This is the structure of the Tet enzyme with DNA. Note the purple ball at the active site, close to which one DNA base is flipped out of the double helix. Also note the degree to which the double helix is bent. Credit: Xiaodong Cheng, Emory University
The finding is important for the field of epigenetics because Tet enzymes chemically modify DNA, changing signposts that tell the cell's machinery "this gene is shut off" into other signs that say "ready for a change."
Tet enzymes' roles have come to light only in the last five years; they are needed for stem cells to maintain their multipotent state, and are involved in early embryonic and brain development and in cancer.
The results, which could help scientists understand how Tet enzymes are regulated and look for drugs that manipulate them, are scheduled for publication in Nature.
Researchers led by Xiaodong Cheng, PhD, determined the structure of a Tet family member from Naegleria gruberi by X-ray crystallography. The structure shows how the enzyme interacts with its target DNA, bending the double helix and flipping out the base that is to be modified.
"This base flipping mechanism is also used by other enzymes that modify and repair DNA, but we can see from the structure that the Tet family enzymes interact with the DNA in a distinct way," Cheng says.
Cheng is professor of biochemistry at Emory University School of Medicine and a Georgia Research Alliance Eminent Scholar. The first author of the paper is research associate Hideharu Hashimoto, PhD. A team led by Yu Zheng, PhD, a senior research scientist at New England Biolabs, contributed to the paper by analyzing the enzymatic activity of Tet using liquid chromatography–mass spectrometry.
Using oxygen, Tet enzymes change 5-methylcytosine into 5-hydroxymethylcytosine and other oxidized forms of methylcytosine. 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) are both epigenetic modifications of DNA, which change how DNA is regulated without altering the letters of the genetic code itself.
5-mC is generally found on genes that are turned off or on repetitive regions of the genome. 5-mC helps shut off genes that aren't supposed to be turned on (depending on the cell type) and changes in 5-mC's distribution underpin a healthy cell's transformation into a cancer cell.
In contrast to 5-mC, 5-hmC appears to be enriched on active genes, especially in brain cells. Having a Tet enzyme form 5-hmC seems to be a way for cells to erase or at least modify the "off" signal provided by 5-mC, although the functions of 5-hmC are an active topic of investigation, Cheng says.
Alterations of the Tet enzymes have been found in forms of leukemia, so having information on the enzymes' molecular structure could help scientists design drugs that interfere with them.
N. gruberi is a single-celled organism found in soil or fresh water that can take the form of an amoeba or a flagellate; its close relative N. fowleri can cause deadly brain infections. Cheng says his team chose to study the enzyme from Naegleria because it was smaller and simpler and thus easier to crystallize than mammalian forms of the enzyme, yet still resembles mammalian forms in protein sequence.
Mammalian Tet enzymes appear to have an additional regulatory domain that the Naegleria forms do not; understanding how that domain works will be a new puzzle opened up by having the Naegleria structure, Cheng says. Journal reference:Nature
Most participants of National Geographic’s Genographic Project can recite their haplogroup as readily as their mother’s maiden name. Yet outside consumer genetics, the word haplogroup is still unknown. Your haplogroup, or genetic branch of the human family tree, tells you about your deep ancestry—often thousands of years ago—and shows you the possible paths of migration taken by these ancient ancestors. Your haplogroup also places you within a community of relatives, some distant, with whom you unmistakably share an ancestor way back when.
DNA Molecule
Haplogroup H1, Genographic’s most common lineage.
Let’s focus here on mitochondrial DNA haplogroup is H1, as it is the Genographic Project’s most common maternal lineage result. You inherited your mitochondrial DNA purely from your mother, who inherited it from her mother, and her mother, and so on. Yet, unlike often is the case with a mother’s maiden name, her maternal haplogroup is passed down through generations. Today, all members of haplogroup H1 are direct descendants from the first H1 woman that lived thousands of years ago. Most H1 members may know their haplogroup as H1a or H1b2 or H1c1a, etc, yet as a single genetic branch, H1 accounts for 15% of Genographic participants. What’s more, in the past few years, anthropologists have discovered and named an astonishing 200 new branches within haplogroup H1; and that number continues to grow.
Haplogroup H3, sister branch to H1
The origin of haplogroup H1 continues to be a debate as well. Most researchers suggest it was born in the Middle East between 10,000 and 15,000 years ago, and spread from there to Europe and North Africa. However, ancient DNA studies show that its ancestral haplogroup H first appears in Central Europe just 8,000 year ago. Its vast diversity and high concentration in Spain and Portugal, suggests H1 may have existed there during the last Ice Age, and spread north after glaciers melted. Yet others postulate that its young age and high frequency indicate it spread as agriculture took shape in Europe.
Any of the scenarios is possible. As technology improves, more DNA is extracted and sequenced from ancient bones, and more people contribute their DNA to the Genographic Project, we will keep learning about H1, and all other haplogroups. It is because of participants contributing their DNA, their stories, and their hypotheses to science that we can carry forward this exciting work uncovering our deep genetic connections.
Basically the researchers, lead by Dr. Srivas Chennu at the University of Cambridge, were trying to see if patients diagnosed as either in a vegetative state (VS) or minimally conscious state (MCS) could pay attention to (count) certain words, called the attended words, when they were embedded in a string of other randomly presented words, called the distracting words. Normal brain wave responses were established by performing the word testing on 8 healthy volunteers. The same testing was then applied to 21 brain damaged individuals, 9 with a clinical diagnosis of vegetative state and 12 with a diagnosis of minimally conscious state. Most of the patients did not respond to the presentation of words as did normal volunteers. But one did.
The patient, described at Patient P1, suffered a traumatic brain injury 4 months prior to testing. He was diagnosed as “behaviorally vegetative,” based on a Coma Recovery Score-Revised (CRS-R) of 7 (8 or greater = MCS). In addition to being able to consciously attend to the key words, this patient could also follow simple commands to imagine playing tennis.
Dr. Chennu was quoted as saying, “we are progressively building up a fuller picture of the sensory, perceptual and cognitive abilities in patients” with vegetative and minimally conscious states. Yes, this is true. But what does it mean if someone previously diagnosed as vegetative can now be shown to perform this sort of task? Dr. Chennu hopes that this information will spur the development of “future technology to help patients in a vegetative state communicate with the outside world.”
I think this is fascinating research and it sheds new insights into how the brain functions, but it also raises a number of important questions. For example, if I can attend to words, does it change my prognosis? Patient P1 was found to have minimal cortical atrophy. Perhaps he is just slow to transition from a vegetative to a MCS. If attending to words is associated with a better prognosis, should that make me a candidate for intensive and expensive rehabilitation? If so, who should pay for this? If I have an advanced directive that says I don’t want to continue to live in a persistent vegetative state, will this level of awareness mean I am not really vegetative. As more and more resources are poured into care for folks with severe brain damage, does it come at a societal cost?
What trade offs are we making, what services are we forgoing, as we spend money developing tools to improve communication in vegetative states
Of course no one has the answer to these questions and I suspect as researchers like those at Cambridge continue to learn more about the functioning of the severely injured brain, the more difficult it will be to clearly say what is really means to be “aware.”
Pope Francis waved from the balcony of St. Peter’s Basilica at the Vatican after his Christmas blessing.
By REUTERS
Published: December 25, 2013 at 7:47 AM ET
VATICAN CITY — Pope Francis, celebrating his first Christmas as Roman Catholic leader, on Wednesday called on atheists to unite with believers of all religions and work for "a homemade peace" that can spread across the world.
Speaking to about 70,000 people from the central balcony of St. Peter's Basilica, the same spot where he emerged to the world as pope when he was elected on March 13, Francis also made another appeal for the environment to be saved from "human greed and rapacity".
The leader of the 1.2 billion-member Church wove his first "Urbi et Orbi" (to the city and world) message around the theme of peace.
"Peace is a daily commitment. It is a homemade peace," he said.
He said that people of other religions were also praying for peace, and - departing from his prepared text - he urged atheists to join forces with believers.
"I invite even non-believers to desire peace. (Join us) with your desire, a desire that widens the heart. Let us all unite, either with prayer or with desire, but everyone, for peace," he said, drawing sustained applause from the crowd.
Francis's reaching out to atheists and people of other religions is a marked contrast to the attitude of former Pope Benedict, who sometimes left non-Catholics feeling that he saw them as second-class believers.
He called for "social harmony in South Sudan, where current tensions have already caused numerous victims and are threatening peaceful coexistence in that young state".
Thousands are believed to have died in violence divided along ethnic lines between the Nuer and Dinka tribes in the country, which seceded from Sudan in 2011 after decades of war.
The pontiff also called for dialogue to end the conflicts in Syria, Nigeria, Democratic Republic of Congo and Iraq, and prayed for a "favorable outcome" to the peace process between Israelis and Palestinians.
"Wars shatter and hurt so many lives!" he said, saying their most vulnerable victims were children, elderly, battered women and the sick.
PERSONAL PEACEMAKERS
The thread running through the message was that individuals had a role in promoting peace, either with their neighbor or between nations.
The message of the birth of Jesus in Bethlehem was directed at "every man or woman who keeps watch through the night, who hopes for a better world, who cares for others while humbly seeking to do his or her duty," he said.
"God is peace: let us ask him to help us to be peacemakers each day, in our life, in our families, in our cities and nations, in the whole world," he said.
Pilgrims came from all over the world for Christmas at the Vatican and some said it was because they felt Francis had brought a breath of fresh air to the Church.
"(He) is bringing a new era into the Church, a Church that is focusing much more on the poor and that is more austere, more lively," said Dolores Di Benedetto, who came from the pope's homeland, Argentina, to attend Christmas Eve Mass.
Giacchino Sabello, an Italian, said he wanted to get a first-hand look at the new pope: "I thought it would be very nice to hear the words of this pope close up and to see how the people are overwhelmed by him."
In his speech, Francis asked God to "look upon the many children who are kidnapped, wounded and killed in armed conflicts, and all those who are robbed of their childhood and forced to become soldiers".
He also called for a "dignified life" for migrants, praying tragedies such as one in which hundreds died in a shipwreck off the coast of the Italian island of Lampedusa are never repeated, and made a particular appeal against human trafficking, which he called a "crime against humanity".
This schematic diagram of Lambda-Cold Dark Matter, accelerated Expansion of the Universe Via Alex Mittelmann, Coldcreation
In August of 2013, physicists made a major breakthrough in our understanding of the early universe in an experiment that successfully reproduced a pattern resembling the cosmic microwave background radiation. This experiment was conducted at the University of Chicago with the aid of ultracold cesium atoms.
“This is the first time an experiment like this has simulated the evolution of structure in the early universe,” according to physics professor Cheng Chin, one of the authors on this project. The goal of the experiment was to simulate the big bang using ultracold atoms in an effort to understand how the universe evolved at the earliest timescales. Tentatively, their experiment seems a tremendous success
The image reveals 13.77 billion-year-old temperature fluctuations—shown as color differences—that correspond to the seeds that grew to become the galaxies. via NASA
The cosmic microwave background (CMB) is one of the only things we have left to analyze the early structure of the universe, and this CMB is a kind of window, allowing us to go back in time to that most volatile period in our universe’s history. Ultimately, it allows us to pull a fingerprint of the universe when it was only 380,000 years old. This pervasive radiation has been mapped over the last few decades. The most recent and most detailed mapping of the CMB comes from the Planck Space Observatory and was completed earlier this year.
Chen-Lung Hung, the lead author on the project, described the methodology of the experiment as follows, “…under certain conditions, a cloud of atoms chilled to a billionth of a degree above absolute zero (-459.67 degrees Fahrenheit) in a vacuum chamber displays phenomena similar to those that unfolded following the Big Bang. At this ultracold temperature, atoms get excited collectively. They act as if they are sound waves in air.” That sound wave action can be observed in the CMB.
The echoing and rippling of spacetime created in the big bang was exaggerated in the period of the universe’s rapid inflation. These ripples reverberated back and forth and interacted with each other creating the foundation for the complicated patterns we see in the universe today. This phenomenon is known as “Sakharov acoustic oscillations” after the scientists who first described them.
The simulated universe comprised of a cloud of 10,000 cesium atoms, chilled to a billionth of a degree above absolute zero. This caused the atoms to form an exotic state of matter called two-dimensional atomic superfluid. This simulated universe measured about 70-microns in diameter, or about the size of a human hair. Even though the universe had a diameter of about 100,000 light-years when emitted the pattern we recognize today as the CMB, the much smaller simulated universe behaved in exactly the same fashion as a large universe would.
(International Business Times By Cameron Fuller) -- Scientists have created what may become the future of prosthetics, a robot “muscle” that can throw something 50 times its own weight five times its length in a surprisingly fast 60 milliseconds. While it’s easy to envision what this means for the future, a Hollywood image of robot arms crushing steel bars with ease comes quickly to mind, don’t fear just yet, the new muscle is currently the size of a microchip.
A schematic for Berkeley Lab's new torsion muscle Care of the DOE's Lawrence Berkeley National Laboratory
“We’ve created a micro-bimorph dual coil that functions as a powerful torsional muscle, driven thermally or electro-thermally by the phase transition of vanadium dioxide,” said Junqiao Wu, the project’s lead scientist at the U.S. Department of Energy’s Lawrence Berkeley National Labs (Berkeley Labs).
The strength of the new robotic muscle comes from the special property that vanadium dioxide possesses. VO2 changes physical state when heated or cooled. The muscle, coincidentally in the shape of a V, is heated causing one dimension to contract while the other two dimensions expand, creating a torsion spring. Think catapult, but on a much smaller scale. While in its current state the muscle demonstrates the potential for what may be the future of artificial neuromuscular systems. Wu’s device functions in a way that creates a proximity sensor, which is very similar to the way biological muscles work. This torsion spring and proximity sensor features “allow the device to remotely detect a target and respond by reconfiguring itself to a different shape. This simulates living bodies where neurons sense and deliver stimuli to the muscles and the muscles provide motion,” according to Wu.
The micro-muscle requires a way of heating to actuate. As it stands, Wu thinks “electric current is the better way to go because it allows for the selective heating of individual micro-muscles and the heating and cooling process is much faster.” However, Berkeley Labs is working on a way for heat from the sun to trigger the device.
This announcement comes just three months after Dr. Adrian Koh of the National University of Singapore’s (NUS) Faculty of Engineering announced a similar muscle able to carry 80 times its own weight in September of this year. Both of these devices are at the forefront of more human-like robotics.
Dr. Koh suggests how these micro-muscles will change the game of humanoid robotics. “Our materials mimic those of the human muscle, responding quickly to electrical impulses, instead of slowly for mechanisms driven by hydraulics. Robots move in a jerky manner because of this mechanism. Now, imagine artificial muscles which are pliable, extendable and react in a fraction of a second like those of a human. Robots equipped with such muscles will be able to function in a more human-like manner – and outperform humans in strength.”
Robots like those seen the big budget Hollywood film “I, Robot” may no longer be an Asimovian dream, finding reality instead through people like Wu and Dr. Koh.
Posted by Miguel Vilar on December 24, 2013 
