The C-Terminus of Histone H2B Is Involved in Chromatin Compaction Specifically at Telomeres, Independently of Its Monoubiquitylation at Lysine 123

Telomeric heterochromatin assembly in budding yeast propagates through the association of Silent Information Regulator (SIR) proteins with nucleosomes, and the nucleosome array has been assumed to fold into a compacted structure. It is believed that the level of compaction and gene repression within heterochromatic regions can be modulated by histone modifications, such as acetylation of H3 lysine 56 and H4 lysine 16, and monoubiquitylation of H2B lysine 123. However, it remains unclear as to whether or not gene silencing is a direct consequence of the compaction of chromatin. Here, by investigating the role of the carboxy-terminus of histone H2B in heterochromatin formation, we identify that the disorderly compaction of chromatin induced by a mutation at H2B T122 specifically hinders telomeric heterochromatin formation. H2B T122 is positioned within the highly conserved AVTKY motif of the αC helix of H2B. Heterochromatin containing the T122E substitution in H2B remains inaccessible to ectopic dam methylase with dramatically increased mobility in sucrose gradients, indicating a compacted chromatin structure. Genetic studies indicate that this unique phenotype is independent of H2B K123 ubiquitylation and Sir4. In addition, using ChIP analysis, we demonstrate that telomere structure in the mutant is further disrupted by a defect in Sir2/Sir3 binding and the resulting invasion of euchromatic histone marks. Thus, we have revealed that the compaction of chromatin per se is not sufficient for heterochromatin formation. Instead, these results suggest that an appropriately arrayed chromatin mediated by H2B C-terminus is required for SIR binding and the subsequent formation of telomeric chromatin in yeast, thereby identifying an intrinsic property of the nucleosome that is required for the establishment of telomeric heterochromatin. This requirement is also likely to exist in higher eukaryotes, as the AVTKY motif of H2B is evolutionarily conserved

An Integration of Genome-Wide Association Study and Gene Expression Profiling to Prioritize the Discovery of Novel Susceptibility Loci for Osteoporosis-Related Traits

Osteoporosis is a complex disorder and commonly leads to fractures in elderly persons. Genome-wide association studies (GWAS) have become an unbiased approach to identify variations in the genome that potentially affect health. However, the genetic variants identified so far only explain a small proportion of the heritability for complex traits. Due to the modest genetic effect size and inadequate power, true association signals may not be revealed based on a stringent genome-wide significance threshold. Here, we take advantage of SNP and transcript arrays and integrate GWAS and expression signature profiling relevant to the skeletal system in cellular and animal models to prioritize the discovery of novel candidate genes for osteoporosis-related traits, including bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), as well as geometric indices of the hip (femoral neck-shaft angle, NSA; femoral neck length, NL; and narrow-neck width, NW). A two-stage meta-analysis of GWAS from 7,633 Caucasian women and 3,657 men, revealed three novel loci associated with osteoporosis-related traits, including chromosome 1p13.2 (RAP1A, p = 3.6×10−8), 2q11.2 (TBC1D8), and 18q11.2 (OSBPL1A), and confirmed a previously reported region near TNFRSF11B/OPG gene. We also prioritized 16 suggestive genome-wide significant candidate genes based on their potential involvement in skeletal metabolism. Among them, 3 candidate genes were associated with BMD in women. Notably, 2 out of these 3 genes (GPR177, p = 2.6×10−13; SOX6, p = 6.4×10−10) associated with BMD in women have been successfully replicated in a large-scale meta-analysis of BMD, but none of the non-prioritized candidates (associated with BMD) did. Our results support the concept of our prioritization strategy. In the absence of direct biological support for identified genes, we highlighted the efficiency of subsequent functional characterization using publicly available expression profiling relevant to the skeletal system in cellular or whole animal models to prioritize candidate genes for further functional validation

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Use clinical data to calculate abdominal aortic calcification score and total length of calcification

[[abstract]]腹主動脈鈣化（Abdominal Aortic Calcification，AAC）是導致心血管疾病的重要因素，洗腎患者每年均須照一次腹部X光片，而此X光片需透過人工方式計算其腹主動脈血管鈣化程度，但可能因每個醫師的標準不同而有不一樣的評分程度以及需耗費不少人力。因此本論文基於人工智慧的遮罩型區域卷積類神經網路（Mask Region based Convolution Neural Networks，Mask R-CNN），利用其實例分割（Instance Segmentation）、語義分割（Semantic Segmentation）和YOLOv5物件偵測（Object Detection）方面卓越的效能，在臨床上對洗腎病人的臨床資料客觀且快速地進行全自動辨識腹主動脈鈣化區域以及計算其腰椎X光照片腹主動脈的鈣化長度用以依照鈣化分數評分標準來計算鈣化分數，藉此統一鈣化分數的評分標準並達到節省人力成本及提高效率的效果。[[abstract]]Abdominal Aortic Calcification (AAC) is an important factor leading to cardiovascular disease. Patients with dialysis must take an abdominal X-ray photo once a year, and this X-ray photo needs to be calculated for the degree of abdominal aortic vascular calcification by doctor. However, there may be different scoring levels and a lot of manpower required due to the different standards of each physician. Therefore, this paper is based on Mask Region based Convolution Neural Networks (Mask R-CNN), takes advantage of its outstanding performance in Instance Segmentation, Semantic Segmentation and YOLOv5 Object Detection. In clinical trials, the X-ray photo of dialysis patients can be used to objectively and quickly identify the abdominal aortic calcification range and calculate the calcification score and length of the abdominal aorta in the lumbar X-ray photo according to the scoring standard of calcification score by Artificial Intelligence(AI) to save labor costs and improve efficiency of doctor

Strategy to Estimate Sample Sizes to Justify the Association between MMP1 SNP and Osteoarthritis

Background: the impact of knee osteoarthritis (OA) poses a formidable challenge to older adults. Studies have reported that genetic factors, such as MMP1, are one of important risk factors for knee OA. Although the relationship between the genetic polymorphism of MMP1 rs1799750 and the risk of knee OA has been explored, conclusions have been nonunanimous and pending due to research sample sizes, one of determinants in studying genetic polymorphisms associated with disease. Objective: to establish a model to assess whether the genetic polymorphism of MMP1 rs1799750 is associated with knee OA based on an estimation of sample sizes. Methods: samples were collected from a case–control and meta-analysis study. In the case–control study, patients who underwent knee X-ray examinations based on the Kellgren–Lawrence Grading System (KL) as diagnostic criteria were recruited at the Health Examination Center of the Tri-Service General Hospital from 2015 to 2019. Gene sequencing was conducted using iPLEX Gold. Those with unsuccessful gene sequencing were excluded. Finally, there were 569 patients in the knee OA group (KL ≥ 2) and 534 participants in the control group (KL < 2). In the meta-analysis, we used the databases PubMed, EMBASE, and Cochrane to search for studies on the relationship between MMP1 rs1799750 and knee OA. Next, we adopted the trial sequential analysis (TSA) method to assess whether sample sizes were sufficient or not to determine the risk of the genetic polymorphism of MMP1 rs1799750 on knee OA in Caucasians and Asians. Results: in Caucasians, the MMP1 rs1799750 was not significantly associated with knee OA with an odds ratios (OR) of 1.10 (95% confidence interval, CI: 0.45–2.68). Some extra 8559 samples were needed to conclude this relationship in Caucasians by the TSA model. In Asians, neither our case–control study results (n = 1103) nor a combination of samples from the case–control and meta-analysis results showed an association between MMP1 rs1799750 and knee OA. The OR (95% CI) was 1.10 (0.81–1.49) in a combination of Asian samples. Some extra 5517 samples were needed to justify this relationship in Asians by the TSA model. Conclusions: this research shows that an extra 8559 and 5517 samples are needed in Caucasians and Asians, respectively, in order to justify the association between MMP1 rs1799750 and knee OA

A rare presentation of adult T-cell leukemia/lymphoma with generalized cutaneous purpuric lesions

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy caused by human T-cell lymphotropic virus type 1. The disease is characterized by the presence of pleomorphic lymphocytes and cutaneous purpuric eruptions with skin, lymph node, visceral organs, central nervous system, and bone marrow involvement. We herein present the case of a 70-year-old man diagnosed with ATLL. The patient developed unique generalized cutaneous purpuric eruptions with systemic involvement including the gastrointestinal tract, peripheral blood, and bone marrow. Despite advanced chemotherapeutic treatment, he died about 5 months later due to a rapid progressive clinical course. Therefore, generalized cutaneous purpuric eruptions could be a poorer prognostic factor in the aggressive subtype of acute ATLL

Preparation of highly pure zeaxanthin particles from sea water-cultivated microalgae using supercritical anti-solvent recrystallization

Xanthophylls, including zeaxanthin, are considered dietary supplements with a potentially positive impact on age-related macular degeneration. Using pilot-scale column fractionation coupled with supercritical anti-solvent (SAS) recrystallization, highly pure zeaxanthin particulates were prepared from ultrasonic extracts of the microalgae, Nannochloropsis oculata, grown in sea water. Column partition chromatography increased the concentration of zeaxanthin from 36.2 mg/g of the ultrasonic extracts to 425.6 mg/g of the collected column fractions. A response surface methodology was systematically designed for the SAS process by changing feed concentration, CO2 flow rate and anti-solvent pressure. Zeaxanthin-rich particles with a purity of 84.2% and a recovery of 85.3% were produced using supercritical anti-solvent recrystallization from the column eluate at a feed concentration of 1.5 mg/mL, CO2 flow rate of 48.6 g/min and pressure of 135 bar

Fiber-Optic Thermal Sensor for TiN Film Crack Monitoring

The study focuses on the thermal and temperature sensitivity behavior of an optical fiber sensor device. In this article, a titanium nitride (TiN)-coated fiber Bragg grating (FBG) sensor fabricated using an ion beam sputtering system was investigated. The reflection spectra of the FBG sensor were tested using R-soft optical software to simulate the refractive index sensitivity. In these experiments, the temperature sensitivity of the TiN FBG was measured at temperatures ranging from 100 to 500 °C using an optical spectrum analyzer (OSA). The results showed that the temperature sensitivity of the proposed TiN FBG sensor reached 12.8 pm/°C for the temperature range of 100 to 300 °C and 20.8 pm/°C for the temperature range of 300 to 500 °C. Additionally, we found that the produced oxidation at temperatures of 400-500 °C caused a crack, with the crack becoming more and more obvious at higher and higher temperatures