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  • richardmitnick 12:50 pm on March 1, 2021 Permalink | Reply
    Tags: "Scientists use Doppler to peer inside cells leading to better faster diagnoses and treatments of infections", A potentially fatal condition called bacterial sepsis or septicemia., Another benefit is the ability to quickly and directly diagnose which bacteria respond to which antibiotics., , , If the cells are not pathogenic the Doppler signal doesn’t change. If they are the Doppler signal changes quite significantly., Immortalized cell lines-cells that will live forever unless you kill them., Letting bacteria come into close contact with antibiotics that do not kill them only makes them more resistant to that antibiotic and more difficult to fight next time., , , Pathogens, , The team isolated living immortalized cells in multi-well plates to study them with Doppler., The team used Doppler to sneak a peek inside cells and track their metabolic activity in real time without having to wait for cultures to grow., These living cells are called “sentinels” and observing their reactions is called a biodynamic assay., Unknown microbes, Unknown microorganisms   

    From Purdue University(US): “Scientists use Doppler to peer inside cells leading to better faster diagnoses and treatments of infections” 

    From Purdue University(US)

    February 24, 2021

    Brittany Steff, writer
    765-494-7833
    bsteff@purdue.edu

    Source:
    David Nolte
    765-494-3013
    nolte@purdue.edu

    1
    David Nolte works with the Doppler apparatus to peer inside living cells, giving him insight into intracellular activity, metabolism, and pathogenicity. Credit: Rebecca McElhoe/Purdue University photo.

    Doppler radar improves lives by peeking inside air masses to predict the weather. A Purdue University team is using similar technology to look inside living cells, introducing a method to detect pathogens and treat infections in ways that scientists never have before.

    In a new study, the team used Doppler to sneak a peek inside cells and track their metabolic activity in real time without having to wait for cultures to grow. Using this ability, the researchers can test microbes found in food, water, and other environments to see if they are pathogens, or help them identify the right medicine to treat antibiotic-resistant bacteria.

    David Nolte, Purdue’s Edward M. Purcell Distinguished Professor of Physics and Astronomy; John Turek, professor of basic medical sciences; Eduardo Ximenes, research scientist in the Department of Agricultural and Biological Engineering; and Michael Ladisch, Distinguished Professor of Agricultural and Biological Engineering, adapted this technique from their previous study on cancer cells in a paper released this month in Communications Biology.

    2
    The team isolated living immortalized cells in multi-well plates to study them with Doppler. Credit: Rebecca McElhoe/Purdue University.

    Using funding from the National Science Foundation as well as Purdue’s Discovery Park Big Idea Challenge, the team worked with immortalized cell lines — cells that will live forever unless you kill them. They exposed the cells to different known pathogens, in this case salmonella and E. coli. They then used the Doppler effect to spy out how the cells reacted. These living cells are called “sentinels” and observing their reactions is called a biodynamic assay.

    “First we did biodynamic imaging applied to cancer, and now we’re applying it to other kinds cells,” Nolte said. “This research is unique. No one else is doing anything like it. That’s why it’s so intriguing.”

    This strategy is broadly applicable when scientists have isolated an unknown microbe and want to know if it is pathogenic — harmful to living tissues — or not. Such cells may show up in food supply, water sources or even in recently melted glaciers.

    “This directly measures whether a cell is pathogenic,” Ladisch said. “If the cells are not pathogenic, the Doppler signal doesn’t change. If they are, the Doppler signal changes quite significantly. Then you can use other methods to identify what the pathogen is. This is a quick way to tell friend from foe.”

    Being able to quickly discern whether a cell is harmful is incredibly helpful in situations where people encounter a living unknown microorganism, allowing scientists to know what precautions to take. Once it is known that a microbe is harmful, they can begin established protocols that allow them to determine the specific identity of the cell and determine an effective antibiotic against the microorganism.

    Another benefit is the ability to quickly and directly diagnose which bacteria respond to which antibiotics. Antibiotic resistance can be a devastating problem in hospitals and other environments where individuals with already compromised bodies and immune systems may be exposed to and infected by increasingly high amounts of antibiotic resistant bacteria. Sometimes this results in a potentially fatal condition called bacterial sepsis or septicemia. This is different from the viral sepsis that has been discussed in connection with COVID-19, though the scientists say their next steps will include investigating viral sepsis.

    Treating sepsis is challenging. Giving the patient broad-spectrum antibiotics, which sounds like a good idea, might not help and could make the situation worse for the next patient. Letting bacteria come into close contact with antibiotics that do not kill them only makes them more resistant to that antibiotic and more difficult to fight next time.

    Culturing the patient’s tissues and homing in on the correct antibiotic to use can take time the patient does not have, usually eight to 10 hours. This new biodynamic process allows scientists to put the patient’s bacterial samples in an array of tiny petri dishes containing the tissue sentinels and treat each sample with a different antibiotic. Using Doppler, they can quickly notice which bacterial samples have dramatic metabolic changes. The samples that do are the ones that have reacted to the antibiotic — the bacteria are dying, being defeated and beaten back by antibiotics.

    “When we treat with antibiotics, the bacteria don’t have to multiply much before they start to affect the tissue sentinels,” Nolte explained. “There are still too few bacteria to see or to measure directly, but they start to affect how the tissues behaves, which we can detect with Doppler.”

    In less than half the time a traditional culture and diagnosis takes, doctors could tell which antibiotic to administer, bolstering the patient’s chances for recovery. The researchers worked closely with the Purdue Research Foundation Office of Technology Commercialization to patent and license their technologies. They plan to further explore whether this method would work for tissue samples exposed to nonliving pathogenic cells or dried spores, and to test for and treat viral sepsis.

    See the full article here .

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    Please help promote STEM in your local schools.

    Stem Education Coalition

    Purdue University(US) is a public land-grant research university in West Lafayette, Indiana, and the flagship campus of the Purdue University system. The university was founded in 1869 after Lafayette businessman John Purdue donated land and money to establish a college of science, technology, and agriculture in his name. The first classes were held on September 16, 1874, with six instructors and 39 students.

    The main campus in West Lafayette offers more than 200 majors for undergraduates, over 69 masters and doctoral programs, and professional degrees in pharmacy and veterinary medicine. In addition, Purdue has 18 intercollegiate sports teams and more than 900 student organizations. Purdue is a member of the Big Ten Conference and enrolls the second largest student body of any university in Indiana, as well as the fourth largest foreign student population of any university in the United States.

    Purdue University is a member of the Association of American Universities and is classified among “R1: Doctoral Universities – Very high research activity”. Purdue has 25 American astronauts as alumni and as of April 2019, the university has been associated with 13 Nobel Prizes.

    In 1865, the Indiana General Assembly voted to take advantage of the Morrill Land-Grant Colleges Act of 1862 and began plans to establish an institution with a focus on agriculture and engineering. Communities throughout the state offered facilities and funding in bids for the location of the new college. Popular proposals included the addition of an agriculture department at Indiana State University, at what is now Butler University(US). By 1869, Tippecanoe County’s offer included $150,000 (equivalent to $2.9 million in 2019) from Lafayette business leader and philanthropist John Purdue; $50,000 from the county; and 100 acres (0.4 km^2) of land from local residents.

    On May 6, 1869, the General Assembly established the institution in Tippecanoe County as Purdue University, in the name of the principal benefactor. Classes began at Purdue on September 16, 1874, with six instructors and 39 students. Professor John S. Hougham was Purdue’s first faculty member and served as acting president between the administrations of presidents Shortridge and White. A campus of five buildings was completed by the end of 1874. In 1875, Sarah A. Oren, the State Librarian of Indiana, was appointed Professor of Botany.

    Purdue issued its first degree, a Bachelor of Science in chemistry, in 1875, and admitted its first female students that autumn.

    Emerson E. White, the university’s president, from 1876 to 1883, followed a strict interpretation of the Morrill Act. Rather than emulate the classical universities, White believed Purdue should be an “industrial college” and devote its resources toward providing a broad, liberal education with an emphasis on science, technology, and agriculture. He intended not only to prepare students for industrial work, but also to prepare them to be good citizens and family members.

    Part of White’s plan to distinguish Purdue from classical universities included a controversial attempt to ban fraternities, which was ultimately overturned by the Indiana Supreme Court, leading to White’s resignation. The next president, James H. Smart, is remembered for his call in 1894 to rebuild the original Heavilon Hall “one brick higher” after it had been destroyed by a fire.

    By the end of the nineteenth century, the university was organized into schools of agriculture, engineering (mechanical, civil, and electrical), and pharmacy; former U.S. President Benjamin Harrison served on the board of trustees. Purdue’s engineering laboratories included testing facilities for a locomotive, and for a Corliss steam engine—one of the most efficient engines of the time. The School of Agriculture shared its research with farmers throughout the state, with its cooperative extension services, and would undergo a period of growth over the following two decades. Programs in education and home economics were soon established, as well as a short-lived school of medicine. By 1925, Purdue had the largest undergraduate engineering enrollment in the country, a status it would keep for half a century.

    President Edward C. Elliott oversaw a campus building program between the world wars. Inventor, alumnus, and trustee David E. Ross coordinated several fundraisers, donated lands to the university, and was instrumental in establishing the Purdue Research Foundation. Ross’s gifts and fundraisers supported such projects as Ross–Ade Stadium, the Memorial Union, a civil engineering surveying camp, and Purdue University Airport. Purdue Airport was the country’s first university-owned airport and the site of the country’s first college-credit flight training courses.

    Amelia Earhart joined the Purdue faculty in 1935 as a consultant for these flight courses and as a counselor on women’s careers. In 1937, the Purdue Research Foundation provided the funds for the Lockheed Electra 10-E Earhart flew on her attempted round-the-world flight.

    Every school and department at the university was involved in some type of military research or training during World War II. During a project on radar receivers, Purdue physicists discovered properties of germanium that led to the making of the first transistor. The Army and the Navy conducted training programs at Purdue and more than 17,500 students, staff, and alumni served in the armed forces. Purdue set up about a hundred centers throughout Indiana to train skilled workers for defense industries. As veterans returned to the university under the G.I. Bill, first-year classes were taught at some of these sites to alleviate the demand for campus space. Four of these sites are now degree-granting regional campuses of the Purdue University system. On-campus housing became racially desegregated in 1947, following pressure from Purdue President Frederick L. Hovde and Indiana Governor Ralph F. Gates.

    After the war, Hovde worked to expand the academic opportunities at the university. A decade-long construction program emphasized science and research. In the late 1950s and early 1960s the university established programs in veterinary medicine, industrial management, and nursing, as well as the first computer science department in the United States. Undergraduate humanities courses were strengthened, although Hovde only reluctantly approved of graduate-level study in these areas. Purdue awarded its first Bachelor of Arts degrees in 1960. The programs in liberal arts and education, formerly administered by the School of Science, were soon split into an independent school.

    The official seal of Purdue was officially inaugurated during the university’s centennial in 1969.

    1

    Consisting of elements from emblems that had been used unofficially for 73 years, the current seal depicts a griffin, symbolizing strength, and a three-part shield, representing education, research, and service.

    In recent years, Purdue’s leaders have continued to support high-tech research and international programs. In 1987, U.S. President Ronald Reagan visited the West Lafayette campus to give a speech about the influence of technological progress on job creation.

    In the 1990s, the university added more opportunities to study abroad and expanded its course offerings in world languages and cultures. The first buildings of the Discovery Park interdisciplinary research center were dedicated in 2004.

    Purdue launched a Global Policy Research Institute in 2010 to explore the potential impact of technical knowledge on public policy decisions.

    On April 27, 2017, Purdue University announced plans to acquire for-profit college Kaplan University and convert it to a public university in the state of Indiana, subject to multiple levels of approval. That school now operates as Purdue University Global, and aims to serve adult learners.

    Campuses

    Purdue’s campus is situated in the small city of West Lafayette, near the western bank of the Wabash River, across which sits the larger city of Lafayette. State Street, which is concurrent with State Road 26, divides the northern and southern portions of campus. Academic buildings are mostly concentrated on the eastern and southern parts of campus, with residence halls and intramural fields to the west, and athletic facilities to the north. The Greater Lafayette Public Transportation Corporation (CityBus) operates eight campus loop bus routes on which students, faculty, and staff can ride free of charge with Purdue Identification.

    Organization and administration

    The university president, appointed by the board of trustees, is the chief administrative officer of the university. The office of the president oversees admission and registration, student conduct and counseling, the administration and scheduling of classes and space, the administration of student athletics and organized extracurricular activities, the libraries, the appointment of the faculty and conditions of their employment, the appointment of all non-faculty employees and the conditions of employment, the general organization of the university, and the planning and administration of the university budget.

    The Board of Trustees directly appoints other major officers of the university including a provost who serves as the chief academic officer for the university, several vice presidents with oversight over specific university operations, and the regional campus chancellors.

    Academic divisions

    Purdue is organized into thirteen major academic divisions.

    College of Agriculture

    The university’s College of Agriculture supports the university’s agricultural, food, life, and natural resource science programs. The college also supports the university’s charge as a land-grant university to support agriculture throughout the state; its agricultural extension program plays a key role in this.

    College of Education

    The College of Education offers undergraduate degrees in elementary education, social studies education, and special education, and graduate degrees in these and many other specialty areas of education. It has two departments: (a) Curriculum and Instruction and (b) Educational Studies.

    College of Engineering

    The Purdue University College of Engineering was established in 1874 with programs in Civil and Mechanical Engineering. The college now offers B.S., M.S., and Ph.D. degrees in more than a dozen disciplines. Purdue’s engineering program has also educated 24 of America’s astronauts, including Neil Armstrong and Eugene Cernan who were the first and last astronauts to have walked on the Moon, respectively. Many of Purdue’s engineering disciplines are recognized as top-ten programs in the U.S. The college as a whole is currently ranked 7th in the U.S. of all doctorate-granting engineering schools by U.S. News & World Report.

    Exploratory Studies

    The university’s Exploratory Studies program supports undergraduate students who enter the university without having a declared major. It was founded as a pilot program in 1995 and made a permanent program in 1999.

    College of Health and Human Sciences

    The College of Health and Human Sciences was established in 2010 and is the newest college. It offers B.S., M.S. and Ph.D. degrees in all 10 of its academic units.

    College of Liberal Arts

    Purdue’s College of Liberal Arts contains the arts, social sciences and humanities programs at the university. Liberal arts courses have been taught at Purdue since its founding in 1874. The School of Science, Education, and Humanities was formed in 1953. In 1963, the School of Humanities, Social Sciences, and Education was established, although Bachelor of Arts degrees had begun to be conferred as early as 1959. In 1989, the School of Liberal Arts was created to encompass Purdue’s arts, humanities, and social sciences programs, while education programs were split off into the newly formed School of Education. The School of Liberal Arts was renamed the College of Liberal Arts in 2005.

    Krannert School of Management

    The Krannert School of Management offers management courses and programs at the undergraduate, master’s, and doctoral levels.

    College of Pharmacy

    The university’s College of Pharmacy was established in 1884 and is the 3rd oldest state-funded school of pharmacy in the United States. The school offers two undergraduate programs leading to the B.S. in Pharmaceutical Sciences (BSPS) and the Doctor of Pharmacy (Pharm.D.) professional degree. Graduate programs leading to M.S. and Ph.D. degrees are offered in three departments (Industrial and Physical Pharmacy, Medicinal Chemistry and Molecular Pharmacology, and Pharmacy Practice). Additionally, the school offers several non-degree certificate programs and post-graduate continuing education activities.

    Purdue Polytechnic Institute

    The Purdue Polytechnic Institute offers bachelor’s, master’s and Ph.D. degrees in a wide range of technology-related disciplines. With over 30,000 living alumni, it is one of the largest technology schools in the United States.

    College of Science

    The university’s College of Science houses the university’s science departments: Biological Sciences; Chemistry; Computer Science; Earth, Atmospheric, & Planetary Sciences; Mathematics; Physics & Astronomy; and Statistics. The science courses offered by the college account for about one-fourth of Purdue’s one million student credit hours.

    College of Veterinary Medicine

    The College of Veterinary Medicine is accredited by the AVMA to offer the Doctor of Veterinary Medicine degree, associate’s and bachelor’s degrees in veterinary technology, master’s and Ph.D. degrees, and residency programs leading to specialty board certification. Within the state of Indiana, the Purdue University College of Veterinary Medicine is the only veterinary school, while the Indiana University School of Medicine is one of only two medical schools (the other being Marian University College of Osteopathic Medicine). The two schools frequently collaborate on medical research projects.

    Honors College

    Purdue’s Honors College supports an honors program for undergraduate students at the university.

    The Graduate School

    The university’s Graduate School supports graduate students at the university.

    Research

    The university expended $622.814 million in support of research system-wide in 2017, using funds received from the state and federal governments, industry, foundations, and individual donors. The faculty and more than 400 research laboratories put Purdue University among the leading research institutions. Purdue University is considered by the Carnegie Classification of Institutions of Higher Education to have “very high research activity”. Purdue also was rated the nation’s fourth best place to work in academia, according to rankings released in November 2007 by The Scientist magazine. Purdue’s researchers provide insight, knowledge, assistance, and solutions in many crucial areas. These include, but are not limited to Agriculture; Business and Economy; Education; Engineering; Environment; Healthcare; Individuals, Society, Culture; Manufacturing; Science; Technology; Veterinary Medicine. The Global Trade Analysis Project (GTAP), a global research consortium focused on global economic governance challenges (trade, climate, resource use) is also coordinated by the University. Purdue University generated a record $438 million in sponsored research funding during the 2009–10 fiscal year with participation from National Science Foundation, National Aeronautics and Space Administration, and the U.S. departments of Agriculture, Defense, Energy, and Health and Human Services. Purdue University was ranked fourth in Engineering research expenditures amongst all the colleges in the United States in 2017, with a research expenditure budget of 244.8 million.

    Purdue University established the Discovery Park to bring innovation through multidisciplinary action. In all of the eleven centers of Discovery Park, ranging from entrepreneurship to energy and advanced manufacturing, research projects reflect a large economic impact and address global challenges. Purdue University’s nanotechnology research program, built around the new Birck Nanotechnology Center in Discovery Park, ranks among the best in the nation.

    The Purdue Research Park which opened in 1961 was developed by Purdue Research Foundation which is a private, nonprofit foundation created to assist Purdue. The park is focused on companies operating in the arenas of life sciences, homeland security, engineering, advanced manufacturing and information technology. It provides an interactive environment for experienced Purdue researchers and for private business and high-tech industry. It currently employs more than 3,000 people in 155 companies, including 90 technology-based firms. The Purdue Research Park was ranked first by the Association of University Research Parks in 2004.

    Purdue’s library system consists of fifteen locations throughout the campus, including an archives and special collections research center, an undergraduate library, and several subject-specific libraries. More than three million volumes, including one million electronic books, are held at these locations. The Library houses the Amelia Earhart Collection, a collection of notes and letters belonging to Earhart and her husband George Putnam along with records related to her disappearance and subsequent search efforts. An administrative unit of Purdue University Libraries, Purdue University Press has its roots in the 1960 founding of Purdue University Studies by President Frederick Hovde on a $12,000 grant from the Purdue Research Foundation. This was the result of a committee appointed by President Hovde after the Department of English lamented the lack of publishing venues in the humanities. Since the 1990s, the range of books published by the Press has grown to reflect the work from other colleges at Purdue University especially in the areas of agriculture, health, and engineering. Purdue University Press publishes print and ebook monograph series in a range of subject areas from literary and cultural studies to the study of the human-animal bond. In 1993 Purdue University Press was admitted to membership of the Association of American University Presses. Purdue University Press publishes around 25 books a year and 20 learned journals in print, in print & online, and online-only formats in collaboration with Purdue University Libraries.

    Sustainability

    Purdue’s Sustainability Council, composed of University administrators and professors, meets monthly to discuss environmental issues and sustainability initiatives at Purdue. The University’s first LEED Certified building was an addition to the Mechanical Engineering Building, which was completed in Fall 2011. The school is also in the process of developing an arboretum on campus. In addition, a system has been set up to display live data detailing current energy production at the campus utility plant. The school holds an annual “Green Week” each fall, an effort to engage the Purdue community with issues relating to environmental sustainability.

    Rankings

    In its 2021 edition, U.S. News & World Report ranked Purdue University the 5th most innovative national university, tied for the 17th best public university in the United States, tied for 53rd overall, and 114th best globally. U.S. News & World Report also rated Purdue tied for 36th in “Best Undergraduate Teaching, 83rd in “Best Value Schools”, tied for 284th in “Top Performers on Social Mobility”, and the undergraduate engineering program tied for 9th at schools whose highest degree is a doctorate.

     
  • richardmitnick 7:39 am on September 14, 2017 Permalink | Reply
    Tags: , Crustacean diseases, Histopathology, , Pathogens, Shrimp studies, , Zoology   

    From U Arizona: “Global Shrimp Industry Depends on UA” 

    U Arizona bloc

    University of Arizona

    Sept. 11, 2017
    Susan McGinley
    UA College of Agriculture and Life Sciences

    1
    Shrimp at the wet lab (live animal) facility at the West Campus Agricultural Center (Photo: Bob Demers/UANews)

    The Aquaculture Pathology Laboratory tests shrimp samples, identifies diseases and certifies disease-free stock to help the nearly $40 billion farmed shrimp industry provide a safe food supply.

    A world-renowned laboratory in Tucson has a quiet presence at the University of Arizona, but within the global farmed shrimp and aquaculture industry it exerts a tremendous influence.

    The Aquaculture Pathology Laboratory, housed within the College of Agriculture and Life Sciences’ School of Animal and Comparative Biomedical Sciences, works with commercial shrimp farming enterprises, research institutions and nongovernmental organizations, or NGOs, from across the world to diagnose infectious diseases of penaeid shrimp and other crustaceans in samples delivered to the UA, certify pathogen-free stock, test feed ingredients, conduct research and train shrimp disease specialists.

    _________________________________________________________________________

    Extra Info

    Facts About the Shrimp Industry

    About 75 percent of world shrimp production is Penaeus vannamei (Pacific white shrimp or king prawn).
    Total world shrimp production in 2014 was approximately 4 million metric tons.
    The shrimp industry has a projected annual growth rate of 4.2 percent.
    The top shrimp producers worldwide are China, India, Thailand, Vietnam, Indonesia and Ecuador.
    EMS (early mortality syndrome) disease was detected for the first time in the U.S. in Texas in July, with the research work carried out in the Aquaculture Pathology Laboratory at the UA: http://www.oie.int/wahis_2/public/wahid.php/Reviewreport/Review?page_refer=MapFullEventReport&reportid=24597.

    _________________________________________________________________________

    Clients pay for these services, which in turn help them maintain the biosecurity of their products and ultimately the health and profitability of their industry. For example, baby and adult stocker shrimp can’t be sold to large shrimp operations around the world — in the U.S., Mexico, South America, the Middle East and Asia — unless they are certified. The laboratory conducts certification testing and validation.

    The laboratory can do this because it is a reference laboratory, the only one in North America, certified for crustacean diseases by the Office International des Epizooties in Paris. It is also an approved laboratory of the U.S. Department of Agriculture Animal and Plant Health Inspection Service.

    “This lab has done a wonderful job of addressing the needs of the shrimp industry in terms of disease diagnosis and disease prevention worldwide,” said Arun K. Dhar, associate professor of shrimp and other crustacean aquaculture and director of the lab since January. He succeeded longtime professor and founding director Donald V. Lightner, who developed and guided the lab for more than 30 years as it became a facility recognized around the world.

    “We identify the pathogen, we get the specifics,” Dhar said. “When a disease emerges, we jump on it to determine the etiology (cause), the methods to detect it and the tools to prevent the spread of the disease. Then we tell that story to various audiences.”

    Wet Lab and Diagnostics Lab

    The UA laboratory includes a wet lab (live animal) facility at the West Campus Agricultural Center and a diagnostics lab of histology (tissue diagnostics) and molecular detection on the main campus.

    A staff of three in the center maintains tanks of specific pathogen-free (SPF) or specific pathogen-resistant quarantined stocks at the wet lab for companies and agencies, and they evaluate live shrimp samples from across the world to detect (or rule out) diseases so virulent that they can’t be tested anywhere near coastal waters. The risk of contamination to commercial shrimp beds would be too great.

    “Because of this, our lab is in the desert. We deal with the worst of the worst in emerging pathogens,” said senior research specialist Brenda Noble, who dips her boots in water when entering and exiting the quarantined areas. “Acute hepatopancreatic necrosis disease, also called EMS — early mortality syndrome — is big now, killing a lot of animals on farms in Asia and Latin America. EMS is bacterial and kills up to 100 percent in a day at the lab, although not on farms, where it is spread out.”

    White spot disease, or WSD, is another highly contagious and lethal viral disease. Shrimp diseases do not infect humans.

    The staff conducts challenge studies on animals (mainly crustaceans) brought in from all over the world to find family lines that are resistant to disease, and also product challenges on SPF animals to find out if ingredients in those products — probiotics, for example — enhance their survival. Two shrimp species form the bulk of the commercial farmed shrimp supply: Penaeus vannamei, Pacific white shrimp or king prawn, and Penaeus monodon, giant tiger prawn or Asian tiger shrimp.

    At the dry lab on campus, a team of seven tests tissue samples sent from the wet lab and from national and international companies and agencies. Most are from Hawaii, Florida and Latin America. Clients specify the tests they want: viral, bacterial, fungus, prokaryote or protozoa.

    In the histology lab, a team of two works on diagnosis via histopathology. Each sample is dissected into pieces, put into a cassette, processed overnight and embedded in wax blocks that cool and harden. The blocks are cut into thin sections, put on racks, cooked in a tissue oven to affix them and then stained. Each section is put into a slide folder to be read and diagnosed.

    These tests are conducted for regular surveillance of a company’s stock, or as a general health check on shrimp to make sure the shrimp population is safe.

    “Our department consists of different labs, but we are a team of lab technicians, scientists and specialists who help diagnose diseases and send results to clients in an ongoing relationship,” research specialist Jasmine Millabas said.

    In the PCR lab, extracts of shrimp feed are run in PCR (polymerase chain reaction) machines to note any presence of disease. Each report includes a picture of the PCR result as a proof of testing.

    “We have run samples from 461 clinical cases so far this year in this lab,” postdoctoral research associate Siddhartha Kanrar said.

    Shrimp Pathology Short Course

    Along with diagnostics, treatment and biosecurity, faculty and staff in the Aquaculture Pathology Laboratory teach an intensive one-week shrimp pathology short course plus several workshops annually, in Tucson and in various countries. The class is for professionals who conduct testing for companies and institutions dealing mainly with farm-raised shrimp.

    Dhar recently taught classes at the Bangladesh Fisheries Research Institute in Bangladesh and at Yangon University in Myanmar. He said shrimp is dubbed “white gold” in Bangladesh because it is the country’s third-largest export in revenue.

    In addition to methods for detecting and diagnosing diseases in farmed shrimp, the hands-on course takes participants through the steps of preparing tissue samples precisely to ensure accurate results when the samples are sent to the Aquaculture Pathology Laboratory. The participants learn about what to look for in cells in diseased animals and how to follow the proper procedures to get the detection correct. The West Campus experimental lab has inoculum for all Office International des Epizooties pathogens, kept in freezer at minus 80 degrees Celsius (minus 112 Fahrenheit) from diseased shrimp to use for testing the real thing in class.

    Nearly every shrimp pathologist in the world has taken the course. In July, the class included 19 participants from nine countries on four continents, mainly from commercial aquaculture businesses.

    While students prepared slides, senior research specialist Luis Fernando Aranguren Caro pointed out areas of slides projected on a screen that showed diseases or abnormalities, noting that “the degree of infection depends on the extent of the disease revealed.” Jessica Fox, director of veterinary services and biosecurity for Tru-Shrimp, a freshwater shrimp production facility in Minnesota, brought three employees to the UA who will prepare the histology samples that are sent to Arizona.

    “We wanted to learn more about the shrimp diseases to help us understand what to watch for, what screening measures we need to do and to help us develop other biosecurity protocols,” Fox said. “Our whole group understands more together. There’s quite a bit of hands-on here. We know what to look for and have done this before in-house, but it’s good to have experts checking your work.”

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    U Arizona campus

    The University of Arizona (UA) is a place without limits-where teaching, research, service and innovation merge to improve lives in Arizona and beyond. We aren’t afraid to ask big questions, and find even better answers.

    In 1885, establishing Arizona’s first university in the middle of the Sonoran Desert was a bold move. But our founders were fearless, and we have never lost that spirit. To this day, we’re revolutionizing the fields of space sciences, optics, biosciences, medicine, arts and humanities, business, technology transfer and many others. Since it was founded, the UA has grown to cover more than 380 acres in central Tucson, a rich breeding ground for discovery.

    Where else in the world can you find an astronomical observatory mirror lab under a football stadium? An entire ecosystem under a glass dome? Visit our campus, just once, and you’ll quickly understand why the UA is a university unlike any other.

     
  • richardmitnick 10:25 am on June 8, 2017 Permalink | Reply
    Tags: , Garry Buchko, , Pathogens, , , Tackling infectious disease — one protein at a time   

    From PNNL: “Tackling infectious disease — one protein at a time” 

    PNNL BLOC
    PNNL Lab

    June 08, 2017
    Tom Rickey
    tom.rickey@pnnl.gov
    (509) 375-3732

    1
    The structure of a protein named thioredoxin. Garry Buchko and colleagues used NMR to solve the structure of the protein, which is found in an infection often conveyed by ticks. Credit: SSGCID

    2
    A protein in the pathogen that causes cryptosporidiosis. The microbe can cause mild to severe diarrhea in people who accidentally swallow a mouthful of contaminated water. Credit: SSGCID

    3
    Buchko and colleagues solved this structure of a protein found in the organism that causes malaria. Credit: SSGCID

    4
    A protein in the microbe that causes melioidosis, which occurs most often in people who live in tropical climates. Infection often starts in the lungs when contaminated dust or soil is inhaled. Credit: SSGCID

    5
    A protein in the micro-organism that causes giardiasis, which translates to nausea, abdominal pain, fatigue and other symptoms in hundreds of millions of people worldwide each year. Credit: SSGCID

    Garry Buchko and his colleagues are at the front line battling some of the most fearsome enemies that humanity has ever known: Tuberculosis. Pneumonia. Ebola. Plague. Botulism.

    But he is not in a hospital or field tent, taking vital signs or administering medications. Instead, Buchko the biochemist is in the laboratory, where the front line is the world of proteins — the molecular workhorses that keep all organisms functioning properly and make life possible. Using some of the highest-tech approaches available, he works with scientists in the Pacific Northwest to uncover crucial information needed to develop better treatments or vaccines against a host of nasty agents that can cause body aches, nausea, fatigue, food poisoning, diarrhea, ulcers, difficulty breathing, and death.

    Buchko does such work as part of the Seattle Structural Genomics Center for Infectious Disease, one of two centers funded by the National Institute of Allergy and Infectious Diseases tasked with solving the structure of proteins that enable pathogens to live, thrive, and infect people. Scientists from four institutions partner in the effort: The Center for Infectious Disease Research, Beryllium Discovery Corp., the University of Washington, and the Department of Energy’s Pacific Northwest National Laboratory, where Buchko does his research.

    This week the team reached a milestone, announcing that its scientists have solved the 3-D structure of the 1,000th protein from more than 70 organisms that cause infectious disease in people. The proteins the team has studied come from microbes that cause several serious diseases, including tuberculosis, Listeria, Giardia, Ebola, anthrax, Clostridium difficile (C. diff) infection, Legionella, Lyme, chlamydia and the flu.

    While the proteins isolated for study are not pathogenic, the structural information provides scientists the opportunity to design molecules that will knock out an essential process in such microbes.

    It is challenging work. Protein shapes are very complex — many look a lot like convoluted roller coasters with multiple twists, turns, and loops, all squeezed into a tiny space just one ten-thousandth the width of a human hair. The arrangement and lengths of these features give each protein its specific biochemical properties — what other molecules they will interact with and precisely what they will do in the body. Knowing the precise shape of proteins provides a blueprint for scientists searching for new ways to disable the pathogens and stop the diseases they can cause.

    Buchko’s expertise is with nuclear magnetic resonance or NMR, which is very similar to the magnetic resonance imaging technique widely used by physicians to diagnose all manner of medical conditions. Buchko scrutinizes proteins from pathogens drawing upon the NMR technology at EMSL, the Environmental Molecular Sciences Laboratory, a DOE Office of Science user facility at PNNL.

    While the end result is an atomic-level picture, it’s not as simple as snapping a photograph. Instead, Buchko places the protein inside an NMR spectrometer and records information about the orientation, energy and other properties of all the atomic nuclei in the molecule. Then he interprets the information and feeds the thousands of pieces of data into a computer program to calculate the position of every atom, resulting in a complete 3-D reconstruction of the protein. Data analysis is crucial to getting the structures correct.

    Buchko has been an author on more than 20 of the team’s studies in the last 10 years. Among his targets are pathogens that cause tuberculosis, malaria, cat scratch fever, and hemorrhagic fevers, as well as water-based parasites that cause severe diarrhea and abdominal pain.

    SSGCID scientists have published more than 100 manuscripts detailing their findings. In addition, all the structures are immediately shared with the scientific community through a public database called the Protein Data Bank. As a result, the structures have been used in nearly 600 scientific papers from other laboratories in academia, research institutes, and pharmaceutical companies around the world that are working on human pathogens. Sharing its findings so that scientists worldwide can make further discoveries is at the heart of SSGCID’s mission.

    The Seattle-based center is one of two centers funded by NIAID (contract # HHSN272201200025C). The other, based in Chicago, is the Center for Structural Genomics of Infectious Diseases and includes another DOE laboratory, Argonne National Laboratory, among its participants. The SSGCID is led by Peter Myler, professor and director of core services at the Center for Infectious Disease Research.

    “When the SSGCID solves protein structures, it lays the foundation for researchers at CID Research and around the world to find new drugs, therapies and vaccine candidates for diseases that kill thousands each year,” said Myler. “I’m very proud of the hard work carried out by our team and our dedicated partners.”

    EMSL, the Environmental Molecular Sciences Laboratory, is a DOE Office of Science User Facility. Located at Pacific Northwest National Laboratory in Richland, Wash., EMSL offers an open, collaborative environment for scientific discovery to researchers around the world. Its integrated computational and experimental resources enable researchers to realize important scientific insights and create new technologies. Follow EMSL on Facebook, LinkedIn and Twitter.

    Full information about the structures the team has solved is available on the SSGCID web site.

    See the full article here .

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    Pacific Northwest National Laboratory (PNNL) is one of the United States Department of Energy National Laboratories, managed by the Department of Energy’s Office of Science. The main campus of the laboratory is in Richland, Washington.

    PNNL scientists conduct basic and applied research and development to strengthen U.S. scientific foundations for fundamental research and innovation; prevent and counter acts of terrorism through applied research in information analysis, cyber security, and the nonproliferation of weapons of mass destruction; increase the U.S. energy capacity and reduce dependence on imported oil; and reduce the effects of human activity on the environment. PNNL has been operated by Battelle Memorial Institute since 1965.

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  • richardmitnick 7:51 am on August 1, 2016 Permalink | Reply
    Tags: , , Open-source drug-discovery, Pathogens   

    From U Washington: “Malaria, cancer drug prospects emerge from open-source test” 

    U Washington

    University of Washington

    07.28.2016
    Bobbi Nodell

    1
    Mosquito netting protects a woman and child. Options for malaria prevention and treatment have narrowed as the disease has grown resistant to known compounds. Bill & Melinda Gates Foundation

    In what is being called the first-ever test of open-source drug-discovery, researchers from around the world have successfully identified compounds to pursue in treating and preventing parasite-borne illnesses such as malaria as well as cancer.

    Starting in late 2011, the Medicines for Malaria Venture, based in Geneva, Switzerland, distributed 400 diverse compounds with antimalarial activity free of charge to 200 labs in 30 countries. One-third of the labs reported their results in a paper published today in PLOS Pathogens, Open source drug discovery with the Malaria Box compound collection for neglected diseases and beyond.

    The results have ignited more a dozen drug-development projects for a variety of diseases.

    2
    The box of 400 active drug-like molecules was distributed at no cost to researchers around the world. Medicines for Malaria Venture

    “The trial was successful not only in identifying compounds to pursue for anti-malarials, but it also identified compounds to treat other parasites and cancer,“ said lead author Wesley Van Voorhis. To help lead the project, Van Voorhis took a sabbatical from his roles as a University of Washington professor of medicine (allergy and infectious diseases) and director of the Center for Emerging and Re-emerging Infectious Diseases.

    The National Cancer Institute is now working on a colon cancer drug that emerged from the testing, Van Voorhis said. Several European labs are working on anti-worm compounds, and numerous U.S. labs are investigating drugs to combat other parasites. Medicines for Malaria Venture is also working with pharmaceutical companies GSK and Novartis on related anti-malarials, he added.

    In their paper, researchers cited the lack of interaction between academia and industry as a major curb to innovation in drug discovery.

    “Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open-source drug discovery, with sharing of information, is clearly a first step towards overcoming that gap,” they wrote.

    The Malaria Box distributed 400 diverse druglike molecules that were most often found in industry collections, helping to bridge the gap between industry and academia.

    This open-access effort was so successful that Medicines for Malaria Venture has begun to distribute another set of compounds with broader potential applicability, called the Pathogen Box. The box is available now to scientific labs globally.

    See the full article here .

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    The University of Washington is one of the world’s preeminent public universities. Our impact on individuals, on our region, and on the world is profound — whether we are launching young people into a boundless future or confronting the grand challenges of our time through undaunted research and scholarship. Ranked number 10 in the world in Shanghai Jiao Tong University rankings and educating more than 54,000 students annually, our students and faculty work together to turn ideas into impact and in the process transform lives and our world. For more about our impact on the world, every day.

    So what defines us — the students, faculty and community members at the University of Washington? Above all, it’s our belief in possibility and our unshakable optimism. It’s a connection to others, both near and far. It’s a hunger that pushes us to tackle challenges and pursue progress. It’s the conviction that together we can create a world of good. Join us on the journey.

     
  • richardmitnick 10:41 am on September 11, 2015 Permalink | Reply
    Tags: , , Pathogens   

    From Broad: “Single-cell analysis helps sort out host-pathogen interactions” 

    Broad Institute

    Broad Institute

    September 10th, 2015
    Veronica Meade-Kelly

    1
    Broad researchers have brought cutting-edge single-cell analytical approaches to bear on the host-pathogen interactions between immune
    cells and bacteria to better understand variability in infection outcomes. Image by Lauren Solomon from source material provided by the Hung lab

    What: When bacteria invade the human body, immune cells rush to our defense, initiating a high-stakes tug-of-war in which macrophages – a type of immune cell that engulfs and digests pathogens and cellular debris – attempt to destroy the invaders while the bacteria look to survive and replicate. The outcomes of these cellular death matches vary from cell to cell: some macrophages engulf bacteria while others remain uninfected, and of those infected, some destroy their invaders while others allow bacteria to thrive.

    Researchers have been able to observe these diverse outcomes for decades, but there hasn’t been a way to look at what is happening at the molecular level to yield such varied results. Instead, interactions between immune cells and bacteria have traditionally been measured across populations of cells, revealing average cell behavior while potentially masking cell-to-cell variation that may be important for understanding the process of infection.

    In a proof-of-concept study published in the September 10 issue of Cell, Broad researchers have brought cutting-edge single-cell analytical approaches to bear on the host-pathogen interactions between immune cells and bacteria to better understand this variability in infection outcomes. The team first infected macrophages with Salmonella, bacteria that have been extensively studied in host-pathogen interaction models. By tagging the Salmonella with fluorescent dyes that allowed them to see whether or not the bacteria survived, the researchers were able to distinguish individual cells based on the outcome (or “infection phenotype”) of the host-pathogen encounter. The team then went on to use an approach called flow cytometry to sort the cells based on infection phenotype and then look at gene expression in each of the sorted cells using a method called single cell RNA-seq (sequencing).

    It turns out, the team found, that Salmonella populations are not homogeneous, They found that in some of the invading Salmonella, a two-component system senses the intracellular environment of the macrophage and can alter the consistency of a substance called lipopolysaccharides (LPS) on the cell wall. This results in subpopulations of Salmonella that have different cell wall structures, triggering different immune responses from the macrophages. This diversity within the Salmonella population may serve to modulate and manipulate the host immune response, helping the pathogen to establish infection.

    Why: “Previously, the variation in infection outcomes was largely ignored because there was no way to look deeply enough into what happens when bacteria and immune cells encounter each other,” explained Roi Avraham, a postdoctoral researcher at the Broad Institute and co-first author of the study. “This paper shows that single-cell approaches can be used successfully to tackle this decades-old problem.”

    Understanding the cellular mechanisms that are influencing host-pathogen interactions and therefore driving bacterial infections could lead to new approaches to treatment.

    Who: Avraham and co-first author Nathan Haseley are postdoctoral and graduate students, respectively, in the lab of Broad core member Deborah Hung, who led the study. Hung is the co-director of the Broad’s Infectious Disease Program. The single-cell analysis methods their team employed were devised in conjunction with the lab of Broad core member Aviv Regev.

    Other researchers who contributed to the work include Douglas Brown, Cristina Penaranda, Humberto Jijon, John Trombetta, Rahul Satija, Alex Shalek, and Ramnik Xavier – who are all affiliated with the Broad Institute.

    Where to find it: Avraham, R., Haseley, N. et al. “Pathogen cell-to-cell variability drives heterogeneity in host immune responses” Cell. Online September 3, 2015. DOI: 10.1016/j.cell.2015.08.027

    See the full article here .

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    The Eli and Edythe L. Broad Institute of Harvard and MIT is founded on two core beliefs:

    This generation has a historic opportunity and responsibility to transform medicine by using systematic approaches in the biological sciences to dramatically accelerate the understanding and treatment of disease.
    To fulfill this mission, we need new kinds of research institutions, with a deeply collaborative spirit across disciplines and organizations, and having the capacity to tackle ambitious challenges.

    The Broad Institute is essentially an “experiment” in a new way of doing science, empowering this generation of researchers to:

    Act nimbly. Encouraging creativity often means moving quickly, and taking risks on new approaches and structures that often defy conventional wisdom.
    Work boldly. Meeting the biomedical challenges of this generation requires the capacity to mount projects at any scale — from a single individual to teams of hundreds of scientists.
    Share openly. Seizing scientific opportunities requires creating methods, tools and massive data sets — and making them available to the entire scientific community to rapidly accelerate biomedical advancement.
    Reach globally. Biomedicine should address the medical challenges of the entire world, not just advanced economies, and include scientists in developing countries as equal partners whose knowledge and experience are critical to driving progress.

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  • richardmitnick 5:16 pm on November 19, 2014 Permalink | Reply
    Tags: , , , Pathogens,   

    From Princeton: “Unique sense of ‘touch’ gives a prolific bacterium its ability to infect anything” 

    Princeton University
    Princeton University

    November 19, 2014
    Morgan Kelly, Office of Communications

    New research has found that one of the world’s most prolific bacteria manages to afflict humans, animals and even plants by way of a mechanism not before seen in any infectious microorganism — a sense of touch. This unique ability helps make the bacteria Pseudomonas aeruginosa ubiquitous, but it also might leave these antibiotic-resistant organisms vulnerable to a new form of treatment.

    Pseudomonas is the first pathogen found to initiate infection after merely attaching to the surface of a host, Princeton University and Dartmouth College researchers report in the journal the Proceedings of the National Academy of Sciences. This mechanism means that the bacteria, unlike most pathogens, do not rely on a chemical signal specific to any one host, and just have to make contact with any organism that’s ripe for infection.

    The researchers found, however, that the bacteria could not infect another organism when a protein on their surface known as PilY1 was disabled. This suggests a possible treatment that, instead of attempting to kill the pathogen, targets the bacteria’s own mechanisms for infection.

    b
    A study led by Princeton University researchers found that one of the world’s most prolific bacteria, Pseudomonas aeruginosa, manages to afflict humans, animals and even plants by way of a mechanism not before seen in any infectious microorganism — a sense of touch. This technique means the bacteria, unlike most pathogens, do not rely on a chemical signal specific to any one host. To demonstrate the bacteria’s versatility, the researchers infected ivy cells (blue rings) with the bacteria (green areas) then introduced amoebas (yellow) to the same sample. Pseudomonas immediately detected and quickly overwhelmed the amoebas. (Image by Albert Siryaporn, Department of Molecular Biology)

    Corresponding author Zemer Gitai, a Princeton associate professor of molecular biology, explained that the majority of bacteria, viruses and other disease-causing agents depend on “taste,” as in they respond to chemical signals unique to the hosts with which they typically co-evolved. Pseudomonas, however, through their sense of touch, are able to thrive on humans, plants, animals, numerous human-made surfaces, and in water and soil. They can cause potentially fatal organ infections in humans, and are the culprit in many hospital-acquired illnesses such as sepsis. The bacteria are largely unfazed by antibiotics.

    “Pseudomonas’ ability to infect anything was known before. What was not known was how it’s able to detect so many types of hosts,” Gitai said. “That’s the key piece of this research — by using this sense of touch, as opposed to taste, Pseudomonas can equally identify any kind of suitable host and initiate infection in an attempt to kill it.”

    The researchers found that only two conditions must be satisfied for Pseudomonas to launch an infection: Surface attachment and “quorum sensing,” a common bacterial mechanism wherein the organisms can detect that a large concentration of their kind is present. The researchers focused on the surface-attachment cue because it truly sets Pseudomonas apart, said Gitai, who worked with first author Albert Siryaporn, a postdoctoral researcher in Gitai’s group; George O’Toole, a professor of microbiology and immunology at Dartmouth; and Sherry Kuchma, a senior scientist in O’Toole’s laboratory.

    To demonstrate the bacteria’s wide-ranging lethality, Siryaporn infected ivy cells with the bacteria then introduced amoebas to the same sample; Pseudomonas immediately detected and quickly overwhelmed the single-celled animals. “The bacteria don’t know what kind of host it’s sitting on,” Siryaporn said. “All they know is that they’re on something, so they’re on the offensive. It doesn’t draw a distinction between one host or another.”

    When Siryaporn deleted the protein PilY1 from the bacteria’s surface, however, the bacteria lost their ability to infect and thus kill the test host, an amoeba. “We believe that this protein is the sensor of surfaces,” Siryaporn said. “When we deleted the protein, the bacteria were still on a surface, but they didn’t know they were on a surface, so they never initiated virulence.”

    Because PilY1 is on a Pseudomonas bacterium’s surface and required for virulence, it presents a comprehensive and easily accessible target for developing drugs to treat Pseudomonas infection, Gitai said. Many drugs are developed to target components in a pathogen’s more protected interior, he said.

    The video [included], captured during a span of 113 minutes, shows that Pseudomonas (gray tubes) grow exponentially — doubling their numbers roughly every 30 minutes — and establish large populations of cells over the course of a few hours. In contrast, eukaryotic organisms such as the amoeba (large organisms) grow much more slowly and can be quickly overwhelmed by a bacterial population. The bacteria’s ability to rapidly multiply in a variety hosts makes a Pseudomonas infection difficult to treat using antibiotics. (Video by Albert Siryaporn, Department of Molecular Biology)

    KC Huang, a Stanford University associate professor of bioengineering, said that the research is an important demonstration of an emerging approach to treating pathogens — by disabling rather than killing them.

    “This work indicates that the PilY1 sensor is a sort of lynchpin for the entire virulence response, opening the door to therapeutic designs that specifically disrupt the mechanical cues for activating virulence,” said Huang, who is familiar with the research but had no role in it.

    “This is a key example of what I think will become the paradigm in antivirals and antimicrobials in the future — that trying to kill the microbes is not necessarily the best strategy for dealing with an infection,” Huang said. “[The researchers’] discovery of the molecular factor that detects the mechanical cues is critical for designing such compounds.”

    Targeting proteins such as PilY1 offers an avenue for combating the growing problem of antibiotic resistance among bacteria, Gitai said. Disabling the protein in Pseudomonas did not hinder the bacteria’s ability to multiply, only to infect.

    Antibiotic resistance results when a drug kills all of its target organisms, but leaves behind bacteria that developed a resistance to the drug. These mutants, previously in the minority, multiply at an astounding rate — doubling their numbers roughly every 30 minutes — and become the dominant strain of pathogen, Gitai said. If bacteria had their ability to infect disabled, but were not killed, the mutant organisms would be unlikely to take over, he said.

    “I’m very optimistic that we can use drugs that target PilY1 to inhibit the whole virulence process instead of killing off bacteria piecemeal,” Gitai said. “This could be a whole new strategy. Really what people should be doing is screening drugs that inhibit virulence but preserve growth. This protein presents a possible route by which to do that.”

    PilY1 also is found in other bacteria with a range of hosts, Gitai said, including Neisseria gonorrhoeae or the large bacteria genus Burkholderia, which, respectively, cause gonorrhea in humans and are, along with Pseudomonas, a leading cause of lung infection in people with cystic fibrosis. It is possible that PilY1 has a similar role in detecting surfaces and initiating infection for these other bacteria, and thus could be a treatment target.

    Frederick Ausubel, a professor of genetics at Harvard Medical School, said that the research could help explain how opportunistic pathogens are able to infect multiple types of hosts. Recent research has revealed a lot about how bacteria initiate an infection, particularly via quorum sensing and chemical signals, but the question about how that’s done across a spectrum of unrelated hosts has remained unanswered, said Ausubel, who is familiar with the research but had no role in it.

    “A broad host-range pathogen such as Pseudomonas cannot rely solely on chemical cues to alert it to the presence of a suitable host,” Ausubel said.

    “It makes sense that Pseudomonas would use surface attachment as one of the major inputs to activating virulence, especially if attachment to surfaces in general rather than to a particular surface is the signal,” he said. “There is probably an advantage to activating virulence only when attached to a host cell, and it is certainly possible that other broad host-range opportunistic pathogens utilize a similar strategy.”

    The paper, Surface attachment induces Pseudomonas aeruginosa virulence, was published online Nov. 10 by the Proceedings of the National Academy of Sciences. The work was supported by a National Institutes of Health Director’s New Innovator Award (grant no. 1DP2OD004389); the National Science Foundation (grant no. 1330288); an NIH National Institute of Allergy and Infectious Diseases postdoctoral fellowship (no. F32AI095002) and grant (no. R37-AI83256-06); and the Human Frontiers in Science Program.

    See the full article, with video, here.

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    About Princeton: Overview

    Princeton University is a vibrant community of scholarship and learning that stands in the nation’s service and in the service of all nations. Chartered in 1746, Princeton is the fourth-oldest college in the United States. Princeton is an independent, coeducational, nondenominational institution that provides undergraduate and graduate instruction in the humanities, social sciences, natural sciences and engineering.

    As a world-renowned research university, Princeton seeks to achieve the highest levels of distinction in the discovery and transmission of knowledge and understanding. At the same time, Princeton is distinctive among research universities in its commitment to undergraduate teaching.

    Today, more than 1,100 faculty members instruct approximately 5,200 undergraduate students and 2,600 graduate students. The University’s generous financial aid program ensures that talented students from all economic backgrounds can afford a Princeton education.

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  • richardmitnick 3:06 pm on August 28, 2014 Permalink | Reply
    Tags: , , , Pathogens   

    From The New York Times: “Parasites Practicing Mind Control” 

    New York Times

    The New York Times

    AUG. 28, 2014
    Carl Zimmer

    An unassuming single-celled organism called Toxoplasma gondii is one of the most successful parasites on Earth, infecting an estimated 11 percent of Americans and perhaps half of all people worldwide. It’s just as prevalent in many other species of mammals and birds. In a recent study in Ohio, scientists found the parasite in three-quarters of the white-tailed deer they studied.

    One reason for Toxoplasma’s success is its ability to manipulate its hosts. The parasite can influence their behavior, so much so that hosts can put themselves at risk of death. Scientists first discovered this strange mind control in the 1990s, but it’s been hard to figure out how they manage it. Now a new study suggests that Toxoplasma can turn its host’s genes on and off — and it’s possible other parasites use this strategy, too.

    image
    A microscopic cyst in the brain of a mouse containing thousands of Toxoplasma gondii parasites. New research has found that the parasite is able to exert a form of mind control by turning its host’s genes on and off. Credit Jitender P. Dubey/U.S.D.A.

    Toxoplasma manipulates its hosts to complete its life cycle. Although it can infect any mammal or bird, it can reproduce only inside of a cat. The parasites produce cysts that get passed out of the cat with its feces; once in the soil, the cysts infect new hosts.

    Toxoplasma returns to cats via their prey. But a host like a rat has evolved to avoid cats as much as possible, taking evasive action from the very moment it smells feline odor.

    Experiments on rats and mice have shown that Toxoplasma alters their response to cat smells. Many infected rodents lose their natural fear of the scent. Some even seem to be attracted to it.

    Manipulating the behavior of a host is a fairly common strategy among parasites, but it’s hard to fathom how they manage it. A rat’s response to cat odor, for example, emerges from complex networks of neurons that detect an odor, figure out its source and decide on the right response in a given moment.

    Within each of the neurons in those networks, thousands of genes are producing proteins and other molecules essential for relaying all of the necessary information throughout the body. Simple Toxoplasma seems ill-equipped to take over such a complicated system.

    But a new study published in the journal Molecular Ecology hints that the parasite can do so by relying on an eerily elegant strategy. Think of the genes in a host as keys on a piano. Toxoplasma, it seems, simply plays some of the keys differently to produce a new melody.

    A rat is made up of lots of different kinds of cells, from the neurons in its brain to the bone-producing cells in its skeleton to the insulin-making cells in its pancreas. Yet all of them carry the same 20,000 genes. Depending on the function of a particular cell, some of its genes are switched on and others are shut down.

    Genes may be switched off, or silenced, by the attachment of molecular caps called methyl groups, a process called methylation. In order to switch a gene on again, the caps are removed.

    Methylation does more than just allow cells to develop into a variety of organs. It lets them change the way they work in response to signals from the outside. In the brain, for example, neurons rely on this process to lay down long-term memories and change how an animal responds to its environment.

    Ajai Vyas, a neurobiologist at Nanyang Technological University in Singapore, wondered if Toxoplasma might wreak changes on rats by changing methylation in the rat brain — an idea “just hiding in plain sight,” he said.

    In earlier research, Dr. Vyas and his colleagues had found that infected rats produced extra amounts of a neurotransmitter called arginine vasopressin. The neurotransmitter is manufactured by a small set of neurons buried in a structure of the brain called the medial amygdala.

    Perhaps, Dr. Vyas thought, the parasite switched on the gene for arginine vasopressin in those cells. To find out, he and his colleagues ran a series of tests.

    First they looked at the gene for arginine vasopressin in the medial amygdala of rats. In infected rats, they found, many of the molecular caps were missing, suggesting that Toxoplasma had “unsilenced” the gene in order to increase production of the neurotransmitter. The arginine vasopressin then might alter their response to cats.

    If that were true, Dr. Vyas reasoned, then counteracting the parasite’s strategy should change the rat’s behavior.

    He and his colleagues injected an extra supply of the molecular caps into infected rats. Some of the caps attached to the arginine vasopressin gene, and the rats became more fearful of the odor of cats.

    That experiment led Dr. Vyas to see if he could make the rats behave as if they were being controlled by parasites — but without the parasites.

    He and his colleagues removed molecular caps from the arginine vasopressin gene, mimicking what Toxoplasma might be doing to its hosts. The rats became reckless, feeling no fear at the whiff of cats.

    “The animals looked like they were infected, even though there was no parasite around,” said Dr. Vyas.

    “I think they could be on to something interesting,” said Michael Eisen, a biologist at the University of California, Berkeley, who has researched Toxoplasma in mice and was not involved in the new study. But he thought more experiments would have to be done to make a compelling case that the parasites really are using methylation to control their hosts.

    Kami Kim of Albert Einstein College of Medicine, who also was not involved in the study, was more enthusiastic about the research. She also suggested that the strategy may be not be uncommon. In a review published this spring in the American Journal of Pathology, Dr. Kim and her colleagues survey a number of species that may use methylation to turn host genes on and off.

    The bacteria that cause leprosy, for example, invade certain kinds of neurons and change some of their molecular caps. This methylation causes the neurons to change into stem cells much like those in an embryo. In this new state, the infected cells leave the nervous system and migrate through the body, spreading the bacteria with them.

    “It looks like it will be a general strategy used by pathogens,” said Dr. Kim.

    See the full article here.

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  • richardmitnick 6:28 pm on August 13, 2014 Permalink | Reply
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    From Stanford via NPR: “Biologists Choose Sides In Safety Debate Over Lab-Made Pathogens” 

    NPR

    National Public Radio (NPR)

    August 13, 2014
    Nell Greenfieldboyce

    A smoldering debate about whether researchers should ever deliberately create superflu strains and other risky germs in the interest of science has flared once again.
    Some scientists think new types of bird flus should arise only in chickens, not in labs.

    bird
    Here a worker collects poultry on a farm in Kathmandu, Nepal, where the H5N1 virus was infecting animals in October 2011.

    Proponents of the work say that in order to protect the public from the next naturally occurring pandemic, they have to understand what risky infectious agents are capable of — and that means altering the microbes in experiments. Critics argue that the knowledge gained from making new strains of these germs isn’t worth the risk, because a lab-made pathogen might escape the laboratory and start spreading among people.

    Now, as scientists on both sides of the dispute have formed groups that have issued manifestos and amassed lists of supporters, it looks like the prestigious will step in to weigh the risks and benefits.

    “ I don’t think we have adequately involved the public so that they understand the possible consequences of mistakes, or errors, or misadventures in performing this kind of science.

    A representative of the National Institutes of Health, which funds this research, says that NIH, too, is “giving deep consideration to the many views expressed by various highly respected parties” about the best way forward.

    In a recent editorial in “mBio,” the journal’s editor-in-chief, Arturo Casadevall, M.D., Ph.D. , urged his colleagues to “lower the level of rhetoric and focus on the scientific questions at hand.”

    Scientists have passionate debates all the time, but it’s usually about the meaning of some experimental result, says Casadevall, a microbiologist at the Albert Einstein College of Medicine in New York.

    “What is different here is that we are facing a set of intangibles,” he says. “And because they involve judgment calls at this point, people are often weighing the risks and the benefits very differently.”

    Dr. David Rellman, a microbiologist at Stanford University, thinks the risks of making a new strain of flu virus that has the potential to cause a pandemic are very real.

    “I don’t think we have adequately involved the public,” Relman says, “so that they understand the possible consequences of mistakes, or errors, or misadventures in performing this kind of science — the kinds of consequences that would result in many, many people becoming ill or dying.”

    “ These viruses are out there. They cause disease; they have killed many, many people in the past. We bring them to the laboratory to work with them.

    • Paul Duprex, Boston University microbiologist

    Controversial work on lab-altered bird flu was halted for more than a year in a , voluntary moratorium after two labs generated new, more contagious forms of the bird flu virus H5N1. Eventually, after federal officials promised more oversight, the experiments started back up and the controversy quieted down. But key questions were never answered, Relman says.

    “One of the big issues that has not been advanced over the last two years is a discussion about whether there are experiments that ought not to be undertaken and, if so, what they look like,” he says, noting that scientists keep publishing more studies that involve genetically altered flu viruses. “You know, every time that one of these experiments comes up, it just ups the ante a bit. It creates additional levels of risk that force the question: Do we accept all of this?”

    Last month, Relman met in Massachusetts with others who are worried. They formed the Cambridge Working Group and issued a statement saying that researchers should curtail any experiments that would lead to new pathogens with pandemic potential, until there’s a better assessment of the dangers and benefits.

    By coincidence, they released their official statement just as the public started hearing news reports of various , such as a forgotten vial of smallpox found in an old freezer, and mishaps involving anthrax and bird flu at the Centers for Disease Control and Prevention.

    What’s more, the unprecedented Ebola outbreak has reminded the public what it looks like when a deadly virus .

    All of this led a different band of scientists to also form a group — to publicly defend research on dangerous pathogens.

    “There are multiple events that have come together in a rather unusual convergence,” says Paul Duprexa microbiologist at Boston University.

    He sees the recent reports of lab mistakes as exceptions — they don’t mean you should shut down basic science that’s essential to protecting public health, he says.

    “These viruses are out there. They cause disease; they have killed many, many people in the past,” Duprex says. “We bring them to the laboratory to work with them.”

    Duprex helped form a group that calls itself Scientists for Science. The group’s position statement emphasizes that studies on already are subject to extensive regulations. It says focusing on lab safety is the best defense — not limiting the types of experiments that can be done.

    Whenever questions about safety are raised, Duprex says, scientists have one of two options. They can keep their heads down, do their experiments and hope it will all go away. Or, he says, they can proactively engage the public and provide an informed opinion.

    His group has taken the latter approach, “because ultimately we’re the people working with these things.”

    Each of these two groups of scientists now has a website, and each website features its own list of more than a hundred supporters, including Nobel Prize winners and other scientific superstars.

    One thing that almost everyone seems to agree on is that, to move forward, there needs to be some sort of independent, respected forum for discussing the key issues.

    The American Society for Microbiology has called on the prestigious National Academy of Sciences to take the lead. A representative of the Academy says NAS does plan to hold a symposium, later this year. The details are still being worked out.

    Tim Donohue, a microbiologist at the University of Wisconsin, Madison who is president of ASM, says a similar kind of debate happened back in the mid-1970s, when brand-new technologies for manipulating DNA forced scientists and the public to tackle thorny questions.

    “And I think that is a productive exercise,” Donohue says, “to have scientists and the public, sitting around the table, making sure each one understands what the benefits and risks are, and putting in place policies that allow these types of experiments to go on so that they are safe and so that society can benefit from the knowledge and innovation that comes out of that work.”

    See the full article, with links, here.

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