Biomarker Genes for Detecting Estrogenic Activity of Endocrine Disruptors via Estrogen Receptors

Endocrine disruptors (EDs) are compounds used in various industrial products, drugs, and cosmetics. They can be found in the environment and disturb the endocrine and reproductive systems, resulting in adverse effects to humans and wildlife such as birth defects and developmental disorders. Since several EDs have a structure similar to that of endogenous steroid hormones such as estrogens, they intend to have an affinity for steroid hormone receptors and alter hormone-mediated metabolism by binding to these receptors. EDs are therefore a global concern and assays should be developed to efficiently determine whether these compounds are detrimental to biological systems. Diverse experimental methods may help determine the endocrine disrupting potential of EDs and evaluate the adverse effects of a single and/or combination of these reagents. Currently, biomarkers have been employed to objectively measure EDs potency and understand the underlying mechanisms. Further studies are required to develop ideal screening methods and biomarkers to determine EDs potency at environmentally relevant concentrations. In this review, we describe the biomarkers for estrogenicity of EDs identified both in vitro and in vivo, and introduce a biomarker, cabindin-D9k (CaBP-9k), that may be used to assess estrogenic activity of EDs

Dark sectors 2016 Workshop: community report

This report, based on the Dark Sectors workshop at SLAC in April 2016, summarizes the scientific importance of searches for dark sector dark matter and forces at masses beneath the weak-scale, the status of this broad international field, the important milestones motivating future exploration, and promising experimental opportunities to reach these milestones over the next 5-10 years

From Spiking Neuron Models to Linear-Nonlinear Models

Neurons transform time-varying inputs into action potentials emitted stochastically at a time dependent rate. The mapping from current input to output firing rate is often represented with the help of phenomenological models such as the linear-nonlinear (LN) cascade, in which the output firing rate is estimated by applying to the input successively a linear temporal filter and a static non-linear transformation. These simplified models leave out the biophysical details of action potential generation. It is not a priori clear to which extent the input-output mapping of biophysically more realistic, spiking neuron models can be reduced to a simple linear-nonlinear cascade. Here we investigate this question for the leaky integrate-and-fire (LIF), exponential integrate-and-fire (EIF) and conductance-based Wang-Buzsáki models in presence of background synaptic activity. We exploit available analytic results for these models to determine the corresponding linear filter and static non-linearity in a parameter-free form. We show that the obtained functions are identical to the linear filter and static non-linearity determined using standard reverse correlation analysis. We then quantitatively compare the output of the corresponding linear-nonlinear cascade with numerical simulations of spiking neurons, systematically varying the parameters of input signal and background noise. We find that the LN cascade provides accurate estimates of the firing rates of spiking neurons in most of parameter space. For the EIF and Wang-Buzsáki models, we show that the LN cascade can be reduced to a firing rate model, the timescale of which we determine analytically. Finally we introduce an adaptive timescale rate model in which the timescale of the linear filter depends on the instantaneous firing rate. This model leads to highly accurate estimates of instantaneous firing rates

Flow-Alignment of Extracellular Vesicles: Structure and Orientation of Membrane Associated Biomacromolecules Studied with Polarized Light

Extracellular vesicles (EVs) are currently in the scientific focus having a great potential to revolutionize the diagnosis and therapy of various diseases. However, numerous aspects of these species are still poorly understood, thus additional insight to molecular level properties, membrane-protein interactions, or membrane rigidity is still needed. We here demonstrate using red blood cell derived EVs (REVs) that polarized light spectroscopy techniques, linear and circular dichroism, can provide molecular level structural information on these systems. Flow-linear dichroism (flow-LD) measurements show that EVs can be oriented by shear force, and indicate that hemoglobin molecules are associated to the lipid bilayer in freshly released REVs. During storage this interaction ceases coupled to major protein conformational changes relative to the initial state. Further on, the degree of orientation gives insight to vesicle rigidity, which decreases in time parallel to changes in protein conformation. In overall, we propose that both LD and circular dichroism (CD) spectra provide simple, rapid, yet efficient ways to track changes in membrane-protein interactions of EV components at the molecular level which may also give insight to processes occurring during vesiculation