Creatures great and small bend to move forward

A wide range of animals that move through air or water have natural propulsors, such as wings and fins, that are not rigid but instead typically bend during motion. Propulsors have evolved over millions of years and among multiple taxonomic groups, and their bending patterns are believed to contribute to the high efficiency of animal movements compared with those of man-made, rigid designs.

John Costello's group at Providence College (RI) uncovered the universal patterns of animal propulsor bending by comparing video sequences of 59 different animal species, from fruit flies to humpback whales. The results show that the propulsors all bend in similar ways within a predictable range of characteristic motions (Nat. Commun. 5, 3293; 2014). The findings provide a new framework from which to design flexible propulsors, such as for airplanes.

Costello's team found that two factors vary only within constrained ranges across all of the species. The first is the ratio of the distance from the propulsor base to the flex point relative to the total propulsor length. The second is the maximum extent that the propulsor bends. These two characteristics are conserved across animal species, suggesting that natural selection has acted in a wide variety of contexts to select specific bending designs. KR

Mutation of MDA5 in autoimmunity

MDA5 is an intracellular viral receptor that detects picornaviruses and other invaders and elicits immune responses accordingly. It has been implicated in autoimmune disorders such as type 1 diabetes, Crohn's disease, psoriasis and systemic lupus erythematosus, but no mechanistic link has been identified. To learn more about its potential role in autoimmunity, Takashi Fujita (Kyoto University, Japan) and his team engineered mice with a missense mutation of MDA5. The mutant mice spontaneously developed symptoms resembling those of the autoimmune disorder lupus, including inflammation of multiple organs, especially the kidney (Immunity 40, 199–212; 2014). Further analysis showed that the missense mutation caused increased expression of MDA5, suggesting that a gain of function led to the observed autoimmune response. A different mutation of MDA5 that is associated with lupus in humans resulted in similar activation of the immune response.

The team speculates that this information could lead to the development of therapies that target the MDA5 pathway to halt autoimmune disease progression. Fujita told The Asahi Shimbun, “Using the mice, we hope to find an effective treatment.”

Fujita's study is the first to find direct evidence that dysregulation of MDA5 can cause autoimmune disorders, offering a new view on the link between innate immunity and autoimmunity. MH

Partnering proteins to improve wound healing

The use of growth factors to stimulate healing is limited by their inability to bind to the extracellular matrix of tissues. To address this problem, a group led by Jeffrey Hubbell (École Polytechnique Fédérale de Lausanne, Switzerland) screened 25 molecules from multiple growth factor families and found that one called PIGF-2 strongly binds to extracellular matrix proteins. The team added this protein to other growth factors known to stimulate wound healing and used the modified molecules to treat the wounds of mice and rats. Their injuries healed much more quickly than those treated with unmodified growth factors (Science 343, 885–888; 2014).

The first model the researchers tested was the diabetic db/db mouse, which has impaired wound healing. Wounds treated with two growth factors that each had been fused with PIGF-2 healed significantly faster than those treated with unmodified growth factors. Angiogenesis, the formation of new blood vessels, was more pronounced in the tissues as well; this process is crucial for the repair of tissue.

The second model they tested was the healing of a skull defect in the rat. Treatment with PIGF-2–fused growth factors led to a marked increase of bone tissue deposition compared to treatment with unmodified growth factors. KR

The shape of monitoring to come

Engineers led by John Rogers (University of Illinois at Urbana-Champaign) have created a three-dimensional, electrode-bearing, elastic membrane that can be wrapped directly around a beating heart and used to measure the electrical, mechanical, chemical and physical properties across its entire surface without disrupting cardiac function (Nat. Commun. doi:10.1038/ncomms4329;). The membrane requires no glue or sutures to hold it in place but maintains full contact with the epicardium.

They tested the membrane in explanted, perfused rabbit hearts; in vivo animal tests are planned. Rogers' team suggests that the membranes could be used to identify critical regions involved in disorders like arrhythmia, ischemia or heart failure. With the incorporation of electrodes to stimulate the heart muscle, they could also be used as next-generation pacemakers. Rogers also believes that similar membranes could be developed for other organs, such as the brain. “The idea could be applied to any organ,” he told The New Scientist. Before any of these applications become reality, however, several obstacles need to be addressed, such as how to power, control, insert and remove the membrane. Advances in other aspects of mechanical engineering, such as wireless power transmission, microscale batteries and dissolvable devices, may help to meet these needs. MH

Drug makes blind mice see the light

Visual impairments such as retinitis pigmentosa and age-related macular degeneration are caused by the degeneration of photoreceptor cells in the retina; these cells are necessary for the perception of light. Now, mice with degenerated photoreceptors have had their light perception restored with a single intraocular injection of a molecule called DENAQ. DENAQ stimulates the retinal ganglion cells to become responsive to light (Neuron 81, 800–813; 2014).

The injection's effects last a few days, which Richard Kramer, the study's lead author, and his team at the University of California, Berkeley, view as an advantage; because the effect wears off, the dosage can be adjusted to maximize efficacy and minimize toxicity.

DENAQ works by acting as a 'photoswitch' for potassium ion channels in retinal ganglion cells. When exposed to visible light with wavelengths in the 450- to 550-nm range, the molecule changes shape and activates the ion channels, allowing the cells to fire. As a result, the retinal ganglion cells become activated in response to light.

It appears that the presence of healthy photoreceptor cells in the retina prevent the action of DENAQ, suggesting that the usefulness of the molecule as a treatment approach is limited to those with visual impairments resulting from degenerated rods and cones. KR

Dual role of cannabinoid receptors in feeding behavior

Activation of cannabinoid type 1 (CB1) receptors is known to increase food intake, but the neuronal mechanisms underlying this relationship are not well understood. The receptors are expressed in many brain regions that control food intake, where they govern both excitatory (GABAergic) and inhibitory (glutamatergic) neurotransmission, in turn possibly suppressing or promoting feeding behavior, respectively. By reducing either excitatory or inhibitory neurotransmission, activation of CB1 receptors might have opposing effects on food intake.

To clarify this interaction, Giovanni Marsicano (Institut National de la Santé et de la Recherche Médicale, Bordeaux, France) and colleagues evaluated food intake in fasted mutant mice that lacked CB1 receptors completely or only in either GABAergic or glutamatergic neurons. Mice lacking GABAergic CB1 receptors had greater food intake than wild-type mice, whereas mice lacking glutamatergic CB1 receptors and mice lacking all CB1 receptors both had lower food intake than wild-type mice (Nat. Neurosci. 13, 281–283; 2014).

The findings suggest that the control of glutamatergic transmission by CB1 receptors contributes to their ability to promote feeding behavior. In addition, they show that CB1 receptors have a dual role in controlling food intake. The study results also confirm that cannabinoid-mediated control of neuronal excitation and inhibition is an important regulator of mammalian behavior. MH