Functional and Molecular Properties of DYT-SGCE Myoclonus-Dystonia Patient-Derived Striatal Medium Spiny Neurons

Myoclonus-dystonia (DYT-SGCE, formerly DYT11) is characterized by alcohol-sensitive, myoclonic-like appearance of fast dystonic movements. It is caused by mutations in the SGCE gene encoding ε-sarcoglycan leading to a dysfunction of this transmembrane protein, alterations in the cerebello-thalamic pathway and impaired striatal plasticity. To elucidate underlying pathogenic mechanisms, we investigated induced pluripotent stem cell (iPSC)-derived striatal medium spiny neurons (MSNs) from two myoclonus-dystonia patients carrying a heterozygous mutation in the SGCE gene (c.298T>G and c.304C>T with protein changes W100G and R102X) in comparison to two matched healthy control lines. Calcium imaging showed significantly elevated basal intracellular Ca²⁺ content and lower frequency of spontaneous Ca²⁺ signals in SGCE MSNs. Blocking of voltage-gated Ca²⁺ channels by verapamil was less efficient in suppressing KCl-induced Ca²⁺ peaks of SGCE MSNs. Ca²⁺ amplitudes upon glycine and acetylcholine applications were increased in SGCE MSNs, but not after GABA or glutamate applications. Expression of voltage-gated Ca²⁺ channels and most ionotropic receptor subunits was not altered. SGCE MSNs showed significantly reduced GABAergic synaptic density. Whole-cell patch-clamp recordings displayed elevated amplitudes of miniature postsynaptic currents and action potentials in SGCE MSNs. Our data contribute to a better understanding of the pathophysiology and the development of novel therapeutic strategies for myoclonus-dystonia.     

Segregation and stability of a binary granular heap

We measure stability of two-dimensional granular mixtures in a rotating drum and relate grain configurations to stability. We use two types of grains which differ in both size and shape, with the larger grains reaching a larger average angle before an avalanche. In our mixtures, the smaller grains cluster near the center of the drum, while the larger grains remain near the outer edge, a pattern suggesting that grain size rather than avalanche angle determines the segregation behavior. One consequence of the size segregation is that the smaller grains heavily influence the stability of the heap. We find that the maximum angle of stability is a non-linear function of composition, changing particularly rapidly when small grains are first added to a homogeneous pile of large grains. We conclude that the grain configuration within the central portion of the heap plays a prominent role in stability. This work was supported in part by the National Science Foundation’s Research Experience for Undergraduates Program under PHY-0243904.     

HELIOS, a nadir-looking sea ice monitoring camera

We present the prototype of a simplified photogrammetric system (HELicopter-borne Ice Observation System, HELIOS) and demonstrate how it can be used to document ground-based and airborne sea ice surveys. The aerial unit consists of a nadir-looking digital camera mounted on a gimbal, a GPS receiver and a computer. It is of low-cost and weight and is designed such that it withstands low temperatures, operates autonomously and fits to any standard helicopter skid. The accuracy of the georeferenced photographs is about ± 15 m for a flight height of 85 m, flight speed of 130 km/h and a GPS sampling rate of 4 Hz. Systematic errors arise from the GPS-based determination of the camera position, the pointing accuracy of the gimbal, and the camera alignment in flight direction. Because most sea ice mapping projects require lesser accuracies than conventional mapping standards (e.g. ≤ 0.5 m for a map scale of 1:600, ASPRS (1994)), HELIOS offers a broad range of applications. This includes the photogrammetric documentation of experimental sites as well as the verification of satellite-, and model-based estimates of sea ice and snow cover properties. Images taken simultaneously with other airborne observations provide a valuable tool to assess the accuracy of those measurements.     

Isolation of new bacterial species from drinking water biofilms and proof of their in situ dominance with highly specific 16S rRNA probes

A polyphasic approach involving cultivation, direct viable counts, rRNA-based phylogenetic classification, and in situ probing was applied for the characterization of the dominant microbial population in a municipal drinking water distribution system. A total of 234 bacterial strains cultivated on R2A medium were screened for bacteria affiliated with the in situ dominating beta subclass of Proteobacteria. The isolates were grouped according to common features of their cell and colony morphologies, and eight representative strains were used for 16S rRNA sequencing and the development of a suite of strain-specific oligonucleotide probes. Phylogenetic analysis indicated that all of the isolates were hitherto unknown bacteria. Three of them, strains B4, B6, and B8, formed a separate cluster of closely related organisms within the beta 1 subclass of Proteobacteria. In situ probing revealed that (i) 67 to 72% of total bacteria, corresponding to more than 80% of beta-subclass bacteria, could be encompassed with the strain-specific probes and (ii) the dominating bacterial species were culturable on R2A medium. Additionally, two-thirds of the autochthonous drinking water population could be shown to be in a viable but nonculturable (VBNC) state by using a direct viable count approach. The comparison of isolation frequencies with the in situ abundances of the eight investigated strains revealed differences in their culturability, indicating variable ratios of culturable to VBNC cells among the strains. The further characterization of biofilms throughout the distribution network demonstrated strains B6 and B8 to be dominant bacterial strains in groundwater and distribution system biofilms. The other strains could be found at various frequencies in the different parts of the distribution system; several strains appeared exclusively in drinking water biofilms obtained from a house installation system.     

The prevalence of high-level exercise in the eating disorders: etiological implications

Among 145 patients treated with recombinant human growth hormone (GH), four developed sleep apnea (two obstructive, two mixed) associated with tonsillar and adenoidal hypertrophy in three. These four patients had no local risk factors predisposing to upper airway obstruction (i.e., frequent pharyngitis or sinusitis). Clinical and/or polysomnographic features of sleep apnea improved following cessation of GH therapy in one patient, and following tonsillectomy and adenoidectomy in all patients. The present observations indicate that, albeit rarely, obstructive and/or central sleep apnea may occur in children treated with GH. Polysomnography should be considered if symptoms of snoring, interrupted sleep, daytime somnolence-particularly if associated with tonsillar hypertrophy-appear in children during GH therapy.     

Flexible Fertigungssysteme als CIM-Bausteine zur Plattenkomplettbearbeitung im Durchlauf

Flexible manufacturing systems will provide medium and long-term advantages rather than short-term. It is easy to realize that complex systems of this kind can only be implemented by detailed planning and project management. A totally computer aided manufacturing system comprises all sectors from order via customer-specific production up to delivery. All staff members up to management are involved. CIM must consider the specific requirements of individual strategy or objective. This paper uses a complete board processing system for furniture production to illustrate the basic concept and realization of a CIM system as well as the advantages of flexible manufacturing.     

Genetic circuit building blocks for cellular computation,communications, and signal processing

In this paper, we review an emerging engineering discipline to programcell behaviors by embedding synthetic gene networks that performcomputation, communications, and signal processing. To accomplishthis goal, we begin with a genetic component library and a biocircuitdesign methodology for assembling these components into compoundcircuits. The main challenge in biocircuit design lies in selectingwell-matched genetic components that when coupled, reliably producethe desired behavior. We use simulation tools to guide circuitdesign, a process that consists of selecting the appropriatecomponents and genetically modifying existing components until thedesired behavior is achieved. In addition to such rational design, wealso employ directed evolution to optimize genetic circuitbehavior. Building on Nature's fundamental principle of evolution,this unique process directs cells to mutate their own DNA until theyfind gene network configurations that exhibit the desired systemcharacteristics. The integration of all the above capabilities infuture synthetic gene networks will enable cells to performsophisticated digital and analog computation, both asindividual entities and as part of larger cell communities. Thisengineering discipline and its associated tools will advance thecapabilities of genetic engineering, and allow us to harness cells fora myriad of applications not previously achievable.     

Modelling local distribution of an Arctic dwarf shrub indicates an important role for remote sensing of snow cover

Despite the intensive research effort directed at predicting the effects of climate change on plants in the Arctic, the impact of environmental change on species' distributions remains difficult to quantify. Predictive habitat distribution models provide a tool to predict the geographical distribution of a species based on the ecological gradients that determine it, and to estimate how the distribution of a species might respond to environmental change. Here, we present a model of the distribution of the dwarf shrub Dryas octopetala L. around the fjord Kongsfjorden, Svalbard. The model was built from field observations, an Advanced Space-borne Thermal Emission and Reflection Radiometer (ASTER) image, a GIS database containing environmental data at a spatial resolution of 20 m, and relied on generalized linear models (GLMs). We used a logistic GLM to predict the occurrence of the species and a Gaussian GLM to predict its abundance at the sites where it occurred. Temperature and topographical exposure and inclination of a site appeared to promote both the occurrence and the abundance of D. octopetala. The occurrence of the species was additionally negatively influenced by snow and water cover and topographical exposure towards the north, whereas the abundance of the species appeared lower on calciferous substrates. Validation of the model using independent data and the resulting distribution map showed that they successfully recover the distribution of D. octopetala in the study area (κ = 0.46, AUC = 0.81 for the logistic GLM [n = 200], r² = 0.29 for the Gaussian GLM [n = 36]). The results further highlight that models predicting the local distribution of plant species in an Arctic environment would greatly benefit from data on the distribution and duration of snow cover. Furthermore, such data are necessary to make quantitative estimates for the impact of changes in temperature and winter precipitation on the distribution of plants in the Arctic.