Tgif1 Counterbalances The Activity Of Core Pluripotency Factors In Mouse Embryonic Stem Cells

Core pluripotency factors, such as Oct4, Sox2, and Nanog, play important roles in maintaining embryonic stem cell (ESC) identity by autoregulatory feedforward loops. Nevertheless, the mechanism that provides precise control of the levels of the ESC core factors without indefinite amplification has remained elusive. Here, we report the direct repression of core pluripotency factors by Tgif1, a previously known terminal repressor of TGF beta/activin/nodal signaling. Overexpression of Tgif1 reduces the levels of ESC core factors, whereas its depletion leads to the induction of the pluripotency factors. We confirm the existence of physical associations between Tgif1 and Oct4, Nanog, and HDAC1/2 and further show the level of Tgif1 is not significantly altered by treatment with an activator/inhibitor of the TGF beta/activin/nodal signaling. Collectively, our findings establish Tgif1 as an integral member of the core regulatory circuitry of mouse ESCs that counterbalances the levels of the core pluripotency factors in a TGF beta/activin/nodal-independent manner.Cancer Prevention Research Institute of Texas (CPRIT) R1106Molecular Bioscience

Exploration of biomedical knowledge for recurrent glioblastoma using natural language processing deep learning models

Abstract Background Efficient exploration of knowledge for the treatment of recurrent glioblastoma (GBM) is critical for both clinicians and researchers. However, due to the large number of clinical trials and published articles, searching for this knowledge is very labor-intensive. In the current study, using natural language processing (NLP), we analyzed medical research corpora related to recurrent glioblastoma to find potential targets and treatments. Methods We fine-tuned the SAPBERT, which was pretrained on biomedical ontologies, to perform question/answering (QA) and name entity recognition (NER) tasks for medical corpora. The model was fine-tuned with the SQUAD2 dataset and multiple NER datasets designed for QA task and NER task, respectively. Corpora were collected by searching the terms recurrent glioblastoma and drug target, published from 2000 to 2020 in the Web of science (N = 288 articles). Also, clinical trial corpora were collected from clinicaltrial.gov using the searching term of recurrent glioblastoma (N = 587 studies). Results For the QA task, the model showed an F1 score of 0.79. For the NER task, the model showed F1 scores of 0.90 and 0.76 for drug and gene name recognition, respectively. When asked what the molecular targets were promising for recurrent glioblastoma, the model answered that RTK inhibitors or LPA-1 antagonists were promising. From collected clinical trials, the model summarized them in the order of bevacizumab, temozolomide, lomustine, and nivolumab. Based on published articles, the model found the many drug-gene pairs with the NER task, and we presented them with a circus plot and related summarization ( https://github.com/bigwiz83/NLP_rGBM ). Conclusion Using NLP deep learning models, we could explore potential targets and treatments based on medical research and clinical trial corpora. The knowledge found by the models may be used for treating recurrent glioblastoma

Tracing the historical origin of Joseon mummies considering the structural similarities between the burial systems of Korean and Chinese dynasties

Joseon mummies have proved to be excellent subjects for scientific research on the health and disease statuses of pre-modern Korean peoples. Despite its academic significance, the origins of the Hoegwakmyo tomb in which the Joseon mummy was discovered have not yet been entirely revealed. Meanwhile, over the past several decades, there have been some reports on mummies and cultural artifacts preserved very well in the tombs of several Chinese dynasties (especially Song, Yuan, Ming and Qing). Although the Chinese tombs were very diverse in structure, we note that some graves among them were structurally very similar to Joseon Hoegwakmyo tombs. Before the Hoegwakmyo tomb in Korea, there were already similar tombs in China, inside which dead persons were mummified like the Joseon mummies. Considering that the Hoegwakmyo tomb of the Joseon Dynasty was established by the influence of the Confucian ideology, the Korean and Chinese mummies might share common cultural origins in history

Estrogen receptor-α gene haplotype is associated with primary knee osteoarthritis in Korean population

Estrogen and estrogen receptors (ERs) are known to play important roles in the pathophysiology of osteoarthritis (OA). To investigate ER-α gene polymorphisms for its associations with primary knee OA, we conducted a case–control association study in patients with primary knee OA (n = 151) and healthy individuals (n = 397) in the Korean population. Haplotyping analysis was used to determine the relationship between three polymorphisms in the ER-α gene (intron 1 T/C, intron 1 A/G and exon 8 G/A) and primary knee OA. Genotypes of the ER-α gene polymorphism were determined by PCR followed by restriction enzyme digestion (PvuII for intron 1 T/C, XbaI for intron 1 A/G, and BtgI for exon 8 G/A polymorphism). There was no significant difference between primary knee OA patients and healthy control individuals in the distribution of any of the genotypes evaluated. However, we found that the allele frequency for the exon 8 G/A BtgI polymorphism (codon 594) was significantly different between primary knee OA patients and control individuals (odds ratio = 1.38, 95% confidence interval = 1.01–1.88; P = 0.044). In haplotype frequency estimation analysis, there was a significant difference between primary knee OA patients and control individuals (degrees of freedom = 7, χ(2 )= 21.48; P = 0.003). Although the number OA patients studied is small, the present study shows that ER-α gene haplotype may be associated with primary knee OA, and genetic variations in the ER-α gene may be involved in OA

Hyperglycemic Hyperosmolar Syndrome Caused by Steroid Therapy in a Patient with Lupus Nephritis

A 51-yr-old female was referred to our outpatient clinic for the evaluation of generalized edema. She had been diagnosed with idiopathic thrombocytopenic purpura (ITP). She had taken no medicine. Except for the ITP, she had no history of systemic disease. She was diagnosed with systemic lupus erythematosus. Immunosuppressions consisting of high-dose steroid were started. When preparing the patient for discharge, a generalized myoclonic seizure occurred at the 47th day of admission. At that time, the laboratory and neurology studies showed hyperglycemic hyperosmolar syndrome. Brain MRI and EEG showed brain atrophy without other lesion. The seizure stopped after the blood sugar and serum osmolarity declined below the upper normal limit. The patient became asymptomatic and she was discharged 10 weeks after admission under maintenance therapy with prednisolone, insulin glargine and nateglinide. The patient remained asymptomatic under maintenance therapy with deflazacort and without insulin or medication for blood sugar control