Daily Science Podcast

The mediodorsal thalamus (MD) shares reciprocal connectivity with the prefrontal cortex (PFC), and decreased MD–PFC connectivity is observed in schizophrenia patients. Patients also display cognitive deficits including impairments in working memory, but a mechanistic link between thalamo–prefrontal circuit function and working memory is missing. Using pathway-specific inhibition, we found directional interactions between mouse MD and medial PFC (mPFC), with MD-to-mPFC supporting working memory maintenance and mPFC-to-MD supporting subsequent choice. We further identify mPFC neurons that display elevated spiking during the delay, a feature that was absent on error trials and required MD inputs for sustained maintenance. Strikingly, delay-tuned neurons had minimal overlap with spatially tuned neurons, and each mPFC population exhibited mutually exclusive dependence on MD and hippocampal inputs. These findings indicate a role for MD in sustaining prefrontal activity during working memory maintenance Consistent with this idea, we found that enhancing MD excitability was sufficient to enhance task performance.

The computing demands of future data-intensive applications will greatly exceed the capabilities of current electronics, and are unlikely to be met by isolated improvements in transistors, data storage technologies or integrated circuit architectures alone. Instead, transformative nanosystems, which use new nanotechnologies to simultaneously realize improved devices and new integrated circuit architectures, are required. Here we present a prototype of such a transformative nanosystem. It consists of more than one million resistive random-access memory cells and more than two million carbon-nanotube field-effect transistors promising new nanotechnologies for use in energy-efficient digital logic circuits and for dense data storage fabricated on vertically stacked layers in a single chip. Unlike conventional integrated circuit architectures, the layered fabrication realizes a three-dimensional integrated circuit architecture with fine-grained and dense vertical connectivity between layers of computing, data storage, and input and output (in this instance, sensing). As a result, our nanosystem can capture massive amounts of data every second, store it directly on-chip, perform in situ processing of the captured data, and produce ‘highly processed’ information. As a working prototype,our nanosystem senses and classifies ambient gases. Furthermore, because the layers are fabricated on top of silicon logic circuitry, our nanosystem is compatible with existing infrastructure for silicon-based technologies. Such complex nano-electronic systems will be essential for future high-performance and highly energy-efficient electronic systems.

Electrochemical capacitors and lithium-ion batteries have seen little change in their electrolyte chemistry since their commercialization, which has limited improvements in device performance. Combining superior physical and chemical properties and a high dielectric-fluidity factor, the use of electrolytes based on solvent systems that exclusively use components that are typically gaseous under standard conditions show a wide potential window of stability and excellent performance over an extended temperature range. Electrochemical capacitors using difluoromethane show outstanding performance from –78° to +65°C, with an increased operation voltage. The use of fluoromethane shows a high coulombic efficiency of ~97% for cycling lithium metal anodes, together with good cyclability of a 4-volt lithium cobalt oxide cathode and operation as low as –60°C, with excellent capacity retention.

Immunotherapy holds tremendous promise for improving cancer treatment. To administer radiotherapy with immunotherapy has been shown to improve immune responses and can elicit the ‘abscopal effect’. Unfortunately, response rates for this strategy remain low. Herein we report an improved cancer immunotherapy approach that utilizes antigen-capturing nanoparticles (AC-NPs). We engineered several AC-NP formulations and demonstrated that the set of protein antigens captured by each AC-NP formulation is dependent on the NP surface properties. We showed that AC-NPs deliver tumour-specific proteins to antigen-presenting cells (APCs) and significantly improve the efficacy of αPD-1 (anti-programmed cell death 1) treatment using the B16F10 melanoma model, generating up to a 20% cure rate compared with 0% without AC-NPs. Mechanistic studies revealed that AC-NPs induced an expansion of CD8+ cytotoxic T cells and increased both CD4+T/Treg and CD8+T/Treg ratios (Treg , regulatory T cells). Our work presents a novel strategy to improve cancer immunotherapy with nanotechnology.

Diet influences health and patterns of disease in populations. How different diets do this and why out- comes of diets vary between individuals are complex and involve interaction with the gut microbiome. A major challenge for predicting health outcomes of the host-microbiome dynamic is reconciling the effects of different aspects of diet (food composition or intake rate) on the system. Here we show that microbial community assembly is fundamentally shaped by a dichotomy in bacterial strategies to ac- cess nitrogen in the gut environment. Consequently, the pattern of dietary protein intake constrains the host-microbiome dynamic in ways that are common to a very broad range of diet manipulation strategies. These insights offer a mechanism for the impact of high protein intake on metabolic health and form the basis for a general theory of the impact of different diet strategies on host-micro- biome outcomes.