Calcium signalling links MYC to NUAK1

NUAK1 is a member of the AMPK-related family of kinases. Recent evidence suggests that NUAK1 is an important regulator of cell adhesion and migration, cellular and organismal metabolism, and regulation of TAU stability. As such, NUAK1 may play key roles in multiple diseases ranging from neurodegeneration to diabetes and metastatic cancer. Previous work revealed a crucial role for NUAK1 in supporting viability of tumour cells specifically when MYC is overexpressed. This role is surprising, given that NUAK1 is activated by the tumour suppressor LKB1. Here we show that, in tumour cells lacking LKB1, NUAK1 activity is maintained by an alternative pathway involving calcium-dependent activation of PKCα. Calcium/PKCα-dependent activation of NUAK1 supports engagement of the AMPK-TORC1 metabolic checkpoint, thereby protecting tumour cells from MYC-driven cell death, and indeed, MYC selects for this pathway in part via transcriptional regulation of PKCα and ITPR. Our data point to a novel role for calcium in supporting tumour cell viability and clarify the synthetic lethal interaction between NUAK1 and MYC

A Gadamerian hermeneutic study of nurses' experiences of recognising and managing patients with clinical deterioration and critical illness in a NHS trust in Wales.

Aim: To interpret nurses' experiences of caring for patients with clinical deterioration and critical illness in a Welsh NHS Trust. Methodology: A Gadamerian hermeneutic study drawing on eight in-depth interviews using a purposive sampling technique of nurses who had experienced caring for patients with clinical deterioration. Data collection occurred during 2004. Other data sources included the historical context and the researcher's preunderstandings of the phenomena: clinical deterioration; suboptimal care and critical illness. Data were analysed using a dialogical approach and guided by conditions necessary for Gadamerian hermeneutic interpretation. Findings: The interpretation revealed that recognition of clinical deterioration included general and focused perception of triggers. These included; vigilance in the observation and scanning of patients; perception of clinical deterioration informed by historical and experiential awareness of triggers; and the use of selective combinations of historical, behavioural, interpersonal and physiological triggers. Response to clinical deterioration was influenced by the professional knowledge and confidence of the nurse, organisational culture, workload balance and skill mix. A model of professional gaze emerged that involved a circle of scanning, focused observation, waiting and balancing conditions for an effective response. Conclusions: What is known is that junior medical and nursing staff lack the knowledge, skills and support network required to recognise and respond effectively to patient clinical deterioration in acute hospital settings. The evidence base to support the clinical effectiveness of national guidelines, produced in 2007, for recognising and responding to physiological evidence of clinical deterioration was inconclusive at the time of this study. What this research adds is a model of professional gaze that highlights the complex and professional clinical decision making process involved in nurses' recognition and response to triggers in patient clinical deterioration. This process begins before physiological changes occur and the model provides a structure for recognising clinical concern that can be applied and tested in clinical settings. The model also highlights nurses' strategies for facilitating effective management of these patients

Evaluation of Commercial Genomic Tests for Maternal Traits in Crossbred Beef Cattle

DNA samples were collected from beef heifers born at the Gudmundsen Sandhills Laboratory and analyzed with a genomic test. Phenotypic data from these females were compiled and used in a regression analysis to evaluate the utility of these genomic scores as predictors for phenotypic outcomes. Th e genomic score for birth body weight (BW) was signifi cantly associated with animal birth BW. Th e genomic score for heifer pregnancy was not a statistically significant predictor of actual pregnancy. Neither dam age or the genomic score for stayability were significant predictors of actual reproductive longevity

Squark Mixing in Electron-Positron Reactions

Squark mixing plays a large role in the phenomenology of the minimal supersymmetric standard model, determining the mass of the lightest Higgs boson and the electroweak interactions of the squarks themselves. We examine how mixing may be investigated in high energy $e^+ e^-$ reactions, both at LEP-II and the proposed linear collider. In particular, off-diagonal production of one lighter and one heavier squark allows one to measure the squark mixing angle, and would allow one to test the mass relations for the light Higgs boson. In some cases off-diagonal production may provide the best prospects to discover supersymmetry. In the context of the light bottom squark scenario, we show that existing data from LEP-II should show definitive evidence for the heavier bottom squark provided that its mass $m_{\tilde{b}_2} \le 120$ GeV.Comment: 22 pages, latex, 6 figure

Running into New Territory in SUSY Parameter Space

The LEP-II bound on the light Higgs mass rules out the vast majority of parameter space left to the Minimal Supersymmetric Standard Model (MSSM) with weak-scale soft-masses. This suggests the importance of exploring extensions of the MSSM with non-minimal Higgs physics. In this article, we explore a theory with an additional singlet superfield and an extended gauge sector. The theory has a number of novel features compared to both the MSSM and Next-to-MSSM, including easily realizing a light CP-even Higgs mass consistent with LEP-II limits, tan(beta) < 1, and a lightest Higgs which is charged. These features are achieved while remaining consistent with perturbative unification and without large stop-masses. Discovery modes at the Tevatron and LHC are discussed.Comment: 15 pages, 5 figures; Typo in equation (4.5) corrected; submitted to JHE

Beautiful Mirrors and Precision Electroweak Data

The Standard Model (SM) with a light Higgs boson provides a very good description of the precision electroweak observable data coming from the LEP, SLD and Tevatron experiments. Most of the observables, with the notable exception of the forward-backward asymmetry of the bottom quark, point towards a Higgs mass far below its current experimental bound. The disagreement, within the SM, between the values for the weak mixing angle as obtained from the measurement of the leptonic and hadronic asymmetries at lepton colliders, may be taken to indicate new physics contributions to the precision electroweak observables. In this article we investigate the possibility that the inclusion of additional bottom-like quarks could help resolve this discrepancy. Two inequivalent assignments for these new quarks are analysed. The resultant fits to the electroweak data show a significant improvement when compared to that obtained in the SM. While in one of the examples analyzed, the exotic quarks are predicted to be light, with masses below 300 GeV, and the Higgs tends to be heavy, in the second one the Higgs is predicted to be light, with a mass below 250 GeV, while the quarks tend to be heavy, with masses of about 800 GeV. The collider signatures associated with the new exotic quarks, as well as the question of unification of couplings within these models and a possible cosmological implication of the new physical degrees of freedom at the weak scale are also discussed.Comment: 21 pages, 4 embedded postscript figures, LaTeX. Two minor corrections performe

Accessory mineral microstructure and chronology reveals no evidence for late heavy bombardment on the asteroid 4-Vesta

A long-standing paradigm in planetary science is that the inner Solar System experienced a period of intense and sustained bombardment between 4.2 and 3.9 Ga. Evidence of this period, termed the Late Heavy Bombardment is provided by the 40Ar/39Ar isotope systematics of returned Apollo samples, lunar meteorites, and asteroidal meteorites. However, it has been largely unsupported by more recent and robust isotopic age data, such as isotopic age data obtained using the U-Pb system. Here we conduct careful microstructural characterisation of baddeleyite, zircon, and apatite in six different eucrites prior to conducting SIMS and LA-ICP-MS measurement of U, Th, and Pb isotopic ratios and radiometric dating. Baddeleyite, displaying complex internal twinning linked to reversion from a high symmetry polymorph in two samples, records the formation of the parent body (4554 ± 3 Ma 2σ; n = 8), while structurally simple zircon records a tight spread of ages representing metamorphism between 4574 ± 14 Ma and 4487 ± 31 Ma (n = 6). Apatite, a more readily reset shock chronometer, records crystallisation ages of ∼4509 Ma (n = 6), with structurally deformed grains (attributed to impact events) yielding U-Pb ages of 4228 Ma (n = 12). In concert, there is no evidence within the measured U-Pb systematics or microstructural record of the eucrites examined in this study to support a period of late heavy bombardment between 4.2 and 3.9 Ga

Higgs Boson Decay into Hadronic Jets

The remarkable agreement of electroweak data with standard model (SM) predictions motivates the study of extensions of the SM in which the Higgs boson is light and couples in a standard way to the weak gauge bosons. Postulated new light particles should have small couplings to the gauge bosons. Within this context it is natural to assume that the branching fractions of the light SM-like Higgs boson mimic those in the standard model. This assumption may be unwarranted, however, if there are non-standard light particles coupled weakly to the gauge bosons but strongly to the Higgs field. In particular, the Higgs boson may effectively decay into hadronic jets, possibly without important bottom or charm flavor content. As an example, we present a simple extension of the SM, in which the predominant decay of the Higgs boson occurs into a pair of light bottom squarks that, in turn, manifest themselves as hadronic jets. Discovery of the Higgs boson remains possible at an electron-positron linear collider, but prospects at hadron colliders are diminished substantially.Comment: 30 pages, 7 figure

The shocking state of apatite and merrillite in shergottite Northwest Africa 5298 and extreme nanoscale chlorine isotope variability revealed by atom probe tomography

The elemental and chlorine isotope compositions of calcium-phosphate minerals are key recorders of the volatile inventory of Mars, as well as the planet’s endogenous magmatic and hydrothermal history. Most martian meteorites have clear evidence for exogenous impact-generated deformation and metamorphism, yet the effects of these shock metamorphic processes on chlorine isotopic records contained within calcium phosphates have not been evaluated. Here we test the effects of a single shock metamorphic cycle on chlorine isotope systematics in apatite from the highly shocked, enriched shergottite Northwest Africa (NWA) 5298. Detailed nanostructural (EBSD, Raman and TEM) data reveals a wide range of distributed shock features. These are principally the result of intensive plastic deformation, recrystallization and/or impact melting. These shock features are directly linked with chemical heterogeneities, including crosscutting microscale chlorine-enriched features that are associated with shock melt and iron-rich veins. NanoSIMS chlorine isotope measurements of NWA 5298 apatite reveal a range of δ37Cl values (-3 to 1 ‰; 2σ uncertainties 37Cl values can be readily linked with different nanostructural states of targeted apatite. High spatial resolution atom probe tomography (APT) data reveal that chlorine-enriched and defect-rich nanoscale boundaries have highly negative δ37Cl values (mean of -15 ± 8 ‰). Our results show that shock metamorphism can have significant effects on chemical and chlorine isotopic records in calcium phosphates, principally as a result of chlorine mobilization during shock melting and recrystallization. Despite this, low-strain apatite domains have been identified by EBSD, and yield a mean δ37Cl value of -0.3 ± 0.6 ‰ that is taken as the best estimate of the primary chlorine isotopic composition of NWA 5298. The combined nanostructural, microscale-chemical and nanoscale APT isotopic approach gives the ability to better isolate and identify endogenous volatile-element records of magmatic and near-surface processes as well as exogenous, shock-related effects

Lunar samples record an impact 4.2 billion years ago that may have formed the Serenitatis Basin

Impact cratering on the Moon and the derived size-frequency distribution functions of lunar impact craters are used to determine the ages of unsampled planetary surfaces across the Solar System. Radiometric dating of lunar samples provides an absolute age baseline, however, crater-chronology functions for the Moon remain poorly constrained for ages beyond 3.9 billion years. Here we present U–Pb geochronology of phosphate minerals within shocked lunar norites of a boulder from the Apollo 17 Station 8. These minerals record an older impact event around 4.2 billion years ago, and a younger disturbance at around 0.5 billion years ago. Based on nanoscale observations using atom probe tomography, lunar cratering records, and impact simulations, we ascribe the older event to the formation of the large Serenitatis Basin and the younger possibly to that of the Dawes crater. This suggests the Serenitatis Basin formed unrelated to or in the early stages of a protracted Late Heavy Bombardment