Scientific publications of the Saarland University
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Metaanalyse und systematisches Review zur genetischen Prädisposition bei Keratokonus anhand von Polymorphismen
Full text linkDer Keratokonus ist eine Hornhauterkrankung, die durch eine progressive Vorwölbung und Ausdünnung der Hornhaut charakterisiert ist. Diese führen zu einem irregulären Astigmatismus und einem verminderten Visus. Brillen, formstabile Kontaktlinsen, aber auch invasive Verfahren wie die perforierende Keratoplastik können zur Behandlung des Refraktionsfehlers dienen. Daneben kann das Crosslinking, welches die Hornhaut stabilisiert, oder der Einsatz intrakornealer Ringsegmente die Progression hemmen. Es gibt bis dato keine kausale Therapiemöglichkeit.
Die Genese des Keratokonus ist multifaktoriell. Neben Umweltfaktoren wie Augenreiben, Atopie oder dem Tragen von Kontaktlinsen deuten familiäre Studien darauf hin, dass auch die Genetik in der Genese des Keratokonus eine tragende Rolle spielt. Untersuchungen in verschiedenen Populationen deuten darauf hin, dass bestimmte Single Nucleotide Polymorphismen (SNPs) auf gewissen Genabschnitten mit dem Keratokonus assoziiert sein könnten.
Die vorliegende Dissertation gibt eine Übersicht über die verfügbare Studienlage zu ausgewählten Genen und Polymorphismen und deren potenzieller Assoziation mit dem Keratokonus. Sie enthält eine Metaanalyse zu den Genen IL1B (rs16944), IL1B (rs1143627), COL4A4 (rs222857) sowie LOX (rs2956540). Die Recherche wurde über die Plattformen PubMed, Web of Science und Google Scholar bis zum 11. Februar 2024 durchgeführt. Für jeden Polymorphismus wurden die Odds Ratio (OR) und das 95%-Konfidenzintervall (95%-CI) des jeweils dominanten und rezessiven Modells berechnet. Zusätzlich wurde auf das Vorliegen eines Publication Bias untersucht. Darüber hinaus umfasst die Arbeit ein systematisches Review der Gene COL5A1 (rs1536482), MPDZ-NF1B (rs1324183), VSX (rs6050307), HGF (rs2286194, rs17501108, rs1014091, rs3735520), COL4A4 (rs2229813), LOX (rs1800449, rs10519694) sowie ZNF469 (rs9938149).
Insgesamt wurden aus 27 Fall-Kontroll-Studien 3927 Keratokonuspatienten und 8877 Kontrollpersonen analysiert. Innerhalb der Metaanalyse konnte das „T“-Allel des rs2228557-Polymorphismus im COL4A4-Gen als statistisch signifikanter protektiver Faktor gegen die Entwicklung eines Keratokonus identifiziert werden. Für andere Polymorphismen zeigten weder die Metaanalyse noch das systematische Review eindeutige Tendenzen.Keratoconus is a corneal disease characterized by progressive bulging and thinning of the cornea. This leads to irregular astigmatism and reduced visual acuity.
Glasses, rigid contact lenses and even invasive procedures such as penetrating keratoplasty can be used to treat the refractive error. In addition, corneal cross-linking, which stabilizes the cornea and the use of intracorneal ring segments can inhibit progression. To date, there is no causal treatment option.
The etiology of keratoconus is multifactorial. In addition to environmental factors such as eye rubbing, atopy, and contact lenses use, family studies indicate that genetics may play a central role in disease development. Studies in different populations indicate that certain single nucleotide polymorphisms (SNPs) on certain gene segments are associated with keratoconus.
This dissertation provides an overview of selected genes and polymorphisms and their association with keratoconus. It contains a meta-analysis of the genes IL1B (rs16944), IL1B (rs1143627), COL4A4 (rs222857) and LOX (rs2956540) available via the Pubmed, Web of Science and Google Scholar platforms up to February 11, 2024. The odds ratio (OR) and the 95% confidence interval (95%-CI) of the dominant and recessive model were calculated for each polymorphism. In addition, the presence of publication bias was investigated. Furthermore, this work includes a systemic review of the genes COL5A1 (rs1536482), MPDZ-NF1B (rs1324183), VSX (rs6050307), HGF (rs2286194, rs17501108, rs1014091, rs3735520), Col4A4 (rs2229813), LOX (rs1800449, rs10519694) and ZNF469 (rs9938149). A total of 3927 keratoconus patients and 8877 control subjects from 27 case-control studies were analyzed.
Within the meta-analysis, the “T”-allele of the rs2228557 polymorphism in the COL4A4 gene was identified as a statistically significant protective factor against the development of keratoconus. No clear statistically significant trends were identified for other polymorphisms
The Influence of Hyperthyroid Metabolic Status on the Coagulation and Fibrinolysis System and the Risk of Thrombosis: A Prospective Cohort Study
Full text linkBackground: Risk assessment in hyperthyroidism remains challenging. The aim of the
present study is to determine the influence of hyperthyroid metabolic status on blood
clotting and an increased risk of thrombosis. Methods: This prospective study included
50 patients after radical thyroidectomy and ablative radioiodine therapy because of thyroid
carcinoma who were compared with 50 control subjects in a euthyroid metabolic state.
Latent hyperthyroid patients with basal thyroid-stimulating hormone (TSH) ≤ 0.15 mU/L
on levothyroxine hormone therapy were included. The control group was selected to
match the patient group based on age and sex. The evaluation data were collected using
laboratory coagulation tests and patient questionnaires. A bleeding and a thrombosis
score were determined. Results: The coagulation parameters between the patient and
control groups showed statistically significant differences. In particular, the patients’ group
showed a significantly shortened activated partial thromboplastin time (aPTT/p = 0.009)
and a significantly higher plasminogen activator inhibitor 1 (PAI-1/p < 0.001) compared to
the control group. Age, sex, and medication use were not found to influence the patients’
laboratory results. Only body mass index was higher in the patient group than in the
control group. Conclusions: Our results support a shift in the coagulation system in latent
hyperthyroid metabolism towards increased coagulability and reduced fibrinolysis. A
latent hyperthyroid metabolic state appears to be associated with an increased risk of
thrombosis. Further prospective cohort studies with large patient populations are needed
to verify the association between (latent) hyperthyroidism and thromboembolic events as
well as to determine therapeutic anticoagulation or to adjust the indication for exogenous
administration of thyroid hormone
The ability to interpret affective states in horses' body language is associated with experience with animals
Full text linkIn light of an increasing interest in the human ability to read equine emotions, Braun et al. (2024) recently showed that horse-experienced individuals performed better in interpreting affective states in horses’ body language than horse-inexperienced individuals. Further, individuals with a high emotion recognition ability performed better in interpreting horses’ affective states than individuals with a low emotion recognition ability. The authors operationalized the ability to interpret affective states from horses’ body language by means of the behavior identification test (BIT). In the BIT, participants are presented with 32 photographs of horses that express different affective states and, for each photograph, are asked to choose which out of eight affective states the depicted horse expresses in its body language. In the present study, we scrutinized the replicability and the robustness of these findings. Further, we tested the idea that a better ability to interpret affective states in horses’ body language is associated with experience with animals in general but even more so with horses in particular. We did so by employing the design by Braun et al. (2024) in a novel sample, expanded by a number of quasi-experimental variables (i.e., animal/horse contact while growing-up; current pet/horse ownership; contact with animals/horses during work). We directly replicated the effect reported by Braun et al. (2024) that horse-experienced individuals outperform horse-inexperienced individuals in the BIT. Further, we demonstrated that a higher emotion recognition ability was associated with a better ability to interpret affective states in horses’ body language. Moreover, we found strong evidence in support of the notion that a better ability to interpret affective states in horses’ body language is associated with experience with animals in general and, more strongly, with horses in particular, be it during childhood or currently. We call future research to test the idea that the ability to interpret affective states in horses’ body language can be trained through contact with horses or other animals by means of experimental designs to identify a potential causal relation
New sensor options for smart fracture implants and wearable devices: Laser-Doppler and white-light spectroscopy allow monitoring of bone regeneration via perfusion measurement
Full text linkThe diagnostic options for monitoring fracture healing are currently limited to methods that expose patients to ionizing radiation, i.e. X-rays or computed tomography. The development of new methods that ideally allow continuous monitoring via smart implants or wearables is urgently needed. Laser-Doppler and white-light spectroscopy, non-invasive light-based methods, could allow to monitor fracture healing via changes in perfusion, but this has never been investigated. It was hypothesized that 1) blood flow (BF) increases before a linear increase in oxygen saturation (SO2) and that 2) SO2 in nonunion cases remains as low as the minimum in union cases. A longitudinal observational cohort study with tibial fracture patients was conducted with additional cross-sectional measurements in nonunion patients and healthy controls. To assess SO2, relative haemoglobin amount (rHb), and BF in the fracture gap, the ‘Oxygen to see’ (O2C) device was used. Thirty-five patients (20 longitudinal, 15 nonunion) and 28 controls were included. In the longitudinal group, SO2 decreased, reaching a minimum (10 mm: 17.96 days, 16 mm: 15.50 days), and subsequently increased. BF increased to a maximum (10 mm: 12.90 days, 16 mm: 33.51 days), followed by a decrease. The SO2 values in the nonunion group were similar to the minimum values in the longitudinal group. Findings in nonunion patients vs. controls differed only in SO2 (10 mm: p < 0.001, 16 mm: p = 0.038), not in rHb or BF. Laser-Doppler and white-light spectroscopy provide characteristic SO2 and BF trajectories that may serve to monitor fracture healing
Role of Ionizing Radiation in Shaping the Complex Multi-Layered Epigenome
Full text linkThe impact of ionizing radiation (IR) with induction of various DNA damage is based not
only on genetic but also on epigenetic effects. Epigenetic modifications determine the chro matin structure and DNA accessibility, thereby regulating cellular functions through the
expression of individual genes or entire groups of genes. However, the influence of DNA
repair processes on the restoration of local chromatin structures and global nuclear architec tures is still insufficiently understood. In multicellular organisms, epigenetic mechanisms
control diverse cellular functions of specific cell types through precise temporal and spatial
regulation of gene expression and silencing. How altered epigenetic mechanisms regulate
the pathophysiological function of cells, tissues, and ultimately entire organs following
IR exposure remains to be investigated in detail. Radiation-induced epigenetic processes
are particularly critical for immature cell populations such as tissue-specific stem and
progenitor cells during development and differentiation of organ tissues. Genome-wide
patterns of DNA and histone modifications are established cell types—specifically during
the development and differentiation of organ tissues but can also be fundamentally altered
in adult organism by stress responses, such as radiation-induced DNA damage. Following
IR exposure, epigenetic factors are not always fully restored to their original state, resulting
in epigenetic dysfunction that causes cells to lose their original identity and function. More over, severe radiation-induced DNA damage can induce premature senescence of cells in
complex tissues, which ultimately leads to signs of aging and age-related diseases such as
cancer. In this work, we provide an overview of the most important epigenetic changes
following IR exposure and their pathophysiological significance for the development of
acute and chronic radiation reactions
Rules of Engagement for Components of Membrane Protein Biogenesis at the Human Endoplasmic Reticulum
Full text linkIn human cells, the biogenesis of membrane proteins, which account for one quarter of
polypeptides and sixty percent of human drug targets, is initiated at the membrane of the
endoplasmic reticulum (ER). This process involves N-terminal signal peptides or trans membrane helices in the membrane protein precursors. Over one hundred proteins enable
membrane-targeting and -insertion of the precursors as well as their folding and covalent
modifications. Four targeting pathways to the Sec61 channel in the ER membrane with
their effectors and three cooperating or independent membrane protein–insertases have
been identified. We combined knock-down of individual components of these pathways
and insertases in HeLa cells with label-free quantitative mass spectrometric analysis of
the proteomes. Differential protein abundance analysis in comparison to control cells was
employed to identify clients of components involved in the targeting or membrane insertion
of precursors. Alternatively, knock-out cells or relevant patient fibroblasts were employed.
The features of the client polypeptides were characterized to identify the client types of the
different components and, ideally, their rules of engagement. In this review/article-hybrid,
the focus is on global lessons from and limitations of the proteomic approach in answering
the cell biological question, as well as on new aspects, such as N-terminal acetylation of
membrane protein precursors
Arc erosion and degradation analysis of carbon nanotube-reinforced silver and copper composites for DC switches
Full text linkHot switching creates an electrical arc that erodes electrodes through ion and electron bombardment. This study characterizes arc erosion craters from a single-break operation of carbon nanotube (CNT)-reinforced composite and reference materials. Crater morphology was analyzed via confocal laser and electron microscopy, in addition to energy dispersive X-ray and Raman spectroscopy. Composites of up to 2 wt% resulted in crater roughness, displaced volume, and crater dimensions similar to reference materials. Higher CNT concentrations led to increased roughness and material displacement. Although CNT did not affect the molten front’s dimensions, it reduced molten pool duration. Raman spectroscopy confirmed CNT structural integrity post-manufacturing, despite minor degradation. CNT-reinforced silver and copper composites (up to 2 wt%) demonstrate potential for cost-effective, durable switching electrodes
Development of probiotic microencapsulated Limosilactobacillus reuteri films using mucoadhesive polymers as a delivery system – strategies to improve bacterial viability
Full text linkDysbiosis, an imbalance within the oral microbiome, is associated with several diseases, particularly periodontitis, which is characterized by a transition towards Gram-negative bacteria. Conventional treatments, including antibiotics and surgery, have limitations, which have led to an exploration of alternative methods. The application of probiotic bacteria to restore a balanced microbiome is such a minimally invasive alternative. In practice, the use of probiotic bacteria is hampered by the insufficient survival rate of the bacteria in the formulations. Using Limosilactobacillus strains as an example, this study addresses these challenges and discusses three concrete measures to extend the duration of the bacterial viability. First, bacterial cultures were exposed to stress inducers during cultivation, such as osmotic stress or acidic pH, to induce protective physiological responses and enhance resilience. Next, the probiotic bacteria were microencapsulated via spray-drying with Eudragit® EPO & RL30D. Besides the protective effects, the aim of microencapsulation is to ensure the gradual release of the bacteria, i.e. Limosilactobacillus reuteri (formerly known as Lactobacillus reuteri). Finally, films comprising mucoadhesive polymers were created with the objective of prolonging the residence of bacteria in the oral cavity through mucoadhesive interactions and rendering the bacteria in a form that is suitable for application. Our research underscores the significance of cultivation conditions in improving bacterial survival in subsequent formulation steps. We confirm the efficacy of microencapsulation of L. reuteri through spray-drying. Its success is evidenced by the controlled release identified during the dissolution process. A suitable method for the production of mucoadhesive polymer films is described. Encountered challenges when embedding microencapsulated bacteria in polymer films are discussed and a set of conditions, including growth phase, pH, and osmotic stress, was evaluated to identify factors influencing survival. In summary, the results enhance the progress of focused measures for preserving dental health, highlighting the capability of mucoadhesive polymer films as delivery vehicles for microencapsulated probiotic bacteria
Viscosity and density measurements on the cytosol of human red blood cells
Full text linkWe introduce an approach for determining the viscosity of the intracellular liquid, called cytosol, of human red blood cells (RBCs). This methodology combines measurements of the mass density distribution of RBCs and the viscosity of the cytosol relative to its water content. The density distribution is obtained through buoyant density centrifugation paired with cell counting. By correlating the Gaussian distribution of cell population densities with the viscosity-density relationship of the cytosol, we derive a log-normal distribution of the cytosol viscosity in healthy RBCs. The viscosity contrast
, which is the ratio between viscosities of the RBC cytosol and blood plasma under physiological conditions, is found to have a mean value of
. This value is notably higher than those cited in existing literature for numerical simulations. The broad range of viscosity values stems from the gradual loss of water from RBCs over their 120-day lifespan. Our findings indicate that older RBCs exhibit more than twice the cytosol viscosity of younger cells, a critical factor for future theoretical studies of physiological conditions
Replicable theory
Full text linkIn addition to the difficulties with replicating experiments or systems from some given theoretical description, we discuss the possibility that already the theory itself is poorly replicable. After explaining what we understand by theory replicability, we propose to scientifically evaluate whether or not the broader field of Logic, Semantics, and Verification in Computer Science suffers from systematic theory replicability problems