Human influence on climate clear, IPCC report says

Sep. 27, 2013 — Human influence on the climate system is clear. This is evident in most regions of the globe, a new assessment by the Intergovernmental Panel on Climate Change (IPCC) concludes.

It is extremely likely that human influence has been the dominant cause of the observed warming since the mid-20th century. The evidence for this has grown, thanks to more and better observations, an improved understanding of the climate system response and improved climate models.

Warming in the climate system is unequivocal and since 1950 many changes have been observed throughout the climate system that are unprecedented over decades to millennia. Each of the last three decades has been successively warmer at Earth's surface than any preceding decade since 1850, reports the Summary for Policymakers of the IPCC Working Group I assessment report, Climate Change 2013: the Physical Science Basis, approved on Friday by member governments of the IPCC in Stockholm, Sweden.

"Observations of changes in the climate system are based on multiple lines of independent evidence. Our assessment of the science finds that the atmosphere and ocean have warmed, the amount of snow and ice has diminished, the global mean sea level has risen and the concentrations of greenhouse gases have increased," said Qin Dahe, Co-Chair of IPCC Working Group I.

Thomas Stocker, the other Co-Chair of Working Group I said: "Continued emissions of greenhouse gases will cause further warming and changes in all components of the climate system. Limiting climate change will require substantial and sustained reductions of greenhouse gas emissions."

"Global surface temperature change for the end of the 21st century is projected to be likely to exceed 1.5°C relative to 1850 to 1900 in all but the lowest scenario considered, and likely to exceed 2°C for the two high scenarios," said Co-Chair Thomas Stocker. "Heat waves are very likely to occur more frequently and last longer. As Earth warms, we expect to see currently wet regions receiving more rainfall, and dry regions receiving less, although there will be exceptions," he added.

Projections of climate change are based on a new set of four scenarios of future greenhouse gas concentrations and aerosols, spanning a wide range of possible futures. The Working Group I report assessed global and regional-scale climate change for the early, mid-, and later 21st century.

"As the ocean warms, and glaciers and ice sheets reduce, global mean sea level will continue to rise, but at a faster rate than we have experienced over the past 40 years," said Co-Chair Qin Dahe. The report finds with high confidence that ocean warming dominates the increase in energy stored in the climate system, accounting for more than 90% of the energy accumulated between 1971 and 2010.

Co-Chair Thomas Stocker concluded: "As a result of our past, present and expected future emissions of CO2, we are committed to climate change, and effects will persist for many centuries even if emissions of CO2 stop."

Rajendra Pachauri, Chair of the IPCC, said: "This Working Group I Summary for Policymakers provides important insights into the scientific basis of climate change. It provides a firm foundation for considerations of the impacts of climate change on human and natural systems and ways to meet the challenge of climate change." These are among the aspects assessed in the contributions of Working Group II and Working Group III to be released in March and April 2014. The IPCC Fifth Assessment Report cycle concludes with the publication of its Synthesis Report in October 2014.

"I would like to thank the Co-Chairs of Working Group I and the hundreds of scientists and experts who served as authors and review editors for producing a comprehensive and scientifically robust summary. I also express my thanks to the more than one thousand expert reviewers worldwide for contributing their expertise in preparation of this assessment," said IPCC Chair Pachauri.

The Summary for Policymakers of the Working Group I contribution to the IPCC Fifth Assessment Report (WGI AR5) is available at www.climatechange2013.org or www.ipcc.ch.

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Microfluidic platform gives clear look at a crucial step in cancer metastasis

Sep. 20, 2013 — Cancer cells metastasize in several stages -- first by invading surrounding tissue, then by infiltrating and spreading via the circulatory system. Some circulating cells work their way out of the vascular network, eventually forming a secondary tumor.

While the initial process by which cancer cells enter the bloodstream -- called intravasation -- is well characterized, how cells escape blood vessels to permeate other tissues and organs is less clear. This process, called extravasation, is a crucial step in cancer metastasis.

Now researchers at MIT have developed a microfluidic device that mimics the flow of cancer cells through a system of blood vessels. Using high-resolution time-lapse imaging, the researchers captured the moments as a cancer cell squeezes its way through a blood vessel wall into the surrounding extracellular matrix. The process is "highly dynamic," as they write in a paper published in the journal Integrative Biology; a better understanding of it may help scientists identify therapies to prevent metastasis.

"Now that we have a model for extravasation, you can think about using it as a screen for drugs that could prevent it," says Roger Kamm, the Cecil and Ida Green Distinguished Professor of Biology and Mechanical Engineering at MIT. "We could take circulating tumor cells from a patient and subject those cells to a handful of factors or drugs. That's ultimately what we'd like to do, but in the process we're learning a lot as we go along."

Kamm's co-authors on the paper include graduate students Michelle Chen, Jordan Whisler and Jessie Jeon.

Seeding blood vessels

As tumor cells make their way through the circulatory system, some "arrest," or pause at a particular location, adhering to a blood vessel's wall -- the first stage of extravasation. Scientists have thought that this cell arrest occurs in one of two ways: A cell may send out sticky projections that grab onto the vessel lining, or it may be too big to pass through, literally becoming trapped within the vessel.

To investigate which possibility is more likely, the researchers grew a network of tiny blood vessels from a solution of human umbilical-cord endothelial cells. They injected a solution containing vascular cells into a small microfluidic device containing a reservoir of hydrogel, along with growth factors normally present in the developing circulatory system. Within days, an intricate system of microvessels took shape, with each about one millimeter long and 10 to 100 microns in diameter -- dimensions similar to the body's small capillaries.

The group then pumped tumor cells through the vascular network, using a line of breast cancer cells known to be particularly invasive. Using high-resolution confocal microscopy, the team watched as tumor cells flowed through the miniature circulatory system. They observed that the majority of cells that arrested along a vessel did so due to entrapment -- that is, they simply became stuck.

A tumor cell finds a way out

With time-lapse images, the researchers took a closer look at the progression of events following cell arrest. Once a tumor cell becomes trapped, they observed that it sends out long, thin filaments that push against a vessel wall, eventually creating a small hole in the endothelial lining. More and more of the cell squeezes through as the holes give way, and eventually, even the cell's nucleus -- thought to be a relatively rigid, nondeformable structure -- is able to escape.

To their surprise, the researchers found that the nucleus made it through the vessel wall earlier and more quickly than they anticipated, squeezing through in about 15 minutes -- "a tiny chunk of the time it takes for this entire cell to extravasate," Chen notes.

Interestingly, Chen points out, once a tumor cell has completely exited a blood vessel, the endothelium appears to heal itself, closing the gaps that the cell initially created. "That suggests that the endothelial barrier has some kind of active role in repairing itself after this invasion by the tumor cell," Chen says.

In addition to observing the extravasation of single tumor cells, the group also looked at the behavior of cell clusters -- two or more cancer cells that accumulate in a blood vessel. From their observations, the researchers found that almost 70 percent of cell clusters broke through a blood barrier, compared with less than 10 percent of single cells.

But some cells that make it out of the circulatory system may still fail to metastasize. To see whether a cell's ability to extravasate correlates with its metastatic potential, the group compared the efficiency of extravasation of different cancer cell lines. The lines included breast cancer cells, cells from fibrosarcoma (a cancer of the connective tissue), and a line of nonmetastatic cancer cells.

Sure enough, the team observed that the most metastatic cells (fibrosarcoma cells) were also the most likely to extravasate, compared with breast cancer and nonmetastatic cells -- a finding suggesting that targeting drugs to prevent extravasation may slow cancer metastasis.

Going forward, the group is looking into how likely a given cancer cell is to proliferate and aggregate with others once it has exited into the surrounding tissue. The researchers are modeling various tissues within the microfluidic platform, including bone, to study how cancer cells form the beginnings of a secondary tumor.

"Although this platform isn't an in-vivo platform and obviously can't capture all the aspects that happen in vivo, we've come a lot closer to creating an in-vitro platform that's even more physiologically relevant, high-resolution and high-throughput than a lot of previous platforms," Chen says.

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AIDS vaccine candidate appears to completely clear virus from the body in monkeys

Sep. 11, 2013 — An HIV/AIDS vaccine candidate developed by researchers at Oregon Health & Science University appears to have the ability to completely clear an AIDS-causing virus from the body. The promising vaccine candidate is being developed at OHSU's Vaccine and Gene Therapy Institute. It is being tested through the use of a non-human primate form of HIV, called simian immunodeficiency virus, or SIV, which causes AIDS in monkeys. Following further development, it is hoped an HIV-form of the vaccine candidate can soon be tested in humans.

These research results were published online today by the journal Nature. The results will also appear in a future print version of the publication.

"To date, HIV infection has only been cured in a very small number of highly-publicized but unusual clinical cases in which HIV-infected individuals were treated with anti-viral medicines very early after the onset of infection or received a stem cell transplant to combat cancer," said Louis Picker, M.D., associate director of the OHSU Vaccine and Gene Therapy Institute. "This latest research suggests that certain immune responses elicited by a new vaccine may also have the ability to completely remove HIV from the body."

The Picker lab's approach involves the use of cytomegalovirus, or CMV, a common virus already carried by a large percentage of the population. In short, the researchers discovered that pairing CMV with SIV had a unique effect. They found that a modified version of CMV engineered to express SIV proteins generates and indefinitely maintains so-called "effector memory" T-cells that are capable of searching out and destroying SIV-infected cells.

T-cells are a key component of the body's immune system, which fights off disease, but T-cells elicited by conventional vaccines of SIV itself are not able to eliminate the virus. The SIV-specific T-cells elicited by the modified CMV were different. About 50 percent of monkeys given highly pathogenic SIV after being vaccinated with this vaccine became infected with SIV but over time eliminated all trace of SIV from the body. In effect, the hunters of the body were provided with a much better targeting system and better weapons to help them find and destroy an elusive enemy.

"Through this method we were able to teach the monkey's body to better 'prepare its defenses' to combat the disease," explained Picker. "Our vaccine mobilized a T-cell response that was able to overtake the SIV invaders in 50 percent of the cases treated. Moreover, in those cases with a positive response, our testing suggests SIV was banished from the host. We are hopeful that pairing our modified CMV vector with HIV will lead to a similar result in humans."

The Picker lab is now investigating the possible reasons why only a subset of the animals treated had a positive response in hopes that the effectiveness of the vaccine candidate can be further boosted.

This research was funded by several grants from the National Institutes of Health, funding from the International AIDS Vaccine Initiative and a CAVD grant from the Bill & Melinda Gates Foundation.

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