Scientific publications of the Saarland University
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Role of Epigenetics in Chronic Lung Disease
Full text linkEpigenetics regulates gene expression and thus cellular processes that underlie
the pathogenesis of chronic lung diseases such as chronic obstructive pulmonary disease
(COPD), asthma, and idiopathic pulmonary fibrosis (IPF). Environmental factors (e.g., air
pollution, smoking, infections, poverty), but also conditions such as gastroesophageal
reflux, induce epigenetic changes long before lung disease is diagnosed. Therefore, epigenetic signatures have the potential to serve as biomarkers that can be used to identify
younger patients who are at risk for premature loss of lung function or diseases such as IPF.
Epigenetic analyses also contribute to a better understanding of chronic lung disease. This
can be used directly to improve therapies, as well as for the development of innovative
drugs. Here, we highlight the role of epigenetics in the development and progression of
chronic lung disease, with a focus on DNA methylation
Decreased PAX6 and DSG1 Protein Expression in Corneal Epithelium of Patients with Epithelial Basal Membrane Dystrophy, Salzmann Nodular Degeneration, and Pterygium
Full text linkBackground/Objectives: Evaluation of stem cell, keratin, retinoic acid metabolism
markers and non-coding micro-RNAs (miRNAs) in conjunctival and corneal samples of patients with epithelial basal membrane dystrophy (EBMD), Salzmann nodular degeneration
(SND), pterygium and congenital aniridia (CA), to detect similarities and differences in their
pathogenesis. Methods: Impression cytology (IC) samples and corneal epithelial samples
(CEs) of patients with EBMD, SND, pterygium, congenital aniridia, and healthy control
subjects have been analyzed. The IC samples were subjected to qPCR, and the epithelial
samples were subjected to qPCR and WB. Limbal epithelial stem cell markers, keratins,
retinoic acid metabolism markers, and miRNAs were analyzed. Results: In conjunctival IC
samples, PAX6 mRNA expression was significantly lower in EBMD, SND, pterygium, and
CA compared to healthy controls (p ≤ 0.02). KRT13 mRNA expression was significantly
higher in EBMD, SND, and pterygium (p ≤ 0.018), and FABP5 was increased in pterygium
samples (p = 0.007). MiRNA-138-5p was significantly higher in aniridia samples than in
normal controls (p = 0.037). In corneal epithelial samples, PAX6 protein, DSG1 mRNA and
protein, miRNA-138-5p, and miR-204-5p expression were significantly lower in EBMD,
SND, and pterygium samples than in controls (p ≤ 0.02). ALDHA1 mRNA expression was
significantly lower (p < 0.0001), and FABP5 mRNA expression was significantly higher
(p = 0.014) in pterygium samples than in controls. Conclusions: PAX6, DSG1, miR-138-5p,
and miR-204-5p expression is decreased in the corneal epithelium of epithelial basal membrane dystrophy, Salzmann nodular degeneration, and pterygium subjects. In addition,
there is a dysregulation of markers of the retinoic acid signaling pathway, such as ADH1A1
and FABP5, in the corneal epithelium of pterygium subjects. These changes may offer
therapeutic targets in the treatment of these ocular surface diseases
Comprehensive Analysis of Rodent-Specific Probasin Gene Reveals Its Evolutionary Origin in Pseudoautosomal Region and Provides Novel Insights into Rodent Phylogeny
Full text linkProbasin protein was originally identified as a basic protein present in rat prostate
epithelium. So far, its physiological role, its origin, and its presence in other species
including humans remain largely elusive. With the ever-growing number of genome
assemblies, thus far, probasin genes (Pbsn/PBSN) have only been predicted in a subset of
rodent genomes. In this study, we addressed the phylogeny of probasin genes and found
them to be exclusively present in members of the superfamily Muroidea. It first emerged
in the so-called pseudoautosomal region, a subtelomeric gene cluster of both mammalian
sex chromosomes. During evolution of the Muroidea lineages, probasin recombined to the
X-specific region of the X-chromosome in mice and hamster species. This event likely saved
the gene from events that other pseudoautosomal genes suffered, namely displaying an
increase in G and C nucleotide composition or accumulation of repetitive elements. We
observed changes to its coding region, e.g., sequence insertions in exon 6, which challenge
the current understanding of rodent phylogeny, in particular regarding the evolutionary
history of tribe formation within the subfamily Murinae. Analyzing the evolution of
probasin genes in Muroidea allows fostering understanding of phylogenetic relationships in
one of the largest groups of mammalian species
Informed but Unvaccinated: A Cross-Sectional Study Among University Students in Ghana
Full text linkDuring the COVID-19 pandemic, vaccination hesitancy (VH) posed an equally
unexpected and significant obstacle to the effectiveness of public health interventions. VH
has not only the potential to stir up public unrest, but it may also impede the success of
entire immunization programs and thus prevent the attainment of herd immunity. This
cross-sectional, quantitative, and descriptive study examined VH and vaccination behavior
(VB) among 3486 university students in Ghana, using a standardized self-administered
questionnaire based on the 5Cs model among other relevant variables. The findings
confirm a significant VH and a VB influenced by both sociodemographic factors, such as
gender (OR: 1.45; [CI: 1.26–1.67]), study program (OR: 0.55; [CI: 0.47–0.64]), and ethnicity
(OR: 1.31; [CI: 1.12–1.52]) and also four of the 5Cs, i.e., Confidence (OR:1.56; [CI: 1.45–1.68]),
Constraints (OR: 0.83; [CI: 0.78–0.87]), Calculation (OR:0.85; [CI: 0.78–0.92]), and Collective
Responsibility (OR:1.27; [CI: 1.16–1.38]), yet not Complacency, nor religion. Notably,
VH was further shaped by previous vaccine experience, information sources, vaccine
attributes, stance on vaccine passport, and conspiracy beliefs, with misinformation from
unofficial sources playing a key role. The multiple regression models explained 11% to
34% of the variance in the 5Cs, indicating varying degrees of explanatory power for each
factor influencing VB and eventually also VH. This study highlights the urgent need for
targeted public health interventions, such as integrating vaccine education into university
orientation programs, streamlining vaccination processes, and leveraging influencers for
trust-building campaigns
New Parameters Based on Ground Reaction Forces for Monitoring Rehabilitation Following Tibial Fractures and Assessment of Heavily Altered Gait
Full text linkInstrumented insoles have created opportunities for patient monitoring via longterm recordings of ground reaction forces (GRFs). As the GRF curve is altered in patients
after lower-extremity fracture, parameters defined on established curve landmarks often
cannot be used to monitor the early rehabilitation process. We aimed to screen several new
GRF curve-based parameters for suitability and hypothesized an interrelation with days
after surgery. In an observational longitudinal study, data were collected from 13 patients
with tibial fractures during straight walking at hospital visits using instrumented insoles.
Parametrized curves were fitted and regression analyses conducted to determine the best
fit, reflected in the highest R2
-value and lowest fitting error. A Wald Test with t-distribution
was employed for statistical analysis. Strides were classified as regular or non-regular, and
changes in this proportion were analyzed. Among the 12 parameters analyzed, those with
the highest R2
-values were the mean force between inflection points (R2 = 0.715, p < 0.001,
t42 = 9.89), the absolute time between inflection points (R2 = 0.707, p < 0.001, t42 = 9.83),
and the highest overall force (R2 = 0.722, p < 0.001, t42 = 10.05). There was a significant
increase in regular strides on both injured (R2 = 0.427, p < 0.001, t42 = 5.83) and healthy
(R2 = 0.506, p < 0.001, t42 = 6.89) sides. The proposed parameters and assessment of the
regular stride ratio enable new options for analyses and monitoring during rehabilitation
after tibial shaft fractures. They are robust to pathologic GRF curves, can be determined
independently from spatiotemporal coherence, and thus might provide advantages over
established methods
Improved Proximity Labeling for Quantitative Proteomic Profiling of Primary Cilia in Previously Inaccessible Cell Types
No full textQuadricuspid aortic valve repair: Results of a phenotype-based approach
Full text linkObjective: Quadricuspid aortic valve (QAV) anatomy is a rare congenital anomaly.
Patients develop relevant aortic regurgitation (AR), commonly between the fourth
and sixth decades of life. Various approaches to repair have been proposed, but
mid-term data are lacking. The present study aimed to investigate late results of
QAV repair using different repair concepts.
Methods: Between 2004 and 2023, 19 patients (32% male; mean age, 46 12 years;
range, 26-60 years) underwent QAV repair. The mean duration of follow-up was
6.3 5 years (range, 4 months to 19 years), and follow-up was 96% complete. Patients underwent surgery for isolated AR (n ¼ 18) or combined valve disease (n ¼ 1).
Three patients (16%) had concomitant ascending aortic dilatation.
Results: The majority of patients underwent design change—tricuspidization
(n ¼ 13; 68%) or bicuspidization (n ¼ 3; 16%)—of the QAV; the valve was left quadricuspid in 3 patients (16%). Sinotubular junction remodeling was performed by
adding a sinotubular suture (n ¼ 7; 37%) or by ascending aortic replacement
(n ¼ 3; 16%). All patients were alive at 5 years and 10 years postoperation; 2
required late aortic valve reoperation. Freedom from reoperation was 82% at
12 years (86% after tricuspidizdation and 67% after bicuspidization). The 3 patients
whose valve remained quadricuspid did not require reoperation after 2 years,
3 years, and 5 years. Overall freedom from AR >2 was 76% at 12 years. At last
follow-up, 2 patients had a mean gradient of 21 mm Hg, both of whom had undergone bicuspidization.
Conclusions: QAVs can be repaired by different methods, including tricuspidization and bicuspidization. If the quadricuspid morphology is preserved, stabilization
of annular and sinotubular dimensions may achieve a stable result. (JTCVS Techniques 2025;30:23-31
Conjoint generalized and trajectory-specific coding of task structure by prefrontal neurons
Full text linkNeurons in the medial prefrontal cortex (mPFC) are spatially tuned. Trajectory-specific firing with distinct
spatial tuning on different paths to reward sites as well as generalized spatial tuning with similar responses
on separate trajectories have been described. However, it is unclear whether such distinct populations
contribute differently to the encoding of task space. Here, we find coexisting populations of neurons with trajectory-specific and generalized tuning profiles in an olfaction-guided spatial memory task in mice. Neurons
with generalized representation show stable spatial tuning within and across days, allow accurate predictions of the animal’s position, and preferentially emerge upon task learning. In contrast, cells with trajectory-specific spatial tuning display dynamically changing tuning functions, are less informative about the current position, and can be identified at a larger proportion early in task learning. These results highlight a role
for neurons with generalized tuning in the efficient and stable representation of task space
A single-cell atlas to map sex-specific gene-expression changes in blood upon neurodegeneration
Full text linkThe clinical course and treatment of neurodegenerative disease are complicated by immune-system interference and chronic inflammatory processes,
which remain incompletely understood. Mapping immune signatures in larger
human cohorts through single-cell gene expression profiling supports our
understanding of observed peripheral changes in neurodegeneration. Here,
we employ single-cell gene expression profiling of over 909k peripheral blood
mononuclear cells (PBMCs) from 121 healthy individuals, 48 patients with mild
cognitive impairment (MCI), 46 with Parkinson’s disease (PD), 27 with Alzheimer’s disease (AD), and 15 with both PD and MCI. The dataset is interactively
accessible through a freely available website (https://www.ccb.uni-saarland.
de/adrcsc). In this work, we identify disease-associated changes in blood cell
type composition and the gene expression in a sex-specific manner, offering
insights into peripheral and solid tissue signatures in AD and PD