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Uhl, G.

Publications and source records attributed to Uhl, G..

13 recordsLinked to original sources

Genomic insights into Candidatus Argioplasma dusa, a bacterial symbiont of the wasp spider Argiope bruennichi

Bacterial symbionts were shown to have significant beneficial impacts on the fitness of their host in insects, but little is known on the symbionts of spiders and their interactions with their hosts. Here, we assembled and investigated the circular 575 kb genome of Candidatus Argioplasma dusa, a novel bacterial symbiont of the wasp spider Argiope bruennichi. Phylogenomic analysis placed this species within the phylum Tenericutes, in a poorly characterized clade that may represent a new order-level lineage or affiliate with the Mycoplasmatales order. With 559 predicted genes, the genome is relatively small compared to other Tenericutes genomes (on average 969 genes) and has a low GC content of ~24%. While the genome encodes genes for proteins involved in glycolysis and fermentative acetate production, it revealed minimal biosynthetic capabilities with pathways for nucleotide, amino acid and vitamin biosynthesis being absent in Ca. Argioplasma dusa. This suggests an intracellular endosymbiotic lifestyle within the spider host. The symbiont was detected in A. bruennichi populations across the distribution range of the spider but appears to be absent in certain populations.

microbiology↗

Quercetin and 6-Br_uercetin antioxidant properties and off target screening results advance glycosylated 6BrQ as a development candidate for Alzheimers disease

Quercetin is an abundant dietary flavonol with interesting in vitro properties that include substrate-selective positive allosteric modulation (PAM) of the activity of the receptor type protein tyrosine phosphatase D (PTPRD) and substantial antioxidant actions. Its in vivo activities include reducing incidence of Alzheimers disease (AD) and reducing AD neurofibrillary pathology in mouse models. Structure-activity studies have identified quercetin analogs with improved in vitro and in vivo properties, including the improved PTPRD PAM 6-bromoquercetin (6BrQ). However, there is no comparison of the antioxidant properties of 6BrQ to those of quercetin. There is no systematic screening for activities of quercetin or of 6BrQ using a panel of targets for most currently-used drugs. We now report that both quercetin and 6BrQ provide equivalent results in cyclic voltammetric and biochemical antioxidant assays. We also report that neither 10-7 M quercetin nor 6BrQ provides any significant (>50%) effects on any of the 104 assays in a Eurofins off-target screening panel. At 10-5 M, both quercetin and 6BrQ exert significant effects in assays for glycogen synthase kinase 3 (GSK3{beta}) as well as those for serotonin 5HT2B receptor, adenosine transport, adenosine A2A receptors, cyclooxygenases COX1 and COX2, phosphodiesterases PDE3A and 4D2 and PPAR gamma. These data extend prior characterization of quercetins biochemical effects, provide novel results for 6BrQ and support the likelihood that both quercetin and 6BrQ can a) directly inhibit GSK3, b) reduce GSK3 activities via enhancement of its dephosphorylation by PTPRD and c) display modest numbers of off target activities at high concentrations, several of which could conceivably contribute to anti-AD activities. These results advance bioavailable glycosylated prodrugs that can be metabolized to 6BrQ as developmental candidates for AD.

neuroscience↗

Pentilludin reduces rat amphetamine and remifentail self-administration with good pharmacologic and toxicologic profiles

Pentilludin is a novel, potent (690 nM) irreversible inhibitor of actions of the receptor type protein tyrosine phosphatase D (PTPRD). Pentilludin displays no in vitro activities in Ames or micronucleus tests, at hERG channels or at targets for currently-licensed drugs. Rats treated with pentilludin doses up to 100 mg/kg/day for two weeks have not been found to display behavioral, hematologic or serum chemistry abnormalities. Treatment with 20 mg/kg sc pentilludin prior to every other M-W-F self-administration session substantially reduces self-administration of amphetamine and more modestly reduces self-administration of remifentanil. Pentilludin provides a novel means for reducing self-administration of psychostimulant and, modestly, opiate drugs in ways that could enhance abstinence in humans.

pharmacology and toxicology↗

Winter temperature effects in a cold-adapted northern population of a range-expanding spider: survival, energy stores, and differential gene expression

Species expand their spatial distribution when environmental conditions are favorable or when mutations arise that allow them to live in previously unfavorable conditions. The European wasp spider, Argiope bruennichi, is known to have expanded its range poleward faster than climate change would predict. Northern edge populations show higher cold tolerance and are genetically differentiated from core populations, suggesting local adaptation to colder winter conditions. To investigate the degree and limits of plasticity in a cold-adapted population, we exposed overwintering juveniles (spiderlings) from Estonia - the northern edge of the distribution - to three winter regimes: two with a strong difference in day/night temperatures and an overall 10 degrees difference (warm and cold treatment) and one with moderate temperatures and less difference between day and night (moderate). We investigated if survival, lipid content, metabolites, and gene expression patterns differ depending on these temperature regimes. The survival probability of the spiderlings and their overall lipid content decreased over winter, with no difference between treatments, suggesting high resilience of the spiderlings towards very different temperature regimes at the edge of the distribution. At the end of winter, the content of saturated and monounsaturated fatty acids per spiderling also did not differ between treatments. However, omega-3 polyunsaturated fatty acids (PUFAs) levels were significantly lower in spiders exposed to the warm winter suggesting increased metabolic activity. We identified 4096 significant differentially expressed genes (DEGs) across the treatments, of which 1389 were specific for the moderate treatment, and 832 specific for the warm treatment, while 69 were unique for the cold treatment, showing a stronger temperature stress response to the moderate and warmer than to the cold treatment. Taken together, our results show that A. bruennichi has physiological plasticity and the ability to cope with very different winter temperature regimes despite being cold adapted. However, warmer winters might come with metabolic costs that could impact on the spiderling[s] survival and foraging success when they emerge from the egg sac in spring.

ecology↗

Multi-ancestry GWAS of major depression aids locus discovery, fine-mapping, gene prioritisation, and causal inference

Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 studies with 88,316 MD cases and 902,757 controls to previously reported data from individuals of European ancestry. This includes samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latinx participants (32%). The multi-ancestry GWAS identified 190 significantly associated loci, 53 of them novel. For previously reported loci from GWAS in European ancestry the power-adjusted transferability ratio was 0.6 in the Hispanic/Latinx group and 0.3 in each of the other groups. Fine-mapping benefited from additional sample diversity: the number of credible sets with [≤]5 variants increased from 3 to 12. A transcriptome-wide association study identified 354 significantly associated genes, 205 of them novel. Mendelian Randomisation showed a bidirectional relationship with BMI exclusively in samples of European ancestry. This first multi-ancestry GWAS of MD demonstrates the importance of large diverse samples for the identification of target genes and putative mechanisms.

genetics↗

Rapid ecological and evolutionary divergence during a poleward range expansion

In response to climate change, a northward range expansion has been observed in many species. The wasp spider, Argiope bruennichi, has expanded from its historic range in the Mediterranean ("core"), now reaching as far as the Baltic States and Scandinavia ("edge"), even faster than the pace of climate change. We explored life history traits, adult phenotypes, offspring cold tolerance, and genomic patterns across the European range of A. bruennichi, and found origin-, environment- and life stage-specific responses to the cold northern climate. Wasp spiders have shifted their phenology at the edge, with females maturing earlier and at a smaller size, but maintaining similar pigmentation, clutch sizes, and hatching success compared to the core region. Using a reciprocal common garden experiment on overwintering offspring from the core and edge, we found evidence for genetic adaptation and considerable phenotypic plasticity. Overwintering survival was lower under the cold winter treatment for spiderlings from both origins. However, the edge-origin spiderlings that survived the winter had lower lethal temperatures and enhanced supercooling ability with reduced phenotypic plasticity in supercooling points compared to core spiderlings, while the chill coma recovery time was similar. Metabolomic analysis revealed accumulations of amino acids and myo-inositol in the cold winter treatment, particularly in spiderlings from the edge population, suggesting a role of these metabolites in improving cold tolerance. Genotype-environment tests showed strong genetic association across the genome to seasonality and minimum winter temperature. The population genomic analysis across the European range splits A. bruennichi into two distinct genetic clusters through the center of Germany, which roughly aligns with turnover from an oceanic to continental climate zone, complementing the genotype-environment test results. Overall, our study highlights the importance of integrating data on phenological shifts, changes in life-history, and life stage-specific phenotypic plasticity and genetic adaptation to understand the impacts of range expansions and shifts. The nuanced processes of acclimation and adaptation we uncovered advocate for holistic investigations of evolutionary fitness and fitness-related traits in the context of organismal responses to novel and changing environments.

ecology↗

Identification of sex chromosomes using genomic and cytogenetic methods in a range-expanding spider, Argiope bruennichi (Araneae: Araneidae)

Differences between sexes in growth, ecology and behavior strongly shape species biology. In some animal groups, such as spiders, it is difficult or impossible to identify the sex of juveniles based on external morphology. This information would be useful for field surveys, behavioral experiments, and ecological studies on e.g. sex ratios and dispersal. In species with sex chromosomes, sex can be determined based on the specific sex chromosome complement. Additionally, information on the sequence of sex chromosomes provides the basis for studying sex chromosome evolution. We combined cytogenetic and genomic data to identify the sex chromosomes in the sexually dimorphic spider Argiope bruennichi, and designed RT-qPCR sex markers. We found that genome size and GC content of this spider falls into the range reported for the majority of araneids. The male karyotype is formed by 24 acrocentric chromosomes with an X1X20 sex chromosome system, with little similarity between X chromosomes, suggesting origin of these chromosomes by X chromosome fission or early duplication of an X chromosome and subsequent independent differentiation of the copies. Our data suggest similarly sized X chromosomes in A. bruennichi. They are smaller chromosomes of the complement. Our findings open the door to new directions in spider evolutionary and ecological research.

genetics↗

Diversification through sexual selection on gustatorial courtship traits in dwarf spiders

Sexual dimorphism can evolve under sexual selection or ecological factors. Sexually dimorphic male prosomal modifications are associated with gustatorial courtship in erigonines. The modifications vary from moderate elevations to bizarre shapes. Males transfer substances from these structures to females, which affect mate acceptance and fecundity. Here, we explore lability of these traits by investigating if modified prosomata are inherently linked to secretory glands, if glands evolved prior to prosomal modifications, and the possibility of convergent evolution and cryptic differentiation, aiming at assessing the possible role of this trait complex in speciation. We reconstructed the positions of glands and the musculature in the anterior part of prosomata of 76 erigonines and three outgroups using micro-CT. We incorporated these characters into an existing morphological character matrix and reanalyzed the phylogeny. Our results support the possession of glands as the ancestral state. The manifold modifications of the prosomal shape have evolved convergently. Differences in glandular positions between species with modified/unmodified prosomata suggest high lability of these traits. Cases of gland loss suggest considerable costs of gustatorial courtship. Our findings demonstrate divergent evolutionary patterns of these traits, and a likely facilitating effect of this type of sexual selection on speciation.

evolutionary biology↗

Reduced PTPRD expression differentially alters brain phosphotyrosine phosphoproteomic profiles of 2 and 12 month-old mice

The receptor type protein tyrosine phosphatase PTPRD is implicated in maturation of synapses of expressing neurons, vulnerability to addictions, reward from addictive substances, vulnerability to restless leg syndrome and densities of neurofibrillary pathology in Alzheimers disease brains by a variety of evidence. However, PTPRDs physiological substrates and adaptations to differences in levels of PTPRD expression in brains of young and aging animals have not been explored in depth. We report phosphoproteomic studies of brains of young and aged mice with different levels of PTPRD expression, gene ontology studies of genes identified in this way and validation of several candidate PTPRD substrates with in vitro assays using recombinant PTPRD phosphatase. PTPRD is well positioned to modulate the extent of phosphorylation of phosphotyrosine phosphoprotein substrates, including those involved in synaptic maturation and adaptation.

neuroscience↗

Chromosome-level reference genome of the European wasp spider Argiope bruennichi: a resource for studies on range expansion and evolutionary adaptation

BackgroundArgiope bruennichi, the European wasp spider, has been studied intensively as to sexual selection, chemical communication, and the dynamics of rapid range expansion at a behavioral and genetic level. However, the lack of a reference genome has limited insights into the genetic basis for these phenomena. Therefore, we assembled a high-quality chromosome-level reference genome of the European wasp spider as a tool for more in-depth future studies. FindingsWe generated, de novo, a 1.67Gb genome assembly of A. bruennichi using 21.5X PacBio sequencing, polished with 30X Illumina paired-end sequencing data, and proximity ligation (Hi-C) based scaffolding. This resulted in an N50 scaffold size of 124Mb and an N50 contig size of 288kb. We found 98.4% of the genome to be contained in 13 scaffolds, fitting the expected number of chromosomes (n = 13). Analyses showed the presence of 91.1% of complete arthropod BUSCOs, indicating a high quality of the assembly. ConclusionsWe present the first chromosome-level genome assembly in the class Arachnida. With this genomic resource, we open the door for more precise and informative studies on evolution and adaptation in A. bruennichi, as well as on several interesting topics in Arachnids, such as the genomic architecture of traits, whole genome duplication and the genomic mechanisms behind silk and venom evolution.

genomics↗

Differential oxidative costs of locomotory and genital damage in an orb-weaving spider

In animals that regularly experience tissue loss, physiological responses may have evolved to overcome the related costs. Changes in oxidative status may reflect such self-maintenance mechanisms. Here, we investigated how markers of oxidative status varied in female orb-weaving spiders (Larinia jeskovi) by mimicking two distinct types of tissue loss they may naturally encounter: damage to their locomotory system and damage to their external genital structure, as inflicted by males to females during copulation (external female genital mutilation). Damage to the locomotory system resulted in a significant shift in the oxidative status reflecting investment into self-maintenance. In contrast, the loss of the genital structure did not result in quantitative changes of oxidative markers. The lack of response to genital mutilation suggests that genital mutilation is physiologically not costly for female spiders. The cost incurred to females rather arises from genital mutilation preventing the females from remating with another male.

evolutionary biology↗

Tissue- and population-level microbiome analysis of the wasp spider Argiope bruennichi identifies a novel dominant bacterial symbiont

Many ecological and evolutionary processes in animals depend upon microbial symbioses. In spiders, the role of the microbiome in these processes remains mostly unknown. We compared the microbiome between populations, individuals, and tissue types of a range-expanding spider, using 16S rRNA gene sequencing. Our study is one of the first to go beyond targeting known endosymbionts in spiders, and characterizes the total microbiome across different body compartments (leg, prosoma, hemolymph, book lungs, ovaries, silk glands, midgut, and fecal pellets). Overall, the microbiome differs significantly between populations and individuals, but not between tissue types. The microbiome of the wasp spider Argiope bruennichi features a novel dominant bacterial symbiont, which is abundant in every tissue type in spiders from geographically distinct populations, and present in offspring. The novel symbiont is affiliated with the Tenericutes, but has low sequence identity (<85%) to all previously named taxa, suggesting that the novel symbiont represents a new bacterial clade. Its presence in offspring implies that it is vertically transmitted. Our results shed light on the processes which shape microbiome differentiation in this species, and raise several questions about the implications of the novel dominant bacterial symbiont on the biology and evolution of its host.

microbiology↗

Visual pathways of the secondary eyes in the brain of a jumping spider

Some animals have evolved task differentiation among their eyes. A particular example is spiders, where most species have eight eyes, of which two (the principal eyes) are used for object discrimination, whereas the other three pairs (secondary eyes) detect movement. In the spider species Cupiennius salei these two eye types correspond to two visual pathways in the brain. Each eye is associated with its own first and second order visual neuropil. The second order neuropils of the principal eyes are connected to the arcuate body, whereas the second order neuropils of the secondary eyes are linked to the mushroom body. However, eye size and visual fields are considerably different in jumping spiders. We explored the principal- and secondary eye visual pathways of the jumping spider Marpissa muscosa. We found that the connectivity of the principal eye pathway is the same as in C. salei, while there are differences in the secondary eye pathways. In M. muscosa, all secondary eyes are connected to their own first order visual neuropils. The first order visual neuropils of the anterior lateral and posterior lateral eyes are further connected with two second order visual neuropils, whereas the posterior median eyes lack second order visual neuropils and their axons project only to the arcuate body. This suggests that the posterior median eyes probably do not serve movement detection in M. muscosa. Furthermore, the second order visual neuropil (L2) in Marpissa muscosa potentially integrates information from the secondary eyes and might thus enable faster movement decisions.

neuroscience↗