Construction of membrane-bound artificial cells using microfluidics: a new frontier in bottom-up synthetic biology

The quest to construct artificial cells from the bottom-up using simple building blocks has received much attention over recent decades and is one of the grand challenges in synthetic biology. Cell mimics that are encapsulated by lipid membranes are a particularly powerful class of artificial cells due to their biocompatibility and the ability to reconstitute biological machinery within them. One of the key obstacles in the field centres on the following: how can membrane-based artificial cells be generated in a controlled way and in high-throughput? In particular, how can they be constructed to have precisely defined parameters including size, biomolecular composition and spatial organization? Microfluidic generation strategies have proved instrumental in addressing these questions. This article will outline some of the major principles underpinning membrane-based artificial cells and their construction using microfluidics, and will detail some recent landmarks that have been achieved

Microfluidic generation of networked droplet collections and lipid membrane constructs

We report on microfluidic strategies to generate several multi-compartment membrane-based structures, including droplet interface bilayer networks and multi-compartment vesicles. These developments allow the current status quo— where microdroplets are used as isolated vessels— to be changed. By linking droplets together with lipid membranes, higher order systems can be generated, with particular ramifications for bottom-up synthetic biology and for functional droplet-based microreactors and biodevices

The Marginal Cost of Frailty Among Medicare Patients on Hemodialysis.

Introduction:Dialysis patients incur disproportionately high costs compared with other Medicare beneficiaries. Care for frail individuals may be even more costly. We examined the extent to which frailty contributes to higher costs among dialysis patients. Methods:We used ACTIVE/ADIPOSE (A Cohort to Investigate the Value of Exercise/Analyses Designed to Investigate the Paradox of Obesity and Survival in ESRD) enrollees (adult hemodialysis patients evaluated from June 2009 to August 2011) in a retrospective cohort analysis. Individuals using Medicare as the primary payer were included. Fried's frailty phenotype was evaluated at baseline, 12, and 24 months. Costs were derived from linkage with the US Renal Data System (USRDS) and Medicare claims data. We used generalized estimating equations (GEEs) incorporating time-updated frailty and costs to evaluate adjusted point estimates and the marginal cost associated with being frail. We also investigated if frail patients who died during the study incurred higher costs than those who survived. Results:Among 771 enrollees in ACTIVE/ADIPOSE, 425 met inclusion criteria. Mean age was 56 ± 13 years, body mass index (BMI) 29.2 ± 7.1 kg/m2, 42.4% were women, and 29.0% were frail at baseline. Over a mean follow-up of 2.3 years, frail individuals incurred 22% (95% confidence interval [CI] 9.6%-35.8%) higher costs compared with nonfrail individuals ($87,600 per patient per year [pppy], 95$71,800 pppy, 95% CI 64,800-79,600), the difference was driven primarily by higher inpatient expenditures. The difference between frail and nonfrail patients' inpatient expenditures was even more pronounced among those who died during the study compared with those who survived. Conclusions:Frail dialysis patients incur a significantly higher cost relative to their nonfrail counterparts, primarily driven by higher inpatient costs. Frail patients near end of life incur even higher costs

Welcome to the Farm

The purpose of this creative scholarship is to examine human relationships to Earth and the implications for a thriving future. This thesis studies the current environmental state of our planet, then looks at sustainability as a model for improving human and planetary health, and ends by visualizing a thriving future beyond sustainability in which we adopt a “caretaker” culture. The key to this trajectory is to untangle and dismantle colonial relationships with the planet and replace them with “caretaker” relationships - relationships rooted in love, honor, and reciprocity with environmental connection, while taking into account past, present, and future generations This thesis is a culmination of four years of coursework in environmental science, environmental studies, Indigenous Knowledge, and climate change. These courses included examples of how political divisions prevent climate action, colonial ideas stall progressive wilderness policy, and resource management decisions are made without sufficient community input. These issues have made me realize that cultural change is most urgently needed to solve or manage major environmental and social issues. To carry out this project, I utilized Western and non-Western concepts. I drew upon lessons learned across many of my courses and read several books and texts to prepare myself for the writing of this thesis. These texts include books, articles, essays, TED talks, and other sources that span environmental, social, economic, and cultural topics. These sources are listed by chapter in the bibliography at the end of this document. This project communicates to the world that how we live our relationship with the planet matters. Time and time again, the biggest obstacle to climate and environmental solutions is the lack of care for the planet. We need to reimagine our relationship with the planet everywhere and in every way. TRANSLATE with x English Arabic Hebrew Polish Bulgarian Hindi Portuguese Catalan Hmong Daw Romanian Chinese Simplified Hungarian Russian Chinese Traditional Indonesian Slovak Czech Italian Slovenian Danish Japanese Spanish Dutch Klingon Swedish English Korean Thai Estonian Latvian Turkish Finnish Lithuanian Ukrainian French Malay Urdu German Maltese Vietnamese Greek Norwegian Welsh Haitian Creole Persian TRANSLATE with COPY THE URL BELOW Back EMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster Portal Bac

The Role of Fatty Acids and Cigarette Smoke Toxicants in Cigarette Smoke-Induced Cardiovascular Disease

Young, healthy smokers have an increased risk of developing cardiovascular disease (CVD), but early identification of these individuals can prevent progression to more severe cardiovascular diseases like atherosclerosis, stroke, and heart attacks. However, methods developed to detect cardiovascular disease in its early stages are limited and very costly. The goal of this project is to identify biomarkers that can be tested in a single blood draw from smokers in order to both assess their risk of developing cardiovascular disease and identify possible therapeutic targets to prevent disease progression. The long term goals of this project are to investigate the association between CVD risk, aryl hydrocarbon receptor (AHR) activity, and polyunsaturated fatty acids (PUFAs) in smokers, and to elucidate the mechanisms of their contribution to cigarette smoke (CS)-induced vascular dysfunction. We have shown that AHR activity and α-linolenic acid (ALA, an n-3 PUFA) are potential biomarkers for CVD risk in young, healthy smokers. It is possible that the biomarkers identified in young, healthy smokers may serve not only as early identification of individuals most at risk of developing CVD, but also as biomarkers for future CVD risk in smokers with early stage CVD. As expected, the biomarkers identified in young, healthy smokers are different from biomarkers identified in older smokers with hypertension, a risk factor for development of CVD. In a second study conducted in subjects between 40 and 70 yrs old with physician-diagnosed hypertension. We found that ALA, which we previously demonstrated to predict flow-mediated dilation (FMD) in young, healthy smokers, is not associated with atherosclerotic cardiovascular disease (ASCVD) risk in smokers with preexisting hypertension. Nonetheless, we found that 13,14-dihydroxydocosapentaenoic acid (DiHDPA), along with 11- and 20-hydroxyeicosatetraenoic acid (HETE), predict ASCVD risk in smokers, whereas 14,15-epoxyeicosatetraenoic acid (EEQ), 13,14- and 16,17-epoxyeicosatetraenoic acid (EDP), and 16,17-DiHDPA predict ASCVD risk in non-smokers. These results suggest that the fatty acids identified in this study may be used to predict CVD risk in subjects with pre-existing CVD risk factors. In order to investigate the specific mechanisms through which n-3 PUFAs protect against CS-induced vascular dysfunction in humans, we generated a mouse model of CS-exposure that resembles what is seen in young, healthy smokers. We made the novel observation that although CS impairs nitric oxide (NO)-dependent flow-mediated dilation (FMD), an n-3 PUFA diet restores FMD by increasing NO-independent dilation. We also found that the vasoprotective properties of n-3 PUFAs may be, at least in part, due to its antioxidant properties and reduction of Cyp1a1 expression. These studies will contribute to the understanding of CVD progression in smokers and the mechanisms of how n-3 PUFAs protect against CS-induced CVD. In addition, these findings will continue to contribute to the development of biomarkers to detect patients at high CVD risk while they are at early stages of the disease

Microfluidic technologies for the synthesis and manipulation of biomimetic membranous nano-assemblies.

Microfluidics has been proposed as an attractive alternative to conventional bulk methods used in the generation of self-assembled biomimetic structures, particularly where there is a desire for more scalable production. The approach also allows for greater control over the self-assembly process, and parameters such as particle architecture, size, and composition can be finely tuned. Microfluidic techniques used in the generation of microscale assemblies (giant vesicles and higher-order multi-compartment assemblies) are fairly well established. These tend to rely on microdroplet templation, and the resulting structures have found use as comparmentalised motifs in artificial cells. Challenges in generating sub-micron droplets have meant that reconfiguring this approach to form nano-scale structures is not straightforward. This is beginning to change however, and recent technological advances have instigated the manufacture and manipulation of an increasingly diverse repertoire of biomimetic nano-assemblies, including liposomes, polymersomes, hybrid particles, multi-lamellar structures, cubosomes, hexosomes, nanodiscs, and virus-like particles. The following review will discuss these higher-order self-assembled nanostructures, including their biochemical and industrial applications, and techniques used in their production and analysis. We suggest ways in which existing technologies could be repurposed for the enhanced design, manufacture, and exploitation of these structures and discuss potential challenges and future research directions. By compiling recent advances in this area, it is hoped we will inspire future efforts toward establishing scalable microfluidic platforms for the generation of biomimetic nanoparticles of enhanced architectural and functional complexity

Manufacturing polymeric porous capsules

Polymeric porous capsules represent hugely promising systems that allow a size-selective through-shell material exchange with their surroundings. They have vast potential in applications ranging from drug delivery and chemical microreactors to artificial cell science and synthetic biology. Due to their porous core-shell structure, polymeric porous capsules possess an enhanced permeability that enables the exchange of small molecules while retaining larger compounds and macromolecules. The cross-capsule transfer of material is regulated by their pore size cut-off, which depends on the molecular composition and adopted fabrication method. This review outlines the main strategies adopted for manufacturing polymeric porous capsules to provide some practical guidance for designing polymeric capsules with controlled pore size

Bilayer networks within a hydrogel shell: A robust chassis for artificial cells and a platform for membrane studies

The ability to make artificial lipid bilayers compatible with a wide range of environments, and with sufficient structural rigidity for manual handling, would open up a wealth of opportunities for their more routine use in realworld applications. Although droplet interface bilayers (DIBs) have been demonstrated in a host of laboratory applications, from chemical logic to biosynthesis reaction vessels, their wider use is hampered by a lack of mechanical stability and the largely manual methods employed in their production. Multiphase microfluidics has enabled us to construct hierarchical triple emulsions with a semipermeable shell, in order to form robust, bilayer-bound, droplet networks capable of communication with their external surroundings. These constructs are stable in air, water, and oil environments and overcome a critical obstacle of achieving structural rigidity without compromising environmental interaction. This paves the way for practical application of artificial membranes or droplet networks in diverse areas such as medical applications, drug testing, biophysical studies and their use as synthetic cells