Search

Background: Reliable predictive models for predicting excessive and poor ovarian response in controlled ovarian stimulation (COS) is currently lacking. The dynamic (D) inhibin B, which refers to increment of inhibin B responding to exogenous gonadotropin, has been indicated as a potential predictor of ovarian response. Objective: To establish mathematical models to predict ovarian response at the early phase of COS using Dinhibin B and other biomarkers. Materials and methods: Prospective cohort study in a tertiary teaching hospital, including 669 cycles underwent standard gonadotropin releasing hormone (GnRH) antagonist ovarian stimulation between April 2020 and September 2020. Early Dinhibin B was defined as an increment in inhibin B from menstrual day 2 to day 6 through to the day of COS. Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression with 5-fold cross-validation was applied to construct ovarian response prediction models. The area under the receiver operating characteristic curve (AUC), prevalence, sensitivity, and specificity were used for evaluating model performance. Results: Early Dinhibin B and basal antimüllerian hormone (AMH) levels were the best measures in building models for predicting ovarian hypo- or hyper-responses, with AUCs and ranges of 0.948 (0.887–0.976) and 0.904 (0.836–0.945) in the validation set, respectively. The contribution of the early Dinhibin B was 67.7% in the poor response prediction model and 56.4% in the excessive response prediction model. The basal AMH level contributed 16.0% in the poor response prediction model and 25.0% in the excessive response prediction model. An online website based tool (http://121.43.113.123:8001/) has been developed to make these complex algorithms available in clinical practice. Conclusion: Early Dinhibin B might be a novel biomarker for predicting ovarian response in IVF cycles. Limiting the two prediction models to the high and the very-low risk groups would achieve satisfactory performances and clinical significance. These novel models might help in counseling patients on their estimated ovarian response and reduce iatrogenic poor or excessive ovarian responses. [ABSTRACT FROM AUTHOR]

Purpose: To establish a more convenient ovarian reserve model with anti-Müllerian hormone (AMH) level and age (the AA model), with blood samples taken at any time in the menstrual cycle. Methods: We have established this AA model for predicting ovarian reserve using the AMH level and age. The outcome variable was defined as poor ovarian response (POR) with <5 oocytes retrieved during assisted reproductive technology treatment cycles. Least Absolute Shrinkage and Selection Operator logistic regression with 5-fold cross validation methods was applied to construct the model, and that with the lowest scaled log-likelihood was selected as the final one. Results: The areas under the receiver operating characteristic curve for the training, inner, and external validation sets were 0.862, 0.843, and 0.854 respectively. The main effects of AMH level and age contributing to the prediction of POR were 95.3% and 1.8%, respectively. The incidences of POR increased with its predicted probability in both the model building and in external validation datasets, indicating its stability. An online website-based tool for assessing the score of ovarian reserve (http://121.43.113.123:9999) has been developed. Conclusions: Based on external validation data, the AA model performed well in predicting POR, and was more cost-effective and convenient than our previous published models. [ABSTRACT FROM AUTHOR]

Guanylate cyclase activating protein 2 (GCAP2) is a recoverin-like Ca2+-sensor protein known to modulate guanylate cyclase activity in photoreceptor outer segments. GCAP2 is also present in photoreceptor ribbon synapses where its function is unknown. Synaptic ribbons are active zone-associated presynaptic structures in the tonically active photoreceptor ribbon synapses and contain RIBEYE as a unique and major protein component. In the present study, we demonstrate by various independent approaches that GCAP2 specifically interacts with RIBEYE in photoreceptor synapses. We show that the flexible hinge 2 linker region of RIBEYE(B) domain that connects the nicotinamide adenine dinucleotide (NADH)-binding subdomain with the substrate-binding subdomain (SBD) binds to the C terminus of GCAP2. We demonstrate that the RIBEYE-GCAP2 interaction is induced by the binding of NADH to RIBEYE. RIBEYE--GCAP2 interaction is modulated by the SBD. GCAP2 is strongly expressed in synaptic terminals of light-adapted photoreceptors where GCAP2 is found close to synaptic ribbons as judged by confocal microscopy and proximity ligation assays. Virus-mediated overexpression of GCAP2 in photoreceptor synaptic terminals leads to a reduction in the number of synaptic ribbons. Therefore, GCAP2 is a prime candidate for mediating Ca2+-dependent dynamic changes of synaptic ribbons in photoreceptor synapses. [ABSTRACT FROM AUTHOR]

The fundamental processes of membrane fission and fusion determine size and copy numbers of intracellular organelles. Although SNARE proteins and tethering complexes mediate intracellular membrane fusion, fission requires the presence of dynamin or dynamin-related proteins. Here we study these reactions in native yeast vacuoles and find that the yeast dynamin homologue Vps1 is not only an essential part of the fission machinery, but also controls membrane fusion by generating an active Qa SNARE-tethering complex pool, which is essential for trans-SNARE formation. Our findings provide new insight into the role of dynamins in membrane fusion by directly acting on SNARE proteins.

Guanylate cyclase activating protein 2 (GCAP2) is a recoverin-like Ca2+-sensor protein known to modulate guanylate cyclase activity in photoreceptor outer segments. GCAP2 is also present in photoreceptor ribbon synapses where its function is unknown. Synaptic ribbons are active zone-associated presynaptic structures in the tonically active photoreceptor ribbon synapses and contain RIBEYE as a unique and major protein component. In the present study, we demonstrate by various independent approaches that GCAP2 specifically interacts with RIBEYE in photoreceptor synapses. We show that the flexible hinge 2 linker region of RIBEYE(B) domain that connects the nicotinamide adenine dinucleotide (NADH)-binding subdomain with the substrate-binding subdomain (SBD) binds to the C terminus of GCAP2. We demonstrate that the RIBEYE-GCAP2 interaction is induced by the binding of NADH to RIBEYE. RIBEYE-GCAP2 interaction is modulated by the SBD. GCAP2 is strongly expressed in synaptic terminals of light-adapted photoreceptors where GCAP2 is found close to synaptic ribbons as judged by confocal microscopy and proximity ligation assays. Virus-mediated overexpression of GCAP2 in photoreceptor synaptic terminals leads to a reduction in the number of synaptic ribbons. Therefore, GCAP2 is a prime candidate for mediating Ca2+-dependent dynamic changes of synaptic ribbons in photoreceptor synapses.