text:
August 2016 - Vol. 11, No. 8
Top Stories
NIH grant supports vaccine research
Dr. Weiping Zhang developing safeguard against ETEC-associated diarrhea
Dr. Weiping Zhang, professor of microbiology in the Department of Diagnostic Medicine/Pahobiology, has been awarded a $2.1 million National Institutes of Health R01 grant for the next five years. The grant will support the development of a vaccine to guard against E. coli-associated diarrhea. NIH has awarded two additional grants to Dr. Zhang in the last three years to develop vaccines against E. coli diarrhea.
Read more ...
Dr. Weiping Zhang (center) credits his team for the success in acquiring grants to support his research on E. coli-related vaccines. From left: Carolina Garcia, grad student; Jiachen Huan, grad student; Dr. Zhang; Dr. Qiangde Duan, postdoc; and Ti Lu, grad student. Not pictured are postdocs Drs. Rahul Nandre, Xiaosai Ruan and Mei Liu.
"Diarrhea continues to be a leading cause of death in children under five years of age, and enterotoxigenic E. coli (ETEC) is the most common bacterial cause of children's diarrhea," Dr. Zhang said. "Currently, there are no available vaccines against ETEC-associated diarrhea. Whole-cell vaccine candidates have been under development, but require further improvements because they provide inadequate protection and produce unwanted adverse effects."
"Effective vaccines for ETEC have proved to be very challenging," said Dr. Frank Blecha, associate dean for research in the veterinary college. "Dr. Zhang's vaccine development strategy for ETEC using multiepitope fusion antigens holds great promise for a vaccine that will limit diarrheal deaths in humans and animals."
Dr. Zhang was trained as a molecular evolutionary biologist and his E. coli pathogenesis and vaccine research and development career began in 2003 when he studied molecular pathogenesis of individual enterotoxins produced by ETEC in diarrheal disease using gnotobiotic or germ-free piglets. By challenging gnotobiotic piglets with isogenic E. coli strains that express heat-labile or heat-stable toxins and analyzing clinical outcomes, he developed a gnotobiotic pig challenge model for ETEC diarrheal disease research and vaccine development.
"Our work has focused most recently on multiepitope fusion antigens (MEFA) for the development of broadly protective ETEC vaccines," Dr. Zhang said. "Different ETEC strains produce immunologically heterogeneous bacterial adhesins to attach host cells and colonize in small intestines, initiating ETEC diarrheal disease. With the inclusion of another adhesin multiepitope fusion antigen, then a subunit vaccine is potentially able to induce antibodies against both toxins and up to 15 prevalent ETEC adhesins, thus effectively protecting against ETEC diarrhea. This grant will allow us to continue our research and study the effectiveness of this approach."
"Grants are critical for providing the resources needed for advancing research and promoting good science," said Dr. M.M. Chengappa, university distinguished professor and head of diagnostic medicine/pathobiology. "The work being conducted by Dr. Zhang has significance for both human and animal health. This grant also recognizes the quality of Dr. Zhang's work, which we truly value in our department and college."
Dr. Zhang said his MEFA technology has attracted attention from funding agencies including Bill and Melinda Gates Foundation, and was featured in a recent Vaccines against Shigella and ETEC (VASE) meeting at Washington D.C. Dr. Zhang's laboratory currently is also working on ETEC vaccine projects funded by PATH Vaccine Solution/Bill and Melinda Gates Foundation.
Research project puts striped skunk rabies on the map
While striped skunks already have a nose-worthy reputation for being avoided, new research at the CVM emphasizes a serious health hazard these skunks pose to animals and humans: rabies.
Read more ...
Researchers in the Kansas State Veterinary Diagnostic Laboratory recently evaluated the spatial and spatio-temporal patterns of infection status among striped skunk cases submitted for rabies testing in the North Central Plains of the United States, including potential eco-climatological drivers of such patterns.
"These animals represent one of the most important terrestrial reservoirs of rabies virus in North America and yet the prevalence of rabies among this host is only passively monitored, and the disease remains largely unmanaged," said Dr. Susan Moore, director of the Rabies Laboratory. "Vaccination campaigns have not efficiently targeted striped skunks. There are occasional spillovers of striped skunk viruses to other animals, including some pets that are routinely recorded in our lab."
Dr. Ram Raghavan, a spatial epidemiologist at the diagnostic laboratory worked closely with the Rabies Laboratory on this project.
"Our findings indicate the year-to-year and spatial origins of rabies occurrences in Kansas and Nebraska are currently stable," Dr. Raghavan said. "Certain physical environment and climatic factors play an important role in determining such temporal and spatial patterns. For example, there is a relatively higher risk of rabies transmission from striped skunks to humans who reside in developed low-intensity areas and highly fragmented landscapes, such as edges of woodlands and agricultural lands than in other places."
The study, "Bayesian Spatiotemporal Pattern and Eco-Climatological Drivers of Striped Skunk Rabies in the North Central Plains," has recently been published in PLOS Neglected Tropical Diseases. The study suggests that daytime temperature range, a climate change indicator that is decreasing at a slow but steady rate, may increase the general risk striped skunks contracting rabies.
Dr. Doug Goodin, professor in the Department of Geography, contributed toward the use of remote-sensing data to help establish some of the explanatory framework for the project.
"We are trying to understand how important the spatial aspects are in regard to infectious diseases and the applications of microclimatology," Dr. Goodin said. "You can't understand the distributions without understanding where things are placed. It seems to be pretty clear that climate will affect the distribution of this disease. The big questions are about which aspects of climate change are going to affect particular disease types. The package of climate variables related to mammals are going to be different than those variables involving diseases spread by insects or athropods."
"Human-related landscape changes and climate change both appear likely to exacerbate the prevalence of rabies in striped skunks," Dr. Moore said. "But, further studies are necessary to more fully understand the dynamics of skunk rabies and its impact upon the prevention of rabies among humans and other animals. The important thing is we now have better tools to help try to eradicate rabies in the future."
CEEZAD receives $2.3 million grant for vaccine research
The Center of Excellence for Emerging Zoonotic and Animal Diseases (CEEZAD) at Kansas State University has recently received a $2.3 million grant from the Defense Threat Reduction Agency (DTRA) to conduct research on the safety in livestock of a newly developed vaccine to protect humans against infection with the Ebola Zaire virus. DTRA is an agency within the US Department of Defense.
Read more ...
The Center of Excellence for Emerging Zoonotic and Animal Diseases (CEEZAD) at Kansas State University has recently received a $2.3 million grant from the Defense Threat Reduction Agency (DTRA) to conduct research on the safety in livestock of a newly developed vaccine to protect humans against infection with the Ebola Zaire virus. DTRA is an agency within the US Department of Defense.
The grant, from DTRA in a collaboration with the commercial firm NewLink Genetics, includes a $100,000 matching contribution from the state of Kansas' NBAF Transition Funds. Kansas State University researchers will study the safety of the vaccine in swine, cattle, and horses in Kansas State University's Biosecurity Research Institute.
The vaccine is called "VSV-ZEBOV." The VSV portion is an acronym for Vesicular Stomatitis Virus. ZEBOV is the acronym for the Zaire strain of Ebola virus, the deadliest strain of Ebola virus that causes Ebola disease in humans. The vaccine uses the VSV virus to carry a small, harmless piece of the Ebola virus that immunizes a vaccinated person. The Ebola virus is thought to be transmitted to people from an as-yet unidentified wild animal reservoir, and then spreads in the human population through human-to-human transmission. The average disease case fatality rate is around 50 percent, but has varied from 25 percent to 90 percent in various outbreaks.
Dr. Juergen A. Richt, the Regents Distinguished Professor, will be the principal investigator for the project. The live, recombinant vaccine consists of an attenuated Indiana strain of VSV, wherein the surface glycoprotein component of VSV has been replaced with the Ebola virus glycoprotein component in order to induce protective immunity against the Ebola Zaire virus.
"We are very excited to begin research to test the safety of this vaccine, the only efficacious Ebola virus vaccine yet, for safety in livestock at Kansas State University,"said Dr. Richt in announcing receipt of the award. "As the world saw with the deadly 2014 outbreak in West Africa, Ebola is one of the most serious emerging zoonotic threats to humans."
Dr. Richt took particular note of "the generous contribution" of $100,000 from the NBAF Transition Funds toward the study.
Zoonotic diseases are those capable of being transmitted from animals to humans and vice-versa. It is thought that Ebola virus, which was first identified in 1976, is introduced into the human population through close contact with infected animals such as chimpanzees, gorillas, bats, monkeys, and maybe antelope and porcupines. It is also possible that the Ebola virus can be transmitted through sexual contact involving already-infected persons. The Zaire species of Ebola virus is one of five species that have been identified, and has been associated with large disease outbreaks in Africa – including the 2014 West African outbreak which infected an estimated 28,600 people and resulted in more than 11,000 deaths.
At Kansas State University, researchers will test the safety of the vaccine in swine, cattle and horses, while it needs to be noted that no infectious Ebola virus will be used during these studies. The work will provide information to supplement the overall safety of the VSV-ZEBOV vaccine.
CEEZAD is a US Department of Homeland Security Center of Excellence established in 2010 at the Kansas State University College of Veterinary Medicine.
CVM labs study amphibians as possible zoonotic disease hosts
Three different laboratories at Kansas State University hopped on board for a unique study that looks at the potential role of amphibians as a vector for the spread of infectious diseases. The project was led by Dr. Yongming Sang, research associate professor of anatomy and physiology in the College of Veterinary Medicine.
Read more ...
"Amphibians have a previously unknown complexity within their antimicrobial interferon system, which is highly and differentially responsive to influenza infections," Dr. Sang explained."This suggests the need to study the possible role of wild amphibians as overlooked reservoirs/end hosts for influenza and other zoonotic pathogenic infections. This study highlights the unique position of the amphibian interferon system in interferon evolution and its potential role in prevention of cross-species viral transmission to humans."
Dr. Sang collaborated with Dr. Frank Blecha, associate dean for research in the College of Veterinary Medicine, Dr. Wenjun Ma, associate professor of diagnostic medicine/pathobiology, and Dr. Scott McVey, Research Leader for the USDA's Arthropod Borne Animal Disease Research Unit, whose respective research laboratories were used to help conduct the basic research. Dr. Peying Fong, associate professor of anatomy and physiology, contributed tissue samples from frogs that were used in the study.
"Reptiles and amphibians are considered as potential vectors/hosts harboring Influenza A viruses (IAV) and other zoonotic pathogens, but their role in zoonoses has received little attention," Dr. Sang said. "To examine this potential epidemiological link, we tested the susceptibility of frog cells to different subtypes of IAVs isolated from several animal species, including avian H9N2, equine H3N8, human H1N1 and swine H1N2 and H3N2 viruses. Compared with the IAV strains isolated from chickens and horses, the pig isolates showed higher infectivity in frog cells, indicating a closer relationship between amphibians and pigs in IAV exchange before the virus jumping to humans."
The results of the study have been published in Nature's Scientific Reports, "Expansion of amphibian intronless interferons revises the paradigm for interferon evolution and functional diversity." (http://www.nature.com/articles/srep29072)
"We learned that amphibians as typical insect eaters could also be critical vectors for other arthropod-borne viruses and intracellular bacteria, which are a major health threats in both humans and animals," Dr. Sang said. "The coordinated regulation of protective responses mediated by IFN signaling in both vector animals and end hosts may provide an integrated approach to discern critical components of conserved, cross-species innate immune mechanisms. Future studies may in turn provide means to control vectored and/or zoonotic infections.
More Headlines
Dr. Philine Wangemann reunites with former postdocs on speaking trip in Korea
While convening with colleagues and peers is a primary objective of scientific conferences and meetings, sometimes one gets an opportunity to reunite with former trainees at such meetings. A recent speaking trip overseas for Kansas State University's Dr. Philine Wangemann turned into a reunion with several former postdoctoral trainees who now live and work in Korea where the biennial meeting of the Barany Society was held.
Click here to read more ...
Dr. Wangemann is a university distinguished professor in the anatomy and physiology department in the College of Veterinary Medicine, who has been at Kansas State University since 1998. She is frequently collaborating with Dr. Daniel C. Marcus, who is also a university distinguished professor. Together they have mentored many postdoctoral fellows who have trained in their laboratories and are now successful professional colleagues.
The individuals that Dr. Wangemann met in Korea included: Dr. Hyoung-Mi Kim, now assistant professor, who was a postdoctoral fellow with Dr. Wangemann from 2008 to 2011; Dr. Sung Huhn Kim, now associate professor, who was a postdoctoral fellow with Dr. Marcus from 2007 to 2009; and Dr. Jun Ho Lee, now full professor, who was a postdoctoral fellow with Dr. Marcus from 2000 to 2002. The three are affiliated with the leading Korean Universities Yonsei and Seoul National.
"It was so much fun to get together for an alumni dinner" said Dr. Wangemann. "To see our former postdocs as successful physician scientists fills me with a lot of pride."
Dr. Wangemann is an internationally recognized expert in the field of inner ear physiology. Her research in mouse models targets pathological mechanisms leading to deafness and loss of balance in individuals carrying mutations of the gene SLC26A4.
"There is a growing interest in mouse models in auditory physiology, and it is very important to contribute to the knowledge base of one of the most frequent forms of hereditary hearing loss in children" Dr. Wangemann said.
She also said her summer of 2016 was busy speaking at conferences. In May, she was invited to speak at the Molecular Biology of Hearing and Deafness meeting in Hinxton, Cambridge, United Kingdom. In June she was invited to speak at the Barany Society meeting and at a symposium in the medical school at Yonsei University in Seoul, Korea, and in July, she was invited to speak at the Auditory System Gordon Research Conference at Bates College in Lewiston, Maine.
Dr. Wangemann announced that in August Dr. Sung Huhn Kim will be returning to Kansas State University for one year to work with her and Dr. Marcus.
Dr. Roman Ganta visits academic institutes in China for CEVBD
Dr. Roman Ganta, professor of diagnostic medicine and pathobiology and director of the Center of Excellence for Vector-Borne Diseases in the College of Veterinary Medicine, was invited to visit three academic institutes June 24-July 1 in China: the Yangzhou University College of Veterinary Medicine, the Shandong University School of Public Health, and the Beijing Institute of Microbiology and Epidemiology. Dr. Ganta lectured at the universities and also discussed research collaborations.
Click here to read more ...
Yangzhou University and the Beijing Institute of Microbiology and Epidemiology expressed strong interest to work on projects of mutual interest, particularly to work on vector-borne diseases currently pursued at the center, Dr. Ganta said. Shandong University would like to send its scientists to be trained through research projects at the center.
Dr. Ganta will follow up in developing strategic collaborations with all three institutes in China.
Top left: Dr. Ganta meets with Prof. Chengming Wang, School of Veterinary Medicine, Yangzhou University, Yangzhou; top right: Dinner with Prof. Xuejie Yu, School of Public Health, Shandong University, Jinan; bottom left: Prof Wu-Chun Cao and Dr. Na Jia, Beijing Institute of Microbiology and Epidemiology, Beijing; and bottom right, giving a talk.
'Science To Art' exhibition features Dr. Annelise Nguyen's 'Eye of the Storm'
A cancerous storm is just one of nine artistic images produced by regional scientists that are now on display in Kansas City, Missouri. "Eye of the Storm" was captured by Dr. Annelise Nguyen, a researcher in the College of Veterinary Medicine at Kansas State University, through a confocal microscope and shows where cell-to-cell communication proteins occur in human breast cancer tissue.
Read more ...
Dr. Nguyen's artwork is part of the Kansas City Area Life Sciences Institute's (KCALSI) third annual Science to Art exhibition, which features intrinsic images found in biomedical research. Such images are usually only displayed on research journal covers.
"The purpose of Science to Art is to provide a platform for scientists to display and describe their research through the visual arts," said Dr. Wayne O. Carter, CEO and president of KCALSI. "Each of the remarkable images chosen for our exhibit tells a personal research story and poetically captures the research performed by the scientists and their teams."
The images for the exhibit were submitted by scientists from Columbia, Missouri, to Manhattan, Kansas, selected by arts and science professionals. They were curated by Kemper Museum, printed by Dolphin Archival Printing, and framed by Dolphin Frames.
Dr. Nguyen, who is an associate professor in the Department of Diagnostic Medicine/Pathobiology in the College of Veterinary Medicine, has research interests focused on cancer biology and the role of gap junctions in intercellular communication.
"I am excited to participate in the movement of incorporating art in STEM, known as STEAM," Dr. Nguyen said. "I am honored to have our work in breast cancer as one of this year Science to Art image to be auctioned and benefited K-12 STEAM education. The innovation, creativity, and inspiration of my work are in part due to art and music classes in secondary education. Thus, I think it's critical to recognize the arts-based training in K-12 education."
The works in the exhibition will be available through a silent auction held at the 2016 KCALSI Annual Dinner at the Arvest Bank Theatre at the Midland on Sept. 22. All proceeds from the 2016 Science to Art auction benefit STEAM (science, technology, engineering, art and mathematics) education in the community through the following organizations: BioGenius, Prep-KC, Science Pioneers and the Kemper Museum of Contemporary Art. The displays runs at the Kemper East museum from July 15 to Sept. 12, located at 200 E. 44th Street in Kansas City, Missouri.
Dr. Susan Nelson offers prevention tips following recent rabies case in areas
With the recent diagnosis by the Kansas State University Rabies Laboratory of a rabies positive cat from Wabaunsee County, a university veterinarian recommends several steps to limit exposure of the disease to humans and animals.
Click to learn more ...
"The virus is secreted in saliva and is usually transmitted to people and animals by a bite from an infected animal," Dr. Nelson said. "Rabies also can be transmitted when saliva from a rabid animal comes in contact with an open cut on the skin or mucous membranes of the eyes, nose or mouth of a person or animal. Rare cases of rabies have been spread via corneal or organ/tissue transplants from an infected donor."
Dr. Nelson says following these eight tips can help minimize rabies exposure in pets and people:
• Dogs, cats, ferrets, horses and select livestock should be vaccinated against rabies as recommended by your veterinarian. Licensed vaccines are available for these species, as well as for cattle and sheep.
• Do not allow your pets to roam free.
• Don't keep wild animals as pets.
• Don't leave uneaten pet food outside and keep garbage cans covered to reduce the attraction of wild and stray animals.
• Never try to touch stray or wild animals. Children should never try to pet an unfamiliar animal, even if it looks friendly.
• Bat-proof your home.
• Report any wild or stray animal that is acting strangely to your local animal control.
Symptoms of rabies are variable and are caused by effects of the virus on the nervous system and brain. Dr. Nelson said these following common symptoms often occur in dogs, cats and ferrets: fearfulness, aggression, excessive drooling, difficulty swallowing, staggering and seizures. Infected horses, cattle, sheep and goats also may act depressed, have increased sensitivity to light or may self-mutilate themselves. She notes, however, that any of these symptoms can occur in any of these species.
International Programs sponsors 'Veterinarians around the world' photo competition
The CVM's office of International Programs announces the launch of the "Veterinarians around the world" photo competition. The theme for the competition is international veterinary medicine. Entries should capture efforts to improve animal health, public health or wildlife/ecosystem health; food security (sustainable production systems); food safety; capacity building; animal welfare; or biological threat reduction. Any other subjects relating to international veterinary medicine will also be considered.
Read more ...
Photograph Requirements
Kansas State Diagnostic Veterinary Laboratory now processing samples for Gold Standard Labs
The Kansas State Veterinary Diagnostic Laboratory at Kansas State University is known for providing bovine testing services to veterinarians and cattle producers nationwide, and is now the new service provider for samples previously submitted to Gold Standard Labs.
Read more ...
|As a Bovine Diagnostic Center of Excellence, the Kansas State Veterinary Diagnostic Laboratory, or KSDVL, uses the same testing platform for bovine viral diarrhea virus persistent infection as Gold Standard Labs utilized in its diagnostic testing services business. The Kansas State lab also has expertise in blood pregnancy testing and other bovine testing services.
Gold Standard Labs has shut down operations at its laboratory facilities located in Jarrell, Texas, and Bowling Green, Kentucky, and will no longer accept samples, making the Kansas State Veterinary Diagnostic Laboratory the primary service provider.
"Located in the central U.S., in the heart of cattle country, KSVDL is a logical choice to transition the diagnostic testing services provided by Gold Standard Labs," said Jeff Baxter, global senior product manager for Gold Standard Labs. "The quality of the bovine diagnostic testing services provided by KSVDL is recognized nationwide. We're excited to help KSVDL expand its footprint for bovine testing, particularly with Kansas State University College of Veterinary Medicine alumni all across the U.S."
The Kansas State Veterinary Diagnostic Laboratory is a full-service, American Association of Veterinary Laboratory Diagnosticians-accredited laboratory, offering a complete range of diagnostic services for all species. The lab's mission is to develop and deliver accurate, innovative, and timely diagnostic and consultative services to the veterinary and animal health community in Kansas and the nation.
Dr. Gary Anderson, director of the Kansas State University lab, said it is ready to provide assistance and support for former customers of Gold Standard Labs.
"We are committed to building a strong working relationship with these new clients," Dr. Anderson said. "We look forward to providing the diagnostic services required for bovine production and health that will achieve our clients' goals."
Forms for ordering testing services are available on the Kansas State Veterinary Diagnostic Laboratory website at www.ksvdl.org. For more information, contact the lab's client care at 866-512-5650 or firstname.lastname@example.com.
Regular features
Alumni Events, Development and Continuing Education
The Veterinary Medical Alumni Association presents its annual alumni recognition awards at the 78th Annual Conference for Veterinarians and the Kansas Veterinary Medical Association presents its annual awards the next day at the conference. Find out who this year's winners are below.
See news and upcoming events below ...
Dr. Linda Johnson to be honored at AVMA alumni reception
Dr. Linda Kassebaum Johnson, Denver, Colorado, has been selected by the Kansas State University College of Veterinary Medicine for its 2016 Alumni Recognition Award to be presented during the annual convention of the American Veterinary Medical Association (AVMA) in San Antonio, Texas, on August 8. The award is given to veterinarians whose careers have served as exemplary role models for future alumni in a professional and community setting.
Dr. Johnson earned a bachelor's degree in 1979, a Doctor of Veterinary Medicine (DVM) degree in 1983, and a master's degree in pathology in 1987, all from Kansas State University. She completed a postdoctoral fellowship and a Master of Public Health degree in 1990 at Johns Hopkins University in Baltimore, Maryland. She is board certified by the American College of Veterinary Pathologists in anatomic pathology and has a specialty in comparative pathology and animal models of human disease. She is currently a professor in the pathology department in the School of Medicine at the Anschutz Medical Campus of the University of Colorado.
"My happiest memories and most significant educational influences occurred at Kansas State University," Dr. Johnson said. "I'm overwhelmed and deeply humbled to receive this honor from my peers. The College of Veterinary Medicine has always attracted and graduated the most talented veterinarians in the country. I have always been indebted and proud of my KSU roots."
"Dr. Johnson has had an amazingly diverse career, having worked in England and Australia, alongside colleagues in human medicine as well as veterinary medicine," said Dr. Tammy Beckham, dean of the College of Veterinary Medicine. "We place great emphasis on international experiences, so we feel Dr. Johnson serves as a valuable role model for our students and future veterinarians. We also value her contributions to the profession as a researcher and educator, so we're very proud to recognize her with this well-deserved award."
Prior to joining the University of Colorado, Dr. Johnson was an associate professor and head of the Anatomy and Pathology Discipline at the School of Veterinary and Biomedical Sciences at James Cook University in Queensland, Australia from 2011 to 2014. She was an associate research professor of comparative pathology at the Tri-Institution's Laboratory of Comparative Pathology, Memorial Sloan-Kettering, in Manhattan, N.Y., from 2008 to 2011. Her earlier career included positions with the Yale University College of Medicine; the Veterinary Laboratories Agency of the UK government in Weybridge, England; Armed Forces Institute of Pathology, Washington, D.C.; and the Albert Einstein College of Medicine in the Bronx, N.Y.
Dr. Johnson is a member of the American College of Veterinary Pathologists, American Veterinary Medical Association, Kansas Veterinary Medical Association, and the CL Davis/SW Thompson DVM Foundation. She has served the latter as a national advisory board member. For the American College of Veterinary Pathologists, she has served on its board of governors and has been secretary and president. Dr. Johnson has co-authored over 50 peer-reviewed scientific articles and has served on the editorial board for the journals: Veterinary Pathology, Lab Animal Science, and the Journal of Toxicologic Pathology.
Dr. Johnson has three children: Kristian, Margot and Elsa.
AVMA Alumni ReceptionMonday, Aug. 8, 7-9 p.m.
Grand Hyatt San Antonio
Texas Ballroom B, Fourth Level
Dr. Linda Johnson, DVM class of 1983, will be presented with an Alumni Recognition Award. Please join us.
Central Veterinary Conference Alumni Reception
Saturday, Aug. 27
Come join us for a K-State Alumni Reception at the 2016 CVC in Kansas City! Drs. Randall and Judy Norton, DVM class of 1989, will be honored.
In Memoriam - Recently Departed Alumni
Dr. Arthur Becker, DVM 1962
Questions about Alumni or CE events?
Ashley McCowan
Dana Parker
Pet Friendly License Plate program in Kansas
The College of Veterinary Medicine has a new way to support shelter medicine in Kansas. The Pet Friendly license plate is available to Kansas residents statewide by visiting your local Kansas county treasurer's office.
See what the Pet Friendly plate looks like ...
News Ticker
More activities and accomplishments in the College of Veterinary Medicine:
Dr. Mike Apley was featured in the JAVMA journal for "Adjusting to reduced drug access, use - Swine Veterinarians face adjustments in disease management, treatment."
Dr. Robert Delong spoke at the RNA nanotechnology conference near Cambridge in the UK. RNA nanotechnology has grown into a mature field composed of several subfields covered by many disciplines such as chemistry, biochemistry, molecular biology, microbiology, biophysics, engineering, and many more.
Second-year student Avery Loyd reports that she attended a horseshoing school this summer to increase her knowledge of the horse and to help bridge the communication gap between the veterinarian and farrier.
Technology checkout available at the Veterinary Medical Library
In addition to our Canon EOS 60D and Nikon DSLR cameras, we also have three new Canon EOS 70D DSLR cameras. What makes these stand out are the professional lenses that come with them and can be used for any occasion. The 70D camera has a standard 18-135mm lens as well as a 70-300mm lens. With their 32GB SanDisk Extreme memory card, they can hold 10,000 plus photos. These cameras are perfect for family outings such as weddings and reunions, and even multiple classroom activities.
We also have four new Lenovo Thinkpad laptops and two Surface Pro 4 tablets. Each Surface Pro 4 tablet is touch screen, has Windows 10 Pro operating system, and comes with a stylus and detachable type keyboard with mouse pad. The Surface Pro 4 also can be propped up via a back panel to easily convert into a laptop from a tablet making it perfect for traveling to conferences and meetings.
To record lectures, lessons, video projects, or any other event in your life, we have added three new camcorders. The Sony FDR-AX33V camcorder has the ability to record in high-definition and up to four hours-worth of HD footage.
There are many more items that have been added to our technology equipment such as LCD projectors, projection screens, and GPSs. Items can be reserved and checked out with the use of your CVM ID badge. Please stop by the library desk to inquire about these new items, call 2-6006, or email Andi Parrish firstname.lastname@example.com.
VHC welcomes residents plus an intern too
VHC recognizes Dr. David Hodgson for mentoring
A list of quotes on the screen behind Dr. David Hodgson tell about his impact as a mentor. Dr. Bonnie Rush presented him with the VHC's resident mentoring award.
The DCS Award for Excellence in Resident Mentoring award recognizes senior faculty members who have demonstrated a commitment to the professional growth of residents. Dr. Hodgson was nominated by Dr. Morgan Murphy, Dr. M. Crumley, and Dr. C. Norkus. Below are a few quotes from the letters.
"An excellent example to me of what it means to be a professional. He is kind and always willing to lend a hand or help solve a problem."
"He is an awesome example of what it means to be an amazing mentor…"
"His influence has absolutely positively impacted the training of residents in nearly all departments. He is always available day or night without reservations to help residents or students."
"His creative mind and ability to bring any idea into a reality is inspiring."
"Dr. Hodgson is a fantastic mentor, has always been and will forever be."
Beef Cattle Institute's Beef Scholars program visit Johnson Farm
Pictured left to right: Dr. Paige Pratt, BC advisory team member; Jason Pratt, owner, Jiena Gu, BCI; Kelly Oliver, BCI; Dr. Venkatesh-Prasad RAnganath, CIS undergraduate student; Emilie Herbst, MS ag economics; Brooke Perry, BCI; Sarah Jones, undergraduate food science and industry; Ali McKiernan, Ph.D. candidate in pathobiology; and Carlee Wollard, third-year student in veterinary medicine.
The Beef Cattle Institute Summer Scholars took their first tour as part of their summer program on Friday, July 8. Paige and Jason Pratt of Johnson Farms near Dwight, Kansas hosted the group of student researchers whose projects range from food safety to mobile app development for producer decision tools.
Veterinary Technician Internship Program welcomes new interns
Second-year students extern in Texas
K-State students lay groundwork for future careers in the pet food industry
Workshop joint event facilitates opportunities for interviews while volunteering
K-State students will once again be in the spotlight at the 2nd annual edition of the Petfood Innovation Workshop and K-State Pet Food Experience. This multi-day joint event will take place on Sept. 13-15, 2016 on Kansas State University's main campus in Manhattan, Kansas. Students play a key role in the production of the event by volunteering to help with the hands-on educational activities and supplier-led demonstrations where attendees create pet food and pet treats using novel proteins and other high impact functional ingredients.
The Petfood Innovation Workshop and K-State Pet Food Experience features leading research on topics that are directly associated with pet food and also work that overlaps at the boundary of pet food, nutrition, and processing technology. There will be networking opportunities with industry professionals, faculty and staff, plus leading local regulatory and governmental officials.
A new feature of this year's event highlights the chance for pet food industry members to schedule job or internship interviews with students in the newly remodeled Career Center, located in the Berney Family Welcome Center.
Registration is now open and expected to sell out quickly, as there are a limited number of registrations offered to ensure quality of the workshop activities and seating in the research sessions. K-State Alumni are welcomed and encouraged to attend for a day or the entire event.
The Pet Food Experience is hosted by the Kansas State Pet Food Program team with the Kansas State University Institute for Commercialization, and utilizes student volunteers as well as facilities within the community. During the Pet Food Experience, attendees will have the opportunity to hear from industry experts as they present their latest research and insight on various topics. An outline of the program schedule is available here.
On Wednesday evening, guests can opt to participate in a dine-around event, as an additional opportunity to engage with industry peers at various local restaurants. The 2016 event aims to infuse attendees with the K-State college experience, while simultaneously providing valuable educational and networking opportunities.
The Kansas State University Institute for Commercialization is dedicated to the start-up and expansion of technology-based, high-growth enterprises and enabling the commercialization of university and under-utilized corporate intellectual property. The organization provides opportunity assessment; strategic partnership design; technology acquisition, management and licensing; business development; and technology transfer support activities for entrepreneurs to commercialize intellectual property emanating from basic research at Kansas State University and other intellectual property portfolios.
The Pet Food Program at Kansas State University was started in 2012 and has established degree programs, short courses, and research concerning pet food and nutrition.
Registration is now open and expected to sell out quickly, as there are a limited number of registrations offered to ensure quality of the workshop activities and seating in the research sessions. After the event, you can stick around in Manhattan to attend the FIRST HOME FOOTBALL GAME OF THE SEASON Sept. 17 at Bill Snyder Family Stadium.
New Arrivals/Recent Departures
Click here to see the New Arrivals/Recent Departures at the CVM ...
Welcome to:
Farewell to:
Lifelines is published each month by the Marketing and Communications Office at the College of Veterinary Medicine. The editor is Joe Montgomery, email@example.com.
Lifelines index
Download a printable version of Lifelines (this is condensed and has less information than above)


text:
We're helping university to redevelop Biology
Finley Structures is helping York University to redevelop its biology school with a state-of-the-art new building.
Finley's helped to complete the first phase of the new Biomedical Sciences building, which opened in December 2014.
And now the Aycliffe steel firm has been awarded a contract from Interserve Construction to fabricate 270 tonnes of steel as part of the second phase of the university's £7.5m redevelopment.
The university's striking new science block was officially opened by Government Chief Scientific Advisor Sir Mark Walport.
It contains teaching and IT laboratories for the Biomedical Science degree, a joint programme of the Biology Department and the Hull York Medical School.
The building also houses facilities for students in the new School of Natural Sciences, who started new courses in October 2015.
It represents the first phase of the redevelopment of the university's Biology department.
This entry was posted onMonday, April 18th, 2016 at 11:05 am and is filed under Latest News. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site. Both comments and pings are currently closed.

subset: commoncrawl


text:
PW 24/7 Recap: WWE, Roman Reigns and the House of Saudi – 10/26/18
Nick: We have a show for you & I was watching Monday Night Raw dude and it floored me, it absolutely floored me, you're going to want to pay attention to this show because I'm telling you what they won't tell you. Whatever media outlets won't tell you, what the WWE won't tell you and listen to this. I don't care. I don't care if I get another guest from WWE, I don't care if I get another guest in the wrestling industry. I'm going to tell you how it is right now. Dude I'm watching Monday Night Raw I've heard some pretty bad things in my time in radio, dude. Pretty damn bad things in my time in radio. I've worked for news outlets both conservative & progressive & what I heard on Monday Night Raw is right up there with the worst of what I've heard. Listen to both conservative & progressive talk radios I've worked for, I've worked in newsrooms, I've interviewed politicians & I took them toe to toe with issues I felt strongly about so I like to believe & I like to acknowledge that I know a little bit about something on how to spin a story. Dude, I like to believe in fact that I know it so when Roman Reigns came out on Monday Night Raw & announced to the world that he has leukemia I nearly threw up. It floored me, man, I was watching LeBron James in an LA Lakers Jersey blow it & the Lakers they're just terrible with or without "The King" I was watching that game when this Roman Reigns announcement this revelation came to light on Monday Night Raw & I nearly threw up. Roman Reigns announces that he has leukemia, I'm sorry, that his leukemia has come back pardon me, then he goes on & relinquishes his WWE Universal Championship.
Now listen & you fools who set there will decide to email me or whatever else on social media, save it dummies, thank you Eli. I'm not attacking Roman Reigns or the validity of his illness, this leukemia, this blood cancer, hell I hope he gets better, gets stronger, returns & whatever else in life, I'm not attacking the dude. Here's what I do have an issue with though in that revelation on Monday Night Raw he said the WWE gave him this and that & believed on him with this and that & whatever else he said in that promo & this is classic, dude. This is politics 101 man, Hollywood for the ugly people: politicians. You know how governments are in deep controversy whether it's your government or ours here in the US.
Deep controversies right, I mean so deep that it's so damn wrong & nobody knows about it that stuff that is swept under or agreed upon in backrooms where only a few people know about meanwhile we, you & I are worried about what's happening on America's Got Talent. You know what I'm talking about? We're so worried about what's happening on American Idol & Colin Kaepernick knelling for the national anthem. You know what I'm talking about? Debating whether we should take a knee, or stand or squat over a theme song. You know what I'm talking about? The stuff that happens in backrooms that we have never, ever (Thank you, Jericho) hear about. Meanwhile NAFTA in some room somewhere is getting demolished, meanwhile immigration in America is being threatened, meanwhile citizens of the US, this country, need a damn passport to go from one state to another in yourown country, oh but that's ok because Jay the Talking Dragon just reached the Finals on America's Got Talent it's ok though because that's what we're worried about. You get where I'm going now?
That anything positive happening gets so much damn attention it's so blatant to hide something backhanded. It's classic deflection dude. Oh no he didn't, yes I did. It's a classic deflection. Is anybody listening to me? We see this all the time mostly in our governments & news, but I wouldn't put it past the WWE, I wouldn't put it past Vince McMahon dude. Save your e-mails I don't want them. I've seen this too much & I believe I see it right now in the WWE and what's that saying: if it walks like a duck, quacks like a duck, it ain't no damn dog dude and the WWE using The Big Dog, Roman Reigns in my opinion to ease their public relations on this damn House of Saud deal. I'm not putting it past the WWE, I'm not putting it past Vince McMahon, not doing it and listen they can continue to monitor the situation which they're still saying even though the report is out today, Thursday that they're going on with the show.
The show must go on, right? They can continue to spot out that they're monitoring the situation, they can continue to have their stupid ass qualification matches on Raw & Smackdown for this damn event. They continue to do that all they want. They can continue to think about whether they're going or not & it still doesn't make it right. They can continue to take the 20-50 Million Dollars per show out of that 10 year deal all they want, but when you try to deflect attention to cover things up, so you and I move on to something more positive in Roman Reigns battle against leukemia, his blood cancer that's where I draw the line dude. Screw that. Roman Reigns battling leukemia & feeling sorry for this dude all of a sudden is supposed to make us forget about Saudi Arabia. Screw you. Him shooting promos in the ring & this is the most important part of the whole story, within that promo Roman Reigns on Monday Night Raw he goes on to say when he was 22 years old I didn't have a job, nobody was there for me, but the WWE. The WWE was there for me man, the WWE's a great company man. BS. Here's the company that shoots out God bless America at every one of their big shows. Here's a company that says during this re-hashed XFL from Vince McMahon stating that all the players all these damn fools are going to stand for the national anthem
Meanwhile, let's go to Saudi Arabia where women just learned how to drive, they just started driving over there meanwhile you're killing Washington Post Journalists they could care less what the hell their fans are saying in the wrestling industry. I don't buy it at all & then that quarter 3 announcement that came out today. Did you hear about this? Vince McMahon was asked & I'll get that damn audio & play it right here and listen I don't care if we get another guest from the WWE. I don't care & we've interviewed a lot. The Boobs & I have interviewed many WWE Superstars I don't care if we get another one of them because it has to be said when the WWE comes out and says we're doing this basically to better our bottom line so our money keeps flowing between the 50 Million they're getting from the House of Saud, excuse me. Are you listening to me? Is anybody listening to me? To hell with you WWE, the hell with you and I said this a lot & nobody wins here. I said this week ago, a month ago, 2 months ago whenever the hell it was there's no winning here.
There's countless companies that said screw you, Saudi Arabia, WWE says bring it on & we're supposed to be happy because Evolution is Sunday? Screw Evolution. We're supposed to be happy for Crown Jewel because of Shane McMahon, Undertaker, Shawn Michaels. Screw them all. If they're going over there, screw them all because they could care less. Get your 2 Million bucks thank you & continue to watch is that what you're telling us, is that what you're saying to us dude. They bring up, how many years has Roman Reigns been in the WWE? 6-7 years & we haven't heard a damn thing about leukemia from NXT to the main roster we haven't heard a damn thing about leukemia from Roman Reigns. How many Octobers the cancer month have gone by since Roman Reigns has been in the WWE we haven't heard one damn thing from the dude, not one word from the organization. Wouldn't that be positive, wouldn't that be telling us that hey we have one of our own battling cancer, let's celebrate how he's defeating cancer every damn October, but it didn't come up until Saudi Arabia until this debate about Saudi Arabia.
Let's ease the tension let's not have wrestling fans, WWE fans talking about Crown Jewel in Saudi Arabia let's not talk about that, lets everybody talk about leukemia & the battle of Roman Reigns and this blood cancer. BS dude. This is classic deflection, this is politics 101, this Hollywood for the ugly people, this is politics dude. Can you not see this? I'll be the only one to say it because I don't care. You can fool Dave Meltzer, you can deceive Mike Johnson, you can deceive all of them, Alvarez, you can deceive them all, not me dude. This is classic deflection I'm not buying it & I'm not saying the illness, I'm not downplaying the validity of leukemia in Roman Reigns, he may very well have it, I'm not saying he doesn't. My issue is not with that. It's the WWE using this illness to say hey stop talking about Saudi Arabia, stop talking about the House of Saud & start talking about Joe Anoai's leukemia.
Q3 finances came out for WWE & Vince McMahon was asked: "What's your thought process about continuing to go to Saudi Arabia where they just dismembered Jamal whatever the hell his last name is you try and pronounce it I'm not?" Oh, we're not going to talk about that it's a sensitive conversation & we're not going to talk about that. I'll bet because it would hurt your damn bottom line, that 20-50 Million Dollars that you get per show is going to hurt. Meanwhile, we should be focusing on the lighter things in life like Roman Reigns he's battling leukemia, let's stay positive for Roman Reigns. Hulk Hogan's going over to Saudi Arabia now, he's Mr. America right. Bullshit.
How many Octobers have we gone through since Roman Reigns has been in the WWE & not one damn word about blood cancer? 7 years, 6 years, whatever the hell it is you do the math I'm not very good. How many Octobers, how many cancer months have we been through since Joe has been in the E? How many feel-good moments did we miss out on celebrating a fighter of this blood cancer? I don't put it past this company one bit to spin, cover-up or deflect from this Saudi Arabia show Crown Jewel, November 2nd and again I'm not questioning the validity of this revelation on Monday Night Raw from Reigns they can go on all they want, but I'm not buying it too damn suspect for me. It's too damn suspect for my liking after 18 years in radio, 18 years in political talk radio, sports radio, whatever, 18 years in radio, my career & more importantly political talk radio I know how to spin a story. I can see a story being spun, I can see a story being deflected, I can see it, I've seen it. Hollywood for the ugly people that's what it is plain and simple.
NBC Sports Radio – Pro Wrestling 24/7


text:
Receive our
(Your shopping cart is empty)
Doc Savage: The Infernal Buddha [Book] #AP079
Alternative Views:
Our Price:
Usually Ships in 24 Hours
Product Code:
Doc Savage: The Infernal Buddha
Will Murray and
Lester Dent, writing as Kenneth Robeson, cover illustration by Joe DeVito
Altus Press is proud to announce the release of the third volume in its acclaimed Wild Adventures of Doc Savage series.
Set in the Fall of 1936,
The Infernal Buddha
tells the epic story of Doc Savages desperate quest to control the Buddha of Ice, a relic of unknown originand what may become the most dangerous object on Earth!
When a mummy arrives at Doc Savages New York headquarters wearing the clothes of his missing assistant, engineer Renny Renwick, Doc, Monk, and Ham rush to Singapore where they get on the trail of a swashbuckling pirate who calls himself the Scourge of the South China Sea, in whose hands a piece of the infernal Buddha has fallen. The trail leads to Pirate Island, the fate of Renny, and a mysterious box containing a terrible, unstoppable power.
But that is only the beginning of the quest into which the Man of Bronze plungesone that will take him to the upper reaches of the Yellow Sea and a series a wild ocean battles against the vicious factions fighting for control on the infernal Buddha.
Before it is all over, every human life on Earth will tremble on the brink of eternity, and Doc Savage will face his greatest test.
This may be my wildest Doc novel to date, says author Will Murray.
The Infernal Buddha
is a fantasy epic full of corsairs, criminals and other culprits. The menace is planetary. The threat, extinction. Doc Savage has a reputation for saving the world. This time he does it on the greatest scale possible. I began this book back in 1992, working from an opening situation Lester Dent started in 1935. Together, we have produced a true Doc Savage epic. And it only took about 75 years .
The Infernal Buddha
features a startling cover painted by Joe DeVito, depicting Doc Savage as the Buccaneer of Bronze! This cover was painted from a still taken in 1964 of legendary model Steve Holland, and is a variant pose shot for famed illustrator James Bamas classic cover to
The Man of Bronze.
There has never been a Doc cover like it!
322 pages, approx. 6"x9"x0.7", approx. 1.2 lb.
About the Series
Doc Savage was the most successful pulp adventure hero of his time. From 1933 to 1949, Lester Dent and other writers penned 182 original exploits of the Man of Bronze and his iron-fisted friends, writing as Kenneth Robeson.
Scientist. Surgeon. Strongman. Superman. Doc Savage was a man without equals. He operated on a global stage, fighting supercrime, discovering lost cities, stopping wars, and uplifting a troubled mankind during the depths of the Great Depression.
Now, in these difficult times, Doc returns in a new series of untold exploits conceived by his originator and brought to life by Lester Dent's natural successor, Will Murray.
The Wild Adventures of Doc Savage is no updating or reimagining of a classic character. This is the authentic Man of Bronze in his own era, taking on new challenges and conquering a new generation of foes and fans.
Doc Savage is back. For real.
Share your knowledge of this product with other customers...
Be the first to write a review
About Us
Privacy Policy
Send Us Feedback
Product Index
Category Index
Copyright ©
Built with


text:
On the last day of San Diego Comic Con 2014, the LEGO Batman 3: Beyond Gotham panel was hosted by IGN's Greg Miller and there were some surprises. TT Games' Phil Ring and Arthur Parsons was on hand as well as some of the voice actors of the video game including Troy Baker, Travis Willingham, Laura Bailey, Scott Porter, Dee Bradley Baker, and Josh Keaton. One surprise that wasn't really a surprise was that Adam West was also on the panel.
During the panel, they did a recap of the new playable characters such as Bat-Cow, Booster Gold & Skeets, Hawkman, Adam West, Arkillo, Krypto, Miss Martian, Batman of Zur-En-Arrh, Blue Beetle, and Mr. Mxyzptlk. These characters were announced at the LEGO booth during SDCC by Arthur Parsons. Something new that was shown was Superboy's outfit which is the New 52 version. The other thing that was new was the 1960's versions of the Batman charcters like Robin, Catwoman, Batgirl, Joker, Riddler, Penguin, Alfred, and the Batmobile.
Some surprises were the LEGO Batman 3 t-shirts and posters that were given away to everyone in attendance. You were given a ticket to bring to the Fulfillment Room at the Hyatt to pick up your items. The only problem was that it was kinda hot walking outside from the convention center to the hotel. The other surprise was for 3 people who asked questions at the panel. Greg Miller had 3 of the LEGO SDCC 2014 Batmobile exclusive sets for people who had the best questions. Not only did those people get the sets, it was also signed by Adam West.
Overall in my opinion, the panel was pretty cool, but it wasn't as cool as last year's panel for the LEGO Marvel Super Heroes video game because there weren't as many surprises. In this panel, we already knew that Adam West was coming but we didn't know Stan Lee was going to be showing up last year. Also the new character reveals was already done at the LEGO booth so I've already seen them before coming to the panel. Check out the pictures I took from the panel below.


text:
Taxi Fare Estimates
Taxi Fare Estimate v1.2 for Windows Phone 8 Update - NFC has now been added to Taxi Fare Estimate! This app takes the guess work out of estimating a cost of taking a taxi in a new country, new city. Don't be caught out not having an estimate of a taxi fare again for the cities covered by 'Taxi Fare Estimate'. If you have to estimate travel expenses before a trip to be sure you are covered this app is just want you need. Maybe you want to be sure the estimate a taxi driver is giving you is in the ball park. This app is useful for: * Estimating fares * Getting the name and phone numbers of taxi companies and launching a call * Building an adhoc fare calculator for cities not covered Covers: * Most major US cities * Many major Canadian cities * Many major capitals around the world This app also feature voice controls - Hold down the home button (middle button on the bottom of the phone): * Say - 'taxi fare go' or 'taxi fare get fare'- to be taken to the fare estimator page * Say - 'taxi fare cabs' - to be taken to the page that looks up cab companies in your area This is a great traveller's companion - and FREE - now how cool is that? www.facebook.com/kgapps


text:
It was a humid Saturday morning as I had one foot clipped into my mountain bike while there must have been thirty of us lined up onto the starting line of this 15 mile mountain bike race. As I stood there I glanced over at the other competitors, some of whom had what looked like a ball of fire in their eyes while others had ripped leg muscles. They all sat onto their bikes, some of witch were carbon fiber bikes, hard tail and full suspension bikes and even a few 29ers. Here I am with only a year of experience riding on single track trails with my Trek full suspension mountain bike as I tried to keep myself pumped up for what could potentially be a very grueling race. Before the gunshot was heard, I kept my hands relaxed on the handle bar grips, only letting go to make sure my gloves were on tight, my helmet was adjusted properly and I took a few sips from the Camelbak hydration system that was strapped to me. Once the gun went off and was heard all over the mountain bike park, we were all in a dash to leave the starting line while clipping in and jockeying for position like a herd of wild animals as we made our way from the open field and into the single track trails. As I kept changing gears, looking around at the riders in front of me and thinking about what I would encounter during the race, I had a thought in the back of my mind.
I thought about what led me to buy a mountain bike, how long would it take before I would become confident enough to ride through rugged terrain, switchback trails and steep hills. Could this new sport help me out in the other endurance sports that I compete in?
With the background of a distance runner, and a triathlete, mountain biking would definitely benefit me. A little more than a year and a half before this race, a friend convinced me to buy an inexpensive hard tail mountain bike to participate in group rides in the winter time where we would be doing a lot hill repeats on a twenty mile loop on pavement. These workouts would keep us in shape through the winter so we would all be better off for the upcoming triathlon season. Once springtime rolled around and I wanted to get into ridding on single track trails that offer switchbacks, rugged terrain and steep hills, I realized that the bike that I currently had was inadequate for this type of ridding. So then I found myself buying a Trek full suspension mountain bike. The more I rode my new bike at the local mountain bike parks, the more I appreciated having an intermediate level bike. He way the dual suspension was forgiving on the terrain of the trails along with how well the tires gave me enough traction through the different trail conditions were just a couple of key features that I began to appreciate about this bike. As I rode my mountain bike on the easy and intermediate trails, I not only realized that I was turning into a better mountain biker, I noticed something else along the way. When I was not making my way though the local mountain bike parks, I was out on the road on my triathlon bike. What I found out about mountain biking is that it forces you to become very good at being able to handle your bike in all different situations. It is that same requirement in mountain biking that made me more confident when riding on road, especially through a village where there are a lot of cars, traffic lights, potholes and other various problems that a cyclist has to be aware of. At the time, while I was still becoming acclimated to this bike that I had bought, I knew that sometime in the future I would like to try a mountain bike race. I also knew that I would have to become a much better mountain biker at this new discipline before I try to do it at a competitive level. I soon found myself waking up very early on a September morning to join a of friends on what was going to be a sixty mile ride on our bikes. We would ride the first thirty five miles on a flat trail and then stop for breakfast and then the fun would really begin. Then twenty five miles of singe track trails and see who could endure the most pain. As the leaves fell off the trees and the snow blanketed the ground, there was yet another opportunity for me. Mountain biking on the snow packed trails while breathing the dry air and trying not to let my tires lose their grip in the snow. Eventually in the middle of the summer, I found myself on vacation visiting a friend in Massachusetts near the New Hampshire border and we mountain biked at various parks in the area. My friend and I rode in parks that offered an endless amount of rocks, boulders, roots, logs, man made bridges over creeks and even a few mosquitoes! At this time I was confident enough in my bike handling that I had registered for my first mountain bike race.
Now here I was in the first of four laps in this grueling mountain bike race while I was thinking about how I got into the sport instead of thinking about the race itself. I was quickly getting exhausted while I tried to keep up with the more experienced athletes in this race. With beads of sweat already dripping down my face and realizing that my mental toughness was slowly fading away, this discipline was beginning to feel a lot harder than distance running and competing in triathlons. I found myself on trails that meandered through the park as well as steep climbs, a few rollers, roots, logs, some rocks and then an open field to have a chance to gain speed. Overall I didn't finish as well as I wanted to, but I plan to compete in more mountain bike races in the future. With the various mountain bike parks around the country, this is a very rewarding sport for a beginner to get into as well as an experienced mountain biker. Both types of mountain bikers will still reap the benefits and enjoyment, while continuously trying to push themselves past their comfort zone.
This is how I got into the sport of mountain biking. This is a sport where I have not only learned a lot about the sport itself, but also about myself as an athlete. I'm sure after reading this you are ready to go out and buy a bike or if you already have a mountain bike, dust it off and take it out to the trails.


text:
SLMS not working after upgrade from version 1.2 to 1.3
This document (7012367) is provided subject to the disclaimer at the end of this document.
SUSE Studio 1.2 and 1.3
SUSE Lifecycle Management Server 1.2 and 1.3
This only happens if you still have some registered nodes against an appliance, that had previously been removed from Studio.
The way of the migration (on-line via wagon, booting the media) does not have any effect on the result.
If you have already upgraded SLMS and you experience the issue, SLMS will report an inconsistence of the database and will fail to syncronize appliances. If it happens,
have a look into the log file of the failed Studio synchronization. You will find lines similar to following:
PDATE "nodes" SET "appliance_id" = NULL WHERE "nodes"."appliance_id" = 2 AND "nodes"."id" IN (2)
Note the ID of the failing appliance following the "appliance_id =" (in this case, 2). Go to
and delete all nodes assigned to the appliance. Afterwards, refreshing appliances will work again.
It will not be possible to update such an appliance any more, unless you install the SLMS maintenance update (version 1.3.2-0.5.2 or greater).
This Support Knowledgebase provides a valuable tool for SUSE customers and parties interested in our products and solutions to acquire information, ideas and learn from one another. Materials are provided for informational, personal or non-commercial use within your organization and are presented "AS IS" WITHOUT WARRANTY OF ANY KIND.
- Document ID:7012367
- Creation Date: 06-May-2013
- Modified Date:03-Mar-2020
- SUSE Studio
- SUSE Lifecycle Management Server
For questions or concerns with the SUSE Knowledgebase please contact: email@example.com


text:
Lobby group questions claims on Caloundra South jobs
THE region's peak residents' association has questioned the capacity of the massive Caloundra South development to generate jobs to support its 50,000 population.
In its submission to Stockland's public environment report, which will be presented to the Federal Government, OSCAR describes as fanciful claims by the developer that Caloundra South will create 39,000 jobs.
Stockland was required to provide employment and economic information in its report to the government.
OSCAR president Ian Christesen said Stockland would need to create an economic miracle to deliver those numbers.
"The Stockland report says that this additional 50,000 people will create 39,000 jobs, which is a new created job for every 1.3 additional people, while presently the population of the Sunshine Coast has a job for every 2.3 resident population," he said.
"No economic development strategy has been produced to back up the claims or identify how the jobs are to be created.
"A real danger is that the development becomes a North Lakes where residents commute into Brisbane. The highway is at peak capacity and with no rail upgrade planned until after 2030, this is a recipe for gridlock."
OSCAR was also critical of other economic information in the report.
It said claims the development would have a combined direct and indirect investment into the regional economy of more than $20 billion meant that each new person coming into Caloundra South would create a $400,000 investment into the economy.
Mr Christesen said OSCAR was also concerned that the Caloundra South development would oversupply a market that had already witnessed an eight-year downward trend in population growth.
OSCAR wants performance-based conditions of approval that are monitored and publicly reported.
Outcomes would determine whether further staged approvals should be granted.
It argues the development should be predicated on the provision of critical transport infrastructure.


text:
George Catlin's North American Indian Portfolio shoots to $116,700
George Catlin's North American Indian Portfolio shoots to $116,700
Despite being desired by US collectors, George Catlin's American Indian Portfolio will stay in Germany
MoreRare Booksnews | View our stock for sale | Learn aboutour 120% Guarantee | Download our iPhone app | Sign-up for your Free Newsletter
With a total of more than 1.6m, Ketterer Kunst's two day auction of Rare Books in Hamburg had an excellent result and even outperformed the spring auction by more than 100,000.
The evening auction alone achieved the impressive sales quota of 86% lots sold.
In the bidding race for George Catlin's North American Indian Portfolio (lot 40), the work almost doubled its starting price of 45,000 with a result of 87,600. Several bidders from the USA were left empty handed. The unique contemporary document of highest rarity will remain in Germany after the heated bidding skirmish.
A striking image from George Caitlin's North American Indian portfolio
"Works in the section of Expressionism were particularly sought after - in the end all but five lots were sold. This is also largely due to the fact that more and more fine art buyers are developing an interest in rare books", noted Robert Ketterer, owner of Ketterer Kunst.
One example is the 15 issues of "Menschen" with 92 original prints by Conrad Felixmller, Otto Dix and others. A German dealer stood his ground against a private fellow countryman and made for a result of 11,040, almost a sixteen-fold of the starting price of 700.
The rare edition of 'Legenda Aurea' - the Golden Legendshows a surprisingly mellow Saint Sebastion
A lot of interest was apparent when the weekly magazine for art and culture "Der Sturm" (lot 114) was called up. A London book dealer offered almost twice the calling price and the most important avant-garde magazine of Expressionism soared up to heights of 52,800.
One of the highlights we focussed on ahead of the sale, the only known German copy of Legenda Aurea... (lot 16) by Jacobus de Voragine was sold to a French private collector. Hitting the stage at 18,000, the two volume work climbed to a remarkable 45,600 result.
Likewise Maria Sibylla Merian's "Over de Voortteeling en Wonderbaerlyke Veranderingen der Surinaamsche Insecten" (lot 35) went to a German dealer for 38,400, and a German private collector made "Biblia Germanica Inferior" (lot 8) his own with a bid of 37,200.
The bookmarklet lets you save things you find to your collections.
Note: Make sure your bookmarks are visible.
Click and drag the Collect It button to your browser's Bookmark Bar.


text:
Burkholderia pseudomallei, the causative agent of melioidosis, is a gram-negative bacterium capable of causing either acute lethal sepsis or chronic but eventually fatal disease in infected individuals. However, despite the clinical importance of this infection in areas where it is endemic, there is essentially no information on the mechanisms of protective immunity to the bacterium. We describe here a murine model of either acute or chronic infection with B. pseudomallei in Taylor Outbred (TO) mice which mimics many features of the human pathology. Intraperitoneal infection of TO mice at doses of >106 CFU resulted in acute septic shock and death within 2 days. In contrast, at lower doses mice were able to clear the inoculum from the liver and spleen over a 3- to 4-week period, but persistence of the organism at other sites resulted in a chronic infection of between 2 and 16 months duration which was eventually lethal in all of the animals tested. Resistance to acute infection with B. pseudomallei was absolutely dependent upon the production of gamma interferon (IFN-γ) in vivo. Administration of neutralizing monoclonal antibody against IFN-γ lowered the 50% lethal dose from >5 × 105 to ca. 2 CFU and was associated with 8,500- and 4,400-fold increases in the bacterial burdens in the liver and spleen, respectively, together with extensive destruction of lymphoid architecture in the latter organ within 48 h. Neutralization of either tumor necrosis factor alpha or interleukin-12 but not granulocyte-macrophage colony-stimulating factor, also increased susceptibility to infection in vivo. Together, these results provide the first evidence of a host protective mechanism against B. pseudomallei. The rapid production of IFN-γ within the first day of infection determines whether the infection proceeds to an acute lethal outcome or becomes chronic.
Melioidosis is a life-threatening infectious disease caused by the gram-negative bacteriumBurkholderia (formerly Pseudomonas)pseudomallei. The organism is endemic in Southeast Asia and Northern Australia and can be isolated from a variety of environmental sources, especially soil, ponds, and rice paddies (8). The disease may well be underreported in other areas of the tropics. Infection occurs in humans and other animals. Natural infection is thought to occur via either skin trauma or inhalation of contaminated aerosols (19). Melioidosis is a major cause of mortality in the Northeast of Thailand, where it accounts for approximately 40% of lethal, community-acquired septicemia (5). B. pseudomallei can cause infection in any organ, although pathology occurs mainly in the lungs, spleen, and liver (24, 36). A striking feature of melioidosis is the extremely varied spectrum of clinical presentation. In many cases, infection presents as an acute illness characterized by septic shock. In contrast, some individuals become latently infected with no obvious signs of disease. However, after impairment of immune defenses, such as is seen in diabetes mellitus, renal failure, and steroid treatment, the organism can be reactivated and cause acute lethal sepsis. In fact, relapse of asymptomatic infection has been reported over 20 years after initial exposure to the organism, suggesting an ability to evade immune defenses (18, 20). The ability of the bacterium to cause a long-term latent infection suggests that B. pseudomallei is capable of surviving in an intracellular environment. Results obtained with cell culture systems support this view, in that virulent B. pseudomallei is able to infect and grow within various cell lines as well as human polymorphonuclear leukocytes (PMNL) and monocytes (11, 16, 25). However, neither the site of latency, the mechanisms by which the organism avoids the bactericidal effects of the host immune response, nor the pathways of protective immunity against this bacterium have been identified.
In many other intracellular bacterial infections, the rapid production of proinflammatory and phagocyte-activating cytokines is a key determinant of resistance of the host. The production of gamma interferon (IFN-γ) is of particular importance in controlling the rate of bacterial growth, as shown by the extreme susceptibility to intracellular pathogens of mice depleted of IFN-γ by either gene deletion or neutralizing monoclonal antibody (MAb) (7, 23). However, in the context of gram-negative infection, IFN-γ has also been associated with the development of septic shock, suggesting that in the presence of lipopolysaccharide, IFN-γ can be either beneficial or detrimental depending on the bacterial burden and time of production (1, 4, 15). Other cytokines, including tumor necrosis factor alpha (TNF-α), interleukin-12 (IL-12), and IL-6 may also confer protection or cause pathology, depending on the experimental system. The role of these cytokines in protective immunity against infection with B. pseudomallei has until now not been examined in an experimental model, although serum levels of TNF-α, IFN-γ, and soluble IL-2 receptors, as well as IL-6 and IL-8, are elevated and correlated with disease severity in patients with severe melioidosis, providing predictive markers of outcome (3, 13, 29).
The purpose of this study was to establish a murine model of melioidosis in order to examine the relative importance of IFN-γ and other proinflammatory cytokines in host resistance. Previous attempts to develop animal models of this disease have used a range of species, including ferrets, guinea pigs, hamsters and, to a limited extent, inbred mice (9, 21, 34, 35). In many cases, infection with relatively low numbers of B. pseudomallei has invariably led to acute lethal sepsis, making it difficult to dissect the mechanism of protection. Generation of models of chronic disease have been reported in some species, but the immunological basis of latency has not been examined (21). We now present evidence that infection of outbred TO mice provides a model of both acute and chronic melioidosis, depending upon the initial inoculum. We report here that, in particular, IFN-γ, as well as IL-12 and TNF-α, are essential mediators of protective immunity. These data provide the first evidence for the mechanism of immune control of this clinically important pathogen.
Bacteria.A gentamicin-sensitive strain (708a) of B. pseudomallei, originally obtained from the splenic abscess of a melioidosis patient, was used in all experiments. This strain was isolated from Sappasitprasong Hospital, Ubon Ratchatani, Thailand. Bacteria were subcultured on Columbia agar (Oxoid) and incubated for 24 h at 37°C. Several young colonies were scraped from the agar and suspended in sterile pyrogen-free saline solution (PFS). The suspension was adjusted to an absorbance (optical density) of 0.50 at a 600-nm wavelength. A frozen stock was prepared at a concentration of 108 CFU/ml in PFS with 10% glycerol (vol/vol) and stored at −70°C. When required to inoculate into mice, the bacteria were thawed, washed once with PFS, and diluted to the required concentration in PFS. Identification of the strain both in the initial inoculum and when isolated from acute and chronic infections was confirmed by API 20NE kits (BioMérieux), and a standard disc diffusion method was used to determine susceptibility to gentamicin.
Animal model of infection.Female, Taylor Outbred (TO) mice (Tuck) or BALB/c mice (Harlan Olac) were used at 10 to 12 weeks of age. In other experiments, mice with a targeted gene deletion of the IFN-γ receptor (G129) were compared with their wild type (129SVEV) as controls. These were originally obtained from Bantin & Kingman (Hull, United Kingdom) and bred at the London School of Hygiene and Tropical Medicine (LSHTM) under aseptic conditions. All animals were maintained with access to food and water ad libitum under Animal Biohazard Containment Level 3 conditions throughout the experiments. Mice were infected intraperitoneally (i.p.) or subcutaneously with various concentrations of viable B. pseudomallei in 0.2 ml of PFS. All infections were performed in a class I Biosafety cabinet, and infected animals were maintained within a negative-pressure, HEPA-filtered flexible film isolator (MDH).
Quantitation of bacterial load and histology.Small sections of spleen and liver from infected mice were taken immediately after the organs had been harvested and placed in 2% neutral buffered formalin for at least 24 h. This procedure fixed and disinfected the tissues, which were then processed for routine histological examination by using 5-μm-thick paraffin-embedded sections stained with hematoxylin and eosin. The remainder of the organs were placed into 5 ml of PFS containing 0.5% (vol/vol) Triton X-100 (BDH) and disrupted by passing through a 100-μm-pore-size nylon mesh sieve (Falcon). Serial 10-fold dilutions of the resulting cell suspensions were spread in duplicate onto Columbia agar, and colonies were counted after 48 h incubation at 37°C. The remainder of the cell suspensions were added into 10 ml of brain heart infusion broth (Oxoid) and incubated at 37°C for up to 1 week. The positive broths were subcultured onto Columbia agar, and the bacteria were identified. All negative broths were subcultured on day 7 before being discarded.
Neutralizing anti-cytokine antibodies.To neutralize specific cytokines in vivo, mice were injected i.p. at the time of infection with either 300 μg of hamster anti-mouse IFN-γ MAb (H22) (provided by R. D. Schreiber, Washington University, St. Louis, Mo.), 300 μg of hamster anti-mouse TNF MAb (TN319.12), 1 mg of rat anti-mouse IL-12 MAb (C17.8) (provided by C. Engwerda, Department of Infectious and Tropical Diseases, LSHTM, and originally obtained from G. Trinchieri, Wistar Institute), or 300 μg of rat anti-mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) MAb (MP1-22E9) diluted in PFS. Control mice were injected with appropriate concentrations of either PFS, hamster isotype control antibody (L2), or purified rat immunoglobulin G (IgG; Sigma, Poole, Dorset, United Kingdom).
Statistics.Statistics analysis (unpaired t test and Kaplan-Meier survival analysis) were performed by using GraphPad Prism software (GraphPad, San Diego, Calif.). A P value of <0.05 was considered significant.
Comparison of susceptibility of BALB/c versus TO mice to B. pseudomallei.In order to establish a model of melioidosis which would encompass both acute and chronic features of the human disease, we compared the course of infection in inbred BALB/c mice versus the outbred mouse strain TO. Mice were injected i.p. with various doses ofB. pseudomallei 708a, and cumulative survival was monitored up to a period of 65 days postinfection. Infection of TO mice resulted in death within 48 h only at a dose of 107 CFU per mouse and delayed mortality between days 25 to 40 at 106CFU (Fig. 1). Lower doses of bacteria generally resulted in chronic infections, after which death of remaining mice occurred in proportion to the initial inoculating dose of bacteria, i.e., mice receiving the lower dose lived longer. In contrast, acute lethal sepsis occurred within 3 days in all BALB/c mice given 107, 106, or 105 CFU ofB. pseudomallei, whereas lower doses were sublethal within the first 2 months of infection (data not shown). In view of their greater resistance, TO mice were subsequently used in all further in vivo experiments.
Time course of bacterial clearance after infection with B. pseudomallei.To investigate the kinetics of bacterial replication in the tissues, TO mice were infected with a sublethal dose (2 × 105 CFU) of B. pseudomallei, and the quantity of bacteria in the spleen and liver was determined at various time intervals. At the earliest time point examined (24 h postinfection), the numbers of bacteria in each organ approximated that in the original infecting dose (Fig. 2). However, the splenic load of bacteria progressively decreased over the following 4 days such that by day 8, two of five mice contained only low numbers of bacteria as demonstrated by viable counts, two of five mice were negative on the basis of direct plating of tissue homogenates but showed positive growth when the homogenates were cultured in enrichment broth, and one of the five animals was found to be sterile by both culture criteria. From one experiment, a single animal which had shown no clinical sign of illness was examined, and multiple abscesses were found in the spleen yielding more than 108 CFU per organ, suggesting that in some cases focal growth of the organism can occur without overt signs of infection. Splenomegaly was a prominent feature of the infection and occurred by day 4 and increased progressively with time in contrast to the bacterial burden, which decreased over this period (data not shown). Histopathological examination of the spleens of sublethally infected mice showed an initial infiltration of neutrophils followed by macrophages and lymphocytes (Fig.3). A similar pattern of progressive reduction of bacterial loads was observed in the liver; however, the clearance of bacteria from this organ was slightly slower than from the spleen (Fig. 2B). Histology sections of the lung showed minimal involvement of this organ by this route of infection.
Role of IFN-γ in resistance to acute infection with B. pseudomallei.IFN-γ has been implicated in both protective immunity and the pathology associated with infection with gram-negative bacteria. To determine the contribution of IFN-γ in resistance toB. pseudomallei, mice were treated with either saline or the neutralizing hamster anti-mouse IFN-γ MAb (H22) immediately prior to infection with a sublethal dose of viable bacteria, and mortality was monitored. Saline-treated, infected mice survived for the duration of the experiment without any clinical signs of infection. In contrast, mice treated with H22 MAb showed visible signs of acute sepsis (i.e., weight loss and lethargy) within 20 h of infection, and all were dead by 40 h after infection (Fig.4). Similar conversion to an acutely lethal event was also observed if neutralization of IFN-γ was delayed until 7 days postinfection, although the mortality kinetics observed in this group indicated that death was slightly delayed. All animals died within 5 days of antibody administration, whereas all control infected mice survived until the termination of the experiment on day 30 (data not shown). Treatment of infected mice with an isotype-matched control hamster IgG (L2) resulted in an identical outcome to the treatment with saline plus B. pseudomallei, whereas mice treated with H22 alone and not infected showed no illness at any point. In contrast to the dramatic effects of neutralizing IFN-γ, MAb to murine GM-CSF at concentrations known to inhibit resistance to other pathogens, including Cryptococcus neoformans, Legionella pneumophila, and Candida albicans (6, 37), had no effect on the outcome of infection (Fig. 4).
To examine the cause of death after IFN-γ depletion, the livers and spleens of infected mice were harvested to quantitate the number of bacteria per organ. Respectively, 4,400- and 8,500-fold more bacteria were isolated from the spleen and liver of anti-IFN-γ MAb-treated, infected mice than from the control group (Fig.5). Although the bacterial loads in both liver and spleen from the IFN-γ-depleted mice were similarly high, the histopathology of these two organs was distinctive. In the spleen, lymphoid architecture, particularly in the red pulp, was extensively destroyed, and large numbers of bacteria were spread throughout the organ and easily observed on hematoxylin and eosin staining (Fig. 3). Spleen sections from control infected mice showed infiltration of lymphocytes and phagocytes, but bacteria were not observed. In contrast to the spleen, the inflammatory response in the liver was more localized, and only a slight increase in tissue damage was observed in IFN-γ-depleted mice compared with infected controls, suggesting that the spleen is particularly sensitive to the necrotic effects of high burdens of B. pseudomallei in vivo.
Susceptibility of IFN-γ-depleted mice to B. pseudomallei.To identify the minimum infecting dose of B. pseudomallei, mice were challenged with serial 10-fold dilutions of bacteria from 2 × 105 CFU or saline alone and treated with either H22 or control L2 antibody. Mice given control MAb showed no sign of illness and survived throughout the period of the experiment with all bacterial inocula (Fig.6). In contrast, all IFN-γ-depleted mice infected with 2 × 105 or 2 × 104 CFU died within 48 h. Furthermore, at the lower inocula (2 × 103, 2 × 102, or 2 × 101 CFU), all anti-IFN-γ-treated mice were dead within 5 days of challenge. Even at an inoculum of 2 × 100 CFU, two of three anti-IFN-γ-treated mice died, whereas controls for this inoculum all survived. Finally, all IFN-γ-depleted mice given a further 10-fold dilution (i.e., 2 × 10−1 CFU) survived excluding any nonspecific immunosuppressive effects of IFN-γ neutralization per se. The accuracy of the infecting doses was confirmed by direct plating of the bacterial suspension used in the challenge. Thus, under these conditions, neutralization of IFN-γ lowered the effective lethal dose of B. pseudomallei by 100,000-fold to approximately two bacteria per animal. The importance of IFN-γ was confirmed in experiments examining the sensitivity of IFN-γ receptor knockout mice (G129) to infection with B. pseudomallei. Control wild-type mice (129SVEV) were extremely susceptible to B. pseudomalleiinfection, and at doses of from 105 to 102CFU/mouse, both IFN-γR+/+ and IFN-γR−/−mice all succumbed within 2 days. Nevertheless, when given 101 CFU per animal, two of three IFN-γR+/+mice died at day 12, whereas all IFN-γR−/− mice succumbed within 2 days. Thus, by using either neutralizing MAb in immunocompetent mice or animals lacking the IFN-γ receptor, functional loss of IFN-γ is associated with increased susceptibility to infection with B. pseudomallei.
The role of TNF-α and IL-12 in resistance to acute infection withB. pseudomallei.In other model systems, the rapid production of IFN-γ is initiated by the production of TNF-α and IL-12 (32). In order to assess the role of these cytokines in melioidosis, TO mice were infected with B. pseudomalleias previously described and given neutralizing MAb specific for either TNF (TN3.19.12), IL-12 (C17.8), or IFN-γ at the time of infection. As expected, neutralization of IFN-γ again resulted in 100% mortality within 48 h (Fig. 7). However, depletion of IL-12 resulted in acute lethal sepsis in four of five animals by 3 days, and three of five animals died by 4 days after neutralization of TNF in vivo. These results suggest that IL-12 and TNF-α, as well as IFN-γ, are also important mediators of resistance to acute infection.
In this report, we have generated murine models of both acute and chronic infection to investigate the mechanisms of protective immunity against the causative agent of human melioidosis. Three major findings arose from this study. First, immunocompetent mice initially clear viable B. pseudomallei from infected tissues but then enter a chronic phase of infection which is invariably lethal after 2 to 16 months. Second, this early control mechanism is absolutely dependent upon the rapid production of IFN-γ. Finally, TNF and IL-12 also play a role in acute resistance to B. pseudomallei in vivo.
Our initial experiments demonstrated that inbred BALB/c mice are relatively susceptible to acute infection with B. pseudomallei, whereas the outbred TO strain was approximately 100-fold more resistant. Furthermore, 129SVEV mice showed even greater susceptibility, with a 50% lethal dose of ca. 100 CFU. Genetic differences in resistance have also been reported in other gram-negative bacterial infections (14), although the basis of the different susceptibilities of the animals to B. pseudomallei has yet to be clarified. The extreme susceptibility of some species to experimental infection with B. pseudomallei has previously hampered investigation of the protective immune response to this organism. Our ability to challenge TO mice with significant numbers of bacteria and generate either an acutely lethal infection or a chronic infection provided us with a practicable model to dissect the involvement of macrophage-activating cytokines on resistance in vivo. A kinetic study of bacterial clearance from the target organs of sublethally infected TO mice showed little evidence of bacterial growth but did show a progressive decline in viable B. pseudomallei over time. Clearance was marginally slower in the liver compared to the spleen, but in both organs 99% of bacteria were removed within 4 days after infection, and the majority of animals progressed to apparent sterilization of these organs by 28 days after infection. This result was associated with progressive splenomegaly and the rapid development of granulomas containing multinucleated giant cells in infected tissues, a feature characteristic of both human melioidosis and infection in other animal species (9, 30, 36). These observations support our recent description of the ability of Burkholderia species (bothB. pseudomallei and B. mallei) to induce cell fusion and giant cell formation in macrophage cell lines in vitro (14a).
Two additional features of infection with B. pseudomalleiare worthy of mention. First, splenic abscesses containing a high number of bacteria were observed in some animals which were otherwise asymptomatic and had negligible numbers of bacteria in other organs, indicating that B. pseudomallei can replicate in a focal manner without causing systemic toxicity. Second, at the doses used in this study, all animals that survived the initial infection entered a chronic phase lasting from 2 to 16 months before ultimately progressing to reactivation and death. The cellular and organ location of the few remaining bacteria which go on to cause reactivating disease have not been identified. However, reactivating lesions were observed at multiple tissue sites, including the foot pad and subcutaneous tissue, as well as in the main target organs of liver and spleen. These features mimic the characteristics of clinical melioidosis, further supporting the relevance of the murine model to the human disease (8).
When mice were depleted of IFN-γ at the time of infection, resistance to B. pseudomallei was completely abolished and all animals died within 40 h, whereas the control infected group survived for several months. Neutralization of IFN-γ blocked the generation of multinucleated giant cells (data not shown), increased the bacterial burden in the spleen and liver by 4,400- and 8,500-fold, respectively, and caused massive destruction of splenic lymphoid architecture. Under these conditions, large numbers of bacteria were observed both extracellularly and intracellularly within macrophages but, unlike the case of Listeria monocytogenes (27), there was no evidence that B. pseudomallei invades and replicates in hepatocytes. The fact that as few as two CFU were capable of causing lethal melioidosis in the absence of IFN-γ implies that resident phagocytic cells such as peritoneal macrophages and Küpffer cells are unable to kill B. pseudomallei in vivo. This idea is supported by reports of intracellular survival of B. pseudomallei in both resident macrophages and PMNL in vitro (11, 16, 25). As yet, we have not identified the mechanisms by which IFN-γ mediates its protective effects. IFN-γ is an established activator of macrophage microbicidal activity and mediates resistance against a wide range of other intracellular pathogens, including Listeria spp., Salmonella spp., andMycobacterium spp., as well as some protozoan parasites (17). Recently, Miyagi and colleagues have demonstrated that IFN-γ activates a murine macrophage cell line to kill B. pseudomallei in vitro by a combination of both oxidative and NO-mediated mechanisms (22). The data presented here are consistent with these in vitro findings and provide direct evidence for the importance of the IFN-γ response in vivo. That IFN-γ depletion increases the susceptibility of mice to B. pseudomallei by more than 100,000-fold (in terms of 50% lethal dose) clearly makes melioidosis one of the most sensitive models of IFN-γ-dependent resistance described to date.
The rapidity with which anti-IFN-γ MAb abolishes resistance suggests an innate rather than an acquired source of this cytokine in the initial phase of infection. H22 MAb-treated mice showed signs of illness within 18 to 24 h, suggesting that even in a naive host,B. pseudomallei stimulates IFN-γ production within this period. To date, there is no information on T-cell responses to this organism in either humans or experimental animals. However, such rapid IFN-γ responses are unlikely to be mediated by the clonal expansion of antigen-specific T cells. Natural killer (NK) cells are an alternative source of IFN-γ and represent the first secreting cells after infection with other intracellular pathogens (2, 10, 28). Several pieces of evidence suggest this pathway may contribute to resistance against B. pseudomallei. First, other gram-negative bacteria, such as Salmonella spp. andFrancisella spp., can also stimulate T-cell-independent IFN-γ responses (12, 26). Second, as shown here, neutralization of either TNF-α or IL-12, which stimulate secretion of IFN-γ by NK cells, increases susceptibility to B. pseudomallei. Third, SCID mice infected with B. pseudomallei show an intermediate pattern of resistance between that of infected versus IFN-γ-depleted mice, surviving up to 20 days (data not shown). This pattern of partial resistance in SCID mice is typical of other pathogens which are known to activate the NK cell IFN-γ pathway (2). Thus, T cells are not required for initial protection against lethal melioidosis but are absolutely necessary for maintenance of the chronic phase of infection. Finally, irradiated B. pseudomallei activate naive SCID spleen cells (which are enriched in NK cells but devoid of both α/β and γ/δ T cells) for secretion of IFN-γ in vitro (19a). Together, these results point to an initial, T-cell-independent pathway of resistance prior to the generation of antigen-specific immunity. It should be noted that TNF-α and IL-12 have other important proinflammatory actions, including the upregulation of adhesion molecules and the promotion of Th1-type T-cell responses, which may also contribute to resistance in the immunocompetent host (17). Finally, the course of chronic infection may also be influenced by the production of IFN-γ since in preliminary experiments neutralization of IFN-γ promoted reactivation and shortened the duration of the latent state (data not shown). Experiments are in progress to identify the cellular source of IFN-γ in the chronically infected host, which is likely to be derived from antigen-specific T cells rather than NK cells (31).
In conclusion, the results presented here provide the first evidence for the cellular basis of protective immunity against B. pseudomallei. A rapid IFN-γ response protects the naive host from acute sepsis after initial contact with the organisms and allows progression into the chronic phase of the disease. This distinguishesB. pseudomallei from immunity to L. monocytogenes, the classical paradigm of IFN-γ-mediated resistance, where infection leads to complete and protective sterilizing immunity (33). Instead, melioidosis shares characteristics with other pathogens, such as M. tuberculosis and Toxoplasma gondii, where a successful IFN-γ response is still unable to eliminate the organism, placing the host at risk of reactivation if immune competence becomes impaired at a later time. It will be interesting to determine whether sterilizing immunity to B. pseudomallei can be achieved under other circumstances, such as after cytokine therapy with exogenous IFN-γ or IL-12 or after vaccination. To date, no information is yet available on the nature of protective immunity in humans infected with this organism. However, patients presenting with lethal melioidosis express high levels of circulating cytokines, including TNF-α and IFN-γ, which correlate with mortality (3, 29). Animal models of septic shock indicate that the same cytokines which confer resistance when produced in a controlled and localized manner (including IFN-γ, TNF-α, and IL-12) promote pathology when produced systemically to an overwhelming bacterial load (1, 4, 15). From the data presented here, we predict that the generation of IFN-γ-dominant NK cell and T-cell responses will be essential for the control of acute human melioidosis and entry into the chronic phase. Experiments to test this hypothesis and assess the effect of known risk factors for reactivation (such as diabetes) on these responses should provide a better understanding of the immunological processes which control infection with this important pathogen.
This work was supported by the Wellcome Trust (project grant 034656/2/91/2). P.S. is supported by grant from the Ministry of Sciences and Technologies of Thailand.
Editor: S. H. E. Kaufmann
- Received 29 June 1998.
- Returned for modification 13 August 1998.
- Accepted 7 April 1999.
- Copyright © 1999 American Society for Microbiology


text:
State-owned property developer Perum Perumnas plans to sell stakes to public investor to snap up Rp1 trillion cash during initial public offering scheduled in the first half of 2011.
Perum Perumnas Chief Executive Officer Arief Sugoto told Insider Stories that the company expects to sell 50,000 units of housing in 2013. The company enables to post annual sales of 20,000 units.
"We need more funds to achieve the target. That is why we plan to go IPO. We are waiting for the government approval to change the company's status from perum to limited," he said.
Perumnas estimates that the company to post Rp32 billion net profit this year from Rp100 billion net loss in the previous year. Sales is expected to rise from Rp1 trillion to Rp1.5 trillion.
Disclosure: No position at the stock mentioned above.
Print This Article