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Multiplex recording of cellular events over time on CRISPR biological tape

ScienceNOW Daily News Feed - Jue, 12/14/2017 - 12:25

Although dynamics underlie many biological processes, our ability to robustly and accurately profile time-varying biological signals and regulatory programs remains limited. Here we describe a framework for storing temporal biological information directly in the genomes of a cell population. We developed a "biological tape recorder" in which biological signals trigger intracellular DNA production that is then recorded by the CRISPR-Cas adaptation system. This approach enables stable recording over multiple days and accurate reconstruction of temporal and lineage information by sequencing CRISPR arrays. We further demonstrate a multiplexing strategy to simultaneously record the temporal availability of three metabolites (copper, trehalose, and fucose) in the environment of a cell population over time. This work enables the temporal measurement of dynamic cellular states and environmental changes and suggests new applications for chronicling biological events on a large scale.

Comprehensive computational design of ordered peptide macrocycles

ScienceNOW Daily News Feed - Jue, 12/14/2017 - 12:25

Mixed-chirality peptide macrocycles such as cyclosporine are among the most potent therapeutics identified to date, but there is currently no way to systematically search the structural space spanned by such compounds. Natural proteins do not provide a useful guide: Peptide macrocycles lack regular secondary structures and hydrophobic cores, and can contain local structures not accessible with l-amino acids. Here, we enumerate the stable structures that can be adopted by macrocyclic peptides composed of l- and d-amino acids by near-exhaustive backbone sampling followed by sequence design and energy landscape calculations. We identify more than 200 designs predicted to fold into single stable structures, many times more than the number of currently available unbound peptide macrocycle structures. Nuclear magnetic resonance structures of 9 of 12 designed 7- to 10-residue macrocycles, and three 11- to 14-residue bicyclic designs, are close to the computational models. Our results provide a nearly complete coverage of the rich space of structures possible for short peptide macrocycles and vastly increase the available starting scaffolds for both rational drug design and library selection methods.

New Products

ScienceNOW Daily News Feed - Jue, 12/14/2017 - 12:25

Enzyme-free nucleic acid dynamical systems

ScienceNOW Daily News Feed - Jue, 12/14/2017 - 12:25

Chemistries exhibiting complex dynamics—from inorganic oscillators to gene regulatory networks—have been long known but either cannot be reprogrammed at will or rely on the sophisticated enzyme chemistry underlying the central dogma. Can simpler molecular mechanisms, designed from scratch, exhibit the same range of behaviors? Abstract chemical reaction networks have been proposed as a programming language for complex dynamics, along with their systematic implementation using short synthetic DNA molecules. We developed this technology for dynamical systems by identifying critical design principles and codifying them into a compiler automating the design process. Using this approach, we built an oscillator containing only DNA components, establishing that Watson-Crick base-pairing interactions alone suffice for complex chemical dynamics and that autonomous molecular systems can be designed via molecular programming languages.

Single-stranded DNA and RNA origami

ScienceNOW Daily News Feed - Jue, 12/14/2017 - 12:25

Self-folding of an information-carrying polymer into a defined structure is foundational to biology and offers attractive potential as a synthetic strategy. Although multicomponent self-assembly has produced complex synthetic nanostructures, unimolecular folding has seen limited progress. We describe a framework to design and synthesize a single DNA or RNA strand to self-fold into a complex yet unknotted structure that approximates an arbitrary user-prescribed shape. We experimentally construct diverse multikilobase single-stranded structures, including a ~10,000-nucleotide (nt) DNA structure and a ~6000-nt RNA structure. We demonstrate facile replication of the strand in vitro and in living cells. The work here thus establishes unimolecular folding as a general strategy for constructing complex and replicable nucleic acid nanostructures, and expands the design space and material scalability for bottom-up nanotechnology.

The nanoscale circuitry of battery electrodes

ScienceNOW Daily News Feed - Jue, 12/14/2017 - 12:25

Developing high-performance, affordable, and durable batteries is one of the decisive technological tasks of our generation. Here, we review recent progress in understanding how to optimally arrange the various necessary phases to form the nanoscale structure of a battery electrode. The discussion begins with design principles for optimizing electrode kinetics based on the transport parameters and dimensionality of the phases involved. These principles are then used to review and classify various nanostructured architectures that have been synthesized. Connections are drawn to the necessary fabrication methods, and results from in operando experiments are highlighted that give insight into how electrodes evolve during battery cycling.

Ultrasound imaging from a single large sensor

physicsworld.com - Jue, 12/14/2017 - 05:23
New technique could leader to faster, smaller and cheaper imagers

A model of Mars-like protoplanets shed light on early solar activity

EurekAlert! - Mié, 12/13/2017 - 23:00
A scientist from Siberian Federal University (SFU) and his colleagues from Austria and Germany constructed a physical and mathematical model of Mars- and Venus-sized planet formation. The team concluded that Mars had no chances to develop a thick atmosphere and biosphere. In the case of Venus it depended on solar activity: according to the scientists, it managed to keep its atmosphere due to the fact that young Sun was not very active. The study was published in Icarus.

Behaviour of millions still shaped by Industrial Revolution

EurekAlert! - Mié, 12/13/2017 - 23:00
The Industrial Revolution of 200 years ago, powered by coal and steam engines, laid the foundations of modern society. World-first QUT-led research has found its effects are still felt and not in a good way. It reveals that people living in the former industrial heartlands of the UK and the US are more disposed to negative emotions such as anxiety and depressive moods, more impulsive and more likely to struggle with planning and self-motivation.

New cellular approach found to control progression of chronic kidney disease

EurekAlert! - Mié, 12/13/2017 - 23:00
Researchers have demonstrated for the first time that extracellular vesicles -- tiny protein-filled structures -- isolated from amniotic fluid stem cells (AFSCs) can be used to effectively slow the progression of kidney damage in mice with a type of chronic kidney disease. The findings, by a research team at the Saban Research Institute of Children's Hospital Los Angeles, provide new insights about the mechanisms of kidney disease and point to a new approach for improved treatments.

Music streaming sites benefit indie singers at the expense of top 100 artists

EurekAlert! - Mié, 12/13/2017 - 23:00
While free or low cost music streaming sources like Spotify decrease the use of paid music platforms, such as iTunes, a new study in the INFORMS journal Marketing Science, shows they significantly increase exposure for and access to lesser known or indie artists that fall outside the top 100 or even top 500 listings.

Offbeat brainwaves during sleep make older adults forget

EurekAlert! - Mié, 12/13/2017 - 23:00
Like swinging a tennis racket during a ball toss to serve an ace, slow and speedy brainwaves during deep sleep must sync up at exactly the right moment to hit the save button on new memories, according to new UC Berkeley research.

Cancer immunotherapy may work better in patients with specific genes

EurekAlert! - Mié, 12/13/2017 - 23:00
Investigators have been trying to understand why and have recently found how an individual's own genes can play a role in the response to the immunotherapy drugs.

Scientists pinpoint gene to blame for poorer survival rate in early-onset breast cancer patients

EurekAlert! - Mié, 12/13/2017 - 23:00
A new study led by scientists at the University of Southampton has found that inherited variation in a particular gene may be to blame for the lower survival rate of patients diagnosed with early-onset breast cancer.

Study finds graspable objects grab attention more than images of objects do

EurekAlert! - Mié, 12/13/2017 - 23:00
Jacqueline Snow, with the University of Nevada, Reno's College of Liberal Arts, and her graduate students, Michael Gomez and Rafal Skiba, recently published findings of their research, "Graspable objects grab attention more than images do." They studied how humans allocate attention to different objects in a scene and examined whether real objects compete more strongly for attention and manual responses compared to matched computerized 2-D and 3-D images of the same objects.

Finding a lethal parasite's vulnerabilities

EurekAlert! - Mié, 12/13/2017 - 23:00
Researchers from Penn's School of Veterinary Medicine have landed on encouraging findings to take on Strongyloides stercoralis, a parasitic nematode that's infected millions of people around the world.

First-of-its-kind chemical oscillator offers new level of molecular control

EurekAlert! - Mié, 12/13/2017 - 23:00
UT researchers successfully constructed a first-of-its-kind chemical oscillator that uses DNA components. DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

NSF-funded researchers find that ice sheet is dynamic and has repeatedly grown and shrunk

EurekAlert! - Mié, 12/13/2017 - 23:00
The East Antarctic Ice Sheet locks away enough water to raise sea level an estimated 53 meters (174 feet), more than any other ice sheet on the planet. It's also thought to be among the most stable, not gaining or losing mass even as ice sheets in West Antarctica and Greenland shrink.

Suicidal thoughts rapidly reduced with ketamine, finds study

EurekAlert! - Mié, 12/13/2017 - 23:00
Ketamine was significantly more effective than a commonly used sedative in reducing suicidal thoughts in depressed patients, according to researchers at Columbia University Medical Center (CUMC). They also found that ketamine's anti-suicidal effects occurred within hours after its administration.

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