Determining the Size Dependence of Colloidal Gold Nanoparticle Uptake in a Tumor-like Interface (Hypoxic)

AbstractColloidal gold nanoparticles (GNPs) are being used as drug delivery vehicles and radiation dose enhancers in cancer therapy. Oxygen concentration in human tumours is highly heterogeneous with many regions at very low levels of oxygen (hypoxia). A majority of tumours contain regions with oxygen pressure values of less than 0.7% in the gas phase. The purpose of this study was to investigate how the size of the NPs affects their uptake process in a tumour-like hypoxic environment. We used GNPs of diameter 15, 50, and 74nm, and carried out our experiment under 0.2% (hypoxic) and 21% (normoxic) oxygen levels using MCF-7 and HeLa cells. Our results showed that NPs of size 50nm had the highest uptake following prolonged exposure to hypoxia. There was no significant toxicity introduced by NPs under hypoxic conditions. These findings will play a vital role in the optimization of GNP-based therapeutics in cancer treatment

Vasculotide, an Angiopoietin-1 mimetic, reduces acute skin ionizing radiation damage in a preclinical mouse model

Abstract Background Most cancer patients are treated with radiotherapy, but the treatment can also damage the surrounding normal tissue. Acute skin damage from cancer radiotherapy diminishes patients’ quality of life, yet effective biological interventions for this damage are lacking. Protecting microvascular endothelial cells from irradiation-induced perturbations is emerging as a targeted damage-reduction strategy. Since Angiopoetin-1 signaling through the Tie2 receptor on endothelial cells opposes microvascular perturbations in other disease contexts, we used a preclinical Angiopoietin-1 mimic called Vasculotide to investigate its effect on skin radiation toxicity using a preclinical model. Methods Athymic mice were treated intraperitoneally with saline or Vasculotide and their flank skin was irradiated with a single large dose of ionizing radiation. Acute cutaneous damage and wound healing were evaluated by clinical skin grading, histology and immunostaining. Diffuse reflectance optical spectroscopy, myeloperoxidase-dependent bioluminescence imaging of neutrophils and a serum cytokine array were used to assess inflammation. Microvascular endothelial cell response to radiation was tested with in vitro clonogenic and Matrigel tubule formation assays. Tumour xenograft growth delay experiments were also performed. Appreciable differences between treatment groups were assessed mainly using parametric and non-parametric statistical tests comparing areas under curves, followed by post-hoc comparisons. Results In vivo, different schedules of Vasculotide treatment reduced the size of the irradiation-induced wound. Although skin damage scores remained similar on individual days, Vasculotide administered post irradiation resulted in less skin damage overall. Vasculotide alleviated irradiation-induced inflammation in the form of reduced levels of oxygenated hemoglobin, myeloperoxidase bioluminescence and chemokine MIP-2. Surprisingly, Vasculotide-treated animals also had higher microvascular endothelial cell density in wound granulation tissue. In vitro, Vasculotide enhanced the survival and function of irradiated endothelial cells. Conclusions Vasculotide administration reduces acute skin radiation damage in mice, and may do so by affecting several biological processes. This radiation protection approach may have clinical impact for cancer radiotherapy patients by reducing the severity of their acute skin radiation damage

NanoMi - An Open Source Transmission Electron Microscope

NanoMi is a project towards an open source modular electron microscope. It will allow to assemble transmission electron microscope (TEM) column, scanning TEM (STEM) column or scanning electron microscope (SEM) column. The goal of the NanoMi project is to establish framework for a community development of an electron microscope. Perhaps most important aspect is the license that covers the development: CERN Open Hardware v2, weakly reciprocal for hardware components. https://cern-ohl.web.cern.ch/ and GPL v3 for software (see below

Phylogenomics and the rise of the angiosperms

International audienceAngiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods 1,2 . A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome 3,4 . Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins 5–7 . However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes 8 . This 15-fold increase in genus-level sampling relative to comparable nuclear studies 9 provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade

Phylogenomics and the rise of the angiosperms.

Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods1,2. A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome3,4. Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins5-7. However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes8. This 15-fold increase in genus-level sampling relative to comparable nuclear studies9 provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade