Reversible unfolding of fructose 6-phosphate, 2-kinase:fructose 2,6-bisphosphatase.

Reversible unfolding of rat testis fructose 6-phosphate,2-kinase:fructose 2,6-bisphosphatase in guanidine hydrochloride was monitored by following enzyme activities as well as by fluorescence methodologies (intensity, emission maximum, polarization, and quenching), using both intrinsic (tryptophan) and extrinsic (5((2-(iodoacetyl)amino) ethyl)naphthalene-1-sulfonic acid) probes. The unfolding reaction is described minimally as a 4-state transition from folded dimer-->partially unfolded dimer-->monomer-->unfolded monomer. The partially unfolded dimer had a high phosphatase/kinase ratio due to preferential unfolding of the kinase domain. The renaturation reaction proceeded by very rapid conversion (less than 1 s) of unfolded monomer to dimer, devoid of any enzyme activity, followed by slow (over 60 min) formation of the active enzyme. The recovery rates of the kinase and the phosphatase were similar. Thus, the refolding appeared to be a reversal of the unfolding pathway involving different forms of the transient dimeric intermediates. Fluorescence quenching studies using iodide and acrylamide showed that the tryptophans, including Trp-15 in the N-terminal peptide, were only slightly accessible to iodide but were much more accessible to acrylamide. Fructose 6-phosphate, but not ATP or fructose 2,6-bisphosphate, diminished the iodide quenching, but all these ligands inhibited the acrylamide quenching by 25%. These results suggested that the N-terminal peptide (containing a tryptophan) was not exposed on the protein surface and may play an important role in shielding other tryptophans from solvent.     

Morphometric analysis of the genusHemerocallis L. (Liliaceae) in Korea

To better understand the patterns of variability and distributions ofHemerocallis in Korea, 53 locations were visited and measurements of 19 morphological and phenological characters were taken on plants directly from their natural habitats. For morphometric analysis, 10 plants from each of 34 populations and five herbarium specimens ofH. middendorffii were used and the data from 12 quantitative characters was analyzed using univariate analysis. Except the littoral populations of Cheju, Hong, Taehuksan, and Sohuksan Islands (H. hongdoensis M. Chung & S. Kang), three peninsular KoreanHemerocallis species can be recognized mainly in South Korea:H. hakuunensis Nakai (=H. micrantha Nakai, growing on southern, central, and northwestern Korea);H. thunbergii Baker (=H. coreana Nakai, found on southeastern and central Korea); andH. middendorffii Tr. et Mey. (central and northeastern Korea). Morphological and phenological features contributing to recognition of the three groups were; color of perianth, shape of roots, shape of inflorescence, flowering time, odor, length of inflorescence, width of the lowest bracts, length of perianth tube enclosing a ovary, width of the inner perianth lobes. Natural hybridization seems to be rare in KoreanHemerocallis. It appears that the KoreanHemerocallis species are relatively well characterized by their distribution patterns, phenology, and habitats compared with the JapaneseHemerocallis species.     

Mother-infant bonding

A study of the research on postpartum mother-infant bonding shows that results from poorly constructed research programs were published in major journals and became a part of hospital policy because the bonding concept was politically useful in the struggle between advocates of natural childbirth and managers of the medical model of birth. The concept was also uncritically accepted because it was consistent with a longstanding ideology of motherhood that sees women as the prime architects of their children’s personalities. Diane Eyer earned her Ph.D. in developmental psychology from the University of Pennsylvania. She is currently writing a book on the ways in which the concepts of bonding and attachment have affected our understanding of appropriate early childcare.     

Genetic studies of water buffalo blood markers. I. Red cell acid phosphatase,albumin, catalase,red cell α-esterase-3, group-specific component,and protease inhibitor

We have developed the methodologies for typing and family studies to establish the modes of inheritance of water buffalo red cell acid phosphatase (Acp), protease inhibitor (Pi), and group-specific component (Gc) on isoelectric focusing and albumin (Alb), red cell -esterase-3 (Est-3), and catalase (Cat) on polyacrylamide gel electrophoresis. Family studies showed that Pi, Gc, Alb, and Cat are coded by autosomal genes with two codominant alleles, while Est-3 is autosomal with two codominant alleles and a recessive null allele and Acp exhibits three codominant alleles.This project was funded by the Australian Centre for International Agricultural Research through Grant PN 8364 and the Malaysian programme for Intensification of Research in Priority Areas through Grant IRPA 1-07-05-057.     

Chicken oocyte growth: receptor-mediated yolk deposition

During the rapid final stage of growth, chicken oocytes take up massive amounts of plasma components and convert them to yolk. The oocyte expresses a receptor that binds both major yolk lipoprotein precursors, vitellogenin (VTG) and very low density lipoprotein (VLDL). In the present study, in vivo transport tracing methodology, isolation of coated vesicles, ligand- and immuno-blotting, and ultrastructural immunocytochemistry were used for the analysis of receptor-mediated yolk formation. The VTG/VLDL receptor was identified in coated profiles in the oocyte periphery, in isolated coated vesicles, and within vesicular compartments both outside and inside membrane-bounded yolk storage organelles (yolk spheres). VLDL particles colocalized with the receptor, as demonstrated by ultrastructural visualization of VLDL-gold following intravenous administration, as well as by immunocytochemical analysis with antibodies to VLDL. Lipoprotein particles were shown to reach the oocyte surface by passage across the basement membrane, which possibly plays an active and selective role in yolk precursor accessibility to the oocyte surface, and through gaps between the follicular granulosa cells. Following delivery of ligands from the plasma membrane into yolk spheres, proteolytic processing of VTG and VLDL by cathepsin D appears to correlate with segregation of receptors and ligands which enter disparate sub-compartments within the yolk spheres. In small, quiescent oocytes, the VTG/VLDL receptor was localized to the central portion of the cell. At onset of the rapid growth phase, it appears that this pre-existing pool of receptors redistributes to the peripheral region, thereby initiating yolk formation. Such a redistribution mechanism would obliterate the need for de novo synthesis of receptors when the oocyte's energy expenditure is to be utilized for plasma membrane synthesis, establishment and maintenance of intracellular topography and yolk formation, and preparation for ovulation.     

Estimating tree-based dynamic treatment regimes using observational data with restricted treatment sequences

A dynamic treatment regime (DTR) is a sequence of decision rules that provide guidance on how to treat individuals based on their static and time-varying status. Existing observational data are often used to generate hypotheses about effective DTRs. A common challenge with observational data, however, is the need for analysts to consider “restrictions” on the treatment sequences. Such restrictions may be necessary for settings where (1) one or more treatment sequences that were offered to individuals when the data were collected are no longer considered viable in practice, (2) specific treatment sequences are no longer available, or (3) the scientific focus of the analysis concerns a specific type of treatment sequences (eg, “stepped-up” treatments). To address this challenge, we propose a restricted tree–based reinforcement learning (RT-RL) method that searches for an interpretable DTR with the maximum expected outcome, given a (set of) user-specified restriction(s), which specifies treatment options (at each stage) that ought not to be considered as part of the estimated tree-based DTR. In simulations, we evaluate the performance of RT-RL versus the standard approach of ignoring the partial data for individuals not following the (set of) restriction(s). The method is illustrated using an observational data set to estimate a two-stage stepped-up DTR for guiding the level of care placement for adolescents with substance use disorder.     

Coherent modeling of longitudinal causal effects on binary outcomes

Analyses of biomedical studies often necessitate modeling longitudinal causal effects. The current focus on personalized medicine and effect heterogeneity makes this task even more challenging. Toward this end, structural nested mean models (SNMMs) are fundamental tools for studying heterogeneous treatment effects in longitudinal studies. However, when outcomes are binary, current methods for estimating multiplicative and additive SNMM parameters suffer from variation dependence between the causal parameters and the noncausal nuisance parameters. This leads to a series of difficulties in interpretation, estimation, and computation. These difficulties have hindered the uptake of SNMMs in biomedical practice, where binary outcomes are very common. We solve the variation dependence problem for the binary multiplicative SNMM via a reparameterization of the noncausal nuisance parameters. Our novel nuisance parameters are variation independent of the causal parameters, and hence allow for coherent modeling of heterogeneous effects from longitudinal studies with binary outcomes. Our parameterization also provides a key building block for flexible doubly robust estimation of the causal parameters. Along the way, we prove that an additive SNMM with binary outcomes does not admit a variation independent parameterization, thereby justifying the restriction to multiplicative SNMMs.     

A latent class model to multiply impute missing treatment indicators in observational studies when inferences of the treatment effect are made using propensity score matching

Analysts often estimate treatment effects in observational studies using propensity score matching techniques. When there are missing covariate values, analysts can multiply impute the missing data to create m completed data sets. Analysts can then estimate propensity scores on each of the completed data sets, and use these to estimate treatment effects. However, there has been relatively little attention on developing imputation models to deal with the additional problem of missing treatment indicators, perhaps due to the consequences of generating implausible imputations. However, simply ignoring the missing treatment values, akin to a complete case analysis, could also lead to problems when estimating treatment effects. We propose a latent class model to multiply impute missing treatment indicators. We illustrate its performance through simulations and with data taken from a study on determinants of children's cognitive development. This approach is seen to obtain treatment effect estimates closer to the true treatment effect than when employing conventional imputation procedures as well as compared to a complete case analysis.     

茜草属药用植物的研究——Ⅲ.11种茜草属药材的组织形成学研究

本文除对主流商品茜草的生药性状和组织构造作了较全面的描述,还利用图、表及照片列出狭叶茜草P.truppeliana Loes、Loeb、小红参(滇茜草)R.yunnomensis Dtels、中华茜草R.chinensis Regel et maack、大叶茜草R.schumanniana Pritz、按针叶茜草R.lanceolata Hayata、大茜草R.magna Hisao、钩毛茜草R.oncotrucha Hand-Mazz、红花茜草R.podantha Diels、金剑草R.alata Wall、新疆茜草(洋茜草)R.tinctorum L等10种与茜草Rubia cordifolia L的主要区别点,并作药材检索表,以利鉴别。     

中药羌活的研究

本文对中药羌活进行了本草考证,概括了羌活的化学成分、药理等方面的研究成果,并对羌活原植物的根进行了显微观察、薄层层析分析等,为正确鉴定药用羌活提供了资料。