The heat is on

 They say that where there's smoke, there's fire, and Weizmann Institute of Science researchers are working hard to investigate that claim, or at least elucidate what constitutes "smoke." In an article published today in PNAS, the scientists reveal an advanced, innovative method that they have developed and used to detect nonvisual traces of fire dating back at least 800,000 years -- one of the earliest known pieces of evidence for the use of fire. The newly developed technique may provide a push toward a more scientific, data-driven type of archaeology, but -- perhaps more importantly -- it could help us better understand the origins of the human story, our most basic traditions and our experimental and innovative nature.

The controlled use of fire by ancient hominins -- a group that includes humans and some of our extinct family members -- is hypothesized to date back at least a million years, to around the time that archaeologists believe Homo habilis began its transition to Homo erectus. That is no coincidence, as the working theory, called the "cooking hypothesis," is that the use of fire was instrumental in our evolution, not only for allowing hominins to stay warm, craft advanced tools and ward off predators but also for acquiring the ability to cook. Cooking meat not only eliminates pathogens but increases efficient protein digestion and nutritional value, paving the way for the growth of the brain. The only problem with this hypothesis is a lack of data: since finding archaeological evidence of pyrotechnology primarily relies on visual identification of modifications resulting from the combustion of objects (mainly, a color change), traditional methods have managed to find widespread evidence of fire use no older than 200,000 years. While there is some evidence of fire dating back to 500,000 years ago, it remains sparse, with only five archaeological sites around the world providing reliable evidence of ancient fire.

"We may have just found the sixth site," says Dr. Filipe Natalio of Weizmann's Plant and Environmental Sciences Department, whose previous collaboration with Dr. Ido Azuri, of Weizmann's Life Core Facilities Department, and colleagues provided the basis for this project. Together they pioneered the application of AI and spectroscopy in archaeology to find indications of controlled burning of stone tools dating back to between 200,000 and 420,000 years ago in Israel. Now they're back, joined by PhD student Zane Stepka, Dr. Liora Kolska Horwitz from the Hebrew University of Jerusalem and Prof. Michael Chazan from the University of Toronto, Canada. The team upped the ante by taking a "fishing expedition" -- casting far out into the water and seeing what they could reel back in. "When we started this project," says Natalio, "the archaeologists who've been analyzing the findings from Evron Quarry told us we wouldn't find anything. We should have made a bet."

Source: ScienceDaily

The benefits of exercise in a pill? Science is closer to that goal

 Researchers at Baylor College of Medicine, Stanford School of Medicine and collaborating institutions report today in the journal Nature that they have identified a molecule in the blood that is produced during exercise and can effectively reduce food intake and obesity in mice. The findings improve our understanding of the physiological processes that underlie the interplay between exercise and hunger.

"Regular exercise has been proven to help weight loss, regulate appetite and improve the metabolic profile, especially for people who are overweight and obese," said co-corresponding author Dr. Yong Xu, professor of pediatrics- nutrition and molecular and cellular biology at Baylor. "If we can understand the mechanism by which exercise triggers these benefits, then we are closer to helping many people improve their health."

"We wanted to understand how exercise works at the molecular level to be able to capture some of its benefits," said co-corresponding author Jonathan Long, MD, assistant professor of pathology at Stanford Medicine and an Institute Scholar of Stanford ChEM-H (Chemistry, Engineering & Medicine for Human Health). "For example, older or frail people who cannot exercise enough, may one day benefit from taking a medication that can help slow down osteoporosis, heart disease or other conditions."

Xu, Long and their colleagues conducted comprehensive analyses of blood plasma compounds from mice following intense treadmill running. The most significantly induced molecule was a modified amino acid called Lac-Phe. It is synthesized from lactate (a byproduct of strenuous exercise that is responsible for the burning sensation in muscles) and phenylalanine (an amino acid that is one of the building blocks of proteins).

In mice with diet-induced obesity (fed a high-fat diet), a high dose of Lac-Phe suppressed food intake by about 50% compared to control mice over a period of 12 hours without affecting their movement or energy expenditure. When administered to the mice for 10 days, Lac-Phe reduced cumulative food intake and body weight (owing to loss of body fat) and improved glucose tolerance.

The researchers also identified an enzyme called CNDP2 that is involved in the production of Lac-Phe and showed that mice lacking this enzyme did not lose as much weight on an exercise regime as a control group on the same exercise plan.

Interestingly, the team also found robust elevations in plasma Lac-Phe levels following physical activity in racehorses and humans. Data from a human exercise cohort showed that sprint exercise induced the most dramatic increase in plasma Lac-Phe, followed by resistance training and then endurance training. "This suggests that Lac-Phe is an ancient and conserved system that regulates feeding and is associated with physical activity in many animal species," Long said.

"Our next steps include finding more details about how Lac-Phe mediates its effects in the body, including the brain," Xu said. "Our goal is to learn to modulate this exercise pathway for therapeutic interventions."

Source: ScienceDaily

Biochemistry researchers repair and regenerate heart muscle cells

 Researchers at the University of Houston are reporting a first-of-its-kind technology that not only repairs heart muscle cells in mice but also regenerates them following a heart attack, or myocardial infarction as its medically known.

Published in the Journal of Cardiovascular Aging, the groundbreaking finding has the potential to become a powerful clinical strategy for treating heart disease in humans, according to Robert Schwartz, Hugh Roy and Lillie Cranz Cullen Distinguished Professor of biology and biochemistry at the UH College of Natural Sciences and Mathematics.

The new technology developed by the team of researchers uses synthetic messenger ribonucleic acid (mRNA) to deliver mutated transcription factors -- proteins that control the conversion of DNA into RNA -- to mouse hearts.

"No one has been able to do this to this extent and we think it could become a possible treatment for humans," said Schwartz, who led the study with recent Ph.D graduate Siyu Xiao and Dinakar Iyer, a research assistant professor of biology and biochemistry.

Synthetic mRNA Contributes to Stem Cell-Like Growth

The researchers demonstrated that two mutated transcription factors, Stemin and YAP5SA, work in tandem to increase the replication of cardiomyocytes, or heart muscle cells, isolated from mouse hearts. These experiments were conducted in vitro on tissue culture dishes.

"What we are trying to do is dedifferentiate the cardiomyocyte into a more stem cell-like state so that they can regenerate and proliferate," Xiao said.

Stemin turns on stem cell-like properties from cardiomyocytes. Stemin's crucial role in their experiments was discovered by Iyer, who said the transcription factor was a "game changer." Meanwhile, YAP5SA works by promoting organ growth that causes the myocytes to replicate even more.

In a separate finding published in the same journal, the team will report that Stemin and YAP5SA repaired damaged mouse hearts in vivo. Notably, myocyte nuclei replicated at least 15-fold in 24 hours following heart injections that delivered those transcription factors.

Bradley McConnell, professor of pharmacology, and graduate student Emilio Lucero in the UH College of Pharmacy, collaborated on the study by producing the infarcted adult mouse model.

"When both transcription factors were injected into infarcted adult mouse hearts, the results were stunning," Schwartz said. "The lab found cardiac myocytes multiplied quickly within a day, while hearts over the next month were repaired to near normal cardiac pumping function with little scarring."

An added benefit of using synthetic mRNA, according to Xiao, is that it disappears in a few days as opposed to viral delivery. Gene therapies delivered to cells by viral vectors raise several biosafety concerns because they cannot be easily stopped. mRNA-based delivery, on the other hand, turns over quickly and disappears.

Source: ScienceDaily

Dissolving implantable device relieves pain without drugs

 A Northwestern University-led team of researchers has developed a small, soft, flexible implant that relieves pain on demand and without the use of drugs. The first-of-its-kind device could provide a much-needed alternative to opioids and other highly addictive medications.

The biocompatible, water-soluble device works by softly wrapping around nerves to deliver precise, targeted cooling, which numbs nerves and blocks pain signals to the brain. An external pump enables the user to remotely activate the device and then increase or decrease its intensity. After the device is no longer needed, it naturally absorbs into the body -- bypassing the need for surgical extraction.

The researchers believe the device has the potential to be most valuable for patients who undergo routine surgeries or even amputations that commonly require post-operative medications. Surgeons could implant the device during the procedure to help manage the patient's post-operative pain.

The study will be published in the July 1 issue of the journal Science. The paper describes the device's design and demonstrates its efficacy in an animal model.

"Although opioids are extremely effective, they also are extremely addictive," said Northwestern's John A. Rogers, who led the device's development. "As engineers, we are motivated by the idea of treating pain without drugs -- in ways that can be turned on and off instantly, with user control over the intensity of relief. The technology reported here exploits mechanisms that have some similarities to those that cause your fingers to feel numb when cold. Our implant allows that effect to be produced in a programmable way, directly and locally to targeted nerves, even those deep within surrounding soft tissues."

A bioelectronics pioneer, Rogers is the Louis Simpson and Kimberly Querrey Professor of Materials Science and Engineering, Biomedical Engineering and Neurological Surgery in the McCormick School of Engineeringand Northwestern University Feinberg School of Medicine. He also is the founding director of the Querrey Simpson Institute for Bioelectronics. Jonathan Reeder, a former Ph.D. candidate in Rogers' laboratory, is the paper's first author.

How it works

Although the new device might sound like science fiction, it leverages a simple, common concept that everyone knows: evaporation. Similar to how evaporating sweat cools the body, the device contains a liquid coolant that is induced to evaporate at the specific location of a sensory nerve.

"As you cool down a nerve, the signals that travel through the nerve become slower and slower -- eventually stopping completely," said study coauthor Dr. Matthew MacEwan of Washington University School of Medicine in St. Louis. "We are specifically targeting peripheral nerves, which connect your brain and your spinal cord to the rest of your body. These are the nerves that communicate sensory stimuli, including pain. By delivering a cooling effect to just one or two targeted nerves, we can effectively modulate pain signals in one specific region of the body."

To induce the cooling effect, the device contains tiny microfluidic channels. One channel contains the liquid coolant (perfluoropentane), which is already clinically approved as an ultrasound contrast agent and for pressurized inhalers. A second channel contains dry nitrogen, an inert gas. When the liquid and gas flow into a shared chamber, a reaction occurs that causes the liquid to promptly evaporate. Simultaneously, a tiny integrated sensor monitors the temperature of the nerve to ensure that it's not getting too cold, which could cause tissue damage.

"Excessive cooling can damage the nerve and the fragile tissues around it," Rogers said. "The duration and temperature of the cooling must therefore be controlled precisely. By monitoring the temperature at the nerve, the flow rates can be adjusted automatically to set a point that blocks pain in a reversible, safe manner. On-going work seeks to define the full set of time and temperature thresholds below which the process remains fully reversible."

Source: ScienceDaily

Scientists engineer synthetic DNA to study 'architect' genes

Researchers at New York University have created artificial Hox genes -- which plan and direct where cells go to develop tissues or organs -- using new synthetic DNA technology and genomic engineering in stem cells.

Their findings, published in Science, confirm how clusters of Hox genes help cells to learn and remember where they are in the body.

Hox genes as architects of the body

Nearly all animals -- from humans to birds to fish -- have an anterior-posterior axis, or a line that runs from head to tail. During development, Hox genes act as architects, determining the plan for where cells go along the axis, as well as what body parts they make up. Hox genes ensure that organs and tissues develop in the right place, forming the thorax or placing wings in the correct anatomical positions.

If Hox genes fail through misregulation or mutation, cells can get lost, playing a role in some cancers, birth defects, and miscarriages.

"I don't think we can understand development or disease without understanding Hox genes," said Esteban Mazzoni, associate professor of biology at NYU and the study's co-senior author.

Despite their importance in development, Hox genes are challenging to study. They are tightly organized in clusters, with only Hox genes in the piece of DNA where they are found and no other genes surrounding them (what scientists call a "gene desert"). And while many parts of the genome have repetitive elements, Hox clusters have no such repeats. These factors make them unique but difficult to study with conventional gene editing without affecting neighboring Hox genes.

Starting anew with synthetic DNA

Could scientists create artificial Hox genes to better study them, rather than relying on gene editing?

"We are very good at reading the genome, or sequencing DNA. And thanks to CRISPR, we can make small edits in the genome. But we're still not good at writing from scratch," explained Mazzoni. "Writing or building new pieces of the genome could help us to test for sufficiency -- in this case, find out what the smallest unit of the genome is necessary for a cell to know where it is in the body."

Mazzoni teamed up Jef Boeke, director of the Institute of System Genetics at NYU Grossman School of Medicine, who is known for his work synthesizing a synthetic yeast genome. Boeke's lab was looking to translate this technology to mammalian cells.

Graduate student Sudarshan Pinglay in Boeke's lab fabricated long strands of synthetic DNA by copying DNA from the Hox genes of rats. The researchers then delivered the DNA into a precise location within pluripotent stem cells from mice. Using the different species enabled the researchers to distinguish between the synthetic rat DNA and the natural cells of mice.

"Dr. Richard Feynman famously opined, 'What I cannot create, I do not understand.' We are now a giant step closer to understanding Hox," said Boeke, who is also a professor of biochemistry and molecular pharmacology at NYU Grossman and is the study's co-senior author.

Source: ScienceDaily

Learning and remembering movement

 From the moment we are born, and even before that, we interact with the world through movement. We move our lips to smile or to talk. We extend our hand to touch. We move our eyes to see. We wiggle, we walk, we gesture, we dance. How does our brain remember this wide range of motions? How does it learn new ones? How does it make the calculations necessary for us to grab a glass of water, without dropping it, squashing it, or missing it?

Technion Professor Jackie Schiller from the Ruth and Bruce Rappaport Faculty of Medicine and her team examined the brain at a single-neuron level to shed light on this mystery. They found that computation happens not just in the interaction between neurons (nerve cells ), but within each individual neuron. Each of these cells, it turns out, is not a simple switch, but a complicated calculating machine. This discovery, published recently in the Science magazine, promises changes not only to our understanding of how the brain works, but better understanding of conditions ranging from Parkinson's disease to autism. And if that weren't enough, these same findings are expected to advance machine learning, offering inspiration for new architectures.

Movement is controlled by the primary motor cortex of the brain. In this area, researchers are able to pinpoint exactly which neuron(s) fire at any given moment to produce the movement we see. Prof. Schiller's team was the first to get even closer, examining the activity not of the whole neuron as a single unit, but of its parts.

Every neuron has branched extensions called dendrites. These dendrites are in close contact with the terminals (called axons) of other nerve cells, allowing the communication between them. A signal travels from the dendrites to the cell's body, and then transferred onwards through the axon. The number and structure of dendrites varies greatly between nerve cells, like the crown of one tree differs from the crown of another.

The particular neurons Prof. Schiller's team focused on were the largest pyramidal neurons of the cortex. These cells, known to be heavily involved in movement, have a large dendritic tree, with many branches, sub-branches, and sub-sub-branches. What the team discovered is that these branches do not merely pass information onwards. Each sub-sub-branch performs a calculation on the information it receives and passes the result to the bigger sub-branch. The sub-branch than performs a calculation on the information received from all its subsidiaries and passes that on. Moreover, multiple dendritic branchlets can interact with one another to amplify their combined computational product. The result is a complex calculation performed within each individual neuron. For the first time, Prof. Schiller's team showed that the neuron is compartmentalised, and that its branches perform calculations independently.

"We used to think of each neuron as a sort of whistle, which either toots, or doesn't," Prof. Schiller explains. "Instead, we are looking at a piano. Its keys can be struck simultaneously, or in sequence, producing an infinity of different tunes." This complex symphony playing in our brains is what enables us to learn and perform an infinity of different, complex and precise movements.

Multiple neurodegenerative and neurodevelopmental disorders are likely to be linked to alterations in the neuron's ability to process data. In Parkinson's disease, it has been observed that the dendritic tree undergoes anatomical and physiological changes. In light of the new discoveries by the Technion team, we understand that as a result of these changes, the neuron's ability to perform parallel computation is reduced. In autism, it looks possible that the excitability of the dendritic branches is altered, resulting in the numerous effects associated with the condition. The novel understanding of how neurons work opens new research pathways with regards to these and other disorders, with the hope of their alleviation.

These same findings can also serve as an inspiration for the machine learning community. Deep neural networks, as their name suggests, attempt to create software that learns and functions somewhat similarly to a human brain. Although their advances constantly make the news, these networks are primitive compared to a living brain. A better understanding of how our brain actually works can help in designing more complex neural networks, enabling them to perform more complex tasks.

This study was led by two of Prof. Schiller's M.D.-Ph.D. candidate students Yara Otor and Shay Achvat, who contributed equally to the research. The team also included postdoctoral fellow Nate Cermak (now a neuroengineer) and Ph.D. student Hadas Benisty, as well as three collaborators: Professors Omri Barak, Yitzhak Schiller, and Alon Poleg-Polsky.

The study was partially supported by the Israeli Science Foundation, Prince funds, the Rappaport Foundation, and the Zuckerman Postdoctoral Fellowship.

source:science daily

Robotic lightning bugs take flight

 Fireflies that light up dusky backyards on warm summer evenings use their luminescence for communication -- to attract a mate, ward off predators, or lure prey.

These glimmering bugs also sparked the inspiration of scientists at MIT. Taking a cue from nature, they built electroluminescent soft artificial muscles for flying, insect-scale robots. The tiny artificial muscles that control the robots' wings emit colored light during flight.

This electroluminescence could enable the robots to communicate with each other. If sent on a search-and-rescue mission into a collapsed building, for instance, a robot that finds survivors could use lights to signal others and call for help.

The ability to emit light also brings these microscale robots, which weigh barely more than a paper clip, one step closer to flying on their own outside the lab. These robots are so lightweight that they can't carry sensors, so researchers must track them using bulky infrared cameras that don't work well outdoors. Now, they've shown that they can track the robots precisely using the light they emit and just three smartphone cameras.

"If you think of large-scale robots, they can communicate using a lot of different tools -- Bluetooth, wireless, all those sorts of things. But for a tiny, power-constrained robot, we are forced to think about new modes of communication. This is a major step toward flying these robots in outdoor environments where we don't have a well-tuned, state-of-the-art motion tracking system," says Kevin Chen, who is the D. Reid Weedon, Jr. Assistant Professor in the Department of Electrical Engineering and Computer Science (EECS), the head of the Soft and Micro Robotics Laboratory in the Research Laboratory of Electronics (RLE), and the senior author of the paper.

He and his collaborators accomplished this by embedding miniscule electroluminescent particles into the artificial muscles. The process adds just 2.5 percent more weight without impacting the flight performance of the robot.

Joining Chen on the paper are EECS graduate students Suhan Kim, the lead author, and Yi-Hsuan Hsiao; Yu Fan Chen SM '14, PhD '17; and Jie Mao, an associate professor at Ningxia University. The research was published this month in IEEE Robotics and Automation Letters.

science daily: