Автор: Administrator 20.11.2013 20:49
Around 20 percent of all humans are persistently colonized with Staphylococcus aureus bacteria, a leading cause of skin infections and one of the major sources of hospital-acquired infections, including the antibiotic-resistant strain MRSA. University of Chicago scientists have recently discovered one of the keys to the immense success of S. aureus-the ability to hijack a primary human immune defense mechanism and use it to destroy white blood cells. The study was published Nov 15 in Science. "These bacteria have endowed themselves with weapons to not only anticipate every immune defense, but turn these immune defenses against the host as well," said Olaf Schneewind, MD, PhD, professor and chair of the Department of Microbiology at the University of Chicago and senior author of the paper. One of the first lines of defense in the human immune response are neutrophils, a type of white blood cell that ensnares invaders in neutrophil extracellular traps (NETs), a web-like structure of DNA and proteins. Captured bacteria are then destroyed by amoeba-like white blood cells known as macrophages. However, S. aureus infection sites are often marked by an absence of macrophages, indicating the bacteria somehow defend themselves against the immune system. To reveal how these bacteria circumvent the human immune response, Schneewind and his team screened a series of S. aureus possessing mutations that shut down genes thought to play a role in infection. They looked to see how these mutated bacteria behaved in live tissue, and identified two strains that were unable to avoid macrophage attack. When these mutations-to the staphylococcal nuclease (nuc) and adenosine synthase A (adsA) genes respectively-were reversed, infection sites were free of macrophages again. Looking for a mechanism of action, the researchers grew S. aureus in a laboratory dish alongside neutrophils and macrophages. The white blood cells were healthy in this environment and could clear bacteria. But the addition of a chemical to stimulate NET formation triggered macrophage death. Realizing that a toxic product was being generated by S. aureus in response to NETs, the team used high performance liquid chromatography and mass spectrometry techniques to isolate the molecule. They discovered that S. aureus were converting NETs into 2'-deoxyadenosine (dAdo), a molecule which is toxic to macrophages. This effectively turned NETs into a weapon against the immune system.
Автор: Administrator 20.11.2013 20:48
About half of all cancer patients have a mutation in a gene called p53, which allows tumors to survive and continue growing even after chemotherapy severely damages their DNA. A new study from MIT biologists has found that tumor cells with mutated p53 can be made much more vulnerable to chemotherapy by blocking another gene called MK2. In a study of mice, tumors lacking both p53 and MK2 shrank dramatically when treated with the drug cisplatin, while tumors with functional MK2 kept growing after treatment. The findings suggest that giving cancer patients a combination of a DNA-damaging drug and an MK2 inhibitor could be very effective, says Michael Yaffe, the David H. Koch Professor in Science and senior author of a paper describing the research in the Nov. 14 issue of the journal Cell Reports. Several drugs that inhibit MK2 are now in clinical trials to treat inflammatory diseases such as arthritis and colitis, but the drugs have never been tested as possible cancer treatments. "What our study really says is that these drugs could have an entirely new second life, in combination with chemotherapy," says Yaffe, who is a member of MIT's Koch Institute for Integrative Cancer Research. "We're very much hoping it will go into clinical trials" for cancer. Sandra Morandell, a postdoc at the Koch Institute, is the paper's lead author.To kill a tumor P53 is a tumor-suppressor protein that controls cell division. Before cell division begins, p53 checks the cell's DNA and initiates repair, if necessary. If DNA damage is too extensive, p53 forces the cell to undergo programmed cell death, or apoptosis. Tumors that lack p53 can avoid this fate. "Usually p53 is the main driver of cell death, and if cells lose this pathway they become very resistant to different treatments that cause cell death," Morandell says. Several years ago, researchers in Yaffe's lab discovered that in cancer cells with mutated p53, the MK2 gene helps counteract the effects of chemotherapy. When cancer cells suffer DNA damage, MK2 puts the brakes on the cell division cycle, giving cells time to repair the damage before dividing. "Our data suggested if you block the MK2 pathway, tumor cells wouldn't recognize that they had DNA damage and they would keep trying to divide despite having DNA damage, and they would end up committing suicide," Yaffe says. In the new study, the researchers wanted to see if this would hold true in tumors in living animals, as well as cells grown in a lab dish. To do that, they used a strain of mice that are genetically programmed to develop non-small-cell lung tumors. The researchers further engineered the mice so they could reversibly turn the MK2 gene on or off, allowing them to study tumors with and without MK2 in the same animal.
Автор: Administrator 20.11.2013 20:46
Collaborative Effort to Further Validate Genetic Variants
The Parkinson's Institute and Clinical Center announced today that they, in partnership with Population Diagnostics, Inc., have discovered a number of new genes relevant to the cause of Parkinson's disease. The innovative approach used for this study focuses first on genome-wide investigation of gene copy number variants (CNVs) followed by targeted sequencing of CNV-identified candidate genes. This strategy dramatically reduces the genome search space as compared to more traditional gene discovery tools such as single nucleotide polymorphism (SNP) analysis or exome sequencing methods. The study revealed a number of candidate genes with compelling new biological links to Parkinson's disease as well as links to previously discovered Parkinson's genes such as alpha-synuclein and LRRK2 (the most common known cause of familial or inherited Parkinson's disease). The genetic variants were originally discovered in a clinical center-based study of 468 patients from the Parkinson's Institute that included familial and sporadic cases. The genome-wide study was performed by Population Diagnostics, Inc., a privately held company with a cutting-edge approach to systematically uncovering the genetic causes of disease. Seed funding for the validation of one novel gene found in the study was provided by The Michael J. Fox Foundation for Parkinson's Research. The Parkinson's Institute and Population Diagnostics established their collaboration focused on genetic discoveries in December 2011. Once confirmed in a second cohort of patients from the Parkinson's Institute, many of these new variants are expected to confer clinical utility and enable earlier disease detection that will allow separation of people living with Parkinson's disease into additional genetic subtypes. Currently known genetic subtypes, such as SNCA, LRRK2, and PARK2, can classify and diagnose only five to ten percent of patients with Parkinson's disease; however, the genetic discoveries from this collaboration are anticipated to dramatically boost the diagnostic yield of genetic testing in Parkinson's patients. The novel variants in genes associated with Parkinson's may help predict disease course and may also accelerate the development of disease-modifying drugs by serving as new therapeutic targets and illuminating new disease pathways.
Автор: Administrator 20.11.2013 20:45
Inovio Pharmaceuticals, Inc. (NYSE MKT: INO) announced today that preclinical testing of a DNA synthetic vaccine for the virulent Middle East Respiratory Syndrome coronavirus (MERS) induced robust and durable immune responses, demonstrating the potential for a SynCon® DNA vaccine to prevent and treat this deadly virus. Since 2012, when the virus was first identified, 153 cases from nine Middle Eastern countries have been reported and, alarmingly, 42% of these cases have been fatal. MERS is similar to the SARS virus which infected 8,000 people several years ago. MERS differs from SARS in that it appears to be less contagious, but MERS is almost five times as fatal as SARS, which killed 10% of those infected. There is no vaccine or effective treatment for MERS.In this study, DNA vaccine constructs targeting multiple MERS antigens were generated using Inovio's SynCon® vaccine platform. These SynCon constructs were administered via Inovio's CELLECTRA® electroporation-based delivery technology. The vaccine constructs were observed to induce strong neutralizing antibodies and broad CD8+ T cells in mice. These findings are vital given the importance of neutralizing antibodies in preventing infection and the role T cells play in clearing infection by killing cells that harbor the virus.Dr. J. Joseph Kim, Inovio's President and CEO, said, "Our SynCon® platform has again generated a synthetic vaccine candidate that shows promise for providing a treatment where there is none. With human data showing the powerful killing effect of T cells generated by our vaccine for HIV and our therapy for HPV-associated cervical dysplasia and various cancers, we look forward to providing Inovio's answer to MERS, a deadly infectious disease that has unknown pandemic potential. What's even more impressive about our candidate vaccine is that it is designed with the goal to universally protect against multiple strains of MERS, which has been shown to have diverse genetic variants. With appropriate external funding, this product could become an effective shield against this deadly virus."
Обновлено 20.11.2013 20:44 Автор: Administrator 20.11.2013 20:41
Built-in hematocrit compensation delivers high accuracy lactate analysis
EKF Diagnostics, the global diagnostics business, announces the launch of the new version of its Lactate Scout+ analyzer. Initially developed to provide coaches and athletes with a precise and easy-to-use mobile lactate test, Lactate Scout’s additional features and functionality – including hematocrit compensation – now mean the device can be used in new medical applications.
EKF’s upgraded Lactate Scout+ with hematocrit compensation
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