Structural conservation in the template/pseudoknot domain of vertebrate telomerase RNA from teleost fish to human

Telomerase synthesizes the telomeric DNA at the 3′ ends of chromosomes and maintains genome integrity. Telomerase RNA (TR) provides the template for telomere-repeat synthesis within a template/pseudoknot (t/PK) domain that is essential for activity. We investigated the structure and dynamics of the t/PK from medaka fish, which contain the smallest vertebrate TR, using NMR and modeling. Despite differences in length, sequence, and predicted secondary structure with human TR, the remarkable similarities between subdomains, including one newly identified in medaka, reveal a conserved architecture for vertebrate t/PK. Combining our model of the full-length pseudoknot and information from the 9-Å structure of Tetrahymena telomerase, we propose models for the interaction of medaka and human t/PK with telomerase reverse transcriptase, providing insight into function

Molecular Mechanism of GTPase Activation at the Signal Recognition Particle (SRP) RNA Distal End

The signal recognition particle (SRP) RNA is a universally conserved and essential component of the SRP that mediates the co-translational targeting of proteins to the correct cellular membrane. During the targeting reaction, two functional ends in the SRP RNA mediate distinct functions. Whereas the RNA tetraloop facilitates initial assembly of two GTPases between the SRP and SRP receptor, this GTPase complex subsequently relocalizes ∼100 Å to the 5′,3′-distal end of the RNA, a conformation crucial for GTPase activation and cargo handover. Here we combined biochemical, single molecule, and NMR studies to investigate the molecular mechanism of this large scale conformational change. We show that two independent sites contribute to the interaction of the GTPase complex with the SRP RNA distal end. Loop E plays a crucial role in the precise positioning of the GTPase complex on these two sites by inducing a defined bend in the RNA helix and thus generating a preorganized recognition surface. GTPase docking can be uncoupled from its subsequent activation, which is mediated by conserved bases in the next internal loop. These results, combined with recent structural work, elucidate how the SRP RNA induces GTPase relocalization and activation at the end of the protein targeting reaction

hDOT1L Links Histone Methylation to Leukemogenesis

SummaryEpigenetic modifications play an important role in human cancer. One such modification, histone methylation, contributes to human cancer through deregulation of cancer-relevant genes. The yeast Dot1 and its human counterpart, hDOT1L, methylate lysine 79 located within the globular domain of histone H3. Here we report that hDOT1L interacts with AF10, an MLL (mixed lineage leukemia) fusion partner involved in acute myeloid leukemia, through the OM-LZ region of AF10 required for MLL-AF10-mediated leukemogenesis. We demonstrate that direct fusion of hDOT1L to MLL results in leukemic transformation in an hDOT1L methyltransferase activity-dependent manner. Transformation by MLL-hDOT1L and MLL-AF10 results in upregulation of a number of leukemia-relevant genes, such as Hoxa9, concomitant with hypermethylation of H3-K79. Our studies thus establish that mistargeting of hDOT1L to Hoxa9 plays an important role in MLL-AF10-mediated leukemogenesis and suggests that the enzymatic activity of hDOT1L may provide a potential target for therapeutic intervention

Prevalence and Molecular Characterization of Cyclospora cayetanensis, Henan, China

To determine prevalence of Cyclospora cayetanensis infection in Henan, China, we conducted a study of 11,554 hospital patients. Prevalence was 0.70% (95% confidence interval 0.70% ± 0.15%), with all age groups infected. Most cases were found in the summer. Minor sequence polymorphisms were observed in the 18S rRNA gene of 35 isolates characterized

Regional segregation or industrial monopoly? Dual labor market segmentation and income inequality in China

Abstract Using data from the 2010 China Family Panel Study and county- and industry-level statistics, we estimate cross-classified multilevel models to examine the determinants of the income gap among Chinese workers. Results show that both regional and industrial differences are important sources of income inequality in China. Taken together, they account for about one fifth of the total variation in individual income. Among them, differences in county explains 7%, while difference in industry accounts for 14% of the total variation. Further analyses demonstrate that county- and industry-level variables have significant independent effects on individual income even after controlling for individual socio-demographic characteristics and human capital resources. We also explore the potential mechanisms through which macro-level factors function in widening income gaps among Chinese workers. Our results show industrial monopolies have been a key driver of the elevated income inequality in China

Prenatal Sex-Selective Abortion and High Sex Ratio at Birth in Rural China: A Case Study in Henan Province

The high sex ratio at birth in China has attracted considerable attentions from demographers. Previous studies assert that female infanticide, underreporting of female births, and prenatal sex-selective abortion were the immediate causes of the initial increase of the sex ratio at birth. Recent studies suggest that prenatal sex selection became the leading immediate cause of more recent increase in the sex ratio at birth. A snowball sampling survey conducted in rural Henan in 2001 collected information on women’s abortion histories. Using these data, we analyze the practice and mechanisms regarding to prenatal sex selection, as well as its impact on SRB. Results show that prenatal sex selection is widely known and commonly practiced in the studied area. The SRB is the highest among births that have only sister(s), and close to normal for other births. Using a population-average model, we found that female fetuses that have only sister(s) are most likely to be aborted. Finally, our imputation suggests that sex-selective abortion has been the predominant, if not the sole, immediate cause of the high SRB

A New Model of Bubble Migration Velocity in Deep Water Wellbore Considering Hydrate Phase Transition

Mass transfer and phase transition have an important effect on the velocity of bubble migration in deepwater wellbores, and accurate prediction of bubble migration velocity is crucial for calculating the safe shut-in period of deepwater oil and gas wells. Therefore, the effect of bubble dissolution mass transfer and hydrate phase transition on bubble migration behavior in the deepwater environment have attracted extensive attention from researchers in the fields of energy, marine chemistry, and marine engineering safety. In this work, a new model of bubble migration velocity in deepwater is developed, which considers the effect of hydrate phase transition and gas-water bidirectional cross-shell mass transfer during bubble migration. Based on the observation data of bubble migration in deepwater, the reliability of the model in predicting bubble migration velocity is verified. Then, the model is used to calculate and analyze the bubble migration velocity and bubble migration cycle under different initial bubble size, different annular fluid viscosity, and density. The results show that the initial size of bubble and the viscosity of annulus fluid are the main factors affecting the migration velocity of the bubble, but the density of annulus fluid has little effect on the migration velocity of the hydrated bubble and clean bubble. In addition, the migration velocity of the clean bubble gradually increases during the migration process from the bottom to the wellhead, while the migration velocity of the hydrated bubble is divided into a gradually decreasing stage and a slowly increasing stage. The gas consumption and the thickening of hydrate shell in the gradually decreasing stage play a dominant role, and the increase of bubble volume caused by the decrease of pressure in the slowly increasing stage is the most important factor. The formation of the hydrated bubble can significantly reduce the migration velocity of the bubble and effectively prolong the safe shut-in period. This study provides a reference for quantitative description and characterization of complex bubble migration behavior with phase change and mass transfer in deepwater environment

Research Progress and Trends of Domestic Smart Learning Environment

In order to explore the main progress and current status of domestic research on smart learning environment, this paper takes 260 core and CSSCI journal papers included in the CNKI database as the research objects, and uses CiteSpace visual analysis software and uses bibliometrics and knowledge graph analysis as the main research methods, summarizes and analyzes the time distribution of the literature, the distribution of institutions and authors, co-occurrence and clustering of keywords, and research hotspots, etc