β Subunit M2–M3 Loop Conformational Changes Are Uncoupled from α1 β Glycine Receptor Channel Gating: Implications for Human Hereditary Hyperekplexia

Hereditary hyperekplexia, or startle disease, is a neuromotor disorder caused mainly by mutations that either prevent the surface expression of, or modify the function of, the human heteromeric α1 β glycine receptor (GlyR) chloride channel. There is as yet no explanation as to why hyperekplexia mutations that modify channel function are almost exclusively located in the α1 to the exclusion of β subunit. The majority of these mutations are identified in the M2–M3 loop of the α1 subunit. Here we demonstrate that α1 β GlyR channel function is less sensitive to hyperekplexia-mimicking mutations introduced into the M2–M3 loop of the β than into the α1 subunit. This suggests that the M2–M3 loop of the α subunit dominates the β subunit in gating the α1 β GlyR channel. A further attempt to determine the possible mechanism underlying this phenomenon by using the voltage-clamp fluorometry technique revealed that agonist-induced conformational changes in the β subunit M2–M3 loop were uncoupled from α1 β GlyR channel gating. This is in contrast to the α subunit, where the M2–M3 loop conformational changes were shown to be directly coupled to α1 β GlyR channel gating. Finally, based on analysis of α1 β chimeric receptors, we demonstrate that the structural components responsible for this are distributed throughout the β subunit, implying that the β subunit has evolved without the functional constraint of a normal gating pathway within it. Our study provides a possible explanation of why hereditary hyperekplexia-causing mutations that modify α1 β GlyR channel function are almost exclusively located in the α1 to the exclusion of the β subunit

Using approximate matching to reduce the volume of digital data

Digital forensic investigators frequently have to search for relevant files in massive digital corpora – a task often compared to finding a needle in a haystack. To address this challenge, investigators typically apply cryptographic hash functions to identify known files. However, cryptographic hashing only allows the detection of files that exactly match the known file hash values or fingerprints. This paper demonstrates the benefits of using approximate matching to locate relevant files. The experiments described in this paper used three test images of Windows XP, Windows 7 and Ubuntu 12.04 systems to evaluate fingerprint-based comparisons. The results reveal that approximate matching can improve file identification – in one case, increasing the identification rate from 1.82% to 23.76%

Combined vibrational spectra of natural wardite

Vibrational spectra (IR, Raman, inelastic neutron scattering) were measured of natural wardite (ideal formula NaAl3(OH)(4)(PO4)(2).2 H2O) from Trauira, Brazil, with the main impurities Fe and Ca. The spectra are discussed on the basis of a symmetry analysis restricted to one layer in the four-layer structure. The band pattern in the nu(OH) region is due to two different Al2OH groups and their correlation coupling; their deformations delta and gamma are assigned based on IR and INS spectra. Contributions of the hydrogen-bonded H2O molecules are discussed, as are the vibrations of the AlO6 octahedra dominating the Raman spectrum. From the fundamentals nu(OH) of the OH groups and their overtones anharmonicity constants have been estimated. (C) 2004 Elsevier B.V. All rights reserved