09.06.07 Forbes.com

SYDNEY (Thomson Financial) – China supports APEC moves to tackle climate change but the ‘main channel’ for international agreement on the global problem should be the United Nations, President Hu Jintao said Thursday.

Australian Prime Minister John Howard has made climate change a key item at the Asia-Pacific Economic Cooperation (APEC) summit and hopes to push leaders towards a declaration here which would set goals on energy efficiency.

But the 21 member economies remain sharply divided over the issue and will not accept Australia’s current draft, which urges developing nations to do more to tackle the problem.

Hu said China took the issue of climate change very seriously and was happy it was being brought up here, but said discussions on a solution needed to be led by the United Nations.

He said he hoped a Sydney declaration ‘will give full expression to the position that the UN Framework Convention on Climate Change should remain the main channel for the international effort to tackle climate change.’

‘And it should also give full expression to the principles set in the convention in the problem of the differentiated responsibilities.’

Some developing economies have said they are opposed to binding targets which would hamper their economic development.

Howard would not comment on reports that the 21 APEC economies remained so divided on the issue.

‘I will wait for the meeting to hear the views of the other economies,’ he said.

JERUSALEM (AP) — Archaeologists digging in northern Israel have discovered evidence of a 3,000-year-old beekeeping industry, including remnants of ancient honeycombs, beeswax and what they believe are the oldest intact beehives ever found.

One of the ancient beehives found at Tel Rehov in Israel.

The findings in the ruins of the city of Rehov this summer include 30 intact hives dating to around 900 B.C., archaeologist Amihai Mazar of Jerusalem’s Hebrew University told The Associated Press. He said it offers unique evidence that an advanced honey industry existed in the Holy Land at the time of the Bible.

Beekeeping was widely practiced in the ancient world, where honey was used for medicinal and religious purposes as well as for food, and beeswax was used to make molds for metal and to create surfaces to write on. While bees and beekeeping are depicted in ancient artwork, nothing similar to the Rehov hives has been found before, Mazar said.

The beehives, made of straw and unbaked clay, have a hole at one end to allow the bees in and out and a lid on the other end to allow beekeepers access to the honeycombs inside. They were found in orderly rows, three high, in a room that could have accommodated around 100 hives, Mazar said.

The Bible repeatedly refers to Israel as a “land of milk and honey,” but that’s believed to refer to honey made from dates and figs — there is no mention of honeybee cultivation. But the new find shows that the Holy Land was home to a highly developed beekeeping industry nearly 3,000 years ago.

“You can tell that this was an organized industry, part of an organized economy, in an ultra-organized city,” Mazar said.

At the time the beehives were in use, Mazar believes Rehov had around 2,000 residents, a mix of Israelites, Canaanites and others.

Ezra Marcus, an expert on the ancient Mediterranean world at Haifa University, said Tuesday the finding was a unique glimpse into ancient beekeeping. Marcus was not involved in the Rehov excavation.

“We have seen depictions of beekeeping in texts and ancient art from the Near East, but this is the first time we’ve been able to actually feel and see the industry,” Marcus said.

The finding is especially unique, Marcus said, because of its location in the middle of a thriving city — a strange place for thousands of bees.

This might have been because the city’s ruler wanted the industry under his control, Marcus said, or because the beekeeping industry was linked to residents’ religious practices, as might be indicated by an altar decorated with fertility figurines that archaeologists found alongside the hives.

(CNN) — A virus found in healthy Australian honey bees may be playing a role in the collapse of honey bee colonies across the United States, researchers reported Thursday.

Honey bees walk on a moveable comb hive at the Bee Research Laboratory, in Beltsville, Maryland.

Colony collapse disorder has killed millions of bees — up to 90 percent of colonies in some U.S. beekeeping operations — imperiling the crops largely dependent upon bees for pollination, such as oranges, blueberries, apples and almonds.

The U.S. Department of Agriculture says honey bees are responsible for pollinating $15 billion worth of crops each year in the United States. More than 90 fruits and vegetables worldwide depend on them for pollination.

Signs of colony collapse disorder were first reported in the United States in 2004, the same year American beekeepers started importing bees from Australia.

The disorder is marked by hives left with a queen, a few newly hatched adults and plenty of food, but the worker bees responsible for pollination gone.

The virus identified in the healthy Australian bees is Israeli Acute Paralysis Virus (IAPV) — named that because it was discovered by Hebrew University researchers.

Although worker bees in colony collapse disorder vanish, bees infected with IAPV die close to the hive, after developing shivering wings and paralysis. For some reason, the Australian bees seem to be resistant to IAPV and do not come down with symptoms.

Scientists used genetic analyses of bees collected over the past three years and found that IAPV was present in bees that had come from colony collapse disorder hives 96 percent of the time.

But the study released Thursday on the Science Express Web site, operated by the journal Science, cautioned that collapse disorder is likely caused by several factors.

“This research give us a very good lead to follow, but we do not believe IAPV is acting alone,” said Jeffery S. Pettis of the U.S. Department of Agriculture’s Bee Research Laboratory and a co-author of the study. “Other stressors on the colony are likely involved.”

This could explain why bees in Australia may be resistant to colony collapse.

“There are no cases … in Australia at all,” entomologist Dave Britton of the Australian Museum told the Sydney Morning Herald last month. “It is a Northern Hemisphere phenomenon.”

Bee ecology expert and University of Florida professor Jamie Ellis said earlier this year that genetic weakness bred into bees over time, pathogens spread by parasites and the effects of pesticides and pollutants might be other factors.

Researchers also say varroa mites affect all hives on the U.S. mainland but are not found in Australia.

University of Georgia bee researcher Keith S. Delaplane said Thursday the study offers a warning — and hope.

“One nagging problem has been a general inability to treat or vaccinate bees against viruses of any kind,” said Delaplane, who has been trying to breed bees resistant to the varroa mite.

“But in the case of IAPV, there is evidence that some bees carry genetic resistance to the disorder. This is yet one more argument for beekeepers to use honey bee stocks that are genetically disease- and pest-resistant.”

Bee researchers will now look for stresses that may combine to kill bees.

“The next step is to ascertain whether IAPV, alone or in concert with other factors, can induce CCD [colony collapse disorder] in healthy bees,” said Ian Lipkin, director of the Center for Infection and Immunity at Columbia University Mailman School of Public Health.

Besides the Columbia and USDA researchers, others involved in the study released Thursday include researchers from Pennsylvania State University, the Pennsylvania Department of Agriculture, the University of Arizona and 454 Life Sciences.

Howard Hughes Medical Institute, September 02, 2007

Two nuclear magnetic resonance spectroscopy tubes containing the hydrogen/deuterium (H/D) exchange data for each prion conformation. The drop shadows behind the tubes represent models of what the corresponding prion structures might be.

Detailed structural studies have revealed new insights into why the same prion protein can have different properties and be either weakly or strongly infectious. The researchers said their observations in prions that infect yeast are likely to hold true for the sorts of prions that infect humans and animals.

A research team led by Howard Hughes Medical Institute investigator Jonathan S. Weissman analyzed the structures of two unmodified yeast Sup35 prion proteins in two infectious conformations. They identified key structural differences that explain the different behaviors of these prions. The researchers published their findings online September 2, 2007, in the journal Nature. Weissman and his colleagues are at the University of California, San Francisco.

“We now appreciate that the same polypeptide can misfold into dramatically different conformations. These different conformations can lead to dramatic changes in the structure of the prion form.”
Jonathan S. Weissman

The scientists studied yeast prions, which are similar to mammalian prions in that they act as infectious proteins. In recent years, mammalian prions have gained increasing notoriety for their roles in such fatal brain-destroying human diseases as Creutzfeldt-Jakob disease and kuru, and in the animal diseases, bovine spongiform encephalopathy (“mad cow” disease) and scrapie.

Yeast and mammalian prions are proteins that transmit their unique characteristics via interactions in which an abnormally shaped prion protein influences a normal protein to assume an abnormal shape. In mammalian prion infections, these abnormal shapes trigger protein clumping that can kill brain cells. In yeast cells, the insoluble prion protein is not deadly; it merely alters a cell’s metabolism. Prions propagate themselves by division of the insoluble clumps to create “seeds” that can continue to grow by causing aggregation of more proteins.

One of the unexplained questions facing prion researchers is how a single prion can apparently assume different conformations — with each conformation having different disease or phenotypic properties. Previous structural studies of prions had not yielded a clear understanding of the basis of strains because the prion protein is large and complex. Due to the size and complexity of prions, studies utilizing x-ray crystallography, a technique commonly used to determine the structure of proteins and other molecules, have been limited to short peptide fragments of the prion protein.

“There have been a number of fairly low-resolution pictures of prions that more or less proved that these different strains were in different conformations; but they really hadn’t established the nature of the different conformations,” Weissman said. “It was really a big black box. We basically didn’t have the conformation of any single prion, let alone the two prion protein strains in two different conformations.”

In their experiments, Weissman and his colleagues used the yeast prion Sup35 because two of its strains, termed “weak” and “strong,” can be unequivocally produced in pure form in the test tube for structural analysis. Rather than using x-ray crystallography, they employed hydrogen/deuterium (H/D) exchange measured by nuclear magnetic resonance spectroscopy (NMR). In this technique, molecules are first placed in a deuterium buffer and their hydrogen atoms are allowed to exchange to deuterium. Using NMR to see which hydrogen atoms exchange and which do not, researchers can then deduce structural information since highly structured regions resist exchange while unstructured regions quickly exchange.

In their analyses, the researchers allowed two strains of the yeast prion to exchange over the course of a week. By comparing the extent of exchange for each residue in both conformations, the researchers identified the well-structured regions responsible for prion activity and were able to clearly map out the structural differences between the two strain variants.

The scientists confirmed their NMR-derived structural information of the two prion variants by conducting in vitro studies. They selectively altered the prion protein through mutation in ways they predicted would and would not disrupt prion function based on the H/D exchange data. Then, they tested the effects of those mutations on prion conversion in vitro, and observed remarkable consistency between the two techniques.

Both the NMR and in vitro studies yielded evidence that each prion strain had the same kind of tightly packed core that was critical to their ability to form amyloid clumps. However, the two strains differed in the nature of a long molecular extension from this core. The strong strain had a less structured extension that might be more easily recognized by chaperone proteins in the cell that help the prion generate new seed prions to propagate the infection, said Weissman.

In contrast, the weak strain had a more structured extension, probably less conducive to chaperone recognition. Importantly, said Weissman, the findings confirmed theories of strain properties based on earlier findings by other researchers who used different methods to study pieces of prions or altered prion proteins.

“In our minds, our findings brought to a certain level of closure the understanding of the structural differences underlying strains,” said Weissman. “Now we understand the structural differences. We also have an idea how those differences lead to the differences in physical properties, and, in turn, how these differences in the physical properties lead to the phenotypic differences. We are starting to go all the way from the structural understanding of the different strains up to in vivo understanding of why they cause different behaviors inside the cell.”

Weissman noted that the findings offer a broader lesson to researchers studying prions and other proteins whose misfolding can cause disease. “Certainly, a bottom line from this study is that the rules of protein folding and the rules of protein misfolding are fundamentally different,” he said. “In many ways, we have to relearn basic principles of how proteins misfold. We have to forget many of the rules we learned from textbooks about protein folding because they are not necessarily applicable.

“We now appreciate that the same polypeptide can misfold into dramatically different conformations. These different conformations can lead to dramatic changes in the structure of the prion form. This difference in structure, in turn, can change the physical properties of prions, which can affect their ability to propagate.”

Ultimately Weissman hopes a better understanding of prion misfolding will lead to therapeutic approaches to diseases caused by misfolded proteins.

“We know that some protein conformations—not only for prion diseases but for the far more common diseases of misfolding like Alzheimer’s and Parkinson’s—seem to be very toxic, whereas others seem to be relatively neutral or even protective,” he said. “We would like to understand the structural basis for the difference between the infectious, toxic or dangerous forms of misfolded proteins, and the neutral or protective forms. And then ultimately, we could try to develop therapies in which we push proteins down the pathways of the less pathogenic or less dangerous conformations.”

Illustration: Brandon Toyama/ Weissman Lab, HHMI at UCSF