Upscaling methane fluxes from peatlands across a drainage gradient in Ireland using PlanetScope imagery and machine learning tools.

Wetlands are one of the major contributors of methane (CH4) emissions to the atmosphere and the intensity of emissions is driven by local environmental variables and spatial heterogeneity. Peatlands are a major wetland class and there are numerous studies that provide estimates of methane emissions at chamber or eddy covariance scales, but these are not often aggregated to the site/ecosystem scale. This study provides a robust approach to map dominant vegetation communities and to use these areas to upscale methane fluxes from chamber to site scale using a simple weighted-area approach. The proposed methodology was tested at three peatlands in Ireland over a duration of 2 years. The annual vegetation maps showed an accuracy ranging from 83 to 99% for near-natural to degraded sites respectively. The upscaled fluxes were highest (2.25 and 3.80 gC m-2 y-1) at the near-natural site and the rehabilitation (0.17 and 0.31 gC m-2 y-1), degraded (0.15 and 0.27 gC m-2 y-1) site emissions were close to net-zero throughout the study duration. Overall, the easy to implement methodology proposed in this study can be applied across various landuse types to assess the impact of peatland rehabilitation on methane emissions by mapping ecological change.

Herceptin-directed nanoparticles activated by an alternating magnetic field selectively kill HER-2 positive human breast cells in vitro via hyperthermia.

PURPOSE: HER-2 is in the EGF tyrosine kinase receptor family, overexpressed by many human cancers and minimally expressed by normal adult tissues. HER-2 expression in human cancers is correlated with reduced survival, increased metastasis, reduced apoptosis and increased proliferation. Herceptin is a humanised mouse antibody that targets and inactivates HER-2. In the present study, Herceptin was used to deliver ferric oxide-enriched nanoparticles to HER-2(+) cancer cells. If exposed to alternating magnetic field (AMF), the nanoparticles heat. We tested the ability of AMF-activated Herceptin-directed nanoparticles to selectively kill HER-2(+) human cancer cells. METHODS: Herceptin-conjugated nanoparticles were incubated with normal human mammary epithelial cells (HMEC)(HER-2(-)) or malignant human mammary epithelial cells (SK-BR-3)(HER-2(+)). Cells were stained to detect Herceptin or iron and the kinetics of binding quantified. Once conditions were optimised for binding, cells were exposed to either antibody-directed or non-antibody-conjugated nanoparticles, washed and sham-treated or exposed to AMF and cell death quantified. RESULTS: SK-BR-3 cells bound Herceptin-directed nanoparticles in increasing amounts over 3 h but did not retain non-antibody conjugated nanoparticles. HMECs did not retain either nanoparticles. SK-BR-3 cells with bound Herceptin-directed-nanoparticles, exposed to AMF, died by apoptosis, quantifiable by Live/Dead and nuclear morphology assays and released LDH. Sham-treated SK-BR-3 cells with Herceptin-directed nanoparticles, HMECs with either nanoparticles, with or without AMF treatment, exhibited no increase in toxicity above baseline cell death using these three assays. CONCLUSIONS: These studies demonstrate Herceptin-directed nanoparticles can selectively kill HER-2(+) cancer cells via hyperthermia after AMF activation.

Challenges in the development of magnetic particles for therapeutic applications.

Certain iron-based particle formulations have useful magnetic properties that, when combined with low toxicity and desirable pharmacokinetics, encourage their development for therapeutic applications. This mini-review begins with background information on magnetic particle use as MRI contrast agents and the influence of material size on pharmacokinetics and tissue penetration. Therapeutic investigations, including (1) the loading of bioactive materials, (2) the use of stationary, high-gradient (HG) magnetic fields to concentrate magnetic particles in tissues or to separate material bound to the particles from the body, and (3) the application of high power alternating magnetic fields (AMF) to generate heat in magnetic particles for hyperthermic therapeutic applications are then surveyed. Attention is directed mainly to cancer treatment, as selective distribution to tumors is well-suited to particulate approaches and has been a focus of most development efforts. While magnetic particles have been explored for several decades, their use in therapeutic products remains minimal; a discussion of future directions and potential ways to better leverage magnetic properties and to integrate their use into therapeutic regimens is discussed.

Male Circumcision and the Epidemic Emergence of HIV-2 in West Africa.

BACKGROUND: Epidemic HIV-2 (groups A and B) emerged in humans circa 1930-40. Its closest ancestors are SIVsmm infecting sooty mangabeys from southwestern Côte d'Ivoire. The earliest large-scale serological surveys of HIV-2 in West Africa (1985-91) show a patchy spread. Côte d'Ivoire and Guinea-Bissau had the highest prevalence rates by then, and phylogeographical analysis suggests they were the earliest epicenters. Wars and parenteral transmission have been hypothesized to have promoted HIV-2 spread. Male circumcision (MC) is known to correlate negatively with HIV-1 prevalence in Africa, but studies examining this issue for HIV-2 are lacking. METHODS: We reviewed published HIV-2 serosurveys for 30 cities of all West African countries and obtained credible estimates of real prevalence through Bayesian estimation. We estimated past MC rates of 218 West African ethnic groups, based on ethnographic literature and fieldwork. We collected demographic tables specifying the ethnic partition in cities. Uncertainty was incorporated by defining plausible ranges of parameters (e.g. timing of introduction, proportion circumcised). We generated 1,000 sets of past MC rates per city using Latin Hypercube Sampling with different parameter combinations, and explored the correlation between HIV-2 prevalence and estimated MC rate (both logit-transformed) in the 1,000 replicates. RESULTS AND CONCLUSIONS: Our survey reveals that, in the early 20th century, MC was far less common and geographically more variable than nowadays. HIV-2 prevalence in 1985-91 and MC rates in 1950 were negatively correlated (Spearman rho = -0.546, IQR: -0.553--0.546, p≤0.0021). Guinea-Bissau and Côte d'Ivoire cities had markedly lower MC rates. In addition, MC was uncommon in rural southwestern Côte d'Ivoire in 1930.The differential HIV-2 spread in West Africa correlates with different historical MC rates. We suggest HIV-2 only formed early substantial foci in cities with substantial uncircumcised populations. Lack of MC in rural areas exposed to bushmeat may have had a role in successful HIV-2 emergence.

Pharmacokinetics and biodistribution of RGD-targeted doxorubicin-loaded nanoparticles in tumor-bearing mice.

We report the biodistribution and pharmacokinetics (PK) of a cyclic RGD-doxorubicin-nanoparticle (NP) formulation in tumor-bearing mice. The NP core was composed of inulin multi-methacrylate with a targeting peptide, cyclic RGD, covalently attached to the NPs via PEG-400. Seventy-two percent of the doxorubicin was attached to the NP matrix via an amide bond; 28% of doxorubicin was entrapped as unconjugated drug. The PK of total, unconjugated and metabolized doxorubicin was examined for 5 days following intravenous (i.v.) administration of the NP formulation (250 microg doxorubicin equiv.), revealing a bi-exponential fix with a terminal half-life of 5.99 h. In addition, the biodistribution studies revealed decreasing drug concentrations over time in the heart, lung, kidney and plasma and accumulating drug concentrations in the liver, spleen and tumor. The drug concentration in these latter tissues peaked between 24 and 48 h with the liver, spleen and tumor containing 56, 3.5 and 1.8% of the administered dose at t=48 h, respectively. In contrast to all of the organs studied, the tumors contained high levels of a doxorubicin metabolite.

Phagocytes mediate targeting of iron oxide nanoparticles to tumors for cancer therapy.

Nanotechnology has great potential to produce novel therapeutic strategies that target malignant cells through the ability of nanoparticles to get access to and be ingested by living cells. However its specificity for accumulation in tumors, which is the key factor that determines its efficacy, has always been a challenge. Here we tested a novel strategy to target and treat ovarian cancer, a representative peritoneal cancer, using iron oxide nanoparticles (IONPs) and an alternating magnetic field (AMF). Peritoneal tumors in general are directly accessible to nanoparticles administered intraperitoneally (IP), as opposed to the more commonly attempted intravenous (IV) administration. In addition, tumor-associated immunosuppressive phagocytes, a predominant cell population in the tumor microenvironment of almost all solid tumors, and cells that are critical for tumor progression, are constantly recruited to the tumor, and therefore could possibly function to bring nanoparticles to tumors. Here we demonstrate that tumor-associated peritoneal phagocytes ingest and carry IONPs specifically to tumors and that these specifically delivered nanoparticles can damage tumor cells after IONP-mediated hyperthermia generated by AMF. This illustrates therapeutic possibilities of intraperitoneal (IP) injection of nanoparticles and subsequent ingestion by tumor-associated phagocytes, to directly impact tumors or stimulate antitumor immune responses. This approach could use IONPs combined with AMF as done here, or other nanoparticles with cytotoxic potential. Overall, the data presented here support IP injection of nanoparticles to utilize peritoneal phagocytes as a delivery vehicle in association with IONP-mediated hyperthermia as therapeutic strategies for ovarian and other peritoneal cancers.