112 research outputs found

    Mutationsanalysen bei GLI3-Morphopathien

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    Hippocampal neurogenesis requires cell-autonomous thyroid hormone signaling

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    Adult hippocampal neurogenesis is strongly dependent on thyroid hormone (TH). Whether TH signaling regulates this process in a cell-autonomous or non-autonomous manner remains unknown. To answer this question, we used global and conditional knockouts of the TH transporter monocarboxylate transporter 8 (MCT8), having first used FACS and immunohistochemistry to demonstrate that MCT8 is the only TH transporter expressed on neuroblasts and adult slice cultures to confirm a necessary role for MCT8 in neurogenesis. Both mice with a global deletion or an adult neural stem cell-specific deletion of MCT8 showed decreased expression of the cell-cycle inhibitor P27KIP1, reduced differentiation of neuroblasts, and impaired generation of new granule cell neurons, with global knockout mice also showing enhanced neuroblast proliferation. Together, our results reveal a cell-autonomous role for TH signaling in adult hippocampal neurogenesis alongside non-cell-autonomous effects on cell proliferation earlier in the lineage

    Limitations of sulforhodamine 101 for brain imaging

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    Since 2004, the red fluorescent dye Sulforhodamine 101 (SR101) has been boosting the functional analysis of astrocytes in a functional environment in an unprecedented way. However, two major limitations have been challenging the usefulness of this tool for cellular imaging: (i) SR101 is not as specific for astrocytes as previously reported; and (ii) discoveries of severe excitatory side effects of SR101 are bearing the risk of unwanted alteration of the system of interest. In this article, we summarize the current knowledge about SR101-labeling protocols and discuss the problems that arise from varying of the staining protocols. Furthermore, we provide a testable hypothesis for the observed hyper-excitability that can be observed when using SR101

    A new Purkinje cell antibody (anti-Ca) associated with subacute cerebellar ataxia: immunological characterization

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    We report on a newly discovered serum and cerebrospinal fluid (CSF) reactivity to Purkinje cells (PCs) associated with subacute inflammatory cerebellar ataxia. The patient, a previously healthy 33-year-old lady, presented with severe limb and gait ataxia, dysarthria, and diplopia two weeks after she had recovered from a common cold. Immunohistochemical studies on mouse, rat, and monkey brain sections revealed binding of a high-titer (up to 1:10,000) IgG antibody to the cerebellar molecular layer, Purkinje cell (PC) layer, and white matter. The antibody is highly specific for PCs and binds to the cytoplasm as well as to the inner side of the membrane of PC somata, dendrites and axons. It is produced by B cell clones within the CNS, belongs to the IgG1 subclass, and activates complement in vitro. Western blotting of primate cerebellum extract revealed binding of CSF and serum IgG to an 80-97 kDa protein. Extensive control studies were performed to rule out a broad panel of previously described paraneoplastic and non-paraneoplastic antibodies known to be associated with cerebellar ataxia. Screening of >9000 human full length proteins by means of a protein array and additional confirmatory experiments revealed Rho GTPase activating protein 26 (ARHGAP26, GRAF, oligophrenin-1-like protein) as the target antigen. Preadsorption of the patient's serum with human ARHGAP26 but not preadsorption with other proteins resulted in complete loss of PC staining. Our findings suggest a role of autoimmunity against ARHGAP26 in the pathogenesis of subacute inflammatory cerebellar ataxia, and extend the panel of diagnostic markers for this devastating disease

    Complication after Aquafilling® gel-mediated augmentation mammoplasty—galactocele formation in a lactating woman: a case report and review of literature

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    Augmentation mammoplasty using hydrogel fillers such as polyacrylamide gel (PAAG) or Aquafilling® has been performed commonly in some countries as an alternative to breast augmentation with saline or silicone implants. However, the safety of this procedure remains controversial, and many complications associated with the use of large-volume hydrogel injection have been reported in recent years. We present the case of a 33-year-old woman with a history of bilateral Aquafilling® injection augmentation mammoplasty who presented with an enlarged left breast while breastfeeding. Based on the clinical presentation and ultrasound findings, the patient underwent surgical incision as abscess formation caused by infection of the filler material could not be ruled out with certainty. Surgery revealed a galactocele with drainage of large amounts of milky fluid. Remaining filler material was removed as thoroughly as possible, and vacuum assisted wound dressing was performed. Galactocele formation in lactating women is a known complication after injection of hydrogel. Hence, it is important to be familiar with this uncommon but possibly severe complication in order to make an accurate diagnosis and initiate adequate treatment. To that end, it is recommended that patients who underwent Aquafilling® injection for breast augmentation should avoid lactation and that women intending to breastfeed should not undergo augmentation mammoplasty with injection of Aquafilling®.Level of Evidence: Level V, risk / prognostic stud

    Оптимизация вычисления обратного БПФ на многоядерном процессоре

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    The article describes the method of calculating the inverse FFT N-point sequence with a N-point complex FFT, also the implementation of similar approach for computing on multi-core computing architecture. The main quality parameters of similar organization such as speedup and efficiency of computing resources were analyzed

    Product lifecycle and choice of transportation modes: Japan’s evidence of import and export

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    Here we test the hypothesis that commodities at their peak valuation are transported by air and those at their birth and maturity are shipped by sea, and that shippers would choose air for transporting high-valued commodities. We empirically investigated how the product lifecycle of commodities is reflected by shippers' choices of air transportation rather than seaborne transportation. We also assumed that the commodities that achieved substantial innovation in their lifecycles would be moved by air transportation so that these commodities could reach the targeted markets as quickly as possible to avoid the opportunity costs that might be generated by missed business chances. We constructed two unbalanced panel data of 18 commodities (the case of import) and 14 commodities (the case of export) for 24 years from Japan’s custom, demographic, and international statistics. By estimating structural equation systems that consisted of commodity-specific import/export and import/export air ratio functions, we found that the product lifecycle of cargo outgoing from Japan exactly matched the upward and downward move of the air ratio, whereas since incoming commodities are raw materials that have little to do with product lifecycle or matured phase in their lifecycle stage, the peak of commodities’ valuations and the use of air transportation were not necessarily synchronized

    Ontogenetic expression of thyroid hormone signaling genes: An in vitro and in vivo species comparison.

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    Thyroid hormone (TH) is essential for brain development. While disruption of TH signaling by environmental chemicals has been discussed as a mechanism of developmental neurotoxicity (DNT) for more than a decade, there remains a paucity of information linking specific TH disrupting chemicals to adverse neurodevelopmental outcomes. This data gap reflects, in part, the fact that the molecular machinery of TH signaling is complex and varies according to cell type and developmental time. Thus, establishing a baseline of the ontogenetic profile of expression of TH signaling molecules in relevant cell types is critical for developing in vitro and alternative systems-based models for screening TH disrupting chemicals for DNT. Here, we characterize the transcriptomic profile of molecules critical to TH signaling across three species-human, rat, and zebrafish-in vitro and in vivo across different stages of neurodevelopment. Our data indicate that while cultured human and rat neural progenitor cells, primary cultures of rat cortical cells, and larval zebrafish all express a fairly comprehensive transcriptome of TH signaling molecules, the spatiotemporal expression profiles as well as the responses to TH vary across species and developmental stages. The data presented here provides a roadmap for identifying appropriate in vitro and in simpler systems-based models for mechanistic studies and screening of chemicals that alter neurodevelopment via interference with TH action

    Single-incision for breast-conserving surgery through round block technique

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    Aims and objectives: The purpose of this study was to assess the feasibility of using the single-incision round block technique in breast-conserving surgery with sentinel lymph node (SLN) retrieval for breast cancer without compromising oncological safety. Materials and methods: A retrospective observational case-control study was conducted from January 2017 to October 2021. The study population consisted of two groups. In both groups, breast-conserving surgery was carried out through the round-block technique. In group A, SLN retrieval was performed using the round-block incision (study group), while in group B, SLN retrieval was conducted through a second skin incision in the axilla (control group). The study was approved by the local ethics committee Zurich (BASEC-Nr. 2020-02857), and written informed consent was obtained from all participants. Results: Overall, 134 patients met the inclusion criteria, of whom 86 women underwent breast-conserving surgery and SLN retrieval using the single-incision approach (group A), and 48 women underwent conventional surgery, using two independent incisions for tumour resection and SLN retrieval (group B). The overall success rate in group A regarding SLN retrieval was 97.7%, whereas most tumours were located in the upper outer (47.7%) and upper inner quadrant (27.9%). Although the technique was equally successful in the other quadrants, the share of tumours in the lower outer, and the lower inner quadrant, and the retroareolar region was smaller, representing 17.4%, 3.5% and 3.5%, respectively. The median number of dissected lymph nodes was two, with a positivity rate of 24.4%. The occurrence of axillary neuralgia and axillary skin retraction was significantly higher in group B along with tendentially more axillary seroma formation. There were no significant differences regarding reintervention rates, in terms of complications, resection margins, locoregional recurrences, or deaths with a mean follow-up of 11 months. Conclusions: The single-incision method through the round block technique is as safe and effective as the standard two-incision approach regarding nodal staging and resection margins, and seems to be applicable for tumours in all breast quadrants. Keywords: Benelli; Breast-conserving surgery; Minimal-access breast surgery; Round block; Single-incision
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