Identification of guanine nucleotide exchange factors that increase Cdc42 activity in primary human endothelial cells

The Rho GTPase family is involved in actin dynamics and regulates the barrier function of the endothelium. One of the main barrier-promoting Rho GTPases is Cdc42, also known as cell division control protein 42 homolog. Currently, regulation of Cdc42-based signalling networks in endothelial cells (ECs) lack molecular details. To examine these, we focused on a subset of 15 Rho guanine nucleotide exchange factors (GEFs), which are expressed in the endothelium. By performing single cell FRET measurements with Rho GTPase biosensors in primary human ECs, we monitored GEF efficiency towards Cdc42 and Rac1. A new, single cell-based analysis was developed and used to enable the quantitative comparison of cellular activities of the overexpressed full-length GEFs. Our data reveal GEF dependent activation of Cdc42, with the most efficient Cdc42 activation induced by PLEKHG2, FGD1, PLEKHG1 and PREX1 and the highest selectivity for FGD1. Additionally, we generated truncated GEF constructs that comprise only the catalytic dbl homology (DH) domain or together with the adjacent pleckstrin homology domain (DHPH). The DH domain by itself did not activate Cdc42, whereas the DHPH domain of ITSN1, ITSN2 and PLEKHG1 showed activity towards Cdc42. Together, our study characterized endothelial GEFs that may directly or indirectly activate Cdc42, which will be of great value for the field of vascular biology

Three-dimensional geometric morphometrics for studying floral shape variation

Variation in floral shape is of major interest to evolutionary and pollination biologists, plant systematists and developmental geneticists. Quantifying this variation has been difficult due to the three-dimensional (3D) complexity of angiosperm flowers. By combining 3D geometric representations of flowers obtained by micro-computed tomography scanning with geometric morphometric methods, well established in zoology and anthropology, floral shape variation can be analyzed quantitatively, allowing for powerful interpretation and visualization of the resulting patterns of variation

Landmark detection in 2D bioimages for geometric morphometrics: a multi-resolution tree-based approach

The detection of anatomical landmarks in bioimages is a necessary but tedious step for geometric morphometrics studies in many research domains. We propose variants of a multi-resolution tree-based approach to speed-up the detection of landmarks in bioimages. We extensively evaluate our method variants on three different datasets (cephalometric, zebrafish, and drosophila images). We identify the key method parameters (notably the multi-resolution) and report results with respect to human ground truths and existing methods. Our method achieves recognition performances competitive with current existing approaches while being generic and fast. The algorithms are integrated in the open-source Cytomine software and we provide parameter configuration guidelines so that they can be easily exploited by end-users. Finally, datasets are readily available through a Cytomine server to foster future research

Incidence and predictive factors for endograft limb patency of the fenestrated Anaconda endograft used for complex endovascular aneurysm repair

Objective: In the present study, we have described the incidence, risk factors, and outcomes of treatment of limb occlusion for patients who had undergone treatment of complex thoracoabdominal aortic aneurysms with the fenestrated Anaconda endograft (Terumo Aortic, Inchinnan, UK). Methods: Between June 2010 and May 2018, 335 patients had undergone elective fenestrated aortic aneurysm repair at 11 participating centers using the fenestrated Anaconda endograft with a median follow-up of 14.3 months (interquartile range, 27.4 months). The primary outcome measure was freedom from limb occlusion. The secondary outcome measures were freedom from limb-related reintervention, secondary patency, and the risk factors associated with limb occlusion. Results: Of the 335 patients, 30 (9.0%) had presented with limb occlusion during follow-up with a freedom from limb occlusion rate of 98.5%, 91.2%, and 81.7% at 30 days and 1 and 5 years, respectively. In 87% of the cases, no obvious cause for limb occlusion was documented. Primary occlusion had occurred within 30 days in 36.7% and within 1 year in 80.0%. Of the 30 patients, 23 (77%) had undergone an occlusion-related reintervention and 7 (23.3%) had been treated conservatively. The freedom from limb occlusion-related reintervention at 30 days and 1 and 5 years was 97.8%, 93.2%, and 88.6%, respectively. Secondary patency was 91.3% after 1 month and 86.2% after 1 and 5 years. Female sex (odds ratio [OR], 3.27; 95% confidence interval [CI], 1.28-8.34; P = .01) was a statistically significant predictor for limb occlusion. A greater proportion of thrombus in the aneurysm sac appeared to be protective for limb occlusion (0% vs 50%: OR, 0.08; 95% CI, 0.020.38; P = .00), as did iliac angulation (OR, 0.99; 95% CI, 0.98-1.00; P = .04). Conclusions: Limb occlusion remains a significant impediment of endograft durability for patients treated with the fenestrated Anaconda endograft, especially for female patients. In contrast, a high aneurysmal thrombus load and a high degree of iliac angulation appeared to be protective for limb occlusion, for which no obvious cause could be identified

Market responses to appointment of women and men as directors: A study of top 40 Johannesburg Stock Exchange-listed companies

Background: This study investigates market reactions to the appointment of women and men as directors on the top 40 Johannesburg Stock Exchange (JSE)-listed company boards. Both the social and business rationale for the appointment of women is contextualised to evaluate the potential bias towards their appointment as directors. This research contributes to the literature by concurrently analysing both genders. Aim: The primary objective of the study was to assess market reactions to the new appointment of women and men as directors of the top 40 JSE-listed companies using an event study. Setting: This study focussed on companies from the top 40 JSE-listed companies’ index. The period analysed was from the year 2015 to 2019. Method: The event study methodology was used to analyse announcements of 17 women and 29 men as directors from companies across 12 sectors of the top 40 JSE-listed companies. Results: The study identified a significant negative market reaction to the appointment of women as directors, potentially because of gender bias. The appointment of men as directors was met with positive market reactions, though the results were statistically insignificant. The results align with prior studies that gender bias may impact the negative reaction towards the appointment of women. Conclusion: The study suggests gender is relevant to shareholders because of different market reactions. Companies should not disregard the benefits of board diversity despite negative reactions in the short term. Contribution: This study informs boards of possible market reactions to gender diversity efforts. It emphasises the economic and ethical benefits and necessitates stakeholder engagement