Activation of type II calcium/calmodulin-dependent protein kinase by Ca^(2+)/calmodulin is inhibited by autophosphorylation of threonine within the calmodulin-binding domain

It is now well established that autophosphorylation of a threonine residue located next to each calmodulin-binding domain in the subunits of type II Ca^(2+)/calmodulin-dependent protein kinase causes the kinase to remain active, although at a reduced rate, after Ca^(2+) is removed from the reaction. This autophosphorylated form of the kinase is still sensitive to Ca2+/calmodulin, which is required for a maximum catalytic rate. After removal of Ca^(2+), new sites are autophosphorylated by the partially active kinase. Autophosphorylation of these sites abolishes sensitivity of the kinase to Ca^(2+)/calmodulin (Hashimoto, Y., Schworer, C. M., Colbran, R. J., and Soderling, T. R. (1987) J. Biol. Chem. 262, 8051-8055). We have identified two pairs of homologous residues, Thr^(305) and Ser^(314) in the alpha subunit and Thr^(306) and Ser^(315) in the beta subunit, that are autophosphorylated only after removal of Ca^(2+) from an autophosphorylation reaction. The sites were identified by direct sequencing of labeled tryptic phosphopeptides isolated by reverse-phase high pressure liquid chromatography. Thr^(305-306) is rapidly dephosphorylated by purified protein phosphatases 1 and 2A, whereas Ser^(314-315) is resistant to dephosphorylation. We have shown by selective dephosphorylation that the presence of phosphate on Thr^(305-306) blocks sensitivity of the kinase to Ca^(2+)/calmodulin. In contrast, the presence of phosphate on Ser^(314-315) is associated with an increase in the Kact for Ca^(2+)/calmodulin of only about 2-fold, producing a relatively small decrease in sensitivity to Ca^(2+)/calmodulin

Following the rivers: historical reconstruction of California voles Microtus californicus (Rodentia: Cricetidae) in the deserts of eastern California

The California vole, Microtus californicus, restricted to habitat patches where water is available nearly year-round, is a remnant of the mesic history of the southern Great Basin and Mojave deserts of eastern California. The history of voles in this region is a model for species-edge population dynamics through periods of climatic change. We sampled voles from the eastern deserts of California and examined variation in the mitochondrial cytb gene, three nuclear intron regions, and across 12 nuclear microsatellite markers. Samples are allocated to two mitochondrial clades: one associated with southern California and the other with central and northern California. The limited mtDNA structure largely recovers the geographical distribution, replicated by both nuclear introns and microsatellites. The most remote population, Microtus californicus scirpensis at Tecopa near Death Valley, was the most distinct. This population shares microsatellite alleles with both mtDNA clades, and both its northern clade nuclear introns and southern clade mtDNA sequences support a hybrid origin for this endangered population. The overall patterns support two major invasions into the desert through an ancient system of riparian corridors along streams and lake margins during the latter part of the Pleistocene followed by local in situ divergence subsequent to late Pleistocene and Holocene drying events. Changes in current water resource use could easily remove California voles from parts of the desert landscape

Introduction: Analytic, Continental and the question of a bridge

This is the peer reviewed version of the following article: Introduction: Analytic, Continental and the question of a bridge, which has been published in final form at 10.1177/1474885115582078. This article may be used for non-commercial purposes in accordance with SAGE’s Terms and Conditions for Self-Archiving.In philosophy and political theory, divisions come and go, but some persist despite beingobviously problematic. The analytic and Continental divide is one such division. Inpolitical philosophy and political theory, the division has been particularly pronounced.Analytic and Continental thinkers are divided not only over substantial issues but also over the very nature of political theorising. In spite of this fundamental nature, theorists often seem to assume that, as a division, the analytic/Continental divide requires no explanation. We suggest that, as a central division within political theory, and despite being acknowledged as problematic for quite some time, it has persisted because it has not been adequately examined. Once examined, the division turns out to be operationally weaker than it once was. In recent years, there has been a growing interest in engaging thinkers from the other side. This has been accompanied by a corresponding tendency, among both analytic and Continental philosophers and political thinkers, to reflect on the nature of their own tradition and ‘philosophy’. Both traditions have entered a self-conscious period of meta-reflection. Such questioning indicates the possibility of transformation within both groups, in the absence of settled frameworks and divisions. However, it is also clear that such signs are the beginning of the possibility of a new relation rather than a sign of the eclipse of the division. The continued institutional separation and the space between their respective philosophical vocabularies suggest that, while the time is ripe for work here, there is still much to be done

Development of Onchocerca volvulus in humanized NSG mice and detection of parasite biomarkers in urine and serum.

BACKGROUND: The study of Onchocerca volvulus has been limited by its host range, with only humans and non-human primates shown to be susceptible to the full life cycle infection. Small animal models that support the development of adult parasites have not been identified. METHODOLOGY/PRINCIPAL FINDINGS: We hypothesized that highly immunodeficient NSG mice would support the survival and maturation of O. volvulus and alteration of the host microenvironment through the addition of various human cells and tissues would further enhance the level of parasite maturation. NSG mice were humanized with: (1) umbilical cord derived CD34+ stem cells, (2) fetal derived liver, thymus and CD34+ stem cells or (3) primary human skeletal muscle cells. NSG and humanized NSG mice were infected with 100 O. volvulus infective larvae (L3) for 4 to 12 weeks. When necropsies of infected animals were performed, it was observed that parasites survived and developed throughout the infection time course. In each of the different humanized mouse models, worms matured from L3 to advanced fourth stage larvae, with both male and female organ development. In addition, worms increased in length by up to 4-fold. Serum and urine, collected from humanized mice for identification of potential biomarkers of infection, allowed for the identification of 10 O. volvulus-derived proteins found specifically in either the urine or the serum of the humanized O. volvulus-infected NSG mice. CONCLUSIONS/SIGNIFICANCE: The newly identified mouse models for onchocerciasis will enable the development of O. volvulus specific biomarkers, screening for new therapeutic approaches and potentially studying the human immune response to infection with O. volvulus

Noise characterization of an atomic magnetometer at sub-millihertz frequencies

Noise measurements have been carried out in the LISA bandwidth (0.1 mHz to 100 mHz) to characterize an all-optical atomic magnetometer based on nonlinear magneto-optical rotation. This was done in order to assess if the technology can be used for space missions with demanding low-frequency requirements like the LISA concept. Magnetometry for low-frequency applications is usually limited by $1/f$ noise and thermal drifts, which become the dominant contributions at sub-millihertz frequencies. Magnetic field measurements with atomic magnetometers are not immune to low-frequency fluctuations and significant excess noise may arise due to external elements, such as temperature fluctuations or intrinsic noise in the electronics. In addition, low-frequency drifts in the applied magnetic field have been identified in order to distinguish their noise contribution from that of the sensor. We have found the technology suitable for LISA in terms of sensitivity, although further work must be done to characterize the low-frequency noise in a miniaturized setup suitable for space missions.Comment: 11 pages, 12 figure

Nonlinear modal coupling in a high-stress doubly-clamped nanomechanical resonator

We present results from a study of the nonlinear intermodal coupling between different flexural vibrational modes of a single high-stress, doubly-clamped silicon nitride nanomechanical beam. The measurements were carried out at 100 mK and the beam was actuated using the magnetomotive technique. We observed the nonlinear behavior of the modes individually and also measured the coupling between them by driving the beam at multiple frequencies. We demonstrate that the different modes of the resonator are coupled to each other by the displacement induced tension in the beam, which also leads to the well known Duffing nonlinearity in doubly-clamped beams.Comment: 15 pages, 7 figure

Are infestations of Cymomelanodactylus killing Acropora cytherea in the Chagos archipelago?

Associations between branching corals and infaunal crabs are well known, mostly due to the beneficial effects of Trapezia and Tetralia crabs in protecting host corals from crown-of-thorns starfish (e.g., Pratchett et al. 2000) and/or sedimentation (Stewart et al. 2006). These crabs are obligate associates of live corals and highly prevalent across suitable coral hosts, with 1–2 individuals per colony (Patton 1994). Cymo melanodactylus (Fig. 1) are also prevalent in branching corals, mostly Acropora, and are known to feed on live coral tissue, but are generally found in low abundance (<3 per colony) and do not significantly affect their host corals (e.g., Patton 1994). In the Chagos archipelago, however, infestations of Cymo melanodactylus were found on recently dead and dying colonies of Acropora cytherea

Optimised configuration of sensors for fault tolerant control of an electro-magnetic suspension system

For any given system the number and location of sensors can affect the closed-loop performance as well as the reliability of the system. Hence, one problem in control system design is the selection of the sensors in some optimum sense that considers both the system performance and reliability. Although some methods have been proposed that deal with some of the aforementioned aspects, in this work, a design framework dealing with both control and reliability aspects is presented. The proposed framework is able to identify the best sensor set for which optimum performance is achieved even under single or multiple sensor failures with minimum sensor redundancy. The proposed systematic framework combines linear quadratic Gaussian control, fault tolerant control and multiobjective optimisation. The efficacy of the proposed framework is shown via appropriate simulations on an electro-magnetic suspension system

Identifying Agile Requirements Engineering Patterns in Industry

Agile Software Development (ASD) is gaining in popularity in today´s business world. Industry is adopting agile methodologies both to accelerate value delivery and to enhance the ability to deal with changing requirements. However, ASD has a great impact on how Requirements Engineering (RE) is carried out in agile environments. The integration of Human-Centered Design (HCD) plays an important role due to the focus on user and stakeholder involvement. To this end, we aim to introduce agile RE patterns as main objective of this paper. On the one hand, we will describe our pattern mining process based on empirical research in literature and industry. On the other hand, we will discuss our results and provide two examples of agile RE patterns. In sum, the pattern mining process identifies 41 agile RE patterns. The accumulated knowledge will be shared by means of a web application.Ministerio de Economía y Competitividad TIN2013-46928-C3-3-RMinisterio de Economía y Competitividad TIN2016-76956-C3-2-RMinisterio de Economía y Competitividad TIN2015-71938-RED