Christina A.

Theories of change have been a staple of sustainability research, but how to connect such overarching concepts to actionable items can be a struggle. This study uses coastal wetlands to demonstrate a potential framework for integrating indicators of conservation enabling conditions into theories of change.

Female genital tract infections (FGTIs) include vaginal infections (e.g., bacterial vaginosis [BV]), endometritis, pelvic inflammatory disease [PID], and chorioamnionitis [amniotic fluid infection]. They commonly occur in women of reproductive age and are strongly associated with multiple adverse health outcomes including increased risk of HIV/sexually transmitted infection acquisition and transmission, infertility, and adverse birth outcomes such as preterm birth. These FGTIs are characterized by a disruption of the cervicovaginal microbiota which largely affects host immunity through the loss of protective, lactic acid-producing Lactobacillus spp. and the overgrowth of facultative and strict anaerobic bacteria. Prevotella species (spp.), anaerobic Gram-negative rods, are implicated in the pathogenesis of multiple bacterial FGTIs. Specifically, P. bivia, P. amnii, and P. timonensis have unique virulence factors in this setting, including resistance to antibiotics commonly used in treatment. Additionally, evidence suggests that the presence of Prevotella spp. in untreated BV cases can lead to infections of the upper female genital tract by ascension into the uterus. This narrative review aims to explore the most common Prevotella spp. in FGTIs, highlight their important role in the pathogenesis of FGTIs, and propose future research in this area.

Triazole antifungals are widely used and exert their action by inhibiting ergosterol biosynthesis. Here, Rybak et al show that these drugs both inhibit ergosterol biosynthesis and induce accumulation of pathway intermediates that directly induce inhibition of sterol synthesis.

Open Access Article by Christina A. Watts Christina A. Watts SciProfiles Scilit Preprints.org

Abstract There are numerous mechanisms by which glioblastoma cells evade immunological detection, underscoring the need for strategic

Human endocannabinoid signaling is primarily mediated by the cannabinoid receptors, CB1 and CB2, which are G protein-coupled receptors (GPCRs). These receptors have been linked to a variety of physiological processes and are being pursued as prospective drug targets due to their potential in treating pain and inflammation. However, because of their homology and shared signaling mechanisms, investigating the individual physiological roles of these receptors and designing subtype-selective ligands has been challenging. Using active-state CB1 and CB2 structures as guides, homologous residues within the orthosteric pocket of each receptor were mutated to alanine to test whether they equally impair CB1 and CB2 activity in response to two high-affinity, nonselective agonists (CP55,940 and AM12033). Interestingly, mutating the Y5.39 position impairs CB1 but not CB2 function. Conversely, mutating residue C6.47 improves CB1 but impairs CB2 signaling. The F7.35A mutation leads to a decrease in CP55,940 potency at CB1 and impairs internalization; however, AM12033 gains potency and promotes CB1 internalization. In CB2, mutation of F7.35A decreases the potency of CP55,940 and neither agonist induces internalization. These observations provide some insight into functional sensitivity of CB1 and CB2 to different agonists when conserved residues are mutated in the orthosteric pocket.

Type 2 diabetes (T2D) is the predominant metabolic epidemic posing a major threat to global health. Growing evidence indicates that gut microbiota (GM) may critically influence the progression from normal glucose tolerance, to pre-diabetes, to T2D. On the other hand, regular exercise contributes to the prevention and/or treatment of the disease, and evidence suggests that a possible way regular exercise favorably affects T2D is by altering GM composition toward health-promoting bacteria. However, research regarding this potential effect of exercise-induced changes of GM on T2D and the associated mechanisms through which these effects are accomplished is limited. This review presents current data regarding the association of GM composition and T2D and the possible critical GM differentiation in the progression from normal glucose, to pre-diabetes, to T2D. Additionally, potential mechanisms through which GM may affect T2D are presented. The effect of exercise on GM composition and function on T2D progression is also discussed.

Abstract Intracellular infections by Gram-negative bacteria are a significant global health threat.

Background: Age-related macular degeneration (AMD) is a multifactorial disorder, and there is growing evidence of immunological involvement in its pathogenesis. To address this, we aimed to identify biomarker candidates related to retinal antigens in patients with neovascular AMD treated with ranibizumab and healthy subjects. Materials and Methods: This study was designed as a prospective, open, parallel-group, interventional, single-center phase IV trial. Fifty subjects with neovascular AMD and twenty healthy volunteers were enrolled. The primary objective was to assess the efficacy of intravitreally (IVT) administered ranibizumab in terms of the change in best-corrected visual acuity in subjects with all subtypes of neovascular AMD and in a subgroup of pretreated AMD subjects. A secondary objective was to assess the efficacy of the same in terms of the change in central retinal thickness (CRT) in the same subjects. Another secondary objective was to identify antibodies against retinal antigens in patients with neovascular AMD treated with ranibizumab and healthy subjects. The last secondary objective was to correlate functional and structural parameters with the identified biomarker candidates to differentiate between initial and deferred responders to IVT administered ranibizumab. Serum was analyzed using customized antigen microarrays containing 58 antigens. Results: After 12 weeks of ranibizumab treatment, treated patients gained 4.02 letters on average. The central retinal thickness (CRT) measured in the complete AMD study population was significantly (p < 0.001) decreased at Week 24 compared to the baseline measurement, and the mean CRT dropped from 393.4 to 296.8 µm. A significant increase in the following autoantibodies was detected between the control group and AMD group at Week 24, as well as in the AMD group between baseline and Week 24: antibodies targeting the proteins serotransferrin, opioid growth factor receptor, 60 kDa chaperonin 2, neurotrophin-4, dermcidin, clusterin and vascular endothelial growth factor. Conclusions: The present trial was able to confirm the efficacy of ranibizumab treatment in neovascular AMD, and treatment-naïve patients benefitted the most. Up- and downregulations of antibodies were observed over the course of treatment with ranibizumab. Some antibodies seemed to have a fair correlation with the classification of initial and deferred responders.

Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany