The contribution of Alu exons to the human proteome.

BackgroundAlu elements are major contributors to lineage-specific new exons in primate and human genomes. Recent studies indicate that some Alu exons have high transcript inclusion levels or tissue-specific splicing profiles, and may play important regulatory roles in modulating mRNA degradation or translational efficiency. However, the contribution of Alu exons to the human proteome remains unclear and controversial. The prevailing view is that exons derived from young repetitive elements, such as Alu elements, are restricted to regulatory functions and have not had adequate evolutionary time to be incorporated into stable, functional proteins.ResultsWe adopt a proteotranscriptomics approach to systematically assess the contribution of Alu exons to the human proteome. Using RNA sequencing, ribosome profiling, and proteomics data from human tissues and cell lines, we provide evidence for the translational activities of Alu exons and the presence of Alu exon derived peptides in human proteins. These Alu exon peptides represent species-specific protein differences between primates and other mammals, and in certain instances between humans and closely related primates. In the case of the RNA editing enzyme ADARB1, which contains an Alu exon peptide in its catalytic domain, RNA sequencing analyses of A-to-I editing demonstrate that both the Alu exon skipping and inclusion isoforms encode active enzymes. The Alu exon derived peptide may fine tune the overall editing activity and, in limited cases, the site selectivity of ADARB1 protein products.ConclusionsOur data indicate that Alu elements have contributed to the acquisition of novel protein sequences during primate and human evolution

A meta-analytic study of the neural systems for auditory processing of lexical tones

The neural systems of lexical tone processing have been studied for many years. However, previous findings have been mixed with regard to the hemispheric specialization for the perception of linguistic pitch patterns in native speakers of tonal language. In this study, we performed two activation likelihood estimation (ALE) meta-analyses, one on neuroimaging studies of auditory processing of lexical tones in tonal languages (17 studies), and the other on auditory processing of lexical information in non-tonal languages as a control analysis for comparison (15 studies). The lexical tone ALE analysis showed significant brain activations in bilateral inferior prefrontal regions, bilateral superior temporal regions and the right caudate, while the control ALE analysis showed significant cortical activity in the left inferior frontal gyrus and left temporo-parietal regions. However, we failed to obtain significant differences from the contrast analysis between two auditory conditions, which might be caused by the limited number of studies available for comparison. Although the current study lacks evidence to argue for a lexical tone specific activation pattern, our results provide clues and directions for future investigations on this topic, more sophisticated methods are needed to explore this question in more depth as well.published_or_final_versio

Cooperation of decay-accelerating factor and membrane cofactor protein in regulating survival of human cervical cancer cells

<p>Abstract</p> <p>Background</p> <p>Decay-accelerating factor (DAF) and membrane cofactor protein (MCP) are the key molecules involved in cell protection against autologus complement, which restricts the action of complement at critical stages of the cascade reaction. The cooperative effect of DAF and MCP on the survival of human cervical cancer cell (ME180) has not been demonstrated.</p> <p>Methods</p> <p>In this study we applied, for the first time, short hairpin RNA (shRNA) to knock down the expression of the DAF and MCP with the aim of exploiting complement more effectively for tumor cell damage. Meanwhile, we investigated the cooperative effects of DAF and MCP on the viability and migration, moreover the proliferation of ME180 cell.</p> <p>Results</p> <p>The results showed that shRNA inhibition of DAF and MCP expression enhanced complement-dependent cytolysis (CDC) up to 39% for MCP and up to 36% for DAF, and the combined inhibition of both regulators yielded further additive effects in ME180 cells. Thus, the activities of DAF and MCP, when present together, are greater than the sum of the two protein individually.</p> <p>Conclusion</p> <p>These data indicated that combined DAF and MCP shRNA described in this study may offer an additional alternative to improve the efficacy of antibody-and complement-based cancer immunotherapy.</p

Novel AroA from Pseudomonas putida Confers Tobacco Plant with High Tolerance to Glyphosate

Glyphosate is a non-selective broad-spectrum herbicide that inhibits 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS, also designated as AroA), a key enzyme in the aromatic amino acid biosynthesis pathway in microorganisms and plants. Previously, we reported that a novel AroA (PpAroA1) from Pseudomonas putida had high tolerance to glyphosate, with little homology to class I or class II glyphosate-tolerant AroA. In this study, the coding sequence of PpAroA1 was optimized for tobacco. For maturation of the enzyme in chloroplast, a chloroplast transit peptide coding sequence was fused in frame with the optimized aroA gene (PparoA1optimized) at the 5′ end. The PparoA1optimized gene was introduced into the tobacco (Nicotiana tabacum L. cv. W38) genome via Agrobacterium-mediated transformation. The transformed explants were first screened in shoot induction medium containing kanamycin. Then glyphosate tolerance was assayed in putative transgenic plants and its T1 progeny. Our results show that the PpAroA1 from Pseudomonas putida can efficiently confer tobacco plants with high glyphosate tolerance. Transgenic tobacco overexpressing the PparoA1optimized gene exhibit high tolerance to glyphosate, which suggest that the novel PpAroA1 is a new and good candidate applied in transgenic crops with glyphosate tolerance in future

Pivotal Role of the α2A-Adrenoceptor in Producing Inflammation and Organ Injury in a Rat Model of Sepsis

Background: Norepinephrine (NE) modulates the responsiveness of macrophages to proinflammatory stimuli through the activation of adrenergic receptors (ARs). Being part of the stress response, early increases of NE in sepsis sustain adverse systemic inflammatory responses. The intestine is an important source of NE release in the early stage of cecal ligation and puncture (CLP)-induced sepsis in rats, which then stimulates TNF-a production in Kupffer cells (KCs) through the activation of the a2-AR. It is important to know which of the three a2-AR subtypes (i.e., a2A, a2B or a2C) is responsible for the upregulation of TNF-a production. The aim of this study was to determine the contribution of a2A-AR in this process. Methodology/Principal Findings: Adult male rats underwent CLP and KCs were isolated 2 h later. Gene expression of a2A-AR was determined. In additional experiments, cultured KCs were incubated with NE with or without BRL-44408 maleate, a specific a2A-AR antagonist, and intraportal infusion of NE for 2 h with or without BRL-44408 maleate was carried out in normal animals. Finally, the impact of a2A-AR activation by NE was investigated under inflammatory conditions (i.e., endotoxemia and CLP). Gene expression of the a2A-AR subtype was significantly upregulated after CLP. NE increased the release of TNF-a in cultured KCs, which was specifically inhibited by the a2A-AR antagonist BRL-44408. Equally, intraportal NE infusion increased TNF-a gene expression in KCs and plasma TNF-a which was also abrogated by co-administration of BRL-44408. NE also potentiated LPS-induced TNF-a release via the a2A-AR in vitro and in vivo. This potentiation of TNF-a release by NE was mediated through the a2A-AR coupled Gai protein and the activation of the p38 MAP kinase. Treatment of septic animals with BRL-44408 suppressed TNF-a, prevented multiple organ injury and significantly improved survival from 45% to 75%. Conclusions/Significance: Our novel finding is that hyperresponsiveness to a2-AR stimulation observed in sepsis is primarily due to an increase in a2A-AR expression in KCs. This appears to be in part responsible for the increased proinflammatory response and ensuing organ injury in sepsis. These findings provide important feasibility information for further developing the a2A-AR antagonist as a new therapy for sepsis

Caregiver awareness of reproductive health issues for women with intellectual disabilities

<p>Abstract</p> <p>Background</p> <p>Limited attention has been paid to the issue of reproductive health as it affects women with intellectual disabilities, despite reproductive health being a vital issue in public health policy for women in the general population. This paper describes caregiver awareness of reproductive health issues relative to women with intellectual disabilities who are being cared for in welfare institutions in Taiwan.</p> <p>Methods</p> <p>The study employed a cross-sectional, questionnaire-based study which recruited 1,152 caregivers (response rate = 71.87%) from 32 registered disability welfare institutions in Taiwan. We classified their understanding/awareness of reproductive health issues into four domains: menstrual (1) and menopause (2) issues, sex education (3), and reproductive health services (4). Each domain had five associated yes/no questions and the total score for the four domains was out of a maximum of 20. Data were analyzed using SPSS 15.0 software.</p> <p>Results</p> <p>We found that most of the caregivers were familiar with matters concerning sex education, menopause, and reproductive health services, but they lacked adequate understanding of issues associated with menstruation in women with ID. Many aspects of reproductive health such as "menstrual pain", "age at menarche", "masturbation", "diet during perimenopause", and "publicly available reproductive health services" were issues in which caregivers lacked adequate knowledge and required further instruction. Logistic regression analysis revealed that female caregivers with a university degree, and those who had experience assisting with reproductive health care were more inclined to have higher reproductive health awareness scores than their counterparts.</p> <p>Conclusions</p> <p>This study highlights that service providers should offer appropriate reproductive health education to institutional caregivers, and that more attention be focused on the personal experiences and concerns of intellectually disabled women in future research.</p

The neck-region polymorphism of DC-SIGNR in peri-centenarian from Han Chinese Population

<p>Abstract</p> <p>Background</p> <p>DC-SIGNR (also called CD209L) has been extensively studied on its role in host genetic predisposition to viral infection. In particular, variable number tandem repeat (VNTR) of the neck-region of DC-SIGNR is highly polymorphic and the polymorphism has been investigated for genetic predisposition to various infectious diseases, though conflicting results had been reported. As infection is a major cause of human death and a mechanism of natural selection, we hypothesized that VNTR polymorphism of DC-SIGNR might have an effect on human life span.</p> <p>Methods</p> <p>Here we collected 361 peri-centenarian individuals (age ≥94 for female and age ≥90 for male) and 342 geographically matched controls (age 22-53, mean 35.0 ± 12.0) from Han Chinese. The VNTR polymorphism of the neck region was determined by PCR and genotype was called by separating the PCR products in agarose gel.</p> <p>Results</p> <p>A total of 11 genotypes and 5 alleles were found in our population. The genotype distribution, allele frequencies and homozygote proportion did not show a significant difference between peri-centenarian and control group. As gender differences in lifespan are ubiquitously observed throughout the animal kingdom, we then stratified the samples by gender. There was more 6/7 genotypes in female peri-centenarian group than that in female control group, at a marginal level of significance (5.56 vs. 1.28%, p = 0.041). The difference was not significant after correction by Bonferroni method. It suggests a possible differential effect of DC-SIGNR VNTR genotypes between sexes. Further studies are warranted to confirm our preliminary findings and investigate the mechanisms of the underlying functions.</p> <p>Conclusions</p> <p>Our study indicated that there was absence of association between the neck region polymorphism of DC-SIGNR and longevity in Han Chinese population. But the question of whether the DC-SIGNR could affect longevity in a gender-specific pattern remains open.</p

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal