An air-liquid interphase approach for modeling the early embryo-maternal contact zone

We developed an air-liquid interphase culture procedure for mammalian oviduct epithelial cells leading to the formation of functional epithelial tissues, which generate oviduct fluid surrogates. These in vitro oviduct epithelia can be co-cultured with living zygotes and enable embryonic development up to the blastocyst stage without addition of embryo culture medium. The described strategy is broadly applicable to analyze early embryo-maternal interactions under standardized in vitro conditions

Backbone-driven host-dopant miscibility modulates molecular doping in NDI conjugated polymers

Molecular doping is the key to enabling organic electronic devices, however, the design strategies to maximize doping efficiency demands further clarity and comprehension. Previous reports focus on the effect of the side chains, but the role of the backbone is still not well understood. In this study, we synthesize a series of NDI-based copolymers with bithiophene, vinylene, and acetylenic moieties (P1G, P2G, and P3G, respectively), all containing branched triethylene glycol side chains. Using computational and experimental methods, we explore the impact of the conjugated backbone using three key parameters for doping in organic semiconductors: energy levels, microstructure, and miscibility. Our experimental results show that P1G undergoes the most efficient n-type doping owed primarily to its higher dipole moment, and better host–dopant miscibility with N-DMBI. In contrast, P2G and P3G possess more planar backbones than P1G, but the lack of long-range order, and poor host–dopant miscibility limit their doping efficiency. Our data suggest that backbone planarity alone is not enough to maximize the electrical conductivity (σ) of n-type doped organic semiconductors, and that backbone polarity also plays an important role in enhancing σ via host–dopant miscibility. Finally, the thermoelectric properties of doped P1G exhibit a power factor of 0.077 μW m−1 K−2, and ultra-low in-plane thermal conductivity of 0.13 W m−1K−1 at 5 mol% of N-DMBI, which is among the lowest thermal conductivity values reported for n-type doped conjugated polymers

Space Tethers: Design Criteria

This document is prepared to provide a systematic process for the selection of tethers for space applications. Criteria arc provided for determining the strength requirement for tether missions and for mission success from tether severing due to micrometeoroids and orbital debris particle impacts. Background information of materials for use in space tethers is provided, including electricity-conducting tethers. Dynamic considerations for tether selection is also provided. Safety, quality, and reliability considerations are provided for a tether project

Topology and Ground State Control In Open-Shell Donor-Acceptor Conjugated Polymers

Donor-acceptor (DA) conjugated polymers (CPs) with narrow bandgaps and open-shell (diradical) character represent an emerging class of materials whose rich behavior emanates from their collective electronic properties and diminished electron pairing. However, the structural and electronic heterogeneities that define these materials complicate bandgap control at low energies and connections linking topology, exchange interactions, and (opto)electronic functionality remain nascent. To address these challenges, we demonstrate structurally rigid and strongly π-conjugated copolymers comprised of a solubilizing thiadiazoloquinoxaline acceptor and cyclopenta[2,1-b:3,4-b′]dithiophene or dithieno[3,2-b:2′,3′-d]thiophene donors. Atom-specific substitution modulates local aromatic character within the donor resulting in dramatic differences in structural, physicochemical, electronic, and magnetic properties of the polymers. These long-range π-mediated interactions facilitate control between low-spin aromatic and high-spin quinoidal forms. This work provides a strategy to understand the evolution of the electronic structure within DA CPs, control the ground state spin multiplicity, tune spin-spin interactions, and articulate the emergence of their novel properties

A Mitochondrial Polymorphism Alters Immune Cell Metabolism and Protects Mice from Skin Inflammation

Several genetic variants in the mitochondrial genome (mtDNA), including ancient polymorphisms, are associated with chronic inflammatory conditions, but investigating the functional consequences of such mtDNA polymorphisms in humans is challenging due to the influence of many other polymorphisms in both mtDNA and the nuclear genome (nDNA). Here, using the conplastic mouse strain B6-mtFVB, we show that in mice, a maternally inherited natural mutation (m.7778G > T) in the mitochondrially encoded gene ATP synthase 8 (mt-Atp8) of complex V impacts on the cellular metabolic profile and effector functions of CD4+ T cells and induces mild changes in oxidative phosphorylation (OXPHOS) complex activities. These changes culminated in significantly lower disease susceptibility in two models of inflammatory skin disease. Our findings provide experimental evidence that a natural variation in mtDNA influences chronic inflammatory conditions through alterations in cellular metabolism and the systemic metabolic profile without causing major dysfunction in the OXPHOS system

C-Peptide Increases Na,K-ATPase Expression via PKC- and MAP Kinase-Dependent Activation of Transcription Factor ZEB in Human Renal Tubular Cells

Replacement of proinsulin C-peptide in type 1 diabetes ameliorates nerve and kidney dysfunction, conditions which are associated with a decrease in Na,K-ATPase activity. We determined the molecular mechanism by which long term exposure to C-peptide stimulates Na,K-ATPase expression and activity in primary human renal tubular cells (HRTC) in control and hyperglycemic conditions.HRTC were cultured from the outer cortex obtained from patients undergoing elective nephrectomy. Ouabain-sensitive rubidium ((86)Rb(+)) uptake and Na,K-ATPase activity were determined. Abundance of Na,K-ATPase was determined by Western blotting in intact cells or isolated basolateral membranes (BLM). DNA binding activity was determined by electrical mobility shift assay (EMSA). Culturing of HRTCs for 5 days with 1 nM, but not 10 nM of human C-peptide leads to increase in Na,K-ATPase α(1)-subunit protein expression, accompanied with increase in (86)Rb(+) uptake, both in normal- and hyperglycemic conditions. Na,K-ATPase α(1)-subunit expression and Na,K-ATPase activity were reduced in BLM isolated from cells cultured in presence of high glucose. Exposure to1 nM, but not 10 nM of C-peptide increased PKCε phosphorylation as well as phosphorylation and abundance of nuclear ERK1/2 regardless of glucose concentration. Exposure to 1 nM of C-peptide increased DNA binding activity of transcription factor ZEB (AREB6), concomitant with Na,K-ATPase α(1)-subunit mRNA expression. Effects of 1 nM C-peptide on Na,K-ATPase α(1)-subunit expression and/or ZEB DNA binding activity in HRTC were abolished by incubation with PKC or MEK1/2 inhibitors and ZEB siRNA silencing.Despite activation of ERK1/2 and PKC by hyperglycemia, a distinct pool of PKCs and ERK1/2 is involved in regulation of Na,K-ATPase expression and activity by C-peptide. Most likely C-peptide stimulates sodium pump expression via activation of ZEB, a transcription factor that has not been previously implicated in C-peptide-mediated signaling. Importantly, only physiological concentrations of C-peptide elicit this effect

Advising overweight persons about diet and physical activity in primary health care: Lithuanian health behaviour monitoring study

BACKGROUND: Obesity is a globally spreading health problem. Behavioural interventions aimed at modifying dietary habits and physical activity patterns are essential in prevention and management of obesity. General practitioners (GP) have a unique opportunity to counsel overweight patients on weight control. The purpose of the study was to assess the level of giving advice on diet and physical activity by GPs using the data of Lithuanian health behaviour monitoring among adult population. METHODS: Data from cross-sectional postal surveys of 2000, 2002 and 2004 were analysed. Nationally representative random samples were drawn from the population register. Each sample consisted of 3000 persons aged 20–64 years. The response rates were 74.4% in 2000, 63.4% in 2002 and 61.7% in 2004. Self-reported body weight and height were used to calculate body mass index (BMI). Information on advising in primary health care was obtained asking whether GP advised overweight patients to change dietary habits and to increase physical activity. The odds of receiving advice on diet and physical activity were calculated using multiple logistic regression analyses according to a range of sociodemographic variables, perceived health, number of visits to GPs and body-weight status. RESULTS: Almost a half of respondents were overweight or obese. Only one fourth of respondents reported that they were advised to change diet. The proportion of persons who received advice on physical activity was even lower. The odds of receiving advice increased with age. A strong association was found between perceived health and receiving advice. The likelihood of receiving advice was related to BMI. GPs were more likely to give advice when BMI was high. More than a half of obese respondents (63.3%) reported that they had tried to lose weight. The association between receiving advice and self-reported attempt to lose weight was found. CONCLUSION: The low rate of dietary and physical activity advice reported by overweight patients implies that more lifestyle counselling should be provided in primary health care. There is an obvious need for improved training and education of GPs in counselling of overweight patients focusing on methods of giving dietary and physical activity advice