A rare polymorphism in the low density lipoprotein (LDL) gene that affects mRNA splicing

Familial hypercholesterolaemia (FH) is usually caused by mutations in the low density lipoprotein (LDL) receptor gene (LDLR) that impair clearance of LDL from the circulation. The increased risk of premature coronary heart disease associated with FH can be reduced by dietary advice and treatment with lipid-lowering drug therapy, but it is important to identify affected individuals at an early stage. Several programmes for genetic diagnosis of FH that rely on identifying nucleotide substitutions in genomic DNA have been initiated, but the validity of these is dependent on distinguishing between a silent nucleotide variant and a mutation that affects LDL-receptor function. Here we describe a single nucleotide substitution in the coding region of exon 9 of LDLR that is an apparently silent polymorphism: CGG (Arg406) to AGG (Arg). Analysis of mRNA from the patient's cells showed that the mutation introduces a new splice site that is used to the exclusion of the natural splice site and causes a deletion of 31 bp from the mRNA, predicted to introduce premature termination four codons after R406. This finding emphasizes the caution needed in genetic diagnosis of FH based on genomic DNA sequence alone

Proteomic analysis of the rat ovary following chronic low-dose exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitously distributed endocrine-disrupting chemical and reproductive toxicant. In order to elucidate low-dose TCDD-mediated effects on reproductive or endocrine functions, female Sprague-Dawley rats were orally administered various concentrations (20, 50, or 125 ng/kg once weekly) TCDD for 29 wk. A proteomic analysis of the ovaries by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization (MALDI) tandem mass spectrometry showed distinct changes in the levels of several proteins that are relevant markers of TCDD toxicity. Serum estradiol (E2) levels of TCDD-treated animals were markedly lower than control. There were no significant differences in bone mineral density (BMD) of femurs. The body weight of the 125-ng/kg TCDD group was significantly decreased relative to control and there was also a significant reduction in absolute and relative ovarian weights. Expressions of selenium binding protein 2, glutathione S-transferase mu type 3, Lrpap1 protein, NADPH, and peptidylprolyl isomerase D were upregulated, while prohibitin and N-ethylmaleimide-sensitive factor expression levels were downregulated. Data provide further insight into the mechanisms by which TCDD disrupts ovarian function by indicating which differential protein expressions following low-dose TCDD exposure

Phase Transformation of Nb in Carburized Zone of 25Cr35NiNb+MA Alloy After Service

Abstract25Cr35NiNb+MA alloy is widely used in ethylene pyrolysis furnace tube, the highest service temperature can be 1100°C, and has high resistance to creep and carburization. Ethylene pyrolysis furnace tube will suffer carburizing during service, which lead to phase transformation. Phase transformation of 25Cr35NiNb+MA heat-resistant ethylene pyrolysis furnace tube was investigated after service and the Nb transition during service was discussed. The phase transformation of ethylene pyrolysis furnace tube was characterized with field emission scanning electron microscopy (FE-SEM) equipped with energy dispersive spectrum (EDS). Results reveal that the microstructure of as-cast 25Cr35NiNb+MA alloy contains NbC carbides on the dendrite boundaries. During service at high temperature, the NbC carbides transform to blocky G-phase (Ni16Nb6Si7) between M23C6 and matrix. As the carburizing process occurs, the blocky G-phase (Ni16Nb6Si7) gradually transforms to granular NbC, and distribute at the center of chromium carbide. The granular NbC will improve resistance of creep

Paclitaxel-octreotide conjugates inhibit growth of human non-small cell lung cancer cells in vitro

Aim: To evaluate the effects of paclitaxel-octreotide conjugates on the growth of cultured non-small cell lung cancer cells. Methods: RT-PCR was performed to detect mRNA for the subtypes of the human somatostatin receptor (SSTR) using specific primers. MTT-based cytotoxicity assay was used to evaluate the cell viability after treatment with paclitaxel and the conjugates. Cell cycle perturbations were determined using a Fluorescence-Activated Cell Sorter. Results: Non-small cell lung cancer A549 and Calu-6 cells expressed mRNA for SSTR2 and SSTR5. Paclitaxel and the conjugates effectively inhibited the growth of A549 and Calu-6 cells in a concentration- and time-dependent manner. In SSTR-negative fibroblasts, the conjugates were less cytotoxic than paclitaxel. The conjugates and paclitaxel could induce the increase of G2/M phase ratio in A549 cells. Conclusion: The paclitaxel-octreotide conjugates can be used as selective-targeted chemotherapeutic agents for treating non-small cell lung cancer.Цель: оценить эффект конъюгатов паклитаксела-октреотида на рост культивированных клеток немелкоклеточного рака легкого человека. Методы: для определения мРНК подтипов рецептора соматостатина человека (SSTR) применяли ОT-ПЦР. Анализ цитотоксичности в МТТ-тесте применяли для оценки выживаемости клеток после их инкубации с паклитакселом и конъюгатами. Нарушения клеточного цикла определяли с применением FACS — клеточного сортера. Результаты: установлено, что клеточные линии немелкоклеточного рака легкого A549 и Calu-6 экспрессируют SSTR2 и SSTR5 мРНК. Отмечено эффективное дозо- и времязависимое угнетение роста клеток A549 и Calu-6 паклитакселом и конъюгатами. Для SSTR-негативных фибробластов конъюгаты менее цитотоксичны, чем паклитаксел. Конъюгаты и паклитаксел могут индуцировать повышение соотношения фаз G2 /M в клетках A549. Выводы: конъюгаты паклитаксел-октреотида могут быть использованы как селективные химиотерапевтические агенты для воздействия на немелкоклеточный рак легкого

Search for the Rare Decays J/Psi --> Ds- e+ nu_e, J/Psi --> D- e+ nu_e, and J/Psi --> D0bar e+ e-

We report on a search for the decays J/Psi --> Ds- e+ nu_e + c.c., J/Psi --> D- e+ nu_e + c.c., and J/Psi --> D0bar e+ e- + c.c. in a sample of 5.8 * 10^7 J/Psi events collected with the BESII detector at the BEPC. No excess of signal above background is observed, and 90% confidence level upper limits on the branching fractions are set: B(J/Psi --> Ds- e+ nu_e + c.c.)<4.8*10^-5, B(J/Psi --> D- e+ nu_e + c.c.) D0bar e+ e- + c.c.)<1.1*10^-5Comment: 10 pages, 4 figure

Long-read sequencing reveals extensive DNA methylations in human gut phagenome contributed by prevalently phage-encoded methyltransferases

DNA methylation plays a crucial role in the survival of bacteriophages (phages), yet the understanding of their genome methylation remains limited. In this study, DNA methylation patterns are analyzed in 8848 metagenome-assembled high-quality phages from 104 fecal samples using single-molecule real-time sequencing. The results demonstrate that 97.60% of gut phages exhibit methylation, with certain factors correlating with methylation densities. Phages with higher methylation densities appear to have potential viability advantages. Strikingly, more than one-third of the phages possess their own DNA methyltransferases (MTases). Increased MTase copies are associated with higher genome methylation densities, specific methylation motifs, and elevated prevalence of certain phage groups. Notably, the majority of these MTases share close homology with those encoded by gut bacteria, suggesting their exchange during phage-bacterium interactions. Furthermore, these MTases can be employed to accurately predict phage-host relationships. Overall, the findings indicate the widespread utilization of DNA methylation by gut DNA phages as an evasion mechanism against host defense systems, with a substantial contribution from phage-encoded MTases

Study of J/psi decays to Lambda Lambdabar and Sigma0 Sigma0bar

The branching ratios and Angular distributions for J/psi decays to Lambda Lambdabar and Sigma0 Sigma0bar are measured using BESII 58 million J/psi.Comment: 11 pages, 5 figure