Real-time tracking of delayed-onset cellular apoptosis induced by intracellular magnetic hyperthermia

AIM: To assess cell death pathways in response to magnetic hyperthermia. MATERIALS & METHODS: Human melanoma cells were loaded with citric acid-coated iron-oxide nanoparticles, and subjected to a time-varying magnetic field. Pathways were monitored in vitro in suspensions and in situ in monolayers using fluorophores to report on early-stage apoptosis and late-stage apoptosis and/or necrosis. RESULTS: Delayed-onset effects were observed, with a rate and extent proportional to the thermal-load-per-cell. At moderate loads, membranal internal-to-external lipid exchange preceded rupture and death by a few hours (the timeline varying cell-to-cell), without any measurable change in the local environment temperature. CONCLUSION: Our observations support the proposition that intracellular heating may be a viable, controllable and nonaggressive in vivo treatment for human pathological conditions

Elucidating the morphological and structural evolution of iron oxide nanoparticles formed by sodium carbonate in aqueous medium

Ferrimagnetic iron oxides are the common choice for many current technologies, especially those with application in biology and medicine. Despite the comprehensive knowledge accumulated about their chemistry in the bulk state, the sequence of changes taking place during the precipitation of iron oxide nanoparticles in aqueous media is much less extensive. We show that using sodium carbonate as a co-precipitating agent for the synthesis of uncoated iron oxide nanoparticles, the reaction proceeds sufficiently slowly to enable a detailed study of both the reaction pathway and products. The effect of pH, temperature and reaction time on particle size, morphology, crystalline phase and its magnetic properties was investigated. The obtained nanoparticles showed an increase in average particle size of about 10 nm per pH unit for the magnetite phase leading to 6.9 ± 0.4 nm, 18 ± 3 nm and 28 ± 5 nm for pH 8, 9 and 10 respectively. Goethite was initially formed by an olation mechanism at room temperature, followed by a slow transformation into magnetite over a 24 h period, as tracked by X-ray diffraction. In another set of experiments where the reaction temperatures were varied, magnetite was obtained directly by the oxolation mechanism at temperatures above 45 °C. The optimization of the experimental parameters led to superparamagnetic nanoparticles with a high saturation magnetization of 82 A m2 kg−1 at 300 K when synthesized at pH 9

Climate Effects and Feedback Structure Determining Weed Population Dynamics in a Long-Term Experiment

Pest control is one of the areas in which population dynamic theory has been successfully applied to solve practical problems. However, the links between population dynamic theory and model construction have been less emphasized in the management and control of weed populations. Most management models of weed population dynamics have emphasized the role of the endogenous process, but the role of exogenous variables such as climate have been ignored in the study of weed populations and their management. Here, we use long-term data (22 years) on two annual weed species from a locality in Central Spain to determine the importance of endogenous and exogenous processes (local and large-scale climate factors). Our modeling study determined two different feedback structures and climate effects in the two weed species analyzed. While Descurainia sophia exhibited a second-order feedback and low climate influence, Veronica hederifolia was characterized by a first-order feedback structure and important effects from temperature and rainfall. Our results strongly suggest the importance of theoretical population dynamics in understanding plant population systems. Moreover, the use of this approach, discerning between the effect of exogenous and endogenous factors, can be fundamental to applying weed management practices in agricultural systems and to controlling invasive weedy species. This is a radical change from most approaches currently used to guide weed and invasive weedy species managements

Early decelerations of the fetal heart rate from occlusion of the umbilical cord

Peer Reviewe

High performance multi-core iron oxide nanoparticles for magnetic hyperthermia: microwave synthesis, and the role of core-to-core interactions

The adoption of magnetic hyperthermia as either a stand-alone or adjunct therapy for cancer is still far from being optimised due to the variable performance found in many iron oxide nanoparticle systems, including commercially available formulations. Herein, we present a reproducible and potentially scalable microwave-based method to make stable citric acid coated multi-core iron oxide nanoparticles, with exceptional magnetic heating parameters, viz. intrinsic loss parameters (ILPs) of up to 4.1 nH m(2) kg(-1), 35% better than the best commercial equivalents. We also probe the core-to-core magnetic interactions in the particles via remanence-derived Henkel and ΔM plots. These reveal a monotonic dependence of the ILP on the magnetic interaction field Hint, and show that the interactions are demagnetising in nature, and act to hinder the magnetic heating mechanism

2,3,9- and 2,3,11-Trisubstituted tetrahydroprotoberberines as D2 dopaminergic ligands

Dopamine-mediated neurotransmission plays an important role in relevant psychiatric and neurological disorders. Nowadays, there is an enormous interest in the development of new dopamine receptors (DR) acting drugs as potential new targets for the treatment of schizophrenia or Parkinson's disease. Previous studies have revealed that isoquinoline compounds such as tetrahydroisoquinolines (THIQs) and tetrahydroprotoberberines (THPBs) can behave as selective D2 dopaminergic alkaloids since they share structural similarities with dopamine. In the present study we have synthesized eleven 2,3,9- and 2,3,11-trisubstituted THPB compounds (six of them are described for the first time) and evaluated their potential dopaminergic activity. Binding studies on rat striatal membranes were used to evaluate their affinity and selectivity towards D1 and D2 DR and establish the structure-activity relationship (SAR) as dopaminergic agents. In general, all the tested THPBs with protected phenolic hydroxyls showed a lower affinity for D1 and D2 DR than their corresponding homologues with free hydroxyl groups. In previous studies in which dopaminergic affinity of 1-benzyl-THIQs (BTHIQs) was evaluated, the presence of a Cl into the A-ring resulted in increased affinity and selectivity towards D2 DR. This is in contrast with the current study since the existence of a chlorine atom into the A-ring of the THPBs caused increased affinity for D1 DR but dramatically reduced the selectivity for D2 DR. An OH group in position 9 of the THPB (9f) resulted in a higher affinity for DR than its homologue with an OH group in position 11 (9e) (250 fold for D2 DR). None of the compounds showed any cytotoxicity in freshly isolated human neutrophils. A molecular modelling study of three representative THPBs was carried out. The combination of MD simulations with DFT calculations provided a clear picture of the ligand binding interactions from a structural and energetic point of view. Therefore, it is likely that compound 9d (2,3,9-trihydroxy-THPB) behave as D2 DR agonist since serine residues cluster are crucial for agonist binding and receptor activation

Site‐specific weed management—constraints and opportunities for the weed research community: Insights from a workshop

The adoption of site‐specific weed management (SSWM) technologies by farmers is not aligned with the scientific achievements in this field. While scientists have demonstrated significant success in real‐time weed identification, phenotyping and accurate weed mapping by using various sensors and platforms, the integration by farmers of SSWM and weed phenotyping tools into weed management protocols is limited. This gap was therefore a central topic of discussion at the most recent workshop of the SSWM Working Group arranged by the European Weed Research Society (EWRS). This insight paper aims to summarise the presentations and discussions of some of the workshop panels and to highlight different aspects of weed identification and spray application that were thought to hinder SSWM adoption. It also aims to share views and thoughts regarding steps that can be taken to facilitate future implementation of SSWM