Maintaining good glucose control early in the course of type 1 diabetes could lessen the long-term risk of kidney disease, as measured by a common test of kidney function. This finding comes from more than two decades of research on preventing life-shortening complications of type 1 diabetes. The National Institutes of Health (NIH) funded the longitudinal study. Results were published online on November 12, 2011 in the New England Journal of Medicine and presented November 12, 2011 at the American Society of Nephrology Kidney Week in Philadelphia. Researchers at the University of Washington (UW) in Seattle and several collaborating institutions in the United States and Canada examined the effects of early, intensive glucose-lowering therapy on glomerular filtration rates (GFR). This measurement estimates how much blood passes each minute through tiny filters in the kidneys. A GFR blood test checks the kidney's ability to rid the body of a muscle-generated waste product, creatinine. If the kidneys can't filter fast enough, the substance builds up in the blood. A low GFR is a dangerous sign of existing diabetic kidney disease that can progress to kidney failure, also called end-stage kidney disease, which requires dialysis or kidney transplantation. Moreover, a low GFR also can contribute to the heart and blood vessel complications of diabetes, the researchers explained. People with type 1 diabetes are prone to kidney disease and related complications resulting in disability and premature death. Until this study, no interventions for this population have been shown to prevent impaired GFR. According to Dr.
A major international study has identified a novel gene mutation that appears to increase the risk of both inherited and sporadic cases of malignant melanoma, the most deadly form of skin cancer. The identified mutation occurs in the gene encoding MITF, a transcription factor that induces the production of several important proteins in melanocytes, the cells in which melanoma originates. While previous research has suggested that MITF may act as a melanoma oncogene, the current study identifies a mechanism by which MITF mutation could increase melanoma risk. The report from researchers from the U.S., the U.K., and Australia was published online in Nature on November 13, 2011. It is expected to appear in a print issue along with a study from French researchers finding that the same mutation increased the risk for the most common form of kidney cancer, for melanoma, or for both tumors. "We previously knew that MITF is a master regulator for production of the pigment melanin; and several years ago we identified a chemical modification, called sumoylation, that represses MITF activity," says Dr. David Fisher, chief of Dermatology at Massachusetts General Hospital (MGH), director of the MGH Cutaneous Biology Research Center and co-senior author of the Nature paper. "The currently discovered mutation appears to block sumoylation of MITF, and the resulting overactivity of MITF significantly increases melanoma risk." While approximately 10 percent of patients with melanoma report a family history of the disease, true hereditary melanoma, involving multiple cases across many generations, probably accounts for 1 percent or less of all cases, says co-senior author Dr. Hensin Tsao, of MGH Dermatology and the Wellman Center for Photomedicine.
Researchers have shown how estrogen receptor (ER)-positive breast cancer tumors become resistant to tamoxifen, the only approved hormonal therapy for premenopausal patients with this type of breast cancer. They also found that introducing a novel histone deacetylase (HDAC) inhibitor in hormone therapy treatment can overcome resistance to hormonal therapy. "We always thought that resistance was primarily an inborn or genetic effect," said Dr. Pamela N. Munster, director of the Early-Phase Clinical Trials Program at the University of California, San Francisco (UCSF). "But this is not the case. Tumors have found a way to modify their genes to become resistant. This process is called 'epigenetics,' where genes are turned on and off, but the sequence of DNA is not altered. We have also found that with this kind of breast cancer, we can prevent that resistance with histone deacetylase inhibitors." Dr. Munster presented the findings at the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics, held November 12-16, 2011 in San Francisco, California. She and her colleagues found that ER-positive breast cancer tumors alter their genes to create more AKT, a protein that spurs actions within the cell to keep it alive — the opposite of what tamoxifen is designed to do. In a preclinical study, researchers introduced the HDAC inhibitor PCI-24781 at an early phase of tamoxifen treatment and found that it reverses the tumor's survival strategy of increasing production of AKT, thus stopping the tumor cells from developing resistance and leading to higher levels of cell death. "The HDACs regulate the response of AKT to tamoxifen, and together, the effects of HDAC inhibitors and tamoxifen lead to more cell death if introduced with hormonal therapy," said Dr. Munster.
Two studies from the Mayo Clinic presented during the this year’s American Society of Nephrology's Annual Kidney Week (November 8-November 13, 2011) provide new information related to high blood pressure during pregnancy. In one study, Dr. Vesna Garovic and her team examined the potential of a test done mid-pregnancy to predict which women will later develop preeclampsia, a late-pregnancy disorder that is characterized by high blood pressure and excess protein in the urine and that affects 3% to 5% of pregnancies. Left untreated, preeclampsia can lead to serious -- even fatal -- complications for a pregnant woman and her baby. Among a group of 315 patients, 15 developed preeclampsia and 15 developed high blood pressure (but not preeclampsia) during pregnancy. All of the patients who developed preeclampsia tested positive in mid-pregnancy in a test that detects the shedding of certain kidney cells called podocytes in the urine. None of those with only high blood pressure tested positive, and none of 44 women with normal pregnancies tested positive. Therefore, this test is highly accurate for predicting preeclampsia, which could alert clinicians to take steps to safeguard against the condition. In another study, Dr. Garovic's team looked at the long-term health effects of high blood pressure during pregnancy. They identified female residents of Rochester, Minnesota, and the surrounding townships in Olmsted County who delivered between 1976 and 1982. The investigators divided the women into two groups -- those with high blood pressure during pregnancy and those without -- and followed them after they reached 40 years of age to monitor their heart and kidney health. A total of 6,051 mothers delivered between 1976 and1982, and 607 women had high blood pressure at the time while 5,444 did not.
For the past 100 years, the Haber-Bosch process has been used to convert atmospheric nitrogen into ammonia, which is essential in the manufacture of fertilizer. Despite the longstanding reliability of the process, scientists have had little understanding of how it actually works. But now a team of chemists, led by Dr. Patrick Holland of the University of Rochester, has gained new insight into how the ammonia is formed. Their findings are published in the November 11, 2011 issue of Science. Dr. Holland calls nitrogen molecules "challenging." While they're abundant in the air around us, which makes them desirable for research and manufacturing, their strong triple bonds are difficult to break, making them highly unreactive. For the last century, the Haber-Bosch process has made use of an iron catalyst at extremely high pressures and high temperatures to break those bonds and produce ammonia, one drop at a time. The question of how this works, though, has not been answered to this day. "The Haber-Bosch process is efficient, but it is hard to understand because the reaction occurs only on a solid catalyst, which is difficult to study directly," said Dr. Holland. "That's why we attempted to break the nitrogen using soluble forms of iron." Dr. Holland and his team, which included Dr. Meghan Rodriguez and Dr. William Brennessel at the University of Rochester and Dr. Eckhard Bill of the Max Planck Institute for Bioinorganic Chemistry in Germany, succeeded in mimicking the process in solution. They discovered that an iron complex combined with potassium was capable of breaking the strong bonds between the nitrogen (N) atoms and forming a complex with an Fe3N2 core, which indicates that three iron (Fe) atoms work together in order to break the N-N bonds.
With an estimated 1.5 million species, fungi represent one of the largest branches of the Tree of Life. They have an enormous impact on human affairs and ecosystem functioning due to their diverse activities as decomposers and pathogens, and their partnership with host organisms for mutual benefit. To use fungi for the benefit of humankind, an accurate understanding of what exactly they do, how they function, and how they interact in natural and synthetic environments is required. Dr. Jason Stajich, an assistant professor of plant pathology and microbiology at the University of California, Riverside, is a member of an international research team that, in collaboration with the Joint Genome Institute of the U.S. Department of Energy, has embarked on a five-year project to sequence 1000 fungal genomes from across the Fungal Tree of Life. Called the "1000 Fungal Genomes" project, the research endeavor aims to bridge the gap in our understanding of fungal diversity and is one of 41 projects funded through the U.S. Department of Energy's 2012 Community Sequencing Program. The funding awards were announced on November 3, 2011 by the DOE. "The overall plan is to fill in gaps in the Fungal Tree of Life by sequencing at least two species from every known fungal family," said Dr. Stajich, a member of UCR's Institute for Integrative Genome Biology. "Once the data is compiled, the project scientists will make use of the data as a starting point for interpreting how these organisms change and use their environment to make a living." Dr. Stajich is co-leading the Fungal Genomes project with Dr. Joey Spatafora, a professor of botany and plant pathology at Oregon State University.
For some time now, artemisinin, derived from a Chinese herb, has been the most powerful treatment available against malaria. To avoid the malaria parasite becoming resistant, the World Health Organization (WHO) strongly recommends combining artemisinin with another anti-malarial drug. But there are different formulations and derivatives, in different combinations, and with dosing schemes. Scientists from the Institute of Tropical Medicine (ITM) carried out a head-to-head comparison of four combination therapies in seven African countries. One combination appeared particularly promising for regions where the risk of re-infection is high. Malaria is caused by several related parasites, of which Plasmodium falciparum is the worst. The parasites have a complicated life cycle, partly in mosquitoes. When an infected mosquito bites a human, parasites are injected with the mosquito saliva into the blood, travel to the liver, where they change form, then infect red blood cells, where they further reproduce. After a few days (depending on the parasite species), the red blood cells burst to release a huge number of new parasites. These bursts cause intense fever, anaemia, and renal problems. Each year, approximately 800,000 people die of malaria. In recent years, the burden of malaria has declined substantially in several sub-Saharan African countries, due to large scale indoor residual spraying of insecticides, massive distribution of insecticide-treated bed nets, and the introduction of artemisinin-based combination treatments, ACTs for short. To treat patients with malaria, the WHO advises each region to choose an ACT based on the local level of resistance to non-artemisinin medicine in the combination. But data on that resistance are scarce.
Shanchol™, a new oral cholera vaccine developed through the International Vaccine Institute (IVI), an international organization established by the United Nations and based in Seoul, Korea, recently received prequalification from the World Health Organization (WHO). Developed for use in developing countries to protect against life-threatening cholera, Shanchol™ is ready to use in a single-dose vial and is administered orally, which facilitates its implementation in large-scale immunization programs. Shanchol™ is produced by Shantha Biotechnics – part of the Sanofi group - in India where the vaccine has been licensed and sold since 2009. "I am immensely pleased by the news that Shanchol™, a vaccine enabled by IVI, received WHO prequalification," said Dr. Christian Loucq, IVI's new Director General. "This stamp of approval shows that public-private partnerships - such as those among IVI, Vabiotech, Shantha, and Sanofi – are essential for successful vaccine development, particularly in developing vaccines against neglected diseases of the poor like cholera." Certification by WHO of Shanchol™ represents a major milestone as it indicates that the vaccine meets WHO standards of quality, safety, and efficacy, and allows the vaccine to be procured by UN agencies and other international organizations for use in countries around the world. It also accelerates international use of the vaccine because WHO prequalification eliminates the need for country-level market authorization in some countries, which can take years to obtain. WHO prequalification of Shanchol™ is the latest achievement in IVI's mission to develop and introduce innovative, safe, and effective vaccines to protect vulnerable populations in poor countries against deadly diseases including cholera.
Current thinking about Parkinson's disease is that it's a disorder of mitochondria, the energy-producing organelles inside cells, causing neurons in the brain's substantia nigra to die or become impaired. A study from Children's Hospital Boston now shows that genetic mutations causing a hereditary form of Parkinson's disease cause mitochondria to run amok inside the cell, leaving the cell without a brake to stop them. Findings appear in the November 11, 2011 issue of Cell. Mitochondrial movement is often a good thing, especially in neurons, which need to get mitochondria to cells' peripheries in order to fuel the axons and dendrites that send and receive signals. However, arresting this movement is equally important, says senior investigator Dr. Thomas Schwarz, of Children's F.M. Kirby Neurobiology Center, because it allows mitochondria to be quarantined and destroyed when they go bad. "Mitochondria, when damaged, produce reactive oxygen species that are highly destructive, and can fuse with healthy mitochondria and contaminate them, too," Dr. Schwarz says. "It's the equivalent of an environmental disaster in the cell." Studying neurons from fruit flies, rats, and mice, as well as cultured human cells, Dr. Schwarz and colleagues provide the most detailed understanding to date of the effects of the gene mutations, which encode the mutated forms of the proteins Parkin and PINK1. They demonstrate how these proteins interact with proteins responsible for mitochondrial movement -- in particular Miro, which literally hitches a molecular motor onto the organelle. Normally, when mitochondria go bad, PINK1 tags Miro to be destroyed by Parkin and enzymes in the cell, the researchers showed. When Miro is destroyed, the motor detaches from the mitochondrion.
A new potential target to slow breast cancer tumor progression and metastasis has been identified by a team of researchers led by Dr. Richard Kremer from the Research Institute of the McGill University Health Centre (RI-MUHC). Complications in breast cancer patients are commonly caused by the spread of the disease through metastasis to other parts of the body, most often to the bones and lungs. The new findings, published online on November 7, 2011 in the Journal of Clinical Investigation (JCI), suggest that a specific protein plays a key role in the progression of the disease outside of the initial tumor area. Researchers showed that this particular target, called parathyroid hormone-related protein (PTHrP), present at high levels in cancers, is involved in key stages of breast cancer initiation, progression, and metastatic spread in mice. "We are hoping for a significant effect on the prevention of breast cancer recurrence, growth, and development by using a strategy to decrease the production of that particular protein," says Dr. Richard Kremer, co-director of the Musculoskeletal Axis of the RI-MUHC and a professor in the Department of Medicine at McGill University. To better understand the role of PTHrP in cancer development, researchers eliminated the production of the hormone from mouse breast cells using a strategy called "conditional knockout" and then studied the progression of the tumor. "The results showed that without the presence of PTHrP in the breast, even before the tumor developed, a reduction of 80 to 90 per cent in the growth of the tumor was observed," explains Dr. Kremer. "The removal of this hormone in the breast and breast tumors blocks not only the growth of the tumors, but also its spread to different organs." In order to bring this strategy one step closer to the patient, Dr.