Mapping recurrent prostate cancer using C-11 choline PET and multiprarmetric MRI

A team of Mayo Clinic researchers has, for the first time, successfully mapped patterns of prostate cancer recurrence, following surgery. Using C-11 choline PET imaging and multiparametric MRI, researchers found an anatomically diverse pattern of recurrence, which may help optimize treatment of patients whose prostate cancer returns after surgery. The research findings are published today in the Journal of Urology.

“This study has important implications for men who have a rising prostate-specific antigen (PSA) test, also known as biochemical recurrence, after radical prostatectomy for prostate cancer,” says Jeffrey Karnes, M.D., a urological surgeon at Mayo Clinic. “In men with biochemical recurrence, determining where the disease has recurred is quite challenging, especially when the PSA level is low.”

According to Dr. Karnes, in the U.S., approximately 30 percent of patients who have had an initial prostate cancer surgically excised will suffer a recurrence and seek treatment. “Current imaging tests like conventional bone and CT scans are not sensitive enough to identify sites of recurrence, especially when the PSA value is lower than 10,” he says.

Dr. Karnes says the combination of C-11 choline PET scanning and multiparametric MRI, helps physicians accurately identify sites of recurrence at an average PSA of 2. More importantly, he says, “This type of staging allows us to identify sites of recurrent disease that can be potentially treated either surgically or with radiation.”

Dr. Karnes and his team also were able to describe patterns of prostate cancer recurrence. They found that nearly two-thirds of men in the study had recurrence limited to the pelvis, which potentially can be targeted for radiation therapy.

Press release: Mayo Clinic researchers map prostate cancer relapse using C-11 choline PET and MRI
Publication: http://dx.doi.org/10.1016/j.juro.2016.07.073

New vaccine targets found for Plasmodium vivax Malaria

Thousands died and more than 13 million people fell ill with malaria caused by the parasite Plasmodium vivax last year. There is no vaccine for the disease, partly because multiple strains of P. vivax circulate globally, making it difficult to develop a vaccine. Now, researchers studying a protein crucial for the parasite’s survival have found two portions of that protein that do not vary across many strains. Antibodies against these portions of the protein protect against disease, according to researchers at Washington University School of Medicine in St. Louis. The study is available online in the Proceedings of the National Academy of Sciences.

“This protein – called Duffy binding protein – is the most promising target for vaccine development because it is almost impossible for the parasite to cause infection without it,” said Niraj Tolia, associate professor of molecular microbiology and the study’s senior author.

If the parasite does not bind to the human protein – either because antibodies block the binding site or because the human protein is missing – the parasite is unable to cause disease. P. vivax is found all over the world, but it causes relatively little disease in Africa, where many people lack this specific protein on their red blood cells.

Tolia and colleagues studied three antibodies that are known to prevent a range of binding proteins from latching on to the human protein, and identified the portion of the binding protein to which the antibodies were bound. Two antibodies bound to the same portion, or epitope, while the third bound at another spot. “Our study helps define what we should be targeting to get universal protection,” Tolia said.

Press release: Vaccine targets identified for deadly form of malaria
DOI: http://dx.doi.org/10.1073/pnas.1600488113

Research shows girls with ADHD are at higher risk for other mental health issues.

Girls with attention deficit hyperactivity disorder are at higher risk than girls without ADHD for multiple mental disorders that often lead to cascading problems such as abusive relationships, teenage pregnancies, poor grades and drug abuse, UCLA psychologists report in the journal Pediatrics.

The researchers, who conducted by far the most comprehensive analysis of girls and ADHD, report: 37.7 percent of girls with ADHD met criteria for an anxiety disorder, compared with only 13.9 percent of girls without ADHD. 10.3 percent of girls with ADHD were diagnosed with depression compared with only 2.9 percent without ADHD. 42 percent of girls with ADHD were diagnosed with oppositional defiant disorder, compared with just 5 percent of girls without it.12.8 percent of girls with ADHD were diagnosed with conduct disorder compared with only 0.8 percent without ADHD. Conduct disorder is similar to oppositional defiant disorder, but with more severe behavioral problems, such as committing violent acts, setting fires and hurting animals.

“We knew the girls with ADHD would have more problems than the girls without ADHD, but we were surprised that conduct disorder and oppositional defiant disorder were at the top of the list, not depression or anxiety,” said Steve Lee, a UCLA associate professor of psychology and senior author of the study.

“These conduct disorders, more than anxiety and depression, predict severe adult impairments, such as risky sexual behavior, abusive relationships, drug abuse and crime.” Symptoms of ADHD include being easily distracted, fidgeting, being unable to complete a single task and being easily bored.
Most ADHD studies focused on boys, or compared girls with ADHD to boys with ADHD – not to girls without ADHD. ADHD is often harder to detect in girls than in boys because girls with the disorder may appear disengaged, forgetful or disorganized, and perceived as “Spacey” and stay “Under the radar” without being referred for assessment and treatment, said lead author Irene Tung, a UCLA graduate student in psychology and National Science Foundation graduate research fellow.

What should concerned parents do? If a child’s negative behavior lasts for months and is adversely affecting her or his social relationships and school performance, then it’s worth having your child evaluated by a psychologist or psychiatrist for ADHD and other mental disorders. “People tend to think of girls as having higher risk for depression and anxiety disorders, and boys as being more likely to exhibit conduct disorders, but we found that ADHD for girls substantially increases their risk for these conduct disorders,” Tung said.

 “The child’s behavior will often get worse before it gets better.” Children with ADHD are two to three times more likely than children without the disorder to develop serious substance abuse problems in adolescence and adulthood, Lee and colleagues reported in 2011.

To receive a diagnosis of ADHD by a child psychologist or psychiatrist, a child must have at least six of nine symptoms of either hyperactivity or inattention, the child’s behavior must be causing problems in his or her life, and the symptoms must not be explainable by any medical condition or any other mental disorder.

Press release: An ADHD diagnosis puts girls at much higher risk for other mental health problems
DOI: 10.1542/peds.2016-0430

Researchers in University of Warwickshire develop 2D mass spectrometry using Linear ion trap.

Professor Peter O’Connor and Dr Maria van Agthoven in the Department of Chemistry have invented a device which makes 2D mass spectrometry – an effective process for analysing and sequencing proteins. This could enable researchers and companies to produce data-driven results on how protein molecules function, more easily and cheaply. 2D mass spectrometry allows chemists to explore the elemental composition and structure of a molecule by breaking it apart, and analysing its fragmented pieces – measuring mass, and gathering data on how the whole molecule functions and interacts with its environment.

High numbers of molecules can be experimented on at the same time in this way, as the various fragments of different broken molecules can be modulated at the same frequencies as the molecule from which they originated. Professor O’Connor and Dr van Agthoven have patented an instrument with which 2D Mass spectrometry can be performed using a linear ion trap – this is a cheaper, smaller, and much more accessible option than was previously available. The device can be added onto existing MS instruments as well as being bought with new instruments.

Mass spectrometry produces precise results during protein sequencing, and this type of data-driven biology will produce quicker, better results than are currently obtained in pharmaceutical and biomedical research.

Dr van Agthoven comments that the breakthrough could have numerous and varied applications: “Two-dimensional mass spectrometry has the potential to exponentially increase our knowledge in all areas, from biochemistry to food safety and environmental chemistry.” Professor O’Connor is confident that this invention will change biomedical research dramatically: “2-Dimensional mass spectrometry in a simple and cheap linear ion trap will revolutionise proteomics and detailed characterisation of complex samples.”

Press release: Breakthrough in analytical sciences could lead to medical revolution 

Sleep Deprivation in children affects brain myelin development

Sleep is vital for humans. If adults remain awake for longer than usual, the brain responds with an increased need for deep sleep. In adults, these deep-sleep waves are most pronounced in the prefrontal cortex – the brain region which plans and controls actions, solves problems and is involved in the working memory.

Sleep deprivation in children increases deep sleep in posterior brain regions For the first time, researchers from University Hospital Zurich  have now demonstrated that curtailed sleep in children also results in locally increased deep sleep. “The deep-sleep effect doesn’t appear in the front regions of the brain like in adults, but rather in the back – in the parietal and occipital lobes.”

The team of researchers also discovered that the heightened need for sleep – measured as an increase in deep sleep – in children is associated with the myelin content in certain nerve fiber bundles: the optic radiation. The level of myelin – a fatty sheath around the nerve fibers, which accelerates the transfer of electrical signals – is a yardstick for brain maturity and increases in the course of childhood and adolescence. Deep-sleep effect depends on extent of brain maturity.

The sleep researchers measured the brain activity in 13 healthy five to 12-year-olds as they slept. On the first occasion, the children went to bed at their normal bedtime; the second time, they stayed awake until late and thus received exactly half the normal amount of sleep. The scientists assume that the quality of sleep is jointly responsible for the neuronal connections to develop optimally during childhood and adolescence. According to international guidelines, the recommended amount of sleep for children aged 6 to 13 is 9 to 11 hours per night.

Publication: Increased Sleep Depth in Developing Neural Networks: New Insights from Sleep Restriction in Children. doi: dx.doi.org/10.3389/fnhum.2016.00456

Press release: Developing brain regions in children hardest hit by sleep deprivation

Understanding roundworm nerve regeneration mechanism and its molecular pathways could help nerve injury treatment.

Certain types of nerve injury, such as those from automobile accidents and falls, can damage or sever the axons that connect neurons and allow them to communicate with each other. Although axons elsewhere in the body can regenerate to some extent after such damage, those in nerves are far less capable, resulting in long-lasting or permanent impairment.

Treating such injuries requires clarification of how certain nerves are induced to regenerate and which molecular pathways are involved. Nerve regeneration after nerve injury is therefore an issue of special interest, but is difficult to study in humans.

To shed light on how damaged nerves are induced to regenerate, the researchers investigated various strains of roundworm in which different genes were mutated or inactivated. When certain proteins encoded by these genes were absent or dysfunctional in the worms, their nerves were less able to regenerate, particularly during adulthood. Authors believe that “Our findings should therefore lead us to targets in humans that we can use to improve recovery after nerve injury by promoting regrowth of damaged axons.”

Publication: The Core Molecular Machinery Used for Engulfment of Apoptotic Cells Regulates the JNK Pathway Mediating Axon Regeneration in Caenorhabditis elegans.
doi: 10.1523/JNEUROSCI.0453-16.2016

Press Release: Unraveling roundworm nerve regeneration mechanism could aid nerve injury treatment

Researchers mapped the signaling processes used by Insulin in Fruit flies.

Fruit flies may be small, but the genetic secrets they can unlock for humans are many. In the current issue of the journal Development, Michigan State University researchers mapped the signaling processes used by insulin in fruit flies.

The significance of the discovery in the tiny Drosophila melanogaster, which have been called “Tiny people with wings, genetically speaking,” sheds light on how these processes may be altered by diabetes in humans. Insulin signaling is an important process for these creatures; past studies have proven that the natural hormone insulin controls growth and development of the fly.

Fruit flies raised on a high-sugar diet consisting solely of bananas can actually develop a diabetic-like state, with metabolic dysfunction similar to humans, said David Arnosti, MSU biochemistry professor, director of MSU’s Gene Expression in Development and Disease Initiative and the study’s senior author. As an extension of these past findings, Yiliang Wei, a graduate student in Arnosti’s lab and study co-author, focused on the insulin receptor protein, which binds to insulin and regulates its effects.

Little was known about how levels of this protein were regulated before the researchers mapped its controlling circuits. One surprising finding was the large number of genetic switches controlling expression of the receptor, which had been previously assumed to possess rather simple regulation. The structure and function of this circuitry is likely to have been sculpted by evolutionary selection.

The researchers predict that the human gene will be similarly regulated, which could open a new chapter in diabetes research to find ways to modulate insulin signaling through control of the receptor, Arnosti said. The tiny fruit fly has once again proven itself as an effective model organism and given the team solid ground on which to move forward.

Press release: Diabetic fruit flies may unlock secrets in humans 

Role of TB specific antibodies in Tuberculosis infection found

A study led by investigators from the Ragon Institute of MGH, MIT, and Harvard finds evidence that antibody protection may help control infection with the bacteria that causes tuberculosis. In their study receiving online publication in Cell, the research team describes finding consistent differences in both the structure and function of antibodies targeting the TB bacteria between individuals with active TB disease and those with latent TB, which neither produces symptoms nor can be transmitted.

“A more effective vaccine against TB could substantially contribute towards that goal, impacting the nearly one in three people worldwide who are infected and addressing the leading killer of individuals infected with HIV.” The only currently available preventive against infection with the TB bacteria – the BCG vaccine – has been available since the 1920s; but its effectiveness against pulmonary TB, the most common form of the disease, has always been uncertain.

Previous investigations into a possible role for antibodies in the immune response to TB have had conflicting results, but the Ragon team – led by Galit Alter, Ph.D., of MGH Department of Medicine and Sarah Fortune, MD, of the Harvard T.H. Chan School of Public Health – used a novel approach.
In addition to binding to their target pathogens and marking them for destruction by the immune system, antibodies also directly stimulate pathogen-killing cells of the innate immune system by binding to a cell-surface protein called the Fc receptor.

The Ragon team profiled TB-specific antibodies from 22 individuals with latent TB and 20 with active TB for 70 different features associated with Fc-mediated antibody function. They first identified nine characteristics that differentiated between antibodies of the two groups of participants, and further investigation identified the biomarker that best distinguished between them.

A key regulator of the Fc-mediated immune function is the addition to antibodies of compounds called glycans, made up of sugar molecules; and distinct differences in glycosylation patterns were found to clearly distinguish latent TB antibodies from active TB antibodies.

To confirm these results in the initial group of participants, who were from South Africa, the team conducted a similar analysis of antibodies from 20 individuals from Texas and Mexico – half with latent and half with active TB – and had the same results. Further experiments revealed that application of latent TB antibodies to TB-infected human macrophages not only increased the activation of several antimicrobial processes but also reduced the survival of the TB bacteria.

Press release: Antibody function may help keep tuberculosis infection under control
Journal article: http://dx.doi.org/10.1016/j.cell.2016.08.072