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IGF1R expression by adult oligodendrocytes is not required in the steady-state but supports neuroinflammation
No full textIn the central nervous system (CNS), insulin-like growth factor 1 (IGF-1) regulates
myelination by oligodendrocyte (ODC) precursor cells and shows anti-apoptotic properties
in neuronal cells in different in vitro and in vivo systems. Previous work also
suggests that IGF-1 protects ODCs from cell death and enhances remyelination in
models of toxin-induced and autoimmune demyelination. However, since evidence
remains controversial, the therapeutic potential of IGF-1 in demyelinating CNS conditions is unclear. To finally shed light on the function of IGF1-signaling for ODCs,
we deleted insulin-like growth factor 1 receptor (IGF1R) specifically in mature ODCs
of the mouse. We found that ODC survival and myelin status were unaffected by the
absence of IGF1R until 15 months of age, indicating that IGF-1 signaling does not
play a major role in post-mitotic ODCs during homeostasis. Notably, the absence of
IGF1R did neither affect ODC survival nor myelin status upon cuprizone intoxication
or induction of experimental autoimmune encephalomyelitis (EAE), models for toxic
and autoimmune demyelination, respectively. Surprisingly, however, the absence of
IGF1R from ODCs protected against clinical neuroinflammation in the EAE model.
Together, our data indicate that IGF-1 signaling is not required for the function and
survival of mature ODCs in steady-state and disease
Etablierung von Lungenorganoiden zur Therapieentwicklung und Wirkstofftestung bei perinatalen Lungenerkrankungen
No full textSpatial temporal learning for surgical tool recognition in laparoscopic videos
No full textDie Analyse laparoskopischer Videos ist ein wichtiger Schlüsselfaktor zum Verständnis von Prozessabläufen während chirurgischer Eingriffe. Dieses Verständnis ist ein entscheidender Schritt für den Wandel heutiger Operationssäle in die nächste, fortschrittliche Generation.
Chirurgische Maßnahmen und Phasen des Eingriffs können über eine exakte Klassifizierung der, während der Eingriffe verwendeten, chirurgischen Instrumente erkannt werden. Der Einsatz von Convolutional neural networks (CNN) ermöglicht eine Identifizierung von chirurgischen Instrumenten in laparoskopischen Bildern. Bildstörungen und eine unausgewogene Verteilung der Daten erschwerten jedoch die Analyse und CNN-Modelle, welche sich ausschließlich auf räumliche Informationen stützen, konnten chirurgische Instrumente in schwierigen Fällen nicht erkennen. Loss-sensitive Lern- und Resampling-Techniken wurden eingesetzt, um die CNN-Leistung zu verbessern. Zwei temporale Modelle bezogen zeitliche Abhängigkeiten in räumliche CNN-Merkmale ein, was in einer deutlichen Verbesserung der Klassifizierungsleistung resultierte. Die erzielten Ergebnisse übertreffen die State-of-the-Art Methoden und verdeutlichen die Bedeutung der Einbeziehung zeitlicher Informationen in die Modellierung für eine korrekte chirurgische Instrumenten Klassifizierung. Die hohe Leistung der CNN-basierten Ansätze, welche an einem spezifischen Datensatz evaluiert wurden, ist jedoch keine Garantie für eine robuste und generalisierbare Übertragbarkeit auf Daten, die in unterschiedlichen chirurgischen Umgebungen erfasst wurden. Die Robustheit von CNN-Modellen gegenüber Daten, die in verschiedenen chirurgischen Umgebungen aufgezeichnet wurden, wurde anhand der Klassifizierung von chirurgischen Instrumenten evaluiert. In diesem Zusammenhang wurde ein mehrstufiger Ansatz zur Merkmalsfusion eingeführt, um die Generalisierungsfähigkeit von CNN-Modellen zu verbessern
Fasting indices of glucose-insulin-metabolism across life span and prediction of glycemic deterioration in children with obesity from new diagnostic cut-offs
No full textThe increasing prevalence of obesity worldwide, particularly in children, leads to a great urgency for the early detection of impairments in glucose-insulin metabolism. This is necessary to prevent the progression of these impairments into manifest type 2 diabetes and its comorbidities.
This large population-based study aimed to examine the patterns of fasting indices of glucose and insulin across the lifespan from early childhood to old age (5-80 years) in individuals with and without obesity. This was done in order to identify more accurate reference values for the earlier detection of impairments in insulin sensitivity, as there were none or just very vague reference values for these indices available. Especially in children, reference values for fasting insulin indices were lacking.
The targeted indices were fasting insulin, HOMA-IR, HOMA2-IR, HOMA-β and McAuley index. The objective was to identify age- and puberty-adapted reference values for these indices and to evaluate their application in children and young adults with obesity in comparison to the common prediabetes and diabetes criteria of the ADA (American Diabetes Association)
Time to eRAASe chronic inflammation: current advances and future perspectives on renin-angiotensin-aldosterone-system and chronic intestinal inflammation in dogs and humans
No full textChronic idiopathic intestinal inflammation is an increasing worldwide problem that
affects companion animals, especially dogs, and human patients. Although these
disease entities have been intensely investigated recently, many questions remain,
and alternative therapeutic options are needed. Diarrhea caused by dysregulation
of intestinal electrolyte transport and subsequent fluid and electrolyte losses often
leads to secondary consequences for the patient. Currently, it is not exactly clear
which mechanisms are involved in the dysregulation of intestinal fluid absorption,
but differences in intestinal electrolyte shifts between human and canine patients
suggest species-specific regulatory or counterregulatory mechanisms. Several
intestinal electrolyte transporters are differentially expressed in human patients
with inflammatory bowel disease (IBD), whereas there are virtually no studies
on electrolyte transporters and their endocrine regulation in canine chronic
inflammatory enteropathy. An important mechanism involved in regulating
fluid and electrolyte homeostasis is the renin-angiotensin-aldosterone-system
(RAAS), which may affect intestinal Na+ transport. While RAAS has previously been
considered a systemic regulator of blood pressure, additional complex roles of
RAAS in inflammatory processes have been unraveled. These alternative RAAS
pathways may pose attractive therapeutic targets to address diarrhea and, thus,
electrolyte shifts in human IBD and canine chronic inflammatory enteropathy.
This article comparatively summarizes the current knowledge about electrolyte
transport in human IBD and canine chronic inflammatory enteropathy and the
role of RAAS and offers perspectives for novel therapeutic avenues
Datendokumentation des Scientific Use File für die repräsentative Studie zum Thema Mobbing in der Arbeitswelt in der Bundesrepublik Deutschland
No full textDie folgende Datendokumentation beschreibt den Scientific Use File (SUF) für die 'Repräsentative Studie zum Thema Mobbing in der Arbeitswelt in der Bundesrepublik Deutschland', der über das Forschungsdatenzentrum der Bundesanstalt für Arbeitsschutz und Arbeitsmedizin (FDZ-BAuA) zur Nutzung für wissenschaftliche Forschungsprojekte zur Verfügung gestellt wird. Die Datendokumentation gibt einen Überblick über die verfügbaren Daten und dient der Dokumentation, wie die Daten erhoben, aufbereitet und in den Scientific Use File übertragen wurden. Die Studie wurde durch das Institut für Sozialmedizin, Arbeitsmedizin und Public Health (ISAP) der Medizinischen Fakultät der Universität Leipzig in Kooperation mit dem Institut und der Poliklinik für Arbeits- und Sozialmedizin (IPAS) der Technischen Universität Dresden, der USUMA GmbH (Berlin) sowie der Bundesanstalt für Arbeitsschutz und Arbeitsmedizin (BAuA) im Zeitraum zwischen November 2022 bis Juni 2024 im Auftrag des Bundesministeriums für Arbeit und Soziales (BMAS) durchgeführt. Die repräsentative Befragung (Erhebungszeitraum 31.08.2023 bis 23.01.2024) soll die Prävalenz von Mobbing bei abhängig Beschäftigten innerhalb der Allgemeinbevölkerung in Deutschland, Rahmenbedingungen der Arbeit, individuelle Erfahrungen und mögliche Präventions- und Unterstützungsangebote mit dem Fokus auf Mobbing in der Arbeitswelt untersuchen. Zu berücksichtigende Schwerpunkte bestehen in der Betrachtung möglicher Auslöser, Ursachen und unternehmenskultureller Aspekte, die Mobbing begünstigen. Des Weiteren wurden arbeitsbezogene Rahmenbedingungen sowie Schutzfaktoren und gesundheitliche Faktoren begleitend erhoben. Die Datenerhebung der Repräsentativbefragung wurde mittels computergestützter Telefoninterviews (CATI) über die USUMA GmbH durchgeführt, bei der es sich um ein etabliertes Markt- und Sozialforschungsinstitut handelt. Die Gesamtstichprobe umfasst 5.015 gültige Interviews
Is iron deficiency caused by BMPR2 mutations or dysfunction in pulmonary arterial hypertension patients?
No full textIron deficiency is common in idiopathic and heritable pulmonary arterial hypertension patients (I/HPAH). A previous report suggested a dysregulation of the iron hormone hepcidin, which is controlled by BMP/SMAD signaling involving the bone morphogenetic protein receptor 2 (BMPR-II). Pathogenic variants in the BMPR2 gene are the most common cause of HPAH. Their effect on patients' hepcidin levels has not been investigated. The aim of this study was to assess whether iron metabolism and regulation of the iron regulatory hormone hepcidin was disturbed in I/HPAH patients with and without a pathogenic variant in the gene BMPR2 compared to healthy controls. In this explorative, cross-sectional study hepcidin serum levels were quantified by enzyme-linked immunosorbent assay. We measured iron status, inflammatory parameters and hepcidin modifying proteins such as IL6, erythropoietin, and BMP2, BMP6 in addition to BMPR-II protein and mRNA levels. Clinical routine parameters were correlated with hepcidin levels. In total 109 I/HPAH patients and controls, separated into three groups, 23 BMPR2 variant-carriers, 56 BMPR2 noncarriers and 30 healthy controls were enrolled. Of these, 84% had iron deficiency requiring iron supplementation. Hepcidin levels were not different between groups and corresponded to the degree of iron deficiency. The levels of IL6, erythropoietin, BMP2, or BMP6 showed no correlation with hepcidin expression. Hence, iron homeostasis and hepcidin regulation was largely independent from these parameters. I/HPAH patients had a physiologically normal iron regulation and no false elevation of hepcidin levels. Iron deficiency was prevalent albeit independent of pathogenic variants in the BMPR2 gene
Temporal variation of mycorrhization rates in a tree diversity experiment
No full textWhile mycorrhization rates have been studied in different contexts, not much is known about their temporal patterns across seasons. Here, we asked how mycorrhization rates of 10 deciduous trees assessed by microscopy changed from winter to spring to early summer. We made use of a tree diversity experiment on nutrient-rich soil (former farmland) in Central Germany. In the experiment, saplings of host species with a preference for either arbuscular mycorrhiza (AM) or ectomycorrhiza (EM) were planted in monocultures, two-species, and four-species mixtures. In addition, mixtures were composed of tree species of only one mycorrhizal type or by AM/EM trees. For almost all species, with the exception of Aesculus hippocastanum and Acer pseudoplatanus (only AM), dual mycorrhization with both types (AM and EM) was found at every sampling time (December, March, and May), although the expected preferences for certain mycorrhizal types were confirmed. The sampling date had a significant influence on mycorrhization rates of both EM and AM tree species. Frequencies of EM and AM were lowest in May, but there were no differences between December and March. The causes of this seasonal variation may be associated with climate-induced differences in carbon allocation to mycorrhizal tree roots in the temperate climate. Within individual trees, mycorrhization rates by AM and EM fungi were not correlated over time, pointing to asynchronous variation between both types and to independent drivers for AM and EM mycorrhization. At the community level, mycorrhiza frequency of either of the two types became more asynchronous from two-species to four-species mixtures. Thus, increased community asynchrony in mycorrhization could be another important mechanism in biodiversity–ecosystem functioning relationships
For the sake of resilience and multifunctionality, let’s diversify planted forests!
No full textAs of 2020, the world has an estimated 290 million ha of planted forests and this
number is continuously increasing. Of these, 131 million ha are monospecific
planted forests under intensive management. Although monospecific planted
forests are important in providing timber, they harbor less biodiversity and are
potentially more susceptible to disturbances than natural or diverse planted
forests. Here, we point out the increasing scientific evidence for increased
resilience and ecosystem service provision of functionally and species diverse
planted forests (hereafter referred to as diverse planted forests) compared to
monospecific ones. Furthermore, we propose five concrete steps to foster the
adoption of diverse planted forests: (1) improve awareness of benefits and practical options of diverse planted forests among land-owners, managers, and
investors; (2) incentivize tree species diversity in public funding of afforestation
and programs to diversify current maladapted planted forests of low diversity;
(3) develop new wood-based products that can be derived from many different
tree species not yet in use; (4) invest in research to assess landscape benefits of
diverse planted forests for functional connectivity and resilience to global-change
threats; and (5) improve the evidence base on diverse planted forests, in particular in currently under-represented regions, where new options could be tested
Perceptual learning of random acoustic patterns: Impact of temporal regularity and attention
No full textPerceptual learning is a powerful mechanism to enhance perceptual abilities
and to form robust memory representations of previously unfamiliar sounds.
Memory formation through repeated exposure takes place even for random
and complex acoustic patterns devoid of semantic content. The current study
sought to scrutinise how perceptual learning of random acoustic patterns is
shaped by two potential modulators: temporal regularity of pattern repetition
and listeners’ attention. To this end, we adapted an established implicit learning paradigm and presented short acoustic sequences that could contain
embedded repetitions of a certain sound segment (i.e., pattern) or not. During
each experimental block, one repeating pattern recurred across multiple trials,
whereas the other patterns were presented in only one trial. During the presentation of sound sequences that contained either temporally regular or jittered within-trial pattern repetitions, participants’ attention was directed
either towards or away from the auditory stimulation. Overall, we found a
memory-related modulation of the event-related potential (ERP) and an
increase in inter-trial phase coherence for patterns that recurred across multiple trials (compared to non-recurring patterns), accompanied by a performance increase in a (within-trial) repetition detection task when listeners
attended the sounds. Remarkably, we show a memory-related ERP effect even
for the first pattern occurrence per sequence when participants attended the
sounds, but not when they were engaged in a visual distractor task. These findings suggest that learning of unfamiliar sound patterns is robust against temporal irregularity and inattention, but attention facilitates access to established
memory representations upon first occurrence within a sequence