Functional elements demarcated by histone modifications in breast cancer cells

AbstractHistone modifications are regarded as one of markers to identify regulatory elements which are DNA segments modulating gene transcription. Aberrant changes of histone modification levels are frequently observed in cancer. We have employed ChIP-Seq to identify regulatory elements in human breast cancer cell line, MCF-7 by comparing histone modification patterns of H3K4me1, H3K4me3, and H3K9/14ac to those in normal mammary epithelial cell line, MCF-10A. The genome-wide analysis shows that H3K4me3 and H3K9/14ac are highly enriched at promoter regions and H3K4me1 has a relatively broad distribution over proximity of TSSs as well as other genomic regions. We identified that many differentially expressed genes in MCF-7 have divergent histone modification patterns. To understand the functional roles of distinctively histone-modified regions, we selected 35 genomic regions marked by at least one histone modification and located from 3 to 10kb upstream of TSS in both MCF-7 and MCF-10A and assessed their transcriptional activities. About 66% and 60% of selected regions in MCF-7 and MCF-10A, respectively, enhanced the transcriptional activity. Interestingly, most regions marked by H3K4me1 exhibited an enhancer activity. Regions with two or more kinds of histone modifications did show varying activities. In conclusion, our data reflects that comprehensive analysis of histone modification profiles under cell type-specific chromatin environment should provide a better chance for defining functional regulatory elements in the genome

Identification of the early and late responder genes during the generation of induced pluripotent stem cells from mouse fibroblasts

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Operative Treatment with a Laparotomy for Anorectal Problems Arising from a Self-Inserted Foreign Body

An anorectal foreign body can cause serious complications such as incontinence, rectal perforation, peritonitis, or pelvic abscess, so it should be managed immediately. We experienced two cases of operative treatment for a self-inserted anorectal foreign body. In one, the foreign body could not be removed as it was completely impacted in the anal canal. We failed to remove it through the anus. A laparotomy and removal of the foreign body was performed by using an incision on the rectum. Primary colsure and a sigmoid loop colostomy were done. A colostomy take-down was done after three months. The other was a rectal perforation from anal masturbation with a plastic device. We performed primary repair of the perforated rectosigmoid colon, and we didea sigmoid loop colostom. A colostomy take-down was done three months later. Immediate and proper treatment for a self-inserted anorectal foreign body is important to prevent severe complications, and we report successful surgical treatments for problems caused by anorectal foreign bodies

Marked Suppression of Ghrelin Concentration by Insulin in Prader-Willi Syndrome

The plasma ghrelin has been reported to be elevated in Prader-Willi syndrome (PWS) and modulated by insulin. It was hypothesized that insulin might have a more pronounced effect on reducing plasma ghrelin in PWS patients, which would influence appetite. This study investigated the degree of ghrelin suppression using an euglycemic hyperinsulinemic clamp in children with PWS (n=6) and normal children (n=6). After a 90-min infusion of insulin, the plasma ghrelin level decreased from a basal value of 0.86±0.15 to 0.58±0.12 ng/mL in the controls, and from 2.38±0.76 to 1.12±0.29 ng/mL in children with PWS (p=0.011). The area under the curve below the baseline level over the 90 min insulin infusion was larger in children with PWS than in controls (-92.82±44.4 vs. -10.41±2.87 ng/mL/90 min) (p=0.011). The insulin sensitivity measured as the glucose infusion rate at steady state was similar in the two groups (p=0.088). The decrease in the ghrelin levels in response to insulin was more pronounced in the children with PWS than in the controls. However, the level of ghrelin was always higher in the children with PWS during the clamp study. This suggests that even though insulin sensitivity to ghrelin is well maintained, an increase in the baseline ghrelin levels is characteristic of PWS

Multiple Endocrine Neoplasia Type 1 with Multiple Leiomyomas Linked to a Novel Mutation in the MEN1 Gene

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited syndrome. MEN1 is characterized by the presence of functioning and nonfunctioning tumors or hyperplasia of the pituitary gland, parathyroid glands, and pancreatic islet cells. In addition, MEN1 carriers can have adrenal or thyroid tumors and non-endocrine tumors, such as lipomas, angiofibromas, and leiomyomas. Although leiomyoma is not a major component of MEN1, it is thought to occur more frequently than expected. However, there has been no report of a case of MEN1 with leiomyoma in Korea so far. This report describes a patient with multiple leiomyomas in MEN1. A 50-year-old woman was referred for further evaluation of elevated calcium levels and osteoporosis. Biochemical abnormalities included hypercalcemia with elevated parathyroid hormone. There was hyperprolactinemia with pituitary microadenoma in sella MRI. An abdominal MRI demonstrated adrenal nodules and leiomyomas in the bladder and uterus. Endoscopic ultrasonography demonstrated esophageal leiomyoma and pancreatic islet cell tumor. A subtotal parathyroidectomy with thymectomy was performed. Sequencing of the MEN1 gene in this patient revealed a novel missense mutation (D350V, exon 7). This is the first case of MEN1 accompanied with multiple leiomyomas, parathyroid adenoma, pituitary adenoma, pancreatic tumor, and adrenal tumor

Biobanking for glomerular diseases: a study design and protocol for KOrea Renal biobank NEtwoRk System TOward NExt-generation analysis (KORNERSTONE)

Abstract Backgrounds Glomerular diseases, a set of debilitating and complex disease entities, are related to mortality and morbidity. To gain insight into pathophysiology and novel treatment targets of glomerular disease, various types of biospecimens linked to deep clinical phenotyping including clinical information, digital pathology, and well-defined outcomes are required. We provide the rationale and design of the KOrea Renal biobank NEtwoRk System TOward Next-generation analysis (KORNERSTONE). Methods The KORNERSTONE, which has been initiated by Korea Centres for Disease Control and Prevention, is designed as a multi-centre, prospective cohort study and biobank for glomerular diseases. Clinical data, questionnaires will be collected at the time of kidney biopsy and subsequently every 1 year after kidney biopsy. All of the clinical data will be extracted from the electrical health record and automatically uploaded to the web-based database. High-quality digital pathologies are obtained and connected in the database. Various types of biospecimens are collected at baseline and during follow-up: serum, urine, buffy coat, stool, glomerular complementary DNA (cDNA), tubulointerstitial cDNA. All data and biospecimens are processed and stored in a standardised manner. The primary outcomes are mortality and end-stage renal disease. The secondary outcomes will be deterioration renal function, remission of proteinuria, cardiovascular events and quality of life. Discussion Ethical approval has been obtained from the institutional review board of each participating centre and ethics oversight committee. The KORNERSTONE is designed to deliver pioneer insights into glomerular diseases. The study design allows comprehensive, integrated and high-quality data collection on baseline laboratory findings, clinical outcomes including administrative data and digital pathologic images. This may provide various biospecimens and information to many researchers, establish the rationale for future more individualised treatment strategies for glomerular diseases. Trial registration NCT03929887

Clonal hematopoiesis is associated with risk of severe Covid-19.

Acquired somatic mutations in hematopoietic stem and progenitor cells (clonal hematopoiesis or CH) are associated with advanced age, increased risk of cardiovascular and malignant diseases, and decreased overall survival. These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH. A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19. Whether CH predisposes to severe Covid-19 or other infections is unknown. Among 525 individuals with Covid-19 from Memorial Sloan Kettering (MSK) and the Korean Clonal Hematopoiesis (KoCH) consortia, we show that CH is associated with severe Covid-19 outcomes (OR = 1.85, 95%=1.15-2.99, p = 0.01), in particular CH characterized by non-cancer driver mutations (OR = 2.01, 95% CI = 1.15-3.50, p = 0.01). We further explore the relationship between CH and risk of other infections in 14,211 solid tumor patients at MSK. CH is significantly associated with risk of Clostridium Difficile (HR = 2.01, 95% CI: 1.22-3.30, p = 6×10-3) and Streptococcus/Enterococcus infections (HR = 1.56, 95% CI = 1.15-2.13, p = 5×10-3). These findings suggest a relationship between CH and risk of severe infections that warrants further investigation

Effects of Children Activity Centered Learning Module on Science Related Attitudes and Conceptual Achievement of Eelmentary School Students

We have used the developed modular teaching-learning materials and evaluated their effects on science related attitudes and conceptual achievement of elementary school students. In order to analyze the effects, we have made two groups of the text aterial: one that followed the 6th elementary science curriculum and the other modular material, that adopted the open education system with the children activity centered learning modules. We have found the children to develop their attitudes about science when their scientific activities are more open and have various explorations. When they have undergone their change of attitude, their behavior becomes affirmative and their affirmative and positive attitudes to the science will be accumulated in obtaining the science concepts