Three-dimensional elemental bio-imaging of Fe, Zn, Cu, Mn and P in a 6-hydroxydopamine lesioned mouse brain

Three dimensional maps of iron (Fe), zinc (Zn), copper (Cu), manganese (Mn) and phosphorous (P) in a 6-hydroxydopamine (6-OHDA) lesioned mouse brain were constructed employing a novel quantitative laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging method known as elemental bio-imaging. The 3D maps were produced by ablating serial consecutive sections taken from the same animal. Each section was quantified against tissue standards resulting in a three dimensional map that represents the variation of trace element concentrations of the mouse brain in the area surrounding the substantia nigra (SN). Damage caused by the needle or the toxin did not alter the distribution of Zn, and Cu but significantly altered Fe in and around the SN and both Mn and Fe around the needle track. A 20% increase in nigral Fe concentration was observed within the lesioned hemisphere. This technique clearly shows the natural heterogeneous distributions of these elements throughout the brain and the perturbations that occur following trauma or intoxication. The method may applied to three-dimensional modelling of trace elements in a wide range of tissue samples. © 2010 The Royal Society of Chemistry

A perspective from extinct radionuclides on a Young Stellar Object: The Sun and its accretion disk

Meteorites, which are remnants of solar system formation, provide a direct glimpse into the dynamics and evolution of a young stellar object (YSO), namely our Sun. Much of our knowledge about the astrophysical context of the birth of the Sun, the chronology of planetary growth from micrometer-sized dust to terrestrial planets, and the activity of the young Sun comes from the study of extinct radionuclides such as 26Al (t1/2 = 0.717 Myr). Here we review how the signatures of extinct radionuclides (short-lived isotopes that were present when the solar system formed and that have now decayed below detection level) in planetary materials influence the current paradigm of solar system formation. Particular attention is given to tying meteorite measurements to remote astronomical observations of YSOs and modeling efforts. Some extinct radionuclides were inherited from the long-term chemical evolution of the Galaxy, others were injected into the solar system by a nearby supernova, and some were produced by particle irradiation from the T-Tauri Sun. The chronology inferred from extinct radionuclides reveals that dust agglomeration to form centimeter-sized particles in the inner part of the disk was very rapid (<50 kyr), planetesimal formation started early and spanned several million years, planetary embryos (possibly like Mars) were formed in a few million years, and terrestrial planets (like Earth) completed their growths several tens of million years after the birth of the Sun.Comment: 49 pages, 9 figures, 1 table. Uncorrected preprin

Profiling the iron, copper and zinc content in primary neuron and astrocyte cultures by rapid online quantitative size exclusion chromatography-inductively coupled plasma-mass spectrometry

Metals often determine the chemical reactivity of the proteins to which they are bound. Each cell in the body tightly maintains a unique metalloproteomic profile, mostly dependent on function. This paper describes an analytical online flow injection quantitative size exclusion chromatography-inductively coupled plasma-mass spectrometry (SEC-ICP-MS) method, which was applied to profiling the metal-binding proteins found in primary cultures of neurons and astrocytes. This method can be conducted using similar amounts of sample to those used for Western blotting (20-150 μg protein), and has a turnaround time of <15 minutes. Metalloprotein standards for Fe (as ferritin), Cu and Zn (as superoxide dismutase-1) were used to construct multi-point calibration curves for online quantification of metalloproteins by SEC-ICP-MS. Homogenates of primary neuron and astrocyte cultures were analysed by SEC-ICP-MS. Online quantification by external calibration with metalloprotein standards determined the mass of metal eluting from the column relative to time (as pg s-1). Total on-column Fe, Cu and Zn detection limits ranged from 0.825 ± 0.005 ng to 13.6 ± 0.7 pg. Neurons and astrocytes exhibited distinct metalloprotein profiles, featuring both ubiquitous and unique metalloprotein species. Separation and detection by SEC-ICP-MS allows appraisal of these metalloproteins in their native state, and online quantification was achieved using this relatively simple external calibration process. © 2013 The Royal Society of Chemistry

Anomaly Equations and Intersection Theory

Six-dimensional supergravity theories with N=(1,0) supersymmetry must satisfy anomaly equations. These equations come from demanding the cancellation of gravitational, gauge and mixed anomalies. The anomaly equations have implications for the geometrical data of Calabi-Yau threefolds, since F-theory compactified on an elliptically fibered Calabi-Yau threefold with a section generates a consistent six-dimensional N=(1,0) supergravity theory. In this paper, we show that the anomaly equations can be summarized by three intersection theory identities. In the process we also identify the geometric counterpart of the anomaly coefficients---in particular, those of the abelian gauge groups---that govern the low-energy dynamics of the theory. We discuss the results in the context of investigating string universality in six dimensions.Comment: 29 pages + appendices, 8 figures; v2: minor corrections, references added; v3: minor corrections, reference adde

Optical Trapping of an Ion

For several decades, ions have been trapped by radio frequency (RF) and neutral particles by optical fields. We implement the experimental proof-of-principle for trapping an ion in an optical dipole trap. While loading, initialization and final detection are performed in a RF trap, in between, this RF trap is completely disabled and substituted by the optical trap. The measured lifetime of milliseconds allows for hundreds of oscillations within the optical potential. It is mainly limited by heating due to photon scattering. In future experiments the lifetime may be increased by further detuning the laser and cooling the ion. We demonstrate the prerequisite to merge both trapping techniques in hybrid setups to the point of trapping ions and atoms in the same optical potential.Comment: 5 pages, 3 figure

Coordination and transfer

We study the ability of subjects to transfer principles between related coordination games. Subjects play a class of order statistic coordination games closely related to the well-known minimum (or weak-link) and median games (Van Huyck et al. in Am Econ Rev 80:234–248, 1990, Q J Econ 106(3):885–910, 1991). When subjects play a random sequence of games with differing order statistics, play is less sensitive to the order statistic than when a fixed order statistic is used throughout. This is consistent with the prediction of a simple learning model with transfer. If subjects play a series of similar stag hunt games, play converges to the payoff dominant equilibrium when a convention emerges, replicating the main result of Rankin et al. (Games Econ Behav 32:315–337, 2000). When these subjects subsequently play a random sequence of order statistic games, play is shifted towards the payoff dominant equilibrium relative to subjects without previous experience. The data is consistent with subjects absorbing a general principle, play of the payoff dominant equilibrium, and applying it in a new related setting

Transplanckian axions !?

We discuss quantum gravitational effects in Einstein theory coupled to periodic axion scalars to analyze the viability of several proposals to achieve superplanckian axion periods (aka decay constants) and their possible application to large field inflation models. The effects we study correspond to the nucleation of euclidean gravitational instantons charged under the axion, and our results are essentially compatible with (but independent of) the Weak Gravity Conjecture, as follows: Single axion theories with superplanckian periods contain gravitational instantons inducing sizable higher harmonics in the axion potential, which spoil superplanckian inflaton field range. A similar result holds for multi-axion models with lattice alignment (like the Kim-Nilles-Peloso model). Finally, theories with $N$ axions can still achieve a moderately superplanckian periodicity (by a $\sqrt{N}$ factor) with no higher harmonics in the axion potential. The Weak Gravity Conjecture fails to hold in this case due to the absence of some instantons, which are forbidden by a discrete $\mathbf{Z}_N$ gauge symmetry. Finally we discuss the realization of these instantons as euclidean D-branes in string compactifications.Comment: 46 pages, 6 figures. Added references, clarifications, and missing factor of 1/2 to instanton action. Conclusions unchange

Bright ligand-activatable fluorescent protein for high-quality multicolor live-cell super-resolution microscopy

We introduce UnaG as a green-to-dark photoswitching fluorescent protein capable of high-quality super-resolution imaging with photon numbers equivalent to the brightest photoswitchable red protein. UnaG only fluoresces upon binding of a fluorogenic metabolite, bilirubin, enabling UV-free reversible photoswitching with easily controllable kinetics and low background under Epi illumination. The on- and off-switching rates are controlled by the concentration of the ligand and the excitation light intensity, respectively, where the dissolved oxygen also promotes the off-switching. The photo-oxidation reaction mechanism of bilirubin in UnaG suggests that the lack of ligand-protein covalent bond allows the oxidized ligand to detach from the protein, emptying the binding cavity for rebinding to a fresh ligand molecule. We demonstrate super-resolution single-molecule localization imaging of various subcellular structures genetically encoded with UnaG, which enables facile labeling and simultaneous multicolor imaging of live cells. UnaG has the promise of becoming a default protein for high-performance super-resolution imaging. Photoconvertible proteins occupy two color channels thereby limiting multicolour localisation microscopy applications. Here the authors present UnaG, a new green-to-dark photoswitching fluorescent protein for super-resolution imaging, whose activation is based on a noncovalent binding with bilirubin

The Mitochondrial Ca(2+) Uniporter: Structure, Function, and Pharmacology.

Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex

A Genetic Screen for Attenuated Growth Identifies Genes Crucial for Intraerythrocytic Development of Plasmodium falciparum

A majority of the Plasmodium falciparum genome codes for genes with unknown functions, which presents a major challenge to understanding the parasite's biology. Large-scale functional analysis of the parasite genome is essential to pave the way for novel therapeutic intervention strategies against the disease and yet difficulties in genetic manipulation of this deadly human malaria parasite have been a major hindrance for functional analysis of its genome. Here, we used a forward functional genomic approach to study P. falciparum and identify genes important for optimal parasite development in the disease-causing, intraerythrocytic stages. We analyzed 123 piggyBac insertion mutants of P. falciparum for proliferation efficiency in the intraerythrocytic stages, in vitro. Almost 50% of the analyzed mutants showed significant reduction in proliferation efficiency, with 20% displaying severe defects. Functional categorization of genes in the severely attenuated mutants revealed significant enrichment for RNA binding proteins, suggesting the significance of post-transcriptional gene regulation in parasite development and emphasizing its importance as an antimalarial target. This study demonstrates the feasibility of much needed forward genetics approaches for P. falciparum to better characterize its genome and accelerate drug and vaccine development