Opko Health: Following Tesla's Formula For A Market Take-Off

Investors are always on the prowl for the next big company capable of providing significant returns in a limited amount of time. Yet in this short-sighted perspective of the market, this popular mindset often boils down to a dependency on shifting market sentiments rather than tangible operational success. After all, enterprises take time to develop and the short-handed impact of rapid market gains aren't often dependent on the cash-generating business changes implemented overnight. Indeed, it is through the proliferation of investor optimism that a company's stock accelerates on the backbone of momentum.

This article takes a look at two particular companies that now find themselves following part of a formula for rapid stock appreciation. These companies are Tesla Motors, Inc. (TSLA) and OPKO Health, Inc. (OPK). In each of these instances, the companies have developed a solid innovation pipeline, the support of a strong financial backer, an unusually large short-interest, and a catalyst for demand. Combined, these attributes appear to design a formula that can lead to rapid stock price appreciation.

TSLA data by YCharts

Tesla Motors

As a company that has already appreciated in a short amount of time, it remains ideal to look at Tesla as a model. Tesla Motors is a premier innovator behind electric vehicle technology. Outlasting its private company peers such as Fisker Automotive and Coda Holdings, Tesla has made its high-end electric vehicles the envy of the automotive industry. The company has very quickly shown its ability to succeed in its target market where larger public companies such as General Motors (GM) and Ford (F) have failed to gain momentum with their own electric vehicle lines.

Tesla's most popular financial backer remains the company CEO himself. As a co-founder for the company, CEO Elon Musk helped to create a valuation premium through his own financial support. Musk owes fortune as the former founder of PayPal. In June 2011, Musk purchased $40.7 million worth of company shares. In May 2013, Musk reinvigorated investor confidence by putting another $100 million into Tesla despite the fact that the company's stock had already appreciated more than 150% in the two months prior.

Although it would ultimately be seen as a crutch to the company, the Department of Energy also played heavy role in supporting Tesla. In 2010, the company received a $465 million loan to help foster the development of advanced-technology vehicles. The catalyst for Tesla would ultimately come in two noteworthy waves. First, Tesla exceeded sales expectations even as its industry peers failed to impress. Second, the company paid back early its loan from U.S. Government while Musk significantly added to his holdings at a much higher price.

In the last 6 months, Tesla has seen its stock rise 382%. Throughout this time, Tesla's short interest remained unusually high. At the end of March, the company's short interest was 31.3 million shares, reflecting a short ratio of 22.91. Based on an average daily volume of 1.37 million shares, it would take roughly 23 days for investors that were short to cover their positions in an environment in which the company's stock was appreciating. Such artificial selling pressure allowed for a stronger acceleration when the stock began to find momentum.

OPKO Health

While being in a truly different industry than Tesla, OPKO Health still carries several unique similarities to the automotive company. Although it may easily be passed off as a mere pharmaceutical and diagnostics company now under development, OPKO Health has maintained an aggressive acquisition strategy that distinguishes it from its peers. The company's management team has brought together a very large suite of products under development, many of which provide unique synergies and address a diverse range of specialty markets.

In the last year alone, OPKO has conducted six strategic acquisitions. Most of these utilized the company's stock as either a partial or full payment for the acquisitions. The company's pipeline is now looking to address markets ranging from chronic kidney disease, to prostate cancer, to growth hormone deficiency, and even to depression. Seeking Alpha contributor Josh Ginsburg breaks down the possible multi-billion dollar markets the company can address over the short- and long-term in his article found here.

As was the case with Tesla, the company's strong financial backer happens to be the company's Chief Executive Officer. CEO Dr. Phillip Frost also serves as the Chairman of Teva Pharmaceuticals (TEVA), a position he eventually acquired after gaining his fortune in Teva's $7.4 billion acquisition of IVAX Corporation in 2005. Frost had founded IVAX and had served as its CEO.

As a result of his newfound wealth, the entrepreneur was quick to reinvest his money into OPKO Health after being appointed the company's CEO in 2007. On a near daily basis since 2007, Frost purchased company stock. Part of this can be seen in the graphic below. According to the latest Form 4 found here, the CEO indirectly owned 142,453,591 shares of OPKO, a position now worth $1.32 billion according to the last share price of $9.24 as of August 30.

(click to enlarge)

On August 30, OPKO Health rose 8.83% on more than four times the average daily volume in a rather unexpected swing. What made the climb unique was that shares had traded more than 2% down until the last half hour of the day. At that time, the company rapidly climbed more than 15% at one point to eventually settle down for an 8.83% gain. The apparent catalyst appeared to be a delayed reaction to the finalization of the company's all-stock acquisition of PROLOR Biotech. The announcement was made the day before. The acquisition greatly diversifies OPKO's potential but was initially met with skepticism in light of Frost's conflict of interest. According to the Form 4 found here, Frost owned 9.8 million shares of PROLOR, which accounted for roughly 15% of the shares outstanding.

(click to enlarge)

What likely contributed to the stock's high volatility is the heavy short interest that now surrounds OPKO Health. As of August 15, there were 31.38 million shares short. With an average 1.91 million shares traded daily, this leads to a short ratio of 16.4 for OPKO. Another catalyst which was sure to complicate the issue was the announcement by OPKO that the conversion right for the company's 3.0% Convertible Senior Notes had been triggered. Because of this trigger, it remains likely that an influx of new share demand set off a wave of investors seeking to cover their short positions.

A Look At The Financial Picture

OPKO Health now trades with a $3.11 billion market capitalization based on its last stock price of $9.24. The company carries a high price-to-sales ratio of 34.35 as its valuation is largely dependent on its future revenue potential. Likewise, the company carried a price-to-book ratio of 9.09. Neglecting its pipeline potential, OPKO may appear overvalued. After all, the company only carries a total shareholder equity of $314.48 million.

However, like Tesla, OPKO has shown no sign of slowing down on the market in light of its future potential. Over the last five years, the company's stock has risen 327%. Above all, it remains adequately capitalized. In all of 2012, the company had a cash outflow from operating activities of only $25.42 million. As of June 30, the company carried roughly $169 million in cash and short-term investments.

The company's markets also remain large and near to being addressed. Some of OPKO's diagnostic products are expected to make an impact this year and the company's pipeline carries multiple Phase 3 products. Seeking Alpha contributor John Ford notes that OPKO's 4KScore diagnostic test could generate over $1.8 billion annually just by addressing the prostate cancer test market alone. This is based on the estimates of outside consultants when asked to determine a fair price for the diagnostics test. Such reoccurring revenue significantly overwhelms the mere $47 million the company realized in 2012 as it continued to develop its existing pipeline.

(click to enlarge)

Conclusion

When we use Tesla Motors as a model case study for rapid stock price appreciation, there are several distinct similarities that stick out about OPKO Health as well. Both companies are led by well-known individuals in their respective markets. Both CEOs have accumulated a large fortune and have willingly been propping up their company's stock. Both companies have found niche and valuable industries in which they are staged to make a significant impact. Additionally, each of these companies have been accumulating a rather large short-interest despite the fact their share prices have been rising.

Most importantly, each company appears to have found a catalyst that can ignite the demand for stock. For Tesla Motors, this was the sales expectations beat along with the early payment of a federal loan. For OPKO, the completion of its most ambitious acquisition also coincided with the triggered conversion right for its largest long-term debt obligation. By releasing the artificial selling pressure created by a large short interest, these companies are proving the power of shifting market sentiments prior to true operational success.

Disclosure: I am long OPK, TEVA. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article. (More...)

View the original article here

Opko Health: Following Tesla's Formula For A Market Take-Off

Investors are always on the prowl for the next big company capable of providing significant returns in a limited amount of time. Yet in this short-sighted perspective of the market, this popular mindset often boils down to a dependency on shifting market sentiments rather than tangible operational success. After all, enterprises take time to develop and the short-handed impact of rapid market gains aren't often dependent on the cash-generating business changes implemented overnight. Indeed, it is through the proliferation of investor optimism that a company's stock accelerates on the backbone of momentum.

This article takes a look at two particular companies that now find themselves following part of a formula for rapid stock appreciation. These companies are Tesla Motors, Inc. (TSLA) and OPKO Health, Inc. (OPK). In each of these instances, the companies have developed a solid innovation pipeline, the support of a strong financial backer, an unusually large short-interest, and a catalyst for demand. Combined, these attributes appear to design a formula that can lead to rapid stock price appreciation.

TSLA data by YCharts

Tesla Motors

As a company that has already appreciated in a short amount of time, it remains ideal to look at Tesla as a model. Tesla Motors is a premier innovator behind electric vehicle technology. Outlasting its private company peers such as Fisker Automotive and Coda Holdings, Tesla has made its high-end electric vehicles the envy of the automotive industry. The company has very quickly shown its ability to succeed in its target market where larger public companies such as General Motors (GM) and Ford (F) have failed to gain momentum with their own electric vehicle lines.

Tesla's most popular financial backer remains the company CEO himself. As a co-founder for the company, CEO Elon Musk helped to create a valuation premium through his own financial support. Musk owes fortune as the former founder of PayPal. In June 2011, Musk purchased $40.7 million worth of company shares. In May 2013, Musk reinvigorated investor confidence by putting another $100 million into Tesla despite the fact that the company's stock had already appreciated more than 150% in the two months prior.

Although it would ultimately be seen as a crutch to the company, the Department of Energy also played heavy role in supporting Tesla. In 2010, the company received a $465 million loan to help foster the development of advanced-technology vehicles. The catalyst for Tesla would ultimately come in two noteworthy waves. First, Tesla exceeded sales expectations even as its industry peers failed to impress. Second, the company paid back early its loan from U.S. Government while Musk significantly added to his holdings at a much higher price.

In the last 6 months, Tesla has seen its stock rise 382%. Throughout this time, Tesla's short interest remained unusually high. At the end of March, the company's short interest was 31.3 million shares, reflecting a short ratio of 22.91. Based on an average daily volume of 1.37 million shares, it would take roughly 23 days for investors that were short to cover their positions in an environment in which the company's stock was appreciating. Such artificial selling pressure allowed for a stronger acceleration when the stock began to find momentum.

OPKO Health

While being in a truly different industry than Tesla, OPKO Health still carries several unique similarities to the automotive company. Although it may easily be passed off as a mere pharmaceutical and diagnostics company now under development, OPKO Health has maintained an aggressive acquisition strategy that distinguishes it from its peers. The company's management team has brought together a very large suite of products under development, many of which provide unique synergies and address a diverse range of specialty markets.

In the last year alone, OPKO has conducted six strategic acquisitions. Most of these utilized the company's stock as either a partial or full payment for the acquisitions. The company's pipeline is now looking to address markets ranging from chronic kidney disease, to prostate cancer, to growth hormone deficiency, and even to depression. Seeking Alpha contributor Josh Ginsburg breaks down the possible multi-billion dollar markets the company can address over the short- and long-term in his article found here.

As was the case with Tesla, the company's strong financial backer happens to be the company's Chief Executive Officer. CEO Dr. Phillip Frost also serves as the Chairman of Teva Pharmaceuticals (TEVA), a position he eventually acquired after gaining his fortune in Teva's $7.4 billion acquisition of IVAX Corporation in 2005. Frost had founded IVAX and had served as its CEO.

As a result of his newfound wealth, the entrepreneur was quick to reinvest his money into OPKO Health after being appointed the company's CEO in 2007. On a near daily basis since 2007, Frost purchased company stock. Part of this can be seen in the graphic below. According to the latest Form 4 found here, the CEO indirectly owned 142,453,591 shares of OPKO, a position now worth $1.32 billion according to the last share price of $9.24 as of August 30.

(click to enlarge)

On August 30, OPKO Health rose 8.83% on more than four times the average daily volume in a rather unexpected swing. What made the climb unique was that shares had traded more than 2% down until the last half hour of the day. At that time, the company rapidly climbed more than 15% at one point to eventually settle down for an 8.83% gain. The apparent catalyst appeared to be a delayed reaction to the finalization of the company's all-stock acquisition of PROLOR Biotech. The announcement was made the day before. The acquisition greatly diversifies OPKO's potential but was initially met with skepticism in light of Frost's conflict of interest. According to the Form 4 found here, Frost owned 9.8 million shares of PROLOR, which accounted for roughly 15% of the shares outstanding.

(click to enlarge)

What likely contributed to the stock's high volatility is the heavy short interest that now surrounds OPKO Health. As of August 15, there were 31.38 million shares short. With an average 1.91 million shares traded daily, this leads to a short ratio of 16.4 for OPKO. Another catalyst which was sure to complicate the issue was the announcement by OPKO that the conversion right for the company's 3.0% Convertible Senior Notes had been triggered. Because of this trigger, it remains likely that an influx of new share demand set off a wave of investors seeking to cover their short positions.

A Look At The Financial Picture

OPKO Health now trades with a $3.11 billion market capitalization based on its last stock price of $9.24. The company carries a high price-to-sales ratio of 34.35 as its valuation is largely dependent on its future revenue potential. Likewise, the company carried a price-to-book ratio of 9.09. Neglecting its pipeline potential, OPKO may appear overvalued. After all, the company only carries a total shareholder equity of $314.48 million.

However, like Tesla, OPKO has shown no sign of slowing down on the market in light of its future potential. Over the last five years, the company's stock has risen 327%. Above all, it remains adequately capitalized. In all of 2012, the company had a cash outflow from operating activities of only $25.42 million. As of June 30, the company carried roughly $169 million in cash and short-term investments.

The company's markets also remain large and near to being addressed. Some of OPKO's diagnostic products are expected to make an impact this year and the company's pipeline carries multiple Phase 3 products. Seeking Alpha contributor John Ford notes that OPKO's 4KScore diagnostic test could generate over $1.8 billion annually just by addressing the prostate cancer test market alone. This is based on the estimates of outside consultants when asked to determine a fair price for the diagnostics test. Such reoccurring revenue significantly overwhelms the mere $47 million the company realized in 2012 as it continued to develop its existing pipeline.

(click to enlarge)

Conclusion

When we use Tesla Motors as a model case study for rapid stock price appreciation, there are several distinct similarities that stick out about OPKO Health as well. Both companies are led by well-known individuals in their respective markets. Both CEOs have accumulated a large fortune and have willingly been propping up their company's stock. Both companies have found niche and valuable industries in which they are staged to make a significant impact. Additionally, each of these companies have been accumulating a rather large short-interest despite the fact their share prices have been rising.

Most importantly, each company appears to have found a catalyst that can ignite the demand for stock. For Tesla Motors, this was the sales expectations beat along with the early payment of a federal loan. For OPKO, the completion of its most ambitious acquisition also coincided with the triggered conversion right for its largest long-term debt obligation. By releasing the artificial selling pressure created by a large short interest, these companies are proving the power of shifting market sentiments prior to true operational success.

Disclosure: I am long OPK, TEVA. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article. (More...)

View the original article here

Biotech: A Scattershot Of Stem Cell Plays Following Yesterday's Bloodbath

(Editors' Note: This article covers micro-cap stocks. Please be aware of the risks associated with these stocks.)

Yesterday, the NASDAQ Biotechnology index (NBI) dropped 3% in reaction to the sell-off in the broader market. Even larger, more stable pharmaceutical companies (those valued at $10B or higher) were down an average of 1.69% by the closing bell. Smaller biotech stocks, valued between $300M-$2B, fared even worse - dropping about 3.23% on average. The pain was experienced across all subsectors of the biotech industry, reflecting the macroeconomic factors that induced yesterday's bearishness.

Stem cell developers, which have been underperformers in 2013, were not spared either despite their recent unpopularity.

This article will discuss some of stem cell companies that were adversely affected by yesterday's trading. We will also identify catalysts that could lead to significant change in the share prices of these companies within the next year.

Pluristem (NASDAQ: PSTI) - This is a rapidly growing and important stem cell company, although it serves as a great example of the unpopularity of stem cell stocks this year. PSTI dropped 5.4% in yesterday's trading on high volume, bringing the stock's YTD performance decisively into the red (-6.6%).

Pluristem grows stem cell lines out of placental stem cells using a special bioreactor designed by the company to create and later harvest what are known as PLX cells. These PLX cells are being studied in a number of disease indications, and can be catered specifically for indications. This includes peripheral artery disease (PAD) indications - critical limb ischemia, and intermittent claudication. PLX cells are also being investigated for muscle injuries.

The stock's most significant near-term upside potential will likely come with progress in the company's trials. One is the big multi-center phase II trial for intermittent claudication, which is currently recruiting patients. This is also going to be a long trial, although completion of enrollment and the promise of interim data next year should spark some interest. Closer in time is the hip repair trial, where PLX cells are expected to improve patient function after 26 weeks. This should provide multiple data-based catalysts throughout 2014.

Neuralstem (NASDAQ: CUR) - the popularity of this stem cell company is increasing this year, along with its valuation. Within the last year, CUR has moved from $.52/share to yesterday's closing price of $1.62/share - a gain of ~212%. Yesterday, Neuralstem dropped 4.14% to $1.62/share - roughly 17% off its 52-week high of $1.96/share.

A number of things have pushed Neuralstem higher this year, although the majority of the credit should be given to the finalized Phase I data that the company presented at The American Association of Neurological Surgeons Annual Meeting in late April (link). This was an early stage trial that tested the company's line of stem cells - NSI-566 - in patients with Lou Gehrig's disease/ALS (Amytrophic Lateral Sclerosis).

The results of a Phase I trial were discussed in further detail in this note, from May 21st 2013 (link):

"The trial, which was conducted on 15 patients with ALS, started in early 2010 and concluded only recently. According to PI Eva Feldman in a recent Neuralstem press release, 6 of the patients in the study experienced stability, slow progression, or even improved disease course 700 to 850 days after implantation with NSI-566 cells. The remaining 9 saw no noticeable improvements, while 6 patients died of ALS within the first few months after the surgery."

Although early stage, the data were very encouraging and seem to allow CUR to stay comfortably in the $1.40-1.70 range. The Phase II ALS trial is undergoing enrollment now, and could provide early data in H1 of next year to potentially induce another rally. A safety study (Phase I) for NSI-566 in the spinal cord injury indication was also approved and will start enrolling in the near future.

Brainstorm Cell Therapeutics (BCLI.OB) - this Israeli stem cell company has been relatively quiet, although activity is beginning to pick up after a recent public offering. BCLI dropped 2.5% in yesterday's trading, and is currently ~28% off its 52-week highs of .27/share.

In July, the company received orphan drug designation in the European Union for NurOwn in the treatment of ALS (Amytrophic Lateral Sclerosis) (link), and has made significant progress in its 12 patient Phase IIa dose-escalation trial at the Hadassah Medical Center in Israel. The most recent group was treated with a 50% higher dose of NurOwn cells relative to the previous, which should allow the company to better calibrate its dosing for the upcoming US Phase II trial.

The company held a conference call on August 14th to discuss its status, although new details on the Israeli trial were not given for legal reasons. It was confirmed that the company's recent raise should be sufficient to set up larger Phase II trials in the US. The company does have to finish its IND application for NurOwn, although this expected to finish quite smoothly due to the prior approval of other stem cell treatments of ALS (specifically NSI-566).

Brainstorm is significantly cheaper than its peers in terms of valuation, likely because of the uncertainty surrounding this company and its status as a more "foreign" company. This could change once the company makes a bigger presence in the United States with Phase II development.

BioTime (NYSE: BTX) - this complicated "multi-purpose" cell company erased a substantial chunk of its gains with a 5.50% drop yesterday.

The company is comprised of 9 subsidiary companies based in four different countries, and may be best known for its acquisition of Geron's former stem cell assets. Most of its potential is locked in early-stage development programs, although the company already generates some revenues through the sale of research products and stem cells.

BTX could see significant movement in reaction to upcoming catalysts that could add significantly to the underlying value of the company. After years of development, the company is close to launching a cell delivery device known as HyStem-Rx, which aims to deliver stem cells in a manner that wouldn't kill them soon after injection. Hystem is scheduled for introduction into Europe through CE marking (it is a device) - possibly as early as 2014.

Stem Cells Inc. (NASDAQ: STEM) - STEM has managed to hold its ground throughout the year, although it is back to square one after yesterday's 2.38% drop. The company grew a line of neural stem cells derived from brain tissue designated as HuCNS-SC. These cells are being developed for a variety of neuron-related disorders, with the most mature development programs currently being in spinal cord injury and Pelizaeus-Merzbacher Disease (PMD). The company can also sell cells to generate side revenues.

Upcoming events for STEM include the continuation and eventual completion of enrollment into the Phase I/II spinal cord injury trial, which has just been expanded into Canada. This trial will look for minor improvements in an expected total of 12 patients recovering 3-12 months after spinal cord injuries, and may have interim data to present soon.

Investors should also look for development in PMD patients that the company is following (link). There should also be much greater investor excitement for the recently initiated Alzheimer's disease program due to the sheer size of that indication and the preclinical data in support of HuCNS-SC.

Notes on Biotech Risk:

Investors should realize that unprofitable biotechnology companies in the development stage experience particularly high volatility, are speculative, and do hold significant risk for loss of wealth. Investors believe that the company's valuation will increase more over time than the rate at which the company will burn cash, which is why the high risks are taken.

Disclosure: I have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it. I have no business relationship with any company whose stock is mentioned in this article. (More...)

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Potential for new antibiotics following finding that protein delays cell division in bacteria

Main Category: Infectious Diseases / Bacteria / Viruses
Also Included In: Genetics
Article Date: 14 Aug 2013 - 0:00 PDT Current ratings for:
Potential for new antibiotics following finding that protein delays cell division in bacteria

In 1958 a group of scientists working in Denmark made the striking observation that bacterial cells are about twice as large when they are cultured on a rich nutrient source than when they are cultured on a meager one. When they are shifted from a nutrient-poor environment to a nutrient-rich one, they bulk up until they have achieved a size more appropriate to their new growth conditions.

It has taken 60 years to figure out how the bacteria are able to sample their surroundings and alter their cell cycles so that they grow to a size suited to the environment.

In 2007 Petra Levin, PhD, a biologist at Washington University in St. Louis, reported in Cell that a soil bacterium named Bacillis subtilis has a protein that senses how much food is available and, when food is plentiful, temporarily blocks the assembly of a constriction ring that pinches a cell in two to create two daughter cells.

Now Norbert Hill, a graduate student in her group, reports in a recent online edition of PLoS Genetics that Escherichia coli uses a similar protein to help ensure cell size is coordinated with nutrient conditions.

Delaying division even just a little bit leads to an increase in daughter cell size. Once stabilized at the new size, cells take advantage of abundant nutrient sources to increase and multiply, doubling their population at regular intervals until the food is exhausted.

Because both the B. subtilis and E. coli proteins interact with essential components of the division machinery, understanding how they function will help in the discovery of antibiotics that block cell division permanently. A group in Cambridge, England, is already working to crystallize the E. coli protein docked on one of the essential components of the constriction ring.

If they are successful they may be able to see exactly how the protein interferes with the ring's assembly. An antibiotic could then be designed that would use the same mechanism to prevent division entirely, killing the bacteria.

Why do bacteria get bigger on a good food source?

Bacteria increase and multiply by a process called binary fission. Each cell grows and then the divides in the middle to produce two daughter cells. What could be simpler?

But the closer you look, the less simple it becomes. For binary fission to work the cell must make a copy of its circular chromosome, unlink and separate the two chromosomes to create a gap between them, assemble a constriction ring in the middle of the cell and coordinate the growth of new cell membrane as the ring cinches tight and pinches the mother cell in two. To complicate matters, bacteria don't necessarily do these steps one by one but can instead work on several steps simultaneously.

Most of the time the goal is to produce daughters the same size as the mother cell. But when food is plentiful, bacteria start making more copies of their DNA (as many as 12) in anticipation of divisions to come, and they can't easily cram all the extra DNA into standard-sized cells. So they grow bigger to accommodate the extra genetic material and remain large as long as the food lasts.

The inventory of partly copied chromosomes fuels rapid population growth, because a cell doesn't start from scratch when it needs another copy of its chromosome. Under optimum conditions, E. coli, for example, divides once every 17 minutes. If they are allowed to grow unhindered this means that in 24 hours 1 bacterium becomes about 5 x 1021 bacteria (that is 5 with 21 zeros after it.)

How do bacteria know the pickings are rich?

In B. subtilis and E. coli the signal is a modified sugar called UDP-glucose. Presumably, the richer the growth medium, the higher the level of this sugar inside the cell.

In both bacteria UDP-glucose binds to a protein and the sugar-protein complex then interferes with the assembly of the constriction ring. In the case of B. subtilis the protein is called UgtP and in the case of E. coli it is OpgH.

"It's interesting," Hill said, "that both organisms, which are more different from one another than we are from bakers' yeast, are using the same system to coordinate changing size in response to nutrient availability."

UgtP and OpgH are bifunctional proteins that are "moonlighting" as elements of the cell-division control systems. In both cases their day jobs are to help build the cell envelope. "We think they are communicating not only how much glucose there is in the cell, but also how fast the cell is growing," Levin said. "The sensor says not only is food abundant, but we're also growing really fast, so we should be bigger."

Both proteins delay division by interfering with FtsZ, the first protein to move to the division site, where it assembles into a scaffold and recruits other proteins to form a constriction ring.

"Very little is known about the assembly of the ring," Hill said. "There are a dozen essential division proteins and we don't know what half of them do. Nor do we understand how the ring develops enough force to constrict."

"We do know FtsZ exists in two states," Hill added. "One is a small monomer and the other is many monomers linked together to form a multi-unit polymer. We think the polymers bind laterally to form a scaffold and then, with the help of other proteins, make a meshwork that goes around the cell.

UgtP and OpgH both interfere with the ability of FtsZ to form the longer polymers necessary for assembly of the constriction ring.

When nutrient levels are low, UgtP and OpgH are sequestered away from the division machinery. FtsZ is then free to assemble into the scaffold supporting the constriction ring so the cell can divide. Because division proceeds unimpeded, cells are smaller when they divide.

What about other bacteria?

This control system helps to explain the 60-year-old observation that bacterial cells get bigger when they are shifted to a nutrient-rich medium.

Comparing the mechanisms that govern cell division in E. coli and B. subtilis reveals conserved aspects of cell size control, including the use of UDP-glucose, a molecule common to all domains of life, as a proxy for nutrient availability, and the use of moonlighting proteins to couple growth-rate-dependent phenomena to the central metabolism.

But much more is known about these model organisms, which many labs study, than the average bacterium. Nobody is sure how many species of bacteria there are - somewhere between 10 million and a billion at a guess - and they don't all divide the way B. subtilis and E. coli do.

The whimsically named giant bacterium Epulopiscium fiselsoni ("Fishelson's guest at a fish's banquet") that lives in the guts of sturgeonfish, has the gene for FtsZ but doesn't divide by binary fission. And then there are bacteria like the pathogen Chlamydia traachomatis that don't have a gene for anything like FtsZ. "We don't know how these bacteria divide, much less maintain an appropriate cell size," Levin said.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our infectious diseases / bacteria / viruses section for the latest news on this subject. Please use one of the following formats to cite this article in your essay, paper or report:

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Identifying teens at risk for PTSD following traumatic events

Main Category: Anxiety / Stress
Also Included In: Pediatrics / Children's Health;  Psychology / Psychiatry
Article Date: 31 Jul 2013 - 1:00 PDT Current ratings for:
Identifying teens at risk for PTSD following traumatic events

While most children cannot be shielded from emotionally traumatic events, clinicians can target those who are most vulnerable to developing post-traumatic stress disorder (PTSD), according to a large study from Boston Children's Hospital. Findings appear online in the August issue of the Journal of the American Academy of Child & Adolescent Psychiatry, accompanied by an editorial.

Researchers led by Katie McLaughlin, PhD, of the Departments of Pediatrics and Psychiatry at Boston Children's, analyzed data on 6,483 teen-parent pairs from the National Comorbidity Survey Replication, a survey of the prevalence and correlates of mental disorders in the United States.

Overall, 61 percent of the teens (ages 13 to 17) had been exposed to at least one potentially traumatic event in their lifetime, including interpersonal violence (such as rape, physical abuse or witnessing domestic violence), injuries, natural disasters and death of a close friend or family member. Nineteen percent had experienced three or more such events.

Risk factors associated most strongly with trauma exposure included:

Lack of both biological parents in the home. Pre-existing mental disorders, particularly behavioral disorders like attention-deficit hyperactivity disorder (ADHD) and oppositional defiant disorder.

Of all teens exposed to trauma, 4.7 percent had experienced PTSD under DSM-IV diagnostic criteria. Risk factors for PTSD included:

Female gender: Of the total sample, girls had a lifetime prevalence of PTSD of 7.3 percent, and boys 2.2 percent. Events involving interpersonal violence: the lifetime prevalence of PTSD was 39 percent for teens who had been raped and 25 percent for those physically abused by a caregiver. Underlying anxiety and mood disorders (also a risk factor for exposure).

Risk factors for lack of recovery from PTSD included underlying bipolar disorder, exposure to an additional traumatic event, living in poverty and being a U.S. native.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
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Katie A. McLaughlin, Ph.D., Karestan C. Koenen, Ph.D., Eric D. Hill, M.S.P.H., Maria Petukhova, Ph.D., Nancy A. Sampson, B.A., Alan M. Zaslavsky, Ph.D., Ronald C. Kessler, Ph.D., Trauma Exposure and Posttraumatic Stress Disorder in a National Sample of Adolescents, Journal of the American Academy of Child & Adolescent Psychiatry, doi:10.1016/j.jaac.2013.05.011

Boston Children's Hospital

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Treatments for tuberculosis, cancer will likely improve following breakthrough in detecting DNA mutations

Main Category: Tuberculosis
Also Included In: Cancer / Oncology;  Genetics
Article Date: 30 Jul 2013 - 0:00 PDT Current ratings for:
Treatments for tuberculosis, cancer will likely improve following breakthrough in detecting DNA mutations

The slightest variation in a sequence of DNA can have profound effects. Modern genomics has shown that just one mutation can be the difference between successfully treating a disease and having it spread rampantly throughout the body.

Now, researchers have developed a new method that can look at a specific segment of DNA and pinpoint a single mutation, which could help diagnose and treat diseases such as cancer and tuberculosis. These small changes can be the root of a disease or the reason some infectious diseases resist certain antibiotics. The findings were published online in the journal Nature Chemistry.

"We've really improved on previous approaches because our solution doesn't require any complicated reactions or added enzymes, it just uses DNA," said lead author Georg Seelig, a University of Washington assistant professor of electrical engineering and of computer science and engineering. "This means that the method is robust to changes in temperature and other environmental variables, making it well-suited for diagnostic applications in low-resource settings."

DNA is a type of nucleic acid, the biological molecule that gives all living things their unique genetic signatures. In a double strand of DNA, known as a double helix, a series of base pairs bond and encode our genetic information. As genomics research has progressed, it's clear that a change of just one base pair - a sequence mutation, an insertion or a deletion - is enough to trigger major biological consequences. This could explain the onset of disease, or the reason some diseases don't respond to usual antibiotic treatment.

Take, for example, tuberculosis ?" a disease that's known to have drug-resistant strains. Its resistance to antibiotics often is due to a small number of mutations in a specific gene. If a person with tuberculosis isn't responding to treatment, it's likely because there is a mutation, Seelig said.

Now, researchers have the ability to check for that mutation preventatively.

Seelig, along with David Zhang of Rice University and Sherry Chen, a UW doctoral student in electrical engineering, designed probes that can pick out mutations in a single base pair in a target stretch of DNA. The probes allow researchers to look in much more detail for variations in long sequences - up to 200 base pairs ?" while current methods can detect mutations in stretches of up to only 20.

"In terms of specificity, our research suggests that we can do quadratically better, meaning that whatever the best level of specificity, our best will be that number squared," said Zhang, an assistant professor of bioengineering at Rice University.

The testing probes are designed to bind with a sequence of DNA that is suspected of having a mutation. The researchers do this by creating a complimentary sequence of DNA to the double-helix strand in question. Then, they allow molecules containing both sequences to mix in a test tube in salt water, where they naturally will match up to one another if the base pairs are intact. Unlike previous technologies, the probe molecule checks both strands of the target double helix for mutations rather than just one, which explains the increased specificity.

The probe is engineered to emit a fluorescent glow if there's a perfect match between it and the target. If it doesn't illuminate, that means the strands didn't match and there was in fact a mutation in the target strand of DNA.

The researchers have filed a patent on the technology and are working with the UW Center for Commercialization. They hope to integrate it into a paper-based diagnostic test for diseases that could be used in parts of the world with few medical resources.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
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The research was funded by the National Institutes of Health, the National Science Foundation and the Department of Defense's Advanced Research Projects Agency.

University of Washington

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