RealClearScience Journal Club

Science Figures Interpreted and Analyzed by RealClearScience

Got Low T? Testosterone Drugs Probably Won't Help

Ross Pomeroy - September 22, 2016

In 2002, Solvay Pharmaceuticals, maker of the testosterone supplement AndroGel, launched a global marketing campaign to pathologize male aging. The gradual and natural decrease in testosterone that all men face was no longer inevitable. Instead, it was a treatable condition called "Low T". The "Testosterone Crisis" was born, and sales skyrocketed.

But while branding can conceal the truth; it cannot change it. The companies behind testosterone supplements like AndroGel, Axiron, and Testim hint that their products can improve mood, boost cognitive function, treat erectile dysfunction, and alleviate depression. The weight of scientific evidence says otherwise.

A new systematic review primarily carried out by researchers at Georgetown University neatly summarizes the available data.

"The prescription of testosterone supplementation for low-T for cardiovascular health, sexual function, physical function, mood, or cognitive function is without support from randomized clinical trials," the reviewers reported in the journal PLoS ONE.

The authors evaluated 156 randomized controlled trials in which testosterone was compared to placebo to treat a variety of conditions. Testosterone did not consistently prevent or treat cardiovascular disease, nor did it consistently improve sexual function or satisfaction, with half of the studies showing positive effects and the other half not showing any effects. It was altogether ineffective at treating erectile dysfunction. The majority of studies showed no effects on psychological well-being or cognitive function.

Testosterone did offer a few benefits. The review indicated a small boost to libido and a robust increase in muscle mass. However, the increase in mass was not accompanied by increases to strength.

As of 2013, roughly 2.2 million American men were taking prescription testosterone. For some, affected by genuine hypogonadism, a condition where the testes do not produce enough testosterone, supplementing the hormone may be called for. But for otherwise healthy men simply undergoing normal aging, testosterone probably won't have much effect. Simpler remedies like exercising and maintaining a healthy weight may provide more of a benefit, the reviewers suggest.

Source: Huo S, Scialli AR, McGarvey S, Hill E, Tügertimur B, Hogenmiller A, et al. (2016) Treatment of Men for “Low Testosterone”: A Systematic Review. PLoS ONE 11(9): e0162480. doi:10.1371/journal.pone.0162480

How Does the Ocean Sunfish Get So Big?

Ross Pomeroy - September 12, 2016

The ocean sunfish (Mola mola) has a radiant name, but its appearance doesn't exactly match its glowing moniker. Wrinkled and colored a sickly shade of gray, the sunfish doesn't exactly shimmer. However, its pallor isn't nearly as distracting as its awkward shape -- the fish is usually taller than it is long. Moreover, the sunfish's mouth is constantly agape, granting it a dumbfounded look of everlasting surprise. With that gaping maw, the sunfish primarily consumes jellies, a less-than-sumptuous prey. Yet it is on this slimy diet that sunfish can attain weights of over 1,000 kilograms and lengths of nearly six feet. The largest sunfish weighed in at 2,300 kilograms and extended over ten feet in length! Not bad for a fish that, as a baby, begins life measuring just four millimeters across.

The ocean sunfish's immense size has earned it the title of "world's largest bony fish." As you might imagine, getting that bulky takes some serious growing. Researchers recorded a captive sunfish ballooning 880 pounds in fifteen months, an average of 1.8 pounds per day. That's far, far above other ray-finned fish, even ones that are similar in size to the sunfish.

Recently, researchers published the first genome sequence of the ocean sunfish. The results rendered insights into the fish's incredible growth rate.

"Several sunfish genes involved in the growth hormone and insulin-like growth factor 1 axis signalling pathway were found to be under positive selection or accelerated evolution, which might explain its fast growth rate and large body size," the researchers noted. 

Indeed insulin-like growth factor 1 (IGF-1) is one of the primary growth hormones in humans, as well. People insensitive to or deficient in the hormone experience stunted growth or dwarfism. The ocean sunfish, on the other hand, seems to produce a boatload of the stuff. This means that with plenty of food, the charismatic fish can grow and grow and grow.

Source: Hailin Pan et. al. "The genome of the largest bony fish, ocean sunfish (Mola mola), provides insights into its fast growth rate." GigaScience 9 Sept 2016 5:36  DOI: 10.1186/s13742-016-0144-3

(Images: Per-Ola Norman , G. David Johnson)

A Simple Phone Game Could Diagnose Autism

Ross Pomeroy - August 25, 2016

Roughly one out of every 68 children in North America has autism spectrum disorder (ASD), a developmental condition broadly characterized by difficulties in social interaction, problems with communication, and repetitive behaviors.

Every ASD diagnosis is a complicated, involved process. The child -- who is often between the ages of two and six -- undergoes a battery of behavioral evaluations overseen by trained professionals, usually in a clinical setting. He or she is observed and tested, sometimes for lengthy periods. Diagnoses can be equally extended.

But researchers from Jagiellonian University in Poland and the University of Strathclyde in the United Kingdom have a plan to streamline the process. They aim to diagnose autism with a simple game played on a phone or tablet. In a recent study published to the journal Scientific Reports, they took a significant stride towards reaching that goal.

Prior research has hinted that children diagnosed with ASD demonstrate distinct patterns in motor control, particularly with their hands. With this in mind, authors Anna Anzulewicz, Krzysztof Sobota, and Jonathan T. Delafield-Butt recruited 37 children between the ages of three and six years old and matched them with 45 typically-developing controls of equal age at the same gender ratio. One-by-one, each child was brought into a room, sat in front of an iPad mini affixed to a table, and instructed to play two basic games for seven minutes each. The duration was split into two minutes of training followed by five minutes of solo play. (Figure below: One game involved sharing a piece of fruit between four characters. The other game involved tracing and coloring different objects.)

In those short and painless moments, the researchers collected heaps of data on the children's finger movements extracted via inertial sensors and the tablet's touchscreen. Machine-learning algorithms subsequently examined the data to determine precise motor patterns associated with ASD. Children with autism touched the screen with more impact force and greater pressure compared to controls. They also swiped faster and tapped the screen more quickly.

Utilizing those touch patterns, the algorithm devised diagnostic criteria for autism based on the children's gameplay. The criteria successfully identified the autistic children with an impressive 93 percent accuracy. The researchers were elated with the results.

"We have shown here that smart tablet technology offers an attractive, new paradigm for clinical autism assessment... enabling engaging, ecological testing of children’s motor behaviour in a fun, accessible format..." they write.

The study is an exciting proof-of-concept, the researchers say, but more work needs to be done. Next, they aim to test their approach on many more subjects in order to refine the algorithm's diagnostic criteria and eliminate potential confounding variables.

Source: Anzulewicz, A. et al. Toward the Autism Motor Signature: Gesture patterns during smart tablet gameplay identify children with autism. Sci. Rep. 6, 31107; doi: 10.1038/srep31107 (2016).

A Lethal Plague Ravaged Florida Corals in 2014

Ross Pomeroy - August 15, 2016

Life's been hard for coral of late. Scarcely a week goes by without dire news for the charismatic ocean invertebrates.

Take the coral depicted above, for example. The first picture, taken August 20th, 2014, shows a healthy colony going about its business just off Florida's Virginia Key. Only a month later (picture B), the coral was left bleached and vulnerable as high water temperatures forced symbiotic algae to vacate. These symbionts, called zooxanthellae, returned roughly six weeks later when temperatures dropped, but by then, the coral colony was imperiled by a new, far more dangerous threat: white plague. You can see its first traces on the colony's lower right side in picture C. Less than a month later (picture D), the coral was dead and buried by sea sediments.

This story was all too common within Florida's coral reefs between September 2014 and September 2015. During that time, an unprecedented and highly lethal outbreak of white plague struck corals situated off Miami-Dade County. Researchers just revealed the extent of the outbreak in the journal Scientific Reports.

White plague deserves any and all comparisons to the bubonic plague that fueled Europe's Black Death from 1346 to 1353. Once a coral is infected, the disease spreads rapidly. Small lesions or blemishes at the base or surface of the colony quickly blossom into an expanding ring of necrotic tissue. A small colony can be engulfed in less than a week, with only a bare, white skeleton left behind.

The variety of white plague that struck off Florida in 2014 and 2015 was likely caused by a bacterium. Another version -- there are two total -- might be viral in origin.

The researchers surveyed a total of 14 sites all along the coast of Miami-Dade County and found that 61% of coral species were infected. Moreover, virtually all infected coral colonies died. That prevalence is unprecedented, the researchers say. Also remarkable is the fact that most of the colonies were spread over a wide area of more than 130 kilometers with limited coral cover, indicating that this strain of white plague could travel in water and was highly contagious.

Eight species of coral were particularly devastated by the outbreak. The figure below shows the number of colonies surveyed (n) and the proportion infected.

The researchers believe that a prior temperature-induced coral bleaching event greatly enhanced the severity of the outbreak, and further suggest that as climate change raises ocean temperatures, coral disease outbreaks will grow more common, more widespread, and more deadly. What occurred in Florida between September 2014 and September 2015 is merely a preview.

"The high prevalence of disease, the number of susceptible species, and the high mortality of corals affected suggests this disease outbreak is arguably one of the most lethal ever recorded on a contemporary coral reef," the researchers say.

Source: Precht, W. F. et al. Unprecedented Disease-Related Coral Mortality in Southeastern Florida. Sci. Rep. 6, 31374; doi: 10.1038/srep31374 (2016).

Greenland Sharks Live 400 Years or More, Making Them the Longest-Lived Vertebrates

Ross Pomeroy - August 11, 2016

In the 1620s, the Mayflower pilgrims landed in what is now Massachusetts, the Thirty Years War raged in Central Europe, Johannes Kepler put forth his laws of planetary motion, and the oldest-known Greenland shark was born.

While the Pilgrims, the Thirty Years War, and Johannes Kepler are enshrined in history books, the realization about the Greenland shark was just made public today in the journal Science.

To uncover the result, Julius Nielsen, a PhD student at the University of Copenhagen, along with an international team of researchers, used radiocarbon dating on the eye lens nuclei of 28 female Greenland Sharks captured between 2010 and 2013.

Crystalline proteins within the eye are formed around the time an animal is born and remain essentially unchanged for life. These proteins contain a fixed amount of Carbon-14, a radioactive isotope of Carbon that decays at a known rate. For the last few hundred years before 1960, when nuclear bomb tests doubled the amount of Carbon-14 in the atmosphere, that level remained relatively consistent. Thus, Nielsen and his colleagues measured the levels of Carbon-14 in the sharks' eye lenses and extrapolated back based on the rate of decay to determine the animals' ages.

The largest shark was determined to be 392 years old, give or take 120 years. Based on the results, the researchers also estimated that the animals might not reach sexual maturity until age 156! (Below: The graph shows the estimated birthdate for each shark. Length (TL) is on the Y-axis. Every blue "hump" corresponds to one shark and covers the range of potential birthdates.)

Greenland sharks live in the frigid waters of the North Atlantic and Arctic Oceans where they mostly feed on fish. Swimming no more than two miles per hour, the hulking beasts move slowly and grow just as slowly, just 0.5 to 1 centimeters per year. Yet they can grow to be more than six or even seven meters in length! This means there are likely even older Greenland sharks out there waiting to be aged.

"Our results show that the Greenland shark is the longest-lived vertebrate known," the researchers write. With the finding, the Greenland shark firmly passes the bowhead whale, which is estimated to live up to 211 years.

Source: Nielsen et. al. "Eye lens radiocarbon reveals centuries of longevity in the Greenland shark (Somniosus microcephalus)." Science. 12 AUGUST 2016 • VOL 353 ISSUE 6300. DOI: 10.1126/science.aaf3617

(Image: NOAA Okeanos Explorer Program)

A New Description of Our Last Universal Ancestor

Ross Pomeroy - July 25, 2016

Meet LUCA.

LUCA is, or rather was, a single-celled organism that lived in an oxygen-free hot spring. Its enzymes were packed with iron along with traces of other transition metals, hinting that LUCA's watery home was also rich in these metals. Within this cozy, metallic habitat, it fed on hydrogen and absorbed carbon dioxide and nitrogen from its surroundings, converting them to organic compounds in the proces. In many respects, LUCA was very similar to modern-day extremophiles dwelling near hydrothermal vents in the deep ocean.

Why should you care about LUCA? Because -- in a sense -- LUCA was your great, great, great, great, great, great (etc.) grandparent; the Last Universal Common Ancestor of all life on Earth. Between 3.5 and 3.8 billion years old! Respect your elders. (Figure Below: LUCA is the black line at the bottom.)

LUCA was just described in new detail in the journal Nature Microbiology. Madeline Weiss and Filipa Sousa led a team based out of Heinrich Heine University Düsseldorf in Germany. Together, they compiled gene families that exist in at least two species of Bacteria and two species of Archaea (Bacteria and Archaea being the most basic forms of life on Earth) and arranged them into phylogenetic trees. 286,514 gene families made the cut. Examining the trees, the researchers found that only 355 gene families descended from a common evolutionary ancestor and weren't shared with any other group.

"These 355 proteins were probably present in LUCA and thus provide a glimpse of LUCA’s genome," they reasoned.

Most of the genes previously had their functions sussed out, and these painted the aforementioned picture of LUCA.

"This new study provides us with a very intriguing insight into life 4 billion years ago," James O. McInerney an esteemed biologist at the University of Manchester, wrote in an accompanying news article. "When we look at the inferred metabolism of LUCA, we are looking at the dominant and most successful kind of metabolism on the planet before the Bacteria and Archaea diverged."

The study also supports the idea that life likely began near hydrothermal vents, where primitive cells may have been boiled into existence out of the building blocks of life. 

Source: Weiss et. al. "The physiology and habitat of the last universal common ancestor." Nature Microbiology. 25 July 2016. DOI: 10.1038/NMICROBIOL.2016.139

(Images: Jon Sullivan, NASA Astrobiology Institute)

Supervolcanoes May Erupt Surprisingly Fast

Ross Pomeroy - July 21, 2016

Once primed, a supervolcano can decompress and erupt in under a year, a new study shows, offering little warning before a potentially cataclysmic event. 

Supervolcanoes, the hulking geological behemoths that they are, slumber for hundreds of thousands or even millions of years in between eruptions. That's a very good thing, for when they blow, they explode with colossal power, spewing hundreds or even thousands of cubic kilometers of ash across thousands of miles, as well as altering the global climate. 

A quarter of all known supervolcanoes are in the United States, with the best-known dwelling below the picturesque, breathing landscape of Yellowstone National Park. If it were to erupt, it would spew ash as far away as New York. But the sooty dusting that the eastern seaboard would receive would pale in comparison to the ashfall in the heart of the country. Nearby states would be buried under as much as six feet of ash!

Such a scenario seems unlikely to occur anytime soon. None of the world's supervolcanoes currently house magma bodies large enough to produce a cataclysmic eruption. The dormancy has afforded modern humans a chance to thrive globally, and given geologists a chance to safely study supervolcanoes.

Geologists Guilherme Gualda of Vanderbilt University and Stephen Sutton of the University of Chicago recently examined quartz crystal formations left by the supervolcano eruption that created the Long Valley Caldera in California more than 760,000 years ago. Patterns and element concentrations in the crystals are used gauge the evolution of a historical body of magma. In this case, the authors focused on the concentration of titanium to measure the growth rate of crystal rims that mark the final stages of an eruption.

From their analysis, Gualda and Sutton determined that a body of magma below a supervolcano can decompress and erupt in under a year. Their finding disagrees with prior analyses conducted on crystals from the same source, suggesting that this process usually takes over a century.

With their results, the researchers created a rough timeline of a supervolcano explosion. Over tens of thousands of years, the volcanic chamber fills with magma mush of melted rock and solid crystal. Eventually, sufficient magma flows into the chamber and the crystals are expelled. Over the next 5,000 years, the bulging chamber builds pressure. Finally, decompression begins, followed swiftly by an eruption.

“Now we have shown that the onset of the process of decompression, which releases the gas bubbles that power the eruption, starts less than a year before eruption,” Gualda said in a press release.

The timeline is potentially terrifying. If true, it means humanity could be afforded comparatively small notice of a coming eruption.

Source: Gualda GAR, Sutton SR (2016) The Year Leading to a Supereruption. PLoS ONE 11(7): e0159200. doi:10.1371/journal.pone.0159200

(Image: Robert B. Smith via AP)

An Asteroid Extinction You Haven't Heard Of

Ross Pomeroy - July 11, 2016

The Manicouagan Crater in the Canadian province of Quebec is the largest plainly visible impact crater on Earth, and the sixth largest overall. Roughly 100 kilometers in diameter -- a little more than half the size of the Chicxulub Crater in Mexico (the crater associated with the extinction of the dinosaurs) -- it forms a tidy ring of water encircling a large island. The asteroid that made Manicouagan was once considered as a possible trigger for the Triassic–Jurassic extinction event, which set the stage for dinosaurs to dominate Earth. Mineral dating, however, shows that the crater was carved more than 12 million years before the mass extinction, so it couldn't have been the cause.

The Manicouagan impact was far from harmless, however. A new study published to Scientific Reports suggests that it prompted a large extinction event of its own, and may have contributed to the eventual Triassic–Jurassic extinction around 200 million years ago. 

Japanese researchers extensively surveyed a claystone layer that accumulated in a deep seafloor environment in an equatorial region of the Panthalassa Ocean (location marked by the red area in the figure above). The Panthalassa Ocean was the vast body of water that surrounded the supercontinent Pangaea. They found that, around 214 to 215 million years ago, approximately the same time of the Manicouagan impact, a great many species of plankton called Radiolarians abruptly disappeared, while tons of new species sprung up. Moreover, the massive turnover in life forms coincided with an anomalous increase in platinum group elements, which the researchers believe originated from an extraterrestrial source. This source -- probably an asteroid -- was between 3.3 and 7.8 kilometers in diameter and slammed the Earth at a speed of around 20 kilometers/second, they estimate. (Figure below: Note that rates of extinction and origination (new species) abruptly increased 214 million years ago.)

The disruption in the ocean food chain almost certainly impacted other species. Shelled, swimming Ammonites, similar in appearance to modern-day nautiluses, experienced significant declines in diversity in the years leading up to the Triassic-Jurassic extinction, while eel-like Conodonts went extinct altogether.

The asteroid impact combined with other catastrophes like volcanic eruptions and sudden depletions of ocean oxygen to drastically thin the number of species on Earth at the end of the Triassic. When the Jurassic period began roughly 201 million years ago, at least half of all known species had vanished.

Source: Onoue, T. et al. Bolide impact triggered the Late Triassic extinction event in equatorial Panthalassa. Sci. Rep. 6, 29609; doi: 10.1038/srep29609 (2016).

(Image: NASA)

"Good" Virus Used to Combat a "Bad" One

Ross Pomeroy - July 5, 2016

Scientists from the University of Texas have successfully used a therapeutic virus to block the spread of a lethal one. The researchers hope their technique will one day be adapted to treat chronic HIV infections.

Integrative biologist Matthew Paff and his colleagues infected colonies of E. coli bacteria with two viruses: one that swiftly kills infected hosts and another that establishes a permanent infection, but does not kill, its hosts. They then closely observed the E. coli populations.

When the therapeutic virus was introduced first, it rapidly spread to infect the bacterial populations. An hour later, the researchers introduced the lethal virus into some of the colonies. In colonies infected with the therapeutic virus, host populations remained fairly stable, while host populations without the therapeutic virus saw their numbers dwindle by two orders of magnitude (see D in the figure below).

The intervention was not as successful when the lethal virus was introduced first, as the bacterial population declined rapidly before the therapeutic virus could impart protection. 

The therapeutic virus, succinctly dubbed "f1", blocks subsequent viral infection by damaging or modifying the pilus of its bacterial host. The pilus is a hairlike appendage which bacteria use to transfer genetic information, and which many viruses co-opt to infect bacterial cells.

With their aptly named "virus wars" system demonstrated in a bacterial host, the authors mused on applying the technique to humans.

"It is too early to identify the actual agents that might be used in an application against a human chronic infection such as HIV, and even if such transmissible agents were known, regulatory issues might thwart implementation in the near future. Our suggested approach is thus futuristic, but it is only a few steps from current practices."

The authors suggest that therapeutic viruses could one day be designed to prevent viral infections or even to destroy malicious viruses upon entry.

The new research was published to the open-access journal PeerJ.

Source: Paff ML, Nuismer SL, Ellington A, Molineux IJ, Bull JJ. (2016) Virus wars: using one virus to block the spread of another. PeerJ 4:e2166

(Image: Reconfirming the Traditional Model of HIV Particle Assembly. Gross L, PLoS Biology Vol. 4/12/2006, e445.)

Three Hypotheses to Explain Mars' Methane

Ross Pomeroy - June 27, 2016

In December 2014, NASA scientists confirmed the presence of methane on Mars. The Curiosity rover detected a massive spike in methane levels over a 60-day period. Levels of the organic compound surged in the atmosphere from roughly 0.7 parts per billion all the way up to 7 parts per billion, and subsequently returned to background levels.

The discovery settled a decade-long debate. Not only does the Red Planet contain appreciable amounts of methane in its atmosphere, levels of the organic compound fluctuate, indicating a potential source on Mars itself. Knowing that Earth's methane is primarily produced by living organisms, Mars enthusiasts were abuzz with excitement. Could life be manufacturing Mars' methane as well?

Indeed, that is one of the explanations entertained by a team of scientists based out of NASA's Jet Propulsion Laboratory and the California Institute of Technology. In a new paper published to the journal Astrobiology, Dr. Renyu Hu and his colleagues confirm that perchlorate salts on Mars underneath Gale Crater can convert to a liquid state. With this in mind, Hu and his team offered up three testable hypotheses for the origin of Mars' methane.

First, the regolith of rocks, dirt, and soil overlying the perchlorate salts at Gale Crater collects methane when dry and releases it when the salts liquefy. This would be a seasonal process, occurring in early Martian winter when the humidity rises to a sufficient level.

Second, there may be a deep subsurface aquifer containing methane, which periodically releases bursts of the compound into the atmosphere. The aquifer could be buried as far as five kilometers deep. Moreover, they may be sealed by ice, similar to tundras on Earth.

Third, yeast-like microorganisms called methanogens convert organic matter in the soil to methane when the perchlorate salts turn to liquid. Like the first hypothesis, this would again ocurr on a seasonal basis. While undoubtedly the most exciting explanation, this is also the most unlikely. The researchers, however, turn to examples on Earth for hope.

"Methanogens thrive in some of the harshest environments on Earth, including extremely acidic environments and inside Greenland glacial ice three kilometers deep, which is analogous to Martian subsurface ice environments."

Unfortunately, this explanation took a significant hit in May as Curiosity watched its second Martian winter pass without a spike in methane levels similar to the first one. This suggests that the methane release was not seasonal in nature.

Each of the competing explanations are constantly tested as the Curiosity rover continues its stay on the Red Plant, the researchers say. One of them may eventually be proven correct.

"Any of the three hypotheses, if confirmed, leads to profound ramifications in our understanding of Mars as an active and potentially habitable world."

Source: Renyu Hu et. al. Hypotheses for Near-Surface Exchange of Methane on Mars. Astrobiology. June 2016 DOI: 10.1089/ast.2015.1410

(Image: NASA)

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