The algorithms are a type of artificial neural network (ANN). Inspired by the way neurons connect and branch in the brain, ANNs are the computational foundations for advanced machine learning. And despite their name, ANNs are not exclusively used to study brains.

Biologists, like Tareen and Kinney, use ANNs to analyze data from an experimental method called a “massively parallel reporter assay” (MPRA) which investigates DNA. Using this data, quantitative biologists can make ANNs that predict which molecules control specific genes in a process called gene regulation.

Cells don’t need all proteins all the time. Instead, they rely on complex molecular mechanisms to turn the genes that produce proteins on or off, as needed. When those regulations fail, disorder and disease usually follow.

“That mechanistic knowledge — understanding how something like gene regulation works — is very often the difference between being able to develop molecular therapies against diseases, and not being able to,” Kinney said.

Unfortunately the way standard ANNs are shaped from MPRA data is very different from how scientists ask questions in the life sciences. This misalignment means that biologists find it difficult to interpret how gene regulation occurs.

Now, Kinney and Tareen developed a new approach that bridges the gap between computational tools and how biologists think. They created custom ANNs that mathematically reflect common concepts in biology concerning genes and the molecules that control them. In this way, the pair are essentially forcing their machine learning algorithms to process data in a way that a biologist can understand.

These efforts, Kinney explained, highlight how modern, industrial AI technologies can be optimized for use in the life sciences. Having verified this new strategy to make custom ANNs, Kinney’s lab is applying it in investigating a wide variety of biological systems, including key gene circuits involved in human disease.

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Materials provided by Cold Spring Harbor Laboratory. Original written by Brian Stallard. Note: Content may be edited for style and length.

The development of artificial intelligence (AI) techniques has been rapidly advancing in recent years and has begun impacting our lives in various ways. Although AI processes information in a manner similar to the human brain, the mechanisms by which human brains operate are still largely unknown. Fundamental brain components, such as neurons and the junctions between them (synapses), have been studied in detail. However, many questions concerning the brain as a collective whole need to be answered. For example, we still do not fully understand how the brain performs such functions as memorization, learning and forgetting, and how the brain becomes alert and returns to calm. In addition, live brains are difficult to manipulate in experimental research. For these reasons, the brain remains a “mysterious organ.” A different approach to brain research?in which materials and systems capable of performing brain-like functions are created and their mechanisms are investigated?may be effective in identifying new applications of brain-like information processing and advancing brain science.

The joint research team recently built a complex brain-like network by integrating numerous silver (Ag) nanowires coated with a polymer (PVP) insulating layer approximately 1 nanometer in thickness. A junction between two nanowires forms a variable resistive element (i.e., a synaptic element) that behaves like a neuronal synapse. This nanowire network, which contains a large number of intricately interacting synaptic elements, forms a “neuromorphic network.” When a voltage was applied to the neuromorphic network, it appeared to “struggle” to find optimal current pathways (i.e., the most electrically efficient pathways). The research team measured the processes of current pathway formation, retention and deactivation while electric current was flowing through the network and found that these processes always fluctuate as they progress, similar to the human brain’s memorization, learning, and forgetting processes. The observed temporal fluctuations also resemble the processes by which the brain becomes alert or returns to calm. Brain-like functions simulated by the neuromorphic network were found to occur as the huge number of synaptic elements in the network collectively work to optimize current transport, in the other words, as a result of self-organized and emerging dynamic processes..

The research team is currently developing a brain-like memory device using the neuromorphic network material. The team intends to design the memory device to operate using fundamentally different principles than those used in current computers. For example, while computers are currently designed to spend as much time and electricity as necessary in pursuit of absolutely optimum solutions, the new memory device is intended to make a quick decision within particular limits even though the solution generated may not be absolutely optimum. The team also hopes that this research will facilitate understanding of the brain’s information processing mechanisms.

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Materials provided by National Institute for Materials Science, Japan. Note: Content may be edited for style and length.

After studying both Anopheles gambiae and Anopheles coluzzii, two major malaria vectors in West Africa, they found that a particular family of binding proteins situated in the insect’s legs were highly expressed in resistant populations.

First author on a paper published today in the journal Nature, Dr Victoria Ingham, explains: “We have found a completely new insecticide resistance mechanism that we think is contributing to the lower than expected efficacy of bed nets. The protein, which is based in the legs, comes into direct contact with the insecticide as the insect lands on the net, making it an excellent potential target for future additives to nets to overcome this potent resistance mechanism.”

Examining the Anopheline mosquitoes, the team demonstrated that the binding protein, SAP2, was found elevated in resistant populations and further elevated following contact with pyrethroids, the insecticide class used on all bed nets. They found that when levels of this protein were reduced, by partial silencing of the gene, susceptibility to pyrethroids were restored; conversely when the protein was expressed at elevated levels, previously susceptible mosquitoes became resistant to pyrethroids.

The increase in insecticide resistance across mosquito populations has led to the introduction of new insecticide treated bed nets containing the synergist piperonyl butoxide (PBO) as well as pyrethroid insecticides. The synergist targets one of the most widespread and previously most potent resistance mechanisms caused by the cytochrome P450s. However, mosquitoes are continually evolving new resistance mechanisms and the discovery of this new resistance mechanism provides an excellent opportunity to identify additional synergists that could be used to restore susceptibility

Professor Hilary Ranson is senior author on the paper. She said: “Long-lasting insecticide treated bed nets remain one of the key interventions in malaria control. It is vital that we understand and mitigate for resistance within mosquito populations in order to ensure that the dramatic reductions in disease rates in previous decades are not reversed. This newly discovered resistance mechanism could provide us with an important target for both the monitoring of insecticide resistance and the development of novel compounds able to block pyrethroid resistance and prevent the spread of malaria.”

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Materials provided by Liverpool School of Tropical Medicine. Note: Content may be edited for style and length.

But, does scientific evidence support the claims made for these diets? In a review article published in the Dec. 26 issue of The New England Journal of Medicine, Johns Hopkins Medicine neuroscientist Mark Mattson, Ph.D., concludes that intermittent fasting does.

Mattson, who has studied the health impact of intermittent fasting for 25 years, and adopted it himself about 20 years ago, writes that “intermittent fasting could be part of a healthy lifestyle.” A professor of neuroscience at the Johns Hopkins University School of Medicine, Mattson says his new article is intended to help clarify the science and clinical applications of intermittent fasting in ways that may help physicians guide patients who want to try it.

Intermittent fasting diets, he says, fall generally into two categories: daily time-restricted feeding, which narrows eating times to 6-8 hours per day, and so-called 5:2 intermittent fasting, in which people limit themselves to one moderate-sized meal two days each week.

An array of animal and some human studies have shown that alternating between times of fasting and eating supports cellular health, probably by triggering an age-old adaptation to periods of food scarcity called metabolic switching. Such a switch occurs when cells use up their stores of rapidly accessible, sugar-based fuel, and begin converting fat into energy in a slower metabolic process.

Mattson says studies have shown that this switch improves blood sugar regulation, increases resistance to stress and suppresses inflammation. Because most Americans eat three meals plus snacks each day, they do not experience the switch, or the suggested benefits.

In the article, Mattson notes that four studies in both animals and people found intermittent fasting also decreased blood pressure, blood lipid levels and resting heart rates.

Evidence is also mounting that intermittent fasting can modify risk factors associated with obesity and diabetes, says Mattson. Two studies at the University Hospital of South Manchester NHS Foundation Trust of 100 overweight women showed that those on the 5:2 intermittent fasting diet lost the same amount of weight as women who restricted calories, but did better on measures of insulin sensitivity and reduced belly fat than those in the calorie-reduction group.

More recently, Mattson says, preliminary studies suggest that intermittent fasting could benefit brain health too. A multicenter clinical trial at the University of Toronto in April found that 220 healthy, nonobese adults who maintained a calorie restricted diet for two years showed signs of improved memory in a battery of cognitive tests. While far more research needs to be done to prove any effects of intermittent fasting on learning and memory, Mattson says if that proof is found, the fasting — or a pharmaceutical equivalent that mimics it — may offer interventions that can stave off neurodegeneration and dementia.

“We are at a transition point where we could soon consider adding information about intermittent fasting to medical school curricula alongside standard advice about healthy diets and exercise,” he says.

Mattson acknowledges that researchers do “not fully understand the specific mechanisms of metabolic switching and that “some people are unable or unwilling to adhere” to the fasting regimens. But he argues that with guidance and some patience, most people can incorporate them into their lives. It takes some time for the body to adjust to intermittent fasting, and to get beyond initial hunger pangs and irritability that accompany it. “Patients should be advised that feeling hungry and irritable is common initially and usually passes after two weeks to a month as the body and brain become accustomed to the new habit,” Mattson says.

To manage this hurdle, Mattson suggests that physicians advise patients to gradually increase the duration and frequency of the fasting periods over the course of several months, instead of “going cold turkey.” As with all lifestyle changes, says Mattson, it’s important for physicians to know the science so they can communicate potential benefits, harms and challenges, and offer support.

This work was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health.