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Monday, August 5, 2013
How Robert Bellah (1927-2013) Changed the Study of Religion ...
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How Robert Bellah (1927-2013) Changed the Study of Religion
Mark Juergensmeyer ("Religion Dispatches," August 1, 2013)
When the great sociologist of religion, Robert Bellah, died suddenly this week he was in the midst of writing the book that was meant to be the successor to his massive and magisterial Religion in Human Evolution. That book started with the Big Bang and ended with the Axial Age in the 6th century BCE. Although it covered much?the emergence of human culture and society in the evolution of the human species?there were still some significant changes in the social shape of religiosity in the last 2500 years that remained to be explored.
What the next book would focus on, Bellah told me, were the remarkable developments of the 16th through the 18th century that in Europe included the Reformation and the Enlightenment. This was a moment of anti-authoritarian popularism in society that resulted in a new social form of religiosity, a communitarian spirit that transformed Christianity and gave rise to a whole new protestant movement.
At the same time, similar movements were emerging in other traditions in other parts of the world. In India, for example, bhakti movements of social rebellion were erupting throughout the subcontinent, eschewing Brahmanical authority for the fellowship of devotees of a new breed of eclectic saints and teachers who could be outcastes, blind, female, or partly Muslim. Elsewhere in Asia, what has been called a ?Protestant Buddhism? was appealing to the masses in the way that a more orthodox clerical order could never do.
What Bellah was exploring in these two books?one recently published and the other, alas, eternally to be unfinished?was a new subject of religious studies: global religion. This is a field of study that tries to show the connection between seemingly disparate forms of religiosity around the world and forces of globalization that effect societies virtually everywhere on the planet.
A recent form of global religion?the emergence of strident religious politics?is related to the worldwide crisis of the nation-state and is a defensive response to the era of global interaction. Bellah shows us that this has happened before, at important moments earlier in history, when global social changes have created religious responses on a virtually global scale. Hence, in his mid-80s, Robert Bellah has once again become a pioneer in religious studies.
Over fifty years ago, in 1957, Bellah rocked the field of religious studies with a different kind of pioneering study, this one focused on Japanese religion. In Tokugawa Religion, Bellah did for Japanese Buddhism, Confucianism and Shinto what Max Weber did for Christianity in The Protestant Ethic and the Spirit of Capitalism. He showed how the social values embedded in religious thinking can help to support certain kinds of social transformations. In the case of Tokugawa Religion these values helped to pave the way for Japanese industrialization and global economic success.
This study made Bellah?s name not only in sociology but also in the emerging field of religious studies, where it showed the social utility of studying religious ideas. Moreover, it showed how concepts from Western scholars such as Max Weber could be applied to different cultures around the world. The essays on religion in China, Japan, Islamic societies, and the United States published in 1970 in his book of essays, Beyond Belief, illustrates that point.
In his 1967 essay in Daedalus on ?Civil Religion,? Bellah founded a whole new enterprise for religious studies scholars: probing the political significance of religious ideas and the religious significance of political ones. In this case it was Emile Durkheim that Bellah evoked, taking up Durkheim?s notion of the spiritual character of all collectivities. In his examination of the inaugural addresses of U.S. Presidents, Bellah showed there was a strain of patriotic religiosity in American public life that was both nationalistic and religious?specificially Protestant Christian. He borrowed the phrase, civil religion, that Jean-Jacques Rousseau coined in The Social Contract to describe the moral underpinnings of public order.
In the American context, however, Bellah saw this moral patriotism as infused with religious images and rhetoric that came from what politicians liked to call ?the Judaeo-Christian tradition,? an imagined homogenous religious stratum underlying American political culture. This interest in the political significance of religion seems obvious now, in an era of strident religious movements and the rise of religious nationalism around the world, but when he first wrote ?Civil Religion,? it was a bold new idea and an innovative way of thinking.
This was when I first knew Bellah, in Berkeley in the late 1960s, when I was a graduate student and later his colleague in the religious studies program. I saw how influential Bellah was on generations of graduate students?not only in sociology but also in religious studies. During those days he frequently reigned over the religion and society colloquia at the adjacent Graduate Theological Union, and it?s fair to say that the impact of his scholarship has been as formative in the fields of comparative religion and sociology of religion as it has been in the social sciences.
The religious concerns of Bellah were present even when his studies seemed to be more centrally focused on purely social issues. The widely-read Habits of the Heart, published in 1985, is an example. The book was written by Bellah, based on the interviews and reports of a team of younger sociologists with whom he had worked for several years. The title comes from a phrase by Alexis deTocqueville, and, like the 19th century French traveler, Bellah and his colleagues were attempting to assess the moral character of American society.
What they found was a profound tension between individualism and commitment to community. The religious expressions of this tension were evident: on the one hand catering to American individualism and indulgent self-expression, while providing havens of communal commitment on the other. Once again, it prompted religious studies scholars to take seriously the social dimensions of religious belief, even?or perhaps especially?when they seem so personal and devoid of social significance.
This brings us to 2011 and the publication of what has been described as Bellah?s magnum opus, the 700-page Religion in Human Evolution, on which he had been working since his retirement in 1997. How will this book make an impact on the field of religious studies in years to come, just as Bellah?s earlier works have done?
For one thing, it will encourage religious studies scholars to locate expressions of religiosity within their socio-historical milieus. What Bellah has convincingly shown in this book, as in his earlier work, is that religion is always a shared experience. That shared social context makes a difference in how one understands religion, and how religion is seen as affecting social life. Bellah?s study is one of sociotheology, a term that has been applied to the study of the interaction of religious ideas and their social contexts.
A second contribution of this volume is Bellah?s understanding of religion itself. Unlike many of the present-day attempts to explain religion away as if the term has no intrinsic meaning, Bellah demures. And he shows what religion is. It is not, however, what you might expect if you remember his long-winded definition of religion that he cobbled together from ideas provided by his friend, Clifford Geertz, some years ago. In his new book, the notion is simple: an awareness of an alternative reality.
The religious instinct, according to Bellah, is the ability to sense an alternative reality and in some way participate in it. The first expressions of this were not cognitive; they were physical. Bellah looks at other species and at earlier moments of the evolution of life on the planet, and finds the origins of religion?and all culture?in play. A creature is able to play when it has satisfied its immediate material needs and can imagine, or act out, alternative ways of being. My guess is that this understanding of religion will eventually have a profound effect on the way that religious scholars conceive of their subject matter, and how to go about studying it in its physical as well as literary expressions.
Finally, Bellah?s last book has made a lasting contribution to our understanding of religion as a global phenomenon. As I said at the outset, once again Robert Bellah has become a pioneer in the social study of religion, as a founder of the field of global religion. In this case he is taking the broadest view imaginable, seeing religion as a part of the reality of life on this planet from its moment of physical conception to the unimaginable future. And that is, indeed, a vision of cosmic proportions from a scholar whose stature, like his ideas, will long endure.
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Source: http://wwrn.org/articles/40369/
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Saturday, August 3, 2013
From soybeans to baseball, Henry has had success
Boston Red Sox majority owner John Henry watches a baseball game between the Red Sox and Arizona Diamondbacks during the second inning at Fenway Park in Boston, Friday, Aug. 2, 2013. (AP Photo/Charles Krupa)
Boston Red Sox majority owner John Henry watches a baseball game between the Red Sox and Arizona Diamondbacks during the second inning at Fenway Park in Boston, Friday, Aug. 2, 2013. (AP Photo/Charles Krupa)
BOSTON (AP) ? John W. Henry took a backward ballclub in a dilapidated park and transformed it into a two-time World Series champion that is one of baseball's model franchises.
As the owner of The Boston Globe, he will try to turn around a newspaper that ? like many other major metro dailies ? is shedding staff, subscribers and advertisers as it makes the transition into the Internet age.
Henry agreed to buy the Globe along with the Worcester Telegram & Gazette and the Boston Metro for $70 million, a fraction of the $1.1 billion The New York Times Co. paid 20 years ago. Henry apparently made this deal without his Red Sox partners, though he said in a statement that more information will soon be available "concerning those joining me in this community commitment and effort."
The son of southern Illinois soybean farmers now worth an estimated $1.5 billion, Henry was a minority owner of the New York Yankees and the sole owner of the Florida Marlins when he led a group that bought the Red Sox for $660 million in 2002. (The original group included The New York Times, which sold the last of its 17.5 percent ownership last year.)
They soon set out to preserve Fenway Park while taking a wrecking ball to most everything else that had mired the franchise in failure for more than eight decades.
Henry, who made his money by taking a mathematical approach to the commodities markets, brought a similar method to the baseball diamond, hiring the statistically savvy Theo Epstein, then 28 years-old, as the youngest general manager in baseball history. They hired statistical pioneer Bill James as a consultant, putting the Red Sox at the forefront of the revolution that had just begun to take hold in front offices long dominated by old-time and hidebound scouting types.
But, perhaps more importantly, the new owners turned what had long been a stagnant family business into a revenue spigot.
They took NESN, which had been almost exclusively an outlet for Red Sox and Boston Bruins games, into a full-fledged sports network. (Not every effort ? like the sports-themed dating show "Sox Appeal" ? was a success.) And they spent more than $285 million turning the once-doomed Fenway Park into a modern ? well, as modern as a 100-year-old ballpark can be, anyway ? sporting venue.
With seats above the Green Monster and a roof deck in right field, a high-tech scoreboard and new concourses and concessions, Fenway sold out 820 consecutive games ? by official count, anyway ? the longest such streak in professional sports history. Thousands more file through the turnstiles 12 months a year, paying up to $16 just to see the park when it is empty.
Though fans sometimes chafed at the team's new businesslike approach, the initiatives helped pay for a player payroll that grew from $75.5 million in 2000 to more than $130 million by 2004. That year, the Red Sox won the World Series for the first time in 86 years, ending one of the longest title droughts in sports.
They won again three years later.
Henry was also a different kind of owner than Bostonians had grown accustomed to.
While most owners of the local franchises had treated their teams like family fiefdoms or corporate cash registers ? or both ? Henry engaged with fans, chatting with them on Internet message boards (he would also became an early adopter on Twitter). He spent less time in his luxury box and more in his dugout-side seats, and was once seen running the bases on the Fenway diamond with the woman who is now his wife.
And Henry kept looking beyond baseball.
Through a sister company, the Red Sox owners bought into NASCAR as co-owners of Roush Fenway Racing; soccer, by purchasing the Liverpool FC of the English Premier League; and basketball, through a sponsorship deal with LeBron James. Their business offshoot, known as New England Sports Ventures, has also dabbled in marketing for college sports and professional golf.
In buying a newspaper, Henry enters an industry in turmoil and joins a progression of publishers who have tried to figure out how to balance the free-flowing information of the internet with the costs of quality journalism.
While providing no clues, Henry vowed to try.
"The Boston Globe's award-winning journalism as well as its rich history and tradition of excellence have established it as one of the most well-respected media companies in the country," he said in his statement. "This is a thriving, dynamic region that needs a strong, sustainable Boston Globe playing an integral role in the community's long-term future."
___
Follow Jimmy Golen on Twitter at http://www.twitter.com/jgolen.
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Michael Dell closes in on prize with sweeter $25 billion deal
By Greg Roumeliotis and Eileen O'Grady
NEW YORK/ROUND ROCK, Texas (Reuters) - Dell Inc and Chief Executive Michael Dell clinched a new $25 billion deal on Friday, boosting the bid and offering a special dividend in hopes of ending months of wrangling with opponents of the founder's proposed buyout of the world's No. 3 PC maker.
The new agreement includes a special dividend of 13 cents per share on top of a 10-cent increase in the sale price to $13.75 per share. In return, Michael Dell and his private equity partner Silver Lake convinced the company's special committee to agree to change the voting rules so that abstentions no longer count as opposing votes, a big boost for their camp.
Dell shares rose after the announcement. But activist investor Carl Icahn, who has amassed an 8.7 percent stake in Dell and has opposed the buyout offer as too low, vowed to keep fighting.
"We are pleased today to have won yet another battle, but the war regarding Dell is far from over," Icahn said in a Friday statement. "We are not satisfied. We believe that an increase of a mere 13 cents is an insult to shareholders."
Icahn has sued the tech company in a Delaware court, trying to block the changes to the voting rules.
Dell shares were up 5 percent at $13.61 in afternoon trading, a sign of increasing optimism that the deal will go through. But not everyone was convinced.
"We do not believe this battle is over yet, especially given yesterday's complaint filed by Carl Icahn," said Topeka Capital's Brian White.
The battle over Dell has raged for months, adding more uncertainty about a company already shrinking along with a rapidly declining PC market. Dell is trying to transform itself into an IBM-like enterprise computing firm.
Michael Dell and Silver Lake say a painful restructuring can best be performed as a private company, away from market scrutiny. Their new deal with the special committee, and a delay in the voting date to September 12, boost the buyout consortium in several ways.
The CEO is effectively agreeing to bankroll the special dividend, a source close to the matter told Reuters.
Abstentions under the previous voting system counted as "no" votes. With an estimated quarter of eligible shares not having been voted either way, that proved a substantial hurdle to overcome. Under the new deal announced Friday, shares that are not voted will be excluded from the tally.
A change in the record date by more than two months is also seen as enfranchising so-called arbitrage investors - hedge funds that bought Dell stock more recently to earn a few cents per share and would thus be more likely support the buyout.
MACHINATIONS
A vote on the buyout has been postponed now three times. The record date, which determines which shareholders are entitled to vote, will be reset to August 13 from June 3.
Under the deal, Dell shareholders will also be entitled to three regular quarterly dividends of 8 cents per share totaling 24 cents, since the first deal with Michael Dell and private equity partner Silver Lake was announced on February 5.
Michael Dell, who started the company in 1984 out of his college dorm room, agreed to swallow a hit to get the deal done, said the source close to the matter.
The special dividend of 13 cents per share will be funded with excess equity resulting from his rolling over his shares in the deal at a lower price, subsidizing Silver Lake's returns, according to the source.
He had previously agreed to roll over his shares at $13.36 per share. Together with the 10 cent per share increase in the buyout offer, this results in an increase in the original $24.4 billion bid by about $350 million to nearly $24.8 billion.
"If you have to go through these machinations to get these things through, it frankly is an excellent demonstration of why management buyouts are so problematic," said Charles Elson, director of the John L. Weinberg Center for Corporate Governance at the University of Delaware.
Although there is no regulatory or legal requirement for the buyout vote tally to include shares that are not voted, changing the rules of the game at this stage will give more ammunition to shareholders challenging the deal in court, legal experts said.
ICAHN: WILD CARD?
Icahn and Southeastern Asset Management intend to contest the new deal, pressing on with their lawsuit.
Last month, the two investors sweetened their share buyback proposal by adding warrants they say would increase the value of their offer to a range of $15.50 to $18 per share from $14 per share. Under their plan, Dell would remain a public company.
Icahn has campaigned hard to get Dell to set a date for an annual shareholder meeting so he could put up his own slate of company directors and implement his proposal.
But Dell refused to give him that chance. It said on Friday the annual meeting would be held on October 17, long after the buyout vote is held.
Another person familiar with the matter said shareholders could challenge the date of the annual meeting in court because it did not comply with rules that dictate it should be held within 13 months of Dell's previous annual meeting, which was held in July 2012.
But given that a new record date has been set for August 13 the special committee would argue that a court cannot ask the company to hold the annual meeting much earlier than October 17, the person added.
Dell's special committee chairman Alex Mandl on Friday explained the company's decision to change the voting standard.
"The original voting standard was set at a time when the decision before the shareholders was between a going-private transaction and a continuation of the status quo," Mandl said in a statement.
"Since then, the nature of the choice facing shareholders has changed because of the emergence of an alternative proposal by certain stockholders. In the context of the current decision, the committee does not believe it is appropriate to count shares that have not been voted as having been voted in support of any particular alternative."
Dell also agreed on Friday to reduce from $450 million to $180 million a break-up fee it would have to pay if the deal with Michael Dell and Silver Lake was terminated, and if within a year it enters into another transaction that does not lead to any party being a majority shareholder.
(Additional reporting by Soyoung Kim, Ross Kerber and Michael Erman in New York, Poornima Gupta in San Franscisco, and Sruthi Ramakrishnan in Bangalore, editing by Andre Grenon, Edwin Chan and David Gregorio)
Source: http://news.yahoo.com/dell-shareholders-convene-third-time-buyout-battle-escalates-040142852.html
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Fullmetal Alchemist Wallpaper for Android
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Friday, August 2, 2013
William Petit's Second Wife Pregnant ? New Life After Traumatic ...
Courtesy of WSFB
Dr. Petit?s life was forever changed after his family was brutally slaughtered in a terrifying invasion of his Connecticut home six years ago. Dr Petit who, barely survived himself, was eventually able to find some peace and remarried a year ago. He and his wife are now expecting a child!
Dr. William Petit?will be welcoming a bundle of joy into his life ? and he certainly deserves this wonderful news.?The victim of an infamous deadly Connecticut home invasion and deliberately set fire that killed his first wife and two daughters in 2007, William finally found love again with?Christine Paluf. The pair married in August 2012 and are now reveal that they are expecting their first child together! Congratulations!
William Petit: Second Wife Welcoming Baby
William got a second chance at love when he started dating?Christine Paluf?in 2011 ? and now he will get more joy in his life.?The pair told?WSFB?on August 1 that the?baby is due on December 3, 2013.
In 2007, Dr. Petit?s first wife and two daughters were followed home by two ex-convicts, from a store where they had shopped. Petit?s wife was raped and strangled to death by the intruders while the couple?s two daughters ? aged 17 and 11 ? were tied down to their beds and left to die after the house was doused in gasoline and set on fire.
William was also brutally beaten, and only narrowly escaped to a neighbor?s house.
William Petit Attended Trials For Two Murders
No matter how difficult it got for him, William sat through two long, sensational trials for the two men involved in his brutal home invasion. By making appearances at the perpetrators? very public multi-phase trials, Dr. Petit got some closure for his family. Steven Hayes was sentenced to death in 2010. His accomplice,?Joshua Komisarjevsky, was sentenced to death by lethal injection in 2012.
William Petit Is Healing From Traumatic Home Invasion
New wife Christine has been very supportive of William?s healing process ? she even worked with his family?s foundation. After tragically losing his first wife and beloved daughters, it must be extremely difficult to move on.
When William and Christine announced their wedding plans in 2012,?Reverend Richard Hawke, William?s former father-in-law, comforted them by explaining that his daughter would have wanted William to have someone like Christine in his life. He also said that he hoped the couple would have children together.
We are so happy that the couple will be welcoming a new baby into their lives.
In the mean time, Christine is getting some baby practice in by babysitting her 2-month-old niece Keegan.
What do YOU think,?HollyMoms? Aren?t you so happy that Dr. Petit will get to experience the joys of being a father again?
WATCH: Dr. Petit: ?A Huge Loss In My Life?
??Kristine Hope Kowalski
More Pregnancy Annoucement News:
- Megan Fox & Brian Austin Green Expecting Second Child
- Autumn Reeser Is Expecting Her Second Son ? Congrats!
- Simon Cowell Expecting Baby With His BFF?s Wife
Source: http://hollywoodlife.com/2013/08/02/william-petit-second-wife-pregnant-home-invasion-murder/
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Vanderbilt studies outline new model for staph bone infections
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Public release date: 1-Aug-2013[ | E-mail |
Share ] Contact: Craig Boerner
craig.boerner@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
Osteomyelitis, a debilitating bone infection most frequently caused by Staphylococcus aureus ("staph") bacteria, is particularly challenging to treat.
Now, Vanderbilt microbiologist Eric Skaar, Ph.D., MPH, and colleagues have identified a staph-killing compound that may be an effective treatment for osteomyelitis, and they have developed a new mouse model that will be useful for testing this compound and for generating additional therapeutic strategies.
James Cassat, M.D., Ph.D., a fellow in Pediatric Infectious Diseases who is interested in improving treatments for children with bone infections, led the mouse model studies. Working with colleagues in the Vanderbilt Center for Bone Biology and the Vanderbilt University Institute of Imaging Science, Cassat developed micro-computed tomography (micro-CT) imaging technologies to visualize a surgically introduced bone infection in progress.
"The micro-CT gives excellent resolution images of the damage that's being done to the bone," said Skaar, the Ernest W. Goodpasture Professor of Pathology. "We found that staph is not only destroying bone, but it's also promoting new bone growth. Staph is causing profound changes in bone remodeling."
Cassat also established methods for recovering -- and counting -- bacteria from the infected bone.
"We're not aware of any other bone infection models where you can pull the bacteria out of a bone and count them in a highly reproducible manner," Skaar said. "From a therapeutic development standpoint, we think this model is going to allow investigators to test new compounds for efficacy against bone infections caused by staph or any other bacteria that cause osteomyelitis."
Several pharmaceutical companies have already approached Skaar and his team about testing compounds in the new bone infection model, which the investigators describe in the June 12 issue of Cell Host & Microbe.
Using the model, the team demonstrated that a certain protein secreted by staph plays a critical role in the pathogenesis of osteomyelitis. Understanding the specific bacterial factors -- and the bone cell signals -- that promote bone destruction and formation during infection could lead to new strategies for restoring bone balance, Skaar said.
"Even if it's not possible to kill the bacteria, compounds that manipulate bone growth or destruction might have some therapeutic benefit."
Still, Skaar is interested in treatments that will eliminate the infection.
The staph bacteria involved in osteomyelitis and in other persistent infections (such as lung infections in cystic fibrosis) are often a sub-class of staph known as "small colony variants." These staph variants grow slowly and are resistant to entire classes of antibiotics commonly used to treat bone and lung infections, Skaar said.
One way that staph bacteria become antibiotic-resistant small colony variants is by changing the way they generate energy. Instead of using respiration, they switch to fermentation, which blocks antibiotic entry and slows bacterial growth.
In a high-throughput screen for compounds that activate a heme-sensing bacterial pathway, graduate student Laura Mike identified a compound that kills fermenting staph. The findings are reported in a recent issue of the Proceedings of the National Academy of Sciences.
"This is a completely new molecular activity," Skaar said. "We don't know of other molecules that are toxic against fermenting bacteria."
The compound -- and derivatives synthesized by Gary Sulikowski, Ph.D., and his team -- might be useful in treating staph small colony variants, or in preventing their emergence.
The investigators demonstrated in culture that treating staph with the antibiotic gentamicin forced it to become a small colony variant and ferment, and that co-treatment with the new compound prevented resistance and killed all of the bacteria.
"We think a really interesting therapeutic strategy for this compound is that it might augment the antimicrobial activity of existing classes of antibiotics by preventing resistance to them -- it might extend the lifetime of these classes of antibiotics," Skaar said.
This would be similar to the drug Augmentin, which combines a traditional penicillin-type antibiotic and a compound that blocks bacterial resistance.
The investigators are excited to test the new compound in the mouse model of osteomyelitis. First, they will treat the mice with gentamicin and assess whether staph small colony variants form. If so, they will co-administer the new compound to test if it prevents resistance, and they will also assess it as a single treatment for the persistent infection.
Skaar stressed that Vanderbilt's collaborative environment made these studies possible. Daniel Perrien, Ph.D., and Florent Elefteriou, Ph.D., in the Vanderbilt Center for Bone Biology and colleagues in the Vanderbilt University Institute of Imaging Science were critical in facilitating development of the bone infection model. Sulikowski and other colleagues in the Vanderbilt Institute of Chemical Biology (VICB) enabled the compound development.
"This is exactly the kind of work the VICB is promoting getting biologists like me together with chemists, to make new therapeutics," Skaar said.
###
The research was supported by the Searle Scholars Program and grants from the National Institutes of Health (AI069233, AI073843, RR027631, AI091856, HD060554), including the Southeastern Regional Center of Excellence for Emerging Infections and Biodefense (AI057157).
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Public release date: 1-Aug-2013[ | E-mail |
Share ] Contact: Craig Boerner
craig.boerner@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
Osteomyelitis, a debilitating bone infection most frequently caused by Staphylococcus aureus ("staph") bacteria, is particularly challenging to treat.
Now, Vanderbilt microbiologist Eric Skaar, Ph.D., MPH, and colleagues have identified a staph-killing compound that may be an effective treatment for osteomyelitis, and they have developed a new mouse model that will be useful for testing this compound and for generating additional therapeutic strategies.
James Cassat, M.D., Ph.D., a fellow in Pediatric Infectious Diseases who is interested in improving treatments for children with bone infections, led the mouse model studies. Working with colleagues in the Vanderbilt Center for Bone Biology and the Vanderbilt University Institute of Imaging Science, Cassat developed micro-computed tomography (micro-CT) imaging technologies to visualize a surgically introduced bone infection in progress.
"The micro-CT gives excellent resolution images of the damage that's being done to the bone," said Skaar, the Ernest W. Goodpasture Professor of Pathology. "We found that staph is not only destroying bone, but it's also promoting new bone growth. Staph is causing profound changes in bone remodeling."
Cassat also established methods for recovering -- and counting -- bacteria from the infected bone.
"We're not aware of any other bone infection models where you can pull the bacteria out of a bone and count them in a highly reproducible manner," Skaar said. "From a therapeutic development standpoint, we think this model is going to allow investigators to test new compounds for efficacy against bone infections caused by staph or any other bacteria that cause osteomyelitis."
Several pharmaceutical companies have already approached Skaar and his team about testing compounds in the new bone infection model, which the investigators describe in the June 12 issue of Cell Host & Microbe.
Using the model, the team demonstrated that a certain protein secreted by staph plays a critical role in the pathogenesis of osteomyelitis. Understanding the specific bacterial factors -- and the bone cell signals -- that promote bone destruction and formation during infection could lead to new strategies for restoring bone balance, Skaar said.
"Even if it's not possible to kill the bacteria, compounds that manipulate bone growth or destruction might have some therapeutic benefit."
Still, Skaar is interested in treatments that will eliminate the infection.
The staph bacteria involved in osteomyelitis and in other persistent infections (such as lung infections in cystic fibrosis) are often a sub-class of staph known as "small colony variants." These staph variants grow slowly and are resistant to entire classes of antibiotics commonly used to treat bone and lung infections, Skaar said.
One way that staph bacteria become antibiotic-resistant small colony variants is by changing the way they generate energy. Instead of using respiration, they switch to fermentation, which blocks antibiotic entry and slows bacterial growth.
In a high-throughput screen for compounds that activate a heme-sensing bacterial pathway, graduate student Laura Mike identified a compound that kills fermenting staph. The findings are reported in a recent issue of the Proceedings of the National Academy of Sciences.
"This is a completely new molecular activity," Skaar said. "We don't know of other molecules that are toxic against fermenting bacteria."
The compound -- and derivatives synthesized by Gary Sulikowski, Ph.D., and his team -- might be useful in treating staph small colony variants, or in preventing their emergence.
The investigators demonstrated in culture that treating staph with the antibiotic gentamicin forced it to become a small colony variant and ferment, and that co-treatment with the new compound prevented resistance and killed all of the bacteria.
"We think a really interesting therapeutic strategy for this compound is that it might augment the antimicrobial activity of existing classes of antibiotics by preventing resistance to them -- it might extend the lifetime of these classes of antibiotics," Skaar said.
This would be similar to the drug Augmentin, which combines a traditional penicillin-type antibiotic and a compound that blocks bacterial resistance.
The investigators are excited to test the new compound in the mouse model of osteomyelitis. First, they will treat the mice with gentamicin and assess whether staph small colony variants form. If so, they will co-administer the new compound to test if it prevents resistance, and they will also assess it as a single treatment for the persistent infection.
Skaar stressed that Vanderbilt's collaborative environment made these studies possible. Daniel Perrien, Ph.D., and Florent Elefteriou, Ph.D., in the Vanderbilt Center for Bone Biology and colleagues in the Vanderbilt University Institute of Imaging Science were critical in facilitating development of the bone infection model. Sulikowski and other colleagues in the Vanderbilt Institute of Chemical Biology (VICB) enabled the compound development.
"This is exactly the kind of work the VICB is promoting getting biologists like me together with chemists, to make new therapeutics," Skaar said.
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The research was supported by the Searle Scholars Program and grants from the National Institutes of Health (AI069233, AI073843, RR027631, AI091856, HD060554), including the Southeastern Regional Center of Excellence for Emerging Infections and Biodefense (AI057157).
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Source: http://www.eurekalert.org/pub_releases/2013-08/vumc-vso080113.php
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