Nanocavities: Optomechanics goes molecular

News and Views.A theoretical framework that interprets Raman scattering as an optomechanical process can be used to understand, and guide, experiments in surface-enhanced Raman spectroscopy.Peer Reviewe

Tailoring the resolution of single-cell RNA sequencing for primary cytotoxic T cells.

Single-cell RNA sequencing in principle offers unique opportunities to improve the efficacy of contemporary T-cell based immunotherapy against cancer. The use of high-quality single-cell data will aid our incomplete understanding of molecular programs determining the differentiation and functional heterogeneity of cytotoxic T lymphocytes (CTLs), allowing for optimal therapeutic design. So far, a major obstacle to high depth single-cell analysis of CTLs is the minute amount of RNA available, leading to low capturing efficacy. Here, to overcome this, we tailor a droplet-based approach for high-throughput analysis (tDrop-seq) and a plate-based method for high-performance in-depth CTL analysis (tSCRB-seq). The latter gives, on average, a 15-fold higher number of captured transcripts per gene compared to droplet-based technologies. The improved dynamic range of gene detection gives tSCRB-seq an edge in resolution sensitive downstream applications such as graded high confidence gene expression measurements and cluster characterization. We demonstrate the power of tSCRB-seq by revealing the subpopulation-specific expression of co-inhibitory and co-stimulatory receptor targets of key importance for immunotherapy

Low-Loss Integrated Nanophotonic Circuits with Layered Semiconductor Materials

Monolayer transition-metal dichalcogenides with direct bandgaps are emerging candidates for optoelectronic devices, such as photodetectors, light-emitting diodes, and electro-optic modulators. Here we report a low-loss integrated platform incorporating molybdenum ditelluride monolayers with silicon nitride photonic microresonators. We achieve microresonator quality factors >3*10^6 in the telecommunication O- to E-bands. This paves the way for low-loss, hybrid photonic integrated circuits with layered semiconductors, not requiring heterogeneous wafer bonding

TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection.

Cytotoxic T cells are essential mediators of protective immunity to viral infection and malignant tumours and are a key target of immunotherapy approaches. However, prolonged exposure to cognate antigens often attenuates the effector capacity of T cells and limits their therapeutic potential <sup>1-4</sup> . This process, known as T cell exhaustion or dysfunction <sup>1</sup> , is manifested by epigenetically enforced changes in gene regulation that reduce the expression of cytokines and effector molecules and upregulate the expression of inhibitory receptors such as programmed cell-death 1 (PD-1) <sup>5-8</sup> . The underlying molecular mechanisms that induce and stabilize the phenotypic and functional features of exhausted T cells remain poorly understood <sup>9-12</sup> . Here we report that the development and maintenance of populations of exhausted T cells in mice requires the thymocyte selection-associated high mobility group box (TOX) protein <sup>13-15</sup> . TOX is induced by high antigen stimulation of the T cell receptor and correlates with the presence of an exhausted phenotype during chronic infections with lymphocytic choriomeningitis virus in mice and hepatitis C virus in humans. Removal of its DNA-binding domain reduces the expression of PD-1 at the mRNA and protein level, augments the production of cytokines and results in a more polyfunctional T cell phenotype. T cells with this deletion initially mediate increased effector function and cause more severe immunopathology, but ultimately undergo a massive decline in their quantity, notably among the subset of TCF-1 <sup>+</sup> self-renewing T cells. Altogether, we show that TOX is a critical factor for the normal progression of T cell dysfunction and the maintenance of exhausted T cells during chronic infection, and provide a link between the suppression of effector function intrinsic to CD8 T cells and protection against immunopathology

The Bgee suite: integrated curated expression atlas and comparative transcriptomics in animals

Bgee is a database to retrieve and compare gene expression patterns in multiple animal species, produced by integrating multiple data types (RNA-Seq, Affymetrix, in situ hybridization, and EST data). It is based exclusively on curated healthy wild-type expression data (e.g., no gene knock-out, no treatment, no disease), to provide a comparable reference of normal gene expression. Curation includes very large datasets such as GTEx (re-annotation of samples as 'healthy' or not) as well as many small ones. Data are integrated and made comparable between species thanks to consistent data annotation and processing, and to calls of presence/absence of expression, along with expression scores. As a result, Bgee is capable of detecting the conditions of expression of any single gene, accommodating any data type and species. Bgee provides several tools for analyses, allowing, e.g., automated comparisons of gene expression patterns within and between species, retrieval of the prefered conditions of expression of any gene, or enrichment analyses of conditions with expression of sets of genes. Bgee release 14.1 includes 29 animal species, and is available at https://bgee.org/ and through its Bioconductor R package BgeeDB

Pyrimidine de novo synthesis inhibition selectively blocks effector but not memory T cell development.

Blocking pyrimidine de novo synthesis by inhibiting dihydroorotate dehydrogenase is used to treat autoimmunity and prevent expansion of rapidly dividing cell populations including activated T cells. Here we show memory T cell precursors are resistant to pyrimidine starvation. Although the treatment effectively blocked effector T cells, the number, function and transcriptional profile of memory T cells and their precursors were unaffected. This effect occurred in a narrow time window in the early T cell expansion phase when developing effector, but not memory precursor, T cells are vulnerable to pyrimidine starvation. This vulnerability stems from a higher proliferative rate of early effector T cells as well as lower pyrimidine synthesis capacity when compared with memory precursors. This differential sensitivity is a drug-targetable checkpoint that efficiently diminishes effector T cells without affecting the memory compartment. This cell fate checkpoint might therefore lead to new methods to safely manipulate effector T cell responses

Cooperative interactions between nano-antennas in a high-Q cavity for unidirectional light sources

We analyse the resonant mode structure and local density of states in high-Q hybrid plasmonic-photonic resonators composed of dielectric microdisks hybridized with pairs of plasmon antennas that are systematically swept in position through the cavity mode. On the one hand, this system is a classical realization of the cooperative resonant dipole–dipole interaction through a cavity mode, as is evident through predicted and measured resonance linewidths and shifts. At the same time, our work introduces the notion of ‘phased array’ antenna physics into plasmonic-photonic resonators. We predict that one may construct large local density of states (LDOS) enhancements exceeding those given by a single antenna, which are ‘chiral’ in the sense of correlating with the unidirectional injection of fluorescence into the cavity. We report an experiment probing the resonances of silicon nitride microdisks decorated with aluminium antenna dimers. Measurements directly confirm the predicted cooperative effects of the coupled dipole antennas as a function of the antenna spacing on the hybrid mode quality factors and resonance conditions