Targeting of synaptotagmin to neurite terminals in neuronally differentiated PC12 cells

We have investigated structural elements that determine the accumulation of synaptotagmin, a major synaptic vesicle protein, in neurite terminals of neuronally differentiated neuroendocrine pheochromocytoma PC12 cells. We performed extensive deletion and point mutagenesis of rat synaptotagmin II, expressed mutant proteins in PC12 cells differentiated by nerve growth factor (NGF) and monitored their intracellular distribution by immunofluorescence. We found a structural element located at the carboxy-terminal domain nf the synaptotagmin molecule, which is necessary for its accumulation at the terminal. Using alanine-scanning mutagenesis, we have identified two amino acids in this element, tryptophan W405 and leucine L408, that are critical for correct targeting of synaptotagmin II to neurite terminals. Changing either one of them to alanine prevents the accumulation of the protein at the terminals, These amino acids are evolutionarily conserved throughout the entire synaptotagmin family and also among synaptotagmin-related proteins, suggesting that different synaptotagmins may have similar mechanisms of targeting to neuronal cell terminals

On the Nature of Black Holes in Loop Quantum Gravity

A genuine notion of black holes can only be obtained in the fundamental framework of quantum gravity resolving the curvature singularities and giving an account of the statistical mechanical, microscopic degrees of freedom able to explain the black hole thermodynamical properties. As for all quantum systems, a quantum realization of black holes requires an operator algebra of the fundamental observables of the theory which is introduced in this study based on aspects of loop quantum gravity. From the eigenvalue spectra of the quantum operators for the black hole area, charge and angular momentum, it is demonstrated that a strict bound on the extensive parameters, different from the relation arising in classical general relativity, holds, implying that the extremal black hole state can neither be measured nor can its existence be proven. This is, as turns out, a result of the specific form of the chosen angular momentum operator and the corresponding eigenvalue spectrum, or rather the quantum measurement process of angular momentum. Quantum mechanical considerations and the lowest, non-zero eigenvalue of the loop quantum gravity black hole mass spectrum indicate, on the one hand, a physical Planck scale cutoff of the Hawking temperature law and, on the other hand, give upper and lower bounds on the numerical value of the Immirzi parameter. This analysis provides an approximative description of the behavior and the nature of quantum black holes

An improved estimate of black hole entropy in the quantum geometry approach

A proper counting of states for black holes in the quantum geometry approach shows that the dominant configuration for spins are distributions that include spins exceeding one-half at the punctures. This raises the value of the Immirzi parameter and the black hole entropy. However, the coefficient of the logarithmic correction remains -1/2 as before.Comment: 5 pages, LaTeX; references and remarks adde

Unification of gravity, gauge fields, and Higgs bosons

We consider a diffeomorphism invariant theory of a gauge field valued in a Lie algebra that breaks spontaneously to the direct sum of the spacetime Lorentz algebra, a Yang-Mills algebra, and their complement. Beginning with a fully gauge invariant action -- an extension of the Plebanski action for general relativity -- we recover the action for gravity, Yang-Mills, and Higgs fields. The low-energy coupling constants, obtained after symmetry breaking, are all functions of the single parameter present in the initial action and the vacuum expectation value of the Higgs.Comment: 12 pages, no figures. v2 minor correction

Discrimination between the superconducting gap and the pseudo-gap in Bi2212 from intrinsic tunneling spectroscopy in magnetic field

Intrinsic tunneling spectroscopy in high magnetic field ($H$) is used for a direct test of superconducting features in a quasiparticle density of states of high-$T_c$ superconductors. We were able to distinguish with a great clarity two co-existing gaps: (i) the superconducting gap, which closes as $H \to H_{c2}(T)$ and $T\to T_c(H)$, and (ii) the $c$-axis pseudo-gap, which does not change neither with $H$, nor $T$. Strikingly different magnetic field dependencies, together with previously observed different temperature dependencies of the two gaps ~\cite{Krasnov}, speak against the superconducting origin of the pseudo-gap.Comment: 4 pages, 4 eps figure

Experiment K-6-22. Growth hormone regulation, synthesis and secretion in microgravity. Part 1: Somatotroph physiology. Part 2: Immunohistochemical analysis of hypothalamic hormones. Part 3: Plasma analysis

The objectives of the 1887 mission were: (1) to determine if the results of the SL-3 pituitary gland experiment (1) were repeatable; and (2) to determine what effect a longer mission would have on the rat pituitary gland growth hormone (GH) system. In the 1887 experiment two issues were considered especially important. First, it was recognized that cells prepared from individual rat pituitary glands should be considered separately so that the data from the 5 glands could be analyzed in a statistically meaningful way. Second, results of the SL-3 flight involving the hollow fiber implant and HPLC GH-variant experiments suggested that the biological activity of the hormone had been negatively affected by flight. The results of the 1887 experiment documented the wisdom of addressing both issues in the protocol. Thus, the reduction in secretory capacity of flight cells during subsequent extended cell culture on Earth was documented statistically, and thereby established the validity of the SL-3 result. The results of both flight experiments thus support the contention that there is a secretory lesion in pituitary GH cells of flight animals. The primary objective of both missions was a clear definition of the effect of spaceflight on the GH cell system. There can no longer be any reasonable doubt that this system is affected in microgravity. One explanation for the reason(s) underlying the better known effects of spaceflight on organisms, viz. changes in bone, muscle and immune systems may very well rest with such changes in bGH. In spite of the fact that rats in the Cosmos 1887 flight were on Earth for two days after flight, the data show that the GH system had still not recovered from the effects of flight. Many questions remain. One of the more important concerns the GRF responsiveness of somatotrophs after flight. This will be tested in an upcoming experiment

Non-Metric Gravity I: Field Equations

We describe and study a certain class of modified gravity theories. Our starting point is Plebanski formulation of gravity in terms of a triple B^i of 2-forms, a connection A^i and a ``Lagrange multiplier'' field Psi^ij. The generalization we consider stems from presence in the action of an extra term proportional to a scalar function of Psi^ij. As in the usual Plebanski general relativity (GR) case, a certain metric can be constructed from B^i. However, unlike in GR, the connection A^i no longer coincides with the self-dual part of the metric-compatible spin-connection. Field equations of the theory are shown to be relations between derivatives of the metric and components of field Psi, as well as its derivatives, the later being in contrast to the GR case. The equations are of second order in derivatives. An analog of the Bianchi identity is still present in the theory, as well as its contracted version tantamount to energy conservation equation.Comment: 21 pages, no figures (v2) energy conservation equation simplified, note on reality conditions added (v3) minor change