The Nicastrin ectodomain adopts a highly thermostable structure

Nicastrin is a type I transmembrane glycoprotein, which is part of the high molecular weight gamma-secretase complex. gamma-Secretase is one of the key players associated with the generation of Alzheimer's disease pathology, since it liberates the neurotoxic amyloid beta-peptide. Four proteins Nicastrin, anterior pharynx-defective-1 (Aph-1), presenilin enhancer-2 (Pen-2) and Presenilin are essential to form the active gamma-secretase complex. Recently it has been shown, that Nicastrin has a key function in stabilizing the mature gamma-secretase complex and may also be involved in substrate recognition. So far no structural data for the Nicastrin ectodomain or any other gamma-secretase component are available. We therefore used Circular Dichroism (CD) spectroscopy to demonstrate that Nicastrin, similar to its homologues, the Streptomyces griseus aminopeptidase (SGAP) and the transferrin receptor (TfR), adopts a thermostable secondary structure. Furthermore, the Nicastrin ectodomain has an exceptionally high propensity to refold after thermal denaturation. These findings provide evidence to further support the hypothesis that Nicastrin may share evolutionary conserved properties with the aminopeptidase and the transferrin receptor family

Signal peptide peptidases and gamma-secretase: Cousins of the same protease family?

Signal peptide peptidase (SPIP) is an unusual aspartyl protease, which mediates clearance of signal peptides by proteolysis within the endoplasmic reticulum (ER). Like presenilins, which provide the proteolytically active subunit of the,gamma-secretase complex, SPP contains a conserved GxGD motif in its C-terminal domain which is critical for its activity. While SPIP is known to be an aspartyl protease of the GxGD type, several presenilin homologues/SPP-like proteins (PSHs/ SPPL) of unknown function have been identified by database searches. In contrast to SPP and SPPL3, which are both restricted to the endoplasmic reticulum, SPPL2b is targeted through the secretory pathway to endosomes/lysosomes. As suggested by the differential subcellular localization of SPPL2b and SPPL3 distinct phenotypes were found upon antisense gripNA-mediated knockdown in zebrafish. spp and sppl3 knockdowns in zebrafish result in cell death within the central nervous system, whereas reduction of sppl2b expression causes erythrocyte accumulation in an enlarged caudal vein. Moreover, expression of D/A mutants of the putative C-terminal active sites of spp, sppl2, and spp13 produced phenocopies of the respective knockdown phenotypes. These data suggest that all investigated PSHs/SPPLs are members of the novel family of GxGD aspartyl proteases. More recently, it was shown that SPPL2b utilizes multiple intramembrane cleavages to liberate the TNF(x intracellular domain into the cytosol and to release the C-terminal counterpart into the lumen. These findings suggest common principles of intramembrane proteolysis by GxGD type aspartyl proteases. In this article,we will review the similarities of SPPs and gamma-secretase based on recent findings by us and others

Simultaenous Retrieval of Surface Roughness Parameters from Combined Active-Passive SMAP Observations

Soil roughness strongly influences processes like erosion, infiltration, moisture and evaporation of soils as well as growth of agricultural plants. An approach to soil roughness based on active-passive microwave covariation is proposed in order to simultaneously retrieve the vertical RMS height (s) and horizontal correlation length (l) of soil surfaces from simultaneously measured radar and radiometer microwave signatures. The approach is based on a retrieval algorithm for active-passive covariation including the improved Integral Equation Method (I2EM). The algorithm is tested with the global active-passive microwave observations of the SMAP mission. The developed roughness retrieval algorithm shows independence of permittivity for > 10 [-] due to the covariation formalism. Results reveal that s and l can be estimated simultaneously by the proposed approach since surface patterns of non-vegetated areas become evident on global scale. In regions with sandy deserts, like the Sahara or the outback in Australia, determined and confirm rather smooth to semi-rough surface roughness patterns with small vertical RMS heights and corresponding higher horizontal correlation lengths

Using digital watermarking to enhance security in wireless medical image transmission

This is the published version of the article. Copyright 2010 Mary Ann Liebert Inc.During the last few years, wireless networks have been increasingly used both inside hospitals and in patients’ homes to transmit medical information. In general, wireless networks suffer from decreased security. However, digital watermarking can be used to secure medical information. In this study, we focused on combining wireless transmission and digital watermarking technologies to better secure the transmission of medical images within and outside the hospital. Methods: We utilized an integrated system comprising the wireless network and the digital watermarking module to conduct a series of tests. Results: The test results were evaluated by medical consultants. They concluded that the images suffered no visible quality degradation and maintained their diagnostic integrity. Discussion: The proposed integrated system presented reasonable stability, and its performance was comparable to that of a fixed network. This system can enhance security during the transmission of medical images through a wireless channel.The General Secretariat for Research and Technology of the Hellenic Ministry of Development and the British Council

A practical attack on the fixed RC4 in the wep mode

Abstract. In this paper we revisit a known but ignored weakness of the RC4 keystream generator, where secret state info leaks to the generated keystream, and show that this leakage, also known as Jenkins’ correlation or the RC4 glimpse, can be used to attack RC4 in several modes. Our main result is a practical key recovery attack on RC4 when an IV modifier is concatenated to the beginning of a secret root key to generate a session key. As opposed to the WEP attack from [FMS01] the new attack is applicable even in the case where the first 256 bytes of the keystream are thrown and its complexity grows only linearly with the length of the key. In an exemplifying parameter setting the attack recoversa16-bytekeyin2 48 steps using 2 17 short keystreams generated from different chosen IVs. A second attacked mode is when the IV succeeds the secret root key. We mount a key recovery attack that recovers the secret root key by analyzing a single word from 2 22 keystreams generated from different IVs, improving the attack from [FMS01] on this mode. A third result is an attack on RC4 that is applicable when the attacker can inject faults to the execution of RC4. The attacker derives the internal state and the secret key by analyzing 2 14 faulted keystreams generated from this key

Physics-Based Retrieval of Surface Roughness Parameters for Bare Soils from Combined Active-Passive Microwave Signatures

In the past the effect of soil roughness was often considered secondary within the determination of soil moisture from remote sensing data. Several studies showed that accurate determination of soil roughness leads to an improved estimation of soil moisture. Two default parameters to describe the surface roughness are the standard deviation of the surface height variation and the surface correlation length with its corresponding autocorrelation function. Both parameters (,) affect the emissivity measured by radiometers as well as the backscattering observed by radars. In this study, we develop a physics-based approach to retrieve and by combining both microwave signals based on active-passive microwave covariation. To test the approach, containing a forward model and a retrieval algorithm, we used active/passive microwave data measured with the ComRAD truck-based SMAP simulator at L-band. Results and validations with corresponding field measurements on ground show that and can be estimated simultaneously when using this approach. The physics-based retrieval algorithm works robustly for two investigated test fields having an RMS-Error of 0.68 cm and 0.69 cm between the microwave-based and field-measured -values, and of 3.13 cm and 3.04 cm for -values. The first validation of the results reveals that the influence of the autocorrelation function, needed within the retrieval, is distinct

Behavior of the melt pool in the lower plenum of the reactor pressure vessel - review of experimental programs and background of the LIVE program

Das Verhalten eines Schmelze-Pools im unteren Plenum eines Reaktordruckbehälters – Überblick über experimentelle Programme und Grundlagen für das LIVE-Versuchsprogramm Die Rückhaltung der Kernschmelze im unteren Plenum des Reaktordruckbehälters (RDB) ist eine der in den letzten Jahren intensiv untersuchten Strategien, um einen hypothetischen Kernschmelzunfall zu beherrschen. In verschiedenen Institutionen weltweit wurden deshalb Experimente durchgeführt, um diese Strategie, welche bereits für das KKW Loviisa (Finnland) und den AP 600 (USA) genehmigt wurde, weiterzuentwickeln. Die wichtigsten Experimente waren dabei: • COPO-Experimente in Fortum Nuclear Services und CEA (Frankreich) • BALI-Experimente bei CEA (Frankreich) • SIMECO-Experimente im KTH (Schweden) • ACOPO-Experimente an der Universität von Kalifornien, Santa Barbara (USA) Diese Untersuchungen wurden nicht nur durchgeführt, um die Möglichkeit der Schmelze-Rückhaltung im RDB zu untersuchen, sondern auch, um das Verhalten eines Schmelzepools im unteren Plenum des RDB grundlegend zu verstehen. Die Ergebnisse dieser Untersuchungen wurden dazu verwendet, Modelle bzw. Korrelationen zu ermitteln, die in Rechencodeszur Untersuchung schwerer Unfälle verwendet werden können. Das Forschungszentrum Karlsruhe beteiligt sich mit der Versuchsanlage LIVE (Late In-Vessel Phase Experiments) an diesen Untersuchungen. Das Hauptziel dieses Berichtes ist es, die Ergebnisse anderer experimenteller Programme zum Schmelzeverhalten im unteren Plenum des RDB’s zusammenzufassen und damit ein Bild des derzeitigen Kenntnisstandes zu geben. Weiterhin soll gezeigt werden, wie die noch offenen Fragen im LIVE-Programm untersucht werden können

Structure and function of SPP/SPPL proteases: insights from biochemical evidence and predictive modeling

More than 20 years ago, signal peptide peptidase (SPP) and its homologues, the signal peptide peptidase-like (SPPL) proteases have been identified based on their sequence similarity to presenilins, a related family of intramembrane aspartyl proteases. Other than those for the presenilins, no high-resolution structures for the SPP/SPPL proteases are available. Despite this limitation, over the years bioinformatical and biochemical data have accumulated, which altogether have provided a picture of the overall structure and topology of these proteases, their localization in the cell, the process of substrate recognition, their cleavage mechanism, and their function. Recently, the artificial intelligence-based structure prediction tool AlphaFold has added high-confidence models of the expected fold of SPP/SPPL proteases. In this review, we summarize known structural aspects of the SPP/SPPL family as well as their substrates. Of particular interest are the emerging substrate recognition and catalytic mechanisms that might lead to the prediction and identification of more potential substrates and deeper insight into physiological and pathophysiological roles of proteolysis

The intramembrane protease SPPL2a promotes B cell development and controls endosomal traffic by cleavage of the invariant chain

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