Rapamycin perfluorocarbon nanoparticle mitigates cisplatin-induced acute kidney injury

For nearly five decades, cisplatin has played an important role as a standard chemotherapeutic agent and been prescribed to 10-20% of all cancer patients. Although nephrotoxicity associated with platinum-based agents is well recognized, treatment of cisplatin-induced acute kidney injury is mainly supportive and no specific mechanism-based prophylactic approach is available to date. Here, we postulated that systemically delivered rapamycin perfluorocarbon nanoparticles (PFC NP) could reach the injured kidneys at sufficient and sustained concentrations to mitigate cisplatin-induced acute kidney injury and preserve renal function. Using fluorescence microscopic imaging and fluorine magnetic resonance imaging/spectroscopy, we illustrated that rapamycin-loaded PFC NP permeated and were retained in injured kidneys. Histologic evaluation and blood urea nitrogen (BUN) confirmed that renal structure and function were preserved 48 h after cisplatin injury. Similarly, weight loss was slowed down. Using western blotting and immunofluorescence staining, mechanistic studies revealed that rapamycin PFC NP significantly enhanced autophagy in the kidney, reduced the expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), as well as decreased the expression of the apoptotic protein Bax, all of which contributed to the suppression of apoptosis that was confirmed with TUNEL staining. In summary, the delivery of an approved agent such as rapamycin in a PFC NP format enhances local delivery and offers a novel mechanism-based prophylactic therapy for cisplatin-induced acute kidney injury

Cutaneous Papilloma and Squamous Cell Carcinoma Therapy Utilizing Nanosecond Pulsed Electric Fields (nsPEF)

10.1371/journal.pone.0043891PLoS ONE78

Variation in Sphingomonas traits across habitats and phylogenetic clades

Whether microbes show habitat preferences is a fundamental question in microbial ecology. If different microbial lineages have distinct traits, those lineages may occur more frequently in habitats where their traits are advantageous. Sphingomonas is an ideal bacterial clade in which to investigate how habitat preference relates to traits because these bacteria inhabit diverse environments and hosts. Here we downloaded 440 publicly available Sphingomonas genomes, assigned them to habitats based on isolation source, and examined their phylogenetic relationships. We sought to address whether: (1) there is a relationship between Sphingomonas habitat and phylogeny, and (2) whether there is a phylogenetic correlation between key, genome-based traits and habitat preference. We hypothesized that Sphingomonas strains from similar habitats would cluster together in phylogenetic clades, and key traits that improve fitness in specific environments should correlate with habitat. Genome-based traits were categorized into the Y-A-S trait-based framework for high growth yield, resource acquisition, and stress tolerance. We selected 252 high quality genomes and constructed a phylogenetic tree with 12 well-defined clades based on an alignment of 404 core genes. Sphingomonas strains from the same habitat clustered together within the same clades, and strains within clades shared similar clusters of accessory genes. Additionally, key genome-based trait frequencies varied across habitats. We conclude that Sphingomonas gene content reflects habitat preference. This knowledge of how environment and host relate to phylogeny may also help with future functional predictions about Sphingomonas and facilitate applications in bioremediation

Digital Fabrication and Its Meanings for Photography and Film

Bazin, Cavell and other prominent theorists have asserted that movies are essentially photographic, with more recent scholars such as Carroll and Gaut protesting. Today CGI stands as a further counter, in addition to past objections such as editing, animation and blue screen. Also central in debates is whether photography is transparent, that is, whether it allows us to see things in other times and places. I maintain photography is transparent, notwithstanding objections citing digital manipulation. However, taking a cue from Cavell—albeit one poorly outlined in his work—I argue this is not so much because of what photography physically is, but because of what “photography” has come to mean. I similarly argue digital technologies have not significantly altered what cinematic media “are” because they have not fundamentally modified what they mean; and that cinema retains a photographic legacy, even when it abandons photographic technologies to digitally manufacture virtual worlds

Radio Astronomy

Contains reports on five research projects.National Aeronautics and Space Administration (Grant NsG-419)National Aeronautics and Space Administration (Contract NSR-22-009-120)Lincoln Laboratory Purchase Order No. 74

Silly Questions and Arguments for the Implicit, Cinematic Narrator

My chapter aims to advance the debate on a problem often raised by philosophers who are skeptical of implied narrators in movies. This is the concern that positing such elusive narrators gives rise to absurd imaginings (Gaut 2004: 242; Carroll 2006: 179-180). Friends of the implied cinematic narrator reply that the questions critics raise about the workings of the implied cinematic narrator are "silly ones" to ask. I examine how the "absurd imaginings" problem arises for all the central arguments for the elusive cinematic narrator and discuss why the questions critics pose about this narrator are legitimate ones to ask

Radio Astronomy

Contains research objectives and reports on six research projects.National Aeronautics and Space Administration (Contract NSR-22-009-120)National Aeronautics and Space Administration (Grant NsG-419)Joint Services Electronics Programs (U. S. Army, U.S. Navy, and U.S. Air Force) under Contract DA 36-039-AMC-03200(E

Genetic analysis of a major international collection of cultivated apple varieties reveals previously unknown historic heteroploid and inbred relationships

Domesticated apple (Malus x domestica Borkh.) is a major global crop and the genetic diversity held within the pool of cultivated varieties is important for the development of future cultivars. The aim of this study was to investigate the diversity held within the domesticated form, through the analysis of a major international germplasm collection of cultivated varieties, the UK National Fruit Collection, consisting of over 2,000 selections of named cultivars and seedling varieties. We utilised Diversity Array Technology (DArT) markers to assess the genetic diversity within the collection. Clustering attempts, using the software STRUCTURE revealed that the accessions formed a complex and historically admixed group for which clear clustering was challenging. Comparison of accessions using the Jaccard similarity coefficient allowed us to identify clonal and duplicate material as well as revealing pairs and groups that appeared more closely related than a standard parent-offspring or full-sibling relations. From further investigation, we were able to propose a number of new pedigrees, which revealed that some historically important cultivars were more closely related than previously documented and that some of them were partially inbred. We were also able to elucidate a number of parent-offspring relationships that had resulted in a number of important polyploid cultivars. This included reuniting polyploid cultivars that in some cases dated as far back as the 18th century, with diploid parents that potentially date back as far as the 13th century