Endoscopic Therapy of Colonic Liver Flexure Mucocele

Colorectal mucoceles usually arise in the appendix, and colonic disease is very rare. We report the first case of a mucocele of the colonic liver flexure that was treated successfully with endoscopy. A 36-year-old man was admitted to our hospital because of abdominal distension persisting for 3 days. Colonoscopic examination revealed a round polyp in the hepatic flexure, and we performed hot snare polypectomy with argon plasma coagulation. Histologically, the polypectomy specimen was confirmed to be a mucocele, with no neoplastic changes. Follow-up examinations at 6 and 12 months showed no evidence of recurrence

Reconstructing phylogenies from noisy quartets in polynomial time with a high success probability

<p>Abstract</p> <p>Background</p> <p>In recent years, quartet-based phylogeny reconstruction methods have received considerable attentions in the computational biology community. Traditionally, the accuracy of a phylogeny reconstruction method is measured by simulations on synthetic datasets with known "true" phylogenies, while little theoretical analysis has been done. In this paper, we present a new model-based approach to measuring the accuracy of a quartet-based phylogeny reconstruction method. Under this model, we propose three efficient algorithms to reconstruct the "true" phylogeny with a high success probability.</p> <p>Results</p> <p>The first algorithm can reconstruct the "true" phylogeny from the input quartet topology set without quartet errors in <it>O</it>(<it>n</it>²) time by querying at most (<it>n </it>- 4) log(<it>n </it>- 1) quartet topologies, where <it>n </it>is the number of the taxa. When the input quartet topology set contains errors, the second algorithm can reconstruct the "true" phylogeny with a probability approximately 1 - <it>p </it>in <it>O</it>(<it>n</it>⁴log <it>n</it>) time, where <it>p </it>is the probability for a quartet topology being an error. This probability is improved by the third algorithm to approximately <inline-formula><m:math name="1748-7188-3-1-i1" xmlns:m="http://www.w3.org/1998/Math/MathML"><m:semantics><m:mrow><m:mfrac><m:mn>1</m:mn><m:mrow><m:mn>1</m:mn><m:mo>+</m:mo><m:msup><m:mi>q</m:mi><m:mn>2</m:mn></m:msup><m:mo>+</m:mo><m:mfrac><m:mn>1</m:mn><m:mn>2</m:mn></m:mfrac><m:msup><m:mi>q</m:mi><m:mn>4</m:mn></m:msup><m:mo>+</m:mo><m:mfrac><m:mn>1</m:mn><m:mrow><m:mn>16</m:mn></m:mrow></m:mfrac><m:msup><m:mi>q</m:mi><m:mn>5</m:mn></m:msup></m:mrow></m:mfrac></m:mrow><m:annotation encoding="MathType-MTEF"> MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGacaGaaiaabeqaaeqabiWaaaGcbaqcfa4aaSaaaeaacqaIXaqmaeaacqaIXaqmcqGHRaWkcqWGXbqCdaahaaqabeaacqaIYaGmaaGaey4kaSYaaSaaaeaacqaIXaqmaeaacqaIYaGmaaGaemyCae3aaWbaaeqabaGaeGinaqdaaiabgUcaRmaalaaabaGaeGymaedabaGaeGymaeJaeGOnaydaaiabdghaXnaaCaaabeqaaiabiwda1aaaaaaaaa@3D5A@</m:annotation></m:semantics></m:math></inline-formula>, where <inline-formula><m:math name="1748-7188-3-1-i2" xmlns:m="http://www.w3.org/1998/Math/MathML"><m:semantics><m:mrow><m:mi>q</m:mi><m:mo>=</m:mo><m:mfrac><m:mi>p</m:mi><m:mrow><m:mn>1</m:mn><m:mo>−</m:mo><m:mi>p</m:mi></m:mrow></m:mfrac></m:mrow><m:annotation encoding="MathType-MTEF"> MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGacaGaaiaabeqaaeqabiWaaaGcbaGaemyCaeNaeyypa0tcfa4aaSaaaeaacqWGWbaCaeaacqaIXaqmcqGHsislcqWGWbaCaaaaaa@3391@</m:annotation></m:semantics></m:math></inline-formula>, with running time of <it>O</it>(<it>n</it>⁵), which is at least 0.984 when <it>p </it>< 0.05.</p> <p>Conclusion</p> <p>The three proposed algorithms are mathematically guaranteed to reconstruct the "true" phylogeny with a high success probability. The experimental results showed that the third algorithm produced phylogenies with a higher probability than its aforementioned theoretical lower bound and outperformed some existing phylogeny reconstruction methods in both speed and accuracy.</p

New approaches to measuring anthelminthic drug efficacy: parasitological responses of childhood schistosome infections to treatment with praziquantel

By 2020, the global health community aims to control and eliminate human helminthiases, including schistosomiasis in selected African countries, principally by preventive chemotherapy (PCT) through mass drug administration (MDA) of anthelminthics. Quantitative monitoring of anthelminthic responses is crucial for promptly detecting changes in efficacy, potentially indicative of emerging drug resistance. Statistical models offer a powerful means to delineate and compare efficacy among individuals, among groups of individuals and among populations.; We illustrate a variety of statistical frameworks that offer different levels of inference by analysing data from nine previous studies on egg counts collected from African children before and after administration of praziquantel.; We quantify responses to praziquantel as egg reduction rates (ERRs), using different frameworks to estimate ERRs among population strata, as average responses, and within strata, as individual responses. We compare our model-based average ERRs to corresponding model-free estimates, using as reference the World Health Organization (WHO) 90 % threshold of optimal efficacy. We estimate distributions of individual responses and summarize the variation among these responses as the fraction of ERRs falling below the WHO threshold.; Generic models for evaluating responses to anthelminthics deepen our understanding of variation among populations, sub-populations and individuals. We discuss the future application of statistical modelling approaches for monitoring and evaluation of PCT programmes targeting human helminthiases in the context of the WHO 2020 control and elimination goals

The Warburg Effect Suppresses Oxidative Stress Induced Apoptosis in a Yeast Model for Cancer

BACKGROUND: Otto Warburg observed that cancer cells are often characterized by intense glycolysis in the presence of oxygen and a concomitant decrease in mitochondrial respiration. Research has mainly focused on a possible connection between increased glycolysis and tumor development whereas decreased respiration has largely been left unattended. Therefore, a causal relation between decreased respiration and tumorigenesis has not been demonstrated. METHODOLOGY/PRINCIPAL FINDINGS: For this purpose, colonies of Saccharomyces cerevisiae, which is suitable for manipulation of mitochondrial respiration and shows mitochondria-mediated cell death, were used as a model. Repression of respiration as well as ROS-scavenging via glutathione inhibited apoptosis and conferred a survival advantage during seeding and early development of this fast proliferating solid cell population. In contrast, enhancement of respiration triggered cell death. CONCLUSION/SIGNIFICANCE: Thus, the Warburg effect might directly contribute to the initiation of cancer formation--not only by enhanced glycolysis--but also via decreased respiration in the presence of oxygen, which suppresses apoptosis

Generating Bessel beams with broad depth-of-field by using phase-only acoustic holograms

[EN] We report zero-th and high-order acoustic Bessel beams with broad depth-of-field generated using acoustic holograms. While the transverse field distribution of Bessel beams generated using traditional passive methods is correctly described by a Bessel function, these methods present a common drawback: the axial distribution of the field is not constant, as required for ideal Bessel beams. In this work, we experimentally, numerically and theoretically report acoustic truncated Bessel beams of flat-intensity along their axis in the ultrasound regime using phase-only holograms. In particular, the beams present a uniform field distribution showing an elongated focal length of about 40 wavelengths, while the transverse width of the beam remains smaller than 0.7 wavelengths. The proposed acoustic holograms were compared with 3D-printed fraxicons, a blazed version of axicons. The performance of both phase-only holograms and fraxicons is studied and we found that both lenses produce Bessel beams in a wide range of frequencies. In addition, high-order Bessel beam were generated. We report first order Bessel beams that show a clear phase dislocation along their axis and a vortex with single topological charge. The proposed method may have potential applications in ultrasonic imaging, biomedical ultrasound and particle manipulation applications using passive lenses.This work was supported by the Spanish Ministry of Economy and Innovation (MINECO) through Project TEC2016-80976-R. NJ and SJ acknowledge financial support from Generalitat Valenciana through grants APOSTD/2017/042, ACIF/2017/045 and GV/2018/11. FC acknowledges financial support from Agencia Valenciana de la Innovacio through grant INNCON00/18/9 and European Regional Development Fund (IDIFEDER/2018/022).Jiménez-Gambín, S.; Jimenez, N.; Benlloch Baviera, JM.; Camarena Femenia, F. (2019). Generating Bessel beams with broad depth-of-field by using phase-only acoustic holograms. Scientific Reports. 9:1-13. https://doi.org/10.1038/s41598-019-56369-zS1139Durnin, J. Exact solutions for nondiffracting beams. i. the scalar theory. J. Opt. Soc. Am. A 4, 651 (1987).Durnin, J., Miceli, J. Jr & Eberly, J. Diffraction-free beams. Physical review letters 58, 1499 (1987).Chu, X. Analytical study on the self-healing property of Bessel beam. Eur. Phys. J. D 66, 259 (2012).McLeod, E., Hopkins, A. B. & Arnold, C. B. Multiscale Bessel beams generated by a tunable acoustic gradient index of refraction lens. Opt. Lett. 31, 3155 (2006).Li, Z., Alici, K. B., Caglayan, H. & Ozbay, E. Generation of an axially asymmetric Bessel-like beam from a metallic subwavelength aperture. Phys. Rev. Lett. 102, 143901 (2009).Fahrbach, F. & Rohrbach, A. Propagation stability of self-reconstructing Bessel beams enables contrast-enhanced imaging in thick media. Nat. Commun. 3, 632 (2011).Lu, J.-y, Zou, H. & Greenleaf, J. F. Biomedical ultrasound beam forming. Ultrasound in medicine & biology 20, 403–428 (1994).Marston, P. L. Scattering of a Bessel beam by a sphere. J. Acous. Soc. Am. 121, 753 (2007).Marston, P. L. Scattering of a Bessel beam by a sphere: Ii. helicoidal case and spherical shell example. The Journal of the Acoustical Society of America 124, 2905–2910 (2008).Lu, J. & Greenleaf, F. Ultrasonic nondiffracting transducer for medical imaging. IEEE Trans. Ultrason. Ferroelec. Freq. Contr. 37, 438 (1990).Lu, J.-Y. & Greenleaf, J. F. Pulse-echo imaging using a nondiffracting beam transducer. Ultrasound in medicine & biology 17, 265–281 (1991).Lu, J.-y, Song, T.-K., Kinnick, R. R. & Greenleaf, J. F. In vitro and in vivo real-time imaging with ultrasonic limited diffraction beams. IEEE transactions on medical imaging 12, 819–829 (1993).Lu, J.-y, Xu, X.-L., Zou, H. & Greenleaf, J. F. Application of Bessel beam for doppler velocity estimation. IEEE transactions on ultrasonics, ferroelectrics, and frequency control 42, 649–662 (1995).Nabavizadeh, A., Greenleaf, J. F., Fatemi, M. & Urban, M. W. Optimized shear wave generation using hybrid beamforming methods. Ultrasound in medicine & biology 40, 188–199 (2014).Marston, P. L. Axial radiation force of a Bessel beam on a sphere and direction reversal of the force. The Journal of the Acoustical Society of America 120, 3518–3524 (2006).Marston, P. L. Negative axial radiation forces on solid spheres and shells in a Bessel beam. The Journal of the Acoustical Society of America 122, 3162–3165 (2007).Marston, P. L. Radiation force of a helicoidal Bessel beam on a sphere. The Journal of the Acoustical Society of America 125, 3539–3547 (2009).Thomas, J.-L. & Marchiano, R. Pseudo angular momentum and topological charge conservation for nonlinear acoustical vortices. Physical review letters 91, 244302 (2003).Volke-Sepúlveda, K., Santillán, A. O. & Boullosa, R. R. Transfer of angular momentum to matter from acoustical vortices in free space. Phys. Rev. Lett. 100, 024302 (2008).Zhang, L. & Marston, P. L. Geometrical interpretation of negative radiation forces of acoustical Bessel beams on spheres. Physical Review E 84, 035601 (2011).Courtney, C. R. et al. Dexterous manipulation of microparticles using Bessel-function acoustic pressure fields. Applied Physics Letters 102, 123508 (2013).Hong, Z., Zhang, J. & Drinkwater, B. W. Observation of orbital angular momentum transfer from Bessel-shaped acoustic vortices to diphasic liquid-microparticle mixtures. Phys. Rev. Lett. 114, 214301 (2015).Baresch, D., Thomas, J.-L. &Marchiano, R. Observation of a single-beam gradient force acoustical trap for elastic particles: Acoustical tweezers. Phys. Rev. Lett. 116 (2016).Marzo, A., Caleap, M. & Drinkwater, B. W. Acoustic virtual vortices with tunable orbital angular momentum for trapping of mie particles. Phys. Rev. Lett. 120, 044301 (2018).Li, Y. et al. Acoustic radiation torque of an acoustic-vortex spanner exerted on axisymmetric objects. Applied Physics Letters 112, 254101 (2018).Riaud, A., Baudoin, M., Thomas, J.-L. & Matar, O. B. Cyclones and attractive streaming generated by acoustical vortices. Physical Review E 90, 013008 (2014).Shi, C., Dubois, M., Wang, Y. & Zhang, X. High-speed acoustic communication by multiplexing orbital angular momentum. Proceedings of the National Academy of Sciences 114, 7250–7253 (2017).Jiang, X., Liang, B., Cheng, J.-C. & Qiu, C.-W. Twisted acoustics: metasurface-enabled multiplexing and demultiplexing. Advanced Materials 30, 1800257 (2018).Hsu, D., Margetan, F. & Thompson, D. O. Bessel beam ultrasonic transducer: fabrication method and experimental results. Appl. Phys. Lett. 55, 2066 (1989).Campbell, J. A. & Soloway, S. Generation of a nondiffracting beam with frequency-independent beamwidth. The Journal of the Acoustical Society of America 88, 2467–2477 (1990).Masuyama, H., Yokoyama, T., Nagai, K. & Mizutani, K. Generation of Bessel beam from equiamplitude-driven annular transducer array consisting of a few elements. Jpn. J. Appl. Phys. 38, 3080 (1999).Fjield, T., Fan, X. & Hynynen, K. A parametric study of the concentric-ring transducer design for mri guided ultrasound surgery. J. Acoust. Soc. Am. 100, 1220 (1996).Chillara, V. K., Pantea, C. & Sinha, D. N. Low-frequency ultrasonic Bessel-like collimated beam generation from radial modes of piezoelectric transducers. Applied Physics Letters 110, 064101 (2017).Burckhardt, C., Hoffmann, H. & Grandchamp, P.-A. Ultrasound axicon: A device for focusing over a large depth. The Journal of the Acoustical Society of America 54, 1628–1630 (1973).Foster, F., Patterson, M., Arditi, M. & Hunt, J. The conical scanner: a two transducer ultrasound scatter imaging technique. Ultrasonic imaging 3, 62–82 (1981).McLeod, J. H. The axicon: A new type of optical element. J. Opt. Soc. Am. 44, 592 (1954).Arlt, J. & Dholakia, K. Generation of high-order Bessel beams by use of an axicon. Optics Communications 177, 297–301 (2000).Golub, I. Fresnel axicon. Optics letters 31, 1890–1892 (2006).Lirette, R. & Mobley, J. Broadband wave packet dynamics of minimally diffractive ultrasonic fields from axicon and stepped fraxicon lenses. The Journal of the Acoustical Society of America 146, 103–108 (2019).Jiménez, N. et al. Acoustic Bessel-like beam formation by an axisymmetric grating. Europhys. Lett. 106, 24005 (2014).Xu, Z., Xu, W., Qian, M., Cheng, Q. & Liu, X. A flat acoustic lens to generate a Bessel-like beam. Ultrasonics 80, 66–71 (2017).Li, Y., Liang, B., Gu, Z.-M., Zou, X.-Y. & Cheng, J.-C. Reflected wavefront manipulation based on ultrathin planar acoustic metasurfaces. Scientific Reports 3, 2546 (2013).Nye, J. & Berry, M. Dislocations in wave trains. Proc. R. Soc. London, Ser. A 336, 165–190 (1974).Jiménez, N. et al. Formation of high-order acoustic Bessel beams by spiral diffraction gratings. Physical Review E 94, 053004 (2016).Wang, T. et al. Particle manipulation with acoustic vortex beam induced by a brass plate with spiral shape structure. Applied Physics Letters 109, 123506 (2016).Jia, Y.-R., Wei, Q., Wu, D.-J., Xu, Z. & Liu, X.-J. Generation of fractional acoustic vortex with a discrete archimedean spiral structure plate. Applied Physics Letters 112, 173501 (2018).Jiménez, N., Romero-Garca, V., Garca-Raffi, L. M., Camarena, F. & Staliunas, K. Sharp acoustic vortex focusing by fresnel-spiral zone plates. Applied Physics Letters 112, 204101 (2018).Baudoin, M. et al. Folding a focalized acoustical vortex on a flat holographic transducer: miniaturized selective acoustical tweezers. Science advances 5, eaav1967 (2019).Muelas-Hurtado, R. D., Ealo, J. L., Pazos-Ospina, J. F. & Volke-Sepúlveda, K. Acoustic analysis of a broadband spiral source for the simultaneous generation of multiple Bessel vortices in air. The Journal of the Acoustical Society of America 144, 3252–3261 (2018).Muelas-Hurtado, R. D., Ealo, J. L., Pazos-Ospina, J. F. & Volke-Sepúlveda, K. Generation of multiple vortex beam by means of active diffraction gratings. Applied Physics Letters 112, 084101 (2018).Wunenburger, R., Lozano, J. I. V. & Brasselet, E. Acoustic orbital angular momentum transfer to matter by chiral scattering. New Journal of Physics 17, 103022 (2015).Terzi, M., Tsysar, S., Yuldashev, P., Karzova, M. & Sapozhnikov, O. Generation of a vortex ultrasonic beam with a phase plate with an angular dependence of the thickness. Moscow University Physics Bulletin 72, 61–67 (2017).Hefner, B. T. & Marston, P. L. An acoustical helicoidal wave transducer with applications for the alignment of ultrasonic and underwater systems. Jour. Acous. Soc. Am. 106, 3313–3316 (1999).Ealo, J. L., Prieto, J. C. & Seco, F. Airborne ultrasonic vortex generation using flexible ferroelectrets. IEEE transactions on ultrasonics, ferroelectrics, and frequency control 58, 1651–1657 (2011).Naify, C. J. et al. Generation of topologically diverse acoustic vortex beams using a compact metamaterial aperture. Applied Physics Letters 108, 223503 (2016).Ye, L. et al. Making sound vortices by metasurfaces. AIP Advances 6, 085007 (2016).Jiang, X., Li, Y., Liang, B., Cheng, J.-C. & Zhang, L. Convert acoustic resonances to orbital angular momentum. Physical review letters 117, 034301 (2016).Esfahlani, H., Lissek, H. & Mosig, J. R. Generation of acoustic helical wavefronts using metasurfaces. Physical Review B 95, 024312 (2017).Jiménez-Gambn, S., Jiménez, N., Benlloch, J. M. & Camarena, F. Holograms to focus arbitrary ultrasonic fields through the skull. Physical Review Applied 12, 014016 (2019).Maimbourg, G., Houdouin, A., Deffieux, T., Tanter, M. & Aubry, J.-F. 3d-printed adaptive acoustic lens as a disruptive technology for transcranial ultrasound therapy using single-element transducers. Physics in Medicine & Biology 63, 025026 (2018).Ferri, M. et al. On the evaluation of the suitability of the materials used to 3d print holographic acoustic lenses to correct transcranial focused ultrasound aberrations. Polymers 11, 1521 (2019).Melde, K., Mark, A. G., Qiu, T. & Fischer, P. Holograms for acoustics. Nature 537, 518 (2016).Brown, M. D., Cox, B. T. & Treeby, B. E. Design of multi-frequency acoustic kinoforms. Applied Physics Letters 111, 244101 (2017).Brown, M., Nikitichev, D., Treeby, B. & Cox, B. Generating arbitrary ultrasound fields with tailored optoacoustic surface profiles. Applied Physics Letters 110, 094102 (2017).Zhu, Y. et al. Fine manipulation of sound via lossy metamaterials with independent and arbitrary reflection amplitude and phase. Nature communications 9, 1632 (2018).Brown, M. D. Phase and amplitude modulation with acoustic holograms. Applied Physics Letters 115, 053701 (2019).Jiménez, N., Romero-Garca, V., Pagneux, V. & Groby, J.-P. Quasiperfect absorption by subwavelength acoustic panels in transmission using accumulation of resonances due to slow sound. Physical Review B 95, 014205 (2017).Tsang, P. W. M. & Poon, T.-C. Novel method for converting digital fresnel hologram to phase-only hologram based on bidirectional error diffusion. Optics Express 21, 23680–23686 (2013).Soret, J. Ueber die durch kreisgitter erzeugten diffractionsphänomene. Annalen der Physik 232, 99–113 (1875).Turunen, J., Vasara, A. & Friberg, A. T. Holographic generation of diffraction-free beams. Applied Optics 27, 3959–3962 (1988).Vasara, A., Turunen, J. & Friberg, A. T. Realization of general nondiffracting beams with computer-generated holograms. JOSA A 6, 1748–1754 (1989).Cunningham, K. B. & Hamilton, M. F. Bessel beams of finite amplitude in absorbing fluids. J. Acous. Soc. Am. 108, 519 (2000).Ding, D. & Y. Lu, J. Higher-order harmonics of limited diffraction Bessel beams. J. Acous. Soc. Am. 107, 1212 (2000).Skeldon, K., Wilson, C., Edgar, M. & Padgett, M. An acoustic spanner and its associated rotational Doppler shift. New J. Phys. 10, 013018 (2008).Wu, J. Acoustical tweezers. J. Acoust. Soc. Am. 89, 2140–2143 (1991).Zhang, L. & Marston, P. L. Angular momentum flux of nonparaxial acoustic vortex beams and torques on axisymmetric objects. Physical Review E 84, 065601 (2011).Yoon, C., Kang, B. J., Lee, C., Kim, H. H. & Shung, K. K. Multi-particle trapping and manipulation by a high-frequency array transducer. Appl. Phys. Lett. 105, 214103 (2014).Marzo, A. et al. Holographic acoustic elements for manipulation of levitated objects. Nat. Commun. 6 (2015).Blackstock, D. T. Fundamentals of physical acoustics (John Wiley & Sons, 2000).Treeby, B. E. & Cox, B. Modeling power law absorption and dispersion for acoustic propagation using the fractional laplacian. The Journal of the Acoustical Society of America 127, 2741–2748 (2010).Treeby, B. E., Jaros, J., Rendell, A. P. & Cox, B. Modeling nonlinear ultrasound propagation in heterogeneous media with power law absorption using a k-space pseudospectral method. The Journal of the Acoustical Society of America 131, 4324–4336 (2012).Jiménez, N. et al. Time-domain simulation of ultrasound propagation in a tissue-like medium based on the resolution of the nonlinear acoustic constitutive relations. Acta Acustica united with Acustica 102, 876–892 (2016)

Cranial biomechanics in basal urodeles: the Siberian salamander (Salamandrella keyserlingii) and its evolutionary and developmental implications

Developmental changes in salamander skulls, before and after metamorphosis, afect the feeding capabilities of these animals. How changes in cranial morphology and tissue properties afect the function of the skull are key to decipher the early evolutionary history of the crown-group of salamanders. Here, 3D cranial biomechanics of the adult Salamandrella keyserlingii were analyzed under diferent tissue properties and ossifcation sequences of the cranial skeleton. This helped unravel that: (a) Mechanical properties of tissues (as bone, cartilage or connective tissue) imply a consensus between the stifness required to perform a function versus the fxation (and displacement) required with the surrounding skeletal elements. (b) Changes on the ossifcation pattern, producing fontanelles as a result of bone loss or failure to ossify, represent a trend toward simplifcation potentially helping to distribute stress through the skull, but may also imply a major destabilization of the skull. (c) Bone loss may be originated due to biomechanical optimization and potential reduction of developmental costs. (d) Hynobiids are excellent models for biomechanical reconstruction of extinct early urodeles

Altering α-dystroglycan receptor affinity of LCMV pseudotyped lentivirus yields unique cell and tissue tropism

BACKGROUND: The envelope glycoprotein of lymphocytic choriomeningitis virus (LCMV) can efficiently pseudotype lentiviral vectors. Some strains of LCMV exploit high affinity interactions with α-dystroglycan (α-DG) to bind to cell surfaces and subsequently fuse in low pH endosomes. LCMV strains with low α-DG affinity utilize an unknown receptor and display unique tissue tropisms. We pseudotyped non-primate feline immunodeficiency virus (FIV) vectors using LCMV derived glycoproteins with high or low affinity to α-DG and evaluated their properties in vitro and in vivo. METHODS: We pseudotyped FIV with the LCMV WE54 strain envelope glycoprotein and also engineered a point mutation in the WE54 envelope glycoprotein (L260F) to diminish α-DG affinity and direct binding to alternate receptors. We hypothesized that this change would alter in vivo tissue tropism and enhance gene transfer to neonatal animals. RESULTS: In mice, hepatic α- and β-DG expression was greatest at the late gestational and neonatal time points. When displayed on the surface of the FIV lentivirus the WE54 L260F mutant glycoprotein bound weakly to immobilized α-DG. Additionally, LCMV WE54 pseudotyped FIV vector transduction was neutralized by pre-incubation with soluble α-DG, while the mutant glycoprotein pseudotyped vector was not. In vivo gene transfer in adult mice with either envelope yielded low transduction efficiencies in hepatocytes following intravenous delivery. In marked contrast, neonatal gene transfer with the LCMV envelopes, and notably with the FIV-L260F vector, conferred abundant liver and lower level cardiomyocyte transduction as detected by luciferase assays, bioluminescent imaging, and β-galactosidase staining. CONCLUSIONS: These results suggest that a developmentally regulated receptor for LCMV is expressed abundantly in neonatal mice. LCMV pseudotyped vectors may have applications for neonatal gene transfer. ABBREVIATIONS: Armstrong 53b (Arm53b); baculovirus Autographa californica GP64 (GP64); charge-coupled device (CCD); dystroglycan (DG); feline immunodeficiency virus (FIV); glycoprotein precursor (GP-C); firefly luciferase (Luc); lymphocytic choriomeningitis virus (LCMV); nuclear targeted β-galactosidase (ntLacZ); optical density (OD); PBS/0.1% (w/v) Tween-20 (PBST); relative light units (RLU); Rous sarcoma virus (RSV); transducing units per milliliter (TU/ml); vesicular stomatitis virus (VSV-G); wheat germ agglutinin (WGA); 50% reduction in binding (C50)

Altering α-dystroglycan receptor affinity of LCMV pseudotyped lentivirus yields unique cell and tissue tropism

BACKGROUND: The envelope glycoprotein of lymphocytic choriomeningitis virus (LCMV) can efficiently pseudotype lentiviral vectors. Some strains of LCMV exploit high affinity interactions with α-dystroglycan (α-DG) to bind to cell surfaces and subsequently fuse in low pH endosomes. LCMV strains with low α-DG affinity utilize an unknown receptor and display unique tissue tropisms. We pseudotyped non-primate feline immunodeficiency virus (FIV) vectors using LCMV derived glycoproteins with high or low affinity to α-DG and evaluated their properties in vitro and in vivo. METHODS: We pseudotyped FIV with the LCMV WE54 strain envelope glycoprotein and also engineered a point mutation in the WE54 envelope glycoprotein (L260F) to diminish α-DG affinity and direct binding to alternate receptors. We hypothesized that this change would alter in vivo tissue tropism and enhance gene transfer to neonatal animals. RESULTS: In mice, hepatic α- and β-DG expression was greatest at the late gestational and neonatal time points. When displayed on the surface of the FIV lentivirus the WE54 L260F mutant glycoprotein bound weakly to immobilized α-DG. Additionally, LCMV WE54 pseudotyped FIV vector transduction was neutralized by pre-incubation with soluble α-DG, while the mutant glycoprotein pseudotyped vector was not. In vivo gene transfer in adult mice with either envelope yielded low transduction efficiencies in hepatocytes following intravenous delivery. In marked contrast, neonatal gene transfer with the LCMV envelopes, and notably with the FIV-L260F vector, conferred abundant liver and lower level cardiomyocyte transduction as detected by luciferase assays, bioluminescent imaging, and β-galactosidase staining. CONCLUSIONS: These results suggest that a developmentally regulated receptor for LCMV is expressed abundantly in neonatal mice. LCMV pseudotyped vectors may have applications for neonatal gene transfer. ABBREVIATIONS: Armstrong 53b (Arm53b); baculovirus Autographa californica GP64 (GP64); charge-coupled device (CCD); dystroglycan (DG); feline immunodeficiency virus (FIV); glycoprotein precursor (GP-C); firefly luciferase (Luc); lymphocytic choriomeningitis virus (LCMV); nuclear targeted β-galactosidase (ntLacZ); optical density (OD); PBS/0.1% (w/v) Tween-20 (PBST); relative light units (RLU); Rous sarcoma virus (RSV); transducing units per milliliter (TU/ml); vesicular stomatitis virus (VSV-G); wheat germ agglutinin (WGA); 50% reduction in binding (C50)

Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay

The decay channel $\psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p})$ is studied using a sample of $1.06\times 10^8$ $\psi^\prime$ events collected by the BESIII experiment at BEPCII. A strong enhancement at threshold is observed in the $p\bar{p}$ invariant mass spectrum. The enhancement can be fit with an $S$-wave Breit-Wigner resonance function with a resulting peak mass of $M=1861^{+6}_{-13} {\rm (stat)}^{+7}_{-26} {\rm (syst)} {\rm MeV/}c^2$ and a narrow width that is $\Gamma<38 {\rm MeV/}c^2$ at the 90% confidence level. These results are consistent with published BESII results. These mass and width values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics