Wednesday, June 9, 2010

TO ATTACK H1N1, OTHER FLU VIRUSES, GOLD NANORODS DELIVER POTENT PAYLOAD

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Future pandemics of seasonal flu, H1N1 and other drug-resistant viruses may be thwarted by a potent, immune-boosting payload that is effectively delivered to cells by gold nanorods, report scientists at the University at Buffalo and the U.S. Centers for Disease Control and Prevention. The work is published in the current issue of the Proceedings of the National Academy of Sciences.

"This joint research by UB and the CDC has the potential to usher in a new generation of antiviral medicines to aggressively treat a broad range of infectious diseases, from H1N1 to avian flu and perhaps Ebola, that are becoming increasingly resistant to the medicines used against them," says UB team leader Paras Prasad, PhD, executive director of the UB Institute for Lasers, Photonics and Biophotonics (ILPB) and SUNY Distinguished Professor in the departments of Chemistry, Physics, Electrical Engineering and Medicine.

The collaborative work between UB and CDC came together through the work of Krishnan Chakravarthy, an MD/PhD candidate at UB and the paper's first author. This research constitutes part of his doctoral degree work that focused on host response to influenza infection and novel drug delivery strategies.

The paper describes the single strand RNA molecule, which prompts a strong immune response against the influenza virus by ramping up the host's cellular production of interferons, proteins that inhibit viral replication.

But, like most RNA molecules, they are unstable when delivered into cells. The gold nanorods produced at UB act as an efficient vehicle to deliver into cells the powerful immune activator molecule.

"It all boils down to how we can deliver the immune activator," says Suryaprakesh Sambhara, DVM, PhD, in CDC's Influenza Division and a co-author on the paper. "The UB researchers had an excellent delivery system. Dr. Prasad and his team are well-known for their contributions to nanoparticle delivery systems."

A key advantage is gold's biocompatibility.

"The gold nanorods protect the RNA from degrading once inside cells, while allowing for more selected targeting of cells," said co-author Paul R. Knight III, MD, Chakravarthy's thesis advisor; professor of anesthesiology, microbiology and infectious diseases in the UB School of Medicine and Biomedical Sciences; and director of its MD/PhD program.

"This work demonstrates that the modulation of host response is going to be critical to the next generation of anti-viral therapies," Chakravarthy explains. "The novelty of this approach is that most of these kinds of RNA viruses share a common host-response immune pathway; that is what we have targeted with our nanoparticle therapy. By enhancing the host immune response, we avoid the difficulty of ongoing viral resistance generated through mutations."

Diseases that could be effectively targeted with this new approach include any viruses that are susceptible to the innate immune response that type 1 interferons trigger, Prasad notes.

Based on these in vitro results, the UB and CDC researchers are beginning animal studies.

"This collaboration has been extraordinary as two disparate research groups at UB and a third at the CDC have managed to maintain progress toward a common goal: treatment of influenza," says co-author Adela Bonoiu, PhD, UB research assistant professor at ILPB.

(Photo: U. Buffalo)

University at Buffalo

STUDY FINDS FAT AROUND THE ABDOMEN ASSOCIATED WITH SMALLER, OLDER BRAINS IN MIDDLE-AGED ADULTS

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Researchers from Boston University School of Medicine (BUSM) have found a significant association between abdominal fat and lower total brain volume. The study, which currently appears in the Annals of Neurology, may improve understanding of the mechanisms underlying the relationship of obesity with dementia and could lead to prevention strategies.

Global body mass and obesity, particularly in midlife, are associated with an increased risk of dementia and Alzheimer disease. Different fat compartments carry differential metabolic risks and there is growing evidence that abdominal obesity and visceral fat are more correlated with vascular risk than global body mass. However, limited data exists demonstrating this concept in association with cognition and dementia.

The BUSM researchers studied more than 700 participants from the Framingham Offspring Cohort. The participants underwent a volumetric multi-detector abdominal CT-scan with quantitative measurement of subcutaneous fat and visceral fat volume as well as a brain MRI.

“We observed an inverse association of body mass index, waist circumference, subcutaneous adipose tissue and visceral adipose tissue with total brain volume, independent of vascular risk factors,” said senior author Sudha Seshadri, MD, an associate professor of neurology at BUSM and an Investigator at the Framingham Heart Study. “More importantly our data suggests that the association between visceral adipose tissue and total brain volume was the strongest and most robust of all, and was also independent of body mass index and insulin resistance,” she added.

According to the researchers, the potential mechanisms underlying the inverse association of obesity and particularly visceral abdominal fat with total brain volume are speculative. Inflammation could be an important mediator as well as diabetes and insulin resistance. In addition, the researchers believe adipose-tissue derived hormones, such as adiponectin, leptin, resistin or ghrelin, could also play a role in the relation between adipose tissue and brain atrophy.

“Although these findings are preliminary they could improve our understanding of the mechanisms underlying the relationship of obesity with dementia with potentially important implications for prevention strategies,” added Seshadri.

Boston University

LOWLY TERMITE, NOT THE LION OR ELEPHANT, MAY BE THE STAR OF AFRICAS SAVANNA

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The majestic animals most closely associated with the African savanna — fierce lions, massive elephants, towering giraffes – may be relatively minor players when it comes to shaping the ecosystem.

The king of the savanna appears to be the termite, say ecologists who’ve found that these humble creatures contribute mightily to grassland productivity in central Kenya via a network of uniformly distributed colonies. Termite mounds greatly enhance plant and animal activity at the local level, while their even distribution over a larger area maximizes ecosystem-wide productivity.

The finding, published in the journal PLoS Biology, affirms a counterintuitive approach to population ecology: Often, it’s the small things that matter most.

“One of the kind of typical things I think that people think about is, what drives a savanna in terms of its structure and function?” said Todd Palmer, one of the paper’s authors and an assistant professor of biology at the University of Florida.”We think about big animals, but these termites are having a massive impact on the system from below.”

Said Robert M. Pringle, a research fellow at Harvard University and the lead author, “As (famed biologist) E.O. Wilson likes to point out, in many respects it’s the little things that run the world.”

Prior research on the Kenya dwarf gecko initially drew Pringle’s attention to the peculiar role of grassy termite mounds, which in this part of Kenya are some 30 feet in diameter and spaced some 180 to 300 feet apart. Each mound teems with millions of termites, who build the mounds over the course of centuries.

After observing unexpectedly high numbers of lizards in the vicinity of mounds, Pringle, Palmer and their colleagues began to quantify ecological productivity relative to mound density. They found that each mound supported dense aggregations of flora and fauna: Plants grew more rapidly the closer they were to mounds, and animal populations and reproductive rates fell off appreciably with greater distance.

What was observed on the ground was even clearer in satellite imagery. Each mound — relatively inconspicuous on the Kenyan grassland — stood at the center of a burst of floral productivity. More important, these bursts were highly organized in relation to one another, evenly dispersed as if squares on a checkerboard. The result is an optimized network of plant and animal output closely tied to the ordered distribution of termite mounds.

“In essence, the highly regular spatial pattern of fertile mounds generated by termites actually increases overall levels of ecosystem production. And it does so in such a profound way,” Palmer said. “Seen from above, the grid-work of termite mounds in the savanna is not just a pretty picture. The over-dispersion, or regular distribution of these termite mounds, plays an important role in elevating the services this ecosystem provides.”

The mechanism through which termite activity is transformed into far-reaching effects on the ecosystem is a complex one. Pringle and Palmer suspect termites import coarse particles into the otherwise fine soil in the vicinity of their mounds. These coarser particles promote water infiltration of the soil, even as they discourage disruptive shrinking and swelling of topsoil in response to precipitation or drought.

The mounds also show elevated levels of nutrients such as phosphorus and nitrogen. All this beneficial soil alteration appears to directly and indirectly mold ecosystem services far beyond the immediate vicinity of the mound.

While further studies will explore the mechanism through which these spatial patterns of termite mounds emerge, Pringle and Palmer suggest that the present work has implications beyond the basic questions of ecology.

“Termites are typically viewed as pests, and as threats to agricultural and livestock production,” Pringle said. “But productivity — of both wild and human-dominated landscapes — may be more intricately tied to the pattern-generating organisms of the larger natural landscape than is commonly understood.”

University of Florida

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