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Decade-long experience of retroviral-modified chimeric antigen receptor T cells for treating cancer

Decade-long experience of retroviral-modified chimeric antigen receptor T cells for treating cancer | Amazing Science |

One child surviving ‘incurable’ cancer is an amazing event, but there is a lot more work to be done to find out how best to use this new technology. At the moment it’s still highly experimental and expensive. It’s only being trialled in a very small number of patients, primarily to make sure it is safe, and so far we’ve seen that it doesn’t work for everyone.


In the case of the child whose cancer came back after treatment, the researchers found that her cancer cells had somehow stopped carrying the T cells’ target molecule. So it’s likely that other targets will need to be identified, to make the treatment more effective for more patients in the future.


On a positive note, there’s no reason why this type of treatment should be restricted to cancers affecting the immune system (namely leukaemia and lymphoma), although they’re much more accessible to the killer T cells. Researchers elsewhere are investigating how to target a range of different types of cancer with this approach.


There are several similar therapies being tested in the lab and in clinical trials around the world, including in the UK. And Cancer Research UK scientists are finding out whether harmless genetically-engineered viruses could be used as therapeutic vaccines, training the immune system to seek and destroy cancer cells.


It’s still early days for these exciting new approaches and there are many hurdles to jump, but we’re looking forward to the day when they can be used to treat patients on a wider scale.

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20,000+ FREE Online Science and Technology Lectures from Top Universities | Amazing Science |



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ppGpp preserves DNA integrity in bacteria despite assault from antibiotics

ppGpp preserves DNA integrity in bacteria despite assault from antibiotics | Amazing Science |

A key biochemical enables bacteria to repair otherwise fatal damage to their DNA, including that caused by antibiotics. That is the finding of a study.


Adjusting the action of a molecule called ppGpp (guanosine-3',5'-(bis)pyrophosphate), with future treatments may disable DNA repair in microbes to make them many times more vulnerable to existing antibiotics, say the study authors. Bacteria repeatedly exposed to the same drugs become resistant to treatment, according to the Centers for Disease Control and Prevention, with related infections linked to 23,000 deaths and 2 million illnesses each year in the United States.


"Most antibiotics have their effect, directly or indirectly, by causing damage to bacterial DNA, so finding ways to cripple DNA repair would represent a significant advance in the treatment of resistant infections," says senior study author Evgeny Nudler, PhD, the Julie Wilson Anderson Professor of Biochemistry, Department of Biochemistry and Molecular Pharmacology, NYU Langone.


"While reducing DNA repair in bacteria could help to overcome antibiotic resistance, we're also excited about the prospect of boosting DNA repair in human cells," says Nudler, also an investigator with the Howard Hughes Medical Institute. "DNA damage accumulates with age and creates risk for degenerative diseases from Alzheimer's to cancer."


The study results revolve around the delicacy of DNA molecules, the letters making up the genetic code. Experts estimate that DNA is damaged thousands of times an hour in each bacterial cell, and perhaps a million times a day in a human cell with larger, more complicated DNA chains. Sunlight and toxins do much of the damage, but the biggest culprit may be highly reactive byproducts created as cells use oxygen to turn sugar into energy.


Given that damaged DNA can result in lethal mistakes in the building of proteins that comprise vital structures and messages, cells evolved early on to have overlapping, split-second DNA repair mechanisms.


In both humans and the bacteria, a key protein complex called RNA polymerase clamps onto and ticks down the DNA chain, reading the code of DNA "letters" as it translates genetic instructions into intermediary RNA molecules on the way to building proteins. Studies in recent years have revealed that the RNA polymerase in bacteria also inspects the DNA chain for damage as it reads.


In 1997, Nudler and colleagues published a paper in Cell that found bacterial RNA polymerase, which moves down the DNA chain in one direction during normal reading, instead stops and slips backward in some instances - a process Nudler called backtracking. If RNA polymerase encounters a lesion in DNA, the theory went, backtracking could make room for repair enzymes to fly in, cut out the damaged section, and rebuild a normal chain in a process called nucleotide excision DNA repair (NER).


Indeed, in 2014, Nudler's team published work in Nature that found the NER enzyme UvrD causes RNA polymerase to backtrack in the bacterial species E. coli. The newly published paper identifies ppGpp (guanosine-3',5'-(bis)pyrophosphate), a compound related in structure to the guanine building block of DNA, as the central controller of UvrD-driven backtracking in the NER pathway. Levels of ppGpp rise rapidly as bacterial RNA polymerase encounters damage and backtracks, then drop as soon as the chain is repaired to return RNA polymerase to normal transcription. The study authors conclude that ppGpp is the sensor that enables RNA polymerase to shift back and forth between DNA transcription and repair, coupling the two processes in bacteria.


Bacteria must be able to repair DNA and preserve their genomic integrity to survive, so targeting this ability is sound strategy for drug development, says Nudler. In seeking to translate this work into new treatments that defeat antibiotic resistance, he says, the field needs to determine whether or not RNA polymerase directly communicates with enzymes that produce ppGpp, and if they do, to design specific inhibitors against them.


Researchers also hope to soon confirm that RNA polymerase backtracking enables related forms of DNA repair in human cells as theorized, an important step toward boosting human DNA repair in the future.

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Duke's Poliovirus Oncolytic Therapy Wins "Breakthrough" Status

Duke's Poliovirus Oncolytic Therapy Wins "Breakthrough" Status | Amazing Science |

The recombinant poliovirus therapy developed at the Preston Robert Tisch Brain Tumor Center at Duke Health has been granted “breakthrough therapy designation” from the U.S. Food and Drug Administration.


Duke’s poliovirus therapy is an immunotherapy developed in the laboratory of Matthias Gromeier, M.D., a professor in the departments of Neurosurgery, Molecular Genetics and Microbiology, and Medicine at Duke University School of Medicine. 


Using a modified form of poliovirus that has been altered to eliminate harm, the therapy preferentially attacks cancer cells, which have an abundance of receptors that work like magnets to attract the poliovirus. The modified poliovirus then kills the infected tumor cells while also igniting an additional immune response.


A phase I clinical trial using the therapy was launched in 2012 to determine an optimal dose of the novel treatment among adult patients with glioblastoma whose cancer had returned after receiving traditional therapy.


Early testing found that lower doses of the treatment were superior to higher doses. Of 23 glioblastoma patients enrolled at the optimal dose level, 15 are still alive and enrollment is ongoing. Three patients treated early using different dosages are still alive more than 36 months after treatment. With current standard therapy, the median survival time for people with glioblastoma is 14.6 months. 


The Duke team is moving to expand its work and open a clinical trial for children with brain tumors, which is expected to begin enrollment before year’s end. The researchers have also received federal grants to explore the therapy’s effect on solid tumors. Laboratory studies are already underway in breast cancer models.

Via Krishan Maggon
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Genome Sequencing Reveals Differences Between Giraffes and Ocapi

Genome Sequencing Reveals Differences Between Giraffes and Ocapi | Amazing Science |

Scientists spot mutations that could explain how giraffes became the world’s tallest living mammals.


Call it a tall task: researchers have decoded the genomes of the giraffe and its closest relative, the okapi. The sequences, published on May 17 in Nature Communications, reveal clues to the age-old mystery of how the giraffe evolved its unusually long neck and legs.


Researchers in the United States and Tanzania analyzed the genetic material of two Masai giraffes (Giraffa camelopardalis tippelskirchi) from the Masai Mara National Reserve in Kenya, one at the Nashville Zoo in Tennessee and an okapi fetus (Okapia johnstoni) from the White Oak Conservation Center in Yulee, Florida.


“This is one more wonderful demonstration of the power of comparative genomics to connect the evolution of animal species on this planet to molecular events that we know must underpin the extraordinary diversity of life on this planet,” says David Haussler, director of the Genomics Institute at the University of California, Santa Cruz.


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The gene hunters 

The gene hunters  | Amazing Science |

Criss-crossing the globe on a quest for unusual DNA, researchers have discovered a rare mutation that promises insights into both epilepsy and autism — and points to a treatment.

Via Integrated DNA Technologies
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Disney’s VertiGo Combines Car, Helicopter to Seemingly Defy Gravity

Disney’s VertiGo Combines Car, Helicopter to Seemingly Defy Gravity | Amazing Science |

From Disney and ETH Zurich, this steam-punkish robot can transition from ground to wall and back again.


VertiGo is a wall-climbing robot that is capable of transitioning from the ground to the wall, created in collaboration between Disney Research Zurich and ETH. The robot has two tiltable propellers that provide thrust onto the wall, and four wheels. One pair of wheels is steerable, and each propeller has two degrees of freedom for adjusting the direction of thrust. By transitioning from the ground to a wall and back again, VertiGo extends the ability of robots to travel through urban and indoor environments. The robot is able to move on a wall quickly and with agility. The use of propellers to provide thrust onto the wall ensures that the robot is able to traverse over indentations such as masonry. The choice of two propellers rather than one enables a floor-to-wall transition – thrust is applied both towards the wall using the rear propeller, and in an upward direction using the front propeller, resulting in a flip onto the wall.

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'Virtual partner' elicits emotional responses from a human partner in real-time

'Virtual partner' elicits emotional responses from a human partner in real-time | Amazing Science |

Can machines think? That's what renowned mathematician Alan Turing sought to understand back in the 1950s when he created an imitation game to find out if a human interrogator could tell a human from a machine based solely on conversation deprived of physical cues. The Turing test was introduced to determine a machine's ability to show intelligent behavior that is equivalent to or even indistinguishable from that of a human. Turing mainly cared about whether machines could match up to humans' intellectual capacities.


But there is more to being human than intellectual prowess, so researchers from the Center for Complex Systems and Brain Sciences (CCSBS) in the Charles E. Schmidt College of Science at Florida Atlantic University set out to answer the question: "How does it 'feel' to interact behaviorally with a machine?"


They created the equivalent of an "emotional" Turing test, and developed a virtual partner that is able to elicit emotional responses from its human partner while the pair engages in behavioral coordination in real-time.


Results of the study, titled "Enhanced Emotional Responses during Social Coordination with a Virtual Partner," are recently published in the International Journal of Psychophysiology. The researchers designed the virtual partner so that its behavior is governed by mathematical models of human-to-human interactions in a way that enables humans to interact with the mathematical description of their social selves.


"Our study shows that humans exhibited greater emotional arousal when they thought the virtual partner was a human and not a machine, even though in all cases, it was a machine that they were interacting with," said Mengsen Zhang, lead author and a Ph.D. student in FAU's CCSBS. "Maybe we can think of intelligence in terms of coordinated motion within and between brains."


The virtual partner is a key part of a paradigm developed at FAU called the Human Dynamic Clamp -- a state-of-the-art human machine interface technology that allows humans to interact with a computational model that behaves very much like humans themselves. In simple experiments, the model -- on receiving input from human movement -- drives an image of a moving hand which is displayed on a video screen. To complete the reciprocal coupling, the subject sees and coordinates with the moving image as if it were a real person observed through a video circuit. This social "surrogate" can be precisely tuned and controlled -- both by the experimenter and by the input from the human subject.


"The behaviors that gave rise to that distinctive emotional arousal were simple finger movements, not events like facial expressions for example, known to convey emotion," said Emmanuelle Tognoli, Ph.D., co-author and associate research professor in FAU's CCSBS. "So the findings are rather startling at first."

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Hunting for hidden life on worlds orbiting old, red stars

Hunting for hidden life on worlds orbiting old, red stars | Amazing Science |

All throughout the universe, there are stars in varying phases and ages. The oldest detected Kepler planets (exoplanets found using NASA's Kepler telescope) are about 11 billion years old, and the planetary diversity suggests that around other stars, such initially frozen worlds could be the size of Earth and could even provide habitable conditions once the star becomes older. Astronomers usually looked at middle-aged stars like our sun, but to find habitable worlds, one needs to look around stars of all ages.


In their work, Ramses M. Ramirez, research associate at Cornell's Carl Sagan Institute and Lisa Kaltenegger, associate professor of astronomy and director of the Carl Sagan Institute, have modeled the locations of the habitable zones for aging stars and how long planets can stay in it. Their research, "Habitable Zones of Post-Main Sequence Stars," is published in the Astrophysical Journal May 16.


The "habitable zone" is the region around a star in which water on a planet's surface is liquid and signs of life can be remotely detected by telescopes.


"When a star ages and brightens, the habitable zone moves outward and you're basically giving a second wind to a planetary system," said Ramirez. "Currently objects in these outer regions are frozen in our own solar system, and Europa and Enceladus -- moons orbiting Jupiter and Saturn -- are icy for now."


Dependent upon the mass (weight) of the original star, planets and their moons loiter in this red giant habitable zone up to 9 billion years. Earth, for example, has been in our sun's habitable zone so far for about 4.5 billion years, and it has teemed with changing iterations of life. However, in a few billion years our sun will become a red giant, engulfing Mercury and Venus, turning Earth and Mars into sizzling rocky planets, and warming distant worlds like Jupiter, Saturn and Neptune -- and their moons -- in a newly established red giant habitable zone.


"Long after our own plain yellow sun expands to become a red giant star and turns Earth into a sizzling hot wasteland, there are still regions in our solar system -- and other solar systems as well -- where life might thrive," says Kaltenegger.


"For stars that are like our sun, but older, such thawed planets could stay warm up to half a billion years in the red giant habitable zone. That's no small amount of time," said Ramirez, who is the lead author of the study.

"In the far future, such worlds could become habitable around small red suns for billions of years, maybe even starting life, just like Earth. That makes me very optimistic for the chances for life in the long run," said Kaltenegger.

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This AI can recreate Nobel Prize-winning experiments

This AI can recreate Nobel Prize-winning experiments | Amazing Science |

Artificial intelligence developed by a group of Australian research teams has replicated a complex experiment which won the Nobel Prize for Physics in 2001. The intelligent machine learned how to run a Bose-Einstein condensation – isolating an extremely cold gas inside a beam of laser light – in under an hour, something the team "didn't expect". Results have been published in the Scientific Reports journal. The algorithm has also been uploaded to GitHub for other researchers working on "quantum experiments".


"A simple computer program would have taken longer than the age of the universe to run through all the combinations and work this out," said Paul Wigley, co-lead researcher of the study and professor at the School of Physics and Engineering at the Australian National University.


The gas was cooled to 1 microkelvin before the artificial intelligence was "handed control" of three laser beams in which to trap the gas. It also did things that "surprised" the team.


"It did things a person wouldn't guess – such as changing one laser's power up and down and compensating with another," said Wigley. "It may be able to come up with complicated ways humans haven't thought of to get experiments colder and more precise".

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Genetically Modified Crops Are Safe, National Academies Report Finds

Genetically Modified Crops Are Safe, National Academies Report Finds | Amazing Science |

Genetically modified crops on the market are not only safe, but appear to be good for people and the environment, experts determined in a report released Tuesday.


But the National Academies of Sciences, Engineering, and Medicine are not just asking people to take their word for it. They're putting the evidence up on a website so skeptics — and they know there are plenty of them — can check for themselves.


"The committee delved into the relevant literature, heard from 80 diverse speakers, and read more than 700 comments from members of the public to broaden its understanding of issues surrounding GE crops," the report reads. Panel members read more than 900 reports.


"It was tiring but worthwhile, because it really brought to our attention a lot of studies we would not have looked at," said Dominique Brossard, chair of the department of Life Sciences Communication at the University of Wisconsin.


"Our process was really, really inclusive and attempted to address as much as possible the concerns that were raised by public comments."


A lot of concern centered on health effects. "The committee received a number of comments from people concerned that GE food consumption may lead to higher incidence of specific health problems including cancer, obesity, gastrointestinal tract illnesses, kidney disease, and such disorders as autism spectrum and allergies," the report reads. "The committee also examined epidemiological data on incidence of cancers and other human-health problems over time and found no substantiated evidence that foods from GE crops were less safe than foods from non-GE crops."


Their conclusions:

  • There is no evidence of large-scale health effects on people from genetically modified foods
  • There is some evidence that crops genetically engineered to resist bugs have benefited people by reducing cases of insecticide poisoning
  • Genetically engineered crops to benefit human health, such as those altered to produce more vitamin A, can reduce blindness and deaths die to vitamin A deficiency
  • Using insect-resistant or herbicide-resistant crops did not damage plant or insect diversity and in some cases increased the diversity of insects.
  • Sometimes the added genes do leak out to nearby plants - a process called gene flow - but there is no evidence it has caused harm.
  • In general, farmers who use GM soybean, cotton, and corn make more money but it does depend on how bad pests are and farming practices.
  • GM crops do reduce losses to pests
  • If farmers use insect-resistant crops but don't take enough care, sometimes pest insects develop resistance

Outside experts said the report was very thorough and scientifically sound. It clearly shows that the anti-GMO hype is non-justified.


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Face recognition app taking Russia by storm may bring end to public anonymity

Face recognition app taking Russia by storm may bring end to public anonymity | Amazing Science |

If the founders of a new face recognition app get their way, anonymity in public could soon be a thing of the past. FindFace, launched two months ago and currently taking Russia by storm, allows users to photograph people in a crowd and work out their identities, with 70% reliability.


It works by comparing photographs to profile pictures on Vkontakte, a social network popular in Russia and the former Soviet Union, with more than 200 million accounts. In future, the designers imagine a world where people walking past you on the street could find your social network profile by sneaking a photograph of you, and shops, advertisers and the police could pick your face out of crowds and track you down via social networks.


In the short time since the launch, Findface has amassed 500,000 users and processed nearly 3m searches, according to its founders, 26-year-old Artem Kukharenko, and 29-year-old Alexander Kabakov.


Kukharenko is a lanky, quietly spoken computer nerd who has come up with the algorithm that makes FindFace such an impressive piece of technology, while Kabakov is the garrulous money and marketing man, who does all of the talking when the pair meet the Guardian.


Unlike other face recognition technology, their algorithm allows quick searches in big data sets. “Three million searches in a database of nearly 1 Billion photographs: that’s hundreds of trillions of comparisons, and all on four normal servers. With this algorithm, you can search through a billion photographs in less than a second from a normal computer,” said Kabakov, during an interview at the company’s modest central Moscow office. The app will give you the most likely match to the face that is uploaded, as well as 10 people it thinks look similar.


Kabakov says the app could revolutionize dating: “If you see someone you like, you can photograph them, find their identity, and then send them a friend request.” The interaction doesn’t always have to involve the rather creepy opening gambit of clandestine street photography, he added: “It also looks for similar people. So you could just upload a photo of a movie star you like, or your ex, and then find 10 girls who look similar to her and send them messages.”


Some have sounded the alarm about the potentially disturbing implications. Already the app has been used by a St Petersburg photographer to snap and identify people on the city’s metro, as well as by online vigilantes to uncover the social media profiles of female porn actors and harass them.

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World's first scanning helium microscope unveiled

World's first scanning helium microscope unveiled | Amazing Science |
Australian researchers build a world-first prototype of a new microscope that will open scientific doors.

Via Mariaschnee, CineversityTV
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Study offers new answer to why Earth's atmosphere became oxygenated

Study offers new answer to why Earth's atmosphere became oxygenated | Amazing Science |
Earth scientists from Rice University, Yale University and the University of Tokyo are offering a new answer to the long-standing question of how our planet acquired its oxygenated atmosphere.


Based on a new model that draws from research in diverse fields including petrology, geodynamics, volcanology and geochemistry, the team's findings were published online this week in Nature Geoscience. They suggest that the rise of oxygen in Earth's atmosphere was an inevitable consequence of the formation of continents in the presence of life and plate tectonics.


"It's really a very simple idea, but fully understanding it requires a good bit of background about how the Earth works," said study lead author Cin-Ty Lee, professor of Earth science at Rice. "The analogy I most often use is the leaky bathtub. The level of water in a bathtub is controlled by the rate of water flowing in through the faucet and the efficiency by which water leaks out through the drain. Plants and certain types of bacteria produce oxygen as a byproduct of photosynthesis. This oxygen production is balanced by the sink: reaction of oxygen with iron and sulfur in the Earth's crust and by back-reaction with organic carbon. For example, we breathe in oxygen and exhale carbon dioxide, essentially removing oxygen from the atmosphere. In short, the story of oxygen in our atmosphere comes down to understanding the sources and sinks, but the 3-billion-year narrative of how this actually unfolded is more complex."


Lee co-authored the study with Laurence Yeung and Adrian Lenardic, both of Rice, and with Yale's Ryan McKenzie and the University of Tokyo's Yusuke Yokoyama. The authors' explanations are based on a new model that suggests how atmospheric oxygen was added to Earth's atmosphere at two key times: one about 2 billion years ago and another about 600 million years ago.


Today, some 20 percent of Earth's atmosphere is free molecular oxygen, or O2. Free oxygen is not bound to another element, as are the oxygen atoms in other atmospheric gases like carbon dioxide and sulfur dioxide. For much of Earth's 4.5-billion-year history, free oxygen was all but nonexistent in the atmosphere.

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Shedding light on the 'dark matter' of the genome

Shedding light on the 'dark matter' of the genome | Amazing Science |

What used to be dismissed by many as "junk DNA" is back with a vengeance as growing data points to the importance of non-coding RNAs (ncRNAs)—genome's messages that do not code for proteins—in development and disease formation. But our progress in understanding these molecules has been slow because of the lack of technologies that allow the systematic mapping of their functions.


Now, Professor Benjamin Blencowe's team at the University of Toronto's Donnelly Centre, including lead authors Eesha Sharma and Tim Sterne-Weiler, have developed a method, described in May 19, 2016 issue of Molecular Cell, that enables scientists to explore in depth what ncRNAs do in human cells. The study is published on the same day with two other papers in Molecular Cell and Cell, respectively, from Dr. Yue Wan's group at the Genome Institute of Singapore and Dr. Howard Chang's group at Stanford University in California, who developed similar methods to study RNAs in different organisms.


Of the 3 billion letters in the human genome, only two per cent make up the protein-coding genes. The genes are copied, or transcribed, into messenger RNA (mRNA) molecules, which provide templates for building proteins that do most of the work in the cell. Much of the remaining 98 per cent of the genome was initially considered by some as lacking in functional importance. However, large swaths of the non coding genome—between half and three quarters of it—are also copied into RNA.


What the resulting ncRNAs might do depends on whom you ask. Some researchers believe that most ncRNAs have no function, that they are just a by-product of the genome's powerful transcription machinery that makes mRNA. However, it is emerging that many ncRNAs have important roles in gene regulation. This view is supported in that some ncRNAs act as carriages for shuttling the mRNAs around the cell, or provide a scaffold for other proteins and RNAs to attach to and do their jobs.


But the majority of available data has trickled in piecemeal or through serendipitous discovery. And with emerging evidence that ncRNAs could drive disease progression, such as cancer metastasis, there was a great need for a technology that would allow a systematic functional analysis of ncRNAs.


"Up until now, with existing methods, you had to know what you are looking for because they all require you to have some information about the RNA of interest. The power of our method is that you don't need to preselect your candidates, you can see what's occurring globally in cells, and use that information to look at interesting things we have not seen before and how they are affecting biology," says Eesha Sharma, a PhD candidate in Blencowe's group who, along with postdoctoral fellow Tim Sterne-Weiler, co-developed the method.


The new tool, called 'LIGR-Seq', captures interactions between different RNA molecules. When two RNA molecules have matching sequences - strings of letters copied from the DNA blueprint - they will stick together like Velcro. The paired RNA structures are then removed from cells and analyzed by state-of-the-art sequencing methods to precisely identify the RNAs that are stuck together. "Most researchers in the life sciences agree that there's an urgent need to understand what ncRNAs do. This technology will open the door to developing a new understanding of ncRNA function," says Blencowe, who is also a professor in the Department of Molecular Genetics.


Not having to rely on pre-existing knowledge is one strength of the method that will boost the discovery of RNA pairs that have never been seen before. The other is that scientists can for the first time look at RNA interactions as they occur in living cells, in all their complexity, unlike in the juices of mashed up cells that they had to rely on before. This is a bit like moving on to explore marine biology from collecting shells on the beach to scuba-diving among the coral reefs where the scope for discovery is so much bigger.

ncRNAs come in multiple flavours: there's rRNA, tRNA, snRNA, snoRNA, piRNA, miRNA, and lncRNA, to name a few, where prefixes reflect the RNA's place in the cell or some aspect of its function. But the truth is that no one really knows the extent to which these ncRNAs control what goes on in the cell, nor how they do this. The new technology developed by Blencowe's group has been able to pick up new interactions involving all classes of RNAs and has already revealed some unexpected findings.

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With a few skin cells, scientists can make mini, thinking version of your brain

With a few skin cells, scientists can make mini, thinking version of your brain | Amazing Science |

Tiny, rolling balls of brain cells knocking around in a lab may one day help keep you from losing your marbles—among other things.

The small cellular balls act like mini-brains, mimicking aspects of the real thing, including forming noggin-like structures and pulsing with electrical signals like a thinking mind, researchers reported Friday at the annual meeting of the American Association for the Advancement of Science in Washington. The mini-brains, which can be personalized based on whose cells they’re made from, may soon help scientists study a wide variety of diseases and health problems—from autism and Parkinson’s to multiple sclerosis and Alzheimer’s, as well as stroke, brain trauma, and infections, such as Zika virus.


“There are a variety of places where a mini brain could be useful,” said Wayne Drevets of Janssen Pharmaceuticals Inc., who was not involved with the research. In some cases, they may offer a cheaper, more ethical, and more realistic model for human health than mice and other animals, he and other researchers said at the conference.


Researchers who developed the wee noodles, led by Thomas Hartung, of Johns Hopkins University Bloomberg School of Public Health, hope to have the mini-brains commercially available this year.

Via Krishan Maggon
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Biochemistry and Cell Biology of Tau in Neurofibrillary Degeneration

Biochemistry and Cell Biology of Tau in Neurofibrillary Degeneration | Amazing Science |

The tau protein is a subunit of one of the major hallmarks of Alzheimer disease (AD), the neurofibrillary tangles, and is therefore of major interest as an indicator of disease mechanisms. Many of the unusual properties of Tau can be explained by its nature as a natively unfolded protein. Examples are the large number of structural conformations and biochemical modifications (phosphorylation, proteolysis, glycosylation, and others), the multitude of interaction partners (mainly microtubules, but also other cytoskeletal proteins, kinases, and phosphatases, motor proteins, chaperones, and membrane proteins). The pathological aggregation of Tau is counterintuitive, given its high solubility, but can be rationalized by short hydrophobic motifs forming β structures. The aggregation of Tau is toxic in cell and animal models, but can be reversed by suppressing expression or by aggregation inhibitors. This review summarizes some of the structural, biochemical, and cell biological properties of Tau and Tau fibers. Further aspects of Tau as a diagnostic marker and therapeutic target, its involvement in other Tau-based diseases, and its histopathology are covered by other chapters in this volume.

Via Krishan Maggon
Krishan Maggon 's curator insight, May 18, 2:01 AM
Cold Spring Harb Perspect Med. 2012 Jul; 2(7): a006247. 
doi: 10.1101/cshperspect.a006247 PMCID: PMC3385935 

Biochemistry and Cell Biology of Tau Protein in Neurofibrillary Degeneration 

Eva-Maria Mandelkow and Eckhard Mandelkow

Image   Visualization of Tau and kinesin bound to microtubules.
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Self-healing, flexible electronic material restores functions after many breaks

Self-healing, flexible electronic material restores functions after many breaks | Amazing Science |

Electronic materials have been a major stumbling block for the advance of flexible electronics because existing materials do not function well after breaking and healing. A new electronic material created by an international team, however, can heal all its functions automatically even after breaking multiple times. This material could improve the durability of wearable electronics.


"Wearable and bendable electronics are subject to mechanical deformation over time, which could destroy or break them," said Qing Wang, professor of materials science and engineering, Penn State. "We wanted to find an electronic material that would repair itself to restore all of its functionality, and do so after multiple breaks."


Self-healable materials are those that, after withstanding physical deformation such as being cut in half, naturally repair themselves with little to no external influence.


In the past, researchers have been able to create self-healable materials that can restore one function after breaking, but restoring a suite of functions is critical for creating effective wearable electronics. For example, if a dielectric material retains its electrical resistivity after self-healing but not its thermal conductivity, that could put electronics at risk of overheating.


The material that Wang and his team created restores all properties needed for use as a dielectric in wearable electronics -- mechanical strength, breakdown strength to protect against surges, electrical resistivity, thermal conductivity and dielectric, or insulating, properties. They published their findings online in Advanced Functional Materials.


Most self-healable materials are soft or "gum-like," said Wang, but the material he and his colleagues created is very tough in comparison. His team added boron nitride nanosheets to a base material of plastic polymer. Like graphene, boron nitride nanosheets are two dimensional, but instead of conducting electricity like graphene they resist and insulate against it.


Via Mariaschnee, CineversityTV
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Autonomous Mini Rally Car Teaches Itself to Powerslide

Autonomous Mini Rally Car Teaches Itself to Powerslide | Amazing Science |

Most autonomous vehicle control software is deliberately designed for well-constrained driving that's nice, calm, and under control. Not only is this a little bit boring, it's also potentially less safe: If your car autonomous vehicle has no experience driving aggressively, it won't know how to manage itself if something goes wrong. 


At Georgia Tech, researchers are developing control algorithms that allow small-scale autonomous cars to power around dirt tracks at ludicrous speeds. They presented some this week at the 2016 IEEE International Conference on Robotics and Automation in Stockholm, Sweden. Using real-time onboard sensing and processing, the little cars maximize their speed while keeping themselves stable and under control. Mostly.


The electrically powered research platform pictured above, which is a scale model one-fifth the size of a vehicle meant for human occupants, is called AutoRally. It's about a meter long, weighs 21kg, and has a top speed of nearly 100 kilometers per hour. It's based on an R/C truck chassis, with some largely 3D-printed modifications to support a payload that includes a GPS, IMU, wheel encoders, a pair of fast video cameras, and a beefy quad-core i7 computer with a Nvidia GTX 750ti GPU and 32 gigs of RAM. All of this stuff is protected inside of an aluminum enclosure that makes crashing (even crashing badly) not that big of a deal.


The researchers attest that most of the crashes in the video happened due to either software crashes (as opposed to failures of the algorithm itself), or the vehicle having trouble adapting to changes in the track surface. Since that video was made, they've upgraded the software to make it able to handle a more realistically dynamic environment. The result: AutoRally is now able to drive continuously on a track that, because of temperature changes, goes from, say, partially frozen to a huge puddle of mud over the course of a couple of hours.

They’ve placed all of AutoRally’s specs online (and made the software available on Github) in the hopes that other vehicle autonomy researchers will be able to take advantage of the platform’s robust, high-performance capabilities. The code is open source and ROS compatible, with an accompanying Gazebo-based simulation.

We're hoping that this algorithm will eventually be mature enough to be tried out on a full-size rally car (maybe in a little friendly competition with a human driver). But if that does ever happen, crashing will be a much bigger deal than it is now.

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Printing metal in midair with laser-assisted direct-ink 3D printing

Printing metal in midair with laser-assisted direct-ink 3D printing | Amazing Science |

"Flat" and "rigid" are terms typically used to describe electronic devices. But the increasing demand for flexible, wearable electronics, sensors, antennas and biomedical devices has led a team at Harvard's Wyss Institute for Biologically Inspired Engineering and the John A. Paulson School of Engineering and Applied Sciences (SEAS) to innovate an eye-popping new way of printing complex metallic architectures -- as though they are seemingly suspended in midair.


Reported online May 16, 2016 in the Proceedings of the National Academy of Sciences, this laser-assisted direct ink writing method allows microscopic metallic, free-standing 3D structures to be printed in one step without auxiliary support material. The research was led by Wyss Core Faculty member Jennifer Lewis, Sc.D., who is also the Hansjörg Wyss Professor of Biologically Inspired Engineering at SEAS.


"I am truly excited by this latest advance from our lab, which allows one to 3D print and anneal flexible metal electrodes and complex architectures 'on-the-fly,' " said Lewis.


Lewis' team used an ink composed of silver nanoparticles, sending it through a printing nozzle and then annealing it using a precisely programmed laser that applies just the right amount of energy to drive the ink's solidification. The printing nozzle moves along x, y, and z axes and is combined with a rotary print stage to enable freeform curvature. In this way, tiny hemispherical shapes, spiral motifs, even a butterfly made of silver wires less than the width of a hair can be printed in free space within seconds. The printed wires exhibit excellent electrical conductivity, almost matching that of bulk silver.


When compared to conventional 3D printing techniques used to fabricate conductive metallic features, laser-assisted direct ink writing is not only superior in its ability to produce curvilinear, complex wire patterns in one step, but also in the sense that localized laser heating enables electrically conductive silver wires to be printed directly on low-cost plastic substrates.

According to the study's first author, Wyss Institute Postdoctoral Fellow Mark Skylar-Scott, Ph.D., the most challenging aspect of honing the technique was optimizing the nozzle-to-laser separation distance.


"If the laser gets too close to the nozzle during printing, heat is conducted upstream which clogs the nozzle with solidified ink," said Skylar-Scott. "To address this, we devised a heat transfer model to account for temperature distribution along a given silver wire pattern, allowing us to modulate the printing speed and distance between the nozzle and laser to elegantly control the laser annealing process 'on the fly.' "

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Combining nanotextured surfaces with the Leidenfrost effect for extreme water repellency

Combining nanotextured surfaces with the Leidenfrost effect for extreme water repellency | Amazing Science |

Combining superhydrophobic surfaces with Leidenfrost levitation--picture a water droplet hovering over a hot surface rather than making physical contact with it--has been explored extensively for the past decade by researchers hoping to uncover the holy grail of water-repellent surfaces.


In a new twist, a group of South Korean researchers from Seoul National University and Dankook University report an anomalous water droplet-bouncing phenomenon generated by Leidenfrost levitation on nano-textured surfaces in Applied Physics Letters.


"Wettability plays a key role in determining the equilibrium contact angles, contact angle hysteresis, and adhesion between a solid surface and liquid, as well as the retraction process of a liquid droplet impinged on the surface," explained Doo Jin Lee, lead author, and a postdoctoral researcher in the Department of Materials and Engineering at Seoul National University.


Non-wetting surfaces tend to be created by one of two methods. "First, textured surfaces enable non-wettability because a liquid can't penetrate into the micro- or nano-features, thanks to air entrapment between asperities on the textured materials," Lee said.


Or, second, the Leidenfrost effect "can help produce a liquid droplet dancing on a hot surface by floating it on a cushion of its own vapor," he added. "The vapor film between the droplet and heated surface allows the droplet to bounce off the surface--also known as the 'dynamic Leidenfrost phenomenon.'"


Lee and colleagues developed a special "non-wetting, nano-textured surface" so they could delve into the dynamic Leidenfrost effect's impact on the material.


"Our nano-textured surface was verified to be 'non-wetting' via thermodynamic analysis," Lee elaborated. "This analytical approach shows that the water droplet isn't likely to penetrate into the surface's nanoholes, which is advantageous for designing non-wetting, water-repellant systems. And the water droplet bouncing was powered by the synergetic combination of the non-wetting surface--often called a 'Cassie surface'--and the Leidenfrost effect."

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Jupiter's moon: Europa's ocean may have an Earthlike chemical balance

Jupiter's moon: Europa's ocean may have an Earthlike chemical balance | Amazing Science |
The ocean of Jupiter's moon Europa could have the necessary balance of chemical energy for life, even if the moon lacks volcanic hydrothermal activity, finds a new study.


Europa is strongly believed to hide a deep ocean of salty liquid water beneath its icy shell. Whether the Jovian moon has the raw materials and chemical energy in the right proportions to support biology is a topic of intense scientific interest. The answer may hinge on whether Europa has environments where chemicals are matched in the right proportions to power biological processes. Life on Earth exploits such niches.


In the new study published in Geophysical Research Letters, a journal of the American Geophysical Union, scientists at NASA's Jet Propulsion Laboratory (JPL), Pasadena, California, compared Europa's potential for producing hydrogen and oxygen with that of Earth, through processes that do not directly involve volcanism. The balance of these two elements is a key indicator of the energy available for life. The study found that the amounts would be comparable in scale; on both worlds, oxygen production is about 10 times higher than hydrogen production.


The work draws attention to the ways that Europa's rocky interior may be much more complex and possibly Earthlike than people typically think, according to Steve Vance, a planetary scientist at JPL and lead author of the new study. "We're studying an alien ocean using methods developed to understand the movement of energy and nutrients in Earth's own systems. The cycling of oxygen and hydrogen in Europa's ocean will be a major driver for Europa's ocean chemistry and any life there, just it is on Earth."


Ultimately, Vance and colleagues want to also understand the cycling of life's other major elements in the ocean: carbon, nitrogen, phosphorus and sulfur.


As part of their study, the researchers calculated how much hydrogen could potentially be produced in Europa's ocean as seawater reacts with rock in a process called serpentinization. In this process, water percolates into spaces between mineral grains and reacts with the rock to form new minerals, releasing hydrogen in the process. The researchers considered how cracks in Europa's seafloor likely open up over time, as the moon's rocky interior continues to cool following its formation billions of years ago. New cracks expose fresh rock to seawater, where more hydrogen-producing reactions can take place.

In Earth's oceanic crust, such fractures are believed to penetrate to a depth of 5 to 6 kilometers (3 to 4 miles). On present-day Europa, the researchers expect water could reach as deep as 25 kilometers (15 miles) into the rocky interior, driving these key chemical reactions throughout a deeper fraction of Europa's seafloor.


The other half of Europa's chemical-energy-for-life equation would be provided by oxidants -- oxygen and other compounds that could react with the hydrogen -- being cycled into the Europan ocean from the icy surface above. Europa is bathed in radiation from Jupiter, which splits apart water ice molecules to create these materials. Scientists have inferred that Europa's surface is being cycled back into its interior, which could carry oxidants into the ocean.

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Complex life on Earth began a billion years earlier than previously thought, study argues

Complex life on Earth began a billion years earlier than previously thought, study argues | Amazing Science |

A claim by researchers that complex life on Earth may have evolved a billion years earlier than previously thought has immediately divided scientists in the field, with some hailing the evidence as rock-solid and others unconvinced.

The researchers, writing in the journal Nature Communications, said they had uncovered fossils showing that complex life on Earth began more than 1.5bn years ago.

After first emerging from the primordial soup, life remained primitive and single-celled for billions of years, but some of those cells eventually congregated like clones in a colony. Scientists took to calling the later part of this period the “boring billion” because evolution seemed to have stalled.

But at some point there was a leap – arguably second in importance only to the appearance of life itself – towards complex organisms with multiple cells.

This transition progressively gave rise to all the plants and animals that have ever existed.

Exactly when multi-celled “eukaryotes” – organisms in which differentiated cells each contain a membrane-bound nucleus with genetic material – showed up has inflamed scientific passions for many decades.

“Our discovery pushes back nearly one billion years the appearance of macroscopic, multi-cellular eukaryotes compared to previous research,” said Maoyan Zhu, a professor at the Nanjing Institute of Geology and Palaeontology.

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Two-beam super-resolution lithography to make 3D photonic 'gyroid' nanostructures

Two-beam super-resolution lithography to make 3D photonic 'gyroid' nanostructures | Amazing Science |

"A team of researchers with Swinburne University of Technology in Australia has found a way to use two-beam super-resolution lithography to create 3D photonic "gyroid" nanostructures—similar to those found in butterfly wings. In their paper published in the journal Science Advances, the team describes their technique and some applications to which it might be applied.

Scientists have known for some time that butterfly wings have "gyroid" nanostructures in them (arranged in grid patterns), that serve the butterflies by manipulating light in useful ways. In addition to their photonic properties, the structures, which are made of intertwining curved surfaces, were also found to be very strong for their size, which has caused scientists to see if they might find a way to create them artificially. Up till now, such efforts have left a lot to be desired—most do not have a high enough resolution or are too fragile. In this new effort, the researchers report that rather than rely on traditional methods, such as two-photon polymerization, the team went with optical two-beam super-resolution lithography—they compare it to direct laser writing techniques, noting that it has two major advantages over other techniques used in the past. The first is that it offers much better resolution and the second is that the resulting structure has more mechanical strength."

Via Mariaschnee
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Bird DNA shows inbreeding linked to shorter lifespan 

Bird DNA shows inbreeding linked to shorter lifespan  | Amazing Science |

Pieces of DNA that predict lifespan are shorter in birds that are inbred – according to new research from the University of East Anglia (UEA). The findings, published today, mean that inbreeding could be linked to a shorter lifespan.


The team also found effects that spanned generations – with the young of inbred mothers also being negatively affected. The DNA pieces in question, known as telomeres, are found in almost all animals - including humans. They act as protective caps at each end of a chromosome - providing protection from damaging substances.


Lead author of the research Kat Bebbington, a PhD student in UEA’s School of Biological Sciences, said: “Telomeres are a bit like the hard plastic ends of a boot lace. Over time, they get broken down and become shorter because they absorb all the damage experienced during life.


“The rate at which this happens reflects how much stress the body is under – and importantly, how long it can continue to function. In humans, things like smoking, eating foods that are bad for you, and putting your body through extreme physical or mental stress all have a shortening effect on telomeres. In the wild, inbred animals are less able to cope when the environment is bad, and the stress of such situations causes further telomere shortening. "In short - the healthier you are, or have been, the better telomeres you have and the less quickly you age. Inbred animals are more susceptible to disease or poorly developed because they don’t have much variation in the genes they carry, plus whenever life gets difficult, they can’t cope as well outbred animals.”


Previous research from UEA revealed that the length of an animal’s telomeres predicts its biological age and how long it will live. However, this new research is the first to suggest that inbreeding - mating between related individuals - is linked to shorter telomeres in their young.


The research team, led by Prof David S Richardson at UEA, studied a 320-strong population of Seychelles warblers - a small island bird endemic to the Seychelles islands. A total of 1,064 DNA samples were collected from 592 birds over 14 years. The researchers used these samples to analyze telomere length and how this shortens over time.

Via Integrated DNA Technologies
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Biological evolution was preceded by a long phase of chemical evolution

Biological evolution was preceded by a long phase of chemical evolution | Amazing Science |

Biological evolution was preceded by a long phase of chemical evolution during which precursors of biopolymers accumulated. LMU chemists have discovered an efficient mechanism for the prebiotic synthesis of a vital class of such compounds.


How did life originate on Earth and what were its chemical building-blocks? One possible source of answers to these questions can be found in outer space. On the surface of comets planetary scientists have detected simple organic molecules that could also have been available on the young Earth – either because they were present in the material from which our planet was formed or were subsequently delivered by comets or meteorites. LMU chemist Thomas Carell and members of his research group have now shown that, under the conditions that prevailed on the young Earth, these simple molecules could indeed have served as precursors for the synthesis of one class of molecules that is an integral part of all forms of life on Earth. In addition, they have validated a plausible reaction mechanism for the production of these compounds. The new findings appear in the leading journal Science (2016).


Before self-replicating systems could be assembled, prebiotic chemistry must first have given rise to the subunits that form the basis for the complex biopolymers found in all modern organisms – the proteins and the nucleic acids that specify their structures. Unfortunately, little is known about the range of small organic compounds that was present on the young Earth. However, recent discoveries made by the European Space Agency’s Rosetta mission to the comet 67/P/Churyumov-Gerasimenko have given us some new leads. When Rosetta’s lander module Philae first made contact with the comet’s surface, it bounced off, and dust was wafted into its mass spectrometer. The ensuing analysis enabled mission scientists to identify 16 simple organics in the sample. In addition to water and carbon monoxide, the catalog included a number of nitrogen-containing components, such as formamide and hydrogen cyanide.


“We have now looked for ways in which these very simple substances could have given rise to the complex organic building-blocks of life under conditions similar to those that are thought to have existed on the young Earth. In particular, we were interested in the synthesis of key components of RNA,” Carell explains. The origin of RNA is central to an understanding of prebiotic chemistry. This is because RNA is potentially capable of catalyzing its own synthesis and facilitating several other biochemical reactions, and also possesses the capacity to store genetic information. A preliminary analysis of possible synthetic routes led the LMU team to a reaction scheme - the so-called FaPy pathway - that could have enabled purines to form under prebiotic conditions. Two of the five types of nucleotide bases that encode the genetic information stored in RNA and DNA are purines. They also form part of the molecules ATP und GTP, both of which serve as energy sources for biochemical reactions and as molecular switches in the control of protein function.


The FaPy pathway begins with the attachment of formamide to aminopyrimidines, nitrogen-containing rings which can be produced by a series of reactions between hydrogen cyanide molecules (and are themselves closely related to the other three bases found in nucleic acids). This gives rise to formamidopyrimidines, hence the acronym FaPy for the pathway as a whole. A subsequent sequence of reaction steps converts formamidopyridines into the purines adenine and guanine, and several of their biologically important derivatives. “Some 70% of the products of the FaPy pathway are purines, with adenosine – an important subunit of RNA – accounting for about 20%. With the FaPy mechanism, we have thus discovered a synthetic pathway that provides central biochemical components of life in high yield and with high specificity,” Carell explains. “So the FaPy mechanism constitutes an experimentally attested scenario that can explain how the process of chemical evolution could have proceeded during the phase prior to the formation of the first cells.”

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Scientists create novel 'liquid wire' material inspired by spiders' capture silk

Scientists create novel 'liquid wire' material inspired by spiders' capture silk | Amazing Science |

Why doesn't a spider's web sag in the wind or catapult flies back out like a trampoline? The answer, according to new research by an international team of scientists, lies in the physics behind a 'hybrid' material produced by spiders.


Pulling on a sticky thread in a garden spider's orb web and letting it snap back reveals that the thread never sags but always stays taut—even when stretched to many times its original length. This is because any loose thread is immediately spooled inside the tiny droplets of watery glue that coat and surround the core gossamer fibers of the web's capture spiral.

This phenomenon is described in the journal PNAS by scientists from the University of Oxford, UK and the Université Pierre et Marie Curie, Paris, France.


The researchers studied the details of this 'liquid wire' technique in spiders' webs and used it to create composite fibers in the laboratory which, just like the spider's capture silk, extend like a solid and compress like a liquid. These novel insights may lead to new bio-inspired technology.


Professor Fritz Vollrath of the Oxford Silk Group in the Department of Zoology at Oxford University said: 'The thousands of tiny droplets of glue that cover the capture spiral of the spider's orb web do much more than make the silk sticky and catch the fly. Surprisingly, each drop packs enough punch in its watery skins to reel in loose bits of thread. And this winching behavior is used to excellent effect to keep the threads tight at all times, as we can all observe and test in the webs in our gardens.'

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