Yale researchers have uncovered the molecular tricks used by bacteria to fight the effects of fluoride, which is commonly used in toothpaste and mouthwash to combat tooth decay.

In the Dec. 22 Online issue of the journal science express, the researchers report that sections of RNA messages called Riboswitches - which control the expression of genes - detect the build-up of fluoride and activate the defenses of bacteria, including those that contribute to tooth decay.

"These riboswitches are detectors made specifically to see fluoride," said Ronald Breaker, The Henry Ford II professor and chair of the Department Of Molecular, Cellular And Developmental Biology and senior author of the study.

Fluoride in over-the-counter and prescription toothpastes is widely credited with the large reduction in dental cavities seen since these products were made available beginning in the 1950s. This effect is largely caused by fluoride bonding to the enamel of our teeth, which hardens them against the acids produced by bacteria in our mouths.

However, it has been known for many decades that fluoride at high concentrations also is toxic to bacteria, causing some researchers to propose that this antibacterial activity also may help prevent cavities.

The riboswitches work to counteract fluoride's effect on bacteria. "If fluoride builds up to toxic levels in the cell, a fluoride riboswitch grabs the fluoride and then turns on genes that can overcome its effects," said breaker.

Since both fluoride and some rna sensor molecules are negatively charged, they should not be able to bind, he notes.

"We were stunned when we uncovered fluoride-sensing riboswitches" said breaker. "Scientists would argue that rna is the worst molecule to use as a sensor for fluoride, and yet we have found more than 2000 of these strange rnas in many organisms."

By tracking fluoride riboswitches in numerous species, the research team concluded that these rnas are ancient - meaning many organisms have had to overcome toxic levels of fluoride throughout their history. Organisms from at least two branches of the tree of life are using fluoride riboswitches, and the proteins used to combat fluoride toxicity are present in many species from all three branches.

"Cells have had to contend with fluoride toxicity for billions of years, and so they have evolved precise sensors and defense mechanisms to do battle with this ion," said breaker, who is also an investigator with the howard hughes medical institute. Now that these sensors and defense mechanisms are known, breaker said, it may be possible to manipulate these mechanisms and make fluoride even more toxic to bacteria.

Fluoride riboswitches and proteins common in bacteria are lacking in humans, and so these fluoride defense systems could be targeted by drugs. For example, the yale team discovered protein channels that flush fluoride out of cells. Blocking these channels with another molecule would cause fluoride to accumulate in bacteria, making it more effective as a cavity fighter.

Fluoride is the 13th most common element in the earth's crust, and it is naturally present in high concentrations throughout the united states and elsewhere. Its use in toothpaste and its addition to city water supplies across the united states sparked a controversy 60 years ago, and the dispute continues to this day. In the united kingdom, and in other european union countries, fluoride is used to a much lesser extent due to fierce public opposition.

The new findings from yale only reveal how microbes overcome fluoride toxicity. The means by which humans contend with high fluoride levels remains unknown, breaker notes. He adds that the use of fluoride has had clear benefits for dental health and that these new findings do not indicate that fluoride is unsafe as currently used.

Other yale authors of the paper include: Jenny l. Baker, narasimhan sudarsan, zasha weinberg and adam roth. Chinese fossils shed light on the evolutionary origin of animals from single-cell ancestors http://www.bristol.ac.uk/ University of Bristol All life evolved from a single-celled universal common ancestor, and at various times in Earth history, single-celled organisms threw their lot in with each other to become larger and multicellular, resulting, for instance, in the riotous diversity of animals. However, fossil evidence of these major evolutionary transitions is extremely rare.

The fossils, reported this week in Science, preserve stages in the life cycle of an amoeba-like organism dividing in asexual cycles, first to produce two cells, then four, eight, 16, 32 and so on, ultimately resulting in hundreds of thousands of spore-like cells that were then released to start the cycle over again. The pattern of cell division is so similar to the early stages of animal (including human) embryology that until now they were thought to represent the embryos of the earliest animals.

The researchers studied the microscopic fossils using high energy X-rays at the Swiss Light Source in Switzerland, revealing the organisation of the cells within their protective cyst walls. The organisms should not have been fossilized - they were just gooey clusters of cells - but they were buried in sediments rich in phosphate that impregnated the cell walls and turned them to stone.

Lead author Therese Huldtgren said: "The fossils are so amazing that even their nuclei have been preserved."

Co-author Dr John Cunningham said: "We used a particle accelerator called a synchrotron as our X-ray source. It allowed us to make a perfect computer model of the fossil that we could cut up in any way that we wanted, but without damaging the fossil in any way. We would never have been able to study the fossils otherwise!"

This X-ray microscopy revealed that the fossils had features that multicellular embryos do not, and this led the researchers to the conclusion that the fossils were neither animals nor embryos but rather the reproductive spore bodies of single-celled ancestors of animals.

Professor Philip Donoghue said: "We were very surprised by our results - we've been convinced for so long that these fossils represented the embryos of the earliest animals - much of what has been written about the fossils for the last ten years is flat wrong. Our colleagues are not going to like the result."

Professor Stefan Bengtson said: "These fossils force us to rethink our ideas of how animals learned to make large bodies out of cells." Paper

Huldtgren, T., Cunningham, J. A., Yin, C., Stampanoni, M., Marone, F., Donoghue, P. C. J. and Bengtson, S. 2011. 'Fossilized nuclei and germination structures identify Ediacaran "animal embryos" as encysting protists' in Science 334.

Therese Huldtgren is a doctoral student at the Department of Palaeozoology, Swedish Museum of Natural History, and Stockholm University, Stockholm, Sweden.

Dr John Cunningham is a Research Associate at the School of Earth Sciences, University of Bristol, UK.

Professor Chongyu Yin is a Researcher at the Institute of Geology, Chinese Academy of Geological Sciences, Beijing, China.

Professor Marco Stampanoni is Head of X-ray Tomography at the Paul Scherrer Institute, Villigen, Switzerland and Assistant Professor for X-ray Microscopy at the Department for Information Technology and Electrical Engineering of ETH Zurich, and Institute of Biomedical Engineering of the University of Zurich and ETH Zurich.

Dr Federica Marone is a beamline scientist at the Paul Scherrer Institute, Villigen, Switzerland.

Professor Philip Donoghue is Professor of Palaeobiology in the School of Earth Sciences, University of Bristol, UK

Professor Stefan Bengtson is Professor of Palaeozoology, Swedish Museum of Natural History, Stockholm, Sweden