by the Universidad de Míchigan

ANN ARBOR, Michigan.— In the quest for new approaches to treating and preventing disease, one appealing route involves turning genes on or off at will, directly intervening in ailments such as cancer and diabetes, which result when genes fail to turn on and off as they should.

Scientists at the University of Michigan and the University of California at Berkeley have taken a step forward on that route by developing small molecules that mimic the behavior and function of a much larger and more complicated natural regulator of gene expression.

The research, by associate professor of chemistry Anna Mapp and coworkers, is described in the [DATE] issue of the journal ACS Chemical Biology.

Molecules that can prompt genes to be active are called transcriptional activators because they influence transcription—the first step in the process through which instructions coded in genes are used to produce proteins. Transcriptional activators occur naturally in cells, but Mapp and other researchers have been working to develop artificial transcription factors (ATFs)—non-natural molecules programmed to perform the same function as their natural counterparts.

These molecules can help scientists probe the transcription process and perhaps eventually be used to correct diseases that result from errors in gene regulation.

In previous work, Mapp and coworkers showed that an ATF they developed was able to turn on genes in living cells, but they weren’t sure it was using the same mechanism that natural activators use. Both natural transcriptional activators

and their artificial through which instructions coded in genes are used to produce proteins. Transcriptional activators occur naturally in cells, but Mapp and other researchers have been working to develop artificial transcription factors (ATFs)—non-natural molecules programmed to perform the same function as their natural counterparts.

These molecules can help scientists probe the transcription process and perhaps eventually be used to correct diseases that result from errors in gene regulation.

In previous work, Mapp and coworkers showed that an ATF they developed was able to turn on genes in living cells, but they weren’t sure it was using the same mechanism that natural activators use. Both natural transcriptional activators

and their artificial latinacounterparts typically have two essential parts: a DNA-binding domain that homes in on the specific gene to be regulated, and an activation domain that attaches itself to the cell’s machinery through a key protein-to-protein interaction

and spurs the gene into action. The researchers wanted to know whether their ATFs attached to the same sites in the transcriptional machinery that natural activators did.

In the current work, the team showed that their ATFs bind to a protein called CBP, which interacts with many natural activators, and that the specific site where their ATFs bind is the same site utilized by the natural activators, even though the natural activators are much larger and more complex.

Then the researchers altered their ATFs in various ways and looked to see how those changes affected both binding and ability to function as transcriptional activators. Any change that prevented an ATF from binding to CBP also prevented it from doing its job. This suggests that, for ATFs as for natural activators, interaction with CBP is key to transcriptional activity.

“Taken together, the evidence suggests that the small molecules we have developed mimic both the function and the mechanism of their natural counterparts,” said Mapp, who has a joint appointment in the College of Pharmacy’s Department of Medicinal Chemistry. Next the researchers want to understand in more detail exactly how the small molecules bind to that site. “Then we’ll use that information

to design better molecules.”

In addition to Mapp, the study’s authors are former graduate students Sara Buhrlage, Brian Brennan, ­Aaron Minter and Chinmay Majmudar, graduate student Caleb Bates, postdoctoral fellow Steven Rowe, associate professor of chemistry and biophysics Hashim AlHashimi, and David Wemmer of the University of California, Berkeley.

Funding was provided by the National Institutes of Health, the National Science Foundation, Novartis, the U-M Chemistry Biology Interface Training Program, Wyeth and the U-M Pharmaceutical Sciences Training Program.

by Marvin Ramírez

Organizan colecta de fondos para ayudar a la viuda y a su hija de 3 años: Marlon Mayorga poses with his dog, which accompanied him until his dead.

Approximately 200 people gathered at a fundra­iser with music and food, to celebrate the life of someone in the community who lost his life to what he helped prevent: street violence in our cities.

Marlon Mayorga, 41, was shot half-a-block from his home, at about 10:30 p.m. in the 3200 block of Champion Street behind St. Jarlath Church. He had been ­walking his husky-German shepherd mix, something he was known to do nightly, police said. Oakland police hadn’t established a motive for the killing but had not ruled out robbery. No arrests have been made.

Mr. Mayorga, a community activist who dedicated his life to caring for individuals and families struggling with substance abuse and survivors of domestic and street violence, was born in Nicaragua in 1968.

He and his family had to leave the country as a devastating civil war engulfed it, and settled in Daly City in the 1980’s. After getting involved in drug use, he successfully overcame the addiction and enrolled at college, earning a Bachelor’s degree and a Masters in Social Work from California State University at San Francisco.

Mr. Mayorga worked in the mental health field for several years and spent the last six months of his life working for the University of California of San Francisco’s Trauma Unit as a Social Worker. He also worked as a manager at Walden House, a well-known substance-abuse treatment center and taught salsa dancing.

“He was here last weekend, said, Oscar Orellana, owner of Club Roccapulco, who offered his club for the fundraiser held on June 7, and which was organized by the San Francisco Bay Area Latino Men’s Circulo, attracting many of his friends and colleagues in the social work community.

Musicians of high caliber performed at the event for free, which included John Santos, Orlando Torriente, Jesus Díaz, Anthony Blea, John Calloway, Camillo Landau, Javier Navarette, Julio Bravo, and others.

Police and Crime Stoppers of Oakland are offering as much as $10,000 in reward money for information leading to the arrest of suspects. Anyone with information may call police at 510-238-3821 or Crime Stoppers at 510-777-8572 or 510-777-3211.

­Mr. Mayorga is survived by his wife and daughter, his father, mother, sisters and brothers who live in the Bay Area and in Miami.

Any one who wish to help his family can send a check in care of the Marlon Mayorga Memorial Fund, Acct #5559675342, Wells Fargo Bank, 151 40th Street, Oakland, California 94611-5236. All funds collected will be for his wife and 3-year-old daughter.

­by the El Reportero’s news services

Mauricio Fumes

Mauricio Funes was inaugurated as president on June 1, completing the first transfer of a right-wing to a left-wing government in El Salvador’s history.

Funes’ inaugural speech, like his cabinet appointments, was a skilful political balancing act. On the one hand, he played to the orthodox wing of the Frente Farabundo Martí para la Liberación Nacional (FMLN) by savaging the political legacy of the outgoing Alianza Republicana Nacionalista (Arena), and announcing his decision to re-establish diplomatic ties with Cuba.

On the other hand, he was careful to dispel concerns at home and abroad that he would move El Salvador into Venezuela’s orbit.

Nicaragua a winner of UN-backed grants for conserving crops

Nicaraguan farmers preserving ancient varieties of potatoes, and Kenyan women revitalizing differing types of millet are among projects in 11 developing countries to win supporting grants for their work, the United Nations Food and Agriculture Organization (FAO) announced today.

A total of more than $500,000 will go to farming projects in Egypt, Kenya, Costa Rica, India, Peru, Senegal, Uruguay, Nicaragua, Cuba, Tanzania and Morocco, according to a news release issued by the agency.

The winners were announced today in Tunis at a meeting of the governing body of the International Treaty for Plant Genetic Resources in Food and Agriculture.

Other winners include on-farm protection of citrus diversity in Egypt, conservation of native potato varieties in Peru, the preservation of mountain varieties of maize and beans in Cuba, and a study of the adaptability of potatoes in Costa Rica to climate change.

Cuba ‘declares victory’ over OAS

Fidel Castro said on Wednesday that the OAS was complicit in ‘crimes’ against Cuba.

Cuba has declared a “major victory” following the decision by the Organization of American States (OAS) to allow it to rejoin the organization, reports have said.

The group voted in favor of Cuba rejoining the organization, 47 years after it was expelled.

But on Thursday, Ricardo Alarcon, the president of Cuba’s national assembly, was quoted by AFP as saying that the OAS vote was “a great victory for Latin America and the Caribbean and also for the Cuban people.”

However, the Caribbean nation said it would not rejoin the group, which it sees as dominated by US interests.

“[The move “does not alter what Cuba thought yesterday, the day before yesterday and today,” Alarcon said as quoted by AFP.

Neither Raul Castro, president of Cuba, or his brother, former president Fidel Castro, have commented publicly on the OAS move so far.

Uribe tight-lipped as Colombia edges towards re-election

Colombia’s senate has fi nally approved the referendum that would allow for the re-election of President Alvaro Uribe for an unprecedented third term in May 2010. Uribe maintains he is still undecided on the matter.

His government, however, has been tirelessly propelling the referendum forward since October 2008. Meanwhile, Uribe’s reticence is putting presidential hopefuls from his ruling coalition in a diffi cult position: the defense minister, Juan Manuel Santos, has resigned from his post in order to run for the presidency – but only if Uribe decides to stand aside.

­Ecuador’s Correa makes cabinet moves

On 4 June President Rafael Correa announced three cabinet appointments. All three ministers are women and loyalists. As Correa’s Movimiento País (MP) will not have a majority in congress, these appointments, coupled with some radical statements about the role of banks in the economy, indicate that Correa’s new administration will attempt major economic changes.

by Jose de la Isla

NEWS ANALYSESHOUSTON, Texas — On May 20, Ari Shapiro of National Public Radio disclosed that back in 2002, an interrogator had received authorization from higher-ups to torture Abu Zubaydah. This was before the U.S. Justice Department had issued the memorandum by John Yoo on “harsh” interrogations.

The techniques applied on Zubaydah, who was picked up on March 28, 2002, were authorized each day. In the first two months psychologist James Mitchell, a CIA contractor, sat at a computer and cabled the CIA counterterrorism center for permission to use enhanced techniques.

Ali Soufan, a former FBI interrogator who was present, testified this month how Mitchell kept requesting “authorization” to apply increasingly harsher methods.

Since the first legal guidance from the Justice Department was not issued until AU9. 1, who was at the other end of the phone authorizing the permission?

The CIA acknowledged, yes, Mitchell did request permission but the agency would not describe what the legal guidance was. The CIA acknowledged, yes, Mitchell did request permission but the agency would not describe what the legal guidance was.

A source in a position to know disclosed to Shapiro on condition of anonymity that the CIA forwarded the request to the White House, where legal counsel Alberto Gonzales signed off on the technique.

Bradford Barenson, a former White House legal counsel staff member, told Shapiro “ordinarily the White House counsel’s office Is not in the business of providing advice to anyone outside the White House itself.”

Barenson was part of the legal staff with the ideological bent fostered by the Federalist Society that populated the Bush White House.

Gonzales’ relationship with the president was very close, very confidential” to the point they were on the telephone in a back-and forth, “informal guidance” that made clear that what the president wanted was being carried out “without having to tee up formal decisions.” He said this about the office culture to Bill Minutaglio for a biography of Gonzáles, The President’s Counselor, published in 2006.

Right before 9/11, the priorities were to make many judicial appointments (consistent with the Federalist Society outlook) and strengthen presidential prerogatives.

On Sept. 14, 2001, a joint congressional resolution gave Bush authorization to respond to the 9/11 attack with military might. Minutaglio wrote that it gave “Bush the muscle to fight the war by any means necessary,” embarking Gonzáles and other counsels “on a clandestine and controversial path.”

In-house, Gonzales argued to prosecute and extract “all conceivable information” from or about suspected terrorists. It meant gathering “every shred of evidence possible,” and to test the previous boundaries.

The Sept. 14 resolution allowed Bush “to use all necessary and appropriate force against those nations, organizations, or persons” involved in 9/11.

The “necessary and appropriate force” notion has been behind the wiretapping and torture controversies. When the Bush Administration was given latitude, situations turned into excesses of some U.S. laws and international treaties.

Each new clue, like Shapiro’s about what went on, further justifies the need for a national commission to provide full disclosure.

There is of course intense public interest to get a straight forward understanding about what took place.

Eventually, clarity and simplicity has to emerge from the labyrinthine details, ­many of which are still cloaked in secrecy, to find out why that particular policy course was chosen. Otherwise the same mistakes will be repeated.

But so far full disclosure and Understanding have taken a back seat to the inevitable embarrassments, and even liabilities, when some people went too far.

On March 17 in a meeting at the U.S. Embassy in Madrid, Spanish prosecutor Javier Zaragoza told officials he would suspend his ongoing investigation of former U.S. Attorney General Alberto Gonzáles and five associates about their role in the torture of six Spanish citizens held at Guantánamo if the United States would undertake its own investigation into the matter, law professor and writer Scott Horton blogged in The Daily Beast.

The other five are former assistant AG (now federal judge) Jay Bybee, former deputy AG John Yoo, former Defense Department general counsel William J. Haynes I I, former VP Cheney’s chief of staff David Addington and former Undersecretary of Defense Douglas J. Feith.

Zaragoza got no answer. NOW, Spanish prosecutors are expected to announce soon they are pressing forward with their investigation. Hispanic Link.