Fangirl Challenge  - [3/10] Relationships - House × Chase (House)

Bringing silicon to life: Scientists persuade nature to make silicon-carbon bonds

A new study is the first to show that living organisms can be persuaded to make silicon-carbon bonds – something only chemists had done before. Scientists at Caltech “bred” a bacterial protein to make the humanmade bonds – a finding that has applications in several industries.

Molecules with silicon-carbon, or organosilicon, compounds are found in pharmaceuticals as well as in many other products, including agricultural chemicals, paints, semiconductors, and computer and TV screens. Currently, these products are made synthetically, since the silicon-carbon bonds are not found in nature.

The new study demonstrates that biology can instead be used to manufacture these bonds in ways that are more environmentally friendly and potentially much less expensive.

“We decided to get nature to do what only chemists could do – only better,” says Frances Arnold, Caltech’s Dick and Barbara Dickinson Professor of Chemical Engineering, Bioengineering and Biochemistry, and principal investigator of the new research, published in the Nov. 24 issue of the journal Science.

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Sketching out magnetism with electricity

In a proof-of-concept study published in Nature Physics, researchers drew magnetic squares in a nonmagnetic material with an electrified pen and then “read” this magnetic doodle with X-rays.

The experiment demonstrated that magnetic properties can be created and annihilated in a nonmagnetic material with precise application of an electric field – something long sought by scientists looking for a better way to store and retrieve information on hard drives and other magnetic memory devices. The research took place at the Department of Energy’s SLAC National Accelerator Laboratory and the Korea Advanced Institute of Science and Technology.

“The important thing is that it’s reversible. Changing the voltage of the applied electric field demagnetizes the material again,” said Hendrik Ohldag, a co-author on the paper and scientist at the lab’s Stanford Synchrotron Radiation Lightsource (SSRL), a DOE Office of Science User Facility.

“That means this technique could be used to design new types of memory storage devices with additional layers of information that can be turned on and off with an electric field, rather than the magnetic fields used today,” Ohldag said. “This would allow more targeted control, and would be less likely to cause unwanted effects in surrounding magnetic areas.”

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“I first ran for Congress in 1999, and I got beat. I just got whooped. I had been in the state legislature for a long time, I was in the minority party, I wasn’t getting a lot done, and I was away from my family and putting a lot of strain on Michelle. Then for me to run and lose that bad, I was thinking maybe this isn’t what I was cut out to do. I was forty years old, and I’d invested a lot of time and effort into something that didn’t seem to be working. But the thing that got me through that moment, and any other time that I’ve felt stuck, is to remind myself that it’s about the work. Because if you’re worrying about yourself—if you’re thinking: ‘Am I succeeding? Am I in the right position? Am I being appreciated?’ – then you’re going to end up feeling frustrated and stuck. But if you can keep it about the work, you’ll always have a path. There’s always something to be done.”

Good vibrations no longer needed for speakers as research encourages graphene to talk

A pioneering new technique that encourages the wonder material graphene to “talk” could revolutionise the global audio and telecommunications industries.

Researchers from the University of Exeter have devised a ground-breaking method to use graphene to generate complex and controllable sound signals. In essence, it combines speaker, amplifier and graphic equaliser into a chip the size of a thumbnail.

Traditional speakers mechanically vibrate to produce sound, with a moving coil or membrane pushing the air around it back and forth. It is a bulky technology that has hardly changed in more than a century.

This innovative new technique involves no moving parts. A layer of the atomically thin material graphene is rapidly heated and cooled by an alternating electric current, and transfer of this thermal variation to the air causes it to expand and contract, thereby generating sound waves.

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Seeing stable topology using instabilities

We are most familiar with the four conventional phases of matter: solid, liquid, gas, and plasma. Changes between two phases, known as phase transitions, are marked by abrupt changes in material properties such as density. In recent decades a wide body of physics research has been devoted to discovering new unconventional phases of matter, which typically emerge at ultra-low temperatures or in specially-structured materials. Exotic “topological” phases exhibit properties that can only change in a quantized (stepwise) manner, making them intrinsically robust against impurities and defects.

In addition to topological states of matter, topological phases of light can emerge in certain optical systems such as photonic crystals and optical waveguide arrays. Topological states of light are of interest as they can form the basis for future energy-efficient light-based communication technologies such as lasers and integrated optical circuits.

However, at high intensities light can modify the properties of the underlying material. One example of such a phenomenon is the damage that the high-power lasers can inflict on the mirrors and lenses. This in turn affects the propagation of the light, forming a nonlinear feedback loop. Nonlinear optical effects are essential for the operation of certain devices such as lasers, but they can lead to the emergence of disorder from order in a process known as modulational instability, as is shown in Figure 1. Understanding the interplay between topology and nonlinearity is a fascinating subject of ongoing research.

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(Image caption: New model mimics the connectivity of the brain by connecting three distinct brain regions on a chip. Credit: Disease Biophysics Group/Harvard University)

Multiregional brain on a chip

Harvard University researchers have developed a multiregional brain-on-a-chip that models the connectivity between three distinct regions of the brain. The in vitro model was used to extensively characterize the differences between neurons from different regions of the brain and to mimic the system’s connectivity.

The research was published in the Journal of Neurophysiology.

“The brain is so much more than individual neurons,” said Ben Maoz, co-first author of the paper and postdoctoral fellow in the Disease Biophysics Group in the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS). “It’s about the different types of cells and the connectivity between different regions of the brain. When modeling the brain, you need to be able to recapitulate that connectivity because there are many different diseases that attack those connections.”

“Roughly twenty-six percent of the US healthcare budget is spent on neurological and psychiatric disorders,” said Kit Parker, the Tarr Family Professor of Bioengineering and Applied Physics Building at SEAS and Core Faculty Member of the Wyss Institute for Biologically Inspired Engineering at Harvard University. “Tools to support the development of therapeutics to alleviate the suffering of these patients is not only the human thing to do, it is the best means of reducing this cost.“

Researchers from the Disease Biophysics Group at SEAS and the Wyss Institute modeled three regions of the brain most affected by schizophrenia  — the amygdala, hippocampus and prefrontal cortex.

They began by characterizing the cell composition, protein expression, metabolism, and electrical activity of neurons from each region in vitro.

“It’s no surprise that neurons in distinct regions of the brain are different but it is surprising just how different they are,” said Stephanie Dauth, co-first author of the paper and former postdoctoral fellow in the Disease Biophysics Group. “We found that the cell-type ratio, the metabolism, the protein expression and the electrical activity all differ between regions in vitro. This shows that it does make a difference which brain region’s neurons you’re working with.”

Next, the team looked at how these neurons change when they’re communicating with one another. To do that, they cultured cells from each region independently and then let the cells establish connections via guided pathways embedded in the chip.

The researchers then measured cell composition and electrical activity again and found that the cells dramatically changed when they were in contact with neurons from different regions.

“When the cells are communicating with other regions, the cellular composition of the culture changes, the electrophysiology changes, all these inherent properties of the neurons change,” said Maoz. “This shows how important it is to implement different brain regions into in vitro models, especially when studying how neurological diseases impact connected regions of the brain.”

To demonstrate the chip’s efficacy in modeling disease, the team doped different regions of the brain with the drug Phencyclidine hydrochloride — commonly known as PCP — which simulates schizophrenia. The brain-on-a-chip allowed the researchers for the first time to look at both the drug’s impact on the individual regions as well as its downstream effect on the interconnected regions in vitro.

The brain-on-a-chip could be useful for studying any number of neurological and psychiatric diseases, including drug addiction, post traumatic stress disorder, and traumatic brain injury.

"To date, the Connectome project has not recognized all of the networks in the brain,” said Parker. “In our studies, we are showing that the extracellular matrix network is an important part of distinguishing different brain regions and that, subsequently, physiological and pathophysiological processes in these brain regions are unique. This advance will not only enable the development of therapeutics, but fundamental insights as to how we think, feel, and survive.”

Zillertal Alps // Tom Klocker

New discovery could be a major advance for understanding neurological diseases

The discovery of a new mechanism that controls the way nerve cells in the brain communicate with each other to regulate our learning and long-term memory could have major benefits to understanding how the brain works and what goes wrong in neurodegenerative disorders such as epilepsy and dementia. The breakthrough, published in Nature Neuroscience, was made by scientists at the University of Bristol and the University of Central Lancashire.   The findings will have far-reaching implications in many aspects of neuroscience and understanding how the brain works.

The human brain contains around 100-billion nerve cells, each of which makes about 10,000 connections to other cells, called synapses. Synapses are constantly transmitting information to, and receiving information from other nerve cells. A process, called long-term potentiation (LTP), increases the strength of information flow across synapses. Lots of synapses communicating between different nerve cells form networks and LTP intensifies the connectivity of the cells in the network to make information transfer more efficient. This LTP mechanism is how the brain operates at the cellular level to allow us to learn and remember. However, when these processes go wrong they can lead to neurological and neurodegenerative disorders.

Precisely how LTP is initiated is a major question in neuroscience. Traditional LTP is regulated by the activation of special proteins at synapses called NMDA receptors. This study, by Professor Jeremy Henley and co-workers reports a new type of LTP that is controlled by kainate receptors.

This is an important advance as it highlights the flexibility in the way synapses are controlled and nerve cells communicate. This, in turn, raises the possibility of targeting this new pathway to develop therapeutic strategies for diseases like dementia, in which there is too little synaptic transmission and LTP, and epilepsy where there is too much inappropriate synaptic transmission and LTP.

Jeremy Henley, Professor of Molecular Neuroscience in the University’s School of Biochemistry in the Faculty of Biomedical Sciences, said: “These discoveries represent a significant advance and will have far-reaching implications for the understanding of memory, cognition, developmental plasticity and neuronal network formation and stabilisation. In summary, we believe that this is a groundbreaking study that opens new lines of inquiry which will increase understanding of the molecular details of synaptic function in health and disease.”

Dr Milos Petrovic, co-author of the study and Reader in Neuroscience at the University of Central Lancashire added: “Untangling the interactions between the signal receptors in the brain not only tells us more about the inner workings of a healthy brain, but also provides a practical insight into what happens when we form new memories. If we can preserve these signals it may help protect against brain diseases.

“This is certainly an extremely exciting discovery and something that could potentially impact the global population. We have discovered potential new drug targets that could help to cure the devastating consequences of dementias, such as Alzheimer’s disease. Collaborating with researchers across the world in order to identify new ways to fight disease like this is what world-class scientific research is all about, and we look forward to continuing our work in this area.”

Directly Reprogramming a Cell's Identity with Gene Editing

Researchers have used CRISPR—a revolutionary new genetic engineering technique—to convert cells isolated from mouse connective tissue directly into neuronal cells.

In 2006, Shinya Yamanaka, a professor at the Institute for Frontier Medical Sciences at Kyoto University at the time, discovered how to revert adult connective tissue cells, called fibroblasts, back into immature stem cells that could differentiate into any cell type. These so-called induced pluripotent stem cells won Yamanaka the Nobel Prize in medicine just six years later for their promise in research and medicine.

Since then, researchers have discovered other ways to convert cells between different types. This is mostly done by introducing many extra copies of “master switch” genes that produce proteins that turn on entire genetic networks responsible for producing a particular cell type.

Now, researchers at Duke University have developed a strategy that avoids the need for the extra gene copies. Instead, a modification of the CRISPR genetic engineering technique is used to directly turn on the natural copies already present in the genome.

These early results indicate that the newly converted neuronal cells show a more complete and persistent conversion than the method where new genes are permanently added to the genome. These cells could be used for modeling neurological disorders, discovering new therapeutics, developing personalized medicines and, perhaps in the future, implementing cell therapy.

The study was published on August 11, 2016, in the journal Cell Stem Cell.

“This technique has many applications for science and medicine. For example, we might have a general idea of how most people’s neurons will respond to a drug, but we don’t know how your particular neurons with your particular genetics will respond,” said Charles Gersbach, the Rooney Family Associate Professor of Biomedical Engineering and director for the Center for Biomolecular and Tissue Engineering at Duke. “Taking biopsies of your brain to test your neurons is not an option. But if we could take a skin cell from your arm, turn it into a neuron, and then treat it with various drug combinations, we could determine an optimal personalized therapy.”

“The challenge is efficiently generating neurons that are stable and have a genetic programming that looks like your real neurons,” says Joshua Black, the graduate student in Gersbach’s lab who led the work. “That has been a major obstacle in this area.”

In the 1950s, Professor Conrad Waddington, a British developmental biologist who laid the foundations for developmental biology, suggested that immature stem cells differentiating into specific types of adult cells can be thought of as rolling down the side of a ridged mountain into one of many valleys. With each path a cell takes down a particular slope, its options for its final destination become more limited.

If you want to change that destination, one option is to push the cell vertically back up the mountain—that’s the idea behind reprogramming cells to be induced pluripotent stem cells. Another option is to push it horizontally up and over a hill and directly into another valley.

“If you have the ability to specifically turn on all the neuron genes, maybe you don’t have to go back up the hill,” said Gersbach.

Previous methods have accomplished this by introducing viruses that inject extra copies of genes to produce a large number of proteins called master transcription factors. Unique to each cell type, these proteins bind to thousands of places in the genome, turning on that cell type’s particular gene network. This method, however, has some drawbacks.

“Rather than using a virus to permanently introduce new copies of existing genes, it would be desirable to provide a temporary signal that changes the cell type in a stable way,” said Black. “However, doing so in an efficient manner might require making very specific changes to the genetic program of the cell.”

In the new study, Black, Gersbach, and colleagues used CRISPR to precisely activate the three genes that naturally produce the master transcription factors that control the neuronal gene network, rather than having a virus introduce extra copies of those genes.

CRISPR is a modified version of a bacterial defense system that targets and slices apart the DNA of familiar invading viruses. In this case, however, the system has been tweaked so that no slicing is involved. Instead, the machinery that identifies specific stretches of DNA has been left intact, and it has been hitched to a gene activator.

The CRISPR system was administered to mouse fibroblasts in the laboratory. The tests showed that, once activated by CRISPR, the three neuronal master transcription factor genes robustly activated neuronal genes. This caused the fibroblasts to conduct electrical signals—a hallmark of neuronal cells. And even after the CRISPR activators went away, the cells retained their neuronal properties.

“When blasting cells with master transcription factors made by viruses, it’s possible to make cells that behave like neurons,” said Gersbach. “But if they truly have become autonomously functioning neurons, then they shouldn’t require the continuous presence of that external stimulus.”

The experiments showed that the new CRISPR technique produced neuronal cells with an epigenetic program at the target genes matching the neuronal markings naturally found in mouse brain tissue.

“The method that introduces extra genetic copies with the virus produces a lot of the transcription factors, but very little is being made from the native copies of these genes,” explained Black. “In contrast, the CRISPR approach isn’t making as many transcription factors overall, but they’re all being produced from the normal chromosomal position, which is a powerful difference since they are stably activated. We’re flipping the epigenetic switch to convert cell types rather than driving them to do so synthetically.”

The next steps, according to Black, are to extend the method to human cells, raise the efficiency of the technique and try to clear other epigenetic hurdles so that it could be applied to model particular diseases.

“In the future, you can imagine making neurons and implanting them in the brain to treat Parkinson’s disease or other neurodegenerative conditions,” said Gersbach. “But even if we don’t get that far, you can do a lot with these in the lab to help develop better therapies.”