bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin D and cancer: a review of molecular mechanisms
Authors: Fleet James C. , Desmet Marsha , Johnson Robert , Li Yan
Published: December 2011

The population-based association between low vitamin D status and increased cancer risk can be inconsistent, but it is now generally accepted. These relationships link low serum 25OHD (25-hydroxyvitamin D) levels to cancer, whereas cell-based studies show that the metabolite 1,25(OH)2D (1,25-dihydroxyvitamin D) is a biologically active metabolite that works through vitamin D receptor to regulate gene transcription. In the present review we discuss the literature relevant to the molecular events that may account for the beneficial impact of vitamin D on cancer prevention or treatment. These data show that although vitamin D-induced growth arrest and apoptosis of tumour cells or their non-neoplastic progenitors are plausible mechanisms, other chemoprotective mechanisms are also worthy of consideration. These alternative mechanisms include enhancing DNA repair, antioxidant protection and immunomodulation. In addition, other cell targets, such as the stromal cells, endothelial cells and cells of the immune system, may be regulated by 1,25(OH)2D and contribute to vitamin D-mediated cancer prevention.
Functional analysis of membranous Fo-a subunit of F1Fo-ATP synthase by in vitro protein synthesis
Authors: Kuruma Yutetsu , Suzuki Toshiharu , Ono Sakurako , Yoshida Masasuke , Ueda Takuya
Published: December 2011

The a subunit of F1Fo (F1Fo-ATP synthase) is a highly hydrophobic protein with five putative transmembrane helices which plays a central role in H+-translocation coupled with ATP synthesis/hydrolysis. In the present paper, we show that the a subunit produced by the in vitro protease-free protein synthesis system (the PURE system) is integrated into a preformed Foa-less F1Fo complex in Escherichia coli membrane vesicles and liposomes. The resulting F1Fo has a H+-coupled ATP synthesis/hydrolysis activity that is approximately half that of the native F1Fo. By using this procedure, we analysed five mutations of F1Fo, where the conserved residues in the a subunit (Asn90, Asp112, Arg169, Asn173 and Gln217) were individually replaced with alanine. All of the mutant Foa subunits were successfully incorporated into F1Fo, showing the advantage over conventional expression in E. coli by which three (N90A, D112A, and Q217A) mutant a subunits were not found in F1Fo. The N173A mutant retained full activity and the mutants D112A and Q217A had weak, but detectable, activity. No activity was observed for the R169A and N90A mutants. Asn90 is located in the middle of putative second transmembrane helix and likely to play an important role in H+-translocation. The present study exemplifies that the PURE system provides an alternative approach when in vivo expression of membranous components in protein complexes turns out to be difficult.
High-current discharge channel contraction in high density gas
Authors: Rutberg Ph. G. , Bogomaz A. A. , Pinchuk M. E. , Budin A. V. , Leks A. G. , Pozubenkov A. A.
Published: December 2011

Research results for discharges at current amplitudes of 0.5–1.6 MA and current rise rate of ∼1010 A/s are presented. The discharge is performed in the hydrogen environment at the initial pressure of 5–35 MPa. Initiation is implemented by a wire explosion. The time length of the first half-period of the discharge current is 70–150 μs. Under such conditions, discharge channel contraction is observed; the contraction is followed by soft x-ray radiation. The phenomena are discussed, which are determined by high density of the gas surrounding the discharge channel. These phenomena are increase of the current critical value, where the channel contraction begins and growth of temperature in the axis region of the channel, where the initial density of the gas increases.
A new mode and its interaction through ponderomotive force in electron-positron-ion plasmas
Authors: Haque Q. , Tsintsadze N. L. , Masood W.
Published: December 2011

A new mode is found in e-p-i plasma in the presence of density and temperature difference of lighter particles. The electron beam induced Cherenkov instability condition for the excitation of positron sound wave is obtained for the system under consideration. Zakharov’s equation with sign modification due to negative Ponderomotive pressure is obtained. Nonlinear Schrödinger wave equation for the envelope type solitary waves is derived. Both stationary and nonstationary solutions are found and the subsonic and supersonic limits are also discussed. In the stationary case, rarefactive type solitary solution is obtained, whereas the nonstationary case yields the ion acoustic shock like structure solution which is very interesting. The importance of the study with relevance to both laboratory and astrophysical plasmas is pointed out.
Dynamic scaling in phase separation kinetics for quasi-two-dimensional membranes
Authors: Camley Brian A. , Brown Frank L. H.
Published: December 2011

We consider the dynamics of phase separation in lipid bilayer membranes, modeled as flat two-dimensional liquid sheets within a bulk fluid, both in the creeping flow approximation. We present scaling arguments that suggest asymptotic coarsening in these systems is characterized by a length scale R(t) ∼ t1/2 for critical (bicontinuous) phase separation and R(t) ∼t1/3 for off-critical concentrations (droplet morphology). In this limit, the bulk fluid is the primary source of dissipation. We also address these questions with continuum stochastic hydrodynamic simulations. We see evidence of scaling violation in critical phase separation, where isolated circular domains coarsen slower than elongated ones. However, we also find a region of apparent scaling where R(t) ∼ t1/2 is observed. This appears to be due to the competition of thermal and hydrodynamic effects. We argue that the diversity of scaling exponents measured in experiment and prior simulations can in part be attributed to certain measurements lying outside the asymptotic long-length-scale regime, and provide a framework to help understand these results. We also discuss a few simple generalizations to confined membranes and membranes in which inertia is relevant.
Rotational spectra and properties of complexes B⋯ICF3 (B = Kr or CO) and a comparison of the efficacy of ICl and ICF3 as iodine donors in halogen bond formation
Authors: Stephens Susanna L. , Walker Nicholas R. , Legon Anthony C.
Published: December 2011

The ground-state rotational spectra of two weakly bound complexes B⋯ICF3 (B = Kr or CO) formed by trifluoroiodomethane have been observed in pulsed jets by using two types of Fourier-transform microwave spectroscopy (chirped-pulse and Fabry-Perot cavity). Both complexes exhibit symmetric-top type spectra, thus indicating that the Kr atom in Kr⋯ICF3 and both the C and O atoms in OC⋯ICF3 lie along the C3 axis of ICF3. The rotational constant B0, the centrifugal distortion constants DJ and DJK, and the iodine nuclear quadrupole coupling constant χaa(I) were determined for each of the isotopologues 84Kr⋯ICF3, 86Kr⋯ICF3, 16O12C⋯ICF3, 16O13C⋯ICF3, and 18O12C⋯ICF3. Interpretation of the spectroscopic constants reveals that the carbon atom of CO is adjacent to I and participates in the weak bond in OC⋯ICF3. Simple models based on unperturbed component geometries lead to the distances r(Kr⋯I) = 3.830(1) Å and r(C⋯I) = 3.428(1) Å in Kr⋯ICF3 and OC⋯ICF3, respectively, and to the quadratic force constants for stretching of the weak bond kσ = 2.80 N m−1 and 3.96 N m−1, respectively. The distances r(Z⋯I) (Z is the acceptor atom in B), the kσ values, and the angular geometries of the pair of complexes B⋯ICF3 and B⋯ICl for a given B are compared when B = Kr, CO, H2O, H2S, or NH3. The comparison reveals that the iodine bond in B⋯ICF3 is systematically longer and weaker than that of B⋯ICl, while the angular geometry of the B⋯I moiety is isomorphic in B⋯ICF3 and B⋯ICl for a given B. It is concluded that −CF3 is less effective than −Cl as an electron-withdrawing group when attached to an I atom and that the angular geometries of the B⋯ICF3 can be predicted by means of a simple rule that holds for many hydrogen- and halogen-bonded complexes.
Analytical solutions for von Kármán streets of hollow vortices
Authors: Crowdy Darren G. , Green Christopher C.
Published: December 2011

New analytical solutions are presented for steadily translating von Kármán vortex streets made up of two infinite rows of hollow vortices. First, the solution for a single row of hollow vortices due to Baker et al. ["Structure of a linear array of hollow vortices of finite cross-section," J. Fluid Mech. 74, 469 (1976)] is rederived, in a modified form, and using a new mathematical approach. This approach is then generalized to find relative equilibria for both unstaggered and staggered double hollow vortex streets. The method employs a combination of free streamline theory and conformal mapping ideas. The staggered hollow vortex streets are compared with analogous numerical solutions for double streets of vortex patches due to Saffman and Schatzman [“Properties of a vortex street of finite vortices,” SIAM (Soc. Ind. Appl. Math.) J. Sci. Stat. Comput. 2, 285 (1981)] and several common features are found. In particular, within the two different inviscid vortex models, the same street aspect ratio of approximately 0.34–0.36 is found to have special significance for the equilibria.
Laser spectroscopy of individual quantum dots charged with a single hole
Authors: Gerardot B. D. , Barbour R. J. , Brunner D. , Dalgarno P. A. , Badolato A. , Stoltz N. , Petroff P. M. , Houel J. , Warburton R. J.
Published: December 2011

We characterize the positively charged exciton (X1+) in single InGaAs quantum dots using resonant laser spectroscopy. Three samples with different dopant species (Be or C as acceptors, Si as a donor) are compared. The p-doped samples exhibit larger inhomogeneous broadening (×3) and smaller absorption contrast (×10) than the n-doped sample. For X1+ in the Be-doped sample, a dot dependent non-linear Fano effect is observed, demonstrating coupling to degenerate continuum states. However, for the C-doped sample, the X1+ lineshape and saturation broadening follows isolated atomic transition behaviour. This C-doped device structure is useful for single hole spin initialization, manipulation, and measurement.
Field-free molecular alignment control by phase-shaped femtosecond laser pulse
Authors: Zhang Shian , Lu Chenhui , Jia Tianqing , Sun Zhenrong , Qiu Jianrong
Published: December 2011

In this paper, we theoretically show that the field-free molecular alignment can be controlled by shaping the femtosecond laser pulse with a periodic phase step modulation, involving the maximum degree and temporal structure of the molecular alignment. We show that the molecular alignment can be completely suppressed or reconstructed as that by the transform-limited laser pulse, the temporal structure of the alignment transient can be controlled with a desired shape, and the molecular alignment and antialignment for any temporal structure can be switched. Furthermore, we also show that both the degree and direction of the molecular alignment at a fix time delay can be continuously modulated.
Annular wave packets at Dirac points in graphene and their probability-density oscillation
Authors: Luo Ji , Valencia Daniel , Lu Junqiang
Published: December 2011

Wave packets in graphene whose central wave vector is at Dirac points are investigated by numerical calculations. Starting from an initial Gaussian function, these wave packets form into annular peaks that propagate to all directions like ripple-rings on water surface. At the beginning, electronic probability alternates between the central peak and the ripple-rings and transient oscillation occurs at the center. As time increases, the ripple-rings propagate at the fixed Fermi speed, and their widths remain unchanged. The axial symmetry of the energy dispersion leads to the circular symmetry of the wave packets. The fixed speed and widths, however, are attributed to the linearity of the energy dispersion. Interference between states that, respectively, belong to two branches of the energy dispersion leads to multiple ripple-rings and the probability-density oscillation. In a magnetic field, annular wave packets become confined and no longer propagate to infinity. If the initial Gaussian width differs greatly from the magnetic length, expanding and shrinking ripple-rings form and disappear alternatively in a limited spread, and the wave packet resumes the Gaussian form frequently. The probability thus oscillates persistently between the central peak and the ripple-rings. If the initial Gaussian width is close to the magnetic length, the wave packet retains the Gaussian form and its height and width oscillate with a period determined by the first Landau energy. The wave-packet evolution is determined jointly by the initial state and the magnetic field, through the electronic structure of graphene in a magnetic field.
Aharonov-Bohm oscillations in the local density of topological surface states
Authors: Fu Zhen-Guo , Zhang Ping , Li Shu-Shen
Published: December 2011

We study Aharonov-Bohm (AB) oscillations in the local density of states (LDOS) for topological insulator (TI) and conventional metal Au(111) surfaces with spin-orbit interaction, which can be probed by spin-polarized scanning tunneling microscopy. We show that the spacial AB oscillatory period in the total LDOS is a flux quantum Φ0 = hc/e (weak localization) in both systems. Remarkably, an analogous weak antilocalization with Φ0/2 periodic spacial AB oscillations in spin components of LDOS for TI surface is observed, while it is absent in Au(111).
Stable dual-wavelength microlaser controlled by the output mirror tilt angle
Authors: Pallas Florent , Herault Emilie , Zhou Jie , Roux Jean-Francois , Vitrant Guy
Published: December 2011

A continuous-wave dual-wavelength solid-state microlaser is presented and a technique for regulating the gain competition between the two wavelengths is proposed, based on the angular tilt of the laser cavity output mirror. Laser behavior is studied and balanced dual-wavelength emission is obtained with output power levels as high as 200 mW for 2 W pump power. Sum frequency mixing is demonstrated making the source promising for Terahertz generation in the 0.5-0.7 THz range through difference frequency generation.
Ga-Sb-Se material for low-power phase change memory
Authors: Lu Yegang , Song Sannian , Gong Yuefeng , Song Zhitang , Rao Feng , Wu Liangcai , Liu Bo , Yao Dongning
Published: December 2011

In this paper, Te-free Ga-Sb-Se material is considered to be a storage medium for phase change memory. Compared with Ge2Sb2Te5, Ga1Sb6Se3 exhibits a better thermal stability, which leads to a brilliant performance for data retention. Ga1Sb6Se3-based phase change memory cell shows reversible switching between reset and set states with a resistance ratio of two orders of magnitude. The minimum reset/set voltages are significantly lower than those of Ge2Sb2Te5-based one. Meanwhile, Ga1Sb6Se3 film possesses a faster switching speed than Ge2Sb2Te5. Thermal simulation confirms the improvement of cell performance originating from the low thermal conductivity and low melting point of Ga1Sb6Se3.
A combined scanning tunneling microscope–atomic layer deposition tool
Authors: Mack James F. , Van Stockum Philip B. , Iwadate Hitoshi , Prinz Fritz B.
Published: December 2011

We have built a combined scanning tunneling microscope–atomic layer deposition (STM-ALD) tool that performs in situ imaging of deposition. It operates from room temperature up to 200 °C, and at pressures from 1 × 10−6 Torr to 1 × 10−2 Torr. The STM-ALD system has a complete passive vibration isolation system that counteracts both seismic and acoustic excitations. The instrument can be used as an observation tool to monitor the initial growth phases of ALD in situ, as well as a nanofabrication tool by applying an electric field with the tip to laterally pattern deposition. In this paper, we describe the design of the tool and demonstrate its capability for atomic resolution STM imaging, atomic layer deposition, and the combination of the two techniques for in situ characterization of deposition.
Dispersion of ferrofluid aggregates in steady flows
Authors: Williams Alicia M. , Vlachos Pavlos P.
Published: December 2011

Using focused shadowgraphs, we investigate steady flows of a magnetically non-susceptible fluid interacting with ferrofluid aggregates comprised of superparamagnetic nanoparticles. The ferrofluid aggregate is retained at a specific site within the flow channel using two different applied magnetic fields. The bulk flow induces shear stresses on the aggregate, which give rise to the development of interfacial disturbances, leading to Kelvin-Helmholtz (K-H) instabilities and shedding of ferrofluid structures. Herein, the effects of bulk Reynolds number, ranging from 100 to 1000, and maximum applied magnetic fields of 1.2 × 105 and 2.4 × 105 A/m are investigated in the context of their impact on dispersion or removal of material from the core aggregate. The aggregate interaction with steady bulk flow reveals three regimes of aggregate dynamics over the span of Reynolds numbers studied: stable, transitional, and shedding. The first regime is characterized by slight aggregate stretching for low Reynolds numbers, with full aggregate retention. As the Reynolds number increases, the aggregate is in-transition between stable and shedding states. This second regime is characterized by significant initial stretching that gives way to small amplitude Kelvin-Helmholtz waves. Higher Reynolds numbers result in ferrofluid shedding, with Strouhal numbers initially between 0.2 and 0.3, wherein large vortical structures are shed from the main aggregate accompanied by precipitous decay of the accumulated ferrofluid aggregate. These behaviors are apparent for both magnetic field strengths, although the transitional Reynolds numbers are different between the cases, as are the characteristic shedding frequencies relative to the same Reynolds number. In the final step of this study, relevant parameters were extracted from the time series dispersion data to comprehensively quantify aggregate mechanics. The aggregate half-life is found to decrease as a function of the Reynolds number following a power law curve and can be scaled for different magnetic fields using the magnetic induction at the inner wall of the vessel. In addition, the decay rate of the ferrofluid is shown to be proportional to the wall shear rate. Finally, a dimensionless parameter, which scales the inertia-driven flow pressures, relative to the applied magnetic pressures, reveals a power law decay relationship with respect to the incident bulk flow.
Epitaxial thin films of p-type spinel ferrite grown by pulsed laser deposition
Authors: Seki Munetoshi , Tabata Hitoshi , Ohta Hiromichi , Inaba Katsuhiko , Kobayashi Shintaro
Published: December 2011

Epitaxial thin films of Ge-substituted Fe3O4 were grown on α-Al2O3 (001) using pulsed laser deposition, and their electrical and magnetic properties were investigated. A target with excess Ge compositions was employed for the film growth to compensate for the volatilization of germanium oxides during the high-temperature deposition. P-type conduction was achieved for the Ge-rich films. The Néel temperature of all the films was above 300 K. Furthermore, the films exhibited an anomalouos Hall effect at 300 K, suggesting that the carriers in the films are spin-polarized.
Broad gain in a bound-to-continuum quantum cascade laser with heterogeneous active region
Authors: Freeman Joshua R. , Brewer Anthony , Madéo Julien , Cavalié Pierrick , Dhillon Sukhdeep S. , Tignon Jérôme , Beere Harvey E. , Ritchie David A.
Published: December 2011

We demonstrate the operation of heterogeneous terahertz quantum cascade lasers with broadened gain by optimising the sub-stacks to align at the same field. In single plasmon waveguides, we find two-colour operation for nearly the entire dynamic range of the lasers with similar performance to homogeneous lasers. Time domain spectroscopy measurements confirm that a flat gain spectrum is present and the sub-stacks align at the same time. When incorporated into metal-metal waveguides, we find that performance is consistent with the constituent sub-stacks and there is broadband operation over 380 GHz.
Hybrid thermal-field emission of ZnO nanowires
Authors: Ulisse Giacomo , Brunetti Francesca , Vomiero Alberto , Natile Marta M. , Sberveglieri Giorgio , Di Carlo Aldo
Published: December 2011

The electron emission properties of an array of ZnO nanowires were studied in the temperature range of 300-473 K. An almost doubling of the current density at 473 K under an electric field of 8 V/μm (j(T=473 K) = 190 μA/cm2, j(T=300 K) = 114 μA/cm2) was observed together with a reduction of the turn-on field from 552 V/μm to 482 V/μm. Theoretical model that combines the thermal-field emission for high electric field and the Schottky emission for the low field can satisfactorily account for temperature dependence of current at low as well as at high applied bias. The obtained effect is particularly appealing for the application in micro-gun for THz vacuum tubes.
Photoconductive gain in solar-blind ultraviolet photodetector based on Mg0.52Zn0.48O thin film
Authors: Han Shun , Zhang Zhenzhong , Zhang Jiying , Wang Likun , Zheng Jian , Zhao Haifeng , Zhang Yechi , Jiang Mingming , Wang Shuangpeng , Zhao Dongxu , Shan ChongXin , Li Binghui , Shen Dezhen
Published: December 2011

An ultraviolet photodetector was fabricated on MgZnO thin film grown by metal-organic chemical vapor deposition. The peak response of the device centers at 238 nm and cutoff wavelength is 253 nm. The peak responsivity is 129 mA/W at 15 V bias, and the UV/visible reject ratio is 4 orders of magnitude. Internal gain is due to the hole trapping at interface that brings low response speed. Native defects at the Au/MgZnO interface degrade the barrier effect, which caused large dark current and high visible response.
Lasing characteristics of random cylindrical microcavity lasers
Authors: Zhu H. , Yu S. F. , Zhang W. F.
Published: December 2011

Room-temperature lasing characteristics of random cylindrical microcavity lasers, which can be realized by coating a layer of random gain medium onto the surface of an optical fiber with various diameters, was studied experimentally. It is shown that closed-loop random modes excited inside the random gain medium are strongly confined along the radial direction so that the spacing of lasing modes is controlled by the diameter of cylindrical microcavity. In addition, lasing threshold of the random gain medium can be reduced by an order of magnitude under the influence of radial optical confinement.
Nanoindentation of high-aspect ratio pillar structures on optical multilayer dielectric diffraction gratings
Authors: Mehrotra K. , Howard H. P. , Jacobs S. D. , Lambropoulos J. C.
Published: December 2011

The mechanical response of optical multilayer dielectric (MLD) diffraction gratings has been studied using nanoindentation. The results are interpreted using a stress-strain model, which reveals a uniaxial yield stress of 4.1 GPa. It is shown that the indentation response of the high-aspect ratio “pillar” geometry (constrained in one transverse direction but free in the other) can be expressed in terms of yield stress rather than material hardness.
Opportunistic evidence: evidence-based policy in the setting of the Australian Government's chlamydia screening pilot
Authors: Crouch Simon R.
Published: December 2011

Objective.
Chlamydia prevention and control form a significant part of the Australian Government’s sexual health policy. This paper examines the evidence for policy development and in particular the role of systematic reviews in evidence-based policy.

Methods.
The author undertook a review of the literature on evidence-based policy. The major theories for evidence-based policy were then linked to the Australian Government’s main chlamydia policy.

Results.
A systematic review on chlamydia screening has been influential in policy development, but like all systematic reviews its validity must be assessed. It has been suggested that methodological appropriateness and the question being asked are perhaps more important than study design per se. Partnerships between researchers and policymakers are important but it should be noted that experts have their own particular biases. Policymaking can also be determined by political ideologies.

Conclusions and implications.
The publication of a systematic review has provided a good summative evaluation of chlamydia screening that has been built upon through partnerships with researchers. The resulting chlamydia screening pilot will provide further evidence for future policy; however, a variety of sources are required to develop robust policy directions.

What is known about the topic?
Systematic reviews are often considered to be the best evidence on which to base policy decisions. In practice it is not always the case that best evidence is used to form policy. As well as systematic reviews, which are not always infallible, there are many other factors that affect the development of national health policy.

What does the paper add?
This paper provides a consideration of the role of systematic reviews in policy-making, as well as some of the pitfalls to this approach. As an example, it provides the Australian Government’s policy on chlamydia control and looks at other factors that may have contributed to the development of this policy.

What are the implications for practitioners?
All practitioners involved in policy decisions should consider the evidence-base from which their policies are derived. They should understand the sound basis of the systematic review while accepting that other pressures may affect the processes leading up to the formation of good health policy.
Cooperative macromolecular device revealed by meta-analysis of static and time-resolved structures
Authors: Ren Zhong , Šrajer Vukica , Knapp James E. , Royer William E.
Published: December 2011

Here we present a meta-analysis of a large collection of static structures of a protein in the Protein Data Bank in order to extract the progression of structural events during protein function. We apply this strategy to the homodimeric hemoglobin HbI from
Scapharca inaequivalvis
. We derive a simple dynamic model describing how binding of the first ligand in one of the two chemically identical subunits facilitates a second binding event in the other partner subunit. The results of our ultrafast time-resolved crystallographic studies support this model. We demonstrate that HbI functions like a homodimeric mechanical device, such as pliers or scissors. Ligand-induced motion originating in one subunit is transmitted to the other via conserved pivot points, where the E and F′ helices from two partner subunits are “bolted” together to form a stable dimer interface permitting slight relative rotation but preventing sliding.
Structural basis for the phosphatase activity of polynucleotide kinase/phosphatase on single- and double-stranded DNA substrates
Authors: Coquelle Nicolas , Havali-Shahriari Zahra , Bernstein Nina , Green Ruth , Glover J. N. Mark
Published: December 2011

Polynucleotide kinase/phosphatase (PNKP) is a critical mammalian DNA repair enzyme that generates 5′-phosphate and 3′-hydroxyl groups at damaged DNA termini that are required for subsequent processing by DNA ligases and polymerases. The PNKP phosphatase domain recognizes 3′-phosphate termini within DNA nicks, gaps, or at double- or single-strand breaks. Here we present a mechanistic rationale for the recognition of damaged DNA termini by the PNKP phosphatase domain. The crystal structures of PNKP bound to single-stranded DNA substrates reveals a narrow active site cleft that accommodates a single-stranded substrate in a sequence-independent manner. Biochemical studies suggest that the terminal base pairs of double-stranded substrates near the 3′-phosphate are destabilized by PNKP to allow substrate access to the active site. A positively charged surface distinct from the active site specifically facilitates interactions with double-stranded substrates, providing a complex DNA binding surface that enables the recognition of diverse substrates.
Inscuteable and NuMA proteins bind competitively to Leu-Gly-Asn repeat-enriched protein (LGN) during asymmetric cell divisions
Authors: Culurgioni Simone , Alfieri Andrea , Pendolino Valentina , Laddomada Federica , Mapelli Marina
Published: December 2011

Coupling of spindle orientation to cellular polarity is a prerequisite for epithelial asymmetric cell divisions. The current view posits that the adaptor Inscuteable (Insc) bridges between Par3 and the spindle tethering machinery assembled on NuMA∶LGN∶G
α
i
GDP
, thus triggering apico-basal spindle orientation. The crystal structure of the Drosophila ortholog of LGN (known as Pins) in complex with Insc reveals a modular interface contributed by evolutionary conserved residues. The structure also identifies a positively charged patch of LGN binding to an invariant EPE-motif present on both Insc and NuMA. In vitro competition assays indicate that Insc competes with NuMA for LGN binding, displaying a higher affinity, and that it is capable of opening the LGN conformational switch. The finding that Insc and NuMA are mutually exclusive interactors of LGN challenges the established model of force generators assembly, which we revise on the basis of the newly discovered biochemical properties of the intervening components.
IκB kinase ε (IKKε) regulates the balance between type I and type II interferon responses
Authors: Ng Sze-Ling , Friedman Brad A. , Schmid Sonja , Gertz Jason , Myers Richard M. , tenOever Benjamin R. , Maniatis Tom
Published: December 2011

Virus infection induces the production of type I and type II interferons (IFN-I and IFN-II), cytokines that mediate the antiviral response. IFN-I (IFN-α and IFN-β) induces the assembly of IFN-stimulated gene factor 3 (ISGF3), a multimeric transcriptional activation complex composed of STAT1, STAT2, and IFN regulatory factor 9. IFN-II (IFN-γ) induces the homodimerization of STAT1 to form the gamma-activated factor (GAF) complex. ISGF3 and GAF bind specifically to unique regulatory DNA sequences located upstream of IFN-I– and IFN-II–inducible genes, respectively, and activate the expression of distinct sets of antiviral genes. The balance between type I and type II IFN pathways plays a critical role in orchestrating the innate and adaptive immune systems. Here, we show that the phosphorylation of STAT1 by IκB kinase epsilon (IKKε) inhibits STAT1 homodimerization, and thus assembly of GAF, but does not disrupt ISGF3 formation. Therefore, virus and/or IFN-I activation of IKKε suppresses GAF-dependent transcription and promotes ISGF3-dependent transcription. In the absence of IKKε, GAF-dependent transcription is enhanced at the expense of ISGF3-mediated transcription, rendering cells less resistant to infection. We conclude that IKKε plays a critical role in regulating the balance between the IFN-I and IFN-II signaling pathways.
Genotyping of Infectious Pancreatic Necrosis Virus Isolates from Mexico State
Authors: Barrera-Mejía Magda , Martínez Simón , Ortega César , Ulloa-Arvizu Raúl
Published: December 2011

The infectious pancreatic necrosis virus (IPNV; genus Aquabirnavirus) affects salmon and trout, causing high mortality in first-feeding fry. The classification of this virus includes nine serotypes and seven genogroups. In Mexico, two different isolates were identified in 2000 and 2008, respectively. Both isolates were classified into genogroup I according to the RNA genome of this virus. As Mexico is importing rainbow trout Oncorhynchus mykiss eggs from different countries, the aim of this study was to genotype IPNV isolates obtained from four rainbow trout producer regions within the state of Mexico. We utilized a fragment of the VP2* (outer capsid protein) gene sequence of Mexican IPNV isolates as a molecular marker to determine the genogroup to which they belong. Although all Mexican IPNV isolates were grouped into genogroup I, we identified genetic diversity among these isolates, and 14 unique nucleotide sequence types were associated with the four producer regions in Mexico State.

Received December 21, 2010; accepted July 27, 2011
A Randomized, Double-Blind, Placebo-Controlled Trial of Selective Digestive Decontamination Using Oral Gentamicin and Oral Polymyxin E for Eradication of Carbapenem-Resistant Klebsiella pneumoniae Carriage
Authors: Saidel-Odes Lisa , Polachek Hana , Peled Nehama , Riesenberg Klaris , Schlaeffer Francisc , Trabelsi Yafa , Eskira Seada , Yousef Baha , Smolykov Rozalia , Codish Shlomi , Borer Abraham
Published: December 2011

Objective.

To assess the effectiveness of selective digestive decontamination (SDD) for eradicating carbapenem-resistant Klebsiella pneumoniae (CRKP) oropharyngeal and gastrointestinal carriage.

Design.

A randomized, double-blind, placebo-controlled trial with 7 weeks of follow-up per patient.

Setting.

A 1,000-bed tertiary-care university hospital.

Patients.

Adults with CRKP-positive rectal swab cultures.

Methods.

Patients were blindly randomized (1:1) over a 20-month period. The SDD arm received oral gentamicin and polymyxin E gel (0.5 g 4 times per day) and oral solutions of gentamicin (80 mg 4 times per day) and polymyxin E (1 × 106 units 4 times per day for 7 days). The placebo arm received oral placebo gel 4 times per day and 2 placebo oral solutions 4 times per day for 7 days. Strict contact precautions were applied. Samples obtained from the throat, groin, and urine were also cultured.

Results.

Forty patients (mean age ± standard deviation, 71 ± 16 years; 65% male) were included. At screening, greater than or equal to 30% of oropharyngeal, greater than or equal to 60% of skin, and greater than or equal to 35% of urine cultures yielded CRKP isolates. All throat cultures became negative in the SDD arm after 3 days (P< .0001). The percentages of rectal cultures that were positive for CRKP were significandy reduced at 2 weeks. At that time, 16.1% of rectal cultures in the placebo arm and 61.1% in the SDD arm were negative (odds ratio, 0.13; 95% confidence interval, 0.02–0.74; P<.0016). A difference between the percentages in the 2 arms was still maintained at 6 weeks (33.3% vs 58.5%). Groin colonization prevalence did not change in either arm, and the prevalence of urine colonization increased in the placebo arm.

Conclusions.

This SDD regimen could be a suitable decolonization therapy for selected patients colonized with CRKP, such as transplant recipients or immunocompromised patients pending chemotherapy and patients who require major intestinal or oropharyngeal surgery. Moreover, in outbreaks caused by CRKP infections that are uncontrolled by routine infection control measures, SDD could provide additional infection containment.

Infect Control Hosp Epidemiol 2012;33(1):14-19
Postdischarge Surgical Site Infection Surveillance Practices in Washington Acute Care Hospitals
Authors: Zarate Roxie , Birnbaum David
Published: December 2011

Little is known about postdischarge surveillance practices currently in place among American hospitals. This survey describes practices used by acute care hospitals covered by Washington State's legislated mandate for public reporting of surgical site infections. While the vast majority of facilities use multiple techniques, wide variation in practices was discovered.

Infect Control Hosp Epidemiol 2012;33(1):8
Relationships Between Simple Grain Quality Parameters for the Estimation of Sorghum and Maize Hardness in Commercial Hybrid Cultivars
Authors: Chiremba Constance , Rooney Lloyd W. , Taylor John R. N.
Published: December 2011

Grain hardness affects sorghum and maize processing properties especially for dry milling. A variety of simple grain quality parameters were assessed on 17 sorghum and 35 white maize hybrid cultivars grown in six and four locations, respectively, in South Africa. The purpose was to determine tests that can be used to distinguish hardness in commercial sorghum and maize. The grains were characterized by test weight (TW), thousand kernel weight (TKW), decortication with the tangential abrasive dehulling device (TADD), and kernel size. Maize was also characterized for susceptibility to breakage, stress cracking, and near‐infrared transmittance (NIT) milling index. Principal component analysis showed that, in nontannin and tannin sorghums, TADD hardness and TW were closely correlated (P < 0.001). In maize, TADD hardness was closely correlated (P < 0.001) with NIT milling index and TW. Hence, TADD hardness and NIT milling index or TADD hardness and TW would be suitable for maize hardness evaluation. A combination of TADD hardness, TW, TKW, and kernel size >3.35 mm can be used together to select sorghum grain for hardness. It thus appears that TADD hardness is an excellent method of estimating both sorghum and maize hardness that can be applied for routine batch analysis and cultivar evaluation.
Optimal Assessment of Paediatric IBD With MRI and Barium Follow‐through
Authors: Giles Edward , Hanci Ozan , McLean Alison , Power Niall , Cole Angela , Croft Nicholas M. , McDonald Kirsteen , Chippington Sam , Naik Sandhia
Published: December 2011

Objectives:

The present UK criterion standard for assessing children with suspected inflammatory bowel disease (IBD) is upper endoscopy, ileocolonoscopy, and barium follow‐through (BaFT). Significant doses of radiation, unpalatable contrast, and volume intolerance are involved with BaFT. Practice in investigating Crohn disease (CD) is changing with the increasing use of magnetic resonance imaging (MRI). The aim of the present study was to compare BaFT and a new abdominal MRI protocol in a paediatric IBD population.

Methods:

All consecutive patients with a new diagnosis of IBD or requiring reassessment from September 2008 to December 2010 were investigated with both abdominal MRI and BaFT in accordance with a specific local paediatric IBD protocol. The studies were reported by nonblinded radiologists with an interest in gastrointestinal imaging. The reports were compared in conjunction with case note review.

Results:

Eighty‐seven patients underwent both BaFT and MRI abdomen. Thirty‐one percent of patients had additional pathology on MRI, not seen on the BaFT. Sixty‐seven percent of patients (n = 59) had an MRI finding equivalent to BaFT. Using histology as a criterion standard for detecting terminal ileal disease, BaFT had a sensitivity and specificity of 76% and 67%, and MRI had a sensitivity and specificity of 83% and 95%, respectively.

Conclusions:

This is the largest series of small bowel MRI in a paediatric population. MRI reports were at least equivalent to BaFT. MRI had higher sensitivity and, particularly, specificity in detecting terminal ileal pathology. These findings suggest that MRI should become the criterion standard investigation in children with IBD in centres with appropriate expertise, with zero radiation exposure being highly advantageous.
Dengue virus strain DEN2 16681 utilizes a specific glycochain of syndecan-2 proteoglycan as a receptor
Authors: Okamoto Kenta , Kinoshita Hitomi , Parquet Maria del Carmen , Raekiansyah Muhareva , Kimura Daisuke , Yui Katsuyuki , Islam Mohammed Alimul , Hasebe Futoshi , Morita Kouichi
Published: December 2011

Dengue virus (DENV) causes fever and severe haemorrhagic symptoms in humans. The DEN2 16681 strain, derived from a dengue haemorrhagic fever patient, has been widely used in studies related to DENV pathogenesis, such as mouse and non-human primate haemorrhagic models and human vascular endothelial-cell permeability. To clarify the entry mechanism of the 16681 strain, we characterized a novel cell receptor for this strain. Our two major findings were as follows: firstly, the SDC2 membrane protein was an effective DEN2 16681 receptor in a cloned K562 cell line. Secondly, a heparan sulfate (HS) glycochain (of four glycochains in SDC2) is the specific binding site of DENV and seems to be involved in tissue-culture adaptation. Our findings present an entry mechanism that could be implicated for DENV adaptation and HS-mediated DENV infection.
The innate antiviral factor APOBEC3G targets replication of measles, mumps and respiratory syncytial viruses
Authors: Fehrholz Markus , Kendl Sabine , Prifert Christiane , Weissbrich Benedikt , Lemon Ken , Rennick Linda , Duprex Paul W. , Rima Bert K. , Koning Fransje A. , Holmes Rebecca K. , Malim Michael H. , Schneider-Schaulies Jürgen
Published: December 2011

The cytidine deaminase APOBEC3G (apolipoprotein B mRNA-editing enzyme-catalytic polypeptide 3G; A3G) exerts antiviral activity against retroviruses, hepatitis B virus, adeno-associated virus and transposable elements. We assessed whether the negative-strand RNA viruses measles, mumps and respiratory syncytial might be affected by A3G, and found that their infectivity was reduced by 1–2 logs (90–99 %) in A3G overexpressing Vero cells, and in T-cell lines expressing A3G at physiological levels. Viral RNA was co-precipitated with HA-tagged A3G and could be amplified by RT-PCR. Interestingly, A3G reduced viral transcription and protein expression in infected cells by 50–70 %, and caused an increased mutation frequency of 0.95 mutations per 1000 nt in comparison to the background level of 0.22/1000. The observed mutations were not specific for A3G [cytidine to uridine (C→U) or guanine to adenine (G→A) hypermutations], nor specific for ADAR (adenosine deaminase acting on RNA, A→G and U→C transitions, with preference for next neighbour-nucleotides U = A>C>G). In addition, A3G mutants with inactivated catalytic deaminase (H257R and E259Q) were inhibitory, indicating that the deaminase activity is not required for the observed antiviral activity. In combination, impaired transcription and increased mutation frequencies are sufficient to cause the observed reduction in viral infectivity and eliminate virus replication within a few passages in A3G-expressing cells.
Plasmacytoid dendritic cells and Toll-like receptor 7-dependent signalling promote efficient protection of mice against highly virulent influenza A virus
Authors: Kaminski Michael M. , Ohnemus Annette , Cornitescu Marius , Staeheli Peter
Published: December 2011

Types I and III interferons (IFNs) elicit protective antiviral immune responses during influenza virus infection. Although many cell types can synthesize IFN in response to virus infection, it remains unclear which IFN sources contribute to antiviral protection in vivo. We found that mice carrying functional alleles of the Mx1 influenza virus resistance gene partially lost resistance to infection with a highly pathogenic H7N7 influenza A virus strain if Toll-like receptor 7 (TLR7) signalling was compromised. This effect was achieved by deleting either the TLR7 gene or the gene encoding the TLR7 adaptor molecule MyD88. A similar decrease of influenza virus resistance was observed when animals were deprived of plasmacytoid dendritic cells (pDCs) at day 1 post-infection. Our results provide in vivo proof that pDCs contribute to the protection of the lung against influenza A virus infections, presumably via signals from TLR7.
Rab11 is phosphorylated by classical and novel protein kinase C isoenzymes upon sustained phorbol ester activation
Authors: Pavarotti Martín , Capmany Anahí , Vitale Nicolas , Colombo María Isabel , Damiani María Teresa
Published: December 2011

Background information

Rab11 is a small GTPase that controls diverse intracellular trafficking pathways. However, the molecular machinery that regulates the participation of Rab11 in those different transport events is poorly understood. In resting cells, Rab11 localizes at the endocytic recycling compartment (ERC), whereas the different protein kinase C (PKC) isoforms display a cytosolic distribution.

Results

Sustained phorbol ester stimulation induces the translocation of the classical PKCα and PKCβII isoenzymes to the ERC enriched in Rab11, and results in transferrin recycling inhibition. In contrast, novel PKCε and atypical PKCζ isoenzymes neither redistribute to the perinucleus nor modify transferrin recycling transport after phorbol ester stimulation. Although several Rabs have been shown to be phosphorylated, there is to date no evidence indicating Rab11 as a kinase substrate. In this report, we show that Rab11 appears phosphorylated in vivo in phorbol ester‐stimulated cells. A bioinformatic analysis of Rab11 allowed us to identify several high‐probability Ser/Thr kinase phosphorylation sites. Our results demonstrate that classical PKC (PKCα and PKCβII but not PKCβI) directly phosphorylate Rab11 in vitro. In addition, novel PKCε and PKCη but not PKCδ isoenzymes also phosphorylate Rab11. Mass spectrometry analysis revealed that Ser 177 is the Rab11 residue to be phosphorylated in vitro by either PKCβII or PKCε. In agreement, the phosphomimetic mutant, Rab11 S177D, retains transferrin at the ERC in the absence of phorbol‐12‐myristate‐13‐acetate stimulus.

Conclusions

This report shows for the first time that Rab11 is differentially phosphorylated by distinct PKC isoenzymes and that this post‐translational modification might be a regulatory mechanism of intracellular trafficking.
TI‐VAMP/VAMP7 is the SNARE of secretory lysosomes contributing to ATP secretion from astrocytes
Authors: Verderio Claudia , Cagnoli Cinzia , Bergami Matteo , Francolini Maura , Schenk Ursula , Colombo Alessio , Riganti Loredana , Frassoni Carolina , Zuccaro Emanuela , Danglot Lydia , Wilhelm Claire , Galli Thierry , Canossa Marco , Matteoli Michela
Published: December 2011

Background information

ATP is the main transmitter stored and released from astrocytes under physiological and pathological conditions. Morphological and functional evidence suggest that besides secretory granules, secretory lysosomes release ATP. However, the molecular mechanisms involved in astrocytic lysosome fusion remain still unknown.

Results

In the present study, we identify tetanus neurotoxin‐insensitive vesicle‐associated membrane protein (TI‐VAMP, also called VAMP7) as the vesicular SNARE which mediates secretory lysosome exocytosis, contributing to release of both ATP and cathepsin B from glial cells. We also demonstrate that fusion of secretory lysosomes is triggered by slow and locally restricted calcium elevations, distinct from calcium spikes which induce the fusion of glutamate‐containing clear vesicles. Downregulation of TI‐VAMP/VAMP7 expression inhibited the fusion of ATP‐storing vesicles and ATP‐mediated calcium wave propagation. TI‐VAMP/VAMP7 downregulation also significantly reduced secretion of cathepsin B from glioma.

Conclusions

Given that sustained ATP release from glia upon injury greatly contributes to secondary brain damage and cathepsin B plays a critical role in glioma dissemination, TI‐VAMP silencing can represent a novel strategy to control lysosome fusion in pathological conditions.
MicroRNAs: critical regulators of epithelial to mesenchymal (EMT) and mesenchymal to epithelial transition (MET) in cancer progression
Authors: Bullock Marc D. , Sayan Abdulkadir E. , Packham Graham K. , Mirnezami Alex H.
Published: December 2011

MicroRNAs (miRNAs) are a class of small highly conserved RNAs that provide widespread expressional control through the translational repression of mRNA. MiRNAs have fundamental roles in the regulation of intracellular processes, and their importance during malignant transformation and metastasis is becoming increasingly well recognized. An important event in the metastatic cascade is epithelial to mesenchymal transition (EMT), a reversible phenotypic switch over, which endows malignant epithelial cells with the capacity to break free from one another and invade the surrounding stroma. Our understanding of EMT has been significantly improved by the characterization of miRNAs that influence the signalling pathways and downstream events that define EMT on a molecular level.

Here, we detail the role of miRNAs in EMT, and in doing so demonstrate their importance in the early stages of the metastatic cascade; we discuss a significant body of data that suggest new opportunities for drug development, and we highlight critical knowledge gaps that remain to be addressed.