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Although it is a relatively rare disease, primarily found in the Caucasian population, uveal melanoma is the most common primary intraocular tumor in adults with a mean age-adjusted incidence of 5.1 cases per million per year. Tumors are located either in iris (4%), ciliary body (6%), or choroid (90%). The host susceptibility factors for uveal melanoma include fair skin, light eye color, inability to tan, ocular or oculodermal melanocytosis, cutaneous or iris or choroidal nevus, and BRCA1-associated protein 1 mutation. Currently, the most widely used first-line treatment options for this malignancy are resection, radiation therapy, and enucleation. There are two main types of radiation therapy: plaque brachytherapy (iodine-125, ruthenium-106, or palladium-103, or cobalt-60) and teletherapy (proton beam, helium ion, or stereotactic radiosurgery using cyber knife, gamma knife, or linear accelerator). The alternative to radiation is enucleation. Although these therapies achieve satisfactory local disease control, long-term survival rate for patients with uveal melanoma remains guarded, with risk for liver metastasis. There have been advances in early diagnosis over the past few years, and with the hope survival rates could improve as smaller tumors are treated. As in many other cancer indications, both early detection and early treatment could be critical for a positive long-term survival outcome in uveal melanoma. These observations call attention to an unmet medical need for the early treatment of small melanocytic lesions or small melanomas in the eye to achieve local disease control and vision preservation with the possibility to prevent metastases and improve overall patient survival.

\"Looks at the life and work of San Francisco, California, native Armin Hansen (1886-1957), an early twentieth-century painter and etcher. Includes approximately 170 illustrations and 25 photographs\"-- Provided by publisher.

Genetically-encoded calcium indicators (GECIs) facilitate imaging activity of genetically defined neuronal populations in vivo. The high intracellular GECI concentrations required for in vivo imaging are usually achieved by viral gene transfer using adeno-associated viruses. Transgenic expression of GECIs promises important advantages, including homogeneous, repeatable, and stable expression without the need for invasive virus injections. Here we present the generation and characterization of transgenic mice expressing the GECIs GCaMP6s or GCaMP6f under the Thy1 promoter. We quantified GCaMP6 expression across brain regions and neurons and compared to other transgenic mice and AAV-mediated expression. We tested three mouse lines for imaging in the visual cortex in vivo and compared their performance to mice injected with AAV expressing GCaMP6. Furthermore, we show that GCaMP6 Thy1 transgenic mice are useful for long-term, high-sensitivity imaging in behaving mice.

The conventional wisdom is that certain classes of bioactive peptides have specific structural features that endow their particular functions. Accordingly, predictions of bioactivity have focused on particular subgroups, such as antimicrobial peptides. We hypothesized that bioactive peptides may share more general features, and assessed this by contrasting the predictive power of existing antimicrobial predictors as well as a novel general predictor, PeptideRanker, across different classes of peptides.We observed that existing antimicrobial predictors had reasonable predictive power to identify peptides of certain other classes i.e. toxin and venom peptides. We trained two general predictors of peptide bioactivity, one focused on short peptides (4-20 amino acids) and one focused on long peptides (> 20 amino acids). These general predictors had performance that was typically as good as, or better than, that of specific predictors. We noted some striking differences in the features of short peptide and long peptide predictions, in particular, high scoring short peptides favour phenylalanine. This is consistent with the hypothesis that short and long peptides have different functional constraints, perhaps reflecting the difficulty for typical short peptides in supporting independent tertiary structure.We conclude that there are general shared features of bioactive peptides across different functional classes, indicating that computational prediction may accelerate the discovery of novel bioactive peptides and aid in the improved design of existing peptides, across many functional classes. An implementation of the predictive method, PeptideRanker, may be used to identify among a set of peptides those that may be more likely to be bioactive.

Active particles, which locally dissipate energy from their environment to function, are useful across disciplines given their dynamic and programmable behaviors. Altering particle shape or surface asymmetry has led to advancements in controlled locomotion or collective behavior for diverse applications such as microrobotics or biomedicine. However, making arbitrary active particles of precise shape and surface composition remains a significant challenge due to limitations in conventional fabrication methods. This paper introduces a fabrication technique that combines two-photon lithography with sacrificial stencil masking to deposit arbitrary metallic patches onto particles of any shape with a limit of resolution as low as 0.2 µm. Using this method, we demonstrate three varieties of active particles displaying nonconventional dynamics: electrokinetic active spheres with tunable three-dimensional motions, catalytic microdiscs with chiral axial spinning, and steric magnetic particles forming self-limiting microrobots. Overall, this high-resolution microstenciling technique offers a versatile strategy to create well-defined active particles and microrobots for numerous practical uses. Active particles are useful for microscale functions, but they lack the necessary complexity to be suitable for wide application. Here, the authors present a fabrication method to create patchy active particles of arbitrary shape by microstenciling.

Cell‐based therapies comprising the administration of living cells to patients for direct therapeutic activities have experienced remarkable success in the clinic, of which macrophages hold great potential for targeted drug delivery due to their inherent chemotactic mobility and homing ability to tumors with high efficiency. However, such targeted delivery of drugs through cellular systems remains a significant challenge due to the complexity of balancing high drug‐loading with high accumulations in solid tumors. Herein, a tumor‐targeting cellular drug delivery system (MAGN) by surface engineering of tumor‐homing macrophages (Mφs) with biologically responsive nanosponges is reported. The pores of the nanosponges are blocked with iron‐tannic acid complexes that serve as gatekeepers by holding encapsulated drugs until reaching the acidic tumor microenvironment. Molecular dynamics simulations and interfacial force studies are performed to provide mechanistic insights into the “ON‐OFF” gating effect of the polyphenol‐based supramolecular gatekeepers on the nanosponge channels. The cellular chemotaxis of the Mφ carriers enabled efficient tumor‐targeted delivery of drugs and systemic suppression of tumor burden and lung metastases in vivo. The findings suggest that the MAGN platform offers a versatile strategy to efficiently load therapeutic drugs to treat advanced metastatic cancers with a high loading capacity of various therapeutic drugs. A tumor‐targeting cellular drug delivery system is developed by surface‐engineering macrophages with biologically responsive nanosponges gated by polyphenol‐based supramolecular “gatekeepers”. The nanosponges enables a high‐loading content of drugs, robust attachment to cellular surfaces, and drug‐controlled release in an acidic tumor microenvironment, which results in the efficient tumor‐targeting delivery of chemotherapeutic drugs and the systemic suppression of tumors in vivo.

Legume seed protein is an important source of nutrition, but generally it is less digestible than animal protein. Poor protein digestibility in legume seeds and seedlings may partly reflect defenses against herbivores. Protein changes during germination typically increase proteolysis and digestibility, by lowering the levels of anti-nutrient protease inhibitors, activating proteases, and breaking down storage proteins (including allergens). Germinating legume sprouts also show striking increases in free amino acids (especially asparagine), but their roles in host defense or other processes are not known. While the net effect of germination is generally to increase the digestibility of legume seed proteins, the extent of improvement in digestibility is species- and strain-dependent. Further research is needed to highlight which changes contribute most to improved digestibility of sprouted seeds. Such knowledge could guide the selection of varieties that are more digestible and also guide the development of food preparations that are more digestible, potentially combining germination with other factors altering digestibility, such as heating and fermentation. Techniques to characterize the shifts in protein make-up, activity and degradation during germination need to draw on traditional analytical approaches, complemented by proteomic and peptidomic analysis of mass spectrometry-identified peptide breakdown products.

Background Acoustophoresis has been utilized successfully in applications including cell trapping, focusing, and purification. One current limitation of acoustophoresis for cell sorting is the reliance on the inherent physical properties of cells (e.g., compressibility, density) instead of selecting cells based upon biologically relevant surface-presenting antigens. Introducing an acoustophoretic cell sorting approach that allows biochemical specificity may overcome this limitation, thus advancing the value of acoustophoresis approaches for both the basic research and clinical fields. Results The results presented herein demonstrate the ability for negative acoustic contrast particles (NACPs) to specifically capture and transport positive acoustic contrast particles (PACPs) to the antinode of an ultrasound standing wave. Emulsification and post curing of pre-polymers, either polydimethylsiloxane (PDMS) or polyvinylmethylsiloxane (PVMS), within aqueous surfactant solution results in the formation of stable NACPs that focus onto pressure antinodes. We used either photochemical reactions with biotin-tetrafluorophenyl azide (biotin-TFPA) or end-functionalization of Pluronic F108 surfactant to biofunctionalize NACPs. These biotinylated NACPs bind specifically to streptavidin polystyrene microparticles (as cell surrogates) and transport them to the pressure antinode within an acoustofluidic chip. Conclusion To the best of our knowledge, this is the first demonstration of using NACPs as carriers for transport of PACPs in an ultrasound standing wave. By using different silicones (i.e., PDMS, PVMS) and curing chemistries, we demonstrate versatility of silicone materials for NACPs and advance the understanding of useful approaches for preparing NACPs. This bioseparation scheme holds potential for applications requiring rapid, continuous separations such as sorting and analysis of cells and biomolecules.

Clarifying gene expression in narrowly defined neuronal populations can provide insight into cellular identity, computation, and functionality. Here, we used next-generation RNA sequencing (RNA-seq) to produce a quantitative, whole genome characterization of gene expression for the major excitatory neuronal classes of the hippocampus; namely, granule cells and mossy cells of the dentate gyrus, and pyramidal cells of areas CA3, CA2, and CA1. Moreover, for the canonical cell classes of the trisynaptic loop, we profiled transcriptomes at both dorsal and ventral poles, producing a cell-class- and region-specific transcriptional description for these populations. This dataset clarifies the transcriptional properties and identities of lesser-known cell classes, and moreover reveals unexpected variation in the trisynaptic loop across the dorsal-ventral axis. We have created a public resource, Hipposeq (http://hipposeq.janelia.org), which provides analysis and visualization of these data and will act as a roadmap relating molecules to cells, circuits, and computation in the hippocampus. Both mouse and human brains are made up of many millions of cells called neurons that are interconnected to form circuits. These neurons are not all the same, because different classes of neurons express different complements of genes. Neurons that express similar genes tend to look and act alike, whereas neurons that express different genes tend to be dissimilar. Cembrowski et al. have used a technique called next-generation RNA sequencing (RNA-seq) to determine which genes are expressed in groups of neurons that represent the main cell types found in a part of the brain called the hippocampus. This brain region is important for memory, and was chosen because the location and appearance of the main cell types in the hippocampus were already well understood. The approach revealed that the main types of neurons in the mouse hippocampus are all very different from each other in terms of gene expression, and that even neurons of the same type can exhibit large differences across the hippocampus. Cembrowski et al. created a website that will allow other researchers to easily navigate, analyze, and visualize gene expression data in these populations of neurons. Future work could next make use of recent technological advances to analyze gene expression in individual neurons, rather than groups of cells, to provide an even more detailed picture. It is also hoped that understanding the differences in gene expression will guide examination of how the hippocampus contributes to memory and what goes wrong in diseases that affect this region of the brain.