Scientific publications of the Saarland University
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Discovering motifs to fingerprint multi-layer networks: a case study on the connectome of C. Elegans
Get PDFMotif discovery is a powerful and insightful method to quantify network structures and explore
their function. As a case study, we present a comprehensive analysis of regulatory motifs in the connectome
of the model organism Caenorhabditis elegans (C. elegans). Leveraging the Efficient Subgraph Counting
Algorithmic PackagE (ESCAPE) algorithm, we identify network motifs in the multi-layer nervous system
of C. elegans and link them to functional circuits. We further investigate motif enrichment within signal
pathways and benchmark our findings with random networks of similar size and link density. Our findings
provide valuable insights into the organization of the nerve net of this well-documented organism and can
be easily transferred to other species and disciplines alike
Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia
Get PDFTracheal tuft cells shape immune responses in the airways. While some of
these effects have been attributed to differential release of either acetylcholine, leukotriene C4 and/or interleukin-25 depending on the activating stimuli,
tuft cell-dependent mechanisms underlying the recruitment and activation of
immune cells are incompletely understood. Here we show that Pseudomonas
aeruginosa infection activates mouse tuft cells, which release ATP via pannexin
1 channels. Taste signaling through the Trpm5 channel is essential for bacterial
tuft cell activation and ATP release. We demonstrate that activated tuft cells
recruit dendritic cells to the trachea and lung. ATP released by tuft cells
initiates dendritic cell activation, phagocytosis and migration. Tuft cell stimulation also involves an adaptive immune response through recruitment of
IL-17A secreting T helper cells. Collectively, the results provide a molecular
framework defining tuft cell dependent regulation of both innate and adaptive
immune responses in the airways to combat bacterial infection
Sex and gender differences in the molecular etiology of Parkinson's disease: considerations for study design and data analysis
Get PDFParkinson’s disease (PD) is more prevalent in men than women, and presents with different clinical features in
each sex. Despite widespread recognition of these differences, females are under-represented in clinical and
experimental studies of PD, and much remains to be elucidated regarding the biological underpinnings of sex
differences in PD. In this review, we summarize known contributors to sex differences in PD etiology across the
life course, with a focus on neurological development and gene regulation. Sex differences that are established
at conception and heightened during adolescence and midlife may partially embed future PD risk, due to
the complex interactions between gonadal hormones, gene regulation, lifestyle factors, and aging. While the
neuroprotective properties of estrogen are strongly implicated in reduced prevalence of PD in women, interactions
with genotype and gender-biased lifestyle factors are incompletely understood. Consideration of sex and genderrelated factors in study design, data analysis, and interpretation have the power to expedite our knowledge of the
etiology of PD in men and in women, and to inform prevention and therapeutic strategies tailored to each sex.
Plain english summary
Parkinson’s disease (PD) more commonly affects men, and is known to have different symptoms in men and
women. While this is in part due to the protective effects of estrogen in women, our understanding of why there
is a sex difference in PD, and how it develops in each sex, is currently incomplete. This article provides an overview
of factors throughout the lifespan that contribute to the differences between men and women in brain health and
risk for PD, with a focus on hormones, gene regulation, and their intersections with lifestyle factors. We also discuss
how researchers can consider sex and gender in future studies to enhance our understanding of how PD develops,
and potentially develop sex-tailored prevention and treatment strategies.
Highlights
• Genetic risk for PD is similar between men and women.
• Transcriptomic and epigenetic differences in men and women with PD have been reported, particularly in
substantia nigra tissue. • Emerging evidence suggests interactions between gene regulation, sex hormones, and lifestyle factors
contribute to disease pathogenesis in each sex.
• Statistical approaches can be used to balance sex ratios and explore sex as a contributor to PD etiology, rather
than a confounder.
• Increasing representation of women in PD clinical studies is a priority for future research endeavors
Uncovering the genetic basis of antiviral polyketide limocrocin biosynthesis through heterologous expression
Get PDFBackground Streptomyces roseochromogenes NRRL 3504 produces clorobiocin, an aminocoumarin antibiotic
that inhibits DNA replication. No other natural products have been isolated from this bacterium so far, despite the
presence of a rich repertoire of specialized metabolite biosynthesis gene clusters (smBGCs) within its genome.
Heterologous expression of smBGCs in suitable chassis speeds up the discovery of the natural products hidden
behind these sets of genes.
Results In this work we focus on one intriguing smBGC of NRRL 3504 bearing some similarity to gene clusters
involved in production of manumycin family polyketides. Through heterologous expression in Streptomyces chassis
strains S. albus Del14 and S. lividans ΔYA9, this smBGC (hereafter referred to as lim BGC) was shown to direct the
production of unusual polyketide limocrocin (LIM) known for its ability to interfere with viral reverse transcriptases.
The organization of lim BGC, data on the structures of revealed metabolites as well as manipulations of lim genes
allowed us to put forward an initial hypothesis about a biosynthetic pathway leading to LIM. We provide initial data
on two LIM derivatives as well as updated NMR spectra for the main product.
Conclusion This study reveals the genetic control of biosynthesis of LIM that remained hidden for the last 70 years.
This, in turn, opens the door to biological routes towards overproduction of LIM as well as generation of its derivatives
Tumor Necrosis Factor-Alpha Inhibits the Replication of Patient-Derived Archetype BK Polyomavirus While Activating Rearranged Strains
Get PDFTo date, no drugs are approved for BK polyomavirus (BKPyV) reactivation, a major cause of nephropathy after kidney
transplantation. Recently, tumor necrosis factor‐α (TNF‐α) blockade has been proposed as a promising therapy, however, the
effect of TNF‐α on the clinically most common archetype (ww) BKPyV remained unclear. Assays in primary renal proximal
tubule epithelial cells (RPTEC) allowed efficient replication only of BKPyV strains with rearranged (rr) non‐coding control
regions (NCCR), which may develop at later disease stages, but not of ww‐BKPyV. Here, we optimized culture conditions
allowing robust replication of patient‐derived ww‐BKPyV, while efficiently preserving their ww‐NCCR. TNF‐α promoted
rr‐BKPyV replication, while the TH1 cytokine IFN‐γ suppressed it, also in the presence of TNF‐α. Surprisingly, TNF‐α alone was
sufficient to suppress all ww‐BKPyV strains tested. Comprehensive analysis using siRNAs, and chimeric or mutated BKPyV‐
strains revealed that the response to TNF‐α depends on the NCCR type, and that the NF‐κB p65 pathway but not the conserved
NF‐κB binding site is essential for the TNF‐α‐induced enhancement of rr‐BKPyV replication. Our data suggest that in immunosuppressed patients with archetype‐dominated infections, TNF‐α blockade could interfere with natural TNF‐α‐mediated
anti‐BKPyviral control, and this could be detrimental when IFN‐γ‐driven TH1 responses are impaired. Ongoing inflammation,
however, could lead to the selection of rearrangements responding to NCCR‐activating pathways downstream of NF‐κB p65
signaling, that may overcome the initial TNF‐α‐mediated suppression. Our findings also highlight the importance of using
clinically relevant BKPyV isolates for drug testing and discovery, for which this new assay paves the way
Evaluation of keratometric and total corneal astigmatism measurements from optical biometers and anterior segment tomographers and mapping to reconstructed corneal astigmatism vector components
Get PDFPurpose
To investigate different measures for corneal astigmatism in the context of reconstructed
corneal astigmatism (recCP) as required to correct the pseudophakic eye, and to derive prediction models to map measured corneal astigmatism to recCP.
Methods
Retrospective single centre study of 509 eyes of 509 cataract patients with monofocal
(MX60P) IOL. Corneal power measured with the IOLMaster 700 keratometry (IOLMK), and
Galilei G4 keratometry (GK), total corneal power (TCP2), and Alpin’s integrated front (CorT)
and total corneal power (CorTTP). Feedforward shallow neural network (NET) and linear
regression (REG) prediction models were derived to map the measured C0 and C45 power
vector components to the respective recCP components.
Results
Both the NET and REG models showed superior performance compared to a constant
model correcting the centroid error. The mean squared prediction errors for the NET/REG
models were: 0.21/0.33 dpt for IOLMK, 0.23/0.36 dpt for GK, 0.24/0.35 for TCP2, 0.23/0.39
dpt for CorT and 0.22/0.36 dpt for CorTTP respectively (training data) and 0.27/0.37 dpt for
IOLMK, 0.26/0.37 dpt for GK, 0.38/0.42 dpt for TCP2, 0.35/0.36 dpt for CorT, and 0.44/0.45
dpt for CorTTP respectively on the test data. Crossvalidation with model optimisation on the training (and validation) data and performance check on the test data showed a slight overfitting especially with the NET models.
Conclusions
Measurement modalities for corneal astigmatism do not yield consistent results. On training
data the NET models performed systematically better, but on the test data REG showed
similar performance to NET with the advantage of easier implementation
The Case for Shared Religious Education
Get PDFThis paper conceptualises ‘shared religious education’ as a way for religious
educators to reflect on how their subject might respond to a global need for cooperation
and mutual understanding. In the context of migration, climate crisis and violent conflict,
European societies are increasingly plural, yet subject to processes of individualization
and competition which undermine people’s ability to cooperate and share across their
respective cultural and ideological differences. We argue that there is an imperative for
sharing and collaboration in response to the dangers we see in our increasingly fractured
social worlds; and that education can play a key role in responding to this urgent need.
Religious education, however, is subject to the sociological reality that it can separate as
well as unite people. Through a critical discussion of the ‘shared education’ model, we
make a case for shared religious education, identifying four core aims for those working
in the fields of religious and worldviews education. Drawing on literature from religious
education, we offer ideas and insights for how those working in the fields of religious and
worldviews education may pursue these aims and so respond to the imperative for sharing
Impact of Bonding Pressure on the Reactive Bonding of LTCC Substrates
Get PDFReactive bonding can overcome the issues associated with conventional soldering
processes, such as potential damage to heat-sensitive components and the creation of
thermomechanical stress due to differing coefficients of thermal expansion. The risk of
such damage can be reduced by using localized heat sources like reactive multilayer
systems (RMS), which is already a well-established option in the field of silicon or metal
bonding. Adapting this process to other materials, such as low temperature co-fired
ceramics (LTCC), is difficult due to their differing properties, but it would open new
technological possibilities. One aspect that significantly affects the quality of the bonding
joints is the pressure applied during the bonding process. To investigate its influence more
closely, various LTCC samples were manufactured, and cross-sections were prepared. The
microscopical analysis reveals that there is an optimum range for the bonding pressure.
While too little pressure results in the formation of lots of voids and gaps, most likely in
poor mechanical and electrical properties, too high pressure seems to cause a detachment
of the metallization from the base material
Elastocaloric can cooler: an exemplary technology transfer to use case application
No full textThe elastocaloric effect offers a promising alternative to conventional
compressor-based heating and cooling systems. This technology leverages
solid-state phase transformations with high energy densities, eliminating the
need for environmentally harmful refrigerants. As a result, elastocaloric systems
can be developed for both heating and cooling applications that are sustainable,
highly efficient, and scalable. In this study, the first elastocaloric “minifridge” operating under tensile load is developed, using air as heat transfer
medium. This system is based on the world’s first continuously operating airto-air elastocaloric machine demonstrator. The primary focus of this study
is to investigate the transition from a generic technology demonstrator to
an application-oriented system. A simulation tool enables investigation and
optimization of various machine parameters such as material dimensions, load
profiles, and latent heats for the intended application. The application targeted
in this study is a “mini-fridge” designed to cool a standard 0.25 L beverage can.
Shape memory alloy wire bundles are subjected to loading and unloading cycles
by a patented energy converter. To effectively harness the latent heat released
during phase transformation, the air must be optimally directed over the wire
bundles. The cooling process is achieved by continuously circulating air around
the bundles, progressively cooling a volume. The simulation tool is employed to
determine the optimal geometric and process parameters for this system. The
study aims to develop the first continuously operating elastocaloric “mini-fridge”
with an internal cooling volume. To validate the entire setup, the inner chamber
is equipped with temperature sensors to monitor the cooling performance.
These sensors are strategically placed along the axis of rotation to measure
the temperature as air enters and exits the chamber. The initial measurements
achieved a temperature difference of approximately 3.5 K within the cooling
chamber versus a simulated value 8.7 K, which did not include all possible losses
present in the system. The simulation suggests a system COP at steady state of
5.8, which must be experimentally verified in future work
Thérapie au subthreshold nanolaser pour la choriorétinopathie centrale séreuse chronique : une étude prospective
No full textPurpose. — To investigate the morphologic and functional outcomes of nanosecond subthreshold
(ST) laser treatment for patients with chronic central serous chorioretinopathy (CSC).
Methods. — In this prospective study, 44 patients were treated with the ST nanosecond laser
with a follow-up period of 12 months. All target variables were measured at 1, 3, 6 and 12
months after the first laser treatment.
Results. — This study showed a significant improvement in macular sensitivity (MS), a significant
reduction in central macular thickness (CMT) as well as a significant reduction in subretinal
fluid height (SRF) after 3 months of treatment. The subfoveal choroidal thickness (SFCT) was
significantly reduced after 12 months of treatment. However, the best-corrected visual acuity
(BCVA) (logMAR) did not change significantly at any time during the study. A high proportion
of patients (85%) showed complete resolution of SRF after 12 months, indicating a positive
response to treatment in the majority of our patients. Conclusion. — This study showed statistically significant functional improvement in MS as well
as significant anatomical reduction in CMT, SFCT and SRF height in CSC patients treated with
ST nanosecond laser therapy. Patients with higher SRF at baseline required repeated laser
treatments to achieve complete resolution of the SRF.Objectif. — Étudier les resultats ´ morphologiques et fonctionnels du traitement au subthreshold
(ST) nanolaser pour les patients atteints de chorioretinopathie ´ centrale sereuse ´ chronique
(CCS).
Methodes. ´ — Dans cette etude ´ prospective, 44 patients ont et ´ e´ traites´ au ST nanolaser avec
une periode ´ de suivi de 12 mois. Toutes les variables ont et ´ e´ mesurees ´ à 1, 3, 6 et 12 mois après
le premier traitement au laser.
Resultats. ´ — Cette etude ´ a demontr ´ e´ une amelioration ´ significative de la sensibilite´ maculaire (SM) et une reduction ´ significative de l’epaisseur ´ maculaire centrale (EMC), ainsi que
de la hauteur du liquide sous-retinien ´ (LSR) après 3 mois de traitement. L’epaisseur ´ choroïdienne sous-foveale ´ (ECSF) n’a et ´ e´ significativement reduite ´ qu’après 12 mois de traitement.
Cependant, la meilleure acuite´ visuelle corrigee´ (MAVC) (logMAR) n’a pas change´ de manière
significative durant l’etude. ´ La majorite´ des patients (85 %) a montre´ une resolution ´ complète
du LSR après 12 mois, ce qui indique une reponse ´ positive au traitement.
Conclusion. — Cette etude ´ a demontr ´ e´ une amelioration ´ statistiquement significative de la SM
ainsi qu’une reduction ´ significative de l’EMT, de l’ECSF et de la hauteur du LSR chez les patients
atteints de CCS traites´ au ST nanolaser. Les patients presentant ´ un LSR plus elev ´ e´ au depart ´
ont dû subir plusieurs traitements pour obtenir une resolution ´ complète du LSR