Identification of a non-purple tartrate-resistant acid phosphatase: an evolutionary link to Ser/Thr protein phosphatases?

BACKGROUND Tartrate-resistant acid phosphatases (TRAcPs), also known as purple acid phosphatases (PAPs), are a family of binuclear metallohydrolases that have been identified in plants, animals and fungi. The human enzyme is a major histochemical marker for the diagnosis of bone-related diseases. TRAcPs can occur as a small form possessing only the ~35 kDa catalytic domain, or a larger ~55 kDa form possessing both a catalytic domain and an additional N-terminal domain of unknown function. Due to its role in bone resorption the 35 kDa TRAcP has become a promising target for the development of anti-osteoporotic chemotherapeutics. FINDINGS A new human gene product encoding a metallohydrolase distantly related to the ~55 kDa plant TRAcP was identified and characterised. The gene product is found in a number of animal species, and is present in all tissues sampled by the RIKEN mouse transcriptome project. Construction of a homology model illustrated that six of the seven metal-coordinating ligands in the active site are identical to that observed in the TRAcP family. However, the tyrosine ligand associated with the charge transfer transition and purple color of TRAcPs is replaced by a histidine. CONCLUSION The gene product identified here may represent an evolutionary link between TRAcPs and Ser/Thr protein phosphatases. Its biological function is currently unknown but is unlikely to be associated with bone metabolism.This work was funded by the Royal Society of Tropical Medicine and Hygiene through a Dennis Burkitt Fellowship to JJM. ARD is supported by the Economic and Social Research Council. JJM is supported by a Wellcome Trust Research Training Fellowship (GR074833MA)

The mechanism of the amidases: mutating the glutamate adjacent to the catalytic triad inactivates the enzyme due to substrate mispositioning

All known nitrilase superfamily amidase and carbamoylase structures have an additional glutamate thatis hydrogen bonded to the catalytic lysine in addition to the Glu, Lys, Cys “catalytic triad.” In the amidase from Geobacillus pallidus, mutating this glutamate (Glu-142) to a leucine or aspartate renders the enzyme inactive. X-ray crystal structure determination shows that the structural integrity of the enzymeismaintained despite themutation with the catalytic cysteine (Cys-166), lysine (Lys-134), and glutamate (Glu- 59)in positions similar to those of the wild-type enzyme. In the case of the E142L mutant, a chloride ion is located in the position occupied by Glu-142 O 1 in the wild-type enzyme andinteracts with the active site lysine. In the case of the E142D mutant, this site is occupied by Asp-142 O1.In neither case is an atom located at the position of Glu-142 O 2 in the wild-type enzyme. The active site cysteine of the E142Lmutant was found to form aMichael adduct with acrylamide, which is a substrate of the wild-type enzyme, due to an interaction that places the double bond of the acrylamide rather than the amide carbonyl carbon adjacent to the active site cysteine. Our results demonstrate that in the wild-type active site a crucial role is played by the hydrogen bond between Glu-142 O 2 and the substrate amino groupin positioning the substrate with the correct stereoelectronic alignment to enable the nucleophilic attack on the carbonyl carbon by the catalytic cysteine

Language change for the worse

Many theories hold that language change, at least on a local level, is driven by a need for improvement. The present volume explores to what extent this assumption holds true, and whether there is a particular type of language change that we dub language change for the worse, i.e., change with a worsening effect that cannot be explained away as a side-effect of improvement in some other area of the linguistic system. The chapters of the volume, written by leading junior and senior scholars, combine expertise in diachronic and historical linguistics, typology, and formal modelling. They focus on different aspects of grammar (phonology, morphosyntax, semantics) in a variety of language families (Germanic, Romance, Austronesian, Bantu, Jê-Kaingang, Wu Chinese, Greek, Albanian, Altaic, Indo-Aryan, and languages of the Caucasus). The volume contributes to ongoing theoretical debates and discussions between linguists with different theoretical orientations

Vacuum-stimulated cooling of single atoms in three dimensions

Taming quantum dynamical processes is the key to novel applications of quantum physics, e.g. in quantum information science. The control of light-matter interactions at the single-atom and single-photon level can be achieved in cavity quantum electrodynamics, in particular in the regime of strong coupling where atom and cavity form a single entity. In the optical domain, this requires permanent trapping and cooling of an atom in a micro-cavity. We have now realized three-dimensional cavity cooling and trapping for an orthogonal arrangement of cooling laser, trap laser and cavity vacuum. This leads to average single-atom trapping times exceeding 15 seconds, unprecedented for a strongly coupled atom under permanent observation.Comment: 4 pages, 4 figure

Early Pliocene Hominid Tooth from Galili, Somali Region, Ethiopia

A fossil hominid tooth was discovered during survey at Galili, Somali region, Ethiopia. The geological and faunal context indicate an Early Pliocene age. The specimen (GLL 33) consists of an almost complete lower right third molar likely representing a male individual of advanced age-at-death. Its comparative metrical, morphological and (micro)structural analysis (supported by a microtomographic record) suggests a tentative taxonomic allocation to Australopithecus cf. A. afarensis

Femtosecond formation dynamics of the spin Seebeck effect revealed by terahertz spectroscopy.

Understanding the transfer of spin angular momentum is essential in modern magnetism research. A model case is the generation of magnons in magnetic insulators by heating an adjacent metal film. Here, we reveal the initial steps of this spin Seebeck effect with <27 fs time resolution using terahertz spectroscopy on bilayers of ferrimagnetic yttrium iron garnet and platinum. Upon exciting the metal with an infrared laser pulse, a spin Seebeck current js arises on the same ~100 fs time scale on which the metal electrons thermalize. This observation highlights that efficient spin transfer critically relies on carrier multiplication and is driven by conduction electrons scattering off the metal-insulator interface. Analytical modeling shows that the electrons' dynamics are almost instantaneously imprinted onto js because their spins have a correlation time of only ~4 fs and deflect the ferrimagnetic moments without inertia. Applications in material characterization, interface probing, spin-noise spectroscopy and terahertz spin pumping emerge

Metal enrichment processes

There are many processes that can transport gas from the galaxies to their environment and enrich the environment in this way with metals. These metal enrichment processes have a large influence on the evolution of both the galaxies and their environment. Various processes can contribute to the gas transfer: ram-pressure stripping, galactic winds, AGN outflows, galaxy-galaxy interactions and others. We review their observational evidence, corresponding simulations, their efficiencies, and their time scales as far as they are known to date. It seems that all processes can contribute to the enrichment. There is not a single process that always dominates the enrichment, because the efficiencies of the processes vary strongly with galaxy and environmental properties.Comment: 18 pages, 8 figures, accepted for publication in Space Science Reviews, special issue "Clusters of galaxies: beyond the thermal view", Editor J.S. Kaastra, Chapter 17; work done by an international team at the International Space Science Institute (ISSI), Bern, organised by J.S. Kaastra, A.M. Bykov, S. Schindler & J.A.M. Bleeke

Gravity Recovery and Interior Laboratory (GRAIL): Extended Mission and End-Game Status

The Gravity Recovery and Interior Laboratory (GRAIL) [1], NASA s eleventh Discovery mission, successfully executed its Primary Mission (PM) in lunar orbit between March 1, 2012 and May 29, 2012. GRAIL s Extended Mission (XM) initiated on August 30, 2012 and was successfully completed on December 14, 2012. The XM provided an additional three months of gravity mapping at half the altitude (23 km) of the PM (55 km), and is providing higherresolution gravity models that are being used to map the upper crust of the Moon in unprecedented detail

Preliminary Results on Lunar Interior Properties from the GRAIL Mission

The Gravity Recovery and Interior Laboratory (GRAIL) mission has provided lunar gravity with unprecedented accuracy and resolution. GRAIL has produced a high-resolution map of the lunar gravity field while also determining tidal response. We present the latest gravity field solution and its preliminary implications for the Moon's interior structure, exploring properties such as the mean density, moment of inertia of the solid Moon, and tidal potential Love number k2. Lunar structure includes a thin crust, a deep mantle, a fluid core, and a suspected solid inner core. An accurate Love number mainly improves knowledge of the fluid core and deep mantle. In the future GRAIL will search for evidence of tidal dissipation and a solid inner core

The CPLEAR Electromagnetic Calorimeter

A large-acceptance lead/gas sampling electromagnetic calorimeter (ECAL) was constructed for the CPLEAR experiment to detect photons from decays of $\pi^0$s with momentum $p_{\pi^0} \le 800$ MeV$/c$. The main purpose of the ECAL is to determine the decay vertex of neutral-kaon decays \ko \rightarrow \pi^0\pi^0 \rightarrow 4 \gamma and \ko \rightarrow \pi^0\pi^0\pi^0 \rightarrow 6 \gamma. This requires a position-sensitive photon detector with high spatial granularity in $r$-, $\varphi$-, and $z$-coordinates. The ECAL --- a barrel without end-caps located inside a magnetic field of 0.44 T --- consists of 18 identical concentric layers. Each layer of $1/3$ radiation length (X${_0}$) contains a converter plate followed by small cross-section high-gain tubes of 2640 mm active length which are sandwiched by passive pick-up strip plates. The ECAL, with a total of $6$ X${_0}$, has an energy resolution of $\sigma (E)/E \approx 13\% / \sqrt{E(\mathrm{GeV})}$ and a position resolution of 4.5 mm for the shower foot. The shower topology allows separation of electrons from pions. The design, construction, read-out electronics, and performance of the detector are described