Biology subjects

Fritsch, M.

Publications and source records attributed to Fritsch, M..

7 recordsLinked to original sources

bioRxiv2024

Altered Hormone and Bioactive Lipid Plasma Profile in Rodent Models of Polycystic Ovarian Syndrome Revealed by Targeted Mass Spectrometry

Polycystic ovarian syndrome (PCOS) symptoms include excessive body or facial hair, irregular periods, reduced fertility, and reoccurring pregnancy loss. Hyperandrogenism and chronic inflammation are hallmarks of PCOS, which is diagnosed by analysing steroid hormones in the blood. Studies suggest that bioactive lipids are contributing to chronic inflammation. To research PCOS, animal models, such as letrozole- and dihydrotestosterone-treated rats, are used. They display similar ovarian and metabolic characteristics, although plasma lipid profiles have not been determined. Therefore, in order to validate the use of these models for PCOS, we have optimised a mass spectrometry based targeted lipidomics workflow which increases the sensitivity of measuring these lipids in rat plasma. Our analysis shows that letrozole caused a significant elevation of 5-androstene-3,17-dione and testosterone. Dihydrotestosterone treatment resulted in increased dehydroepiandrosterone-sulphate and allopregnanolone but a reduction in testosterone, progesterone, pregnenolone, and D-sphingosine. In both models 25-hydroxycholesterol and leukotriene C4 were significantly diminished and 4-cholesten-3-one was significantly increased, and these particular metabolites are not known to be changed in human PCOS. These results suggest that the plasma lipids of these rodent models have some changes akin to human PCOS and other changes that are not.

biochemistry↗

bioRxiv2024

Ischemic lesions to inferior frontal cortex alter the dynamics of conscious visual perception

Whether the prefrontal cortex is part of the neural correlates of conscious visual perception has been subject to longstanding debate. Recent work, using functional magnetic resonance imaging (fMRI) and repetitive transcranial magnetic stimulation (rTMS) to induce virtual lesions, has illustrated a key role of the right inferior frontal cortex (IFC) in the detection and resolution of perceptual ambiguities. Here, we sought to validate an active role of the IFC in conscious perception by evaluating how loss-of-function in patients with ischemic stroke in this region influences processing of ambiguous visual information. To this end, twenty-three patients (11 female, mean age 70.65 {+/-} 1.2 years) with chronic (>6 months), right-hemispheric ischemic stroke lesions within the MCA-territory (9 patients with IFC lesions, 14 without) performed a bistable perception task, having to report the perceived direction of rotation of an ambiguous random-dot-kinematogram (RDK). As hypothesized, patients with IFC lesions showed significantly fewer perceptual changes compared to patients without IFC lesions (IFC 44.9 {+/-} 46.3 s, non-IFC 28.2 {+/-} 37.1 s, T(182.9) =3.1, p = 2.2 x 10-3). Importantly, this effect remained significant when controlling for age, sex, stroke severity and lesion volume (T(5.97) = -2.9, p =0.026). Our results support the notion that the IFC is crucial for resolving perceptual ambiguities, suggesting an active role of frontal cortex in shaping conscious visual experience.

neuroscience↗

bioRxiv2024

N-Methyl-D-aspartate receptor hypofunction causes recurrent and transient failures of perceptual inference

1Perception alternates between an external mode, driven by sensory inputs, and an internal mode, shaped by prior knowledge. We found that the external mode is more prevalent during pharmacologically induced N-Methyl-D-aspartate receptor (NMDAR) hypofunction and in schizophrenia. This NMDAR-dependent increase in external mode suggests that psychotic experiences are caused by recurring dissociations of perception from prior knowledge about the world.

neuroscience↗

bioRxiv2020

Evidence for an Active Role of Inferior Frontal Cortex in Conscious Experience

2In the search for the neural correlates of consciousness, it has remained controversial whether prefrontal cortex determines what is consciously experienced or, alternatively, serves only complementary functions such as introspection or action. Here, we provide converging evidence from computational modeling and two functional magnetic resonance imaging experiments for a key role of inferior frontal cortex in detecting perceptual conflicts that emerge from ambiguous sensory information. Crucially, the detection of perceptual conflicts by prefrontal cortex turned out to be critical in the process of transforming ambiguous sensory information into unambiguous conscious experiences: In a third experiment, disruption of neural activity in inferior frontal cortex through transcranial magnetic stimulation slowed down the updating of conscious experience that occurs in response to perceptual conflicts. These findings show that inferior frontal cortex actively contributes to the resolution of perceptual ambiguities. Prefrontal cortex is thus causally involved in determining the contents of conscious experience. 3 One-sentence SummaryInferior frontal cortex detects and resolves perceptual conflict during bistable perception.

neuroscience↗

bioRxiv2019

Spondweni virus causes fetal harm in a mouse model of vertical transmission and is transmitted by Aedes aegypti mosquitoes

Spondweni virus (SPONV) is the most closely related known flavivirus to Zika virus (ZIKV). Its pathogenic potential and vector specificity have not been well defined. SPONV has been found predominantly in Africa, but was recently detected in a pool of Culex quinquefasciatus mosquitoes in Haiti. Here we show that SPONV can cause significant fetal harm, including demise, comparable to ZIKV, in a mouse model of vertical transmission. Following maternal inoculation, we detected infectious SPONV in placentas and fetuses, along with significant fetal and placental histopathology, together indicating vertical transmission. To test vector competence, we exposed Aedes aegypti and Culex quinquefasciatus mosquitoes to SPONV-infected bloodmeals. Aedes aegypti could efficiently transmit SPONV, whereas Culex quinquefasciatus could not. Our results suggest that SPONV has the same features that made ZIKV a public health risk.

microbiology↗

bioRxiv2018

Zika viruses of both African and Asian lineages cause fetal harm in a vertical transmission model

Congenital Zika virus (ZIKV) infection was first linked to birth defects during the American outbreak 1-3. It has been proposed that mutations unique to the Asian/American-genotype explain, at least in part, the ability of Asian/American ZIKV to cause congenital Zika syndrome (CZS) 4,5. Recent studies identified mutations in ZIKV infecting humans that arose coincident with the outbreak in French Polynesia and were stably maintained during subsequent spread to the Americas 5. Here we show that African ZIKV can infect and harm fetuses and that the S139N mutation that has been associated with the American outbreak is not essential for fetal harm. Our findings, in a vertical transmission mouse model, suggest that ZIKV will remain a threat to pregnant women for the foreseeable future, including in Africa, southeast Asia, and the Americas. Additional research is needed to better understand the risks associated with ZIKV infection during pregnancy, both in areas where the virus is newly endemic and where it has been circulating for decades.

microbiology↗

bioRxiv2018

NLMR and landscapetools: An integrated environment for simulating and modifying neutral landscape models in R

O_LINeutral landscape models (NLMs) simulate landscape patterns based on theoretical distributions and can be used to systematically study the effect of landscape structure on ecological processes. NLMs are commonly used in landscape ecology to enhance the findings of field studies as well as in simulation studies to provide an underlying landscape. However, their creation so far has been limited to software that is platform dependent, does not allow a reproducible workflow or is not embedded in R, the prevailing programming language used by ecologists.\nC_LIO_LIHere, we present two complementary R packages NLMR and land-scapetools, that allow users to generate, manipulate and analyse NLMs in a single environment. They grant the simulation of the widest collection of NLMs found in any single piece of software thus far while allowing for easy manipulation in a self-contained and reproducible workflow. The combination of both packages should stimulate a wider usage of NLMs in landscape ecology. NLMR is a comprehensive collection of algorithms with which to simulate NLMs. landscapetools provides a utility toolbox which facilitates an easy workflow with simulated neutral landscapes and other raster data.\nC_LIO_LIWe show two example applications that illustrate potential use cases for NLMR and landscapetools: First, an agent-based simulation study in which the effect of spatial structure on disease persistence was studied. Here, spatial heterogeneity resulted in more variable disease outcomes compared to the common well-mixed host assumption. The second example shows how increases in spatial scaling can introduce biases in calculated landscape metrics.\nC_LIO_LISimplifying the workflow around handling NLMs should encourage an uptake in the usage of NLMs. NLMR and landscapetools are both generic frameworks that can be used in a variety of applications and are a further step to having a unified simulation environment in R for answering spatial research questions.\nC_LI

ecology↗