Retinal pigment epithelial cells mitigate the effects of complement attack by endocytosis of C5b-9

Retinal pigment epithelial (RPE) cell death is a hallmark of age-related macular degeneration. The alternative pathway of complement activation is strongly implicated in RPE cell dysfunction and loss in age-related macular degeneration; therefore, it is critical that RPE cells use molecular strategies to mitigate the potentially harmful effects of complement attack. We show that the terminal complement complex C5b-9 assembles rapidly on the basal surface of cultured primary porcine RPE cells but disappears over 48 h without any discernable adverse effects on the cells. However, in the presence of the dynamin inhibitor dynasore, C5b-9 was almost completely retained at the cell surface, suggesting that, under normal circumstances, it is eliminated via the endocytic pathway. In support of this idea, we observed that C5b-9 colocalizes with the early endosome marker EEA1 and that, in the presence of protease inhibitors, it can be detected in lysosomes. Preventing the endocytosis of C5b-9 by RPE cells led to structural defects in mitochondrial morphology consistent with cell stress. We conclude that RPE cells use the endocytic pathway to prevent the accumulation of C5b-9 on the cell surface and that processing and destruction of C5b-9 by this route are essential for RPE cell survival

Point-of-Care Testing for Pharyngitis in the Pharmacy.

Pharyngitis (also known as sore throat) is a common, predominately viral, self-limiting condition which can be symptomatically managed without antibiotic treatment. Inappropriate antibiotic use for pharyngitis contributes to the development and spread of antibiotic resistance. However, a small proportion of sore throats caused by group A streptococcal (GAS) infection may benefit from the provision of antibiotics. Establishing the cause of infection is therefore an important step in effective antibiotic stewardship. Point-of-care (POC) tests, where results are available within minutes, can distinguish between viral and GAS pharyngitis and can therefore guide treatment in primary healthcare settings such as community pharmacies, which are often the first point of contact with the healthcare system. In this opinion article, the evidence for the use of POC testing in the community pharmacy has been discussed. Evidence suggests that pharmacy POC testing can promote appropriate antibiotic use and reduce the need for general practitioner consultations. Challenges to implementation include cost, training and 'who prescribes', with country and regional differences presenting a particular issue. Despite these challenges, POC testing for pharyngitis has become widely available in pharmacies in some countries and may represent a strategy to contain antibiotic resistance and contribute to antimicrobial stewardship

Parity and the Spin-Statistics Connection

The spin-statistics connection is obtained in a simple and elementary way for general causal fields by using the parity operation to exchange spatial coordinates in the scalar product of a locally commuting field operator, evaluated at position x, with the same field operator evaluated at -x, at equal times.Comment: 6 page

Traffic of Kv4 K+ channels mediated by KChIP1 is via a novel post-ER vesicular pathway

The traffic of Kv4 K+ channels is regulated by the potassium channel interacting proteins (KChIPs). Kv4.2 expressed alone was not retained within the ER, but reached the Golgi complex. Coexpression of KChIP1 resulted in traffic of the channel to the plasma membrane, and traffic was abolished when mutations were introduced into the EF-hands with channel captured on vesicular structures that colocalized with KChIP1(2–4)-EYFP. The EF-hand mutant had no effect on general exocytic traffic. Traffic of Kv4.2 was coat protein complex I (COPI)–dependent, but KChIP1-containing vesicles were not COPII-coated, and expression of a GTP-loaded Sar1 mutant to block COPII function more effectively inhibited traffic of vesicular stomatitis virus glycoprotein (VSVG) than did KChIP1/Kv4.2 through the secretory pathway. Therefore, KChIP1seems to be targeted to post-ER transport vesicles, different from COPII-coated vesicles and those involved in traffic of VSVG. When expressed in hippocampal neurons, KChIP1 co-distributed with dendritic Golgi outposts; therefore, the KChIP1 pathway could play an important role in local vesicular traffic in neurons

Repartnering: the relevance of parenthood and gender to cohabitation and remarriage among the formerly married

This paper is an exploratory analysis of the impact of current and anticipated parenthood on cohabitation and remarriage among those formerly living in marriage-type relationships. The focus on children is embedded within a broader analysis of repartnering which takes account of other factors, including gender. Quantitative and qualitative analyses are used, with a multivariate analysis of repartnering patterns, using data from the General Household Survey, being complementedby in-depth interview data examining the attitudes of the formerly married to future relationships. The paper demonstrates that parenthood has a statistically significant effect on the likelihood of formerly married women repartnering, with a higher number of children being associated with a lower probability of repartnering. The presence of children can work against repartnering in a variety of ways. Children place demands on their parents and can deter or object to potential partners. Parents may see their parental role as more important than, and a barrier to, new relationships. However, mothers are typically looking for partners for themselves rather than fathers for their children. Among formerly married people without children, the desire to become a parent encourages repartnering. The paper concludes that parenthood should be a key consideration in analyses of repartnering

On the spin-statistics connection in curved spacetimes

The connection between spin and statistics is examined in the context of locally covariant quantum field theory. A generalization is proposed in which locally covariant theories are defined as functors from a category of framed spacetimes to a category of $*$-algebras. This allows for a more operational description of theories with spin, and for the derivation of a more general version of the spin-statistics connection in curved spacetimes than previously available. The proof involves a "rigidity argument" that is also applied in the standard setting of locally covariant quantum field theory to show how properties such as Einstein causality can be transferred from Minkowski spacetime to general curved spacetimes.Comment: 17pp. Contribution to the proceedings of the conference "Quantum Mathematical Physics" (Regensburg, October 2014

Ground states of two-dimensional ±\pmJ Edwards-Anderson spin glasses

We present an exact algorithm for finding all the ground states of the two-dimensional Edwards-Anderson $\pm J$ spin glass and characterize its performance. We investigate how the ground states change with increasing system size and and with increasing antiferromagnetic bond ratio $x$. We find that that some system properties have very large and strongly non-Gaussian variations between realizations.Comment: 15 pages, 21 figures, 2 tables, uses revtex4 macro