TV producers bruised, but unbowed after battles

LOS ANGELES (Hollywood Reporter) – Ann Biderman remembers exactly when she lost faith in NBC.

Television | Media

It was May 19, 2009, when the network announced it was turning the Monday-Friday 10 p.m. slot over to the ultimately ill-fated “Jay Leno Show.”

“That was the first clue that they didn’t know what they were doing,” says Biderman, who feared what the plan meant for “Southland,” her critically acclaimed series about the gritty lives of LAPD cops.

“We were promised that (moving to) 9 p.m. wouldn’t affect content,” she says. “But then, of course, they started worrying.”

So much so that, in early October, a mere three weeks before “Southland’s” Second 2 premiere, the network abruptly canceled the series.

“At first I thought it was a joke,” Biderman says of hearing the news from fellow executive producer John Wells. “Like, where’s the ‘Punk’d’ camera? We were devastated.”

Fortunately, executives at TNT were fans of “Southland” and by November 2 the cable network closed a deal for the show, which was recently picked up for a third season.

For producers like Biderman, the process of crafting quality drama can be every bit as dramatic as the story lines they create.

The challenges to the creative process can be relatively small (wardrobe, scheduling) or utterly vital to a show’s future (deciding the right time to kill a main character or when to kill a series).

For Graham Yost, creator/executive producer of FX’s “Justified,” the obstacle was a cowboy hat.

As worn by Timothy Olyphant, who plays U.S. Marshal Raylan Givens, the hat isn’t merely a wardrobe piece, but a symbol of rebellion against his criminal father.

Author Elmore Leonard, who also serves as an executive producer on the drama, felt strongly about which hat Olyphant should wear. He thought it was a given that the lawman would sport the same well-worn, small-brimmed businessman-style Stetson his character did “Fire in the Hole,” Leonard’s short story in which Givens first appeared.

But a test run on Olyphant left Yost underwhelmed.

“It just didn’t fit right with Tim’s head and face,” he says. “It needed to be bigger.”

Like one of his own tell-it-like-it-is characters, the 84-year-old author stood his ground.

Yost tried to compromise and e-mailed Leonard pictures of Olyphant in numerous hats during the course of the next month. He found himself torn between selecting the right wardrobe for the story and pleasing the man whose books and short stories he’d long admired.

Shortly before production began on the pilot in California, Yost decided to go with a large, crisp cowboy hat he loved.

Leonard still isn’t thrilled. (Lucky for Yost though, the author loves the show. He’s even been inspired to write another Raylan Givens novella.)

The breakneck pace of creating television leaves as little time for wardrobe debates as it does for international casting crises.

Neal Baer discovered this the hard way in 2006 when he offered a guest role on “Law & Order: SVU” to French actress Leslie Caron too close to the start date for her to easily get a work visa.

“We had to go to the late Sen. Kennedy to have his office expedite things,” Baer recalls.

Eager to avoid a similar scenario again last season, the showrunner began courting French movie star Isabelle Huppert in February with an eye toward casting her in the May 11 season finale.

He handcrafted for her the meaty role of a grieving and unstable mother. An impressed Huppert eagerly signed on.

The visa was secured. All was well.

Then, on April 12, as Huppert was preparing to fly from Paris to New York, where “SVU” shoots, the Icelandic volcano erupted and grounded thousands of European flights.

Baer was left scrambling, again.

“‘Can we drive her to Madrid?’ ” he wondered at the time. “Some planes were getting out of there.”

Ultimately, forming a contingency plan was moot. At the last minute, Huppert escaped Paris on an overnight flight and went straight to the New York set.

The actress told Baer she felt “like she did three movies in five days.”

“To have her in the show was thrilling,” he says. “What we went through … it was certainly worth it.”

For “Dexter” executive producer Sara Colleton, Season 4 of her Showtime hit revolved around one pivotal question: Could the drama’s central character — a blood-splatter analyst, husband, new father and serial killer — really have it all?

The most dramatically satisfying answer, of course, was no.

In mapping out the season’s arc, Colleton and her stable of writers decided that Dexter (Michael C. Hall) would need to pay for his hubris, and the price would be steep.

“It had to be what mattered most to him,” Colleton says. “It came to feel inevitable.”

That inevitability became the series’ most shocking moment.

In the finale, having finally disposed of the Trinity Killer (John Lithgow), Dexter returns home to a gruesome scene: His lovely blonde wife Rita (Julie Benz), Trinity’s final victim, lay dead in the bathtub with his baby son Harrison sitting on the floor in a pool of his mother’s blood.

Filming Benz’s death scene was “very emotional,” she says. “The night on set was also respectful, and quiet. Everyone there understood how important that moment was.”

Following through with her creative vision proved more difficult than she anticipated. Colleton calls killing Rita and, as a result, letting go of a series regular she loved, her “toughest decision” of the entire series.

“I hope I never to have to do something like that again on this show,” she says. “I can’t handle it. For me, it was like a death in the family.”

Killing a main character is one thing. Asking network executives to end your series while it’s still Nielsen gold is nearly as wild a notion as a show about an island inhabited by polar bears and a smoke monster.

Luckily, wild notions work well for Carlton Cuse.

During “Lost’s” third season in 2007, the executive producer and his co-showrunner Damon Lindelof thought hard about their drama’s future.

“The audience was recognizing that we’d slowed our narrative storytelling to a crawl,” Cuse says. “But we were really fearful of burning through story fuel too fast because we didn’t know how long the mythology had to last — two years or nine.”

Announcing an end date would reassure fans they had a master plan for the complex ABC drama and hopefully keep them invested, but also save “Lost” from what they saw as a fate worse than brevity.

“We didn’t want an ‘X-Files’ trajectory,” Cuse says. “If Chris Carter had been able to end that show earlier, there would be a vastly different perception of it now. It’s terrible that the end seasons negate the incredible accomplishment of the first ones.”

Although confident in their decision, Cuse felt “high anxiety” when he and Lindelof made their pitch to Stephen McPherson, president of ABC Entertainment Group, and Mark Pedowitz, then the president of ABC Studios.

They were prepared to quit if the execs balked.

But to their immense relief, McPherson and Pedowitz agreed to wrap “Lost” after a total of six seasons, and Cuse and Lindelof signed lucrative deals keeping them at the helm for the extent of the drama’s run.

Today, having secured “Lost’s” legacy as one of the most respected and influential shows in TV history, Cuse is grateful he and Lindelof stuck to their guns.

“Getting the end date was the most significant moment in the history of the show,” he says. “We told the story we wanted to tell and we stand by it.”

Epilepsy linked to disruption of brain development during early childhood

London, August 24 (ANI): Scientists at Beth Israel Deaconess Medical Center (BIDMC) say that a form of partial epilepsy, which is associated with auditory and other sensory hallucinations, may result from the disruption of brain development during early childhood.

The researchers claim that their findings provide the first genetic link between childhood brain development and a seizure disorder that lasts throughout adulthood, and also identify a new pathway that controls how neuron circuits are “pruned” and matured.

“During early childhood – roughly between the ages of one and five – the brain undergoes a period of major circuit remodeling,” Nature magazine quoted senior author Dr. Matthew Anderson, a principal investigator in the Departments of Neurology and Pathology at BIDMC, as saying.

“Our discovery that a familial form of temporal lobe epilepsy can develop at this point demonstrates the fragility of the brain during this critical period,” he added.

In their study report, the researchers have revealed that their findings focus on the development of synapses, the connections between brain cells.

“At birth, the brain is loaded with excitatory synapses which help make nerve cells ‘fire,’” says Anderson, who is also an Assistant Professor of Neurology and Pathology at Harvard Medical School.

“However, if these excess synapses are not adequately ‘pruned,’ they can overgrow, leading to excessive transmission of excitatory signals and the development of pathological conditions, including learning disabilities and autism in addition to epilepsy,” he adds.

Anderson has revealed that his study involved a genetically engineered mouse model, and and brain slice patch-clamp electrophysiology techniques.

He said that his team found that a mutant form of the LGI1 (leucine-rich glioma-inactivated 1) gene was preventing the normal brain development.

“The first clue was our discovery that LGI1 is not expressed until the exact time when excitatory synapses are matured. We subsequently learned that the mLGI1 gene was indeed prohibiting excitatory synapses from being adequately pruned, leading to an increased excitability of circuits in the brain which left it prone to excessive synchronous discharges that are characteristic of epilepsy,” said Anderson.

Autosomal dominant lateral temporal lobe epilepsy (ADLTE) is characterized by frequent partial seizures-two to five per month-that are associated with auditory or other sensory auras.

Tonic-clonic seizures also occur in the majority of ADLTE patients, but are infrequent, developing only about once a year.

“These partial seizures can have a significant impact on a patient’s quality of life. Because patients can be disoriented and excessively tired following a seizure event, their day-to-day lives can sometimes be seriously disrupted. And when it comes to driving and other activities, there is still a real danger associated with this condition,” notes Anderson.

“One important reason to identify genetic causes of epilepsy is the hope that these discoveries will eventually lead to new therapies. By identifying this new pathway, we may have found a new target for future drug development,” he adds.

A research article describing Anderson’s study has been published in the journal Nature Medicine. (ANI)

Breakthrough for AIDS cure

TORONTO: In a major breakthrough for AIDS cure, Canadian scientists have finally found where the HIV virus hides in the human body to become impervious to medical treatment.

This breakthrough could pave the way for a total cure of the deadly disease, claim the scientists who carried out the study with researchers from the US.

The current anti-viral treatment for HIV patients can only subdue, not eliminate, the virus as it hides somewhere to lie low and then attack the system again.

Till now, scientists conjectured that the AIDS virus might be hiding in the kidneys or the brain.

But now the Canadian researchers claim that they have discovered the safe havens where the virus hides in the human body.

Led by Professor Rafick-Pierre Sekaly, researchers said they have found that the virus hides in “long-lived” memory cells in the human body.

These memory cells, which have a long life just like the stem cells
, lie sleepy in the body most of the time until they encounter a new virus or disease-causing agents.

Like stem cells, these memory cells are also capable of replicating themselves. So when the AIDS enters them or attacks them, these memory cells multiply to defend the body.

But the problem is that the once AIDS virus enters these memory cells, it also multiplies with them.

Thus, during the current intense medication – which involves five to six drugs that can prolong life up to 13 years – for a patient, the AIDS virus retreats into these safe havens to stage an attack later.

The researchers said they are finding ways to destroy the virus in its safe havens in the memory cells without harming the immune system.

Their research is the “first clue” to eliminating the AIDS virus, said research leader Sekaly Sunday.

There are over 33 million HIV patients worldwide, with 2.7 million more getting infected each year.

The research study has been published in the journal Nature Medicine.

Eye cells deemed to be retinal stem cells are actually normal adult cells

Washington, March 31 (ANI): Researchers at St. Jude Children’s Research Hospital have found that eye cells believed to be retinal stem cells are actually normal adult cells, and thus therapies to restore vision in people with retinal degeneration should involve other types of stem cells.

Scientists have always believed that retinal stem cells may form the basis for treatments to restore sight to millions of people with blindness caused by retinal degeneration, provided they can be obtained.

The current study suggests that scientists researching into cell therapies to restore blindness better not concentrate on the eye cells previously believed to be retinal stem cells.

The St. Jude researchers say that more promising is research aimed at re-engineering stem cells to develop into the light-sensitive photoreceptor cells that are lost as a result of retinal degeneration, as such studies may lead to implantation of engineered photoreceptor cells into the eye to restore sight.

Dr. Michael Dyer, a member of the St. Jude Department of Developmental Neurobiology, points out that it was reported in 2000 that the layer of ciliary epithelial cells lining the inside of the eye contains retinal stem cells because, when grown in culture dishes, these cells formed tiny spheres of about a thousand cells.

He says that such spheres could be cultured to give rise to more spheres, reminiscent of the self-renewing capability of stem cells.

The researcher also underscores the observation that the cultured sphere cells showed activation of genes characteristic of adult eye cells.

“The first clue that these cells were not stem cells was that they were pigmented. Neural stem cells, in general, and retinal progenitor cells, in particular, are not pigmented. Nevertheless, the previous finding was met with a tremendous amount of enthusiasm because of the promise of introducing these cells into the eye to regenerate photoreceptors lost to blindness,” Dyer said.

During the study, Dyer’s team analysed the sphere-forming cells in detail to find out whether they were really retinal stem cells.

The researchers painstakingly studied each cell in the spheres, and found that all of them were pigmented and had features of ciliary epithelial cells.

Dyer and his colleagues later compared the structure of the sphere-forming cells with those of confirmed stem cells and other immature cells in the developing retina called progenitor cells.

They found fundamental differences between the sphere-forming cells and established stem or progenitor cells.

The team also found that simply culturing the sphere-forming cells in the same growth medium, as is used for stem cells, caused them to activate genes characteristic of stem cells, yet remain adult ciliary epithelial cells.

Dyer said that a particularly promising alternative was the possibility of taking samples of adult cells-such as fibroblasts that form connective tissue-from a patient with retinal degeneration and exposing them to genetic cues that induce them to revert to stem cells.

The researcher believes that such induced pluripotent stem cells may later be manipulated to develop into light-sensing photoreceptor cells that could then be transplanted into the patient’s eyes to restore vision.

“This approach would solve many problems of developing cell-based therapy for blindness,” Dyer said.

“First, these cells are immortal, so they can be grown indefinitely to produce large amounts of cells for treatment. And secondly, they would be immunologically matched to the patient, so there would be no danger of rejection. And thanks to some excellent research during the past 15 years, we know a lot about how to reprogram such stem cells to make them into photoreceptors,” he added.

The study has been published in online edition of the Proceedings of the National Academy of Sciences. (ANI)

Protein key to body’s antibody defence mechanism identified

London, March 9 (ANI): A group of American scientists have identified a protein that plays a significant role in the division and replication of the immune cells called B lymphocytes, rapid generation of which is critical to the body’s antibody defence mechanism.

Researchers at the University of California, San Diego School of Medicine highlight the fact that when B cells grow unchecked, it can lead to immune cell cancers such as multiple myeloma or, when they grow to attack the wrong targets, to autoimmune disease.

They say that the discovery of the role played by the CD98hc protein, it may now be possible to develop new therapy targets for such diseases.

Dr. Mark H. Ginsberg, a professor of medicine in whose laboratory the study was conducted, said that his team’s work describes why CD98hc is essential in order for B lymphocytes to transition into antibody-secreting cells.

He further says that the study also describes how this relates to the protein’s role in the signaling ability of integrins – a large family of adhesion molecules that transfer information between the inside and outside of a cell.

Dr. Joseph Cantor, the first author of the study, points out that scientists have known for nearly 25 years that CD98hc, common to all vertebrates, probably played a role in their adaptive immune system, but it wasn’t known how this protein functioned.

“This protein was used as a marker of activation because it was found in low levels on resting lymphocytes,” said Cantor. “But when B or T lymphocytes were stimulated by antigens – for instance, to protect the body against bacteria – levels of CD98hc went up 20 fold,” Nature magazine quoted him as saying.

For their study, the researchers generated a mouse model that lacked the CD98hc protein in B lymphocytes.

Upon vaccinating the mice, the researchers observed that the animals were unable to mount a normal antibody response to the pathogen.

Cantor says that that was the first clue to the importance of the protein.

“In purifying B lymphocytes without the CD98hc protein, we discovered that the lymphocytes couldn’t divide rapidly,” Cantor said, adding that this proved the protein was essential to expanding the number of immune cells, a necessary step in the immune response.

The researchers said that even though the deletion of the protein did not impair early B cell activation, it did inhibit later activation of elements along the signalling pathway that push the cell forward to divide.

“Since B cells can’t rapidly divide and replicate without CD98hc, perhaps by blocking this protein we could stop the unchecked growth of B lymphocyte cells that can result in cancer or block misdirected B cell attacks that can cause certain autoimmune diseases,” said Ginsberg.

The CD98hc protein functions in cells by helping to transmit integrin signals, as well as transporting amino acids – the building blocks of proteins – into the cell. But it was unclear as to which of these functions was related to the protein’s role in the rapid division of immune cells.

During the current study, the researcher replaced normal CD98hc in B cells with a version that lacked one or the other of these two functions.

They found that the integrin-binding domain of the protein was required, but the amino acid transport function is dispensable for B cell proliferation.

“CD98hc interacts with certain integrin subunits to prompt signalling events that control cell migration, survival and proliferation. Our study shows that the rapid proliferation of B cells, necessary for the body to fight infection, is aided by the CD98hc protein’s support of integrin signalling,” Cantor said.

The study has been published in the online edition of the journal Nature Immunology. (ANI)