Neutron reflectometry studies of Gd/Nb and Cu30Ni70/Nb superlattices

We performed a comparative study of magnetic proximity effects in [Gd(5nm)/Nb(25nm)]12 and [Cu30Ni70(6nm)/Nb(27nm)]12 superlattices of S/F type by means of transport measurements and neutron scattering. Transport measurements have shown that Gd/Nb and CuNi/Nb superlattices shows 3D and 2D type of superconductivity respectively. In the case of proximity coupled Gd/Nb superconductor the effective thickness of the superconducting region, 300nm is enough to expel significant amount of applied magnetic field which was detected by neutron scattering. In decoupled CuNi/Nb superlattice thickness of every superconducting layer is only 27nm which is not enough to expel applied magnetic field. Our study shows how neutron reflectometry can be applied to study proximity coupling in superconducting/ferromagnet heterostructures

The Extracellular Domain of Myelin Oligodendrocyte Glycoprotein Elicits Atypical Experimental Autoimmune Encephalomyelitis in Rat and Species

Atypical models of experimental autoimmune encephalomyelitis (EAE) are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (MS). Conversely, models of classical EAE feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of MS. The study of atypical EAE however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient in gamma-interferon signaling pathways. In this study, atypical EAE was induced in Lewis rats, and a related approach was effective for induction of an unusual neurologic syndrome in a cynomolgus macaque. Lewis rats were immunized with the rat immunoglobulin variable (IgV)-related extracellular domain of myelin oligodendrocyte glycoprotein (IgV-MOG) in complete Freund’s adjuvant (CFA) followed by one or more injections of rat IgV-MOG in incomplete Freund’s adjuvant (IFA). The resulting disease was marked by torticollis, unilateral rigid paralysis, forelimb weakness, and high titers of anti-MOG antibody against conformational epitopes of MOG, as well as other signs of atypical EAE. A similar strategy elicited a distinct atypical form of EAE in a cynomolgus macaque. By day 36 in the monkey, titers of IgG against conformational epitopes of extracellular MOG were evident, and on day 201, the macaque had an abrupt onset of an unusual form of EAE that included a pronounced arousal-dependent, transient myotonia. The disease persisted for 6–7 weeks and was marked by a gradual, consistent improvement and an eventual full recovery without recurrence. These data indicate that one or more boosters of IgV-MOG in IFA represent a key variable for induction of atypical or unusual forms of EAE in rat and Macaca species. These studies also reveal a close correlation between humoral immunity against conformational epitopes of MOG, extended confluent demyelinating plaques in spinal cord and brainstem, and atypical disease induction

Identification of Novel Functional Inhibitors of Acid Sphingomyelinase

We describe a hitherto unknown feature for 27 small drug-like molecules, namely functional inhibition of acid sphingomyelinase (ASM). These entities named FIASMAs (Functional Inhibitors of Acid SphingoMyelinAse), therefore, can be potentially used to treat diseases associated with enhanced activity of ASM, such as Alzheimer's disease, major depression, radiation- and chemotherapy-induced apoptosis and endotoxic shock syndrome. Residual activity of ASM measured in the presence of 10 µM drug concentration shows a bimodal distribution; thus the tested drugs can be classified into two groups with lower and higher inhibitory activity. All FIASMAs share distinct physicochemical properties in showing lipophilic and weakly basic properties. Hierarchical clustering of Tanimoto coefficients revealed that FIASMAs occur among drugs of various chemical scaffolds. Moreover, FIASMAs more frequently violate Lipinski's Rule-of-Five than compounds without effect on ASM. Inhibition of ASM appears to be associated with good permeability across the blood-brain barrier. In the present investigation, we developed a novel structure-property-activity relationship by using a random forest-based binary classification learner. Virtual screening revealed that only six out of 768 (0.78%) compounds of natural products functionally inhibit ASM, whereas this inhibitory activity occurs in 135 out of 2028 (6.66%) drugs licensed for medical use in humans

Application of a model for supporting risk assessment of emerging contaminant in the context of wastewater reuse for irrigation

About 17% of the European territories suffer from water scarcity. The situation is expected to worsen over the next years, with potentially severe socio-economic implications. Recently, EU member states agreed that agricultural reuse of reclaimed urban wastewater should be enhanced whenever this is safe, leading to the proposal of minimum requirements for safe reuse [1]. The proposal also recognized the need of including in the risk assessment (where relevant) contaminants of emerging concern, whose threat for environment and human health is well recognized. Given the general lack of measurements and the challenges inherent to field monitoring, integrated chemical fate models represent valuable tools to (i) predict exposure concentrations (for assessing the current risk) and (ii) to evaluate alternative scenarios (i.e. identify risk minimization strategies). However, these models are usually applied within the boundaries of urban areas or for hypothetical wastewater reuse scenarios [2], lacking significant validation for real cases. In this study, an integrated dynamic model was developed and tested for a highly urbanized area in northern Italy, where treated municipal wastewater is discharged into an irrigation canal. Calibration and validation were performed at different locations and risk indicators were calculated to assess environmental and human health safety associated to the exposure to several emerging contaminants

Observations of Glaucous-winged Gulls preying on passerines at a Pacific Northwest colony

Breeding within a seabird colony can have positive and negative effects for smaller passerine species. For example, they may profit from the anti-predator behavior of the seabirds as well as from the influx of food and nutrients brought into the community. However, these possible benefits might be offset by seabird predation. For instance, gulls are not only fierce defenders of their colony, but also opportunistic feeders. Here, we report predation of Glaucous-winged Gulls (Larus glaucescens) on Sooty Fox Sparrows (Passerella iliaca fuliginosa), Song Sparrows (Melospiza melodia), and a European Starling (Sturnus vulgaris), observed on Mandarte Island, British Columbia, Canada. These observations provide new evidence for dietary supplements of Glaucous-winged Gulls and for a disadvantage of passerine life in a Glaucous-winged Gull colony

An automated platform for high-throughput mouse behavior and physiology with voluntary head-fixation

Transgenic approaches and improvements in functional imaging have necessitated an advance in the behavioral toolkit. Here the authors describe an automated high-throughput voluntary head fixation system for training mice on complex psychophysical decision tasks compatible with concurrent two-photon microscopy