#Gene on-off switch works like backpack strap A research team based in Houston's Texas Medical center has found that the proteins that turn genes on by forming loops in human chromosomes work like the sliding plastic adjusters on a grade-schooler
's backpack. This discovery could provide new clues about genetic diseases and allow researchers to reprogram cells by directly modifying the loops in genomes.
The study, which appears online this week in the Proceedings of the National Academy of Sciences,
is by the same team that published the first high-resolution 3-D maps showing how the human genome folds inside the nucleus of a cell.
The multi-institutional group includes researchers from Baylor College of Medicine Rice university, Stanford university and the Broad Institute.
Every human cell contains a genome, a linear string of DNA. Sequences of DNA bases spell out genes,
much like letters spell out words. For decades, scientists have known that genes that lie far apart on the string can activate one another by looping back
and coming into contact during genome folding. Last year, the team showed that it was possible to map the positions of these loops,
and the researchers created the first atlas of loops in the human genome. But the group couldn't explain how the loops were forming."
what our data really meant, "said senior author Erez Lieberman Aiden, a geneticist and computer scientist with joint appointments at Baylor and Rice."
"Then one day, we realized that we'd been carrying the solution around--literally, on our back--for decades!"
"The human genome contains more than 20,000 genes. In any given cell, only a fraction of these are active,
Aiden, who is also a senior investigator at Rice's Center for Theoretical Biological Physics,
"said study co-first author Adrian Sanborn, a graduate student in the Aiden lab and at Stanford university."
"Aiden, assistant professor of genetics at Baylor and of computer science and computational and applied mathematics at Rice, said Sanborn
and study co-first author Suhas Rao showed that they could combine the tri-glide model with mathematics
and high-performance computation to predict how a genome will fold. The team confirmed their predictions by making tiny modifications in a cell's genome
and showing that the mutations changed the folding pattern exactly as expected. Rao likened the result to a new form of genome surgery:
a procedure that can modify how a genome is folded by design and with extraordinary precision.""We found that changing even one letter in the genetic code was enough to modify the folding of millions of other letters,
"said Rao, a graduate student in the Aiden lab and at Stanford university.""What was stunning was that once we understood how the loops were forming,
the results of these changes became extremely predictable.""Sanborn said the discovery also explains a puzzling pattern that the team noticed
when it published its original atlas of loops.""DNA encodes information, and you can think of each DNA base pair as a letter and of certain sequences of letters as words,
"he said.""In our data, we noticed that when particular keywords appeared, a loop would form.
But the loop would only form if the two keywords were pointing at one another. For example, if one side of the loop read K-E-Y-W-O-R-D,
and the genome is flexible at that scale, "said Sanborn.""If I were a protein,
but they proved mathematically that such packing could not explain the data. Next, the researchers tested a model of DNA folding where tension along the DNA chain caused it to condense like an elastic band,
but this model also did not fit the data. Eventually, they hit on the tri-glide model.
The basic idea is that the tri-glide protein complex lands on the genome and pulls the strand from each side so that a loop forms in the middle--just like the loop someone might make
which acts like a brake,"said Rao, a student in the Aiden lab and at Stanford university."
"Aiden said that one of the most astonishing implications of the new model is that loops on different chromosomes tend not to become entangled."
when two bits of the genome wiggled around and then met inside the cell nucleus, "Aiden said."
"But this process would lead to interweaving loops and highly entangled chromosomes. This is a big problem
if you need those chromosomes to separate again when the cell divides.""The tri-glide takes care of that,
#Cyclic healing removes defects in metals while maintaining strength When designing a new material, whether for an airplane, car, bridge, mobile device,
or biological implant, engineers strive to make the material strong and defect-free. However, methods conventionally used to control the amount of defects in a material,
such as applying heat or mechanical stress, can also have undesirable consequences in terms of the material's strength, structure and performance.
An international team of researchers, including Carnegie mellon University President Subra Suresh, Zhiwei Shan and colleagues from Xi'an Jiaotong University in China, Ming Dao and Ju Li from MIT
and Evan Ma from Johns hopkins university, has developed a new technique called cyclic healing that uses repetitive,
gentle stretching to eliminate preexisting defects in metal crystals. Their results have been published online today (Monday, Oct 19) in the Proceedings of the National Academy of Sciences.
Most materials are made of crystals. When materials fail, it is usually the result of defects in the crystal or in the arrangement of multiple crystals in a polycrystalline structure.
While much research has been done on metal fatigue at larger scales, new technologies are just now allowing researchers to see how atomic-scale defects nucleate,
In this study, the researchers used transmission electron microscopy to look inside sub-micrometer-sized specimens of aluminum crystals as they subjected the samples to stressors like repeated, small-amplitude deformation or fatigue loading.
a process that repetitively stretches the crystal, helps to unpin or shakedown rows of atomic defects known as dislocations in the metal and move these dislocations closer to free surfaces in the sample.
Image forces, which act to minimize the energy of the defects, attract the dislocations closer to the free surfaces and force them out of the crystal.
As a result, the crystal"heals,"becoming essentially free of preexisting dislocations, thereby significantly increasing its strength.
This finding was surprising to researchers because cyclic deformation has an opposite effect in micro-and macro-scale metal crystals.
In these larger samples, repeated stretching generally leads to the creation, accumulation and interaction of defects,
which can lead to cracking and failure.""This work demonstrates how cyclic deformation, under certain controlled conditions, can lead to the removal of defects from crystals of small volume,
"says Suresh, who holds the Henry L. Hillman President's Chair at CMU.""It also points to potential new pathways for engineering the defect structure of metal components in a variety of sub-micro-scale systems
#From good to bad with a copper switch At the molecular level, the difference between Doctor Jekyll and Mr Hyde lies in a metal, copper.
In its physiological form, the prion protein (Prpc) is'good 'and is involved in normal body processes.
and animals (it is responsible for neurodegenerative diseases such as spongiform encephalopathies). According to a new SISSA study, the mechanism underlying this change is a metal, copper,
or rather a particular region of the protein to which the metal binds, which acts as a sort of'switch'that turns Prpc into its terrible alter ego."
"explains Giuseppe Legname, professor at the International school for Advanced Studies (SISSA) in Trieste who coordinated the new study,
"nor do we know any treatments to cure prion diseases. Our research has uncovered finally a critical cofactor,
which binds to an amino acid sequence of the prion protein, known as'fifth copper binding site,
the researchers used multidisciplinary experimental approaches, ranging from structural to cellular biology.""It all started with an intuition we published in the journal Biochemistry in 2012,
"explains Gabriele Giachin, first author of the study and former SISSA Phd student (today at the European Synchrotron radiation Facility, ESRF, in Grenoble, France)."
"On that occasion, we hypothesized that the pathological genetic mutations present in the prion protein could affect copper coordination".
"Starting from this intuition, Giachin and colleagues went on to conduct in depth experiments using XAFS (X-ray absorption fine structure) spectroscopy,
Then, drawing on the consolidated expertise in molecular and cellular biology available at the SISSA Laboratory of Prion Biology coordinated by Legname,
opening the way for the development of new drugs targeting this copper binding site, and thus for new potential treatments".
Giulia Salzano and Federico Benetti) and a group coordinated by the University of Rome"La Sapienza",led by Paola D'Angelo.
(or"bad")form capable of causing degeneration of nervous tissue and diseases, some of which very severe.
Among the diseases are Creutzfeld Jakob disease in humans and"mad cow disease in cattle. Unique in nature
#Super-slick material makes steel better, stronger, cleaner Steel is ubiquitous in our daily lives.
We cook in stainless steel skillets, ride steel subway cars over steel rails to our offices in steel-framed building.
Steel screws hold together broken bones, steel braces straighten crooked teeth, steel scalpels remove tumors.
Most of the goods we consume are delivered by ships and trucks mostly built of steel.
While various grades of steel have been developed over the past 50 years, steel surfaces have remained largely unchanged--and unimproved.
The steel of today is as prone as ever to the corrosive effects of water and salt and abrasive materials such as sand.
Steel surgical tools can still carry microorganisms that cause deadly infections. Now researchers at the Harvard John A. Paulson School of engineering and Applied sciences (SEAS) have demonstrated a way to make steel stronger, safer and more durable.
Their new surface coating, made from rough nanoporous tungsten oxide, is the most durable antifouling and anti-corrosive material to date,
capable of repelling any kind of liquid even after sustaining intense structural abuse. The new material joins the portfolio of other nonstick,
antifouling materials developed in the lab of Joanna Aizenberg, the Amy Smith Berylson Professor of Materials science and core faculty member of the Wyss Institute for Biologically Inspired Engineering at Harvard university.
Aizenberg's team developed Slippery Liquid-Infused Porous Surfaces in 2011 and since then has demonstrated a broad range of applications for the super-slick coating, known as SLIPS.
The new SLIPS-enhanced steel is described in Nature Communications.""Our slippery steel is orders of magnitude more durable than any antifouling material that has been developed before,
"said Aizenberg.""So far, these two concepts-mechanical durability and antifouling-were at odds with each other.
We need surfaces to be textured and porous to impart fouling resistance but rough nanostructured coatings are intrinsically weaker than their bulk analogs.
This research shows that careful surface engineering allows the design of a material capable of performing multiple, even conflicting, functions, without performance degradation."
"The material could have far-ranging applications and avenues for commercialization, including non-fouling medical tools and devices, such as implants and scalpels, nozzles for 3d printing and, potentially, larger-scale applications for buildings and marine vessels.
The biggest challenge in the development of this surface was to figure out how to structure steel to ensure its antifouling capability without mechanical degradation.
The team solved this by using an electrochemical technique to grow an ultrathin film of hundreds of thousands of small and rough tungsten-oxide islands directly onto a steel surface."
"If one part of an island is destroyed, the damage doesn't propagate to other parts of the surface because of the lack of interconnectivity between neighboring islands,
"Electrochemical deposition is already a widely used technique in steel manufacturing, said Aizenberg.""I don't want to create another line that would cost millions
and millions of dollars and that no one would adopt, "Aizenberg said. The goal, she said,
The team tested the material by scratching it with stainless steel tweezers, screwdrivers, diamond-tipped scribers,
biological fluids containing bacteria and blood. Not only did the material repel all the liquid and show anti-biofouling behavior but the tungsten oxide actually made the steel stronger than steel without the coating.
Medical steel devices are one of the material's most promising applications, said Philseok Kim,
co-author of the paper and cofounder and vice president of technology AT SEAS spin-off SLIPS Technologies Inc."Because we show that this material successfully repels bacteria and blood, small medical implants,
tools and surgical instruments like scalpels and needles that require both significant mechanical strength and antifouling property are high value-added products we are exploring for application
and commercialization,"said Kim. Another avenue for application is functional 3d printing and microarray devices, especially in printing highly viscous and sticky biological and polymeric materials where friction and contamination are major obstacles.
U s. Navy spends tens of millions of dollars each year dealing with the ramifications of biofouling on hulls.
Organisms such as barnacles and algae create drag and increased energy expenditure, not to mention the costs of cleaning
and reapplying current antifouling paints, most of which are harmful to the environment. If scaled-up, this material could provide a cleaner, more cost-efficient alternative."
"This research is an example of hard core, classic material science,"said Aizenberg.""We took a material that changed the world
and asked, how can we make it better
#UGR scientists patent an effective drug for treating breast, colon, and skin cancers Scientists from the University of Granada (UGR) have patented an effective drug for treating cancer stem cells (CSCS) in breast, colon, and skin cancers.
The researchers have proved the anti-tumor effects of the drug on immunodeficient mice. The new compound and its derivatives enabled the researchers to reduce tumor activity by 50 percent after 41 days of treatment with the drug,
administered twice a week, to mice with induced tumors. They have managed also to successfully describe the mechanisms by which the drug acts on the cancer stem cells (CSCS.
This crucial scientific breakthrough has been made by the UGR research groups"Research and development of Pharmaceutical Drugs, "directed by Professor Joaquín Campos Rosa, and"Advanced Therapies:
Differentiation, Regeneration and Cancer",directedby Professor Juan Antonio Marchal Corrales. The Córdoba-based company Canvax Biotech has participated also in the development of the patent.
A nontoxic drug One of the major advantages of the drug is that it is nontoxic.
Despite being administered to the mice in high concentrations (150 milligrams per kilo), no adverse effects were observed in the healthy cells.
Moreover, from a pharmaceutical perspective this anti-tumor drug can be produced successfully in large quantities. The researchers were able to obtain the required amount of the synthesis in just five days.
In the initial phases of their research the scientists had managed already to create an effective drug (called Bozepinib) for treating cancer stem cells,
but the process involved in its chemical synthesis was required lengthy and a great deal of time to produce very small quantities of the drug.
Having completed structural modifications of the drug--Bozepinib (by making changes to its molecular architecture),
which maintains the biological activity of its predecessor as an effective anti-tumor drug, but which can also be synthesized
In order to be able to test the new drug on mice and gauge its effectiveness on human tumors,
first of all they had to inject human tumor cells into immunodeficient mice (to ensure they did not reject these cancerous cells).
they discovered that some of the compounds effectively inhibited the growth of the tumor cells and the migration ability of these cells to other healthy tissues,
a huge advantagewhen compared to other cancer treatments such as chemotherapy. Althoughcscs are only found in small quantities in tumors,
from a clinical perspective the ability to target them directly is of fundamental importance, given that they are responsible for originally causing the tumor, relapses and resistance to anticancer treatments.
The next step: Lungs and pancreas Having proved the preclinical effectiveness of the new drug in treating cancer stem cells in breast, colon,
and skin cancers, the scientists will proceed now to study the drug's effect on lung and pancreas cancers, two of the most aggressive types.
They must also complete further ADME-Tox("absorption, distribution, metabolism, excretion and toxicity")studies of the compound's behavior within the organism, a necessary step before carrying out clinical trials.
In the last two months, the research project has received funding of over#124,930 from the public sector from the Ministry of Economy and Finance and the firm Canvax Biotech SL and#20
000 from the private sector
#Another dimension: 3-D cell growth opens new pathway for spinal cord repair Griffith University researchers have opened a new avenue to advance a therapy to repair the paralysed spinal cord.
A paper published in the prestigious Nature group journal Scientific Reports presents a novel technique to grow cells in three dimensions, without the traditional restrictions of matrix or scaffolds.
By using floating liquid marbles, cells can freely associate and form natural structures as they would normally within the human body."
which cells are transplanted into the injury site, "says research supervisor Dr James St john, from Griffith's Eskitis Institute for Drug Discovery.
The technique was developed when neurobiology merged with microfluidic engineering technology. Lead researcher, Griffith Phd student Mr Raja Vadivelu,
and Professor Nam-Trung Nguyen (Queensland Micro-and Nanotechnology Centre) collaborated with Dr Jenny Ekberg (Queensland University of Technology) and scientists in Spain."
"In Australia, more than 12,000 people live with spinal cord paralysis and there is at least one new occurrence every day,
"says Dr St john ."Although rehabilitation medicine has resulted in reductions in mortality, the current outcome for patients is permanent paralysis, with an overall cost to the community of $2 billion a year."
"In light of the overwhelming impact of spinal cord injury, new therapeutic interventions for drug discovery and cell therapy are needed urgently."
"The transplantation of the specialised cell type from the olfactory (sense of smell) system is a promising approach to spinal cord repair."
"Successful partial regeneration of a completely severed spinal cord in a human was achieved recently in an overseas study,
thus demonstrating this therapy can work, "says Mr Vadivelu.""What is needed now is to make the transplantation therapy more effective and suitable for patients with a range of different spinal cord injuries."
"The new method enables transplanted cells to survive and better integrate into the injury site.
In turn, this will help the spinal cord to regenerate more effectively.""Liquid marbles are a remarkably simply way to culture cells in 3d,
"says Dr St john."A droplet of liquid that contains the cells is placed upon a carpet of teflon powder to create a liquid marble
which can then be floated on cell culture medium.""By having an air interface between the liquid marble and the cell culture medium upon
which it floats, the liquid marble easily rotates.""This allows the cells within the liquid marbles to freely associate to form natural structures without the confines imposed upon them by other 3d culturing methods."
"Floating liquid marbles have been known for almost 200 years. In 1830, British explorer Alexander Burnes was travelling through
what is now Pakistan when he observed the Indus river merging with the sea. He noted that"round globules filled with water"floated on the seawater and formed when the freshwater detached sand from the sand banks."
"Burnes probably didn't think they could be used to help develop a therapy for spinal cord repair,
but combining neurobiology and engineering at Griffith University has at last found an incredible use for the'round globules,
'"says Dr St john. The floating liquid marble technique can also be used to grow many other cell types in 3d
and is likely to bring dramatic advances in several biological fields s
#Umbrella-shaped diamond nanostructures make efficient photon collectors Standard umbrellas come out when the sky turns dark,
but in the nanoworld, umbrella shapes may be the next creative way to enhance light emission. Inspired by recent work to enhance the luminescence from diamond nanopillar structures,
a team of researchers in Japan has discovered that"umbrella-shaped"diamond nanostructures with metal mirrors on the bottom are more efficient photon collectors than their diamond nanostructure"cousins"of other shapes.
By tweaking the shape of the diamond nanostructures into the form of tiny umbrellas, researchers from Tokyo Institute of technology experimentally showed that the fluorescence intensity of their structures was three to five times greater than that of bulk diamond.
They report their results in the journal Applied Physics Letters, from AIP Publishing. To get started, the team formed the umbrella-shaped diamond nanostructures by using an original"bottom-up"fabrication technique that relies on selective and anisotropic growth through holes in a metal mask.
The metal mask also serves as a mirror that is self-aligned to the diamond nanostructures."
"Our umbrella-shaped nanostructure has an effect similar to a solid immersion lens, which reduces the chance of total reflection on its upper surface
and focuses the emitted light toward the'upside'of the structure, "explained Mutsuko Hatano, a professor in the Graduate school of Science and Engineering's Department of Physical Electronics at Tokyo Institute of technology.
The self-aligned mirror goes a step further to enhance the efficiency of collecting this light by reflecting it at the lower surface area of the nanostructure."
"Umbrella-shaped diamond provides significantly better photon collection efficiency than bulk diamond or its pillar-shaped diamond counterpart,
which have already been studied extensively,"Hatano noted. The significance of the team's discovery is that they've shown that the brighter fluorescence intensity of umbrella-shaped diamond nanostructures can be achieved by improving the photon collection efficiency of the nitrogen vacancy centers,
which are the numerous point defects in diamonds that happen to boast the property of photoluminescence.
These nitrogen vacancy centers possess unique properties such as optical initialization and detection of its spin states, stable and strong fluorescence even from a single center
and long spin coherence time at room temperature. These properties make nitrogen vacancy centers in diamonds candidates for next-generation spin-based quantum devices such as magnetometers, quantum computers,
and for research or work involving biological observations. Individual nitrogen vacancy centers could essentially function as the basic units of quantum computers.
Brighter fluorescence intensity is an essential aspect of improving the photon collection efficiency from nitrogen vacancy centers.
Due to the high refractive index (2. 4) of diamond, the photon collection efficiency from the nitrogen vacancy centers in bulk diamond is low."
"In other words, diamond works as an effective light waveguide in low-refractive-index environments,"said Hatano. In terms of applications, the team's nanostructures may find use in highly sensitive magnetic sensors for making biological observations or within the computational science realm for quantum computing and cryptographic communications.
Next, Hatano and colleagues plan to pursue better control of the nanostructures'shape, as well as target a smoother surface by optimizing chemical vapor deposition growth conditions."
"Our goal now is to improve the nanostructures'photon collection efficiency, "she said.""We also plan to demonstrate quantum sensors--in particular,
highly sensitive magnetometers intended for life science and medical applications
#Scientists gain insight into origin of tungsten-ditelluride's magnetoresistance Scientists recently discovered that tungsten ditelluride (WTE2) is electronically three-dimensional with a low anisotropy.
Anisotropy reflects the change in properties of a material when the direction of the current or the applied magnetic field is varied.
Similar to graphite consisting of weakly bound graphene layers, WTE2 is layered a material that could be reduced to few layers in thickness
or a monolayer and be used in making nanoscale transistors in other electronics. The material was thought originally to be two-dimensional in nature because of the ease with
which its layers could be separated. WTE2 has been the subject of increased scientific interest since a 2014 research study outlined its unusual magnetoresistance,
which is the ability of a material to change the value of its electrical resistance when subjected to an external magnetic field.
This particular finding"is interesting in its own right because it shows that the mechanical and electrical properties of a material are not always as closely linked as we may assume,
"wrote Kamran Behnia, director of quantum matter research at Le Centre National de la Recherche Scientifique in Paris,
in an opinion piece on the latest research discovery about WTE2 published in journal Physics,
which provides news and commentary on select papers from American Physical Society journals. Researchers also discovered that the anisotropy of WTE2 varies and displays the magnetoresistance behavior of the Fermi liquid state
which is a theoretical model that describes the normal state of most metals at sufficiently low temperatures."
"In addition to its small values, we found that the anisotropy also varies with temperature and follows the magnetoresistance behavior.
The Rice lab of chemist James Tour and colleagues at the Chinese Academy of Sciences, the University of Texas at San antonio and the University of Houston have reported the development of a robust,
Catalysts can split water into its constituent hydrogen and oxygen atoms, a process required for fuel cells.
The latest discovery detailed in Nature Communications, is a significant step toward lower-cost catalysts for energy production, according to the researchers."
"What's unique about this paper is that we show not the use of metal particles, not the use of metal nanoparticles,
but the use of atoms,"Tour said.""The particles doing this chemistry are as small as you can possibly get."
"Even particles on the nanoscale work only at the surface, he said.""There are so many atoms inside the nanoparticle that never do anything.
But in our process the atoms driving catalysis have no metal atoms next to them.
We're getting away with very little cobalt to make a catalyst that nearly matches the best platinum catalysts."
the amount of electricity it needs to begin separating water into hydrogen and oxygen. The new catalyst is mixed as a solution
Tour said single-atom catalysts have been realized in liquids, but rarely on a surface.""This way we can build electrodes out of it,
"he said.""It should be easy to integrate into devices.""The researchers discovered that heat-treating graphene oxide and small amounts of cobalt salts in a gaseous environment forced individual cobalt atoms to bind to the material.
Electron microscope images showed cobalt atoms widely dispersed throughout the samples. They tested nitrogen-doped graphene on its own and found it lacked the ability to kick the catalytic process into gear.
But adding cobalt in very small amounts significantly increased its ability to split acidic or basic water."
He noted platinum-carbon catalysts still boast the lowest onset voltage.""No question, they're the best.
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