Scientific publications of the Saarland University
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Site Defects and Structural Alignment Enhance Interfacial Charge Mobility in Heterostructured Carbon Nitride Catalysts
Engineering interfaces between organic semiconductors is an
effective way to tailor organic electronic device performance, as charge transport
and light interaction efficiency are strongly influenced by electronic coupling at
molecular interfaces. Scanning transmission electron microscopy is routinely
used to analyze interfaces at the atomic scale; however, its use for organic
materials is limited due to the electron beam sensitivity of organic molecules,
buried interfaces, and the semicrystalline nature of organics. In this work, we
developed a workflow to correlate charge behavior at organic interfaces with
their chemistry and structure, even when interface components are chemically
and structurally similar and mixed at the nanoscale. We used this workflow to
reveal the nanoscale mechanism behind enhanced charge transfer at the
heterojunction between two-dimensional carbon nitride catalysts (poly heptazine imide (PHI) and poly-triazine imide (PTI)) during the oxygen
reduction reaction. We found that PHI crystallites grow on PTI layers formed at the gas−liquid interface in the salt melt, following
the [001]PTI/[001]K‑PHI orientation. This crystallographic alignment promotes the charge transfer from PTI to PHI and creates an
electron-rich interface. Electron energy loss spectroscopy showed quaternary N atoms in the heterojunction, which aid O2
adsorption and 2e− reduction to H2O2, as well as a higher proportion of terminal and bridging N atoms, promoting charge separation
during the reaction
Ultrasound Training in the Digital Age: Insights from a Multidimensional Needs Assessment
Background: Digitalisation is transforming medical education, but its integration into ultra sound training remains limited. This study evaluates the needs of students and physicians
regarding digitally supported ultrasound education. Materials and Methods: A multi-year
cross-sectional study (2017–2022) employed two standardised questionnaires. The first
assessed the perceived relevance of ultrasound in medical education, the desirability of
compulsory teaching, and the integration of digital media and case-based learning. The
second explored user-centred requirements for e-learning formats, including functionality,
multimedia design, usability, interactivity, and financing, as well as current use of digital
devices and reference materials. Data were collected using dichotomous and 7-point Likert
scales (1 = high need/strong agreement, 7 = low need/weak agreement). Results: A total
of 3479 responses were analysed (2821 students; 658 physicians). Both groups showed
strong support for integrating ultrasound into curricula (1.3 ± 0.7) and mandatory educa tion (1.4 ± 0.9), with students expressing significantly greater support (p < 0.001). There
was broad agreement on the integration and development of digital media (1.7 ± 1.0), as
well as the use of case studies (1.4 ± 0.8), with no significant differences between groups
(p > 0.05). Case-based learning as a stand-alone format was less favoured (3.4 ± 1.9). In the
user-centred needs analysis, both groups rated features like search functions (1.4 ± 0.8),
usability (1.5 ± 0.9), and learning objective checks (2.7 ± 1.6) as important. High-quality
media (1.5 ± 0.9) and pathology explanations (1.6 ± 1.1) were also highly valued. Students
primarily relied on digital platforms, while physicians used a more varied mix of digital
platforms, guidelines, and textbooks. Conclusions: The study highlights the need for
more extensive, digitally supported ultrasound training, with a focus on functionality and
usability. Standardisation through structured certification processes should be considered
for future implementation
Altered Ocular Surface Temperature in Congenital Aniridia with PAX6 Pathogenic Variants: Impact of Age, Salzmann Nodules and Ocular Surgery
PAX6 haploinsufficiency-related congenital aniridia is frequently associated with ocular
surface disease, including meibomian gland dysfunction (MGD), dry eye, limbal stem cell
deficiency (LSCD), aniridia-associated keratopathy (AAK), and inflammation. This study
measured ocular surface temperature (OST) at the corneal center and four paracentral points
(2 mm from center) in patients with congenital aniridia and examined factors influencing
OST. Forty-five eyes from 26 aniridia patients (55.6% female; 26.29 ± 17.78 years) with
PAX6 pathogenic variants and 47 eyes from 25 controls (68.1% female; 24.81 ± 4.73 years;
p = 0.1639) were included. Body temperature, OSDI, and OST (TG-1000) were recorded;
clinical assessment evaluated MGD, LSCD, AAK, iris malformation, epithelial defects,
Salzmann nodules, glaucoma and previous ocular surgery. Body temperature and OSDI
did not differ in aniridia and controls (p ≥ 0.606). LSCD was mainly Grade 2 (46.7%)
or Grade 4 (40.0%), and AAK Grade 1 (33.3%) or Grade 2 (31.1%). MGD affected 51.1%,
Salzmann nodules 22.2%, epithelial defects 2.2%, glaucoma 60.0%, and previous ocular
surgery 35.5%. Superior OST was higher in aniridia (34.98 ± 0.55 ◦C vs. 34.75 ± 0.47 ◦C;
p = 0.012). Exploratory univariate analyses identified that higher AAK grade correlated
with lower inferior OST (p = 0.030), iris malformation with reduced central/paracentral
OST (p ≤ 0.029), and Salzmann nodules with lower OST overall (p ≤ 0.011). However,
in a multivariate model, age, Salzmann nodular degeneration, and prior ocular surgery
emerged as key determinants of OST. OST may serve as a noninvasive biomarker in
congenital aniridia
FOXC1 Regulates Cytokine Signaling, Inflammatory Pathways, and Retinoid Metabolism to Maintain Limbal Epithelial Cell Homeostasis In Vitro
This study aimed to evaluate FOXC1-mediated regulatory mechanisms on gene and pro tein expression profiles in primary human limbal epithelial cells (pLECs) using siRNA mediated FOXC1 knockdown under basal conditions and following lipopolysaccharide
(LPS) and interleukin-1β (IL-1β)-induced inflammatory conditions. The gene expression
related to inflammation, epithelial differentiation, cell proliferation and remodeling, and
retinoic acid metabolism was analyzed using qPCR. Corresponding protein levels were
assessed through Western blotting and ELISA. FOXC1 silencing significantly downregu lated epithelial differentiation markers KRT12 and KRT13 at the mRNA and protein levels
(p ≤ 0.045), whereas KRT3 and KRT19 were unaffected. Inflammatory signaling was
markedly altered, with a reduced IL-6 and IL-8 mRNA expression (p ≤ 0.029), increased
IL-1α expression (p ≤ 0.015), and condition-dependent changes in IL-6 and IL-8 protein
secretion. CCL2 was increased at the mRNA level only (p = 0.007). VEGFA mRNA was con sistently reduced (p ≤ 0.022) without corresponding protein changes, while TGF-β protein
was increased under non-inflammatory and LPS conditions (p ≤ 0.011). Genes involved in
retinoid metabolism, including CYP1B1, FABP5, CRABP2, RDH10, STRA6, and ALDH3A1,
were significantly downregulated (p ≤ 0.037), with reduced CRABP2 and RDH10 pro tein levels (p ≤ 0.017) and a decreased FABP5/CRABP2 ratio under IL-1β stimulation
(p = 0.006). FOXC1 knockdown affected proliferation-related genes, with decreased FOSL2
(p = 0.048) and increased MKi67 (p = 0.006). FOXC1 silencing disrupts epithelial differen tiation, inflammatory signaling, retinoid metabolism, and selected proliferation-related
pathways at the transcriptional level, with more selective effects on protein levels. Such
changes may potentially predispose the ocular surface to lineage instability, fibrosis, and
impaired regenerative capacity
Sporting Careers After ICD Implantation in Elite Athletes
Background: The use of implantable cardioverter defibrillators (ICDs) in elite athletes
following sudden cardiac arrest (SCA) or the diagnosis of high-risk cardiac conditions
presents a complex interplay of medical, psychological, and legal challenges. Despite
evolving guidelines, data on clinical outcomes and return-to-sport (RTS) trajectories in
elite athletes remain limited. Objective: To describe the clinical profiles, management
strategies, and career outcomes of elite athletes who received ICDs. Methods: A retro spective multilingual media and literature search was performed up to January 2026 to
identify elite athletes with ICDs. Inclusion criteria required evidence of professional or
Olympic-level competition, confirmed ICD implantation, and sufficient clinical and ca reer data. Cases were analyzed for demographics, underlying diagnosis, prevention type,
post-ICD outcomes, and RTS status. Results: Thirty-seven elite athletes were identified
(mean age 25.8 ± 4.3 years). The most common sport was football (n = 25). Hypertrophic
cardiomyopathy, non-ischemic LV scar, and arrhythmogenic cardiomyopathy were the
most frequent diagnoses, although 49% of etiologies remained unspecified. ICDs were
implanted for secondary prevention in 70% of cases. Following ICD implantation, 25
athletes (68%) completed RTS, including 24 (65%) at the professional level. Among these,
nine experienced shocks, and four ultimately discontinued competition. The sole fatality
occurred in an athlete who had voluntarily explanted the ICD. Conclusions: A substantial
proportion of elite athletes with ICDs successfully return to high-level sport, but clinical
outcomes, risk tolerance, and legal frameworks remain variable. These findings support
continued shifts towards personalized shared decision making and highlight the need for
standardized, sport-specific RTS protocols, long-term registries, and psychosocial support
in this population
An Investigation of the Effect of Exercise on Sleep Disturbances and Fatigue Symptoms in Patients Diagnosed with Primary Brain Tumors: A Systematic Review
Background: Patients with primary central nervous system (CNS) tumors often experience
fatigue and sleep disturbances, significantly impacting their quality of life. Exercise has
been shown to improve these symptoms in various cancer populations. The aim of this
study is to evaluate the effects of different types of exercise on fatigue and sleep in less investigated CNS tumor patients. Methods: A literature search was conducted in PubMed,
Scopus, Cochrane Library, and CINAHL. Eligible randomized and non-randomized studies
evaluating exercise interventions in patients diagnosed with primary brain tumors were
systematically reviewed, primarily using a narrative synthesis approach. Cancer-related
fatigue and sleep-related outcomes were extracted as variables of interest. Where possi ble [≥2 Randomized Control Trials (RCTs) available for glioma patients], meta-analyses
were conducted to assess the overall effects of physical therapy on the above-mentioned
outcomes. Results: A total of 15 relevant intervention studies were identified, either RCTs
or other types of studies, such as prospective feasibility cohort studies and case studies. A
total of 448 participants were enrolled, with the majority diagnosed with glioma. There
were single reports on pituitary adenoma after surgery and meningioma patients. In
glioma patients, the overall effect of various modality exercise interventions on fatigue
was non-significant, reflecting the heterogeneous characteristics of studies with diverse
outcomes. However, meta-analysis focusing on combined exercise interventions (aerobic
and resistance training) showed a positive effect on reducing fatigue in these patients
[Standardized Mean Difference (SMD) = 0.866, p = 0.03]. Fatigue in glioma patients may
also improve through yoga and Pilates. Aerobic but not strength exercise seems to improve
sleep in glioma patients (SMD = 1.14, p = 0.02). Sleep quality may also improve through
yoga and combined exercise. Conclusions: Certain types of exercise appear to effectively
reduce fatigue and improve sleep in patients with CNS tumors. Future, well–controlled,
multi-arm, larger-scale studies are necessary to resolve discrepancies, as well as to explore
long-term outcomes and define factors influencing individualized exercise responses
MicroRNA in-situ-Analytik bei Plattenepithelkarzinomen der Lunge
Jährlich sterben viele Menschen weltweit an den Folgen einer Krebserkrankung. Die Liste der Krebstodesfälle wird dabei mit Abstand vom Lungenkarzinom angeführt, was es zu einer gefürchteten Erkrankung werden lässt. Trotz intensiver Forschung hinsichtlich neuer diagnostischer, wie auch therapeutischer Ansätze, besitzt das Lungenkarzinom eine schlechte Prognose. Eine unspezifische und häufig fehlende Symptomatik in den frühen Stadien sowie fehlende Screening-Programme führen zur meist erst späten Erstdiagnose der Erkrankung – eine folgenschwere Tatsache bei einer Erkrankung, deren Prognose stark vom Stadium der Erkrankung abhängig ist.
Als ein mittelhochmaligner Subtyp des Lungenkarzinoms gilt das Plattenepithelkarzinom, welches dem Typus des Nicht-kleinzelligen Lungenkarzinoms zugeordnet wird. Mit circa 30% der Nicht-kleinzelligen Lungenkarzinome ist das Plattenepithelkarzinom der zweithäufigste Subtyp dieser Gruppe. Es weist unter allen Typen des Lungenkarzinoms die stärkste Assoziation zur Exposition von Tabakrauch auf und zeigt insgesamt eine komplexe Molekularpathologie. Trotz multipler, zum Teil bekannter molekularer Veränderungen sind bisher nur wenige Medikamente speziell für das Plattenepithelkarzinom entwickelt worden.
Mit der Entdeckung der MicroRNA in den 90er-Jahren eröffnete sich ein neues Forschungsgebiet, das in seiner gesamten Komplexität noch nicht überblickt werden kann. Die kleinen, einzelsträngigen Ribonukleinsäure-Moleküle, welche den nicht-kodierenden Ribonukleinsäuren zugeordnet werden, scheinen vielfältig in multiplen Regulationsmechanismen des Organismus involviert zu sein. Das große Spektrum der beeinflussten Prozesse und die Vielgestaltigkeit der Beeinflussung erschweren das Verständnis für die MicroRNA, verdeutlichen jedoch gleichzeitig die enorme Komplexität dieses Forschungsgebietes und lassen auf große Durchbrüche für die Medizin mit zunehmendem Verständnis hoffen. In vielen Krebsentitäten, so auch beim Lungenkarzinom, konnten dysregulierte MicroRNA-Expressionen und zum Teil auch Einbindungen in bekannte molekulare Signalwege nachgewiesen werden. Das Interesse an der MicroRNA als molekulares Target wächst.
Das Ziel dieser Arbeit war es, eine neue Methode zur lichtmikroskopischen Visualisierung der MicroRNA beim Plattenepithelkarzinom der Lunge zu etablieren und optimieren. Mittels der chromogenen in-situ-Hybridisierung sollte dabei der Schritt von rein molekularen Nachweisverfahren hin zur Darstellung dieser Moleküle in ihrem Gewebeverband geschafft werden. Im Anschluss wurde anhand ausgewählter, spezifischer MicroRNA-Sonden der Versuch unternommen, in Grundzügen eine histo-morphologische Darstellung des MicroRNA-Expressionsprofils im Plattenepithelkarzinom der Lunge zu generieren und dies qualitativ zu kategorisieren.
Zusammenfassend konnte dabei festgestellt werden, dass die Methode der chromogenen in-situ-Hybridisierung zum Verständnis der MicroRNA einen sinnvollen Beitrag darstellt, indem das Vorhandensein und die Lokalisation der MicroRNA im Gewebe lichtmikroskopisch visualisiert werden konnte. Ein routinemäßiger Einsatz genau dieser Methodik hinsichtlich diagnostischer Zwecke scheint jedoch zum jetzigen Zeitpunkt aufgrund des Aufwands der Methodik noch nicht praktikabel.
In Bezug auf den feingeweblichen Nachweis von insgesamt vier, für das Plattenepithelkarzinom der Lunge charakteristischen, MicroRNAs (MicroRNA 205-5p, 126-3p, 200b-3p, 31-3p), konnten für drei MicroRNAs zuverlässige Visualisierungen erzielt werden (MicroRNA 205-5p, 126-3p, 200b-3p). Anhand dieser Ergebnisse konnte die MicroRNA 126-3p als diejenige MicroRNA identifiziert werden, welche am stabilsten nachgewiesen werden konnte.
Eine direkte Kausalität zur Erklärung der unterschiedlichen Visualisierbarkeit der verschiedenen MicroRNAs im Rahmen der in-situ-Hybridisierung konnte nicht festgestellt werden. Ebenso waren keine Abhängigkeiten der Visualisierbarkeit vom Grading, Probenalter, Geschlecht und der Tumorgröße erkennbar. Es kann jedoch festgehalten werden, dass die deutlich differenzierte Visualisierbarkeit der unterschiedlichen MicroRNAs im Rahmen der Untersuchungsreihen darauf hinweist, dass diese doch sehr individuelle Anforderungen an die Untersuchungsbedingungen stellen und ein Nachweisverfahren im Sinne einer Panel-Analyse, zumindest zum jetzigen Zeitpunkt, nicht zielführend erscheint. Damit können bisherige Forschungsergebnisse, welche die Komplexität und Individualität unterschiedlicher MicroRNAs propagieren, nur bekräftigt werden.
Insgesamt tragen die Resultate dieser experimentellen und methodischen Arbeit somit dazu bei, das bisherige Wissen zur MicroRNA hinsichtlich ihrer Lokalisation und ihres Vorhandenseins in den Tumorzellen des Plattenepithelkarzinoms der Lunge zu erweitern. Zudem konnten zelltyp-spezifische Erkenntnisse für den Nachweis von MicroRNA gewonnen werden, die auch für diagnostisch limitiert vorliegendes Tumorgewebe geeignet sind.Worldwide many people die from the consequences of cancer. Lung cancer is the leading cause of cancer mortality, which makes this disease to be feared. Despite intense scientific research regarding medical diagnosis and therapy, lung cancer has a poor prognosis. Early stage lung cancer can be asymptomatic or present with non-specific symptoms. This, in addition to the lack of adequate screening programs can result in delayed diagnosis, an important factor, considering that prognosis is largely dependent on the stage of the disease.
Squamous Cell Carcinoma of the lung is a type of non-small cell lung cancer. It is the second most frequent type of non-small cell lung cancer, accounting for about 30% of this category. Of all the types of lung cancer, squamous cell carcinoma has the strongest association to tobacco smoke exposure and shows a complex molecular pathology. Despite advances in the molecular understanding of the disease, only a few drugs have been developed that specifically target squamous cell carcinoma.
The development of MicroRNA in the nineties opened a new area of scientific research which cannot be summarized here duo to its complexity. The short, single-stranded ribonucleic acid molecules that belong to the non-coding ribonucleic acids seem to be involved in multiple aspects of molecular regulation in the human body. The wide range of processes regulated by MicroRNA and the multidimensionality of their effect makes an understanding of their function challenging. It explains the complexity of this area of research and raises expectations for future medical applications. Many cancer types, including lung cancer, show aberrant alterations MicroRNA-expression. As the proof of integration in known molecular pathways has become established, the interest in MicroRNA as a molecular target has increased.
The purpose of this research was to establish and optimize a new method for the visualization of MicroRNA in squamous cell carcinoma of the lung for optical microscopes. The use of chromogenic in-situ hybridization would allow the morphologic detection of this molecule in tissue. Furthermore, the present study aimed to generate and qualitatively evaluate this morphologic depiction of MicroRNA expression with specific selected MicroRNA-probes.
In summary, this paper established that chromogenic in-situ hybridization makes a meaningful contribution to the understanding of MicroRNA by showing the availability and localization of MicroRNA in cancer tissue for optical microscopes. The routine use of this method before this point, for example in medical diagnostics, was not practical due to costs and uncertain results.
Analyzing the test of four MicroRNAs, which are specific for squamous cell carcinoma of the lung (MicroRNA 205-5p, 126-3p, 200b-3p, 31-3p), there were three series of experiments that showed positive results, whereas the series with MicroRNA-31-3p showed no positive results. MicroRNA 126-3p was identified as the MicroRNA showing the most stable behavior and best sensitivity and specificity. This suggests that MicroRNA 126-3p holds the most relevance for investigations of squamous cell carcinoma of the lung.
A clear explanation for the different results obtained for the various MicroRNA-probes could not be found. Furthermore, the results did not depend on grading, age of the samples, patient gender or tumor size. It was determined that the conditions affected the results. A panel-analytic seems not to be effective at this point. This work confirmed the complexity and individuality of different MicroRNAs.
In summary, the results of this research contribute to and expand the understanding of MicroRNA and their availability and localization in the tissue of squamous cell carcinomas of the lung and clarify the relevance of different MicroRNAs for this subtype of lung cancer. In addition, new insights for the practical use of MicroRNA could were identified
Wachstumsrate von Meningeomzellen in der Zellkultur unter verschiedenen Bedingungen
Die Anzucht von primären Zellkulturen ist eine etablierte Methode in der Tumorforschung. Hierbei spielt die Wachstumsrate eine wichtige Rolle für die Ergebnisse. Abhängig vom experimentellen und klinischen Setting ist das verwendete Gewebe unterschiedlichen Bedingungen ausgesetzt. Der Einfluss dieser Bedingungen auf das Wachstumsverhalten von Zellkulturen ist bis jetzt noch nicht gut untersucht. In dieser Dissertation werden die Ergebnisse einer experimentellen Analyse von Zellkulturen primärer Meningeomzellen präsentiert, nachdem das Tumorgewebe initial unterschiedlichen Bedingungen ausgesetzt war.
Für diese experimentelle Arbeit wurden im Jahr 2022 von Juni bis Dezember 10 primäre,
humane Meningeome nach Operation in der Neurochirurgischen Klinik der Universität des Saarlandes gesammelt. Um zu untersuchen, ob es eine Änderung im Wachstumsverhalten der Zellen gibt, wenn das Gewebe nicht direkt nach der Operation weiterverarbeitet wird, wurde am Tag der Operation eine primäre Zellkultur (Ansatz A p0) und mit einem zeitlichen Versatz von 24 Stunden eine zweite (Ansatz B p0) angesetzt. Zur Beobachtung des Wachstumsverhaltens von Sekundärkulturen wurden Zellen nach Splitting der p0-Kulturen in zwei p1-Kulturen in flüssigem Stickstoff eingefroren und nach 6-7 Monaten rekultiviert. Ergänzend wurden im Vergleich zu den Primär- und Sekundärkulturen Ansätze aus Gewebe jedes Meningeoms angefertigt, das nativ ohne Nährlösung oder Frostschutz eingefroren wurde. Für jedes Meningeom wurden ein Tupfpräparat und pro Ansatz A und B jeweils ein Tropfpräparat der primären (p1) und der sekundären Zellkultur (p2) angefertigt und der Fluoreszenz-in-situ-Hybridisierung unterzogen. Die Ergebnisse wurden mit denen der Loss-of-Heterozygosity-Analyse (LOH-Analyse) verglichen, um die valide Repräsentation des Tumorgewebes durch die Zellkultur zu überprüfen.
Es wurde gezeigt, dass das Wachstumsverhalten von Meningeomzellkulturen unabhängig vom oben genannten zeitlichen Ansatz war, vorausgesetzt, dass sich ausreichend lebende Zellen im verwendeten Gewebe befanden. Zudem wurde deutlich, dass eine Kultivierung aus nativem, gefrorenem Tumormaterial unter Verwendung derselben Methoden nicht möglich war. Auf der anderen Seite ließen sich die eingefrorenen Zellen sehr gut erneut kultivieren. Insgesamt waren circa 90 % aller Zellkulturen angewachsen. Zudem verifizierten die Ergebnisse der Fluoreszenz-in-situ-Hybridisierung, dass die etablierten primären Zellkulturen das Tumormaterial valide repräsentierten, auch nach dem Einfrieren und Rekultivieren.Cell cultures are an established method in tumor research. Thereby, the growth rate is
important for the results. Depending on the experimental and clinical setting, the tissue used is exposed to different conditions. The influence of these cell and tissue conditions on the growth pattern of cell cultures are not well reported yet. Here, the results of an experimental analysis of cell culture of primary meningioma cells after different initial tissue conditions are presented.
In 2022, from June to December, 10 primary human meningiomas were collected after surgery at the Neurosurgical Department of the Saarland University for this experimental work. In order to investigate whether there is a change in the growth pattern of the cells if the tissue is not processed immediately after surgery, a first cell culture was set up directly on the day of surgery (approach A p0) and a second cell culture (approach B p0) only 24 hours later. Cells were frozen in liquid nitrogen after splitting the p0-cultures into 2 p1-cultures and recultured after 6-7 months to observe the growth pattern of secondary cell cultures. Additionally and in comparison to the primary and secondary cell cultures, approaches were prepared from tissue of each meningioma that was frozen natively without nutrient or antifreeze solution. For each meningioma, a touch preparation was prepared, further a drop preparation of the primary (p1) and the secondary cell culture (p2) for each approach A and B. All preparations were subjected to Fluorescence in situ hybridization. The results were compared with those of the Loss-of-Heterozygosity-Analysis (LOH-Analysis) to verify the valid representation of tumor tissue by cell culture.
It has been shown that the growth pattern of meningioma cell cultures was independent of the time they are set up under the condition that there were enough living cells in the tissue. Further, the culturing of frozen tissues was not possible in the same setting. On the other hand, the frozen cell cultures could be recultivated very well. Moreover, the results of Fluorescence in situ hybridization verified that the established primary cell cultures validly represented the tumor material, even after freezing and recultivating
A Role for Finger Properties in Exploration and Perception of Softness
Individuals with more elastic, more hydrated or
smaller fingers usually show better performance in several passive
touch tasks. In active touch, people use different exploratory proce dures when evaluating object properties, and tune their exploratory
parameters. For example, they indent stimuli to assess softness
and optimize their peak forces to get relevant information. In this
study, we aim to understand whether finger pad size, elasticity and
hydration affect individuals’ force-tuning and discrimination per formance in active softness perception. Participants performed two
softness tasks in two different sessions. In one session, hyaluronic
acid was applied to their finger pads to soften it, in the other
they received no treatment. We assessed individual elasticity and
hydration values with cutometer and corneometer in each session,
and measured finger pad size in three dimension by caliper. In
each task, two pairs of stimuli were presented to the participants
(Young’s Modulus: 41.5 vs. 45.0; 28.7 vs. 31.3 kPa) who chose
the softer stimulus. In the restricted task, they could apply force
only up to 2 Newton, whereas there was no force limit in the
unconstrained task. We found that participants with smaller finger
pad size exerted less force in the restricted task and participants
with more hydrated and elastic fingers exerted less force in the
unconstrained task. The force-tuning disappeared in the uncon strained task when treatment was applied. These results indicate
that people employ strategies according to their finger parameters
and to the availability of cues whereas adaptation to treatment is
likely to need longer practice
Plasma Fibronectin Drives Macrophage Elongation via Integrin β3–Tie2 Axis in Blood Clots
Background/Objectives: Plasma fibronectin (pFN) supports lung metastasis by promoting
tumor cell invasion and survival in the context of blood clotting. Here, we set out to
test if myeloid cells reiterate the clot-invasive mechanisms that have been established for
tumor cells. Methods: We analyzed lung tissue sections from transgenic pFN-deficient
mice for the co-localization of intravenously injected B16F1 tumor cells and the surround ing fibrin with myeloid cells, granulocytes, and macrophages. We also tested the role of
pFN for macrophage differentiation and invasion in a three-dimensional fibrin matrix.
Results: B16F1 melanoma cells, entrapped in the lungs of pFN-competent C57BL/6-Fn(fl/fl)
Mx-Cre− mice, were surrounded by a fibrin matrix, CD11b-positive myeloid cells, and Gr 1-positive granulocytes within 1 h of intravenous injection, while homing F4/80-positive
macrophages to lung-born tumor cells occurred within 16 h. Compared to pFN-competent
C57BL/6-Fn(fl/fl) Mx-Cre− mice, the co-localization of CD11b+
, Gr-1+
, and F4/80+
cells
with B16F1 cells was significantly reduced in the lungs of pFN-deficient C57BL/6-Fn(fl/fl)
Mx-Cre− mice. Mechanistically, we found that fibrin–fibronectin complexes promoted
macrophage adhesion, differentiation, and invasion in clotted plasma. The pro-invasive
function of fibrin–fibronectin depended on the upregulation of integrin β3 and Tie2 ex pression in macrophages and was reversed after knocking-down integrin β3 and Tie2 with
siRNA. Conclusions: Our results suggest that blood clotting plays an important role in the
recruitment of macrophages to circulating tumor cells and that the underlying mechanism
of macrophage recruitment involves fibrin–fibronectin complexes, integrin β3, and Tie2