Genome scan meta-analysis of schizophrenia and bipolar disorder,part III: Bipolar disorder

Genome scans of bipolar disorder (BPD) have not produced consistent evidence for linkage. The rank-based genome scan meta-analysis (GSMA) method was applied to 18 BPD genome scan data sets in an effort to identify regions with significant support for linkage in the combined data. The two primary analyses considered available linkage data for “very narrow” (i.e., BP-I and schizoaffective disorder–BP) and “narrow” (i.e., adding BP-II disorder) disease models, with the ranks weighted for sample size. A “broad” model (i.e., adding recurrent major depression) and unweighted analyses were also performed. No region achieved genomewide statistical significance by several simulation-based criteria. The most significant P values (<.01) were observed on chromosomes 9p22.3-21.1 (very narrow), 10q11.21-22.1 (very narrow), and 14q24.1-32.12 (narrow). Nominally significant P values were observed in adjacent bins on chromosomes 9p and 18p-q, across all three disease models on chromosomes 14q and 18p-q, and across two models on chromosome 8q. Relatively few BPD pedigrees have been studied under narrow disease models relative to the schizophrenia GSMA data set, which produced more significant results. There was no overlap of the highest-ranked regions for the two disorders. The present results for the very narrow model are promising but suggest that more and larger data sets are needed. Alternatively, linkage might be detected in certain populations or subsets of pedigrees. The narrow and broad data sets had considerable power, according to simulation studies, but did not produce more highly significant evidence for linkage. We note that meta-analysis can sometimes provide support for linkage but cannot disprove linkage in any candidate region.     

Degradation of antifouling biocides

The relative biodegradability in seawater of a number of compounds in current use in antifouling paints viz. Sea-Nine? 211 antifoulant (4,5-dichloro-2-n-octyl-4-isothiazolin-3-one), Irgarol(R) 1051 (2-methylthio-4-tert-butylamino-6-cyclopropylamino-s-triazine), diuron (3-(3,4-dichlorophenyl)l-l-dimethylurea), chlorothalonil (tetrachloroisophthalonitrile) and TBTO (tributyltin oxide) was investigated. The disappearance of the each compound from seawater was monitored over 8 w by bioassay using the ship-fouling diatom Amphora coffeaeformis. The results show, that under the test conditions employed, biodegradability ranges from very readily biodegradable (Sea-Nine 211) to non-biodegradable (diuron and Irgarol 1051). The results are discussed in relation to published data on biocide degradation.     

The application of track calculations to radiobiology. III. Analysis of the molecular beam experiment results

Survival data from the molecular beam experiment are used to obtain an estimate of the function gamma (chi), describing the probability for two energy transfers a distance chi apart to produce a lesion. A comparison is made between the functions gamma (chi) obtained using proximity functions calculated with Monte Carlo-generated tracks and with simplifying assumptions (the LET approximation). The results differ substantially, which shows that the results are very sensitive to the degree of detail used in characterizing the physics of the irradiating field.     

Ordination of boreal heath-like vegetation with principal component analysis,correspondence analysis and multidimensional scaling

Four relatively homogeneous field data sets were analyzed, representing boreal, heath-like forest-floor and rock vegetation in Finland, corresponding to Finnish Calluna and Cladina site types. The methods used were principal component analysis (PCA) of covariance matrices, orthogonal correspondence analysis or reciprocal averaging (RA), detrended correspondence analysis (DCA), and linear and nonmetric multidimensional scaling (MDS). RA and DCA gave ordinations in which every species had nearly equal weight. MDS and PCA gave results determined mostly by a few dominant species. MDS and PCA ordinations were very similar to RA and DCA ones when the original data were standardized so that for each species the mean of positive occurrences was the same while quantitative differences within species were retained. RA and PCA were generally very good and reliable, providing that the impact of rare species and outlier relevés was removed in RA. DCA was slightly less reliable than RA. MDS was sensitive to uneven sampling patterns and was the least reliable method compared.     

Predicting chemical carcinogenesis in rodents: The state of the art in light of a comparative exercise

Within a recent comparative exercise, different approaches to the prediction of rodent carcinogenicity were challenged on a common set of chemicals bioassayed by the U.S. National Toxicology Program. The approaches were of very different natures. Some prediction systems looked for relationships between carcinogenicity and other, more quickly detectable biological events (activity-activity relationships, AAR). Some approaches tended to find structure-activity relationships (SAR). To give an objective evaluation of the results of the exercise, we have analyzed the rodent results and the predictions with the multivariate data analysis methods. The calculated performances varied according to the adopted carcinogenicity classification of the chemicals. When the four rodent results were summarized into a final + or − call, the Tennant approach (AAR method) showed the best performance (about 75% accuracy), whereas the best SAR systems had 60–65% accuracy. A common limitation of almost all the systems was the lack of specificity (too many false positives). Based on these results, better concordance was obtained when the input information was the very costly (and closer to the final endpoint) biological data, rather than the inexpensive (and farther from the endpoint) knowledge of the chemical structure. However, when the rodent results were summarized into a carcinogenicity classification that maintained, to some extent, the gradation intrinsic to the original experimental data, the performance of the AAR systems declined, and the SAR approaches showed a better performance. The difficulty in evaluating the various approaches was further complicated because of a fundamental difference in the approaches themselves: some approaches were ‘pure’ prediction methods (i.e. their predictions were rigorously based on information not inclusive of carcinogenicity); other approaches (e.g. Tennant, Weisburger) used ‘mixed’ information, inclusive of known carcinogenicity results from experiments performed before the NTP bioassays. As far as the SAR systems are concerned, their sets of predictions showed a fundamental similarity. This happened in spite of the extremely different procedures adopted to treat the chemical formula (initial information): very simple calculations (Benigni), intuition of the experts (Weisburger and Lijinsky), sophisticated computer programs (TOPKAT and CASE). The results of the Bakale Ke method, based on the experimental measurement of the chemical electrophilicity, and of the Salmonella typhimurium mutagenicity assay were similar to the patterns of predictions of the SAR methods.     

Normalized correlation dimension for heart rate variability analysis.

In this paper we use the concept of large-scale dimension densities to analyze heart rate variability data. This method uses a normalized Grassberger-Procaccia algorithm and estimates the dimension in the rather large scales of the system. This enables us to analyze very short data. First we re-analyze data from the CIC 2002 challenge and can completely distinguish between real data and computer-generated data using only one parameter. We then analyze unfiltered data for 15 patients with atrial fibrillation (AF), 15 patients with congestive heart failure (CHF), 15 elderly healthy subjects, and 18 young healthy subjects. This method can completely separate the AF group from the other groups and the CHF patients show significant differences compared to the young and elderly healthy volunteers. Furthermore, differences are evident in the dimensionality between day and night for healthy persons, but not for the CHF patients. Finally, the results are compared to standard heart rate variability parameters.     

Phylogeny of major lineages of suboscines (Passeriformes) analysed by nuclear DNA sequence data

Phylogenetic relationships among major groups of passeriform birds were studied by analyses of nucleotide sequence data from two nuclear genes, c- myc and RAG-1. The results corroborated both the monophyly of the order Passeriformes, and the major dichotomy into oscine and suboscine passerines previously suggested based on syringeal morphology and DNA-DNA hybridizations. The representatives of the Old World suboscines (families Eurylaimidae, Philepittidae and Pittidae) formed a monophyletic clade. The New World suboscines clustered into two clades. The first contained Conopophaga (Conopophagidae), Furnarius (Furnariidae), Lepidocolaptes (Dendrocolaptidae), Thamnophilus (Formicariidae), and Rhinocrypta (Rhinocryptidae). Previously, the monophyly of this group has been inferred from their possession of a unique, "tracheophone" syrinx, and from DNA-DNA hybridisation data. The second clade of New World suboscines includes Gubernetes and Muscivora (Tyrannidae), Phytotoma (Phytotomidae), Tityra (Cotingidae) and Pipra (Pipridae). This group of families have been considered monophyletic based on morphology (although ambiguously) and DNA-DNA hybridisation. The sister group relationship of Tityra and Phytotoma supports the previously supposed cotingid affinity of Phytotoma . Nuclear DNA data also unambiguously group the lyrebirds Menura with the oscines.
The presented results from the analysis of nuclear DNA agree well with morphology and DNA-DNA hybridisation data. The precise age of the divergences studied herein are unknown but based on interpretations of the fossil record of passerine birds many of them might date back to the early Tertiary. The agreement between data from the nuclear DNA and other sources, along with the fact that neither of the studied genes showed sign of saturation, indicate the great potential of these two nuclear genes to resolve very old divergences in birds.     

Molecular dynamics simulations of the insertion of two ideally amphipathic lytic peptides LK(15) and LK(9) in a 1,2-dimyristoylphosphatidylcholine monolayer.

We present here the results of 1-ns molecular dynamics (MD) simulations of two ideally amphipathic lytic peptides, namely LK(15) and LK(9), in a 1,2-dimyristoylphosphatidylcholine monolayer with two different cross-sectional areas per lipid of 80 A(2) (loose film) and 63 A(2) (tight standard film). These peptides are lytic, ideally amphipathic with a minimalist composition L(i)K(j) and the following sequences: H(2)N-KLLKLLLKLLLKLLK-CO-Ph for LK(15) and H(2)N-KLKLKLKLK-CO-Ph for LK(9). From experimental data, LK(15) exhibits an alpha-helical secondary structure, whereas LK(9) was found to form antiparallel beta-sheets at the interface of a DMPC monolayer. Whatever the specific lipid surface is, the two peptides exhibit very different behavior: the alpha-helix inserts deeply into the monolayer whereas the beta-sheeted peptide stays at the surface within the upper polar part of the monolayer. In all cases, a loose monolayer (80 A(2)) results in noticeable artifacts whereas a monolayer with standard specific surface leads to very reliable behavior well in accordance with experimental data. Despite their different insertion depth, the two peptides exhibit identical lytic efficiency. This is very likely a direct consequence of the very strong Van der Waals interactions between the fatty alkyl chains of the lipids and the highly lipophilic lower part of the peptide, resulting in an identical thinning of the two monolayers.     

Parsimony, likelihood, and simplicity

The latest charge against parsimony in phylogenetic inference is that it involves estimating too many parameters. The charge is derived from the fact that, when each character is allowed a branch length vector of its own (instead of the homogeneous branch lengths assumed in current likelihood models), the results for likelihood and parsimony are identical. Parsimony, however, can also be derived from simpler models, involving fewer parameters. Therefore, parsimony provides (as many authors had argued before) the simplest explanation of the data, or the most realistic, depending on one's views. If (as argued by likelihoodists) phylogenetic inference is to use the simplest model that provides sufficient explanation of the data, the starting point of phylogenetic analyses should be parsimony, not maximum likelihood. If the addition of new parameters (which increase the likelihood) to a parsimony estimation is seen as desirable, this may lead to a preference for results based on current likelihood models. If the addition of parameters is continued, however, the results will eventually come back to the same place where they had started, since allowing each character a branch length of its own also produces parsimony. Parsimony can be justified by very different types of models—either very complex or very simple. This suggests that parsimony does have a unique place among methods of phylogenetic estimation.     

Resolving and dating the phylogeny of Cornales--Effects of taxon sampling, data partitions, and fossil calibrations

The order Cornales descends from the earliest split in the Asterid clade of flowering plants. Despite a few phylogenetic studies, relationships among families within Cornales remain unclear. In the present study, we increased taxon and character sampling to further resolve the relationships and to date the early diversification events of the order. We conducted phylogenetic analyses of sequence data from 26S rDNA and six chloroplast DNA (cpDNA) regions using parsimony (MP), maximum likelihood (ML), and Bayesian inference (BI) methods with different partition models and different data sets. We employed relaxed, uncorrelated molecular clocks on BEAST to date the phylogeny and examined the effects of different taxon sampling, fossil calibration, and data partitions. Our results from ML and BI analyses of the combined cpDNA sequences and combined cpDNA and 26S rDNA data suggested the monophyly of each family and the following familial relationships ((Cornaceae-Alangiaceae)-(Curtisiaceae-Grubbiaceae))-(((Nyssaceae-Davidiaceae)-Mastixiaceae)-((Hydrostachyaceae-(Hydrangeaceae-Loasaceae))). These relationships were strongly supported by posterior probability and bootstrap values, except for the sister relationship between the N-D-M and H-H-L clades. The 26S rDNA data and some MP trees from cpDNA and total evidence suggested some alternative alignments for Hydrostachyaceae within Cornales, but results of SH tests indicated that these trees were significantly worse explanations of the total data. Phylogenetic dating with simultaneous calibration of multiple nodes suggested that the crown group of Cornales originated around the middle Cretaceous and rapidly radiated into several major clades. The origins of most families dated back to the late Cretaceous except for Curtisiaceae and Grubbiaceae which may have diverged in the very early Tertiary. We found that reducing sampling density within families and analyzing partitioned data sets from coding and noncoding cpDNA, 26S rDNA, and combined data sets produced congruent estimation of divergence times, but reducing the number and changing positions of calibration points resulted in very different estimations.     

An adaptive neuro-fuzzy method (<Emphasis Type="Italic">ANFIS</Emphasis>) for estimating single-trial movement-related potentials

This study aims to recover transient, trial-varying evoked potentials (EPs), in particular the movement-related potentials (MRPs), embedded within the background cerebral activity at very low signal-to-noise ratios (SNRs). A new adaptive neuro-fuzzy technique will attempt to estimate movement-related potentials within multi-channel EEG recordings, enabling this method to completely adapt to each input sweep without system training procedures. We assume that one of the sensors is corrupted by noise deriving from other sensors via an unknown function that will be estimated. We will approach this problem by: (1) spatially decorrelating the sensors in the preprocessing phase, (2) choosing the most informative of the filtered channels that will permit the best MRP estimation (input-selection phase) and (3) training the neuro-fuzzy model to fit the noise over the chosen sensor and therefore estimating the buried MRP. We tested this framework with simulations to validate the analytical results before applying them to the real biological data. Whenever it is applied to biological data, this method improves the SNR by more than 12dB, even to very low SNRs. The processing method proposed here is likely to complement other estimation techniques and can be useful to process, enhance and analyse single-trial MRPs.     

用图论方法研究核酸序列的密码子使用与基因表达水平的关系

研究了Escherichiacoli（115个基因）和SacharomycesYeast（97个基因）核酸序列的密码子使用频率与基因表达水平的关系．将同义密码子按使用频率统计值分成三种特性的密码子：最适密码子（H）、非最适密码子（L）和稀有密码子（R）,对每一基因序列的编码区,算出它们各自出现的概率P（H）,P（L）和P（R）．以P（H）和P（R）为指标,用图论法聚类,发现每种生物的高低表达基因明显分开,基因表达水平被分为四级：甚高表达基因（VH）、高表达基因（H）、较低表达基因（LM）和低表达基因（LL）．每类基因的表达水平与实验结果保持了很好的相关性,与E．coli和Yeast的现有资料相比,符合很好．     

气候变化与水稻生长发育及产量形成关系的模拟研究

应用水稻生长日历模拟模型(RICAM1.3)模拟亚洲地区不同地点和不同气候条件下水稻的生育期和产量形成.其中3s-Beta模型被用于预测水稻开花期和描述水稻光温反应的3个连续阶段:基本营养生长期、光敏感期和光敏感后期.从时间与地理梯度的变化对水稻产量进行模拟,以中国、日本和菲律宾作为从北到南的地理梯度,以20世纪80年代气候变化作为时间梯度,应用RICAM1.3进行模拟.结果表明,模型具有广泛的适应性,能较好地模拟不同气候条件和不同水稻品种生育期的变化与产量的形成.     

A quantitative histochemistry technique for measuring regional distribution of acetylcholinesterase in the brain using digital scanning densitometry

Studies of brain acetylcholinesterase (AChE) are traditionally based on biochemical assays, immunoreactivity, and histochemistry. Conventional histochemistry yields rich morphological data from tissue sections but yields quantitative results only with great difficulty. Several histochemical methods developed in recent years, including microdensitometry, microphotometry, and video-based histochemistry, are effective in quantitative and detailed study of AChE in tissue sections. However, they are usually time-consuming. As we report here, we adapted digital scanning densitometry to quantitate AChE histochemical staining in brain sections. The AChE and butyrylcholinesterase (BuChE), as measured by the method, were heterogeneously distributed throughout the brain, results that are consistent with those obtained by biochemical methods. The staining intensity is dependent on section thickness, substrate concentration, and reaction time. The cholinesterase inhibitor methyl paraoxon significantly decreased AChE staining intensity. Furthermore, data acquired from densitometry are similar to those obtained by video-based microscopy or by spectrophotometry. The advantage of the densitometric measurements compared to other quantitative histochemical methods is that it is very rapid while collecting data that are equivalent in quality. Because the digital scanning densitometers provide high quality and sensitive imaging, wide dynamic ranges, and convenient image analysis software, they are very useful tools in quantitative histochemistry.     

Flow cytometric determination of Enterococcus spp. susceptibility to four antimicrobial agents

Two Enterococcus strains (E. faecalis and E. faecium) isolated from 2 patients in an intensive care unit (blood and drain, respectively) were analyzed for susceptibility to 4 antibiotics (penicillin, vancomycin, gentamicin, streptomycin) by agar dilution standard method (MICs), time-kill and flow cytometry. We compared the data from classical methods of antibiotic susceptibility detection, that are compulsory 24 hrs long and flow cytometry results at 5 and 24 hrs cultivation. The results from both classical and flow cytometric analyses were highly cogent and revealed the fact that flow cytometry is very useful in early diagnosis of bacterial resistance to antibiotics.     

香菇栽培种线粒体DNA和核糖体DNA多态性研究初探

本文应用RFLP技术研究了10个香菇主栽品种的线粒体DNA（mtDNA）和核糖体DNA（rDNA）的部分小区段,利用PCR技术扩增了rDNA5．8＋ITS区段及mtDNA的小区段,分析这些片段的限制性酸切图谱,并进行菌株间的遗传相似系数的估算。结果显示：菌株间的rDNA在5．8＋ITS区段差异很小,表明同一种内菌株间的rDNA具有相对的遗传稳定性;不同菌株间未检出mtDNA的差异,表明菌株间在所研究的区段具有很高的遗传相似性。     

Modeling of submerged membrane bioreactor treating cheese whey wastewater by artificial neural network

A submerged membrane bioreactor receiving cheese whey was modeled by artificial neural network and its performance over a period of 100 days at different solids retention times was evaluated with this robust tool. A cascade-forward network was used to model the membrane bioreactor and normalization was used as a preprocessing method. The network was fed with two subsets of operational data, with two-thirds being used for training and one-third for testing the performance of the artificial neural network. The training procedure for effluent chemical oxygen demand (COD), ammonia, nitrate and total phosphate concentrations was very successful and a perfect match was obtained between the measured and the calculated concentrations. The results of the confirmation (or testing) procedure for effluent ammonia and nitrate concentrations were very successful; however, the results of the confirmation procedure for effluent COD and total phosphate concentrations were only satisfactory.     

Joint analysis of single-cell and bulk tissue sequencing data to infer intratumor heterogeneity

Many computational methods have been developed to discern intratumor heterogeneity (ITH) using DNA sequence data from bulk tumor samples. These methods share an assumption that two mutations arise from the same subclone if they have similar mutant allele-frequencies (MAFs), and thus it is difficult or impossible to distinguish two subclones with similar MAFs. Single-cell DNA sequencing (scDNA-seq) data can be very informative for ITH inference. However, due to the difficulty of DNA amplification, scDNA-seq data are often very noisy. A promising new study design is to collect both bulk and single-cell DNA-seq data and jointly analyze them to mitigate the limitations of each data type. To address the analytic challenges of this new study design, we propose a computational method named BaSiC (B ulk tumor a nd Si ngle C ell), to discern ITH by jointly analyzing DNA-seq data from bulk tumor and single cells. We demonstrate that BaSiC has comparable or better performance than the methods using either data type. We further evaluate BaSiC using bulk tumor and single-cell DNA-seq data from a breast cancer patient and several leukemia patients.     

The use of the potentials of the molecular hybridization of nucleic acids as a method for the laboratory diagnosis of influenza in research on vaccinal infection

The data obtained as the result of the complex examination of volunteers immunized with live influenza vaccine, type A (H3N2), showed that the determination of the RNA-containing structures by the method of the molecular hybridization of nucleic acids (MHNA) was highly sensitive and reliable. This method proved to be more sensitive than common laboratory diagnostic tests (the isolation of the virus in chick embryos, the analysis of seroconversion, the antibody fluorescence test) and was not inferior to the complex of clinical tests based on the analysis of microsymptoms. The reliability of the positive (according to the data obtained by MHNA) results was very high: not less than 85% of them were confirmed by other tests.