A catastrophic chromosomal event cures a patient of her rare immunodeficiency disease; a new theory on what drives self-control; a surprising link between weaning and beta cell division; and evidence that our brain's approach to reaching decisions is similar to Alan Turing's approach to code breaking. Enjoy highlights from new research appearing in Cell Press's 32 journals:
Catastrophic chromosomal event cures patient of rare immunodeficiency disease
Chromothripsis is a catastrophic event, first described in cancer, in which a chromosome shatters into pieces and then is put back together imperfectly. In the journal Cell, Philip Murphy, David McDermott, and Ji-Liang Gao from the National Institute of Allergy and Infectious Disease in Maryland and their colleagues describe the first recorded case in which chromothripsis actually cured a patient.
WHIM (warts, hypogammaglobulinemia, recurrent infections, and myelokathexis) syndrome is caused by a genetic mutation in the chemokine receptor CXCR4 that leads to reduced numbers of white blood cells in the blood and increased susceptibility to infection by bacteria and human papillomavirus. As a dominant mutation, it is typically passed from parents to children. The patient suffered from WHIM syndrome from childhood to age 38. However, upon bringing her daughters, both with symptoms of WHIM syndrome, to the US National Institutes of Health for evaluation, she revealed that she herself had not suffered symptoms of the disease for the previous 20 years.
The researchers found that what accounted for this mysterious disease remission was a chromosome-shattering event within a single blood stem cell of this patient. The event deleted the WHIM-causing gene, as well as a number of other genes, on one copy of the disease chromosome. This caused the cell to gain a competitive advantage over other blood stem cells in her body, eventually repopulating her blood supply with cells lacking the WHIM-causing gene and curing her of the disease. Murphy and his collaborators found that they could mimic this scenario in mice by simply deleting one copy of CXCR4 from otherwise normal stem cells and performing competitive transplants with blood stem cells from a mouse model of WHIM syndrome as well as from normal mice, opening the door for the possible development of new therapeutic strategies in humans.
McDermott et al., Chromothriptic Cure of WHIM Syndrome, Cell (2015), http://dx.
Is self-control driven by negative emotions?
You want that brownie, but you don't want to gain weight. You want to stay in bed for another half hour, but you don't want to be late for work. Most cognitive scientists would say that negative emotions, such as guilt or stress, undermine your ability to exercise self-control and not give into such temptations. But in a Trends in Cognitive Sciences opinion paper, University of Toronto Associate Professor of Psychology Michael Inzlicht and colleagues argue that it's these negative feelings about our self-defeating desires (e.g., fear that the brownie will ruin your diet or anxiety about losing your job) that help us exercise cognitive control. Reviewing the fields of cybernetics, animal research, cognitive neuroscience, and psychology, they make the case that negative feelings are actually motivating and lead to more goal-directed behaviors.
Inzlicht et al., Emotional foundations of cognitive control, Trends in Cognitive Sciences (2015), http://dx.
Weaning triggers maturation of insulin-producing beta cells in mice
Scientists interested in the age-related decline of insulin-producing beta cells were surprised to find that young mice acquire the full cellular machinery that regulates glucose only after they are weaned. A team from Hebrew University reports that the dietary transition from fat-rich milk to carbohydrate-rich food enhances the ability of beta cells to secrete insulin in response to glucose and allows glucose to stimulate beta cell replication. The exact molecular signal that sets off these events is still to be determined, but its identification would be an interesting prospect for the treatment of age-related diabetes. The research, published in Developmental Cell, was led by Biochemistry and Molecular Biology Professor Yuval Dor of the Institute of Medical Research Israel-Canada.
Stolovich-Rain et al., Weaning Triggers a Maturation Step of Pancreatic β Cells, Developmental Cell (2015), http://dx.
Similar statistics play role in decision making and World War II code breaking
"The brain reaches a decision by combining samples of evidence in much the way a good statistician would," says Michael Shadlen, a Professor of Neuroscience at the Kavli Institute for Brain Science at Columbia University. In a new paper in Neuron, Shadlen and colleagues from the University of Washington and the Shanghai Institutes for Biological Sciences demonstrate this theory by monitoring the decision-making process in rhesus monkeys to determine how much and what information they need to confidently choose a correct answer.
The monkeys were shown a sequence of shapes that served as clues about the location of a reward. They could look at as few or as many such clues before making their choice. The scientists found that the monkeys' neurons increased or decreased their activity depending on whether the shape in a sequence supported one or the other location (or color). The process halted when the accumulated evidence reach a critical level. This strategy explained both the choice and number of shapes used to make it.
"It's the brain doing a statistically optimal procedure," Shadlen says. "It's nothing less than a basis of rationality. The brain allows us to combine apples and oranges and lemons, so to speak, by assigning them the right kinds of weights so that when we put them together we reason according to the laws of probability."
This statistical way of decision making resembles a process Alan Turning's team did in Bletchley Park, England, to work out the settings of German enigma machines. In order to make use of the large clicking machine--called 'Christopher' in the recent historical drama "The Imitation Game"--Turing's team analyzed pairs of randomly intercepted German messages, aligned them one above the other to accumulate evidence from letter pairs (matched or not) until they reach a threshold level of certainty that the messages were sent on identical enigma machines, or not. Once the threshold was reached, the code breaker would either accept or reject the hypothesis.
"Rejections were common, but acceptance allowed them to take the next step, using the brute force method of the machine toward figuring out the message used to establish the settings of the enigma machine," Shadlen says. "And if they had that, then all codes could be broken that day."
Kira et al., A Neural Implementation of Wald's Sequential Probability Ratio Test, Neuron (2015), http://dx.