The C5a/C5a receptor 1 axis controls tissue neovascularization through CXCL4 release from platelets

Platelets contribute to the regulation of tissue neovascularization, although the specific factors underlying this function are unknown. Here, we identified the complement anaphylatoxin C5a-mediated activation of C5a receptor 1 (C5aR1) on platelets as a negative regulatory mechanism of vessel formation. We showed that platelets expressing C5aR1 exert an inhibitory effect on endothelial cell functions such as migration and 2D and 3D tube formation. Growth factor- and hypoxia-driven vascularization was markedly increased in C5ar1(−/−) mice. Platelet-specific deletion of C5aR1 resulted in a proangiogenic phenotype with increased collateralization, capillarization and improved pericyte coverage. Mechanistically, we found that C5a induced preferential release of CXC chemokine ligand 4 (CXCL4, PF4) from platelets as an important antiangiogenic paracrine effector molecule. Interfering with the C5aR1-CXCL4 axis reversed the antiangiogenic effect of platelets both in vitro and in vivo. In conclusion, we identified a mechanism for the control of tissue neovascularization through C5a/C5aR1 axis activation in platelets and subsequent induction of the antiangiogenic factor CXCL4

The effect of external flow on the feeding currents of sessile microorganisms

Microscopic sessile suspension feeders live attached to surfaces and, by consuming bacteria-sized prey and by being consumed, they form an important part of aquatic ecosystems. Their environmental impact is mediated by their feeding rate, which depends on a self-generated feeding current. The feeding rate has been hypothesized to be limited by recirculating eddies that cause the organisms to feed from water that is depleted of food particles. However, those results considered organisms in still water, while ambient flow is often present in their natural habitats. We show, using a point-force model, that even very slow ambient flow, with speed several orders of magnitude less than that of the self-generated feeding current, is sufficient to disrupt the eddies around perpendicular suspension feeders, providing a constant supply of food-rich water. However, the feeding rate decreases in external flow at a range of non-perpendicular orientations due to the formation of recirculation structures not seen in still water. We quantify the feeding flow and observe such recirculation experimentally for the suspension feeder Vorticella convallaria in external flows typical of streams and rivers

Optic Disc Drusen in Young Adults with Anterior Ischemic Optic Neuropathy: A Multicenter Study (Slides)

Anterior ischemic optic neuropathy (AION) usually occurs in patients over the age of 50 with systemic vascular disease. Lesscommonly, AION occurs in patients younger than 50 years with few or no vascular risk factors. Optic disc drusen (ODD), present in 2% of the general population, have occasionally been reported with AION. The purpose of this study was to examine the prevalence of ODD in young patients with AION

Optic Disc Drusen in Young Adults with Anterior Ischemic Optic Neuropathy: A Multicenter Study (Video)

Anterior ischemic optic neuropathy (AION) usually occurs in patients over the age of 50 with systemic vascular disease. Lesscommonly, AION occurs in patients younger than 50 years with few or no vascular risk factors. Optic disc drusen (ODD), present in 2% of the general population, have occasionally been reported with AION. The purpose of this study was to examine the prevalence of ODD in young patients with AION.kbdopticnervedruse

Optic Disc Drusen in Young Adults with Anterior Ischemic Optic Neuropathy: A Multicenter Study (PDF)

Anterior ischemic optic neuropathy (AION) usually occurs in patients over the age of 50 with systemic vascular disease. Lesscommonly, AION occurs in patients younger than 50 years with few or no vascular risk factors. Optic disc drusen (ODD), present in 2% of the general population, have occasionally been reported with AION. The purpose of this study was to examine the prevalence of ODD in young patients with AION.kbdopticnervedruse

Autonomous Vehicles Require Socio-Political Acceptance—An Empirical and Philosophical Perspective on the Problem of Moral Decision Making

Autonomous vehicles, though having enormous potential, face a number of challenges. As a computer system interacting with society on a large scale and human beings in particular, they will encounter situations, which require moral assessment. What will count as right behavior in such situations depends on which factors are considered to be both morally justified and socially acceptable. In an empirical study we investigated what factors people recognize as relevant in driving situations. The study put subjects in several “dilemma” situations, which were designed to isolate different and potentially relevant factors. Subjects showed a surprisingly high willingness to sacrifice themselves to save others, took the age of potential victims in a crash into consideration and were willing to swerve onto a sidewalk if this saved more lives. The empirical insights are intended to provide a starting point for a discussion, ultimately yielding societal agreement whereby the empirical insights should be balanced with philosophical considerations

Young Adults With Anterior Ischemic Optic Neuropathy: A Multicenter Optic Disc Drusen Study

Purpose: Optic disc drusen (ODD), present in 2% of the general population, have occasionally been reported in patients with nonarteritic anterior ischemic optic neuropathy (NA-AION). The purpose of this study was to examine the prevalence of ODD in young patients with NA-AION. Design: Retrospective, cross-sectional multicenter study. Methods: All patients with NA-AION 50 years old or younger, seen in neuro-ophthalmology clinics of the international ODDS (Optic Disc Drusen Studies) Consortium between April 1, 2017, and March 31, 2019, were identified. Patients were included if ODD were diagnosed by any method, or if ODD were excluded by enhanced-depth imaging optical coherence tomography (EDI-OCT) using ODDS Consortium guidelines. NA-AION eyes with ODD were termed “ODD-AION”; those without were termed “NODD-AION”. Results: A total of 65 patients (127 eyes) with NA-AION were included (mean 41 years old). Of the 74 eyes with NA-AION, 51% had ODD-AION, whereas 43% of fellow eyes without NA-AION had ODD (P =.36). No significant differences were found between ODD-AION and NODD-AION eyes in terms of Snellen best-corrected VA or perimetric mean deviation. According to EDI-OCT results, 28% of eyes with NODD-AION had peripapillary hyperreflective ovoid mass-like structures (PHOMS); 7% had hyperreflective lines, whereas 54% with ODD-AION had PHOMS; and 66% had hyperreflective lines (P =.006 and P <.001, respectively). Conclusions: Most of these young NA-AION patients had ODD. This indicates that ODD may be an independent risk factor for the development of NA-AION, at least in younger patients. This study suggests ODD-AION be recognized as a novel diagnosis

Novel asymmetrically localizing components of human centrosomes identified by complementary proteomics methods

Centrosomes in animal cells are dynamic organelles with a proteinaceous matrix of pericentriolar material assembled around a pair of centrioles. They organize the microtubule cytoskeleton and the mitotic spindle apparatus. Mature centrioles are essential for biogenesis of primary cilia that mediate key signalling events. Despite recent advances, the molecular basis for the plethora of processes coordinated by centrosomes is not fully understood. We have combined protein identification and localization, using PCP-SILAC mass spectrometry, BAC transgeneOmics, and antibodies to define the constituents of human centrosomes. From a background of non-specific proteins, we distinguished 126 known and 40 candidate centrosomal proteins, of which 22 were confirmed as novel components. An antibody screen covering 4000 genes revealed an additional 113 candidates. We illustrate the power of our methods by identifying a novel set of five proteins preferentially associated with mother or daughter centrioles, comprising genes implicated in cell polarity. Pulsed labelling demonstrates a remarkable variation in the stability of centrosomal protein complexes. These spatiotemporal proteomics data provide leads to the further functional characterization of centrosomal proteins