Actin filament assembly by bacterial factors VopL/F: Which end is up?

Competing models have been proposed for actin filament nucleation by the bacterial proteins VopL/F. In this issue, Burke et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201608104) use direct observation to demonstrate that VopL/F bind the barbed and pointed ends of actin filaments but only nucleate new filaments from the pointed end

Do Environmentally Friendly Companies Outperform Environmentally Unfriendly Companies in Financial Markets? An Analysis of Financial Performance & Corporate Social Responsibility

Over the last century, the ideology regarding the relationship between humans and the natural world has shifted from a period of major exploitation to a time of conservation and appreciation. Recent catastrophic events such as Hurricane Katrina in 2005, a result of sea level rise and wetland degradation, have really opened the public\u27s eyes to the negative impacts that humans have on the environment, and what will come if we do not change our ways. Implementing sustainability practices has become a norm, if not a necessity, in the corporate world if companies wish to prosper. Using cross-sectional data from Newsweek\u27s 2015 Green Rankings List and a variety of online financial sources, this study examines the relationship between corporate sustainability efforts, specifically green efforts as reported by Newsweek, and performance in financial markets. Companies may strive for sustainability for its own sake, but they may also hope that their efforts will be rewarded by better financial performance and recognition by the consuming and investing public. To get at the former, this study examines the relationship between Newsweek\u27s Green Ranking and a variety of financial indicators. To address the public perception, using a survey conducted within the Union College community, this study will evaluate how well recognized Newsweek\u27s 2015 Green Rankings environmentally friendly companies are among people with various demographic backgrounds, particularly the millennial age group. The survey will also evaluate how people perceive a company compared to its actual efforts as measured by Newsweek. If there is a relationship between sustainability efforts and financial performance, or public perception, then companies should incorporate environmentally friendly practices into day-to-day operations and learn to market these developments in a way that connects with consumers

Can the care of the patient with a cup arthroplasty of the hip be used as a core experience for the student of nursing in orthopedics and how effective a teaching plan for students in orthopedics can be built about the care of one type patient, namely the patient with a cup arthroplasty of the hip?

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Drosophila Cappuccino alleles provide insight into formin mechanism and role in oogenesis.

During Drosophila development, the formin actin nucleator Cappuccino (Capu) helps build a cytoplasmic actin mesh throughout the oocyte. Loss of Capu leads to female sterility, presumably because polarity determinants fail to localize properly in the absence of the mesh. To gain deeper insight into how Capu builds this actin mesh, we systematically characterized seven capu alleles, which have missense mutations in Capu's formin homology 2 (FH2) domain. We report that all seven alleles have deleterious effects on fly fertility and the actin mesh in vivo but have strikingly different effects on Capu's biochemical activity in vitro. Using a combination of bulk and single- filament actin-assembly assays, we find that the alleles differentially affect Capu's ability to nucleate and processively elongate actin filaments. We also identify a unique "loop" in the lasso region of Capu's FH2 domain. Removing this loop enhances Capu's nucleation, elongation, and F-actin-bundling activities in vitro. Together our results on the loop and the seven missense mutations provides mechanistic insight into formin function in general and Capu's role in the Drosophila oocyte in particular

Autoinhibition of the formin Cappuccino in the absence of canonical autoinhibitory domains.

Formins are a conserved family of proteins known to enhance actin polymerization. Most formins are regulated by an intramolecular interaction. The Drosophila formin, Cappuccino (Capu), was believed to be an exception. Capu does not contain conserved autoinhibitory domains and can be regulated by a second protein, Spire. We report here that Capu is, in fact, autoinhibited. The N-terminal half of Capu (Capu-NT) potently inhibits nucleation and binding to the barbed end of elongating filaments by the C-terminal half of Capu (Capu-CT). Hydrodynamic analysis indicates that Capu-NT is a dimer, similar to the N-termini of other formins. These data, combined with those from circular dichroism, suggest, however, that it is structurally distinct from previously described formin inhibitory domains. Finally, we find that Capu-NT binds to a site within Capu-CT that overlaps with the Spire-binding site, the Capu-tail. We propose models for the interaction between Spire and Capu in light of the fact that Capu can be regulated by autoinhibition

Spire stimulates nucleation by Cappuccino and binds both ends of actin filaments.

The actin nucleators Spire and Cappuccino synergize to promote actin assembly, but the mechanism of their synergy is controversial. Together these proteins promote the formation of actin meshes, which are conserved structures that regulate the establishment of oocyte polarity. Direct interaction between Spire and Cappuccino is required for oogenesis and for in vitro synergistic actin assembly. This synergy is proposed to be driven by elongation and the formation of a ternary complex at filament barbed ends, or by nucleation and interaction at filament pointed ends. To mimic the geometry of Spire and Cappuccino in vivo, we immobilized Spire on beads and added Cappuccino and actin. Barbed ends, protected by Cappuccino, grow away from the beads while pointed ends are retained, as expected for nucleation-driven synergy. We found that Spire is sufficient to bind barbed ends and retain pointed ends of actin filaments near beads and we identified Spire's barbed-end binding domain. Loss of barbed-end binding increases nucleation by Spire and synergy with Cappuccino in bulk pyrene assays and on beads. Importantly, genetic rescue by the loss-of-function mutant indicates that barbed-end binding is not necessary for oogenesis. Thus, increased nucleation is a critical element of synergy both in vitro and in vivo

The impact of circadian rhythms on medical imaging and radiotherapy regimes for the paediatric patient

Daily rhythmic changes are found in cellular events in cell cycle, DNA repair, apoptosis and angiogenesis in both normal and tumour tissue, as well as in enzymatic activity and drug metabolism. In this paper, we hypothesize that circadian rhythms need to be considered in radiation protection and optimization in personalized medicine, especially for paediatric care. The sensitivity of the eye lens to ionizing radiation makes the case for limiting damage to the lens epithelium by planning medical radio-imaging procedures for the afternoon, rather than the morning. Equally, the tumour and normal tissue response to radiotherapy is also subject to diurnal variation enabling optimization of time of treatment

Learning a Static Analyzer from Data

To be practically useful, modern static analyzers must precisely model the effect of both, statements in the programming language as well as frameworks used by the program under analysis. While important, manually addressing these challenges is difficult for at least two reasons: (i) the effects on the overall analysis can be non-trivial, and (ii) as the size and complexity of modern libraries increase, so is the number of cases the analysis must handle. In this paper we present a new, automated approach for creating static analyzers: instead of manually providing the various inference rules of the analyzer, the key idea is to learn these rules from a dataset of programs. Our method consists of two ingredients: (i) a synthesis algorithm capable of learning a candidate analyzer from a given dataset, and (ii) a counter-example guided learning procedure which generates new programs beyond those in the initial dataset, critical for discovering corner cases and ensuring the learned analysis generalizes to unseen programs. We implemented and instantiated our approach to the task of learning JavaScript static analysis rules for a subset of points-to analysis and for allocation sites analysis. These are challenging yet important problems that have received significant research attention. We show that our approach is effective: our system automatically discovered practical and useful inference rules for many cases that are tricky to manually identify and are missed by state-of-the-art, manually tuned analyzers