Sclera-related gene polymorphisms in high myopia

[[abstract]]Purpose: Transforming growth factor-beta 2 (TGF-beta 2), basic fibroblast growth factor (bFGF), and fibromodulin (FMOD) are important extracellular matrix components of the sclera and have been shown to be associated with the development of high myopia. Our aim was to examine the association between myopia and the polymorphisms within TGF-beta 2, bFGF, and FMOD. Methods: The study group comprised of patients (n=195; age range: 17-24 years) with a spherical equivalent of -6.5 diopters (D) or a more negative refractive error. The control group comprised of individuals (n=94; age range: 17-25 years) with a spherical equivalent ranging from -0.5 D to +1.0 D. The subjects with astigmatism over -0.75 D were excluded from the study. High resolution melting (HRM) genotyping and restriction fragment length polymorphism (RFLP) genotyping were used to detect single nucleotide polymorphisms (SNPs). The polymorphisms detected were TGF-beta 2 (rs7550232 and rs991967), bFGF (rs308395 and rs41348645), and FMOD (rs7543418). Moreover, a stepwise logistic regression procedure was used to detect which of the significant SNPs contributed to the main effects of myopia development. Results: There were significant differences in the frequency of the A allele and A/A genotype in TGF-beta 2 ( rs7550232; p=0.0178 and 0.03, respectively). Moreover, the haplotype distribution of haplotype 2 (Ht2; A/A) of TGF-beta 2 differed significantly between the two groups (p=0.014). The results of the stepwise logistic regression procedure revealed that TGF-beta 2 (rs7550232) contributed significantly to the development of high myopia. Conclusions: TGF-beta 2 is an important structure of sclera and might contribute to the formation of myopia. TGF-beta 2 (rs7550232) polymorphisms, A allele and A/A genotype, had a protective role against the development of high myopia

Association of the Lumican Gene Functional 3 '-UTR Polymorphism with High Myopia

[[abstract]]PURPOSE. The lumican gene (LUM) encodes a major extracellular component of the fibrous mammalian sclera. Alteration in the expression levels of extracellular matrix components may influence scleral shape, which in turn could affect visual acuity. Single-nucleotide polymorphisms (SNPs) in the LUM gene were determined in an investigation of whether LUM gene polymorphisms correlate with high myopia. METHODS. Sequences spanning all three exons, intron-exon boundaries, and promoter regions were determined in 50 normal individuals. Five SNPs were identified, one of which was found to be a newly identified polymorphism. Genomic DNA was prepared from peripheral blood obtained from 201 patients with high myopia and 86 control subjects. Genotypes of the SNPs -1554 T/C (rs3759223), -628 A/-(rs17018757), -59 CC/-(rs3832846), c. 601 T/C (rs17853500), and the novel SNP c. 1567 C>T were determined by polymerase chain reaction. RESULTS. Of the five SNPs, one showed a significant difference between patients and control subjects (c. 1567 C>T, P = 0.0016). Haplotype analysis revealed a significantly higher presence of polymorphisms in patients with myopia (P < 0.0001). Moreover, the c. 1567 T polymorphism was determined to have lower reporter gene activity than that of c. 1567 C. CONCLUSIONS. These observations suggest that LUM gene polymorphisms contribute to the development of high myopia. (Invest Ophthalmol Vis Sci. 2010; 51: 96-102) DOI: 10.1167/iovs.09-361

Muscarinic acetylcholine receptor 1 gene polymorphisms associated with high myopia

[[abstract]]Purpose: Numerous studies, including those using animal models of myopia development and human clinical trials, have shown that the non-selective muscarinic antagonist atropine is effective in preventing the axial elongation that leads to myopia development. Among all of the muscarinic acetylcholine receptors (mAChRs), mAChR 1 (M1) was the most effective in preventing myopic eye change. Our specific aim in this study was to examine the association between high myopia and polymorphisms within the muscarinic acetylcholine receptors 1 gene (CHRM1). Methods: The participants comprised of a high myopia group (n=194; age range, 17-24 years) having a myopic spherical equivalent greater than 6.5 diopters (D) and a control group (n=109; age range, 17-25 years) having a myopic spherical equivalent less than 0.5 D. Genotyping was performed using an assay-on-demand allelic discrimination assay. Polymerase chain reaction (PCR) was performed using 96 well plates on a thermal cycler. The polymorphisms detected were S1 (CHRM1 rs11823728), S2 (CHRM1 rs544978), S3 (CHRM1 rs2186410), and S4 (CHRM1 rs542269). Results: There was a significant difference in the distribution of S2 and S4 between the high myopia and control groups (p=2.40 x 10(-6) and 2.38 x 10(-8), respectively). The odds ratios of AA genotype of S2 and GG genotype of S4 were both 0.08 (95% confidence interval [CI]: 0.02-0.29 and 0.02-0.36, respectively). Logistic regression test revealed S1, S2, and S4 CHRM1 as all being significant in the development of high myopia. Moreover, the distributions of haplotype 4 (Ht4; C/A/A/A) differed significantly between the two groups (p=3.4 x 10(-5), odds ratio: 0.1, 95% CI: 0.03-0.34). Conclusions: Our results suggest that the S2 and S4 polymorphisms of CHRM1 are associated with susceptibility for developing high myopia. S1, S2, and S4 CHRM1 had a co-operative association with high myopia

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO’s second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h95%0=3.47×10−25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering

Search for gravitational waves associated with gamma-ray bursts detected by Fermi and Swift during the LIGO–Virgo run O3b

We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC–2020 March 27 17:00 UTC). We conduct two independent searches: a generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave transient was identified in data recorded by the Advanced LIGO detectors on 2015 September 14. The event candidate, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the gravitational wave data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network Circulars, giving an overview of the participating facilities, the gravitational wave sky localization coverage, the timeline and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the electromagnetic data and results of the electromagnetic follow-up campaign will be disseminated in the papers of the individual teams