Why does Gleevec only bind to Abl but not recognize its kin Src?

In the journal Science, Biochemistry Professor Dorothee Kern at Brandeis University, who is also a researcher at Howard Hughes Medical Institute reveals the evolution tour of billions of years of Abl and Src protein and points out the exact evolutionary change which causes the condition that Gleevec binds well with one and binds poorly with the other. Such a new method for enzyme study and their binding sites are likely to have a significant impact on the development of rational anti-cancer drugs. According to the research using recombinant mouse proteins, the researchers knew that the two proteins have only a difference of 146 amino acids, but there is a huge difference between them - i.e. Abl is sensitive to anticancer drug Gleevec, while Src is not.

Developing more drugs like Gleevec which can play a role - referred to as rational drug design - may be possible to create some new therapies targeted to specific enzymes in many cancer types. Unfortunately, scientists don't know why Gleevec is so picky that it only binds to Abl but not recognize its kin Src.

In order to unlock this puzzle, Kern and her team made use of recombinant proteins like recombinant rat proteins and recombinant human proteins and started to find out the common ancestor of Abl and Src a billion years - an original protein which is known as ANC-AS in yeast. They draw a phylogenetic tree and searched for some amino acid changes and molecular mechanisms.

With the ANC-AS evolution in more complex organisms, it began to specialize and branch into a number of proteins which showed different control, roles and catalytic processes - generated Abl and Src. By tracking this process and testing the protein's affinity for Gleevec along this road, Kern and the study group narrowed the reasons which lead to specificity of Gleevec from the differences of 146 amino acids to that of 15 amino acids.

These 15 amino acids play a role in the conformational equilibrium of Abl. Conformational equilibrium refers to the conversion of a protein between two structures. For binding to Gleevec, the main difference between Abl and Src lies in the relative time of protein staying in each conformation, resulting in the great difference in their binding ability. By understanding the causes and mechanism of Gleveec acting on Abl and being ineffective on Src, the researchers obtained a starting point to design other drugs that have high affinity, specificity and can bind to them. Flarebio provides recombinant proteins such as recombinant Ext2 at good prices.

The mystery of Zika virus replication in the host cell has been uncovered

The mystery of Zika virus replication in the host cell has been uncovered. Recently, Yang Haitao research team from Tianjin University published an article in the journal Protein & Cell which also published some other studies on recombinant proteins (including recombinant dog proteins) to show the crystal structure of Zika virus helicase, unlocking the key process and mechanism of Zika virus replication. The results would play a positive role in the development of antiviral drugs.

In the study, Yang Haitao team successfully obtained the 3D image when Zika virus helicase was conducting function and binding to substrate. The researchers also showed the spatial structure of ternary complex formed by Zika virus helicase, adenosine triphosphate and metal catalyst ions at the atomic resolution level. In addition, they also successfully captured the intermediate state of Zika virus helicase binding to ATP and metal ions. This is the first time to reveal the structure when flavivirus family (a mosquito-borne virus, including Zika virus, dengue virus, yellow fever virus, West Nile virus, etc.) helicase binding to natural substrate ATP. Yang Haitao said, "Through the analysis of this structure, we can reveal the mechanism of how Zika virus helicase identifying ATP catalytic metal ions."

To explore the differences between Zika virus with other flavivirus members in the mechanism of replication, the researchers also resolved three-dimensional structure of complex when Zika virus helicase binding to genomic RNA. They found that a pathway across helicase was responsible for "seizing" RNA. Surprisingly, Zika virus helicase would undergo significant conformational changes after binding to RNA, while these kind of conformational changes were quite different to the helicase of dengue virus.

The study indicates that helicase of flavivirus family evolved a conservative molecular "motor" in the evolutionary process. It can turn chemical energy into mechanical energy through nucleoside triphosphate hydrolysis to implement "melting" in the process of viral replication; while making use of different "movement" mode, helicase of different virus members recognize and bind to genomic RNA in a different way to meet the needs of viral replication. Flarebio offers good-quality recombinant proteins such as recombinant EXT2 at competitive prices.

The discovery of new mechanism of hepatitis C helps to improve new effective drugs

Recently, researchers from Osaka University redefined the new mechanism of hepatitis C (HCV) transmission from the angle of enhancing the liver function. They used a mouse model to demonstrate that when a particular enzyme is inhibited, virus particles produced by HCV would be reduced so as to improve pathological liver disease, and thus they determined a new drug target. Some recombinant human proteins also can treat the disease.

Currently, nearly 200 million people worldwide are infected with hepatitis C virus. It can cause fatty liver, cirrhosis, liver cancer and other diseases after infection with hepatitis C virus. In Japan, hepatitis C virus is the culprit which causes liver cancer. Although researchers now have developed many enzymes against the copy of hepatitis C to clear HCV, the presence of a lot of viruses with drug resistance and cancer incidence after clearing the virus can't be explained. So far, removing the core protein of virus in host cell is still the main method, but through many research using recombinant mouse proteins and recombinant rat proteins, we are still not very clear about the mechanism in it.

Associate professor Toru Okamoto and Yoshiharu Matsuura at the Institute of Microbial of Osaka University were responsible for the study. When the enzyme SPP is inhibited, the virus particles are reduced, finally improving the pathological liver disease.

γ- secretase inhibitor is a kind of drugs are now developed and used in the Alzheimer's, but from which the researchers discovered a chemical that can inhibit the enzyme SPP. At the same time, they found that the removal of core proteins mainly relied on the enzyme TRC8, and this enzyme is very easy to be degraded. If the degradation ability is inhibited, the cell would receive great harm due to the stress effect of endoplasmic reticulum, and then the synthetic proteins can't properly fold, which leads to cell damage. Therefore, this degradation process is a novel protein controlling mechanism. The SPP mouse model will enhance the treatment outcomes of patients.

The study showed that SPP inhibitor is a new therapeutic drug of hepatitis C. Besides, observing the formation of proteins through SPP / TRC8 signaling pathway also improves the development of a series of drugs. Flarebio provides you with good-quality recombinant proteins such as recombinant INSRR at good 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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The new mechanism of AMPK signaling regulating autophagy

Autophagy is a process of degrading cytoplasmic proteins and organelles relying on lysosomal pathway, and it has high conservatism in evolution. It exists widely in cells of animals from the yeast, nematodes, and fruit flies to higher vertebrates. In mammals, when cells sense external stimulation and nutritional signals, they would meet the physical needs of cells to promote the body's metabolism of certain proteins by degrading macromolecule like organelles which lose cell function and proteins which lose normal function. Autophagy not only provides recyclable materials for cell repair and cell regeneration but also can help cells resist pathogen invasion and nutritional deficiencies. Therefore, autophagy is generally considered as patron saint of sustaining cell life and maintenance its stability. However, the process of autophagy is extremely complicated, especially the fine regulation mechanism of autophagy. Explore how nutrition and hunger signals autophagy signals are integrated and transmitted to the downstream of autophagy has always been a hot topic of biological research. And all the studies can’t leave the use of different kinds of recombinant proteins such as recombinant horse proteins.

The formation of VPS34-VPS15-Beclin1 core complex would happen in the initial stage of autophagy. With other autophagy-related proteins such as Atg14L (autophagy-related protein 14) adding to the core complex, VPS34 (Ⅲ type phosphatidylinositol muscle alcohol 3-kinase) would gradually be activated and produce PtdIns3 P (phosphatidylinositol 3-phosphate) which plays an important promoting role on autophagic vacuole spreading taking PtdIns (phosphatidylinositol) as a substrate. When autophagy does not happen, Beclin1 would combine with Bcl2 and stay in resting state. Many kinases related to nutrition and growth such as mTOR and EGFR all can conduct phosphorylation on core scaffold protein Beclin1 in VPS34-VPS15-Beclin1 core complex to control the lipase activity of VPS34 in the way of changing the way the components of the complex, thereby affecting whether to conduct autophagy.

AMPK is an important kinase of cellular energy sensing and cell signaling regulation in autophagy process. Through research using recombinant rat proteins, researchers found that glucose would activate AMPK under condition of starvation, leading threonine 388 site in autophagic gene Beclin1 to show phosphorylation, promoting the dissociation of autophagy gene Beclin1 and Bcl2 and promoting the combination of Beclin1, VPS34 and Atg14L. These dissociation and binding changes makes VPS34 show extremely powerful catalytic activity, thereby producing a large number of PtdIns3 P to promote autophagic vacuoles to be generated at a near-hurricane-like velocity speed, greatly contributing to the occurrence and development of autophagy.

The study reveals the important role of Beclin1-T388 site in AMPK-mediated autophagy process during glucose deprivation, which provides important theoretical basis and feasible drug targets to further explore the molecular mechanism of autophagy and treatment of autophagy-related diseases and neurodegenerative diseases. Flarebio provides you with recombinant proteins like recombinant Cdh10 with good quality.

Chinese researchers find the gene that promotes breast cancer to metastasize

A study group led by Professor Gao Hua from Tongji University in China found TM4SF1 gene which promotes breast cancer to metastasize to multiple organs. There are also many other studies on some recombinant proteins that promote tumor metastasis. Related research papers were recently published in the journal Cell. Cutting off or preventing the expression of this gene may be the primary target to treat recurrence and metastasis of breast cancer. "Our research on targeted therapies has got good results." Gao Hua said.

Tumor recurrence and metastasis is the most direct cause of death of the vast majority of cancer patients. In early stage of breast cancer, tumor cells would leave the primary site "seed and grow" to fatal metastases at a plurality of far-end organs like lung, bone and brain. Despite the fact that the recurrence of tumor metastasis has important clinical significance, the related research is very weak, especially whether core genes exist in the process of tumor metastasis to multiple target organs is still unclear.

The human body has a kind of proteins which come across the lipid bilayer, and they are also known as transmembrane proteins. TM4SF1 is a member of transmembrane 4 protein family with specific evolution. They have up-regulated expression in lung cancer, colorectal cancer, breast cancer and ovarian cancer a variety of tumor compared with that in normal tissues. Over the years, Gao Hua study group used a mouse model as a screening tool in vivo to establish a high-throughput, genome-wide-level, function-related genetic screening platform in order to find out the molecules directly related to the recurrence and metastasis of breast cancer, lung cancer, colorectal cancer and other tumors and the cellular and molecular mechanism. In 2014, with the help of recombinant mouse proteins and recombinant dog proteins, the study group found that TM4SF1 played a very important role in self-renewing of normal and cancer stem cells.

On this basis, the study group continued to use immunohistochemical methods to analyze tissue microarray of 147 cases of breast cancer patients who had complete clinical information and found TM4SF1 genes had up-regulated expression in breast cancer patients, and the survival of patients was significantly shorter; Conversely, the survival was significantly prolonged. The computer bioinformatic analysis of 3,455 cases of primary site and metastatic tumor site of breast cancer also showed similar results.

Gao Hua said that according to the strength or weakness of TM4SF1 gene expression, they can predict the length of time of occurrence of breast cancer metastasis. "Currently, we are in accordance with the idea of translational medicine to cooperate with domestic enterprises to conduct treatment research on monoclonal antibodies and small molecule compounds. We have made good progress and achieved good results."

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Get to know the mechanism of air pollution inducing lung cancer

Through in-depth study, Zhou Guangbiao research group from Animal Institute of Chinese Academy of Sciences found the key long-chain non-coding RNA of air pollution-induced lung cancer. Related achievements were published recently in Oncology journal Oncotarge. According to study, some recombinant proteins can inhibit lung cancer.

It is understood that lung cancer has become the cancer with world's highest incidence and most deaths, and 90% of lung cancer is caused by smoking, air pollution and other environmental factors. However, the mechanism of air pollution-induced lung cancer molecular is unclear.

Previous studies have shown that air pollution can make organism genomes show a large number of mutation; inflammatory cytokines CXCL13, CXCL20, miRNA-144 and other factors play an important role in lung cancer air induced by pollution and smoking. In this study, the researchers analyzed the role of long-chain non-coding RNA (lncRNA) in lung cancer caused by air pollution.

It is understood that IncRNA is a class of non-coding RNA which can regulate gene expression in transcription, post-transcriptional and epigenetic levels. By lncRNA chip, the researchers found that lung cancer samples in air pollution area contained more lncRNA with abnormal expression, and CAR10 is a long non-coding RNA associated with air pollution. Studies have shown that high expression of CAR10 is associated with air pollution.

Further studies showed that dibenzanthracene in PAHs family promoted CAR10's expression in lung epithelial cells through transcription factor FoxF2, while after binding to transcription factor YB-1, CAR10 inhibits its degradation by the proteasome and causes accumulation of nucleus YB- 1 protein and promotes expression of epidermal growth factor, thereby promoting cell proliferation and inducing lung cancer. Flarebio provides you with high-quality recombinant proteins such as recombinant CDH11 at competitive prices.

Researchers identify new mechanism of tuberculosis infection

Researchers at UT Southwestern Medical Center have discovered a new way of tuberculosis bacteria entering human body, revealing the potential treatment. One of the world's most deadly diseases, tuberculosis - mainly lung disease, has infected 8 million people and results in 1.5 million deaths each year. Scientists have conducted many studies using recombinant proteins including recombinant horse proteins.

A new study published online in Cell Report determines another way of bacteria entering the body, which may have a significant impact on the development of new therapies for prevention of tuberculosis infection.

Research team led by Dr. Michael Shiloh found that the micro-folding cells (M-cell) transmission is a new, unknown mechanism of Mtb entering human body. M-cell is specialized airway epithelial cell, and its role is to transport particles from the compartment of lower airway mucosal cell surface. Shiloh said, "Our research shows that once inhaling Mtb bacteria, they can also directly enter the body through the connection airway tissues of M-cell and then go to the lymph nodes. This is a key finding, indicating that it is possible that the disease attacks outside alveolar macrophages and the pathogenesis of tuberculosis infection are also very important."

Dr. Shiloh who are interested in producing different recombinant proteins such as recombinant dog proteins said that this M-cell mediated Mtb mechanism may help explain an ancient disease called lymphatic system. In this disease, tuberculosis infection rarely occurs in the lungs but causes cervical lymph node disease.

Although further research is needed, the potential clinical applications found by the team will help to develop methods or drugs which prevent Mtb from entering M-cells. For example, Dr. Shiloh said that to prevent Mtb from attack receptors on the surface of M-cells such as vaccinating anti-bacteria protein - can be prevent bacteria from entering, infecting and spreading to other organs.

Dr. Shiloh and his team are currently working to find out M-cell receptor in human cell surface which involve in Mtb bacteria transmission and the exact mechanism by making bacteria on the surface of cells transfer to the bottom. "We are conducting a number of experimental methods to determine Mtb genes and proteins are involved in this process." The lead author and postdoctoral researcher in internal medicine Dr. Nair said.

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Same DNA fragments can match with each other without the help of other molecules

A new study results show that without the help of other molecules, same DNA fragments can match with each other. Genes (genetic factors) are DNA fragments with genetic effect. The results showed that each encoding gene has specific properties, no matter biological properties or biological functions. However, a gene can't always keep intact. It would often show damages and need diagnosis and repair.

The repair process of encoding genes is called homologous recombination. In this process, a broken or damaged gene can be replaced as the complete DNA sequence of the same gene. Wrong interchange of genes would lead to a variety of genetic diseases such as condition progeria, an accelerated symptom of aging.

Gene repair and homologous recombination is the key to reproduction and evolution, because this restructuring process would recombine the genes we obtain from our parents together. Recombinant protein are involved in replication and gene substitution process. However, in the genetic recombination process, the protein will react spontaneously. But the researchers didn't know how homologous genes found each other at that time. In the human genome, after coiling, DNA strand forms complex gene beam, i.e. chromosome. On the chromosome, there are more than 20,000 genes. Therefore, for different DNA strands, it is not easy to find homologous genes.

Imperial College London and the US National Institutes of Health (NIH) carried out a DNA molecule experiment in 2008, and the results showed that without any outside help (i.e. without any guidance of other proteins and molecules), DNA molecules which have the same genetic code can find their pair fragment.

These results show that two relatively- short double-stranded DNA fragments would spontaneously match with the same types of DNA after being mixed randomly in a container. Professor Mara Prentiss from Harvard University also confirmed in the subsequent study that homologous double-stranded DNA can spontaneously match. Flarebio provides you with high-quality recombinant proteins including recombinant CDH4 at a competitive price.

Nature Cell Biology: p21 protein is not always good

In the past 20 years, p21 is considered a "good" protein to indicate good prognosis of tumor therapy, and it is once even seen as a cancer suppressor protein. However, scientists from institutions including University of Athens and University of Manchester have recently revealed its "bad" side. The findings were published in the journal Nature Cell Biology, which has also published some other studies on recombinant proteins like recombinant human proteins.

As a cyclin kinase inhibitor, p21 has always been considered to have close function link with the famous cancer suppressor protein p53. As we all know, p53 is an important cell division checkpoint protein. It ensures the integrity of the genome of a cell by preventing "problem" DNA with defects to spread through replication and cell division until the defects is repaired, thereby curbing the cancer tendency. To do this, p53 would activate many proteins which inhibit cell growth and promote apoptosis, among which is p21 which can make the process of cell division stay in G1 phase. Based on this knowledge, doctors have long been considered the presence of p21 in tumor to be a good sign, thinking that p53 can inhibit tumor growth more effectively in this situation.

However, the researchers found that when p53 is missing, p21 will dramatically promote tumor growth and spread in the body. The authors said, "Without the normal function of p53, the presence of p21 protein would never be a good thing."

Such a conclusion is not envisaged by the original researchers. They initially hoped to find a way to raise the level of p21 protein to achieve the effect of inhibiting tumor. As a result, researchers found another action mechanism of p21.

When p53 is deleted, the continued accumulation p21 protein can inhibit the activity of CRL4Cdt2 E3 ubiquitin ligase, eventually leading the replication process to get out of control. Originally, CRL4Cdt2 E3 ubiquitin ligase should play its role during cell division S phase (i.e., DNA synthesis phase). It prevents multiple copies of DNA in S phase to ensure only one copy by degrading Cdt1, p21 and Set8 and other proteins. If CRL4Cdt2 E3 ubiquitin ligase is inhibited, then the mechanism of DNA replication origin licensing can't work properly, leading to the problem of replication stress and genomic instability. Thus, without "custody" and guidelines of p53, p21 would step toward a carcinogenic "evil way".

Although this finding makes researchers shocked, it also points out another direction - since p21 is dangerous sometimes, then weakening the activity of p21 at that time will be OK. "We now know that is without the control of p53, p21 can lead to uncontrolled cell proliferation, which is a dangerous sign of cancer. Although this discovery breaks our current knowledge, it provides a new through for the development of anticancer therapy,” co-author of this article Professor Paul who is from Townsend University of Manchester said.

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Scientists have found the cause of various types of congenital defects

Scientists first believe they have found the cause of various types of congenital defects caused by environmental pressure. The breakthrough achieved by scientists at Zhang Renqian research Institute indicated that cell stress may be the key to understanding why many babies show defects in heart, spine, kidney when they are born. The research Institute also conducts much other research on recombinant proteins such as recombinant dog proteins.

The study was led by world-renowned professor Sally Dunwoodie. The researchers analyzed the impact of short-term lack of oxygen during embryonic heart development. "Obviously, we all know that smoking has very bad influence on the unborn baby's health. But the embryo hypoxia can be caused by many things, such as prescription drugs, high blood pressure, high altitude, cord entanglement and carbon monoxide," explained Professor Sally Dunwoodie.

Using a mouse model, the scientists reduced from the indoor oxygen content from 21% which was the normal level to 5.5% for 8 hours. Scientists first discovered that reducing oxygen levels can damage the developing heart. The types of heart defects are the same to the most common types in humans. Importantly, scientists have worked out exactly how the oxygen content damages the developing heart.

"We found that the reduce of oxygen content would trigger embryonic cells to show stress reaction. Embryonic cells try to reduce stress by stop making proteins. In the research, the researchers used recombinant horse proteins to get more results. In the critical stage of heart development, the heart can’t properly develop with a sudden lack of proteins." Dunwoodie Professor disclosed.

Importantly, hypoxia in environment is not the only trigger of cell stress. There are many factors that can lead to hypoxia of embryo, such as viral infections, temperature, high blood sugar, malnutrition and pollution. "This cellular stress reaction may be the key that causes a variety of birth defects not just heart defects. Now, we strongly suspect that this is the mechanism of many different types of birth defects, including vertebrae, kidney and other defects."

"Surprisingly, this cell stress reaction has been used by our body for hundreds of millions of years. But until now, we find out that it could lead to abnormal development of organs like heart." Professor Dunwoodie added. At present, the research results have been received by the journal Development. Flarebio provides you with high-quality recombinant proteins including recombinant CDH2 at a good price.

Scientists find the important role of STING proteins

Recently, a new study found that STING (stimulator of interferon genes) signaling pathway may play a key role in changing the immune system. They got the information through a series studies using various recombinant proteins such as recombinant rat proteins.

A cell biology professor Barber from the University of Miami Miller School of Medicine published a study in the journal Nature in 2008. He found that STING is a new cellular molecule, having the function of recognizing viruses, bacterial infections and initiating the body's defense and immune reaction. In the new study published this time in Cell Reports, Professor Barber found STING's function of inhibiting colorectal cancer.

"Since 2008, we have already known that STING is a key molecule of anti-viral and anti-bacterial reaction," Barber said. "But until now, the role of STING in tumors is still poorly understood. In this new study, we first confirm that STING signaling pathway is inhibited in colorectal cancer and other cancers, leading cells to transform and evade the immune system."

There are 1.2 million people suffering from colorectal cancer in the United States and 150,000 cases of colorectal cancer are newly diagnosed each year, making colorectal cancer the third greatest cancer among men and women. Most colon cancers originate in benign polyps and can be successfully treated if detected early. However, if the tumor metastasizes, the survival rate of these patients is generally low. Recombinant human proteins can’t solve the problem.

Using model of colorectal cancer, the researchers found that signal loss of STING can affect the body's ability to identify cells with DNA damage. In particular, it will cause decline of reparation of certain cytokines tissue and lack of anti-tumor immunity, thus leading to the decline of immune response's elimination role of colorectal cancer.

"In addition, we also found that, degradation of STING signal helps damaged cells escape the immune system," Barber said. "If the body does not recognize and attack cancer cells, these cancer cells would rapidly proliferate and finally metastasize to other sites."

Barber and his colleagues reminded that STING signal can be taken as prognostic factor for colorectal cancer and other cancers. For example, Barber's research shows that cancer cells which lacks for STING signal have high sensitivity to oncotic viruses. Other studies also have shown that the regulation of STING signaling pathway plays an important role in cancer development and treatment. Flarebio offers superior recombinant proteins including recombinant CDH2 at competitive prices.

iRhom2 plays an important role in innate immunity to DNA viruses

Natural immunity is the first line of defense for the body to fight viral infections and plays a key role early-stage antiviral immunity for a host. On July 18th, immunology authoritative journal Nature Immunology published the latest research results in the field of anti-DNA virus of innate immunity by Shu Hongbing Research Group at Wuhan University and the study is titled "iRhom2 is essential for innate immunity to DNA viruses by mediating trafficking and stability of the adaptor STING". They also developed recombinant proteins such as recombinant horse proteins and recombinant dog proteins for the research.

The study firstly reported the important role of rhomboid-like protease in the anti-DNA viral innate immune response, providing new clues for understanding the physiological function of these kinds of proteins. More importantly, the study describes the important regulatory mechanism of body's anti-viral immune response of DNA, providing a potential molecular target for the prevention and treatment of related diseases caused by DNA virus infections and autoimmune diseases.

In the latest study, the Shu Hongbing Research Group found iRhom2 proteases play an important role in the anti-DNA virus natural immunity. They used gene-knockout mouse models to confirm that iRhom2 is essential for the host against DNA viral infections. Experiments of biochemistry and cell biology showed that iRhom2 regulated STING through two relatively-independent pathways. On the one hand, iRhom2 transported related protein TRAPb to STING through bridging to promote STING to be transported from the endoplasmic reticulum to microbody in nuclear periphery region and activate downstream transcription factor IRF3 in the process; on the other hand, iRhom2 recruited deubiquitination enzyme EIF3S5 and maintained stability of STING at protein level by removing K48 connection ubiquitination of STING, thereby promoting the activation of downstream transcription factors IRF3. There are many IRF3 recombinant human proteins on sale in the market.

Back in 2008, research group led by Shu Hongbing Research Group and Glen Barber from University of Miami independently discovered a connector protein STING/MITA which plays a key role in anti-DNA virus innate immune. The discovery aroused widespread attention and soon became a hot topic in the field of immunology, and relevant literature papers had become important documents in the field of immunology.

The research work of this paper was mainly completed by doctoral student Luo Weiwei guided by academician Shu Hongbing and young teacher Dr. Li Shu and other fellows, and Shu Hongbing is the responsible author of the paper. The study was funded by Major National Scientific Research Projects and the National Natural Science Foundation of China. Flarebio provides superior recombinant proteins such as recombinant Pigr at a good price. Please feel free to inquire more.

Chinese institute promotes analysis of important protein structures

Recently, researcher Tang Chun group from Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences made use of the new research technology established and based on the 973 major scientific research program "New technological developments in protein research new approach" to assist Professor Yin Ping at Huazhong Agricultural University to firstly analyze the complex structure of N6 adenine methyltransferase METTL3-METTL14 protein, and the research findings were published in the journal Nature. The journal also provides other studies on recombinant proteins such as recombinant rat proteins.

The study reveals the structural basis of RNA N6 adenine methylation modification process and is a major breakthrough in the field of epigenetics. Tang Chun, associate researcher Gong Zhou and postdoctoral Liu Zhu at Wuhan Institute of Physics and Mathematics were involved in the project. They made use of new methods and technology developed by the research group to provide help in research approach for structural analysis of the protein complex through the method of combining of small angle X-ray scattering and computer simulation.

After nearly three years of efforts, Tang Chun group has developed and established a variety of biological, physical and chemical methods including NMR spectroscopy, small-angle X-ray scattering, chemical cross-linking mass spectrometry analysis, single molecule fluorescence detection and imaging technology. They also developed corresponding integration calculation method for the study of dynamic structure of protein and its conversion process. In addition to completing their own scientific research projects, the research group actively carries out extensive cooperation and exchanges and shared research technologies and methods with domestic and foreign counterparts. Currently, thanks to the implementation of the "New technologies and new approaches of protein dynamics studies" project, the research group has promoted the analysis of many important protein structures and made a series of research results. Their findings were published in world-class journals such as Nature - Chemical Biology and eLife. Flarebio provides you with various recombinant proteins including recombinant ECE1 of good quality at competitive price.

Researchers prevent lung injury in mice by inducing cellular autophagy

Recently, researchers from Drexel University and Yale University found in autophagy research that in the process of autophagy, lung injury caused by exposure to high-concentration oxygen in mice can be reduced. The study has been published American Journal of respiratory and molecular biology in this month, also providing a new way of thinking and methods for the prevention of lung injury in premature children. There are many recombinant proteins used to conduct related research.

Dr. Vineet Bhandari, the head of neonatology at Children's Hospital in St Christopher, said, "When the cells are in extreme stress, autophagy is a process that the cells sacrifice unnecessary organelles to protect themselves. Through research, we believe that if we can enhance the cellular autophagy of lung to effectively reduce cell death, finally protecting the lungs of newborns."

Bhandari is specialized in the study of bronchopulmonary dysplasia (BPD), which is the most common chronic lung disease in preterm children. When the babies are born a few weeks or months before the expected date of birth, their lungs are not fully formed or are not able to make enough surfactant or liquid coating. In order to save their life, doctors often have to manage supplemental oxygen. However, prolonged exposure to excess oxygen can increase lung injury, resulting in lifelong lung problems, which can’t treated easily by recombinant human proteins.

Dr. Vineet Bhandari said, "For some preterm children with a genetic predisposition to lung disease, excessive supplemental oxygen can cause inflammation, leading to cell death. And cell death will cause permanent changes of lung structure. Currently, there are up to 15,000 infants having this problem in United States each year. So the present situation is that babies need supplemental oxygen to save their life, and their lungs should be protected from injury on the other hand.

Autophagy allows cells to survive at ambient pressure. In this process, some unnecessary organelles such as the endoplasmic reticulum or mitochondria disintegrate and fuse into an autophagosome and are swallowed by lysosomes to recycle the contents. "It constitutes the digestion of cellular vacuole and the cells themselves," Bhandari said.

In order to find out whether increasing autophagy in lungs may reduce cell death and ultimately prevent lung injury, Bhandari and his team conducted further studies on a regulatory protein called RPTOR. The research results show that cellular autophagy plays a crucial role on the prevention of lung injury. Flarebio also provides you with excellent recombinant proteins including recombinant INSRR for your research.

Scientists find the "on-off" of antiviral immune cells

How does "Once having identified viruses, natural immune cells would response" happen? Academician Cao Xuetao research team from Chinese Academy of Engineering found that DNA methylation enzyme Dnmt3a can make natural immune cells in highly sensitive state against virus infection. Once identifying viruses, they can produce significant interferon and start antiviral innate immune response. The study was published in the UK journal Nature Immunology. Many other recombinant proteins against viruses are also studied.

In order to figure out why the natural immune cells have the function of rapid resistance "virus invasion", the research team first made the natural immune cells infected with virus and analyzes molecular changes of infected cells expression. They chose "epigenetic regulation elements" which can determine gene expression by regulation of DNA methylation as the breakthrough point. By screening, they discovered that DNA methyltransferase Dnmt3a can promote innate immune cells to efficiently release type I interferons.

"Later they got genome-wide DNA of natural immune cells and ascertained the methylation status of the DNA chain at single nucleotide level and drew 'spectrum'. Take this spectrum as a benchmark, we conducted a study of the mechanism." Said Cao Xuetao. He and immunization doctoral student Li Xia at Zhejiang University, Zhang Qian from Key Laboratory of Medical Immunology at second Military Medical University immunization State discovered the specific effect path: Dnmt3a is bound to HDAC9 distal promoter region and maintains the DNA hypermethylation in the region, thereby antagonizing H3K27me3 in the region and promoting the active histone modification levels of proximal promoter to maintain high HDAC9 expression. Highly-expressed HDAC9 then efficiently induce type I interferon through a certain mechanism, starting antiviral innate immune response. The researchers used various recombinant proteins including recombinant mouse proteins to ensure the research results.

Studies have shown that DNA methylation can maintain high expression of key molecules in antiviral signaling pathway, preparing to efficiently and timely start antiviral immune response native cell during virus invasion. The findings reveal a novel epigenetic mechanism of antiviral immune response and also propose new potential molecular targets for prevention and treatment of viral infectious diseases.

Flarebio Biotech LLC is Flarebio Biotech LLC is a National High-Tech Enterprise with research, production and sales as one. We offer recombinant proteins including recombinant ACSL3, antibodies and other related products.

Coats plus syndrome is partly caused by STN1 gene mutations

A research team from Israel discovered that the gene mutation of STN1 which maintains the end chromosome telomere structure would cause a rare genetic disease Coats plus syndrome. The study "Coats plus syndrome caused by STN1 gene mutations is related to telomere defects of gene and chromosome" was published in the online edition of Experimental Medicine on July 18th. The journal also published some other studies related to recombinant proteins.

Coats plus syndrome can affect many body tissues including the eyes, brain, bone marrow and gastrointestinal tract. The disease is caused by gene mutations in encoding CTC1 protein. CTC1 is a protein which protects telomeric end of chromosomes structure. If the function of telosomes goes wrong, then the cell can't divide and chromosomes would fuse together.

Gideon Rechavi from Sheba Medical Center and Raz Somech from Sarah selig Maimonides Medical Health and Institute of Raz Somech led the study. They also like to conduct experiments on recombinant proteins such as recombinant mouse proteins and recombinant rat proteins. The researchers identified two Pakistan Coat plus syndrome patients without CTC1 gene mutations. Instead, STN1 genes of patients mutated. STN1 is a protein structure which maintains telomere with CTC1 and TEN1 together. The telomere function of cells isolated from a patient's body cell went wrong and the dividing ability of cells reduced.

In order to verify that STN1 mutation causes Coats plus syndrome, researchers together with David Wiest from the US Fox chase cancer center conducted gene knock-out experiments on zebrafish. Genetically-engineered zebrafish formed Coats plus syndrome-like symptoms by modeling, including a lack of red blood cells and blood vessels to dilate and broke. The latter symptoms can correct by thalidomide, and thalidomide is an effective anti-angiogenic agent.

The researchers said in the two subjects, one of whom died of a gastrointestinal hemorrhage. However, they can make use of thalidomide to partly relieve the gastrointestinal bleeding in the second patient, establishing a successful "from clinical - basic - clinical" paradigm. The researchers are planning to explore how STN1 mutations cause patient's symptoms. In addition to maintaining normal structure and function of telomeres, CTC1-STN1-TNE1 protein complex also plays an important role in the DNA replication process in the whole genome. This process also has defect in patients’ cells. "What features the defects of telomere or all gene replication have or the role it has on the defects which have nothing to do with DNA replication have not been elucidated." The researchers said. Flarebio is a National High-Tech Enterprise with research, production and sales as one. It offers recombinant proteins (including recombinant cdh1) and antibodies and many other related products at a reasonable price.

Human bocavirus can inhibit NF-κB signal pathway

Human Bocavirus (HBoV) is a newly-discovered pathogen in 2005 can cause intestinal and respiratory infections which in infants. As a new kind of emerging viral pathogen, its pathogenic mechanisms and the molecular mechanisms of how the virus escapes from innate immune recognition of host and some other important scientific issues have urgent need to be clarified. The natural immune system is the first barrier for our body to prevent pathogens from invading, and NF-κB signaling pathway is an important part of the innate immune system. Recently, Wang Hanzhong research team from Wuhan Institute of Virology, Chinese Academy of Sciences has made significant progress in the mechanism of bocavirus regulating NF-κB signaling pathway, revealing bocavirus NS1 protein inhibits p65 from binding to κB binding site by binding to transcription factor p65NTD area, thereby inhibiting downstream gene transcription mechanism. Researchers also produced recombinant human proteins to complete the research. The papers have been published online in the journal Science Report.

Because of the important role of NF-κB signaling pathway in terms against viruses, many viruses have evolved mechanisms to inhibit NF-κB signaling pathway. The targets of most viruses suppressing NF-κB signaling pathway are located on the cytoplasmic IKK complex, and known viruses in the nucleus which are able to inhibit NF-κB signaling pathway are very less. Through research, Wang Hanzhong research team found that NS1 protein of bocavirus is capable of interacting with p65 and further found that NS1 is capable of binding to p65NTD region, while NTD region is the critical domain for p65 to recognize κB binding sites. By DNA binding experiments, the team found that p65 can inhibit NS1 from binding to the κB binding sites. These results suggest that the NS1 protein of bocavirus binds to p65 NTD region to inhibit the interaction between p65 and κB binding site, thereby inhibiting the transcription of the downstream gene.

The study firstly reported that bocavirus has a regulatory role on NF-κB signaling pathway, providing an important basis for understanding the pathogenicity of the bocavirus. The first author of the paper is doctoral Liu Qingshi and the study is supported by the National Natural Science Foundation of China. Flarebio provides high-quality recombinant proteins such as recombinant ITGB8 at a competitive price.

What is it that leads cells to differentiate into T cells?

Every cell in our body has its own fate. They may become skin cells or perhaps other types of cells, and all these are determined by genes. Scientists from California Institute of Technology have further studied the differentiation of T cells. T-lymphocytes are cells secreted by thymus can swallow the virus-infected cells. Similar to using T cell transformation to promote recombinant proteins such as recombinant horse proteins and recombinant dog proteins, the researchers hope to be able to figure out what leads cells to differentiate into T cells.

The study was published in Nature Immunology on July 4th. The lead author and postdoctoral at the school Hao Yuan Kueh said, "We have already known which kind of genes that control cells' differentiation into T cells, but we want to know what original factors are that make this gene play a role."

They found a group of DNA-binding proteins which contains four proteins and they controlled the opening and closing of T cell genes by overlapping layers. This finding is really a great breakthrough, because in the past, our conception of the role of transcription factors is instantaneous. The study could help doctors get a lot of T cells, which has great application significance to viral infectious diseases including AIDS.

Laboratory staff Kueh said, "In the past, we know that the regulation of genes needs the involvement of a variety of transcription factors, and so it is also the same with T cell differentiation. Multifarious transcription factors can ensure that the right expression of cells."

The authors pointed out that the key of this finding is the real-time video of living cells. They used genetically-engineered mice to conduct fluorescence detection on proteins. The transgenic mice were introduced with Bcl11b genes. When this kind of genes is activated, tissues of mice would shine. Through detection of different transcription factors and proteins, the researchers can distinguish the role of different proteins.

These four proteins together play a role in the process of opening the genes, of which the first two proteins (TCF1 and GATA3) opened the door, Notch protein switched the switch and the fourth protein Runx1 amplified the signal. Flarebio is a biotech company which is specialized in research, production and sales of recombinant proteins (including recombinant KEL) and antibodies and other related products.

Scientists find a new compound which can kill drug-resistant cancer cells

Many cancer deaths are because that cancer has resistance to chemotherapy drugs, which also contributed to the development of overcoming this obstacle in the field. Although more and more recombinant human proteins are developed to fight against cancer, it is no enough. A latest research shows that researchers have discovered a new compound that can kill multidrug resistant cancer cells in mice. The team includes members from Pamplona of Navarre, Spain and Krakow, Poland Jagiellonian University School of Medicine, and they published their findings in the journal Bioorganic and Medicinal Chemistry.

Lead author from the University of Navarra and the Jagiellonian University Dr. Enrique Dominguez said, "Our study reports a new method of fighting against cancer with drug resistance. We know there is more research to be conducted, but we are pleased to be able to develop new possibilities and we feel delighted on these results."

The new study came from 57 kinds of compounds which were identified as having anti-cancer properties, the team believed some of which may enhance the effectiveness of chemotherapy drugs. The study focuses on the so-called "efflux pump", which is exposure to cancer chemotherapy to develop a common defense mechanism. Located within the cell membrane, efflux pump is a protein which excludes toxic compound out of cells, and such a protein is called ABCB1. In the study, recombinant mouse proteins and recombinant rat proteins are widely used.

The team wanted to see whether selenocompounds which was found in previous studies can block ABCB1 efflux pump. After multidrug resistance (MDR) in murine T cell lymphoma running a variety of in-vitro experiments, the researchers found that these compounds can prevent efflux pump more effectively than other compounds. They also found that these compounds can trigger cancer cell apoptosis and cell suicide. The most active selenocompounds cab kills about 80 percent of cancer cells in mice.

They acknowledged that the results are only the beginning of the long process of developing a new drug, and the next step will be to conduct vivo experiments on these compounds. Flarebio offers high-quality recombinant proteins such as recombinant Cdh9. Welcome to get more information on its official website.

Understanding of drug resistance benefits customized therapies for patients

A new study published on Wednesday in the journal New England Journal of Medicine shows that researchers from the University of California, Los Angeles have found the principle of patients with advanced melanoma immunotherapy showing drug resistance with the help of recombinant proteins. "This would help us better design the next generation of therapies," lead author of the study, tumor immunology program director Dr. Antoni Ribas at UCLA said.

Immunotherapy drugs such as Bristol-Myers Squibb's Opdivo and Merck's Keytruda are capable to achieve long-term remission or even cure some cancers. Some recombinant human proteins also have the effect. Other patients may have a response to immunotherapy drugs at the beginning, but a few months or even years later, the cancer recurred in their possession. Melanoma is the most deadly form of skin cancer. Dr. Ribas estimates that 40% of patients with melanoma have a response to immunotherapy, but about a quarter of these patients will relapse within three years after treatment.

UCLA researchers studied melanoma tumor biopsies of cancer recurrence patients after receiving Keytruda treatment. A patient's tumor lost B2M gene, thereby altering the way of immune system recognizing cancer. While the tumors of two other patients showed the defects of blocking JAK1 and JAK2 gene function, limiting the ability of the immune system to kill cancer cells. The researchers have failed to find a similar gene variant in the fourth generation of tumor biopsies.

Dr. Ribas believed that these findings might be commonly applied to all PD-1 therapies. PD-1 protein is a tool used by tumor cells to evade the immune system. He also noted that finding drug resistance mechanism may help explain why some patients completely don't produce immunotherapy response. Dr. Ribas said, "If we understand this process, we may be able to customize better therapy for patients." Flarebio offers high-quality recombinant proteins such as recombinant CDH10.

Natural Communication: In vivo epidermal migration requires focal adhesion targeting of ACF7

Recently, Professor Liang Hong and Yang Feng study group from Guangxi Normal University and Professor Wu Xiaoyang study group at the University of Chicago cooperated together to published a study entitled "In vivo epidermal migration requires focal adhesion targeting of ACF7" in the journal Natural Communication. The research paper clarifies an important molecular mechanism which regulates coordination of cell adhesion and cytoskeleton in the process of directional cellular movement, having important value for tissue repair, regeneration and tumor migration. The research involved in the use of many kinds of recombinant mouse proteins and recombinant rat proteins.

Cell migration is an essential life activity of cells and plays an important role in embryonic development, the formation of the nervous system, immune, tumor metastasis and wound healing process. There exists a class of proteins in mammals, which is a protein only in multicellular organisms and is widely expressed. They are special that they can be directly combined with the cytoskeleton and be cross-linked two cell skeletons. In mammals, ACF7 protein deficiencies will significantly inhibit cell migration and wound healing. ACF7 protein plays a key role in wound healing and skin migrations, which is related to its role in focal adhesion plaques. Focal adhesion turnover would allow cell retraction, which is essential for cell migration process. Mammalian protein ACF7 promotes the cross-linking of microtubule and actin and mediates microtubule to focal adhesion growth, thus contributing to the degradation of focal adhesion. However, how ACF7 facilitate this process is still unclear.

To solve these problems, the researchers resolved the crystal structure of the amino-terminal domain of ACF7. Structural analysis showed that the combination of ACF7 and microfilament is subject to Src / FAK kinase complex. Src / FAK kinases can phosphorylate a key tyrosine residue (Y-259) in ACF7 calponin homology (CH) domain. Use the epidermis as a model, the researchers further confirmed that ACF7 phosphorylation plays an integral role in focal adhesion dynamics and in vivo epidermal migration. This study describes an important signaling process in cell migration process, providing important information for understanding the molecular regulation of cell migration as well as its role in the processes of physiology and disease. The work was funded by the National Natural Science Foundation of China. Flarebio provides recombinant proteins of good quality, such as recombinant Cdh6.

Scientists find new phosphatase inhibitor with higher selectivity and lower polarity

Phosphatase is a regulatory protein which is as important as kinase, and its function is opposite to kinase, so it can be seen as an endogenous kinase inhibitor. The main obstacle of the development of phosphatase inhibitors is selectivity and through-membrane. Phosphatase substrate is a phosphorylated protein, and its activity pocket is mainly bond to phosphate, so high-polarity reactive ligand is very great and the selectivity is very poor. While when the polarity is too great, it can't reach the target location through the cell membrane. Poor selectivity is difficult to be used to accurately study the biological function of phosphatase. The most famous phosphatase is undoubtedly the target for diabetes PTP1B. There are also many phosphatase recombinant proteins in the market.

Many kinases and phosphatases themselves are in an inactive state (usually the combination of regulatory domain and catalytic domain of protein molecules prevents the combination of substrate and catalytic domain), and they require a certain signal to change conformation to be activated. Clotting proteins in an inactive state, namely the protein glue reported by the media, is not a new concept. The first kinase inhibitor drugs Geli Wei which is a non-active conformation combination with ABL. Recombinant proteins such as recombinant horse proteins are used in the development stage. But for phosphatase, it is indeed the first one.

Their screening method is very interesting. The researchers used a peptide known to activate SHP2 to activate half of the SHP2 and left half of the enzyme which was not activated in order to maintain a dynamic equilibrium which was easily broken and to increase the chances of finding a weak lead compound. Then the researchers used the whole protein and catalytic domain to respectively screen a relatively small compound library, so they can only select the allosteric inhibitor. If the compound inhibits the catalytic domain and the entire protein fragment at the same time, then it showed it conducts inhibition by binding with active pocket. The researchers found a sign compound of 12uM, and they found this lead compound with in-vivo activity through a simple optimization. By expressing SHP2 which lost allosteric binding ability but still had catalytic function, researchers showed convincingly that this compound indeed played the role through SHP2. The crystal structure also proved binding mechanism.

The highlights of this work is filtering mode. They only screened 100,000 compounds to find a good lead compound. The activity of lead compound may be not outstanding, but its through-membrane and selectivity is much better than the previous phosphatase inhibitors. If the other phosphatases are also screened in this way of hundreds of millions of DNA encoded chemical libraries, they should find a lot of similar nature phosphatase inhibitors. If the phosphatase inhibitors with high activity, high selectivity and through-membrane can be easier to be found, phosphatases might become the next popular target. Flarebio provides recombinant proteins such as recombinant Nrg2 with good quality.

Target protein may prevent deadly arterial remodeling in pulmonary hypertension

Pulmonary hypertension is a highly fatal disease. Thin flexible pulmonary vessels thicken and vascular dysfunction leads to death. Scientists believe that a protein of high expression in lethal disease is the culprit, but it is also a potentially effective new therapeutic target. Vascular biologist Fulton and Dr. Scott Barman at pharmacology and toxicology department of MCG are the main researchers in this study. They wanted to better understand the role of protein galectin -3 (gal-3) in causing pulmonary vascular chronic and unhealthy remodeling and to find a way to stop it by the use of recombinant proteins.

In disease models of human and animals, MCG scientists found in the media-specific increase gal-3 expression of arterial smooth muscle-rich intermediate layer usually helps to enhance blood vessel strength and toughness. They have shown that at least when culturing in vitro, improving gal-3 levels can increase unnatural proliferation and survival of human smooth muscle cells, while gal-3 cell viability decreased when silencing the expression.

Gal-3 is also related to and cancer, renal fibrosis and liver fibrosis. "Gal-3 also has excessive and unhealthy expression patterns in these diseases," Barman said. A key goal of their research is not only to prevent over expression of new gal 3 in pulmonary hypertension, but also to figure out the reason why smooth muscle cells make it excessive. They also wanted to determine epigenetic mechanism which constitutes persistent cell function changes, explaining cellular erratic behavior in many diseases.

When they were studying the cause of the problem, they were also concerned about whether gal-3 inhibitor GR-MD-02 which had been always studied could continue to be effective in reversing or preventing the disease. Barman and Fulton collaborated with Chief Medical Officer Dr. Peter g. Traber of Atlanta Galectin Therapeutics Ltd to further study the gal-3 inhibitor which was developed by the company and they are testing patients with hepatic fibrosis.

Although the inhibitors would not directly reduce gal-3 level, but they can prevent its effects. The ongoing studies will help to better determine the optimal dose, and the dose they used had shown results in early major diseases reversals. After treatment, the smooth muscle cell grew normally, blood vessel relaxed or smooth and cavity expanded. The new study will include more severe disease models that reflect the situation in many patients the diagnosis phase more closely. Flarebio provides superior recombinant proteins like recombinant COLEC12.

Gene analysis of chromatin can identify the origin of cancer

Researchers from The Jackson Laboratory (JAX) United States have developed a new method to determine the cell type which causes a given type of leukemia through whole genome analysis on open chromatin. This method plays an important role in diagnosis and treatment of leukemia. The study was published in the journal Natural Communication, which also has many other studies on recombinant proteins.

Each cancer begins with a single cell mutation. Having knowing the origin of cancer cells, researchers can analyze cancer subtypes, thus developing new means of treatment. But the existing methods are difficult to identify its original cells from a large number of tumor cell samples.

Chromatin is an important component within the nucleus and is composed of DNA, histones and RNA. It will converge into chromosome at the special stage when cells divide. Each type of cells has a unique chromatin structure: closed chromatin would tightly wrap around the nucleosome which is relatively inactive; the contact degree between open chromatin and nucleosome is relatively loose, but it is more active. Assistant Professor Dr. Jennifer Trowbridge from Jackson Laboratory, who also likes to conduct research on recombinant human proteins, improved the present method of identifying originated cells of tumor cells through analysis of the open chromatin of tumor cells.

Trowbridge led colleagues in the laboratory to build a mouse model with acute myeloid leukemia (AML). They found five kinds of cells from the bone marrow of humans and mice: long-term hematopoietic stem cells, short-term hematopoietic stem cells, multipotent progenitor cells, common myeloid progenitors and granulocyte-macrophage progenitor cells. The AML caused by different origins showed different invasiveness in mice: lesions induced by stem cells were more intrusive, while lesions induced by progenitor cells were much smaller. The occurrence frequency of different invasive cells of leukemia was different: stem cells were higher and progenitor cells were lower.

Researchers analyzed open chromatin of different AML cell samples and compared them with open chromatin pattern of normal cells, and then they determined the features and gene expression patterns of open chromatin in AML cell samples, which allowed them to be able to distinguish AML induced by stem cells and AML induced by progenitor cells.

The researchers said that by further study on open chromatin of stem cells and progenitor cells of healthy populations and AML patient populations, they can more accurately determine cancer biomarker based on cell origin, which is important for the diagnosis and treatment of cancer. Flarebio provides various recombinant proteins (including recombinant CDH4) of good quality.

A protein in drosophila has the similar characteristics with filamentous proteins

According to the report of physical website, every cell in the body has intermediate filaments proteins (IFs) which can help us avoid blisters, cataracts and dementia. But this kind of proteins is not found in the body of insects. Scientists suspect that insects have a different protein which plays a key role of filamentous proteins. But how the protein is like is still a mystery.

Currently, biologist Denise Montell from the University of California, Santa Barbara (UCSB) conducted a study - she and her colleagues unveiled the mystery. With the use of recombinant proteins, they found that there is a protein in drosophila that has the similar characteristics with filamentous proteins. Such unusual tropomyosins exist in every cell type. The study was published in a recent issue of the journal Cell Reports.

Denise said, "Believe it or not, drosophila and humans have a lot of common proteins, including the general tropomyosin. Their evolution comes from tropomyosin by only adding substances to the end of the tropomyosins to become a completely new protein with different features. It is like the intermediate filament protein but unlike ordinary tropomyosin. This new type of protein has an intermediate level, which means that they are greater than filamentous actin and smaller than microtubules. These are two other important structural filaments in cells."

Newly-discovered filamentous protein is equivalent to intermediate filament proteins in the human body. Under normal circumstances, tropomyosin form a rope-like structure - "coiled-coil". This thinner tropomyosin beam is wrapped around in fibrous protein actin and coils in a very small area. The latest discovery of the new type of protein is not like an ordinary tropomyosin. Flarebio provides you with high-quality recombinant proteins including recombinant ITGB2.

New findings on WNT10B gene mutations help to achieve precise treatment of congenital oligodontia

Wenzhou Medical College in China recently announced that the Genome Institute of Medicine school of this school united with Peking University School of Stomatology, Zhengzhou University School of Stomatology, Beijing Anzhen Hospital, Chinese Academy of Sciences Beijing Institute of Life Sciences, American National Institutes of Maxillofacial and Oral to first discovered that WNT10B gene mutations can lead to congenital or hereditary oligodontia. The study was recently published online in the journal Human Genetics, which is a sub-Journal of the American journal Cell. The journal also published some other studies about recombinant human proteins.

The morbidity of congenital hypodontia is 1.6% -9.6%. Oligodontia means hypodontia of six or more teeth, and it is the more serious disorders of tooth agenesis. It may be associated with abnormal development of other ectodermal body tissues, which seriously affects masticatory function and maxillofacial development in patients. It is one of the most difficult clinical oral diseases.

Currently, research on the pathogenic mechanism of oligodontia is still incomplete. The research team used technologies including the technology of recombinant protein and exome sequencing technology - namely detection of the relevant part of the whole genome encodes proteins - to conduct molecular genetic analysis on more than 150 cases of patients with oligodontia. They found that about 5% of patients showed WNT10B gene mutations, which is related to oligodontia especially lateral incisors and premolars missing, including patients with autosomal dominant inheritance and sporadic oligodontia. On this basis, the researchers explained the possible mechanisms of Wnt/beta-catenin signaling pathway the WNT10B genes involve in tooth development and oligodontia. The study found that the mutations which impact WNT10B gene function damaged the regulative ability of Wnt / beta-catenin signaling pathway to downstream TCF transcription factors, significantly reducing the ability of Wnt pathway inducing teeth embryonic stem cells to differentiate into vascular endothelial cells.

It is reported that the research results expand the gene mutation spectrum of human congenital oligodontia, providing a new basis for clinical diagnosis of congenital oligodontia, improving the pathogenesis of the disease and ultimately achieving precise treatment. Flarebio also offers recombinant CDH4 of good quality.

A protein in drosophila has the similar characteristics with filamentous proteins

According to the report of physical website, every cell in the body has intermediate filaments proteins (IFs) which can help us avoid blisters, cataracts and dementia. But this kind of proteins is not found in the body of insects. Scientists suspect that insects have a different protein which plays a key role of filamentous proteins. But how the protein is like is still a mystery.

Currently, biologist Denise Montell from the University of California, Santa Barbara (UCSB) conducted a study - she and her colleagues unveiled the mystery. With the use of recombinant proteins, they found that there is a protein in drosophila that has the similar characteristics with filamentous proteins. Such unusual tropomyosins exist in every cell type. The study was published in a recent issue of the journal Cell Reports.

Denise said, "Believe it or not, drosophila and humans have a lot of common proteins, including the general tropomyosin. Their evolution comes from tropomyosin by only adding substances to the end of the tropomyosins to become a completely new protein with different features. It is like the intermediate filament protein but unlike ordinary tropomyosin. This new type of protein has an intermediate level, which means that they are greater than filamentous actin and smaller than microtubules. These are two other important structural filaments in cells."

Newly-discovered filamentous protein is equivalent to intermediate filament proteins in the human body. Under normal circumstances, tropomyosin form a rope-like structure - "coiled-coil". This thinner tropomyosin beam is wrapped around in fibrous protein actin and coils in a very small area. The latest discovery of the new type of protein is not like an ordinary tropomyosin. Flarebio provides you with high-quality recombinant proteins including recombinant ITGB2.

Reactive oxygen and mitochondria keep balance by autophagy

Excessive increase of reactive oxygen can cause oxidative damage to proteins and lipid molecules. A moderate increase in reactive oxygen can be a signal to induce autophagy and other mechanisms of cell survival. Unhealthy mitochondria increased the production of reactive oxygen, and therefore reactive oxygen-induced mitochondrial autophagy has a positive effect in making impaired mitochondrial produce reactive oxygen, forming a negative feedback intracellular mechanism which induces oxidative damage. The findings are owing to the use of recombinant horse proteins.

Autophagy is a complex biological process, and the processes include start-up, formation of autophagy, lysosomes produce autophagy body lysosome fusion and degradation. Reactive oxygen can induce autophagy, but the internal mechanism of this process is not very clear in the past. A kind of cysteine protease ATG4 is a molecule which is involved in autophagy, and it has recently been determined to be reactive oxygen effector molecule. Oxy-genated ATG4 can promote LC3 lipidation, while LC3 lipidation is the key step of the start of autophagy. Taking into account that the oxidative stress is often a chronic process, researchers suggest that autophagy lysosome fusion may be a key role in the process of oxidative stress, and so are recombinant proteins.

TRPML1 is a TRP (transient receptorpotential) ion channel protein and distributes in intracellular ion and lysosomes. Lysosomes are key organelles which controls the quality of mitochondria. Oxidative stress is a common feature of lysosome dysfunction diseases. Mitochondria are the main source of ROS, while the sites where reactive oxygen produce are very close to lysosomes. Reactive oxygen which comes from mitochondria might have an impact on lysosomes. This lysosomal protein TRPML1 is the receptor of intracellular oxidative stress. Once activated, it can promote the autologous phagocytic activity of cells and accelerate the removal of damaged mitochondria, thereby making the mitochondria produce less free radical.

Free radicals are a "double-edged sword", for it can cause cell damage and activate the protection mechanism at the same time. If there is a chemical compound that can activate this channel, then oxidative stress which leads to aging diseases can reduce, thus playing its role in anti-aging and treating some oxidative damage. Flarebio also offers high-quality recombinant proteins such as recombinant Pigr.

Fluorescence lifetime imaging technology makes the treatment of breast cancer more effective

According to a recently-published study, scientists from UK Cancer Research Centre have taken imaging technology as a new way to identify which treatments of breast cancer that the patients are likely to benefit from. Research team from Imperial College London and scientists at Oxford United Radiation Oncology Institute of Science made use of fluorescence lifetime imaging to determine whether they have been connected together. The process also involved many kinds of recombinant proteins such as recombinant dog proteins.

Fluorescence lifetime imaging is a new technology that can accurately measure the distance between the two protein molecules. In this study, the researchers measured the distance between the two proteins HER2 and HER3 from breast cancer cells of a patient. The researchers believed that the imaging results showed that the patients with these proteins connected together can benefit from HER2 targeting therapy, regardless of whether their tumors have higher levels of HER2.

HER2 is a protein can cause the growth of cancer cells. Positive HER2 which shows high levels in breast cancer cells is taken as drug targets. Blocking its effect can prevent growth of cancer cells. The present drugs which are used include Herceptin and lapatinib. Whether patients benefit from these drugs are mainly determined by detecting whether cancer cells have high levels of HER2 protein. However, in those who have better response to HER2-targeted drugs, this imaging technology implemented in tumor cells may obtain other information about proteins. This technology can also be able to determine which patients may be unsuitable for these treatments.

Professor Tony Ng at Imperial College London said, "This imaging technology can help us determine which patients can benefit from these drugs while it had been ignored before. We should predict which drugs will not work in a patient when applying this test in order to avoid some unnecessary treatments - this can help us better use the drug. The next step is to conduct a clinical trial to see if this test can help patients. We hope that one day it not only can improve the treatment of breast cancer, but also be effective on other cancers including colon cancer and lung cancer."

Nell Barrie from UK Cancer Research said, "There are more than 50,000 new cases of breast cancer. But thanks to the new progress in the study, more people have survived from this disease than before. This research may ultimately provide the doctor with another way for personalized treatment so that patients can receive medications that are more likely to help them." Flarebio offers many other recombinant proteins such as recombinant App of good quality.

Vitamin D is associated with mucosal inflammation of patients with Ulcerative colitis

According to the results of a prospective study, the concentration of serum 25-hydroxy vitamin D and mucosal inflammation in patients with ulcerative colitis are negatively correlated with disease activity. The treatment of UC includes the technologies of recombinant proteins. Related content has been published online in the journal The American Journal of Clinical Nutrition.

"The incidence of Vitamin D deficiency is very high in patients with inflammatory bowel disease." Said Dr. Joel Pekow at Digestion Department of University of Chicago. Pekow and colleagues evaluated concentration of serum 25-hydroxyvitamin D of 230 UC patients [25 (OH) D] (mean age 45.8 years; the average duration, 166 years; 53% male; 90% Caucasian) and compared their inner Mayo endoscopic scores, overall Mayo score and histological activity. They also compared expression concentration of colonic mucosa epithelium connected proteins and inflammatory cytokines in patients with low serum 25 (OH) D concentrations and high serum 25 (OH) D concentrations relatively low serum 25 (OH) D concentrations and high serum 25 (OH) D concentrations to determine whether enough levels of vitamin D is related to the protection of epithelial cell junction proteins and the reduce of gastric mucosa inflammatory cytokines. The research also used various recombinant dog proteins.

"The vast majority of UC patients have deficiency or insufficiency of vitamin D, mucosal inflammation in patients with ulcerative colitis is related to the decrease of serum 25 (OH) D levels," Pekow said. The overall serum 25 (OH) D concentration was 21.8ng / ml, and serum 25 (OH) D concentration Mayo endoscopy score (P = 0.01), overall Mayo score (P = 0.001) and histological activity (P = 0.02) were negatively correlated.

In addition, the condition of serum 25 (OH) D concentration is less than 20ng / ml is related to mucous membranes reduce transcription, vitamin D receptor (VDR) and a closed-cadherin protein expression concentration. In contrast, in patients with serum 25 (OH) D concentrations below 20ng / ml, pro-inflammatory cytokines TNF-α and mucosa transcriptional expression concentration of interleukin-8 increased. "In UC patients, serum 25 (OH) levels were proportional to mucosal expression of VDR and epithelial cell connected proteins and inversely proportional to the pro-inflammatory cytokines. The results support investigation that vitamin D is effective protection of active inflammation of UC." Pekow Said. Flarebio can provide you with high-quality recombinant proteins such as recombinant APP, please stay tuned.

New study may show direction for relevant pharmaceutical researchers of Ebola virus

The Ebola virus which began to spread in West Africa since 2013 is the most serious outbreak of Ebola haemorrhagic fever by far. It has made nearly 30,000 people sick and more than 10,000 deaths, leaving millions of people with the most horrible memories. Although the epidemic has subsided, the high mortality rate of Ebola haemorrhagic fever is very high and still has no effective treatment. Thus, once comeback, it still could result in disastrous consequences. Therefore, researchers from all the nations were nose to the grindstone and are racing against time to develop drugs for the treatments of Ebola hemorrhagic fever. And a new study is expected to indicate a new direction for the relevant pharmaceutical researchers. There used to have some vaccine technologies using recombinant mouse proteins and recombinant rat proteins and they had also won success in animal experiments.

There had been computer simulation, in-vitro and animal studies suggested that some drugs which had been approved for the treatment of other diseases may have certain inhibiting effect on Ebola virus, but the functional mechanism of these drugs was unclear. Researchers from the United Kingdom indicated through experiments that the common painkiller ibuprofen and chemotherapeutic drug Toremifene can be combined with glycoprotein in Ebola virus and reduce its stability. The researchers used X-ray to measure the structures of glycoproteins of Ebola virus before and after they interacted with the two drugs and to determine the parts where drugs interact with glycoproteins. When the Ebola virus tries to infect host cells, it first needs to use its own glycoprotein to adsorb onto the host cells, so many researchers take glycoprotein of Ebola virus as an important target for drug development. Then recombinant animal proteins such as recombinant horse proteins can play their roles in the research.

This study is exciting, because drug-developers can specifically develop the drug treatment of Ebola haemorrhagic fever according the information of these structures. In particular for the drugs which have been approved for marketing, if they are possible to inhibit Ebola virus, the time required for clinical trials may be significantly shorter than new drugs, because the safety of these drugs have been shown without the need of validation through clinical trials. But the experts also warned it still needs a lot of time for us to develop effective drugs, especially the two drugs ibuprofen and toremifene mentioned by the study may not really be able to have effect on the treatment of Ebola hemorrhagic fever in clinical trials. Flarebio is a biocompany which produces recombinant proteins such as recombinant APP of good quality.

The role of mitochondria plays in the development of cancer

As cellular power plants, mitochondria are vital for every organism, because their role is to produce energy and also to control survival. However, their role in cancer is still not completely known. This is particularly important, because in general, the proliferation of tumor cells is faster than that of normal tissues. Scientists have speculated that the mechanism of protecting mitochondrial function is the cause of supporting the tumor proliferation.

Now, scientists at Wistar Institute have found a special protein network structure in the mitochondria of tumor cells. There are also many mitochondria recombinant proteins in the market. This structure is essential for the maintenance of clear function of mitochondria. It not only can make tumor cell proliferate, but also can make tumor cells gain the ability of moving and invading distant organs. After having a clear relationship of them, Wistar Institute scientists were able to greatly reduce the ability of cancer cells to grow and spread by closing single subunit in mesh structure, which is a novel and attractive targeted therapy method. The findings are published in the journal PLoS Biology. "This is an example of how the tumor can quickly adapt to handle a higher self-biosynthesis need," President and CEO of Wistar Institute Cancer Center Dr. Dario C. Altieri said. "Mitochondria play an important role in the process of requiring energy of tumor growth and metastasis. Therefore, to determine the mechanism of how tumors maintaining the mitochondrial function and using it to support the abnormal cell proliferation and metastatic spread may become the latest targeting treatment method for many types of cancer."

The evidence provided by previous study shows that being able to control the folding and stability of protein or maintaining protein balance is very important to reduce cell stress. It is also known as tumor's hijacking mechanism of protein balance advantage, but how it happens in the mitochondria is still largely unknown. With the help of recombinant human proteins, this protein network structure described by scientists at Wistar Institute answered to this riddles and confirmed its important role in tumor pathogenesis. In particular, a component in this network structure - ClpP - is found widely overexpressed in many human primary and metastatic cancers and is associated with shorter survival of patients. Alone in this study, scientists have determined the overexpression of this subunit in breast cancer, prostate cancer, colon cancer, lung cancer, melanoma and lymphoma.

"Many studies show great interest on targeting pathways involving in mitochondrial function, we have identified such a way which can provide multi targeted cancer "drug" therapeutic targets," first author of the study, postdoctoral researcher Jae Ho Seo at Altieri Lab of Wistar Institute said. "Other research studies have shown that, in preclinical models, targeting at mitochondrial protein is feasible, so destroying the network structure determined in this study may be able to shut down the key processes which lead to tumor progression." Flarebio also provides you with superior recombinant proteins like recombinant Vcam1.

Various new tools allow scientists to see proteins in living cells

Proteins are particularly complex molecules. They are bent and enlaced in various ways to execute reactions which cell metabolism and growth need. But how these miniature machines are integrated together to complete the cell function? With the use of recombinant protein technology, they get some answers.

Innovation is emerging. Bewersdorf team is working with two other research teams to study clickable chemical probes: SNAP-tag of New England Biolabs and HaloTag of Promega Biotech companies. These technologies include a shorter target sequence which can be encoded to the interested protein and a dye molecule which can be embedded in the target protein by a simple chemical reaction. Bewersdorf and his colleagues have demonstrated that the two technologies can make use of organic dyes to function on living cells.

While Selvin lab developed a smaller quantum dot with a diameter of approximately 9 nm. The size allows him to glide the quantum dot between nerve cells in the space of 20 to 40 nm, and signal transduction molecules transmit information to neighboring nerve cells via this place. The lab also plans to perforate the cell membrane and then quickly seal it to prevent damage to cells. "We are able to make a bacterial enzyme called streptolysin to drill a tiny hole about 5 nanometers in the cell membrane." Selvin said. This width is enough to let through a fluorescent protein and even a protein joint with antibody in order to find the target object inside the cell. After that, researchers used the unpublished methods to patch holes in 20 minutes using of recombinant horse proteins.

In addition, there are worries that the probes would interfere with the function of the target protein. While biophysicist Jie Xiao at The Johns Hopkins University has put forward an alternative method that will not damage these proteins.

Her molecules probes don't attach to the targeted after getting genetically modified. After being produced, they are immediately split by a kind of enzymes and enter a specific location of the cell membrane. This means that they no longer carry the location information of the target molecules but they are located in a position where they can accurately calculate them, and thereby obtaining accurate count of protein production. At the same time, the protein itself can function freely. This technology is called CoTrAC.

"Quantifying protein levels in living cells is very important," Xiao explained, "People often use fluorescence to indicate the relative change." But the genes she studied regulate few proteins, and it is difficult to image through super-resolution counting. In addition, subtle changes in the precise number of these proteins also can judge whether there is a change in the state of cells. To learn more about how proteins work and what kinds of recombinant proteins (such as recombinant ACSL3) there have, you can visit Flarebio’s website.