Parabrachial CGRP neurons modulate active defensive behavior under a naturalistic threat.

Recent studies suggest that calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) represent aversive information and signal a general alarm to the forebrain. If CGRP neurons serve as a true general alarm, their activation would modulate both passive nad active defensive behaviors depending on the magnitude and context of the threat. However, most prior research has focused on the role of CGRP neurons in passive freezing responses, with limited exploration of their involvement in active defensive behaviors.

Uncovering potential causal genes for undiagnosed congenital anomalies using an in-house pipeline for trio-based whole-genome sequencing.

Background: Congenital anomalies (CAs) encompass a wide spectrum of structural and functional abnormalities during fetal development, commonly presenting at birth. Identifying the cause of CA is essential for accurate diagnosis and treatment. Using a target-gene approach, genetic variants could be found in certain CA patients.

Discovery of organosulfur-based selective HDAC8 inhibitors with anti-neuroblastoma activity.

Histone deacetylases (HDACs) are important epigenetic regulators of gene expression and various cellular processes, and are potential targets for anticancer therapy. In particular, HDAC8 is a promising therapeutic target for childhood neuroblastoma. To date, five HDAC inhibitors have been approved as anticancer drugs; however, all are non-selective HDAC inhibitors with various side effects.

Diagnostic Utility of Whole Genome Sequencing After Negative Karyotyping/Chromosomal Microarray in Infants Born With Multiple Congenital Anomalies.

Background: Achieving a definitive genetic diagnosis of unexplained multiple congenital anomalies (MCAs) in neonatal intensive care units (NICUs) infants is challenging because of the limited diagnostic capabilities of conventional genetic tests. Although the implementation of whole genome sequencing (WGS) has commenced for diagnosing MCAs, due to constraints in resources and faculty, many NICUs continue to utilize chromosomal microarray (CMA) and/or karyotyping as the initial diagnostic approach. We aimed to evaluate the diagnostic efficacy of WGS in infants with MCAs who have received negative results from karyotyping and/or CMA.

Fire-Resistant and Thermal Stability Properties of Fluorosilicone Adhesives by Incorporation of Surface-Modified Aluminum Trihydrate.

Fluorosilicone was combined with aluminum trihydrate (ATH) to induce synergistic flame-retardant and thermal-resistant properties. The surface of ATH was modified with four different silane coupling agents. The flammability and mechanical properties of the fluorosilicone/ATH composites were assessed using an UL94 vertical test and a die shear strength test.

Forensic height estimation using polygenic score in Korean population.

Height is known to be a classically heritable trait controlled by complex polygenic factors. Numerous height-associated genetic variants across the genome have been identified so far. It is also a representative of externally visible characteristics (EVC) for predicting appearance in forensic science.

Feasibility and Safety of transoral robotic parathyroidectomy: Initial experience with a new approach for parathyroid surgery.

Background: We present the initial outcomes of transoral robotic parathyroidectomy (TORP) using the transoral vestibular approach in patients with primary hyperparathyroidism (PHPT).

Method: A retrospective case series analysis was performed on patients diagnosed with PHPT between October 2016 and July 2019 who underwent transoral robotic surgery for parathyroidectomy.

Results: Thirteen patients (five males and eight females) successfully underwent TORP at our institution from October 2016 to July 2019.

SERKs serve as co-receptors for SYR1 to trigger systemin-mediated defense responses in tomato.

Systemin, the first peptide hormone identified in plants, was initially isolated from tomato (Solanum lycopersicum) leaves. Systemin mediates local and systemic wound-induced defense responses in plants, conferring resistance to necrotrophic fungi and herbivorous insects. Systemin is recognized by the leucine-rich-repeat receptor-like kinase (LRR-RLK) receptor SYSTEMIN RECEPTOR1 (SYR1), but how the systemin recognition signal is transduced to intracellular signaling pathways to trigger defense responses is poorly understood.

A genome-wide association scan reveals novel loci for facial traits of Koreans.

DNA-based prediction of externally visible characteristics (EVC) with SNPs is one of the research areas of interest in the forensic field. Based on a previous study performing GWAS on facial traits in a Korean population, herein, we present results stemming from GWA analysis with KoreanChip and novel genetic loci satisfying genome-wide significant level. We discovered a total of 20 signals and 12 loci were found to have novel associations with facial traits, including six loci located in intergenic regions and six loci located at UBE2O, HECTD2, CCDC108, TPK1, FCN2, and FRMPD1.

Frequency of actionable secondary findings in 7472 Korean genomes derived from the National Project of Bio Big Data pilot study.

Exome and genome sequencing (ES/GS) in genetic medicine and research leads to discovering genomic secondary findings (SFs) unrelated to the purpose of the primary test. There is a lack of agreement to return the SF results for individuals undergoing the test. The aim of this study is to investigate the frequency of actionable secondary findings using GS data obtained from the rare disease study and the Korean Genome and Epidemiology Study (KoGES) in the National Project of Bio Big Data pilot study.

Therapeutic Efficacy of Novel HDAC Inhibitors SPA3052 and SPA3074 against Intestinal Inflammation in a Murine Model of Colitis.

Inflammatory bowel diseases (IBD) are digestive tract disorders that involve chronic inflammation with frequent recurrences. This study aimed to evaluate the efficacy of two novel histone deacetylase 8 (HDAC8) inhibitors, namely, SPA3052 and SPA3074, against dextran sulfate sodium (DSS)-induced experimental colitis. Male C57BL/6N mice were subjected to two cycles of 1.

FGFRL1 and FGF genes are associated with height, hypertension, and osteoporosis.

Hypertension and osteoporosis are two major disorders, which interact with each other. Specific genetic signals involving the fibroblast growth factor receptor-like 1 (FGFRL1) gene are related to high blood pressure and bone growth in giraffes. FGFRL1 is associated with cardiovascular system and bone formation.

The potential anti-amyloidogenic candidate, SPA1413, for Alzheimer's disease.

Background And Purpose: Recently, isoflavone derivatives have been shown to have neuroprotective effects against neurological disorders. For instance, genistein attenuated the neuroinflammation and amyloid-β accumulation in Alzheimer's disease animal models, suggesting the potential for use to prevent and treat Alzheimer's disease.

Experimental Approach: Here, 50 compounds, including isoflavone derivatives, were constructed and screened for the inhibitory effects on amyloid-β fibrilization and oligomerization using the high-throughput screening formats of thioflavin T assay and multimer detection system, respectively.

Forensic Analysis of Human Microbiome in Skin and Body Fluids Based on Geographic Location.

High-throughput DNA sequencing technologies have facilitated the forensic analysis of human microbiome. Specific microbial species or communities obtained from the crime scene provide evidence of human contacts and their body fluids. The microbial community is influenced by geographic, ethnic, lifestyle, and environmental factors such as urbanization.

A Genome-Wide Association Study of Novel Genetic Variants Associated With Anthropometric Traits in Koreans.

Most previous genome-wide association studies (GWAS) have identified genetic variants associated with anthropometric traits. However, most of the evidence were reported in European populations. Anthropometric traits such as height and body fat distribution are significantly affected by gender and genetic factors.

Histone deacetylase 8 inhibition alleviates cholestatic liver injury and fibrosis.

Cholestasis is a pathological condition involving blockage of bile flow that results in hepatotoxicity, inflammation, and fibrosis. Although recent studies have shown that histone deacetylases (HDACs) are involved in the progression of fibrosis in various organs, the role of HDAC8 on liver fibrosis has until now remained unexplored. This study presents a newly-synthesized, selective HDAC8 inhibitor SPA3014 composed of a vinyl disulfide-sulfoxide core, and evaluates its therapeutic efficacy against cholestatic liver injury and fibrosis in bile duct-ligated (BDL) mice.

Discovery of 5-Phenoxy-2-aminopyridine Derivatives as Potent and Selective Irreversible Inhibitors of Bruton's Tyrosine Kinase.

As a member of the tyrosine protein kinase Tec (TEC) family, Bruton's tyrosine kinase (BTK) is considered a promising therapeutic target due to its crucial roles in the B cell receptor (BCR) signaling pathway. Although many types of BTK inhibitors have been reported, there is an unmet need to achieve selective BTK inhibitors to reduce side effects. To obtain BTK selectivity and efficacy, we designed a novel series of type II BTK inhibitors which can occupy the allosteric pocket induced by the DFG-out conformation and introduced an electrophilic warhead for targeting Cys481.

Discovery of Tricyclic Pyranochromenone as Novel Bruton's Tyrosine Kinase Inhibitors with in Vivo Antirheumatic Activity.

Bruton's tyrosine kinase (BTK) is an attractive target for treating patients with B cell malignancies and autoimmune diseases. Many BTK inhibitors have been identified; however, like other kinase inhibitors, they lack diversity in their core structures. Therefore, it is important to secure a novel scaffold that occupies the adenine-binding site of BTK.

Zerumbone Restores Gut Microbiota Composition in ETBF Colonized AOM/DSS Mice.

Colorectal cancer (CRC) is the leading cause of common malignant neoplasm worldwide. Many studies have analyzed compositions of gut microbiota associated with various diseases such as inflammatory bowel diseases (IBD) and colon cancer. One of the most representative bacteria involved in CRC is enterotoxigenic (ETBF), a species belonging to phylum Bacteroidetes.

The interaction between FTO rs9939609 and physical activity is associated with a 2-fold reduction in the risk of obesity in Korean population.

Objective: FTO (fat mass and obesity-associated) gene is a well-known genetic risk factor for obesity. We investigated whether physical activity modulates the effect of FTO rs9939609 on obesity in Korean population.

Methods: The study analyzed the correlation between physical activity and obesity in 8840 individuals representing the Korea Association Resource (KARE).