New biomarker for peripheral artery disease A protein biomarker known as beta-2 microglobulin may assist physicians in identifying patients with peripheral artery disease (PAD), according to research led by scientists at Stanford University, the United States. The researchers analysed plasma samples from 45 patients with PAD and 43 patients with risk factors for PAD, but without the disease itself, using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to quantify a total of 1,619 protein peaks. The study confirmed that the peak intensity of beta-2 microglobulin was higher among patients with PAD than among those without PAD. Another study revealed higher levels of the biomarker in the plasma of patients with PAD than in that of patients with coronary artery disease and no PAD. Plasma beta-2 microglobulin level correlated with functional capacity and ankle brachial index, and was an independent predictor of PAD when combined with C-reactive protein level. “This biomarker discovery may provide new insight into the patho-physiology of PAD and may contribute toward the development of our panel of biomarkers to identify patients at risk for PAD,” said Dr. Eric Fung, Chief Scientific Officer of Vermillion Inc., a diagnostics company that aims to work with the researchers to develop a blood test for PAD incorporating the new marker. Source: www.labnews.com Blood protein linked to pancreatic cancer A study led by Dr. Brian M. Wolpin at the Dana-Farber Cancer Institute in Boston, the United States, points to possible link between the blood protein related to body weight and physical exercise levels and pancreatic cancer risk. It supports the link between obesity and a sedentary lifestyle with an increased risk of pancreatic cancer, with a high mortality rate but difficult to catch early. This grim prognosis has prompted scientists to identify the risk factors for pancreatic cancer. The investigators looked at whether blood levels of a protein known as insulin-like growth factor binding protein-1 (IGFBP-1) were related to the risk of developing the cancer. IGFBP-1 inhibits the activity of insulin-like growth factor-1 (IGF-1), a hormone that can assist the growth and spread of cancerous pancreatic cells. The researchers measured levels of IGFBP-1 in 573 subjects enrolled in several large, ongoing clinical trials. Four years later, 144 had developed pancreatic cancer. The men and women with the lowest levels of IGFBP-1 were twice as likely as those with higher levels to develop pancreatic cancer. Low IGFBP-1 levels are typically found in obese and inactive individuals. Several studies have shown that obesity and lack of exercise may raise the risk of pancreatic cancer, with the evidence being stronger for obesity. The current findings therefore indirectly support them as risk factors for pancreatic cancer, said Dr. Wolpin. More importantly, the study points to a reason for the connection. Since IGFBP-1 binds to and “sequesters” IGF-1, Dr. Wolpin explained, people with chronically low IGFBP-1 levels would have more “free” IGF-1 in the circulation, interacting with body cells. In theory, IGF-1 would be better able to promote the growth of pancreatic cancer cells. Source: www.sciam.com New mechanism discovered for DNA recombination and repair A Taiwanese biochemistry research team led by Dr. Andrew H.-J. Wang and Dr. Ting-Fang Wang at the Institute of Biological Chemistry, Academia Sinica (IBCAS), has discovered that the RecA family recombinases function as a new type of rotary motor proteins to repair DNA damages. Homologous recombination (HR) is a mechanism that repairs damaged DNA with perfect accuracy, and it utilizes the homologous sequence from a partner DNA as a template. This process involves the bringing together of two DNA molecules, a search for homologous sequences and exchange of DNA strands. RecA family proteins are the central recombinases for HR. The family includes prokaryotic RecA, archaeal RadA and eukaryotic Rad51, and Dmc1. They have important roles in cell proliferation, genome maintenance and genetic diversity, particularly in higher eukaryotes. Since the discovery of RecA proteins, it has been assumed that RecA (and other homologues) forms only 61 right-handed filaments (six protein monomers per helical turn), and then hydrolyses adenosine triphosphate (ATP) to promote recombinational and HR DNA repair. How the energy of ATP facilitates DNA rotation during the strand exchange reaction was a puzzle. The IBCAS scientists have reported that archaeal sulfolobus solfataricus RadA proteins can also self-polymerize into a 31 right-handed filament with three monomers per helical turn and a 43 right-handed helical filament with four monomers per helical turn. Further analyses revealed that RecA family proteins may couple ATP binding and hydrolysis to the DNA strand exchange reaction in a manner that promotes clockwise axial rotation of nucleoprotein filaments. Specially, the 61 RadA helical filament undergoes clockwise axial rotation in two discrete 120° steps to the 31 extended right-handed filament and then to the 43 left-handed filament. As a result, all the DNA-binding motifs (L1, L2 and HhH) in the RadA proteins move concurrently to mediate DNA binding, homology pairing and strand exchange, respectively. Therefore, the energy of ATP is used to rotate not only DNA substrates but also the RecA protein filaments. Source: www.eurekalert.com New prion protein discovery may shed light on mad cow disease Scientists have discovered a new protein that may offer fresh insights into brain function in mad cow disease. The study was conducted jointly by the Canada’s University of Toronto and University of Alberta, and Case Western Reserve University and McLaughlin Research Institute in the United States. “Our team has defined a second prion protein called ‘Shadoo’ that exists in addition to the well-known prion protein called PrP,” said Prof. David Westaway, Director of the Centre for Prions and Protein Folding Diseases at the University of Alberta. The discovery challenges the long-held view that PrP is a unique nerve protein that folds into an abnormal shape and causes mad cow disease. This is the first discovery since 1985 of a new brain prion protein, though a second prion protein had been earlier inferred by other studies and the examination of DNA sequences. The study has also defined an unexpected alteration in prion infections, says lead author Mr. Joel Watts, a graduate student at the University of Toronto’s Centre for Research in Neurodegenerative Diseases. “As the PrP molecule alters shape and accumulates in a prion-affected brain, the Shadoo protein seems to disappear,” he said. Since proteins in a living cell are the molecules that do the work, this is likely to be significant, Mr. Watts added. Source: www.news.biocompare.com Second protein that doubles muscle-building effect In the United States, Dr. Se-Jin Lee, the Johns Hopkins scientist who first showed that the absence of the protein myostatin leads to oversized muscles, has now found a second protein whose overproduction in mice lacking myostatin doubles the muscle-building effect. Results of Dr. Lee’s new study show that while mice which lack the gene that makes myostatin have roughly twice the amount of body muscle as normal, mice without myostatin that also overproduce follistatin, the second protein, have about four times as much muscle as normal mice. This muscle increase could significantly boost research efforts to “beef up” livestock or promote muscle growth in patients with muscle wasting diseases. Dr. Lee first discovered that follistatin was capable of blocking myostatin activity in muscle cells grown under lab conditions. When he gave it to normal mice, the rodents bulked up, just as would happen if the myostatin gene in these animals was turned off. He then genetically engineered a mouse that both lacked myostatin and made extra follistatin. If follistatin were to increase muscle growth solely by blocking myostatin, then follistatin would have no added effect in the absence of myostatin. Dr. Lee found an additive effect, and noted that these muscular mice averaged a 117 per cent increase in muscle fibre size and a 73 per cent increase in total muscle fibres compared with normal mice. This is significant, as most agents targeting this pathway, including drugs i use, block only myostatin and not other related proteins. Source: www.medicalnewstoday.com