Wednesday, July 30, 2014

Biologist warn of early stages of Earth's sixth mass extinction event

The planet's current biodiversity, the product of 3.5 billion years of evolutionary trial and error, is the highest in the history of life. But it may be reaching a tipping point.



African elephant with calf, Amboseli National Park. Elephants and other large animals face an increased risk of extinction
Credit: © EcoView / Fotolia
In a new review of scientific literature and analysis of data published in Science, an international team of scientists cautions that the loss and decline of animals is contributing to what appears to be the early days of the planet's sixth mass biological extinction event.
Since 1500, more than 320 terrestrial vertebrates have become extinct. Populations of the remaining species show a 25 percent average decline in abundance. The situation is similarly dire for invertebrate animal life.
And while previous extinctions have been driven by natural planetary transformations or catastrophic asteroid strikes, the current die-off can be associated to human activity, a situation that the lead author Rodolfo Dirzo, a professor of biology at Stanford, designates an era of "Anthropocene defaunation."
Across vertebrates, 16 to 33 percent of all species are estimated to be globally threatened or endangered. Large animals -- described as megafauna and including elephants, rhinoceroses, polar bears and countless other species worldwide -- face the highest rate of decline, a trend that matches previous extinction events.
Larger animals tend to have lower population growth rates and produce fewer offspring. They need larger habitat areas to maintain viable populations. Their size and meat mass make them easier and more attractive hunting targets for humans.
Although these species represent a relatively low percentage of the animals at risk, their loss would have trickle-down effects that could shake the stability of other species and, in some cases, even human health.
For instance, previous experiments conducted in Kenya have isolated patches of land from megafauna such as zebras, giraffes and elephants, and observed how an ecosystem reacts to the removal of its largest species. Rather quickly, these areas become overwhelmed with rodents. Grass and shrubs increase and the rate of soil compaction decreases. Seeds and shelter become more easily available, and the risk of predation drops.
Consequently, the number of rodents doubles -- and so does the abundance of the disease-carrying ectoparasites that they harbor.
"Where human density is high, you get high rates of defaunation, high incidence of rodents, and thus high levels of pathogens, which increases the risks of disease transmission," said Dirzo, who is also a senior fellow at the Stanford Woods Institute for the Environment. "Who would have thought that just defaunation would have all these dramatic consequences? But it can be a vicious circle."
The scientists also detailed a troubling trend in invertebrate defaunation. Human population has doubled in the past 35 years; in the same period, the number of invertebrate animals -- such as beetles, butterflies, spiders and worms -- has decreased by 45 percent.
As with larger animals, the loss is driven primarily by loss of habitat and global climate disruption, and could have trickle-up effects in our everyday lives.
For instance, insects pollinate roughly 75 percent of the world's food crops, an estimated 10 percent of the economic value of the world's food supply. Insects also play a critical role in nutrient cycling and decomposing organic materials, which helps ensure ecosystem productivity. In the United States alone, the value of pest control by native predators is estimated at $4.5 billion annually.
Dirzo said that the solutions are complicated. Immediately reducing rates of habitat change and overexploitation would help, but these approaches need to be tailored to individual regions and situations. He said he hopes that raising awareness of the ongoing mass extinction -- and not just of large, charismatic species -- and its associated consequences will help spur change.
"We tend to think about extinction as loss of a species from the face of Earth, and that's very important, but there's a loss of critical ecosystem functioning in which animals play a central role that we need to pay attention to as well," Dirzo said. "Ironically, we have long considered that defaunation is a cryptic phenomenon, but I think we will end up with a situation that is non-cryptic because of the increasingly obvious consequences to the planet and to human wellbeing."
The coauthors on the report include Hillary S. Young, University of California, Santa Barbara; Mauro Galetti, Universidade Estadual Paulista in Brazil; Gerardo Ceballos, Universidad Nacional Autonoma de Mexico; Nick J.B. Isaac, of the Natural Environment Research Council Centre for Ecology and Hydrology in England; and Ben Collen, of University College London.

Journal Reference:
  1. R. Dirzo, H. S. Young, M. Galetti, G. Ceballos, N. J. B. Isaac, B. Collen. Defaunation in the Anthropocene. Science, 2014; 345 (6195): 401 DOI: 10.1126/science.1251817 
Courtesy: ScienceDaily


Monday, July 28, 2014

Researchers eliminate HIV from cultured human cells for first time

HIV-1, the most common type of the virus that causes AIDS, has proved to be tenacious, inserting its genome permanently into its victims' DNA, forcing patients to take a lifelong drug regimen to control the virus and prevent a fresh attack. Now, a team of Temple University School of Medicine researchers has designed a way to snip out the integrated HIV-1 genes for good.


This scanning electron micrograph revealed the presence of the human immunodeficiency virus (HIV-1) (spherical in appearance), which had been co-cultivated with human lymphocytes.
Credit: CDC/C. Goldsmith, P. Feorino, E. L. Palmer, W. R. McManus
 
 
 
 




"This is one important step on the path toward a permanent cure for AIDS," says Kamel Khalili, PhD, Professor and Chair of the Department of Neuroscience at Temple. Khalili and his colleague, Wenhui Hu, MD, PhD, Associate Professor of Neuroscience at Temple, led the work which marks the first successful attempt to eliminate latent HIV-1 virus from human cells. "It's an exciting discovery, but it's not yet ready to go into the clinic. It's a proof of concept that we're moving in the right direction," added Dr. Khalili, who is also Director of the Center for Neurovirology and Director of the Comprehensive NeuroAIDS Center at Temple.
In a study published July 21 by the Proceedings of the National Academy of Sciences, Khalili and colleagues detail how they created molecular tools to delete the HIV-1 proviral DNA. When deployed, a combination of a DNA-snipping enzyme called a nuclease and a targeting strand of RNA called a guide RNA (gRNA) hunt down the viral genome and excise the HIV-1 DNA. From there, the cell's gene repair machinery takes over, soldering the loose ends of the genome back together -- resulting in virus-free cells.
"Since HIV-1 is never cleared by the immune system, removal of the virus is required in order to cure the disease," says Khalili, whose research focuses on the neuropathogenesis of viral infections. The same technique could theoretically be used against a variety of viruses, he says.
The research shows that these molecular tools also hold promise as a therapeutic vaccine; cells armed with the nuclease-RNA combination proved impervious to HIV infection.
Worldwide, more than 33 million people have HIV, including more than 1 million in the United States. Every year, another 50,000 Americans contract the virus, according to the U.S. Centers for Disease Control and Prevention.
Although highly active antiretroviral therapy (HAART) has controlled HIV-1 for infected people in the developed world over the last 15 years, the virus can rage again with any interruption in treatment. Even when HIV-1 replication is well controlled with HAART, the lingering HIV-1 presence has health consequences. "The low level replication of HIV-1 makes patients more likely to suffer from diseases usually associated with aging," Khalili says. These include cardiomyopathy -- a weakening of the heart muscle -- bone disease, kidney disease, and neurocognitive disorders. "These problems are often exacerbated by the toxic drugs that must be taken to control the virus," Khalili adds.
Researchers based the two-part HIV-1 editor on a system that evolved as a bacterial defense mechanism to protect against infection, Khalili says. Khalili's lab engineered a 20-nucleotide strand of gRNA to target the HIV-1 DNA and paired it with Cas9. The gRNA targets the control region of the gene called the long terminal repeat (LTR). LTRs are present on both ends of the HIV-1 genome. By targeting both LTRs, the Cas9 nuclease can snip out the 9,709-nucleotides that comprise the HIV-1 genome. To avoid any risk of the gRNA accidentally binding with any part of the patient's genome, the researchers selected nucleotide sequences that do not appear in any coding sequences of human DNA, thereby avoiding off-target effects and subsequent cellular DNA damage.
The editing process was successful in several cell types that can harbor HIV-1, including microglia and macrophages, as well as in T-lymphocytes. "T-cells and monocytic cells are the main cell types infected by HIV-1, so they are the most important targets for this technology," Khalili says.
The HIV-1 eradication approach faces several significant challenges before the technique is ready for patients, Khalili says. The researchers must devise a method to deliver the therapeutic agent to every single infected cell. Finally, because HIV-1 is prone to mutations, treatment may need to be individualized for each patient's unique viral sequences.
"We are working on a number of strategies so we can take the construct into preclinical studies," Khalili says. "We want to eradicate every single copy of HIV-1 from the patient. That will cure AIDS. I think this technology is the way we can do it."

Journal Reference:
  1. W. Hu, R. Kaminski, F. Yang, Y. Zhang, L. Cosentino, F. Li, B. Luo, D. Alvarez-Carbonell, Y. Garcia-Mesa, J. Karn, X. Mo, K. Khalili. RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection. Proceedings of the National Academy of Sciences, 2014; DOI: 10.1073/pnas.1405186111
Courtesy: ScienceDaily