Anti-inflammatory treatment induced regenerative oligodendrogenesis in parkinsonian mice

Introduction: The adult mammalian brain retains niches for neural stem cells (NSCs), which can generate glial and neuronal components of the brain tissue. However, it is barely established how chronic neuroinflammation, as it occurs in neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease, affects adult neurogenesis and, therefore, modulates the brain’s potential for self-regeneration. Methods: Neural stem cell culture techniques, intraventricular tumor necrosis factor (TNF)-a infusion and the 6-hydroxydopamine mouse model were used to investigate the influence of neuroinflammation on adult neurogenesis in the Parkinson’s disease background. Microscopic methods and behavioral tests were used to analyze samples. Results: Here, we demonstrate that differences in the chronicity of TNF-a application to cultured NSCs result in opposed effects on their proliferation. However, chronic TNF-a treatment, mimicking Parkinson’s disease associated neuroinflammation, shows detrimental effects on neural progenitor cell activity. Inversely, pharmacological inhibition of neuroinflammation in a 6-hydroxydopamine mouse model led to increased neural progenitor cell proliferation in the subventricular zone and neuroblast migration into the lesioned striatum. Four months after surgery, we measured improved Parkinson’s disease-associated behavior, which was correlated with long-term antiinflammatory treatment. But surprisingly, instead of newly generated striatal neurons, oligodendrogenesis in the striatum of treated mice was enhanced. Conclusions: We conclude that anti-inflammatory treatment, in a 6-hydroxydopamine mouse model for Parkinson’s disease, leads to activation of adult neural stem cells. These adult neural stem cells generate striatal oligodendrocytes. The higher numbers of newborn oligodendrocytes possibly contribute to axonal stability and function in this mouse model of Parkinson’s disease and thereby attenuate dysfunctions of basalganglian motorcontrol

Robust Tumor Segmentation with Hyperspectral Imaging and Graph Neural Networks

Segmenting the boundary between tumor and healthy tissue during surgical cancer resection poses a significant challenge. In recent years, Hyperspectral Imaging (HSI) combined with Machine Learning (ML) has emerged as a promising solution. However, due to the extensive information contained within the spectral domain, most ML approaches primarily classify individual HSI (super-)pixels, or tiles, without taking into account their spatial context. In this paper, we propose an improved methodology that leverages the spatial context of tiles for more robust and smoother segmentation. To address the irregular shapes of tiles, we utilize Graph Neural Networks (GNNs) to propagate context information across neighboring regions. The features for each tile within the graph are extracted using a Convolutional Neural Network (CNN), which is trained simultaneously with the subsequent GNN. Moreover, we incorporate local image quality metrics into the loss function to enhance the training procedure's robustness against low-quality regions in the training images. We demonstrate the superiority of our proposed method using a clinical ex vivo dataset consisting of 51 HSI images from 30 patients. Despite the limited dataset, the GNN-based model significantly outperforms context-agnostic approaches, accurately distinguishing between healthy and tumor tissues, even in images from previously unseen patients. Furthermore, we show that our carefully designed loss function, accounting for local image quality, results in additional improvements. Our findings demonstrate that context-aware GNN algorithms can robustly find tumor demarcations on HSI images, ultimately contributing to better surgery success and patient outcome.Comment: 11 pages, 6 figure

Sediment history mirrors Pleistocene aridification in the Gobi Desert (Ejina Basin, NW China)

Central Asia is a large-scale source of dust transport, but it also held a prominent changing hydrological system during the Quaternary. A 223 m long sediment core (GN200) was recovered from the Ejina Basin (synonymously Gaxun Nur Basin) in NW China to reconstruct the main modes of water availability in the area during the Quaternary. The core was drilled from the Heihe alluvial fan, one of the world's largest alluvial fans, which covers a part of the Gobi Desert. Grain-size distributions supported by endmember modelling analyses, geochemical-mineralogical compositions (based on XRF and XRD measurements), and bioindicator data (ostracods, gastropods, pollen and non-pollen palynomorphs, and n-alkanes with leaf-wax delta D) are used to infer the main transport processes and related environmental changes during the Pleistocene. Magnetostratigraphy supported by radionuclide dating provides the age model. Grain- size endmembers indicate that lake, playa (sheetflood), fluvial, and aeolian dynamics are the major factors influencing sedimentation in the Ejina Basin. Core GN200 reached the pre-Quatemary quartz- and plagioclase-rich "Red Clay" formation and reworked material derived from it in the core bottom. This part is overlain by silt-dominated sediments between 217 and 110 m core depth, which represent a period of lacustrine and playa-lacustrine sedimentation that presumably formed within an endorheic basin. The upper core half between 110 and 0 m is composed of mainly silty to sandy sediments derived from the Heihe that have accumulated in a giant sediment fan until modem time. Apart from the transition from a siltier to a sandier environment with frequent switches between sediment types upcore, the clay mineral fraction is indicative of different environments. Mixed-layer clay minerals (chlorite/smectite) are increased in the basal Red Clay and reworked sediments, smectite is indicative of lacustrine-playa deposits, and increased chlorite content is characteristic of the Heihe river deposits. The sediment succession in core GN200 based on the detrital proxy interpretation demonstrates that lake-playa sedimentation in the Ejina Basin has been disrupted likely due to tectonic events in the southern part of the catchment around 1 Ma. At this time Heihe broke through from the Hexi Corridor through the Heli Shan ridge into the northern Ejina Basin. This initiated the alluvial fan progradation into the Ejina Basin. Presently the sediment bulge repels the diminishing lacustrine environment further north. In this sense, the uplift of the hinterland served as a tipping element that triggered landscape transformation in the northern Tibetan foreland (i.e. the Hexi Corridor) and further on in the adjacent northern intracontinental Ejina Basin. The onset of alluvial fan formation coincides with increased sedimentation rates on the Chinese Loess Plateau, suggesting that the Heihe alluvial fan may have served as a prominent upwind sediment source for it

Регулируемый электропривод сталевоза

В данном дипломном проекте был произведен расчет и выбор силового оборудования для электропривода сталевоза грузоподъёмностью 215 тонн. Результатом расчета является выбор электродвигателя постоянного тока; токоограничивающий реактор; тиристорный преобразователь. Для управления электроприводом принята одно-зонная САР, для которой рассчитаны параметры датчиков и регуляторов. Разработаны схемы управления и защит. Расчет переходных процессов электропривода произведен с помощью ЭВМ.In this project, the calculation and selection of power equipment for the electric drive of the lsteel carrier with a lifting capacity of 215 tons was made. The result of the calculation is the choice of a DC motor; current limiting reactor; thyristor converter. To control the drive, a single-zone ATS is adopted, for which the parameters of the sensors and regulators are calculated. The schemes of control and protection are developed. Calculation of transient processes of the electric drive is made with the help of a computer

In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma

CXCR4 is a G-protein-coupled receptor that mediates recruitment of blood cells toward its ligand SDF-1. In cancer, high CXCR4 expression is frequently associated with tumor dissemination and poor prognosis. We evaluated the novel CXCR4 probe [(68)Ga]Pentixafor for in vivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). [(68)Ga]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [(68)Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [(18)F]fluorodeoxyglucose PET/CT scans were rated visually positive. Assessment of blood counts and standard CD34(+) flow cytometry did not reveal significant blood count changes associated with tracer application. Based on these highly encouraging data on clinical PET imaging of CXCR4 expression in a cohort of MM patients, we conclude that [(68)Ga]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4-directed therapeutic approaches in MM and other diseases

The Rho GDI Rdi1 regulates Rho GTPases by distinct mechanisms

© 2008 by The American Society for Cell Biology. Under the License and Publishing Agreement, authors grant to the general public, effective two months after publication of (i.e.,. the appearance of) the edited manuscript in an online issue of MBoC, the nonexclusive right to copy, distribute, or display the manuscript subject to the terms of the Creative Commons–Noncommercial–Share Alike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0).The small guanosine triphosphate (GTP)-binding proteins of the Rho family are implicated in various cell functions, including establishment and maintenance of cell polarity. Activity of Rho guanosine triphosphatases (GTPases) is not only regulated by guanine nucleotide exchange factors and GTPase-activating proteins but also by guanine nucleotide dissociation inhibitors (GDIs). These proteins have the ability to extract Rho proteins from membranes and keep them in an inactive cytosolic complex. Here, we show that Rdi1, the sole Rho GDI of the yeast Saccharomyces cerevisiae, contributes to pseudohyphal growth and mitotic exit. Rdi1 interacts only with Cdc42, Rho1, and Rho4, and it regulates these Rho GTPases by distinct mechanisms. Binding between Rdi1 and Cdc42 as well as Rho1 is modulated by the Cdc42 effector and p21-activated kinase Cla4. After membrane extraction mediated by Rdi1, Rho4 is degraded by a novel mechanism, which includes the glycogen synthase kinase 3β homologue Ygk3, vacuolar proteases, and the proteasome. Together, these results indicate that Rdi1 uses distinct modes of regulation for different Rho GTPases.Deutsche Forschungsgemeinschaf