New effective strategy for treating tobacco addiction

Washington, May 12 (ANI): A group of researchers has developed a novel tea filter to treat cigarette addiction and have discovered the molecular mechanism behind the smoking cessation effect.

Professor Zhao Baolu and his group from the State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences identified theanine as the active ingredient in the tea filter that inhibits nicotine addiction.

Their work entitled “The cessation and detoxification effect of tea filters on cigarette smoke” was published in the X. edition Science of China in 2010.

Cigarette smoking has been linked to many life threatening diseases including heart disease, cancer and chronic obstructive pulmonary disease.

Many methods have been developed for smoking cessation by researchers and clinicians. Despite all efforts, currently available smoking cessation methods produce only modest success rates with frequent relapse. Due to the addictive nature of nicotine, quitting smoking remains an extremely difficult task. Therefore, the need for developing new smoking cessation strategies with better efficacy and fewer side effects is urgent.

Human tests using a newly developed tea filter were conducted at the Addiction Branch of Beijing Military Region General Hospital. A total of more than 100 male smokers participated in this study. The results from the first trial showed that the participants” average daily cigarette consumption decreased by about 43 percent and 56.5 percent after using the tea filters for 1 and 2 months, respectively. The results from the second trial showed that the participants” average daily cigarette consumption decreased by about 48 percent, 83 percent and 91 percent after using the tea filters for 1, 2 and 3 months, respectively.

The average daily cigarettes consumed by the participants decreased from about 24.5 per day to about 3 per day at the end of 3 months of treatment. In addition, most participants indicated that sputum and their smoking-related symptoms were reduced compared with the control group. Physical examinations of the participants did not reveal any apparent side effects.

The mechanism of action (MOA) studies indicated that theanine in the filter exerted an inhibitory effect similar to the nicotine acetylcholine receptor (nAChR) inhibitor. In addition, theanine could significantly inhibit the nicotine-induced increased expression of nAChR and the increase of the neurotransmitter dopamine (DA) released in mouse brains. The toxicological studies showed that the tea filters could significantly reduce the carcinogenic materials such as tar, free radicals, nitrosamine, benzo[a]pyrene, benzo[a]anthracene, chrysene and total polycyclic aromatic hydrocarbons (PAHs) generated in cigarette smoking. Animal studies also revealed that tea filters could significantly reduce the acute toxicity, mutagenicity, lung damage and carboxyhemoglobin (COHb) levels in the blood caused by cigarette smoking. (ANI)

Poplars, just like humans, also feel stressed

Washington, May 7 (ANI): Just like humans, trees too, feel stressed. And scientists have now claimed that hormone suppression could help common poplars— cottonwoods and aspens—deal with stress.

Trees’ stress can come from a lack of water or too much water, from scarcity of a needed nutrient, from pollution or a changing climate.

A new study led by Michigan Technological University scientists, has identified the molecular mechanism that Populus—the scientific name for common poplars—uses to adapt to changing soil conditions, as well as some of the genes that turn the process off or on.

And now they look forward to apply what they’ve learned to find ways to use biotechnology or selective breeding to modify the trees to make them more stress-tolerant.

“Our hope is that by understanding how this works, we can manipulate the system so the plants can adapt faster and better to stressful conditions,” explained Dr. Victor Busov.

The researchers analysed thousands of genes in the Populus genome, the only tree genome that has been completely sequenced.

They were searching for the mechanism that regulates the plant’s decision to grow tall or to spread its roots out in an extensive underground exploration system that can sample the soil near and far until it finds what the rest of the plant needs.

The key players turned out to be a family of hormones called gibberellins, referred to by the scientists as GAs.

“GAs’ role in root development is poorly understood and the role of GAs in lateral root formation is almost completely unknown,” said Busov.

Lateral roots are the tangle of tiny roots that branch out from the primary root of a plant.

”They are the sponges, the ones that go looking for nutrients, for water—the ones that do most of the work,” explained Busov.

The researchers found that GAs interact with other plant hormones such as auxin to tell the plant whether to concentrate on reaching for the sky or on building a bigger, better network of roots under ground.

“The GAs and auxin are definitely talking, molecularly,” said Busov.

Growing poplar seedlings mutated to make them GA-deficient, the scientists compared their root and stem growth to others that contained moderate amounts of GAs and a control group of wild-type plants with normal GAs.

They found that the more GAs, the more a plant’s stem flourished, but its roots remained spindly.

When GA production was shut down, either by using mutants that lacked the necessary genes or by silencing the genes that form the molecular on-off switch, the resulting plants looked dwarfed, but their lateral roots grew luxuriant and full.

Application of GA to the GA-deficient dwarf plants rapidly reversed the process. The plants grew tall, but their lateral root systems shrivelled.

“Clearly, lack of the hormone promotes growth below ground, while the hormone itself promotes growth above ground. This is a natural mechanism that we don’t know much about. It’s always a tradeoff between growth above ground and growth below ground. Normally there is a fine balance, and this balance is a little disturbed under stress,” said Busov.

The study has been published in a recent issue of the journal The Plant Cell. (ANI)

How breast tumor cells break free and start to spread

Washington, May 5 (ANI): Researchers at the University of Kentucky Markey Cancer Center have identified a key mechanism in metastatic breast cancer.

The boffins have found a molecular mechanism in breast cancer that enables tumor cells to spread to adjacent or distant parts of the body in a process called metastasis.

The research, led by Peter Zhou, associate professor of molecular and cellular biochemistry at UK, focused on the process by which tumor cells stop clinging to other cells and become motile, or able to spread throughout the body.

The findings were published in an article in the EMBO Journal, the flagship publication of the European Molecular Biology Organization.

Zhou said: “Scientists at the Markey Cancer Center are currently exploring this idea and are keen to develop drugs that can treat metastatic cancer.”

Breast cancer is the most common cancer in women. Approximately 90 percent of breast cancer deaths are caused by local invasion and distant metastasis of tumor cells, and the average survival after documentation of metastasis is approximately two years.

“An understanding of the mechanism underlying the biology of breast cancer metastasis will provide novel therapeutic approaches to combat this life-threatening disease,” Zhou said. (ANI)

How we can sense temperatures

London, Apr 24 (ANI): A group of experts has shed new light on the molecular mechanism that enables us to sense temperature, such as the heat from a sizzling stove.

The finding by scientists at The Scripps Research Institute and the Genomics Institute of the Novartis Research Foundation (GNF) could one day lead to new therapies for conditions such as acute or chronic inflammatory pain.

The study, which was led by Scripps Research and GNF Professor Ardem Patapoutian, was published in the journal Nature Neuroscience.

To understand temperature sensation, the researchers focused on a protein called TRPV1, which is a member of a small family of proteins known to enable temperature sensation, and is involved in inflammation and the communication of pain to the brain. After producing thousands of mutants of this protein, the scientists were able to identify a region of the protein that enabled temperature sensitivity and to detail some of the molecular mechanisms at work in the molecule.

“Ever since the discovery of these proteins, it has been an outstanding question how they can be activated by temperatures,” said Research Associate Jörg Grandl, a member of the Patapoutian lab and first author of the paper. “The new study addresses this question.”

“Because our ability to sense temperature is closely linked to our ability to sense pain, some of these ion channels are considered targets to treat chronic inflammatory and neuropathic pain indications,” said Patapoutian. “Understanding these proteins could be crucial in designing future drugs that can either activate or block them.” (ANI)

Source of ‘noise’ in HIV identified

Washington, April 21 (ANI): Scientists in the U.S. have discovered a molecular mechanism that the human immunodeficiency virus (HIV) seems to utilize for generating random fluctuations called ‘noise’ in its gene expression.

The research has identified the likely source of HIV gene-expression noise and offers intriguing insight into the role of this noise in driving HIV”s fate decision between active replication and latency.

After infecting a human cell, HIV integrates into the genome and typically begins to actively replicate. However, the virus can also enter a long-lived latent state, which remains the greatest barrier to eradicating virus from the patient.

Senior study author, Dr. Leor S. Weinberger, a molecular virologist and systems biologist from the Department of Chemistry and Biochemistry at the University of California, San Diego, recently showed that noise in HIV gene-expression critically influences the viral decision to enter either active replication or latency. However, the source of the noise was not clear.

To probe the source of this inherent noise in HIV gene expression, Dr. Weinberger and colleagues exploited a technique from electrical engineering that analyzes how noise changes across different levels of expression.

The researchers examined cells carrying a single integrated copy of HIV engineered to produce a quantifiable protein, and measured HIV-1 expression noise at dozens of different viral integration sites which act as distinct genetic environments for viral gene expression.

The researchers found that HIV noise levels are substantially higher than measured in other organisms, and that HIV gene expression occurs in randomly timed bursts.

During these expression bursts, multiple copies of HIV gene products are produced that leads to the high noise levels in HIV gene expression.

The bursting model argues that during active expression HIV cycles between periods of silence and bursting and provides insight into how HIV may be activated by host signaling molecules.

“We know that noise in gene-expression can critically influence HIV”s entry to proviral latency. These new results point to transcriptional bursting as a major source of the noise,” Dr. Weinberger said

“This finding that transcriptional bursting generates an exceptionally noisy HIV promoter, noisier than almost all other measured promoters, supports the theory that latency may be fundamental to the HIV life cycle and that HIV evolved for probabilistic entry into latency,” Dr. Weinberger added.

The study has been published in the April 20th issue of the Biophysical Journal. (ANI)

Molecular mechanism underlying severe form of diabetes in kids identified

Washington, Sept 9 (ANI): University of Iowa researchers have identified a new molecular mechanism underlying a rare and severe form of diabetes in children.

The new mechanism involves a protein called ankyrin and appears to regulate specialized pancreatic cells and insulin secretion

The researchers hope that the new discovery may help identify new molecular targets for treating both rare and common forms of diabetes and hyperinsulinemia.

During the study, the team used animal and cellular models to focus on a gene mutation linked with permanent neonatal diabetes mellitus.

Children with this genetic form of diabetes have symptoms by age 6 months and require lifelong dependence on insulin to maintain proper glucose levels.

They found that the specific human gene mutation disrupts the ability of the protein ankyrin to regulate a key protein complex known as the KATP channel.

“We have known for some time that human mutations in the KATP channel complex may cause diabetes or hyperinsulinemia,” said Faith Kline, Ph.D., the study’s lead author and postdoctoral fellow in internal medicine in the University of Iowa Carver College of Medicine. Now we know something about how this specific KATP channel mutation results in disease.

“The KATP channel essentially functions as a gatekeeper for insulin secretion by pancreatic beta cells. Without proper regulation by this gatekeeper, the pancreatic beta cells are unable to efficiently regulate insulin secretion,” Kline added.

According to the researchers, a key finding in this study was identifying the ankyrin protein in the pancreatic beta cell, which is a type of excitable cell.

Ankyrins also play critical roles for ion channel regulation in other excitable cells, such as neurons and heart cells called cardiomyocytes,”

The team found that the gene mutation prevents most KATP channels from binding with ankyrin, which typically acts as a cellular chaperone. This failure prevents the KATP channels from reaching their normal destination in the cell membrane.

The team also found that the few mutant KATP channels that do reach the pancreatic cell membrane do not respond to alterations in cellular metabolism. As a result, the pancreatic beta cells do not release insulin appropriately.

The study appears in Proceedings of the National Academy of Sciences. (ANI)

New fruit fly model to help scientists study human disease Charcot-Marie-Tooth

Washington, June 23 (ANI): Scientists in Belgium have created the first ever fly model that can help them unravel the molecular mechanism behind Charcot-Marie-Tooth (CMT)-a hereditary disorder of the peripheral nervous system-by putting mutant genes from human patients into fruit flies.

The breakthrough is the result of collaboration between VIB researchers working at the University of Antwerp and the Katholieke Universiteit Leuven.

“By putting mutant genes from human patients into fruit flies, we’ve created the first ever fly model for this kind of neuromuscular disease,” says Albena Jordanova.

“Now we have the opportunity to unravel the molecular mechanism behind Charcot-Marie-Tooth, as well as to start looking for substances with therapeutic value,” the researcher added.

A research article on the study, appearing in the Proceedings of the National Academy of Sciences (PNAS), reveals that CMT patients suffer from progressive motor impairment, muscle wasting and weakness, sensory loss, and foot deformities.

It further states that the disease affects children as well as adults, and that it often starts with minor symptoms, gradually worsening over time. Presently CMT cannot be cured or prevented.

In a previous study, Jordanova and Vincent Timmerman had found that CMT patients in families in Belgium, Bulgaria and the US showed three specific changes in one of the most ubiquitous genes in life: the YARS gene.

YARS is responsible for the production of one of the oldest enzymes in the history of life (tyrosyl-tRNA synthetase), which is vital for the production of proteins. This was an entirely unexpected breakthrough.

Since YARS had been considered a closed chapter in the biology textbooks, no one ever suspected the relationship with specific variants of CMT until the revelation by Jordanova and her colleagues.

These VIB findings open up an entirely new field of research.

The researchers introduced four variants of the YARS gene into fruit flies.

The normal variant, showed no difference in ordinary fruit flies. However, fruit flies with the mutant YARS genes, showed clear symptoms of CMT such as a reduced capacity to move, decreased functioning of the nerve cells and degeneration of the nerve endings. (ANI)

Protein that helps summon DNA repair teams to fix cancer-causing defects identified

London, June 20 (ANI): A tumour-suppressing protein, called BRIT1, gives signal to cellular repair mechanisms to pounce on damaged DNA by overcoming a barrier to DNA access, according to a study.

Led by scientists at The University of Texas M. D. Anderson Cancer Center, the study showed that BRIT1 connects with another protein complex to relax DNA’s tight packaging at the site of the damage.

“Relaxing this barrier allows two different DNA repair pathways greater access to the damage, preventing flawed DNA from being passed on as the cell divides, which causes genomic instability leading to cancer,” Nature magazine quoted senior author Dr. Shiaw-Yih Lin as saying.

BRIT1 is under-expressed in human ovarian, breast and prostate cancer cell lines and researchers had earlier shown that it plays a key role in early detection of DNA damage.

First author Dr. Guang Peng said that chromosomes are made of DNA that is tightly intertwined with proteins called histones to form chromatin, which is a very condensed structure that forms a natural barrier inhibiting access to genes.

ATP-dependent chromatin remodelling is a fundamental mechanism used by cells to relax chromatin in DNA repair, but the detailed molecular mechanism by which it is recruited to DNA lesions in response to damage signalling is not known until now.

“Our studies demonstrate a novel mechanism by which BRIT1 recruits chromatin remodeling factors to DNA lesions to facilitate chromatin relaxation and DNA repair,” said Peng.

After conducting a series of lab experiments, scientists showed that BRIT1 accomplishes this by enhanced binding to a known chromatin remodelling complex called SWI-SNF when a specific site on the complex is phosphorylated.

BRIT1 also maintains the relaxation factor at the damage site.

They demonstrated that normal BRIT1 aids repair of double-stranded DNA breaks by allowing access to two repair pathways: homologous recombination (HR) and non-homologous end joining (NHEC).

Peng said that the findings hold potential to treat cancer cells lacking BRIT1 with PARP inhibitors-drugs that specifically kill HR-deficient cancer cells.

The study has been published online in Nature Cell Biology. (ANI)

New therapeutic target in Alzheimer’s disease identified

Washington, April 14 (ANI): Researchers at University College London (UCL) have identified a protein, known as serum amyloid P component (SAP), which may be a possible therapeutic target in Alzheimer’s disease.

Lead researchers Professor Mark Pepys FRS has even developed a new small molecule drug, CPHPC, which specifically targets SAP and removes it from the blood.

Working in collaboration with Professor Martin Rossor from the Dementia Research Centre of UCL’s Institute of Neurology, Professor Pepys’ team have also shown that the drug also removes SAP from the brains of patients with Alzheimer’s disease.

During a study, the researchers gave the drug to 5 Alzheimer’s disease patients for 3 months, and found SAP to deplete not only from the subjects’ blood but from their brains also.

Lab tests revealed the molecular mechanism responsible for the unique effect, and also disclosed for the first time the way in which SAP accumulates in the brain in Alzheimer’s disease.

The researchers revealed that neither the administration of CPHPC nor the removal of SAP had any side effects in the patients.

“The safety of CPHPC, together with the novel action of the drug in removing SAP from the brain, is very encouraging”, said Professor Rossor.

Although the 3-month treatment period was too short to show any clinical benefit, there was no obvious deterioration.

The researchers are planning longer and larger scale clinical studies to confirm safety and seek evidence of benefit to the patients.

“The complete disappearance of SAP from the brain during treatment with CPHPC could not have been confidently predicted, and the drug, also to our surprise, entered the brain. Coupled with the absence of any side effects, these new findings strongly support further clinical studies to see whether longer term treatment with CPHPC protects against the inexorable mental decline in patients with Alzheimer’s disease,” said Professor Pepys.

The study has been published in the PNAS. (ANI)

Light pulses may prevent future drugs from reaching wrong tissue inside body

London, March 28 (ANI): Biochemists believe that future medicines may feature an in-built system to prevent them from reaching the wrong tissue inside the body, says a report.

Joakim Andreasson at Chalmers University of Technology in Gothenburg, Sweden, says that a light-activated “combination lock”-a molecule that only becomes active when exposed to two distinct colours of light in the right order-has been developed, and that it may help ensure that small packages of drugs deliver their payload only exactly where and when it is needed.

This breakthrough has been achieved in collaboration with researchers from Arizona State University.

Previously designed molecular locks used chemicals as the trigger, which makes for a sluggish system because they diffuse slowly through the body.

Andreasson says that using pulses of light is much faster, and that it also allows the lock to be opened and closed repeatedly, as there are no chemical residues to foul the molecular mechanism.

Describing the lock, the researcher has revealed that it is a complex molecule with three components – two light-sensitive portions called photochromes that act as switches, and a “reporter” unit.

The reporter will fluoresce when both photochromes are switched to the right setting and triggered in the correct order, says the researcher.

The light produced by the reporter could in turn be used to activate or a release a drug or other molecule designed to be sensitive to it, the researcher adds.

“The only input sequence that will [open the lock] is UV light followed by red light,” New Scientist magazine quoted Andreasson as saying.

According to the researchers, green light can be used to reset the lock.

Devens Gust, one of the Arizona research team, believes that the most obvious application of the molecule is as a lock to ensure secure drug delivery at the right location in the body.

Andreasson, however, insists that this will require the technique to be modified to work at light wavelengths that can penetrate tissue, such as the infrared used in prototype brain-scanning headbands.

A research article on this work has been published in Chemistry: A European Journal. (ANI)

Molecule that helps sleep-deprived to mentally rebound identified

Washington, Feb 24 (ANI): Researchers from UT Southwestern Medical Centre researchers have identified a key molecular mechanism that helps the sleep-deprived to mentally rebound.

Mental clarity lost due to few sleepless nights can often be restored with a good night’s rest.

In the study conducted using mouse model, they discovered a molecule called an adenosine receptor that is necessary for sleep-restricted animals to attain adequate levels of slow-wave activity in the brain once normal sleep resumes.

It is this increase in slow-wave activity, or SWA, during rebound sleep that helps restore normal working memory and attention skills to the sleep-deprived.

“Normal society pushes people to burn candles at both ends – going to bed late, getting up early, and somehow performing mentally with lack of adequate sleep,” said senior author Dr. Robert Greene, professor of psychiatry at UT Southwestern.

“We need to have our adenosine receptors intact to do that,” he added.

Adenosine receptors on nerve cells, including brain cells, are akin to docking points for the molecule adenosine. Adenosine levels increase in the brain with each hour of waking activity, and “docking” of the molecule with its receptor is shown in this study to help promote the slow-wave activity (SWA) of sleep.

Greene said that linking the lack of functioning adenosine receptors to depressed normal SWA rebound response might aid in developing treatments for people with sleep-related cognitive deficits.

The study appears in Journal of Neuroscience. (ANI)