Molecular Landscape of Induced Reprogramming: A Dissertation

Recent breakthroughs in creating induced pluripotent stem cells (iPS cells) provide alternative means to obtain embryonic stem (ES) cell-like cells without destroying embryos by introducing four reprogramming factors (Oct3/4, Sox2, and Klf4/c-Myc or Nanog/Lin28) into somatic cells. However, the molecular basis of reprogramming is largely unknown. To address this question, we employed microRNAs, small molecules, and conducted genome-wide RNAi screen, to investigate the regulatory mechanisms of reprogramming. First we showed that depleting miR-21 and miR-29a enhances reprogramming in mouse embryonic fibroblasts (MEFs). We also showed that p53 and ERK1/2 pathways are regulated by miR-21 and miR-29a and function in reprogramming. Second, we showed that computational chemical biology combined with genomic analysis can be used to identify small molecules regulating reprogramming. We discovered that the NSAID Nabumetone and the anti-cancer drug OHTM could replace Sox2 during reprogramming. Nabumetone could also replace c-Myc or Sox2 without compromising self-renewal and pluripotency of derived iPS cells. To identify the cell-fate determinants during reprogramming, we integrated a genome-wide RNAi screen with transcriptome analysis to dissect the molecular requirements in reprogramming. We found that extensive interactions of embryonic stem cell core circuitry regulators are established in mature iPS cells, including Utf1, Nr6a1, Tdgf1, Gsc, Fgf10, T, Chrd, Dppa3, Fgf17, Eomes, Foxa2. Remarkably, genes with non-differential change play the most critical roles in the transitions of reprogramming. Functional validation showed that some genes act as essential or barrier roles to reprogramming. We also identified several genes required for maintaining ES cell properties. Altogether, our results demonstrate the significance of miRNA function in regulating multiple signaling networks involved in reprogramming. And our work further advanced the reprogramming field by identifying several new key modulators

A Compact Dual-Band Circularly Polarized Antenna with Wide HPBWs for CNSS Applications

A compact dual-band circularly polarized antenna with wide half-power beamwidths (HPBWs) for compass navigation satellite system applications is proposed in this paper. The CP radiation is realized by arranging four compact dual-band inverted-F monopoles symmetrically to the center point, where the four monopoles are excited with a 90° phase offset through a compact sequential-phase feeding network. The compactness of the dual-band inverted-F monopole is realized by inserting two chip inductors in the horizontal portion of the monopole. The overall dimension of the antenna is only 0.211λ0 × 0.211λ0 × 0.057λ0, where λ0 is the corresponding free-space wavelength at 1.268 GHz. Experimental results show that the proposed antenna exhibits two overlapped impedance and axial ratio bandwidths of 50 MHz (1.236–1.286 GHz) and 40 MHz (1.532–1.572 GHz). Wide HPBWs of about 120°/125° and 121°/116° (XOZ/YOZ planes) at center frequencies (1.268, 1.561 GHz) of the CNSS-2 B3 and B1 bands are obtained, respectively. With these good performances, the antenna can be a good candidate for CNSS applications

The modulation of hypoxia-inducible factor-1α/plasminogen activator inhibitor-1 axis in human gingival fibroblasts stimulated with cyclosporine A

Background/PurposeThe prominent side effect of the immunosuppressive drug cyclosporine A (CsA) is gingival overgrowth. Hypoxia-inducible factor (HIF)-1α regulates a wide variety of profibrogenic genes, which are closely associated with tissue fibrosis. The aim of this study was to compare HIF-1α expression in normal gingival tissues and CsA-induced gingival overgrowth specimens and further explore the potential mechanisms that may lead to induction of HIF-1α expression.MethodsFifteen CsA-induced gingival overgrowth specimens and five normal gingival tissues were examined by immunohistochemistry. Western blot was used to investigate the effects of CsA on the expression of HIF-1α in cultured human gingival fibroblasts. The effects of CsA on plasminogen activator inhibitor (PAI)-1 expression were evaluated in environmental hypoxia.ResultsHIF-1α staining in gingival tissue was stronger in CsA-induced gingival overgrowth group than normal gingival group (p < 0.05). The expression of HIF-1α was significantly higher in CsA-induced gingival overgrowth specimens with higher levels of inflammatory infiltrates (p = 0.041). CsA was found to upregulate HIF-1α protein in a dose-dependent manner (p < 0.05). Hypoxia increased CsA-induced PAI-1 protein expression than normoxic conditions (p < 0.05).ConclusionThese results suggest that HIF-1α expression is significantly upregulated in CsA-induced gingival overgrowth specimens. The activation of HIF-1α may promote fibrogenesis by an increase of PAI-1 expression and a subsequent elevation of extracellular matrix production in gingival tissues

Semantic segmentation of remote sensing imagery for road extraction via joint angle prediction: comparisons to deep learning

Accurate road network information is required to study and analyze the relationship between land usage type and land subsidence, and road extraction from remote sensing images is an important data source for updating road networks. This task has been considered a significant semantic segmentation problem, given the many road extraction methods developed for remote sensing images in recent years. Although impressive results have been achieved by classifying each pixel in the remote sensing image using a semantic segmentation network, traditional semantic segmentation methods often lack clear constraints of road features. Consequently, the geometric features of the results might deviate from actual roads, leading to issues like road fractures, rough edges, inconsistent road widths, and more, which hinder their effectiveness in road updates. This paper proposes a novel road semantic segmentation algorithm for remote sensing images based on the joint road angle prediction. By incorporating the angle prediction module and the angle feature fusion module, constraints are added to the angle features of the road. Through the angle prediction and angle feature fusion, the information contained in the remote sensing images can be better utilized. The experimental results show that the proposed method outperforms existing semantic segmentation methods in both quantitative evaluation and visual effects. Furthermore, the extracted roads were consecutive with distinct edges, making them more suitable for mapping road updates

Terminalia catappa

High mortality and morbidity rates for hepatocellular carcinoma (HCC) in Taiwan primarily result from uncontrolled tumor metastasis. Previous studies have identified that Terminalia catappa leaf extracts (TCE) exert hepatoprotective, antioxidative, antiinflammatory, anticancer, and antimetastatic activities. However, the effects of TCE on HCC and the underlying molecular mechanisms of its activities have yet to be fully elucidated. The present study's findings demonstrate that TCE concentration dependently inhibits human HCC migration/invasion. Zymographic and western blot analyses revealed that TCE inhibited the activities and expression of matrix metalloproteinase-9 (MMP-9). Assessment of mRNA levels, using reverse transcriptase polymerase chain reaction (PCR) and real-time PCR, and promoter assays confirmed the inhibitory effects of TCE on MMP-9 expression in HCC cells. The inhibitory effects of TCE on MMP-9 proceeded by upregulating tissue inhibitor of metalloproteinase-1 (TIMP-1), as well as suppressing nuclear translocation and DNA binding activity of nuclear factor-kappa B (NF-κB) and activating protein-1 (AP-1) on the MMP-9 promoter in Huh7 cells. In conclusion, TCE inhibits MMP-9 expression and HCC cell metastasis and, thus, has potential use as a chemopreventive agent. Its inhibitory effects are associated with downregulation of the binding activities of the transcription factors NF-κB and AP-1

Epidemiology and Clinical Peculiarities of Norovirus and Rotavirus Infection in Hospitalized Young Children with Acute Diarrhea in Taiwan, 2009

Background/PurposeAcute diarrhea is one of the most common morbidities in pediatrics worldwide. We conducted a study to investigate the incidence of norovirus in young children hospitalized with acute diarrhea in Taiwan and its clinical peculiarity compared with rotavirus gastroenteritis.MethodsBetween January and December, 2009, patients younger than 5 years and admitted to hospital with acute diarrhea were randomly selected; and their stool samples were collected and tested for presence of rotavirus and norovirus by enzyme immunoassay and reverse transcription-polymerase chain reaction, respectively. The clinical manifestations and laboratory findings of the enrolled patients were analyzed.ResultsA total of 989 cases were enrolled with a mean age of 21.6 ± 13.7 months and a male proportion of 56.0%. Rotavirus and norovirus was detected in 20.2% and 14.6% of all patients, respectively. Genogroup II was the predominant strain of norovirus (80.6%). Children aged 6-36 months accounted for the majority of patients positive for rotavirus and norovirus (73.0% and 81.3%, respectively). The incidences of norovirus and rotavirus infection were higher during winter and early spring. Most patients with rotavirus and norovirus diarrhea experienced vomiting (74.9% vs. 74.8%, respectively) and fever (94.7% vs. 71.3%, respectively).ConclusionMost young diarrheal patients presenting with vomiting were likely to have norovirus or rotavirus infection. Patients with norovirus diarrhea experienced an absence of, or low-grade fever and longer duration of vomiting compared with those positive for rotavirus infection. A family history of current gastroenteritis may suggest the possibility of norovirus infection

Pityriasis lichenoid-like mycosis fungoides in a 9-year-old boy: A case report

No abstract availabl