Differential neuronal vulnerability identifies IGF-2 as a protective factor in ALS

The fatal disease amyotrophic lateral sclerosis (ALS) is characterized by the loss of somatic motor neurons leading to muscle wasting and paralysis. However, motor neurons in the oculomotor nucleus, controlling eye movement, are for unknown reasons spared. We found that insulin-like growth factor 2 (IGF-2) was maintained in oculomotor neurons in ALS and thus could play a role in oculomotor resistance in this disease. We also showed that IGF-1 receptor (IGF-1R), which mediates survival pathways upon IGF binding, was highly expressed in oculomotor neurons and on extraocular muscle endplate. The addition of IGF-2 induced Akt phosphorylation, glycogen synthase kinase-3\u3b2 phosphorylation and \u3b2-catenin levels while protecting ALS patient motor neurons. IGF-2 also rescued motor neurons derived from spinal muscular atrophy (SMA) patients from degeneration. Finally, AAV9::IGF-2 delivery to muscles of SOD1G93A ALS mice extended life-span by 10%, while preserving motor neurons and inducing motor axon regeneration. Thus, our studies demonstrate that oculomotor-specific expression can be utilized to identify candidates that protect vulnerable motor neurons from degeneration

Microscopic origins of performance losses in highly efficient Cu In, Ga Se2 thin film solar cells

Thin film solar cells based on polycrystalline absorbers have reached very high conversion efficiencies of up to 23 25 . In order to elucidate the limiting factors that need to be overcome for even higher efficiency levels, it is essential to investigate microscopic origins of loss mechanisms in these devices. In the present work, a high efficiency 21 without anti reflection coating copper indium gallium diselenide CIGSe solar cell is characterized by means of a correlative microscopy approach and corroborated by means of photoluminescence spectroscopy. The values obtained by the experimental characterization are used as input parameters for two dimensional device simulations, for which a real microstructure was used. It can be shown that electrostatic potential and lifetime fluctuations exhibit no substantial impact on the device performance. In contrast, nonradiative recombination at random grain boundaries can be identified as a significant loss mechanism for CIGSe solar cells, even for devices at a very high performance leve

Preferred orientation, grain sizes and grain boundaries of chalcopyrite type thin films

Chalcopyrite type thin films CuInS2, CuInSe2, CuGaSe2, and Cu In,Ga Se2 in various completed solar cells were studied in cross section by means of electron backscatter diffraction EBSD . Valuable information on grain sizes, local grain orientations, film textures, and grain boundaries were extracted from the EBSD linescans and maps. The grain size distributions from the chalcopyrite type thin films can be represented well by lognormal distribution functions. The EBSD measurements on CuGaSe2 thin film reveal a lt;110 gt; fiber texture, in good agreement with x ray diffraction texture analysis performed on the same sample. The EBSD maps from all samples studied exhibit considerable twinning in the chalcopyrite type thin films. Indeed, the most frequent types of grain boundaries in these thin films are near amp; 931;3 60 lt;221 gt; and 71 lt;110 gt; twins. It is shown that rotational 180 lt;221 gt; twins which are symmetrically equivalent to 71 lt;110 gt; are more frequently found than anion or cation terminated 60 lt;221 gt; twin boundarie

Laser capture microscopy coupled with Smart-seq2 for precise spatial transcriptomic profiling.

Laser capture microscopy (LCM) coupled with global transcriptome profiling could enable precise analyses of cell populations without the need for tissue dissociation, but has so far required relatively large numbers of cells. Here we report a robust and highly efficient strategy for LCM coupled with full-length mRNA-sequencing (LCM-seq) developed for single-cell transcriptomics. Fixed cells are subjected to direct lysis without RNA extraction, which both simplifies the experimental procedures as well as lowers technical noise. We apply LCM-seq on neurons isolated from mouse tissues, human post-mortem tissues, and illustrate its utility down to single captured cells. Importantly, we demonstrate that LCM-seq can provide biological insight on highly similar neuronal populations, including motor neurons isolated from different levels of the mouse spinal cord, as well as human midbrain dopamine neurons of the substantia nigra compacta and the ventral tegmental area

Motor neurons with differential vulnerability to degeneration show distinct protein signatures in health and ALS

AbstractThe lethal disease amyotrophic lateral sclerosis (ALS) is characterized by the loss of somatic motor neurons. However, not all motor neurons are equally vulnerable to disease; certain groups are spared, including those in the oculomotor nucleus controlling eye movement. The reasons for this differential vulnerability remain unknown. Here we have identified a protein signature for resistant oculomotor motor neurons and vulnerable hypoglossal and spinal motor neurons in mouse and man and in health and ALS with the aim of understanding motor neuron resistance. Several proteins with implications for motor neuron resistance, including GABAA receptor α1, guanylate cyclase soluble subunit alpha-3 and parvalbumin were persistently expressed in oculomotor neurons in man and mouse. Vulnerable motor neurons displayed higher protein levels of dynein, peripherin and GABAA receptor α2, which play roles in retrograde transport and excitability, respectively. These were dynamically regulated during disease and thus could place motor neurons at an increased risk. From our analysis is it evident that oculomotor motor neurons have a distinct protein signature compared to vulnerable motor neurons in brain stem and spinal cord, which could in part explain their resistance to degeneration in ALS. Our comparison of human and mouse shows the relative conservation of signals across species and infers that transgenic SOD1G93A mice could be used to predict mechanisms of neuronal vulnerability in man

Data publication: Stabilization of nanoscale iron films by self-terminated electrodeposition in sulfate electrolyte

All RBS Data from measurements with both standard RBS as well as liquid cell RBS, including Simulation files in SIMNRA data forma

Advances in magneto-ionic materials and perspectives for their application

The possibility of tuning magnetic material properties by ionic means is exciting both for basic science and, especially in view of the excellentenergy efficiency and room temperature operation, for potential applications. In this perspective, we shortly introduce the functionality ofmagneto-ionic materials and focus on important recent advances in this field. We present a comparative overview of state-of-the-art magneto-ionic materials considering the achieved magnetoelectric voltage coefficients for magnetization and coercivity and the demonstrated timescales for magneto-ionic switching. Furthermore, the application perspectives of magneto-ionic materials in data storage and computing,magnetic actuation, and sensing are evaluated. Finally, we propose potential research directions to push this field forward and tackle thechallenges related to future application