A combination of iron-oxide nanoparticles and an alternating magnetic field, which together generate heat, have activated an immune system response to tumors in mice according to an accepted manuscript by Dartmouth-Hitchcock Norris Cotton Center researchers in the journal Nanomedicine: Nanotechnology, Biology and Medicine released online on February 24, 2014.“The study demonstrates that controlled heating of one tumor can stimulate an immune response that attacks another tumor that has not had the heat treatment,” said Steve Fiering, PhD, Norris Cotton Cancer Center researcher and professor of Microbiology and Immunology, and of Genetics at the Geisel School of Medicine at Dartmouth. “This is one way to try to train the immune system to attack metastatic tumors that may not be recognized yet.”Researchers injected iron-oxide nanoparticles into the tumor and then activated those agents with magnetic energy. Researchers were able to activate antigen-presenting dendritic cells in the body’s immune system. Dendritic cells somewhat serve as “quarterbacks” for body’s immune system by calling for quick coordinated protection against an attack. The “quarterback” cells show the defensive “killer” T cells (CD8+ cells) who to attack and these cells then directly attack tumor cells and send out an alert system to engage other cells in the fight against the cancer. The combination of these two aspects of the immune response reduce risk of recurrence and discourage spreading or metastasis of the cancer. This result was observed in sites close to the primary tumor as well as distant sites. In the experiments conducted as part of this study the primary tumor resisted regrowth for one month following overheating.The magnetic hyperthermia system used was developed by co-author P. Jack Hoopes, DVM, PhD co-director of Norris Cotton Cancer Center’s Nanotechnology Working Group. “It enables very precise control of the heating to keep the temperature at a uniform 43 degrees C for as long as desired,” said Fiering. …Read more
An international team of scientists has traced the origin of Plasmodium vivax, the second-worst malaria parasite of humans, to Africa, according to a study published this week in Nature Communications. Until recently, the closest genetic relatives of human P. vivax were found only in Asian macaques, leading researchers to believe that P. vivax originated in Asia.The study, led by researchers from the Perelman School of Medicine at the University of Pennsylvania, found that wild-living apes in central Africa are widely infected with parasites that, genetically, are nearly identical to human P. vivax.This finding overturns the dogma that P. vivax originated in Asia, despite being most prevalent in humans there now, and also solves other vexing questions about P. vivax infection: how a mutation conferring resistance to P. vivax occurs at high frequency in the very region where this parasite seems absent and how travelers returning from regions where almost all humans lack the receptor for P. vivax can be infected with this parasite.Of Ape and Human ParasitesMembers of the labs of Beatrice Hahn, MD, and George Shaw, MD, PhD, both professors of Medicine and Microbiology at Penn, in collaboration with Paul Sharp, PhD, an evolutionary biologist from the University of Edinburgh, and Martine Peeters, PhD, a microbiologist from the Institut de Recherche pour le Dveloppement and the University of Montpellier, tested over 5,000 ape fecal samples from dozens of field stations and sanctuaries in Africa for P. vivax DNA. …Read more
Oct. 22, 2013 — New research shows that in sub-Saharan Africa the virus responsible for foot and mouth disease (FMD) moves over relatively short distances and the African buffalo are important natural reservoirs for the infection. The study, published in mBio®, the online open-access journal of the American Society for Microbiology, sheds light on how the type of FMD virus called SAT 2 emerged in sub-Saharan Africa and identifies patterns of spread in countries where SAT 2 is endemic.”The data suggest that the common ancestor of all SAT 2 was in [African] buffalo. It’s very clear that historically infections have moved from buffalo to cattle,” says corresponding author Matthew Hall of the University of Edinburgh in Scotland.Foot and mouth disease (FMD) is devastating to livestock all over the world, but it’s a particular problem in Africa, where wildlife that harbor the virus are thought to pass it on to their domesticated cousins.FMD strikes cloven-hoofed animals, presenting as a high fever, blistering in the mouth and feet, decline in milk production in females, and weight loss. Although most animals recover over the course of months, some die of complications from the disease. In wild buffalo, the disease is very rarely symptomatic and animals can be persistently infected for a period of several years. The SAT 2 serotype of the virus is endemic in sub-Saharan Africa, but it has crossed the Sahara and caused outbreaks in North Africa and the Middle East between 1990 and 2012.In the hopes they could eventually predict future outbreaks, Hall and his colleagues wanted a better picture of the diversity of SAT 2 viruses in sub-Saharan Africa and how they move around from one location to another. They used 250 genetic sequences of the VP1 section of the genome from SAT 2 isolates taken from all over sub-Saharan Africa and tracked the appearance of the various unique ‘topotypes’ over the region.Hall says the patterns in which the topotypes appear in different places gives strong support to the idea that the virus is spread by infected hosts in land movements over relatively short distances. What’s more, African buffalo are an important “maintenance host,” meaning they maintain a reservoir of the virus that can re-infect domesticated animals after time and culling has ended an outbreak among livestock. The relationships between the 250 sequences also indicate that it’s possible the original source of the SAT 2 viruses that are now found in wild and domesticated animals was African buffalo.To Hall, these results indicate that genetic tracking of viruses has a lot of potential for making inferences about viral spread and heading off future outbreaks.”We showed that we can demonstrate [virus movement] using genetic data. …Read more
Oct. 15, 2013 — Researchers at Oregon State University and other institutions today announced the successful use of a new type of antibacterial agent called a PPMO, which appears to function as well or better than an antibiotic, but may be more precise and also solve problems with antibiotic resistance.In animal studies, one form of PPMO showed significant control of two strains of Acinetobacter, a group of bacteria of global concern that has caused significant mortality among military personnel serving in Middle East combat.The new PPMOs offer a fundamentally different attack on bacterial infection, researchers say.They specifically target the underlying genes of a bacterium, whereas conventional antibiotics just disrupt its cellular function and often have broader, unwanted impacts. As they are further developed, PPMOs should offer a completely different and more precise approach to managing bacterial infection, or conceptually almost any disease that has an underlying genetic component.The findings were published today in the Journal of Infectious Diseases, by researchers from OSU, the University of Texas Southwestern Medical Center, and Sarepta, Inc., a Corvallis, Ore., firm.”The mechanism that PPMOs use to kill bacteria is revolutionary,” said Bruce Geller, a professor of microbiology in the OSU College of Science and lead author on the study. “They can be synthesized to target almost any gene, and in that way avoid the development of antibiotic resistance and the negative impacts sometimes associated with broad-spectrum antibiotics.”Molecular medicine,” Geller said, “is the way of the future.”PPMO stands for a peptide-conjugated phosphorodiamidate morpholino oligomer — a synthetic analog of DNA or RNA that has the ability to silence the expression of specific genes. Compared to conventional antibiotics, which are often found in nature, PPMOs are completely synthesized in the laboratory with a specific genetic target in mind.In animal laboratory tests against A. baumannii, one of the most dangerous Acinetobacter strains, PPMOs were far more powerful than some conventional antibiotics like ampicillin, and comparable to the strongest antibiotics available today. They were also effective in cases where the bacteria were resistant to antibiotics.PPMOs have not yet been tested in humans. However, their basic chemical structure, the PMO, has been extensively tested in humans and found safe. Although the addition of the peptide to the PPMO poses an uncertain risk of toxicity, the potency of PPMOs reduces the risk while greatly improving delivery of the PMOs into bacterial cells, Geller said.Geller said research is being done with Acinetobacter in part because this pathogen has become a huge global problem, and is often spread in hospitals. It can cause respiratory infection, sepsis, and is a special concern to anyone whose immune system is compromised. …Read more
Sep. 2, 2013 — Candida albicans is a common fungus found living in, and on, many parts of the human body. Usually this species causes no harm to humans unless it can breach the body’s immune defences, where can lead to serious illness or death. It is known as an opportunistic pathogen that can colonise and infect individuals with a compromised immune system. New research, presented today at the Society for General Microbiology’s Autumn Conference, gives us a greater understanding of how mucosal surfaces in the body respond to C. albicans to prevent damage being done during infection.Share This:Researchers from King’s College London focused on oral epithelial cells, a mucosal layer of cells that line the mouth, providing a barrier against microbes. The group challenged oral epithelial cells grown in vitro with C. albicans, looking at gene expression six and 24 hours after infection.The results showed that a molecular signalling pathway know as the ‘PI3 Kinase pathway’ is activated as soon as five minutes after the epithelial cells encounter C. albicans, before the fungus has time to become invasive. This pathway seems to be involved in priming epithelial cells to protect against future damage. …Read more
Sep. 2, 2013 — Helicobacter pylori is a bacterium that establishes a life-long stomach infection in humans, which in some cases can lead to duodenal ulcers or stomach cancer. New research, presented at this week’s Society for General Microbiology Autumn Conference, gives us a clearer understanding of how these bacteria can manipulate the human immune system to survive in the mucosal lining of the stomach.Share This:Researchers from the University of Nottingham have shown that H. pylori is able to supress the body’s normal production of ‘human beta defensin 1’ (hβD1), an antimicrobial factor present in the stomach lining that helps prevent bacterial infection. By collecting stomach tissue biopsies from 54 patients at the Queens Medical Centre, Nottingham, the team showed that patients infected with H. pylori had ten times less hβD1 than uninfected patients. Those with the lowest amount of hβD1 had the most bacteria present in their stomach lining.The most damaging strains of H. pylori make a molecular syringe called the cagT4SS, through which bacterial products are injected into cells of the stomach lining. In vitro work using human gastric epithelial cell lines showed that this activates chemical pathways to suppress hβD1 production. These activated pathways are also involved in the stimulation of an inflammatory response, meaning that these H. …Read more
Aug. 13, 2013 — A strain of bacteria that causes skin and soft tissue infections in humans originally came from cattle, according to a study to be published in mBio®, the online open-access journal of the American Society for Microbiology. The researchers who conducted the genetic analysis of strains of Staphylococcus aureus known as CC97 say these strains developed resistance to methicillin after they crossed over into humans around forty years ago. Today, methicillin-resistant S. aureus (MRSA) strain CC97 is an emerging human pathogen in Europe, North and South America, Africa, and Asia. The findings highlight the potential for cows to serve as a reservoir for bacteria with the capacity for pandemic spread in humans.The researchers sequenced the genomes of 43 different CC97 isolates from humans, cattle, and other animals, and plotted their genetic relationships in a phylogenetic tree. Corresponding author Ross Fitzgerald of the Roslin Institute and the University of Edinburgh in Scotland says strains of CC97 found in cows appear to be the ancestors of CC97 strains from humans.”Bovine strains seemed to occupy deeper parts of the phylogenetic tree — they were closer to the root than the human strains. This led us to conclude that the strains infecting humans originated in cows and that they had evolved from bovine to human host jumps,” says Fitzgerald.Although the CC97 strains from animals were quite genetically diverse, the human isolates cluster together in two tight, distinct “clades,” or relatedness groups, indicating that S. aureus CC97 in cattle crossed over into humans on two separate occasions. Using mutation rates as a molecular clock, the authors determined that the ancestor of clade A jumped from a bovine host to humans between 1894 and 1977 and clade B made the jump between 1938 and 1966.After they made the jump, the human CC97 strains acquired some new capabilities, says Fitzgerald, thanks to genes encoded on portable pieces of DNA called mobile genetic elements.”It seems like these elements, such as pathogenicity islands, phages, and plasmids, are important in order for the bacterium to adapt to different host species,” says Fitzgerald. …Read more
Aug. 6, 2013 — The bacteria Streptococcus pneumoniae harmlessly colonizes the mucous linings of throats and noses in most people, only becoming virulent when they leave those comfortable surroundings and enter the middle ears, lungs or bloodstream. Now, in research published in July in mBio, University at Buffalo researchers reveal how that happens.”We were asking, what is the mechanism behind what makes us sick?” explains Anders P. Hakansson, PhD, assistant professor of microbiology and immunology in the UB School of Medicine and Biomedical Sciences. “We are looking to find ways to interfere with the transition to disease. Few have looked at the specific mechanism that suddenly makes these bacteria leave the nose where they typically prefer to reside and travel into the lungs or the middle ear where they cause disease. If we can understand that process, then maybe we can block it.”Hakansson and his colleagues had previously found that when the pneumococci colonize the nose, they form sophisticated, highly structured biofilm communities.In the current study, the research team grew biofilms of pneumococci on top of human epithelial cells, where the bacteria normally grow. They then infected these bacteria with influenza A virus or exposed them to the conditions that typically accompany the flu, including increased temperature to mimic fever, increased concentrations of ATP (the energy molecule in cells), and the stress hormone norepinephrine, released during flu infection. All three stimuli triggered a sudden release and departure of bacteria from the biofilm in the nose into otherwise normally sterile organs, such as the middle ears and lungs or into the bloodstream. At the same time, the researchers found that the gene expression profile of the bacteria that had dispersed from the biofilms revealed far more virulence.Hakansson says the research demonstrates how the mammalian and bacterial kingdoms interact. …Read more
Aug. 1, 2013 — Breath analysis may prove to be an accurate, noninvasive way to quickly determine the severity of bacterial and other infections, according to a UC Irvine study appearing online today in the open-access journal PLOS ONE.Employing a chemical analysis method developed for air pollution testing, UC Irvine microbiologists and chemists were able to correlate inflammation levels in laboratory mice to the amount of naturally produced carbon monoxide and other gases in breath samples.The findings point to human applications of this technology in emergency rooms and intensive care units, potentially augmenting or replacing blood tests.”Breath analysis has been showing promise as a diagnostic tool in a number of chronic diseases,” said Dr. Alan Barbour, professor of microbiology & molecular genetics and medicine. “This study provides the first evidence … that it can be used for rapid clinical assessment of infections, which can lead to prompt institution of effective treatments.”Barbour collaborated with UC Irvine chemist Donald Blake, utilizing a gas analysis method devised for the Rowland-Blake lab’s atmospheric chemistry research, which measures the level of trace gases that contribute to local and regional air pollution. It’s one of the few research groups in the world recognized for its ability to gauge precisely at the parts-per-trillion level. Previous breath sampling work by the Rowland-Blake lab has involved diabetes, cystic fibrosis and kidney failure.Barbour believed that breath analysis could additionally be used on infections, which elicit strong inflammatory responses in the body. Several compounds, or “biomarkers,” are by-products of these responses. They can be identified in blood but also detected in exhaled breath.Studying mice with bacterial blood infections, the researchers found that increases in the severity of infection elicited significantly higher amounts of carbon monoxide in relation to carbon dioxide in breath samples, making carbon monoxide a reliable biomarker for the presence and intensity of infection. Importantly, the carbon monoxide returned to normal levels soon after an antibiotic was given.”Using a breath analysis method like this could help physicians in the emergency room and ICU make critical decisions about serious infections more quickly than if they had to wait for blood tests to come back from the lab,” Barbour said.He and Blake will next expand their research to human breath samples. Their diagnostic method is currently under patent review.Charlotte Hirsch, Arash Ghalyanchi Langeroudi, Simone Meinardi, Eric Lewis and Azadeh Shojaee Estabragh of UC Irvine also contributed to the study, which was funded by a National Institute of Allergy & Infectious Diseases grant to the Pacific Southwest Regional Center of Excellence for Biodefense & Emerging Infectious Diseases (AI-065359).Read more
July 26, 2013 — Humans are far more than merely the sum total of all the cells that form the organs and tissues. The digestive tract is also home to a vast colony of bacteria of all varieties, as well as the myriad viruses that prey upon them. Because the types of bacteria carried inside the body vary from person to person, so does this viral population, known as the virome.By closely following and analyzing the virome of one individual over two-and-a-half years, researchers from the Perelman School of Medicine at the University of Pennsylvania, led by professor of Microbiology Frederic D. Bushman, Ph.D., have uncovered some important new insights on how a viral population can change and evolve — and why the virome of one person can vary so greatly from that of another. The evolution and variety of the virome can affect susceptibility and resistance to disease among individuals, along with variable effectiveness of drugs.Their work was published in the Proceedings of the National Academy of Sciences.Most of the virome consists of bacteriophages, viruses that infect bacteria rather than directly attacking their human hosts. However, the changes that bacteriophages wreak upon bacteria can also ultimately affect humans.”Bacterial viruses are predators on bacteria, so they mold their populations,” says Bushman. “Bacterial viruses also transport genes for toxins, virulence factors that modify the phenotype of their bacterial host.” In this way, an innocent, benign bacterium living inside the body can be transformed by an invading virus into a dangerous threat.At 16 time points over 884 days, Bushman and his team collected stool samples from a healthy male subject and extracted viral particles using several methods. They then isolated and analyzed DNA contigs (contiguous sequences) using ultra-deep genome sequencing .”We assembled raw sequence data to yield complete and partial genomes and analyzed how they changed over two and a half years,” Bushman explains. The result was the longest, most extensive picture of the workings of the human virome yet obtained.The researchers found that while approximately 80 percent of the viral types identified remained mostly unchanged over the course of the study, certain viral species changed so substantially over time that, as Bushman notes, “You could say we observed speciation events.”This was particularly true in the Microviridae group, which are bacteriophages with single-stranded circular DNA genomes. Several genetic mechanisms drove the changes, including substitution of base chemicals; diversity-generating retroelements, in which reverse transcriptase enzymes introduce mutations into the genome; and CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats), in which pieces of the DNA sequences of bacteriophages are incorporated as spacers in the genomes of bacteria.Such rapid evolution of the virome was perhaps the most surprising finding for the research team. …Read more
July 23, 2013 — A benign crystal protein, produced naturally by bacteria and used as an organic pesticide, could be a safe, inexpensive treatment for parasitic worms in humans and provide effective relief to over a billion people around the world. Researchers from the University of California, San Diego, La Jolla, CA, report on this potentially promising solution in a study published ahead of print in the journal Applied and Environmental Microbiology.Hookworms, and other intestinal parasites known as helminths infect more than 1 billion people in poverty-stricken, tropical nations, sucking the vitality from the body, and leaving hundreds of millions of children physically and mentally stunted. Current drugs are insufficiently effective, and resistance is rising, but little effort has been made to develop better drugs because the relevant populations do not represent a profitable market for drug companies.”The challenge is that any cure must be very cheap, it must have the ability to be mass produced in tremendous quantities, safe, and able to withstand rough conditions, including lack of refrigeration, extreme heat, and remote locations,” says Raffi Aroian, a researcher on the study.In earlier research, Aroian and his collaborators described a protein, Cry5B, that can kill intestinal nematode parasites — such as human hookworms — in infected test animals (hamsters). Cry5B belongs to a family of proteins that are generally accepted as safe for humans. These proteins are produced naturally in Bacillus thuringiensis (Bt), a bacterium which is applied to crops as a natural insecticide on some organic farms, and CryB proteins have been engineered into food crops such as corn and rice, to render them pest resistant.As shown for the first time in this paper, Cry5B can also be expressed in a species of bacterium, Bacillus subtilis, which is closely related to Bacillus thuringiensis, and which is also related to bacteria which are present in some probiotics, says Aroian. In the current research researchers showed that a small dose of Cry5B, expressed in this bacterium can achieve a 93 percent elimination of hookworm parasites from infected hamsters. That, says Aroian, is substantially better than current drugs.The scientific significance of the research, he says, is that “bacteria similar to those that are food grade — which are cheap and can readily be mass produced–can be engineered to produce molecules that can cure parasitic diseases.”Read more
July 9, 2013 — The H7N9 avian flu strain that emerged in China earlier this year has subsided for now, but it would be a mistake to be reassured by this apparent lull in infections. The virus has several highly unusual traits that paint a disquieting picture of a pathogen that may yet lead to a pandemic, according to lead scientists from the National Institute of Allergy and Infectious Diseases. David Morens, Jeffery Taubenberger, and Anthony Fauci, in a paper published in mBio®, the online open-access journal of the American Society for Microbiology, describe the history of H7 viruses in animal and human disease and point out that H7 influenza has a tendency to become established in bird, horse, and swine populations and may spillover repeatedly into humans.”The evidence as a whole is complex and the implications of past outbreaks for predicting the future course of the current H7N9 epizootic [an epidemic among animals] are uncertain,” write the authors.The outbreak of H7N9 earlier this year led China to temporarily close scores of live poultry markets in an effort to limit the spread of the virus. Although this previously unrecognized strain of avian influenza A has now been associated with 132 confirmed human infections and 39 related deaths (as of June 14), the rate at which new cases are recognized has dwindled in recent weeks.In their minireview, Morens, Taubenberger and Fauci point out that despite this apparent hiatus, viruses like H7N9, which have subtype 7 hemagglutinin, are a cause for heightened concern because of several highly unusual characteristics. First, H7 viruses have repeatedly been involved in numerous explosive poultry outbreaks including incidents in New York, Canada, Mexico, the Netherlands, and Italy, and in almost all of these cases the virus eventually spilled over into humans. Also, H7 viruses have the ability to mutate from a low pathogenicity form to a high pathogenicity form in birds, a scenario that can lead to large-scale culling and ultimately to human exposure to the virus among poultry workers.H7N9 also shares many characteristics with another influenza strain that continues to spillover into humans: highly pathogenic avian influenza H5N1. Among other commonalities, both viruses have a clinical picture that includes bilateral pneumonia, acute respiratory distress syndrome, and multi-organ failure, and it appears they are both currently unable to easily infect most humans but cause severe disease in individuals with uncharacterized genetic susceptibilities.The fact that many H7 viruses tend to infect conjunctival cells is also cause for concern. Some, but not all, cases of human H7 infection feature prominent signs and symptoms in the eyes, including itching, swelling, and tearing, that could enhance person-to-person spread in an H7N9 outbreak.The authors point out that many H7 viruses have adapted to infect mammals, including horses and pigs, which raises the possibility that H7N9 could adapt in a similar fashion. The possibility that H7N9 might infect pigs is particularly troubling, as swine are considered a “mixing vessel” for viruses — a breeding ground for novel viral reassortants like the 2009 H1N1 pandemic influenza strain commonly known as “swine flu.”The sum of these observations is this: we do not know what H7N9 will do next. Although avian influenza viruses have not caused widespread human transmission in 94 years of surveillance, there have been numerous instances of avian influenza spillover and H7N9 “might arguably be more likely than other avian viruses to become human-adapted,” write the authors.Regardless of its future, H7N9 certainly holds lessons for preventing human and animal pandemics. …Read more
July 8, 2013 — Deep in the ocean exist super salty anoxic basins that form ‘islands’ allowing evolution to vary between communities of ciliated plankton. These unique communities are presented in BioMed Central’s open access journal BMC Microbiology, and provide an opportunity to observe multiple results of evolution from the same stock and different solutions to environmental difficulties.Share This:About five and a half million years ago the Mediterranean sea dried up. This resulted in salty sediment, known as Messinian evaporites, in basins which were covered by sea water as the area reflooded. Salts from these basins are slowly leaching out but, since this water is denser than the surrounding sea, they are unmixable and it remains a briny column.The ciliate plankton which live in these brines all began from the same stock, but over time have had the potential to evolve differently. Researchers from University of Kaiserslautern in collaboration with Woods Hole Oceanographic Institution, USA and CNR- Institute for Coastal Marine Environment, Italy, investigated how isolated these communities are, and whether there has been mixing between them and the surrounding ciliates in the sea.The researchers found that there was some mixing of ciliate communities at the interfaces immediately above four different brines, and that these communities were very similar to each other. However the communities living at the heart of the brines were very different from each other even though the physical properties of each island were the same.Dr Thorsten Stoeck who led this project said, “The isolation of these very similar habitats means that we can study alternative courses of evolution. Each of our four communities had taken a subtly different route in adapting to anoxia and hypersalinity, resulting in four very different communities. Other ancient isolated habits which also occur in the Red Sea and Gulf of Mexico may also contain ‘hot spots’ of as-of-yet unstudied and potentially highly divergent ecosystems.”Share this story on Facebook, Twitter, and Google:Other social bookmarking and sharing tools:|Story Source: The above story is reprinted from materials provided by BioMed Central Limited. Note: Materials may be edited for content and length. For further information, please contact the source cited above. …Read more
July 2, 2013 — The strain of cholera that has sickened thousands in Haiti came from a single source and was not repeatedly introduced to the island over the past three years as some have thought, according to a new study published in mBio®, the online open-access journal of the American Society for Microbiology.The results of this latest study are consistent with earlier findings that indicate Vibrio cholerae bacteria were introduced to Haiti by United nations soldiers between July and October 2010, when Nepalese soldiers arrived to assist recovery efforts after the January 2010 earthquake in that country. The genome sequences of V. cholerae strains from Haiti reveal they have not gained any new genetic material since their introduction and that they have a limited ability to acquire genes from other organisms through a process called transformation.This new information may help public health authorities understand future cholera outbreaks in Haiti and elsewhere, according to the authors. “The use of high resolution sequence data that is amenable to evolutionary analysis will greatly enhance our ability to discern transmission pathways of virulent clones such as the one implicated in this epidemic,” write the authors.The earthquake in January 2010 killed tens of thousands of Haitians, and it was followed several months later by an outbreak of cholera, a disease that had never before been documented in Haiti. Studies of the outbreak indicate that poor sanitation at a United Nations camp resulted in sewage contamination of local water supplies, and phylogenetic analysis of the Haiti V. cholerae strains and strains from around the globe indicate the strain was most likely accidentally brought to the camp by U.N. troops from Nepal.Earlier “fingerprinting” of Haiti’s V. cholerae isolates using pulse-field gel electrophoresis (PFGE) has shown the bacterium has changed somewhat since the epidemic began in October 2010, but because of the nature of PFGE, the significance of those changes was not known. Were the changes meaningful? Were the bacteria gaining or losing genes that could impact the course of disease? …Read more
July 2, 2013 — More people die from heart-disease during the winter months, and according to a new study published in the journal Cell Metabolism, the increase in mortality is possibly due to the accelerated growth of atherosclerotic plaque in the blood vessels caused by the activation of brown fat by the cold.It has long been known that the number of deaths from cardiovascular diseases increases during the winter. It has been speculated that this might be the result of over-exertion while shovelling snow and a general decrease in physical activity, although the underlying mechanisms have been unclear. The present study, which has been conducted by researchers at Karolinska Institutet, and Linköping University in Sweden, and three universities in China, demonstrates a new principle by which the cold increases the risk of atherosclerosis.The researchers conducted their study on a strain of mice genetically modified with a propensity for atherosclerosis. Mice, like humans, have both white and brown body fat. Normal rolls of fat consist mainly of white fat, which is a repository of surplus calories; brown adipose tissue, on the other hand, can convert fat into heat. This heat-generation process is activated by cold temperatures and has been considered beneficial to the health since it can reduce the amount of unnecessary white adipose tissue in the body.”At first, we thought that the cold activation of brown fat would only make the mice thinner and healthier,” says Yihao Cao at the Department of Microbiology, Tumour and Cell Biology at Karolinska Institutet, and the Department of Medicine and Health at Linköping University. “Instead, we found that they ended up having more fat stored in the blood vessels. This came as a surprise and was the opposite of what we thought would happen.”It turned out that exposure to low temperatures accelerated the formation of atherosclerotic plaque in the mice, which can cause myocardial infarction and brain haemorrhaging. Moreover, the cold made the plaque less stable, and if such plaque ruptures, stored fat can leak into the blood, blocking vessels in the heart and brain. The cold-activated breakdown of fatty acids in the mice’s brown fat led to the accumulation of low-density lipoproteins (LDL) in the blood and an increase in fat storage in the plaque.”If this is also true for humans, it might be wise to recommend that people who suffer from cardiovascular disease should avoid exposure to the cold and to put on warm clothes when they are outside during the winter,” says Professor Yihai Cao.The researchers hope to be able to extend their work on mice to studies on humans.”It would be an extremely important discovery if we found this to be the case in humans too,” says Professor Yihai Cao. …Read more
July 1, 2013 — Cells of the placenta may have a unique ability to prevent viruses from crossing from an expectant mother to her growing baby and can transfer that trait to other kinds of cells, according to researchers at Magee-Womens Research Institute (MWRI) and the University of Pittsburgh School of Medicine. Their findings, published in the early online version of the Proceedings of the National Academy of Sciences, shed new light on the workings of the placenta and could point to new approaches to combat viral infections during pregnancy.It is imperative that the fetus be protected from infections of its mother in order to develop properly, said co-senior investigator Yoel Sadovsky, M.D., Elsie Hilliard Hillman Chair of Women’s Health Research, professor of obstetrics, gynecology and reproductive medicine, Pitt School of Medicine, and MWRI director. But how the placenta, long thought to be just a passive barrier between mother and child, accomplishes this feat has not been clear.”Our findings reveal some of the complex and elegant mechanisms human placental cells, called trophoblasts, have evolved to keep viruses from infecting cells,” Dr. Sadovsky said. “We hope that we can learn from this to devise new therapies against viral infections.”Led by Dr. Sadovsky and co-senior investigator Carolyn Coyne, Ph.D., associate professor, Department of Microbiology and Molecular Genetics at Pitt and MWRI member, the research team studied human trophoblast cells in the lab, exposing them to a panel of viruses. Unlike non-placental cells, trophoblasts were resistant to viral infection, but that trait was not a result of an inability of viruses to bind or enter the cells.The researchers noted that when the medium, or fluid environment, in which the trophoblasts were cultured was transferred to non-placental cells, such as those that line blood vessels, they became resistant to viral infection, too.The team noted that when the medium was exposed to sonication, which involves exposure to sound waves, viral resistance was no longer transferred to non-placental cells. This finding led them to take a closer look at exosomes, which are tiny spheres called nanovesicles that are secreted by trophoblasts and are sensitive to sonication. They found that fragments of genetic material called microRNAs contained within the exosomes, as well as lab-synthesized mimics of them, were able to induce autophagy, a mechanism of prolonged cellular recycling and survival. Blocking autophagy at least partially restored the cells’ vulnerability to viral infections.”Our results suggest this pathway could be a powerful evolutionary adaptation to protect the fetus and mother from viral invaders,” Dr. …Read more
June 17, 2013 — Mannitol, a sugar alcohol produced by fungi, bacteria, and algae, is a common component of sugar-free gum and candy. The sweetener is also used in the medical field — it’s approved by the FDA as a diuretic to flush out excess fluids and used during surgery as a substance that opens the blood/brain barrier to ease the passage of other drugs.Now Profs. Ehud Gazit and Daniel Segal of Tel Aviv University’s Department of Molecular Microbiology and Biotechnology and the Sagol School of Neuroscience, along with their colleague Dr. Ronit Shaltiel-Karyo and PhD candidate Moran Frenkel-Pinter, have found that mannitol also prevents clumps of the protein α-synuclein from forming in the brain — a process that is characteristic of Parkinson’s disease.These results, published in the Journal of Biological Chemistry and presented at the Drosophila Conference in Washington, DC in April, suggest that this artificial sweetener could be a novel therapy for the treatment of Parkinson’s and other neurodegenerative diseases. The research was funded by a grant from the Parkinson’s Disease Foundation and supported in part by the Lord Alliance Family Trust.Seeing a significant differenceAfter identifying the structural characteristics that facilitate the development of clumps of α-synuclein, the researchers began to hunt for a compound that could inhibit the proteins’ ability to bind together. In the lab, they found that mannitol was among the most effective agents in preventing aggregation of the protein in test tubes. The benefit of this substance is that it is already approved for use in a variety of clinical interventions, Prof. Segal says.Next, to test the capabilities of mannitol in the living brain, the researchers turned to transgenic fruit flies engineered to carry the human gene for α-synuclein. To study fly movement, they used a test called the “climbing assay,” in which the ability of flies to climb the walls of a test tube indicates their locomotive capability. In the initial experimental period, 72 percent of normal flies were able to climb up the test tube, compared to only 38 percent of the genetically-altered flies.The researchers then added mannitol to the food of the genetically-altered flies for a period of 27 days and repeated the experiment. …Read more
June 13, 2013 — A toxin dangerous to humans may help E. coli fend off aquatic predators, enabling strains of E. coli that produce the toxin to survive longer in lake water than benign counterparts, a new study finds.Researchers from the University at Buffalo and Mercyhurst University reported these results online June 7 in the journal Applied and Environmental Microbiology.”The take-home lesson is that E. coli that produce Shiga toxin persisted longer in recreational water than E. coli that don’t produce this toxin,” said UB Professor of Biological Sciences Gerald Koudelka, PhD, who led the study. “This is because the toxin appears to help E. coli resist predation by bacterial grazers.”The findings have implications for water quality testing. They suggest that measuring the overall population of E. coli in a river or lake — as many current tests do — may be a poor way to find out whether the water poses a danger to swimmers.Past research has shown that overall E. coli concentrations don’t always correlate with the levels of dangerous, Shiga toxin-producing E. …Read more
June 5, 2013 — A phase 1 clinical trial for the first treatment to reset the immune system of multiple sclerosis (MS) patients showed the therapy was safe and dramatically reduced patients’ immune systems’ reactivity to myelin by 50 to 75 percent, according to new Northwestern Medicine research.In MS, the immune system attacks and destroys myelin, the insulating layer that forms around nerves in the spinal cord, brain and optic nerve. When the insulation is destroyed, electrical signals can’t be effectively conducted, resulting in symptoms that range from mild limb numbness to paralysis or blindness.”The therapy stops autoimmune responses that are already activated and prevents the activation of new autoimmune cells,” said Stephen Miller, the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine. “Our approach leaves the function of the normal immune system intact. That’s the holy grail.”Miller is the co-senior author of a paper on the study, which will be published June 5 in the journal Science Translational Medicine. The study is a collaboration between Northwestern’s Feinberg School, University Hospital Zurich in Switzerland and University Medical Center Hamburg-Eppendorf in Germany.The human trial is the translation of more than 30 years of preclinical research in Miller’s lab.In the trial, the MS patients’ own specially processed white blood cells were used to stealthily deliver billions of myelin antigens into their bodies so their immune systems would recognize them as harmless and develop tolerance to them.Current therapies for MS suppress the entire immune system, making patients more susceptible to everyday infections and higher rates of cancer.While the trial’s nine patients — who were treated in Hamburg, Germany — were too few to statistically determine the treatment’s ability to prevent the progression of MS, the study did show patients who received the highest dose of white blood cells had the greatest reduction in myelin reactivity.The primary aim of the study was to demonstrate the treatment’s safety and tolerability. It showed the intravenous injection of up to 3 billion white blood cells with myelin antigens caused no adverse affects in MS patients. Most importantly, it did not reactivate the patients’ disease and did not affect their healthy immunity to real pathogens.As part of the study, researchers tested patients’ immunity to tetanus because all had received tetanus shots in their lifetime. One month after the treatment, their immune responses to tetanus remained strong, showing the treatment’s immune effect was specific only to myelin.The human safety study sets the stage for a phase 2 trial to see if the new treatment can prevent the progression of MS in humans. Scientists are currently trying to raise $1.5 million to launch the trial, which has already been approved in Switzerland. Miller’s preclinical research demonstrated the treatment stopped the progression of relapsing-remitting MS in mice.”In the phase 2 trial we want to treat patients as early as possible in the disease before they have paralysis due to myelin damage.” Miller said. …Read more
May 30, 2013 — Treatments against hepatitis C virus have only been partially successful. A major problem is that antivirals generate drug resistance. Now Seong-Wook Lee of Dankook University, Yongin, Republic of Korea and his collaborators have developed agents that bind to the business end of a critical protein, disabling it so successfully that no resistance has arisen. The research is published in the June 2013 issue of the Journal of Virology.
The target protein for the new agents is the NS5B replicase protein, which is the central catalytic enzyme in HCV replication. The researchers developed “RNA aptamers” which bind tightly to the part of that protein that performs the catalysis, disabling the replicase. Aptamers are short nucleic acids or peptides that provide the same level of recognition and binding ability that is common to antibodies.
The aptamers inhibited HCV replication without generating escape mutants, says Lee. Moreover, the aptamers inhibited diverse genotypes of HCV, neither causing toxicity nor inducing innate immunity, he says. Lee notes that in the study, therapeutic quantities of ligand-conjugated aptamer penetrated the liver tissue in the mice, raising the likelihood that therapeutically effective quantities could ultimately be achieved in HCV patients.
Roughly 170 million people worldwide are infected with HCV, says Lee, and it is the major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. There is as yet “no efficient and specific single regimen against HCV,” says Lee. Current treatments are associated with many side effects, partly because rapid generation of drug-resistant virus has forced clinicians to use combinations of several drugs, resulting in greater numbers of side effects in patients than if a single agent could be used. And even with the drug combinations only some patients can generate a sustained antiviral response.
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- C. H. Lee, Y. J. Lee, J. H. Kim, J. H. Lim, J.-H. Kim, W. Han, S.-H. Lee, G.-J. Noh, S.-W. Lee. Inhibition of Hepatitis C Virus (HCV) Replication by Specific RNA Aptamers against HCV NS5B RNA Replicase. Journal of Virology, 2013; 87 (12): 7064 DOI: 10.1128/JVI.00405-13
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