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Genes of the major histocompatibility complex (MHC) are indispensable for pathogen defence in vertebrates. With wild-caught three-spined sticklebacks ( Gasterosteus aculeatus) we conducted the first study to relate individual reproductive parameters to both MHC class I and II diversities. An optimal MHC class II B diversity was found for male nest quality. However, male breeding colouration was most intense at a maximal MHC class I diversity. One MHC class I allele was associated with male redness. Similarly, one MHC class II B allele was associated with continuous rather than early female reproduction, possibly extending the reproductive period. Both alleles occurred more frequently with increasing individual allele diversity. We suggest that if an allele is currently not part of the optimum, it had not been propagated by choosy females. The parasite against which this allele provides resistance is therefore unlikely to have been predominant the previous year – a step to negative frequency-dependent selection. [ABSTRACT FROM AUTHOR]

Gütermann AG is one of the most important manufacturers of sewing thread for industrial and home use worldwide. From summer 2002 to spring 2003, in-plant energy and material flow management was implemented at the company with support provided by the Baden-Württemberg State Institute for Environmental Protection. This article presents the project and outlines the present state of implementation and planned activities for the future. The two primary goals of the project are also presented in this article.

Neuroinflammation and blood-cerebrospinal fluid barrier (BCB) disruption could be key elements in schizophrenia-spectrum disorderś(SSDs) etiology and symptom modulation. We present the largest two-stage individual patient data (IPD) meta-analysis, investigating the association of BCB disruption and cerebrospinal fluid (CSF) alterations with symptom severity in first-episode psychosis (FEP) and recent onset psychotic disorder (ROP) individuals, with a focus on sex-related differences. Data was collected from PubMed and EMBASE databases. FEP, ROP and high-risk syndromes for psychosis IPD were included if routine basic CSF-diagnostics were reported. Risk of bias of the included studies was evaluated. Random-effects meta-analyses and mixed-effects linear regression models were employed to assess the impact of BCB alterations on symptom severity. Published (6 studies) and unpublished IPD from n = 531 individuals was included in the analyses. CSF was altered in 38.8 % of individuals. No significant differences in symptom severity were found between individuals with and without CSF alterations (SMD = -0.17, 95 %CI -0.55-0.22, p = 0.341). However, males with elevated CSF/serum albumin ratios or any CSF alteration had significantly higher positive symptom scores than those without alterations (SMD = 0.34, 95 %CI 0.05-0.64, p = 0.037 and SMD = 0.29, 95 %CI 0.17-0.41p = 0.005, respectively). Mixed-effects and simple regression models showed no association (p > 0.1) between CSF parameters and symptomatic outcomes. No interaction between sex and CSF parameters was found (p > 0.1). BCB disruption appears highly prevalent in early psychosis and could be involved in positive symptomś severity in males, indicating potential difficult-to-treat states. This work highlights the need for considering BCB breakdownand sex-related differences in SSDs clinical trials and treatment strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Treatment of severe mental illness (SMI) symptoms, especially negative symptoms and cognitive dysfunction in schizophrenia, remains a major unmet need. There is good evidence that SMIs have a strong genetic background and are characterized by multiple biological alterations, including disturbed brain circuits and connectivity, dysregulated neuronal excitation-inhibition, disturbed dopaminergic and glutamatergic pathways, and partially dysregulated inflammatory processes. The ways in which the dysregulated signaling pathways are interconnected remains largely unknown, in part because well-characterized clinical studies on comprehensive biomaterial are lacking. Furthermore, the development of drugs to treat SMIs such as schizophrenia is limited by the use of operationalized symptom-based clusters for diagnosis., Methods: In line with the Research Domain Criteria initiative, the Clinical Deep Phenotyping (CDP) study is using a multimodal approach to reveal the neurobiological underpinnings of clinically relevant schizophrenia subgroups by performing broad transdiagnostic clinical characterization with standardized neurocognitive assessments, multimodal neuroimaging, electrophysiological assessments, retinal investigations, and omics-based analyzes of blood and cerebrospinal fluid. Moreover, to bridge the translational gap in biological psychiatry the study includes in vitro investigations on human-induced pluripotent stem cells, which are available from a subset of participants., Results: Here, we report on the feasibility of this multimodal approach, which has been successfully initiated in the first participants in the CDP cohort; to date, the cohort comprises over 194 individuals with SMI and 187 age and gender matched healthy controls. In addition, we describe the applied research modalities and study objectives., Discussion: The identification of cross-diagnostic and diagnosis-specific biotype-informed subgroups of patients and the translational dissection of those subgroups may help to pave the way toward precision medicine with artificial intelligence-supported tailored interventions and treatment. This aim is particularly important in psychiatry, a field where innovation is urgently needed because specific symptom domains, such as negative symptoms and cognitive dysfunction, and treatment-resistant symptoms in general are still difficult to treat., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Krčmář, Jäger, Boudriot, Hanken, Gabriel, Melcher, Klimas, Dengl, Schmoelz, Pingen, Campana, Moussiopoulou, Yakimov, Ioannou, Wichert, DeJonge, Zill, Papazov, de Almeida, Galinski, Gabellini, Hasanaj, Mortazavi, Karali, Hisch, Kallweit, Meisinger, Löhrs, Neumeier, Behrens, Karch, Schworm, Kern, Priglinger, Malchow, Steiner, Hasan, Padberg, Pogarell, Falkai, Schmitt, Wagner, Keeser and Raabe.)

Background: Schizophrenia spectrum disorders (SSDs) are presumed to be associated with retinal thinning. However, evidence is lacking as to whether these retinal alterations reflect a disease-specific process or are rather a consequence of comorbid diseases or concomitant microvascular impairment., Methods: The study included 126 eyes of 65 patients with SSDs and 143 eyes of 72 healthy controls. We examined macula and optic disc measures by optical coherence tomography (OCT) and OCT angiography (OCT-A). Additive mixed models were used to assess the impact of SSDs on retinal thickness and perfusion and to explore the association of retinal and clinical disease-related parameters by controlling for several ocular and systemic covariates (age, sex, spherical equivalent, intraocular pressure, body mass index, diabetes, hypertension, smoking status, and OCT signal strength)., Results: OCT revealed significantly lower parafoveal macular, macular ganglion cell-inner plexiform layer (GCIPL), and macular retinal nerve fiber layer (RNFL) thickness and thinner mean and superior peripapillary RNFL in SSDs. In contrast, the applied OCT-A investigations, which included macular and peripapillary perfusion density, macular vessel density, and size of the foveal avascular zone, did not reveal any significant between-group differences. Finally, a longer duration of illness and higher chlorpromazine equivalent doses were associated with lower parafoveal macular and macular RNFL thickness., Conclusions: This study strengthens the evidence for disease-related retinal thinning in SSDs., (© 2022. The Author(s).)

Objective: Our aims were to investigate the motivation for therapy, the understanding and valuation of potential treatment toxicities in melanoma patients offered adjuvant therapies., Methods: Between September 2018 and September 2019 49 adjuvant patients with stage III and IV melanoma received a self-created, pre-treatment questionnaire. Furthermore, the patients were handed out the REPERES-G, EQ-5D-3L and EORTC QLQ C-30 questionnaires., Results: Eight patients (18.3 %) decided against adjuvant therapy (mean age 71.6 years). Four of these had stage IIIA melanoma. The majority of patients (73.4 %) decided for adjuvant treatment with PD1-inhibitors despite their potential high grade, persistent, irreversible or even fatal toxicities. About a third of patients with BRAF V600 mutated melanoma who decided for therapy chose targeted therapy (31.3 %). These patients were younger (mean age 49 years), still working and had families with children. The REPERES-G questionnaire showed that our patients were generally satisfied with medical care. The average scores in the EQ-5D-3L and EORTC QLQ C-30 questionnaires indicated good subjective general health., Conclusions: Despite the associated toxicities as well as the required time and effort for a one-year treatment the majority of patients decided for adjuvant treatments., (© 2020 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

The abrasion response of cross sectional areas of enamel was studied by sliding a rounded diamond conical nano-indenter tip across the surface. The nano-indenter tip (radius approximately 1,200 nm) was scanned over a specific squared area with a load of 400 microN. Two different environments were chosen: Hank's balanced salt solution (HBSS) and atmospheric laboratory condition. SEM (Scanning Electron Microscopy) and AFM (Atomic Force Microscopy) were used to characterize the final abraded areas. In addition, single scratches with linear incremented load were performed. The normal load and displacement data were utilized in a complementary manner to support the proposed deformation mechanisms. Greater orientation dependence for the case of the single scratches in relation to the abrasion tests was found. The latter results are discussed in terms of plastic deformation effects. The abrasion mechanisms were found to be the same for both wet and dry measurements and similar to that described in a previous study (Guidoni et al., Wear 266:60-68, 2009; Guidoni, Nano-scale mechanical and tribological properties of mineralized tissues. PhD. Montan University Leoben, Leoben, Austria, 2008). However, scratch deformation under fluid measurements shows greater recovery effects and abrasion resistance.

Active millimeter-wave images typically exhibit characteristic speckle noise, due to the coherence of artificial millimeter-wave sources. We study the Hadamard speckle contrast reduction (SCR) technique, which has been successfully used in laser projection systems, in the context of millimeter-wave imaging. We show the impact of Hadamard pattern order and size and of image and pattern resolution on speckle reduction efficiency. Practical limitations of Hadamard pattern implementations and their effect on speckle reduction efficiency are also discussed.

Inbreeding depression and its consequences for mate choice have been extensively studied in free-living animals. However, very little is known about its significance for parasites, although it is well recognized that the mating systems of parasites can have important implications for their epidemiology and evolution. In this article, we show that the cestode Schistocephalus solidus shows incestuous mate preference despite evidence for very strong inbreeding depression. When given the simultaneous choice between mating with a sibling and an unrelated partner, on average, the cestode preferred its sibling. To explain this surprising result, we present three hypotheses that suggest different benefits to fitness of incestuous mating, which could, alone or in concert, outweigh the cost of inbreeding depression.

The roots of Rubia tinctorum L. have a long tradition of being used in dyeing processes of textiles from centuries ago until the present time. The colouring principles belong to the class of hydroxyanthraquinones. Concern arose because several of these compounds were recognised as mutagenic in vitro and even carcinogenic in rodents. To assess the possible risk to humans caused by coloured textiles, mutagenicity was investigated with two madder root samples of different origin (Iran and Bhutan) along the entire dyeing process from root extracts to the dyed wool. The Salmonella/microsome test (Ames assay) with the strains TA98, TA100 and TA1537 was used. Significant mutagenic effects could be detected in madder root extracts and also in the final product, the dyed wool. Madder root from Iran showed considerably higher mutagenic responses than samples from Bhutan. Analytical investigations of the extracts by HPLC showed the presence of a spectrum of anthraquinones typical for madder root. Three mutagenic compounds, lucidine, rubiadine and purpuroxanthine, together with the non-mutagenic alizarine could be detected. The mutagenic response of the different samples was positively correlated with the concentration of the mutagenic anthraquinones, and with lucidine in particular. Based on these investigations a risk to dye-house workers and users of textiles dyed with R. tinctorum must be anticipated.

We studied experimental double infections of the cestode Schistocephalus solidus in its stickleback host. In particular, we were interested in how two important components of the cestode's transmission success-establishment and growth within the fish host-were affected by the relatedness of the two parasites in a double exposure and by the timing of the two exposures, that is, whether they occurred simultaneously or sequentially. We found that male sticklebacks more often became infected (singly or doubly) if the two cestodes in the exposures were related, whereas female sticklebacks were more easily infected (singly or doubly) when exposed to two unrelated cestodes. Irrespective of the fish's gender, successful infections more often contained both cestodes when they were related. In sequential exposures with related as well as unrelated cestodes, the cestode in the later exposure survived better and also grew larger than the cestode from the first exposure, despite being one week younger. Our results emphasize that within-host dynamics and factors acting at this level can play an important role in determining a parasite's transmission success.

Many animals, including humans, can visually judge the absolute size of objects regardless of changes in viewing distance and thus despite the resulting dramatic differences in the size of the actual retinal images. For animals that have to judge the size of aerial objects from underwater views, this can be a formidable problem; our calculations show that considerable and strongly viewpoint-dependent corrections are needed to compensate for the effects of light refraction. Archer fish face these optical difficulties because they have to shoot down aerial insects over a wide range of horizontal and vertical distances. We show here that these fish can learn to acquire size constancy with remarkable precision and are thus fully capable of taking complex viewpoint dependency into account. Moreover, we demonstrate that archer fish solve the problem not by interpolating within a set of stored views and distances but by learning the laws that connect apparent size with the fish's relative position to the target. This enables the fish to readily judge the absolute sizes of objects from completely novel views.

Textile dyes used within the European Union (EU) were examined for available published and unpublished mutagenicity data. Fifty-three dye products that had so far not been investigated for mutagenicity were tested in the bacterial reverse mutation assay with Salmonella typhimurium (Ames test) according to a modification of the OECD 471 guidelines (instead of five strains, only TA98 and/or TA100 were used with and without metabolic activation (S9-mix)). About 28% (15 out of 53) of the dye samples were positive in the Ames test. Fifteen samples showed positive results with TA98, two were positive in TA100. The mutagenicity of nine Ames-positive textile dye products was further investigated in the mouse lymphoma assay (MLA) (OECD 476). Sixty-seven percent (6 out of 9) induced genotoxic effects in the MLA. The induction rates (IR) were between 2.1 and 132 in the bacterial reverse mutation assay and between 2.1 and 15.2 in the MLA. The results confirm previous findings that dye products are marketed that are not sufficiently tested and that show mutagenic effects in in vitro tests.

Within an EU-funded research project, 281 textile dye products in use at nine textile finishing companies from eight European countries were assessed for potential mutagenic properties. Most of the dyes belonged to the so-called existing substances. Data sources considered were data published in the literature, unpublished industrial data provided by dye producing companies, and laboratory testing. Data on mutagenicity are virtually absent for many of the dyes. Unpublished test results performed on behalf of the dye manufacturing industry proved to be an important data source that is not accessible under usual circumstances. Four dye stuffs contained in seven dye products in use at the textile finishing companies were judged to be mutagenic, based on published data from the literature. Mutagenicity testing using Salmonella typhimurium, strains TA98 and TA100, revealed positive results for about 28% (15 out of 53) of the dye products investigated. Upon further testing with the mouse lymphoma assay (L5178Y/TK(+/-)) 67% (6 out of 9) of Ames-positive dyes proved to be mutagenic in this mammalian cell test. All data sources combined led to an overall assessment of 14 dye products out of 281 being mutagenic. For 16 there is a suspicion of mutagenicity due to positive responses in one test but 71 of the dye products are without any data on mutagenicity. This paper describes the data aggregation process, evaluation criteria and the overall assessment, and exemplifies controversial evaluations., (Copyright 2004 John Wiley & Sons, Ltd.)

The deformation behavior of certain biologic macromolecules is modeled by the "sticky chain," a freely jointed chain with weak bonds between subsequent joints. Straining the chain leads to thermally assisted breaking of the weak bonds, yielding a characteristic shape of the force-elongation curve, usually with a pronounced plateau, but sometimes displaying a pseudo-Hookean behavior over a wide range of deformations. The number of individual links is assumed to be large, so the stochastic time evolution of the individual events can be approximated by a differential equation. The cases of individual and collective bond breaking are treated and formulae given for various measurable quantities. A threshold strain rate is found, below which the deformation force no longer depends on the deformation velocity. The method is applied to experimental results for the deformation of single molecules like titin or DNA and the results agree with the parameters deduced from the same experiments by the original authors using Monte Carlo (MC) calculations. Despite its intrinsic continuous character, the model, therefore, is applicable even for the deformation of macromolecules with only a few discrete unfolding elements, yielding physical quantities from experimental results using simple formulae instead of a host of MC computations.

Both elastic modulus and fracture stress are known to increase with the amount of mineral deposited within collagen fibrils. Current mechanical models of mineralized fibrils, where mineral platelets are arranged in parallel arrays, reproduce the first effect but fail to predict an increase in fracture stress. Here, we propose a model with a staggered array of platelets that is in better agreement with results on molecular packing in collagen fibrils and that accounts for an increase of both elastic modulus and fracture stress with the amount of mineral in the fibril. Finally, we explore the dependence of the mechanical properties within the model, when the degree of mineralization and the thickness of the platelets as well as their distance varies.