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This spring, a team of scientists has been driving around a small island in Guangzhou, southern China, releasing more than half a million mosquitoes from plastic pots on board trucks.
Rather than chasing the researchers away, families have welcomed their incursion: “Some residents have even asked to get mosquitoes from us to release in their own home,” said Xi Zhiyong of Michigan State University, who heads the project. The sight of the insects might set the skin crawling, but people know the alternative could be worse: this is one of several innovative attempts to tackle dengue fever by diluting the mosquito population with insects that don’t carry the disease.
The mosquito-borne sickness causes pain so agonizing it is also known as “breakbone disease” and last year saw China’s worst outbreak in two decades, with more than 47,000 cases, almost all in Guangdong province.
Catch one strain and you will be immune to the virus in future — but if bitten by a mosquito carrying another of the strains, you are more likely to develop severe dengue, also known as dengue hemorrhagic fever. No vaccine or treatment is available and recently it has caused about 22,000 deaths a year worldwide, mostly among children.
Before 1970, only nine countries had severe dengue epidemics; now it is endemic in more than 100 countries.
Yang Zhicong, deputy director of Guangzhou’s Center for Disease Control and Prevention, said authorities had hired anti-mosquito squads and quarantined dengue patients. Mr. Xi and his colleagues have released mosquitoes infected with Wolbachia bacteria, which make the males sterile and limit the insects’ ability to carry dengue.
Last year’s outbreak has helped persuade residents to embrace the pilot scheme, as has Mr. Xi’s willingness to plunge his hand into mosquito pots to prove that the males they are releasing do not bite. And while the Chinese government has not approved the release of genetically modified creatures, it accepted this trial because Wolbachia occurs naturally in many insects.
In the first phase, the team aims to reduce the mosquito population, as sterile males breed with wild females. In the second, Wolbachia infected females will be released to replace the wild, dengue-transmitting population, so mosquitoes from other areas face competition if they try to move in.
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A highly unusual clinical trial in Guinea has shown for the first time that an Ebola vaccine protects people from the deadly virus. The study, published online today by The Lancet, shows that the injection offered contacts of Ebola cases 100% protection starting 10 days after they received a single shot of the vaccine, which is produced by Merck. Scientists say the vaccine could help to finally bring an end to the epidemic in West Africa, now more than 18 months old.
“This will go down in history as one of those hallmark public health efforts,” says Michael Osterholm, the director of the Center for Infectious Disease Research and Policy in Twin Cities, Minnesota, who wasn’t involved in the study. “We will teach about this in public health schools.”
“It’s a wonderful result and a fantastic illustration of how vaccines can be developed very quickly and can be used in an outbreak situation to control the disease,” says Adrian Hill, a vaccine researcher at the University of Oxford in the United Kingdom, also not involved in the work.
The vaccine, first developed by researchers at the Public Health Agency of Canada, consists of the Vesicular Stomatitis Virus (VSV), which causes disease in livestock but not people, with the Ebola surface protein stitched into it. It is one of two vaccines currently being tested in the Ebola-stricken countries; the other one is produced by GlaxoSmithKline (GSK). The study of the Merck vaccine was led by Ana Maria Henao-Restrepo of the World Health Organization (WHO) in Geneva, together with colleagues at the Norwegian Institute of Public Health in Oslo, the Guinean Ministry of Health, and others.
The decision to start the trial was taken in October, but it didn’t get off the ground until March. By then, Ebola cases had already begun to plummet, and they were scattered across a large area in Guinea. To show efficacy in a standard randomized controlled trial, the researchers would have had to enroll far more people than was feasible.
Instead, they opted for a design called ring vaccination, in which only contacts of new Ebola patients, as well as the contacts’ contacts, were vaccinated. The rings, or clusters, were randomized; in 48 of them, vaccination occurred as soon as possible after the detection of the Ebola case in their community. In the 42 other clusters, the vaccination teams came to give the shots three weeks later. The researchers then counted the number of new Ebola cases in each ring; because they weren’t sure how long it takes for the vaccine’s protection to kick in, they only included cases that occurred at least 10 days after vaccination in their primary analysis of the data. There were zero such cases among the 2014 people who were vaccinated right away, and 16 among the 2380 who got the shot 3 weeks later. That translates to 100% vaccine efficacy, at least in this study, the researchers write.
The idea of a ring vaccination design, never before used in a formal vaccine study, “was absolutely very creative,” says Osterholm, and it allowed the team to follow the epidemic wherever it went. “Had this been a standard, straightforward randomized controlled trial, we would never had this answer.”
“It surprised me how quickly you can intervene with a vaccination and have an effect,” says Jeremy Farrar, the head of the Wellcome Trust research charity, which co-funded the study. “It’s possible to do that sort of complex work in very, very complex environments—ethically, socially, culturally and scientifically. You can do it. That is a revelation for many people.” The outcome was so convincing that the trial’s data and safety monitoring board-an independent group watching over the safety of participants—recommended to end it in its current form, and start vaccinating all clusters immediately from now on, which the team has now started doing. The vaccine should also be rolled out in Sierra Leone, says Osterholm, which also still has cases. It may well help to finally bring the number of cases to zero, he says.
WHO director-general Margaret Chan called the study “exciting” at a press conference this morning but cautioned that follow-up studies are needed. “If proven effective this is going to be a game-changer. It will change the management of the current Ebola outbreak and future outbreaks,” Chan said.
There were only seven new cases of Ebola last week, WHO reported its most recent situation report on the epidemic: four in Guinea and three in Sierra Leone. That’s the lowest in well over a year, but WHO has warned that the disease can easily flare up again. There were only 12 cases one week in May, for instance, but the virus bounced back to more than 30 cases per week in July.
With reporting by Kai Kupferschmidt
Original Article : AAAS/Science
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Researchers at the University of Illinois at Chicago and Northwestern University have engineered a tethered ribosome that works nearly as well as the authentic cellular component, or organelle, that produces all the proteins and enzymes within the cell. The engineered ribosome may enable the production of new drugs and next-generation biomaterials and lead to a better understanding of how ribosomes function.
The artificial ribosome, called Ribo-T, was created in the laboratories of Alexander Mankin, director of the UIC College of Pharmacy’s Center for Biomolecular Sciences, and Northwestern’s Michael Jewett, assistant professor of chemical and biological engineering. The human-made ribosome may be able to be manipulated in the laboratory to do things natural ribosomes cannot do.
When the cell makes a protein, mRNA (messenger RNA) is copied from DNA. The ribosomes’ two subunits, one large and one small, unite on mRNA to form the functional unit that assembles the protein in a process called translation. Once the protein molecule is complete, the ribosome subunits — both of which are themselves made up of RNA and protein — separate from each other.
In a new study in the journal Nature, the researchers describe the design and properties of Ribo-T, a ribosome with subunits that will not separate. Ribo-T may be able to be tuned to produce unique and functional polymers for exploring ribosome functions or producing designer therapeutics — and perhaps one day even non-biological polymers.
No one has ever developed something of this nature.
“We felt like there was a small — very small — chance Ribo-T could work, but we did not really know,” Mankin said.
Mankin, Jewett and their colleagues were frustrated in their investigations by the ribosomes’ subunits falling apart and coming together in every cycle of protein synthesis. Could the subunits be permanently linked together? The researchers devised a novel designer ribosome with tethered subunits – Ribo-T.
“What we were ultimately able to do was show that by creating an engineered ribosome where the ribosomal RNA is shared between the two subunits and linked by these small tethers, we could actually create a dual translation system,” Jewett said.
“It was surprising that our hybrid chimeric RNA could support assembly of a functional ribosome in the cell. It was also surprising that this tethered ribosome could support growth in the absence of wild-type ribosomes,” he said.
Ribo-T worked even better than Mankin and Jewett believed it could. Not only did Ribo-T make proteins in a test-tube, it was able to make enough protein in bacterial cells that lacked natural ribosomes to keep the bacteria alive.
Jewett and Mankin were surprised by this. Scientists had previously believed that the ability of the two ribosomal subunits to separate was required for protein synthesis.
“Obviously this assumption was incorrect,” Jewett said.
“Our new protein-making factory holds promise to expand the genetic code in a unique and transformative way, providing exciting opportunities for synthetic biology and biomolecular engineering,” Jewett said.
“This is an exciting tool to explore ribosomal functions by experimenting with the most critical parts of the protein synthesis machine, which previously were ‘untouchable,’” Mankin added.
Co-authors on the Nature paper are Cedric Orelle, Teresa Szal and Tanja Florin of UIC’s Center for Biomolecular Sciences and Erik Carlson of the department of chemical and biological engineering and the Chemistry of Life Processes Institute at Northwestern University.
The study was funded by the Defense Advanced Research Projects Agency, the National Science Foundation and the David and Lucille Packard Foundation Fellowship.
Original News : Sam Hostettler July 29, 2015