Publications by authors named "Sangho Lee"

155 Publications

Mesenchymal Stem Cells Suppress Severe Asthma by Directly Regulating Th2 Cells and Type 2 Innate Lymphoid Cells.

Mol Cells 2021 Aug;44(8):580-590

Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.

Patients with severe asthma have unmet clinical needs for effective and safe therapies. One possibility may be mesenchymal stem cell (MSC) therapy, which can improve asthma in murine models. However, it remains unclear how MSCs exert their beneficial effects in asthma. Here, we examined the effect of human umbilical cord blood-derived MSCs (hUC-MSC) on two mouse models of severe asthma, namely, Alternaria alternata-induced and house dust mite (HDM)/diesel exhaust particle (DEP)-induced asthma. hUC-MSC treatment attenuated lung type 2 (Th2 and type 2 innate lymphoid cell) inflammation in both models. However, these effects were only observed with particular treatment routes and timings. co-culture showed that hUC-MSC directly downregulated the interleukin (IL)-5 and IL-13 production of differentiated mouse Th2 cells and peripheral blood mononuclear cells from asthma patients. Thus, these results showed that hUC-MSC treatment can ameliorate asthma by suppressing the asthmogenic cytokine production of effector cells. However, the successful clinical application of MSCs in the future is likely to require careful optimization of the route, dosage, and timing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14348/molcells.2021.0101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424137PMC
August 2021

Trajectories of clinical and laboratory characteristics associated with COVID-19 in hemodialysis patients by survival.

Hemodial Int 2021 Aug 10. Epub 2021 Aug 10.

Global Medical Office, Fresenius Medical Care, Waltham, Massachusetts, USA.

Introduction: The clinical impact of COVID-19 has not been established in the dialysis population. We evaluated the trajectories of clinical and laboratory parameters in hemodialysis (HD) patients.

Methods: We used data from adult HD patients treated at an integrated kidney disease company who received a reverse transcription polymerase chain reaction (RT-PCR) test to investigate suspicion of a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection between May 1 and September 1, 2020. Nonparametric smoothing splines were used to fit data for individual trajectories and estimate the mean change over time in patients testing positive or negative for SARS-CoV-2 and those who survived or died within 30 days of first suspicion or positive test date. For each clinical parameter of interest, the difference in average daily changes between COVID-19 positive versus negative group and COVID-19 survivor versus nonsurvivor group was estimated by fitting a linear mixed effects model based on measurements in the 14 days before (i.e., Day -14 to Day 0) Day 0.

Results: There were 12,836 HD patients with a suspicion of COVID-19 who received RT-PCR testing (8895 SARS-CoV-2 positive). We observed significantly different trends (p < 0.05) in pre-HD systolic blood pressure (SBP), pre-HD pulse rate, body temperature, ferritin, neutrophils, lymphocytes, albumin, and interdialytic weight gain (IDWG) between COVID-19 positive and negative patients. For COVID-19 positive group, we observed significantly different clinical trends (p < 0.05) in pre-HD pulse rate, lymphocytes, neutrophils, and albumin between survivors and nonsurvivors. We also observed that, in the group of survivors, most clinical parameters returned to pre-COVID-19 levels within 60-90 days.

Conclusion: We observed unique temporal trends in various clinical and laboratory parameters among HD patients who tested positive versus negative for SARS-CoV-2 infection and those who survived the infection versus those who died. These trends can help to define the physiological disturbances that characterize the onset and course of COVID-19 in HD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/hdi.12977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444916PMC
August 2021

Exergy Analysis of a Direct Contact Membrane Distillation (DCMD) System Based on Computational Fluid Dynamics (CFD).

Membranes (Basel) 2021 Jul 13;11(7). Epub 2021 Jul 13.

School of Civil and Environmental Engineering, Kookmin University, 77, Jeongneung-ro, Seongbuk-gu, Seoul 027072, Korea.

Understanding the energy efficiency of direct contact membrane distillation (DCMD) is important for the widespread application and practical implementation of the process. This study analyzed the available energy, known as exergy, in a DCMD system using computational fluid dynamics (CFD). A CFD model was developed to investigate the hydrodynamic and thermal conditions in a DCMD module. After the CFD model was verified, it was used to calculate the temperature polarization coefficient (TPC) and exergy destruction magnitudes under various operating conditions. The results revealed that slight decreases and increases in the TPC occurred with distance from the inlet in the module. The TPC was found to increase as the feed temperature was reduced and the feed and permeate flow rates were increased. The exergy destruction phenomenon was more significant under higher feed temperatures and higher flux conditions. Although the most significant exergy destruction in the permeate occurred near the feed inlet, the effect became less influential closer to the feed outlet. An analysis of exergy flows revealed that the efficiency loss in the permeate side corresponded to 32.9-45.3% of total exergy destruction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/membranes11070525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303652PMC
July 2021

Phosphorylation of OGFOD1 by Cell Cycle-Dependent Kinase 7/9 Enhances the Transcriptional Activity of RNA Polymerase II in Breast Cancer Cells.

Cancers (Basel) 2021 Jul 8;13(14). Epub 2021 Jul 8.

National Creative Research Center for Epigenome Reprogramming Network, Department of Biomedical Sciences, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Korea.

2-oxoglutarate and iron-dependent oxygenase domain-containing protein 1 (OGFOD1) expression is upregulated in a variety of cancers and has been related to poor prognosis. However, despite this significance to cancer progression, the precise oncogenic mechanism of OGFOD1 is not understood. We demonstrated that OGFOD1 plays a role in enhancing the transcriptional activity of RNA polymerase II in breast cancer cells. OGFOD1 directly binds to the C-terminal domain of RNA polymerase II to alter phosphorylation status. The elimination of OGFOD1 resulted in decreased tumor development. Additionally, cell cycle-dependent kinase 7 and cell cycle-dependent kinase 9, critical enzymes for activating RNA polymerase II, phosphorylated serine 256 of OGFOD1, whereas a non-phosphorylated mutant OGFOD1 failed to enhance transcriptional activation and tumor growth. Consequently, OGFOD1 helps promote tumor growth by enhancing RNA polymerase II, whereas simultaneous phosphorylation of OGFOD1 by CDK enzymes is essential in stimulating RNA polymerase II-mediated transcription both in vitro and in vivo, and expression of target genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13143418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304009PMC
July 2021

Analysis of Polyvinylidene Fluoride Membranes Fabricated for Membrane Distillation.

Membranes (Basel) 2021 Jun 10;11(6). Epub 2021 Jun 10.

School of Civil and Environmental Engineering, Kookmin University, Seoul 02707, Korea.

The optimization of the properties for MD membranes is challenging due to the trade-off between water productivity and wetting tendency. Herein, this study presents a novel methodology to examine the properties of MD membranes. Seven polyvinylidene fluoride (PVDF) membranes were synthesized under different conditions by the phase inversion method and characterized to measure flux, rejection, contact angle (CA), liquid entry pressure (LEP), and pore sizes. Then, water vapor permeability (), salt leakage ratio (), and fiber radius () were calculated for the in-depth analysis. Results showed that the water vapor permeability and salt leakage ratio of the prepared membranes ranged from 7.76 × 10 s/m to 20.19 × 10 s/m and from 0.0020 to 0.0151, respectively. The calculated using the Purcell model was in the range from 0.598 μm to 1.690 μm. Since the was relatively small, the prepared membranes can have high LEP (more than 1.13 bar) even at low CA (less than 90.8°). The trade-off relations between the water vapor permeability and the other properties could be confirmed from the results of the prepared membranes. Based on these results, the properties of an efficient MD membrane were suggested as a guideline for the membrane development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/membranes11060437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230010PMC
June 2021

Impact of 2D-3D Heterointerface on Remote Epitaxial Interaction through Graphene.

ACS Nano 2021 Jun 3;15(6):10587-10596. Epub 2021 Jun 3.

Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

Remote epitaxy has drawn attention as it offers epitaxy of functional materials that can be released from the substrates with atomic precision, thus enabling production and heterointegration of flexible, transferrable, and stackable freestanding single-crystalline membranes. In addition, the remote interaction of atoms and adatoms through two-dimensional (2D) materials in remote epitaxy allows investigation and utilization of electrical/chemical/physical coupling of bulk (3D) materials 2D materials (3D-2D-3D coupling). Here, we unveil the respective roles and impacts of the substrate material, graphene, substrate-graphene interface, and epitaxial material for electrostatic coupling of these materials, which governs cohesive ordering and can lead to single-crystal epitaxy in the overlying film. We show that simply coating a graphene layer on wafers does not guarantee successful implementation of remote epitaxy, since atomically precise control of the graphene-coated interface is required, and provides key considerations for maximizing the remote electrostatic interaction between the substrate and adatoms. This was enabled by exploring various material systems and processing conditions, and we demonstrate that the rules of remote epitaxy vary significantly depending on the ionicity of material systems as well as the graphene-substrate interface and the epitaxy environment. The general rule of thumb discovered here enables expanding 3D material libraries that can be stacked in freestanding form.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.1c03296DOI Listing
June 2021

Different pyrolysis kinetics and product distribution of municipal and livestock manure sewage sludge.

Environ Pollut 2021 Sep 21;285:117197. Epub 2021 Apr 21.

School of Environmental Engineering, University of Seoul, Seoul, 02504, Republic of Korea. Electronic address:

Thermogravimetric analysis and pyrolyzer-gas chromatography/mass spectrometry measurements were taken to examine the kinetic behavior and product distribution on the thermal and catalytic pyrolysis of different types of sewage sludge. Compared to livestock manure sewage sludge (LMSS), municipal sewage sludge (MSS) had larger ash (30.3%) and lower fixed carbon (7.9%) contents. The peak intensities for the 1 decomposition region (200-380 °C) on the derivative thermogravimetric curve of MSS were higher than those of LMSS. In contrast, the peak height in the 2 temperature region (>380 °C) of MSS was lower than that of LMSS. The activation energy for the pyrolysis of MSS (Avg. 186.5 kJ/mol) was lower than that of LMSS (Avg. 263.4 kJ/mol) over the entire conversion range. MSS produced larger amounts of fatty acids and cholesterol than LMSS. The in-situ catalytic pyrolysis of MSS over HBeta using a pyrolyzer-gas chromatography/mass spectrometry also produced larger amounts of aromatic hydrocarbons than LMSS, suggesting that its better feedstock properties strongly influence the final product oil quality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2021.117197DOI Listing
September 2021

Correlation between the Perfusion Index and Intraoperative Hypothermia: A Prospective Observational Pilot Study.

Medicina (Kaunas) 2021 Apr 8;57(4). Epub 2021 Apr 8.

Department of Anesthesiology and Pain Medicine, College of Medicine, Kyung Hee University, Seoul 02447, Korea.

We examined the association between the baseline perfusion index (PI) and changes in intraoperative body temperature during general anesthesia. The PI reflects the peripheral perfusion state. The PI may be associated with changes in body temperature during general anesthesia because the degree of redistribution of body heat from the central to the peripheral compartment varies depending on the peripheral perfusion state. Thirty-eight patients who underwent brain surgery were enrolled in this study. The baseline PI and body temperature of the patients were measured on entering the operating room. Body temperature was recorded every 15 min after induction of anesthesia using an esophageal temperature probe. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for intraoperative hypothermia. Eighteen patients (47 %) developed hypothermia intraoperatively. The baseline PI was significantly lower among patients in the hypothermia group (1.8 ± 0.7) than among those in the normothermia group (3.0 ± 1.2) ( < 0.001). The baseline PI and body temperature were independently associated with intraoperative hypothermia (PI: odds ratio [OR], 0.270; 95% confidence interval [CI], 0.105-0.697; = 0.007, baseline body temperature: OR, 0.061; 95% CI, 0.005-0.743; = 0.028). This study showed that low baseline PI was the factor most related to the development of intraoperative hypothermia. Future studies should consider the PI as a predictor of intraoperative hypothermia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/medicina57040364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068332PMC
April 2021

DRER: Deep Learning-Based Driver's Real Emotion Recognizer.

Sensors (Basel) 2021 Mar 19;21(6). Epub 2021 Mar 19.

Department of Automobile and IT Convergence, Kookmin University, 77, Jeongneung-ro, Seongbuk-gu, Seoul 02707, Korea.

In intelligent vehicles, it is essential to monitor the driver's condition; however, recognizing the driver's emotional state is one of the most challenging and important tasks. Most previous studies focused on facial expression recognition to monitor the driver's emotional state. However, while driving, many factors are preventing the drivers from revealing the emotions on their faces. To address this problem, we propose a deep learning-based driver's real emotion recognizer (DRER), which is a deep learning-based algorithm to recognize the drivers' real emotions that cannot be completely identified based on their facial expressions. The proposed algorithm comprises of two models: (i) facial expression recognition model, which refers to the state-of-the-art convolutional neural network structure; and (ii) sensor fusion emotion recognition model, which fuses the recognized state of facial expressions with electrodermal activity, a bio-physiological signal representing electrical characteristics of the skin, in recognizing even the driver's real emotional state. Hence, we categorized the driver's emotion and conducted human-in-the-loop experiments to acquire the data. Experimental results show that the proposed fusing approach achieves 114% increase in accuracy compared to using only the facial expressions and 146% increase in accuracy compare to using only the electrodermal activity. In conclusion, our proposed method achieves 86.8% recognition accuracy in recognizing the driver's induced emotion while driving situation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s21062166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003797PMC
March 2021

Crystal Structure of the Pneumococcal Vancomycin-Resistance Response Regulator DNA-Binding Domain.

Mol Cells 2021 Mar;44(3):179-185

School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.

Vancomycin response regulator (VncR) is a pneumococcal response regulator of the VncRS two-component signal transduction system (TCS) of Streptococcus pneumoniae. VncRS regulates bacterial autolysis and vancomycin resistance. VncR contains two different functional domains, the N-terminal receiver domain and C-terminal effector domain. Here, we investigated VncR C-terminal DNA binding domain (VncRc) structure using a crystallization approach. Crystallization was performed using the micro-batch method. The crystals diffracted to a 1.964 Å resolution and belonged to space group P212121. The crystal unit-cell parameters were a = 25.71 Å, b = 52.97 Å, and c = 60.61 Å. The structure of VncRc had a helix-turn-helix motif highly similar to the response regulator PhoB of . In isothermal titration calorimetry and size exclusion chromatography results, VncR formed a complex with VncS, a sensor histidine kinase of pneumococcal TCS. Determination of VncR structure will provide insight into the mechanism by how VncR binds to target genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14348/molcells.2021.2235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019601PMC
March 2021

Enhancement of anti-inflammatory and immunomodulatory effects of adipose-derived human mesenchymal stem cells by making uniform spheroid on the new nano-patterned plates.

Biochem Biophys Res Commun 2021 05 19;552:164-169. Epub 2021 Mar 19.

R&D Center, YidoBio, Inc., 123 Beolmal-ro, Anyang-si, Gyeonggi-do, 14056, South Korea. Electronic address:

Human mesenchymal stem cells (MSCs) are known to have anti-inflammatory and immunomodulatory functions; thus, several MSC products have been applied as cell therapy in clinical trials worldwide. Recent studies have demonstrated that MSC spheroids have superior anti-inflammatory and immunomodulatory functions to a single cell suspension. Current methods to prepare MSC spheroids include hanging drop, concave microwell aggregation, spinner flask, and gravity circulation. However, all these methods have limitations such as low scalability, easy cell clumping, low viability, and irregular size distribution. Here, we present a nano-patterned culture plasticware named PAMcell™ 3D plate to overcome these limitations. Nano-sized silica particles (700 nm) coated with RGD peptide were arrayed into fusiform onto the PLGA film. This uniform array enabled the seeded MSCs to grow only on the silica particles, forming uniform-sized semi-spheroids within 48 h. These MSC spheroids have been shown to have enhanced stemness, anti-inflammatory, and immunomodulatory functions, as revealed by the increased expression of stem cell markers (Oct4, Sox2, and Nanog), anti-inflammatory (IL-10, TSG6, and IDO), and immunomodulatory molecules (HGF, VEGF, CXCR4) both at mRNA and protein expression levels. Furthermore, these MSC spheroids demonstrated an increased palliative effect on glycemic control in a multiple low-dose streptozotocin-induced diabetes model compared with the same number of MSC single cell suspensions. Taken together, this study presents a new method to produce uniform-sized MSC spheroids with enhanced anti-inflammatory and immunomodulatory functions in vitro and in vivo.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2021.03.026DOI Listing
May 2021

Bioorthogonally surface-edited extracellular vesicles based on metabolic glycoengineering for CD44-mediated targeting of inflammatory diseases.

J Extracell Vesicles 2021 03 12;10(5):e12077. Epub 2021 Mar 12.

School of Chemical Engineering Sungkyunkwan University Suwon Republic of Korea.

Extracellular vesicles (EVs) are essential mediators in intercellular communication that have emerged as natural therapeutic nanomedicines for the treatment of intractable diseases. Their therapeutic applications, however, have been limited by unpredictable in vivo biodistribution after systemic administration. To control the in vivo fate of EVs, their surfaces should be properly edited, depending on the target site of action. Herein, based on bioorthogonal copper-free click chemistry (BCC), surface-edited EVs were prepared by using metabolically glycoengineered cells. First, the exogenous azide group was generated on the cellular surface through metabolic glycoengineering (MGE) using the precursor. Next, PEGylated hyaluronic acid, capable of binding specifically to the CD44-expressing cells, was labelled as the representative targeting moiety onto the cell surface by BCC. The surface-edited EVs effectively accumulated into the target tissues of the animal models with rheumatoid arthritis and tumour, primarily owing to prolonged circulation in the bloodstream and the active targeting mechanism. Overall, these results suggest that BCC combined with MGE is highly useful as a simple and safe approach for the surface modification of EVs to modulate their in vivo fate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jev2.12077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953464PMC
March 2021

Accuracy of noninvasive continuous arterial pressure monitoring using ClearSight during one-lung ventilation.

Medicine (Baltimore) 2021 Mar;100(11):e25152

Department of Anesthesiology and Pain Medicine, College of Medicine, Kyung Hee University, Seoul, Korea.

Abstract: Noninvasive continuous arterial pressure monitoring may be clinically useful in patients who require continuous blood pressure monitoring in situations where arterial catheter placement is limited. Many previous studies on the accuracy of the noninvasive continuous blood pressure monitoring method reported various results. However, there is no research on the effectiveness of noninvasive arterial pressure monitoring during one-lung ventilation. The purpose of this study was to compare arterial blood pressure obtained through invasive method and noninvasive method by using ClearSight during one-lung ventilation.In this retrospective observational study, a total of 26 patients undergoing one-lung ventilation for thoracic surgery at a single institution between March and July 2019 were recruited. All patients in this study were cannulated on their radial artery to measure continuously invasive blood pressures and applied ClearSight on the ipsilateral side of the cannulated arm. We compared and analyzed the agreement and trendability of blood pressure recorded with invasive and noninvasive methods during one-lung ventilation.Blood pressure and pulse rate showed a narrower limit of agreement with a percentage error value of around 30%. In addition, the tracking ability of each measurement could be determined by the concordance rate, all of which were below acceptable limits (92%).In noninvasive arterial blood pressure monitoring using ClearSight, mean blood pressure and pulse rate show acceptable agreement with the invasive method.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000025152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982160PMC
March 2021

Bending Behavior and Directed Self-Assembly of Rod-Coil Block Copolymers.

ACS Appl Mater Interfaces 2021 Mar 19;13(8):10437-10445. Epub 2021 Feb 19.

Department of Materials Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.

The formation of zigzags, chevrons, Y-junctions, and line segments is demonstrated in thin films formed from cylindrical morphology silicon-containing conformationally asymmetric rod-coil diblock copolymers and triblock terpolymers under solvent annealing. Directed self-assembly of the block copolymers within trenches yields well-ordered cylindrical microdomains oriented either parallel or transverse to the sidewalls depending on the chemical functionalization of the sidewalls, and the location and structure of concentric bends in the cylinders is determined by the shape of the trenches. The innate etching contrast, the spontaneous sharp bends and junctions, and the range of demonstrated periodicity and line/space ratios make these conformationally asymmetric rod-coil polymers attractive for nanoscale pattern generation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.0c22177DOI Listing
March 2021

GORI, encoding the WD40 domain protein, is required for pollen tube germination and elongation in rice.

Plant J 2021 03 21;105(6):1645-1664. Epub 2021 Jan 21.

Graduate School of Biotechnology and Crop Biotech Institute, Kyung Hee University, Yongin, 17104, Republic of Korea.

Successful delivery of sperm cells to the embryo sac in higher plants is mediated by pollen tube growth. The molecular mechanisms underlying pollen germination and tube growth in crop plants remain rather unclear, although these mechanisms are crucial to plant reproduction and seed formation. By screening pollen-specific gene mutants in rice (Oryza sativa), we identified a T-DNA insertional mutant of Germinating modulator of rice pollen (GORI) that showed a one-to-one segregation ratio for wild type (WT) to heterozygous. GORI encodes a seven-WD40-motif protein that is homologous to JINGUBANG/REN4 in Arabidopsis. GORI is specifically expressed in rice pollen, and its protein is localized in the nucleus, cytosol and plasma membrane. Furthermore, a homozygous mutant, gori-2, created through CRISPR-Cas9 clearly exhibited male sterility with disruption of pollen tube germination and elongation. The germinated pollen tube of gori-2 exhibited decreased actin filaments and altered pectin distribution. Transcriptome analysis revealed that 852 pollen-specific genes were downregulated in gori-2 compared with the WT, and Gene Ontology enrichment analysis indicated that these genes are strongly associated with cell wall modification and clathrin coat assembly. Based on the molecular features of GORI, phenotypical observation of the gori mutant and its interaction with endocytic proteins and Rac GTPase, we propose that GORI plays key roles in forming endo-/exocytosis complexes that could mediate pollen tube growth in rice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tpj.15139DOI Listing
March 2021

Machine Learning Predictions of Block Copolymer Self-Assembly.

Adv Mater 2020 Dec 18;32(52):e2005713. Epub 2020 Nov 18.

Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

Directed self-assembly of block copolymers is a key enabler for nanofabrication of devices with sub-10 nm feature sizes, allowing patterning far below the resolution limit of conventional photolithography. Among all the process steps involved in block copolymer self-assembly, solvent annealing plays a dominant role in determining the film morphology and pattern quality, yet the interplay of the multiple parameters during solvent annealing, including the initial thickness, swelling, time, and solvent ratio, makes it difficult to predict and control the resultant self-assembled pattern. Here, machine learning tools are applied to analyze the solvent annealing process and predict the effect of process parameters on morphology and defectivity. Two neural networks are constructed and trained, yielding accurate prediction of the final morphology in agreement with experimental data. A ridge regression model is constructed to identify the critical parameters that determine the quality of line/space patterns. These results illustrate the potential of machine learning to inform nanomanufacturing processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adma.202005713DOI Listing
December 2020

Blocking of the IL-33/ST2 Signaling Axis by a Single-Chain Antibody Variable Fragment (scFv) Specific to IL-33 with a Defined Epitope.

Int J Mol Sci 2020 Sep 22;21(18). Epub 2020 Sep 22.

Department of Biological Sciences, Sungkyunkwan University, Suwon 16419, Korea.

Interleukin 33 (IL-33) is an IL-1 family cytokine that plays a central role in immune system by regulating and initiating inflammatory responses. The binding of IL-33 to the suppressor of tumorigenicity 2 (ST2) receptor induces mitogen-activated protein kinases (MAPK) and nuclear factor κB (NF-κB) pathways, thereby leading to inflammatory cytokines production in type 2 helper T cells and type 2 innate lymphoid cells. To develop an antibody specific to IL-33 with a defined epitope, we characterized a single-chain antibody variable fragments (scFvs) clone specific to IL-33, C2_2E12, which was selected from a human synthetic library of scFvs using phage display. Affinity () of C2_2E12 was determined to be 38 nM using enzyme-linked immunosorbent assay. C2_2E12 did not show cross-reactivity toward other interleukin cytokines, including closely related IL-1 family cytokines and unrelated proteins. Mutational scanning analysis revealed that the epitope of IL-33 consisted of residues 149-158 with key residues being L150 and K151 of IL-33. Structural modeling suggested that L150 and K151 residues are important for the interaction of IL-33 with C2_2E12, implicating that C2_2E12 could block the binding of ST2 to IL-33. Pull-down and in-cell assays supported that C2_2E12 can inhibit the IL-33/ST2 signaling axis. These results suggest that the scFv clone characterized here can function as a neutralizing antibody.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21186953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554688PMC
September 2020

ClpL is a functionally active tetradecameric AAA+ chaperone, distinct from hexameric/dodecameric ones.

FASEB J 2020 11 10;34(11):14353-14370. Epub 2020 Sep 10.

Department of Biological Sciences, Sungkyunkwan University, Suwon, Korea.

AAA+ (ATPases associated with diverse cellular activities) chaperones are involved in a plethora of cellular activities to ensure protein homeostasis. The function of AAA+ chaperones is mostly modulated by their hexameric/dodecameric quaternary structures. Here we report the structural and biochemical characterizations of a tetradecameric AAA+ chaperone, ClpL from Streptococcus pneumoniae. ClpL exists as a tetradecamer in solution in the presence of ATP. The cryo-EM structure of ClpL at 4.5 Å resolution reveals a striking tetradecameric arrangement. Solution structures of ClpL derived from small-angle X-ray scattering data suggest that the tetradecameric ClpL could assume a spiral conformation found in active hexameric/dodecameric AAA+ chaperone structures. Vertical positioning of the middle domain accounts for the head-to-head arrangement of two heptameric rings. Biochemical activity assays with site-directed mutagenesis confirmed the critical roles of residues both in the integrity of the tetradecameric arrangement and activities of ClpL. Non-conserved Q321 and R670 are crucial in the heptameric ring assembly of ClpL. These results establish that ClpL is a functionally active tetradecamer, clearly distinct from hexameric/dodecameric AAA+ chaperones.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1096/fj.202000843RDOI Listing
November 2020

Deep learning-based automated detection algorithm for active pulmonary tuberculosis on chest radiographs: diagnostic performance in systematic screening of asymptomatic individuals.

Eur Radiol 2021 Feb 28;31(2):1069-1080. Epub 2020 Aug 28.

Department of Radiology, Seoul National University College of Medicine, Seoul, South Korea.

Objectives: Performance of deep learning-based automated detection (DLAD) algorithms in systematic screening for active pulmonary tuberculosis is unknown. We aimed to validate DLAD algorithm for detection of active pulmonary tuberculosis and any radiologically identifiable relevant abnormality on chest radiographs (CRs) in this setting.

Methods: We performed out-of-sample testing of a pre-trained DLAD algorithm, using CRs from 19.686 asymptomatic individuals (ages, 21.3 ± 1.9 years) as part of systematic screening for tuberculosis between January 2013 and July 2018. Area under the receiver operating characteristic curves (AUC) for diagnosis of tuberculosis and any relevant abnormalities were measured. Accuracy measures including sensitivities, specificities, positive predictive values (PPVs), and negative predictive values (NPVs) were calculated at pre-defined operating thresholds (high sensitivity threshold, 0.16; high specificity threshold, 0.46).

Results: All five CRs from four individuals with active pulmonary tuberculosis were correctly classified as having abnormal findings by DLAD with specificities of 0.959 and 0.997, PPVs of 0.006 and 0.068, and NPVs of both 1.000 at high sensitivity and high specificity thresholds, respectively. With high specificity thresholds, DLAD showed comparable diagnostic measures with the pooled radiologists (p values > 0.05). For the radiologically identifiable relevant abnormality (n = 28), DLAD showed an AUC value of 0.967 (95% confidence interval, 0.938-0.996) with sensitivities of 0.821 and 0.679, specificities of 0.960 and 0.997, PPVs of 0.028 and 0.257, and NPVs of both 0.999 at high sensitivity and high specificity thresholds, respectively.

Conclusions: In systematic screening for tuberculosis in a low-prevalence setting, DLAD algorithm demonstrated excellent diagnostic performance, comparable with the radiologists in the detection of active pulmonary tuberculosis.

Key Points: • Deep learning-based automated detection algorithm detected all chest radiographs with active pulmonary tuberculosis with high specificities and negative predictive values in systematic screening. • Deep learning-based automated detection algorithm had comparable diagnostic measures with the radiologists for detection of active pulmonary tuberculosis on chest radiographs. • For the detection of radiologically identifiable relevant abnormalities on chest radiographs, deep learning-based automated detection algorithm showed excellent diagnostic performance in systematic screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-020-07219-4DOI Listing
February 2021

Ectopic Expression of OsPYL/RCAR7, an ABA Receptor Having Low Signaling Activity, Improves Drought Tolerance without Growth Defects in Rice.

Int J Mol Sci 2020 Jun 11;21(11). Epub 2020 Jun 11.

Metabolic Engineering Division, National Institute of Agricultural Sciences, RDA, Jeonju, Jeollabuk-do 54874, Korea.

Overexpression of abscisic acid (ABA) receptors has been reported to enhance drought tolerance, but also to cause stunted growth and decreased crop yield. Here, we constructed transgenic rice for all monomeric ABA receptors and observed that only transgenic rice over-expressing showed similar phenotype with wild type, without total yield loss when grown under normal growth condition in a paddy field. Even though transgenic rice over-expressing / showed neither an ABA-sensitivity nor an osmotic stress tolerance in plate assay, it showed drought tolerance. We investigated the ABA-dependent interaction with OsPP2CAs and ABA signaling induction by OsPYL/RCAR7. In yeast two hybrid assay, OsPYL/RCAR7 required critically higher ABA concentrations to interact with OsPP2CAs than other ABA receptors, and co-immunoprecipitation assay showed strong interaction under ABA treatment. When ABA-responsive signaling activity was monitored using a transient expression system in rice protoplasts, OsPYL/RCAR7 had the lowest ABA-responsive signaling activity as compared with other ABA receptors. OsPYL/RCAR7 also showed weak suppression of phosphatase activity as compared with other ABA receptors in vitro. Transcriptome analysis of transgenic rice over-expressing suggested that only a few genes were induced similar to control under without exogenous ABA, but a large number of genes was induced under ABA treatment compared with control. We conclude that OsPYL/RCAR7 is a novel functional ABA receptor that has low ABA signaling activity and exhibits high ABA dependence. These results lay the foundation for a new strategy to improve drought stress tolerance without compromising crop growth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21114163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312952PMC
June 2020

Atomic structures determined from digitally defined nanocrystalline regions.

IUCrJ 2020 May 10;7(Pt 3):490-499. Epub 2020 Apr 10.

Department of Chemistry and Biochemistry, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.

Nanocrystallography has transformed our ability to interrogate the atomic structures of proteins, peptides, organic molecules and materials. By probing atomic level details in ordered sub-10 nm regions of nanocrystals, scanning nanobeam electron diffraction extends the reach of nanocrystallography and in principle obviates the need for diffraction from large portions of one or more crystals. Scanning nanobeam electron diffraction is now applied to determine atomic structures from digitally defined regions of beam-sensitive peptide nanocrystals. Using a direct electron detector, thousands of sparse diffraction patterns over multiple orientations of a given crystal are recorded. Each pattern is assigned to a specific location on a single nanocrystal with axial, lateral and angular coordinates. This approach yields a collection of patterns that represent a tilt series across an angular wedge of reciprocal space: a scanning nanobeam diffraction tomogram. Using this diffraction tomogram, intensities can be digitally extracted from any desired region of a scan in real or diffraction space, exclusive of all other scanned points. Intensities from multiple regions of a crystal or from multiple crystals can be merged to increase data completeness and mitigate missing wedges. It is demonstrated that merged intensities from digitally defined regions of two crystals of a segment from the OsPYL/RCAR5 protein produce fragment-based solutions that can be refined to atomic resolution, analogous to structures determined by selected-area electron diffraction. In allowing atomic structures to now be determined from digitally outlined regions of a nanocrystal, scanning nanobeam diffraction tomography breaks new ground in nanocrystallography.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1107/S2052252520004030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201287PMC
May 2020

Vertical Lamellae Formed by Two-Step Annealing of a Rod-Coil Liquid Crystalline Block Copolymer Thin Film.

ACS Nano 2020 Apr 23;14(4):4289-4297. Epub 2020 Mar 23.

Department of Materials Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.

Silicon-containing block copolymer thin films with high interaction parameter and etch contrast are ideal candidates to generate robust nanotemplates for advanced nanofabrication, but they typically form in-plane oriented microdomains as a result of the dissimilar surface energies of the blocks. Here, we describe a two-step annealing method to produce vertically aligned lamellar structures in thin film of a silicon-containing rod-coil thermotropic liquid crystalline block copolymer. The rod-coil block copolymer with the volume fraction of the Si-containing block of 0.22 presents an asymmetrical lamellar structure in which the rod block forms a hexatic columnar nematic liquid crystalline phase. A solvent vapor annealing step first produces well-ordered in-plane cylinders of the Si-containing block, then a subsequent thermal annealing promotes the phase transition from in-plane cylinders to vertical lamellae. The pathways of the order-order transition were examined by microscopy and using grazing incidence small-angle X-ray scattering and wide-angle X-ray scattering.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.9b09702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309319PMC
April 2020

Heterogeneous integration of single-crystalline complex-oxide membranes.

Nature 2020 02 5;578(7793):75-81. Epub 2020 Feb 5.

Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

Complex-oxide materials exhibit a vast range of functional properties desirable for next-generation electronic, spintronic, magnetoelectric, neuromorphic, and energy conversion storage devices. Their physical functionalities can be coupled by stacking layers of such materials to create heterostructures and can be further boosted by applying strain. The predominant method for heterogeneous integration and application of strain has been through heteroepitaxy, which drastically limits the possible material combinations and the ability to integrate complex oxides with mature semiconductor technologies. Moreover, key physical properties of complex-oxide thin films, such as piezoelectricity and magnetostriction, are severely reduced by the substrate clamping effect. Here we demonstrate a universal mechanical exfoliation method of producing freestanding single-crystalline membranes made from a wide range of complex-oxide materials including perovskite, spinel and garnet crystal structures with varying crystallographic orientations. In addition, we create artificial heterostructures and hybridize their physical properties by directly stacking such freestanding membranes with different crystal structures and orientations, which is not possible using conventional methods. Our results establish a platform for stacking and coupling three-dimensional structures, akin to two-dimensional material-based heterostructures, for enhancing device functionalities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-020-1939-zDOI Listing
February 2020

Comparison of papanicolaou smear and human papillomavirus (HPV) test as cervical screening tools: can we rely on HPV test alone as a screening method? An 11-year retrospective experience at a single institution.

J Pathol Transl Med 2020 Jan 15;54(1):112-118. Epub 2020 Jan 15.

Department of Pathology, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea.

Background: The decrease in incidence of cervical dysplasia and carcinoma has not been as dramatic as expected with the development of improved research tools and test methods. The human papillomavirus (HPV) test alone has been suggested for screening in some countries. The National Cancer Screening Project in Korea has applied Papanicolaou smears (Pap smears) as the screening method for cervical dysplasia and carcinoma. We evaluated the value of Pap smear and HPV testing as diagnostic screening tools in a single institution.

Methods: Patients co-tested with HPV test and Pap smear simultaneously or within one month of each other were included in this study. Patients with only punch biopsy results were excluded because of sampling errors. A total of 999 cases were included, and the collected reports encompassed results of smear cytology, HPV subtypes, and histologic examinations.

Results: Sensitivity and specificity of detecting high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC) were higher for Pap smears than for HPV tests (sensitivity, 97.14%; specificity, 85.58% for Pap smears; sensitivity, 88.32%; specificity, 54.92% for HPV tests). HPV tests and Pap smears did not differ greatly in detection of low-grade squamous intraepithelial lesion (85.35% for HPV test, 80.31% for Pap smears). When atypical glandular cells were noted on Pap smears, the likelihood for histologic diagnosis of adenocarcinoma following Pap smear was higher than that of high-risk HPV test results (18.8 and 1.53, respectively).

Conclusions: Pap smears were more useful than HPV tests in the diagnosis of HSIL, SCC, and glandular lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4132/jptm.2019.11.29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986973PMC
January 2020

Selection and functional identification of a synthetic partial ABA agonist, S7.

Sci Rep 2020 01 8;10(1). Epub 2020 Jan 8.

Metabolic Engineering Division, Department of Agricultural Biotechnology, National Institute of Agricultural Sciences, RDA, Jeonju, Jeollabuk-do, 54874, Republic of Korea.

The stress hormone abscisic acid (ABA) helps plants to survive under abiotic stresses; however, its use as an agrochemical is limited by its chemical instability and expense. Here, we report the development of an in vivo screening system to isolate chemicals able to induce ABA signalling responses in rice (Oryza sativa) protoplasts. This system consists of an ABA-hypersensitive synthetic promoter containing ABRE and DRE motifs driving a luciferase reporter gene. After efficiently transfecting rice protoplasts with this construct, we screened chemicals library with a similar molecular weight and chemical structure to ABA and identified one chemical, S7, that induced ABA signalling by mediating interactions between the group I and II OsPYL receptors and certain OsPP2CAs in a yeast two-hybrid assay. In an in vitro pulldown assay, S7 was found to mediate a weak interaction between OsPYL5/8 and various OsPP2CAs. S7 treatments did not affect seedling growth or seed germination, but could reduce water loss. Rice seedlings treated with S7 exhibited transcriptome profiles that partially overlapped those treated with ABA. Taken together, we concluded that S7 is a new partial ABA agonist, which has potential use in future dissections of ABA signalling and as an agrochemical.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-56343-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949257PMC
January 2020

Pharmacological Stimulation of Nurr1 Promotes Cell Cycle Progression in Adult Hippocampal Neural Stem Cells.

Int J Mol Sci 2019 Dec 18;21(1). Epub 2019 Dec 18.

Department of Core Research Laboratory, Medical Science Research Institute, Kyung Hee University Hospital at Gangdong, Seoul 134-727, Korea.

Nuclear receptor related-1 (Nurr1) protein performs a crucial role in hippocampal neural stem cell (hNSC) development as well as cognitive functions. We previously demonstrated that the pharmacological stimulation of Nurr1 by amodiaquine (AQ) promotes spatial memory by enhancing adult hippocampal neurogenesis. However, the role of Nurr1 in the cell cycle regulation of the adult hippocampus has not been investigated. This study aimed to examine changes in the cell cycle-related molecules involved in adult hippocampal neurogenesis induced by Nurr1 pharmacological stimulation. Fluorescence-activated cell sorting (FACS) analysis showed that AQ improved the progression of cell cycle from G/G to S phase in a dose-dependent manner, and MEK1 or PI3K inhibitors attenuated this progression. In addition, AQ treatment increased the expression of cell proliferation markers MCM5 and PCNA, and transcription factor E2F1. Furthermore, pharmacological stimulation of Nurr1 by AQ increased the expression levels of positive cell cycle regulators such as cyclin A and cyclin-dependent kinases (CDK) 2. In contrast, levels of CDK inhibitors p27 and p57 were reduced upon treatment with AQ. Similar to the in vitro results, RT-qPCR analysis of AQ-administered mice brains revealed an increase in the levels of markers of cell cycle progression, PCNA, MCM5, and Cdc25a. Finally, AQ administration resulted in decreased p27 and increased CDK2 levels in the dentate gyrus of the mouse hippocampus, as quantified immunohistochemically. Our results demonstrate that the pharmacological stimulation of Nurr1 in adult hNSCs by AQ promotes the cell cycle by modulating cell cycle-related molecules.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21010004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982043PMC
December 2019

Genome-Wide Study Updates in the International Genetics and Translational Research in Transplantation Network (iGeneTRAiN).

Front Genet 2019 15;10:1084. Epub 2019 Nov 15.

Division of Transplantation Department of Surgery, University of Pennsylvania, Philadelphia, PA, United States.

The prevalence of end-stage renal disease (ESRD) and the number of kidney transplants performed continues to rise every year, straining the procurement of deceased and living kidney allografts and health systems. Genome-wide genotyping and sequencing of diseased populations have uncovered genetic contributors in substantial proportions of ESRD patients. A number of these discoveries are beginning to be utilized in risk stratification and clinical management of patients. Specifically, genetics can provide insight into the primary cause of chronic kidney disease (CKD), the risk of progression to ESRD, and post-transplant outcomes, including various forms of allograft rejection. The International Genetics & Translational Research in Transplantation Network (iGeneTRAiN), is a multi-site consortium that encompasses >45 genetic studies with genome-wide genotyping from over 51,000 transplant samples, including genome-wide data from >30 kidney transplant cohorts (n = 28,015). iGeneTRAiN is statistically powered to capture both rare and common genetic contributions to ESRD and post-transplant outcomes. The primary cause of ESRD is often difficult to ascertain, especially where formal biopsy diagnosis is not performed, and is unavailable in ∼2% to >20% of kidney transplant recipients in iGeneTRAiN studies. We overview our current copy number variant (CNV) screening approaches from genome-wide genotyping datasets in iGeneTRAiN, in attempts to discover and validate genetic contributors to CKD and ESRD. Greater aggregation and analyses of well phenotyped patients with genome-wide datasets will undoubtedly yield insights into the underlying pathophysiological mechanisms of CKD, leading the way to improved diagnostic precision in nephrology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2019.01084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6873800PMC
November 2019

Extracorporeal membrane oxygenation for takotsubo cardiomyopathy that developed after mitral valve replacement.

Acute Crit Care 2020 Feb 12;35(1):51-55. Epub 2019 Apr 12.

Department of Thoracic and Cardiovascular Surgery, Kyung Hee University School of Medicine, Seoul, Korea.

Takotsubo cardiomyopathy is a transient systolic and diastolic left ventricular dysfunction that presents several wall-motion abnormalities, while the coronary artery shows normal findings. Because patients with Takotsubo cardiomyopathy present with symptoms similar to acute coronary syndrome, the initial diagnosis and treatment are often difficult. The condition is often precipitated by acute emotional or physical stress and frequently occurs in postmenopausal women. Takotsubo cardiomyopathy may also occur in the perioperative period after cardiac and noncardiac surgery; surgery-associated Takotsubo cardiomyopathy reportedly accounts for 3%-23% of all cases. Of these perioperative cases, cardiothoracic surgery accounted for 16%. However, few cases have been reported in patients undergoing cardiac surgery and managed with extracorporeal membrane oxygenation (ECMO). We report a case of Takotsubo cardiomyopathy managed with ECMO in a patient in the intensive care unit after mitral valve replacement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4266/acc.2018.00304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056952PMC
February 2020

Engineering of human brain organoids with a functional vascular-like system.

Nat Methods 2019 11 7;16(11):1169-1175. Epub 2019 Oct 7.

Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA.

Human cortical organoids (hCOs), derived from human embryonic stem cells (hESCs), provide a platform to study human brain development and diseases in complex three-dimensional tissue. However, current hCOs lack microvasculature, resulting in limited oxygen and nutrient delivery to the inner-most parts of hCOs. We engineered hESCs to ectopically express human ETS variant 2 (ETV2). ETV2-expressing cells in hCOs contributed to forming a complex vascular-like network in hCOs. Importantly, the presence of vasculature-like structures resulted in enhanced functional maturation of organoids. We found that vascularized hCOs (vhCOs) acquired several blood-brain barrier characteristics, including an increase in the expression of tight junctions, nutrient transporters and trans-endothelial electrical resistance. Finally, ETV2-induced endothelium supported the formation of perfused blood vessels in vivo. These vhCOs form vasculature-like structures that resemble the vasculature in early prenatal brain, and they present a robust model to study brain disease in vitro.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41592-019-0586-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918722PMC
November 2019

Differential Regulation of in Sertoli Cells of the Testes during Postnatal Development.

Cells 2019 09 27;8(10). Epub 2019 Sep 27.

Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea.

Spermatogenesis is a process by which haploid cells differentiate from germ cells in the seminiferous tubules of the testes. TLE3, a transcriptional co-regulator that interacts with DNA-binding factors, plays a role in the development of somatic cells. However, no studies have shown its role during germ cell development in the testes. Here, we examined TLE3 expression in the testes during spermatogenesis. TLE3 was highly expressed in mouse testes and was dynamically regulated in different cell types of the seminiferous tubules, spermatogonia, spermatids, and Sertoli cells, but not in the spermatocytes. Interestingly, TLE3 was not detected in Sertoli cells on postnatal day 7 (P7) but was expressed from P10 onward. The microarray analysis showed that the expression of numerous genes changed upon knockdown in a Sertoli cell line TM4. These include 1597 up-regulated genes and 1452 down-regulated genes in -knockdown TM4 cells. Ingenuity Pathway Analysis (IPA) showed that three factors were up-regulated and two genes were down-regulated upon knockdown in TM4 cells. The abnormal expression of the three factors is associated with cellular malfunctions such as abnormal differentiation and Sertoli cell formation. Thus, is differentially expressed in Sertoli cells and plays a crucial role in regulating cell-specific genes involved in the differentiation and formation of Sertoli cells during testicular development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cells8101156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848928PMC
September 2019
-->