Genome Of West Nile Mosquito Decoded By International Team Of Scientists

The genome, or DNA code of the mosquito (Culex pipens quinquefasciatus) that transmits West Nile virus has been decoded by scientists from various countries, an article published in Sciencereveals. The mosquito also transmits the St. Louisencephalitis virus as well as the tiny worm which causes elephantiasis.

Researchers from 39 universities in the USA and Europe reported in two separate papers published in the journal Science that they had mapped the DNA of the Southern House Mosquito(Culex pipens quinquefasciatus), all the 18,883 genes.

Co-author, Stephen Higgs, a professor at the University of Texas Medical Branch at Galveston (UTMB), said:

Culex pipiens quinquefasciatus is the most widely distributed mosquito in the world, and in terms of disease transmission to humans it's one of the three most important mosquito species. This work gives us a terrific platform to improve our understanding of the dynamics of infection, which has to be done if we're going to find ways to interrupt disease transmission.

Higgs had identified the genome of the malaria-transmitting mosquito Anopheles gambiae, which was published in 2002, and the yellow-fever and dengue fevertransmitting mosquito Aedes aegypti, which was published in 2007.

Co-author, UTMB assistant professor Dana Vanlandingham, said:

This is really exciting for us, because we can finally perform experiments that we've wanted to do for seven or eight years. Our basic question is why do certain mosquito species transmit a particular virus and other mosquito species do not? Why don't they all carry all the viruses? We don't know, but now we have three different systems for comparative studies to investigate interactions between viruses and mosquitoes.

By identifying all the 18,883 genes of the mosquito that transmits West Nile virus, scientists will have greater insight into what determines its behavior and how its immune system reacts to bacterial, viral and parasitical infections.

Higgs said:

Culex quinquefasciatus is the main vector* for West Nile - it's common here along the Gulf Coast of Texas, but closely related species are found all over the country, and it bites both birds and humans. There have been about a million human infections with West Nile in the United States and, presumably, hundreds of millions of bird infections. Almost every one of those infections was started by a mosquito bite.

‘Firefly’ stem cells may help repair damaged hearts

Stem cells that glow like fireflies could someday help doctors heal damaged hearts without cutting into patients’ chests.

In his University of Central Florida lab, Steven Ebert engineered stem cells with the same enzyme that makes fireflies glow. The “firefly” stem cells glow brighter and brighter as they develop into healthy heart muscle, allowing doctors to track whether and where the stem cells are working.

Researchers are keenly interested in stem cells because they typically morph into the organs where they are transplanted. But why and how fast they do it is still a mystery. Now Ebert’s cells give researchers the ability to see the cells in action with the use of a special camera lens that picks up the glow under a microscope.

“The question that we answered was, ‘How do you follow these cells in the lab and find out where they’re going?’” said Ebert, an associate professor in UCF’s College of Medicine.

If doctors can figure out exactly how the cells repair and regenerate cardiac tissue, stem cell therapies could offer hope to more than 17.6 million Americans who suffer from coronary disease. The glow of the enzyme also means therapies would no longer require cutting into patients’ chest cavities to monitor the healing.

The study, funded by the National Institutes of Health and the American Heart Association, is a featured cover story in this month’s highly ranked Stem Cell and Development Journal. 

Now that scientists can track the stem cells, Ebert said he hopes to use them in disease models to determine how they heal a damaged heart and what conditions are most suitable for the stems cells to thrive.

Scientists discover a new way our bodies control blood pressure: the P450-EET system

New research in the FASEB Journal suggests that increasing the level of the P450 protein causes the creation of molecules called EETs, which lower blood pressure

If you are one of the millions of Americans with high blood pressure, more help is on the way. That’s because a new research study published in the October 2010 print issue of The FASEB Journal(http://www.fasebj.org) shows that a protein, called P450, metabolizes arachidonic acid in our blood vessel walls to create a tiny molecule with a big nameA—epoxyeicosatrienoic acid (EET)A—which in mice, turns off genes responsible for vascular inflammation and ultimately relaxes blood vessels to lower blood pressure. This protein and genes are also present in humans.

“We hope these results will help advance the development of new blood pressure lowering agents that increase EETs,” said Craig R. Lee, M.D., from the National Institutes of Health’s National Institute of Environmental Health Sciences in Research Triangle Park, N.C. “In particular, we hope that targeted-use of these new therapies in individuals with a poorly functioning P450-EET system will ultimately prove to be an effective treatment for patients with high blood pressure.”

Lee and colleagues discovered this new protein using genetically modified mice with human P450 present in the cells lining the blood vessels, and using normal mice as a control group. The scientists found that the P450 caused the mice to produce EETs, which in turn caused the relaxation of blood vessels and lower blood pressure. When the mice were exposed to substances that increased blood pressure, the P450 mice had lower blood pressure and less damage to the kidneys than the normal mice. These results show that the P450-EET pathway is a target for the development of new blood pressure medications, and these findings may influence drug development for other diseases, such as coronary artery disease, stroke, and cancer.

“Whether you’re a Type A personality, overweight and out of shape, or genetically wired to have high blood pressure, this research offers real hope,” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal “Having discovered a pivotal role for the P450-EET system, scientists can now develop a new class of drugs not only for lowering blood pressure, but also for preventing strokes and heart attacks.”

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Receive monthly highlights from The FASEB Journal by e-mail. Sign up athttp://www.faseb.org/fjupdate.aspx. The FASEB Journal (http://www.fasebj.org) is published by the Federation of the American Societies for Experimental Biology (FASEB). The journal has been recognized by the Special Libraries Association as one of the top 100 most influential biomedical journals of the past century and is the most cited biology journal worldwide according to the Institute for Scientific Information.

FASEB comprises 23 societies with more than 90,000 members, making it the largest coalition of biomedical research associations in the United States. FASEB enhances the ability of scientists and engineers to improveA—through their researchA—the health, well-being and productivity of all people. FASEB’s mission is to advance health and welfare by promoting progress and education in biological and biomedical sciences through service to our member societies and collaborative advocacy.

Key leukemia defense mechanism discovered by VCU Massey Cancer Center!

Richmond, Va. (September 30, 2010) A– Virginia Commonwealth University Massey Cancer Center researcher Steven Grant, M.D., and a team of VCU Massey researchers have uncovered the mechanism by which leukemia cells trigger a protective response when exposed to a class of cancer-killing agents known as histone deacetylase inhibitors (HDACIs). The findings, published in the Journal of Biological Chemistry, could lead to more effective treatments in patients with leukemia and other cancers of the blood.

“Our findings provide new insights into the ways such cancer cells develop resistance to and survive treatment,” says Grant, associate director for translational research and professor of medicine. “This knowledge will now allow us to focus our efforts on strategies designed to prevent these self-protective responses, potentially rendering the cancer cell incapable of defense and increasing the effectiveness of therapy.”

The discovery centers on modification of a protein known as NEMO. Researchers have known for some time that HDACIs trigger a protective response in leukemia cells by activating a survival signaling pathway known as NF-IºB, which limits the ability of HDACIs to initiate a cancer cell suicide program known as apoptosis. However, it was previously thought this process occurred through activation of receptors residing on the cancer cell surface. What VCU Massey researchers discovered was that HDACIs initially induce DNA damage within the cell nucleus, leading to modification of the NEMO protein, which then triggers the cytoprotective NF-IºB pathway. By disrupting modifications of the NEMO protein, NF-IºB activation can be prevented, and as a consequence, the cancer-killing capacity of HDACIs increases dramatically.

HDACIs represent an approved form of treatment for certain forms of lymphoma, and VCU Massey Cancer Center has been working for over seven years to develop strategies designed to improve their effectiveness in leukemia and other blood cancers. Grant’s team is now focusing on ways to capitalize on this discovery by designing strategies that interrupt NEMO modifications through the use of pharmacologic agents and other means.

“Our goal is to move these findings from the laboratory to the bedside as quickly as we possibly can. There are currently several drugs in early stages of development that hold promise in disrupting the NEMO-related NF-IºB pathway, but further research defining their safety and effectiveness will be required before we can incorporate them into new therapies,” says Grant.

A Possible Vaccination for HIV?

There are 31.1 million adults and 2.1 million children living with HIV in the world.  There is no cure for the disease. But what if there was a vaccine that could be administered to everyone to stop the spread of HIV? The HIV/AIDS epidemic would be over.

One way to produce an HIV vaccination is to teach the immune system to recognize certain protein structures on the surface of the HIV virus and produce antibodies that will bind to the structures and neutralize HIV. To do this, scientists must identify a certain viral structure, cut it off, and then find some way to present them to the immune system. However, when some parts of the surface of HIV is remove antibodies don’t recognize it or bind to them. A research team at the National Institute of Allergy and Infectious Diseases (NIAID) has developed a way to avoid this problem.

The team has found a way to extract a portion of the surface of HIV that is recognizable to the antibody, known as an epitope, into a computer designed protein scaffold. The scaffold locks the epitope shape recognized by the immune system. The scientists believe that when this epitope is injected into an animal, and eventually a human, it will be recognized by the immune system. The immune system will make antibodies against it. These antibodies could serves as an army ready to attack the virus from invading the body.

To demonstrate this scaffolding technique, the scientists applied it to a shape-changing epitope on the surface of HIV that is recognized by an HIV-neutralizing antibody known as 2F5. The epitope is a helical or spiral shape when removed from the surface of HIV, but the 2F5 antibody-recognizable version of this epitope has an irregular, kinked shape. The scientists placed copies of the kinked epitope into scaffolds that locked it in that form. Then the researchers injected these scaffold-bound epitopes into guinea pigs. The animals' immune systems made antibodies very similar to 2F5 that bound tightly to the epitope.

This study demonstrates that the making of protein scaffolds can be a potentially useful approach in vaccine design. The NIAID researchers are continuing to refine this technique and apply it to the design of vaccines for HIV/AIDS as well as other infectious diseases.

A Big Step for Nanotechnology

Scientists can now learn how drugs work in clinical trials thanks to an innovative technological advance that makes nanoscale protein measurements.

"We are making progress toward the goal of understanding how drugs work in different individuals," which Alice C. Fan, M.D., instructor in the division of oncology at Stanford University School of Medicine, was quoted as saying. "Using new technologies makes it possible to measure effects of therapeutic agents in tumor cells and different cell populations within our patients. Now that we can make these measurements, we are one step closer to being able to tailor therapy for each patient."

Research on cancer agent activity currently requires patients to undergo numerous invasive biopsies to generate enough cells required for testing.  Dr. Fan and colleagues developed the nano-immunoassay (NIA), a highly sensitive test that can make nanoscale protein measurements in cells from invasive blood draws or fine needle aspirates.

NIA was studied in several clinical trial settings by Dr. Fan and her team of researchers.  Diagnostic testing results showed that protein profiles in the RAS and MAP kinase pathways could help distinguish tumor cells from normal cells, and later be used to group different types of tumors. 

Proteins in cells from patients with lymphoma or yelodysplastic syndrome were analyzed by researchers.  According to Fan, two novel treatments for these diseases had a measureable effect on protein activity in tumor cells.
The team then used NIA in conjunction with flow cytometry to determine a drug's differential effects in tumor cells vs. normal cells within each patient.

"These results have immediate application because they can identify which drugs actually hit protein targets in patient cells," Dr. Fan added.
Nanoscale approaches may eventually affect all stages of cancer care.
"The ability to make meaningful protein measurements using minute quantities of tissue will allow for earlier discovery of tumors, characterization of small amounts of residual disease and detection of recurrence," Fan concluded.

NIA could be predominantly beneficial in studying rare cell populations such as circulating tumor cells and cancer stem cells.

Tumor Cells May Provide Information on a Patient’s Disease

Circulating tumor cells may create a new alternative and non-invasive source for biomarker assessment a new study shows.

According to the National Cancer Institute, the major cause of mortality in patients with cancer is caused by tumor cells that escape from the primary tumor into the bloodstream and travel through the circulation to distant sites where they develop into secondary tumors. These are called circulating tumor cells or CTC, and they provide a link between the primary tumor and metastatic sites.

“The basic idea is that CTCs can provide real time information about a patient’s current disease state, acting as a “liquid biopsy,” Siminder Kaur Atway, PhD, senior research associate at Genentech was quoted saying. “ They are much less invasive than tumor biopsies because they can be detected from a blood draw and don’t require surgical intervention.”

Researchers at Genentech compared the CTC capture efficiency of the drug CellSearch with two biochip platforms using tumor cell lines spiked into whole blood. They tried to detect EGFR protein in patients with lung cancer and HER2 in patients with metastatic breast cancer.

Results showed that in some cases, CTC might offer a real time view of a patient's biomarker status that is different from diagnostic tissue. Researchers say some improvements are necessary before the technology can be generally useful in clinical biomarkers and future studies will look for other biomarkers in CTCs to determine if they represent a patient's tumor.