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    Displaying items by tag: pathogens
    Thursday, 10 April 2014 10:33

    Tobacco plants are struggling with virus

    Tobacco plants are struggling with virusInternational research group led by Professor Chen has developed a new generation of potentially safer and more cost-effective therapies against West Nile virus etc, and other pathogens.

    Scientists applied therapy based on monoclonal antibodies and their derivatives.

    For the purposes of the study monoclonal antibodies are derived from tobacco plants, which is promising to change the image of the plant, which are believed to cause cancer of the lung.

    The antibodies are directed against proteins located on the surface of the virus.

    The main objective of the study is to create innovative, sustainable and affordable therapy that also be a cheap solution to combat the global threat of West Nile virus.

    One approach is the development of therapeutic antibodies that bind to receptors which may help of the monoclonal antibodies to cross into the brain.

    In a new study, the researchers developed a half-dozen new options that could assist in the implementation monoclonal antibodies that can be effectively targeted to the brain and to neutralize the dangerous virus.

    The final results of the study show 90% success in preventing letalnit development in experimental conditions.

    This is the first case of such an effect, leading to the neutralization of the virus.

    Dr. Chen results are motivating the development of plant-based therapy that dramatically reduce the cost of commercial production of monoclonal antibodies.

    The virus is spread by infected mosquitoes and affect the central nervous system.

    Infection can cause serious, life-altering and even fatal disease.

    Until now, however, is not available or effective drug therapy for dealing with infection.

    Published in News

    A molecular technique that will help the scientific community to analyze-on a scale previously impossible-molecules that play a critical role in regulating gene expression has been developed by a research team led by a chemist and a plant biologist at Penn State University. The scientists developed a method that enables more-accurate prediction of how ribonucleic acid molecules (RNAs) fold within living cells, thus shedding new light on how plants-as well as other living organisms-respond to environmental conditions. A paper by the research team-led by Sarah M. Assmann, Waller Professor of Biology, and Philip Bevilacqua, professor of chemistry-is scheduled for early online publication in the journal Nature on 24 November 2013.
    "Scientists have studied a few individual RNA molecules, but now we have data on almost all the RNA molecules in a cell-more than 10,000 different RNAs," Assmann said. "We are the first to determine, on a genome-wide basis, the structures of the RNA molecules in a plant, or in any living organism."

    eterna-rna-main
    Temperature and drought are among the environmental stress factors that affect the structure of RNA molecules, thereby influencing how genes are "expressed"-how their functions are turned on or turned off. "Climate change is predicted to cause increasingly extreme and unpredictable heat waves and droughts, which would impact our food crops, in part by affecting the structures of their RNA molecules and so influencing their translation into proteins," Bevilacqua said. "The more we understand about how environmental factors affect RNA structure and thereby influence gene expression, the more we may be able to breed-or develop with biotechnological methods-crops that are more resistant to those stresses. Such crops, which could perform better under more-marginal conditions, could help feed the world's growing population."
    The scientific achievement of the Penn State research team-postdoctoral scholar Yiliang Ding, graduate students Yin Tang and Chun Kit Kwok, and Professor of Statistics Yu Zhang, along with Assmann and Bevilacqua-involved determining the structures of the varieties of RNA molecules in a plant named Arabidopsis thaliana. This plant is used worldwide as a model species for scientific research.
    Arabidopsis thaliana, commonly known as mouse-ear cress, is an ideal organism for RNA studies, the researchers say, because it is the first plant species to have its full genome sequenced and has the greatest number of genetic tools available.
    RNA is the intermediate molecule between DNA and proteins in all living things. It is a critical component in the pathway of gene expression, which controls an organism's function. Unlike the double-stranded DNA molecule, which is compressed into cells by twisting and wrapping around proteins, RNA is single stranded, and folds back on itself. The researchers set out to answer the question, How exactly does RNA fold in a cell and how does that folding regulate gene function?
    "We needed a tool to answer that question," says Bevilacqua. "That tool involves introducing a chemical into the plant that can modify some segments of the RNA but not others, which then gives a readout of the structure of the RNA. Using this technique we can figure out which classes of genes are associated with certain RNA structural traits. And we can try to understand how these RNA structural changes relate to certain biological functions."
    "Previously, researchers would query the structures of individual RNAs in a cell one by one, and it was a tedious process," says Assmann. "You can't abstract rules or generalities about how RNAs are behaving just from knowing the structures of one or a few RNAs-you can't get a pattern. Now that we have genome-wide information for a particular organism, we can start to abstract patterns of how RNA structure influences gene expression and ultimately plant function. Other scientists can query their organisms of interest and ask what rules they can abstract. Are there universal rules that will be true for all organisms for how RNA structure influences gene expression?"
    Bevilacqua adds, "Because RNA is so central in its role in gene regulation, the tools we've developed can be transferred to scientists who are working with essentially any biological system."
    Long-term potential implications of the methodology include human health-for example, how an infection-induced fever could affect the RNA structures of both humans and pathogens.

    Published in News
    Wednesday, 17 July 2013 16:38

    Self-cleaning screens even killed E. coli

    dirty-smartphone-products-taq-pcr-elisa-targatt-accupower-elisa-kits

    A survey by the magazine Which? Conducted in 2010, the surface of a cell phone contains 18 times more harmful bacteria than a button in a public toilet cistern. For this reason, the company Corning introduces coating displays antimicrobial properties which kills virtually emptied microorganisms on it.

    CEO Jeff Evarsan says that innovative coverage will be effective against drug resistant bacteria and viruses. Originally designed for use in biomedical institutions, creators see huge potential and applied to the standard personal phones.

    Evarsan demonstrate some of the properties of the coating in public places such as fluorescently labeled bacteria Escherichia coli usually of glass and a specially crafted their antibacterial glass. While on common glass bacteria live undisturbed and full potential to infect someone on these patented by Corning coverage are completely destroyed in less than two hours.

    Escherichia coli is a Gram-negative rod-shaped bacterium that is a major cause of food poisoning and severe forms of gastrointestinal disorders. Study of the American Health Organization in 2012 concluded that one in six mobile phones is seriously contaminated with a large number of pathogens, mainly E. coli.
     
    The company informed that the first phones with their innovative hygienic coverage will reach the market by 2015

    Published in News

    White blood cells are reign as the heroes of the immune system. When the infection, the cells produced in the bone marrow, the race through the blood to combat pathogens. But new research shows that different bodies may also play a role in immune defense, which is essentially your own hero. In a study of a rare and deadly brain infection, researchers at Rockefeller University have discovered that the brain cells of healthy people can produce their own immune system molecules, demonstrating the "intrinsic immunity" that is crucial to stop the infection.

    Interfering with interferon Herpes simplex virus-infected neurons

    Interfering with interferon. Herpes simplex virus-infected neurons (above)
    are from patients with a genetic defect that impairs their brain’s ability to make
    interferon, an important immune system protein, and leaves their brain
    cells unable to fight off the infection. Healthy people, in turn,
    have an intrinsic immune response to the virus. (Credit: Image courtesy of Rockefeller University)


    Shen-Ying Zhang, clinical researcher at St. Giles Laboratory of Human Genetics of Infectious Diseases, has been studying children with herpes simplex encephalitis, a potentially deadly brain infection herpes virus, HSV-1, which may be important to brain damage. Scientists already knew from previous work that children with encephalitis have a genetic defect that affects the functions of the immune system receptor - Toll-like receptor 3 (TLR3) - in the brain. For this study we wanted to see how a defect in TLR3 prevent the brain's ability to fight herpes infection.
    When TLR3 recognizes pathogen that causes an immune response that causes the release of proteins known as interferons, and ringing "interfere" with the replication of the pathogen. Most commonly associated with white blood cells that are present within the body, but in this case researchers examines the existence of the receptor in neurons and other brain cells.
    "One interesting thing for these patients is that they have none of the other symptoms, the most frequent herpes. They had an infection of the skin or mouth only in their brains. Therefore hypothesis that TLR3 responses should be specifically responsible for the maintenance of herpes virus infects the brain and is not necessary in other parts of the body, "says Zhang.
    The laboratory, directed by Jean-Laurent Casanova, together with scientists from Harvard Medical School and the Institute of Memorial Sloan-Kettering Cancer to create induced pluripotent stem cells. Made from the patient's own tissue, the stem cells are converted into cells of the central nervous system, which leads to patient genetic defects. Zhang cells exposed to HSV-1 and synthetic double-stranded RNA, which mimics the product of the virus that stimulates Toll-like receptor activity. By measuring the levels of interferon, Zhang revealed that TLR3 response of patients was in fact defective, cells were making these important immune system proteins, preventing them from fighting infection.
    Zhang also exposed to the blood cells of patients with the virus and it was found that TLR3 defect is no problem there, as in the brain - interferons were released in another manner.
    Because Toll-like receptors in neurons was vital to prevent infection, encephalitis, researchers concluded that brain cells use as an internal mechanism to fight infection, rather than relying on the white blood cells. When the function deteriorates, patients who can not be improved.
    "This is proof of intrinsic immunity, recently discovered function of the immune system," says Zhang. "It is very likely that other organs also have their own specific tools to fight infection."
    Researchers are putting together a pilot study to test interferon-based therapy in patients with encephalitis, believing that will help speed recovery and increase survival when used in combination with antiviral drugs. They have also examined whether the brain shows intrinsic immunity to other viral infections.

    Published in News
    Monday, 24 June 2013 14:37

    Silver and antibiotics - star duo

    antibioticsAntibiotic resistance - the ability of pathogens to evolve and overcome the antibiotic preparations is about to collide with an unexpected ending. New research allows the silver to deter frighteningly rapid adaptation of microorganisms to the drugs, which the discovery of penicillin has increase exponentially. Currently, data on resistance to accumulate and it proved to be amplified, while the amount of new antibiotics in development or on the market falls.

    There are thousands of written information about the healing power of silver. Today there are many homeopathic preparations containing precious metals. According to proponents of homeopathy silver enhances immunity and heals the body. These therapies, however, are unpredictable and sometimes have an effect sometimes - not. What is certain and confirmed, however we offer James Collins, a researcher from the University "Boston" Massachusetts.

    His team has discovered how the metal in the form of dissolved ions, damaging bacteria. It makes them more membrane permeable and disrupts intracellular harmony of balance, leading to over-production of highly reactive and toxic oxygen compounds. When using silver solution in relatively small quantities as a supplement to the antibiotic, the scientific team found that the antibiotic kills from 10 to 1,000 times more bacteria. More permeable membranes allow more antibiotics to invade rogue cells, exacerbating the drug repeatedly.

    Development of a pill is still in its infancy, as it should be considered the optimal amount of silver - enough to help, not harm. Even in moderate doses, it causes argyria - a disease in which the skin becomes permanent blue color. At higher doses, toxic effects are much more dangerous - mainly damage the cardiovascular system.
     
    Scientists hope to understand the mechanism by which silver affects the cell walls and create a synthetic compound that perform the same functions, without incurring the side effects of the metal.

    Published in News

    Abstract

    There is much evidence that some pathogens manipulate the behaviour of their mosquito hosts to enhance pathogen transmission. However, it is unknown whether this phenomenon exists in the interaction of Anopheles gambiae sensu stricto with the malaria parasite, Plasmodium falciparum - one of the most important interactions in the context of humanity, with malaria causing over 200 million human cases and over 770 thousand deaths each year. Here we demonstrate, for the first time, that infection with P. falciparum causes alterations in behavioural responses to host-derived olfactory stimuli in host-seeking female An. gambiae s.s. mosquitoes. In behavioural experiments we showed that P. falciparum-infected An. gambiae mosquitoes were significantly more attracted to human odors than uninfected mosquitoes. Both P. falciparum-infected and uninfected mosquitoes landed significantly more on a substrate emanating human skin odor compared to a clean substrate. However, significantly more infected mosquitoes landed and probed on a substrate emanating human skin odor than uninfected mosquitoes. This is the first demonstration of a change of An. gambiae behaviour in response to olfactory stimuli caused by infection with P. falciparum. The results of our study provide vital information that could be used to provide better predictions of how malaria is transmitted from human being to human being by An. gambiae s.s. females. Additionally, it highlights the urgent need to investigate this interaction further to determine the olfactory mechanisms that underlie the differential behavioural responses. In doing so, new attractive compounds could be identified which could be used to develop improved mosquito traps for surveillance or trapping programmes that may even specifically target P. falciparum-infected An. gambiae s.s. females.

    Introduction

    There is evidence that some parasites manipulate the behavior of their vectors to enhance pathogen transmission. For example, the malaria mosquito Anopheles gambiae, infected with transmissible sporozoite stages of the human malaria parasite Plasmodium falciparum, takes larger and more frequent blood meals than uninfected mosquitoes or those infected with non-transmissible oocyst forms. This parasite-mediated manipulation of behavior in An. gambiae is likely to facilitate parasite transmission from human to mosquito.

    It would be even more advantageous for the parasite if its vector is more responsive to host odors, as this is the dominant cue used to find a blood meal. Indeed, Rossignol et al. found that a higher percentage of Aedes aegypti mosquitoes respond to guinea pig odor in an olfactometer when infected with the avian malaria parasite P. gallinaceum compared to uninfected females, demonstrating that parasites affect the host-seeking behavior of mosquitoes. However, it is unknown whether this phenomenon exists in other, biologically more important, systems.

    We investigated whether parasite manipulation exists in the An. gambiae sensu stricto - P. falciparum parasite interaction, responsible for one of the most important human infectious diseases. We hypothesized that infection with P. falciparum causes alterations in olfactory-mediated behavioral responses to host-derived stimuli in host-seeking An. gambiae mosquitoes. Indeed, our study demonstrates that females of An. gambiae infected with sporozoites of P. falciparum, are significantly more attracted in a laboratory setting to human odors than uninfected mosquitoes.

    Results and Discussion

    We collected human odors using a nylon matrix for the attraction of host-seeking An. gambiae mosquitoes. The matrix, and a control matrix which did not contain human odor, was presented to the mosquitoes in a cage olfactometer to measure the landing responses. At the time of the experiment, mosquitoes were either uninfected or infected with sporozoite-stage P. falciparum.

    Statistical analysis revealed a significant effect on the mosquito landing rate response of both the odor source used and the presence of P. falciparum, and a significant interaction between the two factors (P<0.001, P = 0.014, and P = 0.018, respectively). As expected, both infected and uninfected mosquitoes showed a low rate of landing on the matrix without human odor. However, infected mosquitoes responded significantly more to the matrix on which human odor was collected than uninfected (Figure 1A). Malaria-infected mosquitoes performed significantly more landings and probing attempts in response to human odor than did uninfected mosquitoes (P = 0.0017). These results suggest that malaria-infectious females are more attracted to human odors than uninfected mosquitoes (Figure 1A). This is the first indication of a change in An. gambiae s.s. behavior in response to human odor, caused by infection with P. falciparum. So far, most studies of An. gambiae mosquito behavior have been conducted with uninfected mosquitoes, but our data demonstrate that such results may not be representative of infected mosquitoes. Mathematical models incorporating malaria transmission are considered important tools for development of malaria eradication strategies. A number of mathematical models take into consideration various factors that affect R0, the basic reproductive number, which describes the number of secondary human infections that arise from a primary infection, but do not address the influence of parasites on vector-host interactions.

    journal.pone.0063602.g001

    Figure 1. Attraction of malaria infected mosquitoes to human odor.
    (A) Total number of landings by uninfected (green bars) and P. falciparum infected (red bars) An. gambiae s.s. females in response to no odor (left bars) or human odor (right bars). Error bars represent the standard error of the mean. (B) Simplified overview of our hypothesis on the effect of P. falciparum infection of An. gambiae s.s. on human malaria risk via alterations in the olfactory system of the vector (OBPs: odorant-binding proteins, ORs/IRs: olfactory and ionotropic receptors; R0: the basic reproductive number).
    doi:10.1371/journal.pone.0063602.g001

    Naturally, it would be most advantageous for a parasite if its vector is more responsive to host odors once the parasite has developed into the transmissible stage, and not at an earlier stage. To study this aspect properly, the host-seeking response of uninfected vectors and vectors infected with immature and mature parasite stages should be compared. Indeed, Anderson et al. showed that changes in An. stephensi females feeding behaviour were dependent on the developmental stage of the parasite P. yoelii nigeriensis (a malaria parasite of rodents). Therefore, for the primary study, described in this paper, we studied the effect of the stage of P. falciparum transmissible to human beings. Because these initial results supported our hypothesis, we have already initiated robust behavioural studies to ensure that our preliminary findings are repeatable and determine in more detail whether the effect on the host-seeking behaviour of An. gambiae s.s. depends on the lifecycle stage of P. falciparum and in this study we will test odors from multiple human subjects.

    Lefèvre et al. showed that infection with the rodent malaria parasite, P. berghei, altered levels of 12 protein spots in the head of An. gambiae infected with sporozoites, including synapse-associated proteins, likely affecting the olfactory system. Therefore, it is likely that the mechanism underlying the behavioral difference in infected mosquitoes lies within the olfactory system, possibly mediated by alteration of odorant-binding proteins (OBPs) or olfactory and ionotropic receptors (ORs and IRs; Figure 1B) tuned to host-derived semiochemicals. Further studies on the identification of new attractants for improved mosquito surveillance or trapping programs specifically targeting P. falciparum-infected An. gambiae s.s. females may provide powerful tools for the global agenda of malaria eradication.

    Materials and Methods

    Mosquitoes

    Anopheles gambiae sensu stricto mosquitoes (Ngousso strain from Cameroon) were reared according standard procedures at the insectaries of Radboud University Nijmegen (The Netherlands). 9-Days-old female mosquitoes had been given the opportunity to blood feed on human blood, either uninfected or infected with Plasmodium falciparum parasites, by using a membrane glass feeding system. Unfed females were removed from the cages. All groups of females were given an opportunity to oviposit 3 days post blood feeding.

    Infected female mosquitoes were obtained by feeding on gametocytes of the chloroquine-sensitive NF54 strain of P. falciparum, as described previously. Per cage, 10 blood-engorged mosquitoes were dissected at day 7 post blood feeding showing that 95% of the females were infected with on average 10 oocysts per mosquito (N = 20).

    All mosquitoes received another human blood meal nine days after the previous blood meal. Twenty one days after the first blood meal, cages (30×30×30 cm) were prepared, some containing 20 uninfected females, and others containing 20 infectious females. On day 22, after the bioassay had been conducted, salivary glands of 10 females per cage (N = 40) were dissected showing that P. falciparum sporozoites had migrated into 84% of the glands. Twenty mosquitoes were dissected to determine the average of 18.125 sporozoites per mosquito. The cages were randomly numbered and only the technician who prepared the mosquitoes (not the experimenter) was aware of their infectivity status.

    Bioassay

    Considering the high degree of anthropophily of An. gambiae s.s. females and the practical and effective use of human foot odor in vitro, human foot odor was collected on a nylon matrix as described previously (20 Den panty sock, HEMA, The Netherlands, worn during 20 hours prior to the day on which the bioassay was performed by a male volunteer of whom the relative attractiveness to An. gambiae s.s. compared to 47 other men is known). A clean matrix was used as the control. Prior and between experiments, matrixes were kept, individually, in clean glass jars.

    The bioassay was conducted between 8 and 11 am, in a BSL-3 climate cell (26±1°C, 80±10% R.H.). During the bioassay the room was dark except for a light bulb of 15 Watt (Osram, France) pointed at the wall behind the cage being observed. For each cage the number of landings in the area directly underneath the odor-treated matrix or the clean matrix was recorded over 3 minutes.

    Statistics

    After completion of the bioassay, the infectivity status corresponding with the numbers on the cages were revealed to the scientist who subsequently analyzed the results. We used the rate of landing (i.e. the number of landings per mosquito), rather than total number of landings as this takes into account the fact that a particular mosquito may land more than once. The rate of landing was calculated by dividing the total number of landings by the total number of mosquitoes used in the bioassay to give the mean landing rate per mosquito. This response was then analysed using a two-way ANOVA to compare the effect of odor and Plasmodium infection, and their interaction (GenStat version 15.2.0.8821) The Least Significant Differences (LSDs) were used to calculate P-values for the significant difference between the treatments.

    Ethics

    The author/experimenter performed odour collection on herself by wearing nylon stockings.

    Mosquitoes were bloodfed using membrane and a Hemotek blood feeding system. The blood was obtained from Sanguin, Nijmegen, The Netherlands and the blood donors signed an informed consent. No human volunteers were used for feeding the mosquitoes. The rearing of mosquitoes using this procedure is standard practice in many laboratories. The blood is not used for experimental purposes. No volunteers were recruited, therefore, ethical approval was not necessary.

    Published in News