Mutant p53 succumbs to starvation

While the wild type form of p53 possesses strong tumor-suppressive activities, the p53 proteins that are commonly mutated in cancer often endow more malignant properties to the cancers they inhabit. There are several lines of evidence supporting such oncogenic gain of function of mutant p53. Compared with p53-null mice, knock-in mice harboring mutant p53 proteins display different and more metastatic tumor spectra. Such mutant proteins are frequently present at far higher levels than the wild-type protein in tumors; in fact, the p53 protein present in the knock-in mice accumulates in tumors despite being inherently unstable in normal tissues,3 suggesting that stabilization of mutant p53 protein is required for its oncogenic activity. Consistently, knockdown of mutant p53 protein in human cancer cell lines leads to reduced cell proliferation, invasion, motility, tumorigenicity and resistance to anticancer drugs. Since epidemiological studies indicate that high levels of mutant p53 proteins correlate with tumor aggressiveness and poorer outcomes, it is important to understand how mutant p53 is stabilized in tumors and how it can be eliminated. This article proposes questions brought up by earlier studies on mutant p53 proteins

Titanium oxide Films Prepared by Sputtering, Sol Gel and Dip Coating Methods for Photovoltaic Application

AbstractDye-sensitized solar cells (DSCs) without using transparent conducting oxides (TCO) electrode can be produced at much lower cost with a flexible structure. A new type of DSCs using flexible stainless steel mesh sheets based electrode is reported in this research. The working electrode of DSCs is processed with conductive and flexible stainless mesh coated with metal oxides (TiO2) layer either by sputtering, sol gel or dip coating methods. Structures of the TCO-less DSCs sample is a stainless mesh for working electrode/dye sensitized TiO2 layer/liquid type electrolyte with polymer film/Pt doped Ti plate for counter electrode. The metal oxide coated stainless mesh sample showed higher photo-current conversion efficiency in general. The best cell performance in this experiment showed the efficiency of 3.11% (Voc = 0.58V, Jsc = 11.98mA/cm2, ff = 0.45)

Secondary Science Teachers' Views about Purposes of Practical Works in School Science

The purpose of this paper was to examine views of secondary school science teachers about purposes to use practical works in school science. The instrument to survey consisted eighteen items, which were categorized into four components as follows: 'Scientific inquiry', 'Scientific knowledge', 'Science-related attitude', and 'STS (science-technology-society)'. Subjects were 152 secondary school science teachers (male 70 and female 82; middle school 50 and high school 102), who are teaching in 42 schools of 8 provinces. On the survey, science teachers were asked to answer on 5-point Lickert scale (from 1 to 5) how they thought of using practical works on purposes with domains of science objectives in school. They had positive views about using practical works for improving scientific inquiry process skills, science-related attitudes, and perceptions about STS literacy, and acquiring scientific knowledge. They would have the most willingness of using practical works for 'Scientific Inquiry' among domains of science objectives in school

MiR-31/SDHA Axis Regulates Reprogramming Efficiency through Mitochondrial Metabolism

Metabolism is remodeled when somatic cells are reprogrammed into induced pluripotent stem cells (iPSCs), but the majority of iPSCs are not fully reprogrammed. In a shift essential for reprogramming, iPSCs use less mitochondrial respiration but increased anaerobic glycolysis for bioenergetics. We found that microRNA 31 (miR-31) suppressed succinate dehydrogenase complex subunit A (SDHA) expression, vital for mitochondrial electron transport chain (ETC) complex II. MiR-31 overexpression in partially reprogrammed iPSCs lowered SDHA expression levels and oxygen consumption rates to that of fully reprogrammed iPSCs, but did not increase the proportion of fully reprogrammed TRA1-60(+) cells in colonies unless miR-31 was co-transduced with Yamanaka factors, which resulted in a 2.7-fold increase in full reprogramming. Thus switching from mitochondrial respiration to glycolytic metabolism through regulation of the miR-31/SDHA axis is critical for lowering the reprogramming threshold. This is supportive of multi-stage reprogramming whereby metabolic remodeling is fundamental

Metastatic Lymph Node Ratio of Central Neck Compartment Has Predictive Values for Locoregional Recurrence in Papillary Thyroid Microcarcinoma

Objectives This study aimed to evaluate the significance of metastatic lymph node ratio (the ratio between the metastatic lymph node and the harvested lymph nodes; MLNR) in the central neck for the prediction of locoregional recurrence in patients with papillary thyroid microcarcinoma. Methods After reviewing medical records of papillary thyroid microcarcinoma patients who received total thyroidectomy with central neck node dissection, 573 consecutive adult patients were enrolled in this study, with a follow-up period of more than 36 months. Regarding the risk of recurrence, multivariate analyses were performed with the following variables; sex, age, multiplicity of the primary tumor, presence of pathological extrathyroidal extension, the level of postoperative stimulated serum thyroglobulin, the number of harvested lymph nodes, the number of lymph node metastasis and MLNR. Results The MLNR showed a predictive significance for the locoregional recurrence (P<0.05). Most recurrences were occurred in the lateral neck (n=12, 80%) with a median interval of 20 months. The lowest cutoff value of the MLNR for a meaningful separation of disease recurrence was 0.44 (hazard ratio, 8.86; 95% confidence interval, 1.49 to 52.58; P=0.001). Conclusion When the MLNR is higher than 0.44, there is an increased risk of locoregional recurrence mostly in the lateral neck. Therefore, MLNR of the central neck in a permanent or frozen biopsy may be helpful in decision making in the extent of thyroidectomy and/or the need for contralateral central neck lymph nodes dissection

Extracellular matrix cues regulate the differentiation of pluripotent stem cell-derived endothelial cells

The generation of endothelial cells (ECs) from human pluripotent stem cells (PSCs) has been a promising approach for treating cardiovascular diseases for several years. Human PSCs, particularly induced pluripotent stem cells (iPSCs), are an attractive source of ECs for cell therapy. Although there is a diversity of methods for endothelial cell differentiation using biochemical factors, such as small molecules and cytokines, the efficiency of EC production varies depending on the type and dose of biochemical factors. Moreover, the protocols in which most EC differentiation studies have been performed were in very unphysiological conditions that do not reflect the microenvironment of native tissue. The microenvironment surrounding stem cells exerts variable biochemical and biomechanical stimuli that can affect stem cell differentiation and behavior. The stiffness and components of the extracellular microenvironment are critical inducers of stem cell behavior and fate specification by sensing the extracellular matrix (ECM) cues, adjusting the cytoskeleton tension, and delivering external signals to the nucleus. Differentiation of stem cells into ECs using a cocktail of biochemical factors has been performed for decades. However, the effects of mechanical stimuli on endothelial cell differentiation remain poorly understood. This review provides an overview of the methods used to differentiate ECs from stem cells by chemical and mechanical stimuli. We also propose the possibility of a novel EC differentiation strategy using a synthetic and natural extracellular matrix

Quality of Life in Patients with Osteoporotic Vertebral Fractures

Study DesignA case-control study.PurposeTo examine several dimensions of health-related quality of life (HRQL) in postmenopausal women with osteoporotic vertebral fractures, compared with a control group.Overview of LiteratureOsteoporotic vertebral fractures are a major cause of morbidity among postmenopausal women. There have been many reports of a decrease in the quality of life in patients with osteoporotic vertebral fractures. However,few reports have analyzed which dimensions contribute to the decline in quality of life.MethodsOne thousand five hundred forty-five postmenopausal women aged 50 years and older from 17 study sites in nationwide hospitals were in enrolled in the study (between April 2008 and January 2009). HRQL was measured using the European Quality of Life 5 Domains (EQ-5D), and visual analogue scale (VAS).ResultsThe average VAS of the case group was 57.80, and that of the control group was 64.10 (p=0.001). All domains of the EQ-5D score were significantly worse in the case group (p=0.001). Among the case group, the average VAS of the 559 patients (45%) who were operated on was 56.8, and that of the remaining 680 patients (55%) who were treated conservatively was 58.6 (p=0.135). Among the case group, the averages of each EQ-5D domain of the 559 patients (45%) who were operated on were: 1.87 in mobility, 1.81 in self-care, 1.99 in usual activities, 2.11 in pain, and 1.62 in anxiety or depression. Those of the 680 patients (55%) who were treated conservatively were: 1.72 in mobility, 1.60 in self-care, 1.76 in usual activities, 1.98 in pain, and 1.57 in anxiety or depression. Except for the domain of anxiety or depression, scores for the other domains were all significantly worse in the patients who were operated on (p=0.001).ConclusionsHealth related quality of life in the patients with osteoporotic vertebral fractures was significantly worse in both the EQ-5D domains and VAS. Among the osteoporotic vertebral fracture patients, the patients who were operated on had a worse quality of life in EQ-5D