Identification of a Copy Number Variation on Chromosome 20q13.12 Associated with Osteoporotic Fractures in the Korean Population

Osteoporotic fractures (OFs) are critical hard outcomes of osteoporosis and are characterized by decreased bone strength induced by low bone density and microarchitectural deterioration in bone tissue. Most OFs cause acute pain, hospitalization, immobilization, and slow recovery in patients and are associated with increased mortality. A variety of genetic studies have suggested associations of genetic variants with the risk of OF. Genome-wide association studies have reported various single-nucleotide polymorphisms and copy number variations (CNVs) in European and Asian populations. To identify CNV regions associated with OF risk, we conducted a genome-wide CNV study in a Korean population. We performed logistic regression analyses in 1,537 Korean subjects (299 OF cases and 1,238 healthy controls) and identified a total of 8 CNV regions significantly associated with OF (p < 0.05). Then, one CNV region located on chromosome 20q13.12 was selected for experimental validation. The selected CNV region was experimentally validated by quantitative polymerase chain reaction. The CNV region of chromosome 20q13.12 is positioned upstream of a family of long non-coding RNAs, LINC01260. Our findings could provide new information on the genetic factors associated with the risk of OF

Clinical Applications of the Microbiome in Obstetrics

Human microbiome refers to the genetic material of approximately 1013 microorganisms present in the human body. These microbiomes interact significantly with the physiological, metabolic, and immune systems, particularly during pregnancy. Microbiome dysbiosis in pregnant women and their fetuses is associated with obstetric complications and poor neonatal outcomes. Oral and gut microbiomes can influence the placenta, uterus, and fetus via hematogenous translocation. Through ascending translocation, vaginal microbiota can directly affect the uterine environment. Current research focuses on the presence of the placental microbiome, which is characterized by low biomass. However, more well-controlled studies are required to specifically address the contamination issues. Use of antibiotics during pregnancy and the mode of delivery, specifically cesarean section, have been linked to the establishment of the neonatal gut microbiome. Probiotic supplementation may be beneficial during pregnancy, particularly for women receiving antibiotic treatment

Effect of the submandibular push exercise using visual feedback from pressure sensor: an electromyography study

We developed a new exercise method called the submandibular push exercise that can strengthen the suprahyoid muscle by inducing only the motion of the hyoid bone without neck flexion. In this study, we aimed to investigate and compare the muscle activity of the suprahyoid and infrahyoid muscles in the course of performing three different swallowing exercises. Twenty healthy participants and fifteen patients with dysphagia were recruited. Each participant consecutively performed three exercises: Shaker, CTAR, and submandibular push exercises. To investigate muscle activation, surface electromyography was performed on the suprahyoid, infrahyoid, and SCM muscles, during the exercises. Root mean square (RMS) was measured. In healthy participants, the submandibular push exercise showed a significantly higher RMS value in the suprahyoid and infrahyoid muscles than the Shaker and CTAR exercises using repeated ANOVA with Tukey&apos;s post hoc test (p&lt;0.05). In patients with dysphagia, the submandibular push and Shaker exercises showed significantly higher RMS value in the suprahyoid and infrahyoid muscles than the CTAR exercise. However, no significant difference was found between the submandibular push and Shaker exercises. In both healthy and patients with dysphagia, the mean RMS values of the SCM muscles during the submandibular push exercise were significantly lower than those during the Shaker exercise using repeated ANOVA with Tukey&apos;s post hoc test (p&lt;0.05). In conclusion, considering the relatively superior selectiveness in suprahyoid and infrahyoid muscle contraction, the submandibular push exercise using visual feedback from pressure sensor could be an efficient supplementary exercise to the conventional swallowing muscle exercises. However, further studies may be necessary to confirm the improvement in swallowing difficulty

5′-Triphosphate-RNA-independent activation of RIG-I via RNA aptamer with enhanced antiviral activity

RIG-I is a cytosolic receptor for non-self RNA that mediates immune responses against viral infections through IFNα/β production. In an attempt to identify novel tools that modulate IFNα/β production, we used SELEX technology to screen RNA aptamers that specifically target RIG-I protein. Most of the selected RIG-I aptamers contained polyU motifs in the second half regions that played critical roles in the activation of RIG-I-mediated IFNβ production. Unlike other known ligands, RIG-I aptamer bound and activated RIG-I in a 5′-triphosphate-independent manner. The helicase and RD domain of RIG-I were used for aptamer binding, but intact RIG-I protein was required to exert aptamer-mediated signaling activation. Furthermore, replication of NDV, VSV and influenza virus in infected host cells was efficiently blocked by pre- or post-treatment with RIG-I aptamer. Based on these data, we propose that RIG-I aptamer has strong potential to be an antiviral agent that specifically boosts the RIG-I-dependent signaling cascade

Transcription Factor Sp1 Is Involved in Expressional Regulation of Coxsackie and Adenovirus Receptor in Cancer Cells

Coxsackie and adenovirus receptor (CAR) was first known as a virus receptor. Recently, it is also known to have tumor suppressive activity such as inhibition of cell proliferation, migration, and invasion. It is important to understand how CAR expression can be regulated in cancers. Based on an existence of putative Sp1 binding site within CAR promoter, we investigated whether indeed Sp1 is involved in the regulation of CAR expression. We observed that deletion or mutation of Sp1 binding motif (−503/−498) prominently impaired the Sp1 binding affinity and activity of CAR promoter. Histone deacetylase inhibitor (TSA) treatment enhanced recruitment of Sp1 to the CAR promoter in ChIP assay. Meanwhile, Sp1 binding inhibitor suppressed the recruitment. Exogenous expression of wild-type Sp1 increased CAR expression in CAR-negative cells; meanwhile, dominant negative Sp1 decreased the CAR expression in CAR-positive cells. These results indicate that Sp1 is involved in regulation of CAR expression

Impact of Body Mass Index on the relationship of epicardial adipose tissue to metabolic syndrome and coronary artery disease in an Asian population

<p>Abstract</p> <p>Background</p> <p>In a previous study, we demonstrated that the thickness of epicardial adipose tissue (EAT), measured by echocardiography, was increased in patients with metabolic syndrome (MS) and coronary artery disease (CAD). Several studies on obese patients, however, failed to demonstrate any relationship between EAT and CAD. We hypothesized that body mass index (BMI) affected the link between EAT and MS and CAD.</p> <p>Methods</p> <p>We consecutively enrolled 643 patients (302 males, 341 females; 59 ± 11 years), who underwent echocardiography and coronary angiography. The EAT thickness was measured on the free wall of the right ventricle at the end of diastole. All patients were divided into two groups: high BMI group, ≥27 kg/m²(n = 165), and non-high BMI group, < 27 kg/m²(n = 478).</p> <p>Results</p> <p>The median and mean EAT thickness of 643 patients were 3.0 mm and 3.1 ± 2.4 mm, respectively. In the non-high BMI group, the median EAT thickness was significantly increased in patients with MS compared to those without MS (3.5 vs. 1.9 mm, p < 0.001). In the high BMI group, however, there was no significant difference in the median EAT thickness between patients with and without MS (3.0 vs. 2.5 mm, p = 0.813). A receiver operating characteristic (ROC) curve analysis predicting MS revealed that the area under the curve (AUC) of the non-high BMI group was significantly larger than that of the high BMI group (0.659 vs. 0.506, p = 0.007). When compared to patients without CAD, patients with CAD in both the non-high and high BMI groups had a significantly higher median EAT thickness (3.5 vs. 1.5 mm, p < 0.001 and 4.0 vs. 2.5 mm, p = 0.001, respectively). However, an ROC curve analysis predicting CAD revealed that the AUC of the non-high BMI group tended to be larger than that of the high BMI group (0.735 vs. 0.657, p = 0.055).</p> <p>Conclusions</p> <p>While EAT thickness was significantly increased in patients with MS and CAD, the power of EAT thickness to predict MS and CAD was stronger in patients with BMI < 27 kg/m². These findings showed that the measurement of EAT thickness by echocardiography might be especially useful in an Asian population with a non-high BMI, less than 27 kg/m².</p

Impact of Depression on Work Productivity and Its Improvement after Outpatient Treatment with Antidepressants

AbstractObjectiveDepressive disorders influence socioeconomic burden at both the individual and organizational levels. This study estimates the lost productive time (LPT) and its resulting cost among workers with major depressive disorder (MDD) compared with a comparison group. It also estimates the change in productivity after 8 weeks of outpatient psychiatric treatment with antidepressants.MethodsWorking patients diagnosed with MDD without other major physical or mental disorders were recruited (n = 102), along with age- and sex-matched healthy controls from the Seoul Metropolitan area (n = 91). The World Health Organization's Health and Work Performance Questionnaire and the Hamilton Rating Scale for Depression were utilized to measure productivity and severity of depression, respectively, at baseline and at 8 weeks of treatment.ResultsThe LPT from absenteeism and presenteeism (reduced performance while present at work) was significantly higher among the MDD group. Workers with MDD averaged costs due to LPT at 33.4% of their average annual salary, whereas the comparison group averaged costs of 2.5% of annual salary. After 8 weeks of treatment, absenteeism and clinical symptoms of depression were significantly reduced and associated with significant improvement in self-rated job performance (31.8%) or cost savings of $7508 per employee per year.ConclusionsWe confirmed that significant productivity loss arises from MDD and that this loss can be reduced with psychiatric intervention after a time period as short as 8 weeks. Mental health professionals should work with employers to devise a cost-effective system to provide workers with accessible quality care

Single-cell analysis of early antiviral gene expression reveals a determinant of stochastic IFNB1 expression

RIG-I-like receptors (RLRs) are cytoplasmic sensors of viral RNA that trigger the signaling cascade that leads to type I interferon (IFN) production. Transcriptional induction of RLRs by IFN is believed to play the role of positive feedback to further amplify viral sensing. We found that RLRs and several other IFN-stimulated genes (ISGs) are induced early in viral infection independent of IFN. Expression of these early ISGs requires IRF3/IRF7 and is highly correlated amongst them. Simultaneous detection of mRNA of IFNB1, viral replicase, and ISGs revealed distinct populations of IFNB1 expressing and non-expressing cells which are highly correlated with the levels of early ISGs but are uncorrelated with IFN-dependent ISGs and viral gene expression. Individual expression of RLRs made IFNB1 expression more robust and earlier, suggesting a causal relation between levels of RLR and induction of IFN.112Ysciescopu

Formyl-methionine as an N-degron of a eukaryotic N-end rule pathway

In bacteria, nascent proteins bear the pretranslationally generated N-terminal (Nt) formyl-methionine (fMet) residue. Nt-fMet of bacterial proteins is a degradation signal, termed fMet/N-degron. In contrast, proteins synthesized by cytosolic ribosomes of eukaryotes were presumed to bear unformylated Nt-Met. Here we found that the yeast formyltransferase Fmt1, although imported into mitochondria, could also produce Nt-formylated proteins in the cytosol. Nt-formylated proteins were strongly up-regulated in stationary phase or upon starvation for specific amino acids. This up-regulation strictly required the Gcn2 kinase, which phosphorylates Fmt1 and mediates its retention in the cytosol. We also found that the Nt-fMet residues of Nt-formylated proteins act as fMet/N-degrons, and identified the Psh1 ubiquitin ligase as the recognition component of this eukaryotic fMet/N-end rule pathway, which destroys Nt-formylated proteins