University Times

Humans, orangutans said to share ancestors

New evidence underscores the theory of human origin that suggests humans most likely share a common ancestor with orangutans, according to research from Pitt and the Buffalo Museum of Science.

Reporting in the June 18 edition of the Journal of Biogeography, Pitt anthropology professor Jeffrey H. Schwartz, president of the World Academy of Art and Science, and John Grehan, director of science at the Buffalo Museum, reject as “problematic” the popular suggestion, based on DNA analysis, that humans are related most closely to chimpanzees, which they maintain is not supported by fossil evidence.

Schwartz and Grehan scrutinized the hundreds of physical characteristics often cited as evidence of evolutionary relationships among humans and other great apes — chimps, gorillas and orangutans — and selected 63 that could be verified as unique within this group.

Of these features, the analysis found that humans shared 28 unique physical characteristics with orangutans, compared to only two features with chimpanzees, seven with gorillas and seven with all three apes. Gorillas and chimpanzees shared 11 unique characteristics.

Schwartz and Grehan then examined 56 features uniquely shared among modern humans, fossil hominids — ancestral humans such as Australopithecus — and fossil apes. They found that orangutans shared eight features with early humans and Australopithecus and seven with Australopithecus alone. The occurrence of orangutan features in Australopithecus contradicts the expectation generated by DNA analysis that ancestral humans should have chimpanzee similarities, Schwartz and Grehan write. Chimpanzees and gorillas were found to share only those features found in all great apes.

Schwartz and Grehan pooled humans, orangutans and the fossil apes into a new group called “dental hominoids,” named for their similarly thick-enameled teeth. They labeled chimpanzees and gorillas as African apes and wrote in the Journal of Biogeography that although they are a sister group of dental hominoids, “the African apes are not only less closely related to humans than are orangutans, but also less closely related to humans than are many” other fossil apes.

The researchers acknowledge, however, that early human and ape fossils are largely found in Africa, whereas modern orangutans are found in southeast Asia. To account for the separation, they propose that the last common human-orangutan ancestor migrated between Africa, Europe and Asia at some point that ended at least 12 million-13 million years ago. Plant fossils suggest that forests once extended from southern Europe, through central Asia, and into China prior to the formation of the Himalayas, Schwartz and Grehan write, proposing that the ancestral dental hominoid lived and roamed throughout this vast area; as the Earth’s surface and local ecosystems changed, descendant dental hominoids became geographically isolated from one another.

Schwartz and Grehan contend in the Journal of Biogeography that the clear physical similarities between humans and orangutans have long been overshadowed by molecular analyses that link humans to chimpanzees, but that those molecular comparisons are often flawed: There is no theory holding that molecular similarity necessarily implies an evolutionary relationship; molecular studies often exclude orangutans and focus on a limited selection of primates without an adequate “outgroup” for comparison, and molecular data that contradict the idea that genetic similarity denotes relation often are dismissed.

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Sustainability research funded

Pitt’s Mascaro Center for Sustainable Innovation has awarded a $40,000 grant to professors William Clark and Laura Schaefer of mechanical engineering and materials science for “Development of Smart Insulation for Building Retrofits.”

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Radiotherapy safe for cancer patients

Researchers from the University of Pittsburgh Cancer Institute (UPCI) have found that stereotactic body radiotherapy (SBRT) is safe for patients with recurrent head and neck cancers and may improve their quality of life. Results of the phase I study were reported in the International Journal of Radiation Oncology, Biology, Physics.

Each year approximately 500,000 cases of squamous cell carcinoma of the head and neck are diagnosed worldwide. While treatment has improved with advances in surgery, radiation and chemotherapy, more than half of patients will die from recurrent disease.

Treatment options for patients with recurrent disease are limited and, for many, surgery may not be an option, according to principal investigator Dwight E. Heron, professor of radiation oncology and director of radiation oncology services for UPMC Cancer Centers.

“Chemotherapy alone can provide this patient population some palliation and pain relief, but it doesn’t prolong survival,” said Heron. “A few patients may be able to receive additional radiation treatments, but head and neck cancers, by their very nature, develop in very delicate areas of the body, which provide significant retreatment challenges.”

SBRT uses CyberKnife technology, which delivers high doses of radiation with more precision than conventional techniques. Most patients complete treatment within 10 days.

In the trial, 31 patients with recurrent, inoperable head and neck cancers were treated over a two-week period. PET-CT also was used to develop an individualized radiation treatment plan for each patient, allowing radiation oncologists to more accurately target the cancer while sparing healthy tissue.

Heron noted SBRT treatment was well tolerated. No maximum tolerated dose was reached, and no toxicities occurred that caused researchers to limit the dosing.

“Ultimately, SBRT offers patients a better quality of life. Instead of having to go through six or seven weeks of treatments that are often associated with significant toxicities, patients can receive treatment over a shorter course and still get the same outcomes compared to the current standard of care,” said Heron.

Study co-authors included Robert L. Ferris, Michalis Karamousiz, Regiane S. Andrade, Erin L. Deeb, Steven Burton, William E. Gooding, Barton F. Branstetter, James M. Mountz, Jonas T. Johnson, Anthanassios Argiris, Jennifer R. Grandis and Stephen Y. Lai, all of UPCI.

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Emphysema enzyme fights lung infections

An enzyme known to play a key role in the development of emphysema serves as the first line of defense against bacterial infection of the lung, according to School of Medicine researchers, who also found that the antimicrobial activity comes from a small portion of the enzyme that is structurally and sequentially unique.

Their findings were published in the journal Nature.

Lead author A. McGarry Houghton, professor in the Division of Pulmonary, Allergy and Critical Care Medicine, said that prior to this discovery scientists thought that the enzyme, called macrophage elastase, matrix metalloproteinase-12 or MMP-12, which is produced in excess in smokers, didn’t do anything but degrade the lung’s elastic fibers, thereby contributing to the tissue destruction of emphysema.

“But we found that mice that didn’t have the gene to make this enzyme could not clear bacteria well and were more likely to die of infection,” he said. “They couldn’t make this small protein, which kills bacteria by poking holes in cell membranes.”

Steven D. Shapiro, chair of the Department of Medicine, said, “While not the initial purpose of this study, finding novel antimicrobial mechanisms is extremely important.” His research teams cloned the MMP-12 gene almost 20 years ago and conducted the work that showed its role in emphysema. “Many microorganisms have adapted to circumvent our current and stagnant arsenal of antibiotics. We must find new weapons so that we don’t fall back to the public health problems we had prior to penicillin.”

MMP-12 is stored in macrophages, the cells that swallow up invading bacteria. Macrophages are present in very high numbers in the lungs and the peritoneum, which is the lining of the abdomen.

When Staphylococcus aureus was injected into healthy and MMP-12-deficient mice, the two-week mortality rate was about the same. However, the amount of bacteria was much greater in the lungs of MMP-12-deficient mice. In models of pneumonia and peritonitis, MMP-12-deficient mice were much less likely to survive the infection.

“Our experiments also showed that while the MMP-12-deficient macrophages were able to ingest bacteria, they couldn’t kill them,” Houghton said. “The intracellular bacteria level escalated rather than diminished.”

The researchers then looked for what gave MMP-12 its antibacterial properties. While one portion of the enzyme degrades lung tissue in emphysema, another portion kills microbes.

Protein fragments were tested to identify a chain of 20 amino acids that could kill Staph aureus in culture dishes. “Humans, mice, rats and rabbits all have that special sequence and structure in MMP-12, but not in other MMPs,” Houghton noted.

The team plans to study whether the same part of the enzyme is able to kill viruses and fungi, and whether there are any connections between MMP-12’s roles in emphysema and infection defense.

Clinton S. Robbins, postdoctoral fellow in the Division of Pulmonary, Allergy and Critical Care Medicine, was among the study co-authors.

The research was supported by grants from the National Institutes of Health and Spanish and European public agencies.

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Hypothermia therapy protocol developed

UPMC neonatologist Richard Telesco, professor in the School of Medicine’s Department of Pediatrics, has developed the region’s first specialized protocol to expand the use of induced hypothermia to infants with hypoxic ischemic encephalopathy (HIE), a potentially fatal brain injury caused by a lack of oxygen near the time of birth. The protocol outlines how this treatment will be used at Children’s Hospital and Magee-Womens Hospital.

HIE occurs in 1-2 of every 1,000 infants who are carried to term. It is fatal in up to 40 percent of infants and is associated with long-term disabilities in up to 40 percent of those who survive. This lack of blood flow and oxygen leads to brain swelling, which in turn can cause a cascade of other issues including organ failure.

Until recently, there was no recognized therapy for HIE. Recent multicenter trials have demonstrated a benefit to cooling infants who have suffered from HIE, and the American Academy of Pediatrics has endorsed cooling when used within the practice of a defined protocol, such as UPMC has developed.

“For the best chance of success, infants should be treated with whole-body cooling within six hours of life,” Telesco said. “It’s vital that health professionals are made aware of this treatment so that it can be administered within that six-hour window. It has been extensively studied and found to be both safe and effective and reduces mortality or long-term disabilities in about 25 percent of infants.”

The hypothermia protocol requires that patients with HIE be greater than 36 weeks’ gestation; have a birth weight greater than 1.8 kilograms, and be younger than 6 hours old. Patients who fit that and certain other medical criteria will be cooled by 6.3 degrees, to 92.3 degrees, for a period of 72 hours.

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