Biology subjects

Schulz, S.

Publications and source records attributed to Schulz, S..

45 records · Page 3Linked to original sources

bioRxiv2019

A major locus controls a biologically active pheromone component in Heliconius melpomene

Understanding the production, response, and genetics of signals used in mate choice can inform our understanding of the evolution of both intraspecific mate choice and reproductive isolation. Sex pheromones are important for courtship and mate choice in many insects, but we know relatively little of their role in butterflies. The butterfly Heliconius melpomene uses a complex blend of wing androconial compounds during courtship. Electroantennography in H. melpomene and its close relative H. cydno showed that responses to androconial extracts were not species-specific. Females of both species responded equally strongly to extracts of both species, suggesting conservation of peripheral nervous system elements across the two species. Individual blend components provoked little to no response, with the exception of octadecanal, a major component of the H. melpomene blend. Supplementing octadecanal on the wings of octadecanal-rich H. melpomene males led to an increase in the time until mating, demonstrating the bioactivity of octadecanal in Heliconius. Using quantitative trait locus (QTL) mapping, we identified a single locus on chromosome 20 responsible for 41% of the parental species difference in octadecanal production. This QTL does not overlap with any of the major wing color or mate choice loci, nor does it overlap with known regions of elevated or reduced FST. A set of 16 candidate fatty acid biosynthesis genes lies underneath the QTL. Pheromones in Heliconius carry information relevant for mate choice and are under simple genetic control, suggesting they could be important during speciation.

evolutionary biology↗

bioRxiv2019

Parameters and determinants of responses to selection in antibody libraries

Antibody repertoires contain binders to nearly any target antigen. The sequences of these antibodies differ mostly at few sites located on the surface of a scaffold that itself consists of much less varied amino acids. What is the impact of this scaffold on the response to selection of a repertoire? To gauge this impact, we carried out quantitative phage display experiments with three antibody libraries based on distinct scaffolds harboring the same diversity at randomized sites, which we selected for binding to four arbitrary targets. We first show that the response to selection of an antibody library is captured by a simple and measurable parameter with direct physical and information-theoretic interpretations. Second, we identify a major determinant of this parameter which is encoded in the scaffold, its degree of evolutionary maturation. Antibodies undergo an accelerated evolutionary process, called affinity maturation, to improve their affinity to a given target antigen as part of the adaptive immune response. We find that libraries of antibodies built around such maturated scaffolds have a lower response to selection to other arbitrary targets than libraries built around naive scaffolds of germline origin. Our results are a first step towards quantifying and controlling the evolutionary potential of biomolecules.

biophysics↗

bioRxiv2019

Species specificity and intraspecific variation in the chemical profiles of Heliconius butterflies across a large geographic range

In many animals, mate choice is important for the maintenance of reproductive isolation between species. Traits important for mate choice and behavioural isolation are predicted to be under strong stabilising selection within species, however such traits can also exhibit variation at the population level driven by neutral and adaptive evolutionary processes. Here, we describe patterns of divergence among androconial and genital chemical profiles at inter- and intra-specific levels in mimetic Heliconius butterflies. Most variation in chemical bouquets was found between species, but there were also quantitative differences at the population level. We found a strong correlation between interspecific chemical and genetic divergence, however, this correlation varied in intraspecific comparisons. We identified indicator compounds characteristic of particular species that included known biologically active compounds, suggesting an approach for identification of candidate compounds for future behavioural studies in novel systems. Overall, the strong signal of species identity suggests a role for these compounds in species recognition, but with additional potentially neutral variation at the population level.

evolutionary biology↗

bioRxiv2019

Quantitative Mass Spectrometry Imaging Reveals Mutation Status-independent Lack of Imatinib Penetration into Liver Metastases of Gastrointestinal Stromal Tumors

Mass spectrometry imaging (MSI) is an enabling technology for label-free drug disposition studies at high spatial resolution in life science- and pharmaceutical research. We present the first extensive clinical matrix-assisted laser desorption/ionization (MALDI) quantitative mass spectrometry imaging (qMSI) study of drug uptake and distribution in clinical specimen, analyzing 56 specimens of tumor and corresponding non-tumor tissues from 28 imatinib-treated patients with biopsy-proven gastrointestinal stromal tumors (GIST). For validation, we compared MALDI-TOF-qMSI with conventional UPLC-ESI-QTOF-MS-based quantification from tissue extracts and with ultra-high resolution MALDI-FTICR-qMSI. We introduced a novel generalized nonlinear calibration model of drug quantities based on focused computational evaluation of drug-containing areas that enabled better data fitting and assessment of the inherent method nonlinearities. Imatinib tissue spatial maps revealed striking inefficiency in drug penetration into GIST liver metastases even though the corresponding healthy liver tissues in the vicinity showed abundant imatinib levels beyond the limit of quantification (LOQ), thus providing evidence for secondary drug resistance independent of mutation status. Taken together, these findings underline the important application of MALDI-qMSI for studying the spatial distribution of molecularly targeted therapeutics in oncology.

pharmacology and toxicology↗

bioRxiv2018

Heteromerization of endogenous mu and delta opioid receptors tunes mu opioid receptor signaling and trafficking

Increasing evidence indicates that native mu and delta opioid receptors can associate to form heteromers in discrete brain neuronal circuits. However, little is known about their signaling and trafficking. Using double fluorescent knock-in mice, we investigated the impact of neuronal co-expression on the internalization profile of mu and delta opioid receptors in primary hippocampal cultures and in vivo. We established ligand selective mu-delta co-internalization upon activation by exogenous ligands and provide evidence for mu-delta co-internalization by the endogenous opioid peptide met-enkephalin, but not {beta}-endorphin. Co-internalization was driven by the delta opioid receptor, required an active conformation of both receptors and led to sorting to the lysosomal compartment. This alteration in the mu opioid receptor intracellular fate was accompanied by sustained ERK1/2 phosphorylation. In addition, increased mu-delta neuronal co-localization in the rostral ventromedial medulla in a chronic neuropathic state suggests that mu-delta heteromers are involved in the regulation of nociceptive transmission

neuroscience↗

bioRxiv2018

Two dispersers are better than one: a ‘bird-fig’ attracts bats via nocturnal scent

The plant genus Ficus is a keystone resource in tropical ecoystems. One of the unique features of figs is the diversity of fruit traits, which in many cases match their various dispersers, the so-called fruit syndromes. The classic example of this is the strong phenotypic differences found between figs with bat and bird dispersers (color, size, and presentation). The bird-fig Ficus colubrinae represents an exception to this trend since it attracts the small frugivorous bat species Ectophylla alba at night, but during the day attracts bird visitors. Here we investigate the mechanism by which this bird-fig attracts bats despite its fruit traits, which should appeal solely to birds. We performed feeding experiments with Ectophylla alba to assess the role of fruit scent in the detection of ripe fruits. Ectophylla alba was capable of finding ripe figs by scent alone under exclusion of other sensory cues. This suggests that scent is the main foraging cue for Ectophylla alba. Analyses of odor bouquets from the bat- and bird-dispersal phases (i.e. day and night) differed significantly in their composition of volatiles. The combination of these two findings raises the question whether E. alba and F. colubrinae resemble a co-adaptation that enables a phenotypically classic bird-fig to attract bat dispersers by an olfactory signal at night thus maximizing dispersal.

ecology↗

bioRxiv2018

Male pheromone composition depends on larval but not adult diet in Heliconius melpomene

Condition-dependent traits can act as honest signals of mate quality, with fitter individuals able to display preferred phenotypes. Nutrition is known to be an important determinant of individual condition, with diet known to affect many secondary sexual traits. In Heliconius butterflies, male chemical signalling plays an important role in female mate choice. Heliconius pheromones are sexually dimorphic, found only in mature males, but it is unclear what information they convey to the female. Here, we manipulate both the larval and adult diet of male Heliconius melpomene rosina to test for environmental effects on wing and genital pheromone production. We find no evidence that adult pollen consumption affects pheromone production in the first ten days after eclosion. We also find strong overlap in the chemical profiles of individuals reared on different larval host plants. However, individual compounds were found in different amounts between host plant treatments. Further electrophysiological and behavioural experiments will be needed to determine the biological significance of these differences.

ecology↗

bioRxiv2018

Schizophrenia-related cognitive dysfunction in the Cyclin-D2 knockout mouse model of ventral hippocampal hyperactivity

Elevated activity at the output stage of the anterior hippocampus has been described as a physiological endophenotype of schizophrenia, and its development maps onto the transition from its prodromal to its psychotic state. Interventions that halt the spreading glutamatergic over-activity in this region and thereby the development of overt schizophrenia could be promising therapies. However, animal models with high construct validity to support such pre-clinical development are scarce. The Cyclin-D2 knockout (CD2-KO) mouse model shows a hippocampal Parvalbumin-interneuron dysfunction and its pattern of hippocampal over-activity shares similarities with that seen in prodromal patients. In a comprehensive phenotyping of CD2-KO mice, we found that they displayed novelty-induced hyperlocomotion (a correlate in the positive symptom domain), that was largely resistant against D1- and D2-dopamine receptor antagonism, but responsive to the mGluR2/3-agonist LY379268. In the negative symptom domain, CD2-KO mice showed transiently reduced sucrose-preference (anhedonia), but enhanced interaction with novel mice and objects, as well as normal nest building and incentive motivation. Also, unconditioned anxiety, perseveration, and motor impulsivity were unaltered. However, in the cognitive domain, CD2-knockouts showed reduced executive function in assays of rule-shift and rule-reversal learning, but also an impairment in working memory, that was resistant against LY379268. In contrast, sustained attention and forms of spatial and object-related memory that are mediated by short-term habituation of stimulus-specific attention were intact. Our results suggest, that CD2-KO mice are a valuable model in translational research targeted at the pharmacoresistant cognitive symptom domain in causal relation to hippocampal over-activity in the prodrome-to-psychosis transition.

animal behavior and cognition↗

bioRxiv2017

Agonist-Dependent And -Independent Kappa Opioid Receptor Phosphorylation Showed Distinct Phosphorylation Patterns And Resulted In Different Cellular Outcomes

We reported previously that the selective agonist U50,488H promoted phosphorylation of the mouse kappa opioid receptor (KOPR) at residues S356, T357, T363 and S369. Here, we found that agonist (U50,488H)-dependent KOPR phosphorylation at all the residues were mediated by Gi/o proteins and multiple protein kinases [GRKs2, 3, 5 and 6 and protein kinase C (PKC)]. In addition, PKC activation by phorbol ester induced agonist-independent KOPR phosphorylation. Compared with U50,488H, PKC activation promoted much higher S356/T357 phosphorylation, much lower T363 phosphorylation and similar levels of S369 phosphorylation. Following U50,488H, GRKs, but not PKC, were involved in agonist-induced KOPR internalization. In contrast, PKC activation caused a lower level of agonist-independent KOPR internalization, compared to U50,488H. U50,488H-induced activation of extracellular signal regulated kinase 1/2 (ERK1/2) was G protein-, but not {beta}-arrestin-, dependent. After U50,488H, GRK- mediated, but not PKC-mediated, KOPR phosphorylation followed by {beta}-arrestin recruitment desensitized U50,488H-induced ERK1/2 response. Therefore, agonist-dependent (GRK- and PKC-mediated) and agonist-independent (PKC-promoted) KOPR phosphorylations show distinct phosphorylation patterns, leading to diverse cellular outcomes.\n\nAbbreviations

pharmacology and toxicology↗