Algal Viruses: The (Atomic) Shape of Things to Come

This is the final version. Available on open access from MDPI via the DOI in this recordVisualization of algal viruses has been paramount to their study and understanding. The direct observation of the morphological dynamics of infection is a highly desired capability and the focus of instrument development across a variety of microscopy technologies. However, the high temporal (ms) and spatial resolution (nm) required, combined with the need to operate in physiologically relevant conditions presents a significant challenge. Here we present a short history of virus structure study and its relation to algal viruses and highlight current work, concentrating on electron microscopy and atomic force microscopy, towards the direct observation of individual algae⁻virus interactions. Finally, we make predictions towards future algal virus study direction with particular focus on the exciting opportunities offered by modern high-speed atomic force microscopy methods and instrumentation.The previously unpublished AFM images shown in this manuscript were generated in the Plymouth Marine Laboratory and University of Exeter Environmental Single Cell Genomics Facility which was supported by the UK’s Natural Environment Research Council (NERC) and The Wolfson Foundation. C.T.E. is supported by an EPSRC and Bristol Nano Dynamics Ltd PhD studentship

BOOK REVIEW

Some years ago, those members of a Friends of IANDS support group who were not near-death experiencers (NDErs) found themselves deeply frustrated. Month after month the group had met, but although the nonexperiencers had enthusiastically discussed the NDE and its implications and meanings, the near-death experiencers themselves had said almost nothing: there was little reporting of experiences, no sharing of what they had learned-just silence. Then one night an out-of-town NDEr came to speak. She not only described her own experience, but admitted to having some difficulties in adjustment after her medical recovery, and asked the others what life was like for them now. She might as well have opened the valves of Hoover Dam; the previously silent NDErs couldn't talk fast enough. Out it all tumbled: anger at having had the light "taken back," frustration with families and friends who did not understand, and confusion about the lives to which they had been so abruptly returned. The outpouring continued for perhaps ten minutes, until another member of the group, not herself an experiencer, cried in dismay, "But you Ms. Bush is currentl

Effect of water vapor on the spallation of thermal barrier coating systems during laboratory cyclic oxidation testing.

The effect of water and water vapor on the lifetime of Ni-based superalloy samples coated with a typical thermal barrier coating system—b-(Ni,Pt)Al bond coat and yttria stabilized zirconia (YSZ) top coat deposited by electron beam physical vapor deposition (EB-PVD) was studied. Samples were thermally cycled to 1,150 C and subjected to a water-drop test in order to elucidate the effect of water vapor on thermal barrier coating (TBC) spallation. It was shown that the addition of water promotes spallation of TBC samples after a given number of cycles at 1,150 C. This threshold was found to be equal to 170 cycles for the present system. Systems based on b-NiAl bond coat or on Pt-rich c/c0 bond coat were also sensitive to the water-drop test. Moreover, it was shown that water vapor in ambient air after minutes or hours at room temperature, promotes also TBC spallation once the critical number of cycles has been reached. This desktop spalling (DTS) can be prevented by locking up the cycled samples in a dry atmosphere box. These results for TBC systems confirm and document Smialek’s theory about DTS and moisture induced delayed spalling (MIDS) being the same phenomenon. Finally, the mechanisms implying hydrogen embrittlement or surface tension modifications are discussed

A Non-Destructive, Tuneable Method to Isolate Live Cells for High-Speed AFM Analysis

Suitable immobilisation of microorganisms and single cells is key for high-resolution topographical imaging and study of mechanical properties with atomic force microscopy (AFM) under physiologically relevant conditions. Sample preparation techniques must be able to withstand the forces exerted by the Z range-limited cantilever tip, and not negatively affect the sample surface for data acquisition. Here, we describe an inherently flexible methodology, utilising the high-resolution three-dimensional based printing technique of multiphoton polymerisation to rapidly generate bespoke arrays for cellular AFM analysis. As an example, we present data collected from live Emiliania huxleyi cells, unicellular microalgae, imaged by contact mode High-Speed Atomic Force Microscopy (HS-AFM), including one cell that was imaged continuously for over 90 min

Minimal Conformal Technicolor and Precision Electroweak Tests

We study the minimal model of conformal technicolor, an SU(2) gauge theory near a strongly coupled conformal fixed point, with conformal symmetry softly broken by technifermion mass terms. Conformal symmetry breaking triggers chiral symmetry breaking in the pattern SU(4) -> Sp(4), which gives rise to a pseudo-Nambu-Goldstone boson that can act as a composite Higgs boson. The top quark is elementary, and the top and electroweak gauge loop contributions to the Higgs mass are cut off entirely by Higgs compositeness. In particular, the model requires no top partners and no "little Higgs" mechanism. A nontrivial vacuum alignment results from the interplay of the top loop and technifermion mass terms. The composite Higgs mass is completely determined by the top loop, in the sense that m_h/m_t is independent of the vacuum alignment and is computable by a strong-coupling calculation. There is an additional composite pseudoscalar A with mass larger than m_h and suppressed direct production at LHC. We discuss the electroweak fit in this model in detail. Corrections to Z -> bb and the T parameter from the top sector are suppressed by the enhanced Sp(4) custodial symmetry. Even assuming that the strong contribution to the S parameter is positive and usuppressed, a good electroweak fit can be obtained for v/f ~ 0.25, where v and f are the electroweak and chiral symmetry breaking scales respectively. This requires fine tuning at the 10% level.Comment: 34 pages, 4 figures; v2: updated precision electroweak fi

Spontaneous Parity Violation in SUSY Strong Gauge Theory

We suggest simple models of spontaneous parity violation in supersymmetric strong gauge theory. We focus on left-right symmetric model and investigate vacuum with spontaneous parity violation. Non-perturbative effects are calculable in supersymmetric gauge theory, and we suggest two new models. The first model shows confinement, and the second model has a dual description of the theory. The left-right symmetry breaking and electroweak symmetry breaking are simultaneously occurred with the suitable energy scale hierarchy. The second model also induces spontaneous supersymmetry breaking.Comment: 14 page

Flavor in Minimal Conformal Technicolor

We construct a complete, realistic, and natural UV completion of minimal conformal technicolor that explains the origin of quark and lepton masses and mixing angles. As in "bosonic technicolor", we embed conformal technicolor in a supersymmetric theory, with supersymmetry broken at a high scale. The exchange of heavy scalar doublets generates higher-dimension interactions between technifermions and quarks and leptons that give rise to quark and lepton masses at the TeV scale. Obtaining a sufficiently large top quark mass requires strong dynamics at the supersymmetry breaking scale in both the top and technicolor sectors. This is natural if the theory above the supersymmetry breaking also has strong conformal dynamics. We present two models in which the strong top dynamics is realized in different ways. In both models, constraints from flavor-changing effects can be easily satisfied. The effective theory below the supersymmetry breaking scale is minimal conformal technicolor with an additional light technicolor gaugino. We argue that this light gaugino is a general consequence of conformal technicolor embedded into a supersymmetric theory. If the gaugino has mass below the TeV scale it will give rise to an additional pseudo Nambu-Goldstone boson that is observable at the LHC.Comment: 37 pages; references adde

Phenotypic covariance of longevity, immunity and stress resistance in the Caenorhabditis nematodes

Background \ud Ageing, immunity and stresstolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulin– like growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. Here we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four \ud Caenorhabditis species. \ud \ud Methodology/Principal Findings \ud We show using phenotypic analysis of DAF-16 influenced phenotypes that among four closely related Caenorhabditis nematodes, the gonochoristic species (Caenorhabditis remanei and Caenorhabditis brenneri) have diverged \ud significantly with a longer lifespan, improved stress resistance and higher immunity than the hermaphroditic species (C. elegans and Caenorhabditis briggsae). Interestingly, we also observe significant differences in expression levels between the daf-16 homologues in these species using Real-Time PCR, which positively correlate with the observed phenotypes. Finally, we provide additional evidence in support of a role for DAF-16 in regulating phenotypic coupling by using a combination of wildtype isolates, constitutively active daf-16 mutants and bioinformatic analysis. \ud \ud Conclusions \ud The gonochoristic species display a significantly longer lifespan (p < 0.0001)and more robust immune and stress response (p<0.0001, thermal stress; p<0.01, heavy metal stress; p<0.0001, pathogenic stress) than the hermaphroditic species. Our data suggests that divergence in DAF-16 mediated phenotypes may underlie many of the differences observed between these four species of Caenorhabditis nematodes. These findings are further supported by the correlative higher daf-16 expression levels among the gonochoristic species and significantly higher lifespan, immunity and stress tolerance in the constitutively active daf-16 hermaphroditic mutants

Block of NMDA receptor channels by endogenous neurosteroids: implications for the agonist induced conformational states of the channel vestibule

N-methyl-D-aspartate receptors (NMDARs) mediate synaptic plasticity, and their dysfunction is implicated in multiple brain disorders. NMDARs can be allosterically modulated by numerous compounds, including endogenous neurosteroid pregnanolone sulfate. Here, we identify the molecular basis of the use-dependent and voltage-independent inhibitory effect of neurosteroids on NMDAR responses. The site of action is located at the extracellular vestibule of the receptor's ion channel pore and is accessible after receptor activation. Mutations in the extracellular vestibule in the SYTANLAAF motif disrupt the inhibitory effect of negatively charged steroids. In contrast, positively charged steroids inhibit mutated NMDAR responses in a voltage-dependent manner. These results, in combination with molecular modeling, characterize structure details of the open configuration of the NMDAR channel. Our results provide a unique opportunity for the development of new therapeutic neurosteroid-based ligands to treat diseases associated with dysfunction of the glutamate system