Viral infection disrupts intestinal homeostasis via Sting-dependent NF-κB signaling in Drosophila.

Host-microbe interactions influence intestinal stem cell (ISC) activity to modulate epithelial turnover and composition. Here, we investigated the functional impacts of viral infection on intestinal homeostasis and the mechanisms by which viral infection alters ISC activity. We report that Drosophila A virus (DAV) infection disrupts intestinal homeostasis in Drosophila by inducing sustained ISC proliferation, resulting in intestinal dysplasia, loss of gut barrier function, and reduced lifespan. We found that additional viruses common in laboratory-reared Drosophila also promote ISC proliferation. The mechanism of DAV-induced ISC proliferation involves progenitor-autonomous epidermal growth factor receptor (EGFR) signaling, c-Jun N-terminal kinase (JNK) activity in enterocytes, and requires Sting-dependent nuclear factor κB (NF-κB) (Relish) activity. We further demonstrate that activating Sting-Relish signaling is sufficient to induce ISC proliferation, promote intestinal dysplasia, and reduce lifespan in the absence of infection. Our results reveal that viral infection can significantly disrupt intestinal physiology, highlight a novel role for Sting-Relish signaling, and support a role for viral infection in aging.

An Aqueous Analog MAC Machine.

Using ions in aqueous milieu for signal processing, like in biological circuits, may potentially lead to a bioinspired information processing platform. Studies, however, have focused on individual ionic diodes and transistors rather than circuits comprising many such devices. Here a 16 × 16 array of new ionic transistors is developed in an aqueous quinone solution. Each transistor features a concentric ring electrode pair with a disk electrode at the center. The electrochemistry of these electrodes in the solution provides the basis for the transistor operation. The ring pair electrochemically tunes the local electrolytic concentration to modulate the disk's Faradaic reaction rate. Thus, the disk current as a Faradaic reaction to the disk voltage is gated by the ring pair. The 16 × 16 array of these transistors performs analog multiply-accumulate (MAC) operations, a computing modality hotly pursued for low-power artificial neural networks. This exploits the transistor's operating regime where the disk current is a multiplication of the disk voltage and a weight parameter tuned by the ring pair gating. Such disk currents from multiple transistors are summated in a global reference electrode to complete a MAC task. This ionic circuit demonstrating analog computing is a step toward sophisticated aqueous ionics.

Multiplex enzymatic synthesis of DNA with single-base resolution.

Enzymatic DNA synthesis (EDS) is a promising benchtop and user-friendly method of nucleic acid synthesis that, instead of solvents and phosphoramidites, uses mild aqueous conditions and enzymes. For applications such as protein engineering and spatial transcriptomics that require either oligo pools or arrays with high sequence diversity, the EDS method needs to be adapted and certain steps in the synthesis process spatially decoupled. Here, we have used a synthesis cycle comprising a first step of site-specific silicon microelectromechanical system inkjet dispensing of terminal deoxynucleotidyl transferase enzyme and 3' blocked nucleotide, and a second step of bulk slide washing to remove the 3' blocking group. By repeating the cycle on a substrate with an immobilized DNA primer, we show that microscale spatial control of nucleic acid sequence and length is possible, which, here, are assayed by hybridization and gel electrophoresis. This work is distinctive for enzymatically synthesizing DNA in a highly parallel manner with single base control.

CMOS electrochemical pH localizer-imager.

pH controls a large repertoire of chemical and biochemical processes in water. Densely arrayed pH microenvironments would parallelize these processes, enabling their high-throughput studies and applications. However, pH localization, let alone its arrayed realization, remains challenging because of fast diffusion of protons in water. Here, we demonstrate arrayed localizations of picoliter-scale aqueous acids, using a 256-electrochemical cell array defined on and operated by a complementary metal oxide semiconductor (CMOS)-integrated circuit. Each cell, comprising a concentric pair of cathode and anode with their current injections controlled with a sub-nanoampere resolution by the CMOS electronics, creates a local pH environment, or a pH "voxel," via confined electrochemistry. The system also monitors the spatiotemporal pH profile across the array in real time for precision pH control. We highlight the utility of this CMOS pH localizer-imager for high-throughput tasks by parallelizing pH-gated molecular state encoding and pH-regulated enzymatic DNA elongation at any selected set of cells.