Galactofuranose (Galf) containing molecules have been described at the cell surface of several eukaryotes and shown to contribute to the virulence of the parasite Leishmania major and the fungus Aspergillus fumigatus. It is anticipated that a number of the surface glycoconjugates such as N-glycans or glycolipids are galactofuranosylated in the Golgi apparatus. This raises the question of how the substrate for galactofuranosylation reactions, UDP-Galf, which is synthesized in the cytosol, translocates into the organelles of the secretory pathway. Here we report the first identification of a Golgi-localized nucleotide sugar transporter, named GlfB, with specificity for a UDP-Galf. In vitro transport assays established binding of UDP-Galf toGlfB and excluded transport of several other nucleotide sugars. Furthermore, the implication of glfB in the galactofuranosylation of A. fumigatus glycoconjugates and galactomannan was demonstrated by a targeted gene deletion approach. Our data reveal a direct connection between galactomannan and the organelles of the secretory pathway that strongly suggests that the cell wall-bound polysaccharide originates from its glycosylphosphatidylinositol-anchored form.

Background: Understanding the mechanisms of cell wall biogenesis is important for development of antifungal strategies. Results: Biosynthesis of the fungal polysaccharide galactomannan requires import of GDP-mannose into the Golgi apparatus. Conclusion: It differs from the biosynthesis of other fungal cell wall polysaccharides.Significance: This provides a new paradigm for cell wall polysaccharide biosynthesis.

Background and aims: Despite the high prevalence of perceived problems relating to symptoms of hypersexual disorder (HD), important aspects remain underinvestigated. This study examines symptoms of depression, symptoms of problematic cybersex, and coercive sexual behavior in a large online sample from a German-speaking population. Methods: In an online survey, N = 1,194 (n = 564 women) participated in this study and completed measures including self-report questionnaires to assess depressive symptoms (PHQ-9), HD (HBI-19), symptoms of problematic cybersex (s-IATsex), as well as questions characterizing participants sexually, including fantasies and actual sexual coercive behaviors. Results: Men reported increased levels of HD symptom severity, pornography consumption, masturbation, and partnered sexual activity. Moreover, 59% of men and 18% of women reported fantasies of sexual coercion, whereas 21% of men and 4% of women reported acts of sexual coercion. Moderated regression analyses showed that symptoms of depression as well as sexual coercive fantasies and behaviors were associated with levels of HD symptom severity. Problematic cybersex, total sexual outlet (TSO), pornography consumption, and number of sexual partners were also associated with HD symptom severity. Interaction effects indicated that, in women, the connection of TSO as well as pornography was more strongly associated with levels of HD symptom severity than in men. Conclusions: This survey indicated that levels of HD symptom severity are often associated with severe intraand interpersonal difficulties. Furthermore, the amount of sexual activity seems to be more strongly connected to levels of HD symptom severity in women than in men.

The mannosyltransferase Och1 is the key enzyme for synthesis of elaborated protein N-glycans in yeast. In filamentous fungi genes implicated in outer chain formation are present, but their function is unclear. In this study we have analyzed the Och1 protein of Aspergillus fumigatus. We provide first evidence that poly-mannosylated N-glycans exist in A. fumigatus and that their synthesis requires AfOch1 activity. This implies that AfOch1 plays a similar role as S. cerevisiae ScOch1 in the initiation of an N-glycan outer chain. A Δafoch1 mutant showed normal growth under standard and various stress conditions including elevated temperature, cell wall and oxidative stress. However, sporulation of this mutant was dramatically reduced in the presence of high calcium concentrations, suggesting that certain proteins engaged in sporulation require N-glycan outer chains to be fully functional. A characteristic feature of AfOch1 and Och1 homologues from other filamentous fungi is a signal peptide that clearly distinguishes them from their yeast counterparts. However, this difference does not appear to have consequences for its localization in the Golgi. Replacing the signal peptide of AfOch1 by a membrane anchor had no impact on its ability to complement the sporulation defect of the Δafoch1 strain. The mutant triggered a normal cytokine response in infected murine macrophages, arguing against a role of outer chains as relevant Aspergillus pathogen associated molecular patterns. Infection experiments provided no evidence for attenuation in virulence; in fact, according to our data the Δafoch1 mutant may even be slightly more virulent than the control strains.

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Problems arising from hypersexual behavior are often seen in clinical settings. We aimed to extend the knowledge about the clinical characteristics of individuals with hypersexual disorder (HD). A group of people who fulfilled the proposed diagnostic criteria for HD (men with HD, n = 50) was compared to a group of healthy controls (n = 40). We investigated differences in sociodemographic, neurodevelopmental, and family factors based on self-report questionnaires and clinical interviews. Men with HD reported elevated rates of sexual activity, paraphilias, consumption of child abusive images, and sexual coercive behavior compared to healthy controls. Moreover, rates of affective disorders, attachment difficulties, impulsivity, and dysfunctional emotion regulation strategies were higher in men with HD. Men with HD seem to have experienced various forms of adverse childhood experiences, but there were no further differences in sociodemographic, neurodevelopmental factors, and family factors. Regression analyses indicated that attachment-related avoidance and early onset of masturbation differentiated between men with HD and healthy controls. In conclusion, men with HD appear to have the same neurodevelopment, intelligence levels, sociodemographic background, and family factors compared to healthy controls, but they report different and adverse experiences in childhood, problematic sexual behavior, and psychological difficulties.

Glycosylphosphatidylinositol (GPI) attaches a variety of eukaryotic proteins to the outer leaflet of the plasma membrane. In fungi, these proteins may also be transferred to the cell wall, to which they are covalently linked via a remnant of the GPI-anchor. They play crucial physiological roles in cell-cell interactions, adhesion or cell wall biogenesis. The biosynthesis of GPI-anchors in the endoplasmic reticulum, their transfer to proteins, early remodelling and transport to the Golgi apparatus has been fairly well described. In contrast, almost nothing is known about the genes and enzymes involved in adding glycan side chains to GPI after protein attachment. In this study, we characterized an α1,3-mannosyltransferase involved in maturation of GPI-anchors from the pathogenic fungus Aspergillus fumigatus. This enzyme shows homology to Cryptococcus neoformans Cap59p, a putative glycosyltransferase involved in capsule formation and virulence, and was thus named Cap59-like protein A (ClpA). Targeted deletion of the clpA gene in A. fumigatus led to absence of α1,3-mannose from mature GPI-anchors. The enzyme was further located to the Golgi-like apparatus of A. fumigatus and was shown to be active in the yeast Saccharomyces cerevisiae.

Introduction Exploratory analysis of characteristics and reduction of risk factors for child sexual abuse (CSA) in a sample treated in the Prevention Projects Dunkelfeld Hannover and Regensburg. Aim To evaluate a treatment program aimed at reducing dynamic risk factors (DRF) for CSA. Methods Using a psychometric test battery based on self-report questionnaires, intergroup analysis between treatment group (TG, n = 35), treatment refusers (TR, n = 51), and drop-out group (DO, n = 14) was conducted with pretreatment data. Intragroup analysis compared data of TG from pre- and posttreatment. The test battery included sociodemographic and sociosexual data, as well as questionnaires measuring DRF. Main Outcome Measure This study investigated effects of treatment on pedophilic men who are at risk for offending and observed reductions in important risk factors for CSA. Results TG, TR (consisting of persons who were offered but refused therapy), and DO did not differ regarding sociodemographic and sociosexual variables before therapy. There were no significant differences in education, relationship status, living solitarily, and being a father/stepfather. TR and DO lived farther away from treatment site than TG. In the TG, a reduction in offense-supportive attitudes, coping self-efficacy deficits, and child identification were revealed at second assessment. In TG no participants started the consumption of child abuse content during the course of the study. Clinical Implications Future treatment concepts should focus on the reduction of empirically relevant risk factors for child sexual offending. Strength & Limitations The present article is the first that compares TG to TR and DO before assessment regarding DRF and sociosexual variables. Moreover, it is only the second study that investigated treatment effects on a population of pedophilic men who are at risk for offending. These preliminary findings are limited by moderate group size and a missing control group. Conclusion A reduction in some but not all assessed risk factors for sexual offending against minors could be seen within the time frame of therapy. Findings are in line with results from a previous evaluation study.