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  • 1
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 3 ( 2023-01-18), p. 1943-
    Abstract: The transcription factor SOX11 is a tumor-associated antigen with low expression in normal cells, but overexpression in glioblastoma (GBM). So far, conventional surgery, chemotherapy, and radiotherapy have not substantially improved the dismal prognosis of relapsed/refractory GBM patients. Immunotherapy is considered a promising strategy against GBM, but there is a fervent need for better immunotargets in GBM. To this end, we performed an in silico prediction study on SOX11, which primarily yielded ten promising HLA-A*0201-restricted peptides derived from SOX11. We defined a novel peptide FMACSPVAL, which had the highest score according to in silico prediction (6.02 nM by NetMHC-4.0) and showed an exquisite binding affinity to the HLA-A*0201 molecule in the peptide-binding assays. In the IFN-γ ELISPOT assays, FMACSPVAL demonstrated a high efficiency for generating SOX11-specific CD8+ T cells. Nine out of thirty-two healthy donors showed a positive response to SOX11, as assessed by the ELISPOT assays. Therefore, this novel antigen peptide epitope seems to be promising as a target for T cell-based immunotherapy in GBM. The adoptive transfer of in vitro elicited SOX11-specific CD8+ T cells constitutes a potential approach for the treatment of GBM patients.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 2
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 2 ( 2022-01-14), p. 903-
    Abstract: Chimeric-antigen-receptor (CAR)-T-cell therapy is already widely used to treat patients who are relapsed or refractory to chemotherapy, antibodies, or stem-cell transplantation. Multiple myeloma still constitutes an incurable disease. CAR-T-cell therapy that targets BCMA (B-cell maturation antigen) is currently revolutionizing the treatment of those patients. To monitor and improve treatment outcomes, methods to detect CAR-T cells in human peripheral blood are highly desirable. In this study, three different detection reagents for staining BCMA-CAR-T cells by flow cytometry were compared. Moreover, a quantitative polymerase chain reaction (qPCR) to detect BCMA-CAR-T cells was established. By applying a cell-titration experiment of BCMA-CAR-T cells, both methods were compared head-to-head. In flow-cytometric analysis, the detection reagents used in this study could all detect BCMA-CAR-T cells at a similar level. The results of false-positive background staining differed as follows (standard deviation): the BCMA-detection reagent used on the control revealed a background staining of 0.04% (±0.02%), for the PE-labeled human BCMA peptide it was 0.25% (±0.06%) and for the polyclonal anti-human IgG antibody it was 7.2% (±9.2%). The ability to detect BCMA-CAR-T cells down to a concentration of 0.4% was similar for qPCR and flow cytometry. The qPCR could detect even lower concentrations (0.02–0.01%). In summary, BCMA-CAR-T-cell monitoring can be reliably performed by both flow cytometry and qPCR. In flow cytometry, reagents with low background staining should be preferred.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    MDPI AG ; 2022
    In:  Sensors Vol. 22, No. 24 ( 2022-12-19), p. 10015-
    In: Sensors, MDPI AG, Vol. 22, No. 24 ( 2022-12-19), p. 10015-
    Abstract: In recent years, the use of indoor localization techniques has increased significantly in a large number of areas, including industry and healthcare, primarily for monitoring and tracking reasons. From the field of radio frequency technologies, an ultra-wideband (UWB) system offers comparatively high accuracy and is therefore suitable for use cases with high precision requirements in position determination, for example for localizing an employee when interacting with a machine tool on the shopfloor. Indoor positioning systems with radio signals are influenced by environmental obstacles. Although the influence of building structures like walls and furniture was already analysed in the literature before, the influence of metal machine tools was not yet evaluated concerning the accuracy of the position determination. Accordingly, the research question for this article is defined: To what extent is the positioning accuracy of the UWB system influenced by a metal machine tool?The accuracy was measured in a test setup, which consists of a total of four scenarios in a production environment. For this purpose, the visual contact between the transmitter and the receiver modules, including the influence of further interfering factors of a commercially available indoor positioning system, was improved step by step from scenario 1 to 4. A laser tracker was used as the reference measuring device. The data was analysed based on the type A evaluation of standard uncertainty according to the guide to the expression of uncertainty in measurement (GUM). It was possible to show an improvement in standard deviation from 87.64cm±32.27cm to 6.07cm±2.24cm with confidence level 95% and thus provides conclusions about the setup of an indoor positioning system on the shopfloor.
    Type of Medium: Online Resource
    ISSN: 1424-8220
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2052857-7
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  • 4
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 9 ( 2021-04-28), p. 1907-
    Abstract: With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer’s disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid β peptides (Aβ1-40, Aβ1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examination (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at approximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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  • 5
    In: Metabolites, MDPI AG, Vol. 12, No. 2 ( 2022-01-19), p. 93-
    Abstract: Plants are continuously interacting with other organisms to optimize their performance in a changing environment. Mycorrhization is known to affect the plant growth and nutrient status, but it also can lead to adjusted plant defense and alter interactions with other trophic levels. Here, we studied the effect of Laccaria bicolor-mycorrhization on the poplar (Populus x canescens) metabolome and volatilome on trees with and without a poplar leaf beetle (Chrysomela populi) infestation. We analyzed the leaf and root metabolomes employing liquid chromatography–mass spectrometry, and the leaf volatilome employing headspace sorptive extraction combined with gas-chromatography–mass spectrometry. Mycorrhization caused distinct metabolic adjustments in roots, young/infested leaves and old/not directly infested leaves. Mycorrhization adjusted the lipid composition, the abundance of peptides and, especially upon herbivory, the level of various phenolic compounds. The greatest change in leaf volatile organic compound (VOC) emissions occurred four to eight days following the beetle infestation. Together, these results prove that mycorrhization affects the whole plant metabolome and may influence poplar aboveground interactions. The herbivores and the mycorrhizal fungi interact with each other indirectly through a common host plant, a result that emphasizes the importance of community approach in chemical ecology.
    Type of Medium: Online Resource
    ISSN: 2218-1989
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662251-8
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  • 6
    In: Cells, MDPI AG, Vol. 10, No. 11 ( 2021-10-20), p. 2805-
    Abstract: Background: Although several approaches have revealed much about individual factors that regulate pancreatic development, we have yet to fully understand their complicated interplay during pancreas morphogenesis. Gfi1 is transcription factor specifically expressed in pancreatic acinar cells, whose role in pancreas cells fate identity and specification is still elusive. Methods: In order to gain further insight into the function of this factor in the pancreas, we generated animals deficient for Gfi1 specifically in the pancreas. Gfi1 conditional knockout animals were phenotypically characterized by immunohistochemistry, RT-qPCR, and RNA scope. To assess the role of Gfi1 in the pathogenesis of diabetes, we challenged Gfi1-deficient mice with two models of induced hyperglycemia: long-term high-fat/high-sugar feeding and streptozotocin injections. Results: Interestingly, mutant mice did not show any obvious deleterious phenotype. However, in depth analyses demonstrated a significant decrease in pancreatic amylase expression, leading to a diminution in intestinal carbohydrates processing and thus glucose absorption. In fact, Gfi1-deficient mice were found resistant to diet-induced hyperglycemia, appearing normoglycemic even after long-term high-fat/high-sugar diet. Another feature observed in mutant acinar cells was the misexpression of ghrelin, a hormone previously suggested to exhibit anti-apoptotic effects on β-cells in vitro. Impressively, Gfi1 mutant mice were found to be resistant to the cytotoxic and diabetogenic effects of high-dose streptozotocin administrations, displaying a negligible loss of β-cells and an imperturbable normoglycemia. Conclusions: Together, these results demonstrate that Gfi1 could turn to be extremely valuable for the development of new therapies and could thus open new research avenues in the context of diabetes research.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2661518-6
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  • 7
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 4 ( 2022-02-18), p. 1074-
    Abstract: Symptoms of Parkinson’s disease (PD) can be controlled well, but treatment often requires expert judgment. Telemedicine and sensor-based assessments can allow physicians to better observe the evolvement of symptoms over time, in particular with motor fluctuations. In addition, they potentially allow less frequent visits to the expert’s office and facilitate care in rural areas. A variety of systems with different strengths and shortcomings has been investigated in recent years. We designed a multimodal telehealth intervention (TelePark) to mitigate the shortcomings of individual systems and assessed the feasibility of our approach in 12 patients with PD over 12 weeks in preparation for a larger randomized controlled trial. TelePark uses video visits, a smartphone app, a camera system, and wearable sensors. Structured training included setting up the equipment in patients’ homes and group-based online training. Usability was assessed by questionnaires and semi-standardized telephone interviews. Overall, 11 out of 12 patients completed the trial (5 female, 6 male). Mean age was 65 years, mean disease duration 7 years, mean MoCA score 27. Adherence was stable throughout the study and 79% for a short questionnaire administered every second day, 62% for medication confirmation, and 33% for an electronic Hauser diary. Quality of life did not change in the course of the study, and a larger cohort will be required to determine the effect on motor symptoms. Interviews with trial participants identified motivations to use such systems and areas for improvements. These insights can be helpful in designing similar trials.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 8
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 2 ( 2021-01-18), p. 347-
    Abstract: Background: Familial multiple coagulation factor deficiencies (FMCFDs) are a group of inherited hemostatic disorders with the simultaneous reduction of plasma activity of at least two coagulation factors. As consequence, the type and severity of symptoms and the management of bleeding/thrombotic episodes vary among patients. The aim of this study was to identify the underlying genetic defect in patients with FMCFDs. Methods: Activity levels were collected from the largest cohort of laboratory-diagnosed FMCFD patients described so far. Genetic analysis was performed using next-generation sequencing. Results: In total, 52 FMCFDs resulted from coincidental co-inheritance of single-factor deficiencies. All coagulation factors (except factor XII (FXII)) were involved in different combinations. Factor VII (FVII) deficiency showed the highest prevalence. The second group summarized 21 patients with FMCFDs due to a single-gene defect resulting in combined FV/FVIII deficiency or vitamin K–dependent coagulation factor deficiency. In the third group, nine patients with a combined deficiency of FVII and FX caused by the partial deletion of chromosome 13 were identified. The majority of patients exhibited bleeding symptoms while thrombotic events were uncommon. Conclusions: FMCFDs are heritable abnormalities of hemostasis with a very low population frequency rendering them orphan diseases. A combination of comprehensive screening of residual activities and molecular genetic analysis could avoid under- and misdiagnosis.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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  • 9
    Online Resource
    Online Resource
    MDPI AG ; 2021
    In:  Diagnostics Vol. 11, No. 2 ( 2021-02-12), p. 295-
    In: Diagnostics, MDPI AG, Vol. 11, No. 2 ( 2021-02-12), p. 295-
    Abstract: The mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is an uncommon cause of cardiac hypertrophy, fibrosis, and dysfunction. It shares similar features to numerous other causes of left ventricular hypertrophy, and therefore, because of its rarity, may not be immediately considered as a diagnosis. Prompt recognition of clinical and cardiac imaging features may expedite diagnosis and management. We report the case of a 38-year-old man admitted with neurological symptoms and in whom the diagnostic workup led to the diagnosis of MELAS syndrome with cardiac involvement.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662336-5
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  • 10
    In: Microorganisms, MDPI AG, Vol. 7, No. 9 ( 2019-09-09), p. 335-
    Abstract: Anthropogenic disturbances can have strong impacts on lichen communities, as well as on individual species of lichenized fungi. Traditionally, lichen monitoring studies are based on the presence and abundance of fungal morphospecies. However, the photobionts, as well photobiont mycobiont interactions also contribute to the structure, composition, and resilience of lichen communities. Here we assess the genetic diversity and interaction patterns of algal and fungal partners in lichen communities along an anthropogenic disturbance gradient in Białowieża Forest (Poland). We sampled a total of 224 lichen thalli in a protected, a managed, and a disturbed area of the forest, and sequenced internal transcribed spacer (ITS) ribosomal DNA (rDNA) of both, fungal and algal partners. Sequence clustering using a 97% similarity threshold resulted in 46 fungal and 23 green algal operational taxonomic units (OTUs). Most of the recovered photobiont OTUs (14 out of 23) had no similar hit in the NCBI-BLAST search, suggesting that even in well studied regions, such as central Europe, a lot of photobiont diversity is yet undiscovered. If a mycobiont was present at more than one site, it was typically associated with the same photobiont OTU(s). Generalist species, i.e., taxa that associate with multiple symbiont partners, occurred in all three disturbance regimes, suggesting that such taxa have few limitations in colonizing or persisting in disturbed areas. Trebouxia jamesii associated with 53% of the fungal OTUs, and was generally the most common photobiont OTU in all areas, implying that lichens that associate with this symbiont are not limited by the availability of compatible photobionts in Central European forests, regardless of land use intensity.
    Type of Medium: Online Resource
    ISSN: 2076-2607
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2720891-6
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