Primary intracranial leiomyosarcoma in an HIV-infected patient

Primary intracranial leiomyosarcomas are rare tumors arising from the mesenchymal cells of the dura matter or the cerebral blood vessels. Only 14 cases of primary intracranial leiomyosarcoma are reported in the literature. We report a case of primary intracranial leiomyosarcoma in an human immunodeficiency virus-positive patient with a CD4 count of 14 cells/μL. Additionally, in-situ hybridization of Epstein–Barr virus (EBV) early RNA stained sections highlighted the tumor cells, consistent with the presence of EBV. Review of the literature strongly suggests an association between AIDS, EBV, and primary intracranial leiomyosarcoma. Given the paucity of information in the literature, we review possible chemotherapeutic agents for treatment of primary intracranial leiomyosarcoma in patients refractory to surgical resection and radiation therapy.

source: international journal of oncology

Oral premalignant lesions: from a clinical perspective

In this review article, the clinical and histopathological characteristics of oral premalignant lesions, and primarily oral leukoplakia, are noted and the risk factors for malignant transformation of oral leukoplakia are discussed. Malignant transformation rates of oral leukoplakia range from 0.13 to 17.5%. The risk factors of malignant transformation in the buccal mucosa and labial commissure are male gender with chewing tobacco or smoking in some countries such as India, or older age and/or being a non-smoking female in other countries. Some authors have reported that leukoplakia on the tongue or the floor of the mouth showed a high risk of malignant transformation, although others have found no oral subsites at high risk. In concurrence with some authors, the authors of this review view epithelial dysplasia as an important risk factor in malignant transformation; however, there are conflicting reports in the literature. Many authors believe that nonhomogeneous leukoplakia is a high risk factor without exception, although different terms have been used to describe those conditions. The large size of lesions and widespread leukoplakia are also reported risk factors. According to some studies, surgical treatment decreased the rate of malignant transformation; however, many review articles state that no definitive treatment including surgery can decrease the malignant transformation rate of oral leukoplakia because of the lack of randomized control trials of treatment. Tobacco chewing and smoking may be causative agents for cancerization of oral leukoplakia in some groups, and evidence for a role of human papilloma virus in the malignant transformation of oral leukoplakia is inconsistent. Further research to clarify its role in malignant transformation is warranted.


Lucy Had a Spring in Her Step

The petite 3.2-million-year-old skeleton called Lucy is one of the most famous and most complete of human ancestors. But she was found without her foot bones, so researchers have debated whether she walked as we do or retained some apelike adaptations for climbing in trees that altered her gait. Now, a 3.2-million-year-old foot bone from a member of Lucy’s species, Australopithecus afarensis, reveals that this hominin was no flat foot: It had already evolved arches and a stiff midfoot similar to living humans. That means if Lucy were alive today, she could fit in high heels or march for miles without breaking her feet. “This discovery puts the spring back into afarensis‘s step,” says co-author Donald Johanson of the Institute of Human Origins at Arizona State University (ASU), Tempe.

When Johanson and his colleagues discovered Lucy’s partial skeleton in 1974, it showed that she walked upright, confirming that our ancestors did so before their brains started getting larger. But did she walk upright most of the time like a modern human or still spend plenty of time in the trees evading predators? Mysterious footprints left at Laetoli in Tanzania show that a hominin of this time, 3.7 million years ago, did indeed have arches in its feet. But researchers couldn’t be sure who left those prints, because it wasn’t clear whether A. afarensis had an arch, says co-author William Kimbel, a paleoanthropologist at ASU.

Now, researchers think they’ve solved the mystery of Lucy’s footwork, thanks to an analysis of about 35 new individuals of A. afarensis uncovered at Hadar, Ethiopia, in the past 15 years. The key is the fourth metatarsal, a long bone that connects the toe to the rest of the foot. The way the two ends of the bone were twisted in relation to each other in the fossils suggests that when one end was on the ground, the other end was raised about 8˚ to attach to the rest of the foot, says lead author Carol Ward, a paleoanthropologist at the University of Missouri, Columbia, in a study reported online today in Science. This torsion is found in feet with well-formed arches, which are stiff enough to use the foot like a lever to push off the ground but flexible enough to also work like shock absorbers.

The bone also shows that A. afarensis had abandoned the flexible midfoot that apes use to grasp tree branches, in favor of an arch that makes upright walking more efficient. “This tells you that climbing in the trees was not nearly as important as walking on the ground,” says Ward.

Paleoanthropologist Will Harcourt-Smith of the American Museum of Natural History in New York City isn’t willing to go that far. Although he agrees that A. afarensis had some arching, it may have lacked the most important arching on the inside of the foot. Lucy’s fingers and toes also were more curved than those of living humans and her shoulder was more apelike—traits useful for tree-climbing. “It’s hard to envisage an animal that had entirely made the leap to full, obligate bipedalism,” he says.

But paleoanthropologist Jeremy DeSilva of Boston University says that the new foot bone, along with a “laundry list of other features of the lower limb” make it more likely that A. afarensis was a “terrestrial biped with little time spent in the trees.” It also suggests that it was indeed A. afarensis that walked in the mud at Laetoli. “Finally,” says paleoanthropologist Bruce Latimer of Case Western Reserve University in Cleveland, Ohio, “we can put the mystery hominid at Laetoli to rest.”

lccysource: science now

The Staph Bug’s


Targeting the RNA recycling machinery of Staphylococcus aureus could lead to a new type of antibiotic.
Credit: Janice Haney Car/CDC

Staphylococcus aureus is a hard bug to kill. The bacterium is responsible for more U.S. deaths each year than HIV/AIDS, in part because it quickly develops resistance to antibiotics. Scientists have had a hard time figuring out how it ticks, but now researchers think they may have found a way to conquer S. aureus by blocking its ability to perform a critical task: recycling.

Recycling is so important that even bacteria do it. They chop up the RNA blueprints needed to design proteins and reassemble them into new instructions. Researchers have known for more than 20 years how so-called gram-negative bacteria like Escherichia coli degrade and recycle their RNA. But the process for gram-positive bacteria like S. aureus has remained unclear.

In the new study, researchers led by Paul Dunman, an infectious disease specialist at the University of Rochester in New York, identified genes that were more active when S. aureus was rapidly recycling RNA. Blocking the activity of a protein known as RnpA stopped the recycling, indicating that Dunman’s team had found a key enzyme.

The discovery of RnpA is important, says Dunman, because it provides a new target for antibiotic development. If a bacterium couldn’t recycle its RNA, two major problems would arise. For one, Dunman says, the bug would waste energy following outdated instructions and turning RNA into proteins it no longer needed. More important, it would run out of raw material with which to print its instructions, grinding everything in the cell to an abrupt halt. “If you can stop the enzymes involved in that process with a small molecule or chemical,” says Dunman, “that chemical could be an antibiotic.”

Toward that end, the team screened nearly 30,000 small molecules to identify compounds that inhibit the action of RnpA. The researchers found 14 that did the trick, but one molecule—named RNPA1000—was especially effective against S. aureus. RNPA1000 killed cells from all 12 major strains of methicillin-resistant S. aureus (MRSA), a major scourge of hospitals in the United States and elsewhere. It was also effective against strains of antibiotic-resistant, gram-positive Streptococcus pneumoniae, S. pyogenes, and Enterococcus faecium, which cause diseases from meningitis to cardiac infections.

The team showed that RNPA1000 can boost the potency of antibiotics already on the market, although they don’t yet know how. The chemical also kills S. aureus biofilms, which are a common cause of infection on implanted catheters and other medical devices and are notoriously resistant to the actions of antibiotics.

The drug worked in mice, too. Half of S. aureus-infected mice recovered from their infections when treated with RNPA1000, whereas none of the untreated mice did, the team reports online today in PLoS Pathogens.

RNPA1000 did show some toxicity when applied at high doses in human cells, so Dunman’s group is searching for compounds closely related to RNPA1000 that can still inhibit RnpA but without the toxic side effects.

What’s more, says Dunman, bacteria will eventually develop resistance against any antibiotic, no matter how methodically selected. RNPA1000 is no exception, he says, “but the frequency [of resistance] in a laboratory setting is extremely, extremely low.” This means that bacteria should develop resistance to RNPA1000 more slowly than other antibiotics.

Robert Daum, director of the MRSA Research Center at the University of Chicago in Illinois, calls the study “creative” and says it provides a new route to target the MRSA epidemic. “What’s important about this to me is not necessarily that this very work might be the answer to the problem,” he says, “but that we look at how this bug does its dirty work in patients and how can we stop that.”

source” science now

ScienceNOW – Up to the minute news from Science Outcast Planets Could Support Life

If aliens exist, where are they? Many astronomers look to the nearest stars, in the hope that they harbor a warm, wet planet like Earth. But now a pair of researchers believe extraterrestrial life could exist on a rogue planet that has been ejected from its birthplace.

Astronomers have never spotted a rogue planet with certainty, but computer simulations suggest that our galaxy could be teeming with them. Slingshotted out of their planetary system by the gravity of a bigger planet, these lone worlds zoom far from their parent suns, slowly freezing in the cold of outer space. Any water fit for life would freeze, too. Yet in a paper submitted to The Astrophysical Journal Letters, planetary scientists Dorian Abbot and Eric Switzer of the University of Chicago in Illinois suggest that a rogue planet could support a hidden ocean under its blanket of ice, kept warm by geothermal activity.

They call such a world a Steppenwolf planet after a novel by the German-Swiss author Hermann Hesse, because “any life … would exist like a lone wolf wandering the galactic steppe.” If Steppenwolf planets do exist, there’s a chance that some of them could be lurking in space between Earth and nearby stars. If so, they might be a more realistic human destination for the search of alien life than another planetary system, which would be at least several light-years away. There is even a chance—albeit very small—that a Steppenwolf planet crashing into our solar system billions of years ago was the origin of life on Earth.

Abbot and Switzer came to their conclusion by simulating an isolated planet between 1/10th and 10 times the size of Earth. By comparing the rate at which heat would be lost through an ice shell with the rate at which heat would be produced by geothermal activity, they calculated that a planet with Earth’s composition of rock and water but three times as big would generate enough heat to maintain a hidden ocean. If the planet had much more water than Earth, say Abbot and Switzer, it would need to be only about a third as big as our planet. “Several kilometers of water ice make an excellent blanket that could be sufficient to support liquid water at its base,” says Switzer.

The Chicago researchers are not the first to consider the possibility of liquid water on rogue planets. In 1999, planetary scientist David Stevenson of the California Institute of Technology in Pasadena, calculated that liquid water could exist if a planet had a dense atmosphere of hydrogen—so dense that a greenhouse effect would trap warmth on the surface without the need for ice. But Abbot thinks the new result is more surprising because they are considering a more generic planet, without an extraordinary atmosphere.

“This is certainly an interesting study regarding the extent of the possible locations where life could arise, or be sustained, in the universe,” says David Ehrenreich, a planetary scientist at the Joseph Fourier University in Grenoble, France. “However, it will certainly be very difficult to actually detect life on such a world, since it would be buried under an ice shell.”

Switzer admits detection would be difficult. An astronomer would need to spot a Steppenwolf planet by looking for its infrared emission to see if it is as warm as he and Abbot predict. But at present, even the best observatories could detect rogue planets only within about 100 billion miles of Earth—not a huge distance in astronomical terms—and Switzer says the probability of a Steppenwolf planet existing in this range is just one in a billion.

Still, as planetary scientist Gaetano Di Achille of the University of Colorado, Boulder, points out, that might mean that the first occupied planet humans set foot on is not in another planetary system, but in the lonely depths of outer space. “If the hypothesis of oceans on rogue planets is correct, we will certainly have to expand the inventory of places with a high potential for life,” he says.

source: science now