GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Phenotypical and Myopathological Consequences of Compound Heterozygous Missense and Nonsense Variants in SLC18A3
    MDPI AG ; 2021
    In:  Cells Vol. 10, No. 12 ( 2021-12-09), p. 3481-
    Details
    In: Cells, MDPI AG, Vol. 10, No. 12 ( 2021-12-09), p. 3481-
    Abstract: Background: Presynaptic forms of congenital myasthenic syndromes (CMS) due to pathogenic variants in SLC18A3 impairing the synthesis and recycling of acetylcholine (ACh) have recently been described. SLC18A3 encodes the vesicular ACh transporter (VAChT), modulating the active transport of ACh at the neuromuscular junction, and homozygous loss of VAChT leads to lethality. Methods: Exome sequencing (ES) was carried out to identify the molecular genetic cause of the disease in a 5-year-old male patient and histological, immunofluorescence as well as electron- and CARS-microscopic studies were performed to delineate the muscle pathology, which has so far only been studied in VAChT-deficient animal models. Results: ES unraveled compound heterozygous missense and nonsense variants (c.315G 〉 A, p.Trp105* and c.1192G 〉 C, p.Asp398His) in SLC18A3. Comparison with already-published cases suggests a more severe phenotype including impaired motor and cognitive development, possibly related to a more severe effect of the nonsense variant. Therapy with pyridostigmine was only partially effective while 3,4 diaminopyridine showed no effect. Microscopic investigation of the muscle biopsy revealed reduced fibre size and a significant accumulation of lipid droplets. Conclusions: We suggest that nonsense variants have a more detrimental impact on the clinical manifestation of SLC18A3-associated CMS. The impact of pathogenic SLC18A3 variants on muscle fibre integrity beyond the effect of denervation is suggested by the build-up of lipid aggregates. This in turn implicates the importance of proper VAChT-mediated synthesis and recycling of ACh for lipid homeostasis in muscle cells. This hypothesis is further supported by the pathological observations obtained in previously published VAChT-animal models.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells10123481
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2661518-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Differential Diagnosis of Acquired and Hereditary Neuropathies in Children and Adolescents—Consensus-Based Practice Guidelines
    MDPI AG ; 2021
    In:  Children Vol. 8, No. 8 ( 2021-08-09), p. 687-
    Details
    In: Children, MDPI AG, Vol. 8, No. 8 ( 2021-08-09), p. 687-
    Abstract: Disorders of the peripheral nerves can be caused by a broad spectrum of acquired or hereditary aetiologies. The objective of these practice guidelines is to provide the reader with information about the differential diagnostic workup for a target-oriented diagnosis. Following an initiative of the German-speaking Society of Neuropaediatrics, delegates from 10 German societies dedicated to neuroscience worked in close co-operation to write this guideline. Applying the Delphi methodology, the authors carried out a formal consensus process to develop practice recommendations. These covered the important diagnostic steps both for acquired neuropathies (traumatic, infectious, inflammatory) and the spectrum of hereditary Charcot–Marie–Tooth (CMT) diseases. Some of our most important recommendations are that: (i) The indication for further diagnostics must be based on the patient’s history and clinical findings; (ii) Potential toxic neuropathy also has to be considered; (iii) For focal and regional neuropathies of unknown aetiology, nerve sonography and MRI should be performed; and (iv) For demyelinated hereditary neuropathy, genetic diagnostics should first address PMP22 gene deletion: once that has been excluded, massive parallel sequencing including an analysis of relevant CMT-genes should be performed. This article contains a short version of the guidelines. The full-length text (in German) can be found at the Website of the “Arbeitsgemeinschaft der Wissenschftlichen Medizinischen Fachgesellschaften e.V. (AWMF), Germany.
    Type of Medium: Online Resource
    ISSN: 2227-9067
    URL: Article
    DOI: 10.3390/children8080687
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2732685-8
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Impact of Hypermannosylation on the Structure and Functionality of the ER and the Golgi Complex
    MDPI AG ; 2023
    In:  Biomedicines Vol. 11, No. 1 ( 2023-01-06), p. 146-
    Details
    In: Biomedicines, MDPI AG, Vol. 11, No. 1 ( 2023-01-06), p. 146-
    Abstract: Proteins of the secretory pathway undergo glycosylation in the endoplasmic reticulum (ER) and the Golgi apparatus. Altered protein glycosylation can manifest in serious, sometimes fatal malfunctions. We recently showed that mutations in GDP-mannose pyrophosphorylase A (GMPPA) can cause a syndrome characterized by alacrima, achalasia, mental retardation, and myopathic alterations (AAMR syndrome). GMPPA acts as a feedback inhibitor of GDP-mannose pyrophosphorylase B (GMPPB), which provides GDP-mannose as a substrate for protein glycosylation. Loss of GMPPA thus enhances the incorporation of mannose into glycochains of various proteins, including α-dystroglycan (α-DG), a protein that links the extracellular matrix with the cytoskeleton. Here, we further characterized the consequences of loss of GMPPA for the secretory pathway. This includes a fragmentation of the Golgi apparatus, which comes along with a regulation of the abundance of several ER- and Golgi-resident proteins. We further show that the activity of the Golgi-associated endoprotease furin is reduced. Moreover, the fraction of α-DG, which is retained in the ER, is increased. Notably, WT cells cultured at a high mannose concentration display similar changes with increased retention of α-DG, altered structure of the Golgi apparatus, and a decrease in furin activity. In summary, our data underline the importance of a balanced mannose homeostasis for the secretory pathway.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines11010146
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2720867-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Genotype-Phenotype Comparison in POGZ-Related Neurodevelopmental Disorders by Using Clinical Scoring
    MDPI AG ; 2022
    In:  Genes Vol. 13, No. 1 ( 2022-01-15), p. 154-
    Details
    In: Genes, MDPI AG, Vol. 13, No. 1 ( 2022-01-15), p. 154-
    Abstract: POGZ-related disorders (also known as White-Sutton syndrome) encompass a wide range of neurocognitive abnormalities and other accompanying anomalies. Disease severity varies widely among POGZ patients and studies investigating genotype-phenotype association are scarce. Therefore, our aim was to collect data on previously unreported POGZ patients and perform a large-scale phenotype-genotype comparison from published data. Overall, 117 POGZ patients’ genotype and phenotype data were included in the analysis, including 12 novel patients. A severity scoring system was developed for the comparison. Mild and severe phenotypes were compared with the types and location of the variants and the predicted presence or absence of nonsense-mediated RNA decay (NMD). Missense variants were more often associated with mild phenotypes (p = 0.0421) and truncating variants predicted to escape NMD presented with more severe phenotypes (p 〈 0.0001). Within this group, variants in the prolin-rich region of the POGZ protein were associated with the most severe phenotypes (p = 0.0004). Our study suggests that gain-of-function or dominant negative effect through escaping NMD and the location of the variants in the prolin-rich domain of the protein may play an important role in the severity of manifestations of POGZ–associated neurodevelopmental disorders.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes13010154
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527218-4
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Early Alterations of RNA Binding Protein (RBP) Homeostasis and ER Stress-Mediated Autophagy Contributes to Progressive Retinal Degeneration in the rd10 Mouse Model of Retinitis Pigmentosa (RP)
    MDPI AG ; 2023
    In:  Cells Vol. 12, No. 7 ( 2023-04-06), p. 1094-
    Details
    In: Cells, MDPI AG, Vol. 12, No. 7 ( 2023-04-06), p. 1094-
    Abstract: The retinal degeneration 10 (rd10) mouse model is widely used to study retinitis pigmentosa (RP) pathomechanisms. It offers a rather unique opportunity to study trans-neuronal degeneration because the cell populations in question are separated anatomically and the mutated Pde6b gene is selectively expressed in rod photoreceptors. We hypothesized that RNA binding protein (RBP) aggregation and abnormal autophagy might serve as early pathogenic events, damaging non-photoreceptor retinal cell types that are not primarily targeted by the Pde6b gene defect. We used a combination of immunohistochemistry (DAB, immunofluorescence), electron microscopy (EM), subcellular fractionation, and Western blot analysis on the retinal preparations obtained from both rd10 and wild-type mice. We found early, robust increases in levels of the protective endoplasmic reticulum (ER) calcium (Ca2+) buffering chaperone Sigma receptor 1 (SigR1) together with other ER-Ca2+ buffering proteins in both photoreceptors and non-photoreceptor neuronal cells before any noticeable photoreceptor degeneration. In line with this, we found markedly altered expression of the autophagy proteins p62 and LC3, together with abnormal ER widening and large autophagic vacuoles as detected by EM. Interestingly, these changes were accompanied by early, prominent cytoplasmic and nuclear aggregation of the key RBPs including pTDP-43 and FET family RBPs and stress granule formation. We conclude that progressive neurodegeneration in the rd10 mouse retina is associated with early disturbances of proteostasis and autophagy, along with abnormal cytoplasmic RBP aggregation.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells12071094
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2661518-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Characterization of a Novel Aspect of Tissue Scarring Following Experimental Spinal Cord Injury and the Implantation of Bioengineered Type-I Collagen Scaffolds in the Adult Rat: Involvement of Perineurial-like Cells?
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 6 ( 2022-03-16), p. 3221-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 6 ( 2022-03-16), p. 3221-
    Abstract: Numerous intervention strategies have been developed to promote functional tissue repair following experimental spinal cord injury (SCI), including the bridging of lesion-induced cystic cavities with bioengineered scaffolds. Integration between such implanted scaffolds and the lesioned host spinal cord is critical for supporting regenerative growth, but only moderate-to-low degrees of success have been reported. Light and electron microscopy were employed to better characterise the fibroadhesive scarring process taking place after implantation of a longitudinally microstructured type-I collagen scaffold into unilateral mid-cervical resection injuries of the adult rat spinal cord. At long survival times (10 weeks post-surgery), sheets of tightly packed cells (of uniform morphology) could be seen lining the inner surface of the repaired dura mater of lesion-only control animals, as well as forming a barrier along the implant–host interface of the scaffold-implanted animals. The highly uniform ultrastructural features of these scarring cells and their anatomical continuity with the local, reactive spinal nerve roots strongly suggest their identity to be perineurial-like cells. This novel aspect of the cellular composition of reactive spinal cord tissue highlights the increasingly complex nature of fibroadhesive scarring involved in traumatic injury, and particularly in response to the implantation of bioengineered collagen scaffolds.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23063221
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Histology of human glioblastoma transplanted on chicken chorioallantoic membrane
    MDPI AG ; 2009
    In:  Medicina Vol. 45, No. 2 ( 2009-02-10), p. 123-
    Details
    In: Medicina, MDPI AG, Vol. 45, No. 2 ( 2009-02-10), p. 123-
    Abstract: Glioblastoma is the most malignant tumor in the range of cerebral astrocytic gliomas. A lot of experimental models are used to evaluate various properties of glioblastoma. Chicken chorioallantoic membrane model is one of them. Objective. To evaluate histology and survival of glioblastoma tumors taken immediately from operating theatre and transplanted on chicken chorioallantoic membrane. Materials and methods. Glioblastoma samples obtained from 10 patients were transplanted onto 200 eggs. Overall, we used 15 tumors; only 5 of them were not glioblastomas as it was revealed later. Results. The transplanted tumors survive up to 6 days. Transplants do not survive longer because during embryo’s development the nourishing membrane dries. Transplanted glioblastomas exhibited the same features as original glioblastomas – necrosis, endothelium proliferation, cellular polymorphism – while transplanted glioblastomas also showed glial fibrillary acidic protein (GFAP), vimentin, Ki67, S100 protein, neurofilament immunoreactivity, and infiltration of macrophages (CD68) and T cells (CD3+, CD8+). Transplanted glioblastomas did not show any immunoreactivity of p53. Invasion of vessels from the chicken into transplanted tumor is not observed. Chicken erythrocytes did not appear within the transplants, and tumor cells invade chicken tissue at the minimum. Conclusion. Our data show that transplanted pieces of glioblastoma survive with all cytological features. The presence of macrophages (marker CD68) and T cells (markers CD3+ and CD8+) can be registered in the transplant. The data revealed that transplanted glioblastoma remains as insulated unit, which survives from nourishment of the chorioallantoic membrane apparently only by diffusion. The features of original tumor-host reaction of the patient remained too.
    Type of Medium: Online Resource
    ISSN: 1648-9144
    URL: Article
    DOI: 10.3390/medicina45020016
    Language: English
    Publisher: MDPI AG
    Publication Date: 2009
    detail.hit.zdb_id: 2088820-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...