Search

Capitellid polychaetes are ubiquitous throughout the world’s oceans and are often encountered in high abundance. We used an extensive dataset of species abundance and distribution records of the Capitella capitata complex, C. aciculata, C. jonesi, Heteromastus filiformis, Mediomastus ambiseta, and M. californiensis from Tampa Bay, Florida, USA, as a model system of closely related species filling a similar ecological niche. We sought to (1) characterize the spatial distribution of each species, (2) determine if a single species abundance modeling strategy could be applied to them all, and (3) assess environmental drivers of species distribution and abundance. We found that all species had a zero-inflated abundance distribution and there was spatial autocorrelation by bay regions. Lorenz curves were an effective tool to assess spatial patterns of species abundance across large areas. Bay segment, depth, and dissolved oxygen were the most important environmental drivers. Modeling was accomplished by comparing 6 different approaches: 4 generalized additive models (GAMs: Poisson, negative binomial, Tweedie, and zero-inflated Poisson distributions), hurdle models, and boosted regression trees. There was no single model with top performance for every species. However, GAM-Tweedie and hurdle models performed well overall and may be useful for studies of other benthic marine invertebrates.

Due to cholesteatoma's slowly progressive and destructive growth there is a risk of intracranial and potentially life-threatening complications. That's why every cholesteatoma is a basically absolute indication for surgery. Only asymptomatic and small retractions, so-called prae-cholesteatomas, may be under observation. While the first part of this article focused on the basics of pathogenesis and diagnostics, this one provides an overview of current surgical strategies, both proven and new ones.

Scholars have argued that the exploitation–exploration interaction provides a source of competitive advantage beyond that provided by each individually. However, we know little about the mutual effects of exploitation and exploration on either incremental or radical innovation performance. To address this gap, we examine data from 171 manufacturing firms. We find incremental innovation performance is highest when exploitation interacts with an intermediary level of exploration. Radical innovation performance, however, is solely driven by exploration. A coupling with exploitation is not effective. We contribute to the extant literature, first, by disentangling the interaction effects of exploitation and exploration on radical and incremental innovation performance, respectively. Second, we extend extant literature that agrees that maintaining an appropriate balance of exploitation and exploration is critical for innovation performance and that has conceptualized this balance as symmetrical presence and magnitude of exploitation and exploration. In particular, we provide evidence in support of an asymmetric relationship.

Mammalian transglutaminases (TGs) catalyze calcium-dependent irreversible posttranslational modifications of proteins and their enzymatic activities contribute to the pathogenesis of several human neurodegenerative diseases. Although different transglutaminases are found in many different tissues, the TG6 isoform is mostly expressed in the CNS. The present study was embarked on/undertaken to investigate expression, distribution and activity of transglutaminases in Huntington disease transgenic rodent models, with a focus on analyzing the involvement of TG6 in the age- and genotype-specific pathological features relating to disease progression in HD transgenic mice and a tgHD transgenic rat model using biochemical, histological and functional assays. Our results demonstrate the physical interaction between TG6 and (mutant) huntingtin by co-immunoprecipitation analysis and the contribution of its enzymatic activity for the total aggregate load in SH-SY5Y cells. In addition, we identify that TG6 expression and activity are especially abundant in the olfactory tubercle and piriform cortex, the regions displaying the highest amount of mHTT aggregates in transgenic rodent models of HD. Furthermore, mHTT aggregates were colocalized within TG6-positive cells. These findings point towards a role of TG6 in disease pathogenesis via mHTT aggregate formation.

Das Cholesteatom als chronische Entzündung des Mittelohrs führt zu einer fortschreitenden knöchernen Destruktion des Felsenbeins. Leitsymptome sind fötide Otorrhö, Schwerhörigkeit und Schwindel. Unbehandelt kann das Cholesteatom durch intrakranielle Komplikationen letal verlaufen. Es folgt eine Darstellung des aktuellen und allgemein anerkannten Kenntnisstandes zur Genese, Klinik und präoperativen Diagnostik. Ausführungen zur operativen Therapie folgen in einem 2. Teil.

Early development of the polychaetesCapitellasp. TF from Tampa, Florida andCapitellasp. TV from Tamiahua Lagoon, Veracruz was studied under laboratory conditions. Our observations indicate that hermaphrodites occur inCapitellasp. TF, but not inCapitellasp. TV. Length and volume of larvae and early juveniles were measured daily. Both species appear to have lecithotrophic development. Sizes and duration of the developmental stages varied widely, as in most known species ofCapitella. Characteristic features ofCapitellasp. TF include very small hermaphrodites with a distinct dorsal pigmentation pattern and characteristically shaped brood tubes with a centrally thickened region. Embryos forced to abandon the brood did not survive more than 3 days, and handling the brood produced alterations in timing. Ciliated metatrochophores fromCapitellasp. TV survived inside the brood without the female for at least 14 days and some larvae hatched and died during settling. Some of these larvae were abnormal, with two rounded protuberances in the two ends. Mortality was high. Fungi and protozoans appeared in the dishes and probably partially induced the production of thicker mucus in the brood tubes, delay in metamorphosis, juvenile mortality, worm length and failure in coupling. Size and duration of the developmental stages were distinctly different from the other putative lecithotrophic species of the complex. These differences and other characteristics of each species discard the possibility that they belong to a previously described species. Our results are applicable to future ecological, morphological and molecular studies of each species, habitat and phylogenetics.

To date, most studies on the relationship between chemosensory performance and quality of life have focused on orthonasal measures of olfactory function. In the current investigation, we examined the predictive value of orthonasal and flavor identification indices of olfactory function on a wide spectrum of health and sociopsychological factors, including quality of life, life satisfaction, overall health, and depressive symptoms. Participants were 178 ENT patients (Mage = 58 ± 1), representing various causes of olfactory loss: idiopathic smell loss (n = 51; Mage = 63 ± 2), sinunasal disease (n = 27; Mage = 56 ± 3), head trauma (n = 33; Mage = 51 ± 2), and infections of the upper respiratory tract (n = 67; Mage = 59 ± 2). They completed self-report questionnaires and underwent olfactory testing using Sniffin’ Sticks (orthonasal olfactory testing) and “Taste Powder” (intraorally applied flavors for retronasal olfactory testing, additionally inducing taste sensation). Data were analyzed with hierarchical regression models wherein the first step included subjects’ sex, age, and orthonasal olfaction score. In the second step, we included the “Taste Powder” score. Tested models revealed that the first step was not significantly predicting variables of interest; however, there was an improvement of the model’s predictive value when the “Taste Powder” score was added. Results of this study suggest that flavor identification significantly improves predictions of health and sociopsychological functioning of ENT patients with various etiologies.

α-Synuclein (aSyn) is a protein implicated in physiological functions such as neurotransmitter release at the synapse and the regulation of gene expression in the nucleus. In addition, pathological aSyn assemblies are characteristic for a class of protein aggregation disorders referred to as synucleinopathies, where aSyn aggregates appear as Lewy bodies and Lewy neurites or as glial cytoplasmic inclusions. We recently discovered a novel post-translational pyroglutamate (pGlu) modification at Gln79 of N-truncated aSyn that promotes oligomer formation and neurotoxicity in human synucleinopathies. A priori, the appearance of pGlu79-aSyn in vivo involves a two-step process of free N-terminal Gln79 residue generation and subsequent cyclization of Gln79 into pGlu79. Prime candidate enzymes for these processes are matrix metalloproteinase-3 (MMP-3) and glutaminyl cyclase (QC). Here, we analyzed the expression of aSyn, MMP-3, QC and pGlu79-aSyn in brains of two transgenic mouse models for synucleinopathies (BAC-SNCA and ASO) by triple immunofluorescent labellings and confocal laser scanning microscopy. We report a co-localization of these proteins in brain structures typically affected by aSyn pathology, namely hippocampus in BAC-SNCA mice and substantia nigra in ASO mice. In addition, Western blot analyses revealed a high abundance of QC, MMP-3 and transgenic human aSyn in brain stem and thalamus but lower levels in cortex/hippocampus, whereas endogenous mouse aSyn was found to be most abundant in cortex/hippocampus, followed by thalamus and brain stem. During aging of ASO mice, we observed no differences between controls and transgenic mice in MMP-3 levels but higher QC content in thalamus of 6-month-old transgenic mice. Transgenic human aSyn abundance transiently increased and then showed decrease in oldest ASO mice analyzed. Immunohistochemistry revealed a successive increase in intraneuronal and extracellular formation of pGlu79-aSyn in substantia nigra during aging of ASO mice. Together, our data are supportive for a role of MMP-3 and QC in the generation of pGlu79-aSyn in brains affected by aSyn pathology.

We implemented a new video project in a marine invertebrate zoology undergraduate class The project required students to produce 3–5 min videos about a particular invertebrate or any aspect of invertebrate biology they were interested in The development of this assignment was prompted by the limitations for lab activities due to COVID-19 and three short-term campus closures in response to threats of inclement weather This assignment can be completed individually on a flexible schedule, without physical access to campus, and culminates in an Invertebrate Film Festival during the last lab period The project was assigned at the start of the term with only minimal instructions to promote creativity Students completed the project over the course of the 14-week semester, with several checkpoints, most notably a peer review of the movie script 2 weeks prior to the due date To support the video production, students were encouraged to attend workshops and schedule individual tutoring sessions offered by the Studio in the campus's Center for Academic Learning Support Surveys at the beginning and the end of the semester revealed that the perception of the video project was overall positive, although some students were apprehensive in the beginning Video topics, techniques, and software used by students varied widely, but overall the video quality exceeded our expectations Many students took pride in their videos and agreed to make them available as supplementary material for this article If we repeat this assignment in future semesters, we will streamline the peer review process and possibly offer short video tutorials for video-editing software © 2021 American Microscopical Society

In Australia, the deep-water (bathyal and abyssal) benthic invertebrate fauna is poorly known in comparison with that of shallow (subtidal and shelf) habitats. Benthic fauna from the deep eastern Australian margin was sampled systematically for the first time during 2017 RV ‘Investigator’ voyage ‘Sampling the Abyss’. Box core, Brenke sledge, and beam trawl samples were collected at one-degree intervals from Tasmania, 42°S, to southern Queensland, 24°S, from 900 to 4800 m depth. Annelids collected were identified by taxonomic experts on individual families around the world. A complete list of all identified species is presented, accompanied with brief morphological diagnoses, taxonomic remarks, and colour images. A total of more than 6000 annelid specimens consisting of 50 families (47 Polychaeta, one Echiura, two Sipuncula) and 214 species were recovered. Twenty-seven species were given valid names, 45 were assigned the qualifier cf., 87 the qualifier sp., and 55 species were considered new to science. Geographical ranges of 16 morphospecies extended along the eastern Australian margin to the Great Australian Bight, South Australia; however, these ranges need to be confirmed with genetic data. This work providing critical baseline biodiversity data on an important group of benthic invertebrates from a virtually unknown region of the world’s ocean will act as a springboard for future taxonomic and biogeographic studies in the area.

Bioluminescence is widespread throughout the phylum Annelida and occurs in terrestrial and marine lineages. Among marine taxa, bioluminescence has been documented in eight families and anecdotally reported in six additional families. Although new bioluminescent systems have been recently described in annelids, there are still many other families whose light emission mechanisms have not been sufficiently studied. Some of these include luminescent species belonging to the Polynoidae family, also known as scale worms, whose iterations of dorsal elytra (scales) have the ability to emit intense light when stimulated. Depending on the degree of stimulation, some polynoids can autotomize these luminous elytra and posterior segments, which could potentially give them an advantage in evading attacks by predators. It is believed that Polynoidae bioluminescence is associated with a membrane enzyme known as “polynoidin,” which was isolated during the early 1980s fromMalmgrenia lunulata. However, the characterization and properties of this enzyme, as well as the chemical nature of its substrate or additional potential cofactors, have never been fully described and remain largely unknown. As such, this paper seeks to revisit previous research involving bioluminescence studies in Polynoidae, as well as the morphological, phylogenetic and ecological aspects related to this emission of light.

During a search for bioluminescent marine annelids around the island of Carrie Bow Cay, Belize, we discovered bioluminescence in the sipunculan worm Nephasoma pellucidum. The identification of N. pellucidum was verified by DNA barcoding of ∼650 bp of the mitochondrial cytochrome c oxidase I gene, using sequences of the same species from previous studies as references. Our study constitutes the first record of a bioluminescent sipunculan species. Green luminescence was detected in four of the five individuals of N. pellucidum collected from coral rubble from a shallow reef flat and one deeper (14 m) site. To test for bioluminescent activity, all collected annelids (including sipunculans) were sorted into morphotypes and identified to the lowest taxonomic level possible. After several hours of dark adaptation, they were mechanically stimulated, and luminescent reactions were noted and recorded by photography and/or video whenever possible. Of a total of nine examined sipunculan species, N. pellucidum was the only one that showed bioluminescent activity. The underlying biochemical processes for the bioluminescence are so far unknown, but transcriptome data indicate the presence of proteins with similarities to Renilla-type luciferases. We did not find similarities to any known photoproteins. Our findings broaden the known diversity of bioluminescent annelid taxa and support the notion that bioluminescence arose multiple times in annelids. The bioluminescent properties of N. pellucidum add a new reason to pursue this species as a model species, as has been previously proposed.

Climate models predict an increase in extent, frequency, and duration of marine hypoxia events in the twenty first century. A better understanding of organismal responses to hypoxia in individual species is a crucial step for predicting ecosystem responses. We experimentally subjected a common invertebrate, the bearded fireworm (Hermodice carunculata) to two levels of chronic hypoxia and, in a separate experiment, to intermittent hypoxia. We found components of the conserved hypoxia-inducible factor (HIF) pathway and show a modulated response to hypoxia depending on the severity of hypoxic stress: under mild hypoxia, only the HIF-1α subunit is upregulated, while expression of the other subunit, aryl hydrocarbon nuclear translator, only increases significantly at more severe hypoxia levels. The chronic trials revealed down-regulation of genes related to cell adhesion, transport, development and heme-binding, and up-regulation of genes related to glycolysis, oxygen binding, cell differentiation, digestive and reproductive function. The intermittent hypoxia trials revealed an upregulation of heme transporter activity during hypoxia, and our time series analysis characterized nine clusters of genes with similar expression patterns. Our findings suggest that H. carunculata is likely to tolerate, and be resilient to, predicted future hypoxia conditions.

Hypoxia is a widespread and increasing phenomenon in marine environments, including coral reefs. The bearded fireworm (Hermodice carunculata) is a large corallivorous amphinomid polychaete, with a high tolerance of environmental stress, including temperature, salinity, and dissolved oxygen (DO). Currently, little is known about the response of H. carunculata to chronic (≥ 18 h) hypoxia, although this knowledge is crucial to understand its impact on coral reef health under hypoxia scenarios. We tested the hypothesis that the number of branchial filaments (previously used as a diagnostic character for species identification) increases in response to chronic hypoxia. We subjected wild-caught fireworms to two levels of reduced DO (Mid: 4.5 ± 0.25 mg O2 L−1 and Low: 2.5 ± 0.25 mg O2 L−1) to explore their morphological and physiological responses to seven days of chronic hypoxia. Hypoxia exposure resulted in a higher number of branchial filaments (low = 57.2 ± 5.3, mid = 57.4 ± 6.1, and normal = 47.4 ± 11.2) after seven days. Fireworms exposed to hypoxia further reduced their rate of regeneration, but returned to normal regenerative rates after fifteen weeks under normoxic conditions. There was no difference in regeneration rates between low and mid DO groups. Our results demonstrate the importance of considering multiple physiological and morphological endpoints as well as phenotypic plasticity in species delimitations. Indeed, the results suggest that morphological variation can be indicative of environmental conditions.

Due to cholesteatoma's slowly progressive and destructive growth there is a risk of intracranial and potentially life-threatening complications. That's why every cholesteatoma is a basically absolute indication for surgery. Only asymptomatic and small retractions, so-called prae-cholesteatomas, may be under observation. While the first part of this article focused on the basics of pathogenesis and diagnostics, this one provides an overview of current surgical strategies, both proven and new ones.

The northern Gulf of Mexico has been an important source for crude oil and natural gas extraction since the 1930s. Thousands of fixed platforms and associated equipment have been installed on the Gulf of Mexico continental shelf, leading to a pervasive ‘ocean sprawl’. After decommissioning, hundreds of these structures have been converted to artificial reefs under the federal ‘Rigs-to-Reefs’ program, in addition to artificial reefs specifically designed to enhance fisheries and/or benefit the recreational diving industry. Apart from a few natural banks, which reach to approximately 55 ft below the surface, artificial reefs provide the only shallow-water hard substrate for benthic organisms in the deeper waters of the northern Gulf of Mexico. This vast expansion in available habitat has almost exclusively occurred over a relatively short span of time (~ 50 years). The ecological interactions of artificial and natural reefs in the northern Gulf of Mexico are complex. Artificial reefs in general, and oil and gas structures in particular, have often been invoked as stepping stones for non-native and invasive species (e.g. Tubastrea cup corals, lionfish). The pilings are covered with fouling communities which remain largely unstudied. While the risks of these fouling organisms for invading natural reefs are being broadly discussed, other impacts on the ecological and economic health of the Gulf of Mexico, such as the potential to facilitate jellyfish blooms or increase the incidence of ciguatera fish poisoning, have received less attention. Artificial reefs also provide ecosystem services, particularly as habitat for economically important fish species like red snapper. Here we revisit the potential role of artificial reefs as ‘stepping stones’ for species invasions and for fisheries enhancement. Beyond concerns about ecological effects, some of these topics also raise public health concerns. We point out gaps in current knowledge and propose future research directions.

Oxygen is necessary for all marine animals to support metabolic functions. When chronic low dissolved oxygen (DO) conditions occur, organisms must adjust to overcome this stressor’s effect on metabolic rates. The bearded fireworm, Hermodice carunculata, is a widespread species frequently exposed to hypoxic conditions in areas within its broad distribution which may impact metabolism, wound healing, and regeneration. To study the impact of hypoxia on their metabolic rates, we exposed fireworms to two levels of lower than normal DO conditions (low 2.5 ± 0.25 mg O2 L−1 and mid 4.5 ± 0.25 mg O2 L−1) for 7 days by pumping nitrogen into their holding tanks. During a chronic hypoxia trial, we quantified oxygen consumption in each experimental group and subsequently determined post-hypoxia oxygen consumption of individuals from the lowest oxygen level. During the hypoxic exposure, the oxygen uptake rates declined in low and mid DO conditions, while remaining relatively constant for the normoxic (7.0 ± 0.25 mg O2 L−1) control. We then compared the oxygen consumption rates from the lowest DO condition to fireworms likely never exposed to hypoxia and fireworms from a location likely to be exposed to hypoxia. We found higher oxygen consumption rates in the experimentally hypoxia-exposed worms. These results suggest prolonged negative impacts of hypoxic exposure, leading to a lasting elevation of metabolic rates of these marine invertebrates. The increase in metabolic rates may lead to increased predation on their prey of choice, economically and commercially important coral, causing increased degradation of already threatened coral reef ecosystems.

The bearded fireworm,Hermodice carunculata,is a common species in the marine annelid taxon Amphinomidae. It has a widespread distribution throughout the Atlantic, Gulf of Mexico, the Caribbean, Mediterranean and Red Seas. We review its environmental tolerances, defence mechanisms and feeding habits to evaluate its potential to survive in changing ocean conditions, to increasingly emerge as a nuisance species and to invade new geographic areas.Hermodice carunculatatolerates a wide range of environmental conditions, including temperature, salinity, oxygen saturation and various types of pollution. It has few natural predators because it is protected by its sharp chaetae and probably by toxins.Hermodice carunculatais best known for consuming live cnidarians, and has been implicated in transmitting coral pathogens, but it also feeds non-selectively on detritus. In the short term, we predict thatH. carunculatawill be able to withstand many future ecological challenges and possibly contribute to coral reef decline. In the long term, ocean acidification may negatively impact its defence mechanisms and survival. Its invasive potential may be significant. We highlight the gaps in our knowledge about the reproduction and development of this species, the nature and origin of its toxins and role of microbes in their feeding behaviour and defensive strategies.

Cholesteatoma is a chronic inflammation of the middle ear, which leads to a progressive bony destruction of the petrous bone. Main symptoms are fetid otorrhea, hearing loss and dizziness. Left untreated, cholesteatoma may be fatal due to intracranial complications. The following overview is intended to illustrate the current and generally recognized knowledge of genesesi, clinical symptoms und preoperative diagnostical procedure. Surgical therapie will be focussed in a second part.Das Cholesteatom als chronische Entzündung des Mittelohrs führt zu einer fortschreitenden knöchernen Destruktion des Felsenbeins. Leitsymptome sind fötide Otorrhö, Schwerhörigkeit und Schwindel. Unbehandelt kann das Cholesteatom durch intrakranielle Komplikationen letal verlaufen. Es folgt eine Darstellung des aktuellen und allgemein anerkannten Kenntnisstandes zur Genese, Klinik und präoperativen Diagnostik. Ausführungen zur operativen Therapie folgen in einem 2. Teil.

Viral infections are associated with increased incidence of severe sepsis. Particularly during the early stages, type I interferons (IFNs) are known mediators of detrimental effects. However, the functional role of early interferon &beta, (IFN&beta, ) and its cellular source during sepsis in the context of preexisting viral infections has not been defined. Using the colon ascendens stent peritonitis (CASP) model, we demonstrate that IFN&beta, &minus, /&minus, and type I IFN receptor (IFNAR1)&minus, mice were less susceptible to sepsis after pre-stimulation with the viral mimetic poly(I:C). Wild type (WT) mice treated with poly(I:C) exhibited altered expression patterns of TNF and IL-12p40 during CASP which were dependent on IFN&beta, or IFNAR1, suggesting a mechanism for the increased sepsis susceptibility of WT mice. Using a double cytokine reporter mouse model, we present novel data on the simultaneous expression of IFN&beta, and IL-12p40 on a single cell level during polymicrobial sepsis in vivo. Conventional dendritic cells (cDCs) were identified as primary source of IFN&beta, and the protective cytokine IL-12p40 after CASP surgery irrespective of poly(I:C) pre-stimulation. These data demonstrated that if polymicrobial sepsis is preceded by a viral infection, IFN&beta, and IL-12p40 are expressed by polyfunctional cDCs suggesting that these cells can play both detrimental and beneficial roles during sepsis development.

Capitella capitata was traditionally used as a biological indicator species due to its ubiquitous distribution and high densities in disturbed and polluted marine and estuarine sediments. Based on allozyme and developmental studies, it is now clear that C. capitata is a species complex consisting of multiple distinct lineages worldwide, including the recently described C. teleta, a model species for spiralian development. The coast of the northern Gulf of Mexico, with its numerous bays and estuaries and frequently occurring natural and anthropogenic disturbances, provides an appropriate region for such studies. We sequenced a fragment of the mitochondrial cytochrome c oxidase subunit I gene for individuals of C. cf. capitata and C. cf. aciculata (distinguished by acicular spines on the first two chaetigers) collected from Texas and Florida coasts and analyzed them in conjunction with data available in GenBank. Our results indicate the presence of a Gulf of Mexico clade that is distinct from populations in Canada and the Indo-Pacific. Populations in the northern Gulf of Mexico are structured geographically, with support for Texas and Florida clades, and there do not seem to be clear boundaries between C. cf. capitata and C. cf. aciculata. This is corroborated by the fact that multiple specimens were morphologically intermediate between the two species. In future studies, we aim to clarify whether the intermediate morphologies represent ontogenetic stages, neutral morphological variation, phenotypic plasticity, or sexual dimorphism in a single species or whether several lineages with incomplete reproductive barriers are present.

Phascolosoma agassizii, a commonly reported species of sipunculan worm, occurs at various depths throughout the north Pacific. However, previous studies have shown that this nominal species is actually comprised of two genetically divergent lineages. Phascolosoma agassizii is isolated to the eastern Pacific, whereas a second species, here referred to Phascolosoma sp., is located in the western Pacific and represents a unique, non-sister taxon to P. agassizii. Both species exhibit the same developmental mode with a long-lived, planktotrophic, pelagosphera larval stage, which may facilitate long-distance dispersal, although developmental timing differs. Using an inter-simple sequence repeat polymerase chain reaction (ISSR-PCR) genetic fingerprinting approach, this study examines non-coding polymorphic regions of the nuclear genomes of P. agassizii from four eastern Pacific populations and of Phascolosoma sp. from six western Pacific locations. Small-scale spatial genetic variation was analysed separ...

A series of seven oxyprenylated phenylpropanoids and naphthoquinones were tested regarding their ability to activate transient receptor potential ankyrin subtype 1 channel (TRPA1). Three of the assayed compounds, namely, boropinal (3), juglone (5), and plumbagin (7), acted as strong modulators of TRPA1 channels with EC50 values of 9.8, 1.7, and 0.5 mu M, respectively, as assessed by Ca2+ assays. Moreover, the compounds elicited TRPA1 currents in electrophysio-logical whole cell recordings. We additionally provide evidence that plumbagin activated TRPA1-positive neurons isolated from mouse dorsal root ganglion neurons but did not affect sensory neurons from TRPAl-deficient mice. The high potencies of plumbagin and juglone to activate TRPA1 channels may explain the molecular basis of the mucosal irritant properties of these compounds as well as of related naphthoquinones and phytopreparations, as widely reported in the literature.

Background Guo and Huang recently showed that Huntingtin protein (Htt) forms a complex with Hap40 protein. This interaction may affect structure and function of Htt. In HD patient derived fibroblasts an Hap40 upregulation was shown, leading to alterations in endosome motility underpinning a role for Hap40 in HD pathology. Likewise, a second protein of interest is FKBP51, a co-chaperone of the steroid receptor complex and regulatory protein of the HPA–axis. As HD patients often display signs of depression and anxiety including a pre-symptomatic increase in HPA–axis activity, alterations in FKBP51 expression may explain the observed symptoms. Aims Despite their different functions, the potential impact of Hap40 and FKBP51 on development and progression of HD appears to be of equal importance. Here we report on the expression and local distribution in brains of transgenic mouse and rat models of HD. Methods/techniques Hap40 and FKBP51 are studied in the congenic F344 rat model of HD and further on in BACHD and zQ175DN ki x C57BL/6N mice. The histological pattern and a potential co-localization of both proteins with Htt will be investigated with immunohistological methods. In addition, the expression on protein and mRNA level will be analysed using Western Blot and RTqPCR. Results For the first time, comprehensive histological analysis of Hap40 and FKBP51 in HD rat brains will be presented. So far, we established corresponding antibodies to both proteins for immunohistological investigations. Specific primers for FKBP51 and Hap40 were generated and are currently tested for RTqPCR. In addition, Western Blots will be performed on selected brain regions. Results will be presented in further detail on the EHDN Meeting. Conclusion The expression pattern of Htt-stabilizing protein Hap40 and of stress-regulatory protein FKBP51 is investigated in the F344 HD model to detect possible alterations that contribute to disease pathology.

Background Mammalian transglutaminases (TGs) catalyze calcium-dependent irreversible post-translational modifications of proteins. In the nervous system, at least four different transglutaminase isoforms are found with TG6 representing the neuronal isoform. Their enzymatic activities contribute to the pathogenesis of several human neurodegenerative diseases. Aims The present study was outlined to investigate expression, distribution and activity of transglutaminases, especially TG6, in Huntington´s disease rodent models. Methods/techniques To analyze the involvement of TG6 in the age- and genotype-specific pathological progressions in rodent HD animal models, protein, histological and functional assays were used. Results/outcome We demonstrate the physical interaction between TG6 and (mutant) huntingtin by co-immunoprecipitation analysis. In addition, we describe that TG6 expression and activity were especially abundant in the olfactory tubercle and piriform cortex, the regions displaying the highest amount of mHTT aggregates in HD transgenic rats. Furthermore, mHTT aggregates were found within TG6-positive cells. Conclusions Our data strongly suggest a prominent role for TG6 in the post-translational modification of (m)HTT thus pointing away from TG2, so far being investigated most frequently. Our results suggest that TG6 activity on mHTT may be causative for the modification of mHTT fragments that would result to be more prone to aggregation. Furthermore, the aggregation process seems to depend more on the regional distribution and physical proximity of transglutaminases and mHTT, rather than on differences in total protein amounts. Further studies analyzing the impact of TG6 knock-out/inactivation on mHTT aggregation and disease progression will finally elucidate the pathological relevance of our findings.