siRNA Knockdown of Ribosomal Protein Gene RPL19 Abrogates the Aggressive Phenotype of Human Prostate Cancer

We provide novel functional data that posttranscriptional silencing of gene RPL19 using RNAi not only abrogates the malignant phenotype of PC-3M prostate cancer cells but is selective with respect to transcription and translation of other genes. Reducing RPL19 transcription modulates a subset of genes, evidenced by gene expression array analysis and Western blotting, but does not compromise cell proliferation or apoptosis in-vitro. However, growth of xenografted tumors containing the knocked-down RPL19 in-vivo is significantly reduced. Analysis of the modulated genes reveals induction of the non-malignant phenotype principally to involve perturbation of networks of transcription factors and cellular adhesion genes. The data provide evidence that extra-ribosomal regulatory functions of RPL19, beyond protein synthesis, are critical regulators of cellular phenotype. Targeting key members of affected networks identified by gene expression analysis raises the possibility of therapeutically stabilizing a benign phenotype generated by modulating the expression of an individual gene and thereafter constraining a malignant phenotype while leaving non-malignant tissues unaffected

Esophageal cancer presenting with atrial fibrillation: A case report

<p>Abstract</p> <p>Introduction</p> <p>Atrial fibrillation was previously reported in patients with esophageal cancer as a complication of total esophagectomy or photodynamic therapy. Here, we propose that atrial fibrillation may also be caused by external compression of the left atrium by esophageal cancer.</p> <p>Case presentation</p> <p>We present a 58-year-old man who developed atrial fibrillation with rapid ventricular rate in the emergency room while being evaluated for dysphagia and weight loss. Atrial fibrillation lasted less than 12 hours and did not recur. Echocardiogram did not reveal any structural heart disease. A 10-cm, ulcerated mid-esophageal mass was seen during esophagogastroscopy. Microscopic examination showed squamous cell carcinoma. Computed tomography of the chest revealed esophageal thickening compressing the left atrium.</p> <p>Conclusion</p> <p>External compression of the left atrium was previously reported to provoke atrial fibrillation. Similarly, esophageal cancer may precipitate atrial fibrillation by mechanical compression of the left atrium or pulmonary veins, triggering ectopic beats in susceptible patients.</p

High-pressure rheological analysis of CO2-induced melting point depression and viscosity reduction of poly(ε-caprolactone)

High-pressure rheology has been used to assess the effects of supercritical carbon dioxide (scCO2) on the melting point (Tm) and viscosity of poly (ε-caprolactone) (PCL) over a range of temperatures and pressures up to 300 bar over a wide range of shear rates. Plots of the storage and loss moduli against temperature show a significant shift of Tm to lower temperatures in the presence of CO2, indicating that the polymer crystals melt at temperatures much lower than the ambient pressure Tm. Furthermore, a significant decrease in the viscosity of two PCL grades with different molecular weight (Mn ~ 10 kDa and 80 kDa) was also detected upon increasing the CO2 pressure to 300 bar. Experimental viscosity data were fitted to the Carreau model to quantify the extent of the plasticising effects on the zero-shear viscosity and relaxation time under different conditions. Similar analyses were conducted under high-pressure nitrogen, to compare the effects obtained in the presence of a non-plasticising gas

Simultaneous ALS and SCA2 associated with an intermediate-length ATXN2 CAG-repeat expansion

Spinocerebellar ataxia type 2 (SCA2) and amyotrophic lateral sclerosis (ALS) share a common molecular basis: both are associated with CAG-repeat expansion of ATXN2 and TDP-43-positive neuronal cytoplasmic inclusions. To date, the two disorders are viewed as clinically distinct with ALS resulting from 30-33 CAG-repeats and SCA2 from >34 CAG-repeats. We describe a 67-year old with a 32 CAG-repeat expansion of ATXN2 who presented with simultaneous symptoms of ALS and SCA2. Our case demonstrates that the clinical dichotomy between SCA2 and ATXN2-ALS is false. We suggest instead that CAG-repeat expansion length determines the timing of SCA2 clinical symptoms relative to onset of ALS; consistent with this age of onset of SCA2 but not ATXN2-ALS, is dependent upon expansion length. Review of the literature and our local cohort provides evidence for occurrence of ALS in late stage SCA2, which may be under-recognised by clinicians who think of the two diseases as distinct

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

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