Extrolites of Wallemia sebi, a very common fungus in the built environment.

Wallemia sebi has been primarily known as a spoilage fungus of dried, salted fish and other foods that are salty or sweet. However, this fungus is also very common in house dust. The health effects of chronic exposure to mold and dampness are known to be associated with both allergens and various inflammatory compounds, including the secondary metabolites of building associated fungi and their allergens. IgE sensitization to W. sebi has been long reported from housing and occupational exposures. However, its allergens have not been described previously. Strains from food have been reported to produce a number of compounds with modest toxicity. Strains from the built environment in Canada produced a number of metabolites including the known compound walleminone and a new compound 1-benzylhexahydroimidazo [1,5-α] pyridine-3,5-dione which we call wallimidione. Based on an in silico analysis, wallimidione is likely the most toxic of the metabolites reported to date from W. sebi. We found that the primary human antigen of W. sebi is a 47 kDa excreted cellulase present in high concentrations in W. sebi arthrospores. This species is a basidiomycete and, unsurprisingly, the antigen was not found in extracts of other fungi common in the built environment, all ascomycetes.

Pharmaco-proteomics opportunities for individualizing neurovascular treatment.

Neurovascular disease often involves multi-organ system injury. For example, patent foramen ovale (PFO) related ischemic strokes involve not just the brain, but also the heart, the lung, and the peripheral vascular circulation. For higher-risk but high-reward systemic therapy (e.g., thrombolytics, therapeutic hypothermia (TH), PFO closure) to be implemented safely, very careful patient selection and close monitoring of disease progression and therapeutic efficacy are imperative. For example, more than a decade after the approval of therapeutic hypothermic and intravenous thrombolysis treatments, they both remain extremely under-utilized, in part due to lack of clinical tools for patient selection or to follow therapeutic efficacy. Therefore, in understanding the complexity of the global effects of clinical neurovascular diseases and their therapies, a systemic approach may offer a unique perspective and provide tools with clinical utility. Clinical proteomic approaches may be promising to monitor systemic changes in complex multi-organ diseases - especially where the disease process can be 'sampled' in clinically accessible fluids such as blood, urine, and CSF. Here, we describe a 'pharmaco-proteomic' approach to three major challenges in translational neurovascular research directly at bedside - in order to better stratify risk, widen therapeutic windows, and explore novel targets to be validated at the bench - (i) thrombolytic treatment for ischemic stroke, (ii) therapeutic hypothermia for post-cardiac arrest syndrome, and (iii) treatment for PFO related paradoxical embolic stroke. In the future, this clinical proteomics approach may help to improve patient selection, ensure more precise clinical phenotyping for clinical trials, and individualize patient treatment.

Adaptive response in frogs chronically exposed to low doses of ionizing radiation in the environment.

Using the micronucleus assay, decreased levels of DNA damage were found after high dose ionizing radiation exposure of liver cells taken from frogs inhabiting a natural environment with above-background levels of ionizing radiation, compared to cells taken from frogs inhabiting background areas. The data obtained from a small number of animals suggest that stress present in the above-background environment could induce an adaptive response to ionizing radiation. This study did not reveal harmful effects of exposure to low levels of radioactivity. On the contrary, stress present in the above-background area may serve to enhance cellular defense mechanisms.

Anionic facial amphiphiles from cholic acid.

[structure:see text] Anionic facial amphiphiles have been prepared from cholic acid. These compounds offer antipodes of recently reported cationic amphiphiles derived from cholic acid. The synthesis of the anionic amphiphiles was accomplished in few steps from a common intermediate. In contrast to many other anionic facial amphiphiles, the cholic acid derived amphiphiles appeared to aggregate at relatively low concentration.

Statistical and historical analyses of nations which deviate from the size-density law.

We examine nations which deviate significantly from the -2/3 size-density slope previously observed for the aggregated political subdivisions of 98 modern nations and previously derived from the theory of time-minimization. We correct Stephan's original list of deviant nations, demonstrate that all slopes more negative than -2/3 were due to the erroneous inclusion of cities in the original data sets, develop a theory to account for the less negative deviant slopes, and test the theory both through statistical manipulation of current data and through analysis of available historical data.