Evidence for methane and ammonia in the coma of comet P/Halley

Methane and ammonia abundances in the coma of Halley are derived from Giotto IMS data using an Eulerian model of chemical and physical processes inside the contact surface to simulate Giotto HIS ion mass spectral data for mass-to-charge ratios (m/q) from 15 to 19. The ratio m/q = 19/18 as a function of distance from the nucleus is not reproduced by a model for a pure water coma. It is necessary to include the presence of NH_3 , and uniquely NH_3 , in coma gases in order to explain the data. A ratio of production rates Q(NH_3)/Q(H20) = 0.01-Q.02 results in model values approximating the Giotto data. Methane is identified as the most probable source of the distinct peak at m/q = 15. The observations are fit best with Q(CH_4)/Q(H_20) = 0.02. The chemical composition of the comet nucleus implied by these production rate ratios is unlike that of the outer planets. On the other hand, there are also significant differences from observations of gas phase interstellar material

Small but crucial : the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans

Peer reviewedPublisher PD

Gold Nanoparticle Delivery of Modified CpG Stimulates Macrophages and Inhibits Tumor Growth for Enhanced Immunotherapy

Gold nanoparticle accumulation in immune cells has commonly been viewed as a side effect for cancer therapeutic delivery; however, this phenomenon can be utilized for developing gold nanoparticle mediated immunotherapy. Here, we conjugated a modified CpG oligodeoxynucleotide immune stimulant to gold nanoparticles using a simple and scalable selfassembled monolayer scheme that enhanced the functionality of CpG in vitro and in vivo. Nanoparticles can attenuate systemic side effects by enhancing CpG delivery passively to innate effector cells. The use of a triethylene glycol (TEG) spacer on top of the traditional poly-thymidine spacer increased CpG macrophage stimulatory effects without sacrificing DNA content on the nanoparticle, which directly correlates to particle uptake. In addition, the immune effects of modified CpGAuNPs were altered by the core particle size, with smaller 15 nm AuNPs generating maximum immune response. These TEG modified CpG-AuNP complexes induced macrophage and dendritic cell tumor infiltration, significantly inhibited tumor growth, and promoted survival in mice when compared to treatments with free CpG

Non-PEGylated liposomes for convection-enhanced delivery of topotecan and gadodiamide in malignant glioma: initial experience

Convection-enhanced delivery (CED) of highly stable PEGylated liposomes encapsulating chemotherapeutic drugs has previously been effective against malignant glioma xenografts. We have developed a novel, convectable non-PEGylated liposomal formulation that can be used to encapsulate both the topoisomerase I inhibitor topotecan (topoCED™) and paramagnetic gadodiamide (gadoCED™), providing an ideal basis for real-time monitoring of drug distribution. Tissue retention of topoCED following single CED administration was significantly improved relative to free topotecan. At a dose of 10 μg (0.5 mg/ml), topoCED had a half-life in brain of approximately 1 day and increased the area under the concentration–time curve (AUC) by 28-fold over free topotecan (153.8 vs. 5.5 μg day/g). The combination of topoCED and gadoCED was found to co-convect well in both naïve rat brain and malignant glioma xenografts (correlation coefficients 0.97–0.99). In a U87MG cell assay, the 50% inhibitory concentration (IC50) of topoCED was approximately 0.8 μM at 48 and 72 h; its concentration–time curves were similar to free topotecan and unaffected by gadoCED. In a U87MG intracranial rat xenograft model, a two-dose CED regimen of topoCED co-infused with gadoCED greatly increased median overall survival at dose levels of 0.5 mg/ml (29.5 days) and 1.0 mg/ml (33.0 days) vs. control (20.0 days; P < 0.0001 for both comparisons). TopoCED at higher concentrations (1.6 mg/ml) co-infused with gadoCED showed no evidence of histopathological changes attributable to either agent. The positive results of tissue pharmacokinetics, co-convection, cytotoxicity, efficacy, and lack of toxicity of topoCED in a clinically meaningful dose range, combined with an ideal matched-liposome paramagnetic agent, gadoCED, implicates further clinical applications of this therapy in the treatment of malignant glioma

Diffuse glioma growth: a guerilla war

In contrast to almost all other brain tumors, diffuse gliomas infiltrate extensively in the neuropil. This growth pattern is a major factor in therapeutic failure. Diffuse infiltrative glioma cells show some similarities with guerilla warriors. Histopathologically, the tumor cells tend to invade individually or in small groups in between the dense network of neuronal and glial cell processes. Meanwhile, in large areas of diffuse gliomas the tumor cells abuse pre-existent “supply lines” for oxygen and nutrients rather than constructing their own. Radiological visualization of the invasive front of diffuse gliomas is difficult. Although the knowledge about migration of (tumor)cells is rapidly increasing, the exact molecular mechanisms underlying infiltration of glioma cells in the neuropil have not yet been elucidated. As the efficacy of conventional methods to fight diffuse infiltrative glioma cells is limited, a more targeted (“search & destroy”) tactic may be needed for these tumors. Hopefully, the study of original human glioma tissue and of genotypically and phenotypically relevant glioma models will soon provide information about the Achilles heel of diffuse infiltrative glioma cells that can be used for more effective therapeutic strategies

ICAR: endoscopic skull‐base surgery

n/

Metopic synostosis

Premature closure of the metopic suture results in a growth restriction of the frontal bones, which leads to a skull malformation known as trigonocephaly. Over the course of recent decades, its incidence has been rising, currently making it the second most common type of craniosynostosis. Treatment consists of a cranioplasty, usually preformed before the age of 1 year. Metopic synostosis is linked with an increased level of neurodevelopmental delays. Theories on the etiology of these delays range from a reduced volume of the anterior cranial fossa to intrinsic malformations of the brain. This paper aims to provide an overview of this entity by giving an update on the epidemiology, etiology, evolution of treatment, follow-up, and neurodevelopment of metopic synostosis