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 which also publishes other studies on recombinant horse proteins.

"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. Flarebio provides you with good-quality recombinant proteins including recombinant NRG3 at good prices.

Get to know the greatest athlete in the world!

When speaking of the greatest athletes in the world, you may think of the names like Usain Bolt or Yohan Blake generally. It's amazing that scientists now find the greatest athletes may be the in the water and covered in scales through study using recombinant proteins - They are fish.

They discovered that fish are far more effective at delivering oxygen throughout their body than almost any other animal. This advantage gives them the athletic edge over other species.

"Fish exploit a mechanism that is up to 50-times more effective in releasing oxygen to their tissues than that found in humans," says study lead author, Dr Jodie Rummer from the ARC Centre of Excellence for Coral Reef Studies at James Cook University.

Haemoglobin in fish, the protein in blood that transports oxygen, is more sensitive to changes in pH than ours and more than the haemoglobins in other animals. It is quite important for fish during times of stress, to escape from predators, or when they are living in water that is low in oxygen. They can double or even triple oxygen delivery to their tissues during these critical times.

In the last decade, researchers have been using rainbow trout to investigate oxygen delivery in fish. They first discovered and tested this mechanism by monitoring muscle oxygen levels in real-time in trout. Now they have determined just how powerful that system can be and have compared the results with medical studies on humans.

It shows us how fish have adapted this very important process of getting oxygen and delivering it to where it needs to be so that they can live in all kinds of conditions such as warm or cold water, or nd water with high or low oxygen levels. For these athletic fish, enhanced oxygen delivery may be the most important adaptations during their long evolutionary years. Flarebio provides good-quality recombinant proteins like recombinant NRG3 at competitive prices.

A protein that plays an important role in the development and progression of cancer

Researchers at the Sylvestre Cancer Research Center in the United States have discovered a protein that plays an important role in the development and progression of cancer through research using recombinant dog proteins, and this protein accumulates in dormant cancer cells and forms amyloid small body. Once this amyloid decomposition, cancer cells will be re-active. The study was published in the journal Developmental Cell.

We know that these amyloid bodies are related to the occurrence and development of Alzheimer's disease and Parkinson's disease, the relation of deposition of starch bodies and cancer is not clear. This study suggests that we can apply the knowledge of neuroscience to cancer so as to obtain a variety of types of cancer treatment.

"We found that these proteins are abundantly present in dormant cancer cell bodies, while the heat shock pathway breaks down the amyloid bodies formed by this protein deposition, which in turn restores dormant cancer cells," the experts said.

The study also found that ribosomal non-coding genes control the formation of amyloid bodies in cancer cells, so we can also take this gene as a target to produce drugs. If we can prevent the decomposition of amyloid in cancer cells, then we may be able to keep the cancer cells dormant indefinitely. In addition, we can also try to find another way for cancer cells to produce such amyloid bodies, thus making the active state of cancer cells to dormant state.

Through this study, we can imagine in the future that we may not have to completely remove the cancer cells. We can just keep it in a dormant state. Experts say that they are confident they can develop a new kind of cancer drugs. These drugs take related genes and pathways as targets, and some related drugs have been put into the market, while other drugs are still in the research process. Flarebio provides good-quality recombinant proteins such as recombinant NRG3 at competitive prices.

To teach protein knowledge through playing games

Gamers players defeated the trained scientists to complete an accurate model of a specific protein at full speed in the same biochemical data obtained conditions through a science-based online game Foldit.

"In this way, they can improve research progress and the knowledge of recombinant proteins such as recombinant horse proteins." Co-author of the study, James Bardwell from the University of Michigan Michigan said.

This game involved 469 Foldit players, two highly-trained experts in crystallography, and two computer algorithms to see who can accurately establish YPL067C protein model through translating electron density map. Eventually, gamers united and established the most accurate version through painful trial and error in the protein modeling experience, Stubbs was the first Quebec.

Organizers stated that the game results show competition may be an effective way to educate students about the protein modeling knowledge. Because compared to the traditional way of learning, competition makes this time-consuming process more interesting. And it encourages cooperation.

"We can see that the players learned a lot of knowledge about proteins in the process of playing the game," co-author, Scott Horowitz from University of Michigan Hoorn said, "We spend weeks of time trying to put these into the brains of students, but Foldit players naturally learn them, because this is very interesting."

Even cooler is that organizers say the gamers may have discovered a new protein that may control the formation of plaque, which can bring more understanding of Alzheimer's after in-depth study. New findings have been published in the journal Nature Communications. Flarebio provides you with superior recombinant proteins like recombinant NRG3 at good prices.

The trails of preventing deterioration of DLBCL

Recently, a new therapeutic drug is in its clinical Phase II experiments. The drug is mainly for those patients with deterioration of diffuse large B-cell lymphoma (DLBCL), because most of these patients will show tumor metastasis over time. The main target of this drug is histone modifying enzyme, and this target shows obvious effect on some tumor with genetic variation. The design of experiments was mainly done by Sarit Assouline, a blood disease oncologist in Jewish hospital and he is also very interested in producing recombinant proteins like recombinant horse proteins. And the research results have been published in Blood, which is the top journal in Hematology.

Dr. Assouline, associate professor of medical oncology at McGill University said, "DLBCL is a relatively common form in lymphoma and has relatively-high invasiveness. With the deterioration of the disease, there is no effective clinical treatment. The patients have an average life expectancy of 6 months. Our task is to find a new specific target in turn to improve the prognosis of patients, but many clinical trials are just focusing on the patient's response to different treatments. Our aim is to be able to better improve the effectiveness of the treatment on the basis of understanding the mechanism of disease."

Among DLBCL patients, up to 40% of them who receive conventional chemical immunotherapy, stem cell transplantation or several joint treatments still show no effects. New treatment method has a stronger against nature on the basis of deeply explaining molecular structures. Almost all of DLBCL patients contain mutations of histone modifying enzyme gene, so histone acetyl transferase inhibitors have a significant effect on the level of improving the treatment of patients.

In the experiment, subjects went through complex genetic analysis and strict distinction. 28% of patients respond well to the above treatment, and the expression of MEF2B gene was closely related to the curative effect of patients. By analysis of collected biopsy and blood samples, the study revealed that this drug can affect a series of proteins in the body of these patients. If we can take advantage of the latest diagnostic technology to assist, the effect will be better. Flarebio provides superior recombinant proteins like recombinant NRG3 at competitive prices.

The growth of abdominal aortic aneurysm may be inhibited by the tea polyphenol in green tea

A research team at Kyoto University announced in August 18, 2016 that they demonstrated through mice experiments that tea polyphenol in green tea can prevent the spread and magnification of abdominal aortic aneurysm. Researchers from Kyoto University accomplished the experiments using recombinant mouse proteins, and detailed findings have been published in the renowned medical journal Journal of Vascular Surgery on July 26th.

Once abdominal aortic aneurysm is ruptured, the mortality of a patient is more than 50%. During the period from the onset to the tumor rupture, the patients often show no noticeable symptoms, so it is difficult to detect. The larger the diameter of tumor is, the higher the risk of rupture is.

In this study, the team members divided the mice with abdominal aortic aneurysm into two groups. In two weeks' time, one group was provided with normal drinking water, while another group was provided with drinking water mixed with green tea with tea polyphenol. Two weeks later, through serving elastase and other substances, they established experimental mice models of abdominal aortic aneurysm.

Through four weeks' observation after the establishment of models, the researchers found that compared with the group served with normal drinking water, the group served with drinking water containing green tea polyphenol, the growth of abdominal aortic aneurysm was significantly suppressed. Besides, green tea polyphenol also promotes the synthesis of elastin. Elastin is the main component protein of aorta wall, and the increased content of makes abdominal aortic aneurysm difficult to break. The researchers confirmed that inflammation caused by abdominal aortic aneurysm was also suppressed. Although excessive intake of green tea polyphenol may cause liver dysfunction, the amount of this experiment didn't cause the adverse effects.

Green tea polyphenol has a physiological role in inflammatory and anti-oxidation and can play a preventive effect on cancer and cardiovascular disease. Researchers at Kyoto University said the results of this study show the possibility of effect of green tea on human health and life extension. Flarebio provides recombinant proteins of good quality like recombinant NRG3 at competitive prices.

Nature: toremifene is expected to be an anti-Ebola drug

Fatal infections caused by Ebola virus (EBOV) break out frequently in recent years, and Ebola outbreak in West Africa caused a large number of deaths. There are no approved effective drugs or vaccines against EBOV. Since 2013, scientists have adopted a large number of small molecules and marketed drugs in vitro mouse model tests and computer virtual screening to find compounds of anti EBOV. In 2013, Johansen, LM et al., conducted experiments on a series of selective estrogen receptor modulators including anticancer drug toremifene, finding that they have potential inhibitory effect on EBOV virus. But they did not clarify the mechanism.

Recently, David I. Stuart and other researchers from the University of Oxford took EBOV outer membrane glycoprotein (GP) as the study object and found that toremifene can combine GP and reduce its stability, thereby blocking viral fusion with the endosomal membrane and playing anti-viral effect. They also resolved the crystal structure of GP protein and the complex of GP protein, toremifene and ibuprofen, clarifying the action mechanism of toremifene.

EBOV outer membrane has a three-glycoproteins (GP, furin protein is cut into two subunits GP1 and GP2), which is solely responsible for host cell attachment, fusion kernel entry and film. Thus, GP is the primary target for the development of antiviral drugs. The researchers used recombinant protein - recombinant EBOV outer membrane glycoprotein (GP) to test whether the nine compounds would bind directly to proteins through the method of protein thermal transfer. Experimental results showed that when the dose of toremifene was 100 μM and pH value was 5.2, it can significantly reduce the melting temperature (Tm) of EBOV GP to 14 ℃. This is opposite to the previously-reported research result that inhibitors reducing the melting temperature of proteins will increase the stability of protein structure. In contrast, ibuprofen showed only a very critical effect (Tm decrease rate was less than 2 ℃), lacking for potential virus inhibition.

The researchers also first reported EBOV GP protein with no ligand and high-resolution crystal structure of the GP and toremifene and ibuprofen complex. Surprisingly, toremifene and ibuprofen all combined in a hole between the subunits GP1 and GP2. This hole is located in a huge tunnel entrance, and this big tunnel can be connected with other similar tunnels. The interactions of drug and GP1, GP2 are mainly hydrophobic effect. In filamentous virus, amino acid residues which combine with these drugs are highly conserved, excepting Marburg virus (MARV), indicating that the Marburg virus probably will not be combined with these drugs. This work illustrates the suppression mechanism of drugs on viruses, providing a viable direction for the development of more anti-EBOV drugs. Flarebio Biotech LLC is a National High-Tech Enterprise with research, production and sales as one. And high-quality recombinant proteins such as recombinant NRG3 are offered at competitive prices.

The replication of EBOV (Ebola virus) requires a modified human protein

The replication of EBOV (Ebola virus) requires a modified human protein. Although many recombinant human proteins have been developed, this new discovery may open a new door for the treatment of EBOV.

EBOV is one of the deadliest known human pathogens and can cause severe hemorrhagic fever. When EBOV replicate themselves within the cell, it makes its own proteins passes through the basic mechanisms of taking over and hijack the host cells.

In this study, virus fragments with no infectious were used to study viral gene expression. Small molecule drugs were used to inhibit the function of cellular pathways related to protein synthesis. These drugs and other pathways can reduce the viral gene expression, suggesting that the pathway blocked by the drugs may prevent EBOV replication. To confirm this, the research team cooperated with the University of Texas Medical Branch. Researchers at the university tested that when a small molecule they studied existed, the self-replication capacity of EBOV would show some changes. They found that when adding the drugs, the number of self-replication of EBOV reduced. The findings were published in the journal mBio, which also publishes some other studies on recombinant proteins.

In order to investigate the cause of this phenomenon, the study looked at what happened to certain viral proteins when the pathway opened and closed. They found that one of the proteins of EBOV, VP30, would accumulate in cells when the pathway opened, while it wouldn't accumulate when the pathway was closed. These results indicated that VP30 protein was the only viral protein that causes the phenomenon above.

"A protein synthesized by a virus needs an unusual part of the mechanism of a host protein synthesis. We have found that if blocking the function of this part, the viruses would show some problems when replicating themselves. Therefore, reducing the ability of a certain kind of proteins in viral replication, the entire replication cycle could be affected." explained Dr. John Connor, the corresponding author, associate professor of microbiology at Boston University school of Medicine.

According to the researchers, these findings identified a necessary and uniquely-modified human protein for Ebola virus to grow in cells. "Aiming at this human protein may present a new target for treatment of Ebola. These studies can help us understand and fight active or dormant Ebola virus infection." He added.

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