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2016年5月10日星期二

What is the key factor that decides whether you can grow inversely

Years will leave traces on everyone, but the depth of this trace is individual. A recent study published in the journal Current Biology reports that whether you look young or not depends on your genes. MC1R gene will make people grow red hair and pale skin. Now scientists have found that the perception of the individual variation and age-related gene on. Carry a particular variant MC1R people look two years older than their actual age. "This is the first to find such genes," Manfred Kayser Netherlands, Erasmus MC University.

Previous studies have shown that a person's perception of age affected by genetic and environmental factors in a group. Interestingly, the perception seems to predict an individual's age, health and death. This shows that our biological age and state of health and appearance important link.

Kayser and colleagues of 2,000 six hundred elderly genome and face digital photos in-depth analysis. Studies have shown that the elderly age and looks MC1R gene variant strongly associated with carrying a particular variant MC1R people look two years older than their actual age. This relationship MC1R mutation and age perception is not affected by age, sex, skin color, sunburn and other factors. In addition to affecting the color, MC1R also inflammation, DNA damage repair work in the process. MC1R gene may affect human physical appearance it is through this way, we decided to look not years of age. Such studies can help people learn more about the nature of health and aging.

Aging makes us the original luxuriant hair is more sparse, or even completely disappear. Science magazine two papers, in the form of a commentary article, reveals the mysterious mechanisms behind this process, describes the relationship between aging, hair loss and dry cells. Tokyo Medical and Dental University research team found that aging will damage the hair follicle stem cells to make them into the skin. As time goes by slowly, this problem occurs on a growing number of stem cells, eventually leading to hair follicles to shrink and disappear.

In the last journey of life, the body functions gradually aging degradation, getting closer and closer to death. A comprehensive understanding of human aging is not easy, because the process is quite complex. Researchers Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing published in Cell Systems magazine articles, first proposed four levels of aging, aging research and discusses some of the problems in this framework. Corresponding author of the article is Pei Liu (De-Pei Liu) early academicians and Dr. Hou-Zao Chen.

Joslin Diabetes Center scientists hava conducted aging research at one millimeter-long nematode. They found different ways (such as caloric restriction and rapamycin therapy) to extend the life will affect the expression of collagen and other extracellular matrix proteins (ECM). Extracellular matrix is an important framework that provides support matrix for the tissues, organs and bones. Related papers are published in the journal Nature.

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2016年4月28日星期四

Scientists have developed a new technology to joint DNA barcode in a single cell

According to the latest issue of Molecular Systems Biology, Canada researchers have developed a new technology that can joint DNA (deoxyribonucleic acid) barcode in a single cell to search interaction among millions protein pairs.

In recent years, DNA barcode technology enables scientists to carry out high-parallel test (many different types of cells in the same test tube) possible, and develop next-generation DNA sequencing technology, to further improve the counting and the barcode reading results of efficiency.

However, the number of tests carried out in the same test tube, but is limited by the number of cell type-coded. All along, DNA barcodes are one-dimensional, which is a bar code can only do one test. Allow barcode together in the cell, which means scientists can now break this barrier. The new technology can significantly increase the number of experiments carried out in a single test tube, under the same conditions can cost 10 times more efficient.

Widely used in yeast two-hybrid (Y2H) method, carry a "bait" proteins in yeast cells and carry a "prey" proteins in yeast cells mate. After Y2H manipulate the system, only the "bait" and "prey" protein cells stick together to survive, so that scientists can observe the correlation between what each protein. It is named "Fusion barcode Genetics - yeast two-hybrid (BFG-Y2H)" new technologies, carrying thousands of "bait" and "prey" protein pair in the same cell culture dish.

The novelty of the method is that the BFG-Y2H by cells programmed from the "bait" and "prey" DNA barcoding cells connected together to form a "fusion barcode", then use the next-generation DNA sequencing methods for fusion barcode testing.

The researchers said the ultimate goal of this study is to establish a three-dimensional view of protein interaction network rather than a static map. By establishing effective protein interaction maps contain richer information, BFG-Y2H method can extend the researchers' understanding of the mechanism of cells, proteins and show interaction among proteins which only take place under certain environmental condition, thus accelerating the understanding of gene functions and human disease.

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2016年4月12日星期二

New method of storing data by DNA

According to the University of Washington (UW) official website news, research scientists from the university and Microsoft in terms of DNA data storage goes a step further: they passed the 1's and 0 transcoding adenine, guanine, cytosine, and thymine this DNA nucleotide sequence of the four kinds of constitution, and the success of the pictures and videos stored in the DNA fragment, and a lossless data is read, the latest research will revolutionize computer or storage.

According to a report from the British Daily Mail recently, the amount of data of humanity "digital universe" is expected to reach 44 trillion GB in 2020. At that time it will exceed our storage capacity. In order to compensate for the lack of storage space, scientists are trying to store data information into DNA. UW associate professor of computer science and engineering Luis Sezi said, "Life creates the amazing molecule of DNA, which is capable of efficiently storing various data which are related with human genes and life systems. It is very compact and durable."

In the latest study, researchers converted 0 and 1 long sequence from the digital data of images and video into four basic components of DNA sequences. Subsequently, the digital data is divided into pieces and stored by being synthesized as a large number of artificial synthetic DNA molecules. Such molecules can be dehydrated and stored for a long time. Moreover, with the use of DNA sequencing technology, the researchers were able to "read" the data and convert it into original form, and a lossless image reading can be achieved. This study compresses digital data which can fill the entire Wal-Mart to the size of a lump of sugara.

Sezi said, "We used a series of molecular biology experiments to demonstrate the feasibility of our system design. We have succeeded in the data storage in the DNA and performance of random can read back to the original value."

The researchers explained that compared with the current digital storage technology, DNA molecules improves the tightness of data storage by hundreds of times. At the same time, the data storage devices we currently use such as flash memory, hard disk, magnetic disk and optical storage media would be damaged in a few years, but the new method can save the information for centuries.

However, the researchers said they are also facing a huge challenge, namely, to enhance the cost and efficiency of the new method so that it can be applied on a large scale.

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2016年4月11日星期一

HIV shows its resistance to gene scissor

There is new evidence showing that HIV is fickle and difficult to cure. Chinese and Canadian scientists published an article in the American journal Cell Report on the 7th reporting that the HIV now can also soon show resistance response to the popular "gene scissors" therapy, but this therapy is still expected to be improved to continue to be anti-AIDS.

Scientists discovered that bacteria can obtain partial DNA (deoxyribonucleic acid) fragment and integrate it into the genome to form memory after a virus infection. When invaded again by this time, bacteria will transcribe corresponding RNA (ribonucleic acid) and use the "location information" therein to guide the locating and cutting of Cas protein complexes, thus destroying the invading virus DNA.

In recent years, the popular "gene scissors" therapy - genome editing technology CRISPR just uses this principle, using a customized RNA to lead Cas9 enzyme which acts as a role of scissor responsible scissors effect. Scientists cut the DNA viruses imported by HIV into host cells according to presupposed sites, thus preventing the proliferation of HIV replication.

But according to these new reports, their experiments confirmed that HIV can escape under gene scissors rapidly. The sequencing of the genome with HIV escape indicates that this virus had changed the DNA target sequence identified by CRISPR technology.

Liang Chen pointed out that the appearance of HIV's escape or a "resistance" is not accident. What surprised them was that further analysis showed that the changes of HIV were mostly not caused by virus reverse transcriptase which was generally considered by the scientific community. He thought the changes happened when host cells were trying to restore the cracked DNA because of cutting after Cas9 enzyme cut the DNA of HIV. "In other words, the therapy also helps in the escape of the virus when inhibiting the proliferation of HIV."

The researchers proposed two improved schemes to treat AIDS using gene scissors: one is to attack multiple HIV genomic sites to increase the difficulty of escape for virus; the second one is to use scissors enzyme except Cas9.

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2016年4月1日星期五

Scientists identify that change of DNA can decrease 3 years of human life

Scientists identify that change of DNA can decrease 3 years of human life. Scientists have found that the differences between the two independent DNA regions of human chromosomes may affect the person's life. These two changes, called variant, relatively common in humans. There are more than two thirds of humans would inherit a single copy of a variant from father or mother.

The study found there is a variant of the single-copy might reduce human life expectancy of up to one year, about two-thousandths people inherit two copies of the variant of the research team predict the average person's life may be reduction of 3 years. One variant associated with increased lung cancer risk and a serious respiratory disease associated genes. Another variant occurs in a gene associated with high cholesterol and Alzheimer's disease.

The study also found that the impact of these variants for male and female life expectancy is different. Genes associated with Alzheimer's disease a greater impact on women, and lung disease associated with a greater impact on men variability.

Researchers at the University of Edinburgh, by analyzing more than 152,000 people have the information they found that these people were involved in UK Biobank study, which is a long record of thousands of volunteers, health information projects. The study has been published in Nature Communications and is funded by the Medical Research Council.

Peter Arthur Population Health and Information Sciences Institute of the University of Edinburgh, Dr. Joshi said that although the impact of these big people life mutation on a little surprised, but remember this is only part of the situation, it is very important. The greatest impact on life is our way of life, which we can control.

Jim Wilson from Arthur Population Health and Information Sciences Institute of the University of Edinburgh said the finding is just tip of the iceberg. With the accumulation of this data, we expect more discoveries. What is exciting is that some may be beneficial to health.

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2016年3月30日星期三

The new progress of the liquid biopsy technology

High-throughput sequencing of Circulating tumor DNA (ctDNA) is expected to achieve a personalized cancer treatment. However, the cell-free DNA (cfDNA) in blood is limited, limiting the analytical sensitivity. To this end, researchers at Stanford University have developed a method for correcting errors can be detected frequencies as low as 0.004% of the mutant allele.

In the study published in the journal Nature Biotechnology on Monday, the researchers introduced the approach called integrated digital error suppression (IDES). It is based on the Stanford team developed before a ctDNA detection technology called CAPP-seq, and it has been acquired by Roche.

Previously, the limit of detection CAPP-seq technology is 0.02%, but many have the wrong sequencing fragments. To resolve these errors, the research team first devised a molecular barcodes strategy. Many ctDNA detection developers also use this program to reduce the error rate. Single-stranded DNA and double-stranded DNA barcodes strategies exist, but there are drawbacks. Double-stranded DNA barcodes in reducing errors on better, but less efficient than single-stranded DNA barcoding is therefore not suitable ctDNA limited amount of samples.

To this end, they set out to design a hybrid strategy. First, they devised sequencing connector that can be used for molecular barcodes of single and double stranded. Each strand of the double-stranded molecule of the first four-base mark a bar code, bar code called an index. Then they add two dinucleotide barcode on each of the two strands of the joint, called an insertion bar code. After sequencing, the bar code can be inserted into a complementary match to reconstruct the original double-stranded DNA molecule.

The second step, the Stanford team designed a computational tool that can correct sequencing or PCR system error. To achieve this, they first samples of 12 healthy adults carry CAPP-seq detection. The researchers reported that, despite all kinds of SNV has a background error, but the most common is a G → T transversion, and the error C → T and G → A also has.

They found that, G → T error occurs because the Hybrid Capture Process oxidative damage. They used a computational method to suppress these errors. The combination of these two strategies, so that the error rate has dropped by 15 times, which is by 30 healthy control samples and 142 samples of non-small cell lung cancer confirmed.

Researchers are also NSCLS samples on this verification test. First, they examined 41 patients with advanced NSCLS EGFR mutation hotspot. They detected 88 plasma samples to 412 EGFR mutation, all variations have been confirmed by a tumor biopsy sample. In addition, this test did not check out any false positives.

They then assessed the technical limitations in the detection of the reference cell lines. They created a reference cell lines mixture, wherein the frequency of allelic variation at 0.05-1.6%. They found that the bar code policy and calculation methods are complementary correction, combined with better results. Theoretical detection limit of this method is 0.00025%.

Finally, they used this method to monitor the 30 NSCLC patients with mutations; these patients have had tumor genotyping. The researchers found that they could detect the mutation frequency as low as 0.004%. "To our knowledge, this is the minimum amount of ctDNA with deep sequencing detection by far," the authors wrote.

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2016年3月17日星期四

Obesity parents are more likely to have fat daughters than fat boys

Researchers have found that the adverse impact of diet on health can happen through egg and sperm cells to their offspring even it is not under the case of DNA mutations. A mice study recently published in the journal Nature Genetics provides the most powerful evidence for the non-genetic inheritance of organisms' acquired traits by far. Moreover, although previous studies have shown that sperm cells can carry epigenetic factor, this is the first time that such effects were observed in the egg cell.

Scientists have long suspected that parents' lifestyle and behavior choices will affect the child's health through epigenetics. While the DNA or chromosome chemically modified protein can affect gene expression, but it does not change the gene sequence. Therefore, these changes can be inherited remains controversial.

In the latest study, the German Research Center for Environmental Health endocrinologist Peter Huypens and colleagues for 6 weeks to genetically identical mice fed three kinds of food - high fat, low fat or standard laboratory chow - one. Unsurprisingly, eat a high fat diet mice began to gain weight, and damage tolerance to glucose, which are the early symptoms of type 2 diabetes.

Subsequently, the team from the three groups of mice was taken out of the egg and sperm cells, in vitro fertilization and embryo transplantation to get healthy "surrogate" mother's body. Their idea is that if one kind of behavior or physical characteristics can be observed in the offspring, then it can only be transmitted through the egg or sperm cells.

As the offspring of mice subsequently when fed a high-fat diet, obesity has parents who seem to be more likely to gain weight, and glucose intolerance occur, especially if the parents are obese, then. Parents are relatively thin offspring weight gain to a minimum.

Surprisingly, the authors report the difference between the male and female offspring: If the parents are obese, the daughter seems more likely to gain weight, and the son often only shows glucose intolerance. Compared to the father, the mother's diet style seems to have a greater impact on the offspring's metabolism. Huypens said that this is very interesting, because a similar pattern in some human epidemiological studies also appeared.

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2016年3月3日星期四

Epigenetic label on DNA controls can decide the fate of cells

Epigenetic modification is a kind of important regulatory mechanisms without changing DNA sequence. Epigenetic label on DNA controls the switch of genes and can decide the fate of cells. Currently-known DNA modifications are accidentally discovered by scientists.

MIT and the University of Florida researchers recently developed a systematic approach to exploring the unknown DNA modification, and published in the PNAS journal PNAS on 29 February. "We have developed a technology platform to discover new nucleic acid modification," Peter Dedon MIT professor of Road.

Researchers used bioanalytical chemistry, comparative genomics and long read sequencing combined in bacteria and found a new DNA modification. Such modification can help bacteria resist the invaders, to protect their genome. Dedon and his colleagues believe, bacteria and viruses, there should be a variety of unknown DNA modification, which is expected to become a new tool for new targets antibiotics or genetic engineering.

Braid queuosine and Old purine archeosine are two RNA modified microorganisms, and they come from a common precursor --preQ0. University of Florida professor Valérie de Crécy-Lagard had examined the RNA required for gene modification. Through comparative genomics, she found that many bacteria DNA may also have such modifications. Researchers confirmed by mass spectrometry, DNA of these bacteria do carry similar preQ0 structure. They named this DNA modification dADG.

Studies have shown that these bacteria dADG modification is part of the defense system. There is no invasion of virus DNA such modifications, will be degraded to produce bacterial restriction enzyme. Dedon and de Crécy-Lagard other bacteria are exploring other features dADG epigenetic modification.

The researchers used a single molecule real time sequencing (SMRT) technology dADG modifications were analyzed. SMRT sequencing of DNA modification in the face will produce a signal "to adjust the software will be able to obtain the correct signal to understand DNA modification in what position in the genome," Dedon said. "This technology can locate the full genomic DNA modification." The study will SMRT sequencing, comparative genomics and biochemical analysis combine to provide people with the search for and identification of new DNA modification an effective way.

In recent years, especially Epigenetics DNA methylation research has aroused great enthusiasm. With the help of the chip and second-generation sequencing technology, the researchers detected by epigenetic state of the genome, worthy of further study identified a large number of methylated regions. How should these areas be further studied or how to verify it? A large number of samples for genome-wide scan clearly unrealistic and cost of doing so is too high. In fact, there is no need for some areas to detect whole genome DNA, tools described in this article is sufficient to accomplish this task.

N6-methyladenine (6mA) is a widely exists in prokaryotes methylation bases, mainly play a role in host defense system. Recently, scientists have found 6mA also more common in eukaryotes, and undertake the important biological functions. Professor He Chuan Shi Yang, a professor at Harvard University and the University of Chicago published an article in the authoritative journal Nature Reviews Molecular Cell Biology, reviewed the research progress recently achieved in eukaryotes 6mA. This article shows the detection 6mA for people in the genome of a variety of methods, such as within specific antibodies and 6mA sensitive restriction enzyme. In addition, the article also describes mediated 6mA of DNA methyltransferase and demethylase.

Human life can be said to be an ongoing process to make a choice, such as deciding whether to go on a diet, exercise or smoking. These choices will bring our life with better or bad influence, but scientists still know little about the molecular mechanisms. University of Edinburgh research team published an article pointed out, a large map of the lifestyle and environment affect methylation, methylation patterns can actually predict the death of the journal Genome biology. They take methylation patter as an epigenetic clock of measuring physiological status, which determines every individual's life span.

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2015年11月15日星期日

New metabarcoding approach to boost population of honeybees

Researchers at the Ohio State University are using the latest DNAhttp://www.cusabio.com/ sequencing technology and a supercomputer in order to uncover what honey bees rely on. After several months' research from beehives, they developed a multi-locus metabarcoding approach to identify which plants, and what proportions of each, are present in pollen samples they collected. A beehive can collect pollen from different plant species, and the pollen is a strong evidence of the hive's foraging behavior and nutrition preferences. "Knowing the degree to which certain plants are being foraged upon allows us to infer things like the potential for pesticide exposure in a given landscape, the preference of certain plant species over others, and the degree to which certain plant species contribute to the honey bee diet," says Rodney Richardson, graduate student from the Ohio State University. "One of the major interests of our lab is researching honey bee foraging preferences so we can enhance landscapes to sustain robust honey bee populations." Richardson and his colleagues took metabarcoding as the key to this research. It is a DNA analysis method that enables researchers to identify biological specimens. It works by comparing short genetic sequence "markers" from unidentified biological specimens to libraries of known reference sequences. Metabarcoding can be used to detect biological contaminants in water and food, characterize animal diets from dung samples, and even test air samples for bacteria and fungal spores. When it comes to pollen, it could save a lot of time for researchers to identify and count individual pollen grains under a microscope. The researchers used three specific locations in the genome, or loci, as markers, to devise the new metabarcoding method and found that using multiple loci simultaneously produced the best metabarcoding results for pollen. In their publication in the November issue of Applications in Plant Sciences, they described the entire procedure including DNA extraction, sequencing, and marker analysis. "With a tool like this, we could more easily assess what plants various bee species are relying on, helping to boost their populations as well as the economic and ecological services they provide to our agricultural and natural landscapes." Richardson says, "While the honey bee is seen as our most economically important pollinator, it's only one of several hundred bee species in Ohio, the vast majority of which are greatly understudied in terms of their foraging ecology." The new tool can help humans to assess what plants various bee species are relying on more easily, thus helping to boost their populations. Since the honey bee is seen as the most economically important pollinator, their prosperous population can improve the economic and ecological services they provide to our agricultural and natural landscapes. You may like this>>>http://www.cusabio.com/Clone/VV10542-1089591.html

2015年10月14日星期三

A new study shows that external environment and oxidation threats DNA most

Recently a study has found that forces from external environment and oxidation may be the greatest threats to an organism's ability to repair damage to its own DNA.
The results are published in the journal of the Proceedings of the National Academy of Sciences. The results are based on the first comprehensive, whole genome analysis of spontaneous mutation in the bacterium Escherichia coli.
"Our study investigated 11 DNA repair pathways previously identified as resulting in spontaneous mutations," said Foster, a professor in the IU Bloomington College of Arts and Sciences' Department of Biology. "The striking result was that only loss of the ability to prevent or repair oxidative DNA damage significantly impacted mutation rates. ... All other forms of DNA damage arising within the organism did not disturb the overall accuracy of DNA replication in normally growing cells.
"These results suggest that DNA repair pathways may exist primarily to defend against externally induced damage to the genome," she said. Foster's lab and her work concentrates on DNA mutagenesis and repair.
E. coli is a bacterium discovered in mammalian digestive tracts. It's more known as a source of food poisoning. It was chosen for the research because the biological pathways that control DNA repair have changed little as more complex organisms evolved, increasing the chances that the study's results are applicable to higher forms of life, including humans.
Foster's lab created the world's most comprehensive picture of genetic mutation in the species by tracing changes in E. coli's complete genome over the course of 200,000 generations.
The IU team concentrated on 11 processes identified in other studies as causing mutation when deactivated, to focus their investigation on the relative importance of the pathways that repair DNA damage to genetic mutation. The pathways were isolated using 11 different strains of E. coli, each defective for one of the specific pathways.
After investigation, the DNA repair pathways under investigation fell into three broad categories. They were the activities of error-prone DNA polymerases, repair of internally induced DNA damage, including oxidation, and repair of DNA damage due to external agents. Each pathway is more or less specific for a given type of DNA damage.
External agents such as radiation, chemical compounds and platinum-based compounds, are forces that affect DNA. And internal agents that damage DNA are produced by the body's own normal processes. Oxidation occurs in the body as a result of metabolic processes that use oxygen, creating molecules known as "free radicals" that steal electrons from other molecules in the body, causing damage. Many types of cancer and even aging have been linked to DNA oxidation
The IU scientists used whole genome sequencing to catalog the specific genetic changes that resulted from loss of each repair pathway.
Foster said that, surprisingly, the IU team found that none of the pathways resulted in mutations except the ones that deal with damage from oxidation. This means that the other types of damage—from either internal or external causes—are not a great threat to normally growing cells.
These pathways may be important, however, when cells are exposed to external agents or other forms of stress.
The more complete picture of genetic mutation—made possible by the IU team's previous documentation of the bacterium's evolution over 200,000 generations—is likely responsible for the difference in the study's results compared to previous research implicating all 11 DNA repair pathways in genetic mutation, Foster said.
"Previous studies on mutational processes have relied on reporter genes"—single genes that signal larger changes across the genome—"to detect mutations, and these may not be representative of the genome as a whole," she said. "While reporter genes can reveal important mutational processes that occur at particular spots in the DNA, when the whole genome is the target, these localized errors don't appear to contribute to overall mutation."
Foster's next step is investigate DNA repair functions in cells under stress, which may provide a more complete model for mutational processes in living human cells existing in different states and environments all over the body.
The experiments and research can help scientists understand more about DNA repair in our body and the importance of them.
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2015年10月13日星期二

How does DNA operate to drive cell activities?

A research group from Baylor College of Medicine revealed in unparalleled detail the three-dimensional structure of biologically active DNA. Their report is published in the journal Nature Communications online.
"The beautiful double-helical structure we all know and love is not the actual active form of DNA," said Dr. Lynn Zechiedrich, professor in the department of molecular virology and microbiology, and co-contributing author with Dr. Wah Chiu, professor in the Verna and Marrs McLean Department of Biochemistry and Molecular Biology.
Chiu and Zechiedrich, cooperating with Dr. Steven Ludtke and Dr. Michael Schmid, who is also at Baylor College of Medicine, and Dr. Sarah A. Harris of the University of Leeds in the United Kingdom, examined tiny DNA minicircles containing only 336 base pairs, using methods from chemistry, physics, math and computer modeling. Base pairs are the building blocks of genetic material.
Previous studies were on short fragments of linear DNA, but human DNA is constantly moving around in our body, and it coils and uncoils. Researchers can't coil linear DNA and study it, so they had to make circles so the ends would trap the different degrees of winding, according to Zechiedrich.
In the human body, each cell holds about a meter of DNA which is ten million times longer than the tiny circles the team made. In the research, the researchers wound or unwound a single turn when the DNA double helix comprising their circles and used very powerful microscopes to see how the winding changed what the circles looked like.
They did a test to ensure the tiny twisted up DNA circles that they made in the lab were biologically active. They used purified human topoisomerase II alpha. It's an essential enzyme that manipulates DNA and important target of anticancer drugs. The results indicate that the circles must look and act like the much longer DNA that topoisomerases encounter in human cells.
"Being able to observe individual DNA circles allows us to understand the different structures of biologically active DNA. Each of these different structures facilitates how DNA interacts with proteins, other DNA and RNA, and anticancer drugs, adapting to the cell processes required," said Dr. Jonathan Fogg, the other lead author of the publication, also of Baylor College of Medicine.
The researchers hoped to see the opening of base pairs when the DNA was underwound, but they were surprised to see the opening for the overwound DNA. They supposed this disruption of base pairs may cause flexible hinges, allowing the DNA to sharply bend, and it may help to explain how a meter of DNA can be pushed into a single human cell.
What the researchers will be aimed at is to add other components of the cell or anticancer drugs to figure out how the DNA shapes change. More researchers are joining in to get new findings.
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2015年10月11日星期日

New technology developed to sequence genes: faster, better and cheaper

If DNA is called the blueprint of life, RNA is the construction contractor who interprets it. Therefore, it is quite important to sequence RNA for it shows you what is happening inside a cell.
Recently, researchers from UConn Institute of Systems Genomics have sequenced the RNA of the most complicated gene known in nature. What they use is a hand-held sequencer which is not as big as a cell phone.
Genomicists Brenton Graveley from the UConn Institute of Systems Genomics, postdoctoral fellow Mohan Bolisetty, and graduate student Gopinath Rajadinakaran together with UK-based Oxford Nanopore Technologies to show that the company's MinION nanopore sequencer can sequence genes faster, better, and at a much lower cost than the standard technology. Their findings were published in Genome Biology on Sept. 30.
If your genome was a library and every gene was a book, some genes would be straightforward reads, but some would be more like a "Choose Your Own Adventure" novel. Researchers tend to know which version of the gene is actually expressed in the body, but for complicated choose-your-own-adventure genes, it has been impossible. The researchers solved the problem in two parts.
The first was to find a better gene-sequencing technology. They used the old existing technology to sequence genes. This technique won't work for choose-your-own-adventure genes, because if you copy them the way the body does, using RNA, each copy can be slightly or very different from the next. Such different versions of the same gene are called isoforms. When the different isoforms get chopped up and sequenced, it becomes impossible to accurately compare the pieces and figure out which versions of the gene you started with.
Last year, the impossible things became possible. Oxford Nanopore, a company based in the UK, released its new nanopore sequencer, and offered one to Graveley's lab. The nanopore sequencer, called a MinION, works by feeding a single strand of DNA through a tiny pore. The pore can only hold five DNA bases - the 'letters' that spell out our genes - at a time. There are four DNA bases, G, A, T, and C, and 1,024 possible five-base combinations. Each combination creates a different electrical current in the nanopore. GGGGA makes a different current than AGGGG, which is different again than CGGGG. By feeding the DNA through the pore and recording the resulting signal, researchers can read the sequence of the DNA.
In the second part, the researchers chose the most complex one known, Down Syndrome cell adhesion molecule 1 (Dscam1), which controls the wiring of the brain in fruit flies. Dscam1 has the potential of making 38,016 possible isoforms, and every fruit fly has the potential to make every one of them, yet how many of these versions are actually made remains unknown.
Dscam1 looks like this: X-12-X-48-X-33-X-2-X, where X's denote sections that are always the same, and the numbers indicate sections that can vary (the number itself shows how many different options there are for that section).
The researchers had to convert Dscam1 RNA into DNA to study how many different isoforms of Dscam1 actually exist in a fly's brain. If DNA is the book or set of instructions, RNA is the transcriber that copies the book so that it can be translated into a protein. The DNA includes the instructions for all 38,016 isoforms of the Dscam1 gene, while each individual Dscam1 RNA contains the instructions for just one. No one had yet used a MinION to sequence copies of RNA, and though it was likely it could be done, demonstrating it and showing how well it worked would be a substantial advance in the field.
Rajadinakaran took a fruit fly brain, extracted the RNA and converted it into DNA, isolated the DNA copies of the Dscam1 RNAs, and then ran them through the MinION's nanopores. In this one experiment, they not only found 7,899 of the 38,016 possible isoforms of Dscam1 were expressed but also that many more, if not all versions are likely to be expressed.
The study shows that gene sequencing technology can now be accessed by more researchers than before, since the MinION is both relatively inexpensive and highly portable.
"This type of cutting-edge work puts UConn at the forefront of technology development and strengthens our portfolio of genomics research," says Marc Lalande, director of UConn's Institute for Systems Genomics. "Also, thanks to the investments in genomics through the University's Academic Plan, Brent Graveley can leverage his expertise so that faculty and students across our campuses will successfully compete for grant dollars and launch bioscience ventures."
The researchers are planning to sequence every bit of RNA from beginning to end inside a single cell. This can't be done by traditional gene sequencers. This new technology is supposed to transform the way we study RNA biology and the type information.
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2015年10月8日星期四

Observe living cells by use of a new DNA stain

Though bio-imaging is helpful to visualize the inner workings of a cell while it is still alive, the living cells put under the microscope risk being killed by the light and the fluorescent dyes used to highlight their structures. It is much like sunburnt - live cells are sensitive to intense light and the ultraviolet and blue lights used in live-cell imaging are the most dangerous. Now, EPFL scientists have developed a new DNA stain that can be used to safely image live mammalian cells for days even under demanding imaging conditions.
The work about this new DNA stain is published in Nature Communications.
Fluorescent stains that light up a cell's DNA allow people to track key biological processes such as cell division thus they are popular in live-cell imaging. But current DNA stains are themselves toxic or require types of light that can damage the cells. Ideally, a safe DNA fluorescent stain would be activated in the safer far-red spectrum of light.
What's more, a lot of DNA stains are not compatible with super-resolution microscopy, a modern imaging technique that can capture images of cells at higher resolution than that allowed by regular microscopes. So the bio-imaging community has been waiting for a DNA stain that shows low toxicity, works with far-red light and can be used in superresolution microscopy.
The lab of Kai Johnsson at EPFL has now developed a DNA stain that can satisfy all of the needs. The scientists combined two molecules together - One is a fluorescent molecule (silicon rhodamine or SiR) that works in the far-red spectrum and was previously developed in Johnsson's lab, and the other one is a well-known DNA stain Hoechst (the chemical name is bisbenzimide). Finally, the scientists named the DNA stain "SiR-Hoechst".
The new stain works by binding to a part of the DNA helix known as the "minor groove". Once bound, it turns on and emits a bright fluorescent red light. This is a tremendous advantage, as the stain produces very little noise - if it has not found its target, it stays "off". More importantly, SiR-Hoechst can bind to DNA without affecting its biological function in the cell. And because all cells possess DNA, the probe can be used across numerous species, types of cells, and tissues.
There is little risk of damage to cells because SiR-Hoechst works with far-red light. Besides, the light that it emits can be easily distinguished from any background fluorescence of living cells. These features give SiR-Hoechst a clear advantage over other DNA stains - it can safely maintain high-quality staining in live cells for over 24 hours, allowing biologists to identify individual cells in tissue or culture, or track delicate processes in real time.
This stain can be used in live-cell super-resolution imaging, helping to solve problems in DNA imaging in cells and biological tissues with exquisite resolution.
The SiR-Hoechst makes bioimaging safer. That is, it realizes the dream of observing details of nature without impacting them.
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2015年9月21日星期一

DNA sequencing device helps to treat UTIs

A new research from the University of East Anglia suggest that a new DNA sequencing device can treat Urinary tract infections (UTIs) more quickly and efficiently. This device is called MinION. It was used to perform nanopore sequencing to characterise bacteria from urine samples four times more quickly than using traditional methods of culturing bacteria.
The method can also detect antibiotic resistance, which improve the efficiency of treatment and stewardship of diminishing antibiotic reserves.
Urinary tract infections are among the most common reasons for prescribing antibiotics. Most are mild and only affect the lower urinary tract, but a few are more troublesome. These 'ascending' UTIs cause a growing burden of hospitalisations, mostly of elderly patients. Infection spills into the bloodstream, leading to a condition called urosepsis, which can be fatal.
Antibiotics are vital, and it must be given urgently especially when bacteria has entered the bloodstream. But unfortunately it takes two days to grow the bacteria in the lab and test which antibiotics kill them.
The research team used a new small DNA sequencing device called Nanopore MinION from Oxford Nanopore Technologies to investigate UTIs quickly - without culturing the bacteria.
The device is about the size of a USB stick. It could detect the bacteria in heavily infected urine and provide its DNA sequence in just 12 hours, which is too much faster than conventional microbiology. This technology is rapid and capable not only of identifying the bacteria in UTIs, but also detecting drug-resistance at the point of clinical need.
There are still more limitations to be overcome. This method currently only works with heavily-infected urine and can't yet predict those resistances that arise by mutation. But as the study is still going on and the technology is developing, more can be achieved.
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2015年9月15日星期二

New technology developed to unlock DNA secrets of elusive vaquita

The vaquita is one of the most endangered marine mammals on Earth. Protecting these enigmatic animals is extremely urgent. Surprisingly, a new method of teasing information from scarce and highly degraded samples is helping NOAA Fisheries and Mexican scientists unlock the genetic heritage of the endangered Mexican based animal.

Genetic studies can help scientists unlock the DNA secrets of the vaquita. For example, through the study we can get to know the story of how and how long ago the animals evolved into a unique species adapted to warm desert environment when most porpoises live in cool waters. All these information can do great help.

The scientists are faced with a great problem. Fewer than 100 vaquita remain living in the murky waters of the northern Gulf of California. It's hard to find them and collecting samples of their DNA since they are so wary and skittish. Most of the available genetic samples of vaquita come from animals inadvertently killed in fishing nets, which is a chief cause of mortality. They usually have been deteriorated by the time they reach a laboratory.

A small biotechnology company based in Ann Arbor, Michigan, called Enter Swift Biosciences, has developed new methods for dealing with damaged and highly degraded DNA. Traditional methods require sizeable samples of intact DNA in its double-stranded form. The Swife's "next-generation" DNA sample preparation approach can extract genetic material even from bits and pieces of single-stranded DNA which have severely degraded for a long time.

You can obtain useful information though they're not that much. But it is a valuable tools to protect our wildlife resources.

Morin's team then applied the technology to 12 samples of vaquita DNA - including some that were even more degraded and of poorer quality than the harbor porpoise samples. The Swift sample preparation system produced useful data from all of the vaquita samples.

"It was a pleasant surprise to find that we had been able to generate genetic information that had seemed beyond reach without the Swift technologies," said Barbara Taylor, the SWFSC's leading vaquita biologist.

There is not much of a fossil record for porpoises, so genetics also provides the only real way to understand the animal's evolutionary history. Initial findings from the new research now confirm that vaquita apparently split from another species of porpoise from the Southern Hemisphere about 2 to 3 million years ago and have since survived on their own, in relatively small numbers.

The lab plans to apply the technology to other degraded DNA samples to find more evolutionary clues of other animals. The data will be a precious part for preserving endangered animals.

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