Induction of human macrophage cell death by Neisseria gonorrhoeae

The obligate human pathogen Neisseria gonorrhoeae is responsible for the sexually transmitted disease, gonorrhea. This pathogen colonizes mucosal surfaces, and is most commonly found in the urogenital tract. The genital mucosa is comprised of various cells from epithelial to immune cells including the macrophage. Macrophages are abundant immune cells within the genital submucosa. Though the cytokine response of macrophages following N. gonorrhoeae infection is well characterized, survival of these cells following infection has not been well described. In this study, we examined the ability of N. gonorrhoeae strain FA1090B to modulate cell death in differentiated THP-1 cells (dTHP-1) and human monocyte-derived macrophages (MDMs) harvested from peripheral blood. N. gonorrhoeae was demonstrated to induce cell death in both macrophage types in a dose-dependent manner as measured at 6 hours post-stimulation. Cell death did not proceed via classical apoptosis but was associated with activation of immune caspases-1 and -4, required for the canonical and non-canonical pyroptotic pathways, respectively. MDM cell death was found to be dependent on immune caspase activity and associated with intracellular bacteria. Furthermore, caspase-4-associated MDM cell death was also observed with cytosolic N. gonorrhoeae-purified lipooligosaccharide (LOS). We did not however observe differences in the induction of pyroptosis by a penta-acylated non-immune stimulating LOS mutant strain, 1291ΔmsbB, as compared to the isogenic wild type strain 1291, or strain FA1090B. Activation of pyroptosis correlated with increased production of the pro-inflammatory mediators IL-1β, IL-6 and TNF-α. Pre-treatment of dTHP-1 cells with conditioned media from bacterial stimulated samples had little effect on N. gonorrhoeae induced cell death. Collectively, our results demonstrate that N. gonorrhoeae induces pyroptosis in human macrophages due, in part, to LOS. We postulate that N. gonorrhoeae induced pyroptosis of macrophages may partially contribute to lack of immunological memory and continual neutrophil recruitment, a hallmark of N. gonorrhoeae infection

Iron-Catalyzed Polymerization of Isoprene and Other 1,3-Dienes

Chemistry and Chemical Biolog

Identifikation genetischer Marker bei Kindern mit VACTERL-Assoziation

The VACTERL association is a rare malformation complex consisting of vertebral defects, anorectal malformation, cardiovascular defects, tracheoesophageal fistulae with esophageal atresia, renal malformation, and limb anomalies. As far as currently known, VACTERL is based on a multifactorial pathogenesis including genomic alterations. The aim of this study was to improve our understanding of the genetic processes involved in the development of VACTERL. For this purpose, the genetic background was investigated with a focus on cardiovascular development, signalling pathways and cilia function. The study was designed as a genetic association study. Whole-exome sequencing (WES) followed by functional enrichment analysis was performed in 21 patients with VACTERL or VACTERL-like phenotype. To investigate the inheritance, the parents were examined by WES respectively Sanger sequencing. In this study a genetic background for vascular disorders was identified in patients with VACTERL. This supports the theory, that congenital vascular defects may indicate other malformations in the spectrum of the VACTERL association. Additionally, this study indicates three more damage mechanisms for VACTERL. These are a general disruption of Shh- and Wnt signalling pathway by changes in signalling pathway activity, a structural cilia defect and a disruption of the ciliary signal transduction. Our work unites these damage mechanisms in different, partly hereditary combinations and thus offers an explanation for the heterogeneity of the VACTERL association. Follow-up studies in cell and animal models should further address these combined damage mechanisms

Iron-Catalyzed 1,4-Hydroboration of 1,3-Dienes

A chemo-, regio-, and stereoselective iron-catalyzed 1,4-hydroboration of dienes that affords γ-disubstituted allylboranes has been developed. 1,4-Hydroboration of 2-substituted dienes forms allylborane products with (E)-trisubstituted double bonds exclusively.Chemistry and Chemical Biolog

Scanning Electron Microscopy of the Surface of Human Duodenum in Patients With and Without Duodenal Ulcer Disease

Endoscopic biopsy specimens of normal human duodenum from patients with duodenal ulcer disease were studied by light microscopy and by scanning electron microscopy. For scanning, the tissue was dried by the critical point-drying technique. SEM criteria for both normal and abnormal duodenal surfaces were determined. SEM evidence for the presence of tuft cells similar to those found on the surface of rat duodenum was found in both the normal and abnormal human material. Although other reports have described the favorable effects of carbenoxolone sodium treatment on duodenal ulcer disease, our SEM studies of four patients found that this treatment had no effect on the duodenal surface

Rolle der hepatic arterial buffer response für das Hyperperfusionssyndrom bei der small-for-size Leber

Ziel dieser Studie war es, die der Prävention einer Hyperperfusion in der Small-for-size-Leber zugrundeliegenden Mechanismen aufzuklären, mit besonderem Augenmerk auf die enge Beziehung zwischen dem Blutfluss in der Pfortader und der Leberarterie. Dazu wurden Wistar-Ratten einer stufenweisen, partiellen Hepatektomie von 30-90% unterzogen, wobei bei einigen Tieren zuvor eine Splenektomie oder eine Splenektomie mit anschließender Ligatur der A. hepatica erfolgte. Der portalvenöse und hepatoarterielle Blutfluss sowie der Sauerstoffpartialdruck des Lebergewebes und weitere Werte wurden ermittelt

Olfaction and anxiety are differently associated in men and women in cognitive physiological and pathological aging

Background: Olfaction impairment in aging is associated with increased anxiety. We explored this association in cognitively healthy controls (HCs), Mild Cognitive Impairment (MCI) and Parkinson’s disease (PD) patients. Both olfaction and anxiety have sex differences, therefore we also investigated these variances. Objectives: Investigate the association of olfaction with anxiety in three distinct clinical categories of aging, exploring the potential role of sex. Methods: 117 subjects (29 HCs, 43 MCI, and 45 PD patients) were assessed for olfaction and anxiety. We used regression models to determine whether B-SIT predicted anxiety and whether sex impacted that relationship. Results: Lower olfaction was related to greater anxiety traits in all groups (HCs: p = 0.015; MCI: p = 0.001 and PD: p = 0.038), significantly differed by sex. In fact, in HCs, for every unit increase in B-SIT, anxiety traits decreased by 7.63 in men (p = 0.009) and 1.5 in women (p = 0.225). In MCI patients for every unit increase in B-SIT, anxiety traits decreased by 1.19 in men (p = 0.048) and 3.03 in women (p = 0.0036). Finally, in PD patients for every unit increase in B-SIT, anxiety traits decreased by 1.73 in men (p = 0.004) and 0.41 in women (p = 0.3632). Discussion: Olfaction and anxiety are correlated in all three distinct diagnostic categories, but differently in men and women

Atlas-Based Interpretable Age Prediction

Age prediction is an important part of medical assessments and research. It can aid in detecting diseases as well as abnormal ageing by highlighting the discrepancy between chronological and biological age. To gain a comprehensive understanding of age-related changes observed in various body parts, we investigate them on a larger scale by using whole-body images. We utilise the Grad-CAM interpretability method to determine the body areas most predictive of a person's age. We expand our analysis beyond individual subjects by employing registration techniques to generate population-wide interpretability maps. Furthermore, we set state-of-the-art whole-body age prediction with a model that achieves a mean absolute error of 2.76 years. Our findings reveal three primary areas of interest: the spine, the autochthonous back muscles, and the cardiac region, which exhibits the highest importance

Corynebacterium oculi-related bacterium may act as a pathogen and carrier of antimicrobial resistance genes in dogs: a case report.

BACKGROUND The genus Corynebacterium comprises well-known animal and human pathogens as well as commensals of skin and mucous membranes. Species formerly regarded as contaminants are increasingly being recognized as opportunistic pathogens. Corynebacterium oculi has recently been described as a human ocular pathogen but has so far not been reported in dogs. CASE PRESENTATION Here we present two cases of infection with a novel Corynebacterium sp., a corneal ulcer and a case of bacteriuria. The two bacterial isolates could not be identified by MALDI-TOF MS. While 16 S rRNA gene (99.3% similarity) and rpoB (96.6% identity) sequencing led to the preliminary identification of the isolates as Corynebacterium (C.) oculi, whole genome sequencing revealed the strains to be closely related to, but in a separate cluster from C. oculi. Antimicrobial susceptibility testing showed high minimal inhibitory concentrations of lincosamides, macrolides, tetracycline, and fluoroquinolones for one of the isolates, which also contained an erm(X) and tet-carrying plasmid as well as a nonsynonymous mutation leading to an S84I substitution in the quinolone resistance determining region of GyrA. CONCLUSIONS While the clinical signs of both dogs were alleviated by antimicrobial treatment, the clinical significance of these isolates remains to be proven. However, considering its close relation with C. oculi, a known pathogen in humans, pathogenic potential of this species is not unlikely. Furthermore, these bacteria may act as reservoir for antimicrobial resistance genes also in a One Health context since one strain carried a multidrug resistance plasmid related to pNG3 of C. diphtheriae