On the Use of Factor Scores for Prediction

There are two types of indeterminacy problems in factor analysis: the indeterminacy of the parameters, which is also known as the problem of identification, and the indeterminacy of the factor scores. The second problem, which will be treated here, is of great importance to the social sciences, given that the factor analysis model was historically developed with the theory of measuring intelligence, where the main interest was to determine one person's intelligence numerically. As a consequence of the indeterminacy of factor scores we will show, by means of a numerical example, that any criterion, including the dates of easter sunday, can be perfectly predicted by the intelligence factors.     

Structural understanding of quorum-sensing inhibitors by molecular modeling study in Pseudomonas aeruginosa

Inhibitors of 3OC12, an initial signal molecule of the quorum sensing (QS) signaling cascade in Pseudomonas aeruginosa have been developed. Eight inhibitor candidates were synthesized by substituting the head part of 3-oxododecanoyl-homoserine lactone (3OC12) with different aromatic rings, and their docking poses and scores (binding energies) were predicted by in silico modeling study. All compounds gave better docking scores than 3OC12 and good inhibition effects on LasR activity in the in vivo bioassay. Like the modifications in the tail part of 3OC12 in our previous study Kim et al. (2008), the head-part modifications also showed inhibition activity in a fairly good proportion to the docking scores from the modeling analysis. This implies that the head part of 3OC12 also contributes significantly to forming the active conformation of the LasR-3OC12 complex, and its modification could effectively induce the inactive conformation of the complex. We suggest that the head part of 3OC12 is also a good target moiety to develop the structure-based Pseudomonas QS inhibitors.     

中性粒细胞弹性蛋白酶在小鼠实验性结肠炎中的表达及意义

目的：观察中性粒细胞弹性蛋白酶（NE）在葡聚糖硫酸钠（DSS）诱导的小鼠实验性结肠炎中的表达情况并探讨其表达的意义。方法：健康雄性BALB/c小鼠随机分为正常对照组、模型组。模型组小鼠予5%DSS溶液自由饮用制备小鼠急性实验性结肠炎模型,正常对照组小鼠予蒸馏水自由饮用。每日观察小鼠的一般状况及疾病活动指数（DAI）评分,于实验第5、9天分批处死小鼠,取小鼠结肠行组织学损伤评分;ELISA法检测小鼠血浆中性粒细胞弹性蛋白酶浓度;Western blot法检测远端结肠组织中NE蛋白的表达。结果：与正常对照组相比,模型组小鼠在实验第5天及第9天DAI评分显著升高（P〈0.001）、结肠组织学损伤评分明显升高（P〈0.01）、血浆NE浓度明显升高（P〈0.01）、远端结肠NE蛋白表达增加显著（P〈0.001）。在实验第5天及第9天,模型组小鼠DAI评分与组织学损伤评分呈显著正相关（P〈0.05）,血浆中NE浓度及结肠中NE蛋白的表达与DAI评分、组织学评分均呈显著正相关（P〈0.05）。结论：NE在实验性结肠炎小鼠血浆及结肠组织中表达明显增加,且与疾病活动指数及组织学评分呈正相关,提示NE可能参与实验性结肠炎小鼠的发病。     

LOD Score Exclusion Analyses for Candidate QTLs using Random Population Samples

While extensive analyses have been conducted to test for, no formal analyses have been conducted to test against, the importance of candidate genes as putative QTLs using random population samples. Previously, we developed an LOD score exclusion mapping approach for candidate genes for complex diseases. Here, we extend this LOD score approach for exclusion analyses of candidate genes for quantitative traits. Under this approach, specific genetic effects (as reflected by heritability) and inheritance models at candidate QTLs can be analyzed and if an LOD score is < or = -2.0, the locus can be excluded from having a heritability larger than that specified. Simulations show that this approach has high power to exclude a candidate gene from having moderate genetic effects if it is not a QTL and is robust to population admixture. Our exclusion analysis complements association analysis for candidate genes as putative QTLs in random population samples. The approach is applied to test the importance of Vitamin D receptor (VDR) gene as a potential QTL underlying the variation of bone mass, an important determinant of osteoporosis.     

Association study of single nucleotide polymorphisms in JAK2 and STAT5B genes and their differential mRNA expression with mastitis susceptibility in Chinese Holstein cattle

The JAK–STAT pathway plays a key role in mediating immune responses. The genetic effects of single nucleotide polymorphisms (SNPs) in JAK2 and STAT5B were investigated for serum cytokines, mastitis indicators and productions traits in a population of 468 Chinese Holstein cattle. Pooled DNA sequencing revealed one SNP (BTA8:g.39645396A>G) in JAK2 and two SNPs (BTA19:g.43673888A>G and BTA19:g.43660093T>C) in STAT5B. A fixed effect model considering the effects of SNPs, parity, herd, season and year of calving was used by way of the general linear model procedure of sas . Genotype frequencies of these SNPs in the population were in Hardy–Weinberg equilibrium (P > 0.05). A novel SNP (g.39645396A>G) in JAK2 was predicted to change the amino acid from lysine to asparagine and was significantly associated with the somatic cell count (SCC) and somatic cell score (SCS), whereas g.43673888A>G in STAT5B was significantly associated with SCC, SCS and interleukin‐4 (IL‐4) (P < 0.05). The dominant effect of g.39645396A>G in JAK2 was significant for SCS, and its additive effect was significant for SCC, whereas the dominant effect of g.43673888A>G in STAT5B was significant for SCS and IL‐4 (P < 0.05). The combination of g.39645396A>G in JAK2 and g.43673888A>G in STAT5B showed a significant effect on SCC, SCS, IL‐4 and TNF‐α (P < 0.05). As for mRNA expression analysis, the AA genotype g.39645396A>G and GG genotype g.43673888A>G indicated higher mRNA expression level and were significantly different from other genotypes (P < 0.05). The results imply that JAK2 and STAT5B genes could be useful candidate genes, and the identified polymorphisms might potentially be strong genetic markers for selection of dairy cattle against mastitis development.     

Comparison of microsatellites and amplified fragment length polymorphism markers for parentage analysis

This study compares the properties of dominant markers, such as amplified fragment length polymorphisms (AFLPs), with those of codominant multiallelic markers, such as microsatellites, in reconstructing parentage. These two types of markers were used to search for both parents of an individual without prior knowledge of their relationships, by calculating likelihood ratios based on genotypic data, including mistyping. Experimental data on 89 oak trees genotyped for six microsatellite markers and 159 polymorphic AFLP loci were used as a starting point for simulations and tests. Both sets of markers produced high exclusion probabilities, and among dominant markers those with dominant allele frequencies in the range 0.1-0.4 were more informative. Such codominant and dominant markers can be used to construct powerful statistical tests to decide whether a genotyped individual (or two individuals) can be considered as the true parent (or parent pair). Gene flow from outside the study stand (GFO), inferred from parentage analysis with microsatellites, overestimated the true GFO, whereas with AFLPs it was underestimated. As expected, dominant markers are less efficient than codominant markers for achieving this, but can still be used with good confidence, especially when loci are deliberately selected according to their allele frequencies.     

On the bias produced by quality scores in meta-analysis,and a hierarchical view of proposed solutions

Results from better quality studies should in some sense be more valid or more accurate than results from other studies, and as a consequence should tend to be distributed differently from results of other studies. To date, however, quality scores have been poor predictors of study results. We discuss possible reasons and remedies for this problem. It appears that 'quality' (whatever leads to more valid results) is of fairly high dimension and possibly non-additive and nonlinear, and that quality dimensions are highly application-specific and hard to measure from published information. Unfortunately, quality scores are often used to contrast, model, or modify meta-analysis results without regard to the aforementioned problems, as when used to directly modify weights or contributions of individual studies in an ad hoc manner. Even if quality would be captured in one dimension, use of quality scores in summarization weights would produce biased estimates of effect. Only if this bias were more than offset by variance reduction would such use be justified. From this perspective, quality weighting should be evaluated against formal bias-variance trade-off methods such as hierarchical (random-coefficient) meta-regression. Because it is unlikely that a low-dimensional appraisal will ever be adequate (especially over different applications), we argue that response-surface estimation based on quality items is preferable to quality weighting. Quality scores may be useful in the second stage of a hierarchical response-surface model, but only if the scores are reconstructed to maximize their correlation with bias.     

Varroa Mite Infestations in Elevated Honey Bee Brood Cells: Effects of Context and Caste

The Varroa mite infestation level of honey bee, Apis mellifera, worker larvae reared in individual raised cells was 6-fold higher than in the adjacent six cells surrounding them; this differential infestation rate is similar to published values of higher mite infestations of drone cells compared to worker cells. Infestation levels in control cells were the same as in the surrounding cells. In contrast to infestation of these individually raised cells, Varroa mites invaded worker larvae in raised cells along the perimeter of a patch of raised cells (10 by 21 rows) 2.5 times more often than surrounding unraised cells, and similarly ca. 2.5 times more often than in the remaining raised cells (interior) of this patch. In similarly prepared frames of drone comb, Varroa mites invaded individually raised drone cells 3.3-fold more often than the adjacent surrounding cells and control cells. On the other hand, Varroa mites infested drone larvae in the interior of the raised-patch area as often as drones in raised cells along the perimeter of the raised-patch, and this rate was ca. 2.5-fold higher than for drone larvae in unraised cells surrounding the raised-patch and drone larvae in control cells. The higher levels of infestation of raised cells did not come at the expense of the surrounding cells, i.e., the infestation levels of the adjacent surrounding cells were the same as in control cells. For worker larvae, the increased number of mites invading individual raised cells and edge cells of the raised patch were proportional to the number of surrounding nonraised cells. The relationship between raised cell-edges, observations of mite walking behavior on comb surfaces, and larval-to-cell-rim distances are discussed in relation to their possible roles in eliciting mite invasion of honey bee larval cells and contrasted to the putative role of kairomones in larval-host location.