The rockefeller university

Over millions of years, biological systems. have evolved wide varieties of nanoparticles. Naturally occurring nanoparticles show great diversity: they may be intracellular or extracellular, formed of organic or inorganic materials and have wide-ranging biological roles. Despite this diversity, nanoparticles found in nature possess several characteristics that make them attractive for biomedical purposes. This review presents an overview of the most common biological nanoparticles and outlines the potential applications of natural and modified biological nanoparticles.

Environmental Surveyor of Natural Product Diversity (eSNaPD) is a web-based bioinformatics and data aggregation platform that aids in the discovery of gene clusters encoding both novel natural products and new congeners of medicinally relevant natural products using (meta) genomic sequence data. Using PCR-generated sequence tags, the eSNaPD data-analysis pipeline profiles biosynthetic diversity hidden within (meta) genomes by comparing sequence tags to a reference data set of characterized gene clusters. Sample mapping, molecule discovery, library mapping, and new clade visualization modules facilitate the interrogation of large (meta) genomic sequence data sets for diverse downstream analyses, including, but not limited to, the identification of environments rich in untapped biosynthetic diversity, targeted molecule discovery efforts, and chemical ecology studies. eSNaPD is designed to generate a global atlas of biosynthetic diversity that can facilitate a systematic, sequence-based interrogation of nature's biosynthetic potential.

The skin protects mammals from insults, infection and dehydration and enables thermoregulation and sensory perception. Various skin-resident cells carry out these diverse functions. Constant turnover of cells and healing upon injury necessitate multiple reservoirs of stem cells. Thus, the skin provides a model for studying interactions between stem cells and their microenvironnients, or niches. Advances in genetic and imaging tools have brought new findings about the lineage relationships between skin stem cells and their progeny and about the mutual influences between skin stem cells and their niches. Such knowledge may offer novel avenues for therapeutics and regenerative medicine.

T follicular helper (T-FH) cells select high-affinity, antibody-producing B cells for clonal expansion in germinal centers (GCs), but the nature of their interaction is not well defined. Using intravital imaging, we found that selection is mediated by large but transient contacts between T-FH and GC B cells presenting the highest levels of cognate peptide bound to major histocompatibility complex II. These interactions elicited transient and sustained increases in T-FH intracellular free calcium (Ca2+) that were associated with T-FH cell coexpression of the cytokines interleukin-4 and -21. However, increased intracellular Ca2+ did not arrest T-FH cell migration. Instead, T-FH cells remained motile and continually scanned the surface of many GC B cells, forming short-lived contacts that induced selection through further repeated transient elevations in intracellular Ca2+.

Ethnopharmacological relevance: Antrodia cinnamomea - a medicinal fungus that is indigenous to Taiwan - has been used as a health tonic by aboriginal tribes and the Asian population. Recent studies indicate that Antrodia cinnamomea extracts exhibit hepato-protective, anti-hypertensive, anti-oxidative, anti-inflammatory, immuno-modulatory, and anti-cancer effects on cultured cells and laboratory animals. This study aims to explore the anti-inflammatory activity of an Antrodia cinnamomea ethanol extract (ACEE) and elucidate its underlying mechanisms of action using lipopolysaccharide (LPS)-primed, ATP-stimulated human THP-1 macrophages. Materials and methods: The effects of ACEE on cell viability were studied using the MTT assay. The expressions of genes, proteins, and pro-inflammatory cytokines were measured by quantitative real-time RT-PCR, Western blotting and ELISA, respectively. The ACEE was further investigated for its effects on reactive oxygen species (ROS) production using ROS detection kit. Results: Our results showed that ACEE significantly inhibits ATP-induced secretion of interleukin-1 beta (IL-1 beta), interleukin-18 (IL-18) and tumor necrosis factor-alpha (TNF-alpha) by LPS-primed macrophages. ACEE also suppresses the transcription and activation of caspase-1, which is responsible for the cleavage and activation of IL-1 beta and IL-18. Of note, ACEE not only reduces expression of the inflammasome component NLRP3 and the purinergic receptor P2X(7)R but also inhibits ATP-induced ROS production and caspase-1 activation. Furthermore, the anti-inflammatory properties of ACEE correlate with reduced activation of the MAPK and NF-kappa B pathways. Conclusion: The results of the present study indicate that Antrodia cinnamomea suppresses the secretion of IL-1 beta and IL-18 associated with inhibition of the NLRP3 inflammasome in macrophages. These findings suggest that ACEE may have therapeutic potential for the treatment of inflammatory diseases. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Aim This study investigates how founder size may affect local genetic diversity and spatial genetic structure of the invasive American eastern grey squirrel (Sciurus carolinensis) in European areas. It also examines whether dispersal propensity and invasion rate may be related to founder size, genetic diversity and structure. Location Piedmont, Italy; Northern Ireland, Northumberland and East Anglia, UK. Methods Across the invaded range in Europe, 315 squirrels from 14 locations, grouped in four areas, were sampled and examined at 12 highly polymorphic microsatellite loci. We estimated both genetic variation and population structure using AMOVA, Mantel tests and Bayesian analysis. We also estimated migration rates and range expansion rates. Results Genetic diversity varied in accordance with numbers of founders across populations. For instance, the Italian population had the smallest founder size and lowest genetic variability, whereas Northumberland had high values for both. Significant levels of genetic differentiation were observed in all the examined regions. Gene flow, migration and population range expansion rate were also higher in England and Ireland than in Italy. Main conclusions Populations descending from human-mediated releases of few individuals were more genetically depauperate and more differentiated than populations established from a greater number of founders. Propagule pressure is therefore a significant factor in squirrel invasions. There is a trend whereby larger founder sizes were associated with greater genetic diversity, more dispersal, less local genetic differentiation and faster range expansion rate in squirrels. These findings have important management implications for controlling spread rate of squirrels and other invasive species: good practice should prioritize preventing further releases and the merging of genetically distinct populations as these events can augment genetic diversity.

Elucidating the molecular details of how chromatin-associated factors deposit, remove and recognize histone post-translational modification (PTM) signatures remains a daunting task in the epigenetics field. We introduce a versatile platform that greatly accelerates biochemical investigations into chromatin recognition and signaling. This technology is based on the streamlined semisynthesis of DNA-barcoded nucleosome libraries with distinct combinations of PTMs. Chromatin immunoprecipitation of these libraries, once they have been treated with purified chromatin effectors or the combined chromatin recognizing and modifying activities of the nuclear proteome, is followed by multiplexed DNA-barcode sequencing. This ultrasensitive workflow all-owed us to collect thousands of biochemical data points revealing the binding preferences of various nuclear factors for PTM patterns and how preexisting PTMs, alone or synergistically, affect further PTM deposition via cross-talk mechanisms. We anticipate that the high throughput and sensitivity of the technology will help accelerate the decryption of the diverse molecular controls that operate at the level of chromatin.

Latent reservoirs of HIV-1-infected cells are refractory to antiretroviral therapies (ART) and remain the major barrier to curing HIV-1. Because latently infected cells are long-lived, immunologically invisible, and may undergo homeostatic proliferation, a "shock and kill" approach has been proposed to eradicate this reservoir by combining ART with inducers of viral transcription. However, all attempts to alter the HIV-1 reservoir in vivo have failed to date. Using humanized mice, we show that broadly neutralizing antibodies (bNAbs) can interfere with establishment of a silent reservoir by Fc-FcR-mediated mechanisms. In established infection, bNAbs or bNAbs plus single inducers are ineffective in preventing viral rebound. However, bNAbs plus a combination of inducers that act by independent mechanisms synergize to decrease the reservoir as measured by viral rebound. Thus, combinations of inducers and bNAbs constitute a therapeutic strategy that impacts the establishment and maintenance of the HIV-1 reservoir in humanized mice.

A search for new resonances decaying to WW, ZZ, or WZ is presented. Final states are considered in which one of the vector bosons decays leptonically and the other hadronically. Results are based on data corresponding to an integrated luminosity of 19.7 fb(-1) recorded in proton-proton collisions at root s= 8 TeV with the CMS detector at the CERN LHC. Techniques aiming at identifying jet substructures are used to analyze signal events in which the hadronization products from the decay of highly boosted W or Z bosons are contained within a single reconstructed jet. Upper limits on the production of generic WW, ZZ, or WZ resonances are set as a function of the resonance mass and width. We increase the sensitivity of the analysis by statistically combining the results of this search with a complementary study of the all-hadronic final state. Upper limits at 95% confidence level are set on the bulk graviton production cross section in the range from 700 to 10 fb for resonance masses between 600 and 2500 GeV, respectively. These limits on the bulk graviton model are the most stringent to date in the diboson final state.