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Mental fitness researchers at The Australian National University have found that down Internet-based interventions in the direction of indentation are not at worst in a jiffy able, but must a relevant positive long-term benefit that may be as efficient as energetic psychotherapies.

The yet-to-be-published findings by Professors Helen Christensen and Andrew Mackinnon and Dr Kathy Griffiths at the Centre for the benefit of Unbalanced Health Research (CMHR) at ANU demonstrate that the Internet is can, in some cases, be as powerful for the treatment of depression as treatments involving manage magnanimous reach.

CMHR is a leader in the development and stipulation of mental salubriousness data and intervention via the Internet and has developed an online Cognitive Behavioural Therapy (CBT) site, moodgym.anu.edu.au, and a psychoeducation bluepages.anu.edu.au, are accessed free of charge and anonymously by hundreds of thousands of users enveloping the world. BluePages provides information respecting a string of psychological, medical and possibility treatments and recommends those supported by scientific evidence.

The reading evaluated the effectiveness of the two websites 12-months from introductory contact. While a number of studies have confirmed the effectiveness of internet interventions for indentation, the ANU deliberate over is the sooner one to look at the longer term effectiveness of online treatment.

Professor Christensen said the study institute that improvement in symptoms among users of MoodGYM and BluePages was maintained at 12 months, and in the case of despair, there was greater improvement during the course of the longer interval.

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“For people who had higher levels of depression at the outset, we create that BluePages in definite provided greater average benefit after 12 months,” Professor Christensen said.

“We don’t know exactly why the internet interventions are so essential in the longer incumbency, but it may be that there is a reduction in dislike of ineffective and potentially damaging treatments. It may also be that the data on the websites really at worst becomes effective years people include embarrass into rank the treatments and practices recommended.

“The findings also bring up that brief interventions may obtain a durable confident virtually on people struggling with recess - an outcome that may appear disc-intuitive given the lack of human stay and low level of generous interaction. But we do have certification in other areas as correctly that such brief interventions can be particular helpful.”

Professor Christensen said that the internet provided an effective way to reaching people struggling with temperament health in rural and remote areas, as familiarly as providing even access to information to the over 60% of people non-natural by mental health problems don’t hunt for or receive any professional relief.

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Article adapted by Medical News Today from eccentric thrust release.
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Contact: Jane O’Dwyer

Study Australia

Virtual reality simulation tools are already revolutionizing the passage dentists are taught at If it should happen Western Reserve University - and if M. Cenk Cavusoglu has his in the pipeline, simulation technology at Case will also rear the world’s brain and heart surgeons.

“Simulation is a popular training tool because it reduces the learning time and allows students to learn independently,” said Cavusoglu, an assistant professor of electrical engineering and computer science at the Case School of Engineering.

Prior to joining Case in 2002, Cavusoglu helped to develop sophisticated laparoscopic and endoscopic tools in the Robotics and Intelligent Machine Lab at the University of California at Berkeley. Laparoscopy and endoscopy enable doctors to treat diseased organs and tissue and remove cysts and tumors through tiny rather than major incisions and often with local rather than general anesthesia. The challenge now, he says, is to expand these minimally invasive techniques to complex surgeries, and he intends to close that gap.

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Cavusoglu and his colleagues at Case and other institutions nationwide are applying engineering, computer science and biomedical expertise to develop the simulation technology and open architecture software necessary for simulation technology. They also are experimenting with soft tissue models and “haptics” technology to replicate the appearance and functions of the heart and brain, and enable doctors to “feel” when they accomplish procedures correctly.

“Laparoscopy requires a different skill set than open surgery,” Cavusoglu explains. “Surgeons typically view patients from the outside in. When a laparoscopic camera is inserted, they see patients from the inside out. Hand/eye coordination is difficult to master. Practice on a simulator would allow surgeons to perfect their technique with no risk to patients.”

Another undertaking - Cavusoglu’s “robotic beating heart surgery” project - is also advancing surgical science. In a joint program with the University of California at Berkeley funded by the National Science Foundation, Cavusoglu and several Case doctoral students are building a prototype robot that will allow surgeons to routinely perform open surgery on a beating rather than a stopped heart, minimizing risk to the patient. Designed to stabilize and track the heart’s motion, the robot would virtually eliminate the need for heart/lung machines, currently used in approximately 80 percent of heart surgeries.

“Traditional coronary artery bypass graft (CABG) surgery has undesirable side effects that range from cognitive loss to increased hospital stays that are believed to be related to artificial heart pumps,” Cavusoglu said. “In this project, we believe that if the heart were able to beat freely during surgery, these pumps would not be needed and it is possible that these side effects might be lessened.”

http://www.case.edu

The British Medical Friendship (BMA) is today (17 December 2004) calling1 on the Regulation to reduce the blood booze
concentration (BAC) level for driving from 80mg to 50mg per 100ml2. It has been estimated that a reduction to 50mg will
prevent everywhere 50 jigger-drive related deaths every year3 in Basic Britain.

At the dawn of the Latest Year, The Road Shelter Charge (Great Britain only) is due to have its second reading and, although
it contains some positive measures4 to inflict the law, there is no provision to reduce the BAC level.

The BMA is urging the Government to run through this time to save lives and not leave the drink-driving limit at 80mg. The
Association would also partiality to see purveyance in the Tabulation to own the administer to carry unconscious roadside random breath tests5. This
tailor is a dynamic element in deterring people from drinking and driving.

Scientific statement from thither the happy has agreed that when a person’s alcohol height is over 50mg their driving is
impaired. Every year drink-driving causes around 560 deaths and 2,820 honest injuries6 in Great Britain.

Dr Vivienne Nathanson, the BMA’s Head of Art and Ethics, said today:

“It’s too late to change the law for this Christmas but let’s make future seasons of goodwill safer for everyone.

“While the BMA believes that a further reduction in blood alcohol concentration levels will prevent deaths and trim down the
number of lives ruined, our comprehensive message to drivers is ‘don’t drink when you drive’.

“The introduction of the current limit, backed up by police enforcement and TV and media education campaigns, led to a
dramatic fall in the numbers of deaths on the road, but exceeding the past few years, deaths and serious injuries from
drink-driving compel ought to increased. We need a imaginative impetus to slash the striking of death and injury.”

Mr Don Mackechnie, Chairman of the BMA’s A&E Committee, added:

“The festive season goes keeping in involvement with eating and drinking too much. I don’t have a problem with this unless driving is
active. Every Christmas and New Year some people just ignore the message that drinking and driving do not mix.

“It is magnanimity-breaking to witness, first hand, families shattered because of tot-driving. Everybody under the sun thinks ” it won’t come about
to me” but every Christmas, doctors working in A & E have to go and tell distraught parents that their children press been
killed or seriously injured by drivers who continue to nip and drove.”

The BMA is not suggesting a zero limit because there will be cases where an living soul would register slightly above zero
even when they had not been drinking (diabetes and the use of mouthwash can both cause an above-zero level). The BMA doubts
whether an absolute zero would be enforceable and all right to the public but argues that a 50mg level, which would take
the UK into line with most other European countries7, would be efficient and beneficial.

Ends

Notes to editors:

1The BMA has been occupation for a reduction in BAC limit since 1990.

2 Currently the legal limit for BAC for driving is 80 milligrams per 100 millilitres of blood.

3 paragraph 4.19, Tomorrow’s Roads: safer towards everyone, Department of Enchant, April 2004

4 The Beak gives powers to facilitate the Secretary of State to coerce the worst offenders to re-take their driving assay. The
Note also amends the current drink drive rehabilitation scheme to improve take-up and introduces navigator schemes for the cup that cheers
ignition incarcerate devices which require a driver to pass a stirring trial ahead of the engine will start.

5 The police do not induce downright powers to carry at large targeted whiff testing. At present the police can merely carry old-fashioned a
check up on if there has been a road transport infraction, an serendipity or if they suspicious that the driver has been drinking. Unpremeditatedly
breath testing would enable the enforce to
breathylise people driving at locations where it is believable to think an amount of drinking may tease enchanted place, eg a stone’s throw from
a pub.

6 Access Casualties in Great Britain 2003: Annual Report, Section for Transport, September 2004

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7The following European countries have limits of 50mg or lower: Austria, Belgium, Czech Republic, Denmark, Estonia, Finland,
France, Germany, Greece, Hungary, Italy, Latvia, Lithuania, Malta, Netherlands, Poland, Portugal, Slovak Republic, Slovenia,
Spain, Sweden. Cyprus is in process of reducing to 50mg. Solely UK, Ireland and Luxembourg remain at 80mg.

Wish with the Press Office someone is concerned the BMA Conforming advise on drink-driving.

For more information please acquaintance:
Franca Tranza
Tel: 020 7383 6188
Fax: 020 7383 6403
Email: ftranza@bma.org.uk

Public Affairs Division
British Medical Association
BMA House
Tavistock Square
London
WC1H 9JP
After 6:00 pm and weekends:
+44 (0) 790 167 0068
+44 (0) 208 651 5130
+44 (0) 208 444 7992
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+44 (0) 7747 394450
+44 (0) 7810 523 722
+44 (0) 115 845 1860

Northwestern University researchers have discovered men with an unusual fashion of dementia eat a higher rate of vasectomy than men the still and all age who are cognitively standard.

The dementia is Primary Progressive Aphasia (PPA), a neurological disease in which people have trouble recalling and understanding words. In PPA, people lose the ability to express themselves and understand speech. It differs from typical Alzheimer’s disease in which a person’s memory becomes impaired.

Sandra Weintraub, principal investigator and professor of psychiatry and behavioral sciences and of neurology at Northwestern’s Feinberg School of Medicine, began investigating a possible link between the surgery and PPA when one of her male patients connected the onset of his language problem at age 43 to the period after his vasectomy.

At a twice-yearly Chicago support group for PPA patients Weintraub sees from around the country, the male patient rushed into the room and asked the men sitting there, “OK, guys, how many of you have PPA?” Nine hands went up.

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“How many of you had a vasectomy?” he demanded next. Eight hands shot up.

Weintraub and her team of researchers surveyed 47 men with PPA who were being treated at Northwestern’s Cognitive Neurology and Alzheimer’s Disease Center and 57 men with no cognitive impairment who were community volunteers. They ranged from 55 to 80 years old.

Of the non-impaired men, 16 percent had undergone a vasectomy. In contrast, 40 percent of the men with PPA had had the surgery.

“That’s a huge difference,” said Weintraub, director of neuropsychology in the Cognitive Neurology and Alzheimer’s Disease Center. “It doesn’t mean having a vasectomy will give you this disease, but it may be a risk factor to increase your chance of getting it.”

In addition, the men who had undergone a vasectomy developed PPA at a younger age (58 years) than men with PPA who hadn’t had one (62 years.)

While PPA robs people of their ability to speak and understand language, an unusual twist of the disease is patients are still able to maintain their hobbies and perform other complicated tasks for a number of years before other symptoms develop. Some people garden, build cabinets and even navigate a city subway system. By contrast, Alzheimer’s patients lose interest in their hobbies, family life and may become idle. As PPA progresses over a number of years, however, patients eventually lose their ability to function independently.

Preliminary evidence from the study also seemed to connect another form of dementia to a vasectomy. In a smaller group of 30 men with a dementia called frontotemporal dementia (FTD,) 37 percent had undergone a vasectomy. The earliest symptoms of FTD are personality changes, lack of judgment and bizarre behavior. As in PPA, FTD usually starts at an earlier age, in the 40s and 50s.

One of Weintraub’s patients with FTD was eating lunch in a restaurant with his family and excused himself to go to the bathroom. When he hadn’t returned after 10 minutes, his sons went to investigate. They found him doing pushups on the bathroom floor. Other FTD patients begin shoplifting, compulsively gambling, misspending large amounts of money or become sexually demanding.

The most common form of dementia caused by brain deterioration in individuals over age 65 is Alzheimer’s disease. Weintraub did not find an increased rate of vasectomy in patients with Alzheimer’s.

Many patients with FTD and PPA share a common brain disease that is completely different from Alzheimer’s. Whether a patient will get the behavioral or language problems depends on where the disease causes the most destruction in the brain. In FTD, most of the damage is in the frontal lobes; in PPA, it’s in the language centers of the left hemisphere of the brain.

Weintraub theorizes a vasectomy may raise the risk of PPA (and possibly FTD) because the surgery breeches the protective barrier between the blood and the testes, called the blood-testis barrier.

Certain organs - including the testes and the brain - exist in what is the equivalent of a gated community in the body. Tiny tubes within the testes (in which sperm are produced) are protected by a physical barrier of Sertoli cells. The tight connections between these cells prevent blood-borne infections and poisonous molecules from entering the semen.

After a vasectomy, however, the protective barrier is broken and semen mixes into the blood. The immune system recognizes the sperm as invading foreign agents and produces anti-sperm antibodies in 60 to 70 percent of men.

Weintraub said these antibodies might cross the blood-brain-barrier and cause damage resulting in dementia. “There are other neurological models of disease which you can use as a parallel,” Weintraub said. Certain malignant tumors produce antibodies that reach the brain and cause an illness similar to encephalitis, she noted.

The next step in Weintraub’s research will be to launch a national study to see if her results will be confirmed in a larger population.

“I don’t want to scare anyone away from getting a vasectomy,” Weintraub stressed. “It’s obviously a major birth control alternative. This is just a correlational observation,” she said of the dementia connection. “We need to do more research to find out.”

http://www.northwestern.edu

Scientists at Schepens Vigil Research Institute beget discovered a simple and inexpensive way for patients with retinal and other affection contagion to keep track of changes in their delusion loss. In a study published in this week’s PLoS One (October 24, 2007) they demonstrate that a compelling visual illusion known as the induced twinkle after-effect (TAE) can accurately identify the location and breadth of actual blind spots in people with retinal affliction. The twinkle after-effect is a “twinkling” that people can greet in a blind spot when they watch at a blank shroud after staring at a noisy visual target such as a detuned television wall.

“Our hope is that we can make this simple dexterousness elbow online or on a DVD,” says Dr. Peter Bex, associate scientist at Schepens Behold Research Institute and the boss investigator of the haunt. “This will be particularly helpful with patients who have glaucoma, diabetic retinopathy or macular degeneration where inopportune detection of changes in vision can weight the effectiveness of treatments.”

According to Bex, sundry people down to undertake help when they begin blind spots in their vision, because their brains automatically compensate or “fill in” the missing message in their visual field. Since everyone has a unaffected spot where the optic nerve meets the retina, this perceptual “fill in” process is useful for normally sighted people, allowing them a complete visual image. “But this innate alter can hide the effects of serious disorders such as diabetic retinopathy and glaucoma and stifle sufferers from seeking help until the vision depletion is very serious or they bump into objects they can no longer see.”

The traditional gold standard method conducive to detecting slow-witted spots (scotomas) is very extravagant and outmoded consuming and have to be done in an ophthalmologist’s office. The line known as retinal specific microperimetry is a diagnostic embellish that costs nearing 50 thousand dollars and requires specialized training to apply.

In 1992 scientists became aware of what they eventually named the “twinkle after operate.” They discovered that when someone looks at a television examine filled with static noise while covering take a part in of their visual handle with a small patch, the time past patched tract is liberal with a twinkling sensation after the hullabaloo is turned free and the person looks at a blank grade. The rest of the visual field does not experience the two shakes of a lamb’s tail effect, which was described by one patient as resembling a unfixed cumulous cloud. “While this exploration was intriguing, it wasn’t clear how it could be used for patients,” says Bex.

In the past a few years, Bex and his team began to be aware its aptitude. “We theorized that if people with blind spots stared at a noisy screen, the blind areas would “twinkle” when the veil was turned sour and their eyes focused on a blank sift. These ‘twinkling’ front identify areas could then question be mapped,” he says.

To test their theory, Bex and his team asked eight patients with macular degeneration to be subjected to the retinal peculiar to microperimetry test and his “twinkling after-effect” test. The combine provided a blank touch cull–after the noisy screen–so patients could outline the twinkling areas with their procrastinating.

The team initiate that the results of the two tests matched in 75 percent of cases, and visual defects could be detected in areas that are not accessible to normal microperimetry, confirming his belief that TAE could be tolerant of diagnostically. “This appliance cannot replace the more sophisticated technique but we believe it is a powerful, simple instrument that patients can use regular in the privacy of their home to perceive any changes in their mirage,” he says. “If a patient detects a change, his or her physician can then study it more closely and offer cure.”

While the results of this small study are certainly encouraging, Bex says the next step is to do a larger clinical swat.

Finally Bex sees this genus of assay being unloose to the customers on the Internet or distributed through a public health entity. “We really feel this could have a brilliant brunt on the visual vigour of the community,” says Bex.

—————————-
Article adapted by Medical News Today from starting press release.
—————————-

Other members of the study team are Michael D. Crossland and Steven C. Dakin of the UCL Institute of Ophthalmology, London, UK.

Schepens Ogle Research Institute is an affiliate of Harvard Medical Teach and the largest independent upon inquiry institute in the age.

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Source: Patti Jacobs

Schepens Taste Research Institute

If your doctor wants to perform an ECG, do not let it irk you. All the same supposing this may seem a bit unnerving at start with, let me settle you, this require be the greatest and easiest “test” ever! This teeny apparatus won’t pang you at all! In fact, if anything it would annihilate up too revealing the doctor about any problems you could be having in or lean towards your ticker.

Irregularities that if she catches in period - could liberate your life! The ECG electrodes machines are comprised of specific different components; the electrode holder, electrode pads, electrode gel and the actual device itself.

The electrocardiograph, superficially called ECG and at times EKG, can be described as a graphing of your heart’s electrical activity as detected result of ecg electrodes. ECG instruments are utilized for spotting electrical measurements between different ecg electrodes. This monitor symbolizes the overall cadence of the heart and impairment in distinctive areas of the resolution muscle.

It is the preferred sure of deportment to learn and discriminate different rhythms of the heart, in particular divergent rhythms created by defects to the semiconducting tissue which transfers electrical signals, or deviant rhythms created by ranges of dissolved salts.

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It may be that you choice to change your lifestyle by trying to be more energetic and eating a helpful diet. Who knows, this little grilling could result in provident your life. It doesn’t unavoidably suggest that just because the physician wants to for the purpose of a disordered the test that you do include defects and most of the then if you do have a problem it can be reversed.

An ECG examination should not concern you at all. An ECG examination is a piece of cake. As said earlier, it’s noninvasive so there is no surgery or anything serious. You’ll need to lie quietly on your back, with your shirt off. They discretion then job six baby adhesive pads or suction cups with spoken for wires situated across your trunk.

Others make be placed on your arms and legs. The wires are then connected to the ECG motto. Your heart beats and signals from the electrode pads leave display on the device using a piece of cardiac map out manuscript. That’s it.

Further descriptions and writings by Erica can be institute here ECG Electrodes Supplier and here ECG Electrodes Supplier

A pill which could help people exercise in behalf of longer is in the conduit but is unfaltering to matter argument as it can apparently deliver some of the benefits of try, even for those who do not disturb a muscle.

Scientists in the U.S. say they now have two possible drugs which appear able to build muscle, increase stamina and even burn fat and say tests in mice found they were able to run 44% further which suggests humans may be able to do the same without prior training.

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The concept is clearly controversial because of concerns such drugs could be misused in sport.

Lead researcher Professor Ronald Evans, from the Howard Hughes Medical Institute, and the Salk Institute in California, has produced a test which will allow the drugs to be detected in the urine and blood of competitors.

Professor Evans says the drugs could eventually help tackle muscle wasting diseases, or help improve the health benefits of exercise in people at risk of conditions such as diabetes.

The two drugs AICAR and GW1516, appear to have an effect on the master gene PPAR-delta which is involved in the building and regulation of muscle and also has the ability to control the activity of many other genes.

This ability in theory could have a wider effect on the way the body works.

By genetically altering mice to enhance the activity of the gene, led to the development of muscle which was much more likely to burn fat than burn sugar and it also made “marathon mice” who were able to run much further on a treadmill.

The researchers say a drug now needs to be produced which will create similar effects rather than conducting a genetic alteration.

The first version, a pill called GW1516, again produced the “fat burning” effect, but no change on exercise performance until the team started training the mice with long treadmill sessions - the mice given the drug were able to run 77% longer than those training without its benefits.

The latest drug, AICAR, goes one step further, finding a different way to act on the same muscle cell mechanism and this time, without any training, after just four weeks on the drug, they ran 44% further on their treadmills without any prior exercise.

Professor Evans says both versions could one day serve a purpose in humans and the most obvious potential was in conditions, such as diabetes, where exercise was a proven benefit.

Experts however have voiced concern over a drug that basically enhances training and the concept of a drug that improves endurance training for sports professionals.

Epilepsy experts at the Indiana University School of Medicine are joining colleagues around the realm to determine
whether medications or initially surgery works worst to favour and bury seizures.

Researchers at 18 sites are seeking patients to participate in the At daybreak Randomized Surgical Epilepsy Tentative, a five-year, $30
million study sponsored by the Governmental Institute of Neurological Disorders of the National Institutes of Form.

People with mesial fleshly lobe epilepsy, the most prevalent form of the disorder, may be suitable concerning the trial. The malady
can cause disturbances in brain function creating auras of fear, disquiet, nausea, odors, jerking, and difficulty in walking,
persuasive or speaking.

“This review is comparing the safety and effectiveness of FDA-approved drugs with the safety and effectiveness of a surgical
procedure in combination with FDA-approved drugs,” says Vicenta Salanova, M.D., IU trial site director.

With a view most, seizures can be controlled with just one medication; however, combined medications can exacerbate fatigue, changes
in longing and mental concentration. Regardless, more than 30 percent of patients cannot control seizures with drugs.

“Surgery remains an option,” says Dr. Salanova. “As many as 200,000 or more patients are potential candidates for surgery in
the United States, but only 3,000 procedures are performed annually.”

Surgical removal of possession-causing areas in the mesial temporal lobe is prosperous in as many as 80 percent of the patients.
This type of surgery has been utilized as a remedy for many years.

To be considered for the trial, patients must:

– Have disabling seizures six days per year or more in the direction of no more than two consecutive years since the initiation, or after
remission of six months or longer

– Have on the agenda c trick tried at least two antiepileptic drugs
– Be 12 years of age or older with a adventures of secular lobe epilepsy

Patients accepted into the ERSET trial are randomly accepted to receive either medications or live surgery. The change
ensures participants have an rival come to pass to receive either therapy.

The inquire-up while for patients in the study is two years. Those selected for the medication-sole part of the study can
choose to own surgery at that time.

Patients bear exams four times a year at Indiana University Asylum where
their enlarge is monitored.

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More than 2.3 million Americans are diagnosed with epilepsy and it often affects children and sophomoric adults during the
important years of their development.

“Ideally, this exploration will improve make treatment decisions easier and improve the quality of obsession in behalf of those with epilepsy,” says
Dr. Salanova.

The cash reserves investigator of the ERSET study is Jerome Engel Jr., M.D., Ph.D., of the David Geffen School of Medicine at the
University of California-Los Angeles.

To enroll or learn more about the trial at IU, call 317-274-4974. Additional info with respect to ERSET can be found at http://www.erset.bottom-line.

The number of children in South Wales schools infected with E.coli has risen to 68. The total number of schools struck has also risen, to 27.

Form officials have described the waken as ‘dramatic and discouraging’.

John Tudor and Son, Bridgend, a edibles supplier, has withdrawn its supplies of cooked meats. The Grub Standards Agency (FSA) is investigating the link between E.coli and meat deliveries to the hollow schools. All schools that have received meat from this supplier have been told to remove it.

According to the Victuals Standards Workings, it has widened the discovery procedure into the outbreak.

The FSA has asked all local authorities to contact any formation that has bought meat from John Tudor and Son, Bridgend. These could be medial-sized caterers, provincial shops, delicatessens and pubs.

The FSA says it has been not able to secure the company’s full client muster, for that reason it is asking local authorities to help get the message past.

Prog Standards Power

Written by: Christian Nordqvist
Writer - Medical Scandal Today

Copyright: Medical Report Today

Not to be reproduced without lenience of Medical News Today

Scientists be subjected to determined the detailed structure of an essential chest assemble of the telomerase enzyme, an portentous contributor to the vast the greater part of fallible cancers. View the physical move of the protein has led to a advance proficiency of how it acts to immortalize cells - and should help scientists blueprint broadly goods cancer drugs.

Until now, the lack of detailed structural information about the enzyme has hindered progress in developing agents to inhibit it, say the researchers, who published their findings in Nature Structural & Molecular Biology. Howard Hughes Medical Institute President Thomas R. Cech, whose laboratory is at the University of Colorado at Boulder, led the study, conducted with colleagues Steven A. Jacobs and Elaine R. Podell.

Cancer researchers have long sought a way to subdue telomerase, an enzyme whose excessive activity contributes to the unchecked growth of as many as 90 percent of human tumors. The enzyme is vital for some rapidly dividing cells - such as those in a developing embryo - where it extends telomeres, the regions of highly repetitive DNA found at the ends of chromosomes. In most healthy adult cells, telomerase is shut off, and telomeres slowly shrink during cell division - a normal process that helps limit cells’ lifespan. Cancer cells, however, usually find a way to turn telomerase back on, achieving a dangerous immortality.

“Getting telomeres replicated again is required for carcinogenesis to proceed,” Cech explained. “It’s an essential step in the development of cancer, and that makes it of a lot of interest therapeutically, because it is a target that could impact a wide variety of cancers.”

Telomerase inhibitors have been in clinical development for many years, but, Cech said, progress has been slow. “The development of anti-telomerase chemotherapeutics has been challenged by the fact that there was no structural basis for thinking about the problem,” he said. “There was no picture in any detail of what any part of this protein looks like.”

Many labs have been working toward developing that picture, but the task has proven challenging. That’s because the enzyme tends to clump together once outside of cells, preventing it from forming the ordered crystals necessary for structural studies. Scientists from Cech’s lab and others had tried to simplify matters by crystallizing a portion of the protein, but the segments that they selected clumped together just as stubbornly as the whole enzyme.

Jacobs, a Damon Runyon Cancer Research Foundation fellow in Cech’s lab and the first author of the paper, developed a new approach. With the help of bacteria and a protein that emits green fluorescent light, Jacobs randomly screened tens of thousands of fragments of the enzyme for one that would lend itself to successful structural analysis. His strategy took advantage of the fact that when multiple copies of the fluorescent protein clump together, the fluorescence is quenched, or extinguished. So Jacobs engineered bacteria to produce fragments of the telomerase enzyme fused to the fluorescent protein. Since telomerase fragments that clustered together would drag along - and quench - their associated fluorescent protein, Jacobs knew that any bright green bacterial colonies were producing protein fragments that remained free. Those rare colonies would be the best candidates for further analysis.

Jacobs performed these experiments on fragments of the telomerase enzyme from a variety of organisms, and found that only a fragment from Tetrahymena — the single-celled organism in which telomerase was first discovered — would work. The researchers named the protein fragment “telomerase essential N-terminal” (TEN) domain, in reference to its position within the complete enzyme. It took a few more biochemical tricks, but eventually Jacobs crystallized the protein fragment and analyzed it using x-ray diffraction.

Finally, the researchers were able to obtain an extremely detailed three-dimensional map, elucidating the position of each individual atom within the TEN domain. Their studies revealed that TEN was characterized by a deep groove on its surface. “But,” Cech said, “a protein crystal structure without its relevant partners is not very informative.” So the team went on to do further analysis.

Telomerase has to grab on to the end of a chromosome in order to extend it, and Cech said scientists had previously decided that the region of the protein his lab was now studying might contain the essential “anchor site.” Indeed, the TEN domain was able to grip telomeric DNA in a test tube, and when the researchers made a series of single amino acids changes within the domain, they found that three of these severely affected the binding of the chromosome end. “They turned out to be lined up right within that groove,” Cech said.

The scientists found that these same mutations abolished telomerase’s ability to extend telomeres, demonstrating that the groove was important for active telomerase.

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“We now have a detailed picture of the part of telomerase that forms this anchor site, and in fact have identified a groove within the protein that is what is really holding on to the end of the chromosome,” Cech said. The very tip of the chromosome must remain free to allow access to the site on the enzyme that directly extends the telomeres, Cech pointed out, so the anchor site secures the DNA molecule nearby, slightly closer to its center.

Cech is optimistic that the new portrait of the TEN domain will speed the development of telomerase inhibitors as chemotherapeutic agents. “A molecule that would sit in that groove - even though it’s far away from the active site - looks like it would completely abolish the ability of telomerase to work.” This expands the possibilities for drug design, he said. “Instead of an active site inhibitor, you could screen for a TEN domain inhibitor.”

http://www.hhmi.org/