Biology subjects

Richter, A.

Publications and source records attributed to Richter, A..

At least 55 records · Page 3Linked to original sources

bioRxiv2022

Inhibitory temporo-parietal effective connectivity is associated with explicit memory performance in older adults

Successful explicit memory encoding is associated with inferior temporal activations and medial parietal deactivations, which are attenuated in aging. Here we used Dynamic Causal Modeling (DCM) of functional magnetic resonance imaging data to elucidate effective connectivity patterns between hippocampus, parahippocampal place area (PPA) and precuneus during encoding of novel visual scenes. In 117 young adults, DCM revealed pronounced activating input from the PPA to the hippocampus and inhibitory connectivity from the PPA to the precuneus during novelty processing, with both being enhanced during successful encoding. This pattern could be replicated in two cohorts (N = 141 and 148) of young and older adults. In both cohorts, older adults selectively exhibited attenuated inhibitory PPA-precuneus connectivity, which correlated negatively with memory performance. Our results provide insight into network dynamics underlying explicit memory encoding and suggest that age-related differences in memory-related network activity are, at least partly, attributable to altered temporo-parietal neocortical connectivity.

neuroscience↗

bioRxiv2022

Plasma concentrations of anti-inflammatory cytokine TGF-β are associated with hippocampal structure related to explicit memory performance in older adults

Human cognitive abilities, and particularly hippocampus-dependent memory performance typically decline with increasing age. Immunosenescence, the age-related disintegration of the immune system, is increasingly coming into the focus of research as a considerable factor contributing to cognitive decline. In the present study, we investigated potential associations between plasma levels of pro- and anti-inflammatory cytokines and learning and memory performance as well as hippocampal anatomy in young and older adults. Plasma concentrations of the inflammation marker CRP as well as the pro-inflammatory cytokines IL-6 and TNF- and the anti-inflammatory cytokine TGF-{beta}1 were measured in 142 healthy adults (57 young, 24.47 {+/-} 4.48 years; 85 older, 63.66 {+/-} 7.32 years) who performed tests of explicit memory (Verbal Learning and Memory Test, VLMT; Wechsler Memory Scale, Logical Memory, WMS) with an additional delayed recall test after 24 hours. Hippocampal volumetry and hippocampal subfield segmentation were performed using FreeSurfer, based on T1-weighted and high-resolution T2-weighted MR images. When investigating the relationship between memory performance, hippocampal structure, and plasma cytokine levels, we found that TGF- {beta}1 concentrations were positively correlated with the volumes of the hippocampal CA4-dentate gyrus region in older adults. These volumes were in turn positively associated with better performance in the WMS, particularly in the delayed memory test. Our results support the notion that endogenous anti-inflammatory mechanisms may act as protective factors in neurocognitive aging.

neuroscience↗

bioRxiv2022

Openness to experience is associated with neural and performance measures of memory in older adults

Age-related decline in episodic memory performance is a well-replicated finding across numerous studies. Recent studies focusing on aging and individual differences found that the Big Five personality trait Openness to Experience is associated with better episodic memory performance in older adults, but the associated neural mechanisms are largely unclear. Here we investigated the relationship between Openness and memory network function in a sample of 352 participants (143 older adults, 50-80 years; 209 young adults, 18-35 years). Participants underwent functional magnetic resonance imaging (fMRI) during a visual memory encoding task. Functional memory brain-network integrity was assessed using the SAME scores (similarity of activations during memory encoding), which reflect the similarity of a participants memory network activity compared to prototypical fMRI activity patterns of young adults. Openness was assessed using the NEO Five Factor Inventory (NEO-FFI). Older vs. young adults showed lower memory performance and higher deviation of fMRI activity patterns (i.e., lower SAME scores). Specifically in older adults, high Openness was associated with better memory performance, and mediation analysis showed that this relationship was partially mediated by higher SAME scores. Our results suggest that trait Openness may constitute a protective factor in cognitive aging by better preservation of the brains memory network.

neuroscience↗

bioRxiv2022

Pharmacological inhibition of bromodomain and extra-terminal proteins induces NRF-2-mediated inhibition of SARS-CoV-2 replication and is subject to viral antagonism

Inhibitors of bromodomain and extra-terminal proteins (iBETs), including JQ-1, have been suggested as potential therapeutics against SARS-CoV-2 infection. However, molecular mechanisms underlying JQ-1-induced antiviral activity and its susceptibility to viral antagonism remain incompletely understood. iBET treatment transiently inhibited infection by SARS-CoV-2 variants and SARS-CoV, but not MERS-CoV. Our functional assays confirmed JQ-1-mediated downregulation of ACE2 expression and multi-omics analysis uncovered induction of an antiviral NRF-2-mediated cytoprotective response as an additional antiviral component of JQ-1 treatment. Serial passaging of SARS-CoV-2 in the presence of JQ-1 resulted in predominance of ORF6-deficient variants. JQ-1 antiviral activity was transient in human bronchial airway epithelial cells (hBAECs) treated prior to infection and absent when administered therapeutically. We propose that JQ-1 exerts pleiotropic effects that collectively induce a transient antiviral state that is ultimately nullified by an established SARS-CoV-2 infection, raising questions on their clinical suitability in the context of COVID-19.

microbiology↗

bioRxiv2022

Taurine as a key intermediate for host-symbiont interaction in the tropical sponge Ianthella basta

Marine sponges are critical components of marine benthic fauna assemblages where their filter-feeding and reef-building capabilities provide bentho-pelagic coupling and crucial habitat. As potentially the oldest representation of a metazoan-microbe symbiosis, they also harbor dense, diverse, and species-specific communities of microbes, which are increasingly recognized for their contributions to dissolved organic matter (DOM) processing. Recent omics-based studies of marine sponge microbiomes have proposed numerous pathways of dissolved metabolite exchange between the host and symbionts within the context of the surrounding environment, but few studies have sought to experimentally interrogate these pathways. By using a combination of metaproteogenomics and laboratory incubations coupled with isotope-based functional assays, we showed that the dominant gammaproteobacterial symbiont Candidatus Taurinisymbion ianthellae residing in the marine sponge, Ianthella basta, expresses a pathway for the import and dissimilation of taurine, a ubiquitously occurring sulfonate metabolite in marine sponges. Candidatus Taurinisymbion ianthellae incorporates taurine-derived carbon and nitrogen while, at the same time, oxidizing the dissimilated sulfite into sulfate for export. Furthermore, we found that taurine-derived ammonia is exported by the symbiont for immediate oxidation by the dominant ammonia-oxidizing thaumarchaeal symbiont Candidatus Nitrosospongia ianthellae. Metaproteogenomic analyses also indicate that Candidatus Taurinisymbion ianthellae likely imports DMSP and possesses both pathways for DMSP demethylation and cleavage, enabling it to use this compound as a carbon and sulfur source for biomass, as well as for energy conservation. These results highlight the important role of biogenic sulfur compounds in the interplay between Ianthella basta and its microbial symbionts.

microbiology↗

bioRxiv2022

Multimodal Brain Signal Complexity Predicts Human Intelligence

Spontaneous brain activity builds the foundation for human cognitive processing during external demands. Neuroimaging studies based on functional magnetic resonance imaging (fMRI) identified specific characteristics of spontaneous (intrinsic) brain dynamics to be associated with individual differences in general cognitive ability, i.e., intelligence. However, fMRI research is inherently limited by low temporal resolution, thus, preventing conclusions about neural fluctuations within the range of milliseconds. Here, we used resting-state electroencephalographical (EEG) recordings from 144 healthy adults to test whether individual differences in intelligence (Ravens Advanced Progressive Matrices scores) can be predicted from the complexity of temporally highly resolved intrinsic brain signals. We compared different operationalizations of brain signal complexity (multiscale entropy, Shannon entropy, Fuzzy entropy, and specific characteristics of microstates) regarding their relation to intelligence. The results indicate that associations between brain signal complexity measures and intelligence are of small effect sizes (r ~ .20) and vary across different spatial and temporal scales. Specifically, higher intelligence scores were associated with lower complexity in local aspects of neural processing, and less activity in task-negative brain regions belonging to the defaultmode network. Finally, we combined multiple measures of brain signal complexity to show that individual intelligence scores can be significantly predicted with a multimodal model within the sample (10-fold cross-validation) as well as in an independent sample (external replication, N = 57). In sum, our results highlight the temporal and spatial dependency of associations between intelligence and intrinsic brain dynamics, proposing multimodal approaches as promising means for future neuroscientific research on complex human traits. Significance StatementSpontaneous brain activity builds the foundation for intelligent processing - the ability of humans to adapt to various cognitive demands. Using resting-state EEG, we extracted multiple aspects of temporally highly resolved intrinsic brain dynamics to investigate their relationship with individual differences in intelligence. Single associations were of small effect sizes and varied critically across spatial and temporal scales. However, combining multiple measures in a multimodal cross-validated prediction model, allows to significantly predict individual intelligence scores in unseen participants. Our study adds to a growing body of research suggesting that observable associations between complex human traits and neural parameters might be rather small and proposes multimodal prediction approaches as promising tool to derive robust brain-behavior relations despite limited sample sizes.

neuroscience↗

bioRxiv2022

Structural and functional MRI data differentially predict chronological age and behavioral memory performance

Human cognitive abilities decline with increasing chronological age, with decreased explicit memory performance being most strongly affected. However, some older adults show "successful aging", that is, relatively preserved cognitive ability in old age. One explanation for this could be higher brain structural integrity in these individuals. Alternatively, the brain might recruit existing resources more efficiently or employ compensatory cognitive strategies. Here, we approached this question by testing multiple candidate variables from structural and functional neuroimaging for their ability to predict chronological age and memory performance, respectively. Prediction was performed using support vector machine (SVM) classification and regression across and within two samples of young (N = 106) and older (N = 153) adults. The candidate variables were (i) behavioral response frequencies in an episodic memory test, (ii) recently described fMRI scores reflecting preservation of functional memory networks, (iii) whole-brain fMRI contrasts for novelty processing and subsequent memory, (iv) resting-state fMRI maps quantifying voxel-wise signal fluctuation and (v) gray matter volume estimated from structural MR images. While age group could be reliably decoded from all variables, chronological age within young and older subjects was best predicted from gray matter volume. In contrast, memory performance was best predicted from task-based fMRI contrasts and particularly single-value fMRI scores, whereas gray matter volume has no predictive power with respect to memory performance in healthy adults. Our results suggest that superior memory performance in healthy older adults is better explained by efficient recruitment of memory networks rather than by preserved brain structure.

neuroscience↗

bioRxiv2022

Evolution and systematics of the Aculeata and kin (Hymenoptera),with emphasis on the ants (Formicoidea: {dagger}@@@idae fam. nov., Formicidae).

Fossils provide unique opportunity to understand the tempo and mode of evolution and are essential for modeling the history of lineage diversification. Here, we interrogate the Mesozoic fossil record of the Aculeata, with emphasis on the ants (Formicidae), and conduct an extended series of ancestral state estimation exercises on distributions of tip-dated combined-evidence phylogenies. We developed and illustrated from ground-up a series of 576 morphological characters which we scored for 144 extant and 431 fossil taxa, including all families of Aculeata, Trigonaloidea, Evanioidea, and {dagger}Ephialtitoidea. We used average posterior probability support to guide composition of a target matrix of 303 taxa, for which we integrated strongly filtered ultraconserved element (UCE) data for 115 living species. We also implemented reversible jump MCMC (rjMCMC) and hidden state methods to model complex behavioral characters to test hypotheses about the pathway to obligate eusociality. In addition to revising the higher classification of all sampled groups to family or subfamily level using estimated character polarities to diagnose nodes across the phylogeny, we find that the mid-Cretaceous genera {dagger}Camelomecia and {dagger}Camelosphecia form a clade which is robustly supported as sister to all living and fossil Formicidae. For this reason, we name this extinct clade as {dagger}@@@idae fam. nov. and provide a definition for the expanded Formicoidea. Based on our results, we recognize three major phases in the early evolution of the ants: (1) origin of Formicoidea as ground-adapted huntresses during the Late Jurassic in the "stinging aggressor" guild (Aculeata) among various lineages of "sneaking parasitoids" (non-aculeate Vespina); (2) the first formicoid radiation during the Early Cretaceous, by the end of which all major extant linages originated; and (3) turnover of the Formicoidea at the end-Cretaceous leading to the second formicoid radiation. We conclude with a concentrated series of considerations for future directions of study with this dataset and beyond.

evolutionary biology↗

bioRxiv2022

Non-productive exposure of PBMCs to SARS-CoV-2 induces cell-intrinsic innate immunity responses

Cell-intrinsic responses mounted in vivo in PBMCs during mild and severe COVID-19 differ quantitatively and qualitatively. Whether they are triggered by signals emitted by productively infected cells of the respiratory tract or are, at least partially, resulting from physical interaction with virus particles, remains unclear. Here, we analyzed susceptibility and expression profiles of PBMCs from healthy donors upon ex vivo exposure to SARS-CoV and SARS-CoV-2. In line with the absence of detectable ACE2 receptor expression, human PBMCs were refractory to productive infection. Bulk and single cell RNA-sequencing revealed JAK/STAT-dependent induction of interferon-stimulated genes, but not pro-inflammatory cytokines. This SARS-CoV-2-specific response was most pronounced in monocytes. SARS-CoV-2-RNA-positive monocytes displayed a lower ISG signature as compared to bystander cells of the identical culture. This suggests a preferential invasion of cells with a low ISG base-line profile or delivery of a SARS-CoV-2-specific sensing antagonist upon efficient particle internalization. Together, non-productive physical interaction of PBMCs with SARS-CoV-2-but not SARS-CoV particles stimulates JAK/STAT-dependent, monocyte-accentuated innate immune responses that resemble those detected in vivo in patients with mild COVID-19.

immunology↗

bioRxiv2022

Summary statistics of memory-related fMRI activity reflect dissociable neuropsychological and anatomical signatures of neurocognitive aging

Memory-related functional magnetic resonance imaging (fMRI) activations show age-related differences across multiple brain regions that can be captured in summary statistics like single-value scores. Recently, we described two single-value scores reflecting deviations from prototypical whole-brain fMRI activity of young adults during novelty processing and successful encoding. Here, we investigate the brain-behavior associations of these scores with age-related neurocognitive changes in 153 healthy older adults. All scores were associated with episodic recall performance. The memory network scores, but not the novelty network scores, additionally correlated with medial temporal gray matter and a composite measure comprising pro-active inhibition, episodic memory, tonic alertness, flexibility, and working memory. Our results thus suggest that novelty-network-based fMRI scores show high brain-behavior associations with episodic memory and that encoding-network-based fMRI scores additionally capture individual differences in global cognitive function. More generally, our results suggest that single-value scores of memory-related fMRI provide a comprehensive measure of individual differences in network dysfunction that may contribute to age-related cognitive decline.

neuroscience↗

bioRxiv2021

Post-entry, spike-dependent replication advantage of B.1.1.7 and B.1.617.2 over B.1 SARS-CoV-2 in an ACE2-deficient human lung cell line

Epidemiological data demonstrate that SARS-CoV-2 variants of concern (VOC) B.1.1.7 and B.1.617.2 are more transmissible and infections are associated with a higher mortality than non-VOC virus infections. Phenotypic properties underlying their enhanced spread in the human population remain unknown. B.1.1.7 virus isolates displayed inferior or equivalent spread in most cell lines and primary cells compared to an ancestral B.1 SARS-CoV-2, and were outcompeted by the latter. Lower infectivity and delayed entry kinetics of B.1.1.7 viruses were accompanied by inefficient proteolytic processing of spike. B.1.1.7 viruses failed to escape from neutralizing antibodies, but slightly dampened induction of innate immunity. The bronchial cell line NCI-H1299 supported 24- and 595-fold increased growth of B.1.1.7 and B.1.617.2 viruses, respectively, in the absence of detectable ACE2 expression and in a spike-determined fashion. Superior spread in NCI-H1299 cells suggests that VOCs employ a distinct set of cellular cofactors that may be unavailable in standard cell lines.

microbiology↗

bioRxiv2021

Lowland plant migrations into alpine ecosystems amplify soil carbon loss under climate warming

Climate warming is releasing carbon from soils around the world1-3, constituting a positive climate feedback. Warming is also causing species to expand their ranges into new ecosystems4-9. Yet, in most ecosystems, whether range expanding species will amplify or buffer expected soil carbon loss is unknown10. Here we used two whole-community transplant experiments and a follow-up glasshouse experiment to determine whether the establishment of herbaceous lowland plants in alpine ecosystems influences soil carbon content under warming. We found that warming (transplantation to low elevation) led to a negligible decrease in alpine soil carbon content, but its effects became significant and 52% {+/-} 31% (mean {+/-} 95% CIs) larger after lowland plants were introduced at low density into the ecosystem. We present evidence that decreases in soil carbon content likely occurred via lowland plants increasing rates of root exudation, soil microbial respiration and CO2 release under warming. Our findings suggest that warming-induced range expansions of herbaceous plants have the potential to alter climate feedbacks from this system, and that plant range expansions among herbaceous communities may be an overlooked mediator of warming effects on carbon dynamics.

ecology↗

bioRxiv2021

The Hidden Side Of Diversity: Effects Of Imperfect Detection On Multiple Dimensions Of Biodiversity

O_LIStudies on ecological communities often address patterns of species distribution and abundance, but few consider uncertainty in counts of both species and individuals when computing diversity measures. C_LIO_LIWe evaluated the extent to which imperfect detection may influence patterns of taxonomic, functional, and phylogenetic diversity in ecological communities. C_LIO_LIWe estimated the true abundance of fruit-feeding butterflies sampled in canopy and understory strata in a subtropical forest. We compared the diversity values calculated by observed and estimated abundance data through the hidden diversity framework. This framework evaluates the deviation of observed diversity when compared with diversities derived from estimated true abundances, and if such deviation represents a bias or a noise in the observed diversity pattern. C_LIO_LIThe hidden diversity values differed between strata for all diversity measures, except for functional richness. The taxonomic measure was the only one where we observed an inversion of the most diverse stratum when imperfect detection was included. Regarding phylogenetic and functional measures, the strata showed distinct responses to imperfect detection, despite the tendency to overestimate observed diversity. While the understory showed noise for the phylogenetic measure, since the observed pattern was maintained, the canopy had biased diversity for the functional metric. This bias occurred since no significant differences were found between strata for observed diversity, but rather for estimated diversity, with the canopy being more clustered. C_LIO_LIWe demonstrate that ignore imperfect detection may lead to unrealistic estimates of diversity and hence, to erroneous interpretations of patterns and processes that structure biological communities. For fruit-feeding butterflies, according to their phylogenetic position or functional traits, the undetected individuals triggered different responses in the relationship of the diversity measures to the environmental factor. This highlights the importance to evaluate and include the uncertainty in species detectability before calculating biodiversity measures to describe communities. C_LI

ecology↗

bioRxiv2021

FishPhyloMaker: An R package to generate phylogenies for ray-finned fishes

Phylogenies summarize evolutionary information that is essential in the investigation of ecological and evolutionary causes of diversity patterns. They allow investigating hypotheses from trait evolution to the relationship between evolutionary diversity and ecosystem functioning. However, obtaining a comprehensive phylogenetic hypothesis can be difficult for some groups, especially those with a high number of species, that is the case for fishes, particularly tropical ones. The lack of species in phylogenetic hypotheses, called Darwinian shortfalls, can hinder ecological and evolutionary studies involving this group. To tackle this problem, we developed FishPhyloMaker, an R package that facilitates the generation of phylogenetic trees through a reliable and reproducible procedure, even for a large number of species. The package adopts well-known rules of insertion based on cladistic hierarchy, allowing its use by specialists and non-specialists in fish systematics. We tested the reliability of our algorithm in maintaining important properties of phylogenetic distances running a sensitivity analysis. We also exemplified the use of the FishPhyloMaker package by constructing complete phylogenies for fishes inhabiting the four richest freshwater ecoregions of the world. Furthermore, we proposed a new method to calculate Darwinian shortfalls and mapped this information for the major freshwater drainages of the world. FishPhyloMaker will expand the range of evolutionary and ecological questions that can be addressed using ray-finned fishes as study models, mainly in the field of community phylogenetics, by providing an easy and reliable way to obtain comprehensive phylogenies. Further, FishPhyloMaker presents the potential to be extended to other taxonomic groups that suffer from the same difficulty in the obtention of comprehensive phylogenetic hypothesis. HighlightsO_LIWe provide the first automated procedure to check species names, construct phylogenetic trees and calculate Darwinian shortfalls for ray-finned fishes (Actinopterygii) by the R package FishPhyloMaker. C_LIO_LIThis package provides functions to assemble phylogenies through a fast, reliable, and reproducible method, allowing its use and replicability by specialists and non-specialists in fish systematics. C_LIO_LIThe package also provides an interactive procedure that gives more flexibility to the user when compared with other existing tools that construct phylogenetic trees for other highly speciose groups. C_LIO_LIThe package includes a new method to compute Darwinian shortfalls for ray-finned fishes, but the rationale of the provided algorithm can be extended in future studies to be used in other groups of organisms C_LI

evolutionary biology↗

bioRxiv2021

Motivational learning biases are differentially modulated by genetic determinants of striatal and prefrontal dopamine function

Dopaminergic neurotransmission plays a pivotal role in appetitively motivated behavior in mammals, including humans. Notably, action and valence are not independent in motivated tasks, and it is particularly difficult for humans to learn the inhibition of an action to obtain a reward. We have previously observed that the carriers of the DRD2/ANKK1 TaqIA A1 allele, that has been associated with reduced striatal dopamine D2 receptor expression, showed a diminished learning performance when required to learn response inhibition to obtain rewards, a finding that was replicated in two independent cohorts. In the present study, we first report a replication of this finding in a third independent cohort of 99 participants. Interestingly, after combining all three cohorts (total N = 281), exploratory analyses regarding the COMT Val108/158Met polymorphism suggest that homozygotes for the Met allele, which has been linked to higher prefrontal dopaminergic tone, show a lower learning bias. Our results corroborate the importance of genetic variability of the dopaminergic system in individual learning differences of action-valence interaction and, furthermore, suggest that motivational learning biases are differentially modulated by genetic determinants of striatal and prefrontal dopamine function.

neuroscience↗

bioRxiv2021

A comprehensive score reflecting memory-related fMRI activations and deactivations as potential biomarker for neurocognitive aging

Older adults and particularly those at risk for developing dementia typically show a decline in episodic memory performance, which has been associated with altered memory network activity detectable via functional magnetic resonance imaging (fMRI). To quantify the degree of these alterations, a score has been developed as a putative imaging biomarker for successful aging in memory for older adults (Functional Activity Deviations during Encoding, FADE; Duzel et al., 2011). Here, we introduce and validate a more comprehensive version of the FADE score, termed FADE-SAME (Similarity of Activations during Memory Encoding), which differs from the original FADE score by considering not only activations but also deactivations in fMRI contrasts of stimulus novelty and successful encoding, and by taking into account the variance of young adults activations. We computed both scores for novelty and subsequent memory contrasts in a cohort of 217 healthy adults, including 106 young and 111 older participants, as well as a replication cohort of 117 young subjects. We further tested the stability and generalizability of both scores by controlling for different MR scanners and gender, as well as by using different data sets of young adults as reference samples. Both scores showed robust age-group-related differences for the subsequent memory contrast, and the FADE-SAME score additionally exhibited age-group-related differences for the novelty contrast. Furthermore, both scores correlate with behavioral measures of cognitive aging, namely memory performance. Taken together, our results suggest that single-value scores of memory-related fMRI responses may constitute promising biomarkers for quantifying neurocognitive aging.

neuroscience↗

bioRxiv2021

Indole-3-glycerolphosphate synthase, a branchpoint for the biosynthesis of tryptophan, indole, and benzoxazinoids in maize

The maize (Zea mays) genome encodes three indole-3-glycerolphosphate synthase enzymes (IGPS1, 2, and 3) catalyzing the conversion of 1-(2-carboxyphenylamino)-l-deoxyribulose-5-phosphate to indole-3-glycerolphosphate. Three further maize enzymes (BX1, benzoxazinoneless 1; TSA, tryptophan synthase subunit; and IGL, indole glycerolphosphate lyase) convert indole-3-glycerolphosphate to indole, which is released as a volatile defense signaling compound and also serves as a precursor for the biosynthesis of tryptophan and defense-related benzoxazinoids. Phylogenetic analyses showed that IGPS2 is similar to enzymes found in both monocots and dicots, whereas maize IGPS1 and IGPS3 are in monocot-specific clades. Fusions of yellow fluorescent protein (YFP) with maize IGPS enzymes and indole-3-glycerolphosphate lyases were all localized in chloroplasts. In bimolecular fluorescence complementation assays, IGPS1 interacted strongly with BX1 and IGL, IGPS2 interacted primarily with TSA, and IGPS3 interacted equally with all three indole-3-glycerolphosphate lyases. Whereas IGPS1 and IGPS3 expression was induced by insect feeding, IGPS2 expression was not. Transposon insertions in IGPS1 and IGPS3 reduced the abundance of both benzoxazinoids and free indole. Spodoptera exigua (beet armyworm) larvae show improved growth on igps1 mutant maize plants. Together, these results suggest that IGPS1 and IGPS3 function mainly in the biosynthesis of defensive metabolites, whereas IGPS2 may be involved in the biosynthesis of tryptophan. This metabolic channeling is similar, though less exclusive than that proposed for the three maize indole-3-glycerolphosphate lyases.

plant biology↗

bioRxiv2020

Pallidal deep brain stimulation alters cortico-striatal synaptic communication in dystonic hamsters

BackgroundDeep brain stimulation (DBS) of the globus pallidus internus (GPi) is considered to be the most relevant therapeutic option for patients with severe dystonias, which are thought to arise from a disturbance in striatal control of the GPi, possibly resulting in thalamic disinhibition. The mechanisms of GPi-DBS are far from understood. Hypotheses range from an overall silencing of target nuclei (due to e.g. depolarisation block), via differential alterations in thalamic firing, to disruption of oscillatory activity in the {beta}-range. Although a disturbance of striatal function is thought to play a key role in dystonia, the effects of DBS on cortico-striatal function are unknown. ObjectiveWe hypothesised that DBS, via axonal backfiring, or indirectly via thalamic and cortical coupling, alters striatal network function. We aimed to test this hypothesis in the dtsz-hamster, an animal model of inherited generalised, paroxysmal dystonia. MethodsHamsters (dtsz-dystonic and non-dystonic controls) were bilaterally implanted with stimulation electrodes targeting the entopeduncular nucleus (EPN, equivalent of human GPi). DBS (130 Hz), and sham DBS, were performed in unanaesthetised animals for 3 hours. Synaptic cortico-striatal field potential responses, as well as miniature excitatory postsynaptic currents (mEPSC) and firing properties of medium spiny striatal neurons were subsequently recorded in brain slice preparations obtained from these animals immediately after EPN-DBS, to gauge synaptic responsiveness of cortico-striatal projections, their inhibitory control, and striatal neuronal excitability. ResultsDBS increased cortico-striatal responses in slices from control, but not dystonic animals. Inhibitory control of these responses, in turn, was differentially affected: DBS increased inhibitory control in dystonic, and decreased it in healthy tissue. A modulation of presynaptic mechanisms is likely involved, as mEPSC frequency was reduced strongly in dystonic, and less prominently in healthy tissues, while cellular properties of medium-spiny neurons remained unchanged. ConclusionDBS leads to dampening of cortico-striatal communication with restored inhibitory tone.

neuroscience↗