The feasibility study of non-invasive fetal trisomy 18 and 21 detection with semiconductor sequencing platform

Objective: Recent non-invasive prenatal testing (NIPT) technologies are based on next-generation sequencing (NGS). NGS allows rapid and effective clinical diagnoses to be determined with two common sequencing systems: Illumina and Ion Torrent platforms. The majority of NIPT technology is associated with Illumina platform. We investigated whether fetal trisomy 18 and 21 were sensitively and specifically detectable by semiconductor sequencer: Ion Proton. Methods: From March 2012 to October 2013, we enrolled 155 pregnant women with fetuses who were diagnosed as high risk of fetal defects at Xiamen Maternal & Child Health Care Hospital (Xiamen, Fujian, China). Adapter-ligated DNA libraries were analyzed by the Ion Proton??? System (Life Technologies, Grand Island, NY, USA) with an average 0.3 ?? sequencing coverage per nucleotide. Average total raw reads per sample was 6.5 million and mean rate of uniquely mapped reads was 59.0%. The results of this study were derived from BWA mapping. Z-score was used for fetal trisomy 18 and 21 detection. Results: Interactive dot diagrams showed the minimal z-score values to discriminate negative versus positive cases of fetal trisomy 18 and 21. For fetal trisomy 18, the minimal z-score value of 2.459 showed 100% positive predictive and negative predictive values. The minimal z-score of 2.566 was used to classify negative versus positive cases of fetal trisomy 21. Conclusion: These results provide the evidence that fetal trisomy 18 and 21 detection can be performed with semiconductor sequencer. Our data also suggest that a prospective study should be performed with a larger cohort of clinically diverse obstetrics patients.open2

Proteomics of Buccal Cavity Mucus in Female Tilapia Fish (Oreochromis spp.): A Comparison between Parental and Non-Parental Fish

Mouthbrooding is an elaborate form of parental care displayed by many teleost species. While the direct benefits of mouthbrooding such as protection and transportation of offsprings are known, it is unclear if mouthbrooding offers additional benefits to embryos during incubation. In addition, mouthbrooding could incur negative costs on parental fish, due to limited feeding opportunities. Parental tilapia fish (Oreochromis spp.) display an elaborated form of parental care by incubating newly hatched embryos in oral buccal cavity until the complete adsorption of yolk sac. In order to understand the functional aspects of mouthbrooding, we undertake a proteomics approach to compare oral mucus sampled from mouthbrooders and non-mouthbrooders, respectively. Majority of the identified proteins have also been previously identified in other biological fluids or mucus-rich organs in different organisms. We also showed the upregulation of 22 proteins and down regulation of 3 proteins in mucus collected from mouthbrooders. Anterior gradient protein, hemoglobin beta-A chain and alpha-2 globin levels were lower in mouthbrooder samples. Mouthbrooder oral mucus collectively showed increase levels of proteins related to cytoskeletal properties, glycolytic pathway and mediation of oxidative stress. Overall the findings suggest cellular stress response, probably to support production of mucus during mouthbrooding phase

Early programming of the oocyte epigenome temporally controls late prophase I transcription and chromatin remodelling

Oocytes are arrested for long periods of time in the prophase of the first meiotic division (prophase I). As chromosome condensation poses significant constraints to gene expression, the mechanisms regulating transcriptional activity in the prophase I-arrested oocyte are still not entirely understood. We hypothesized that gene expression during the prophase I arrest is primarily epigenetically regulated. Here we comprehensively define the Drosophila female germ line epigenome throughout oogenesis and show that the oocyte has a unique, dynamic and remarkably diversified epigenome characterized by the presence of both euchromatic and heterochromatic marks. We observed that the perturbation of the oocyte's epigenome in early oogenesis, through depletion of the dKDM5 histone demethylase, results in the temporal deregulation of meiotic transcription and affects female fertility. Taken together, our results indicate that the early programming of the oocyte epigenome primes meiotic chromatin for subsequent functions in late prophase I

Rapamycin Blocks Production of KSHV/HHV8: Insights into the Anti-Tumor Activity of an Immunosuppressant Drug

Infection with Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) often results in the development of fatal tumors in immunocompromised patients. Studies of renal transplant recipients show that use of the immunosuppressant drug rapamycin, an mTOR inhibitor, both prevents and can induce the regression of Kaposi's sarcoma (KS), an opportunistic tumor that arises within a subset of this infected population. In light of rapamycin's marked anti-KS activity, we tested whether the drug might directly inhibit the KSHV life cycle. We focused on the molecular switch that triggers this predominantly latent virus to enter the lytic (productive) replication phase, since earlier work links this transition to viral persistence and tumorigenesis.In latently infected human B cell lines, we found that rapamycin inhibited entry of the virus into the lytic replication cycle, marked by a loss of expression of the lytic switch protein, replication and transcription activator (RTA). To test for viral-specific effects of rapamycin, we focused our studies on a B cell line with resistance to rapamycin-mediated growth inhibition. Using this line, we found that the drug had minimal effect on cell cycle profiles, cellular proliferation, or the expression of other cellular or latent viral proteins, indicating that the RTA suppression was not a result of global cellular dysregulation. Finally, treatment with rapamycin blocked the production of progeny virions.These results indicate that mTOR plays a role in the regulation of RTA expression and, therefore, KSHV production, providing a potential molecular explanation for the marked clinical success of rapamycin in the treatment and prevention of post-transplant Kaposi's sarcoma. The striking inhibition of rapamycin on KSHV lytic replication, thus, helps explain the apparent paradox of an immunosuppressant drug suppressing the pathogenesis of an opportunistic viral infection

Gene-Gene and Gene-Environmental Interactions of Childhood Asthma: A Multifactor Dimension Reduction Approach

Background: The importance of gene-gene and gene-environment interactions on asthma is well documented in literature, but a systematic analysis on the interaction between various genetic and environmental factors is still lacking. Methodology/Principal Findings: We conducted a population-based, case-control study comprised of seventh-grade children from 14 Taiwanese communities. A total of 235 asthmatic cases and 1,310 non-asthmatic controls were selected for DNA collection and genotyping. We examined the gene-gene and gene-environment interactions between 17 singlenucleotide polymorphisms in antioxidative, inflammatory and obesity-related genes, and childhood asthma. Environmental exposures and disease status were obtained from parental questionnaires. The model-free and non-parametrical multifactor dimensionality reduction (MDR) method was used for the analysis. A three-way gene-gene interaction was elucidated between the gene coding glutathione S-transferase P (GSTP1), the gene coding interleukin-4 receptor alpha chain (IL4Ra) and the gene coding insulin induced gene 2 (INSIG2) on the risk of lifetime asthma. The testing-balanced accuracy on asthma was 57.83 % with a cross-validation consistency of 10 out of 10. The interaction of preterm birth and indoor dampness had the highest training-balanced accuracy at 59.09%. Indoor dampness also interacted with many genes, including IL13, beta-2 adrenergic receptor (ADRB2), signal transducer and activator of transcription 6 (STAT6). We also used likelihood ratio tests for interaction and chi-square tests to validate our results and all tests showed statistical significance

Sleep-disordered breathing-do we have to change gears in heart failure?

The majority of patients with heart failure have sleep-disordered breathing (SDB)-with central (rather than obstructive) sleep apnoea becoming the predominant form in those with more severe disease. Cyclical apnoeas and hypopnoeas are associated with sleep disturbance, hypoxaemia, haemodynamic changes, and sympathetic activation. Such patients have a worse prognosis than those without SDB. Mask-based therapies of positive airway pressure targeted at SDB can improve measures of sleep quality and partially normalise the sleep and respiratory physiology, but recent randomised trials of cardiovascular outcomes in central sleep apnoea have been neutral or suggested the possibility of harm, likely from increased sudden death. Further randomised outcome studies (with cardiovascular mortality and hospitalisation endpoints) are required to determine whether mask-based treatment for SDB is appropriate for patients with chronic systolic heart failure and obstructive sleep apnoea, for those with heart failure with preserved ejection fraction, and for those with decompensated heart failure. New therapies for sleep apnoea-such as implantable phrenic nerve stimulators-also require robust assessment. No longer can the surrogate endpoints of improvement in respiratory and sleep metrics be taken as adequate therapeutic outcome measures in patients with heart failure and sleep apnoea

Within- and cross-language contributions of morphological awareness to word reading development in Chinese-English bilingual children

A growing body of cross-linguistic research has suggested that morphological awareness plays a key role in both L1 and L2 word reading among bilingual readers. However, little is known about the interaction and development of L1 and L2 morphological awareness in relation to word reading. We addressed this issue by evaluating the unique contributions of L1 Chinese and L2 English morphological awareness to word reading in both Chinese and English across Grades 2 (N = 150), 5 (N = 158), and 8 (N = 159) Hong Kong Chinese–English bilingual children. Children completed five tasks of Chinese morphological awareness which tapped for compounding awareness, homophone awareness, homographic awareness, semantic radical awareness, and affix awareness, and six English morphological judgment and analogy tasks that assessed morphological awareness at three levels: inflection, derivation, and compounding. English phonological awareness, Chinese and English vocabulary, and nonverbal ability were measured as controls. Word reading was assessed in both languages. Within-language analyses revealed that Chinese morphological awareness accounted for 27, 22, and 12% of unique variances in Chinese word reading above the control measures in Grades 2, 5, and 8 respectively. In contrast, English morphological awareness explained small but significant unique variances in English word reading, i.e., 4, 8, and 2%, across Grades 2, 5, and 8 respectively. Critically, there were cross-language influences: Chinese morphological awareness explained 4% of unique variance in English word reading in Grade 2 after controlling for IQ, English vocabulary, English phonological awareness, and English morphological awareness; English morphological awareness explained significant variances in Chinese word reading, i.e., 4, 3, and 4% in Grades 2, 5, and 8 respectively, after the relevant controls. These findings suggest a bi-directional cross-language transfer of morphological awareness to word reading in L1 Chinese and L2 English. However, the direction of its transfer may be constrained by some language-specific morphological features

On the capacitance of vacuum microelectronic devices with different field emitter shapes

In this paper, capacitance of diode vacuum microelectronic devices with different field emitter shapes are studied. By using finite difference method, electric field and capacitance of field emitters with five different shapes are calculated. Calculation results show that the emitter shape has a larger effect on the field enhancement than on the capacitance. When the anode diameter is decreased from 8 mu m to 4 mu m, the capacitance can be decreased by ten times for the sharp tin-on-post field emitter. When the distance between the cathode and the and and the height of the field emitter are increased by 2 mu m, the capacitance can be increased by about 30% for the sharp tip-on-post field emitter

Effect of lead on tissue deposition of mercury in mice

10.1007/BF01609758Bulletin of Environmental Contamination and Toxicology341438-445BECT