COVER This image depicts a variety of sperm trying to reach an oocyte. Some sperm are abnormal, and some of those are patched up—alluding to treatments that can overcome some types of sperm abnormalities to achieve viable offspring. Conversely, some healthy sperm are blocked by walls, which represent contraception. See the special section on human reproduction beginning on page 148.

Illustration: Sara Gironi Carnevale

ONLINE COVER An artist’s rendering of an optoelectronic memory device based on negative differential resistance (NDR) diodes and a micro-ring resonator. The coming end of Moore-like growth of computational power has increased focus on alternative computing architectures, such as electro-optical computing where light carries information in the circuit rather than electrons. Gherabli et al. demonstrate a fully CMOS-compatible electro-optical memory device, based on a new type of NDR-diode. The new diode is based on a horizontal PN-junction in silicon implemented into a photonic micro-ring resonator to create a bi-stable device with fully optical read-out in the telecom regime.

ONLINE COVER Intertwined Lineages. This month’s cover depicts two trees whose trunks have grown together and physically attached, a natural phenomenon known as inosculation. These trees represent two separate developmental lineages of T cells that can both yield T follicular regulatory (Tfr) cells. Using single-cell analysis techniques to study Tfr cells isolated from human tonsils, Le Coz et al. documented the presence of distinct Tfr subsets derived from either natural regulatory T cells or T follicular helper cells, each with distinct functional properties and localization within lymphoid tissues.

ONLINE COVER Robust robots. The ability of robots to endure severe damage, as well as offer the possibility for repair, can enable their deployment in challenging settings. Kim et al. have developed aerial robots that can endure several punctures while sustaining controlled flight. The dielectric elastomer actuators on the robots were also designed to be repairable by using laser ablation to isolate the defects and recover their performance. This month’s cover is a photograph of the aerial robot showing one dielectric elastomer actuator pierced with fiberglass needles.

ONLINE COVER This week, Gabriel and Streicher show in mice that opioids activate a pathway in the spine that inhibits their efficacy. This pathway is mediated by the kinase AMPK and can be blocked by HSP90 inhibitors. The image shows opioid-induced phosphorylation of ERK (green) in the spinal cord of mice that lack AMPK in certain neurons.

ONLINE COVER A Cloak for Pancreatic Pseudoislets. The cover shows wild-type (top and left) and engineered hypoimmune (bottom and right) pancreatic pseudoislets derived from primary human pancreatic islet cells. The top and right pseudoislets were stained for somatostatin (blue), insulin (green), and glucagon (red). The bottom and left pseudoislets were stained for major histocompatibility complex (MHC) class I (red), CD47 (yellow), and nuclei (blue). Allogeneic pancreatic islet transplantation has been used to improve glycemic control in patients with diabetes but can provoke inflammatory reactions as well as allo- and autoimmunity, necessitating lifelong use of immunosuppressants by recipients. Hu et al. engineered allogeneic primary human pancreatic cells to lack MHC class I and II molecules, thereby hiding the cells from the recipient immune system. The engineered pancreatic cells were aggregated into pseudoislets which were then transplanted into immunocompetent, allogeneic, diabetic humanized mice. The hypoimmune pseudoislets survived and ameliorated diabetes in the mice without the need for treatment with immunosuppressants.