The Story Behind a Potential Protein Treatment for Achondroplasia

Injecting sFGFR3 induces bone growth in wildtype mice (WT) and achondroplastic mice (Fgfr3ach/+). Adapted from Fig. 2 (1).
Injecting sFGFR3 induces bone growth in wildtype mice (WT) and achondroplastic mice (Fgfr3 ach/+). Adapted from Fig. 2 (1).

Earlier this week, several news outlets reported on a decoy protein as a potential treatment for achondroplasia or, more commonly, dwarfism, but made no mention of its origins.

From the New York Times:

Injections of a decoy protein can restore normal bone growth in mice with dwarfism characteristics, according to a new study, suggesting a possible treatment for humans with the condition.

People born with achondroplasia, the most common form of dwarfism, tend to be short in stature with short arms and legs and a relatively larger head, sometimes resulting in problems with the spine and with hearing and breathing. The condition is caused by a single mutation in the gene Fgfr3, which provides instructions for making a protein involved in the development of bone and brain tissue.

The Fgfr3 gene codes for fibroblast growth factor receptor 3 (FGFR3), a protein found on the surface of cells that in essence serves as an antenna that cells use to communicate with each other.  Continue reading

Battle of the Sperms

Inside every Drosophila melanogaster (fruit fly) female is a battleground where sperm from two different males jockey with each other for the honor of fertilizing her eggs. By sequentially mating females with males genetically-engineered to produce sperm that glow either green or red (see video below), scientists have been able to directly observe sperm competing in what looks like the fruit fly version of Tron. Color coding the sperm in this way allows researchers to distinguish one male’s sperm from another’s and determine who the winners are.

“Sperm from two different males genetically-engineered to express either green or red fluorescent proteins compete within the female reproductive tract of the fruit fly Drosophila melanogaster.”

Surprisingly, it’s not always the fastest sperm that wins.

Continue reading

Rhino horns: From traditional medicine to recreational drug

Rhino horns are a precious commodity. On the black market, they can fetch an absurd price upwards of $60,000/kg. That’s more than the price of gold. Put in a different perspective, drop me a kilo of rhino horn and that pays two years of my graduate stipend…plus a Christmas bonus.* But that price also cost 618 rhinos their lives in 2012. This all-time high continues a rapidly increasing trend dating back to 2008 when poachers killed 83 rhinos–a noticeable uptick from the yearly average of 15 rhinos killed from 2000-2007. The practice is in no way humane, as poachers often cut horns off of tranquilized rhinos and then leave them to die from their wounds. I’ll spare you the grisly photos, but gruesome Internet images abound.

Adapted from Infographic- Understanding the rhino wars
Adapted from Infographic- Understanding the rhino wars

Fueling this demand for rhino horns are East Asian countries like China and Vietnam (I’m shaking my head in disapproval at you, my peoples in Vietnam). There, rhino horns are coveted by practitioners of traditional Chinese medicine who believe its extract can be used for treating fevers as well as other “conditions.” While most news coverage is quick to point out that rhino horns are little more than keratin (the protein found in our hair and nails) and that they lack any curative properties, little discussion is devoted to any actual research on their medicinal value. While published data is scarce–this probably reflects the obstacles in obtaining rhino horns for research–what little that has been published certainly doesn’t support using rhino horn as medicine.

In the early 1990s, Chinese researchers published in the Journal of Ethnopharmacology two studies that tested the ability of rhino horn extract to reduce fever (1,2). In the first study, researchers induced fever in rats by injecting them with turpentine oil, a known fever-causing agent. This was followed by injections of rhino horn extract prepared in either saline or in the herbal concoction traditionally prescribed for fevers. Both preparations of rhino horn extract were able to slightly decrease fevers in rats, but the effect required using rhino horn extract at 20 times the concentration normally prescribed by traditional medicine. Furthermore, the researchers observed that similarly high concentrations of horn extracts from saiga antelope, water buffalo, and cattle, also reduced fever in rats. This result meant that there was nothing special or magical about rhino horns in particular. The researchers concluded that, at least for the purpose of traditional medicine, rhino horns could be swapped out for horns from non-endangered animals.

Image credit: Jim Epler
Rhino horn. Image credit: Jim Epler

Still, the Chinese studies had two other problems. First, they injected the rhino horn extract into the rats, whereas in traditional medicine rhino horn extract is ingested. Second, their study didn’t compare how effective rhino horn extract reduced fever against known anti-fever drugs. These issues were addressed by Laburn and Mitchell, who published their results in the Journal of Basic and Clinical Physiology and Pharmacology (3). In their study, rabbits were injected with bacterial lipopolysaccharide (LPS), a component of bacterial cell walls. Since LPS is foreign to the rabbit’s body, it triggers the rabbit’s immune system and induces fever. To test their fever-reducing abilities, either rhino horn extract, reedbuck (a non-endangered African antelope) horn extract, indomethacin (an anti-fever drug), or water was fed “gavage-style” to the LPS-injected rabbits. This meant that the samples were pumped directly into the rabbit’s stomach through a tube passed through its mouth. To monitor the effect of each agent on fever, rectal temperature was monitored over the course of 250 minutes. The researchers found that neither the rhino nor the reedbuck horn extract did anything to reduce fever in rabbits. More importantly, indomethacin was very effective at reducing the fever. These findings are similar to another report which found that acetaminophen was more effective than rhino horn extract at reducing fever in children.

Rabbits were injected with bacterial lipopolysaccharide (LPS) to induce fever and simultaneously administered rhino horn extract (black circle), reedbuck extract (white square), water (white circle), or the anti-fever drug, indomethacin (black triangle). Rectal temperature was measured to monitor fever over the course of 250 minutes. Only indomethacin (black triangle) was able to reduce LPS-induced fever after about 75 minutes.
Rabbits were injected with bacterial lipopolysaccharide (LPS) to induce fever and simultaneously administered rhino horn extract (black circles), reedbuck extract (white squares), water (white circles), or the anti-fever drug, indomethacin (black triangles). Rectal temperature was measured to monitor fever over the course of 250 minutes. Only indomethacin (black triangles) was able to reduce LPS-induced fever after about 75 minutes (3).

Despite little scientific support for using rhino horns as medicine, the demand for rhino horns in China and Vietnam continues to soar. This week, in response to the growing poaching problem, Vietnam signed a no-poaching agreement with South Africa, where the majority of rhinos have been killed. Whether this will have any appreciable effect on poaching, however, is debatable considering that the demand for rhino horns in Vietnam has overshadowed its own conservation efforts. In 2010, the last of the Javan rhino subspecies native to Vietnam was killed by poachers.

Dehorned rhino
A dehorned rhino just looks so sad. Brent Stirton/National Geographic

Other ways to curb poaching have also been explored, such as routinely shaving off rhino horns. While rhino horns eventually grow back, this practice is unpopular among conservationists since rhinos depend on their horns for defense. It’s also worth noting that many dehorning advocates are also rhino owners whose true financial motives may lie in their support for legalizing the rhino horn trade. Another suggestion that’s been floated around to reduce poaching is to implant GPS devices into rhino horns. This would serve as a sort of RhinoJack that can be used to track down poachers. Others, on the other hand, suggest taking even more drastic actions.

These measures, of course, serve only to make poaching less desirable without dealing directly with demand. What’s troubling is that the demand for rhino horns is now being propped up by new and kookier, unscientific ideas, which extend far beyond its traditional use. Reports from China and Vietnam indicate that con men are peddling rhino horn extract as a miracle cure for whatever malady suits their fancy. As John Platt, of SciAm blogs, reports, “In Vietnam con men recently started marketing rhino horn as a cure for cancer or as a party drug to lessen the effects of alcohol.” (Do I smell a pseudo-cure for Asian Glow as well?) In other cases, rhino horns are being crushed and snorted like cocaine, sprinkled on food, or mixed with alcoholic cocktails as over-the-top displays of wealth popular among Vietnam’s “nouveaux riches.” By linking rhino horns with status symbols, the affluent are only driving up prices. Unfortunately for rhinos, as the price for their horns go up, so does the incentive for poachers. 

*We don’t receive Christmas bonuses.

Featured image: 

untitled (Walter Corno) / CC BY-NC-SA 3.0

References:

1. But PP, Lung LC, Tam YK. Ethnopharmacology of rhinoceros horn. I: Antipyretic
effects of rhinoceros horn and other animal horns. J Ethnopharmacol. 1990
Sep;30(2):157-68. PubMed PMID: 2255207.

2. But PP, Tam YK, Lung LC. Ethnopharmacology of rhinoceros horn. II: Antipyretic
effects of prescriptions containing rhinoceros horn or water buffalo horn. J
Ethnopharmacol. 1991 May-Jun;33(1-2):45-50. PubMed PMID: 1943172.

3. Laburn HP, Mitchell D. Extracts of rhinoceros horn are not antipyretic in
rabbits. J Basic Clin Physiol Pharmacol. 1997;8(1-2):1-11. PubMed PMID: 9363565.

 

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Dog-day Cicada

Found this little bugger on my tire this morning.

A photo posted by Viet Le (@amasianv) on

This past spring, my girlfriend and I were in Virginia for a wedding when the 17-year Brood II cicadas were just starting to emerge. We were excited by the possibility of seeing some on our trip, but unfortunately, we didn’t spot any–I think we were too early?

Well, I can rest easy now after finding this lil’ bugger perched on the tire of my car yesterday morning. I believe this is a “dog-day” cicada, or annual cicada, which is different from the 13- and 17-year periodic cicadas that have been all up in the news. Dog-day cicadas typically have a 2-5 year life cycle and their broods are not synchronized. Overlapping broods ensure that dog-days cicadas appear every summer, usually in July and August, but it also means they don’t swarm like their periodic cousins.

Still pretty cool looking nonetheless.

Photo 51

Rosalind Franklin doodle

Today’s Google Doodle honors Rosalind Franklin, whose work on X-ray diffraction was instrumental in determining the double helix structure of DNA. In the Doodle she’s staring at an X-ray diffraction image, known as Photo 51, that got the ball rolling. If you’d like to learn more about how the structure of DNA was determined, Nova has a great interactive dissection of Photo 51 that helps unravel the double helix structure from what looks like just an “X.”

After her work on DNA, she “conducted pioneering work into the structure of viruses.” Sadly, she died due to complications of ovarian cancer in 1958–four years before the Nobel Prize was awarded to Watson and Crick for their research on nucleic acids, and at the time much of her contribution was overlooked.

I can’t help but wonder what else she would have accomplished had she not passed away.

Alien Faces or Larval Butts?

Crane Flies  spiracles
Image credit: Chen Young

These might look like mugshots of unsavory patrons that frequent the Mos Eisley Cantina, but they’re actually the posterior ends of larvae from 6 different species of crane flies. The dark circles that resemble eyes are in fact breathing holes called spiracles. Instead of lungs, insects have a respiratory system made of a network of tubes and ducts, called trachea and tracheaoles, connected directly to the outside world by spiracles. These breathing holes are used by both the larva and adult forms of insects and can be found running along the length of the insect’s body.

Spiracles
Spiracles on the side of catepillar.

Just below the spiracles is the larva’s anus surrounded by anal pads, which give the “alien face” the appearance of a mouth or teeth (imagine having a set of nostrils right above your anus!).

Ponda Baba and Muftak meme

The larvae of many crane fly species are aquatic or are found in wet environments. Since crane fly larvae do the majority of their breathing through their posterior spiracles the odd, tentacle-like protrusions may be adaptations that  help them breathe. For instance,  the hairs and bristles covering the protrusions can trap air when the larvae are submerged in water.

cranefly larva posterior
Posterior spiracles of a crane fly larva.

Adult crane flies are often confused for being male mosquitos or even mosquito hunters, despite the fact that they generally feed on nectar or in some cases nothing at all–the adult flies of some species exist only to mate. You’ve all probably seen crane flies before, wobbly flittering around looking like drunk daddy longlegs with wings.

Tipula paludosa
Adult Tipula paludosa crane fly
The Mos Eisley Cantina scene from Star Wars Episode IV – A New Hope:

Related Reading

Should I start patenting the cDNAs I’ve made in the lab?

In a unanimous decision today, the SCOTUS struck down patents for genes by ruling against Myriad Genetics in Association for Molecular Pathology vs. Myriad Genetics. The Court, however, did leave some wiggle room for companies to patent cDNAs, or complementary DNA.

“In Myriad, the high court held cDNA is patentable, because it involves actual work in the laboratory and inverts the normal process found in nature. The synthetic DNA is an edited version of a gene, stripped of non-coding regions that the court said makes it “not naturally occurring.”

Critics say even the edited sequences are directly analogous to naturally occurring DNA.”

In many labs, cDNAs are routinely made, manipulated, and used for research. cDNA is DNA that is engineered in reverse using messenger RNA (mRNA) as the template. As the above quote alludes, a cDNA is not a carbon copy of its corresponding gene. Interspersed along the length of a gene are regions of non-coding DNA sequence. These are segments of DNA that aren’t represented in the sequence of the encoded protein. When a gene is initially transcribed into mRNA some of these non-coding regions, called introns, are included. Introns, however, are ultimately removed by the cell before the mRNA is translated into protein. Since mRNA is used to make cDNA, the introns are excluded from the cDNA sequence.

gene expression
During gene expression, a gene is first transcribed into a primary RNA transcript, which includes non-coding introns (blue). Through a process called splicing the introns are removed from the transcript resulting in a mature mRNA molecule. The sequences found in mRNA are called exons (red and yellow). The mRNA is  then translated into protein. Since cDNA is made from mature mRNA, it will consist only of exon sequences.

Although gene and cDNA are different, they both carry essentially the same DNA sequence for a protein. (It should be noted, however, that many genes encode multiple forms of a protein, for which each form has its own corresponding cDNA.) So, I’m not sure why the “patentable” emphasis is on cDNAs as opposed to making mutations* to the underlying sequence that result in say, new or altered function of a protein. At least there I could see an inventive process happening–or am I missing something here?

*I’m talking about generating novel mutations. Of course, I’m not sure what should happen if said mutations are discovered to be “naturally occurring” after the fact.

Related Reading:

Patents on Nature

 

 

Crossposted at Scientopia

It’s An Evolutionary Trap!!!

Snyder-frog-banner-990x603
“A Cuban Tree Frog tries to eat a Christmas light. Photo by James Snyder. National Geographic My Shot”

You might be wondering why a frog would eat a Christmas light, but it may have simply confused the glowing bulb for a luminescent insect it normally feasts on. This is just one example of how even the mundane ways we’ve changed the environment can trip up other creatures–and sometimes with evolutionary consequences. As Carl Zimmer explains in a blog post over at The Loom,

We have altered the environment in a vast number of ways, both small and large. And when animals try to read the cues from our human environment, they can get tricked. They can end up doing something that kills them, loses them the opportunity to reproduce, or simply wastes their time. Scientists call these situations evolutionary traps.

Hydropsyche pellucidula
Caddisfly species Hydropsyche pellucidula
While the Cuban tree frog ultimately spit out its mistaken meal and survived its run-in with holiday lighting, other organisms are not as fortunate.

When caddis flies become adults and are ready to mate, they need to get to a body of water. Without Google Maps to help them, they do what their ancestors have done for countless generations: they take advantage of the fact that ponds and streams change the reflection of moonlight, altering its polarization. Unfortunately, large plate glass windows can polarize light in the same way, with the result that caddis flies will sometimes blanket the glass, mate, and lay their eggs there.

Carl Zimmer goes on to mention several other examples of evolutionary traps, like the Australian beetles that vigorously try to mate with empty beer bottles, and also discusses ways that we might disarm them. Head over there and have a read.

It's an evolutionary trap

I couldn’t resist.

 

Cultural Comic Books for Educating Asian Americans about Hepatitis B

photonovels 750

May is Asian-Pacific American Heritage Month and also Hepatitis Awareness Month. Coincidentally, Asian Americans are at great risk for hepatitis B, yet have the lowest rates of screening and vaccination. According to the CDC, of the estimated 1 million Americans with chronic hepatitis B about half are from the Asian/Pacific Islander (API) communities. For comparison, Asian Americans make up roughly 5% of the US population. Nearly 1 in 12 Asian Americans are chronically infected with hepatitis B, but many are unaware of their status.

How might we raise hepatitis B awareness for this cultural diverse group? Why, cultural comic books (sorta) of course!

There’s the story of a young Chinese American couple planning on getting married, but on the day of the proposal the bride-to-be confesses to her fiance that she has hepatitis B. Then there’s the one about a Korean immigrant family in which the father, who prefers traditional Asian medicine over Western medicine, discovers that his brother has liver cancer. Lastly, there’s the story of a Vietnamese American nail salon owner whose husband is diagnosed with hepatitis B, which was probably contracted by sharing razors with an infected roommate in college. No, these are are not vignettes from an Asian American film about coincidence. These are cautionary tales used in cultural, comic book-like photonovels that were developed to raise hepatitis B awareness among Asian Americans–the racial/ethnic group with the greatest risk of contracting hepatitis B.

You can read more of my post at PLOS Blogs

Blight-Resistant Potato: an “Acceptable” GMO?

1280px-Phytophtora_infestans-effects
“Potato Blight Effects”

Last week, I wrote about a disease-causing nematode that infects the roots of soybean plants and  a mutation in one strain of soybeans that makes them resistant to these nematodes. In the post I mused,

what if an already existing gene variant with a desired trait from one organism is genetically engineered into another organism of the same species? Would this make GMOs a little bit more palatable to their detractors?

While intended to be more of a thought experiment, a commenter alerted me to a very similar scenario playing out in Ireland, where potato crops are still affected by blight–yes, as in the blight responsible for the Great Famine of the mid-1840s. Blight makes potatoes rot and is caused by infestation of a fungus-like organism (oomycetes) called Phytophthora infestans.

In recent years, scientists have developed blight-resistant GMO strains of potato plants by introducing a blight-resistance gene called RB into the potato’s genome. This gene was identified in Solanum bulbocastanum, a wild potato plant native to Mexico that is closely-related to potatoes. Resistance to blight most likely developed as a result of coevolving with P. infestans, which is considered to be native to Mexico as well.

The scenario facing GMO potatoes, however, is a little bit different from the question I posed earlier since the RB gene isn’t found in cultivated potato plants. Furthermore, traditional breeding methods have been unsuccessful in making hybrids between cultivated potatoes and S. bulbocastanum, therefore necessitating genetic engineering. There are, however, other blight-resistant wild Solanum plants, such as Solanum venturii, that can be hybridized with cultivated potatoes. But using the RB gene from S. bulbocastanum remains the most attractive option because S. bulbocastanum is resistant to the most number of blight-causing P. infestans strains

The response from one anti-GM campaigner to using genetic engineering in this case?

It is just there to make GM more palatable to the general public. The fact that it comes from a related plant doesn’t make it any different. The real danger is the process.

I guess that answers my question.

Immigration Reform: A Second Chance for Undocumented Immigrant Health?

When the Affordable Care Act was signed into law in March of 2010, many immigration advocates were disappointed that the bill left undocumented immigrants out in the cold. While the law kickstarts the process of bridging the gap for millions of uninsured Americans, specific language was written into the legislation to bar undocumented immigrants from being “eligible for public insurance or any type of private coverage obtained through exchanges.” At the time of the bill’s signing, approximately 7 million out of an estimated 11 million undocumented immigrants in the US were without insurance, and many of whom were living in poverty. These numbers are only expected to increase [1]. With immigration reform highly visible in Obama’s second term, immigration advocates are now viewing this as a second chance to address a growing public health concern.

Read more at PLOS Blogs…