1,964 research outputs found

    Cultivation of tropical red seaweeds in the BIMP-EAGA region

    Get PDF
    The Brunei–Indonesia–Malaysia–Philippines East Asia Growth Area (BIMP-EAGA) is located within the Coral Triangle, known to have the world’s richest biodiversity in marine flora and fauna. This region lies within the 10° N and 10° S of the Equator where natural populations of both Kappaphycus and Eucheuma grow luxuriantly and abundantly. It is in this same region where commercial cultivation of Kappaphycus and Eucheuma began in the Philippines around the mid-1960s. Commercial farming of Kappaphycus (which was originally called Eucheuma) was successful in the Philippines from the early 1970s, after which the technology was transferred to Indonesia and Malaysia in the late 1970s. No seaweed cultivation has been reported in Brunei. At present, carrageenophytes are cultivated in sub-tropical to tropical countries circumferentially around the globe within the 10° N and S of the Equator. However, their combined production is still low as compared to Indonesia, the Philippines, and Malaysia. Notably, few improvements in farming techniques have been made since its first introduction. Some of the major improvements were the introduction of deep-water farming using hanging long lines, multiple rafts, and spider webs in the Philippines; the use of short and long ‘loops’, instead of plastic ‘tie-tie’ in Indonesia; and mechanization in harvesting and use of solar “greenhouse” drying in Malaysia. Commercial cultivation of tropical red seaweeds in the BIMP-EAGA region is dominated by Kappaphycus and Eucheuma (carrageenophytes) and Gracilaria (agarophytes) and the area became the major region for the production of carageenophytes and agarophytes globally. In particular, Indonesia is a major center for the production of Gracilaria. There is an increasing demand for other agarophytes / carrageenophytes in the international market such as Gelidium spp., Pterocladia spp., Porphyroglossum sp., and Ptilophora sp. for paper and ethanol production in Indonesia and Malaysia, and Halymenia for phycoerythrin pigments in the Philippines currently pursued in an experimental stage. A summary of the present status, problems, sustainability, and challenges for the cultivation of tropical red seaweeds in the BIMP-EAGA region are discussed in this paper

    Emergent group level navigation: an agent-based evaluation of movement patterns in a folivorous primate.

    Get PDF
    The foraging activity of many organisms reveal strategic movement patterns, showing efficient use of spatially distributed resources. The underlying mechanisms behind these movement patterns, such as the use of spatial memory, are topics of considerable debate. To augment existing evidence of spatial memory use in primates, we generated movement patterns from simulated primate agents with simple sensory and behavioral capabilities. We developed agents representing various hypotheses of memory use, and compared the movement patterns of simulated groups to those of an observed group of red colobus monkeys (Procolobus rufomitratus), testing for: the effects of memory type (Euclidian or landmark based), amount of memory retention, and the effects of social rules in making foraging choices at the scale of the group (independent or leader led). Our results indicate that red colobus movement patterns fit best with simulated groups that have landmark based memory and a follow the leader foraging strategy. Comparisons between simulated agents revealed that social rules had the greatest impact on a group's step length, whereas the type of memory had the highest impact on a group's path tortuosity and cohesion. Using simulation studies as experimental trials to test theories of spatial memory use allows the development of insight into the behavioral mechanisms behind animal movement, developing case-specific results, as well as general results informing how changes to perception and behavior influence movement patterns

    Increasing Therapy Related Myeloid Neoplasms in Multiple Myeloma

    Get PDF
    © 2018 Stichting European Society for Clinical Investigation Journal Foundation. This document is made available under the CC-BY-NC 4.0 license http://creativecommons.org/licenses/by-nc /4.0/ This document is the submitted version of a published work that appeared in final form in European Journal of Clinical Investigation.Background: Despite the longer survival achieved in multiple myeloma (MM) patients due to new therapy strategies, a concern is emerging regarding an increased risk of secondary primary malignancies (SPMs) and how to characterize those patients at risk. We performed a retrospective study covering a 28‐year follow‐ up period (1991‐2018) in a tertiary single institution. Material and Methods: Data of 403 MM patients were recorded and compared with the epidemiologic register of the population area covered by our centre, calculating the standardize incidence ratio (SIR) for the different types of SPMs diagnosed in the MM cohort. Fine and Gray regression models were used to identify risk factors for SPMs. Results: Out of the 403 MM patients, 23 (5.7%) developed SPMs: 13 therapyrelated myeloid (TRM) malignancies (10 of them (77%) myelodysplastic syndrome (MDS), 1 acute lymphoid leukaemia and 9 solid neoplasms. In the MM cohort, the relative risk of MDS was significantly higher than in the general population. Survival of patients with TRM malignancies was poor with a median of 4 months from the diagnosis, and most of them showed complex karyotype. Within the MM subset, multivariable analysis showed a higher risk of TRM malignancies in patients that previously received prolonged treatment with lenalidomide (>18 months). Conclusions: Though the improvement in MM outcome during the last decades is an unprecedented achievement, it has been accompanied by the rise in TRM malignancies with complex cytogenetic profile and poor prognosis that are in the need of an improved biologic and therapeutic approach

    Laterally Coupled Nanowire Lasers: Bifurcations, Dynamics and High-Speed Potential

    Get PDF
    Regions of stability in two laterally-coupled InP nanowire lasers are analysed in terms of their separation, difference in resonant frequencies and pumping rate. The frequency of periodic oscillations for realistic laser separations and pumping is estimated to be of order 100-1000 GHz

    Patients' experiences with quality of hospital care: the Consumer Quality Index Cataract Questionnaire

    Get PDF
    Background. Patients' feedback is of great importance in health care policy decisions. The Consumer Quality Index Cataract Questionnaire (CQI Cataract) was used to measure patients' experiences with quality of care after a cataract operation. This study aims to evaluate the reliability and the dimensional structure of this questionnaire and assesses its ability to measure differences between hospitals in patients' experiences with quality of care. Methods. Survey data of 4,635 respondents were available. An exploratory factor analysis was performed to evaluate the construct validity of the questionnaire and item-correlations and inter-factor correlations were calculated. Secondly, Cronbach's alpha coefficients were calculated to assess the internal consistency of the scales. Thirdly, to evaluate the ability of the questionnaire to discriminate between hospitals, multilevel analyses were performed with patients hierarchically nested within hospitals. Results. Exploratory factor analysis resulted in 14 quality of care items subdivided over three factors (i.e. communication with ophthalmologist, communication with nurses, and communication about medication). Cronbach's alpha coefficients of 0.89, 0.76 and 0.79 indicated good internal consistency. Multilevel analyses showed that the questionnaire was able to measure differences in patients' experiences with hospital care regarding communication with ophthalmologist and communication about medication. In addition, there was variation between hospitals regarding ophthalmologist ratings, hospital ratings and one dichotomous information item. Conclusion. These findings suggest that the CQI Cataract is a reliable and valid instrument. This instrument can be used to measure patients' experiences with three domains of hospital care after a cataract operation and is able to assess differences in evaluated care between hospitals

    Epigenetic reprogramming at estrogen-receptor binding sites alters 3D chromatin landscape in endocrine-resistant breast cancer

    Get PDF
    Endocrine therapy resistance frequently develops in estrogen receptor positive (ER+) breast cancer, but the underlying molecular mechanisms are largely unknown. Here, we show that 3-dimensional (3D) chromatin interactions both within and between topologically associating domains (TADs) frequently change in ER+ endocrine-resistant breast cancer cells and that the differential interactions are enriched for resistance-associated genetic variants at CTCF-bound anchors. Ectopic chromatin interactions are preferentially enriched at active enhancers and promoters and ER binding sites, and are associated with altered expression of ER-regulated genes, consistent with dynamic remodelling of ER pathways accompanying the development of endocrine resistance. We observe that loss of 3D chromatin interactions often occurs coincidently with hypermethylation and loss of ER binding. Alterations in active A and inactive B chromosomal compartments are also associated with decreased ER binding and atypical interactions and gene expression. Together, our results suggest that 3D epigenome remodelling is a key mechanism underlying endocrine resistance in ER+ breast cancer

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

    Full text link
    [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).JimĂ©nez-GambĂ­n, 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-SepĂșlveda, K., SantillĂĄn, 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).JimĂ©nez, 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).JimĂ©nez, 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).JimĂ©nez, 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-SepĂșlveda, 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-SepĂșlveda, 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).JimĂ©nez-Gambn, S., JimĂ©nez, 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).JimĂ©nez, 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 diffractionsphĂ€nomene. 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).JimĂ©nez, 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)

    Hypervariable intronic region in NCX1 is enriched in short insertion-deletion polymorphisms and showed association with cardiovascular traits

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Conserved non-coding regions (CNR) have been shown to harbor gene expression regulatory elements. Genetic variations in these regions may potentially contribute to complex disease susceptibility.</p> <p>Methods</p> <p>We targeted CNRs of cardiovascular disease (CVD) candidate gene, <it>Na(+)-Ca(2+) exchanger (NCX1) </it>with polymorphism screening among CVD patients (n = 46) using DHPLC technology. The flanking region (348 bp) of the 14 bp indel in intron 2 was further genotyped by DGGE assay in two Eastern-European CVD samples: essential hypertension (HYPEST; 470 cases, 652 controls) and coronary artery disease, CAD (CADCZ; 257 cases, controls 413). Genotype-phenotype associations were tested by regression analysis implemented in PLINK. Alignments of primate sequences were performed by ClustalW2.</p> <p>Results</p> <p>Nine of the identified <it>NCX1 </it>variants were either singletons or targeted by commercial platforms. The 14 bp intronic indel (rs11274804) was represented with substantial frequency in HYPEST (6.82%) and CADCZ (14.58%). Genotyping in Eastern-Europeans (n = 1792) revealed hypervariable nature of this locus, represented by seven alternative alleles. The alignments of human-chimpanzee-macaque sequences showed that the major human variant (allele frequency 90.45%) was actually a human-specific deletion compared to other primates. In humans, this deletion was surrounded by other short (5-43 bp) deletion variants and a duplication (40 bp) polymorphism possessing overlapping breakpoints. This indicates a potential indel hotspot, triggered by the initial deletion in human lineage. An association was detected between the carrier status of 14 bp indel ancestral allele and CAD (<it>P </it>= 0.0016, OR = 2.02; Bonferroni significance level alpha = 0.0045), but not with hypertension. The risk for the CAD development was even higher among the patients additionally diagnosed with metabolic syndrome (<it>P </it>= 0.0014, OR = 2.34). Consistent with the effect on metabolic processes, suggestive evidence for the association with heart rate, serum triglyceride and LDL levels was detected (<it>P </it>= 0.04).</p> <p>Conclusions</p> <p>Compared to SNPs targeted by large number of locus-specific and genome-wide assays, considerably less attention has been paid to short indel variants in the human genome. The data of genome dynamics, mutation rate and population genetics of short indels, as well as their impact on gene expressional profile and human disease susceptibility is limited. The characterization of <it>NCX1 </it>intronic hypervariable non-coding region enriched in human-specific indel variants contributes to this gap of knowledge.</p
    • 

    corecore