‘The function of commerce warfare in an Anglo-German conflict to 1914’

The origins of the Great War of 1914-18 are the subject of continuing debate. The maritime aspects are no less complex with long-running arguments about the cogency of the strategies devised by the nations with substantial navies for the achieving of power at sea.

Determinants of Blood Pressure Response to Low‐Salt Intake in a Healthy Adult Population

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88057/1/j.1751-7176.2011.00523.x.pd

PP1 and PP2A use opposite phospho-dependencies to control distinct processes at the kinetochore

PP1 and PP2A-B56 are major serine/threonine phosphatase families that achieve specificity by colocalizing with substrates. At the kinetochore, however, both phosphatases localize to an almost identical molecular space and yet they still manage to regulate unique pathways and processes. By switching or modulating the positions of PP1/PP2A-B56 at kinetochores, we show that their unique downstream effects are not due to either the identity of the phosphatase or its precise location. Instead, these phosphatases signal differently because their kinetochore recruitment can be either inhibited (PP1) or enhanced (PP2A) by phosphorylation inputs. Mathematical modeling explains how these inverse phospho-dependencies elicit unique forms of cross-regulation and feedback, which allows otherwise indistinguishable phosphatases to produce distinct network behaviors and control different mitotic processes. Furthermore, our genome-wide analysis suggests that these major phosphatase families may have evolved to respond to phosphorylation inputs in opposite ways because many other PP1 and PP2A-B56-binding motifs are also phospho-regulated

Using explicit knowledge models and best practice guidelines to improve humanitarian outcomes through the development of a knowledge tool for international health workers

This study attempts to improve Red Cross health workers’ access and use of information to improve decision making processes through understanding the deficiencies and limitations that currently exist within the Red Cross movement around knowledge management. The development of mobile computing and communication devices is transforming how aid organisations collect, use and transform data into actionable knowledge. A portable reference resource has been developed for humanitarian health workers along with a proposed modified decision-making framework

A fine balancing act:a delicate kinase-phosphatase equilibrium that protects against chromosomal instability and cancer

Cancer cells rewire signalling networks to acquire specific hallmarks needed for their proliferation, survival, and dissemination throughout the body. Although this is often associated with the constitutive activation or inactivation of protein phosphorylation networks, there are other contexts when the dysregulation must be much milder. For example, chromosomal instability is a widespread cancer hallmark that relies on subtle defects in chromosome replication and/or division, such that these processes remain functional, but nevertheless error-prone. In this article, we will discuss how perturbations to the delicate kinase-phosphatase balance could lie at the heart of this type of dysregulation. In particular, we will explain how the two principle mechanisms that safeguard the chromosome segregation process rely on an equilibrium between at least two kinases and two phosphatases to function correctly. This balance is set during mitosis by a central complex that has also been implicated in chromosomal instability – the BUB1/BUBR1/BUB3 complex – and we will put forward a hypothesis that could link these two findings. This could be relevant for cancer treatment because most tumours have evolved by pushing the boundaries of chromosomal instability to the limit. If this involves subtle changes to the kinase-phosphatase equilibrium, then it may be possible to exacerbate these defects and tip tumour cells over the edge, whilst still maintaining the viability of healthy cells

BubR1 promotes Bub3-dependent APC/C inhibition during Spindle Assembly Checkpoint signaling.

The spindle assembly checkpoint (SAC) prevents premature sister chromatid separation during mitosis. Phosphorylation of unattached kinetochores by the Mps1 kinase promotes recruitment of SAC machinery that catalyzes assembly of the SAC effector mitotic checkpoint complex (MCC). The SAC protein Bub3 is a phospho-amino acid adaptor that forms structurally related stable complexes with functionally distinct paralogs named Bub1 and BubR1. A short motif ("loop") of Bub1, but not the equivalent loop of BubR1, enhances binding of Bub3 to kinetochore phospho-targets. Here, we asked whether the BubR1 loop directs Bub3 to different phospho-targets. The BubR1 loop is essential for SAC function and cannot be removed or replaced with the Bub1 loop. BubR1 loop mutants bind Bub3 and are normally incorporated in MCC in vitro but have reduced ability to inhibit the MCC target anaphase-promoting complex (APC/C), suggesting that BubR1:Bub3 recognition and inhibition of APC/C requires phosphorylation. Thus, small sequence differences in Bub1 and BubR1 direct Bub3 to different phosphorylated targets in the SAC signaling cascade