A Plague Like No Other
Although the bacterium that causes the plague – Yersinia pestis -- is still around and infects about 2,000 people worldwide each year, it appears that the highly lethal version responsible for the "Black Death" in 14th-century Europe has been relegated to the history books.
Verena Schuenemann, of the University of Tubingen in Germany, and colleagues extracted DNA from the bones and teeth of 109 people from the East Smithfield mass burial site in London – all victims of the Black Death buried from 1348 to 1350. As a control, they also retrieved DNA from 10 people buried at another site before the time of the plague. Y. pestis genes were found in samples from the mass burial site but not the control site.
The researchers found that, although there were some similarities between the ancient and modern Y. pestis genomes, the bacterium responsible for the medieval plague had important differences from present-day isolates.
"Our data reveal that the Black Death in medieval Europe was caused by a variant of Y. pestis that may no longer exist," the researchers wrote in the Proceedings of the National Academy of Sciences.
How CRP May Be Like Spider-Man
Readers of old Spider-Man comics may remember when, thanks to newspaper publisher J. Jonah Jameson's relentless hostility, New Yorkers thought the Webhead was a criminal, even as he was actually fighting crime.
It could be that C-reactive protein (CRP) has been similarly misperceived, according to new research led by Alexander J. Szalai, PhD, of the University of Alabama at Birmingham.
The protein is widely used as a marker of inflammation in rheumatoid arthritis and other conditions and has been assumed to play some role in promoting symptoms.
But Szalai and colleagues found that mice bred to lack CRP actually developed collagen-induced arthritis that was more severe and progressed more quickly than did transgenic mice with human CRP or wild-type animals. Not only that, but the inflammatory response associated with collagen-induced arthritis was "dramatically attenuated" in the transgenic CRP-enhanced mice.
Writing in the September issue of Arthritis & Rheumatism, the researchers noted that this seeming paradox disappears if CRP is not just a marker of inflammation, but an anti-inflammatory factor that is upregulated in the presence of inflammation.
"At least in mice, CRP actively participates in these processes, as opposed to being merely associated with these processes," they wrote.
They also suggested that baseline CRP levels in healthy people could be inversely correlated with their risk for developing rheumatoid arthritis and called for an observational study to explore the possibility.
Old Dads' Bad Seed
Fathering a child late in life boosts its risk of schizophrenia and other neurodevelopmental disease, which may be due to genetic copy number problems, according to a report in Translational Psychiatry by researchers at several Australian labs.
In mice, young mothers with older fathers gave birth to offspring with six distinct copy number variations whereas none of their offspring carried these genetic mutations when the fathers were young.
Two of the variants were associated with behavioral or neuroanatomical features in the offspring.
In humans, those variants have been linked to autism as well as schizophrenia and brain development.
"The age of parenthood is increasing in many societies, and thus it is feasible that the incidence of paternal-age related de novo copy number variations will increase over time," the researchers warned in the paper.
Telomeres: Clues to the Long Story of Cancer
A major growth-preserving mechanism for cancer cells plays a role in the development of substantially more cancer types than previously recognized, investigators reported.
Once believed limited to a few sarcomas and astrocytomas, the alternative lengthening of telomeres (ALT) mechanism has shown up in tissue specimens from a variety of common epithelial malignancies.
As reported in The American Journal of Pathology, investigators found ALT in 228 of 6,110 (3.73%) human tumor specimens versus none of 541 specimens of benign neoplasms and 264 samples of normal tissue. ALT-positive specimens included carcinomas of the bladder, cervix, endometrium, esophagus, gallbladder, kidney, liver, and lung.
The results have potential therapeutic implications, as ALT-positive tumors have been predicted to exhibit resistance to drugs that target the growth-maintenance enzyme telomerase, said author Alan K. Meeker, PhD, of Johns Hopkins, in a statement. Evaluation of several anti-telomerase drugs has progressed to phase I/II clinical trials, he added.
The study also led to the first reported identification of ALT in medulloblastomas, oligodendrigliomas, meningiomas, schwannomas, and pediatric glioblastoma multiforme.
As DNA end caps of chromosomes, telomeres protect chromosomes from degradation and fusion with other chromosomes. With each cycle of cell divisions, telomeres shorten, eventually leading to normal cell death or apoptosis. ALT reverses the process and causes telomeres to lengthen, preventing apoptosis and promoting unrestrained cell growth.