The Nuclear Matrix Protein, NRP/B, Acts as a Transcriptional Repressor of E2F-mediated Transcriptional Activity

Background: NRP/B, a family member of the BTB/Kelch repeat proteins, is implicated in neuronal and cancer development, as well as the regulation of oxidative stress responses in breast and brain cancer. Our previous studies indicate that the NRP/B-BTB/POZ domain is involved in the dimerization of NRP/B and in a complex formation with the tumor suppressor, retinoblastoma protein. Although much evidence supports the potential role of NRP/B as a tumor suppressor, the molecular mechanisms of NRP/B action on E2F transcription factors have not been elucidated. Methods: Three-dimensional modeling of NRP/B was used to generate point mutations in the BTB/Kelch domains. Tet-on inducible NRP/B expression was established. The NRP/B deficient breast cancer cell line, MDA-MB-231, was generated using lentiviral shNRP/B to evaluate the effect of NRP/B on cell proliferation, invasion and migration. Immunoprecipitation was performed to verify the interaction of NRP/B with E2F and histone deacetylase (HDAC-1), and the expression level of NRP/B protein was analyzed by Western blot analysis. Changes in cell cycle were determined by flow cytometry. Transcriptional activities of E2F transcription factors were measured by chloramphenicol acetyltransferase (CAT) activity. Results: Ectopic overexpression of NRP/B demonstrated that the NRP/B-BTB/POZ domain plays a critical role in E2F-mediated transcriptional activity. Point mutations within the BTB/POZ domain restored E2-promoter activity inhibited by NRP/B. Loss of NRP/B enhanced the proliferation and migration of breast cancer cells. Endogenous NRP/B interacted with E2F and HDAC1. Treatement with an HDAC inhibitor, trichostatin A (TSA), abolished the NRP/B-mediated suppression of E2-promoter activity. Gain or loss of NRP/B in HeLa cells confirmed the transcriptional repressive capability of NRP/B on the E2F target genes, Cyclin E and HsORC (Homo sapiens Origin Recognition Complex). Conclusions: The present study shows that NRP/B acts as a transcriptional repressor by interacting with the co-repressors, HDAC1, providing new insight into the molecular mechanisms of NRP/B on tumor suppression

Crystallization and preliminary X-ray analysis of neoagarobiose hydrolase from Saccharophagus degradans 2-40

Many agarolytic bacteria degrade agar polysaccharide into the disaccharide unit neoagarobiose [O-3,6-anhydro-α-L-galactopyranosyl-(1→3)-D-galactose] using various β-agarases. Neoagarobiose hydrolase is an enzyme that acts on the α-1,3 linkage in neoagarobiose to yield D-galactose and 3,6-anhydro-L-galactose. This activity is essential in both the metabolism of agar by agarolytic bacteria and the production of fermentable sugars from agar biomass for bioenergy production. Neoagarobiose hydrolase from the marine bacterium Saccharophagus degradans 2-40 was overexpressed in Escherichia coli and crystallized in the monoclinic space group C2, with unit-cell parameters a = 129.83, b = 76.81, c = 90.11 Å, β = 101.86°. The crystals diffracted to 1.98 Å resolution and possibly contains two molecules in the asymmetric unit

Synthetic biology for evolutionary engineering: from perturbation of genotype to acquisition of desired phenotype

With the increased attention on bio-based industry, demands for techniques that enable fast and effective strain improvement have been dramatically increased. Evolutionary engineering, which is less dependent on biological information, has been applied to strain improvement. Currently, synthetic biology has made great innovations in evolutionary engineering, particularly in the development of synthetic tools for phenotypic perturbation. Furthermore, discovering biological parts with regulatory roles and devising novel genetic circuits have promoted high-throughput screening and selection. In this review, we first briefly explain basics of synthetic biology tools for mutagenesis and screening of improved variants, and then describe how these strategies have been improved and applied to phenotypic engineering. Evolutionary engineering using advanced synthetic biology tools will enable further innovation in phenotypic engineering through the development of novel genetic parts and assembly into well-designed logic circuits that perform complex tasks.This work was supported by the Bio & Medical Technology Development Program (NRF-2018M3A9H3020459) and the C1 Gas Refnery Program (NRF2016M3D3A1A01913561) through the National Research Foundation (NRF) funded by Ministry of Science and ICT (MSIT). JY was partially supported by Basic Science Research Program (NRF-2018R1C1B6005764) through the National Research Foundation (NRF) funded by MSIT and SWS was partially supported by Creative-Pioneering Researchers Program through Seoul National University (SNU)

Self supervised convolutional kernel based handcrafted feature harmonization: Enhanced left ventricle hypertension disease phenotyping on echocardiography

Radiomics, a medical imaging technique, extracts quantitative handcrafted features from images to predict diseases. Harmonization in those features ensures consistent feature extraction across various imaging devices and protocols. Methods for harmonization include standardized imaging protocols, statistical adjustments, and evaluating feature robustness. Myocardial diseases such as Left Ventricular Hypertrophy (LVH) and Hypertensive Heart Disease (HHD) are diagnosed via echocardiography, but variable imaging settings pose challenges. Harmonization techniques are crucial for applying handcrafted features in disease diagnosis in such scenario. Self-supervised learning (SSL) enhances data understanding within limited datasets and adapts to diverse data settings. ConvNeXt-V2 integrates convolutional layers into SSL, displaying superior performance in various tasks. This study focuses on convolutional filters within SSL, using them as preprocessing to convert images into feature maps for handcrafted feature harmonization. Our proposed method excelled in harmonization evaluation and exhibited superior LVH classification performance compared to existing methods.Comment: 11 pages, 7 figure

Who Are Less Likely to Receive Subsequent Chemotherapy Beyond First-Line Therapy for Advanced Non-small Cell Lung Cancer?: Implications for Selection of Patients for Maintenance Therapy

BackgroundProspective studies have implied that maintenance therapy for non-small cell lung cancer (NSCLC) has its effect by giving active drugs earlier to patients who otherwise die without receiving second-line therapy. The purpose of this study was to select patients with NSCLC who could most benefit from maintenance therapy, by evaluating which patients would be less likely to receive second-line therapy.MethodsClinicopathologic data of patients with advanced NSCLC who received four cycles of first-line chemotherapy followed by time-off therapy and eventual disease progression or death were reviewed retrospectively. Patients were grouped into ones with first-line therapy only or ones with more than first-line therapy. Clinical characteristics between the two groups were compared.ResultsA total of 271 patients were eligible for analysis, and 39 patients (14.4%) received only first-line therapy. Patients significantly more likely to receive only first-line therapy had performance status of two or three after first-line therapy, large volume of initial target lesions (sum of long diameters ≥70 mm), or smaller decrease in target lesions (decrease <20%) after first-line therapy. Median overall survival of the 143 patients (52.8%) with at least one of these characteristics (16.3 months) was significantly shorter than that of patients without any of these characteristics (23.5 months, p = 0.007).ConclusionMaintenance therapy may be of greater benefit to patients with NSCLC who have clinical characteristics including poor performance status after first-line therapy, large initial target lesions, or smaller decrease in target lesions after first-line therapy

Realization of robust boundary modes and non-contractible loop states in photonic Kagome lattices

Corbino-geometry has well-known applications in physics, as in the design of graphene heterostructures for detecting fractional quantum Hall states or superconducting waveguides for illustrating circuit quantum electrodynamics. Here, we propose and demonstrate a photonic Kagome lattice in the Corbino-geometry that leads to direct observation of non-contractible loop states protected by real-space topology. Such states represent the "missing" flat-band eigenmodes, manifested as one-dimensional loops winding around a torus, or lines infinitely extending to the entire flat-band lattice. In finite (truncated) Kagome lattices, however, line states cannot preserve as they are no longer the eigenmodes, in sharp contrast to the case of Lieb lattices. Using a continuous-wave laser writing technique, we experimentally establish finite Kagome lattices with desired cutting edges, as well as in the Corbino-geometry to eliminate edge effects. We thereby observe, for the first time to our knowledge, the robust boundary modes exhibiting self-healing properties, and the localized modes along toroidal direction as a direct manifestation of the non-contractible loop states

Ovarian Gynandroblastoma with a Juvenile Granulosa Cell Tumor Component in a Postmenopausal Woman: A Case Report and Literature Review

Gynandroblastoma is an extremely rare sex cord-stromal tumor with both female (granulosa cell tumor) and male (Sertoli-Leydig cell tumor) elements. Juvenile granulosa cell tumors are also very rare and are so named because they usually occur in children and adolescents. A 71-year-old woman with right upper quadrant abdominal pain visited our hospital. Pelvic computed tomography showed a large multilocular cystic mass, suspected to be of ovarian origin. We performed a total abdominal hysterectomy (total abdominal hysterectomy was performed) with bilateral salpingo-oophorectomy. A 13-cm multilocular cystic mass with serous fluid was observed in her right ovary. Upon microscopic examination, the solid component of the mass showed both Sertoli-Leydig cell and juvenile granulosa cell differentiation, which we diagnosed as gynandroblastoma. Gynandroblastoma with a juvenile granulosa cell tumor component is extremely rare and, until now, only six cases have been reported in the English literature. We report the first gynandroblastoma with a juvenile granulosa cell tumor component diagnosed in an elderly patient, along with a literature review

Development of a CHO cell line for stable production of recombinant antibodies against human MMP9

Abstract Background Human matrix metalloproteinase 9 (hMMP9) is a biomarker in several diseases, including cancer, and the need for developing detectors and inhibitors of hMMP9 is increasing. As an antibody against hMMP9 can be selectively bound to hMMP9, the use of anti-MMP9 antibody presents new possibilities to address hMMP9-related diseases. In this study, we aimed to establish a stable Chinese hamster ovary (CHO) cell line for the stable production of antibodies against hMMP9. Results Weconstructed recombinant anti-hMMP9 antibody fragment-expressing genes and transfected these to CHO cells. We chose a single clone, and successfully produced a full-sized antibody against hMMP9 with high purity, sensitivity, and reproducibility. Subsequently, we confirmed the antigen-binding efficiency of the antibody. Conclusions We developed a novel recombinant anti-hMMP9 antibody via a CHO cell-based mammalian expression system, which has a high potential to be used in a broad range of medical and industrial areas

The Relation between Birth Weight and Insulin Resistance in Korean Adolescents

Low birth weight is associated with insulin resistance and type 2 diabetes in adults. The fetal programming hypothesis has shown that insulin resistance and its associated metabolic disturbances result from a poor gestational environment, for which low birth weight is a surrogate. An at-home questionnaire survey was performed on 660 middle school students (12-15 years) in Seoul, Korea, and 152 cases were randomly selected based on their birth weight. Subjects were divided into three groups according to birth weight. We recorded their birth weight and measured their current anthropometric data, blood pressure, lipid profile, HOMA-IR, and HOMA-β, and compared these parameters among the groups. The relation of birth weight to physiological characteristics in adolescence was examined. Systolic blood pressure, lipid profiles, and fasting plasma glucose, HOMA-β were not significantly different among the groups, but diastolic blood pressure was lower in the third tertile. Insulin, C-peptide, and HOMA-IR were higher in the lower birth weight tertile. After adjustment for confounding factors, birth weight was inversely related to diastolic blood pressure, insulin, C-peptide, and HOMA-IR. We conclude that low birth weight may predict the risk of the insulin resistance and its progression over age, and that adequate gestational nutrition is therefore necessary to prevent low birth weight

Genome sequence of the moderately halophilic bacterium Salinicoccus carnicancri type strain CrmT (= DSM 23852T)

Salinicoccus carnicancri Jung et al. 2010 belongs to the genus Salinicoccus in the family Staphylococcaceae. Members of the Salinicoccus are moderately halophilic and originate from various salty environments. The halophilic features of the Salinicoccus suggest their possible uses in biotechnological applications, such as biodegradation and fermented food production. However, the genus Salinicoccus is poorly characterized at the genome level, despite its potential importance. This study presents the draft genome sequence of S. carnicancri strain Crm(T) and its annotation. The 2,673,309 base pair genome contained 2,700 protein-coding genes and 78 RNA genes with an average G+C content of 47.93 mol%. It was notable that the strain carried 72 predicted genes associated with osmoregulation, which suggests the presence of beneficial functions that facilitate growth in high-salt environments.