Johns Hopkins scientists have unearthed clues about which protein signaling molecules are allowed into hollow, hair-like "antennae," called cilia, that alert cells to critical changes in their environments.

Researchers found that the size limit for entry is much greater than previously thought, allowing most of a cell`s proteins into cilia.

The researchers believe that the specific collection of proteins in each cilium, customized to the needs of each cell type, is determined by whether and how cilia keep proteins inside once they enter-not which ones they allow in initially.

"According to our experiments, 90 percent of the proteins in mammalian cells should be able to fit inside cilia based on their size," said Takanari Inoue, Ph.D., assistant professor of cell biology at the Johns Hopkins University School of Medicine.

"But most of them have never been found [inside the cilia], so we think that most proteins do wander in at some point, but only certain ones remain inside," Inoue added.

So-called "primary cilia" have been attracting intense attention as recent research has confirmed their role in monitoring the cell`s exterior environment and conveying information to the rest of the cell using an arsenal of signals stored inside the thin interior of each antenna-like cilium.

The results of this study have helped explain how that arsenal is developed.

Primary cilia are found protruding from most cells in a wide variety of organisms, and defects in cilia have been implicated in everything from polycystic kidney disease to vision and hearing loss.

In the kidney, they monitor the flow of urine; in the eye, they sense the wavelength of light; in cartilage, they sense pressure; and in the heart, blood flow. No matter where they are, Inoue said, their job is to translate such mechanical forces-or, in some cases, chemical ones-into molecular signals for the cell, so that it can respond appropriately to its environment.

The signaling molecules inside cilia are tailored to the required responses. For example, some are proteins that bind to DNA to modify gene activity, letting a cell respond to environmental cues by producing more of a particular protein. The only way into the cilial column is through a hole at its base.

"A cilium forms like a short drinking straw being pushed outwards from inside an inflated balloon. What we don`t know is whether there is some sort of cap over the hole, regulating what goes in and out. We found that more signaling molecules could enter the straw than we thought," explained Inoue.

Previous research in other laboratories suggests that a fixed pore exists at the base of a cilium that only allows relatively small molecules inside. By developing more sensitive experimental methods, the Inoue group was able to show that molecules almost 10 times larger than those known before could enter.

Specifically, they first engineered an anchor-like molecule that selectively embedded itself in the membranes of cilia. On the inside end of the anchor was half of a "molecular snapper." Inside the watery interior of the cell, the team placed fluorescent molecules of known size, fitted with the other half of the molecular snapper. If these fluorescent molecules entered cilia, they would carry their fluorescence with them and be trapped inside when the snappers clicked together, allowing the researchers to easily take images of them.

By repeating this experiment many times with molecules of increasing size, the Inoue team was able to show that every molecular size they tested was able to enter the cilia. The only difference between the molecules of different sizes was their rate of entry: Smaller molecules entered more quickly than larger ones.
Figuring out how cilia select their captives is a question for another study, Inoue noted.

The results of this study will be published online in the journal Nature Chemical Biology.

University of Alabama at Birmingham (UAB) exercise and nutrition experts have offered tips for those in search of a summer slim down.

EatRight by UAB Weight Management Services Clinical Dietitian Lindsey Lee R.D., said nutrition is necessary to support weight loss efforts.

"Incorporate good nutrition habits - eating fruits and vegetables, low-fat dairy products, whole grains and lean protein sources - to get the calories you need to maintain an exercise program," Lee said.

"If you restrict calories too much, you could start to feel burn out," Lee stated.

To bolster the burn, Lee suggested: Fill up on lower calorie fruits and vegetables, choose water over high calorie sodas and decrease high calorie, high fat options.

The expert suggests switching up food preparation: Instead of steaming vegetables, grill them or toss unique vegetables like skewered okra or fresh asparagus on the grill.

"The one important thing to remember is to limit the fat source you use. Try different herbs and spices to season your veggies instead of heavy amounts of olive oil, canola oil, or butter," Lee said.

Restaurant meals can be deceptive and pose a special challenge to healthy eating.

"Even meals you think are healthy in restaurants are loaded with calories because of cooking methods that add a lot of fat and sodium, so ask to have foods prepared as light as possible to avoid extra calories," Lee suggested.
She also suggests that people generally underestimate the calories they take in, and they overestimate the calories they burn. The best bet, she said, is to watch the calories consumed daily and get in at least 30 minutes of physical activity five days per week.

UAB School of Education Associate Professor of Health Education Retta Evans, Ph.D., said to start by adding a walk or bike ride to a daily routine, then mix it up with other activities to keep things interesting.

"Piloxing, which is a combo of Pilates and kickboxing, is fun," Evans said.

"There are also a variety of yoga disciplines to try, as well as barre fitness dance classes. Mixing it up with different activities is a good way to ramp up your program," she added.

Evans said a personal trainer could take physical activity and weight loss goals to another level.

"They can sit down with you and map out a timeline to meet your goals, and then they can be there as a motivator to keep reaching those," Evans explained.

If a personal trainer is not in the cards, Evans suggests looking to the internet for free exercise programming instruction. Either way, properly setting expectations is important.

"In a three month period, you can expect to drop up to three percent of your body composition. Some people will drop more, and some will drop less. But in that time frame, you`ll start to see changes in how your body looks and feels," she asserted.

With nearly 73,000 women dying every year, India has the highest number of cervical cancer deaths in the world, according to a report released today by a US-based research and advocacy group.

India represents 26.4 per cent of all women dying of cervical cancer globally, with China, Bangladesh, Pakistan, Indonesia and Thailand also showing high death incidence, says the "Cervical Cancer Global Crisis Card" released by the Cervical Cancer-Free Coalition.

According to the report card, cervical cancer kills an estimated 275,000 women every year and 500,000 new cases reported worldwide. This entirely preventable disease is the second largest cancer killer of women in low and middle-income countries, with most women dying in the prime of life, it said.

Using data from the WHO, United Nations, the World Bank and IARC Globocan, the Crisis Card has ranked 50 countries in the descending order of cancer mortality rates.

The Crisis Card report also highlighted the startling disparities between women in the developed and developing world personified by cervical cancer.

"A woman in Zambia is 25 times more likely to die from cervical cancer than a woman in Australia and India has 750 times more deaths than Norway. This level of inequity is also reflected across gender indicators with girls less likely to attend school but more likely to be malnourished and married as a child," said the report.

Recent data released by India`s Health Ministry based on the National Cancer Registry Programme (NCRP) report in 2009 the number of cervical cancer cases were 101938 which has increased to 107690 in 2012.

In Uttar Pradesh a total of 17367 cases were reported in 2009 and it increased to 18692 in 2012. After Uttar Pradesh the number of cases of cervical cancer in 2012 which has shown an increasing trend are Maharashtra (9892), Bihar (9824), West Bengal (8396), Andhra Pradesh (7907), Tamil Nadu (7077) and others.

"Cervical cancer can happen to anyone. Certain women are at greater risk. These include women who started sexual activity at an early age, had multiple pregnancies, had multiple partners themselves, or their partners have multiple partners," said Dr Neerja Bhatla, Professor, Department of Obstetrics and Gynaecology at All India Institute of Medical Sciences (AIIMS).
Dr Bhatla said, "Also, women with STIs like chlamydia, gonorrhoea, herpes simplex, women with immune suppression, for example, HIV or transplant recipients, smokers and prolonged use of oral contraceptives have a higher risk. There is thought to be a small element of genetic predisposition as well."

It is being estimated that the number of cervical cancer cases and deaths are estimated to increase by 2025 to 203,757 and 115,171, respectively.

Cervical cancer is caused by the human papillomavirus (HPV), a fairly ubiquitous virus that will be acquired by about 80 per cent of women some time during their lives. Most women clear this virus by their immune system, but in about 8-10 percent of cases the infection remains persistent.

These women are at risk of the disease and in the presence of certain co-factors, risk factors; they can go on to develop precancerous lesions called CIN (cervical intraepithelial neoplasia). Again, if left untreated, some of these women will develop cervical cancer. The main spread of HPV is by sexual contact, but spread by fomites and mother to child transmission are reported.

"If you have found out you have cervical cancer, it does not mean that it is the end. Cervical cancer is a treatable cancer if found early enough. Just go through the treatments, they are hard and the side effects are awful, but life will continue as normal after everything is done," said Genevieve Sambhi, former Miss Universe Runner Up and a cervical cancer survivor.

Genevieve who was diagnosed with cervical cancer at the age of 35 said initially she had no symptoms, a little abnormal bleeding but nothing that made her think she had cancer.

She then went for a Pap smear and that`s when she found out she had cancer.
"Cervical cancer, like all cancers, may be asymptomatic in its precancerous phase and while it is an early cancer. Symptoms that point to the cancer include, inter menstrual and post coital bleeding, postmenopausal bleeding and persistent vaginal discharge," said Dr Bhatla.

Recently, Ghulam Nabi Azad, Minister of Health and Family Welfare had responded to a starred question in Lok Sabha.

"Data of the Indian Council of Medical Research (ICMR) of the number of breast and cervical cancer cases among women has increased in the country. At present the Government of India is looking for alternative techniques and affordability to implement test to be used for detection of cervical cancer."

The minister further added that while health is a state subject, the Centre has launched the national programme for prevention and control of cancer, diabetes, cardiovascular disease and stroke (NPCDCS) in 2010 in 100 districts across 21 states.

Strengthening of government medical college and erstwhile regional Cancer Centres (RCC) across the country as Tertiary Cancer Centre (TCC) for providing comprehensive Cancer care was also undertaken as well as campaigns are carried out through print and electronic media, he said.

Eating food, which contains even a small amount of nicotine, like peppers and tomatoes, may help reduce risk of developing Parkinson`s disease, a new study has claimed.

According to the research, Solanaceae-a flowering plant family with some species producing foods that are edible sources of nicotine-may provide a protective effect against Parkinson`s disease.

Parkinson`s disease is a movement disorder that is caused by loss of brain cells that produce dopamine. Its symptoms include facial, hand, arm, and leg tremors, stiffness in the limbs, loss of balance, and slower overall movement.

For the present population-based study Dr. Susan Searles Nielsen and her colleagues from the University of Washington in Seattle recruited 490 patients newly diagnosed with Parkinson`s disease at the university`s Neurology Clinic or a regional health maintenance organization, Group Health Cooperative.

Another 644 unrelated people without neurological conditions were used as controls.

Questionnaires were used to assess their lifetime diets and tobacco use, which researchers defined as ever smoking more than 100 cigarettes or regularly using cigars, pipes or smokeless tobacco.

Vegetable consumption in general did not affect Parkinson`s disease risk, but as consumption of edible Solanaceae increased, Parkinson`s disease risk decreased, with peppers displaying the strongest association.

Researchers noted that the apparent protection from Parkinson`s occurred mainly in men and women with little or no prior use of tobacco, which contains much more nicotine than the foods studied.

Nielsen said that similar to the many studies that indicate tobacco use might reduce risk of Parkinson`s, their findings suggests a protective effect from nicotine, or perhaps a similar but less toxic chemical in peppers and tobacco.
The study has been published in Annals of Neurology, a journal of the American Neurological Association and Child Neurology Society.

Johns Hopkins researchers believe they may have solved the mystery behind sleepless nights associated with restless legs syndrome (RLS), a symptom that persists even when the disruptive, overwhelming nocturnal urge to move the legs is treated successfully with medication.

Neurologists have long believed RLS is related to a dysfunction in the way the brain uses the neurotransmitter dopamine, a chemical used by brain cells to communicate and produce smooth, purposeful muscle activity and movement.
Disruption of these neurochemical signals, characteristic of Parkinson`s disease, frequently results in involuntary movements. Drugs that increase dopamine levels are mainstay treatments for RLS, but studies have shown they don`t significantly improve sleep.

The small new study, headed by Richard P. Allen, Ph.D., an associate professor of neurology at the Johns Hopkins University School of Medicine, used MRI to image the brain and found glutamate - a neurotransmitter involved in arousal - in abnormally high levels in people with RLS. The more glutamate the researchers found in the brains of those with RLS, the worse their sleep.

"We may have solved the mystery of why getting rid of patients` urge to move their legs doesn`t improve their sleep. We may have been looking at the wrong thing all along, or we may find that both dopamine and glutamate pathways play a role in RLS," Allen said.

For the study, Allen and his colleagues examined MRI images and recorded glutamate activity in the thalamus, the part of the brain involved with the regulation of consciousness, sleep and alertness.

They looked at images of 28 people with RLS and 20 people without. The RLS patients included in the study had symptoms six to seven nights a week persisting for at least six months, with an average of 20 involuntary movements a night or more.

The researchers then conducted two-day sleep studies in the same individuals to measure how much rest each person was getting. In those with RLS, they found that the higher the glutamate level in the thalamus, the less sleep the subject got. They found no such association in the control group without RLS.

Previous studies have shown that even though RLS patients average less than 5.5 hours of sleep per night, they rarely report problems with excessive daytime sleepiness. Allen said the lack of daytime sleepiness is likely related to the role of glutamate, too much of which can put the brain in a state of hyperarousal - day or night.

If confirmed, the study`s results may change the way RLS is treated, Allen said, potentially erasing the sleepless nights that are the worst side effect of the condition.

Dopamine-related drugs currently used in RLS do work, but many patients eventually lose the drug benefit and require ever higher doses. When the doses get too high, the medication actually can make the symptoms much worse than before treatment.

As more is understood about this neurobiology, the findings may not only apply to RLS, he said, but also to some forms of insomnia .

The findings are published in the May issue of the journal Neurology.