Alien Registration- Mcneill, Helen W. (Bath, Sagadahoc County)

https://digitalmaine.com/alien_docs/8908/thumbnail.jp

Coupling Planar Cell Polarity Signaling to Morphogenesis

Epithelial cells and other groups of cells acquire a polarity orthogonal to their apical–basal axes, referred to as Planar Cell Polarity (PCP). The process by which these cells become polarized requires a signaling pathway using Frizzled as a receptor. Responding cells sense cues from their environment that provide directional information, and they translate this information into cellular asymmetry. Most of what is known about PCP derives from studies in the fruit fly, Drosophila. We review what is known about how cells translate an unknown signal into asymmetric cytoskeletal reorganization. We then discuss how the vertebrate processes of convergent extension and cochlear hair-cell development may relate to Drosophila PCP signaling

Analyzing the role of body composition and diet in plasma apelin levels of normal healthy adults

The purpose of this study was to determine if diet and/or body composition influences resting plasma apelin concentration. Apelin concentration appears to be influenced by the amount of fat in the body and by blood glucose concentration. However, most of the studies that have investigated blood apelin concentration have utilized obese or diabetic subjects. Little is known about how body composition, body fat distribution or diet may influence apelin in apparently healthy, young individuals. More specifically, the purposes of this study were to determine if baseline resting plasma apelin concentration in young, apparently healthy adult subjects is influenced by amount of fat in the body, location of fat, the macronutrient composition in their diet and if the total amount of antioxidant micronutrients (vitamins A, C, E and zinc). The proposed cohort group consisted of twelve apparently healthy young adults between the ages of 18-35.The amount of body fat, body mass index, sagittal diameter and the waist to hip ratio were utilized as covariates to determine if these factors influenced apelin concentration at rest. The data was analyzed to ascertain if there are any relationships with the listed anthropometric measures, the nutrition factors and plasma apelin concentration. Each subject’s body composition was classified via body mass index (BMI), sagittal abdominal diameter (SAD), waist circumference (WC) and 7-site skinfold analysis. In addition, Each subject completed a three day diet record prior to their three visits which were analyzed for total calories, macronutrient percent calories and amount of micronutrient antioxidants; vitamin A, C, E, and zinc. They were instructed on how to log 3 day diet records and were asked to repeat the diets as close as possible on their 2nd and 3rd visits to keep this information as consistent as possible. Significant relationships were found for body composition factors including Siri % body fat (r=0.631, P=0.028*), Brozek % body fat (r=0.642, P=0.024*), and BMI (r=0.649, P=0.022*). Body composition factors showed varied results. A significant association was found between sagittal abdominal diameter and plasma apelin concentrations at rest (r=0.628, p=0.029*), however waist circumference approached significance (r=0.061, P=0.061) and waist-to-hip ratio did not demonstrate a significant relationship (r=0.178, P=0.579). Only two subjects reported consuming high fat diets (>35% of total kilocalorie intake), therefore no relationships could be analyzed regarding plasma apelin concentration at rest and high fat diets. No significant relationships were found between individual micronutrients and plasma apelin concentrations at rest, besides vitamin E (r=0.658, P=0.020*). In conclusion this small cohort of subjects had stable resting plasma apelin levels across visits and does not appear that dietary factors influenced plasma apelin concentrations. In contrast, % BF and SAD suggest that these factors are significantly related to resting plasma apelin, with WC also approaching significance. More research should be done with a larger cohort of subjects including a wider range of diet and anthropometric measures

The Hippo pathway regulates axis formation and morphogenesis in Hydra

How did cells of early metazoan organisms first organize themselves to form a body axis? The canonical Wnt pathway has been shown to be sufficient for induction of axis in Cnidaria, a sister group to Bilateria, and is important in bilaterian axis formation. Here, we provide experimental evidence that in cnidaria

Ancestral roles of atypical cadherins in planar cell polarity

Fat, Fat-like, and Dachsous family cadherins are giant proteins that regulate planar cell polarity (PCP) and cell adhesion in bilaterians. Their evolutionary origin can be traced back to prebilaterian species, but their ancestral function(s) are unknown. We identified Fat-like and Dachsous cadherins in Hydra, a member of phylum Cnidaria a sister group of bilaterian. We found Hydra does not possess a true Fat homolog, but has homologs of Fat-like (HyFatl) and Dachsous (HyDs) that localize at the apical membrane of ectodermal epithelial cells and are planar polarized perpendicular to the oral-aboral axis of the animal. Using a knockdown approach we found that HyFatl is involved in local cell alignment and cell-cell adhesion, and that reduction of HyFatl leads to defects in tissue organization in the body column. Overexpression and knockdown experiments indicate that the intracellular domain (ICD) of HyFatl affects actin organization through proline-rich repeats. Thus, planar polarization of Fat-like and Dachsous cadherins has ancient, prebilaterian origins, and Fat-like cadherins have ancient roles in cell adhesion, spindle orientation, and tissue organization

Four-jointed knock-out delays renal failure in an ADPKD model with kidney injury

Autosomal Dominant Polycystic Kidney Disease is characterised by the development of fluid-filled cysts in the kidneys which lead to end-stage renal disease (ESRD). In the majority of cases, the disease is caused by a mutation in the Pkd1 gene. In a previous study, we demonstrated that renal injury can accelerate cyst formation in Pkd1 knock-out (KO) mice. In that study, we found that after injury four-jointed (Fjx1), an upstream regulator of planar cell polarity and the Hippo pathway, was aberrantly expressed in Pkd1 KO mice compared to WT. Therefore, we hypothesised a role for Fjx1 in injury/repair and cyst formation. We generated single and double deletion mice for Pkd1 and Fjx1, and we induced toxic renal injury using the nephrotoxic compound 1,2-dichlorovinyl-cysteine. We confirmed that nephrotoxic injury can accelerate cyst formation in Pkd1 mutant mice. This caused Pkd1 KO mice to reach ESRD significantly faster; unexpectedly, double KO mice survived significantly longer. Cyst formation was comparable in both models, but we found significantly less fibrosis and macrophage infiltration in double KO mice. Taken together, these data suggest that Fjx1 disruption protects the cystic kidneys against kidney failure by reducing inflammation and fibrosis. Moreover, we describe, for the first time, an interesting (yet unidentified) mechanism that partially discriminates cyst growth from fibrogenesis. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland

Transgenic force sensors and software to measure force transmission across the mammalian nuclear envelope in vivo

Nuclear mechanotransduction is a growing field with exciting implications for the regulation of gene expression and cellular function. Mechanical signals may be transduced to the nuclear interior biochemically or physically through connections between the cell surface and chromatin. To define mechanical stresses upon the nucleus in physiological settings, we generated transgenic mouse strains that harbour FRET-based tension sensors or control constructs in the outer and inner aspects of the nuclear envelope. We knocked-in a published esprin-2G sensor to measure tensions across the LINC complex and generated a new sensor that links the inner nuclear membrane to chromatin. To mitigate challenges inherent to fluorescence lifetime analysis in vivo, we developed software (FLIMvivo) that markedly improves the fitting of fluorescence decay curves. In the mouse embryo, the sensors responded to cytoskeletal relaxation and stretch applied by micro-aspiration. They reported organ-specific differences and a spatiotemporal tension gradient along the proximodistal axis of the limb bud, raising the possibility that mechanical mechanisms coregulate pattern formation. These mouse strains and software are potentially valuable tools for testing and refining mechanotransduction hypotheses in vivo

The inner nuclear membrane protein NEMP1 supports nuclear envelope openings and enucleation of erythroblasts

Nuclear envelope membrane proteins (NEMPs) are a conserved family of nuclear envelope (NE) proteins that reside within the inner nuclear membrane (INM). Even though Nemp1 knockout (KO) mice are overtly normal, they display a pronounced splenomegaly. This phenotype and recent reports describing a requirement for NE openings during erythroblasts terminal maturation led us to examine a potential role for Nemp1 in erythropoiesis. Here, we report that Nemp1 KO mice show peripheral blood defects, anemia in neonates, ineffective erythropoiesis, splenomegaly, and stress erythropoiesis. The erythroid lineage of Nemp1 KO mice is overrepresented until the pronounced apoptosis of polychromatophilic erythroblasts. We show that NEMP1 localizes to the NE of erythroblasts and their progenitors. Mechanistically, we discovered that NEMP1 accumulates into aggregates that localize near or at the edge of NE openings and Nemp1 deficiency leads to a marked decrease of both NE openings and ensuing enucleation. Together, our results for the first time demonstrate that NEMP1 is essential for NE openings and erythropoietic maturation in vivo and provide the first mouse model of defective erythropoiesis directly linked to the loss of an INM protein