Rice method is first to yield cartilage-like cells, engineer human cartilage
HOUSTON, Sept. 6, 2007 – Rice University biomedical engineers have developed a new technique for growing cartilage from human embryonic stem cells, a method that could be used to grow replacement cartilage for the surgical repair of knee, jaw, hip, and other joints.
“Because native cartilage is unable to heal itself, researchers have long looked for ways to grow replacement cartilage in the lab that could be used to surgically repair injuries,” said lead researcher Kyriacos A. Athanasiou, the Karl F. Hasselmann Professor of Bioengineering. “This research offers a novel approach for producing cartilage-like cells from embryonic stem cells, and it also presents the first method to use such cells to engineer cartilage tissue with significant functional properties.”
The results are available online and slated to appear in the September issue of the journal Stem Cells. The study involved cells from an NIH-sanctioned stem cell line.
Using a series of stimuli, the researchers developed a method of converting the stem cells into cartilage cells. Building upon this work, the researchers then developed a process for using the cartilage cells to make cartilage tissue. The results show that cartilages can be generated that mimic the different types of cartilage found in the human body, such as hyaline articular cartilage — the type of cartilage found in all joints — and fibrocartilage — a type found in the knee meniscus and the jaw joint. Athanasiou said the results are exciting, as they suggest that similar methods may be used to convert the stem cell-derived cartilage cells into robust cartilage sections that can be of clinical usefulness.
Tissue engineers, like those in Athanasiou’s research group, are attempting to unlock the secrets of the human body’s regenerative system to find new ways of growing replacement tissues like muscle, skin, bone and cartilage. Athanasiou’s Musculoskeletal Bioengineering Laboratory at Rice University specializes in growing cartilage tissues.
The idea behind using stem cells for tissue engineering is that these primordial cells have the ability to become more than one type of cell. In all people, there are many types of “adult” stem cells at work. Adult stem cells can replace the blood, bone, skin and other tissues in the body. Stem cells become specific cells based upon a complex series of chemical and biomechanical cues, signals that scientists are just now starting to understand.
Unlike adult stem cells, which can become only a limited number of cell types, embryonic stem cells can theoretically become any type of cell in the human body.
Athanasiou’s group has been one of the most successful in the world at studying cartilage cells and, especially, engineering cartilage tissues. He said that for his research the primary advantage that embryonic stem cells have over adult stem cells is their ability to remain malleable.
“Identifying a readily available cell source has been a major obstacle in cartilage engineering,” Athanasiou said. “We know how to convert adult stem cells into cartilage-like cells. The more problematic issue comes in trying to maintain a ready stock of adult stem cells to work with. These cells have a strong tendency to convert from stem cells into a more specific type of cell, so the clock is always ticking when we work with them.”
By contrast, Athanasiou said his research group has found it easier to grow and maintain a stock of embryonic stem cells. Nonetheless, he is quick to point out that there is no clear choice about which type of stem cell works best for cartilage engineering.
“We don’t know the answer to that,” Athanasiou said. “It’s extremely important that we study all potential cell candidates, and then compare and contrast those studies to find out which works best and under what conditions. Keep in mind that these processes are very complicated, so it may well be that different types of cells work best in different situations.”
Athanasiou began studying embryonic stem cells in 2005. Since funding for the program was limited, he asked two new graduate students in his group if they were interested in pursuing the work as a secondary project to their primary research. Those students, Eugene Koay and Gwen Hoben, are co-authors of the newly published study. Both are enrolled in the Baylor College of Medicine Medical Scientist Training Program, a joint program that allows students to concurrently earn their medical degree from Baylor while undertaking Ph.D. studies at Rice.
“Eugene and Gwen are both outstanding students,” Athanasiou said. “Each earned their undergraduate degree from Rice and each worked in my laboratory as undergraduate students. They have chosen to do this research because they think this may represent the future of regenerative medicine.”
The research was funded by Rice University.
Contact: Jade Boyd
Study of 123 ungulate species shows males are born with smaller molars, expecting shorter lives
In the September issue of The American Naturalist, Juan Carranza (Biology and Ethology Unit, University of Extremadura, Spain) and Javier Pérez-Barbería (Macaulay Institute, United Kingdom) offer a new explanation for why males of ungulate species subjected to intense competition are born with lower survival expectancies than females. The research reveals that male ungulates have smaller molars relative to their body size – and hence less durable teeth that will wear out sooner, which might contribute to their shorter lives compared with females.
Roaring male Iberian red deer with females
(photograph by Juan Carranza)
Natural selection favors reproduction rather than survival; the cost of reproduction compromises survival. Males of species subjected to intense male-male competition for access to females are known to have shorter life expectancies than females. Earlier aging in males might be related to higher reproductive costs, especially when lifetime reproductive success in males takes place within the few years when they can win contests and maintain their dominance.
By comparing body and dental size of males and females of 123 species of ungulates, the authors offer another compelling explanation for why male ungulates lead shorter lives. They estimated the pattern of change of these traits along the evolutionary development of the group and found that for species where a single male has many females and where the males and females are different sizes, the rate of increase of dental size was lower than that of body size. As a result, smaller teeth (in comparison to body size) are produced in males. It is possible that natural selection did not produce larger, more durable teeth because there was no reproductive return from it, since males in these species do not generally increase their success by living longer after prime age.
“These findings,” the authors state, “provide us with interesting insights into how natural and sexual selection design our bodies and their longevity.”
Juan Carranza and F. Javier Pérez-Barbería, “Sexual selection and senescence: male size-dimorphic ungulates evolved relatively smaller molars than females”, The American Naturalist (2007) volume 170:370–380. DOI: 10.1086/519852
As a retired advanced weather spotter for the National Weather Service in Pontiac Michigan, I have observed numerous weather phenomon. I have “ball lightning” on video.
St. Elmo’s Fire is an electrical weather phenomenon in which visible plasma is created by a coronal discharge originating from a grounded object in an atmospheric electric field (such as those generated by thunderstorms).
St. Elmo’s fire is named after Erasmus of Formiae (also called St. Elmo), the patron saint of sailors (who sometimes held its appearance to be auspicious). Alternatively, Peter Gonzalez is said to be the St. Elmo after whom St. Elmo’s fire has its name.
Ball lightning is often erroneously identified as St. Elmo’s Fire. They are separate and distinct meteorological phenomena.(Wikipedia)
Physically, St. Elmo’s Fire is a bright blue or violet glow, appearing like fire in some circumstances, from tall, sharply pointed structures such as lightning rods, masts, spires and chimneys, and on aircraft wings. St. Elmo’s Fire can also appear on leaves, grass, and even at the tips of cattle horns. Often accompanying the glow is a distinct hissing or buzzing sound.
Benjamin Franklin correctly observed in 1749 that it is electric in nature.
Although referred to as “fire”, St. Elmo’s Fire is in fact plasma. The electric field around the object in question causes ionization of the air molecules, producing a faint glow easily visible in low-light conditions. Approximately 1,000 – 30,000 volts per centimeter is required to induce St. Elmo’s Fire; however, this number is greatly dependant on the geometry of the object in question. Sharp points tend to require lower voltage levels to produce the same result because electric fields are more concentrated in areas of high curvature, thus discharges are more intense at the end of pointed object.
The nitrogen and oxygen in earth’s atmosphere causes St. Elmo’s Fire to fluoresce with blue or violet light; this is similar to the mechanism that causes neon lights to glow.
Whole-genome transfer raises questions about evolution, sequencing
Scientists at the University of Rochester and the J. Craig Venter Institute have discovered a copy of the entire genome of a bacterial parasite residing inside the genome of its host species.
The finding, reported in today’s Science, suggests that lateral gene transfer—the movement of genes between unrelated species—may happen much more frequently between bacteria and multicellular organisms than scientists previously believed, posing dramatic implications for evolution.
Such large-scale heritable gene transfers may allow species to acquire new genes and functions extremely quickly, says Jack Werren, a principle investigator of the study.
Wolbachia in yellow with host cells in red.
The results also have serious repercussions for genome-sequencing projects. Bacterial DNA is routinely discarded when scientists are assembling invertebrate genomes, yet these genes may very well be part of the organism’s genome, and might even be responsible for functioning traits.
“This study establishes the widespread occurrence and high frequency of a process that we would have dismissed as science fiction until just a few years ago,” says W. Ford Doolittle, Canada Research Chair in Comparative Microbial Genomics at Dalhousie University, who is not connected to the study. “This is stunning evidence for increased frequency of gene transfer.”
Fruit fly ovaries showing wolbachia infection within.
“It didn’t seem possible at first,” says Werren, professor of biology at the University of Rochester and a world-leading authority on the parasite, called Wolbachia. “This parasite has implanted itself inside the cells of 70 percent of the world’s invertebrates, coevolving with them. And now, we’ve found at least one species where the parasite’s entire or nearly entire genome has been absorbed and integrated into the host’s. The host’s genes actually hold the coding information for a completely separate species.”
Wolbachia may be the most prolific parasite in the world—a “pandemic,” as Werren calls it. The bacterium invades a member of a species, most often an insect, and eventually makes its way into the host’s eggs or sperm. Once there, the Wolbachia is ensured passage to the next generation of its host, and any genetic exchanges between it and the host also are much more likely to be passed on.
Since Wolbachia typically live within the reproductive organs of their hosts, Werren reasoned that gene exchanges between the two would frequently pass on to subsequent generations. Based on this and an earlier discovery of a Wolbachia gene in a beetle by the Fukatsu team at the University of Tokyo, Japan, the researchers in Werren’s lab and collaborators at J. Craig Venter Institute (JCVI) decided to systematically screen invertebrates. Julie Dunning-Hotopp at JCVI found evidence that some of the Wolbachia genes seemed to be fused to the genes of the fruitfly, Drosophila ananassae, as if they were part of the same genome.
Michael Clark, a research associate at Rochester then brought a colony of ananassae into Werren’s lab to look into the mystery. To isolate the fly’s genome from the parasite’s, Clark fed the flies a simple antibiotic, killing the Wolbachia. To confirm the ananassae flies were indeed cured of the wolbachia, Clark tested a few samples of DNA for the presence of several Wolbachia genes.
To his dismay, he found them.
“For several months, I thought I was just failing,” says Clark. “I kept administering antibiotics, but every single Wolbachia gene I tested for was still there. I started thinking maybe the strain had grown antibiotic resistance. After months of this I finally went back and looked at the tissue again, and there was no Wolbachia there at all.”
Clark had cured the fly of the parasite, but a copy of the parasite’s genome was still present in the fly’s genome. Clark was able to see that Wolbachia genes were present on the second chromosome of the insect.
Clark confirmed that the Wolbachia genes are inherited like “normal” insect genes in the chromosomes, and Dunning-Hotopp showed that some of the genes are “transcribed” in uninfected flies, meaning that copies of the gene sequence are made in cells that could be used to make Wolbachia proteins.
Werren doesn’t believe that the Wolbachia “intentionally” insert their genes into the hosts. Rather, it is a consequence of cells routinely repairing their damaged DNA. As cells go about their regular business, they can accidentally absorb bits of DNA into their nuclei, often sewing those foreign genes into their own DNA. But integrating an entire genome was definitely an unexpected find.
Werren and Clark are now looking further into the huge insert found in the fruitfly, and whether it is providing a benefit. “The chance that a chunk of DNA of this magnitude is totally neutral, I think, is pretty small, so the implication is that it has imparted of some selective advantage to the host,” says Werren. “The question is, are these foreign genes providing new functions for the host” This is something we need to figure out.”
Evolutionary biologists will certainly take note of this discovery, but scientists conducting genome-sequencing projects around the world also may have to readjust their thinking.
Before this study, geneticists knew of examples where genes from a parasite had crossed into the host, but such an event was considered a rare anomaly except in very simple organisms. Bacterial DNA is very conspicuous in its structure, so if scientists sequencing a nematode genome, for example, come across bacterial DNA, they would likely discard it, reasonably assuming that it was merely contamination—perhaps a bit of bacteria in the gut of the animal, or on its skin.
But those genes may not be contamination. They may very well be in the host’s own genome. This is exactly what happened with the original sequencing of the genome of the anannassae fruitfly—the huge Wolbachia insert was discarded from the final assembly, despite the fact that it is part of the fly’s genome.
In the early days of the Human Genome Project, some studies appeared to show bacterial DNA residing in our own genome, but those were shown indeed to be caused by contamination. Wolbachia is not known to infect any vertebrates such as humans.
“Such transfers have happened before in the distant past” notes Werren. “In our very own cells and those of nearly all plants and animals are mitochondria, special structures responsible for generating most of our cells’ supply of chemical energy. These were once bacteria that lived inside cells, much like Wolbachia does today. Mitochondria still retain their own, albeit tiny, DNA, and most of the genes moved into the nucleus in the very distant past. Like wolbachia, they have passively exchanged DNA with their host cells. It’s possible wolbachia may follow in the path of mitochondria, eventually becoming a necessary and useful part of a cell.
“In a way, wolbachia could be the next mitochondria,” says Werren. “A hundred million years from now, everyone may have a wolbachia organelle.”
“Well, not us,” he laughs. “We’ll be long gone, but wolbachia will still be around.”
This research was funded by the National Science Foundation.
Analysis of 43 US cities during 1918-1919 Spanish flu pandemic uncovers strong link between social restrictions and lower death rates
ANN ARBOR, Mich. — Although physicians have imposed quarantine orders since at least 1374, when the Port of Venice officially isolated foreigners and shippers for 40 days to keep out infectious scourges, there has been no definitive evidence that public health measures like quarantining the sick and isolating people after exposure to ill people would save lives during an influenza pandemic.
In a study published in the Aug. 8 Journal of the American Medical Association, a team of University of Michigan medical historians and epidemiologists from the federal Centers for Disease Control and Prevention say that social restrictions allowed 43 U.S. cities to save thousands of lives during the Spanish influenza pandemic of 1918-1919.
Although these urban communities had neither effective vaccines nor antiviral medicines, they were able to organize and execute a suite of classic public health measures – called non-pharmaceutical interventions or NPIs – before the pandemic gained full force.
The new study finds that cities whose NPIs were sustained and layered with multiple tactics had the best outcomes. In addition to quarantine and isolation, the NPIs examined in this study were school closures and cancellation of public gatherings.
“Public health is everyone’s responsibility. In a world faced by the threat of newly emerging and re-emerging infectious diseases, it is critical to determine if costly and potentially socially harsh NPI measures can save lives and reduce the numbers of those infected,” says lead author Howard Markel, M.D., Ph.D., the George E. Wantz Distinguished Professor of the History of Medicine, professor of pediatrics and communicable diseases, and director of the U-M Center for the History of Medicine. “Now we know the answer is ‘yes.’ ”
Markel adds that in today’s world, implementing these measures in a layered, sustained fashion would also provide a cushion of time for the development and distribution of effective vaccines and antivirals, while reducing the crush on essential infrastructure.
“By better understanding what worked in the past, we can better prepare for the future,” says senior author Martin Cetron, M.D., director of the CDC’s Division of Global Migration and Quarantine. “Communities that were most successful during the 1918 pandemic quickly enacted a variety of measures. Those planning for the next pandemic need to carefully consider how to best use these strategies to protect people and decrease the potential impact of the next pandemic in their communities.”
The 43 cities in the study were scattered from coast to coast and represented a combined population of approximately 23 million. In an exhaustive review of 1,144 primary and secondary sources that included U.S. census data, municipal records, newspapers and handbills covering a 24-week period – Sept. 8, 1918 through Feb. 22, 1919 – the researchers identified which NPIs were used in each city and when officials turned them on and off.
Using both actual death rates from pneumonia and influenza, and baseline rates for what would have been normal without a pandemic, the researchers found there were 115,340 excess pneumonia and influenza deaths attributable to the pandemic in these cities during the period studied. In comparing the death rates to when NPIs were turned on and off, they found that NPIs did mitigate the death rate, with a statistically significant association between increased duration of NPIs and reduced mortality.
Further, they discovered that city-to-city variation in mortality was associated with the timing, duration and combination of NPIs. St. Louis, Missouri, for example, closed schools and cancelled public gatherings relatively early in the pandemic and sustained these measures for about 10 weeks. The analysis shows that St. Louis had one of the largest drops in mortality while the NPIs were in force.
As a whole, the study’s findings contrast markedly with the conventional wisdom that the Spanish Flu ravaged the United States and elsewhere, with little that could be done to stop its deadly toll.
Markel predicts that NPI measures will be socially painful in the next pandemic, but that the public’s acceptance of NPIs is essential.
“We need to have informed concern about what to do in a pandemic – and why,” concludes Markel.
Citation: JAMA, Nonpharmaceutical Interventions Implemented by US Cities During the 1918 -1919 Influenza Pandemic, Aug. 8, 2007, p. 644-654, Vol. 298, No. 6.
Other collaborators on the research were Alexandra Minna Stern, Ph.D., associate director, Center for the History of Medicine; J. Alexander Navarro, Ph.D., senior researcher, Center for the History of Medicine; Joseph R. Michalsen, research associate, Center for the History of Medicine; Alexandra Sloan, research associate, Center for the History of Medicine; and Harvey B. Lipman, Ph.D., (insert title), Centers for Disease Control and Prevention.
This work was funded by the Centers for Disease Control and Prevention and conducted by the University of Michigan Center for the History of Medicine and the CDC Division of Global Migration and Quarantine.
The complete bibliography of the 1,144 primary and secondary sources is available as an online supplement at http://www.cdc.gov/ncidod/dq/index.htm. The supplement provides access to data specific to each of the 43 cities.
The Center for the History of Medicine also has a Web-based source of materials that cover the 1918-919 influenza pandemic, which can be viewed at http://www.med.umich.edu/medschool/chm/influenza/.
More information about community strategies for pandemic influenza is available at http://www.pandemicflu.gov/plan/community/commitigation.html.
The 43 cities examined in this study were:
CA: Los Angeles, Oakland, San Francisco
CT: New Haven
LA: New Orleans
MA: Boston, Cambridge, Fall River, Lowell, Worcester
MI: Grand Rapids
MN: Minneapolis, St. Paul
MO: Kansas City, St. Louis
NY: Albany, Buffalo, New York, Rochester, Syracuse
OH: Cincinnati, Cleveland, Columbus, Dayton, Toledo
PA: Philadelphia, Pittsburgh
WA: Seattle, Spokane
Contact: Mary Beth Reilly
University of Michigan Health System
In spite that the causes of depression have not still been fully identified, scientists acknowledge that genetic and environmental factors play a common role in the onset of this disorder. One of the environmental risk factors more often related to depression is exposure to threatening life events. On the other side, from a genetic point of view, the serotonin transporter gene, with a crucial role in communication between neurons, could predispose to depression.
An international group of scientists, headed by professors Jorge Cervilla Ballesteros and Blanca Gutiérrez Martínez, from the department of Legal Medicine, Toxicology and Psychiatry of the University of Granada, has recently published in the prestigious journal Molecular Psychiatry the pioneering study PREDICT-gene, confirming the relation between allele s in the serotonin transporter gene and exposure to threatening life events in the onset of depression. The study proves, for a population sample accounting for gender, age and family history of psychiatric disorders, that 24% of the Spanish population, comprising people with the s/s genotype, need minimal exposure to threatening life events, unlike individuals with s/l or l/l genotypes, thus confirming the relation between genetic and environmental factors in this mental disorder.
The most important consequence of research on interaction between genetic and environmental factors is that, in a foreseeable future, scientists will be able to produce measures to predict response to antidepressants taking into account each individual’s genotype, i. e. they will be able to design tailor-made drugs according to each person’s genetic configuration and their exposure to environmental factors.
The research group headed by professor Cervilla Ballesteros and Gutiérrez Martínez is currently working at the University of Granada to open roads for psycho-pharmaco-genetics, a field that will allow for individual treatments, tailor-made drugs, for each patient with depression, a disorder affecting one in every five Spaniards visiting the doctor’s.
This study is framed in the international project PREDICT and is funded by the European Union and the Spanish Ministry of Education and Science. One of its most important novelties is that it has been carried out through a very representative sample: a total of 737 people agreed to participate in the genetic tests, with ages ranging from 18 to 75, patients of nine primary care centres in the South of Spain. That is why this is the first representative population-based replication of earlier research, as until now research had been done into restricted population samples, comprising only women, adolescents, twins or people with affective disorders.
Contact: Professor Jorge Cervilla Ballesteros
Universidad de Granada
The most accurate measures of European daily temperatures ever indicate that the length of heat waves on the continent has doubled and the frequency of extremely hot days has nearly tripled in the past century. The new data shows that many previous assessments of daily summer temperature change underestimated heat wave events in western Europe by approximately 30 percent.
Paul Della-Marta and a team of researchers at the University of Bern in Switzerland compiled evidence from 54 high-quality recording locations from Sweden to Croatia and report that heat waves last an average of 3 days now—with some lasting up to 4.5 days—compared to an average of around 1.5 days in 1880. The results are published 3 August in the Journal of Geophysical Research-Atmospheres, a publication of the American Geophysical Union. The researchers suggest that their conclusions contribute to growing evidence that western Europe’s climate has become more extreme and confirm a previously hypothesized increase in the variance of daily summer temperatures since the 19th century.
The study adds evidence that heat waves, such as the devastating 2003 event in western Europe, are a likely sign of global warming; one that perhaps began as early as the 1950s, when their study showed some of the highest trends in summer mean temperature and summer temperature variance.
“These results add more evidence to the belief among climate scientists that western Europe will experience some of the highest environmental and social impacts of climate change and continue to experience devastating hot summers like the summer of 2003 more frequently in the future,” Della-Marta said.
The authors note that temperature records were likely overestimated in the past, when thermometers were not kept in modern Stevenson screens, which are instrument shelters used to protect temperature sensors from outside influences that could alter its readings. The researchers corrected for this warm bias and other biases in the variability of daily summer temperatures and show that nearly 40 percent of the changes in the frequency of hot days are likely to be caused by increases in summer temperatures’ variability. This finding demonstrates that even a small change in the variance of daily summer temperatures can radically enhance the number of extremely hot days.
“These findings provide observational support to climate modeling studies showing that European summer temperatures are particularly sensitive to global warming,” Della-Marta said. “Due to complex reactions between the summer atmosphere and the land, the variability of summer temperatures is expected to [continue to] increase substantially by 2100.”
The research was supported by the European Environment and Sustainable Development Program, the Swiss National Science Foundation and the National Center for Excellence in Climate Research (NCCR Climate).
Contact: Jonathan Lifland
American Geophysical Union
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