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Hesse, S.

Publications and source records attributed to Hesse, S..

6 recordsLinked to original sources

Amygdala metabolic activity on FDG PET is associated with survival, response to immune checkpoint inhibition, and tumor immune signaling in non-small cell lung cancer

Amygdala metabolic activity (AmygAc) measured by [18F]FDG PET has been associated with chronic psychological stress and adverse clinical outcomes, but its relationship with antitumor immunity and treatment response remains incompletely understood. We investigated AmygAc as a host-derived imaging biomarker in non-small cell lung cancer (NSCLC) and examined its association with survival, response to immune checkpoint inhibition (ICI), and the tumor immune microenvironment. Methods: In this multicenter retrospective study, baseline [18F]FDG PET scans from 256 treatment-naive patients with NSCLC were analyzed to quantify AmygAc. Overall survival was assessed in the full cohort, and treatment response was evaluated in 79 patients who subsequently received neoadjuvant ICI therapy. AmygAc was integrated with clinical and tumor-derived imaging parameters. To investigate its biological correlates, tumor tissue from a selected subcohort was analyzed using multiplex immunofluorescence and spatial transcriptomics.

cancer biology↗

Parasite defense covaries with reproductive timing, not with resistance

Defense is the ability of a host to minimize fitness loss to parasites. It is among the most variable phenotypes in host populations, and this variation facilitates rapid adaptation under parasite-mediated selection. We do not, however, know the underlying host traits that explain this variation in defense against parasites. A common assumption is that the most defended hosts are the most resistant, meaning they limit the establishment and growth of infecting parasites. Under this assumption, resistance traits should evolve readily under parasite selection. Resistance is, however, just one of many strategies hosts use to defend against parasites, and it does not consistently covary with fitness in the presence of parasites. We accordingly asked: which host traits covary with defense against parasites? We use controlled exposures to characterize genetic variation in defense of the nematode Caenorhabditis elegans against its natural microsporidian parasites. We report extensive variation in defense among wild strains of C. elegans: some strains lost 60% of fecundity under parasite exposure, while others were unaffected. We then tested the covariance of defense with two prominent host traits, resistance and reproductive timing. Our results did not support the hypothesis that resistance covaries with defense: strains with lower parasite burden did not have higher relative fecundity under exposure. Our results instead supported the hypothesis that life history covaries with defense: host strains that reproduced quickly had higher relative fecundity under exposure, consistent with the idea that parasites diminish future reproductive opportunities. The observed variation in defense among host strains indicates significant potential for wild C. elegans populations to evolve in response to their natural parasites. Because reproductive timing underpins this variation in defense, parasite-mediated selection could operate directly on host life history traits and should also be highly sensitive to shifts in life history driven by other biotic and abiotic factors. AUTHOR SUMMARYSome hosts fare much better than others in the face of parasite infection. What traits differentiate defended hosts from undefended hosts? The answer to this question is critical for identifying the strategies that best protect hosts from their parasites. It also allows us to predict and interpret the evolution of host populations over the course of epidemics. To address this question, we surveyed wild strains of a tractable model host, the nematode Caenorhabditis elegans, for their response to two species of microsporidian parasites. We found that, on average, parasite exposure substantially impaired the ability of hosts to reproduce. Host strains, however, varied widely: some experienced major losses in fecundity with exposure, while others were highly defended, showing little to no change. We identified reproductive timing as a key trait that differentiated defended hosts from undefended hosts. Our results suggest that reproducing quickly may have been protective, by allowing hosts to make most of their offspring before parasites impaired reproduction. We did not find evidence that resistance was protective: host strains with lower parasite burdens did not reproduce better than those with high parasite burdens. These findings give added weight to life history as a major component of host defense against parasites.

evolutionary biology↗

Different dopaminergic circuits defined by D2/D3 receptor availablity patterns show structure-specific links to memory in ageing

Cognitive ageing is marked by progressive decline in episodic memory and dopaminergic function, yet the extent to which individual differences in dopaminergic system integrity influence memory under motivational contexts remains unclear. In this study, we investigated how baseline D2/D3 receptor availability (BPND0) in key dopaminergic pathways relates to reward-modulated memory performance in healthy older adults. Thirty-three healthy seniors (aged 64-85) underwent two session concurrent MR-PET imaging with [1F]fallypride involving scene categorisation task with high- and low-motivational contexts. We quantified BPND0 across nine dopaminergic regions of interest and examined their relationships with recognition memory performance at short ([~]15m) and long ([~]24h) delays. Baseline D2/D3 receptor availability showed high test-retest reliability and regionally distinct profiles, suggesting it reflects a stable neurochemical characteristic in healthy ageing, and principal axis factor analysis revealed two partially independent dopaminergic subsystems (dorsal striatal vs mesolimbic) based on interindividual patterns in receptor densities. Region-specific associations further linked D2/D3 receptor availability to distinct memory outcomes. Higher caudate D2/D3 receptor availability was associated with a liberal response bias (increased hits and false alarms both), whereas higher putamen D2/D3 predicted more durable long-term memory retention. Greater thalamic D2/D3 receptor availability correlated with fewer short-term false memories, while greater D2/D3 receptor availability in the amygdala was associated with better recognition at longer delays. In contrast, higher midbrain (substantia nigra and ventral tegmental area) D2/D3 availability which was linked to poorer reward-related memory performance. These findings suggest several complementary dopaminergic circuits supporting episodic memory. Our results highlight dopaminergic neuromodulation as a key factor in cognitive ageing and a potential target for interventions to bolster memory in late life. Patient consent and ethics approvalAll subjects who were included in this study have provided their consent prior to their participation, following the guidelines of the ethics committee at University Hospital Magdeburg in Magdeburg, Germany.

neuroscience↗

JuSpace: A tool for spatial correlation analyses of magnetic resonance imaging data with positron emission tomography derived neurotransmitter maps

Recent studies have shown that drug-induced spatial alteration patterns in resting state functional activity as measured using magnetic resonance imaging (rsfMRI) are associated with the distribution of specific receptor systems targeted by respective compounds. Based on this approach, we introduce a toolbox (JuSpace) allowing for cross-modal correlation of MRI- based measures with nuclear imaging derived estimates covering various neurotransmitter systems including dopaminergic, serotonergic, noradrenergic, and GABAergic (gamma- aminobutric acid) neurotransmission. We apply JuSpace to two datasets covering Parkinsons disease patients (PD) and risperidone-induced changes in rsfMRI and cerebral blood flow (CBF). Consistently with the predominant neurodegeneration of dopaminergic and serotonergic system in PD, we find significant spatial associations between rsfMRI activity alterations in PD and dopaminergic (D2) and serotonergic systems (5-HT1b). Risperidone induced CBF alterations were correlated with its main targets in serotonergic and dopaminergic systems. JuSpace provides a biologically meaningful framework for linking neuroimaging to underlying neurotransmitter information.

neuroscience↗

Unravelling the effects of methylphenidate on the dopaminergic and noradrenergic functional circuits

Functional magnetic resonance imaging (fMRI) can be combined with drugs to investigate the system-level functional responses in the brain to such challenges. However, most psychoactive agents act on multiple neurotransmitters, limiting the ability of fMRI to identify functional effects related to actions on discrete pharmacological targets. We recently introduced a multimodal approach, REACT (Receptor-Enriched Analysis of functional Connectivity by Targets), which offers the opportunity to disentangle effects of drugs on different neurotransmitters and clarify the biological mechanisms driving clinical efficacy and side effects of a compound. Here, we focus on methylphenidate (MPH), which binds to the dopamine transporter (DAT) and the norepinephrine transporter (NET), to unravel its effects on dopaminergic and noradrenergic functional circuits in the healthy brain at rest. We then explored the relationship between these target-enriched resting state functional connectivity (FC) maps and inter-individual variability in behavioural responses to a reinforcement-learning task encompassing a novelty manipulation to disentangle the molecular systems underlying specific cognitive/behavioural effects. Results showed a significant MPH-induced FC increase in sensorimotor areas in the functional circuit associated with DAT. We also found that MPH-induced variations in DAT-and NET-enriched FC were significantly correlated with inter-individual differences in effects of MPH on key behavioural responses associated with the reinforcement-learning task. Our findings show that MPH-related FC changes are specifically associated with DAT and provide evidence that when compounds have mixed pharmacological profiles, REACT may be able to capture regional functional effects that are underpinned by the same cognitive mechanism but are related to distinct molecular targets.

neuroscience↗

Sleep Deprivation alters the influence of biological sex on active-phase sleep behavior

Poor sleep is a hazard of daily life that oftentimes cannot be avoided. Gender differences in daily sleep and wake patterns are widely reported; however, it remains unclear how biological sex, which is comprised of genetic and endocrine components, directly influences sleep regulatory processes. In the majority of model systems studied thus far, sex differences in daily sleep amount are predominant during the active (wake) phase of the sleep-wake cycle. The pervasiveness of sex differences in sleep amount throughout phylogeny suggests a strong underlying genetic component. The goal of the current study is to determine if sex differences in active-phase sleep amount are dependent on sex chromosomes in mice. Sleep was examined in the four-core genotype (FCG) mouse model, whose sex chromosome complement (XY, XX) is independent of sex phenotype (male or female). In this line, sex phenotype is determined by the presence or absence of the Sry gene, which is dissociated from the Y chromosome. Polysomnographic sleep recordings were obtained from gonadectomized (GDX) FCG mice to examine spontaneous sleep states and the ability to recover from sleep loss. We report that during the active-phase, the presence of the Sry gene accounts for most sex differences during spontaneous sleep; however, during recovery from sleep loss, sex differences in sleep amount are partially driven by sex chromosome complement. These results suggest that genetic factors on the sex chromosomes encode the homeostatic response to sleep loss.

neuroscience↗