articles related to science

7/31/2019 Articles Related to Science

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It Took Earth Ten Million Years to Recover fromGreatest Mass Extinction

ScienceDaily (May 27, 2012) It tooksome 10 million years for Earth torecover from the greatest massextinction of all time, latest research hasrevealed.

Life was nearly wiped out 250 million years ago,with only 10 per cent of plants and animalssurviving. It is currently much debated how liferecovered from this cataclysm, whether quickly orslowly.Recent evidence for a rapid bounce-back is evaluated in a new review article by Dr Zhong-Qiang Chen, from the China University of Geosciences in Wuhan, and Professor MichaelBenton from the University of Bristol. They find that recovery from the crisis lasted some 10million years, as explained May 27 in Nature Geoscience. There were apparently two reasons for the delay, the sheer intensity of the crisis, andcontinuing grim conditions on Earth after the first wave of extinction.The end-Permian crisis, by far the most dramatic biological crisis to affect life on Earth, wastriggered by a number of physical environmental shocks -- global warming, acid rain, oceanacidification and ocean anoxia. These were enough to kill off 90 per cent of living things onland and in the sea.Dr Chen said: "It is hard to imagine how so much of life could have been killed, but there isno doubt from some of the fantastic rock sections in China and elsewhere round the worldthat this was the biggest crisis ever faced by life."Current research shows that the grim conditions continued in bursts for some five to sixmillion years after the initial crisis, with repeated carbon and oxygen crises, warming andother ill effects.Some groups of animals on the sea and land did recover quickly and began to rebuild theirecosystems, but they suffered further setbacks. Life had not really recovered in these earlyphases because permanent ecosystems were not established.Professor Benton, Professor of Vertebrate Palaeontology at the University of Bristol, said:

"Life seemed to be getting back to normal when another crisis hit and set it back again. Thecarbon crises were repeated many times, and then finally conditions became normal againafter five million years or so."Finally, after the environmental crises ceased to be so severe, more complex ecosystemsemerged. In the sea, new groups, such as ancestral crabs and lobsters, as well as the firstmarine reptiles, came on the scene, and they formed the basis of future modern-styleecosystems.Professor Benton added: "We often see mass extinctions as entirely negative but in this mostdevastating case, life did recover, after many millions of years, and new groups emerged. Theevent had re-set evolution. However, the causes of the killing -- global warming, acid rain,ocean acidification -- sound eerily familiar to us today. Perhaps we can learn something from

these ancient events."


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It's in the Genes: Research Pinpoints How PlantsKnow When to Flower

ScienceDaily (May 26, 2012) Scientists believe they'vepinpointed the last crucial piece of the 80-year-old puzzle of howplants "know" when to flower.

Determining the proper time to flower,important if a plant is to reproducesuccessfully, involves a sequence of molecular events, a plant's circadian clock and sunlight.Understanding how flowering works in the simple plant used in this study -- Arabidopsis --should lead to a better understanding of how the same genes work in more complex plantsgrown as crops such as rice, wheat and barley, according to Takato Imaizumi, a University of Washington assistant professor of biology and corresponding author of a paper in the May 25issue of the journal Science ."If we can regulate the timing of flowering, we might be able to increase crop yield byaccelerating or delaying this. Knowing the mechanism gives us the tools to manipulate this,"Imaizumi said. Along with food crops, the work might also lead to higher yields of plantsgrown for biofuels.At specific times of year, flowering plants produce a protein known as FLOWERINGLOCUS T in their leaves that induces flowering. Once this protein is made, it travels from theleaves to the shoot apex, a part of the plant where cells are undifferentiated, meaning they caneither become leaves or flowers. At the shoot apex, this protein starts the molecular changesthat send cells on the path to becoming flowers.Changes in day length tell many organisms that the seasons are changing. It has long beenknown that plants use an internal time-keeping mechanism known as the circadian clock tomeasure changes in day length. Circadian clocks synchronize biological processes during 24-hour periods in people, animals, insects, plants and other organisms.Imaizumi and the paper's co-authors investigated what's called the FKF1 protein, which theysuspected was a key player in the mechanism by which plants recognize seasonal change and

know when to flower. FKF1 protein is a photoreceptor, meaning it is activated by sunlight."The FKF1 photoreceptor protein we've been working on is expressed in the late afternoonevery day, and is very tightly regulated by the plant's circadian clock," Imaizumi said. "Whenthis protein is expressed during days that are short, this protein cannot be activated, as there isno daylight in the late afternoon. When this protein is expressed during a longer day, thisphotoreceptor makes use of the light and activates the flowering mechanisms involvingFLOWERING LOCUS T. The circadian clock regulates the timing of the specificphotoreceptor for flowering. That is how plants sense differences in day length."This system keeps plants from flowering when it's a poor time to reproduce, such as the deadof winter when days are short and nights are long.The new findings come from work with the plant Arabidopsis, a small plant in the mustard

family that's often used in genetic research. They validate predictions from a mathematical


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model of the mechanism that causes Arabidopsis to flower that was developed by AndrewMillar, a University of Edinburgh professor of biology and co-author of the paper."Our mathematical model helped us to understand the operating principles of the plants' day-length sensor," Millar said. "Those principles will hold true in other plants, like rice, wherethe crop's day-length response is one of the factors that limits where farmers can obtain good

harvests. It's that same day-length response that needs controlled lighting for laying chickensand fish farms, so it's just as important to understand this response in animals."The proteins involved in animals are not yet so well understood as they are in plants but weexpect the same principles that we've learned from these studies to apply."First author on the paper is Young Hun Song, a postdoctoral researcher in Imaizumi's UWlab. The other co-authors are Benjamin To, who was a UW undergraduate student when thiswork was being conducted, and Robert Smith, a University of Edinburgh graduate student.The work was funded by the National Institutes of Health, and the United Kingdom'sBiotechnology and Biological Sciences Research Council.


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New Type of Male Contraceptive? Key Gene Essential forSperm Development Discovered

ScienceDaily (May 24, 2012) Anew type of male contraceptivecould be created thanks to thediscovery of a key gene essentialfor sperm development.

The finding could lead to alternatives tothe conventional male contraceptives thatrely on disrupting the production of hormones, such as testosterone. These

treatments can cause side-effects such as irritability, mood swings and acne.Research, led by the University of Edinburgh, has shown how a gene -- Katnal1 -- is criticalto enable sperm to mature in the testes.If scientists can regulate the Katnal1 gene in the testes, they could prevent sperm frommaturing completely, making them ineffective without changing hormone levels.The research, which is published in the journal PLoS Genetics , could also help in findingtreatments for cases of male infertility when malfunction of the Katnal1 gene hampers spermdevelopment.Dr Lee Smith, Reader in Genetic Endocrinology at the University of Edinburgh's Centre forReproductive Health, said: "If we can find a way to target this gene in the testes, we couldpotentially develop a non-hormonal contraceptive.

"The important thing is that the effects of such a drug would be reversible because Katnal1only affects sperm cells in the later stages of development, so it would not hinder the earlystages of sperm production and the overall ability to produce sperm."Although other research is being carried out into non-hormonal male contraceptives,identification of a gene that controls sperm production in the way Katnal1 does is a uniqueand significant step forward in our understanding of testis biology."Scientists found that male mice that were modified so they did not have the Katnal1 genewere infertile.Further investigation showed that this was because the gene was needed to allow the sperm todevelop and mature.The researchers showed that Katnal1 was needed to regulate the scaffolding structures knownas microtubules, which form part of the cells that support and provide nutrients to developingsperm.Breaking down and rebuilding these microtubules enables the sperm cells to move within thetestes as they mature. Katnal1 acts as the essential controller of this process.


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Asteroid Nudged by Sunlight: Most PreciseMeasurement of Yarkovsky Effect

ScienceDaily (May 24, 2012) Scientists onNASA's asteroid sample return mission,Origins, Spectral Interpretation, ResourceIdentification, Security, Regolith Explorer (OSIRIS-REx), have measured the orbit of their destination asteroid, 1999 RQ36, withsuch accuracy they were able to directlymeasure the drift resulting from a subtle butimportant force called the Yarkovsky effect --the slight push created when the asteroidabsorbs sunlight and re-emits that energy asheat.

"The new orbit for the half-kilometer (one-third mile) diameter 1999 RQ36 is the mostprecise asteroid orbit ever obtained," said OSIRIS-REx team member Steven Chesley of theNASA Jet Propulsion Laboratory, Pasadena, Calif. He presented the findings May 19 at theAsteroids, Comets and Meteors 2012 meeting in Niigata, Japan.Observations that Michael Nolan at Arecibo Observatory in Puerto Rico made in September2011, along with Arecibo and Goldstone radar observations made in 1999 and 2005, when1999 RQ36 passed much closer to Earth, show that the asteroid has deviated from its gravity-

ruled orbit by roughly 100 miles, or 160 kilometers, in the last 12 years, a deviation causedby the Yarkovsky effect.The Yarkovsky effect is named for the nineteenth-century Russian engineer who firstproposed the idea that a small rocky space object would, over long periods of time, benoticeably nudged in its orbit by the slight push created when it absorbs sunlight and then re-emits that energy as heat."The Yarkovsky force on 1999 RQ36 at its peak, when the asteroid is nearest the sun, is onlyabout a half ounce -- about the weight of three grapes on Earth. Meanwhile, the mass of theasteroid is estimated to be about 68 million tons. You need extremely precise measurementsover a fairly long time span to see something so slight acting on something so huge."Nolan and his team measured the distance between the Arecibo Observatory and 1999 RQ36

to an accuracy of 300 meters, or about a fifth of a mile, when the asteroid was 30 millionkilometers, or 20 million miles, from Earth."That's like measuring the distance between New York City and Los Angeles to an accuracyof two inches, and fine enough that we have to take the size of the asteroid and of AreciboObservatory into account when making the measurements," Nolan said.Chesley and his colleagues used the new Arecibo measurements to calculate a series of 1999RQ36 approaches closer to Earth than 7.5 million kilometers (4.6 million miles) from theyears 1654 to 2135. There turned out to be 11 such encounters.By combining the radar results from Arecibo Observatory with infrared results from NASA'sSpitzer Space Telescope, the scientists also learned that asteroid 1999 RQ36 is very light -- ithas around the same density as water, Chesley reported."This study is an important step in better understanding the Yarkovsky effect -- a subtle forcethat contributes to the orbital evolution of new Near-Earth Objects," said Dante Lauretta, the


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mission's principal investigator and professor of planetary science at the University of Arizona.Lauretta added that "this information is critical for assessing the likelihood of an impact fromour target asteroid and provides important constraints on its mass and density, allowing us tosubstantially improve our mission design."

The OSIRIS-REx spacecraft is to launch in 2016, reach asteroid (101955) 1999 RQ36 in2019, examine it up close during a 505-day rendezvous, then return at least 60 grams (~1.9ounces) of it to Earth in 2023."In addition to the exciting Yarkovsky results, the low density shows that 1999 RQ36 isprobably a loose aggregate of rocks--a so called rubble pile," said Jason Dworkin, themission's project scientist and Chief of Astrochemistry at NASA's Goddard Space FlightCenter in Greenbelt, Md. "This makes it an ideal target for OSIRIS-REx to collect loosesurface material."


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'Personality Genes' May Help Account for Longevity

ScienceDaily (May 24, 2012) "It's in their genes" is a common refrain from

scientists when asked about factors that allow centenarians to reach age 100and beyond. Up until now, research has focused on genetic variations thatoffer a physiological advantagesuch as high levels of HDL ("good")cholesterol. But researchers at

Albert Einstein College of Medicineand Ferkauf Graduate School of Psychology of Yeshiva Universityhave found that personality traits

like being outgoing, optimistic,easygoing, and enjoying laughter as well as staying engaged inactivities may also be part of thelongevity genes mix.

The findings, published online May 21 in the journal Aging , come from Einstein's Longevity GenesProject, which includes over 500 Ashkenazi Jews over the age of 95, and 700 of their offspring.Ashkenazi (Eastern European) Jews were selected because they are genetically homogeneous, makingit easier to spot genetic differences within the study population.

Previous studies have indicated that personality arises from underlying genetic mechanisms that maydirectly affect health. The present study of 243 of the centenarians (average age 97.6 years, 75 percentwomen) was aimed at detecting genetically-based personality characteristics by developing a brief measure (the Personality Outlook Profile Scale, or POPS) of personality in centenarians."When I started working with centenarians, I thought we'd find that they survived so long in partbecause they were mean and ornery," said Nir Barzilai, M.D., the Ingeborg and Ira Leon RennertChair of Aging Research, director of Einstein's Institute for Aging Research and co-correspondingauthor of the study. "But when we assessed the personalities of these 243 centenarians, we foundqualities that clearly reflect a positive attitude towards life. Most were outgoing, optimistic andeasygoing. They considered laughter an important part of life and had a large social network. Theyexpressed emotions openly rather than bottling them up." In addition, the centenarians had lowerscores for displaying neurotic personality and higher scores for being conscientious compared with arepresentative sample of the U.S. population."Some evidence indicates that personality can change between the ages of 70 and 100, so we don'tknow whether our centenarians have maintained their personality traits across their entire lifespans,"continued Dr. Barzilai. "Nevertheless, our findings suggest that centenarians share particularpersonality traits and that genetically-based aspects of personality may play an important role inachieving both good health and exceptional longevity."The study is titled "Positive attitude towards life and emotional expression as personality phenotypesfor centenarians." The POPS was developed by lead author Kaori Kato, Psy.D., now at Weill CornellMedical College, who validated it through comparisons with two previously established measures of personality traits. Other authors of the study were Richard Zweig, Ph.D., assistant clinical professor of

psychiatry and behavioral sciences at Einstein and director of the Older Adult Program at Ferkauf,and Gil Atzmon, Ph.D., assistant professor of medicine and of genetics at Einstein.


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Thousands of Invisibility Cloaks Trap a Rainbow

ScienceDaily (May 25, 2012)

Many people anticipating thecreation of an invisibility cloak mightbe surprised to learn that a group of

American researchers has created25,000 individual cloaks.

But before you rush to buy one from yourlocal shop, the cloaks are just 30 micrometresin diameter and are laid out together on a 25millimetre gold sheet.

This array of invisibility cloaks is the first of its kind and has been created by researchersfrom Towson University and University of Maryland who present their study on May 25,in the Institute of Physics and GermanPhysical Society's New Journal of Physics. Although the well-reported intention to makeeveryday objects disappear with a HarryPotter-style cloak is beyond this array of cloaks, they could be used to slow down, oreven stop, light, creating what is known as a"trapped rainbow."The trapped rainbow could be utilised in tinybiosensors to identify biological materialsbased on the amount of light they absorb andthen subsequently emit, which is known as fluorescence spectroscopy. Slowed-down lighthas a stronger interaction with molecules than light travelling at normal speeds, so it enablesa more detailed analysis.Lead author of the study, Dr Vera Smolyaninova, said: "The benefit of a biochip array is thatyou have a large number of small sensors, meaning you can perform many tests at once. Forexample, you could test for multiple genetic conditions in a person's DNA in just one go."In our array, light is stopped at the boundary of each of the cloaks, meaning we observe thetrapped rainbow at the edge of each cloak. This means we could do 'spectroscopy on-a-chip'and examine fluorescence at thousands of points all in one go."The 25 000 invisibility cloaks are uniformly laid out on a gold sheet, with each having amicrolens that bends light around itself, effectively hiding an area in its middle. As the lightsqueezes through the gaps between each of the cloaks, the different components of light, orcolours, are made to stop at ever narrower points, creating the rainbow.To construct the array of invisibility cloaks, a commercially available microlens array,containing all of the individual microlenses, was coated with a gold film. This was thenplaced, gold-side down, onto a glass slide which had also been coated with gold, creating adouble layer. A laser beam was directed into the array to test performance of the cloaks at

different angles.


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The researchers believe that this type of array could also be used to test the performance of individual invisibility cloaks, especially in instances where they may be positioned closetogether. In this study, for example, the cloaks worked very well when light was shone alongthe rows; however, when it was shown at different angles, imperfections were clearly visible.


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Organic Carbon from Mars, but Not Biological

ScienceDaily (May 24, 2012)

Molecules containing large chains of carbon and hydrogen--the buildingblocks of all life on Earth--have beenthe targets of missions to Mars fromViking to the present day. While thesemolecules have previously been foundin meteorites from Mars, scientistshave disagreed about how this organic

carbon was formed and whether or notit came from Mars.

A new paper led by Carnegie's Andrew Steele provides strong evidence that this carbon didoriginate on Mars, although it is not biological. These findings give researchers insight intothe chemical processes taking place on Mars and will help aid future quests for evidence of ancient or modern Martian life. The work is published May 24 in Science Express .There has been little agreement among scientists about the origin of the large carbonmacromolecules detected in Martian meteorites. Theories about their origin includecontamination from Earth or other meteorites, the results of chemical reactions on Mars, orthat they are the remnants of ancient Martian biological life.Steele's team examined samples from 11 Martian meteorites whose ages span about 4.2billion years of Martian history. They detected large carbon compounds in 10 of them. Themolecules were found inside of grains of crystallized minerals.Using an array of sophisticated research techniques, the team was able to show that at leastsome of the macromolecules of carbon were indigenous to the meteorites themselves and notcontamination from Earth. Next the team looked at the carbon molecules in relation to otherminerals in the meteorites to see what kinds of chemical processing these samples enduredbefore arriving on Earth. The crystalline grains encasing the carbon compounds provided awindow into how the carbon molecules were created. Their findings indicate that the carbonwas created during volcanism on Mars and show that Mars has been doing organic chemistryfor most of its history."These findings show that the storage of reduced carbon molecules on Mars occurredthroughout the planet's history and might have been similar to processes that occurred on theancient Earth," Steele said. "Understanding the genesis of these non-biological, carbon-containing macromolecules on Mars is crucial for developing future missions to detectevidence of life on our neighboring planet."In a separate paper published by American Mineralogist, available online, Steele and his teamstudied a meteorite called Allan Hills 84001 that was reported to contain relicts of ancientbiological life on Mars. The paper demonstrated that these supposed remnants could havebeen created by chemical reactions involving the graphite form of carbon, rather thanbiological processes. Both of these papers reveal a pool of reduced carbon on Mars and will

help scientist involved in future Mars missions distinguish these non-biologically formedmolecules from potential life.


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Device May Inject a Variety of Drugs Without Using Needles

ScienceDaily

(May 24, 2012) MITresearchers haveengineered a device thatdelivers a tiny, high-pressure jet of medicinethrough the skin without theuse of a hypodermic needle.The device can be programmed to deliver a range of doses to various

depths -- an improvement over similar jet-injection systems that are nowcommercially available.

The researchers say that among other benefits, the technology may help reduce the potentialfor needle-stick injuries; the Centers for Disease Control and Prevention estimates thathospital-based health care workers accidentally prick themselves with needles 385,000 timeseach year. A needleless device may also help improve compliance among patients who mightotherwise avoid the discomfort of regularly injecting themselves with drugs such as insulin."If you are afraid of needles and have to frequently self-inject, compliance can be an issue,"says Catherine Hogan, a research scientist in MIT's Department of Mechanical Engineeringand a member of the research team. "We think this kind of technology gets around someof the phobias that people may have about needles."The team reports on the development of this technology in the journal Medical Engineering& Physics .Pushing past the needle In the past few decades, scientists have developed various alternatives to hypodermic needles.For example, nicotine patches slowly release drugs through the skin. But these patches canonly release drug molecules small enough to pass through the skin's pores, limiting the typeof medicine that can be delivered.With the delivery of larger protein-based drugs on the rise, researchers have been developingnew technologies capable of delivering them -- including jet injectors, which produce a high-velocity jet of drugs that penetrate the skin. While there are several jet-based devices on themarket today, Hogan notes that there are drawbacks to these commercially available devices.The mechanisms they use, particularly in spring-loaded designs, are essentially "bang ornothing," releasing a coil that ejects the same amount of drug to the same depth every time.Breaching the skin Now the MIT team, led by Ian Hunter, the George N. Hatsopoulos Professor of MechanicalEngineering, has engineered a jet-injection system that delivers a range of doses to variabledepths in a highly controlled manner. The design is built around a mechanism called aLorentz-force actuator -- a small, powerful magnet surrounded by a coil of wire that'sattached to a piston inside a drug ampoule. When current is applied, it interacts with themagnetic field to produce a force that pushes the piston forward, ejecting the drug at very

high pressure and velocity (almost the speed of sound in air) out through the ampoule'snozzle -- an opening as wide as a mosquito's proboscis.


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The speed of the coil and the velocity imparted to the drug can be controlled by the amount of current applied; the MIT team generated pressure profiles that modulate the current. Theresulting waveforms generally consist of two distinct phases: an initial high-pressure phase inwhich the device ejects drug at a high-enough velocity to "breach" the skin and reach thedesired depth, then a lower-pressure phase where drug is delivered in a slower stream that can

easily be absorbed by the surrounding tissue.Through testing, the group found that various skin types may require different waveforms todeliver adequate volumes of drugs to the desired depth."If I'm breaching a baby's skin to deliver vaccine, I won't need as much pressure as I wouldneed to breach my skin," Hogan says. "We can tailor the pressure profile to be able to do that,and that's the beauty of this device."Samir Mitragotri, a professor of chemical engineering at the University of California at SantaBarbara, is developing new ways to deliver drugs, including via jet injection. Mitragotri, whowas not involved with the research, sees the group's technology as a promising step beyond

jet injection designs currently on the market."Commercially available jet injectors provide limited control, which limits their applications to certain drugs or patient populations," Mitragotri says. "[This] design providesexcellent control over jet parameters, including speed and doses this will enhance theapplicability of needleless drug devices."The team is also developing a version of the device for transdermal delivery of drugsordinarily found in powdered form by programming the device to vibrate, turning powderinto a "fluidized" form that can be delivered through the skin much like a liquid. Hunter saysthat such a powder-delivery vehicle may help solve what's known as the "cold-chain"problem: Vaccines delivered to developing countries need to be refrigerated if they are inliquid form. Often, coolers break down, spoiling whole batches of vaccines. Instead, Huntersays a vaccine that can be administered in powder form requires no cooling, avoiding thecold-chain problem.


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Like Curry? New Biological Role Identified for CompoundUsed in Ancient Medicine

ScienceDaily (May 25, 2012) Oregon State University scientists just identified a new reason whysome curry dishes, made withspices humans have used for thousands of years, might be goodfor you.

New research has discovered that curcumin,

a compound found in the cooking spiceturmeric, can cause a modest but measurableincrease in levels of a protein that's known to be important in the "innate" immune system,helping to prevent infection in humans and other animals.This cathelicidin antimicrobial peptide, or CAMP, is part of what helps our immune systemfight off various bacteria, viruses or fungi even though they hadn't been encountered before.Prior to this, it was known that CAMP levels were increased by vitamin D.Discovery of an alternative mechanism to influence or raise CAMP levels is of scientificinterest and could open new research avenues in nutrition and pharmacology, scientists said.Turmeric is a flavorful, orange-yellow spice and an important ingredient in many curries,commonly found in Indian, South Asian and Middle Eastern cuisine. It has also been used for

2,500 years as a medicinal compound in the Ayurvedic system of medicine in India -- not tomention being part of some religious and wedding ceremonies. In India, turmeric is treatedwith reverence.The newest findings were made by researchers in the Linus Pauling Institute at OSU andpublished in the Journal of Nutritional Biochemistry , in collaboration with scientists from theUniversity of Copenhagen in Denmark. The work was supported by the National Institutes of Health."This research points to a new avenue for regulating CAMP gene expression," said AdrianGombart, an associate professor of biochemistry and biophysics in the Linus PaulingInstitute. "It's interesting and somewhat surprising that curcumin can do that, and couldprovide another tool to develop medical therapies."The impact of curcumin in this role is not nearly as potent as that of vitamin D, Gombart said,but could nonetheless have physiologic value. Curcumin has also been studied for its anti-inflammatory and antioxidant properties."Curcumin, as part of turmeric, is generally consumed in the diet at fairly low levels,"Gombart said. "However, it's possible that sustained consumption over time may be healthyand help protect against infection, especially in the stomach and intestinal tract."In this study, Chunxiao Guo, a graduate student, and Gombart looked at the potential of bothcurcumin and omega-3 fatty acids to increase expression of the CAMP gene. They found noparticular value with the omega-3 fatty acids for this purpose, but curcumin did have a cleareffect. It caused levels of CAMP to almost triple.There has been intense scientific interest in the vitamin D receptor in recent years because of potential therapeutic benefits in treating infection, cancer, psoriasis and other diseases, the


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researchers noted in their report. An alternative way to elicit a related biological responsecould be significant and merits additional research, they said.The CAMP peptide is the only known antimicrobial peptide of its type in humans,researchers said. It appears to have the ability to kill a broad range of bacteria, includingthose that cause tuberculosis and protect against the development of sepsis.


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Structure of Human Protein Critical for Silencing Genes Solved

ScienceDaily (May 25, 2012) In a study published in the

journal Cell on May 24, ColdSpring Harbor Laboratory(CSHL) scientists describe thethree-dimensional atomicstructure of a human proteinbound to a piece of RNA that"guides" the protein's ability tosilence genes. The protein,

Argonaute-2, is a key player inRNA interference (RNAi), apowerful cellular phenomenonthat has important roles indiverse biological processes, including an organism's development.

"Detailed knowledge of the structure of human Argonaute-2 and the way it interacts with itsRNA guides will greatly improve our understanding of its biological mechanism of action,"says CSHL Professor and HHMI Investigator Leemor Joshua-Tor, Ph.D., the study's leader."Such precise structural information of the human Argonaute bound to an important RNA

guide could potentially aid both basic research to understand the function of genes and alsoadvance the development of RNAi as a therapeutic strategy in clinical settings."Upon the activation of a gene within a cell, the gene's DNA is copied into a messenger RNA(mRNA) "transcript." The instructions encoded within this transcript are then used as ablueprint by the cell's protein synthesis machinery to generate a working protein. The gene is"silenced" or prevented from giving rise to the protein, however, when an Argonaute-2protein that is bound to a small piece of "guide" RNA -- either a short-interfering RNA or amicroRNA -- intercepts the mRNA molecule. The guide RNA, whose nucleotide sequencematches that of the target mRNA, acts as a homing device that helps the Argonaute-2 proteinzero in on the mRNA target.A few years ago, Joshua-Tor collaborated with CSHL Professor and HHMI InvestigatorGregory Hannon, Ph.D., who is also a co-author in this study, to show that Argonauteproteins, which are made up of different domains or parts, act like a pair of molecular scissorsthat slice up target mRNAs, thus preventing proteins from being made and enforcing thesilencing of their genes. The discovery of the Argonautes' "slicer" activity stemmed in partfrom solving the crystal structure of an Argonaute protein from Pyrococcus furiosus, anarchebacterium that thrives in extremely high temperatures."But we still know nothing about the biological functions or mechanisms of action of archebacterial Argonautes," says Joshua-Tor. "We therefore next focused on solving thestructures of Argonautes from higher organisms such as mammals, in which Argonautefunctions and target recognition are well documented."Joshua-Tor's team and other research groups subsequently determined the atomic structuresof individual parts of Argonaute proteins from higher organisms. While these studies


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revealed several important details -- for example, the interaction between two parts of theArgonaute protein, called the PAZ and Mid domains, with the two ends of guide RNAs --Joshua-Tor's goal was to solve the structure of the entire human Argonaute protein incomplex with a single human guide RNA.Overcoming a complicated series of technical challenges, her team has achieved this goal by

analyzing the structure of a full-length human Argonaute-2 protein bound to a small RNAcalled miR-20a, which is known to play a role in cancer development. Although Argonautesfrom higher organisms diverged from their archebacterial cousins more than three billionyears ago, the team's analysis shows remarkable similarity between the two structures,especially in the regions that are important for target recognition and slicing activity."Our structure shows that the guide RNA, which is anchored at both ends by the PAZ andMid domains, kinks and twists its way through the structure of the entire protein, makingseveral points of contact within each domain and with the linker loops that join them,"explains Joshua-Tor. "The guide RNA thus acts like a backbone that rigidly locks togetherthe otherwise flexible Argonaute protein and gives it stability."The researchers speculate that the path threaded through the Argonaute by the guide RNAscould have evolved to maximize mutual stability, in turn making the protein-RNA complexeslong-lived. This long life is critical for many biological processes that are mediated byArgonautes. "This is also the kind of information that might help us to design better syntheticguide RNAs for therapeutic use," explains Joshua-Tor. "It will also be useful to researcherswho are trying to find more precise ways of blocking Argonaute activity."


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First Private Craft Docks with SpaceStation

High above northwestern Australia, a robotic arm on the International Space Stationgrabbed onto a cargo capsule floating 10 meters away.

With that penultimate act, the Space Exploration Technologies Corporation of Hawthorne,Calif., or SpaceX , made history as the first private company to send a craft, the Dragon, to thestation. The grab which NASA refers to as a grapple occurred at 9:56 a.m. Eastern time onFriday.It looks like weve got us a Dragon by the tail, said Donald R. Pettit , the NASA astronauton the station who was operating the robotic arm.Andre Kuipers , an European Space Agency astronaut, then took over the robotic arm to pullthe Dragon to a docking port on the station, locking it there just after noon. After the hatches

are opened on Saturday, the astronauts aboard the station will spend six days unloading thecargo brought up by the Dragon and replacing it with items to take back to Earth. The Dragonis to undock on Thursday and parachute into the Pacific Ocean off California.SpaceX launched the Dragon capsule on top of its Falcon 9 rocket on Tuesday. The companyand NASA spent several days conducting tests to check the Dragons operations. OnThursday, it flew 1.5 miles beneath the station to test its communication and navigationsystems.It passed those tests, then looped around the space station to begin its final approach. Bydesign, the approach was slow, with built-in pauses. As part of the testing process, the crewsent commands to the capsule to stop or temporarily move away, ensuring that Dragon couldbe safely sent off if something went badly awry.
http://www.spacex.com/http://www.spacex.com/http://www.spacex.com/http://www.jsc.nasa.gov/Bios/htmlbios/pettit.htmlhttp://www.jsc.nasa.gov/Bios/htmlbios/pettit.htmlhttp://www.jsc.nasa.gov/Bios/htmlbios/pettit.htmlhttp://www.esa.int/esaHS/ESAMWUZUMOC_astronauts_0.htmlhttp://www.esa.int/esaHS/ESAMWUZUMOC_astronauts_0.htmlhttp://www.esa.int/esaHS/ESAMWUZUMOC_astronauts_0.htmlhttp://www.jsc.nasa.gov/Bios/htmlbios/pettit.htmlhttp://www.spacex.com/


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SpaceX did run into some difficulties with Dragons navigation sensors, one that took thermal images and one that bounced laser pulses, and that delayed the capture by a couple of hours.This is, I think, going to be recognized as a si gnificantly historical step forward in spacetravel, SpaceXs chief executive, Elon Musk, said during a news conference. Hopefully the

first of many to come. Mr. Musks dreams are far grander than delivering cargo to the space station. Although hewould like to carry astronauts to the station in a few years, that would still be merelyretracing accomplishments that the American and Russian space programs achieved decadesago. Its evolutionary, not revolutionary, Mr. Musk agreed in an interview last mo nth.To accomplish Mr. Musks very long -term goal sending people to Mars , which he regardsas essential for ensuring the survival of humanity SpaceX must create new technologiesthat fundamentally change the current equation of space travel, in which most of the vehicleis thrown away each time.Mr. Musk talks of reusable rockets, but his first attempt to accomplish that recovering thefirst stage of the Falcon 9 via parachute failed. Twice, in 2010, SpaceX tried this method,but each time the rocket stage disintegrated as it fell. On this flight, SpaceX gave up trying.A new idea is for the engines to fire again after they drop off, and the rocket stages would flyback to land to be refueled. SpaceX plans to begin tests of this vertical takeoff and landingconcept, dubbed Grasshopper , this year.Mr. Musk also talks of building a giant rocket powered by next-generation engines using newfuels, bigger than the Falcon Heavy rocket he is hoping to launch within the next two years.Its going to be very big, he said. Very huge. Bigger than the Saturn V that launched NASA astronauts to the moon?Could be, he said with a smile. He said he would provide more details later this year or in2013.SpaceX has also consistently underestimated the time it would take to accomplish its tasks. In2006, when NASA selected it to develop the cargo ship, SpaceX said the first trip to thestation would take three years; it took six. SpaceX also has a large backlog of commercialsatellites it is under contract to launch.This track record may be relevant to Mr. Musks stated goal: he said he thought SpaceXcould send people to Mars in 15 years 20 years at most.In that prediction, he said he hoped he was not off by a factor of two. Ill be 80, he said.
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Dams Flow Limit Loosened to Feed

Grand Canyon

The Interior Department announced a plan on Wednesday to allow periodic increases inthe flow of Colorado River water through the Grand Canyon, alleviating theenvironmental disruption caused by the construction of the Glen Canyon Dam in Arizonain the 1960s.

The secretary of the interior, Ken Salazar, said the plan would allow t he rivers managers torelease excess water more than twice as much as average flows through and over thehydroelectric dam at will to help propel silt and sediment downstream into the canyon. Bymimicking the rivers original dynamics, Interior Department officials said, the flows couldhelp restore the backwater ecosystems in which native fish are most at home.

The goal is partly to enhance sandbars that create backwaters for an endangered fish,the humpback chub . The excess sand also nourishes beaches used by wildlife, hikers andrafters.Environmental groups like the Grand Canyon Trust strongly support the high-flow releases,which have been carried out experimentally three times before, most recently in 2008.In a telephone news conference, Mr. Salazar said the releases would be timed for whenstorms or snowmelt have carried large amounts of silt just downriver from the dam. The firsthigh-flow release under the new protocol will probably come this fall, he added.The triggering conditions are related to the amount of sediment in the system, he said.When heavy rains occur in the Paria River watershed, which drains rocky territory insouthwestern Utah, they frequently flush tons of silt into the Colorado, which the Paria meets

below the dam.
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The flexible flow plan will remain in effect through 2020. While normal flows through theturbines of the Glen Canyon Dam range from 8,000 to 22,500 cubic feet per second, the high-flow events could reach 45,000 cubic feet per second and last anywhere from one hour tofour days.At the highest flow, there is too much water to go through the hydroelectric turbines, and the

excess is funneled over the dam.Anne Castle, assistant interior secretary for water and science, said in the news conferencethat the delivery of power to the six million customers served by the dam would not besignificantly affected.The department also announced plans to change its management of nonnative trout in theriver. The agency has been killing nonnative trout, which crowd out the humpback chub, atsites along the Colorado. The practice brought protests from American Indian groups,including the Zuni tribe, for whom these areas are sacred, Interior Department officials said.The new plan, described as experimental, instead envisions live removal of the trout f orrestocking in other waters, Ms. Castle said. Were trying to understand better the impact of those changes on the nonnative fish that are being removed and on the endangered fish, shesaid.
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Computer Model Pinpoints Prime Materials forEfficient Carbon Capture

ScienceDaily (May 27, 2012) Whenpower plants begin capturing their carbon emissions to reducegreenhouse gases -- and to most inthe electric power industry, it's aquestion of when, not if -- it will be anexpensive undertaking.

Current technologies would use about one-third

of the energy generated by the plants -- what'scalled "parasitic energy" -- and, as a result,substantially drive up the price of electricity.But a new computer model developed byUniversity of California, Berkeley, chemistsshows that less expensive technologies are on the horizon. They will use new solid materialslike zeolites and metal oxide frameworks (MOFs) that more efficiently capture carbondioxide so that it can be sequestered underground."The current on-the-shelf process of carbon capture has problems, including environmentalones, if you do it on a large scale," said Berend Smit, Chancellor's Professor in thedepartments of chemical and biomolecular engineering and of chemistry at UC Berkeley anda faculty senior scientist in the Materials Sciences Division at Lawrence Berkeley NationalLaboratory (LBNL). "Our calculations show that we can reduce the parasitic energy costs of carbon capture by 30 percent with these types of materials, which should encourage theindustry and academics to look at them."Smit and his colleagues at UC Berkeley, LBNL, Rice University and the Electric PowerResearch Institute (EPRI) in Palo Alto, Calif., who will publish their results online May 27 inadvance of publication in the journal Nature Materials , already are integrating their databaseof materials into power plant design software."Our database of carbon capture materials is going to be coupled to a model of a full plantdesign, so if we have a new material, we can immediately see whether this material makessense for an actual design," Smit said.Guiding new materials research There are potentially millions of materialsthat can capture carbon dioxide, but it's physicallyand economically impossible for scientists and engineers to synthesize and test them all, Smitsaid. Now, a researcher can upload the structure of a proposed material to Smit's website, andthe new computer model will calculate whether it offers improved performance over theenergy consumption figures of today's best technology for removing carbon."What is unique about this model is that, for the first time, we are able to guide the directionfor materials research and say, 'here are the properties we want, even if we don't know whatthe ultimate material will look like,'" said Abhoyjit Bhown, a co-author of the study and atechnical executive at EPRI, which conducts research and development for the electric power

industry and the public. "Before, people were trying to figure out what materials they shouldshoot for, and that question was unanswered until now."


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Fossil fuel-burning power plants, in particular coal-burning units, are a major source of thecarbon dioxide that is rapidly warming the planet and altering the climate in ways that couldimpact crops and water supplies, raise sea level and lead to weather extremes. Even with themove toward alternative, sustainable and low-carbon sources of energy, ranging from solarand wind to hydrothermal, coal- and natural gas-burning power plants are being built at an

increasing rate around the world. At some point, Smit said, carbon capture will be the onlyway to reduce carbon emissions sufficiently to stave off the worst consequences of climatechange.Although no commercial power plants currently capture carbon dioxide on a large scale, afew small-scale and pilot plants do, using today's best technology: funneling emissionsthrough a bath of nitrogen-based amines, which grab carbon dioxide from the flue gases. Theamines are then boiled to release the CO 2. Additional energy is required to compress thecarbon dioxide so that it can be pumped underground.The energy needed for this process decreases the amount that can go into making electricity.Calculations show that for a coal-fired power plant, that could amount to approximately 30percent of total energy generated.Solid materials should be inherently more energy-efficient than amine scrubbing, because theCO 2 can be driven off at lower temperatures. But materials differ significantly in how tightlythey grab CO 2 and how easily they release it. The best process will be a balance between thetwo, Smit said.Smit and his UC Berkeley group worked with Bhown and EPRI scientists to establish thebest criteria for a good carbon capture material, focusing on the energy costs of capture,release and compression, and then developed a computer model to calculate this energyconsumption for any material. Smit then obtained a database of 4 million zeolite structurescompiled by Rice University scientists and ran the structures through his model. Zeolites areporous materials made of silicon dioxide, the same composition as quartz.The team also computed the energy efficiency of 10,000 MOF structures, which arecomposites of metals like iron with organic compounds that, together, form a porousstructure. That structure has been touted as a way to store hydrogen for fuel or to separategases during petroleum refining."The surprise was that we found many materials, some already known but othershypothetical, that could be synthesized" and work more energy efficiently than amines, Smitsaid. The best materials used 30 percent less energy than the amine process, though futurematerials may work even better. The computer model will work for structures other thanzeolites and MOFs, Smit said.Bhown said that the theoretically best material will probably have a parasitic energy cost of about 10 percent, so processes that use 20 percent or less are more attractive.

GPUs dramatically speed calculations Key to the team's success was using graphics processing units (GPUs) instead of standardcomputer central processing units (CPUs), GPUs reduced each structure's calculation, whichinvolves complex quantum chemistry, from 10 days to 2 seconds.Bhown noted that most people believe that some economic incentives or regulatoryframeworks are needed to implement carbon capture, and the EPRI's goal is to help theindustry identify the best technologies for doing so. A survey that EPRI conducted recentlysuggested that developing any new technology would take 10-15 years even with adequatefunding."The collaboration between different parts of the Department of Energy illustrates what canbe achieved if researchers working on the most fundamental aspects of carbon capture

collaborate with their industry counterparts" says Karma Sawyer, DOE program director.


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"This study shows how engineering and fundamental science can speed-up the process of discovery and implementation of promising materials ready to test in the field.""The hope is that there is a system set up such that, when someone comes up with apromising material, we can rapidly test it and get it to a readiness level pretty quickly," hesaid. "We are all excited by this work and look forward to pursuing it further."

Other coauthors of the study are graduate students Li-Chiang Lin and Joseph A. Swisher of UC Berkeley; Adam H. Berger of the EPRI; Richard L. Martin, Chris H. Rycroft and MaciejHaranczyk of LBNL's Computational Research Division; post-doctoral fellows Jihan Kimand Kuldeep Jariwala of LBNL's Materials Science Division; and Michael W. Deem of theDepartments of Bioengineering and Physics and Astronomy at Rice University.This work has been supported by the Department of Energy through National EnergyTechnology Laboratory, Advanced Research Projects Agency -- Energy (ARPA-E) andOffice of Science, and through EPRI's Office of Technology Innovation. Smit is also directorof the Department of Energy-funded Energy Frontier Research Center at UC Berkeley.


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Does Death Exist?

Many of us fear death. We believe in death because we have been told we will die. Weassociate ourselves with the body, and we know that bodies die. But a new scientific theorysuggests that death is not the terminal event we think.

Although individual bodies are destined to self- destruct, the I feeling is just a fountain of energy operating in the brain. But this energy doesnt just go away at death.

One well-known aspect of quantumphysics is that certain observations cannotbe predicted absolutely. Instead, there is a

range of possible observations each with adifferent probability. One mainstreamexplanation, the many -worldsinterpretation, states that each of thesepossible observations corresponds to adifferent universe (the multiverse). Anew scientific theory called biocentrism refines these ideas.There are an infinite number of universes,and everything that could possibly happenoccurs in some universe. Death does not

exist in any real sense in these scenarios. All possible universes exist simultaneously,regardless of what happens in any of them. Although individual bodies are destined to self-destruct, the alive feeling the Who am I? - is just a 20-watt fountain of energy operating inthe brain. But this energy doesn t go away at death. One of the surest axioms of science isthat energy never dies; it can neither be created nor destroyed. But does this energy transcendfrom one world to the other?Consider an experiment that was recently published in the journal Science showing thatscientists could retroactively change something that had happened in the past. Particles had todecide how to behave when they hit a beam splitter. Later on, the experimenter could turn asecond switch on or off. It turns out that what the observer decided at that point, determinedwhat the particle did in the past. Regardless of the choice you, the observer, make, it is you

who will experience the outcomes that will result. The linkages between these varioushistories and universes transcend our ordinary classical ideas of space and time. Think of the20-watts of energy as simply holo-projecting either this or that result onto a screen. Whetheryou turn the second beam splitter on or off, its still the same battery or agent responsible for the projection.According to Biocentrism, space and time are not the hard objects we think. Wave your handthrough the air if you take everything away, whats left? Nothing. The same thing appliesfor time. You cant see anything through the bone that surr ounds your brain. Everything yousee and experience right now is a whirl of information occurring in your mind. Space andtime are simply the tools for putting everything together.Death does not exist in a timeless, spaceless world. In the end, even Einst ein admitted, NowBesso (an old friend) has departed from this strange world a little ahead of me. That meansnothing. People like usknow that the distinction between past, present, and future is only a
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stubbornly persistent illusion. Immortality doesnt mean a perpetual existence in timewithout end, but rather resides outside of time altogether.This was clear with the death of my sister Christine. After viewing her body at the hospital, Iwent out to speak with family members. Christines husband Ed started to sobuncontrollably. For a few moments I felt like I was transcending the provincialism of time. I

thought about the 20-watts of energy, and about experiments that show a single particle canpass through two holes at the same time. I could not dismiss the conclusion: Christine wasboth alive and dead, outside of time.Christine had had a hard life. She had finally found a man that she loved very much. Myyounger sister couldnt make it to her wedding because she had a card game that had beenscheduled for several weeks. My mother also couldnt make the wedding due to an importantengagement she had at the Elks Club. The wedding was one of the most important days inChristines life. Since no one else from our side of the family showed, Christi ne asked me towalk her down the aisle to give her away.Soon after the wedding, Christine and Ed were driving to the dream house they had justbought when their car hit a patch of black ice. She was thrown from the car and landed in abanking of snow.Ed, she said I cant feel my leg. She never knew that her liver had been ripped in half and blood was rushing into herperitoneum.After the death of his son, Emerson wrote Our life is not so much threatened as our perception. I grieve that grief can tea ch me nothing, nor carry me one step into real nature. Whether its flipping the switch for the Science experiment, or turning the driving wheel everso slightly this way or that way on black- ice, its the 20 -watts of energy that will experiencethe result. In some cases the car will swerve off the road, but in other cases the car willcontinue on its way to my sisters dream house. Christine had recently lost 100 pounds, and Ed had bought her a surprise pair of diamondearrings. Its going to be hard to w ait, but I know Christine is going to look fabulous in themthe next time I see her.


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Powerful New Approach to Attack Flu Virus

ScienceDaily (May 27, 2012) An international research team hasmanufactured a new protein that can combat deadly flu epidemics.

The paper, featured on the cover of the current issue of Nature Biotechnology , demonstratesways to use manufactured genes as antivirals, which disable key functions of the flu virus,said Tim Whitehead, assistant professor of chemical engineering and materials science atMichigan State University."Our most potent design has proven effective on the vulnerable sites on many pandemicinfluenza viruses, including several H1N1 (Spanish flu, Swine flu) and H5N1 (Avian flu)subtypes," said Whitehead, the paper's co-lead author. "These new therapeutics are urgentlyneeded, so we were especially pleased to see that it neutralizes H1N1 viruses with potency."From its earlier research, the team used computer-aided design to engineer proteins thattargeted vulnerable sites on the highly adaptable virus. From there, researchers optimizedtheir designer proteins by comprehensively mapping the mutations that gave the proteins astrong advantage when attacking the viruses' targeted areas.The team improved its proteins through a process called "DNA deep sequencing." Thisallowed Whitehead and his colleagues to simultaneously sequence millions of variants of their manufactured proteins, identify and keep the beneficial mutations and optimize theproteins' performance."By taking only the best mutations, we can reprogram our proteins to burrow into viruses atkey locations and render them harmless," he said. "Our work demonstrates a new approach toconstruct therapeutic proteins, which we hope will spur development of new protein drugs by

the biopharmaceutical industry."This research also laid the groundwork for future treatments of all flu viruses as well as otherdiseases such as smallpox, Whitehead added.Whitehead's co-authors included researchers from the University of Washington, the ScrippsResearch Institute (La Jolla, Calif.), Naval Health Research Center (San Diego) and theWeizmann Institute of Science (Rehovot, Israel).The research was funded by Defense Research Projects Agency, the Defense ThreatReduction Agency, the National Institutes of Health, the National Institute of Allergy andInfectious Diseases and the National Institute of General Medical Sciences.


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Super-Sensitive Tests Could Detect Diseases Earlier

ScienceDaily (May 27, 2012) Scientists have developed an ultra-sensitive test that should enable them to detect signs of a disease in its

earliest stages, in research published May 27in the journal Nature Materials.

The scientists, from Imperial College London and the University of Vigo, have created a testto detect particular molecules that indicate the presence of disease, even when these are invery low concentrations. There are already tests available for some diseases that look for suchbiomarkers using biological sensors or 'biosensors'. However, existing biosensors becomeless sensitive and predictable at detecting biomarkers when they are in very lowconcentrations, as occurs when a disease is in its early stages.In the new study, the researchers demonstrated that the new biosensor test can find abiomarker associated with prostate cancer, called Prostate Specific Antigen (PSA). However,the team say that the biosensor can be easily reconfigured to test for other diseases or viruseswhere the related biomarker is known.Professor Molly Stevens, senior author of the study from the Departments of Materials andBioengineering at Imperial College London, said: "It is vital to detect diseases at an earlystage if we want people to have the best possible outcomes -- diseases are usually easier totreat at this stage, and early diagnosis can give us the chance to halt a disease beforesymptoms worsen. However, for many diseases, using current technology to look for earlysigns of disease can be like finding the proverbial needle in a haystack. Our new test canactually find that needle. We only looked at the biomarker for one disease in this study, butwe're confident that the test can be adapted to identify many other diseases at an early stage."The team demonstrated the effectiveness of their biosensor by testing PSA biomarkersamples in solutions containing a complex mixture of blood derived serum proteins.Monitoring the levels of PSA at ultralow concentrations can be crucial in the early diagnosisof the reoccurrence of prostate cancer, but classic detection approaches are not sensitiveenough to carry out this analysis with a high degree of accuracy. The new test could enablemore reliable diagnosis, but more research will need to be done to further explore itspotential.In their study, the team detected PSA at 0.000000000000000001 grams per millilitre, whichis at the limits of current biosensor performance. By comparison, an existing test called anEnzyme-Linked Immunosorbent Assay (ELISA) test can detect PSA at 0.000000001 gramsper millilitre, which is nine orders of magnitude more concentrated.

The biosensors used in the new study consist of nanoscopic-sized gold stars floating in asolution containing other blood derived proteins. Attached to the surface of these gold starsare antibodies, which latch onto PSA when they detect it in a sample. A secondary antibody,which has an enzyme called glucose oxidase attached to it, recognises the PSA and creates adistinctive silver crystal coating on the gold stars, which is more apparent when the PSAbiomarkers are in low concentrations. This silver coating acts like a signal that PSA ispresent, and it can be easily detected by scientists using optical microscopes.The next stage of the research will see the team carrying out further clinical testing to assessthe efficacy of the biosensor in detecting a range of different biomarkers associated withconditions such as HIV and other infections. They will also explore ways of commercialisingtheir product.

This research was funded by the European Research Council and via a Marie Curiefellowship.


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Disease That Stunts Infants' Growth Traced to Same Gene ThatMakes Kids Grow Too Fast

ScienceDaily (May 27, 2012) UCLA geneticists have identified the

mutation responsible for IMAGe syndrome, a rare disorder that stuntsinfants' growth. The twist? The mutation occurs on the same gene thatcauses Beckwith-Wiedemann syndrome, which makes cells grow too fast,leading to very large children.

Published in the May 27 edition of Nature Genetics , the UCLA findings could lead to newways of blocking the rapid cell division that allows tumors to grow unchecked. The discoveryalso offers a new tool for diagnosing children with IMAGe syndrome, which until now hasbeen difficult to accurately identify.The discovery holds special significance for principal investigator Dr. Eric Vilain, a professor

of human genetics, pediatrics and urology at the David Geffen School of Medicine at UCLA.Nearly 20 years ago, as a medical resident in his native France, Vilain cared for two boys,ages 3 and 6, who were dramatically short for their ages. Though unrelated, both childrenshared a mysterious malady marked by minimal fetal development, stunted bone growth,sluggish adrenal glands, and undersized organs and genitals."I never found a reason to explain these patients' unusual set of symptoms," explained Vilain,who is also director of the UCLA Institute for Society and Genetics. "I've been searching forthe cause of their disease since 1993."When Vilain joined UCLA as a genetics fellow, the two cases continued to intrigue him. Hismentor, then UCLA geneticist Dr. Edward McCabe, recalled a similar case from his previouspost at Baylor College of Medicine. The two of them obtained blood samples from the three

cases and analyzed the patients' DNA for mutations in suspect genes, but uncovered nothing.Vilain and McCabe approached the Journal of Clinical Endocrinology and Metabolism , andin 1999 published the first description of the syndrome, which they dubbed IMAGe, anacronym of sorts for the condition's symptoms: intrauterine growth restriction, metaphysealdysplasia, adrenal hypoplasia and genital anomalies.Over the next decade, about 20 cases were reported around the world. But the cause of IMAGe syndrome remained a mystery.Help arrived unexpectedly last year when Vilain received an email from Argentinianphysician Dr. Ignacio Bergada, who had unearthed the 1999 journal article. He told Vilainabout a large family he was treating in which eight members suffered the same symptomsdescribed in the study. All of the family members agreed to send their DNA samples toUCLA for study.Vilain realized that he had stumbled across the scientific equivalent of winning the lottery.He assembled a team of UCLA researchers to partner with Bergada and Londonendocrinologist Dr. John Achermann."At last we had enough samples to help us zero in on the gene responsible for the syndrome,"Vilain said. "Sequencing technology had also advanced in sophistication over the past twodecades, allowing us to quickly analyze the entire family's DNA samples."Vilain's team performed a linkage study, which identifies disease-related genetic markerspassed down from one generation to another. The results steered Vilain to a huge swath of Chromosome 11.The UCLA Center for Clinical Genomics performed next-generation sequencing, a powerfulnew technique that enabled the scientists to scour the enormous area in just two weeks and


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tease out a slender stretch that held the culprit mutation. The team also uncovered the samemutation in the original three cases described by Vilain in 1999.A word of explanation: Located on 23 pairs of chromosomes, human genes hold the codes formaking cellular proteins, the building blocks for our bodies. Most of the human diseasesresulting from mutations in a single gene can be blamed on changes in a protein-coding

sequence. By scanning the entire exome, or protein-coding factory of the genome, clinicalgeneticists can interpret every gene variant to track down the mutations that produce apatient's disease and rapidly reach a clear-cut diagnosis."We discovered a mutation in a tiny sliver of the chromosome that appeared in every familymember affected by IMAGe syndrome," said Vilain. "This was a big step forward. Now wecan use gene sequencing as a tool to screen for the disease and diagnose children earlyenough for them to benefit from medical intervention."We were a little surprised, because the mutation was located on a famous gene recognizedfor causing Beckwith-Wiedemann syndrome," he added. "The two diseases are polaropposites of each other."Children born with Beckwith-Wiedemann syndrome -- named for the two doctors whodiscovered it -- grow very large with big adrenal glands, elongated bones and oversizedinternal organs. Because their cells grow so fast, children with the disorder typically die of cancer at a young age. The disease affects one in 15,000 births."Finding opposite functions in the same gene is a rare biological phenomenon" emphasizedVilain. "When the mutation appeared in the slim section we identified, the infant developedIMAGe syndrome. If the mutation fell anywhere else in the gene, the child was born withBeckwith-Wiedemann. That's really quite remarkable."IMAGe syndrome patients also tend to die young due to poor adrenal activity, whichphysicians treat with hormone-replacement therapy.The findings proved that Vilain and his colleagues had identified the correct mutation,bringing his 20-year odyssey to a successful end."Our findings leave no doubt that this set of symptoms is a true syndrome and not just afigment of my imagination," said Vilain."What makes this special for me is finally being able to unravel what caused the life-threatening disease in the two patients I saw nearly 20 years ago," he added. "As a clinicalscientist, the reward for successful research is uncovering new clues that allow us to helppatients feel better by improving their medical care."The IMAGe mutation's ability to miniaturize organisms and halt growth could offerintriguing clinical benefits, he noted."Our next effort will focus on manipulating the mutation's strong influence on growth toshrink tumors in the adrenal glands and other internal organs," explained Vilain.

Vilain's coauthors included first author Valerie Arboleda, Hane Lee, Alice Fleming, Abhik Banerjee, Emmanuele Delot, Imilce Rodriguez-Fernandez, Esteban Dell'Angelica, StanleyNelson and Julian Martinez-Agosto, all of UCLA; Bruno Ferraz-de-Souza of University of San Paulo in Brazil; Bergada of Hospital de Ninos Ricardo Gutierrez, Argentina; andAchermann of University College London Institute of Child Health.The study was funded by the Doris Duke Charitable Foundation, Wellcome Trust andNational Institute of Child Health and Human Development (grants RO1HD068 and1F31HD068136).


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Garlic Constituent Blocks Biofilm Formation, Could BenefitCystic Fibrosis Patients and Others

ScienceDaily (May 27, 2012) E Pluribus Unum , th e de facto motto of the

United States, could just as well apply to biofilm-forming bacteria. Bacterialbiofilms are far more resistant than individual bacteria to the armories of antibiotics we have devised to combat them. Now Tim Holm Jakobsen andMichael Givskov of the University of Copenhagen, and their manycollaborators have pinpointed a constituent of garlic that attacks a key stepin the development of biofilms, in an effort they hope may offer help inparticular for patients with cystic fibrosis.

The research is published in the May 2012 issue of Antimicrobial Agents and Chemotherapy .In earlier work, Givskov and his colleagues showed that "crude extracts of garlic inhibit the

expression of a large number of genes that are controlled by bacterial quorum sensing[communication among bacterial cells involved in biofilm development], and that extractspromote a rapid clearing of pulmonary Pseudomonas aeruginosa infection in mice," he says."These findings encouraged us to identify and assess the efficacy of the pure activecompound."That compound turned out to be ajoene, the major constituent of a multitude of sulfur-containing compounds produced when garlic is crushed, says Jakobsen. The team thenshowed in P. aeruginosa that ajoene inhibits expression of 11 genes that are controlled byquorum sensing. "These key genes are regarded as crucial for the ability of P. aeruginosa tocause disease," he says."We also found ajoene to reduce the production of rhamnolipid, a compound that shields thebiofilm bacteria from the white blood cells that otherwise would destroy bacteria, and that bycombining ajoene with the antibiotic tobramycin, it was possible to kill over 90 percent of bacteria living in a biofilm," says Jakobsen."Our study is part of a series of comprehensive investigations of natural compounds targetingbacterial quorum sensing systems, and it further strengthens previous proof of conceptresearch we conducted on the potential of compounds which block communication amongpathogen cells in contrast to simply killing bacteria, as conventional antibiotics do," saysJakobsen. Such alternative approaches "may postpone or minimize development of antibioticresistance," he adds.Jakobsen says the garlic project grew out of a major donation from the German CysticFibrosis Association. "In CF patients, P. aeruginosa infection leads to bronchieciasis,pulmonary fibrosis, respiratory failure, and death," he says. "Despite intensive antibiotictraatment, CF patients have a life expectancy of about 40 years, and the main cause of deathin CF patients remains complications associated with [this infection]." Jakobsen's team andthe German CF Association have patented the action of ajoene against biofilms, and areseeking a pharmacutical partner to develop antimicrobial drugs based on ajoene.Jakobsen notes that garlic has been used medicinally "for thousands of years." Garlic not onlyhas antibacterial properties; it has anti-viral, anti-fungal, and anti-protozoal properties as well,and it has beneficial effects on the cardiovascular and immune systems, as well, he says.


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New Prostate Cancer Screening Guidelines Face a ToughSell, Study Suggests

ScienceDaily (May 26, 2012) Recent recommendations from the U.S.Preventive Services Task Force (USPSTF) advising elimination of routineprostate-specific antigen (PSA) screening for prostate cancer in healthymen are likely to encounter serious pushback from primary care physicians,according to results of a survey by Johns Hopkins investigators.

In a survey of 125 primary care doctors, the researchers found that while doctors agreed witholder recommendations to curtail routine screening in men over age 75 and among those notexpected to live 10 or more years, a large number said they faced significant barriers tostopping PSA testing in men who had been receiving it regularly. The most frequently citedreason by 74.4 percent of physicians was, "My patients expect me to continue getting yearly

PSA tests," followed by 66 percent of them who said, "It takes more time to explain why I'mnot screening than to just continue screening." More than half of those surveyed in the newstudy believed that, "By not ordering a PSA, it puts me at risk for malpractice."The survey was conducted in November 2011, right after draft recommendations were madeto end routine screening of all men, but before last week, when the draft recommendationswere officially approved."It can be very difficult for doctors to break down the belief that all cancer screening tests areinvariably good for all people all the time," says Craig E. Pollack, M.D., M.H.S., an assistantprofessor in the Division of General Internal Medicine at the Johns Hopkins UniversitySchool of Medicine, and leader of the study published online in the

journal Cancer. "Everyone agrees that PSA screening isn't as good as we want it to be. If wehad a test that was a slam dunk, it would be different. But now we know that for many men,the benefits may be small and the harms significant."Each year, more than 33,000 American men die of prostate cancer, and 20 million get thePSA test to detect the disease early.According to the USPSTF, evidence suggests the potential harms caused by PSA screening of healthy men as a means of identifying prostate cancer outweigh its potential to save lives andthat routine annual screening should be eliminated in the healthy. Elevated PSA readings arenot necessarily evidence of prostate cancer, and can lead to unnecessary prostate biopsy. Inaddition, even when biopsies reveal signs of prostate cancer cells, evidence shows that a largeproportion will never cause harm, even if left untreated. The disease in older men oftenprogresses slowly so that those who have it frequently die of other causes.Treatments for prostate cancer can include the removal of the prostate, radiation or othertherapies, each of which has the potential to cause serious problems like erectile dysfunction,complete impotence, urinary incontinence or bowel damage. And men who choose to "watchand wait" after elevated PSA readings must live with the anxiety of knowing they have anuntreated cancer that could start to progress.In the new study, Pollack and his colleagues found that while most physicians said they took age and life expectancy into account when deciding to order PSA screening, many also saidthey had a hard time estimating life expectancy in their patients and could use a better tool.H. Ballentine Carter, M.D., a professor of urology at Johns Hopkins and the seniorinvestigator on the study, is planning to investigate the potential of individualized prostate

cancer screening recommendations. Specifically, he and colleagues plan to create a decision-


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making tool that incorporates age, life expectancy, family history and prior PSA results inorder to help doctors and their patients make better choices for prostate cancer screening.In another report derived from results of Pollack's and Carter's survey, published in April inthe Archives of Internal Medicine, the researchers say nearly half of the providers agreedwith the new USPSTF recommendations to eliminate routine screening for healthy men. Still,

less than two percent said they would no longer order routine PSA screening in response tothe draft recommendations; 21.9 percent said they would be much less likely to do so; 38.6percent said they would be somewhat less likely to do so; and 37.7 percent said they wouldnot change their screening practices."Men often expect PSA screening to be part of their annual physical," Pollack says. "Tochange their minds, we need to address their perceptions about screening, allow time forscreening discussions and reduce concerns regarding malpractice litigation."The studies were supported in part by a Maryland Cigarette Restitution Fund Research Grantto Johns Hopkins.Other Johns Hopkins researchers involved with the studies included Elizabeth A. Platz,Sc.D., M.P.H.; Nrupen A. Bhavsar, Ph.D., M.P.H.; Gary Noronha, M.D.; Gene E. Green,M.D.; and Sean Chen, B.A.


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Tongue Analysis Software Uses Ancient ChineseMedicine to Warn of Disease

ScienceDaily (May 26, 2012) For 5,000 years, the Chinese have used asystem of medicine based on the flow and balance of positive and negativeenergies in the body. In this system, the appearance of the tongue is one of the measures used to classify the overall physical status of the body,or zheng . Now, University of Missouri researchers have developedcomputer software that combines the ancient practices and modernmedicine by providing an automated system for analyzing images of thetongue.

"Knowing your zheng classification can serve as a pre-screening tool and help withpreventive medicine," said Dong Xu, chair of MU's computer science department in theCollege of Engineering and study co-author. "Our software helps bridge Eastern and Westernmedicine, since an imbalance in zheng could serve as a warning to go see a doctor. Within ayear, our ultimate goal is to create an application for smartphones that will allow anyone totake a photo of their tongue and learn the status of their zheng ."The software analyzes images based on the tongue's color and coating to distinguish betweentongues showing signs of "hot" or "cold" zheng . Shades of red and yellow are associated withhot zheng , whereas a white coating on the tongue is a sign of cold zheng ."Hot and cold zheng doesn't refer directly to body temperature," said Xu, who is also on thefaculty of the Bond Life Sciences Center. "Rather, it refers to a suite of symptoms associatedwith the state of the body as a whole."For example, a person with cold zheng may feel chills and coolness in the limbs and show apale flushing of face. Their voice may have a high pitch. Other symptoms of cold sheng areclear urine and loose stool. They also may prefer hot foods and drinks and desire warmenvironments.In Chinese traditional medicine both hot and cold zheng can be symptoms of gastritis, aninflammation of the stomach lining frequently caused by bacterial infection.For the study, 263 gastritis patients and 48 healthy volunteers had their tongues analyzed. Thegastritis patients were classified by whether they showed infection by a certain bacteria,known as Helicobacter pylori , as well as the intensity of their gastritis symptoms. In addition,most of the gastritis patients had been previously classified with either hot or cold zheng . Thisallowed the researchers to verify the accuracy of the software's analysis."Our software was able to classify people based on their zheng status," said study co-authorYe Duan, associate professor of computer science at MU."As we continue to work on the software we hope to improve its ability," Duan said."Eventually everyone will be able to use this tool at home using webcams or smartphoneapplications. That will allow them to monitor their zheng and get an early warning aboutpossible ailments."The study "Automated Tongue Feature Extraction for ZHENG Classification in TraditionalChinese Medicine" was accepted for publication in the journal Evidence Based Complementary and Alternative Medicine. The study's first author was doctoral student

Ratchadaporn Kanawong and the second author was post-doctoral researcher Tayo Obafemi-Ajayi.


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Why More Parasite Diversity isGood News for Frogs

The enemy of my enemy is my friend especially if Im afrog and my enemies are competing parasites. A recen tstudy in PNAS found that frogs populations exposedto a more diverse set of flukes actually had lower rates of infection, with fewer frogs in the group afflicted with tiny hitchhikers.Researchers at the University of Colorado-Boulder bredPacific chorus frogs in a lab and put their tadpoles indifferent tanks with anywhere from one to six different

types of flukes. On average, 40% of the frogs that came intocontact with only a single fluke species developedinfections, while 34% of frogs exposed to four flukes and23% of frogs exposed to six flukes were infected (thenumbers for two, three flukes followed a roughly similartrend). Additionally, some of the fluke species make frogssicker than others, and oddly enough, the frogs exposed to agreater variety of flukes had a lower proportion of infectionsfrom these dangerous species.Most research on host-parasite interactions has focused onehost one parasite, but as this study shows, its a lot morecomplicated in the natural world. Preserving biodiversity even biodiversity of creatures, whether flukes or microbes,that were not fond of might be an important part of keeping disease down. Why that is isnt exactly clear the scientists who did this study, forinstance, arent sure why frogs were better off with lots of flukes around. But it could be analogous to what happens in humans who have the biodiversity of their gutmicrobes disturbed by antibiotics. Once healthy, or at least relatively harmless, microbes are wiped out, its easy for dangerous bacteria like C. difficile to take over their real estateand cause life-threatening disease. Something similar seems to happen with viruses: havingcertain viruses in your body can keep you from getting infected by other, more harmfulpathogens.In fighting off infections, thus, it could help to have allies among the enemy.
http://blogs.discovermagazine.com/80beats/2012/05/24/why-more-parasite-diversity-is-good-news-for-frogs/http://blogs.discovermagazine.com/80beats/2012/05/24/why-more-parasite-diversity-is-good-news-for-frogs/http://blogs.discovermagazine.com/80beats/2012/05/24/why-more-parasite-diversity-is-good-news-for-frogs/http://www.pnas.org/content/early/2012/05/16/1201790109.full.pdf+html?with-ds=yeshttp://en.wikipedia.org/wiki/Trematodahttp://en.wikipedia.org/wiki/Clostridium_difficilehttp://en.wikipedia.org/wiki/Clostridium_difficilehttp://blogs.discovermagazine.com/80beats/2012/03/20/gut-infections-are-killing-the-elderly-at-frightening-rates/http://blogs.discovermagazine.com/crux/2011/11/01/viral-infections-might-be-our-best-hope-against-aids-other-confounding-diseases/#more-209http://blogs.discovermagazine.com/crux/2011/11/01/viral-infections-might-be-our-best-hope-against-aids-other-confounding-diseases/#more-209http://blogs.discovermagazine.com/crux/2011/11/01/viral-infections-might-be-our-best-hope-against-aids-other-confounding-diseases/#more-209http://blogs.discovermagazine.com/crux/2011/11/01/viral-infections-might-be-our-best-hope-against-aids-other-confounding-diseases/#more-209http://blogs.discovermagazine.com/crux/2011/11/01/viral-infections-might-be-our-best-hope-against-aids-other-confounding-diseases/#more-209http://blogs.discovermagazine.com/crux/2011/11/01/viral-infections-might-be-our-best-hope-against-aids-other-confounding-diseases/#more-209http://blogs.discovermagazine.com/80beats/2012/03/20/gut-infections-are-killing-the-elderly-at-frightening-rates/http://en.wikipedia.org/wiki/Clostridium_difficilehttp://en.wikipedia.org/wiki/Trematodahttp://www.pnas.org/content/early/2012/05/16/1201790109.full.pdf+html?with-

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