Placental Complement Activation in Fetal and Neonatal Alloimmune Thrombocytopenia: An Observational Study

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease that causes thrombocytopenia and a risk of bleeding in the (unborn) child that result from maternal alloantibodies directed against fetal, paternally inherited, human platelet antigens (HPA). It is hypothesized that these alloantibodies can also bind to the placenta, causing placental damage. This study aims to explore signs of antibody-mediated placental damage in FNAIT. We performed a retrospective study that included pregnant women, their newborns, and placentas. It comprised 23 FNAIT cases, of which nine were newly diagnosed (14 samples) and 14 were antenatally treated with intravenous immune globulins (IVIg) (21 samples), and 20 controls, of which 10 had anti-HLA-class I antibodies. Clinical information was collected from medical records. Placental samples were stained for complement activation markers (C1q, C4d, SC5b-9, and mannose-binding lectin) using immunohistochemistry. Histopathology was examined according to the Amsterdam criteria. A higher degree of C4d deposition was present in the newly diagnosed FNAIT cases (10/14 samples), as compared to the IVIg-treated FNAIT cases (2/21 samples, p = 0.002) and anti-HLA-negative controls (3/20 samples, p = 0.006). A histopathological examination showed delayed maturation in four (44%) placentas in the newly diagnosed FNAIT cases, five (36%) in the IVIg-treated FNAIT cases, and one in the controls (NS). C4d deposition at the syncytiotrophoblast was present in combination with low-grade villitis of unknown etiology in three newly diagnosed FNAIT cases that were born SGA. We conclude that a higher degree of classical pathway-induced complement activation is present in placentas from pregnancies with untreated FNAIT. This may affect placental function and fetal growth.     

Purinergic Signalling in Allogeneic Haematopoietic Stem Cell Transplantation and Graft-versus-Host Disease

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for blood cancers and other haematological disorders. However, allo-HSCT leads to graft-versus-host disease (GVHD), a severe and often lethal immunological response, in the majority of transplant recipients. Current therapies for GVHD are limited and often reduce the effectiveness of allo-HSCT. Therefore, pro- and anti-inflammatory factors contributing to disease need to be explored in order to identify new treatment targets. Purinergic signalling plays important roles in haematopoiesis, inflammation and immunity, and recent evidence suggests that it can also affect haematopoietic stem cell transplantation and GVHD development. This review provides a detailed assessment of the emerging roles of purinergic receptors, most notably P2X7, P2Y₂ and A_2A receptors, and ectoenzymes, CD39 and CD73, in GVHD.     

Overexpression of Tropomyosin Isoform Tpm3.1 Does Not Alter Synaptic Function in Hippocampal Neurons

Tropomyosin (Tpm) has been regarded as the master regulator of actin dynamics. Tpms regulate the binding of the various proteins involved in restructuring actin. The actin cytoskeleton is the predominant cytoskeletal structure in dendritic spines. Its regulation is critical for spine formation and long-term activity-dependent changes in synaptic strength. The Tpm isoform Tpm3.1 is enriched in dendritic spines, but its role in regulating the synapse structure and function is not known. To determine the role of Tpm3.1, we studied the synapse structure and function of cultured hippocampal neurons from transgenic mice overexpressing Tpm3.1. We recorded hippocampal field excitatory postsynaptic potentials (fEPSPs) from brain slices to examine if Tpm3.1 overexpression alters long-term synaptic plasticity. Tpm3.1-overexpressing cultured neurons did not show a significantly altered dendritic spine morphology or synaptic activity. Similarly, we did not observe altered synaptic transmission or plasticity in brain slices. Furthermore, expression of Tpm3.1 at the postsynaptic compartment does not increase the local F-actin levels. The results suggest that although Tpm3.1 localises to dendritic spines in cultured hippocampal neurons, it does not have any apparent impact on dendritic spine morphology or function. This is contrary to the functional role of Tpm3.1 previously observed at the tip of growing neurites, where it increases the F-actin levels and impacts growth cone dynamics.     

The Inflammatory Profile of Obesity and the Role on Pulmonary Bacterial and Viral Infections

Obesity is a globally increasing health problem, entailing diverse comorbidities such as infectious diseases. An obese weight status has marked effects on lung function that can be attributed to mechanical dysfunctions. Moreover, the alterations of adipocyte-derived signal mediators strongly influence the regulation of inflammation, resulting in chronic low-grade inflammation. Our review summarizes the known effects regarding pulmonary bacterial and viral infections. For this, we discuss model systems that allow mechanistic investigation of the interplay between obesity and lung infections. Overall, obesity gives rise to a higher susceptibility to infectious pathogens, but the pathogenetic process is not clearly defined. Whereas, viral infections often show a more severe course in obese patients, the same patients seem to have a survival benefit during bacterial infections. In particular, we summarize the main mechanical impairments in the pulmonary tract caused by obesity. Moreover, we outline the main secretory changes within the expanded adipose tissue mass, resulting in chronic low-grade inflammation. Finally, we connect these altered host factors to the influence of obesity on the development of lung infection by summarizing observations from clinical and experimental data.     

Effects of Berry Anthocyanins on Cognitive Performance,Vascular Function and Cardiometabolic Risk Markers: A Systematic Review of Randomized Placebo-Controlled Intervention Studies in Humans

Supplementation with anthocyanins, which are a type of flavonoids mainly found in various berries, is hypothesized to be a promising approach to lower the risk of developing cognitive decline. The aim of this systematic review was to provide a comprehensive overview of dietary intervention trials describing effects of berry anthocyanins on cognitive performance in humans, while also addressing potential underlying mechanisms. A total of 1197 articles were identified through a systematic search, and 49 studies reporting effects on cognitive performance (n = 18), vascular function (n = 22), or cardiometabolic risk markers (n = 32) were included. Significant improvements were observed on memory, while some of the studies also reported effects on attention and psychomotor speed or executive function. Vascular function markers such as brachial artery flow-mediated vasodilation were also affected and consistent evidence was provided for the beneficial effects of berry anthocyanins on endothelial function. Finally, studies reported improvements in blood pressure, but effects on metabolic risk markers (e.g. carbohydrate and lipid metabolism) were less consistent. In conclusion, this review provides evidence for the beneficial effects of berry anthocyanins on cognitive performance as memory improved. Whether observed anthocyanin-induced improvements in vascular function and blood pressure underlie beneficial effects on cognitive performance warrants further study.     

A study on the optimal fabrication method for micro-scale gyroscopes using a hybrid process consisting of electric discharge machining,chemical etching or micro-mechanical milling

For productive manufacturing of an accurate small-scale wine-glass gyroscope, a hybrid fabrication process consisting of either electric discharge machining, chemical etching, or micro-mechanical milling have been proposed. A comparison of silicon cavity fabrication processes has been conducted in terms of productivity, quality and geometrical accuracy, aiming at the use of the cavity as a mold for creating a thin wall diamond hemisphere, which is the main component of a wine-glass gyroscope. The results have shown that the EDM process, combined with chemical etching, can yield the highest productivity but with limited shape accuracy. The use of mechanical micro-milling, while less productive than EDM and etching, produces a superior quality and geometric accuracy.     

Design of Lu2O3-reinforced Cf/SiC-ZrB2-ZrC ultra-high temperature ceramic matrix composites: Wetting and interfacial reactivity by ZrSi2 based alloys

The wettability and infiltration of molten ZrSi₂ and ZrSi₂-Lu₂O₃ alloys into C_f/SiC and B₄C-infiltrated C_f/SiC composites were investigated to understand the interfacial interactions that occur during the development of C_f/SiC-ZrC and C_f/SiC-ZrB₂-ZrC-Lu₂O₃ materials. A significant evaporation of Si from the liquid affected the wetting behaviour of the alloy when tested in a vacuum at 1670 °C. The better wetting and spreading of the alloy over the surface was observed for the composites with lower overall porosity (12 %). On the other hand, the formation of an outer dense layer, followed up by the uniform infiltrated region up to ～ 1 mm was observed for the C_f/SiC with higher porosity (21 %). The infiltrated alloy reacted with SiC matrix to form ZrC or with B₄C-infiltrated SiC matrix to form ZrB₂-ZrC-SiC. The Lu₂O₃ particles were not wetted by the melt, and were pushed away of the reaction zone by the solidification front.     

Nanolayer CrAlN/TiSiN coating designed for tribological applications

With the goal to produce a hard and tough coating intended for tribological applications, CrAlN/TiSiN nanolayer coating was prepared by alternative deposition of CrAlN and TiSiN layers. In the first part of the article, a detailed study of phase composition, microstructure, and layer structure of CrAlN/TiSiN coating is presented. In the second part, its mechanical properties, fracture and tribological behavior are compared to the nanocomposite TiSiN coating. An industrial magnetron sputtering unit was used for coating deposition. X-ray photoelectron spectroscopy, energy dispersive X-ray spectroscopy, X-ray diffraction, scanning electron microscopy, and transmission electron microscopy were used for compositional and microstructural analysis. Mechanical properties and fracture behavior were studied by instrumented indentation and focused ion beam techniques. Tribological properties were evaluated by ball-on-disk test in a linear reciprocal mode. A complex layer structure was found in the nanolayer coating. The TiSiN layers were epitaxially stabilized inside the coating which led to formation of dislocations at interfaces, to introduction of disturbances in the coating growth, and as a result, to development of fine-grained columnar microstructure. Indentation load required for the onset of fracture was twice lower for the nanolayer CrAlN/TiSiN, compared to the nanocomposite TiSiN coating. This agrees very well with their mechanical properties, with H³/E² being twice higher for the TiSiN coating. However, the nanolayer coating experienced less severe damage, which had a strong impact on tribological behavior. A magnitude of order lower wear rate and four times lower steady state friction coefficient were found for the nanolayer coating.