Bayesian Bootstrap Clones for Censored Markov Chains

In this article, we consider r observations from a non‐homogeneous censored Markov chain, with transition probability matrix P. For the product estimator of P proposed by Aalen and Johansen (1978) and Phelan (1988), we investigate the behavior of Bayesian bootstrap clones to approximate the sampling distribution of , and then construct approximate confidence interval. It is shown that the approximation based on the random‐weighted distribution is first‐order consistent. The performance of the Bayesian bootstrap clones (BBC) is also discussed by small sample simulation. Finally, we illustrate the BBC procedure in the application to the WHO malaria survey data (cf. Singer and Cohen 1970).     

The influence of ethanol on the functional status of GABA(A) receptors

Gamma aminobutyric acid (GABA) is one of the main inhibitory neurotransmitters in the mammalian brain. Its effects are realized via GABA_A, GABA_B, and GABA_C receptors. GABA_A is the most abundant type of GABA receptors. It consists of six classes of subunits, , , , , , and . Acute and chronic exposures to ethanol are accompanied by changes in structure and function of GABA_A receptors. These changes may be a basis for altered behavior seen in alcoholism.     

Descriptive morphology of the reared eggs,larvae, and juveniles of the marine atherinid fish <Emphasis Type="Italic">Atherinomorus duodecimalis</Emphasis>

Embryonic, larval, and juvenile development of the marine atherinid Atherinomorus duodecimalis are described from laboratory-reared specimens. The eggs, measuring 1.15–1.24mm in diameter, were demersal and almost spherical in shape with numerous chorionic filaments. Hatching occurred 7 or 8 days after spawning, the newly hatched larvae measuring 4.5–5.1mm in body length (BL) and having 5+34=39 myomeres. Notochord flexion started at 6.9mm BL and finished at 8.3mm BL. Aggregate numbers of all fin rays were completed by 14mm BL. Eggs of this species could be distinguished from other known atherinid eggs on the basis of egg diameter and the arrangement, length, and number of chorionic filaments. Larvae were also distinctive in myomere counts, pigmentation, and locations of the anus and second dorsal fin origin.     

Micropropagation of Phalaenopsis and Doritaenopsis by culturing shoot tips of flower stalk buds

Green Protocorm-like Bodies (PLB) with high multiplication capacity were induced from shoot tips of flower stalk buds having 1 or 2 leaf primordia using New Dogashima Medium (NDM) containing 0.1 mg l^–1 -naphthaleneacetic acid (NAA) and 1 mg 1^–1 6-benzylaminopurine (BAP). These PLB were subcultured on the same medium. More than 10,000 PLBs were obtained from a few buds on a single flower stalk within one year. After transfer onto NDM containing no plant growth regulator (PGR), the PLB developed into plantlets. The micropropagation method formulated in this study was applicable to 12 different genotypes. These results suggest that the methodology could be used on a commercial scale for vegetative propagation of Phalaenopsis and Doritaenopsis.Abbreviations PLB protocorm-like body - PGR plant growth regulator - NAA -naphthaleneacetic acid - BAP 6-benzylaminopurine - NDM New Dogashima Medium     

Murine MHC class Ib gene,<Emphasis Type="Italic"> H2-M2,</Emphasis> encodes a conserved surface-expressed glycoprotein

We have determined the genomic sequence of H2-M2 in seven haplotypes from nine inbred strains of mice and in five wild-derived haplotypes. Except for the spretus haplotype sp1 with a premature stop codon, we found only limited polymorphism. Four of the five amino acid substitutions in the -helices are at positions that would point out from the antigen-binding groove, indicating that the polymorphism might influence receptor recognition rather than antigen binding. The rat homologue, RT1.M2^lv1, has 89% identity to H2-M2 at the nucleotide level and 91% at the amino acid level, and it also encodes an intact MHC class I glycoprotein. Chimeric proteins with ₁₂ or ₃-transmembrane domains encoded by H2-Q9 were detectable on the surface of transfectants with monoclonal antibodies against Qa2, and the full-length M2 protein, labeled by fusion with green fluorescent protein, was detectable with S19.8 monoclonal antibodies. The H2-M2 protein was thus expressed on the cell surface, even in TAP-deficient RMA-S cells at 37 °C, suggesting that it is TAP-independent. We conclude that H2-M2 is a conserved mouse class Ib gene that is translated to a surface-expressed MHC class I molecule with a function still to be elucidated.The nucleotide sequences reported in this paper have been submitted to GenBank with the accession numbers AY302188–AY302217 for all H2-M2 sequences and AY302218 for RT1.M2, AY326271 for RT1.M2-2, and AY327254 for the RT1.M2 microsatellite marker     

Precision of the age–length increments of three cyprinids: effects of fish number and sub‐sampling strategy

The effects of number of fish that are aged and scale sub‐sampling strategies on the precision of estimates of mean age–length increments from populations of Rutilus rutilus, Leuciscus leuciscus and Leuciscus cephalus were tested. Analyses used data derived from river fish communities in eastern England, U.K.. Regarding the number of fishes analysed in each age group, for each species and mean fork‐length increment at age, significant relationships were detected between sample size (n) and the coefficient of variation of the mean (Z) and mean length increment and measured variance (s²). This enabled calculation of the number of scales for producing a mean length increment at age according to . Outputs indicated that the number of scales requiring ageing increased substantially as precision increased, but with little variation between species per age category. Ageing between seven and 12 scales per age group would thus provide estimates at 10% precision. As the ages of fishes are not known in advance of scale ageing, the effect of scale sub‐sampling regime on precision was also tested using randomized strategies of 10 fish per 5 mm, five per 5 mm, three per 5 mm, 10 per 10 mm, five per 10 mm and three per 10 mm. These were applied to the datasets and the consequences of their reduction in the number of scales for precision were determined using . When compared to no sub‐sampling, three per 10 mm always significantly reduced data precision, whereas 10 per 5 mm never significantly reduced precision. These outputs can thus be applied to the design of fish sampling protocols where age and growth estimates are required, with the randomized sub‐sampling likely to be the most useful strategy.     

Effects of some growth regulators on in vitro tuberization in Dioscorea alata L. ‘Brazo fuerte’ and D. abyssinica Hoch.

Summary Nodal cuttings of Dioscorea alata L. Brazo fuerte and D. abyssinica Hoch. were cultured in vitro to assess the influence of NAA on the production of microtubers. In D. alata, high concentrations of NAA (27 and 54 M) favored the production of large microtubers, whereas the highest number of microtubers was obtained with 2.7 M. D. abyssinica was found to be more sensitive to NAA since concentrations higher than 0.27 M promoted the growth of callus on the root system. In this species, the production of the largest microtubers was obtained at 2.7 M whereas the number of microtubers was not affected by any concentration tested. In D. alata, the effects of ABA and BAP were also evaluated. The weight of the microtubers increased with increasing concentrations of ABA. This effect, however, was observed only on expiants cultured under 8 h photoperiod, but not on those cultured under 16 h. Finally the presence of BAP at concentrations as low as 0.22 M adversely affected the survival of the explants.Abbreviations ABA abscissic acid - BAP benzyl aminopurine - NAA -naphthaleneacetic acid - MS Murashige and Skoog     

Construction of Prediction Intervals in Location-Scale Families

Let x₁ ≤x₂ ≤x₃ … ≤x_r be the r smallest observations out of n observations from a location-scale family with density $ \frac{1}{\sigma}f\left({\frac{{x - \mu}}{\sigma}} \right) $ where μ and σ are the location and the scale parameters respectively. The goal is to construct a prediction interval of the form $ \left({\hat \mu + k_1 \hat \sigma,\,\hat \mu + k_2 \hat \sigma} \right) $ for a location-scale invariant function, T(Y) = T(Y₁, …, Y_m), of m future observations from the same distribution. Given any invariant estimators $ \hat \mu $ and $ \hat \sigma $, we have developed a general procedure for how to compute the values of k₁ and k₂. The two attractive features of the procedure are that it does not require any distributional knowledge of the joint distribution of the estimators beyond their first two raw moments and $ \hat \mu $ and $ \hat \sigma $ can be any invariant estimators of μ and σ. Examples with real data have been given and extensive simulation study showing the performance of the procedure is also offered.     

Cremart: A new chemical for efficient induction of micronuclei in cells and protoplasts for partial genome transfer

Summary Results on efficient induction of micronuclei by Cremart in suspension cells and protoplasts of potato are reported. Cremart is a highly effective phosphoric amide herbicide, which acts on the mitotic spindle, and induces micronuclei through modification of mitosis. After treatment with Cremart, metaphase chromosomes changed directly into micronuclei without centromere division and chromatid separation. When suspension cells were treated with Cremart (3.7–15.0 M) for 48h, and subsequently incubated in a mixture of cell wall-digesting enzymes in the presence of cytochalasin-B and Cremart for 18h, the frequency of micronucleation in the cell/protoplast mixture increased significantly, as compared to that obtained after treatment of suspension cells with Cremart (3.7–15.0 M) for 48 h. Sieving after enzyme incubation resulted in the recovery of protoplasts, showing mass induction of micronuclei. Also synchronized suspension cells of Nicotiana plumbaginifolia responded with high frequency of micronucleation after Cremart (3.7 M) treatment. The application of this procedure for partial genome transfer is discussed.Abbreviations APM Amiprophos-methyl - BAP 6-Benzyl aminopurine - CB Cytochalasin-B - MI Mitotic index - MN Micronuclei - MS Murashige and Skoog - NAA 1-Naphthalene acetic acid     

On the accuracy of some mark-recapture estimators

Summary The behaviour of the mark-recapture estimators of Petersen, Bailey (triple catch) and Jolly and Seber are examined theoretically and empirically by means of simulation techniques. The correlation between the parameter and its associated variance is shown to be significant for all the estimators. This correlation makes the estimated variance an insensitive measure of the accuracy of the estimate except at very high sampling intensities. Such sampling intensities are rarely achieved in experimental work and so the method of mark-recapture must be considered of very limited use. At the sampling intensities necessary to give a coefficient of variation of less than 0.05 it does not seem likely that the correlation between and its variance will produce serious underestimation but the minimum confidence limits are recommended.     

Introns: Mighty Elements from the RNA World

The discovery of RNA-based enzymatic activity by Thomas Cechs and Sidney Altmans laboratories was a momentous event that led Walter Gilbert to the concept of an RNA world—a primitive ancient stage of life that existed before the appearance of DNA and protein molecules. A year later, Gilbert formulated the exon theory of genes, which hypothesized that introns are very ancient genetic elements present at the earliest stages of life in the RNA world. This theory has been fiercely debated and still has vigorous supporters and opponents. In this communication, we explore peculiarities in the RNA-protein world and their effect on intron–exon structures. We demonstrate that these peculiarities, which exist in the absence of DNA, could shed light on introns original functions as well as the important role they might have played in the origin of life. For ancient DNA-lacking cells, a crucial problem existed in distinguishing two distinct subsets of RNAs: those messenger molecules coding for proteins and those heritable genetic molecules complementary to messenger RNAs that propagate the genetic information through generations. We propose that ancient introns could act as markers of RNA subsets, directing them to different functions.Reviewing Editor: Dr. Manyuan Long     

speed‐ne: Software to simulate and estimate genetic effective population size (Ne) from linkage disequilibrium observed in single samples

The genetic effective population size, N_e, can be estimated from the average gametic disequilibrium () between pairs of loci, but such estimates require evaluation of assumptions and currently have few methods to estimate confidence intervals. speed‐ne is a suite of matlab computer code functions to estimate from with a graphical user interface and a rich set of outputs that aid in understanding data patterns and comparing multiple estimators. speed‐ne includes functions to either generate or input simulated genotype data to facilitate comparative studies of estimators under various population genetic scenarios. speed‐ne was validated with data simulated under both time‐forward and time‐backward coalescent models of genetic drift. Three classes of estimators were compared with simulated data to examine several general questions: what are the impacts of microsatellite null alleles on , how should missing data be treated, and does disequilibrium contributed by reduced recombination among some loci in a sample impact . Estimators differed greatly in precision in the scenarios examined, and a widely employed estimator exhibited the largest variances among replicate data sets. speed‐ne implements several jackknife approaches to estimate confidence intervals, and simulated data showed that jackknifing over loci and jackknifing over individuals provided ~95% confidence interval coverage for some estimators and should be useful for empirical studies. speed‐ne provides an open‐source extensible tool for estimation of from empirical genotype data and to conduct simulations of both microsatellite and single nucleotide polymorphism (SNP) data types to develop expectations and to compare estimators.     

Parametric and jackknife confidence interval estimators for two-factor mating design genetic variance ratios

Summary Confidence interval estimators have not been defined for dominance to additive genetic variance () and average degree of dominance () for the nested, factorial, and backcross mating designs. The objective of this paper was to describe interval estimators for these parameters. Approximate F random variables were defined for expected mean square (EMS) ratios for linear models with one environmental effect. Approximate 1– parametric interval estimators were defined for and using these random variables. Random variables defined for linear models with no environmental effects are not approximately distributed as F random variables because common EMS are involved in the numerators and denominators of the EMS ratios. Delete-one jackknife (jackknife) interval estimators were defined for and for linear models with zero or one environmental effect(s); In transformed analysis of variance point estimates were used in pseudovalue estimators.Oregon Agricultural Experiment Station Technical Paper No. 8067     

Organization of the genes encoding chalcone synthase in Pisum sativum

To analyze the regulation of defense-related genes by signal molecules produced by phytopathogens, we isolated genes that encode chalcone synthase (CHS) in Pisum sativum. We have obtained seven independent genomic clones that contain at least seven classes of CHS genes, identified by the hybridization analysis to CHS cDNA and by the restriction mapping analysis. Two of the genomic clones (clone 5 and 6) each contain two CHS genes in a tandem repeat. The nucleotide sequence analysis of CHS genomic clone 5 revealed that PsCHS1 and PsCHS2 were corresponding genes of the CHS cDNA clones, pCC6 and pCC2, respectively, as reported earlier. Both genes are interrupted by a single intron of 88 nucleotides with identical sequences, although exonic sequences and 5-flanking sequences are divergent. Nucleotide sequences of the introns in five other classes of CHS genes showed that three classes had an intron of 87 nt with a striking homology to each other, but that the intron of the other two classes of CHS genes showed heterogeneity both in size and nucleotide sequence. 5-upstream regions of PsCHS1 and PsCHS2 did not show sequence homology except the 31 bp identical sequence that contains the CCTACC motif resembling the box-1 sequence. Both PsCHS1 and PsCHS2 genes are shown to be induced by fungal elicitor by a primer extension analysis and a transient transformation analysis using pea protoplasts prepared from suspension cultured-cells.     

Water chemistry in the microenvironment of rainbow trout Oncorhynchus mykiss embryos is affected by development,the egg capsule and crowding

The hypothesis tested was that embryonic metabolism affects the water chemistry in the boundary layer. In addition, embryo crowding would further compound the metabolic effect on the water chemistry in the boundary layer. As development progressed, the magnitude of the boundary layer gradients for O₂ and pH, but not for NH, increased. The presence of the egg capsule hindered the diffusion of O₂ into and H⁺ and NH out of the embryo. The magnitude of the O₂, pH and NH boundary layer gradient was significantly increased when embryos were surrounded by either sham embryos or live embryos. The majority of this crowding effect on embryo boundary layers was due to changes in water flow rather than due to metabolism directly. These results clearly show that the microenvironment adjacent to the developing rainbow trout Oncorhynchus mykiss embryo becomes more stagnant as development progresses in the presence of the egg capsule and is further intensified with embryo crowding.     

Quantitative expression proteomics and phosphoproteomics profile of brain from PINK1 knockout mice: insights into mechanisms of familial Parkinson's disease

Parkinson's disease (PD) is an age‐related, neurodegenerative motor disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta and presence of α‐synuclein‐containing protein aggregates. Mutations in the mitochondrial Ser/Thr kinase PTEN‐induced kinase 1 (PINK1) are associated with an autosomal recessive familial form of early‐onset PD. Recent studies have suggested that PINK1 plays important neuroprotective roles against mitochondrial dysfunction by phosphorylating and recruiting Parkin, a cytosolic E3 ubiquitin ligase, to facilitate elimination of damaged mitochondria via autophagy‐lysosomal pathways. Loss of PINK1 in cells and animals leads to various mitochondrial impairments and oxidative stress, culminating in dopaminergic neuronal death in humans. Using a 2‐D polyacrylamide gel electrophoresis proteomics approach, the differences in expressed brain proteome and phosphoproteome between 6‐month‐old PINK1‐deficient mice and wild‐type mice were identified. The observed changes in the brain proteome and phosphoproteome of mice lacking PINK1 suggest that defects in signaling networks, energy metabolism, cellular proteostasis, and neuronal structure and plasticity are involved in the pathogenesis of familial PD.

     

Cytogenetic and immuno-FISH analysis of the 4q subtelomeric region,which is associated with facioscapulohumeral muscular dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) is caused by the shortening of a copy-number polymorphic array of 3.3 kb repeats (D4Z4) at one allelic 4q35.2 region. How this contraction of a subtelomeric tandem array causes FSHD is unknown but indirect evidence suggests that a short array has a cis effect on a distant gene or genes. It was hypothesized that the length of the D4Z4 array determines whether or not the array and a large proximal region are heterochromatic and thereby controls gene expression in cis. To test this, we used fluorescence in situ hybridization probes with FSHD and control myoblasts to characterize the distal portion of 4q35.2 with respect to the following: intense staining with the chromatin dye 4,6-diamidino-2-phenylindole; association with constitutively heterochromatic foci; extent of binding of heterochromatin protein 1; histone H3 methylation at lysine 9 and lysine 4; histone H4 lysine 8 acetylation; and replication timing within S-phase. Our results indicate that 4q35.2 does not resemble constitutive heterochromatin in FSHD or control myoblasts. Furthermore, in these analyses, the allelic 4q35.2 regions of FSHD myoblasts did not behave differently than those of control myoblasts. Other models for how D4Z4 array contraction causes long-distance regulation of gene expression in cis need to be tested.Communicated by S. Gerbi     

Exploring the information in p-values for the analysis and planning of multiple-test experiments

Summary A new methodology is proposed for estimating the proportion of true null hypotheses in a large collection of tests. Each test concerns a single parameter δ whose value is specified by the null hypothesis. We combine a parametric model for the conditional cumulative distribution function (CDF) of the p‐value given δ with a nonparametric spline model for the density g(δ) of δ under the alternative hypothesis. The proportion of true null hypotheses and the coefficients in the spline model are estimated by penalized least squares subject to constraints that guarantee that the spline is a density. The estimator is computed efficiently using quadratic programming. Our methodology produces an estimate of the density of δ when the null is false and can address such questions as “when the null is false, is the parameter usually close to the null or far away?” This leads us to define a falsely interesting discovery rate (FIDR), a generalization of the false discovery rate. We contrast the FIDR approach to Efron's (2004, Journal of the American Statistical Association 99, 96–104) empirical null hypothesis technique. We discuss the use of in sample size calculations based on the expected discovery rate (EDR). Our recommended estimator of the proportion of true nulls has less bias compared to estimators based upon the marginal density of the p‐values at 1. In a simulation study, we compare our estimators to the convex, decreasing estimator of Langaas, Lindqvist, and Ferkingstad (2005, Journal of the Royal Statistical Society, Series B 67, 555–572). The most biased of our estimators is very similar in performance to the convex, decreasing estimator. As an illustration, we analyze differences in gene expression between resistant and susceptible strains of barley.     

Inheritance of high oleic acid content in the seed oil of soybean mutant M23

A mutant line, M23, of soybean [Glycine max (L.) Merr.] was found to have two fold increases in oleic acid content in the seed oil compared with the original variety, Bay. Our objective was to determine the inheritance of the high oleic acid content in this mutant. Reciprocal crosses were made between M23 and Bay. There were no maternal and cytoplasmic effects for oleic acid content. The F₁ seeds and F₁ plants were significantly different from either parents or the midparent value, indicating partial dominance of oleic acid content in these crosses. The oleic acid content segregated in the F₂ seeds and F₂ plants in a trimodal pattern with normal, intermediate and high classes, satisfactorily fitting a 121 ratio. The seeds of a backcross between M23 and F₁ segregated into intermediate and high classes in a ratio of 11. These results indicated that oleic acid content was controlled by two alleles at a single locus with a partial dominant effect. Thus, the allele in M23 was designated ol and the genotypes of M23 and Bay were determined to be olol and 0l0l, respectively. The oleic acid contents of the F₂ seeds and F₂ plants were inversely related with the linoleic acid content which segregated in a trimodal pattern with normal, intermediate and low classes in a 121 ratio. Thus, it was assumed that the low linoleic acid content in M23 was also controlled by the ol alleles. Because a diet with high oleic acid content reduces the content of low density lipoprotein cholesterol in blood plasma, the mutant allele, ol, would be useful in improving soybean cultivars for high oleic acid content.