Dynein activating adaptor BICD2 controls radial migration of upper-layer cortical neurons in vivo

For the proper organization of the six-layered mammalian neocortex it is required that neurons migrate radially from their place of birth towards their designated destination. The molecular machinery underlying this neuronal migration is still poorly understood. The dynein-adaptor protein BICD2 is associated with a spectrum of human neurologi

Antibodies to TRIM46 are associated with paraneoplastic neurological syndromes.

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

Lipid-Iron Nanoparticle with a Cell Stress Release Mechanism Combined with a Local Alternating Magnetic Field Enables Site-Activated Drug Release

Simple Summary A novel active release system magnetic sphingomyelin-containing liposome encapsulated with indocyanine green, fluorescent marker, or the anticancer drug cisplatin was evaluated. The liposomal sphingomyelin is a target for the sphingomyelinase enzyme, which is released by stressed cells. Thus, sphingomyelin containing liposomes behave as a sensitizer for biological stress situations. In addition, the liposomes were engineered by adding paramagnetic beads to act as a receiver of outside given magnetic energy. The enzymatic activity towards liposomes and destruction caused by the applied magnetic field caused the release of the content from the liposomes. By using these novel liposomes, we could improve the drug release feature of liposomes. The improved targeting and drug-release were shown in vitro and the orthotopic tongue cancer model in mice optical imaging. The increased delivery of cisplatin prolonged the survival of the targeted delivery group versus free cisplatin. Most available cancer chemotherapies are based on systemically administered small organic molecules, and only a tiny fraction of the drug reaches the disease site. The approach causes significant side effects and limits the outcome of the therapy. Targeted drug delivery provides an alternative to improve the situation. However, due to the poor release characteristics of the delivery systems, limitations remain. This report presents a new approach to address the challenges using two fundamentally different mechanisms to trigger the release from the liposomal carrier. We use an endogenous disease marker, an enzyme, combined with an externally applied magnetic field, to open the delivery system at the correct time only in the disease site. This site-activated release system is a novel two-switch nanomachine that can be regulated by a cell stress-induced enzyme at the cellular level and be remotely controlled using an applied magnetic field. We tested the concept using sphingomyelin-containing liposomes encapsulated with indocyanine green, fluorescent marker, or the anticancer drug cisplatin. We engineered the liposomes by adding paramagnetic beads to act as a receiver of outside magnetic energy. The developed multifunctional liposomes were characterized in vitro in leakage studies and cell internalization studies. The release system was further studied in vivo in imaging and therapy trials using a squamous cell carcinoma tumor in the mouse as a disease model. In vitro studies showed an increased release of loaded material when stress-related enzyme and magnetic field was applied to the carrier liposomes. The theranostic liposomes were found in tumors, and the improved therapeutic effect was shown in the survival studies.Peer reviewe

Galaxy bulges and their massive black holes: a review

With references to both key and oft-forgotten pioneering works, this article starts by presenting a review into how we came to believe in the existence of massive black holes at the centres of galaxies. It then presents the historical development of the near-linear (black hole)-(host spheroid) mass relation, before explaining why this has recently been dramatically revised. Past disagreement over the slope of the (black hole)-(velocity dispersion) relation is also explained, and the discovery of sub-structure within the (black hole)-(velocity dispersion) diagram is discussed. As the search for the fundamental connection between massive black holes and their host galaxies continues, the competing array of additional black hole mass scaling relations for samples of predominantly inactive galaxies are presented.Comment: Invited (15 Feb. 2014) review article (submitted 16 Nov. 2014). 590 references, 9 figures, 25 pages in emulateApJ format. To appear in "Galactic Bulges", E. Laurikainen, R.F. Peletier, and D.A. Gadotti (eds.), Springer Publishin

Joint Observation of the Galactic Center with MAGIC and CTA-LST-1

MAGIC is a system of two Imaging Atmospheric Cherenkov Telescopes (IACTs), designed to detect very-high-energy gamma rays, and is operating in stereoscopic mode since 2009 at the Observatorio del Roque de Los Muchachos in La Palma, Spain. In 2018, the prototype IACT of the Large-Sized Telescope (LST-1) for the Cherenkov Telescope Array, a next-generation ground-based gamma-ray observatory, was inaugurated at the same site, at a distance of approximately 100 meters from the MAGIC telescopes. Using joint observations between MAGIC and LST-1, we developed a dedicated analysis pipeline and established the threefold telescope system via software, achieving the highest sensitivity in the northern hemisphere. Based on this enhanced performance, MAGIC and LST-1 have been jointly and regularly observing the Galactic Center, a region of paramount importance and complexity for IACTs. In particular, the gamma-ray emission from the dynamical center of the Milky Way is under debate. Although previous measurements suggested that a supermassive black hole Sagittarius A* plays a primary role, its radiation mechanism remains unclear, mainly due to limited angular resolution and sensitivity. The enhanced sensitivity in our novel approach is thus expected to provide new insights into the question. We here present the current status of the data analysis for the Galactic Center joint MAGIC and LST-1 observations

MAGIC and H.E.S.S. detect VHE gamma rays from the blazar OT081 for the first time: a deep multiwavelength study

https://pos.sissa.it/395/815/pdfPublished versio

Mechanische Thrombektomie bei akuten Schlaganfällen mithilfe eines manuell expandierbaren Stentretrievers (Tigertriever)

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 <3) wurden 39,3 % der Patienten und Patientinnen entlassen. Subarachnoidalblutungen traten in 11,5 % der Fälle auf. Insgesamt zeigte unsere Auswertung, dass es sich bei dem Tigertriever um ein erfolgsversprechendes Device zur mechanischen Thrombektomie handelt, welches insbesondere dann noch gute Ergebnisse liefert, wenn andere Devices weniger Erfolg zeigten

Insights in interaction between soil biodiversity and root disease suppression in organic production systems - preliminary results

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 effect

Dynein activating adaptor BICD2 controls radial migration of upper-layer cortical neurons in vivo

For the proper organization of the six-layered mammalian neocortex it is required that neurons migrate radially from their place of birth towards their designated destination. The molecular machinery underlying this neuronal migration is still poorly understood. The dynein-adaptor protein BICD2 is associated with a spectrum of human neurological diseases, including malformations of cortical development. Previous studies have shown that knockdown of BICD2 interferes with interkinetic nuclear migration in radial glial progenitor cells, and that Bicd2-deficient mice display an altered laminar organization of the cerebellum and the neocortex. However, the precise in vivo role of BICD2 in neocortical development remains unclear. By comparing cell-type specific conditional Bicd2 knock-out mice, we found that radial migration in the cortex predominantly depends on BICD2 function in post-mitotic neurons. Neuron-specific Bicd2 cKO mice showed severely impaired radial migration of late-born upper-layer neurons. BICD2 depletion in cortical neurons interfered with proper Golgi organization, and neuronal maturation and survival of cortical plate neurons. Single-neuron labeling revealed a specific role of BICD2 in bipolar locomotion. Rescue experiments with wildtype and disease-related mutant BICD2 constructs revealed that a point-mutation in the RAB6/RANBP2-binding-domain, associated with cortical malformation in patients, fails to restore proper cortical neuron migration. Together, these findings demonstrate a novel, cell-intrinsic role of BICD2 in cortical neuron migration in vivo and provide new insights into BICD2-dependent dynein-mediated functions during cortical development