Biology subjects

Fritz, J.

Publications and source records attributed to Fritz, J..

11 recordsLinked to original sources

bioRxiv2026

Annexin A2 Regulates Surfactant Dysfunction During Injurious Ventilation.

The Acute Respiratory Distress Syndrome (ARDS) is a life-threatening cause of respiratory failure, and patients who develop ARDS frequently require mechanical ventilation, which puts them at risk of developing ventilator induced lung injury (VILI). Both VILI and ARDS can induce pulmonary surfactant dysfunction, but the mechanisms are not known. Here we report a novel role for a phospholipid binding protein, Annexin A2 (AnxA2), in the regulation of surfactant composition and function following injurious ventilation. Wild type and AnxA2-/-mice were subjected to injurious ventilation and we found that AnxA2-/- mice developed stiffer lungs following VILI that was not due to differences in barrier permeability or inflammation. Furthermore, we found that pulmonary surfactant from AnxA2-/- mice had reduced surface tension lowering properties and that this was due to a reduction in 1-palmitoyl-2-oleoylphosphatidylglycerol, or POPG. Quantitative analysis of surface tension-surface area hysteresis loops obtained from surfactant isolated from AnxA2-/- mice showed a defect in phase transitions during compression. In summary, Annexin A2 regulates surfactant function during injurious ventilation and may serve as a novel therapeutic target to prevent surfactant dysfunction in patients with ARDS who require mechanical ventilation.

molecular biology↗

bioRxiv2025

Similar Dynamic Frontal Cortex Representations of Auditory Stimuli Cueing Opposite Actions and Rewards

Frontal Cortex (FC) plays a pivotal role in controlling actions and their dynamics in response to incoming sensory stimuli. We explored FC representations of the same stimuli when signifying diametrically opposite behavioral meanings depending on task context. Two groups of ferrets performed Go-NoGo auditory categorization tasks with opposite contingencies and rewards, and varied stimuli. Remarkably, despite the opposite stimulus-action associations, single-unit responses were similar across all tasks, being more sustained and stronger to (Target) sounds signaling a change in action, than to (Reference) sounds indicating maintenance of ongoing actions, especially during task engagement. Three major dynamic response profiles were extracted from the overall responses, and their combination defined separate neuronal clusters that exhibited different roles in relation to task events. Decoding based on the temporal structure of the population responses revealed distinct decoders that were aligned to different task events. Furthermore, the {beta}-band power, extracted from the FC local field potentials, was similarly and strongly modulated during Target stimuli in all tasks despite opposite behavioral actions. Based on these findings, we propose a model of pathway-specific functional projections from the tripartite FC neuronal clusters to the basal ganglia that is consistent with previous evidence for the conjoint roles of the FC and striatum in adaptive motor control.

neuroscience↗

bioRxiv2024

Temporal Coherence Shapes Cortical Responses to Speech Mixtures in a Ferret Cocktail Party

Segregation of complex sounds such as speech, music and animal vocalizations as they simultaneously emanate from multiple sources (referred to as the "cocktail party problem") is a remarkable ability that is common in humans and animals alike. The neural underpinnings of this process have been extensively studied behaviorally and physiologically in non-human animals primarily with simplified sounds (tones and noise sequences). In humans, segregation experiments utilizing more complex speech mixtures are common; but physiological experiments have relied on EEG/MEG/ECoG recordings that sample activity from thousands of neurons, often obscuring the detailed processes that give rise to the observed segregation. The present study combines the insights from animal single-unit physiology with segregation of speech-like mixtures. Ferrets were trained to attend to a female voice and detect a target word, both in presence or absence of a concurrent, equally salient male voice. Single neuron recordings were obtained from primary and secondary ferret auditory cortical fields, as well as frontal cortex. During task performance, representation of the female words became more enhanced relative to those of the (distractor) male in all cortical regions, especially in the higher auditory cortical field. Analysis of the temporal and spectral response characteristics during task performance reveals how speech segregation gradually emerges in the auditory cortex. A computational model evaluated on the same voice mixtures replicates and extends these results to different attentional targets (attention to female or male voices). These findings are consistent with the temporal coherence theory whereby attention to a target voice anchors neural activity in cortical networks hence binding together channels that are coherently temporally-modulated with the target, and ultimately forming a common auditory stream.

neuroscience↗

bioRxiv2023

Multi-variate statistical and machine learning reveals the interplay between sex and age in antibody responses to de novo SARS-CoV-2 infection and vaccination

Prevention of negative COVID19 infection outcomes and infection/vaccine-acquired immunity is associated with the quality of antibody responses, whose variance by age and sex are poorly understood. Integrated, network approaches, identified sex and age effects in antibody responses and neutralization potential of de novo infection and vaccination throughout the Covid-19 pandemic. Cluster analysis found neutralization values followed SARS-CoV-2 specific receptor binding RIgG, spike SIgG and S and RIgA levels based on COVID19 status. Stochastic behavior tests and other analytical methods revealed sex differences only in persons <40y.o. Serum IgA antibody titers correlated with neutralization only in females 40-60y.o. Network analysis found males could improve IgA responses after vaccination dose 2, unlike >60y.o. females. Complex correlation analyses found vaccination induced less antibody isotype switching and neutralization in older persons, especially in females. Sex dependent antibody & neutralization behavior decayed fastest in older males and with vaccination. Such sex and age characterization by machine learning can direct studies integrating cell mediated responses to define yet elusive correlates of protection and inform age and sex precision-focused vaccine design.

immunology↗

bioRxiv2021

Invalidity of light sensor data in field studies and a proposal of an algorithmic approach for detection and filtering of non-wear time

Wearable light sensors are increasingly used in intervention and population-based studies investigating the consequences of environmental light exposure on human physiology. An important step in such analyses is the reliable detection of non-wear time. We observed in light data that days with less wear-time also have lower variability in the light signal, and we sought to test if the standard deviation of the change between subsequent samples can detect this condition. In this study, we propose and validate an easy-to-implement algorithm designed to discriminate between days with a non-wear time >4h ("invalid days") vs. [≤]4h ("valid days") and investigate to which extent values of commonly used physiologically meaningful light variables differ between invalid days, valid days, and algorithm-selected non-wear days. We used 83 days of light data from a field study with high participant compliance, complemented by 47 days of light data where free-living individuals were instructed not to wear the sensor for varying amounts of time. Light data were recorded every two minutes using the pendant-worn f.luxometer light sensor; validity was derived from daily logs where participants recorded all non-wear time. The algorithm-derived score discriminated well between valid and invalid days (area under the curve (AUC): 0.77, 95% CI: 0.67-0.87). The best cut-off value (i.e., highest Youden index) correctly recognized valid days with a probability of 87% ("sensitivity"), and invalid days with a probability of 63% ("specificity"). Values of various light variables derived from algorithm-selected days only (median: 264.3 (Q1: 153.6, Q3: 420.0) for 24h light intensity (in lux); 496.0 (404.0, 582.0) for time spent above 50-lux) gave values close to those derived from self-reported valid days only. However, these values did not significantly differ when derived across all days compared to self-reported valid days. Our results suggest that our proposed algorithm discriminates well between valid and invalid days. However, in high compliance cohorts, distortions in aggregated light measures of individual-level environmental light recordings across days appear to be small, making the application of our algorithm optional, but not necessary.

neuroscience↗

bioRxiv2021

Halfway to self-sustainability: Reintroduced migratory European Northern Bald Ibises (Geronticus eremita) still need management interventions for population viability

Northern Bald Ibis (NBI) have disappeared from Europe already in Middle Age. Since 2003 a migratory population is reintroduced in Central Europe. We conducted demographic analyses of survival and reproduction of 384 NBI over a period of 12 years (2008-2019). These data also formed the basis for a population viability analysis (PVA) simulating the possible future development of the NBI population in different scenarios. We tested life-stage specific survival rates for differences between these stages, raising types and colonies as well as the influence of stochastic events and NBI supplements on the population growth. Stage specific survival rates ranged from 0.64 to 0.78. 61% of the mature females reproduce with a mean fecundity of 2.15 fledglings per nest. The complementary PVA indicated that the release population is close to self-sustainability with a given lambda 0.95 and 24% extinction probability within 50 years. Of the 326 future scenarios tested, 94 % reached the criteria of <5% extinction probability and population growth rates >1. In case of positive population growth, stochastic events had a limited effect. Of 820 sub-scenarios with different stochastic event frequencies and severities 87 % show population growth despite the occurrence of stochastic events. Predictions can be made based on the results of the individual-based model as to whether and under what circumstances the reintroduced NBI population can survive. This study shows that a PVA can support reintroduction success that should work closely together with the project in the field for mutual benefit, to optimize future management decisions.

ecology↗

bioRxiv2020

How human intervention and climate change shaped the fate of the Northern Bald Ibis from ancient Egypt to the present: an interdisciplinary approach to extinction and recovery of an iconic bird species

Once widespread around the Mediterranean, the Northern Bald Ibis (Geronticus eremita) became one of the rarest birds in the world. We trace the history of this species through different epochs to the present. A particular focus is on its life and disappearance in ancient Egypt, where it attained the greatest mythological significance as a hieroglyphic sign for blessed ancestor spirits, and on modern endeavours to rewild and restore the species. The close association of the Northern Bald Ibis with human culture in ancient Egypt, as in other regions, is caused by primarily two reasons, the characteristic appearance and behaviour, as well as the need for open foraging areas. In consequence, a mutualistic relationship between humans and birds was formed in some cultures. The benefit for the Northern Bald Ibis was mainly the availability of feeding habitats, which were cleared by humans for farming or grazing and might have contributed to the spread of the species. The benefit to people was primarily cultural and mythological, whereby the bird was worshiped in ancient Egypt and in Muslim cultures, while Christian cultures in Europe rather regarded it as bad omen or nuisance, like any black bird species. Another benefit was profane in nature, the species was also hunted for food, mainly in Europe. But alike many other species, proximity to humans also carried a high risk for the Northern Bald Ibis. We discuss various kinds of human impacts that were driving causes for the extinction of the species in almost all regions. However, the historical disappearance of populations also correlates markedly with changes in climate, especially in ancient Egypt and the Middle Ages. This fact has important implications for current conservation efforts, especially since international action plans for the Northern Bald Ibis have taken little account of climate change effects so far. The Northern Bald Ibis is an outstanding example of how an interdisciplinary cultural-historical and natural-scientific approach significantly promotes the interpretation of historical evidence as well as the implementation of current rewilding and restoration efforts.

ecology↗

bioRxiv2020

The pleiotropic effects of the MNK1/2-eIF4E axis support immune suppression and metastasis in a model of postpartum breast cancer.

PurposeBreast cancer diagnosed within 10 years following childbirth is defined as postpartum breast cancer (PPBC) and is highly metastatic. Interactions between immune cells and other stromal cells within the involuting mammary gland are fundamental in facilitating an aggressive tumor phenotype. The MNK1/2-eIF4E axis promotes the translation of pro-metastatic mRNAs in tumor cells, but its role in modulating the function of non-tumor cells in the PPBC microenvironment, and in particular its activity in human PPBC, has not been explored. Experimental designWe used a combination of in vivo PPBC models and in vitro assays to study the effects of phospho-eIF4E deficiency on the pro-tumor function of select cells of the TME. Furthermore, we employed Imaging Mass Cytometry on PPBC and non-PPBC patient samples, to chart the expression of the MNK1/2-eIF4E axis components in the TME. ResultsHere, we show that phospho-eIF4E deficient (eIF4ES209A) PPBC mice are protected against lung metastasis and reveal differences in the lung immune microenvironment of the WT and eIF4ES209A mice. Moreover, we show that the expression of fibroblast-derived IL-33, an alarmin known to induce invasion, was repressed upon MNK1/2-eIF4E axis inhibition. Imaging Mass Cytometry results indicated that human PPBC contain phospho-eIF4E high-expressing tumor cells and CD8+ T cells displaying an activated dysfunctional phenotype. Finally, we block lung metastasis in PPBC mice, using combined MNK1/2 inhibition and anti-PD-1 therapy. ConclusionsThese findings implicate the involvement of the MNK1/2-eIF4E axis during PPBC metastasis and suggest a promising immunomodulatory route to enhance the efficacy of immunotherapy by blocking phospho-eIF4E. Translational relevancePostpartum breast cancer (PPBC) is highly aggressive. It is hypothesized that involution-induced changes in the postpartum breast microenvironment, which include an influx of inflammatory immune cells and activation of resident fibroblasts, facilitate the invasiveness of an existing neoplasm. We used imaging mass cytometry to do an in-depth profiling of the MNK1-eIF4E axis in the TME of a unique cohort of PPBC and non-PPBC patients. We observed patterns of phospho-eIF4E in non-tumor cells that were specific to the TME of PPBC. We also noted that the CD8+ T cells present in PPBC express an activated dysfunctional phenotype characterized by the co-expression of HLA-DR and PD-1. This study represents a first look at the expression of the MNK1-eIF4E axis in the stromal cells of metastatic breast cancer and has therapeutic implications as we show, in an animal model of PPBC, that MNK1/2 inhibition can be used to sensitize tumors to anti-PD1 immunotherapy.

cancer biology↗

bioRxiv2018

Endocrine aryl hydrocarbon receptor signaling is induced by moderate cutaneous exposure to ultraviolet light

Links between solar UV exposure and immunity date back to the ancient Greeks with the development of heliotherapy. Skin contains several UV-sensitive chromophores and exposure to sunlight can produce molecules, such as vitamin D3, that act in an endocrine manner. We investigated whether the aryl hydrocarbon receptor (AHR), an environmental sensor and ligand-regulated transcription factor activated by numerous planar compounds of dietary or environmental origin, could be the target of endocrine photoproducts produced by cutaneous UV exposure. 15-to 30-minute exposure of cells to a minimal erythemal dose of UVB irradiation in vitro induced translocation of the AHR to the nucleus, rapidly inducing site-specific DNA binding and target gene regulation. Importantly, ex vivo studies with Ahr wild-type or null fibroblasts showed that serum from mice whose skin was exposed to a 15 min UVB dose, but not control serum, contained agonist activity within 30 min of UV irradiation, inducing AHR-dependent gene expression. Moreover, a 15-min cutaneous UVB exposure induced AHR site-specific DNA binding and target gene regulation in vivo within 3-6 hr post-irradiation in blood and in peripheral tissues, including intestine. These results show that cutaneous exposure of mice to a single minimal erythemic dose of UVB induces rapid AHR signaling in multiple peripheral organs, providing compelling evidence that moderate sun exposure can exert endocrine control of immunity through the AHR.

molecular biology↗

bioRxiv2018

Laminar profile of task-related plasticity in ferret primary auditory cortex

Rapid task-related plasticity is a neural correlate of selective attention in primary auditory cortex (A1). Top-down feedback from higher-order cortex may drive task-related plasticity in A1, characterized by enhanced neural representation of behaviorally meaningful sounds during auditory task performance. Since intracortical connectivity is greater within A1 layers 2/3 (L2/3) than in layers 4-6 (L4-6), we hypothesized that enhanced representation of behaviorally meaningful sounds might be greater in A1 L2/3 than L4-6. To test this hypothesis and study the laminar profile of task-related plasticity, we trained 2 ferrets to detect pure tones while we recorded laminar activity across a 1.8 mm depth in A1. In each experiment, we analyzed current-source densities (CSDs), high-gamma local field potentials (LFPs), and multi-unit spiking in response to identical acoustic stimuli during both passive listening and active task performance. We found that neural responses to auditory targets were enhanced during task performance, and target enhancement was greater in L2/3 than in L4-6. Spectrotemporal receptive fields (STRFs) computed from CSDs, high-gamma LFPs, and multi-unit spiking showed similar increases in auditory target selectivity, also greatest in L2/3. Our results suggest that activity within intracortical networks plays a key role in shaping the underlying neural mechanisms of selective attention.

neuroscience↗

bioRxiv2017

Task Engagement Enhances Population Encoding of Stimulus Meaning in Primary Auditory Cortex

The main functions of primary sensory cortical areas are classically considered to be the extraction and representation of stimulus features. In contrast, higher cortical sensory association areas are thought to be responsible for combining these sensory representations with internal motivations and learnt associations. These regions generate appropriate neural responses that are maintained until a motor command is executed. Within this framework, responses of the primary sensory areas during task performance are expected to carry less information about the behavioral meaning of the stimulus than higher sensory, association, motor and frontal cortices. Here we demonstrate instead that the neuronal population responses in the early primary auditory cortex (A1) display many aspects of responses generally associated with higher-level areas. A1 activity was recorded in awake ferrets while they were either passively listening or actively discriminating two periodic click trains of different rates in a Go/No-Go paradigm. By applying population-level dimensionality reduction techniques, we found that task-engagement induced a shift in the nature of the encoding from a sensory-driven representation of the two stimuli to a behaviorally relevant representation of the two categories that specifically enhances the target stimulus. We demonstrate that this shift in encoding relies partly on a novel mechanism of change in spontaneous activity patterns upon engagement in the task. We show that this population-level representation of stimuli in A1 population activity bears strong similarities to responses in the frontal cortex, but appears earlier following stimulus presentation. Analysis of neural activity recorded in various Go/No-Go tasks, with different sounds and reinforcement paradigms, reveals that this striking population-level enhancement of target representation is a general property of task engagement. These findings indicate that primary sensory cortices play a highly flexible role in the processing of incoming stimuli and implement a crucial change in the structure of population activity in order to extract task-relevant information during behavior.

neuroscience↗