Copy number variation at leptin receptor gene locus associated with metabolic traits and the risk of type 2 diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Recent efforts have been made to link complex human traits and disease susceptibility to DNA copy numbers. The leptin receptor (LEPR) has been implicated in obesity and diabetes. Mutations and genetic variations of <it>LEPR </it>gene have been discovered in rodents and humans. However, the association of DNA copy number variations at the <it>LEPR </it>gene locus with human complex diseases has not been reported. In an attempt to study DNA copy number variations associated with metabolic traits and type 2 diabetes mellitus (T2DM), we targeted the <it>LEPR </it>gene locus in DNA copy number analyses.</p> <p>Results</p> <p>We identified DNA copy number variations at the <it>LEPR </it>gene locus among a Korean population using genome-wide SNP chip data, and then quantified copy numbers of the E2 DNA sequence in the first two exons overlapped between <it>LEPR </it>and <it>LEPROT </it>genes by the quantitative multiplex PCR of short fluorescent fragment (QMPSF) method. Among the non-diabetic subjects (n = 1,067), lower E2 DNA copy numbers were associated with higher fasting glucose levels in men (<it>p </it>= 1.24 × 10^-7) and women (<it>p </it>= 9.45 × 10^-5), as well as higher total cholesterol levels in men (<it>p </it>= 9.96 × 10^-7). In addition, the significant association between lower E2 DNA copy numbers and lower level of postprandial 2hr insulin was evident only in non-diabetic women, whereas some obesity-related phenotypes and total cholesterol level exhibited significant associations only in non-diabetic men. Logistic regression analysis indicated that lower E2 DNA copy numbers were associated with T2DM (odds ratio, 1.92; 95% CI, 1.26~2.96; p < 0.003) in our nested case-control study. Interestingly, the E2 DNA copy number exhibited a negative correlation with LEPR gene expression, but a positive correlation with LEPROT gene expression.</p> <p>Conclusions</p> <p>This work suggests that a structural variation at the <it>LEPR </it>gene locus is functionally associated with complex metabolic traits and the risk of T2DM.</p

Whole Genome Analysis of the Red-Crowned Crane Provides Insight into Avian Longevity

The red-crowned crane (Grus japonensis) is an endangered, large-bodied crane native to East Asia. It is a traditional symbol of longevity and its long lifespan has been confirmed both in captivity and in the wild. Lifespan in birds is known to be positively correlated with body size and negatively correlated with metabolic rate, though the genetic mechanisms for the red-crowned crane&apos;s long lifespan have not previously been investigated. Using whole genome sequencing and comparative evolutionary analyses against the grey-crowned crane and other avian genomes, including the long-lived common ostrich, we identified red-crowned crane candidate genes with known associations with longevity. Among these are positively selected genes in metabolism and immunity pathways (NDUFA5, NDUFA8, NUDT12, SOD3, CTH, RPA1, PHAX, HNMT, HS2ST1, PPCDC, PSTK CD8B, GP9, IL-9R, and PTPRC). Our analyses provide genetic evidence for low metabolic rate and longevity, accompanied by possible convergent adaptation signatures among distantly related large and long-lived birds. Finally, we identified low genetic diversity in the red-crowned crane, consistent with its listing as an endangered species, and this genome should provide a useful genetic resource for future conservation studies of this rare and iconic species

Isolation and Characterization of a Defensin-Like Peptide (Coprisin) from the Dung Beetle, Copris tripartitus

The antibacterial activity of immune-related peptides, identified by a differential gene expression analysis, was investigated to suggest novel antibacterial peptides. A cDNA encoding a defensin-like peptide, Coprisin, was isolated from bacteria-immunized dung beetle, Copris tripartitus, by using differential dot blot hybridization. Northern blot analysis showed that Coprisin mRNA was up-regulated from 4 hours after bacteria injection and its expression level was reached a peak at 16 hours. The deduced amino acid sequence of Coprisin was composed of 80 amino acids with a predicted molecular weight of 8.6 kDa and a pI of 8.7. The amino acid sequence of mature Coprisin was found to be 79.1% and 67.4% identical to those of defensin-like peptides of Anomala cuprea and Allomyrina dichotoma, respectively. We also investigated active sequences of Coprisin by using amino acid modification. The result showed that the 9-mer peptide, LLCIALRKK-NH2, exhibited potent antibacterial activities against Escherichia coli and Staphylococcus aureus

The origin and composition of Korean ethnicity analyzed by ancient and present-day genome sequences

Koreans are thought to be an ethnic group of admixed northern and southern subgroups. However, the exact genetic origins of these two remain unclear. In addition, the past admixture is presumed to have taken place on the Korean peninsula, but there is no genomic scale analysis exploring the origin, composition, admixture, or the past migration of Koreans. Here, 88 Korean genomes compared with 91 other present-day populations showed two major genetic components of East Siberia and Southeast Asia. Additional paleogenomic analysis with 115 ancient genomes from Pleistocene hunter-gatherers to Iron Age farmers showed a gradual admixture of Tianyuan (40 ka) and Devil&apos;s gate (8 ka) ancestries throughout East Asia and East Siberia up until the Neolithic era. Afterward, the current genetic foundation of Koreans may have been established through a rapid admixture with ancient Southern Chinese populations associated with Iron Age Cambodians. We speculate that this admixing trend initially occurred mostly outside the Korean peninsula followed by continuous spread and localization in Korea, corresponding to the general admixture trend of East Asia. Over 70% of extant Korean genetic diversity is explained to be derived from such a recent population expansion and admixture from the South

Predictive Capability of Anorectal Physiologic Tests for Unfavorable Outcomes Following Biofeedback Therapy in Dyssynergic Defecation

The purpose of this study is to evaluate the predictive capability of anorectal physiologic tests for unfavorable outcomes prior to the initiation of biofeedback therapy in patients with dyssynergic defecation. We analyzed a total of 80 consecutive patients who received biofeedback therapy for chronic idiopathic functional constipation with dyssynergic defecation. After classifying the patients into two groups (responders and non-responders), univariate and multivariate analyses were performed to determine the predictors associated with the responsiveness to biofeedback therapy. Of the 80 patients, 63 (78.7%) responded to biofeedback therapy and 17 (21.3%) did not. On univariate analysis, the inability to evacuate an intrarectal balloon (P=0.028), higher rectal volume for first, urgent, and maximal sensation (P=0.023, P=0.008, P=0.007, respectively), and increased anorectal angle during squeeze (P=0.020) were associated with poor outcomes. On multivariate analysis, the inability to evacuate an intrarectal balloon (P=0.018) and increased anorectal angle during squeeze (P=0.029) were both found to be independently associated with a lack of response to biofeedback therapy. Our data show that the two anorectal physiologic test factors are associated with poor response to biofeedback therapy for patients with dyssynergic defecation. These findings may assist physicians in predicting the responsiveness to therapy for this patient population

Liquid Metal Embrittlement of Galvanized TRIP Steels in Resistance Spot Welding

Liquid metal embrittlement (LME) in Zn-coated steels is a serious issue in automotive design. The risk of rising LME surface cracks in resistance spot welding (RSW) of Zn-coated high strength steels has triggered significant research activities across the globe. This paper presents a state-of-the-art review of the various phenomena and issues related to LME during RSW. Various aspects of LME surface cracks have been described in this review, focusing on the macro- and microscopic features of LME, spot weld cracks, the sensitivity of the LME cracks towards surface locations, welding conditions, and susceptibility to high strength and galvanized steels. We also focus on the effects of various processing factors, such as temperature, stress, microstructure, and the nature of the galvanized layer, related to studies with actual spot welds LME cracks. Finally, we summarize the possible mechanisms of embrittlement and the remedies for minimizing LME cracks, with suitable guidelines to suppress surface cracks during RSW

Staged revision still works for chronic and deep infection of total elbow arthroplasty?

Purpose: Infected total elbow arthroplasty (TEA) is challenging. We evaluate the clinical and radiologic outcomes for chronic and deep infection of TEA with two-stage revision surgery. Methods: A total of 10 elbows were included in the study. The mean age was 69.1 ± 15 years (range, 34–83 years). The mean follow-up was 62 (range, 24–108) months. The clinical outcomes were assessed using a visual analog scale (VAS), range of motion (ROM) arc, and Mayo elbow performance score (MEPS). Moreover, radiographic outcomes, time to revision, pathogenic bacteria, preoperative complications, and disease period were evaluated. Results: Mean preoperative VAS score of 6.1 had improved to 3.3. Mean preoperative ROM was 68° (flexion-extension), which improved to 86.7°. Mean preoperative MEPS was 46 (range, 0–70), which improved to 75.5 (range, 35–85). The mean disease duration was 8.4 months (range, 5–20 months). The most common causative organism was methicillin-resistant Staphylococcus aureus. The second revision rate was 80% at the final follow-up. Radiographic outcome at final follow-up showed that 3 (30%) of 10 patients exhibited radiolucency evidence around the components. Three patients showed nonprogressive radiolucency around the implant interfaces without other indications of infection at the most recent follow-up. Conclusion: In patients with chronic and deep infection of TEA, two-stage revision can be an affordable option for eradication of the infection, relieving pain, and restoring joint function. However, the high second revision rate owing to bone and soft-tissue deficits remains a critical issue. Level of evidence: Level IV, Case series, Treatment stud