Imaging the P‐Wave Velocity Structure of Arctic Subsea Permafrost Using Laplace‐Domain Full‐Waveform Inversion

Climate change in the Arctic has recently become a major scientific issue, and detailed information on the degradation of subsea permafrost on continental shelves in the Arctic is critical for understanding the major cause and effects of global warming, especially the release of greenhouse gases. The subsea permafrost at shallow depths beneath the Arctic continental shelves has significantly higher P‐wave velocities than the surrounding sediments. The distribution of subsea permafrost on Arctic continental shelves has been studied since the 1970s using seismic refraction methods. With seismic refraction data, the seismic velocity and the depth of the upper boundary of subsea permafrost can be determined. However, it is difficult to identify the lower boundary and the internal shape of permafrost. Here, we present two‐dimensional P‐wave velocity models of the continental shelf in the Beaufort Sea by applying the Laplace‐domain full‐waveform inversion method to acquired multichannel seismic reflection data. With the inverted P‐wave velocity model, we identify anomalous high seismic velocities that originated from the subsea permafrost. Information on the two‐dimensional distribution of subsea permafrost on the Arctic continental shelf area, including the upper and lower bounds of subsea permafrost, are presented. Also, the two‐dimensional P‐wave velocity model allows us to estimate the thawing pattern and the shape of subsea permafrost structures. Our proposed P‐wave velocity models were verified by comparison with the previous distribution map of subsea permafrost from seismic refraction analyses, geothermal modeling, and well‐log data

A mutation in the major autophagy gene, WIPI2, associated with global developmental abnormalities

We describe a large consanguineous pedigree from a remote area of Northern Pakistan, with a complex developmental disorder associated with wide-ranging symptoms, including mental retardation, speech and language impairment and other neurological, psychiatric, skeletal and cardiac abnormalities. We initially carried out a genetic study using the HumanCytoSNP-12 v2.1 Illumina gene chip on nine family members and identified a single region of homozygosity shared amongst four affected individuals on chromosome 7p22 (positions 3059377–5478971). We performed whole-exome sequencing on two affected individuals from two separate branches of the extended pedigree and identified a novel nonsynonymous homozygous mutation in exon 9 of the WIPI2 (WD-repeat protein interacting with phosphoinositide 2) gene at position 5265458 (c.G745A;pV249M). WIPI2 plays a critical role in autophagy, an evolutionary conserved cellular pathway implicated in a growing number of medical conditions. The mutation is situated in a highly conserved and critically important region of WIPI2, responsible for binding PI(3)P and PI(3,5)P2, an essential requirement for autophagy to proceed. The mutation is absent in all public databases, is predicted to be damaging and segregates with the disease phenotype. We performed functional studies in vitro to determine the potential effects of the mutation on downstream pathways leading to autophagosome assembly. Binding of the V231M mutant of WIPI2b to ATG16L1 (as well as ATG5–12) is significantly reduced in GFP pull-down experiments, and fibroblasts derived from the patients show reduced WIPI2 puncta, reduced LC3 lipidation and reduced autophagic flux

Genetic approaches to understanding the causes of stuttering

Stuttering is a common but poorly understood speech disorder. Evidence accumulated over the past several decades has indicated that genetic factors are involved, and genetic linkage studies have begun to identify specific chromosomal loci at which causative genes are likely to reside. A detailed investigation of one such region on chromosome 12 has identified mutations in the GNPTAB gene that are associated with stuttering in large families and in the general population. Subsequent studies identified mutations in the functionally related GNPTG and NAGPA genes. Mutations in these genes disrupt the lysosomal targeting pathway that generates the Mannose 6-phosphate signal, which directs a diverse group of enzymes to their target location in the lysosome of the cell. While mutations in these three genes can be identified in less than 10% of cases of familial stuttering, this knowledge allows a variety of new studies that can help identify the neuropathology that underlies this disorder

Validation of Biomarker-Based ABCD Score in Atrial Fibrillation Patients with a Non-Gender CHA2DS2-VASc Score 0-1:A Korean Multi-Center Cohort

PURPOSE: Atrial fibrillation (AF) patients with low to intermediate risk, defined as non-gender CHA(2)DS(2)-VASc score of 0–1, are still at risk of stroke. This study verified the usefulness of ABCD score [age (≥60 years), B-type natriuretic peptide (BNP) or N-terminal pro-BNP (≥300 pg/mL), creatinine clearance (<50 mL/min/1.73 m(2)), and dimension of the left atrium (≥45 mm)] for stroke risk stratification in non-gender CHA(2)DS(2)-VASc score 0–1. MATERIALS AND METHODS: This multi-center cohort study retrospectively analyzed AF patients with non-gender CHA(2)DS(2)-VASc score 0–1. The primary endpoint was the incidence of stroke with or without antithrombotic therapy (ATT). An ABCD score was validated. RESULTS: Overall, 2694 patients [56.3±9.5 years; female, 726 (26.9%)] were followed-up for 4.0±2.8 years. The overall stroke rate was 0.84/100 person-years (P-Y), stratified as follows: 0.46/100 P-Y for an ABCD score of 0; 1.02/100 P-Y for an ABCD score ≥1. The ABCD score was superior to non-gender CHA(2)DS(2)-VASc score in the stroke risk stratification (C-index=0.618, p=0.015; net reclassification improvement=0.576, p=0.040; integrated differential improvement=0.033, p=0.066). ATT was prescribed in 2353 patients (86.5%), and the stroke rate was significantly lower in patients receiving non-vitamin K antagonist oral anticoagulant (NOAC) therapy and an ABCD score ≥1 than in those without ATT (0.44/100 P–Y vs. 1.55/100 P-Y; hazard ratio=0.26, 95% confidence interval 0.11–0.63, p=0.003). CONCLUSION: The biomarker-based ABCD score demonstrated improved stroke risk stratification in AF patients with non-gender CHA(2)DS(2)-VASc score 0–1. Furthermore, NOAC with an ABCD score ≥1 was associated with significantly lower stroke rate in AF patients with non-gender CHA(2)DS(2)-VASc score 0–1

Albuminuria, Cerebrovascular Disease and Cortical Atrophy: among Cognitively Normal Elderly Individuals

We tested the hypothesis that decreased glomerular filtration rate and albuminuria have different roles in brain structure alterations. We enrolled 1,215 cognitively normal individuals, all of whom underwent high-resolution T1-weighted volumetric magnetic resonance imaging scans. The cerebral small vessel disease burdens were assessed with white matter hyperintensities (WMH), lacunes, and microbleeds. Subjects were considered to have an abnormally elevated urine albumin creatinine ratio if the value was ≥17 mg/g for men and ≥25 mg/g for women. Albuminuria, but not estimated glomerular filtration rate (eGFR), was associated with increased WMH burdens (p = 0.002). The data was analyzed after adjusting for age, sex, education, history of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease, stroke, total cholesterol level, body mass index, status of smoking and alcohol drinking, and intracranial volume. Albuminuria was also associated with cortical thinning, predominantly in the frontal and occipital regions (both p < 0.01) in multiple linear regression analysis. However, eGFR was not associated with cortical thickness. Furthermore, path analysis for cortical thickness showed that albuminuria was associated with frontal thinning partially mediated by WMH burdens. The assessment of albuminuria is needed to improve our ability to identify individuals with high risk for cognitive impairments, and further institute appropriate preventive measures

A Genome-Wide Association Study Uncovers a Genetic Locus Associated with Thoracic-to-Hip Ratio in Koreans.

The thoracic-to-hip circumference ratio (THR) is an anthropometric marker recently described as a predictor of type 2 diabetes. In this study, we performed a genome-wide association study (GWAS) followed by confirmatory analyses to identify genetic markers associated with THR. A total of 7,240 Korean subjects (4,988 for the discovery stage and 2,252 for the confirmatory analyses) were recruited for this study, and genome-wide single nucleotide polymorphism (SNP) genotyping of the initial 4,988 individuals was performed using Affymetrix Human SNP array 5.0. Linear regression analysis was then performed to adjust for the effects of age, sex, and current diabetes medication status on the THR of the study subjects. In the initial discovery stage, there was a statistically nominal association between minor alleles of SNP markers on chromosomes 4, 8, 10, and 12, and THR changes (p < 5.0 × 10-6). The subsequent confirmatory analyses of these markers, however, only detected a significant association between two SNPs in the HECTD4 gene and decreased THRs. Notably, this association was detected in male (rs11066280: p = 1.14 × 10-2; rs2074356: p = 1.10 × 10-2), but not in female subjects. Meanwhile, the combined results from the two analyses (initial and confirmatory) indicated that minor alleles of these two intronic variants exhibited a significant genome-wide association with decreased THR in the male subjects (n = 3,155; rs11066280: effect size = -0.008624, p = 6.19 × 10-9; rs2074356: effect size = -0.008762, p = 1.89 × 10-8). Furthermore, minor alleles of these two SNPs exhibited protective effects on patients' risks for developing type 2 diabetes. In conclusion, we have identified two genetic variations in HECTD4 that are associated with THR, particularly in men

Application of Genomic Big Data in Plant Breeding: Past, Present, and Future

Plant breeding has a long history of developing new varieties that have ensured the food security of the human population. During this long journey together with humanity, plant breeders have successfully integrated the latest innovations in science and technologies to accelerate the increase in crop production and quality. For the past two decades, since the completion of human genome sequencing, genomic tools and sequencing technologies have advanced remarkably, and adopting these innovations has enabled us to cost down and/or speed up the plant breeding process. Currently, with the growing mass of genomic data and digitalized biological data, interdisciplinary approaches using new technologies could lead to a new paradigm of plant breeding. In this review, we summarize the overall history and advances of plant breeding, which have been aided by plant genomic research. We highlight the key advances in the field of plant genomics that have impacted plant breeding over the past decades and introduce the current status of innovative approaches such as genomic selection, which could overcome limitations of conventional breeding and enhance the rate of genetic gain

Constructing a Reference Genome in a Single Lab: The Possibility to Use Oxford Nanopore Technology

The whole genome sequencing (WGS) has become a crucial tool in understanding genome structure and genetic variation. The MinION sequencing of Oxford Nanopore Technologies (ONT) is an excellent approach for performing WGS and it has advantages in comparison with other Next-Generation Sequencing (NGS): It is relatively inexpensive, portable, has simple library preparation, can be monitored in real-time, and has no theoretical limits on reading length. Sorghum bicolor (L.) Moench is diploid (2n = 2x = 20) with a genome size of about 730 Mb, and its genome sequence information is released in the Phytozome database. Therefore, sorghum can be used as a good reference. However, plant species have complex and large genomes when compared to animals or microorganisms. As a result, complete genome sequencing is difficult for plant species. MinION sequencing that produces long-reads can be an excellent tool for overcoming the weak assembly of short-reads generated from NGS by minimizing the generation of gaps or covering the repetitive sequence that appears on the plant genome. Here, we conducted the genome sequencing for S. bicolor cv. BTx623 while using the MinION platform and obtained 895,678 reads and 17.9 gigabytes (Gb) (ca. 25× coverage of reference) from long-read sequence data. A total of 6124 contigs (covering 45.9%) were generated from Canu, and a total of 2661 contigs (covering 50%) were generated from Minimap and Miniasm with a Racon through a de novo assembly using two different tools and mapped assembled contigs against the sorghum reference genome. Our results provide an optimal series of long-read sequencing analysis for plant species while using the MinION platform and a clue to determine the total sequencing scale for optimal coverage that is based on various genome sizes

Magnification of association plots of the <i>HECTD4</i> region on chromosome 12.

<p>The image depicts a 1-Mb (megabase) chromosomal region containing variant rs11066280 at its center. Panel A represents the genome-wide association study (GWAS) results for all the subjects (both male and female) and panel B represents the GWAS results for the male subjects.</p