Monday, May 31, 2010

Father Ted - Mrs Doyle

Nigel Hawthorne

Yes Prime Minister

"I worked with Morecambe & Wise"

Chris Riddell - The Observer

RNA viruses and how they replicate themselves.

Science Daily (May 30, 2010)

How RNA Viruses Copy Themselves: Hijack Cellular Enzyme to Create Viral Replication Factories on Cell Membranes

Nihal Altan-Bonnet, assistant professor of cell biology, Rutgers University in Newark, and her research team have made a significant new discovery about RNA (ribonucleic acid) viruses and how they replicate themselves.

Certain RNA viruses -- poliovirus, hepatitis C virus and coxsackievirus -- and possibly many other families of viruses copy themselves by seizing an enzyme from their host cell to create replication factories enriched in a specific lipid, explains Altan-Bonnet. Minus that lipid -- phosphatidylinositol-4-phosphate (Pl4P) -- these RNA viruses are not able to synthesize their viral RNA and replicate. The key structural components on cell membranes, lipids often serve as signaling molecules and docking sites for proteins.

Viral replication is the process by which virus particles make new copies of themselves within a host cell. Those copies then can go on to infect other cells. An RNA virus is a virus that has RNA, rather than DNA, as its genetic material. Many human pathogens are RNA viruses, including SARS virus, West Nile virus, HIV, and the ones Altan-Bonnet has been studying.

Altan-Bonnet and her co-researchers for the first time have uncovered that certain RNA viruses take control of a cellular enzyme to design a replication compartment on the cell's membrane filled with PI4P lipids. Those lipids, in turn, allow the RNA viruses to attract and stimulate the enzymes they need for replication. In uninfected cells, the levels of PI4P lipids are kept low, but in virally infected cells those levels increase dramatically. The findings by Altan-Bonnet and her colleagues not only open several possibilities for preventing the spread of various viral infections, but also may help to shed new light on the regulation of RNA synthesis at the cellular level and potentially on how some cancers develop.

"The goal of the virus is to replicate itself," notes Altan-Bonnet. "For its replication machines to work, the virus needs to create an ideal lipid environment which it does by hijacking a key enzyme from its host cell."

Altan-Bonnet and her team also were able to identify the viral protein (the so-called 3A protein in poliovirus and coxsackievirus infections) that captures and recruits the cellular enzyme (phosphatidylinositol-4-kinase III beta). Additionally, her lab was able to impede the replication process by administering a drug that blocked the activity of the cellular enzyme once it had been hijacked. Drug therapies to prevent viral replication potentially also could be targeted to prevent the hijacking of the enzyme.

Once that enzyme is hijacked, cells are prevented from normally operating their secretory pathway, the process by which they move proteins to the outside of the cell. In many cases, the impeding of that process can result in the slow death of the cell, leading to such problems as cardiac and vascular complications in those infected with the coxsackievirus and neurological damage in those with poliovirus.

Utilizing their recent findings, Altan-Bonnet and her team now plan to investigate PI4P dependence in other viruses as well as the role other lipids may play in different virus families. For example, the SARS virus also requires a lipid-rich environment for its replication, so her lab now is working with SARS researchers on determining what lipid is necessary for that virus's replication. In addition, they will be examining the role of lipids in regulating RNA synthesis in cells, potentially providing new insight into some of the cellular mutations that occur in cancer.

"Given that a lot of what we know about cellular processes historically comes from the study of viruses, our studies may provide insight into the novel roles lipids play in regulating the expression of genetic material in cells," notes Altan-Bonnet.

Reference:

Viral Reorganization of the Secretory Pathway Generates Distinct Organelles for RNA Replication.
Nai-Yun Hsu, Olha Ilnytska, Georgiy Belov, Marianita Santiana, Ying-Han Chen, Peter M. Takvorian, Cyrilla Pau, Hilde van der Schaar, Neerja Kaushik-Basu, Tamas Balla.
Cell, 2010; 141 (5): 799- 811 DOI: 10.1016/j.cell.2010.03.050

Link to Cell abstract

Link to Science Daily article

revised WHO treatment guidelines


Carole Leach-Lemens for Aidsmap (May 31, 2010)

New WHO treatment criteria could prevent 90% of vertical transmission

Link to Aidsmap article

The Fat Loss Syndrome called Lipodystrophy

Michael Carter for Aidsmap (May 31, 2010)

Fat loss caused by some anti-HIV drugs persists in the long-term

The fat loss that can be caused by some anti-HIV drugs appear to persist in the long-term despite discontinuation of the drugs which cause it, US investigators report in a study published in the online edition of AIDS.

Researchers from the prospective Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study found that significant differences in fat distribution were evident between HIV-positive patients and HIV-negative controls persisted over five years.

Stopping d4T (stavudine, Zerit), the anti-HIV drug most associated with fat loss, was associated with only modest gains in limb fat.

Soon after it was introduced, combination antiretroviral therapy became associated with changes in body fat distribution and metabolic alterations associated with a long-term risk of cardiovascular disease. This syndrome of side-effects is called lipodystrophy.

Fat gain around the abdomen (visceral adiposity) and fat loss from the limbs and face (lipoatrophy) were observed in some patients. Protease inhibitors were originally thought to be the cause, but it became apparent that a major cause of fat loss was the mitochondrial toxicity caused by some nucleoside reverse transcriptase inhibitors (NRTIs), especially d4T, and to a lesser extent AZT (zidovudine, Retrovir, also in the combination pills Combivir and Trizivir.

Stopping or changing HIV treatment became an established strategy for treating lipodostrophy.

A lot of research has been undertaken in lipodystrophy, one of the major projects being the FRAM study.

In this study, investigators used MRI scans to compare the body fat distribution of HIV-positive patients and HIV-negative controls. Their initial analysis found that patients with HIV had significantly lower levels of subcutaneous fat than their HIV-negative peers.

The investigators wished to see if these differences persisted in the long-term. They therefore repeated their analysis after five years of follow-up.

The investigators conclude that “there is no relative recovery from lipoatrophy when HIV-infected participants are compared to controls.”

They add, “these data must be considered when studying the potential mechanisms underlying HIV-associated lipodystrophy. It remains to be determined whether there was destruction of adipose cells and precursors…or whether other factors continue to contribute to the persistence of lipoatrophy in HIV infection.”

Reference

Regional adipose tissue measured by MRI over 5 years in HIV-infected and control participants indicates persistence of HIV-associated lipoatrophy.
Grunfeld, Carl; Saag, Michael; Cofrancesco, Joseph Jr; Lewis, Cora Elizabeth; Kronmal, Richard; Heymsfield, Steven; Tien, Phyllis C; Bacchetti, Peter; Shlipak, Michael; Scherzer,
Rebecca; for the Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM)
AIDS., published ahead of print , 24 May 2010doi: 10.1097/QAD.0b013e32833ac7a2

Link to AIDS abstract

Link to Aidsmap article

Oh! What a Lovely War

Memorial Day

Sunday, May 30, 2010

Pleasure At Her Majesty's (1976)

Father Ted - Time For Tea

Bremner, Bird & Fortune

A morally sensitive agent

Florida State University News

Researcher Considers Role of Morality in Modern Economic Theory

The worldwide financial crisis in 2008, which led to what many in the United States now call the "Great Recession," has caused researchers to rethink traditional economic theories of financial markets and the corporate world. Even renowned financial theorist Michael Jensen, whose widely cited work has laid the foundation for the broad use of stock options as an executive compensation tool, has called on his fellow researchers to incorporate "integrity" into their economic models.

Douglas Stevens, an associate professor of accounting at The Florida State University, is among those who for years have proposed incorporating morality within traditional economic theory. He has published a number of experimental studies documenting that economic decision-makers frequently factor morality into their judgments and behavior.

Now, Stevens and a colleague have published a paper that incorporates morality into the economic theory of the firm that Jensen made dominant in accounting and finance. The paper, by Stevens and Alex Thevaranjan, an associate professor of accounting at Syracuse University, is titled "A Moral Solution to the Moral Hazard Problem." It was recently published in the peer-reviewed journal Accounting, Organizations and Society.

In that dominant economic theory of the firm, known as principal-agent theory, a principal must hire an agent to perform some productive effort. A "moral hazard" arises, however, because the principal cannot observe the effort of the agent and the agent is motivated to shirk. Under the traditional assumptions of the model, the principal must pay the agent a financial incentive to induce any effort from the agent.

The principal-agent model has been useful in accounting and finance because it addresses conflicts of interest that arise within the firm, according to Stevens. However, a common complaint is that it relies too heavily on financial incentives to solve the moral hazard problem. The high-powered financial incentives prescribed by the theory have been criticized for generating excessive executive compensation and risk-taking -- which analysts say precipitated the recent financial crisis.

Stevens and Thevaranjan extend the traditional principal-agent model by endowing the agent with "moral sensitivity" -- that is, a disutility for breaking a previous agreement. Thus, their model answers Jensen's call to incorporate integrity into economic theory. This is significant because principal-agent theory, the most mathematically formal economic theory of the firm, has previously been closed to moral content.

Incorporating moral sensitivity into the traditional principal-agent model allows Stevens and Thevaranjan to make several contributions to the theory. First, they are able to contrast the efficiency of their moral solution with the traditional incentive solution that becomes necessary when moral sensitivity is assumed to be zero. Second, they are able to demonstrate the benefit of the agent's moral sensitivity to both the principal and the agent, and thereby point out the potential cost of ignoring this moral sensitivity.

Stevens and Thevaranjan conclude that adding moral sensitivity increases the descriptive, prescriptive, and pedagogical usefulness of the model.

"We know from simple observation that the traditional principal-agent model is not fully descriptive of real-world behavior," Stevens said. "A majority of people are paid a fixed salary in their jobs and yet provide sufficient effort for their pay. This is particularly true in professions and nonprofit firms where the financial incentives required by the traditional model are difficult if not impossible to arrange. The traditional principal-agent model can't explain this behavior. Our model, however, demonstrates that a principal can pay a morally sensitive agent a fixed salary that is increasing in the productivity of the agent's effort."

Their model also demonstrates the value of moral sensitivity to the firm and society.

"Our model suggests that moral sensitivity increases the efficiency of principal-agent relationships within the firm -- which makes more of these relationships possible -- and allows the agent to receive a fixed salary that is increasing in his or her productivity or skill," Stevens said. "Thus, moral sensitivity increases the general welfare of society by decreasing unemployment and increasing the productivity and pay of those who are employed. This explains the emphasis placed on moral training within the firm and society at large. This also provides a warning against letting moral sensitivity diminish."

Stevens and Thevaranjan have used their model to teach accounting and MBA students the importance of professional ethics. Whether the traditional approach of ignoring morality and emphasizing financial incentives caused the financial meltdown is debatable, but Stevens believes it is time for business schools to return to emphasizing professional ethics.

"Every financial crisis and scandal is a wake-up call -- for both practitioners and academics," Stevens said. "Hopefully, we won't waste yet another financial crisis

reference

A Moral Solution to the Moral Hazard Problem
Douglas E. Stevens and Alex Thevaranjan,
(May 22, 2008).
Available at Social Science Research Network SSRN

Link to SSRN abstract

Link to FSU news report

Bird & Fortune

Theory of Mind

Science Daily (May 27, 2010)

An Underlying Cause for Psychopathic Behavior?

Psychopaths are known to be characterized by callousness, diminished capacity for remorse, and lack of empathy. However, the exact cause of these personality traits is an area of scientific debate. The results of a new study, reported in the May 2010 issue of Elsevier's Cortex, show striking similarities between the mental impairments observed in psychopaths and those seen in patients with frontal lobe damage.

One previous explanation for psychopathic tendencies has been a reduced capacity to make inferences about the mental states of other people, an ability known as Theory of Mind (ToM). On the other hand, psychopaths are also known to be extremely good manipulators and deceivers, which would imply that they have good skills in inferring the knowledge, needs, intentions, and beliefs of other people. Therefore, it has been suggested recently that ToM is made up of different aspects: a cognitive part, which requires inferences about knowledge and beliefs, and another part which requires the understanding of emotions.

Dr Simone Shamay-Tsoory, from the University of Haifa in Israel, along with colleagues from The Shalvata Mental Health Care Center and the Rambam Medical Center, tested the hypothesis that impairment in the emotional aspects of these abilities may account for psychopathic behavior. Earlier research from the same group had shown that patients with damage to the frontal lobes of the brain lack some of the emotional aspects of Theory of Mind, so they speculated that psychopathy may also be linked to frontal lobe dysfunction.

The emotional and cognitive aspects of Theory of Mind abilities were examined for participants in the new study, which consisted of a number of different groups: criminal offenders, who had been diagnosed as having antisocial personality disorder with highly psychopathic tendencies, patients with damage to the frontal lobes of the brain, patients with damage to other areas of the brain, and healthy control subjects. The pattern of impairments in the psychopathic participants showed a remarkable resemblance to those in the participants with frontal lobe damage, suggesting that an underlying cause of the behavioral disturbances observed in psychopathy may be dysfunction in the frontal lobes.

Reference:

The role of the orbitofrontal cortex in affective theory of mind deficits in criminal offenders with psychopathic tendencies.
Simone G. Shamay-Tsoory, Hagai Harari. Judith Aharon-Peretz, Yechiel Levkovitz
Cortex, 2010; 46 (5): 668 - 677 DOI: 10.1016/j.cortex.2009.04.008

Link to Cortex abstract

Link to Science Daily article

Saturday, May 29, 2010

Pleasure At Her Majesty's (1976)

Pleasure At Her Majesty's (1976)

Father Ted- Mrs. Doyle

Honeybees : "Colony Collapse Disorder"

Science Daily (May 25, 2010)

Microbial Team May Be Culprit in Colony Collapse Disorder

— New research from the United States Department of Agriculture (USDA) identifies a new potential cause for "Colony Collapse Disorder" in honeybees. A group of pathogens including a fungus and family of viruses may be working together to cause the decline. Scientists report their results May 25 at the 110th General Meeting of the American Society for Microbiology in San Diego.

"There might be a synergism between two very different pathogens," says Jay Evans of the USDA Agricultural Research Service, a researcher on the study. "When they show up together there is a significant correlation with colony decline."

Beginning in October 2006, some beekeepers began reporting losses of 30-90 percent of their hives. Although colony losses are not unexpected during winter weather, the magnitude of loss suffered by some beekeepers was highly unusual.

"Domesticated honey bees face numerous pests and pathogens, tempting hypotheses that colony collapses arise from exposure to new or resurgent pathogens," says Evans.

To better understand the cause of these collapses, in early 2007 Evans and his colleagues collected bees from both healthy and declining colonies across the country but primarily from California and Florida where most of the commercial pollination activity takes place. They have screened these samples and similar samples from each year since then for both known and novel pathogens.

They found a slightly higher incidence of a fungal pathogen known as Nosema ceranae in sick colonies, but it was not statistically significant until they began pairing it with other pathogens.

"Levels of the fungus were slightly higher in sick colonies, but the presence of that fungus and 2 or 3 RNA viruses from the family Dicistroviridae is a pretty strong predictor of collapse," says Evans.

Nosema are transferred between bees via the fecal-oral route. When a bee initially ingests the microbes and they get to the mid-gut, they harpoon themselves into the gut wall and live inside the epithelial cells there. Evans believes that the slightly higher numbers of the fungus somehow compromise the gut wall and allow the viruses to overwhelm the bees. In colonies with higher Nosema numbers they found virus levels to be 2-3 times greater than healthy colonies.

While this is a working theory and they are still in the discovery phase looking for new pathogens, Evans and his colleagues are also actively looking for a way to boost bee defenses against Nosema.

"A way to protect against Nosema might be the key for now," says Evans.

Link to Science Daily article