G protein-coupled receptor kinase 5 mediates Tazarotene-induced gene 1-induced growth suppression of human colon cancer cells

<p>Abstract</p> <p>Background</p> <p>Tazarotene-induced gene 1 (TIG1) is a retinoid-inducible type II tumour suppressor gene. The B isoform of TIG1 (TIG1B) inhibits growth and invasion of cancer cells. Expression of TIG1B is frequently downregulated in various cancer tissues; however, the expression and activities of the TIG1A isoform are yet to be reported. Therefore, this study investigated the effects of the TIG1A and TIG1B isoforms on cell growth and gene expression profiles using colon cancer cells.</p> <p>Methods</p> <p>TIG1A and TIG1B stable clones derived from HCT116 and SW620 colon cancer cells were established using the GeneSwitch system; TIG1 isoform expression was induced by mifepristone treatment. Cell growth was assessed using the WST-1 cell proliferation and colony formation assays. RNA interference was used to examine the TIG1 mediating changes in cell growth. Gene expression profiles were determined using microarray and validated using real-time polymerase chain reaction, and Western blot analyses.</p> <p>Results</p> <p>Both TIG1 isoforms were expressed at high levels in normal prostate and colon tissues and were downregulated in colon cancer cell lines. Both TIG1 isoforms significantly inhibited the growth of transiently transfected HCT116 cells and stably expressing TIG1A and TIG1B HCT116 and SW620 cells. Expression of 129 and 55 genes was altered upon induction of TIG1A and TIG1B expression, respectively, in stably expressing HCT116 cells. Of the genes analysed, 23 and 6 genes were upregulated and downregulated, respectively, in both TIG1A and TIG1B expressing cells. Upregulation of the G-protein-coupled receptor kinase 5 (GRK5) was confirmed using real-time polymerase chain reaction and Western blot analyses in both TIG1 stable cell lines. Silencing of TIG1A or GRK5 expression significantly decreased TIG1A-mediated cell growth suppression.</p> <p>Conclusions</p> <p>Expression of both TIG1 isoforms was observed in normal prostate and colon tissues and was downregulated in colon cancer cell lines. Both TIG1 isoforms suppressed cell growth and stimulated GRK5 expression in HCT116 and SW620 cells. Knockdown of GRK5 expression alleviated TIG1A-induced growth suppression of HCT116 cells, suggesting that GRK5 mediates cell growth suppression by TIG1A. Thus, TIG1 may participate in the downregulation of G-protein coupled signaling by upregulating GRK5 expression.</p

Age, Sex, and Socio-Economic Status Affect the Incidence of Pediatric Spinal Cord Injury: An Eleven-Year National Cohort Study

Few studies focus on pediatric spinal cord injury (SCI) and there is little information regarding the cause, anatomic level, and high risk population of SCI in children. This study aims to investigate the incidence and risk factors of pediatric SCI.A nationwide cohort of 8.7 million children aged<18 years in an 11-year period was analyzed for causes, age at injury, anatomic sites, disability, and familial socio-economic factors. Incidence rates and Cox regression analysis were conducted.<0.05).In the pediatric population, the overall SCI incidence rate is 5.99 per 100,000 person-years, with traumatic cervical SCI accounting for the majority. The incidence rate increases abruptly in male teenagers. Gender, age, and socio-economic status are independent risk factors that should be considered

Magnetotransport in an aluminum thin film on a GaAs substrate grown by molecular beam epitaxy

Magnetotransport measurements are performed on an aluminum thin film grown on a GaAs substrate. A crossover from electron- to hole-dominant transport can be inferred from both longitudinal resistivity and Hall resistivity with increasing the perpendicular magnetic field B. Also, phenomena of localization effects can be seen at low B. By analyzing the zero-field resistivity as a function of temperature T, we show the importance of surface scattering in such a nanoscale film

A T3 and T7 Recombinant Phage Acquires Efficient Adsorption and a Broader Host Range

It is usually thought that bacteriophage T7 is female specific, while phage T3 can propagate on male and female Escherichia coli. We found that the growth patterns of phages T7M and T3 do not match the above characteristics, instead showing strain dependent male exclusion. Furthermore, a T3/7 hybrid phage exhibits a broader host range relative to that of T3, T7, as well as T7M, and is able to overcome the male exclusion. The T7M sequence closely resembles that of T3. T3/7 is essentially T3 based, but a DNA fragment containing part of the tail fiber gene 17 is replaced by the T7 sequence. T3 displays inferior adsorption to strains tested herein compared to T7. The T3 and T7 recombinant phage carries altered tail fibers and acquires better adsorption efficiency than T3. How phages T3 and T7 recombine was previously unclear. This study is the first to show that recombination can occur accurately within only 8 base-pair homology, where four-way junction structures are identified. Genomic recombination models based on endonuclease I cleavages at equivalent and nonequivalent sites followed by strand annealing are proposed. Retention of pseudo-palindromes can increase recombination frequency for reviving under stress

The Potential Role of ORM2 in the Development of Colorectal Cancer

Colorectal cancer (CRC) is the third most common malignancy in the world. The risk of death is closely correlated to the stage of CRC at the time of primary diagnosis. Therefore, there is a compelling need for the identification of blood biomarkers that can enable early detection of CRC. We used a quantitative proteomic approach with isobaric labeling (iTRAQ) to examine changes in the plasma proteome of 10 patients with CRC compared to healthy volunteers. Enzyme-Linked Immunosorbnent Assay (ELISA) and Western blot were used for further validation. In our quantitative proteomics analysis, we detected 75 human plasma proteins with more than 95% confidence using iTRAQ labeling in conjunction with microQ-TOF MS. 9 up-regulated and 4 down-regulated proteins were observed in the CRC group. The ORM2 level in plasma was confirmed to be significantly elevated in patients suffering from CRC compared with the controls. ORM2 expression in CRC tissues was significantly increased compared with that in corresponding adjacent normal mucous tissues (P<0.001). ITRAQ together with Q-TOF/MS is a sensitive and reproducible technique of quantitative proteomics. Alteration in expression of ORM2 suggests that ORM2 could be used as a potential biomarker in the diagnosis of CRC

Effects of NFKB1 and NFKBIA Gene Polymorphisms on Susceptibility to Environmental Factors and the Clinicopathologic Development of Oral Cancer

encoding IkappaBalpha (IκBα) with both the susceptibility to develop OSCC and the clinicopathological characteristics of the tumors.<.05), compared with those patients CC homozygotes. 519 might be a predictive factor for the distal metastasis of OSCC in Taiwanese

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

The persistent shadow of the supermassive black hole of M 87

In April 2019, the Event Horizon Telescope (EHT) Collaboration reported the first-ever event-horizon-scale images of a black hole, resolving the central compact radio source in the giant elliptical galaxy M 87. These images reveal a ring with a southerly brightness distribution and a diameter of ∼42 μas, consistent with the predicted size and shape of a shadow produced by the gravitationally lensed emission around a supermassive black hole. These results were obtained as part of the April 2017 EHT observation campaign, using a global very long baseline interferometric radio array operating at a wavelength of 1.3 mm. Here, we present results based on the second EHT observing campaign, taking place in April 2018 with an improved array, wider frequency coverage, and increased bandwidth. In particular, the additional baselines provided by the Greenland telescope improved the coverage of the array. Multiyear EHT observations provide independent snapshots of the horizon-scale emission, allowing us to confirm the persistence, size, and shape of the black hole shadow, and constrain the intrinsic structural variability of the accretion flow. We have confirmed the presence of an asymmetric ring structure, brighter in the southwest, with a median diameter of 43.3−3.1+1.5 μas. The diameter of the 2018 ring is remarkably consistent with the diameter obtained from the previous 2017 observations. On the other hand, the position angle of the brightness asymmetry in 2018 is shifted by about 30° relative to 2017. The perennial persistence of the ring and its diameter robustly support the interpretation that the ring is formed by lensed emission surrounding a Kerr black hole with a mass ∼6.5 × 109 M⊙. The significant change in the ring brightness asymmetry implies a spin axis that is more consistent with the position angle of the large-scale jet

The persistent shadow of the supermassive black hole of M 87 I. Observations, calibration, imaging, and analysis

Please read abstract in article.https://www.aanda.org/PhysicsNon