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Seit 2015 hat sich die mechanische Thrombektomie mit dem StentRetriever als kausale Therapie des ischämischen Schlaganfalls etabliert. Ein besonderer StentRetriever ist der manuell expandierbare Tigertriever. Diesen haben wir in unserer retrospektiven Studie hinsichtlich Sicherheit und Effektivität hin untersucht. Am Universitätsklinikum Knappschaftskrankenhaus Bochum wurden in dem Zeitraum von Januar 2018 bis Januar 2020 insgesamt 68 mechanische Thrombektomien mit dem Tigertriever durchgeführt. Eine erfolgreiche Rekanalisation konnte in 85,3 % der Fälle erreicht werden. Mit einem guten klinischen Outcome (mRS

Soil health and biodiversity are fundamental features for both organic production systems and of an agroecological approach. Soil health and functional biodiversity are effects of the dynamics imposed by environmental factors and crop management, and are closely related to the dynamics in soil organic matter. Within the framework of CORE Organic project ”GreenResilient”, crop rotations for “business as usual” (BAU) and innovative (INN) organic greenhouse cropping systems were designed according to local preconditions in the five countries hosting the experimental sites: Belgium (BE), Switzerland (CH), Denmark (DK), France (FR) and Italy (IT). The choice and order of crops within the various BAU and INN systems differed between countries. Soil microbial activity and biodiversity were analysed using fluorescein diacetate activity (FDA) and metagenomic analysis (Illumina MiSeq) of fungi (ITS) and bacteria (16S) at three key events, namely start, midterm and end of the two-year crop rotation. Samples were collected from three blocks (in some cases four) at a density of three replicates (resulting in 9 or 12 replicate samples per treatment). Specific disease suppressiveness was evaluated with respect to Fusarium oxysporum f.sp. lycopersici (FOL). There was no general trend with respect to microbial activity for the different cropping systems. Interestingly, the microbial activity initially rose in many of the systems (midterm) but decreased to a lower level mostly similar or insignificantly higher to the starting point. A general significant decrease in microbial activity was found at all cropping systems in IT from the start to the end of the experiment. Likewise, soil bacterial and fungal alpha diversity varied between the different sampling incidents with respect to both species richness and evenness (Chao1 index, Shannon diversity index). Interestingly, a strong shift towards richer fungal community was found for the CH-BAU systems as compared to the CH-INN systems over time (based on % change from initial sample). CH-INN systems displayed a richer bacterial community than CH-BAU systems. Similar observations were found sporadically in other systems, displaying changes in beta-diversity between systems over time. Shifts in relative abundance was found for some phyla over time within systems, but no general trend applying to all BAU or INN was registered. A presence of several types of fungal pathogens were observed in all countries, independent of production system. Microbial activity did not conclusively explain variations in microbial diversity for fungi or bacteria. No differences were found in plant performance when assessing specific suppressiveness towards FOL. As plant performance in control samples was much better than those detected in fresh soil samples, with or without amendment of FOL, the general build-up of pathogenic organisms during the crop rotations might mask direct effects

Paraneoplastic neurological syndromes (PNS) are often characterized by the presence of antineuronal antibodies in patient serum or cerebrospinal fluid. The detection of antineuronal antibodies has proven to be a useful tool in PNS diagnosis and the search for an underlying tumor. Here, we describe three patients with autoantibodies to several epitopes of the axon initial segment protein tripartite motif 46 (TRIM46). We show that anti‐TRIM46 antibodies are easy to detect in routine immunohistochemistry screening and can be confirmed by western blotting and cell‐based assay. Anti‐TRIM46 antibodies can occur in patients with diverse neurological syndromes and are associated with small‐cell lung carcinoma.

Summary Neuronal dendrites are characterized by an anti-parallel microtubule organization. The mixed oriented microtubules promote dendrite development and facilitate polarized cargo trafficking; however, the mechanism that regulates dendritic microtubule organization is still unclear. Here, we found that the kinesin-14 motor KIFC3 is important for organizing dendritic microtubules and to control dendrite development. The kinesin-14 motor proteins (Drosophila melanogaster Ncd, Saccharomyces cerevisiae Kar3, Saccharomyces pombe Pkl1, and Xenopus laevis XCTK2) are characterized by a C-terminal motor domain and are well described to organize the spindle microtubule during mitosis using an additional microtubule binding site in the N terminus [1, 2, 3, 4]. In mammals, there are three kinesin-14 members, KIFC1, KIFC2, and KIFC3. It was recently shown that KIFC1 is important for organizing axonal microtubules in neurons, a process that depends on the two microtubule-interacting domains [5]. Unlike KIFC1, KIFC2 and KIFC3 lack the N-terminal microtubule binding domain and only have one microtubule-interacting domain, the motor domain [6, 7]. Thus, in order to regulate microtubule-microtubule crosslinking or sliding, KIFC2 and KIFC3 need to interact with additional microtubule binding proteins to connect two microtubules. We found that KIFC3 has a dendrite-specific distribution and interacts with microtubule minus-end binding protein CAMSAP2. Depletion of KIFC3 or CAMSAP2 results in increased microtubule dynamics during dendritic development. We propose a model in which CAMSAP2 anchors KIFC3 at microtubule minus ends and immobilizes microtubule arrays in dendrites., Graphical Abstract, Highlights • KIFC3 localizes to dendrites and controls dendrite branching • KIFC3 interacts with minus-end binding protein CAMSAP2 • CAMSAP2 and KIFC3 immobilize microtubule arrays in dendrites, Neuronal dendrites are characterized by an anti-parallel microtubule organization. The mechanism that regulates dendritic microtubule organization is still unclear. Cao et al. demonstrate that the microtubule minus-end binding protein CAMSAP2 and kinesin-14 motor KIFC3 work together to organize dendritic microtubules and control dendrite branching.

Additional file 1: Fig. S1. Bicd2 is expressed by RGPs and post-mitotic neurons in the cortex of control mice, but abolished after cell-type-specific depletion of BICD2 in cKO mice. a. Coronal cryo-sections of E17.5 brains from cell-type-specific conditional Bicd2 KO and control mice - Bicd2fl/fl;Nex-Cre+/− (=Nex-KO), Bicd2fl/fl;Emx1-Cre+/− (=Emx1-KO) and Bicd2fl/fl;Cre−/− (=Nex-WT/Emx1-WT) respectively - were stained against BICD2. Scale bars are 500 μm. b. Coronal cryo-sections of E17.5 cortices from Nex-KO, Emx1-KO and Nex-WT/Emx1-WT mice were stained against BICD2 (red). DAPI is shown in blue. Scale bars are 100 μm. c. Zooms from BICD2 staining shown in (b). d + e. Western Blots (WBs) of whole E17.5 cortex lysates from Nex-KO, Emx1-KO, and their control littermates Nex-WT and Emx1-WT. WBs were stained with commercial anti-BICD2 (atlas), home-made anti- BICD2 (#2294), home-made anti-BICD1/2(#2293), anti-actin or anti-tubulin. M = marker. Molecular weight of the marker bands are indicated on the left in kDa. (N = 3). f. Radial diameter of the cortex from ventricular to pial surface of Nex-WT, Nex-KO, Emx1-WT and Emx1-KO mice (in μm) (N = 16–17). *** p

Summary The motor protein kinesin-1 plays an important role in polarized sorting of transport vesicles to the axon. However, the mechanism by which the axonal entry of kinesin-1-dependent cargo transport is regulated remains unclear. Microtubule-associated protein MAP7 (ensconsin in Drosophila) is an essential kinesin-1 cofactor and promotes kinesin-1 recruitment to microtubules. Here, we found that MAP7 family member MAP7D2 concentrates at the proximal axon, where it overlaps with the axon initial segment and interacts with kinesin-1. Depletion of MAP7D2 results in reduced axonal cargo entry and defects in axon development and neuronal migration. We propose a model in which MAP7D2 in the proximal axon locally promotes kinesin-1-mediated cargo entry into the axon., Graphical Abstract, Highlights • The microtubule-binding domain of MAP7D2 targets the proximal axon • MAP7D2 is required for axon development • MAP7D2 associates with all three kinesin-1 family members • MAP7D2 promotes kinesin-1-mediated cargo transport in axons, Kinesin-1 is well known for transporting vesicles and organelles into to the axon. Pan et al. show that MAP7D2 concentrates at the proximal axon, regulates kinesin-1 activity, and locally promotes kinesin-1-mediated cargo trafficking into axons. Specific microtubule-associated proteins (MAPs) that locally control motor activities is an emerging concept.

Establishment of neuronal polarity depends on local microtubule (MT) reorganization. The endoplasmic reticulum (ER) consists of cisternae and tubules and, like MTs, forms an extensive network throughout the entire cell. How the two networks interact and control neuronal development is an outstanding question. Here we show that the interplay between MTs and the ER is essential for neuronal polarity. ER tubules localize within the axon, whereas ER cisternae are retained in the somatodendritic domain. MTs are essential for axonal ER tubule stabilization, and, reciprocally, the ER is required for stabilizing and organizing axonal MTs. Recruitment of ER tubules into one minor neurite initiates axon formation, whereas ER retention in the perinuclear area or disruption of ER tubules prevent neuronal polarization. The ER-shaping protein P180, present in axonal ER tubules, controls axon specification by regulating local MT remodeling. We propose a model in which feedback-driven regulation between the ER and MTs instructs neuronal polarity. Farías et al. report that the localization of the endoplasmic reticulum (ER) in the axon is controlled by the interaction between ER-shaping proteins and the microtubule cytoskeleton. Local ER and microtubule crosstalk promotes ER tubule-microtubule stabilization and drives neuronal polarity.

The actin cytoskeleton is essential for many fundamental biological processes, but tools for directly manipulating actin dynamics are limited to cell-permeable drugs that preclude single-cell perturbations. Here we describe DeActs, genetically encoded actin-modifying polypeptides, which effectively induce actin disassembly in eukaryotic cells. We demonstrate that DeActs are universal tools for studying the actin cytoskeleton in single cells in culture, tissues, and multicellular organisms including various neurodevelopmental model systems.