Recent research from University of Copenhagen sheds light on previously unknown facts about muscular dystrophy at molecular level. The breakthrough is hoped to improve future diagnosis and treatment of the disease. Researchers have developed a method that will make it easier to map the proteins that have an important kind of sugar monomer, mannose, attached. This is an important finding, as mannose deficiency can lead to diseases such as muscular dystrophy.
About 3,000 people in Denmark suffer from one of the serious muscle-related diseases that come under the heading of muscular dystrophy. Some patients diagnosed with muscular dystrophy die shortly after birth, others become severely retarded and develop eye problems, while certain groups are confined to life in a wheelchair. Common to all muscular dystrophy sufferers is the difficulty of their muscle cells to attach themselves to each other and to the surrounding tissue. However, little is actually known about the root causes of the disease.

New basic research from University of Copenhagen now offers insight into previously unknown facts about muscular dystrophy that may improve future diagnosis and treatment of the disease.

‘Our new research findings may shed light on some of the cellular processes that take place in connection with, for example, muscular dystrophy. This is important information because it is crucial for us to gain as detailed an understanding as possible about the individual cell components. Although the journey from the current basic research to any potential treatment options or diagnostic tools is a long one, our discoveries give grounds for optimism,’ says postdoc Malene Bech Vester-Christensen – who carried out the new experiments from her base at the Faculty of Health and Medical Sciences, University of Copenhagen, and has since taken up a research position at Novo Nordisk.
The new method developed by researchers makes it easier to map the proteins that The protein previously associated with muscular dystrophy is a so-called glycoprotein – a protein with chains of sugar molecules attached. The special kind of sugar attached to these glycoproteins is called mannose. A functional pathway for binding mannose to the proteins is key to the functioning of the human organism, and genetic defects in the process that attaches mannose to the proteins – known as O-mannosylation – can lead to diseases such as muscular dystrophy.

‘To date, only one single protein has been identified and characterised where the mannose deficiency on the protein leads to muscular dystrophy, but our method enables us to faster identify many new proteins that have mannose attached and therefore potentially play a key role for the disease,’ says Adnan Halim, who is associated with the research project and a postdoc with the Danish National Research Foundation, Copenhagen Center for Glycomics. University of Copenhagen

A pilot study by a multi-disciplinary team of investigators at Georgetown University suggests that a simple dot test could help doctors gauge the extent of dopamine loss in individuals with Parkinson’s disease (PD).

‘It is very difficult now to assess the extent of dopamine loss — a hallmark of Parkinson’s disease — in people with the disease,’ says lead author Katherine R. Gamble, a psychology PhD student working with two Georgetown psychologists, a psychiatrist and a neurologist. ‘Use of this test, called the Triplets Learning Task (TLT), may provide some help for physicians who treat people with Parkinson’s disease, but we still have much work to do to better understand its utility,’ she adds.

Gamble works in the Cognitive Aging Laboratory, led by the study’s senior investigator, Darlene Howard, PhD, Davis Family Distinguished Professor in the department of psychology and member of the Georgetown Center for Brain Plasticity and Recovery.

The TLT tests implicit learning, a type of learning that occurs without awareness or intent, which relies on the caudate nucleus, an area of the brain affected by loss of dopamine.

The test is a sequential learning task that does not require complex motor skills, which tend to decline in people with PD. In the TLT, participants see four open circles, see two red dots appear, and are asked to respond when they see a green dot appear. Unbeknownst to them, the location of the first red dot predicts the location of the green target. Participants learn implicitly where the green target will appear, and they become faster and more accurate in their responses.

Previous studies have shown that the caudate region in the brain underlies implicit learning. In the study, PD participants implicitly learned the dot pattern with training, but a loss of dopamine appears to negatively impact that learning compared to healthy older adults.
‘Their performance began to decline toward the end of training, suggesting that people with Parkinson’s disease lack the neural resources in the caudate, such as dopamine, to complete the learning task,’ says Gamble.

In this study of 27 people with PD, the research team is now testing how implicit learning may differ by different PD stages and drug doses.

‘This work is important in that it may be a non-invasive way to evaluate the level of dopamine deficiency in PD patients, and which may lead to future ways to improve clinical treatment of PD patients,’ explains Steven E. Lo, MD, associate professor of neurology at Georgetown University Medical Center, and a co-author of the study.

They hope the TLT may one day be a tool to help determine levels of dopamine loss in PD. EurekAlert

The sensitivity of the GLP-1 hormone, which is secreted by the gastrointestinal tract, can predict the metabolic efficacy of a gastric bypass. The use of a GLP1 challenge could thus function as a novel predictive biomarker for personalised treatment of type 2 diabetes and obesity
The gastric bypass is one of the most commonly performed surgical procedures in the treatment of obesity. In most patients, it quickly produces substantial body weight loss. Moreover, even before the weight loss, the procedure leads to improved glucose tolerance. However, these metabolic improvements vary considerably from patient to patient.
A hormone test may be able to predict the extent of metabolic improvement caused by the gastric bypass. These are the results of a study on a rodent model conducted by Prof. Dr. Matthias Tschöp and his colleagues from the Institute of Diabetes and Obesity (IDO), Helmholtz Diabetes Center at Helmholtz Zentrum München together with a team of researchers led by Dr. Kirk Habegger at the Metabolic Disease Institute of the University of Cincinnati.
After gastric bypass surgery, the concentration of the gut hormone GLP-1 (glucagon-like peptide 1) in the blood rises significantly. GLP-1 increases insulin secretion and contributes to improved blood glucose levels and blood lipids. As the rat studies by the Tschöp and Habegger research teams showed, GLP-1 responsiveness varied considerably with regard to glucose metabolism. More importantly, the more responsive the animals were to GLP-1, the greater the efficacy of the gastric bypass turned out to be regarding glucose metabolism improvements.
Thus, the responsiveness to GLP-1 could be a key indicator for the success of the gastric bypass. ‘If our results are confirmed in clinical trials with patients, the hormone response could be tested before the planned surgery and surgeons would be able to predict how much an individual patient’s glucose metabolism would benefit,’ said Tschöp. ‘This will contribute to the development of personalized therapies for type 2 diabetes and obesity. For surgical procedures such as gastric bypass this is particularly compelling because such operations are complex and cannot be easily reversed.’
The numerous secondary diseases related to excess weight and obesity, such as type 2 diabetes, are among the most common diseases in Germany. These diseases are the focus of research at Helmholtz Zentrum München, a partner in the German Center for Diabetes Research (DZD). Helmholtz Zentrum München

A way of using nanoparticles to investigate the mechanisms underlying ‘mystery’ cases of infertility has been developed by scientists at Oxford University.
The technique `could eventually help researchers to discover the causes behind cases of unexplained infertility and develop treatments for affected couples. The method involves loading porous silica nanoparticle ‘envelopes’ with compounds to identify, diagnose or treat the causes of infertility.
The researchers demonstrated that the nanoparticles could be attached to boar sperm with no detrimental effects on their function.
‘An attractive feature of nanoparticles is that they are like an empty envelope that can be loaded with a variety of compounds and inserted into cells,’ says Dr Natalia Barkalina, lead author of the study from the Nuffield Department of Obstetrics and Gynaecology at Oxford University. ‘The nanoparticles we use don’t appear to interfere with the sperm, making them a perfect delivery vessel.’
Dr Barkalina added: ‘We will start with compounds to investigate the biology of infertility, and within a few years may be able to explain or even diagnose rare cases in patients. In future we could even deliver treatments in a similar way.’
Sperm are difficult to study owing to their small size, unusual shape and short lifetime outside of the body. Yet this is a vital part of infertility research, as senior author Dr Kevin Coward explains: ‘To discover the causes of infertility, we need to investigate sperm to see where the problems start. Previous methods involved complicated procedures in animals and introduced months of delays before the sperm could be used.
‘Now, we can simply expose sperm to nanoparticles in a petri dish. It’s so simple that it can all be done quickly enough for the sperm to survive perfectly unharmed.’
The team, based at the Institute of Reproductive Sciences, used boar sperm because of its similarities to human sperm, as study co-author Celine Jones explains: ‘It is similar in size, shape and activity. Now that we have proved the system in boar sperm, we hope to replicate our findings in human sperm and eventually see if we can use them to deliver compounds to eggs as well.’ Oxford University

Headaches, anxiety, irritability—these and other symptoms of nicotine withdrawal can significantly deter smokers from being able to kick the habit. Now, in what may be a significant step toward alleviating those symptoms, UMass Medical School neuroscientist Andrew R. Tapper, PhD, and colleagues have identified the region of the brain in which they originate.
‘We were surprised to find that one population of neurons within a single brain region could actually control physical nicotine withdrawal behaviours,’ said Dr. Tapper, associate professor of psychiatry and interim director of the Brudnick Neuropsychiatric Research Institute at UMMS.
The Tapper lab discovered that physical nicotine withdrawal symptoms are triggered by activation of GABAergic neurons (neurons that secrete GABA, the brain’s predominant inhibitory neurotransmitter), in the interpeduncular nucleus, an area deep in the midbrain that has recently been shown to be involved in nicotine intake.
‘Most of the work in the field has been focused on the immediate effects of nicotine, the addictive component in tobacco smoke, on reward circuits in the brain,’ Tapper explained. ‘But much less is known regarding what happens when you take nicotine away from someone who has been smoking for a long time that causes all these terrible withdrawal symptoms. Our main goal was to understand what brain regions are activated—or deactivated—to cause nicotine withdrawal symptoms.
They did this through a series of experiments performed in mouse models with sophisticated neurochemistry and brain imaging methods, including recently developed optogenetics techniques in which specific neurons can be activated by light.
Most surprising was their discovery that nicotine withdrawal symptoms can be activated or deactivated independent of nicotine addiction. ‘When we activated the GABAergic neurons in the interpeduncular nucleus, mice suffered withdrawal symptoms even if they had no previous nicotine exposure,’ Tapper noted.
These findings are promising because existing treatments intended to help people quit smoking are not always effective. ‘There are very few treatments to help people quit smoking,’ Tapper said. ‘If you can dampen the activity of this brain region chemically during nicotine withdrawal then you would hopefully be able to help someone quit smoking because you could reduce some of the withdrawal symptoms that they are experiencing.’ University of Massachusetts