1,399 research outputs found

    MIF proteins and their role in mediating neutrophil activity and survival

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    Strategy use in number line tasks of students with mathematical difficulties: an eye-tracking study

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    The number line is an important mathematical tool, especially in primary education. Previous research suggests that students with mathematical difficulties (MD) tend to have difficulties in empty number line tasks, but little is known about marked number lines. The aim of this study was to investigate if students with MD differ in their strategy use from students without MD in marked number line tasks. In our empirical study with fifth-grade students with and without MD (each n=20), we used eye tracking (ET), the recording of eye movements to gain insights into students’ strategies. Based on ET video data, we inductively developed a category system of student strategies using qualitative content analysis. Our data analysis revealed significant differences: Students with MD used counting strategies more often—and less direct locating

    Development of stabilized NTS₁R and CXCR4 PET ligands using Nω-carbamoylated arginines for label attachment

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    The neuropeptide neurotensin (NT), mainly expressed in the CNS and the gastrointestinal tract, is involved in, e.g., the regulation of feeding, body temperature and nociception. One of the NT receptors, the G-protein coupled neurotensin receptor 1 (NTS₁R), represents an interesting target concerning tumor diagnosis and therapy, as its overexpression was reported for a variety of tumors such as breast cancer and pancreatic adenocarcinoma. The bioactive fragment of NT, NT(8-13), has served as a lead structure for the preparation of molecular tools useful for investigations at the NTS₁R. However, the development of radiolabeled NTS₁R ligands for in vivo applications such as tumor imaging by positron emission tomography (PET), is challenging due to proteolytic degradation of the peptidic compounds by peptidases. Therefore, appropriate structural modifications of NT(8-13) derivatives are necessary to enable an application as PET tracers. The aim of this work was the development of stabilized analogs of NT(8-13) with high NTS₁R affinity including compounds useful for PET imaging, i.e., ¹⁸F- or ⁶⁸Ga-labeled derivatives. Therefore, a series of NT(8-13) analogs was prepared by SPPS, applying modifications such as Nα-methylation or the replacement of amino acids by non-natural amino acids. The synthesized peptides were investigated with respect to in vitro plasma stability and NTS₁R affinity. The incorporation of amino-functionalized Nω-carbamoylated arginines instead of natural Arg enabled the conjugation of the respective NT(8-13) congeners to a prosthetic group of choice. After acylation of the amino group with 4-pentynoic acid, “cold” analogs of ¹⁸F-labeled PET tracers were prepared by click chemistry-based attachment of a fluorinated glycosyl azide onto the modified arginine side chain. Using the corresponding [¹⁸F]fluorinated azido sugar, the precursor of the most promising candidate (3.21), which showed an excellent half-life of > 24 h in vitro in human and mouse plasma and a Ki value of 4.3 nM at the NTS₁R, was used for ¹⁸F-labeling in cooperation with the Department of Nuclear Medicine, Molecular Imaging and Radiochemistry at the Friedrich-Alexander-University Erlangen-Nürnberg. Biodistribution and PET imaging studies with [¹⁸F]3.21 in tumor-bearing mice revealed a high tumor-to-muscle ratio of 30 at 90 min p.i. and a specific accumulation of the tracer in subcutaneous NTS₁R-expressing HT-29 tumors. However, fast in vivo degradation of [¹⁸F]3.21 (70% degradation after 10 min p.i.) necessitates further improvement of the tracer. Likewise, the amino-functionality of the carbamoylated arginines was used for the conjugation to chelators such as DOTA, suitable for the insertion of Ga³⁺. Considering the overall performance of the “cold” forms of these NTS₁R PET ligands (receptor affinity, plasma stability, synthetic accessibility), ⁶⁸Ga-labeled analogs of the most promising candidates were prepared in cooperation with the Department of Nuclear Medicine at the University Hospital Regensburg. UR-LS130 (compound 4.56) displayed high NTS₁R affinity (Ki = 1.2 nM) combined with excellent in vitro stability in human plasma (t1/2 > 24 h), and its radiolabeled congener [⁶⁸Ga]4.56 showed high specific accumulation in HT-29 tumors with a tumor-to-muscle ratio of 16 at 45 min p.i. in biodistribution and PET imaging studies performed with tumor-bearing mice. Notably, [⁶⁸Ga]4.56 exhibited high in vivo stability, which can be attributed to the replacement of Tyr¹¹ by β,β-dimethyl-tyrosine. Taken together, two high-affinity NTS₁R PET ligands for tumor imaging with promising in vivo performance were developed. The identified stabilizing effect of β,β-dimethyl-tyrosine in position 11 of the peptide core structure, not affecting NTS₁R binding, will support the future development of NT(8-13)-derived tumor imaging probes. A second project of this work aimed at fluorinated potential PET ligands for the CXCR4. This G-protein coupled chemokine receptor is overexpressed in different types of cancer, such as prostate or breast cancer. The “cold” forms of CXCR4 PET ligands derived from the reported peptidic CXCR4 antagonist FC131 were prepared by application of the replacement of Arg by an amino-functionalized Nω-carbamoylated arginine, subsequent alkyne-functionalization and coupling to the aforementioned fluoroglycosyl azide. Investigations regarding their antagonistic activities at the CXCR4 and in vitro plasma stabilities revealed that compound 5.24, displaying a pKb value of 7.15 and a half-life of > 24h, may serve as a lead structure for the development of optimized fluorinated CXCR4 PET ligands in future studies

    Wie Kinder mit Schwierigkeiten im Rechnenlernen am markierten Zahlenstrahl vorgehen: Eine Eye-Tracking-Studie

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    Zusammenfassung. Der vorliegende Beitrag stellt eine Untersuchung zur Nutzung von Vorgehensweisen bei Aufgaben am markierten Zahlenstrahl von Kindern mit und ohne Schwierigkeiten im Rechnenlernen (SR) vor, bei dem Eye-Tracking (ET) verwendet und anhand der Blickbewegungen Vorgehensweisen identifiziert wurden. Es zeigte sich, dass Kinder mit SR Vorgehensweisen weniger aufgabenadäquat nutzten als Kinder ohne SR, wobei Kinder mit SR häufiger zählende Vorgehensweisen nutzen

    Influence of controlled masticatory muscle activity on dynamic reactive balance

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    Background The influence of the stomatognatic system on human posture control has been investigated under static conditions, but the effects on dynamic balance have not yet been considered. Objective Investigating the influence of different functional stomatognatic activities (jaw clenching (JAW), tongue pressing (TON) and habitual jaw position (HAB)) on postural performance during a dynamic reactive balance task. Methods Forty-eight physically active and healthy adults were assigned to three groups differing in oral-motor tasks (JAW, TON or HAB). Dynamic reactive balance was assessed by an oscillating platform which was externally perturbed in four directions. Performance was quantified by means of Lehr\u27s damping ratio. Mean speeds of the selected anatomical regions (head, trunk, pelvis, knee and foot) were analysed to determine significant performance differences. Results The groups differed significantly in balance performance in direction F (i.e., forwards acceleration of the platform). Post hoc tests revealed that the JAW group had significantly better performance compared with both the HAB and TON groups. Better performance was associated with a decreased mean speed of the analysed anatomical regions. Conclusion JAW can improve dynamic reactive balance but the occurrence of positive effects seems to be task-specific and not general. TON seems not to have any observable effects on dynamic reactive balance performance, at least when evaluating it with an oscillating platform. JAW might be a valuable strategy which could possibly reduce the risk of falls in elderly people; however, further investigations are still needed

    A heuristic framework for video-based teaching and learning scenarios in higher education

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    Video has been proven to be an effective tool for enhancing the professional vision of higher education students, which is a crucial situation-specific skill within their professional competence. To ensure the successful integration of video in higher education teaching and learning, several implementation actions and processes need to be considered. This paper proposes a heuristic framework for implementing video-based teaching and learning scenarios across various disciplines in higher education. The framework combines existing research strands on professional vision, video implementation, technological pedagogical content knowledge (TPACK), and interactive, constructive, active, and passive (ICAP) learning activities. To highlight the interdisciplinary nature of the framework, examples from four different higher education disciplines (Catholic moral theology, Communication science, German as a second and foreign language, Medicine) are provided. These examples serve to underscore the framework’s applicability across a range of academic fields

    Insertion of Nanoluc into the Extracellular Loops as a Complementary Method To Establish BRET-Based Binding Assays for GPCRs

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    Luminescence-based techniques play an increasingly important role in all areas of biochemical research, including investigations on G protein-coupled receptors (GPCRs). One quite recent and popular addition has been made by introducing bioluminescence resonance energy transfer (BRET)-based binding assays for GPCRs, which are based on the fusion of nanoluciferase (Nluc) to the N-terminus of the receptor and the occurring energy transfer via BRET to a bound fluorescent ligand. However, being based on BRET, the technique is strongly dependent on the distance/orientation between the luciferase and the fluorescent ligand. Here we describe an alternative strategy to establish BRET-based binding assays for GPCRs, where the N-terminal fusion of Nluc did not result in functioning test systems with our fluorescent ligands (e.g., for the neuropeptide Y Y1 receptor (Y1R) and the neurotensin receptor type 1 (NTS1R)). Instead, we introduced Nluc into their second extracellular loop and we obtained binding data for the fluorescent ligands and reported standard ligands (in saturation and competition binding experiments, respectively) comparable to data from the literature. The strategy was transferred to the angiotensin II receptor type 1 (AT1R) and the M1 muscarinic acetylcholine receptor (M1R), which led to affinity estimates comparable to data from radioligand binding experiments. Additionally, an analysis of the binding kinetics of all fluorescent ligands at their respective target was performed using the newly described receptor/Nluc-constructs

    Anterior Column Reconstruction of Destructive Vertebral Osteomyelitis at the Thoracolumbar Spine with an Expandable Vertebral Body Replacement Implant: A Retrospective, Monocentric Radiological Cohort Analysis of 24 Cases

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    Background: Vertebral osteomyelitis (VO) often necessitates surgical intervention due to bone loss-induced spinal instability. Anterior column reconstruction, utilizing expandable vertebral body replacement (VBR) implants, is a recognized approach to restore stability and prevent neurological compromise. Despite various techniques, clinical evidence regarding the safety and efficacy of these implants in VO remains limited. Methods: A retrospective cohort analysis, spanning 2000 to 2020, was conducted on 24 destructive VO cases at a Level 1 orthopedic trauma center. Diagnosis relied on clinical, radiological, and microbiological criteria. Patient demographics, clinical presentation, surgical interventions, and radiological outcomes were assessed. Results: The study included 24 patients (62.5% male; mean age 65.6 ± 35.0 years), with 58% having healthcare-associated infections (HAVO). The mean radiological follow-up was 137.2 ± 161.7 weeks. Surgical intervention significantly improved the bi-segmental kyphotic endplate angle (BKA) postoperatively (mean −1.4° ± 13.6°). However, a noticeable loss of correction was observed over time. The study reported a mortality rate of 1/24. Conclusions: Anterior column reconstruction using expandable VBR effectively improved local spinal alignment in destructive VO. However, the study underscores the necessity for prolonged follow-up and continuous research to refine surgical techniques and postoperative care. Addressing long-term complications and refining surgical approaches will be pivotal as the field progresses
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