Pebbles and sand on Mars best evidence that a river ran through it (Science)

Pebble-rich rock slabs have been observed on Mars, suggesting the presence of an ancient stream bed (Source: Science)

By Morgan Kelly, Office of Communications

Pebbles and sand scattered near an ancient Martian river network may present the most convincing evidence yet that the frigid deserts of the Red Planet were once a habitable environment traversed by flowing water.

Scientists with NASA’s Mars Science Laboratory mission reported May 30 in the journal Science the discovery of sand grains and small stones that bear the telltale roundness of river stones and are too heavy to have been moved by wind. The researchers estimated that the sediment was produced by water that moved at a speed between that of a small stream and a large river, and had a depth of roughly an inch to nearly 3 feet.

Co-author Kevin Lewis, a Princeton associate research scholar in geosciences and a participating scientist on the Mars mission, said that the rocks and sand are among the best evidence so far that water once flowed on Mars, and suggest that the planet’s past climate was wildly different from what it is today.

“This is one of the best pieces of evidence we’ve seen on the ground for flowing water,” Lewis said. “The shape of these rocks and sand is exactly the same kind of thing you’d see if you went out to any streambed. It suggests a very similar environment to the Earth’s.”

The researchers analyzed sediment taken from a Martian plain that abuts a sedimentary deposit known as an alluvial fan. Alluvial fans are comprised of sediment leftover when a river spreads out over a plain then dries up, and are common on Earth in arid regions such as Death Valley.

Yet Death Valley is a refreshing spring compared to Mars today, Lewis said. Satellite images taken in preparation for the 2012 landing of NASA’s Curiosity Mars rover had revealed ancient river channels carved into the land on and around Mount Sharp, a 3.5-mile high mound similar in size to Alaska’s Mt. McKinley that would become the rover’s landing site. A major objective of the Curiosity mission is to explore Mars’ past habitability.

Nonetheless, liquid water itself is most likely rare on Mars’ currently cold and dusty landscape where wind is the dominant force. Lewis was co-author on a paper in the May 2013 edition of the journal Geology that suggested that Mount Sharp, thought to be the remnant of a massive lake, is most likely a giant dust pile produced by Mars’ violent, swirling winds.

Strong as it might be, however, wind cannot move sediment grains with a diameter larger than a few millimeters, Lewis said. The sand and stones he and his colleagues analyzed had diameters ranging from one to 40 millimeters, or roughly the size of a mustard seed to being only slightly smaller than a golf ball. The roundness of the sediment also suggested a prolonged eroding force, Lewis said.

“Once you get above a couple of millimeters the wind will not be able to mobilize sediment. A number of the grains we see in this outcrop are substantially bigger than that,” Lewis said. “That really leaves us with fluvial transport as the most likely process. We knew Curiosity was landing near the fan, but to land right on top of these rocks that suggest the presence of water was really fortuitous.”

If the sediment does mean a river ran through Mars, the researchers must next determine when, where it came from and how it dried up, a project that will be a “major scientific project over the coming year,” Lewis said. The mystery also centers on the potential relationship of the river to the scars on Mount Sharp: Did the river flow down it? Was the mound a source of water after all?

“This evidence tells us that there were a diverse set of geological processes happening at roughly the same time within the proximity of [the landing site], and it gives us a picture of a much more dynamic Mars than we see today,” Lewis said. “Finding out how exactly they relate will be an exciting story.”

Read the abstract.

Citation: Williams, R.M.E., et al. 2013. Martian fluvial conglomerates at Gale Crater. Science. Article first published online: May. 30, 2013. DOI: 10.1126/science.1237317

This work was supported in part by grants from NASA Mars Program Office.

DNA Gridlock – Cells undo glitches to prevent mutations (Nature)

By Catherine Zandonella, Office of the Dean for Research

The diagram shows a G-quadruplex (G4) on the upper of the two strands that make up DNA. The purple shape represents DNA polymerase, which is blocked by the G4 in its attempt to copy DNA. Regions of the genome that are especially susceptible to forming G-quadruplexes are ones rich in guanine, which is one of the four nucleotides, designated by the letters G, A, C, and T, in DNA. Adapted from Nature Genetics, 2012.

Roughly six feet of DNA are packed into every human cell, so it is not surprising that our genetic material occasionally folds into odd shapes such as hairpins, crosses and clover leafs. But these structures can block the copying of DNA during cell division, leading to gene mutations that could have implications in cancer and aging.

Now researchers based at Princeton University have uncovered evidence that cells contain a built-in system for eliminating one of the worst of these roadblocks, a structure known as a G-quadruplex. In a paper published earlier this month in Nature, a group of researchers led by Princeton’s Virginia Zakian reported that an enzyme known as the Pif1 helicase can unfold these structures both in test tubes and in cells, bringing DNA replication back on track.

Given that Pif1 mutations have been associated with an increased risk of breast cancer, Zakian said, the study of how Pif1 ensures proper DNA replication could be relevant to human health. Zakian is Princeton’s Harry C. Wiess Professor in the Life Sciences.

Most DNA is made of up of two strands twisted about each other in a way that resembles a spiral staircase. Every time a cell divides, each DNA molecule must be duplicated, a process that involves unwinding the staircase so that an enzyme known as DNA polymerase can work down each strand, copying each letter in the DNA code. During this exposed period, regions of the unwound single strands can fold into G-quadruplexes (see diagram).

Like a car that encounters a pile-up on an Interstate, the DNA polymerase halts when it encounters a G-quadruplex, explained Matthew Bochman, a postdoctoral researcher who was a co-first author with Katrin Paeschke, now an independent investigator at University of Würzburg in Germany. The work also included Princeton graduate student Daniela Garcia.

“The DNA that is folded into a G-quadruplex cannot be replicated, so essentially it is skipped,” Bochman said. “Failure to copy specific areas of DNA that you really need is a serious problem, especially in regions that control genes that either suppress or contribute to cancer,” Bochman said.

Last year, the Zakian group in collaboration with human geneticists at the University of Washington reported that a mutation in human Pif1 is associated with an increased risk of breast cancer, suggesting that the ability to unwind G-quadruplexes could be important for protecting against cancer. The finding was published in the journal PLoS One.

G-quadruplexes could also be implicated in the process of aging, according to the researchers. The structures are thought to form at the ends of chromosomes in regions called telomeres, said Zakian, an expert on telomere biology. Damaged or shortened telomeres are associated with premature aging and cancer.

To explore the role of Pif1 helicases in tackling G-quadruplexes, Bochman and Paeschke purified Pif1 helicases from yeast and bacteria and found that in test tubes, all of the Pif1 helicases unwind G-quadruplex structures extremely fast and very efficiently, much better than other helicases tested in the same way.

Next, these investigators set up an experiment to determine if Pif1 acts on G-quadruplexes inside cells. Using a system that could precisely evaluate the effects of G-quadruplex structures on the integrity of chromosomes, the researchers found that normal cells had no problem with the addition of a G-quadruplex structure, but when cells lack Pif1 helicases, the G-quadruplex induced a high amount of genome instability.

“To me, the most remarkable aspect of the study was the demonstration that Pif1-like helicases taken from species ranging from bacteria to humans and placed in yeast cells can suppress G-quadruplex-induced DNA damage,” Zakian said. “This finding suggests that resolving G-quadruplexes is an evolutionarily conserved function of Pif1 helicases.”

The Zakian lab also found that replicating through G-quadruplexes in the absence of Pif1 helicases results not only in mutations of the DNA at the site of the G-quadruplex but also in intriguing “epigenetic” effects on expression of nearby genes that were totally unexpected. Epigenetic events cause changes in gene expression that are inherited, yet they do not involve loss or mutation of DNA. Graduate student Daniela Garcia has proposed that the epigenetic silencing of gene expression that occurs near G-quadruplexes in the absence of Pif1 helicases is a result of the addition or removal of molecular tags on histones, which are proteins that bind DNA and regulate gene expression. This hypothesis is currently being studied.

The study involved contributions from Petr Cejka and Stephen C. Kowalczykowski of the University of California-Davis, and Katherine Friedman of Vanderbilt University.

Read the abstract.

Paeschke, Katrin, Matthew L. Bochman, P. Daniela Garcia, Petr Cejka, Katherine L. Friedman, Stephen C. Kowalczykowski & Virginia A. Zakian. Pif1 family helicases suppress genome instability at G-quadruplex motifs. Nature. 2013. doi:10.1038/nature12149.

This research was supported by the National Institutes of Health (V.A.Z., GM026938-34; S.C.K.GM041347), the National Science Foundation (K.L.F., MCB-0721595), the German Research Foundation (DFG), the New Jersey Commission on Cancer Research (K.P.) and the American Cancer Society (M.L.B., PF-10-145-02-01).

How the ice ages ended (Nature)

by Catherine Zandonella, Office of the Dean for Research

Antarctica. Photo credit: Harley D. Nygren, NOAA

A study of sediment cores collected from the deep ocean supports a new explanation for how glacier melting at the end of the ice ages led to the release of carbon dioxide from the ocean.

The study published in Nature suggests that melting glaciers in the northern hemisphere caused a disruption of deep ocean currents, leading to the release of trapped carbon dioxide from the Southern Ocean around Antarctica.

Understanding what happened when previous glaciers melted could help climate researchers make accurate predictions about future global temperature increases and their effects on the planet.

The evidence is strong that ice ages are driven by periodic changes in the amount of sunlight reaching the poles due to cyclic changes in Earth’s rotation and orbit. Yet scientists have been puzzled by evidence that although the timing of ice ages are best explained by changes in sunlight in the northern part of the globe, the warming at the end of ice ages occurred first in the southern hemisphere, with a rise in carbon dioxide levels appearing to be cued from the south.

The new study suggests that changes in ocean currents, connecting the north to the south through the deep ocean, were to blame.

As glaciers melted in the northern reaches of the globe (far upper left), the influx of freshwater, which is naturally less dense than salt-laden ocean water, caused a reduction in the normally strong sinking of water in that region. This allowed silicate-rich deep water to rise upward into the shallower ocean waters (upward blue arrows), stimulating the production of opal by diatoms, while warm surface water mixed downward (red arrows) into the southern-sourced deep water. The rising silicate-rich water drew dense cold water from near Antarctica, yielding a cycle of water movement (in yellow). The new circulation pattern caused carbon dioxide stored in the deep water to be released to the atmosphere near Antarctica (far upper right). Image source: Daniel Sigman.

Part of this story was suggested more than a decade ago and is already accepted by many climate scientists: As glaciers in the north started melting, the influx of fresh water diluted the salty waters that today flow to the north from the tropics as an extension of the Gulf Stream. Normally, these salty waters become cool and sink into the deep ocean, forming cold and dense water that flows southward, and allowing more salty tropical water to take its place in a sort of ocean conveyor belt. But the influx of fresh water due to melting glaciers stalled the conveyor belt.

So how did this lead to changes in the southern hemisphere?

The new research suggests that the shutdown in northern sinking water allowed southern-sourced water to fill up the deep Atlantic, setting up a new ocean circulation pattern. This new circulation pattern brought deep-sea water, which was rich in carbon dioxide due to sunken dead marine algae, to the surface near Antarctica, where the gas escaped into the atmosphere and acted to drive global warming. (See diagram.)

The researchers included investigators from ETH Zürich, Princeton University, the University of Miami, the University of British Columbia, and the University of Bremen and the Alfred Wegener Institute in Germany. The Princeton effort was led by Daniel Sigman, the Dusenbury Professor of Geological and Geophysical Sciences.

The team tracked these historic movements of water through the study of sediment cores that are rich in silicon dioxide, or opal. Tiny marine algae known as diatoms make their cell walls out of opal, and when the organisms die, their opal remains sink to the deep sea bed.

The researchers looked at opal in sediment core samples drilled from deep beneath the ocean floor off the coast of northwest Africa and Antarctica. The team found that each period of glacier melting, which occurred five times over the last 550 thousand years, corresponded to a spike in the amount of the opal in the sediment, signaling an increase in diatom growth. The timing of the opal spikes provides evidence that the deep, opal-rich waters in the south were drawn to the surface in response to new meltwater entering the northern ocean.

The mechanism clashes with a previously offered explanation of why the melting of the northern glaciers, or deglaciations, leads to the release of ocean carbon dioxide from the Southern Ocean – the theory that the melting glaciers in the north increased southern hemisphere westerly winds, which in turn caused upwelling of Southern Ocean deep waters. “While distinguishing between these alternatives is important,” says Sigman, “the greater challenge is to test and understand a premise that is shared by both of these scenarios: that ice age conditions around Antarctica caused the deep ocean to be sluggish and rich in carbon dioxide. If this was really how the ice age ocean operated, then it calls for us to reconsider how we expect deep ocean circulation to respond to modern global warming.”

Read the abstract.

A. N. Meckler, D. M. Sigman, K. A. Gibson, R. François, A. Martínez-García, S. L. Jaccard, U. Röhl, L. C. Peterson, R. Tiedemann & G. H. Haug. 2013. Deglacial pulses of deep-ocean silicate into the subtropical North Atlantic Ocean. Nature 495 (7442), 495-498. doi:10.1038/nature12006. Published online 27 March, 2013.

This research used samples provided by the ODP, which is sponsored by the US National Science Foundation (NSF) and participating countries under the management of the Joint Oceanographic Institutions. XRF data were acquired at the XRF Core Scanner Lab at MARUM – Center for Marine Environmental Sciences, University of Bremen, with support from the DFG-Leibniz Center for Surface Process and Climate Studies at the University of Potsdam. Further support was provided by the US NSF through grant OCE-1060947 to D.M.S. and by NSERC and CFCAS to R.F.

Shape from sound — new methods to probe the universe (Physical Review Letters)

By Morgan Kelly, Office of Communications

As the universe expands, it is continually subjected to energy shifts, or “quantum fluctuations,” that send out little pulses of “sound” into the fabric of spacetime. In fact, the universe is thought to have sprung from just such an energy shift.

A recent paper in the journal Physical Review Letters reports a new mathematical tool that should allow one to use these sounds to help reveal the shape of the universe. The authors reconsider an old question in spectral geometry that asks, roughly, to what extent can the shape of a thing be known from the sound of its acoustic vibrations? The researchers approached this problem by breaking it down into small workable pieces, according to author Tejal Bhamre, a Princeton University graduate student in the Department of Physics.

To understand the authors’ method, consider a vase. If one taps a vase with a spoon, it will make a sound that is characteristic of its shape. Similarly, the technique Bhamre and her coauthors developed could, in principle, determine the shape of spacetime from the perpetual ringing caused by quantum fluctuations.

The researchers’ technique also provides a unique connection between the two pillars of modern physics — quantum theory and general relativity — by using vibrational wavelengths to define the geometric property that is spacetime.

Bhamre worked with coauthors David Aasen, a physics graduate student at Caltech, and Achim Kempf, a Waterloo University professor of physics of information.

Read the abstract.

David Aasen, Tejal Bhamre and Achim Kempf. 2013. Shape from Sound: Toward New Tools for Quantum Gravity. Physical Review Letters. Article first published online: March 18, 2013. DOI: 10.1103/PhysRevLett.110.121301.

This research was supported by the Natural Sciences and Engineering Research Council of Canada.

Serendipity Pays Off (Science)

By Catherine Zandonella, Office of the Dean for Research

Serendipity – the act of finding something good or useful while not specifically searching for it – can sometimes pay off. Now Princeton University chemistry researchers report that this non-specific type of searching has yielded a new method of building molecules for use in new drugs, new agricultural chemicals and even new perfumes.

In a paper published today in the journal Science, Princeton’s David MacMillan and his team describe the discovery of a new chemical reaction – not noted before in nature or in any lab – that could assist pharmaceutical chemists and others who routinely create new chemicals for a variety of industries.

Until now, no one realized this chemical reaction – which involves adding atoms to a specific carbon atom on a molecule – could occur, according to MacMillan, the James S. McDonnell Distinguished University Professor of Chemistry at Princeton. “If you show this chemical reaction to most chemists, they immediately say ‘that’s impossible,’” MacMillan said.

In this case, the team discovered this “impossible” reaction using an approach MacMillan pioneered that he calls “accelerated serendipity.” The researchers use robotic arms to conduct thousands of reactions per day by combining in test tubes different combinations of chemicals along with catalysts that spur the reactions. When the investigators find a reaction that makes an interesting product, they study it to understand how the reaction occurs.

“We didn’t invent this new reaction – nature did that,” MacMillan said, “but we figured out how to get the reaction to happen in the lab.” said MacMillan. His team, which included graduate student Michael Pirnot, postdoctoral researcher David Martin and former postdoctoral researcher Danica Rankic, uses ordinary light bulbs as catalysts, a technique developed in MacMillan’s lab and published in Science in 2008, to spur the reactions.

Going forward, chemists can add this new reaction to their tool box of methods for building up molecules, which they do in a way analogous to joining together pieces of Kinex or Tinker Toys, by swapping in new parts to increase the function of the molecule. In the new reaction published today, the team discovered a way to join so-called “functional groups” to a specific carbon atom (see diagram) in larger structures known as ketones and aldehydes. The ability to add functional groups to that carbon atom was thought impossible until now.

Caption: Upper and lower left: Green spots indicate carbon atoms known to undergo reactions. Right panel: Purple spot indicates a carbon atom thought not to undergo reactions. The team discovered, using accelerated serendipity, a way to cause this carbon to react, resulting in addition of functional groups, and potentially leading to new drugs or other important industrial chemicals. (Source: Science)

This new chemical reaction has wide applications, MacMillan said. “This is a fundamental reaction which any chemist can start using.”

For example, a chemist who is building a drug to treat Alzheimer’s disease might desire to add a chemical group to the reluctant carbon atom. Normally that would require the chemist to conduct several different chemical reactions over several weeks, but with the new reaction the chemist could build the drug in two days and be testing drug candidates much more quickly.

Similarly a chemist at a fragrance company could use the new reaction to experiment with the creation of new perfume formulations.

MacMillan’s original paper on accelerated serendipity, published in 2011 in Science, successfully discovered a reaction now used in the drug industry. Yet it was controversial because other scientists interpreted the robotic searches as random searches, when in fact they were not random. “We chose chemicals that had never been shown to react with each other – those are the ones we believe might lead to as-yet undiscovered reactions.” MacMillan said that these reactions may have been created in the past by chemists who didn’t recognize what they were.

Read the abstract.

Michael T. Pirnot, Danica A. Rankic, David B. C. Martin, David W. C. MacMillan. Photoredox Activation for the Direct β-Arylation of Ketones and Aldehydes. Science 29 March 2013. Vol. 339 no. 6127 pp. 1593-1596.

This research was supported by the National Institute of General Medical Sciences grant R01 GM103558-01 and gifts from Merck, Amgen, Abbott, and Bristol-Myers Squibb.

Younger cancer patients experience greater increase in religiosity (Social Science Research)

By Michael Hotchkiss, Office of Communications

People diagnosed with cancer at younger ages are more likely to become more religious than their counterparts diagnosed at older ages, researchers including a Princeton research scholar have found.

Overall, the researchers found that people diagnosed with cancer experienced a one-time increase in religiosity, with the greater increase among those who experienced a diagnosis at a younger age, what’s known as an “off-time diagnosis.”

“Off-time diagnoses may also be related to increased religiosity because the meaning of having cancer may be different for those in middle adulthood compared to older adulthood,” the researchers said. The results come from a review of surveys of more than 3,400 people conducted in 1994-95 and 2004-06.

The research, detailed in an article in the March issue of Social Science Research, was conducted by Michael McFarland, a postdoctoral researcher at Princeton’s Office of Population Research, Tetyana Pudrovska, an assistant professor at Pennsylvania State University; Scott Schieman, a professor at the University of Toronto; Christopher Ellison, a professor at the the University of Texas at San Antonio; and Alex Bierman, an assistant professor at the University of Calgary.

Read the abstract.

McFarland, Michael J., Tetyana Pudrovska, Scott Schieman, Christopher G. Ellison, and Alex Bierman. March 2013. Does a cancer diagnosis influence religiosity? Integrating a life course perspective. Social Science Research. Vol. 42, Issue 2, pp. 311–20.

Drug-resistant MRSA bacteria – here to stay in both hospital and community (PLoS Pathogens)

By Catherine Zandonella, Office of the Dean for Research

A colorized scanning electron micrograph of a white blood cell eating an antibiotic resistant strain of Staphylococcus aureus bacteria, commonly known as MRSA. (Source: National Institute of Allergy and Infectious Diseases (NIAID))

The drug-resistant bacteria known as MRSA, once confined to hospitals but now widespread in communities, will likely continue to exist in both settings as separate strains, according to a new study.

The prediction that both strains will coexist is reassuring because previous projections indicated that the more invasive and fast-growing community strains would overtake and eliminate hospital strains, possibly posing a threat to public health.

Researchers at Princeton University used mathematical models to explore what will happen to community and hospital MRSA strains, which differ genetically. Originally MRSA, which is short for methicillin-resistant Staphylococcus aureus, was confined to hospitals. However, community-associated strains emerged in the past decade and can spread widely from person to person in schools, athletic facilities and homes.

Both community and hospital strains cause diseases ranging from skin and soft-tissue infections to pneumonia and septicemia. Hospital MRSA is resistant to numerous antibiotics and is very difficult to treat, while community MRSA is resistant to fewer antibiotics.

The new study found that these differences in antibiotic resistance, combined with more aggressive antibiotic usage patterns in hospitals versus the community setting, over time will permit hospital strains to survive despite the competition from community strains. Hospital-based antibiotic usage is likely to successfully treat patients infected with community strains, preventing the newcomer strains from spreading to new patients and gaining the foothold they need to out-compete the hospital strains.

The researchers made their predictions by using mathematical models of MRSA transmission that take into account data on drug-usage, resistance profiles, person-to-person contact, and patient age.

Published February 28 in the journal PLOS Pathogens, the study was conducted by postdoctoral researcher Roger Kouyos, now a scholar at the University of Zurich, and Eili Klein, a graduate student who is now an assistant professor in the Johns Hopkins School of Medicine. They conducted the work under the advisement of Bryan Grenfell, Princeton’s Kathryn Briger and Sarah Fenton Professor of Ecology and Evolutionary Biology and Public Affairs at Princeton’s Woodrow Wilson School of International and Public Affairs.

Read the article (open access).

Kouyos R., Klein E. & Grenfell B. (2013). Hospital-Community Interactions Foster Coexistence between Methicillin-Resistant Strains of Staphylococcus aureus. PLoS Pathogens, 9 (2) e1003134. PMID: 23468619

RK was supported by the Swiss National Science Foundation (Grants PA00P3_131498 and PZ00P3_142411). EK was supported by Princeton University (Harold W. Dodds Fellowship), as well as the Models of Infectious Disease Agent Study (MIDAS), under Award Number U01GM070708 from the National Institute of General Medical Sciences. BG was supported by the Bill and Melinda Gates Foundation; the Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directorate, Department of Homeland Security; and the Fogarty International Center, National Institutes of Health.

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