Role of a ribosomal RNA phosphate oxygen during the EF-G-triggered hydrolysis

Elongation factor-catalyzed GTP hydrolysis is a key reaction during the ribosomal elongation cycle. Recent crystal structures of G proteins, such as elongation factor G (EF-G) bound to the ribosome, as well as many biochemical studies, provide evidence that the direct interaction of translational GTPases (trGTPases) with the sarcin-ricin loop (SRL) of ribosomal RNA (rRNA) is pivotal for hydrolysis. However, the precise mechanism remains elusive and is intensively debated. Based on the close proximity of the phosphate oxygen of A2662 of the SRL to the supposedly catalytic histidine of EF-G (His87), we probed this interaction by an atomic mutagenesis approach. We individually replaced either of the two nonbridging phosphate oxygens at A2662 with a methyl group by the introduction of a methylphosphonate instead of the natural phosphate in fully functional, reconstituted bacterial ribosomes. Our major finding was that only one of the two resulting diastereomers, the SP methylphosphonate, was compatible with efficient GTPase activation on EF-G. The same trend was observed for a second trGTPase, namely EF4 (LepA). In addition, we provide evidence that the negative charge of the A2662 phosphate group must be retained for uncompromised activity in GTP hydrolysis. (1) In summary, our data strongly corroborate that the nonbridging proSP phosphate oxygen at the A2662 of the SRL is critically involved in the activation of GTP hydrolysis. A mechanistic scenario is supported in which positioning of the catalytically active, protonated His87 through electrostatic interactions with the A2662 phosphate group and H-bond networks are key features of ribosome-triggered activation of trGTPases.

The CODE MGEX orbit and clock solution

The Center for Orbit Determination in Europe (CODE) is contributing as a global Analysis center to the International GNSS Service (IGS) since many years. The processing of GPS and GLONASS data is well established in CODE’s ultra-rapid, rapid, and final product lines. With the introduction of new signals for the established and new GNSS, new challenges and opportunities are arising for the GNSS data management and processing. The IGS started the Multi-GNSS-EXperiment (MGEX) in 2012 in order to gain first experience with the new data formats and to develop new strategies for making optimal use of these additional measurements. CODE has started to contribute to IGS MGEX with a consistent, rigorously combined triple-system orbit solution (GPS, GLONASS, and Galileo). SLR residuals for the computed Galileo satellite orbits are of the order of 10 cm. Furthermore CODE established a GPS and Galileo clock solution. A quality assessment shows that these experimental orbit and clock products allow even a Galileo-only precise point positioning (PPP) with accuracies on the decimeter- (static PPP) to meter-level (kinematic PPP) for selected stations.

A novel CYP17A1 deletion causes a functional knockout of the steroid enzyme 17-hydroxylase and 17,20-lyase in a Turkish family and illustrates the precise role of the CYP17A1 gene

A novel homozygous long-range deletion of the CYP17A1 gene abolished protein expression and caused the severest form of 17-hydroxylase deficiency in one kindred of a Turkish family. The affected subjects presented with 46,XY sex reversal and 46,XX lack of pubertal development as well as severe hypertension.

Bern's positioning strategies: Escaping the fate of a secondary capital city?

Bern is a classic example of a so-called secondary capital city, which is defined as a capital city that is not the primary economic center of its nation. Such capital cities feature a specific political economy characterized by a strong government presence in its regional economy and its local governance arrangements. Bern has been losing importance in the Swiss urban system over the past decades due to a stagnating economy, population decline and missed opportunities for regional cooperation. To re-position itself in the Swiss urban hierarchy, political leaders and policymakers established a non-profit organization called “Capital Region Switzerland” in 2010 arguing that a capital city should not be measured by economic success only, but by its function as a political center where political decisions are negotiated and implemented. This city profile analyses Bern's strategy and discusses its ambitions and limitations in the context of the city's history, socio-economic and political conditions. We conclude that Bern's positioning strategy has so far been a political success, yet that there are severe limitations regarding advancing economic development. As a result, this re-positioning strategy is not able to address the fundamental economic development challenges that Bern faces as a secondary capital city.

Fine-grained indoor positioning and tracking systems

Indoor positioning has attracted considerable attention for decades due to the increasing demands for location based services. In the past years, although numerous methods have been proposed for indoor positioning, it is still challenging to find a convincing solution that combines high positioning accuracy and ease of deployment. Radio-based indoor positioning has emerged as a dominant method due to its ubiquitousness, especially for WiFi. RSSI (Received Signal Strength Indicator) has been investigated in the area of indoor positioning for decades. However, it is prone to multipath propagation and hence fingerprinting has become the most commonly used method for indoor positioning using RSSI. The drawback of fingerprinting is that it requires intensive labour efforts to calibrate the radio map prior to experiments, which makes the deployment of the positioning system very time consuming. Using time information as another way for radio-based indoor positioning is challenged by time synchronization among anchor nodes and timestamp accuracy. Besides radio-based positioning methods, intensive research has been conducted to make use of inertial sensors for indoor tracking due to the fast developments of smartphones. However, these methods are normally prone to accumulative errors and might not be available for some applications, such as passive positioning. This thesis focuses on network-based indoor positioning and tracking systems, mainly for passive positioning, which does not require the participation of targets in the positioning process. To achieve high positioning accuracy, we work on some information of radio signals from physical-layer processing, such as timestamps and channel information. The contributions in this thesis can be divided into two parts: time-based positioning and channel information based positioning. First, for time-based indoor positioning (especially for narrow-band signals), we address challenges for compensating synchronization offsets among anchor nodes, designing timestamps with high resolution, and developing accurate positioning methods. Second, we work on range-based positioning methods with channel information to passively locate and track WiFi targets. Targeting less efforts for deployment, we work on range-based methods, which require much less calibration efforts than fingerprinting. By designing some novel enhanced methods for both ranging and positioning (including trilateration for stationary targets and particle filter for mobile targets), we are able to locate WiFi targets with high accuracy solely relying on radio signals and our proposed enhanced particle filter significantly outperforms the other commonly used range-based positioning algorithms, e.g., a traditional particle filter, extended Kalman filter and trilateration algorithms. In addition to using radio signals for passive positioning, we propose a second enhanced particle filter for active positioning to fuse inertial sensor and channel information to track indoor targets, which achieves higher tracking accuracy than tracking methods solely relying on either radio signals or inertial sensors.

Sural nerve conduction studies using ultrasound-guided needle positioning: Influence of age and recording location.

INTRODUCTION The aim of this study was to compare orthodromic sural nerve conduction study (NCS) results using ultrasound-guided needle positioning (USNP) to surface electrode recordings. METHODS 51 healthy subjects aged 24 - 80 years, divided into 5 age groups, were examined. Electrical stimuli were applied behind the lateral malleolus. Sensory nerve action potentials (SNAPs) were recorded 8 and 15 cm proximally with surface and needle electrodes. RESULTS Mean SNAP amplitudes in µV (surface/needle electrodes) averaged 12.7 (SD 7.6)/40.6 (SD 20.8), P<0.001, for subjects aged 20-29 years, and 5.0 (SD 2.4)/19.8 (SD 9.8), P<0.01, for subjects aged > 60 years. SNAP amplitudes were smaller at the proximal recording location. DISCUSSION NCS using USNP yield higher amplitude responses than surface electrodes in all age groups at all recording sites. SNAP amplitudes are smaller at proximal recording locations due to sural nerve branching. This article is protected by copyright. All rights reserved.

Static GPS measurements and elevation model in the hinterland of Neumayer

As part of the CryoSat Cal/Val activities and the pre-site survey for an ice core drilling contributing to the International Partnerships in Ice Core Sciences (IPICS), ground based kinematic GPS measurements were conducted in early 2007 in the vicinity of the German overwintering station Neumayer (8.25° W and 70.65° S). The investigated area comprises the regions of the ice tongues Halvfarryggen and Søråsen, which rise from the Ekströmisen to a maximum of about 760 m surface elevation, and have an areal extent of about 100 km x 50 km each. Available digital elevation models (DEMs) from radar altimetry and the Antarctic Digital Database show elevation differences of up to hundreds of meters in this region, which necessitated an accurate survey of the conditions on-site. An improved DEM of the Ekströmisen surroundings is derived by a combination of highly accurate ground based GPS measurements, satellite derived laser altimetry data (ICESat), airborne radar altimetry (ARA), and radio echo sounding (RES). The DEM presented here achieves a vertical accuracy of about 1.3 m and can be used for improved ice dynamic modeling and mass balance studies.

Ice velocities of Nordenskiöldbreen glacier, Svalbard

Precise measurements of ice-flow velocities are necessary for a proper understanding of the dynamics of glaciers and their response to climate change. We use stand-alone single-frequency GPS receivers for this purpose. They are designed to operate unattended for 1-3 years, allowing uninterrupted measurements for long periods with hourly temporal resolution. We present the system and illustrate its functioning using data from 9 GPS receivers deployed on Nordenskiöldbreen, Svalbard, for the period 2006-2009. The accuracy of the receivers is 1.62 m based on the standard deviation in the average location of a stationary reference station (NBRef). Both the location of NBRef and the observed flow velocities agree within one standard deviation with DGPS measurements. Periodicity (6, 8, 12, 24 h) in the NBRef data is largely explained by the atmospheric, mainly ionospheric, influence on the GPS signal. A (weighed) running-average on the observed locations significantly reduces the standard deviation and removes high frequency periodicities, but also reduces the temporal resolution. Results show annual average velocities varying between 40 and 55 m/yr at stations on the central flow-line. On weekly to monthly time-scales we observe a peak in the flow velocities (from 60 to 90 m/yr) at the beginning of July related to increased melt-rates. No significant lag is observed between the timing of the maximum speed between different stations. This is likely due to the limited temporal resolution after averaging in combination with the relatively small distance (max. ±13 km) between the stations.