Autism genes converge on asynchronous development of shared neuron classes.

Genetic risk for autism spectrum disorder (ASD) is associated with hundreds of genes spanning a wide range of biological functions. The alterations in the human brain resulting from mutations in these genes remain unclear. Furthermore, their phenotypic manifestation varies across individuals.

Spatial mapping of protein composition and tissue organization: a primer for multiplexed antibody-based imaging.

Tissues and organs are composed of distinct cell types that must operate in concert to perform physiological functions. Efforts to create high-dimensional biomarker catalogs of these cells have been largely based on single-cell sequencing approaches, which lack the spatial context required to understand critical cellular communication and correlated structural organization. To probe in situ biology with sufficient depth, several multiplexed protein imaging methods have been recently developed.

Multiscale 3D phenotyping of human cerebral organoids.

Brain organoids grown from human pluripotent stem cells self-organize into cytoarchitectures resembling the developing human brain. These three-dimensional models offer an unprecedented opportunity to study human brain development and dysfunction. Characterization currently sacrifices spatial information for single-cell or histological analysis leaving whole-tissue analysis mostly unexplored.

Elasticizing tissues for reversible shape transformation and accelerated molecular labeling.

We developed entangled link-augmented stretchable tissue-hydrogel (ELAST), a technology that transforms tissues into elastic hydrogels to enhance macromolecular accessibility and mechanical stability simultaneously. ELASTicized tissues are highly stretchable and compressible, which enables reversible shape transformation and faster delivery of probes into intact tissue specimens via mechanical thinning. This universal platform may facilitate rapid and scalable molecular phenotyping of large-scale biological systems, such as human organs.

Whole-Brain Analysis of Cells and Circuits by Tissue Clearing and Light-Sheet Microscopy.

In this photo essay, we present a sampling of technologies from laboratories at the forefront of whole-brain clearing and imaging for high-resolution analysis of cell populations and neuronal circuits. The data presented here were provided for the eponymous Mini-Symposium presented at the Society for Neuroscience's 2018 annual meeting.

Depolarization signatures map gold nanorods within biological tissue.

Owing to their electromagnetic properties, tunability and biocompatibility, gold nanorods (GNRs) are being investigated as multifunctional probes for a range of biomedical applications. However, detection beyond the reach of traditional fluorescence and two-photon approaches and quantitation of their concentration in biological tissue remain challenging tasks in microscopy. Here we show how the size and aspect ratio that impart GNRs with their plasmonic properties also make them a source of entropy.

Multiplexed and scalable super-resolution imaging of three-dimensional protein localization in size-adjustable tissues.

The biology of multicellular organisms is coordinated across multiple size scales, from the subnanoscale of molecules to the macroscale, tissue-wide interconnectivity of cell populations. Here we introduce a method for super-resolution imaging of the multiscale organization of intact tissues. The method, called magnified analysis of the proteome (MAP), linearly expands entire organs fourfold while preserving their overall architecture and three-dimensional proteome organization.

Whole-brain imaging reaches new heights (and lengths).

Advances in microscopy and sample preparation have led to the first ever mapping of individual neurons in the whole mouse brain.

Secreted biomolecules alter the biological identity and cellular interactions of nanoparticles.

A nanoparticle's physical and chemical properties at the time of cell contact will determine the ensuing cellular response. Aggregation and the formation of a protein corona in the extracellular environment will alter nanoparticle size, shape, and surface properties, giving it a "biological identity" that is distinct from its initial "synthetic identity". The biological identity of a nanoparticle depends on the composition of the surrounding biological environment and determines subsequent cellular interactions.

Tumour-on-a-chip provides an optical window into nanoparticle tissue transport.

Nanomaterials are used for numerous biomedical applications, but the selection of optimal properties for maximum delivery remains challenging. Thus, there is a significant interest in elucidating the nano-bio interactions underlying tissue accumulation. To date, researchers have relied on cell culture or animal models to study nano-bio interactions.

Simultaneous quantification of cells and nanomaterials by inductive-coupled plasma techniques.

We demonstrate that endogenous cellular magnesium levels can be used as an accurate determinant of total cell number by inductively coupled plasma techniques, increasing the throughput and reproducibility of nanoparticle-uptake studies. Uptake of either gold nanoparticles or quantum dots did not affect intracellular concentration of Mg. To demonstrate this technique, we show the decreased uptake of nano-urchins in A549 cells compared with gold nanospheres.

The effect of nanoparticle size, shape, and surface chemistry on biological systems.

An understanding of the interactions between nanoparticles and biological systems is of significant interest. Studies aimed at correlating the properties of nanomaterials such as size, shape, chemical functionality, surface charge, and composition with biomolecular signaling, biological kinetics, transportation, and toxicity in both cell culture and animal experiments are under way. These fundamental studies will provide a foundation for engineering the next generation of nanoscale devices.

Effect of gold nanoparticle aggregation on cell uptake and toxicity.

Aggregation appears to be a ubiquitous phenomenon among all nanoparticles and its influence in mediating cellular uptake and interactions remain unclear. Here we developed a simple technique to produce transferrin-coated gold nanoparticle aggregates of different sizes and characterized their uptake and toxicity in three different cell lines. While the aggregation did not elicit a unique toxic response, the uptake patterns were different between single and aggregated nanoparticles.

Rough around the edges: the inflammatory response of microglial cells to spiky nanoparticles.

The versatility of nanoparticle design has established nanotechnology as a potential "one-stop solution" to many biological and medical applications. The capacity to control nanoparticle size, shape, and surface chemistry has enabled their use as imaging contrast agents or carriers for drugs and other compounds. However, concerns of nanoparticle toxicity have surfaced that could limit their clinical translation.

Impact of protective IL-2 allelic variants on CD4+ Foxp3+ regulatory T cell function in situ and resistance to autoimmune diabetes in NOD mice.

Type I diabetes (T1D) susceptibility is inherited through multiple insulin-dependent diabetes (Idd) genes. NOD.B6 Idd3 congenic mice, introgressed with an Idd3 allele from T1D-resistant C57BL/6 mice (Idd3(B6)), show a marked resistance to T1D compared with control NOD mice.

Functional waning of naturally occurring CD4+ regulatory T-cells contributes to the onset of autoimmune diabetes.

Objective: In this study, we asked whether a possible quantitative or qualitative deficiency in naturally occurring Foxp3(+)CD4(+) regulatory T-cells (nT(reg)), which display potent inhibitory effects on T-cell functions in vitro and in vivo, may predispose to the development of type 1 diabetes.

Research Design And Methods: We assessed the frequency and function of Foxp3(+) nT(reg) cells in primary and secondary lymphoid tissues in the NOD animal model of type 1 diabetes.

Results: We show that the cellular frequency of Foxp3(+) nT(reg) cells in primary and secondary lymphoid tissues is stable and does not decline relative to type 1 diabetes-resistant mice.