Robin Lovejoy

This article describes the Robin Lovejoy collection at the National Library of Australia.Australia Council, La Trobe University, National Library of Australia, Holding Redlich, Arts Victori

Murine Fig4 is dispensable for muscle development but required for muscle function

Abstract Background Phosphatidylinositol phosphates (PIPs) are low-abundance phospholipids that participate in a range of cellular processes, including cell migration and membrane traffic. PIP levels and subcellular distribution are regulated by a series of lipid kinases and phosphatases. In skeletal muscle, PIPs and their enzymatic regulators serve critically important functions exemplified by mutations of the PIP phosphatase MTM1 in myotubular myopathy (MTM), a severe muscle disease characterized by impaired muscle structure and abnormal excitation–contraction coupling. FIG4 functions as a PIP phosphatase that participates in both the synthesis and breakdown of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2). Mutation of FIG4 results in a severe neurodegenerative disorder in mice and a progressive peripheral polyneuropathy in humans. The effect of FIG4 mutation on skeletal muscle has yet to be examined. Methods Herein we characterize the impact of FIG4 on skeletal muscle development and function using the spontaneously occurring mouse mutant pale tremor (plt), a mouse line with a loss of function mutation in Fig4. Results In plt mice, we characterized abnormalities in skeletal muscle, including reduced muscle size and specific force generation. We also uncovered ultrastructural abnormalities and increased programmed cell death. Conversely, we detected no structural or functional abnormalities to suggest impairment of excitation–contraction coupling, a process previously shown to be influenced by PI(3,5)P2 levels. Conditional rescue of Fig4 mutation in neurons prevented overt muscle weakness and the development of obvious muscle abnormalities, suggesting that the changes observed in the plt mice were primarily related to denervation of skeletal muscle. On the basis of the ability of reduced FIG4 levels to rescue aspects of Mtmr2-dependent neuropathy, we evaluated the effect of Fig4 haploinsufficiency on the myopathy of Mtm1-knockout mice. Male mice with a compound Fig4 +/−/Mtm1 –/Y genotype displayed no improvements in muscle histology, muscle size or overall survival, indicating that FIG4 reduction does not ameliorate the Mtm1-knockout phenotype. Conclusions Overall, these data indicate that loss of Fig4 impairs skeletal muscle function but does not significantly affect its structural development.http://deepblue.lib.umich.edu/bitstream/2027.42/112676/1/13395_2013_Article_83.pd

Infrared Quasi Fixed Point Structure in Extended Yukawa Sectors and Application to R-parity Violation

We investigate one-loop renormalization group evolutions of extended sectors of Yukawa type couplings. It is shown that Landau Poles which usually provide necessary low energy upper bounds that saturate quickly with increasing initial value conditions, lead in some cases to the opposite behaviour: some of the low energy couplings decrease and become vanishingly small for increasingly large initial conditions. We write down the general criteria for this to happen in typical situations, highlighting a concept of {\sl repulsive} quasi-fixed points, and illustrate the case both within a two-Yukawa toy model as well as in the minimal supersymmetric standard model with R-parity violation. In the latter case we consider the theoretical upper bounds on the various couplings, identifying regimes where $\lambda_{kl3}, \lambda'_{kkk}, \lambda''_{3kl}$ are dynamically suppressed due to the Landau Pole. We stress the importance of considering a large number of couplings simultaneously. This leads altogether to a phenomenologically interesting seesaw effect in the magnitudes of the various R-parity violating couplings, complementing and in some cases improving the existing limits.Comment: Latex, 33 pages, 6 figure

Methamphetamine Use and Methicillin-Resistant Staphylococcus aureus Skin Infections

Drug use may be contributing to the spread of MRSA in a rural southeastern US community

Crowdsourcing Methods for Data Collection in Geophysics: State of the Art, Issues, and Future Directions

Data are essential in all areas of geophysics. They are used to better understand and manage systems, either directly or via models. Given the complexity and spatiotemporal variability of geophysical systems (e.g., precipitation), a lack of sufficient data is a perennial problem, which is exacerbated by various drivers, such as climate change and urbanization. In recent years, crowdsourcing has become increasingly prominent as a means of supplementing data obtained from more traditional sources, particularly due to its relatively low implementation cost and ability to increase the spatial and/or temporal resolution of data significantly. Given the proliferation of different crowdsourcing methods in geophysics and the promise they have shown, it is timely to assess the state‐of‐the‐art in this field, to identify potential issues and map out a way forward. In this paper, crowdsourcing‐based data acquisition methods that have been used in seven domains of geophysics, including weather, precipitation, air pollution, geography, ecology, surface water and natural hazard management are discussed based on a review of 162 papers. In addition, a novel framework for categorizing these methods is introduced and applied to the methods used in the seven domains of geophysics considered in this review. This paper also features a review of 93 papers dealing with issues that are common to data acquisition methods in different domains of geophysics, including the management of crowdsourcing projects, data quality, data processing and data privacy. In each of these areas, the current status is discussed and challenges and future directions are outlined

Function of a mutant ryanodine receptor (T4709M) linked to congenital myopathy

Abstract Physiological muscle contraction requires an intact ligand gating mechanism of the ryanodine receptor 1 (RyR1), the Ca2+-release channel of the sarcoplasmic reticulum. Some mutations impair the gating and thus cause muscle disease. The RyR1 mutation T4706M is linked to a myopathy characterized by muscle weakness. Although, low expression of the T4706M RyR1 protein can explain in part the symptoms, little is known about the function RyR1 channels with this mutation. In order to learn whether this mutation alters channel function in a manner that can account for the observed symptoms, we examined RyR1 channels isolated from mice homozygous for the T4709M (TM) mutation at the single channel level. Ligands, including Ca2+, ATP, Mg2+ and the RyR inhibitor dantrolene were tested. The full conductance of the TM channel was the same as that of wild type (wt) channels and a population of partial open (subconductive) states were not observed. However, two unique sub-populations of TM RyRs were identified. One half of the TM channels exhibited high open probability at low (100 nM) and high (50 μM) cytoplasmic [Ca2+], resulting in Ca2+-insensitive, constitutively high Po channels. The rest of the TM channels exhibited significantly lower activity within the physiologically relevant range of cytoplasmic [Ca2+], compared to wt. TM channels retained normal Mg2+ block, modulation by ATP, and inhibition by dantrolene. Together, these results suggest that the TM mutation results in a combination of primary and secondary RyR1 dysfunctions that contribute to disease pathogenesis

Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase

The Pyst1 and Pyst2 mRNAs encode closely related proteins, which are novel members of a family of dual-specificity MAP kinase phosphatases typified by CL100/MKP-1. Pyst1 is expressed constitutively in human skin fibroblasts and, in contrast to other members of this family of enzymes, its mRNA is not inducible by either stress or mitogens. Furthermore, unlike the nuclear CL100 protein, Pyst1 is localized in the cytoplasm of transfected Cos-1 cells. Like CL100/ MKP-1, Pyst1 dephosphorylates and inactivates MAP kinase in vitro and in vivo. In addition, Pyst1 is able to form a physical complex with endogenous MAP kinase in Cos-1 cells. However, unlike CL100, Pyst1 displays very low activity towards the stress-activated protein kinases (SAPKs) or RK/p38 in vitro, indicating that these kinases are not physiological substrates for Pyst1. This specificity is underlined by the inability of Pyst1 to block either the stress-mediated activation of the JNK-1 SAP kinase or RK/p38 in vivo, or to inhibit nuclear signalling events mediated by the SAP kinases in response to UV radiation. Our results provide the first evidence that the members of the MAP kinase family of enzymes are differentially regulated by dual-specificity phosphatases and also indicate that the MAP kinases may be regulated by different members of this family of enzymes depending on their subcellular location