Dual Selection Research Articles

Protein-coding structured RNAs: A computational survey of conserved RNA secondary structures overlapping coding regions in drosophilids

Functional RNA elements can be embedded also within exonic sequences coding for functional proteins. While not uncommon in viruses, only a few examples of this type have been described in some detail for eukaryotic genomes. Here we use RNAz and RNAcode, two comparative genomics methods that measure signatures of stabilizing selection acting on RNA secondary structure and peptide sequence, resp., to survey the fruit fly genomes. We estimate that there might be on the order of 1000 loci that are subject to dual selection pressure. The used genome-wide screens also expose the limitations of the currently available methods.

Co-cultivation of murine BMDCs with 67NR mouse mammary carcinoma cells give rise to highly drug resistant cells

BackgroundTumor tissue resembles chronically inflamed tissue. Since chronic inflammatory conditions are a strong stimulus for bone marrow-derived cells (BMDCs) it can be assumed that recruitment of BMDCs into cancer tissue should be a common phenomenon. Several data have outlined that BMDC can influence tumor growth and metastasis, e.g., by inducing a paracrine acting feedback loop in tumor cells. Likewise, cell fusion and horizontal gene transfer are further mechanisms how BMDCs can trigger tumor progression.ResultsHygromycin resistant murine 67NR-Hyg mammary carcinoma cells were co-cultivated with puromycin resistant murine BMDCs from Tg(GFPU)5Nagy/J mice. Isolation of hygromycin/puromycin resistant mBMDC/67NR-Hyg cell clones was performed by a dual drug selection procedure. PCR analysis revealed an overlap of parental markers in mBMDC/67NR-Hyg cell clones, suggesting that dual resistant cells originated by cell fusion. By contrast, both STR and SNP data analysis indicated that only parental 67NR-Hyg alleles were found in mBMDC/67NR-Hyg cell clones favoring horizontal gene transfer as the mode of origin. RealTime-PCR-array analysis showed a marked up-regulation of Abcb1a and Abcb1b ABC multidrug transporters in mBMDC/67NR-Hyg clones, which was verified by Western Blot analysis. Moreover, the markedly increased Abcb1a/Abcb1b expression was correlated to an efficient Rhodamine 123 efflux, which was completely inhibited by verapamil, a well-known Abcb1a/Abcb1b inhibitor. Likewise, mBMDCs/67NR-Hyg clones revealed a marked resistance towards chemotherapeutic drugs including 17-DMAG, doxorubicin, etoposide and paclitaxel. In accordance to Rhodamine 123 efflux data, chemotherapeutic drug resistance of mBMDC/67NR-Hyg cells was impaired by verapamil mediated blockage of Abc1a/Abcb1b multidrug transporter function.ConclusionCo-cultivation of mBMDCs and mouse 67NR-Hyg mammary carcinoma cells gave rise to highly drug resistant cells. Even though it remains unknown whether mBMDC/67NR-Hyg clones originated by cell fusion or horizontal gene transfer, our data indicate that the exchange of genetic information between two cellular entities is crucial for the origin of highly drug resistant cancer (hybrid) cells, which might be capable to survive chemotherapy.

Investigating the Host Binding Signature on the Plasmodium falciparum PfEMP1 Protein Family

The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family plays a central role in antigenic variation and cytoadhesion of P. falciparum infected erythrocytes. PfEMP1 proteins/var genes are classified into three main subfamilies (UpsA, UpsB, and UpsC) that are hypothesized to have different roles in binding and disease. To investigate whether these subfamilies have diverged in binding specificity and test if binding could be predicted by adhesion domain classification, we generated a panel of 19 parasite lines that primarily expressed a single dominant var transcript and assayed binding against 12 known host receptors. By limited dilution cloning, only UpsB and UpsC var genes were isolated, indicating that UpsA var gene expression is rare under in vitro culture conditions. Consequently, three UpsA variants were obtained by rosette purification and selection with specific monoclonal antibodies to create a more representative panel. Binding assays showed that CD36 was the most common adhesion partner of the parasite panel, followed by ICAM-1 and TSP-1, and that CD36 and ICAM-1 binding variants were highly predicted by adhesion domain sequence classification. Binding to other host receptors, including CSA, VCAM-1, HABP1, CD31/PECAM, E-selectin, Endoglin, CHO receptor “X”, and Fractalkine, was rare or absent. Our findings identify a category of larger PfEMP1 proteins that are under dual selection for ICAM-1 and CD36 binding. They also support that the UpsA group, in contrast to UpsB and UpsC var genes, has diverged from binding to the major microvasculature receptor CD36 and likely uses other mechanisms to sequester in the microvasculature. These results demonstrate that CD36 and ICAM-1 have left strong signatures of selection on the PfEMP1 family that can be detected by adhesion domain sequence classification and have implications for how this family of proteins is specializing to exploit hosts with varying levels of anti-malaria immunity.

Influence of Major HIV-1 Protease Inhibitor Resistance Mutations on CTL Recognition

HIV-1 protease is subjected to dual selection pressure exerted by protease inhibitors (PIs) and cytotoxic T lymphocytes (CTL). Recently, we identified KMIGGIGGF (KF9) as a HLA-B*1501-restricted CTL epitope, including several major PI resistance mutations (M46I/L, I47A/V, G48V, I50V). To assess potential interactions between KF9-specific CTL and emergence of these important resistance mutations, we studied CTL recognition of the mutations and analyzed protease sequences in an HLA-I–typed patient cohort. CTL recognition of KF9 and resistance mutations in KF9 were studied in 38 HLA-B*1501-positive HIV-1–infected patients using variant KF9 peptides in interferon-g enzyme-linked immunospot assays. Protease sequences were analyzed in 302 HLA-I–typed HIV-1–infected patients. G48V abolished KF9 recognition by CTL in all patients. Furthermore, M46I, I47A, and I50V could impair or abolish CTL recognition in many patients. In contrast, M46L and I47V showed good CTL recognition in nearly all patients. HIV-1 protease sequence analysis showed no statistical correlation between the occurrence of resistance mutations in KF9 and HLA-B*1501. Viral load in patients failing therapy with KF9 mutations was significantly lower in HLA-B*1501-positive patients in comparison with HLA-B*1501-negative patients. PI mutations, G48V, M46I, and I47A, can abrogate CTL recognition, indicating potential interactions between development of drug resistance and CTL response. However, we could not find evidence that development of these PI mutations is influenced by KF9-specific CTL.

QSAR Analysis for Some Diaryl‐substituted Pyrazoles as CCR2 Inhibitors by GA‐Stepwise MLR

Quantitative relationships between calculated molecular structure and 26 diaryl-substituted pyrazoles CCR2 inhibitors were investigated by GA-stepwise multiple linear regression. In multiple linear regression analysis, the quantitative structure-activity relationship models were constructed by grouping descriptors and also dual selection of variables using genetic algorithm and stepwise selection methods from each group of the pool of all calculated descriptors. The accuracy of the proposed multiple linear regression model was demonstrated using the following evaluation techniques: cross-validation, validation through an external test set, and Y-randomization. Furthermore, the domain of applicability that shows the area of reliable predictions was defined. The prediction results were in good agreement with the experimental values.

Dual selection mechanisms drive efficient single-gene reverse genetics for rotavirus

Current methods for engineering the segmented double-stranded RNA genome of rotavirus (RV) are limited by inefficient recovery of the recombinant virus. In an effort to expand the utility of RV reverse genetics, we developed a method to recover recombinant viruses in which independent selection strategies are used to engineer single-gene replacements. We coupled a mutant SA11 RV encoding a temperature-sensitive (ts) defect in the NSP2 protein with RNAi-mediated degradation of NSP2 mRNAs to isolate a virus containing a single recombinant gene that evades both selection mechanisms. Recovery is rapid and simple; after two rounds of selective passage the recombinant virus reaches titers of ≥10(4) pfu/mL. We used this reverse genetics method to generate a panel of viruses with chimeric NSP2 genes. For one of the chimeric viruses, the introduced NSP2 sequence was obtained from a pathogenic, noncultivated human RV isolate, demonstrating that this reverse genetics system can be used to study the molecular biology of circulating RVs. Combining characterized RV ts mutants and validated siRNA targets should permit the extension of this "two-hit" reverse genetics methodology to other RV genes. Furthermore, application of a dual selection strategy to previously reported reverse genetics methods for RV may enhance the efficiency of recombinant virus recovery.

Conditional means of the dependent variable in a double-selection model: The roles of diet and exercise in body weight

We derive the conditional means of the dependent variables and their marginal effects in a dual ordinal selection model with log-transformed and untransformed dependent variables. Results are applied to a body mass index equation with endogenous diet and exercise treatments.

Average Level Crossing Rate of Dual Selection Diversity in Correlated Rician Fading with Rayleigh Cochannel Interference

We present an infinite-series representation for the average level crossing rate (LCR) of dual selection combining (SC) receivers, operating over correlated Rician fading channels, in the presence of Rayleigh cochannel interference (CCI). Numerical results are presented to illustrate the proposed mathematical analysis and to point out the effect of the branch correlation and fading severity on the average LCR.

Assessment of dual selection in grid based selectivity systems

Herein we propose a method to assess dual selection in grid based selectivity systems. This method takes into account the parameter “grid contact likelihood” (C grid ), which can be interpreted as the proportion of fish that actually makes an attempt to escape through the grid. In a case study of the Barents Sea cod and haddock trawl fishery, we demonstrate that our model describes the experimental data better than the models previously used to fit similar data. For both cod and haddock, C grid was significantly smaller than 1.0, which demonstrated the relevance of the proposed model. C grid was higher for haddock than for cod, which might be due to behavioral differences between the species. The C grid values for both species suggest that the grid functions well, as on average more than 75% of the cod and more than 94% of the haddock were predicted to able to attempt an escape through the device. For both species the contact L50 for the grid (L50 grid ) was significantly higher than the L50 for the codend (L50 codend ). These values agree with the experimental observations that most of the escaping fish use the grid to escape, whereas only a very few escape occurs through the codend. By parametric simulation and using the case study results as the baseline, we investigated and compared the precision of the selectivity parameters estimated with our model for two different experimental setups. The results show that except for some extreme situations, the data for such studies need to be collected with a three-compartment setup to avoid imprecise estimates of C grid , L50 grid , SR grid , L50 codend , and SR codend . In general, only the combined selectivity of the grid and the codend could be estimated with acceptable precision using a standard two-compartment sampling approach.

Exercise and global well-being in community-dwelling adults with fibromyalgia: a systematic review with meta-analysis

BackgroundExercise has been recommended for improving global-well being in adults with fibromyalgia. However, no meta-analysis has determined the effects of exercise on global well-being using a single instrument and when analyzed separately according to intention-to-treat and per-protocol analyses. The purpose of this study was to fill that gap.MethodsStudies were derived from six electronic sources, cross-referencing from retrieved studies and expert review. Dual selection of randomized controlled exercise training studies published between January 1, 1980 and January 1, 2008 and in which global well-being was assessed using the Fibromyalgia Impact Questionnaire (FIQ) were included. Dual abstraction of data for study, subject and exercise program characteristics as well as assessment of changes in global well-being using the total score from the FIQ was conducted. Risk of bias was assessed using the Cochrane bias assessment tool. Random-effects models and Hedge's standardized effect size (g) were used to pool results according to per-protocol and intention-to-treat analyses.ResultsOf 1,025 studies screened, 7 representing 5 per-protocol and 5 intention-to-treat outcomes in 473 (280 exercise, 193 control) primarily female (99%) participants 18-73 years of age were included. Small, statistically significant improvements in global well-being were observed for per-protocol (g and 95% confidence interval, -0.39, -0.69 to -0.08) and intention-to-treat (-0.34, -0.53 to -0.14) analyses. No statistically significant within-group heterogeneity was found (per-protocol, Qw = 6.04, p = 0.20, I2 = 33.8%; intention-to-treat, Qw = 3.19, p = 0.53, I2 = 0%) and no between-group differences for per-protocol and intention-to-treat outcomes were observed (Qb = 0.07, p = 0.80). Changes were equivalent to improvements of 8.2% for per-protocol analyses and 7.3% for intention-to-treat analyses.ConclusionsThe results of this study suggest that exercise improves global well-being in community-dwelling women with fibromyalgia. However, additional research on this topic is needed, including research in men as well as optimal exercise programs for improving global well-being in adults.

The stratification of military service and combat exposure, 1934–1994

Previous research has suggested that men who were exposed to combat during wartime differed from those who were not. Yet little is known about how selection into combat has changed over time. This paper estimates sequential logistic models using data from the Panel Study of Income Dynamics to examine the stratification of military service and combat exposure in the US during the last six decades of the 20th century. It tests potentially overlapping hypotheses drawn from two competing theories, class bias and dual selection. It also tests a hypothesis, drawn from the life course perspective, that the processes by which people came to see combat have changed historically. The findings show that human capital, institutional screening, and class bias all determined who saw combat. They also show that, net of historical change in the odds of service and combat, the impact of only one background characteristic, race, changed over time.

Ion Transport Across Membranes Facilitated by a Dynamic Combinatorial Library

AbstractA dynamic combinatorial library (DCL) consisting of dialdehydes and diamines has been used to facilitate the transport of calcium ions across a supported liquid membrane (SLM). In a dual selection process, the calcium ions first select matching macrocycles 3 or 5 from the DCL. Then only one of the macrocycle–calcium complexes (5·Ca2+) efficiently transports the calcium ions due to its better balance between lipo‐ and hydrophilicity. The special setup of a DCL combined with an SLM directly finds suitable carriers for ion transport starting from diamine and dialdehyde building blocks 1, 2 and 4. The synthesis of the new, more lipophilic 4‐pentoxypyridine‐2,6‐dicarbaldehyde (4) is also described, and the first transport experiments with liposomes are discussed.

Dual Selectivity Expressed in [2 + 2 + 1] Dynamic Clipping of Unsymmetrical [2]Catenanes

A pi-templated dynamic [2 + 2 + 1] clipping protocol is established for the synthesis of [2]catenanes from two parts dialdehyde, two parts diamine, and one part tetracationic cyclophane. It is further diversified for the selective formation of an unsymmetrical [2]catenane showing great translational selectivity by employing two different dialdehydes in a one-pot reaction. The dual selectivity and the dynamic nature are verified by (1)H NMR spectroscopy, X-ray single-crystal structural studies, and exchange experiments.

Switching rates of two-branch selection diversity in correlated Doppler fading

The switching rate of a correlated dual branch selection diversity combiner in Rayleigh and Rician fading is derived in noise-free conditions. Balanced and unbalanced branches are considered. Numerical results are presented for a space-diversity system with horizontally spaced omnidirectional antennas at a mobile station.

Diacylglycerol Kinase ϵ Is Selective for Both Acyl Chains of Phosphatidic Acid or Diacylglycerol

The phosphatidylinositol (PI) cycle mediates many cellular events by controlling the metabolism of many lipid second messengers. Diacylglycerol kinase epsilon (DGK epsilon) has an important role in this cycle. DGK epsilon is the only DGK isoform to show inhibition by its product phosphatidic acid (PA) as well as substrate specificity for sn-2 arachidonoyl-diacylglycerol (DAG). Here, we show that this inhibition and substrate specificity are both determined by selectivity for a combination of the sn-1 and sn-2 acyl chains of PA or DAG, respectively, preferring the most prevalent acyl chain composition of lipids involved specifically in the PI cycle, 1-stearoyl-2-arachidonoyl. Although the difference in rate for closely related lipid species is small, there is a significant enrichment of 1-stearoyl-2-arachidonoyl PI because of the cyclical nature of PI turnover. We also show that the inhibition of DGK epsilon by PA is competitive and that the deletion of the hydrophobic segment and cationic cluster of DGK epsilon does not affect its selectivity for the acyl chains of PA or DAG. Thus, this active site not only recognizes the lipid headgroup but also a combination of the two acyl chains in PA or DAG. We propose a mechanism of DGK epsilon regulation where its dual acyl chain selectivity is used to negatively regulate its enzymatic activity in a manner that ensures DGK epsilon remains committed to the PI turnover cycle. This novel mechanism of enzyme regulation within a signaling pathway could serve as a template for the regulation of enzymes in other pathways in the cell.

여성의 유치원.보육시설 및 사교육 선택유형 분석

The purpose of this study was to analyze women`s selection pattern on kindergarten/child care centers and private tutoring for young children. For this purpose, 1,810 women whose young children`s age was between 2 and 6 were selected from KLoWF data. After categorizing the education centers as daycare center, kindergarten, and private institute, it was investigated the women`s characteristics related to their decision making for selection of the centers. The results of survey data analyses showed that younger children`s mothers preferred to send their children to daycare centers, older children`s mothers did to kindergarten. In terms of their dual selection on education centers, the frequency of 6-old-year children attending kindergarten and private institutes was very high. As the children`s age was increasing, the frequency of women`s multiple selection on daycare center, kindergarten and private institute was also increasing. In addition, regardless of the women`s job pattern and existence, they preferred to send children to daycare centers. With these findings, limitations and suggestions for the future studies were also discussed.

Switching rates of dual selection diversity in noisy fading channels

The effect of noise on the switching rate of a dual branch selection diversity combiner in noisy fading channels is examined. A closed-form solution is derived for independent and identically distributed (i.i.d.) and independent and nonidentically distributed (i.n.d.) fading channels. The switching rate in noisy fading channels is compared to that in noise-free conditions.

Monitoring neonicotinoid resistance in biotype B of Bemisia tabaci in Florida

Biotype B of the sweetpotato whitefly, Bemisia tabaci (Genn.), is a worldwide pest that has developed resistance to many insecticides, including the neonicotinoid class. Florida field populations were monitored for susceptibility to the neonicotinoids imidacloprid and thiamethoxam using a cut leaf petiole bioassay method. Average RR(50) values for imidacloprid increased from 3.7 in 2000 to 12.0 in 2003; decreased to 5.0 and 2.5 in 2004 and 2005, respectively; and then increased to 26.3 and 23.9 in 2006 and 2007, respectively. Populations with RR(50) values of about 50 to 60 during generation one reverted to RR(50) values of < or =4 in six generations, when reared without further exposure to imidacloprid. Average RR(50) values for thiamethoxam increased from 2.0 in 2003 to 24.7 in 2006 and decreased to 10.4 in 2007. Populations with RR(50) values of about 22, 32 and 53 during generation one declined to 8, 5 and 6, respectively, after being reared for five generations without exposure to thiamethoxam. The correlation coefficient from the 26 populations that were bioassayed both with imidacloprid and thiamethoxam showed a significant positive correlation (R(2) = 0.58) between these populations. The high level of RR(50) values to imidacloprid and thiamethoxam suggest an unstable decline in the susceptibility of B. tabaci to imidacloprid and thiamethoxam, with possible cross-resistance or predisposition for dual resistance selection.

Exploring the Complementary Selectivity of Immunocapture and MS Detection for the Differentiation between hCG Isoforms in Clinically Relevant Samples

Whereas numerous immunoassays have been developed to ensure detection of the entire spectrum of isoforms displayed by the human chorionic gonadotropin (hCG) molecule, significant variation has been demonstrated in how these isoforms are recognized by the antibodies in different immunoassays. The aim of this study was to establish a method using the dual selectivity of the immunoextraction and the mass spectrometry detection for the differentiation between various hCG isoforms in clinically relevant samples. Immunoextraction of endogenous hCG isoforms using a monoclonal antibody (E27) on a 96-well microtitier plate, followed by in-well tryptic digestion, and SIM monitoring of the selected signature peptides, resulted in the qualitative differentiation between several hCG isoforms in serum or urine. We conclude that the orthogonal selectivity conferred by the combination of immunoaffinity extraction and LC-MS analysis offers valuable complementary information to the conventional immunoassays.

Performance Analysis of Dual-Branch Selection Combining Over Correlated Rician Fading Channels for Desired Signal and Cochannel Interference

System performances of dual selection combining over fading channels are analyzed. Fading between the diversity branches and between interferences is correlated and Rician distributed. Infinite series expressions for the probability density function, and the cumulative distribution function of the output signal-to-interference ratio are derived, which is the main contribution of this paper. Outage probability and the average bit error probability for noncoherent modulation schemes are also presented. Numerical results, presented in this paper, point out the effects of fading severity and correlation on the system performances.