Human Astrocytes Transfer Aggregated Alpha-Synuclein via Tunneling Nanotubes.

Many lines of evidence suggest that the Parkinson's disease (PD)-related protein α-synuclein (α-SYN) can propagate from cell to cell in a prion-like manner. However, the cellular mechanisms behind the spreading remain elusive. Here, we show that human astrocytes derived from embryonic stem cells actively transfer aggregated α-SYN to nearby astrocytes via direct contact and tunneling nanotubes (TNTs). Failure in the astrocytes' lysosomal digestion of excess α-SYN oligomers results in α-SYN deposits in the trans-Golgi network followed by endoplasmic reticulum swelling and mitochondrial disturbances. The stressed astrocytes respond by conspicuously sending out TNTs, enabling intercellular transfer of α-SYN to healthy astrocytes, which in return deliver mitochondria, indicating a TNT-mediated rescue mechanism. Using a pharmacological approach to inhibit TNT formation, we abolished the transfer of both α-SYN and mitochondria. Together, our results highlight the role of astrocytes in α-SYN cell-to-cell transfer, identifying possible pathophysiological events in the PD brain that could be of therapeutic relevance.SIGNIFICANCE STATEMENT Astrocytes are the major cell type in the brain, yet their role in Parkinson's disease progression remains elusive. Here, we show that human astrocytes actively transfer aggregated α-synuclein (α-SYN) to healthy astrocytes via direct contact and tunneling nanotubes (TNTs), rather than degrade it. The astrocytes engulf large amounts of oligomeric α-SYN that are subsequently stored in the trans-Golgi network region. The accumulation of α-SYN in the astrocytes affects their lysosomal machinery and induces mitochondrial damage. The stressed astrocytes respond by sending out TNTs, enabling intercellular transfer of α-SYN to healthy astrocytes. Our findings highlight an unexpected role of astrocytes in the propagation of α-SYN pathology via TNTs, revealing astrocytes as a potential target for therapeutic intervention

High-Density Microwell Chip for Culture and Analysis of Stem Cells

With recent findings on the role of reprogramming factors on stem cells, in vitro screening assays for studying (de)-differentiation is of great interest. We developed a miniaturized stem cell screening chip that is easily accessible and provides means of rapidly studying thousands of individual stem/progenitor cell samples, using low reagent volumes. For example, screening of 700,000 substances would take less than two days, using this platform combined with a conventional bio-imaging system. The microwell chip has standard slide format and consists of 672 wells in total. Each well holds 500 nl, a volume small enough to drastically decrease reagent costs but large enough to allow utilization of standard laboratory equipment. Results presented here include weeklong culturing and differentiation assays of mouse embryonic stem cells, mouse adult neural stem cells, and human embryonic stem cells. The possibility to either maintain the cells as stem/progenitor cells or to study cell differentiation of stem/progenitor cells over time is demonstrated. Clonality is critical for stem cell research, and was accomplished in the microwell chips by isolation and clonal analysis of single mouse embryonic stem cells using flow cytometric cell-sorting. Protocols for practical handling of the microwell chips are presented, describing a rapid and user-friendly method for the simultaneous study of thousands of stem cell cultures in small microwells. This microwell chip has high potential for a wide range of applications, for example directed differentiation assays and screening of reprogramming factors, opening up considerable opportunities in the stem cell field

Surface Covering of Downed Logs: Drivers of a Neglected Process in Dead Wood Ecology

Many species use coarse woody debris (CWD) and are disadvantaged by the forestry-induced loss of this resource. A neglected process affecting CWD is the covering of the surfaces of downed logs caused by sinking into the ground (increasing soil contact, mostly covering the underside of the log), and dense overgrowth by ground vegetation. Such cover is likely to profoundly influence the quality and accessibility of CWD for wood-inhabiting organisms, but the factors affecting covering are largely unknown. In a five-year experiment we determined predictors of covering rate of fresh logs in boreal forests and clear-cuts. Logs with branches were little covered because they had low longitudinal ground contact. For branchless logs, longitudinal ground contact was most strongly related to estimated peat depth (positive relation). The strongest predictor for total cover of branchless logs was longitudinal ground contact. To evaluate the effect on cover of factors other than longitudinal ground contact, we separately analyzed data from only those log sections that were in contact with the ground. Four factors were prominent predictors of percentage cover of such log sections: estimated peat depth, canopy shade (both increasing cover), potential solar radiation calculated from slope and slope aspect, and diameter of the log (both reducing cover). Peat increased cover directly through its low resistance, which allowed logs to sink and soil contact to increase. High moisture and low temperatures in pole-ward facing slopes and under a canopy favor peat formation through lowered decomposition and enhanced growth of peat-forming mosses, which also proved to rapidly overgrow logs. We found that in some boreal forests, peat and fast-growing mosses can rapidly cover logs lying on the ground. When actively introducing CWD for conservation purposes, we recommend that such rapid covering is avoided, thereby most likely improving the CWD's longevity as habitat for many species

Konkurrenssituationen på den svenska bankmarknaden

Validerat; 20101217 (root

UWB-based wireless sensor network with medical application

This master thesis aims to develop a prototype of a wireless sensor network (WSN) using ultra wideband (UWB) radio and communication. The WSN consists of five sensor nodes and one sink which is connected to an Android smartphone. The smartphone acts as a sensor data management unit and has the ability to display sensor measurements. The sensor nodes include the sensors of an inertial measurement unit, an electrocardiogram (ECG) electrode set, a temperature sensor, a humidity sensor, and three ultrasonic sensors, and they are responsible for making measurements, sending the measurements to, and forwarding the measurements from other sensor nodes to the destination. The sink node receives the measurements from the sensor nodes, and the measurements are displayed on the smartphone. The sensor nodes and the sink are equipped with DecaWave's DWM1000 UWB transceiver which is compliant with the IEEE 802.15.4-2011 communication standard and enables the UWB communications, and a microcontroller, ATmega328, that handles sensor data reading and transmission. Due to UWB pulses having high time resolution, a location-based routing protocol based on time of flight distance estimates is implemented. A prototype of a UWB-based WSN has been developed, tested and evaluated. The resulting prototype can operate in a peer-to-peer topology with multi-hop capabilities. The results of the evaluation show that lower data rate, lower center frequency and wider bandwidth increases radio range and a longer preamble sequence increases ranging accuracy. This comes at the cost of increased time of channel occupation and power consumption. From this thesis project it is indicated that UWB radio is a good choice for short-distance radio communication applications such as WSNs. The measurement errors in range estimates can be within 10 cm in line-of-sight. Networks compliant with the IEEE 802.15.4-2011 communication standard should have low throughput requirements as channel access mechanisms and functions related to reliable data transfers introduce latency

Miljökrav och konkurrenskraft i primäraluminiumbranschen

Validerat; 20101217 (root

UWB-based wireless sensor network with medical application

This master thesis aims to develop a prototype of a wireless sensor network (WSN) using ultra wideband (UWB) radio and communication. The WSN consists of five sensor nodes and one sink which is connected to an Android smartphone. The smartphone acts as a sensor data management unit and has the ability to display sensor measurements. The sensor nodes include the sensors of an inertial measurement unit, an electrocardiogram (ECG) electrode set, a temperature sensor, a humidity sensor, and three ultrasonic sensors, and they are responsible for making measurements, sending the measurements to, and forwarding the measurements from other sensor nodes to the destination. The sink node receives the measurements from the sensor nodes, and the measurements are displayed on the smartphone. The sensor nodes and the sink are equipped with DecaWave's DWM1000 UWB transceiver which is compliant with the IEEE 802.15.4-2011 communication standard and enables the UWB communications, and a microcontroller, ATmega328, that handles sensor data reading and transmission. Due to UWB pulses having high time resolution, a location-based routing protocol based on time of flight distance estimates is implemented. A prototype of a UWB-based WSN has been developed, tested and evaluated. The resulting prototype can operate in a peer-to-peer topology with multi-hop capabilities. The results of the evaluation show that lower data rate, lower center frequency and wider bandwidth increases radio range and a longer preamble sequence increases ranging accuracy. This comes at the cost of increased time of channel occupation and power consumption. From this thesis project it is indicated that UWB radio is a good choice for short-distance radio communication applications such as WSNs. The measurement errors in range estimates can be within 10 cm in line-of-sight. Networks compliant with the IEEE 802.15.4-2011 communication standard should have low throughput requirements as channel access mechanisms and functions related to reliable data transfers introduce latency

Design principles for intuitivity in complex systems

Det kan vara svårt att uppnå intuitivitet i komplexa system. Denna studie syftar till att identifieravilka designprinciper som främjar intuitivitet i komplexa system samt rekommendationer om hursystemutvecklare bör arbeta i utvecklingsprocessen för att göra systemen intuitiva. Teori somrelaterar till komplexa system, användbarhet och intuition har undersökts. Etableradedesignprinciper för gränssnittsdesign har utvärderats för att identifiera vilka designprinciper somblir centrala för komplexa system. En kvalitativ studie har använts för att utforska och identifieraförbättringsområden i utvecklingsprocessen av ett intuitivt system. De identifieradedesignprinciperna för intuitivitet i komplexa system presenteras och användes för att gerekommendationer. Detta baserades på de förbättringsområden som upptäcktes under desemistrukturerade intervjuer med ett utvalt företaget. Resultatet jämförs med teorikapitlet omintuition. Slutligen presenteras studiens slutsatser och förslag till vidare studier.It can be difficult to achieve intuitiveness in complex systems. This study aims to identify whichdesign principles promotes intuitiveness in complex systems as well as recommendations ofhow developers can work in developing these systems. Literature of complex systems, usabilityand intuition have been surveyed. Established principles of design have been evaluated toidentify which principles relates to complex systems. A qualitative study was used to exploreand identify areas of improvement in the development of an intuitive system. The identifiedprinciples for intuitiveness in complex systems are presented and then used to providerecommendations for the areas of improvement identified in interviews. The results arecompared with theory on intuition. Lastly, the concluding remarks and suggestions for furtherstudies are presented