Genome-wide alternative polyadenylation in animals: insights from high-throughput technologies.

Alternative polyadenylation (APA) plays an important role in gene expression by affecting mRNA stability, translation, and translocation in cells. However, genome-wide APA events have only recently been subjected to more systematic analysis with newly developed high-throughput methods. In this review, we focus on the recent technological development of APA analyses on a genome-wide scale, as well as the impact of APA switches on a number of critical biological processes in animals, including cell proliferation, differentiation, and oncogenic transformation.

A dual-targeting hybrid platinum(IV) prodrug for enhancing efficacy.

A multifunctional hybrid platinum(IV) prodrug, which consists of both the mitochondria-targeting drug DCA and the DNA-crosslinking drug cisplatin, was synthesized and tethered to a carrier polymer to further self-assemble into micelles for intracellular delivery.

6-[(1-naphthylmethyl)sulfanyl]-9H-purine induces G2/M phase arrest and apoptosis in human hepatocellular carcinoma HepG2 cells.

Due to the increasing incidence of cancer, a leading cause of death worldwide, discovery of new therapeutic drugs is urgently needed. By screening for agents with low toxicity that selectively target cancer cells, we found that 6-[(1-naphthylmethyl) sulfanyl]-9H-purine (NMMP), a derivative of 6-mercaptopurine (6-MP), could reduce the viability of five human cancer cell lines. Further study suggested that NMMP inhibition of the proliferation of hepatocellular carcinoma (HepG2) cells was associated with G2/M phase cell cycle arrest, and reduced cyclin-dependent kinase (CDK) 4 and cyclin B1/D1 levels.

Dynamic landscape of tandem 3' UTRs during zebrafish development.

Tandem 3' untranslated regions (UTRs), produced by alternative polyadenylation (APA) in the terminal exon of a gene, could have critical roles in regulating gene networks. Here we profiled tandem poly(A) events on a genome-wide scale during the embryonic development of zebrafish (Danio rerio) using a recently developed SAPAS method. We showed that 43% of the expressed protein-coding genes have tandem 3' UTRs.

The use of polymeric platinum(IV) prodrugs to deliver multinuclear platinum(II) drugs with reduced systemic toxicity and enhanced antitumor efficacy.

Two dinuclear platinum(IV) prodrugs were prepared from cisplatin and oxaliplatin, and tethered to amphiphilic biodegradable block copolymers. The polymeric dinuclear platinum(IV) prodrugs were allowed to self-assemble into nanomicelles, which showed reduced systemic toxicity, relatively long blood circulation, and enhanced antitumor efficacy. In this way, the bottleneck of present multinuclear platinum drugs, especially their severe systemic toxicity, might be overcome.

Sensory neuronopathy involves the spinal cord and brachial plexus: a quantitative study employing multiple-echo data image combination (MEDIC) and turbo inversion recovery magnitude (TIRM).

Introduction: Sensory neuronopathy (SNN) is a distinctive subtype of peripheral neuropathies, specifically targeting dorsal root ganglion (DRG). We utilized MRI to demonstrate the imaging characteristics of DRG, spinal cord (SC), and brachial plexus at C7 level in SNN.

Methods: We attempted multiple-echo data image combination (MEDIC) and turbo inversion recovery magnitude (TIRM) methods in nine patients with sensory neuronopathy and compared with those in 16 disease controls and 20 healthy volunteers.

Staging and follow-up of lacrimal gland carcinomas by 18F-FDG PET/CT imaging.

A 74-year-old man with right eye proptosis, diplopia, and orbital discomfort for 3 to 4 months underwent biopsy, the specimen of which showed transitional cell carcinoma of the lacrimal gland. 18F-FDG PET/CT was also performed for staging purposes. Six months after orbital exenteration, a follow-up CT scan demonstrated soft tissue thickening along the nasal bridge but could not differentiate between postsurgical changes and cancer recurrence.

Expression and electrophysiological characteristics of P2X3 receptors in interstitial cells of Cajal in rats with partial bladder outlet obstruction.

Unlabelled: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: In the urinary bladder, histological studies suggest a network of functionally connected interstitial cells of Cajal (ICCs) are located between the urothelium and sensory nerve endings, which might transfer signals directly between them. Purinergic P2X3 receptors may play roles in the micturition reflex pathway, and its expression profiles in ICCs could be altered in urinary bladder dysfunction. The present experiments showed a novel time-dependent P2X3 receptor up-regulation in ICCs in an experimental rat model of partial bladder outlet obstruction.

Synthesis and insecticidal activities of novel anthranilic diamides containing acylthiourea and acylurea.

Two series of anthranilic diamides containing acylthiourea and acylurea linkers were designed and synthesized, with changed length and flexibility of the linkers to compare to known anthranilic diamide insecticides. In total, 26 novel compounds were synthesized, and all compounds were characterized by (1)H nuclear magnetic resonance and high-resolution mass spectrometry. Their insecticidal activities against oriental armyworm (Mythimna separata), mosquito larvae (Culex pipiens pallens), and diamondback moth (Plutella xylostella) were evaluated.

Inositol hexakisphosphate suppresses excitatory neurotransmission via synaptotagmin-1 C2B domain in the hippocampal neuron.

Inositol hexakisphosphate (InsP(6)) levels rise and fall with neuronal excitation and silence, respectively, in the hippocampus, suggesting potential signaling functions of this inositol polyphosphate in hippocampal neurons. We now demonstrate that intracellular application of InsP(6) caused a concentration-dependent inhibition of autaptic excitatory postsynaptic currents (EPSCs) in cultured hippocampal neurons. The treatment did not alter the size and replenishment rate of the readily releasable pool in autaptic neurons.

Identification of cross-linked peptides from complex samples.

We have developed pLink, software for data analysis of cross-linked proteins coupled with mass-spectrometry analysis. pLink reliably estimates false discovery rate in cross-link identification and is compatible with multiple homo- or hetero-bifunctional cross-linkers. We validated the program with proteins of known structures, and we further tested it on protein complexes, crude immunoprecipitates and whole-cell lysates.

Investigation of hyperpolarization-activated cyclic nucleotide-gated channels in interstitial cells of Cajal of human bladder.

Objective: To investigate the expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) protein in the interstitial cells of Cajal (ICCs) of the human bladder and to determine the relative expression of the HCN subtypes.

Methods: A total of 30 bladder specimens were obtained, and each bladder sample was divided into 2 parts. Part I, which included mucosa, submucosa, and muscle, was used for immunofluorescence study.

N-Benzoyl-12-nitrodehydroabietylamine-7-one, a novel dehydroabietylamine derivative, induces apoptosis and inhibits proliferation in HepG2 cells.

The high biological activity of dehydroabietylamine derivatives has been reported previously. In this study, we aimed to screen 73 dehydroabietylamine derivatives as potential candidate inhibitors in liver cancer cells. Initially, the compounds structural activity relationship analysis was explored and N-benzoyl-12-nitrodehydroabietylamine-7-one (compound 81) was shown to have significant growth inhibitory activity in the human liver carcinoma cell line, HepG2.

17βH-Periplogenin, a cardiac aglycone from the root bark of Periploca sepium Bunge.

The title compound {systematic name: 4-[(3S,5S,8R,9S,10R,13R,14S,17S)-3,5,14-trihy-droxy-10,13-dimethyl-hexa-deca-hydro-1H-cyclo-penta-[a]phenanthren-17-yl]furan-2(5H)-one}, C(23)H(34)O(5), was isolated from the roots of Periploca sepium Bunge, a famous Chinese traditional herbal medicine. The three six-membered rings adopt chair conformations, the cyclo-pentane ring displays an approximate envelope conformation (with the C atom bearing the methyl substituent at the flap) and the five-membered lactone ring adopts an essentially planar [maximum deviation of 0.004 (8) Å] conformation.

The threonine protease activity of testes-specific protease 50 (TSP50) is essential for its function in cell proliferation.

Background: Testes-specific protease 50 (TSP50), a newly discovered threonine enzyme, has similar amino acid sequences and enzymatic structures to those of many serine proteases. It may be an oncogene. TSP50 is up-regulated in breast cancer epithelial cells, and ectopic expression of TSP50 in TSP50-deficient Chinese hamster ovary (CHO) cells has been found to promote cell proliferation.

Juglanthraquinone C, a novel natural compound derived from Juglans mandshurica Maxim, induces S phase arrest and apoptosis in HepG2 cells.

Juglanthraquinone C (1,5-dihydroxy-9,10-anthraquinone-3-carboxylic acid, JC), a naturally occurring anthraquinone isolated from the stem bark of Juglans mandshurica, shows strong cytotoxicity in various human cancer cells in vitro. Here, we first performed a structure-activity relationship study of six anthraquinone compounds (JC, rhein, emodin, aloe-emodin, physcion and chrysophanol) to exploit the relationship between their structural features and activity. The results showed that JC exhibited the strongest cytotoxicity of all compounds evaluated.

Influence of achieved low-density lipoprotein cholesterol level with atorvastatin therapy on stabilization of coronary plaques: sub-analysis of the TWINS study.

Background: Previously the stabilization of coronary plaque with atorvastatin was demonstrated in the TWINS (evaluaTion With simultaneous angIoscopy and iNtravascular ultraSound) study. The influence of the low-density lipoprotein cholesterol (LDL-C) level on plaque stabilization was analyzed.

Methods And Results: Patients (n=29) with hypercholesterolemia and coronary artery disease (CAD) were analyzed.

MRI features in children with desmoplastic medulloblastoma.

Desmoplastic medulloblastoma (DMB) is a variant that has a more favorable prognosis compared to classical medulloblastoma, but its MRI features have not been as well described. We retrospectively reviewed the MRI features in children with pathologically proven DMB, including T2-weighted, fluid-attenuated inversion recovery (FLAIR) and contrast enhanced images, with isotropic diffusion-weighted (DW) MRI also performed in some patients. There were 16 tumors in 12 patients; one patient had five discrete lesions.

Computed tomography and magnetic resonance features of gliosarcoma: a study of 54 cases.

Objective: To investigate the features of pathologically confirmed gliosarcomas using computed tomography (CT) and magnetic resonance (MR) imaging.

Methods: We retrospectively reviewed the cross-sectional CT and MR images of 54 patients (37 males and 17 females; mean age, 44.5 years; range, 13-74 years) with gliosarcomas confirmed by histopathology.

Clinical utility of (18)F-fluoride PET/CT in benign and malignant bone diseases.

(18)F labeled sodium fluoride is a positron-emitting, bone seeking agent with more favorable skeletal kinetics than conventional phosphate and diphosphonate compounds. With the expanding clinical usage of PET/CT, there is renewed interest in using (18)F-fluoride PET/CT for imaging bone diseases. Growing evidence indicates that (18)F fluoride PET/CT offers increased sensitivity, specificity, and diagnostic accuracy in evaluating metastatic bone disease compared to (99m)Tc based bone scintigraphy.

Association of vascular fluoride uptake with vascular calcification and coronary artery disease.

Objective: The feasibility of a fluoride positron emission tomography/computed tomography (PET/CT) scan for imaging atherosclerosis has not been well documented. The purpose of this study was to assess fluoride uptake of vascular calcification in various major arteries, including coronary arteries.

Methods: We retrospectively reviewed the imaging data and cardiovascular history of 61 patients who received whole-body sodium [¹⁸F]fluoride PET/CT studies at our institution from 2009 to 2010.

Regioselective synthesis of novel 3-thiazolidine acetic acid derivatives from glycosido ureides.

A series of 3-thiazolidine acetic acid-2-(per-O-acetylglycosyl)-1'-imino-α-(substituted)-4-oxo ethyl ester derivatives (3a-t) were prepared via the reaction of substituted amino acid-N-[(per-O-acetylglycosylamino)thioxomethyl]-ethyl ester with ethyl bromoacetate. The crystal structure of 3-thiazolidine acetic acid-2-(2',3',4',6'-tetra-O-acetyl-β-D-galactoyranosyl)-1'-imino-α-methyl-4-oxo ethyl ester 3g and ¹H-¹³C HMBC (2D NMR experiments) measurements of 3-thiazolidine acetic acid-2-(2',3',4',6'-tetra-O-acetyl-β-D-galactopyranosyl)-1'-imino-α-(1-methylthio)ethyl-4-oxo ethyl ester 3j revealed the exclusive regioselectivity during the closure of these rings toward the N-2 position of the thiourea moiety. Furthermore, the crystal structure of compound 3g showed that the attack of N-1 was blocked by sugar ring owing to the steric effect.

Functional conservation and innovation of amphioxus RIP1-mediated signaling in cell fate determination.

Recently, receptor interacting protein (RIP)-1 has been recognized as an intracellular sensor at the crossroads of apoptosis, necroptosis, and cell survival. To reveal when this crucial molecule originated and how its function in integrating stress signals evolved, in this study we report on two RIP1 homologs in Chinese amphioxus (Branchiostoma belcheri tsingtauense), designated B. belcheri tsingtauense RIP1a and B.