COVER A powerful tropical thunderstorm exhibits an overshooting top that may inject water vapor into the lower stratosphere. Supercell thunderstorms, in particular, can excite hydraulic jumps at the tropopause, substantially increasing the local hydration of the lower stratosphere. Enhanced understanding of this feature has the potential to improve severe weather forecasts. See pages 1194 and 1248.
Photo: Santiago Borja

ONLINE COVER Evoking the mystery of nature, this image features a Jeff Koons–inspired representation of the SbmA transporter structure. The ice block represents the cryo-electron microscopy used to determine the structure. By unraveling the protein structure, Ghilarov et al. were able to establish the molecular mechanism behind bacteria’s sensitivity to certain antibiotics. This research could aid in designing new antibacterial agents.

Credit: Alina Kurokhtina/Dmitry Ghilarov

ONLINE COVER Critical Crossroads. This month's cover features an immunofluorescence image of a murine tumor-draining lymph node containing metastatic melanoma cells (GFP-expressing YUMM1.7 cells; cyan). Tumor cells reach the tumor-draining lymph node via afferent lymphatic vessels that intersect with the subcapsular and interfollicular sinuses (sinus-lining lymphatic endothelial cells stained with anti-LYVE-1; orange). The sinuses run around and between B cell follicles (B cells stained with anti-B220; purple). A Review by du Bois, Heim, and Lund summarizes our current understanding of the structural biology of tumor-draining lymph nodes, how they are primed to receive metastasizing tumor cells, and their unique impact on prognosis and immunotherapy.

Credit: Haley du Bois and Annie L. Chen/NYU Grossman School of Medicine

ONLINE COVER Special Issue on Human-Robot Interaction. Prosthetic systems that provide a strong sense of agency and ownership between the user and the prosthesis will improve performance and reduce the rate of device abandonment. Marasco et al. have developed a neural-machine interface for a bionic prosthetic arm that leverages the sense of touch to enhance physical ownership and provides grip kinesthesia to enhance agency. This month's cover is a photograph of the inside socket of a bionic prosthetic arm (see also Focus by Ortiz-Catalan).

Credit: Courtney Shell, Dylan Beckler, Zachary Thumser, and Paul Marasco/Laboratory for Bionic Integration, Cleveland Clinic

ONLINE COVER This week, Hu et al. show that opioids induce a cytokine-to-chemokine pathway in astrocytes that impairs the analgesic effects of opioids in neurons. The image shows immunofluorescence staining for the cytokine IL-33 (green) and its receptor ST2 (red) in the mouse dorsal horn.

Credit: Hu et al./Science Signaling

ONLINE COVER Translating Antitumor Immunity. This image shows CD8 T cells (green), CD4 T cells (red), and regulatory T cells (yellow) in a murine melanoma tumor after intratumoral treatment with cytokine-encoding mRNAs. Nuclei are shown in blue. Cytokine-based immunotherapies for cancer have had limited clinical success due to off-target toxicity and difficulty of intratumoral delivery. Here, Hotz et al. developed a mixture of four mRNAs encoding interleukin (IL)-12 single chain, interferon-α, granulocyte-macrophage colony-stimulating factor, and IL-15 sushi. Intratumoral administration of these mRNAs led to antitumor immune responses and control of tumor burden in multiple mouse models. These results support further investigation into cytokine-encoding mRNAs as cancer immunotherapies.

Credit: Hotz et al./Science Translational Medicine