Researchers build largest protein interaction map to date

ScienceDaily (Oct. 27, 2011) — Researchers have built a map that shows how thousands of proteins in a fruit fly cell communicate with each other. This is the largest and most detailed protein interaction map of a multicellular organism, demonstrating how approximately 5,000, or one third, of the proteins cooperate to keep life going.

"My group has been working for decades, trying to unravel the precise connections among the proteins and gain insight into how the cell functions as a whole," says Spyros Artavanis-Tsakonas, Harvard Medical School professor of cell biology and senior author on the paper. "For me, and hopefully researchers studying protein interactions, this map is a dream come true."

The study is published October 28 in the journal Cell.

While genes are a cell's data repository, containing all the instructions necessary for life, proteins are its labor force, talking to each other constantly and channeling vital information through vast and complicated networks to keep life stable and healthy. Humans and fruit flies are both descended from a common ancestor, and in most cases, both species still rely on the same ancient cellular machinery for survival. In that respect, the fruit fly's map serves as sort of a blueprint, a useful guide into the cellular activity of many higher organisms.

Understanding how proteins behave normally is often the key to their disease-causing behavior.

For this study, Artavanis-Tsakonas and his colleagues provide the first large-scale map of this population of proteins. Their map, which is not yet fully complete, reveals many of the relationships these myriad proteins make with each other as they collaborate, something which, to date, has been to a large degree an enduring mystery among biologists.

"We already know what approximately one-third of these proteins do," Artavanis-Tsakonas said. "For another third of them we can sort of guess. But there's another third that we know nothing about. And now through this kind of analysis we can begin to explore the functions of these proteins. This is giving us extraordinary insight into how the cell works."

One significant use for such a map is to assess how a cell responds to changes in metabolic conditions, such as interactions with drugs or in conditions where genetic alterations occur. Finding such answers might lead to future drug treatments for disease, and perhaps to a deeper understanding of what occurs in conditions such as cancer.

"This is of extraordinary translational value," Artavanis-Tsakonas said. "In order to know how the proteins work you must know who they talk to. And then you can examine whether a disease somehow alters this conversation."

A pivotal part of this research involved a scientific technique called mass spectrometry, which is relatively new to the science of biology. The ultra-precise mass spectrometry experiments were done by HMS professor of cell biology Steven Gygi. Mass spectrometry is used to measure the exact weight (the mass) and thus identify each individual protein in a sample. It is a technique originally devised by physicists for analyzing atomic particles. But in recent years mass spectrometry was adapted and refined for new and powerful uses in basic biological research. Other studies using similar techniques to date have focused on small groups of related proteins or single celled model organisms such as bacteria and yeast.

Despite the huge amount already known about the fruit fly and its genetic endowment, much about the function of thousands of proteins remains a mystery. This map, however, now gives us precise clues about their function. Filling in the detailed protein map can help scientists gain important insights into the process of development, that is, how a creature is put together, maintained and operated.

"Our analyses also sheds light on how proteins and protein networks have evolved in different animals," said K. G. Guruharsha, a postdoctoral fellow in Artavanis-Tsakonas's lab and a first author on the paper.

Co-lead authors on the paper included Jean-Francois Rual, also a postdoctoral fellow in Artavanis-Tsakonas's lab, and Julian Mintseris and Bo Zhai, both research fellows in Gygi's lab.

Also important in this effort was the work of K. VijayRaghavan, at the National Centre for Biological Sciences in Bangalore, India. Similarly, crucial contributions to this work also came from the University of California, in Berkeley, where Susan E. Celniker collaborated through her studies in the fruit fly genome center.

This research was funded by the National Institutes of Health.

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The above story is reprinted from materials provided by Harvard Medical School. The original article was written by Robert Cooke.

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Watermelon reduces atherosclerosis, animal study finds

ScienceDaily (Oct. 27, 2011) — In a recent study by University of Kentucky researchers, watermelon was shown to reduce atherosclerosis in animals.

The animal model used for the study involved mice with diet-induced high cholesterol. A control group was given water to drink, while the experimental group was given watermelon juice. By week eight of the study, the animals given watermelon juice had lower body weight than the control group, due to decrease of fat mass. They experienced no decrease in lean mass. Plasma cholesterol concentrations were significantly lower in the experimental group, with modestly reduced intermediate and low-density lipoprotein cholesterol concentrations as compared to the control group.

A measurement of atherosclerotic lesion areas revealed that the watermelon juice group also experienced statistically significant reductions in atherosclerotic lesions, as compared to the control group.

"Melons have many health benefits," said lead investigator Dr. Sibu Saha. "This pilot study has found three interesting health benefits in mouse model of atherosclerosis. Our ultimate goal is to identify bioactive compounds that would improve human health."

The study was conducted by Sibu Saha, UK Department of Surgery; Aruna Poduri, UK Saha Cardiovascular Research Center (UK Saha CRVC); Debra L. Rateri, UK Saha CVRC; Shubin Saha of Purdue Univ.; and Alan Daugherty, director, UK Saha CVRC.

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Three new planets and a mystery object discovered outside our solar system

ScienceDaily (Oct. 27, 2011) — Three planets -- each orbiting its own giant, dying star -- have been discovered by an international research team led by a Penn State University astronomer.

Using the Hobby-Eberly Telescope, astronomers observed the planets' parent stars -- called HD 240237, BD +48 738, and HD 96127 -- tens of light years away from our solar system. One of the massive, dying stars has an additional mystery object orbiting it, according to team leader Alex Wolszczan, an Evan Pugh Professor of Astronomy and Astrophysics at Penn State, who, in 1992, became the first astronomer ever to discover planets outside our solar system. The new research is expected to shed light on the evolution of planetary systems around dying stars. It also will help astronomers to understand how metal content influences the behavior of dying stars.

The research will be published in December in the Astrophysical Journal. The first author of the paper is Sara Gettel, a graduate student from Penn State's Department of Astronomy and Astrophysics, and the paper is co-authored by three graduate students from Poland.

The three newly-discovered planetary systems are more evolved than our own solar system. "Each of the three stars is swelling and has already become a red giant -- a dying star that soon will gobble up any planet that happens to be orbiting too close to it," Wolszczan said. "While we certainly can expect a similar fate for our own Sun, which eventually will become a red giant and possibly will consume our Earth, we won't have to worry about it happening for another five-billion years." Wolszczan also said that one of the massive, dying stars -- BD +48 738 -- is accompanied not only by an enormous, Jupiter-like planet, but also by a second, mystery object. According to the team, this object could be another planet, a low-mass star, or -- most interestingly -- a brown dwarf, which is a star-like body that is intermediate in mass between the coolest stars and giant planets. "We will continue to watch this strange object and, in a few more years, we hope to be able to reveal its identity," Wolszczan said.

The three dying stars and their accompanying planets have been particularly useful to the research team because they have helped to illuminate such ongoing mysteries as how dying stars behave depending on their metallicity. "First, we know that giant stars like HD 240237, BD +48 738, and HD 96127 are especially noisy. That is, they appear jittery, because they oscillate much more than our own, much-younger Sun. This noisiness disturbs the observation process, making it a challenge to discover any companion planets," Wolszczan said. "Still, we persevered and we eventually were able to spot the planets orbiting each massive star."

Once Wolszczan and his team had confirmed that HD 240237, BD +48 738, and HD 96127 did indeed have planets orbiting around them, they measured the metal content of the stars and found some interesting correlations. "We found a negative correlation between a star's metallicity and its jitteriness. It turns out that the less metal content each star had, the more noisy and jittery it was," Wolszczan explained. "Our own Sun vibrates slightly too, but because it is much younger, its atmosphere is much less turbulent."

Wolszczan also pointed out that, as stars swell to the red-giant stage, planetary orbits change and even intersect, and close-in planets and moons eventually get swallowed and sucked up by the dying star. For this reason, it is possible that HD 240237, BD +48 738, and HD 96127 once might have had more planets in orbit, but that these planets were consumed over time. "It's interesting to note that, of these three newly-discovered stars, none has a planet at a distance closer than 0.6 astronomical units -- that is, 0.6 the distance of the Earth to our Sun," Wolszczan said. "It might be that 0.6 is the magic number at which any closer distance spells a planet's demise."

Observations of dying stars, their metal content, and how they affect the planets around them could provide clues about the fate of our own solar system. "Of course, in about five-billion years, our Sun will become a red giant and likely will swallow up the inner planets and the planets' accompanying moons. However, if we're still around in, say, one-billion to three-billion years, we might consider taking up residence on Jupiter's moon, Europa, for the remaining couple billion years before that happens," Wolszczan said. "Europa is an icy wasteland and it is certainly not habitable now, but as the Sun continues to heat up and expand, our Earth will become too hot, while at the same time, Europa will melt and may spend a couple billion years in the Goldilocks zone -- not to hot, not to- old, covered by vast, beautiful oceans."

Penn State's Center for Exoplanets and Habitable Worlds is organizing a conference in January 2012 to discuss planets and their dying stars. The conference will be held in Puerto Rico and is scheduled to take place at exactly 20 years from when Wolszczan used the 1,000-foot Arecibo radiotelescope to detect three planets orbiting a rapidly spinning neutron star -- the very first discovery of planets outside our solar system. This discovery opened the door to the current intense era of planet hunting by suggesting that planet formation could be quite common throughout the universe and that planets can form around different types of stellar objects. More information about the conference is online.

In addition to Wolszczan and Gettel at Penn State, other members of the research team include Andrzej Niedzielski and Gracjan Maciejewski; and three graduate students, Grzegorz Nowak, Monika Adamów, and Pawel Zielinski, who are all from Nicolaus Copernicus University in Torun, Poland.

Funding for this research was provided by NASA and the Polish Ministry of Science and Higher Education.

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Planets smashed into dust near supermassive black holes

ScienceDaily (Oct. 28, 2011) — Fat doughnut-shaped dust shrouds that obscure about half of supermassive black holes could be the result of high speed crashes between planets and asteroids, according to a new theory from an international team of astronomers.

The scientists, led by Dr. Sergei Nayakshin of the University of Leicester, are publishing their results in the journal Monthly Notices of the Royal Astronomical Society.

Supermassive black holes reside in the central parts of most galaxies. Observations indicate that about 50% of them are hidden from view by mysterious clouds of dust, the origin of which is not completely understood. The new theory is inspired by our own Solar System, where the so-called zodiacal dust is known to originate from collisions between solid bodies such as asteroids and comets. The scientists propose that the central regions of galaxies contain not only black holes and stars but also planets and asteroids.

Collisions between these rocky objects would occur at colossal speeds as large as 1000 km per second, continuously shattering and fragmenting the objects, until eventually they end up as microscopic dust. Dr. Nayakshin points out that this harsh environment -- radiation and frequent collisions -- would make the planets orbiting supermassive black holes sterile, even before they are destroyed. "Too bad for life on these planets," he says, "but on the other hand the dust created in this way blocks much of the harmful radiation from reaching the rest of the host galaxy. This in turn may make it easier for life to prosper elsewhere in the rest of the central region of the galaxy."

He also believes that understanding the origin of the dust near black holes is important in our models of how these monsters grow and how exactly they affect their host galaxies. "We suspect that the supermassive black hole in our own Galaxy, the Milky Way, expelled most of the gas that would otherwise turn into more stars and planets," he continues, "Understanding the origin of the dust in the inner regions of galaxies would take us one step closer to solving the mystery of the supermassive black holes."

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Sergei Nayakshin, Sergey Sazonov, Rashid Sunyaev. Are SMBHs shrouded by 'super-Oort' clouds of comets and asteroids? Monthly Notices of the Royal Astronomical Society, 2011; (submitted) [link]

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New approach to overcome key hurdle for next-generation superconductors

ScienceDaily (Oct. 27, 2011) — Researchers from North Carolina State University have developed a new computational approach to improve the utility of superconductive materials for specific design applications -- and have used the approach to solve a key research obstacle for the next-generation superconductor material yttrium barium copper oxide (YBCO).

A superconductor is a material that can carry electricity without any loss -- none of the energy is dissipated as heat, for example. Superconductive materials are currently used in medical MRI technology, and are expected to play a prominent role in emerging power technologies, such as energy storage or high-efficiency wind turbines.

One problem facing systems engineers who want to design technologies that use superconductive materials is that they are required to design products based on the properties of existing materials. But NC State researchers are proposing an approach that would allow product designers to interact directly with the industry that creates superconductive materials -- such as wires -- to create superconductors that more precisely match the needs of the finished product.

"We are introducing the idea that wire manufacturers work with systems engineers earlier in the process, utilizing computer models to create better materials more quickly," says Dr. Justin Schwartz, lead author of a paper on the process and Kobe Steel Distinguished Professor and head of NC State's Department of Materials Science and Engineering. "This approach moves us closer to the ideal of having materials engineering become part of the product design process."

To demonstrate the utility of the process, researchers tackled a problem facing next-generation YBCO superconductors. YBCO conductors are promising because they are very strong and have a high superconducting current density -- meaning they can handle a large amount of electricity. But there are obstacles to their widespread use.

One of these key obstacles is how to handle "quench." Quench is when a superconductor suddenly loses its superconductivity. Superconductors are used to store large amounts of electricity in a magnetic field -- but a quench unleashes all of that stored energy. If the energy isn't managed properly, it will destroy the system -- which can be extremely expensive. "Basically, the better a material is as a superconductor, the more electricity it can handle, so it has a higher energy density, and that makes quench protection more important, because the material may release more energy when quenched," Schwartz says.

To address the problem, researchers explored seven different variables to determine how best to design YBCO conductors in order to optimize performance and minimize quench risk. For example, does increasing the thickness of the YBCO increase or decrease quench risk? As it turns out, it actually decreases quench risk. A number of other variables come into play as well, but the new approach was effective in helping researchers identify meaningful ways of addressing quench risk.

"The insight we've gained into YBCO quench behavior, and our new process for designing better materials, will likely accelerate the use of YBCO in areas ranging from new power applications to medical technologies -- or even the next iteration of particle accelerators," Schwartz says.

"This process is of particular interest given the White House's Materials Genome Initiative," Schwartz says. "The focus of that initiative is to expedite the process that translates new discoveries in materials science into commercial products -- and I think our process is an important step in that direction."

The paper was co-authored by Dr. Wan Kan Chan, a research associate at NC State. The paper is available online from IEEE Transactions on Applied Superconductivity. The research was funded by the Air Force Research Laboratory.

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Wan Kan Chan, Justin Schwartz. Three-Dimensional Micrometer-Scale Modeling of Quenching in High-Aspect-Ratio YBa2Cu3O7-d Coated Conductor Tapes -- Part II: Influence of Geometric and Material Properties and Implications for Conductor Engineering and Magnet Design. IEEE Transactions on Applied Superconductivity, 2011; DOI: 10.1109/TASC.2011.2169670

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Snakes with big hearts may help yours: Fatty acids involved in python heart growth could benefit diseased human heart

ScienceDaily (Oct. 27, 2011) — Identification of three fatty acids involved in the extreme growth of Burmese pythons' hearts following large meals could prove beneficial in treating diseased human hearts, according to research co-authored by a University of Alabama scientist and publishing in the Oct. 28 issue of Science.

Growth of the human heart can be beneficial when resulting from exercise -- a type of growth known as physiological cardiac hypertrophy -- but damaging when triggered by disease -- growth known as pathological hypertrophy. The new research shows a potential avenue by which to make the unhealthy heart growth more like the healthy version.

"We may later be able to turn the tables, in a sense, in the processes involved in pathological hypertrophy by administering a combination of fatty acids that occur in very high concentrations in the blood of digesting pythons," said Dr. Stephen Secor, associate professor of biological sciences at UA and one of the paper's co-authors. "This could trigger, perhaps, something more akin to the physiological form of hypertrophy."

The research, conducted in collaboration with multiple researchers at the University of Colorado working in the lab of Dr. Leslie Leinwand, identified three fatty acids, myristic acid, palmitic acid and palmitoleic acid, for their roles in the snakes' healthy heart growths following a meal.

Researchers took these fatty acids from feasting pythons and infused them into fasting pythons. Afterward, those fasting pythons underwent heart-rate growths similar to that of the feasting pythons. In a similar fashion, the researchers were able to induce comparable heart-rate growths in rats, indicating that the fatty acids have a similar effect on the mammalian heart.

The paper, whose lead author was Dr. Cecilia Riquelme of the University of Colorado, also showed that the pythons' heart growth was a result of the individual heart cells growing in size, rather than multiplying in number.

By studying gene expression in the python hearts -- which genes are turned on following feasting -- the research, Secor said, shows that the changes the pythons' hearts undergo is more like the positive changes seen in a marathon runner rather than the types of changes seen in a diseased, or genetically altered, heart.

"Cyclists, marathon runners, rowers, swimmers, they tend to have larger hearts," Secor said. "It's the heart working harder to move blood through it. The term is 'volume overload,' in reference to more blood being pumped to tissues. In response, the heart's chambers get larger, and more blood is pushed out with every contraction, resulting in increased cardiac performance."

However, the time-frame of this increased heart performance of a python blows away even the most physically-fit distance runner, Secor said.

"Instead of experiencing elevated cardiac performance for several hours with running, the Burmese python is maintaining heightened cardiac output for five to six days, non-stop, while digesting their large meal."

Another interesting finding of the research, Secor said, is even with the increased volume of triglycerides circulating in the snakes after feeding, those lipids are not remaining within the snakes' hearts or vascular systems after the completion of digestion.

"The python hearts are using the circulating lipids to fuel the increase in performance."

Traditionally, mice have been the preferred animal model used to study the genetic heart disease known as hypertrophic cardiomyopathy, characterized by heart growth and contractile dysfunction. However, the snakes' unusual physiological responses render them more insightful models, in some cases, Secor said.

Pythons are infrequent feeders, sometimes eating only once or twice a year in the wild. When they do eat, they undergo extreme physiologic and metabolic changes that include increases in the size of the heart, along with the liver, pancreas, small intestine and kidney. Three days after a feeding, a python's heart mass can increase as much as 40 percent, before reverting to its pre-meal size once digestion is completed, Secor said.

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Cecilia A. Riquelme, Jason A. Magida, Brooke C. Harrison, Christopher E. Wall, Thomas G. Marr, Stephen M. Secor, Leslie A. Leinwand. Fatty Acids Identified in the Burmese Python Promote Beneficial Cardiac Growth. Science, 2011; 334 (6055): 528-531 DOI: 10.1126/science.1210558

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Lower dose of corticosteroids just as effective as higher for shoulder pain, study finds

ScienceDaily (Oct. 27, 2011) — Although corticosteroid injections are one of the most common treatments for shoulder pain, there have been relatively few high-quality investigations of their efficacy and duration of action. In a study scheduled for publication in the December issue of the Archives of Physical Medicine and Rehabilitation, researchers report on the first comparative study of the two most commonly corticosteroid doses administered for shoulder pain. They found that lower doses were just as effective as higher doses in terms of reduction of pain, improved range of motion and duration of efficacy.

"There has been no guidance for adequate corticosteroid doses during subacromial injection. Physicians have depended mainly on their experience for the selection of dose," commented lead investigator Seung-Hyun Yoon, MD, PhD, Assistant Professor, Department of Physical Medicine and Rehabilitation, Ajou University School of Medicine, Suwon, Republic of Korea. "This is the first study to assess the efficacy of corticosteroid according to two different doses, which are the most widely used in subacromial injection for participants with periarticular shoulder disorders. Initial use of a low dose is encouraged because there was no difference in efficacy according to dose, and the effect of corticosteroid lasted up to 8 weeks."

Investigators conducted a randomized, triple-blind, placebo-controlled clinical trial in which 79 patients with at least one month's duration of pain were enrolled. Subjects were randomly assigned to three groups with 27 participants receiving a 40 mg dose of triamcinolone acetonide; 25 a 20 mg dose and 27 a placebo injection. All were followed up at 2, 4, and 8 weeks after treatment. All injections were performed using ultrasound guidance to insure proper placement of the therapeutic agent in the bursa.

Participants were asked to rate their degree of shoulder pain on a 0 to 10 scale and to answer a Shoulder Disability Questionnaire. They also were asked to move their shoulders slowly until they experienced pain, and evaluators measured the Active Range of Motion (AROM) in 4 different directions (forward flexion, abduction, internal rotation, and external rotation of the shoulder in a standing position).

Compared with pretreatment (within-group comparisons), the high- (40 mg) and low-dose corticosteroid (20 mg) groups both showed improvement in pain, disability, and AROM, while the placebo group showed no difference. Importantly, this study showed no significant inter-group differences between the high- and low-dose corticosteroid groups. Because a higher dose may increase the incidence of local and general complications, a lower dose is indicated at the initial treatment stage.

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The above story is reprinted from materials provided by Elsevier Health Sciences.

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Ji Yeon Hong, Seung-Hyun Yoon, Do Jun Moon, Kyu-Sung Kwack, Bohyun Joen, Hyun Young Lee. Comparison of High- and Low-Dose Corticosteroid in Subacromial Injection for Periarticular Shoulder Disorder: A Randomized, Triple-Blind, Placebo-Controlled Trial. Archives of Physical Medicine and Rehabilitation, December 2011; DOI: 10.1016/j.apmr.2011.06.033

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