A New Stellar Atmosphere Grid and Comparisons with HST/STIS Calspec Flux Distributions

The Space Telescope Imaging Spectrograph (STIS) has measured the spectral energy distributions (SEDs) for several stars of types O, B, A, F, and G. These absolute fluxes from the CALSPEC database are fit with a new spectral grid computed from the ATLAS-APOGEE ATLAS9 model atmosphere database using a chi-square minimization technique in four parameters. The quality of the fits are compared for complete LTE grids by Castelli & Kurucz (CK04) and our new comprehensive LTE grid (BOSZ). For the cooler stars, the fits with the MARCS LTE grid are also evaluated, while the hottest stars are also fit with the NLTE Lanz & Hubeny OB star grids. Unfortunately, these NLTE models do not transition smoothly in the infrared to agree with our new BOSZ LTE grid at the NLTE lower limit of Teff =15,000K. The new BOSZ grid is available via the Space Telescope Institute MAST archive and has a much finer sampled IR wavelength scale than CK04, which will facilitate the modeling of stars observed by the James Webb Space Telescope (JWST). Our result for the angular diameter of Sirius agrees with the ground- based interferometric value.Comment: 11 figure

Methods for automating the analysis of live-cell single-molecule FRET data

Single-molecule FRET (smFRET) is a powerful imaging platform capable of revealing dynamic changes in the conformation and proximity of biological molecules. The expansion of smFRET imaging into living cells creates both numerous new research opportunities and new challenges. Automating dataset curation processes is critical to providing consistent, repeatable analysis in an efficient manner, freeing experimentalists to advance the technical boundaries and throughput of what is possible in imaging living cells. Here, we devise an automated solution to the problem of multiple particles entering a region of interest, an otherwise labor-intensive and subjective process that had been performed manually in our previous work. The resolution of these two issues increases the quantity of FRET data and improves the accuracy with which FRET distributions are generated, increasing knowledge about the biological functions of the molecules under study. Our automated approach is straightforward, interpretable, and requires only localization and intensity values for donor and acceptor channel signals, which we compute through our previously published smCellFRET pipeline. The development of our automated approach is informed by the insights of expert experimentalists with extensive experience inspecting smFRET trajectories (displacement and intensity traces) from live cells. We test our automated approach against our recently published research on the metabotropic glutamate receptor 2 (mGluR2) and reveal substantial similarities, as well as potential shortcomings in the manual curation process that are addressable using the algorithms we developed here

Detecting G protein-coupled receptor complexes in postmortem human brain with proximity ligation assay and a Bayesian classifier

Despite the controversy regarding the existence and physiological relevance of class A G protein-coupled receptor dimerization, there is substantial evidence for functional interactions between the dopamine D2 receptor (D2R) and the adenosine A2A receptor (A2AR). A2AR-D2R complexes have been detected in rodent brains by proximity ligation assay; however, their existence in the human brain has not been demonstrated. In this study, we used Brightfield proximity ligation assay, combined with a systematic sampling and a parameter-free naive Bayesian classifier, and demonstrated proximity between the D2R and the A2AR in the adult human ventral striatum, consistent with their colocalization within complexes and the possible existence of D2R-A2AR heteromers. These methods are applicable to the relative quantification of proximity of two proteins, as well as the expression levels of individual proteins

Mitochondria-Targeted Antioxidants SkQ1 and MitoTEMPO Failed to Exert a Long-Term Beneficial Effect in Murine Polymicrobial Sepsis

Mitochondrial-derived reactive oxygen species have been deemed an important contributor in sepsis pathogenesis. We investigated whether two mitochondria-targeted antioxidants (mtAOX; SkQ1 and MitoTEMPO) improved long-term outcome, lessened inflammation, and improved organ homeostasis in polymicrobial murine sepsis. 3-month-old female CD-1 mice (n=90) underwent cecal ligation and puncture (CLP) and received SkQ1 (5 nmol/kg), MitoTEMPO (50 nmol/kg), or vehicle 5 times post-CLP. Separately, 52 SkQ1-treated CLP mice were sacrificed at 24 h and 48 h for additional endpoints. Neither MitoTEMPO nor SkQ1 exerted any protracted survival benefit. Conversely, SkQ1 exacerbated 28-day mortality by 29%. CLP induced release of 10 circulating cytokines, increased urea, ALT, and LDH, and decreased glucose but irrespectively of treatment. Similar occurred for CLP-induced lymphopenia/neutrophilia and the NO blood release. At 48 h post-CLP, dying mice had approximately 100-fold more CFUs in the spleen than survivors, but this was not SkQ1 related. At 48 h, macrophage and granulocyte counts increased in the peritoneal lavage but irrespectively of SkQ1. Similarly, hepatic mitophagy was not altered by SkQ1 at 24 h. The absence of survival benefit of mtAOX may be due to the extended treatment and/or a relatively moderate-risk-of-death CLP cohort. Long-term effect of mtAOX in abdominal sepsis appears different to sepsis/inflammation models arising from other body compartments

Optical characterization of dopamine release in the globus pallidus and striatum

The measurement of dopamine neurotransmission in the brain has evolved alongside techniques for measuring neuronal activity. This evolution has progressed from coarse physical inspection (using lesions or dialysis approaches) to measuring electrical signatures of the phenomena of interest. Most recently, an optical revolution has taken hold within the neurosciences. We present an optical dopamine measurement technique as a companion to burgeoning neural activity monitors such as GCaMP. The electrical consequences of individual glutamate molecules impinging upon a postsynaptic membrane can be captured in an electrophysiological trace. On the other hand, dopamine has no consistent, measureable postsynaptic effects and therefore cannot easily be measured electrophysiologically. Researchers have instead used the electrochemical features of dopamine to measure samples of it in physical space. This approach, termed cyclic voltammetry, has generated nearly all of the existing knowledge about the precise characteristics of dopamine release. While a reliable method for measuring dopamine release from heavily innervated areas, cyclic voltammetry lacks the resolving power to establish release from dopamine terminals in other areas of interest. One such area is the external globus pallidus (GPe), the focus of this work. Research performed nearly thirty years prior to this thesis established the presence of sparsely distributed dopamine varicosities within the GPe. Here, we leverage FFN102, a newly developed optical method used as a proxy for dopamine release, to measure dopamine release in this area. Based on previous literature showing that dopamine varicosities were present in the GPe and that dopamine receptors exist on principal cells in the area, we hypothesized that these dopamine varicosities were capable of releasing FFN102. Moreover, previous work had shown that anatomically, the most prominent dopaminergic innervation to the GPe came from the substantia nigra. By validating the FFN102 method in the GPe, we showed that a substance is released which likely reflects dopamine vesicle release. Moreover, the use of two dopamine depletion mouse models allowed us to conclude that FFN102 is released exclusively from dopamine terminals. Finally, we advanced the understanding of dopamine release in the area by examining whether pharmacological manipulation could alter the amount of FFN102 released from dopamine terminals

Achieving Peace of Mind: The Benefits of Neurobiological Evidence for Battered Women Defendants

Despite its potential to diminish the culpability of battered women accused of crimes, neurobiological evidence has yet to be meaningfully deployed in the interest of these defendants. This Article describes how neurobiological evidence can provide insights into the effects of battering, at both an individual and ecological level. Domestic violence prevention advocates and medical professionals are becoming increasingly conscious of the neurobiological consequences of battering, producing a wellspring of evidence with potential relevance to the battered woman\u27s case. By distilling this evidence into tangible assertions admissible in myriad legal settings, this Article lays a foundation for the integration of neurobiological evidence into the defense of battered women

Synthesis, characterisation and antimicrobial activity of bis(phthalazine-1-hydrazone)-2,6-diacetylpyridine and its complexes with Co-III, Ni-II, Cu-II and Zn-II

Four new complex compounds of bis(phthalazine-1-hydrazone)-2,6-diacetylpyridine (Hz(2)DAP) ligand with Ni-II, Co-III, Cu-II and Zn-II metal centres were synthesised and characterised by single-crystal X-ray diffraction and IR spectral data. The antimicrobial activity of Hz(2)DAP and the obtained complexes [Co(Hz(2)DAP-H)Cl-2]center dot MeOH, [Ni(Hz(2)DAP-H)]Cl center dot MeOH, [Cu(Hz(2)DAP-H)Cl] and [Zn(Hz(2)DAP-2H)]center dot H2O were tested in vitro against selected Gram(-) and Gram(+) bacterial strains and fungi. The antimicrobial activity of the ligand is negligible, while its complexes with Ni-II, Co-III and Cu-II show considerable activity against Escherichia coli, Staphylococcus aureus and Micrococcus lysodeikticus. On the contrary, [Zn(Hz(2)DAP-2H)]center dot H2O promotes the growth of Candida albicans, while its antibacterial activity is negligible. On the basis of thermal data and those from coupled TG/MS measurements the decomposition mechanisms were determined and evaluated. (C) 2014 Elsevier Ltd. All rights reserved