DNA World

Jan 27, 2018

DNA-based compound may reduce damages of Alzheimer's disease: study

Researchers at Washington University School of Medicine in St. Louis have created a kind of DNA-base molecule targeting APOE protein. APOE is a major Alzheimer's risk gene.

The study has been published on Dec. 6 in the journal Neuron.

The molecule, known as an antisense oligonucleotide, interferes with the instructions for building the APOE protein.

The researchers injected the compound into the fluid surrounding the brains of newborn mice. For comparison, they gave other newborn mice either saltwater or a placebo "oligo" that does not interfere with the APOE instructions. Levels of APOE protein dropped by about half in mice given the APOE compound as compared with those that received the placebo oligo or saltwater.

Two months later, the researchers gave the mice a booster dose of the treatment or the saltwater. They examined the mice's brains at 4 months old. The mice that received the APOE antisense oligos had about half as many amyloid plaques as mice given saltwater. Each plaque triggered only half as much damage to nearby neurons, an indicator that the compound had prevented some of the neurological damage that leads to Alzheimer' s disease.

The researchers then tested whether giving the APOE compound after amyloid plaques appear could prevent further changes to the brain. They introduced either the APOE compound or saltwater into the fluid surrounding the brains of 6-week old mice, and then examined the mice's brains at 4 months old. They found no difference in the number of plaques or the total amount of amyloid beta between the mice that received the compound and those given just saltwater. The compound failed to reduce the amount of amyloid in the mice's brains.

However, in the mice treated with the APOE compound, each plaque triggered only about half as much damage to the surrounding neurons. This suggests that even a late start could reduce the harm posed by amyloid beta.

"If you wanted to target APOE to affect the amyloid process, the best thing would be to start before the plaques form," said senior author David Holtzman, professor and head of the Department of Neurology of Washington University at St. Louis. "But even if you start later, you still may reduce the amount of damage caused by the plaques."

Alzheimer's, which affects one in 10 people over age 65, is marked by brain plaques made of a sticky protein known as amyloid beta. The plaques start forming in the brains of Alzheimer's patients years before the characteristic symptoms of memory loss and confusion appear. APOE4 raises the risk of Alzheimer's partly by encouraging amyloid beta to collect into damaging plaques. People with APOE4 face up to 12 times the risk of developing Alzheimer's than the general population.

"Scientists have been interested in APOE for years but there are only a few examples where researchers have targeted it with a compound in living animals," said Holtzman. "Our findings indicate that APOE is not just involved in Alzheimer's risk and disease progression, but it could potentially be a real target for treatment or prevention."

DNA lab for identifying missing persons opens in The Hague

The International Commission on Missing Persons (ICMP) on Tuesday opened a state-of-the-art DNA laboratory at its new headquarters in The Hague.

The laboratory system focuses exclusively on missing persons identification and utilizes Next Generation Sequencing (NGS), a technique that is expected to deliver an exponential increase in the power of DNA identification, according to ICMP, a treaty-based international organization with a mandate to secure the cooperation of governments and others in locating and identifying missing persons.

Since 2001, ICMP has operated a DNA laboratory system to assist governments in identifying large numbers of persons missing from conflict, human rights abuses, natural and manmade disasters, organized crime, irregular migration and other circumstances where persons go missing for involuntary reasons.

The system, which is designed to work on the most challenging cases, operates on a high-throughput scale. It has generated DNA results on more than 50,000 cases of degraded skeletal remains and contributed to the identification of around 20,000 persons worldwide.

With the new laboratory, ICMP aspires to maintain a capacity of up to 10,000 cases a year.

Over the course of two decades, ICMP has responded to a wide variety of complex missing persons scenarios in over 40 countries.

Scientists create DNA robots for future delivering drugs in human body

Scientists have created miniature robots out of DNA that can autonomously "walk" around a surface, pick up certain molecules and drop them off in designated locations, a new study published Thursday in the U.S. journal Science said.

"Just like electromechanical robots are sent off to faraway places, like Mars, we would like to send molecular robots to minuscule places where humans can't go, such as the bloodstream," said LuLu Qian, assistant professor of bioengineering of the California Institute of Technology.

Such technology could one day be used for a wide range of applications, including synthesizing therapeutic chemicals in an artificial molecular factory, delivering drugs in bloodstreams or cells, or sorting molecular components in trash for recycling, Qian said.

To create a DNA robot, Qian's team constructed three basic building blocks, including a "leg" with two "feet" for walking, an "arm" and "hand" for picking up cargo, and a segment that can recognize a specific drop-off point and signal to the hand to release its cargo.

Each of these components is made of just a few nucleotides within a single strand of DNA.

In principle, these modular building blocks could be assembled in many different ways to complete different tasks.

For example, a DNA robot with several hands and arms, could be used to carry multiple molecules simultaneously.

In the work described in the Science paper, the Qian group built a robot that could explore a molecular surface, pick up two different molecules and then distribute them to two distinct regions on the surface.

"The DNA robot moves around on a 58-nanometer-by-58-nanometer pegboard on which the pegs are made of single strands of DNA complementary to the robot's leg and foot," Qian's team said in a statement.

"The robot binds to a peg with its leg and one of its feet -- the other foot floats freely," the team said.

"When random molecular fluctuations cause this free foot to encounter a nearby peg, it pulls the robot to the new peg and its other foot is freed. This process continues with the robot moving in a random direction at each step."

Since one step for the little guy takes five minutes, and allows it to move six nanometers, it may take a day for the robot to explore the entire board, the team said.

"Along the way, as the robot encounters cargo molecules tethered to pegs, it grabs them with its 'hand' components and carries them around until it detects the signal of the drop-off point," it said.

"The process is slow, but it allows for a very simple robot design that utilizes very little chemical energy."

In a summary on the robot, the Science magazine called Qian's work "one small step for a DNA robot, one giant leap for mankind."

"The future is here," the summary wrote.

Ancient Eurasian DNA sequencing reveals how modern humans migrate

Chinese researchers are discovering unexpected genetic connections between individuals on opposing sides of Eurasia with direct DNA sequencing.

Their study suggests a complex history that may represent early gene flow across Eurasia or an early population structure that eventually led to Europeans and Asians.

In a review published in the journal Trends in Genetics on Thursday, scientists at the Chinese Academy of Sciences in Beijing discuss the genetics of ancient individuals from Europe and Western Asia between 45,000 to 7,500 years ago.

The authors summarized work that investigated the genomes of more than 70 ancients in the Eurasian family tree.

"Aside from these individuals, it is a fact that sampling for the Eurasian region is sparse for all time periods except the present-day," says the correspondent author Fu Qiaomei, a paleogeneticist at the Chinese Academy of Sciences.

"But with the information from the several individuals available for ancient DNA sequencing we do have hints at interesting population structure, migration and interaction in East Asia."

The researchers learned that in Eurasia between 35,000 and 45,000 years ago, at least four distinct populations were present. These were early Asian and Europeans, as well as populations with ancestry hardly found or not at all in modern populations.

It shows that, by 7,500 to 14,000 years ago, the populations across Eurasia shared genetic similarities, suggesting greater interactions between geographically distant populations.

These analyses also revealed at least two Neanderthal population mixing events, one approximately 50,000 to 60,000 years ago and a second more than 37,000 years ago.

Fu and colleagues hope to extend this type of sequencing and analysis to learn more about the genetic prehistory of East Asia and other regions, including Oceania, Africa, and the Americas.

"All of those areas have a rich human prehistory, particularly in Africa, so any ancient DNA from those continents will likely resolve some major questions on human migration," she says.

DNA Modification/Epigenetics

Analysis of Mitotic Checkpoint Function in Xenopus Egg Extracts

Yinghui Mao

Cold Spring Harb Protoc 2018; doi:10.1101/pdb.prot099853

Abstract Full Text (PDF)

Analysis of DNA Methylation in Mammalian Cells

Paul M. Lizardi, Qin Yan, and Narendra Wajapeyee

Cold Spring Harb Protoc 2017; doi:10.1101/pdb.top094821

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Jan 27, 2018

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