Neuropeptides and small-molecule amine transmitters: cooperative signaling in the nervous system.

Neuropeptides are expressed in cell-specific patterns throughout mammalian brain. Neuropeptide gene expression has been useful for clustering neurons by phenotype, based on single-cell transcriptomics, and for defining specific functional circuits throughout the brain. How neuropeptides function as first messengers in inter-neuronal communication, in cooperation with classical small-molecule amine transmitters (SMATs) is a current topic of systems neurobiology. Questions include how neuropeptides and SMATs cooperate in neurotransmission at the molecular, cellular and circuit levels; whether neuropeptides and SMATs always co-exist in neurons; where neuropeptides and SMATs are stored in the neuron, released from the neuron and acting, and at which receptors, after release; and how neuropeptides affect 'classical' transmitter function, both directly upon co-release, and indirectly, via long-term regulation of gene transcription and neuronal plasticity. Here, we review an extensive body of data about the distribution of neuropeptides and their receptors, their actions after neuronal release, and their function based on pharmacological and genetic loss- and gain-of-function experiments, that addresses these questions, fundamental to understanding brain function, and development of neuropeptide-based, and potentially combinatorial peptide/SMAT-based, neurotherapeutics.

Peptide- and Amine-Modified Glucan Particles for the Delivery of Therapeutic siRNA.

Translation of siRNA technology into the clinic is limited by the need for improved delivery systems that target specific cell types. Macrophages are particularly attractive targets for RNAi therapy because they promote pathogenic inflammatory responses in a number of important human diseases. We previously demonstrated that a multicomponent formulation of ß-1,3-d-glucan-encapsulated siRNA particles (GeRPs) can specifically and potently silence genes in mouse macrophages. A major advance would be to simplify the GeRP system by reducing the number of delivery components, thus enabling more facile manufacturing and future commercialization. Here we report the synthesis and evaluation of a simplified glucan-based particle (GP) capable of delivering siRNA in vivo to selectively silence macrophage genes. Covalent attachment of small-molecule amines and short peptides containing weak bases to GPs facilitated electrostatic interaction of the particles with siRNA and aided in the endosomal release of siRNA by the proton-sponge effect. Modified GPs were nontoxic and were efficiently internalized by macrophages in vitro. When injected intraperitoneally (i.p.), several of the new peptide-modified GPs were found to efficiently deliver siRNA to peritoneal macrophages in lean, healthy mice. In an animal model of obesity-induced inflammation, i.p. administration of one of the peptide-modified GPs (GP-EP14) bound to siRNA selectively reduced the expression of target inflammatory cytokines in the visceral adipose tissue macrophages. Decreasing adipose tissue inflammation resulted in an improvement of glucose metabolism in these metabolically challenged animals. Thus, modified GPs represent a promising new simplified system for the efficient delivery of therapeutic siRNAs specifically to phagocytic cells in vivo for modulation of inflammation responses.

Instant Postsynthesis Aqueous Dispersion of Sb-Doped SnO2 Nanocrystals: The Synergy between Small-Molecule Amine and Sb Dopant Ratio.

Direct printing of transparent conducting oxide (TCO) nanocrystal dispersions holds great promise in solution-processed optoelectronics due to its advantages of low material waste and direct patterning on substrates. An essential prerequisite for printable TCO colloidal solutions is the effective stabilization of TCO nanocrystals to prevent their strong aggregation. In situ stabilization uses long-chain ligands to provide interparticle steric repulsion between TCO nanocrystals during the growth of TCO nanocrystals. In sharp contrast, the postsynthesis dispersion of TCO nanocrystals is particularly challenging since the agglomeration already occurs, especially for TCO nanocrystals synthesized without protection by any organic species. Herein, we propose an instant postsynthesis strategy for aqueous colloidal dispersions of Sb-doped SnO2 (ATO) nanocrystals using small-molecule amines of propylamine, ethylenediamine, monoethanolamine, and triethylamine. The average size of ATO secondary particles in aqueous dispersions can be instantly reduced from around 400 to about 25 nm using these amines. The increased Sb dopant ratio also plays a synergistic role in the dispersion effect. The small-molecule amines are found to be preferably adsorbed onto the Sb sites exposed on ATO nanocrystal surface. A higher Sb dopant ratio would facilitate the adsorption of more amines and induce stronger surface charge repulsion that benefits the stable dispersion of ATO nanocrystals. TCO films fabricated with the ATO nanocrystal dispersions have a high transparency of 80.6% and low sheet resistance of 492 Ω/sq, showing promising application in electrochromic devices.

Nitrogen-doped graphene oxide monoliths crosslinked by short chain aliphatic amines.

Nitrogen-doped graphene oxide monoliths (NGOMs) were readily fabricated by crosslinking graphene oxide (GO) using four different short chain aliphatic amines, i.e., ethylenediamine (EDA), dimethylaminopropylamine (DMPDA), N-isopropylethylenediamine (IPEDA), and triethylenetetramine (TETA). Depending on the structure of the amine crosslinkers, the generated monoliths showed various morphologies with different d spacing, layer thickness, and microspore size. Fourier transform-infrared (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses provided evidence for the formation of covalent CN or CN bonds in all cases, indicating that the interaction of GO with amine crosslinkers involved the ring-opening reaction between GO epoxides and amine groups. The formation of both quaternary nitrogen and some nitrogen-containing heterocyclic composition inside the graphene oxide sheet were also suggested. X-Ray Diffraction (XRD) results indicated that the interspatial distance between GO sheets was increased after crosslinking. The fabricated NGOM-TETA demonstrates potential application as an adsorbent material due to its efficient removal of copper ions.