.pisum secondary endosymbiont) virus at the same time. When combined, both micro-organisms work together in the aphid to produce a toxic protein which kills the wasp larvae over 90% of the time.

Unfortunately for the pea aphid, the virus frequently disappears from the scene outside lab conditions, leaving the aphid vulnerable.

In lab conditions, the alliance between bacterium and virus is a very stable one, but in the wild, H.defensa has a bad habit of spontaneously losing its all-important phage lodger. Even within a single aphid, only some bacteria have viral genes integrated into their own. No one knows why the virus should disappear so frequently. Perhaps it’s not an entirely welcome tenant and its presence carries some sort of cost that occasionally outweighs its benefits. Perhaps only phage-free H.defensa can be passed on from aphid to aphid.

The bacteria is essentially useless for defense without the virus.

Faced with an enemy that threatens them all, the virus, the bacterium and the aphid have formed an evolutionary alliance, with infection as its foundation.

Bacteriophages currently play an important role for studying genetics in the laboratory. Their ability to infect bacteria may allow them to play a future role in defeating multi drug resistant strains of disease causing bacteria.

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So… Why Sleep?

Jerome Siegel, UCLA professor of psychiatry and director of the Center for Sleep Research at the Semel Institute for Neuroscience and Human Behavior at UCLA and the Sepulveda Veterans Affairs Medical Center is one scientist who is delving into the reasons behind our need for sleep.

It was thought that sleep has to provide a neurological benefit which cannot be attained during an awake state because sleep puts an animal in a vulnerable state, and prevents other functions from being carried out, such as a searching for food. Different species have varying requirements as far as sleep duration and patterns. Migrating birds can be awake for days at a time, whereas bears go into hibernation in the winter.

Siegel’s lab conducted a new survey of the sleep times of a broad range of animals, examining everything from the platypus and the walrus to the echidna, a small, burrowing, egg-laying mammal covered in spines. The researchers concluded that sleep itself is highly adaptive, much like the inactive states seen in a wide range of species, starting with plants and simple microorganisms; these species have dormant states — as opposed to sleep — even though in many cases they do not have nervous systems. That challenges the idea that sleep is for the brain, said Siegel.

Animals, including humans, have a selective system which can shift from a sleeping state to an awake state in milliseconds if the right stimulus occurs. The answer then has to do with metabolism and energy conservation.

In humans, the brain constitutes, on average, just 2 percent of total body weight but consumes 20 percent of the energy used during quiet waking, so these savings have considerable adaptive significance. Besides conserving energy, sleep invokes survival benefits for humans too — “for example,” said Siegel, “a reduced risk of injury, reduced resource consumption and, from an evolutionary standpoint, reduced risk of detection by predators.”

“This Darwinian perspective can explain age-related changes in human sleep patterns as well,” he said. “We sleep more deeply when we are young, because we have a high metabolic rate that is greatly reduced during sleep, but also because there are people to protect us. Our sleep patterns change when we are older, though, because that metabolic rate reduces and we are now the ones doing the alerting and protecting from dangers.”

It is an interesting hypothesis, but it still remains to be seen if it is in fact correct. If you are interested in this subject and would like a more in depth analysis, we recommend reading The Neural Control of Sleep and Waking.

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