Polyfluoroalkyl Compounds in Texas Children from Birth through 12 Years of Age

Background: For > 50 years, polyfluoroalkyl compounds (PFCs) have been used worldwide, mainly as surfactants and emulsifiers, and human exposure to some PFCs is widespread

Root Suberin Forms an Extracellular Barrier That Affects Water Relations and Mineral Nutrition in Arabidopsis

Though central to our understanding of how roots perform their vital function of scavenging water and solutes from the soil, no direct genetic evidence currently exists to support the foundational model that suberin acts to form a chemical barrier limiting the extracellular, or apoplastic, transport of water and solutes in plant roots. Using the newly characterized enhanced suberin1 (esb1) mutant, we established a connection in Arabidopsis thaliana between suberin in the root and both water movement through the plant and solute accumulation in the shoot. Esb1 mutants, characterized by increased root suberin, were found to have reduced day time transpiration rates and increased water-use efficiency during their vegetative growth period. Furthermore, these changes in suberin and water transport were associated with decreases in the accumulation of Ca, Mn, and Zn and increases in the accumulation of Na, S, K, As, Se, and Mo in the shoot. Here, we present direct genetic evidence establishing that suberin in the roots plays a critical role in controlling both water and mineral ion uptake and transport to the leaves. The changes observed in the elemental accumulation in leaves are also interpreted as evidence that a significant component of the radial root transport of Ca, Mn, and Zn occurs in the apoplast

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Vision, challenges and opportunities for a Plant Cell Atlas

With growing populations and pressing environmental problems, future economies will be increasingly plant-based. Now is the time to reimagine plant science as a critical component of fundamental science, agriculture, environmental stewardship, energy, technology and healthcare. This effort requires a conceptual and technological framework to identify and map all cell types, and to comprehensively annotate the localization and organization of molecules at cellular and tissue levels. This framework, called the Plant Cell Atlas (PCA), will be critical for understanding and engineering plant development, physiology and environmental responses. A workshop was convened to discuss the purpose and utility of such an initiative, resulting in a roadmap that acknowledges the current knowledge gaps and technical challenges, and underscores how the PCA initiative can help to overcome them.</jats:p

Regulation of Fat Cell Mass by Insulin in Drosophila melanogaster▿

A phylogenetically conserved response to nutritional abundance is an increase in insulin signaling, which initiates a set of biological responses dependent on the species. Consequences of augmented insulin signaling include developmental progression, cell and organ growth, and the storage of carbohydrates and lipids. Here, we address the evolutionary origins of insulin's positive effects on anabolic lipid metabolism by selectively modulating insulin signaling in the fat body of the fruit fly, Drosophila melanogaster. Analogous to the actions of insulin in higher vertebrates, those in Drosophila include expansion of the insect fat cell mass both by increasing the adipocyte number and by promoting lipid accumulation. The ability of insulin to accomplish the former depends on its capacity to bring about phosphorylation and inhibition of the transcription factor Drosophila FOXO (dFOXO) and the serine/threonine protein kinase shaggy, the fly ortholog of glycogen synthase kinase 3 (GSK3). Increasing the amount of triglyceride per cell also depends on the phosphorylation of shaggy but is independent of dFOXO. Thus, the findings of this study provide evidence that the control of fat mass by insulin is a conserved process and place dFOXO and shaggy/GSK3 downstream of the insulin receptor in controlling adipocyte cell number and triglyceride storage, respectively

The Ricochet-Scepter Technique: A Balloon-Assisted Technique to Achieve Outflow Access During Pipeline-Assisted Coil Embolization of a Near-Giant Internal Carotid Artery Ophthalmic Aneurysm.

BACKGROUND: Flow diversion with or without coil embolization has become the first-line treatment for large or giant paraclinoid internal carotid artery intracranial aneurysms. Oftentimes, these sizable aneurysms impose anatomical challenges to endovascular treatment through limiting both distal outflow access and maintenance of distal vessel purchase during catheter reduction, which are required for successful stent placement. Various strategies to obtain and maintain distal access within the parent vessel have been described previously; however, new techniques may need to be employed when more standard maneuvers fail. CASE DESCRIPTION: This paper depicts a case of successful flow diversion of a near-giant internal carotid artery ophthalmic aneurysm in a middle-aged female patient using a balloon-assisted technique, designated the Ricochet-Scepter technique, to achieve distal outflow access followed by secondary system reduction via a stent retriever after standard maneuvers had failed. CONCLUSIONS: Giant, wide-neck aneurysms present treatment challenges that may require using adjunctive devices and advanced endovascular techniques. When routine strategies for gaining distal outflow access fail, the Ricochet-Scepter technique is a viable option for achieving distal access

The majority of ruptured aneurysms are small with low rupture risk scores.

BACKGROUND: Understanding the rupture risk of unruptured intracranial aneurysms has important clinical implications given the morbidity and mortality associated with subarachnoid hemorrhage (SAH). The ISUIA, UCAS, and PHASES studies provide rupture risk calculations. OBJECTIVE: We apply the risk calculations to a series ruptured intracranial aneurysms to assess the rupture risk for each aneurysm (had they been discovered in the unruptured state). METHODS: This is a retrospective study of 246 patients with SAH from a ruptured saccular aneurysm. The ISUIA, UCAS, and PHASES calculators were applied to each patient/aneurysm to demonstrate a theoretical annual risk of rupture dichotomized by aneurysm location. RESULTS: The average diameter of the aneurysms was 5.5 ± 3.1 mm. Three quarters (75%) of the aneurysms measured48.8% were(Acomm) was the most common location of rupture (24.7%). Posterior communicating artery aneurysms (Pcomm) were the third most common at 16.2%. The average ISUIA 1-year rupture risk was 0.46 ± 0.008%. The average UCAS 1-year rupture risk was 0.93% ± 0.01. The annualPHASESrupture risk was0.32 ± 0.004%. The highest risk locations were the vertebral artery (up to 10.3% per year) and superior cerebellar artery (up to 2.7% per year). On average, Acomm aneurysms had 1 year risk no higher than 1.1% and Pcomm aneurysms no higher than 1.2% per year. CONCLUSION: We observed that in a small retrospective series of ruptured aneurysms, the majority wereaneurysms, had they been discovered in the unruptured state, is low