The cellular cause of birth defects like cleft palates, missing teeth and problems with fingers and toes has been a tricky puzzle for scientists.
Now Professor Emily Bates and her biochemistry students at Brigham Young University have placed an important piece of the developmental puzzle. They studied an ion channel that regulates the electrical charge of a cell. In a new study they show that blocking this channel disrupts the work of a protein that is supposed to carry marching orders to the nucleus.
Without those instructions, cells don’t become what they were supposed to become – be that part of a palate, a tooth or a finger. Though there are various disorders that lead to birth defects, this newly discovered mechanism may be what some syndromes have in common.
Bates and her graduate student, Giri Dahal, now want to apply the findings toward the prevention of birth defects – particularly those caused by fetal alcohol syndrome and fetal alcohol spectrum disorder.
‘What we think might be the case is that this is the target for a few similar disorders,’ Bates said. ‘The big thing that we have right now is that this ion channel is required for protein signalling, which means that developmental signalling pathways can sense the charge of a cell. And that’s exciting for a lot of different reasons.’
For example, the new study might also have implications for the battle against cancer. With cancer, the problem is that cells are receiving a bad set of instructions that tells them to multiply and spread. If they can devise a way to block the ion channel, it may stop those cancerous instructions from getting through.
‘This protein signalling pathway is the same one that tells cancer cells to metastasise,’ Bates said. ‘We’re planning to test a therapy to specifically block this channel in just the cells that we want to stop.’ Brigham Young University

Researchers from Sainte-Justine University Hospital Center and University of Montreal have identified several novel genes that make some children more efficient than others in the way their immune system responds to malaria infection. This world-first in integrative efforts to track down genes predisposing to specific immune responses to malaria and ultimately to identify the most suitable targets for vaccines or treatments was published by lead author Dr. Youssef Idaghdour and senior author Pr. Philip Awadalla, whose laboratory has been performing world-wide malaria research for the past 13 years.
‘Malaria is a major health problem world-wide, with over 3 billion individuals at risk and hundreds of thousands of deaths annually, a majority of which are African children under the age of 5. Why are some children prone to infection, while others are resistant and efficiently fight the disease? These are the questions we sought to answer with our study’, Idaghdour says.
However, to succeed where many other studies have failed, the team used an approach different from the classic in vitro one, where the genome is analysed using cells grown in a laboratory. Instead, they used an in vivo approach, analysing blood samples of children from the Republic of Benin, West Africa, collected with the help of collaborators in the city of Cotonou and the nearby village of Zinvié. ‘This approach allowed us to identify how the ‘environment’ engages in an arms race to define the clinical course of the disease, in this case the environment being the number of parasites detected in the child’s blood running against the genetic make-up of the infected child’, Idaghdour explains.
‘We used an innovative combination of technologies that assessed both genetic variation among children and the conditions in which their genes are ‘expressed’. By doing so, we increased the power of our analysis by permitting us not only to detect the mutations, but also to capture their effect depending on how they affect genes being turned ‘on’ or ‘off’ in presence of the parasite’, Awadalla explains. ‘Our approach made us successful, where million-dollar studies have failed in the past. There has never been this many genes associated with malaria discovered in one study.’
This major milestone in understanding how the genetic profile affects the ability of children to cope with infection could pave the way to the development of low-cost genetic profiling tests in a not so far future. ‘Accurate diagnosis of the infectious agent is critical for appropriate treatment, of course. However, determining a patient’s genetic predisposition to infection would allow us to be more aggressive in our treatment of patients, whether we are speaking of vaccines or preventive drugs’, Awadalla says. EurekAlert

Men worried about prostate cancer have a new online resource, freely available, to help them assess their risk. The multi-step Prostate Cancer Risk Calculator, has been created by the founders of the European Randomized Study of Screening for Prostate Cancer (ERSPC). It is easy and simple for people to use. Men can use the first two calculators to assess their individual risk of developing prostate cancer without needing any medical expertise. The first starts with family history and general health information. The second is for use if you also have the results of a simple blood test to assess the level of prostate specific antigen (PSA). Prostate cancer is one of the most common cancers in men but recent improvements in treatment and diagnosis mean that more men will survive the disease. The on-line resource provides a range of helpful information about the disease, which includes the benefits and disadvantages of going for a PSA test when you do not have symptoms. PSA levels tend to increase as men age and can be a sign of prostate disease, though not always cancer. A further five risk calculators have been created for clinicians to use as part of their clinical practice. They are based on robust evidence gained from research carried out by the ERSPC, the world’s largest study into screening for prostate cancer. They calculate whether clinicians can avoid subjecting men to additional, and invasive, diagnostics tests such as biopsy, or if they can safely be monitored on a more conservative ‘active surveillance’ programme. An additional feature calculates a patient’s risk of having an aggressive form of cancer; and this further helps to decide if a biopsy is needed.

Women who go into early menopause are twice as likely to suffer from coronary heart disease and stroke, new Johns Hopkins-led research suggests. The association holds true in patients from a variety of different ethnic backgrounds, the study found, and is independent of traditional cardiovascular disease risk factors, the scientists say.
‘If physicians know a patient has entered menopause before her 46th birthday, they can be extra vigilant in making recommendations and providing treatments to help prevent heart attacks and stroke,’ says Dhananjay Vaidya, Ph.D., an assistant professor in the Division of General Internal Medicine at the Johns Hopkins University School of Medicine, and leader of the study.
‘Our results suggest it is also important to avoid early menopause if at all possible.’
For example, he says, research has shown that smokers reach menopause, on average, two years earlier than non-smokers do, so quitting smoking may delay it.
Notably, the researchers said, their findings about the negative impact of early menopause were similar whether the women reached it naturally or surgically, via removal of reproductive organs, he says, though more research is needed. Often, Vaidya says, women who undergo hysterectomies have their ovaries removed, which precipitates rapid menopause. ‘Perhaps ovary removal can be avoided in more instances,’ he says, which might protect patients from heart disease and stroke by delaying the onset of menopause.
Cardiovascular disease is the number one killer of women in the United States, according to the Centers for Disease Control and Prevention.
Previous studies, Vaidya says, have shown a link between early menopause and heart disease and stroke among white women, but similar associations had not been demonstrated in more diverse populations. Hispanic and African-American women, he says, tend, on average, to go through menopause somewhat earlier than women of European descent.
Vaidya and his colleagues examined data from 2,509 women involved in the Multi-Ethnic Study of Atherosclerosis, a longitudinal, ethnically diverse cohort study of men and women aged 45 to 84 years, all enrolled between 2000 and 2002 and followed until 2008. Of the women, 28 percent reported early menopause, or menopause that occurs before the age of 46. Vaidya emphasizes that although the risk of heart attack and stroke was doubled in these groups, the actual number of cardiac and stroke events recorded among study participants was small. Only 50 women in the study suffered heart events, while 37 had strokes.
Menopause is a process during which a woman’s reproductive and hormonal cycles slow, her periods (menstruation) eventually stop, ovaries stop releasing eggs for fertilization and produce less estrogen and progesterone, and the possibility of pregnancy ends. A natural event that takes place in most women between the ages of 45 and 55, menopausal onsets and rates are influenced by a combination of factors including heredity, smoking, diet and exercise.
Vaidya says some women are treated with hormone replacement therapy (HRT) to control menopause symptoms such as profuse sweating and hot flashes, but its widespread long-term use has been limited after large clinical trials showed that it increased the risk of heart attacks in some women. In Vaidya’s study, no role was detected for HRT in potentially modifying the impact of early menopause.
‘Cardiovascular disease processes and risks start very early in life, even though the heart attacks and strokes happen later in life,’ he says. ‘Unfortunately, young women are often not targeted for prevention, because cardiovascular disease is thought to be only attacking women in old age. What our study reaffirms is that managing risk factors when women are young will likely prevent or postpone heart attacks and strokes when they age.’ Johns Hopkins

Vitamin D, best known for its role in calcium uptake and bone density has also been shown to have beneficial effects on the immune system, with some studies demonstrating a correlation between higher vitamin D intake and a lower incidence of cancer, and that adequate vitamin D levels may also decrease the risk of autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. Now, a recent study, conducted by doctors across London hospitals and published in the Proceedings of the National Academy of Sciences, has shown that tuberculosis (TB) patients recovered more quickly when given both the vitamin and antibiotics. This idea is reminiscent of earlier times when TB patients, in the days before antibiotics, were prescribed sunbathing, which increases vitamin D production. This study found that recovery was almost two weeks faster when vitamin D was added to the treatment regime, with patients clearing the infection in 23 days on average, compared to 36 days for patients given antibiotics and a placebo. Vitamin D treatment will not replace antibiotics, but might well become a useful extra weapon, particularly with the increasing prevalence of drug-resistant TB. The vitamin seems to work by reducing the inflammatory response to the infection and helping the lungs to heal more quickly. If these lung cavities heal more quickly, patients are infectious for a shorter period of time and may also suffer less lung damage. Stronger evidence and trials to find the best dose and form of vitamin D will be needed before the treatment is put into widespread use.

http://www.pnas.org/