bluuebunny/crossref_metadata_2025 huggingface dataset:
Combining two‐point genetic linkage analyses using mapping functions
Authors: Schaid Daniel J. , Elston Robert C.
Published: June 2005

A likelihood ratio statistic is proposed for combining two‐point genetic linkage analyses when the two‐point analyses are between a trait and a well‐defined map of markers. It is assumed that the two‐point analyses are independent, as in the case of choosing only the most informative marker per family. The asymptotic distribution of the likelihood ratio statistic is derived under the null hypothesis of no linkage of the trait with a map of 2 markers, with intermarker genetic distance δ. This distribution is shown to be a chi‐square mixture distribution with mixing probability depending on δ and the assumed mapping function. We use this asymptotic result to approximate the distribution of the likelihood ratio statistic for the more general case of more than 2 markers. Simulation results indicate that this may be reasonable. Power is evaluated by simulations and results indicate that this approach, which constrains the intermarker distances to their known values, tends to be more powerful than other methods proposed in the literature. © 1994 Wiley‐Liss, Inc.
Linkage between the APOB gene and serum apoB levels in a large pedigree from the Bogalusa heart study
Authors: Laing A. E. , Amos C. I. , DeMeester C. , Diep A. , Xia Y. R. , Elston R. C. , Srinivasan S. R. , Berenson G. S. , Lusis A. J.
Published: June 2005

Maximum likelihood linkage analyses were performed to test for linkage between serum apoB levels and several candidate gene markers including apolipoprotein B, lipoprotein lipase, hepatic lipase, cholesterol ester transfer protein, and apolipoprotein AI in a large pedigree. Parameters of general Mendelian inheritance derived from maximum likelihood segregation analysis of the serum apoB levels were used in the linkage analysis. The highest two‐point lod score between the quantitative trait and a marker defined by a single restriction digest was 1.86 at recombination fraction (θ) = 0. This was observed for linkage between serum apoB levels and the presence or absence of a PvuII digestion site in the apoB gene. Linkage between serum apoB levels and polymorphisms of the apoB gene defined by the two restriction digests EcoR1 and PvuII was supported by a lod score of 3.30, while inclusion of VNTR typings led to a lod score of 2.33. None of the other candidate genes gave positive evidence of linkage. © 1994 Wiley‐Liss, Inc.

This article is a US government work and, as such, is in the public domain in the United States of America.
Sibling correlations and segregation analysis of age‐related maculopathy: The beaver dam eye study
Authors: Heiba Ibrahim M. , Elston Robert C. , Klein Barbara E. K. , Klein Ronald
Published: June 2005

Sibling correlations were evaluated and segregation analysis was performed on age‐dependent maculopathy scores of the right and left eyes of individuals from 564 families in the Beaver Dam Eye study. There is evidence of significant sibling correlations. The data fit a mixture of two normal distributions, especially after undergoing the Box and Cox power transformation. In each eye, the hypothesis of mendelian transmission of a major effect cannot be rejected under the τ'ABfree model, but is rejected under the τ's free model. The hypothesis of a random environmental major effect is rejected. Similar major gene parameter estimates are found for both eyes. The results are consistent with a major effect accounting for 62% and 59%, in the right and left eyes, respectively, of the determination of age‐related maculopathy scores. A single major gene can account for about 89% and 97% of this variability due to a major effect, or for about 55% and 57% of the total variability, in the right and left eyes, respectively. © 1994 Wiley‐Liss, Inc.
The weighted rank pairwise correlation statistic for linkage analysis: Simulation study and application to Alzheimer's disease
Authors: Commenges D. , Olson J. , Wijsman E.
Published: June 2005

The weighted rank pairwise correlation (WRPC) statistic has been proposed as a robust test of genetic linkage, particularly adapted to the analysis of large and complex pedigrees and for age‐dependent and heterogeneous diseases. In this paper a simulation study is presented. Validity and power of the WRPC test are studied and compared to the Haseman‐Elston sibpair method for various types of problems. The power of the WRPC test is slightly lower than the Haseman‐Elston method for analyzing a large number of small randomly chosen pedigrees. It is higher however in presence of genetic heterogeneity or for analyzing large individual pedigrees. Recently, evidence of linkage of Alzheimer's disease with a locus on chromosome 14, D14s43, has been obtained by the Lod‐score method. We reanalyze these data using the WRPC test, essentially confirming the results of the Lod‐score method. The WRPC test statistic is higher than the equivalent Lod‐score statistic for the two pedigrees which show strong evidence of linkage with the two methods. The global WRPC test statistic is slightly lower than the Lod‐score test statistic. The WRPC test, however, makes no hypothesis of a specific genetic transmission model and can be computed very quickly; in addition, an exact P‐value can be computed by simulation for individual pedigrees. © 1994 Wiley‐Liss, Inc.
Lods, wrods, and mods: The interpretation of lod scores calculated under different models
Authors: Hodge Susan E. , Elston Robert C.
Published: June 2005

In this paper we examine the relationships among classical lod scores, “wrod” scores (lod scores calculated under the wrong genetic model), and “mod” scores (lod scores maximized over genetic model parameters). We compare the behavior of these scores when the state of nature is linkage to their behavior when the state of nature is no linkage. We describe sufficient conditions for mod scores to be valid and discuss their use to determine the correct genetic model. We show that lod scores represent a likelihood‐ratio test for independence. We explain the “ascertainment‐assumption‐free” aspect of using mod scores to determine mode of inheritance and we set this aspect into a well‐established statistical framework. Finally, we summarize practical guidelines for the use of mod scores.
The contribution of maternal epilepsy and its treatment to the etiology of oral clefts: A population based case‐control study
Authors: Abrishamchian Ahmad R. , Khoury Muin J. , Calle Eugenia E.
Published: June 2005

The associations between maternal epilepsy and anticonvulsant drug therapy with the risk of oral clefts in the offspring were investigated using data from a population‐based case‐control study. Cases included 238 infants with cleft lip ± cleft palate (CLP) and 107 infants with cleft palate (CP) ascertained through the Metropolitan Atlanta Congenital Defects Program (MACDP) between 1968 and 1980. Controls included 3029 population‐based normal infants. Histories of maternal epilepsy and drug therapy during pregnancy were compared between cases and controls using maternal interviews and reviews of hospital medical records. Maternal epilepsy was associated with increased risk of nonsyndromic CLP (OR = 3.78, 95% C.I. 1.65–7.88), and less with CP (OR = 1.75, 95% C.I. 0.20–6.99). Therapy during pregnancy was associated with the greatest excess risk (CLP OR = 7.77, C.I. 2.02–26.0; CP OR = 3.61, C.I. 0.08–26.5). The use of polytherapy was associated with the highest risk (CLP OR = 10.5, C.I. 1.52–59.9). Adjustment for potential confounding variables in the study did not change these findings. In this well‐defined population, maternal epilepsy and its treatment account for a small proportion of nonsyndromic oral clefts (attributable fraction CLP = 3.3%, CP = 0.9%). © 1994 Wiley‐Liss, Inc.
Direction of causation: Reply to commentaries
Authors: Neale Michael C. , Duffy David L. , Martin Nicholas G.
Published: June 2005

We reply to the commentaries on the lead papers by Neale et al. [1994a] and Duffy and Martin [1994]. Topics covered include power calculations, cross‐sectional measurement vs. lifetime reports, the appropriateness of the direction of causation (DOC) model, extensions to study causation between the latent variables, sampling of subjects, and heterogeneity. We consider the potential of combining genetically informative research designs with multivariate longitudinal and experimental methods. © 1994 Wiley‐Liss, Inc.
Depression and parental bonding: Cause, consequence, or genetic covariance?
Authors: Neale Michael C. , Walters Ellen , Heath Andrew C. , Kessler Ronald C. , Pérusse Daniel , Eaves Lindon J. , Kendler Kenneth S.
Published: June 2005

It is shown how information on the direction of causation between variables may be obtained from a cross‐sectional study of pairs of relatives. This method is applied to the study of the relationship between ratings of parents' rearing style and depression in their offspring. Adult female twins ascertained from a population‐based registry in Virginia completed the Center for Epidemiological Studies ‐ Depression Scale (CESD) and a 7‐item short form of the Parental Bonding Instrument (PBI) about each of their parents. Two dimensions of parental behavior, overprotectiveness and coldness, were analyzed jointly with depression data in both genetic factor and directional genetic models. Models that specify ratings of parents as a cause of depression in the offspring fit the data significantly better than models that specify depression as a cause of ratings of parents. A still better fit is obtained with models that specify common genetic variance to depression and ratings, though causal models with error variance perform almost as well. In general, ratings of fathers show more genetic and less shared environmental variance than ratings of mothers, which might arise from more consistent treatment of offspring by mothers than by fathers. No effect of children eliciting parental rearing style was detected with these data. The relative merits of instrumental variable, longitudinal, and family approaches to testing causal models are discussed. © 1994 Wiley‐Liss, Inc.
Robust multipoint linkage analysis: An extension of the Haseman‐Elston method
Authors: Olson Jane M.
Published: June 2005

The use of multiple markers, rather than a single marker, can increase the likelihood of detecting linkage to a locus underlying a quantitative trait. In this paper, the Haseman‐Elston sibpair method is extended to include information from multiple markers. The result is a linear regression of the squared pair trait difference on the jointly estimated proportions of genes shared identical by descent at the two closest flanking marker loci. The results strengthen the theoretical motivation for the interval mapping technique proposed by Fulker and Cardon [1994: Am J Hum Genet 54:1092–1103] and extend the method to include information from multiple markers, account for a trait dominance component, and examine the region just outside that defined by the markers. Simulations show that modest increases in power and substantial decreases in bias of parameter estimates are obtained when identity‐by‐descent probabilities are jointly estimated. The regression relationship is also developed for other types of relative pairs. © 1995 Wiley‐Liss, Inc.
Complex segregation analysis of familial diseases with variable age of onset: Comparison of different methods by a simulation study
Authors: Abel Laurent , Garcia André , Demenais Florence
Published: June 2005

Standard methods of segregation analysis, such as originally developed in the unified model (UM) or the regressive logistic model (RLM) do not account for age of onset, and use instead age at examination. To take into account age of onset, models should be formulated using survival analysis concepts, as it was recently proposed with a model based on a logistic hazard function (LHM). A simulation study was conducted to compare the performances of the three methods (UM, RLM, and LHM) in analyzing generated familial data with variable age of onset. When the data were simulated under a polygenic hypothesis, all analysis models were robust with respect to the false conclusion of a major gene, if the tests of transmission probabilities were performed properly. When the data were generated under a major gene hypothesis, two main results were observed: (1) the use of the LHM markedly increased the power to detect a major gene, in particular when a genotype by age interaction was introduced in the model; and (2) in the situation of disease‐specific mortality, the use of either UM (whether specific mortality was accounted for or not) or RLM led to both spurious conclusions and bias in parameter estimates. These latter results obtained with the UM and the RLM can be explained by the violation of one constraint of both models observed in a situation of disease‐specific mortality, i.e., given all covariates, the probability of being affected and that of not being affected should sum to 1. The use of methods based on survival analysis concepts is recommended in the study of familial diseases with variable age of onset, especially in the case of a correlation between age of onset and age at examination which is induced by disease‐specific mortality. ©1995 Wiley‐Liss, Inc.
Polymorphism at VNTR Locus 3′ to the apolipoprotein B gene in a tunisian population: Difference from other ethnic groups
Authors: Buresi Catherine , Desmarais Eric , Vigneron Suzanne , Rayana Chiheb Ben , Chaabouni Habiba , Roizes Gérard
Published: June 2005

The Hypervariable Region (HVR) detected at the 3′ end of the apolipoprotein B (Apo B) locus has been the subject of numerous studies. As for many VNTR (variable number of tandem repeat), this locus is highly polymorphic and until now about 20 alleles have been described. The genotype distribution in all populations follows the Hardy‐Weinberg predictions. A bimodal pattern of allele frequency distribution is apparent in all Caucasoid populations. We have analyzed the frequencies of different alleles in a Tunisian population (123 individuals) by the polymerase chain reaction technique and compared our results to those obtained in several ethnic groups. It appears that the distributions of the allele frequencies are very different: for Caucasoid populations, there are two peaks of frequencies for alleles with 36 and 48 repeats, but alleles of intermediate lengths are more frequent. Hixson et al. [(1993) Hum Genet 91:475–479] have shown a similar difference between black and white American populations. We found the same results in a black African group.

Some of the repeat units of this HVR contain a Ssp I restriction site and digestion of the PCR products by this enzyme gives different patterns on gradient acrylamide gel [Desmarais et al., 1993, Nucleic Acids Res 21:2179–2184.] The DNA of African individuals (42) has been analyzed to discover the origin of this new allele. Preliminary results indicate that these particular alleles probably arose by introgression from the African population into the Tunisian one. ©1995 Wiley‐Liss, Inc.
Segregation analysis of breast cancer in a population‐based sample of postmenopausal probands: The Iowa women's health study
Authors: Chen Ping‐Ling , Sellers Thomas A. , Rich Stephen S. , Potter John D. , Folsom Aaron R.
Published: June 2005

Inheritance of a major susceptibility gene for breast cancer has been primarily investigated in families with early‐onset disease. However, familial clustering of late‐onset breast cancer is well documented, and genetic factors may also be relevant. In the Iowa Women's Health Study, we evaluated evidence for a major gene after allowing for measured environmental risk factors. Two hundred sixty‐five incident breast cancer probands were identified from a prospective cohort study of 41,837 women aged 55 to 69 years at baseline in 1986. A pedigree development form was mailed to the probands to ascertain all first‐degree female relatives. A questionnaire and body measurement protocol were mailed to identified living relatives or surrogates. Segregation analyses were conducted on a total of 1,145 women in 251 families using regressive models as implemented in S.A.G.E. Mendelian codominant inheritance of an allele that produced an earlier age‐at‐onset provided the best fit to the data. Incorporation of measured environmental risk factors as covariates yielded no significant improvements in the likelihoods. Approximately 50% of this population could be expected to carry a late‐onset breast cancer susceptibility gene, and 23% of the population is susceptible because of the environment in which they live. Homozygous gene carriers are predicted to have a mean age‐at‐onset of 48 years, over 20 years earlier than heterozygotes; few cases would be expected among non‐gene carriers. In conclusion, the transmission pattern of late‐onset breast cancer may be determined by a common susceptibility gene. ©1995 Wiley‐Liss, Inc.
Genetic analysis of durations: Correlated frailty model applied to survival of Danish twins
Authors: Yashin Anatoli I. , Iachine Ivan A.
Published: June 2005

Population studies of changes in human morbidity and mortality require models which take into account the influence of genetic and environmental factors on life‐related durations, such as age at onset of the disease or disability, age at death, etc. In this paper we show how a bivariate survival model based on the concept of correlated individual frailty can be used for the genetic analysis of durations. Six genetic models of frailty are considered and applied to Danish twin survival data. The results of statistical analysis allow us to conclude that at least 50% of variability in individual frailty is determined by environmental factors. The approach suggests a method of estimation of the lower bound for the biological limit of human longevity. Directions for further research are discussed. ©1995 Wiley‐Liss, Inc.
Screening a 2 cM genetic map for allelic association: A simulated oligogenic trait
Authors: Duffy David L.
Published: June 2005

In this paper, we explore the use of a variety of familial transmission tests (and case‐control analyses) to screen for allelic associations in simulated marker data of a quality (2 cM map) that will feasibly arise from genomic scans within the next 5‐10 years. We demonstrate a form of the transmission‐disequilibrium test extended to multiallele systems. The methods used were log‐linear and related models implemented largely using standard statistical packages. ©1995 Wiley‐Liss, Inc.
Logistic transmission modeling of simulated data
Authors: Harley John B. , Moser Kathy L. , Neas Barbara R.
Published: June 2005

A nonparametric method for linkage analysis has been developed and applied to the Problem 1 data set of the Genetic Analysis Workshop 9. Basically, the univariate matched pair strategy of the transmission disequilibrium test has been adapted to multivariate modeling using the conditional logistic function. After setting the critical value for significance at p ⩽ 0.0001, models at only D5G23 and D1G31 appear to be significant (p < 10−7). Logistic transmission modeling is a powerful method for establishing linkage by disequilibrium. ©1995 Wiley‐Liss, Inc.
Segregation and linkage analysis of the complex trait Q1
Authors: Atwood Larry D. , Mitchell Braxton D. , Stowell Nicole C.
Published: June 2005

Segregation and linkage analysis of GAW9 Problem 2 quantitative trait 1 (Q1) was performed. Eight segregation models comprising all possible combinations of the environmental factor (EF), quantitative trait 2 (Q2), and quantitative trait 3 (Q3) as covariates were considered. Seven of the eight segregation models showed strong evidence for a major gene, the other model was marginal. When all genotypes are known, some evidence for linkage (lod > 2) was found to all three of the markers that affect Q1. Furthermore, four of the eight models each showed some linkage (lod > 2) to two of the three markers that affect Q1 with no false positives. Each of these segregation analysis major genes is a hybrid combination of the true multiple loci that affect Q1. © 1995 Wiley‐Liss, Inc.
Relative‐risk regression models using cases and their parents
Authors: Schaid Daniel J.
Published: June 2005

Relative‐risk regression models are presented for studies of the association of genetic markers with disease status when the study design uses affected cases and their parents, with or without unaffected sibs. These models generalize the “haplotype relative‐risk” method and allow for censored unaffected sibs; in this sense, these models resemble proportional hazards models that are commonly used in survival analysis. A critical distinction between these models and the usual Cox proportional hazards model is that the frequencies of the genotypes of the cases are compared to controls based on Mendelian expectations, and not simply to the genotypes of the sib controls who are at risk of disease. These models allow modeling of the contribution of specific alleles to the relative risk of disease, as well as interactions of allelic effects with environmental risk factors. To demonstrate the application of these models, we have fit them to the binary affection status of the Problem 2 data set. Four candidate‐gene loci were found to have a significant association with affection status, after allowance for relative risks that decrease with age; two of these associations correctly identified two of the major gene loci, and the other two were false‐positive associations. © 1995 Wiley‐Liss, Inc.
Identification and mapping of mendelian subtypes of disease
Authors: Vieland Veronica J. , Mérette Chantal , Goodman Dan , Rouillard Eric
Published: June 2005

We took as our working hypothesis the premise that there could be a single locus of major effect underlying a subset of cases in the simulated Problem 2 data set, and took as our primary goal the task of mapping that locus. Treating the disease as dichotomous and using discriminant function analysis, we were able to separate affected individuals into two disease categories: Disease Type I (DT‐I) cases, whose disease was by hypothesis caused by the major locus; and Disease Type II (DT‐II) cases, whose disease was by hypothesis produced by other causes. Segregation analysis showed evidence of simple recessive inheritance among the DT‐I individuals. Linkage analysis under the best‐fitting recessive model gave clear evidence of linkage to D1G2. In the generating model, this marker is linked to a major gene for disease with recombination fraction θ = 0, and the mode of inheritance at that locus is recessive (when the trait is considered as a dichotomy). We conclude that when the true model is complex, focussing on subtypes of disease that show evidence of simple Mendelian inheritance may be a useful first step in determining the underlying model and mapping major genes. © 1995 Wiley‐Liss, Inc.
Analysis of breast cancer pedigrees using affected sibship methods
Authors: Barrett Jennifer H. , Rigby Alan S.
Published: June 2005

Haplotype‐sharing was examined in sets of affected siblings in the Breast Cancer Linkage Consortium pedigrees [Easton et al., 1993], using both identity‐by‐descent and identity‐by‐state methods. Linkage of the disease susceptibility locus to markers on chromosome 17 was confirmed. Substantial genetic heterogeneity was found, with more young cases being attributable to the putative gene. No differences were found between breast and ovarian cancer, and there was no evidence against a simple dominant mode of inheritance. © 1995 Wiley‐Liss, Inc.
Detection of genome similarity as an exploratory tool for mapping complex traits
Authors: Guo Sun‐Wei
Published: June 2005

For one‐ and two‐trait‐locus models, we show that the lod score based on affected relative pairs or trios is a monotonically increasing function of the genome similarity measured by the proportion of alleles shared identical by descent (IBD) conditional on observed marker data. These results can be generalized to multitrait‐locus models. Thus, we can use conditional probability of genes shared IBD as a tool to reveal chromosomal segments that are likely to harbor the genes underlying the complex traits. © 1995 Wiley‐Liss, Inc.
Changes in gonads and the thyroid gland after hypophysectomy in Ophicephalus punctatus Bloch
Authors: Belsare D. K.
Published: June 2005

Hypophysectomy in O. punctatus results in the atrophy of gonads and low activity of thyroid gland. The pituitary gland does not exert its influence on immature ova, but has decisive control over mature and maturing ova as well as over the germ cells in the testis. Changes in thyroid follicles in the absence of the pituitary gland are reduction in number, flattened epithelial cells, and accumulation of colloid in the follicles.
Biometrical problems in the study of early mammalian embryos in vitro
Authors: Biggers J. D. , Brinster R. L.
Published: June 2005

During recent years techniques have been evolved which permit the development of embryonic mouse cleavage stages in vitro. These methods are now sufficiently reliable for use in quantitative experiments such as the mapping of concentration‐response surfaces to discover the interaction of effects produced by various components of the medium. In studies on the development of mouse embryos in vitro conducted in our laboratory, a series of specialized biometrical problems has arisen.

In the present paper, the theoretical basis for analyzing the responses of two‐cell mouse ova in vitro is discussed. The responses are quantal in nature and are transformed before statistical treatment. The application of the angular and probit transformation to this data is illustrated. In certain cases, allowances must be made for a control portion of embryos failing to develop. The analyses are illustrated by two examples, one concerned with the determination of optimum conditions, and the other with the estimation of the median effective dose of a metabolic inhibitor.
Fat body cycling and experimental evidence for its adaptive significance to ovarian follicle development in the lizard Uta stansburiana
Authors: Hahn William E. , Tinkle Donald W.
Published: June 2005

The annual fat body cycle in the lizard Uta stansburiana is associated with reproduction. In females fat bodies decline in late winter and early spring when deutoplasm is deposited in the ovarian follicles. Males have a similar fat cycle, but fat bodies are much smaller. Ovariectomy eliminated rapid lipid mobilization from the fat bodies which occurs in sham operated controls. Fat body removal from early estrus females induces high incidence of follicular atresia and retards the rate of yolk deposition. Follicular growth is delayed or inhibited if fat bodies are excised from preestrus animals. The amount of extractable lipid in the pre‐estrus fat body is nearly equivalent to the lipid in a typical egg clutch. The adaptive value of the fat bodies is apparently associated with the formation of the first egg clutch which in accordance with population studies is the most important clutch.
The stimulus for case‐building activity in caddis‐worms (Trichoptera)
Authors: Merrill Dorothy
Published: June 2005

In four species of caddis‐worms,‐Ptilostomis semifasciata (Say), Platycentropus radiatus (Say), Limnephilus indivisus Walker, and Pycnopsyche guttifer (Walker), —removal of the anal hooks and the posterior hair sensilla significantly prolonged case‐building activity with a resulting increase in case production. The extensive building was of the rough provisional type, which is normally completed within a few hours. There were differences among the species with regard to the amount of excessive building and the relative importance of the hairs.

Transection of the ventral nerve cord appeared to block the extensive building that normally followed hook removal.

It is proposed that the stimulus for building is an endogenous process which causes excitatory impulses to be emitted from the several ganglia. The impulses go forward to the integrative areas controlling the animal's building apparatus and stimulate building. The emission of impulses from the ganglia is inhibited by sensory input from contact with the case.
Hypertrophy of the islets of Langerhans of frog tadpoles after partial pancreatectomy
Authors: Frye B. E.
Published: June 2005

Subsequent to incomplete surgical removal of the dorsal pancreatic rudiment of Rana pipiens embryos, islets of Langerhans arise in the pancreas, but in smaller amount than normal. Conpensatory hypertrophy of the beta cells occurs, and the islets are transformed from a larval into an adult histological type. Larval growth and metamorphosis is otherwise unaffected. The evidence supports the hypothesis that metamorphic maturation of the islets of Langerhans is a consequence of an increase in the functional demand on the islets of the frog as compared to the tadpole, and not to direct metamorphic effects of thyroxine. Possible causes for a relatively higher insulin requirement of the frog include (1) an increase in the carbohydrate load on the islets, (2) an increase in the secretion of hyperglycemic hormones, and (3) a higher rate of insulin inactivation.
Target discrimination by the echolocation of bats
Authors: Griffin D. R. , Friend J. H. , Webster F. A.
Published: June 2005

Myotis lucifugus first learned to catch mealworms mechanically projected into the air in a laboratory flight room, and were then trained to distinguish mealworms from small metal or plastic disks (3.0 × 12.5 mm and 0.5 × 6.3 mm). These three targets were presented singly in a semi‐random sequence, traveling along very similar trajectories. The most skillful bats caught 98% of the mealworms while avoiding any contact with 85 to 90% of the two types of disks. Echoes of 100–20 kc pulses (similar to the bats' orientation sounds) were measured from all three targets in almost all possible angular orientations. There was great overlap in intensity both in the peak amplitudes and in each of the ten 8 kc bands from 100–20 kc. These bats thus seem capable of some qualitative discrimination based on the “fine structure” of echoes from small moving targets.
An investigation of lactate dehydrogenase activity in early amphibian development
Authors: Adams Ellen , Finnegan Cyril V.
Published: June 2005

The ontogeny of the enzyme LDH has been studied in two species of amphibians (Amblystoma gracile and Rana aurora) as it provides a sensitive gauge of the state of differentiation of the organism, since the number and proportions of LDH isozymes present exhibit temporal and species specificity, thereby reflecting the degree of activity of the controlling genes. The presence of LDH in all stages of both species examined was establishd by assaying embryo homogenates for LDH activity, and the LDH was resolved into isozymic patterns by the methods of starch gels and disc electrophoresis. Specific enzyme activity for each developmental stage was correlated with the developmental events then occurring and the isozyme patterns obtained were discussed in terms of an increase in complexity during Anuran ontogeny while an extension of the current LDH isozyme hypothesis was advanced to account for some of the Urodele experimental findings.
Isozymes of isocitrate dehydrogenase: Subunit structure and intracellular location
Authors: Henderson Nanine S.
Published: June 2005

Isocitrate dehydrogenase (IDH) exists in mammalian tissues as three enzymes, one specific for NAD and two specific for NADP. The two NADP isozymes differ in electrophoretic mobility, immunological characteristics, and tissue and subcellular location. ONe is found mainly in the mitochondrial fraction and one in the supernatant fraction of tissue homogenates. Two allelic forms of the supernatant NADP isocitrate dehydrogenase have been described in inbred strains of mice. In a heterozygote containing both alleles, three forms of the supernatant NADP‐IDH are generated in a ratio of 1:2:1. This implies that the supernatant enzyme is a dimer. The mitochondrial form is not affected by the gene, indicating separate genetic control. Liver mitochondria contain both the supernatant and the mitochondrial isozymes. Thus at least one protein found in the mitochondria is encoded in a nuclear gene.
Duration of stimulus and latent periods preceding furrow formation in sand dollar eggs
Authors: Rappaport R. , Ebstein R. P.
Published: June 2005

Because information concerning the time relations of the cleavage stimulus should prove useful in characterizing both the stimulus and the nature of the response in the cell surface, methods were devised for determining how long the surface must be acted upon by the asters to produce a furrow and the duration of the latent period between the end of this stimulus period and appearance of the furrow. Eggs of the sand dollar Echinorachnius parma were used in experiments wherein unstimulated surface was brought close to the interastral zone of the mitotic apparatus for specified periods. Since this modification subjected the cell to physical stress or constraint, several different methods were used. As was anticipated, the times determined differed somewhat according to the method used. Exposure of the surface to the interastral zone for about one minute subsequently produces an active furrow. The latent period between the end of the stimulus period and the appearance of the furrow is about two and one‐half minutes and the total time from the beginning of stimulation to appearance of the furrow is between two and three and one‐half minutes.

The mitotic apparatus can repeatedly elicit new furrows within the same cell despite visible loss of distinctness from frequent handling. This suggests that stimulation is accomplished by a fundamentally simple relationship between asters and surface. During the latent period the presumptive furrow area has greater ability to retain its contour despite inncreased tension at the surface than does non‐furrow surface. The undiminished capacity for division that persists in cells subjected to frequent and extensive cytoplasmic shifting which accompanies relocation of the mitotic apparatus by pressure displacement implies that after stimulation, completion of the cleavage process is independent of any specific subsurface cytoplasmic configuration.
Periodic motility of normal and spinal chick embryos between 8 and 17 days of incubation
Authors: Hamburger Viktor , Balaban Martin , Oppenheim Ronald , Wenger Eleanor
Published: June 2005

Previous studies of the spontaneous cyclic motility of the chick embryo were extended to incubation day 17. The activity and inactivity phases of the cycle were recorded on a polygraph, for a 15‐minute observation period. The percentage of time spent in activity rises steadily from less than 10% at the beginning of motility at three and one‐half days to 80% at day 13. This peak is maintained up to day 17; subsequently, motility declines. The mean duration of activity phases increases and that of the inactivity phases decreases until the high plateau is reached, though both values change independently of each other. In order to study the effect of the brain on spontaneous motility, spinal embryos were obtained by extirpation of part of the cervical cord in two‐day embryos. The spinal embryos retain their capacity for cyclic motility. However, the activity is reduced by approximately 10–20% at all stages between the eighth and the seventeenth day. The brain influence asserts itself in a lengthening of the duration of the activity phases and in a shortening of the inactivity phases. An inhibitory effect was not observed at any stage.
The cytological and chemical organization of the prostatic epithelium of Didelphis virginiana Kerr
Authors: Martan Jan , Allen John M.
Published: June 2005

The prostatic complex of Didelphis virginiana Kerr has been studied by a variety of cytological and cytochemical means. Segment I was characterized by an apocrine type secretory mechanism. The apical parts of the epithelial cells, which were shed into the glandular lumen, contained vesicles which give positive cytochemical reactions for acid phosphatase, aliesterase, 5′‐nucleotidase, and nucleoside diphosphatase. These vesicles also contained material which was reactive with the periodic acid‐Schiff test for mucopolysaccharide and Baker's test for phospholipid. Segment II was characterized by the presence of two types of cells in the glandular epithelium. Type A cells contained large rounded secretory granules which gave positive reactions for acid mucopolysaccharides but not for proteins. Type B cells contained large elongate secretory granules which gave positive reactions for proteins but not for polysaccharides. Electronmicrographs indicated these secretory granules to have distinctive morphologies and to contain complex crystalloid material. No cells with characteristics intermediate between those of the A and B types were observed. Segment III of the prostatic complex was characterized by the presence of large amounts of glycogen both in the epithelial cells and within the glandular lumen. These observations indicate a remarkable degree of morphological and biochemical heterogeneity on the part of the prostatic complex of this animal.
Effects of ultraviolet microbeam irradiation on morphogenesis in Euplotes
Authors: Wise Benjamin N.
Published: June 2005

Developmental mechanisms in Euplotes plumipes were analyzed in terms of theresponse to damage produced by a UV microbeam. Individual animals, representing all stages of the morphogenetic cycle, were irradiated at a variety of cortical sites, including bases of mature cirri and membranelles, primordial structures, and non‐ciliated regions; they were then observed and fixed for silver‐staining.

Immediate damage is restricted to cortical and ciliary structures directly irradiated. Irradiated cirri and membranelles, including their associated basal structures (infraciliature), are effectively destroyed after about two minutes exposure to the UV microbeam. Contrary to what might be expected from the reports of earlier workers using microsurgical techniques, no regeneration response ensues following such damage in these animals. Damage to cirri perists until these organelles are replaced during normal pre‐division morphogenesis; damage to adoral membranelles, which are not normally replaced at division, persists indefinitely through succeeding generations of proters. It is concluded that destruction of infraciliary structures does not, in itself, provide a sufficient stimulus to regeneration in Euplotes.

Irradiation of either mature or primordial cortical organelles can be effective, however, in causing the temporary arrest of normal pre‐division morphogenesis, including resorption of all primordial stuctures, and the arrest or disappearance of macronuclear replication bands. The probability that resorption will occur depends, in part, on the developmental stage of the structures irradiated: irradiation of primordial structures during early stages induces this response more frequently than does irradiation of late stage primordia or mature organelles. These results are discussed in terms of the functional relationship between infraciliary structures and the mechanisms controlling development.
Inductive tissue interaction in the development of the mouse lens in vitro
Authors: Muthukkaruppan V.
Published: June 2005

Inductive tissue interaction involved in lens differentiation in the mouse embryo has been studied using millipore filter culture methods. The entire eye rudiment (nine day embryo) comprising optic vesicle, surrounding mesenchyme and overlying ectoderm differentiated in vitro into lens and retina, essentially as in normal development. Individual tissue components of trypsin‐separated lens primordia lost their structural organization when cultured alone, but lens epithelium in combination with mesenchyme was maintained as a vesicle without obvious lens fiber formation. Tissue recombination experiments show that differentiation of lens fibers in the presumptive lens ectoderm as well as in the lens placode depends on the inductive influence of optic cup. This influence can pass through a millipore filter barrier of 25 μ thickness and 0.45 μ porosity. Differentiation of lens fibers in the anterior lens epithelium of later embryos was also dependent on the inductive action of neural retina, suggesting the presence of continued inductive interaction in lens formation. The initial influence of optic vesicle on the presumptive lens ectoderm seems to be critical and of short duration, leading to the formation of a placode which has acquired stabilized lens forming property. Continued realization of this property depends on further inductive action.
Lactate dehydrogenase isozyme patterns of fish
Authors: Markert Clement L. , Faulhaber Ilse
Published: June 2005

Representatives of 30 species of fish were examined for their content of LDH isozymes. One major isozyme system was found in all fish. In addition, two minor systems restricted to eyes and to gonads were found in many fish. Fish may be classified into four groups on the basis of their possession of one, two, three, or five major isozymes of LDH. The major isozyme patterns can be attributed to the polymers of two protein subunits under the control of two genes, as in mammals and birds, but the variety of heteropolymers produced varies in different species. The fluke and other flatfish are exceptional in that they synthesize only one kind of subunit which polymerizes to form a single variety of LDH. All other fish produced at least two major isozymes presumably the homopolymers of A and B subunits. The three‐isozyme fish produce, in addition, a single heteropolymer. A few fish produce three heteropolymers and two homopolymers to produce the characteristic pattern of five isozymes seen in mammals.

In populations of the whiting, which has five major isozymes, two mutant alleles at the B locus were discovered. Each of these alleles produced polypeptides with characteristic electrophoretic mobilities. Consequently, heterozygous individuals contained more than 15 isozymes.

A variety of minor isozymes that appear on zymograms may represent modifications of the major isozymes. However, the minor isozyme systems of the gonad and the eye seem to be genetically distinct molecular systems, separate from and in addition to the major isozyme system.
Implantation of ferret ova fertilized by mink sperm
Authors: Chang M. C.
Published: June 2005

Epididymal mink (Mustela vison) sperm were inseminated into the uterine horns of ferrets (Mustela furo) at various times before or after ovulation which was induced by intraperitoneal injection of H.C.G. The Fallopian tubes or uterine horns of each animal were examined at different times. The ova were recovered and examined microscopically for the evidence of fertilization at 60–66 hours. Cleavage of ova, blastocyst formation during 4–12 days, and the development of embryos during 22 to 42 days were also ascertained.

The fertilization rate is rather low, ranging between 8–41%, probably depending on the number of sperm inseminated and the time of insemination in relation to ovulation. The cleavage rate is lower than either the ferret or mink ova, but no delayed implantation was observed as in the case of the mink. The fertilized ova developed and implanted, but degeneration occurred at various stages, although some of them went to advanced stages.
Influence of the adrenal glands on DNA synthesis in normal and compensating kidneys
Authors: Reiter Russel J. , McCreight Charles E.
Published: June 2005

The role of the adrenal glands in controlling the synthesis of deoxyribonucleic acid in normal and compensating kidneys of rats given saline drinking fluid was studied using tritiated‐thymidine and radioautography. Adrenalectomy alone increased significantly the labeling indices of the renal cortex and medulla of otherwise intact rats.

Two days following unilatral nephrectomy of rats with intact adrenal glands, the number of labeled nuclei in the remaining kidney increased by factors of about 4 and 2.5 in the cortex and the medulla, respectively. Adrenalectomy moderately decreased the hyperplastic response of the cortex of the remaining kidney, but increased still further the labeling index of the medulla.

By five days after unilateral nephrectomy of rats with intact adrenal glands, neither the cortex nor the medulla of the remaining kidney exhibited a marked hyperplastic response. In adrenalectomized animals, also, unilateral nephrectomy caused only slight increases in the labeling indices of the cortex and the medulla of the remaining kidney.
Alcohol dehydrogenases: A polymorphism in Drosophila melanogaster
Authors: Ursprung Heinrich , Leone Janet
Published: June 2005

By means of a rapid microelectrophoretic technique suitable for single‐fly analysis, two types of alcohol dehydrogenase (ADH) isozyme patterns were found, each true breeding in homozygous stocks. A cross of these two types produces offspring with a third type of ADH pattern, containing hybrid ADH molecules in addition to the parental forms. Various strains were analyzed and found to contain flies of the three ADH types in various proportions indicating different gene frequencies.

When octanol was used as a substrate instead of ethanol, an additional isozyme system was found, for which some strains are polymorphic also.

The results obtained thus far are consistent with the assumption that ADH in Drosophila is a dimer.
Differentiation of transplanted larval salivary glands of Drosophila hydei in adults of the same species
Authors: Berendes H. D. , Holt Th. K. H.
Published: June 2005

Salivary glands implanted in adult milieu without simultaneous implantation of larval ring glands showed further development and differentiation. The development of the glands was tested by thymidine‐H3 and uridine‐H3 incorporation in the chromosomes and by proline‐H3 incorporation in the cytoplasm. Differentiation was evaluated on the basis of the presence or absence of mucopolysaccharide synthesis in the cells.

Chromosomal thymidine incorporation was observed to proceed for a longer period in the adult milieu. DNA measurements revealed that at least in some cells of glands which were implanted at a mid third instar stage the level of polyteny is increased to a level which is never reached during normal development.

Glands implanted at a mid third instar stage showed chromosomal uridine incorporation until at least 18 days after implantation.

Comparison of the chromosomal puffing patterns in normal and implanted glands revealed that the chromosomes are still able to produce specific puffs after at least three weeks of implantation.

In general, glands which were implanted at younger stages of normal development showed a higher response to the adult milieu than glands implanted at a stage near to puparium formation. Also the individual cells of implanted glands showed obvious differences in their response to the adult milieu. It was concluded that the growth and differentiation of the gland cells proceeds but that the regulation and coordination of the processes are disturbed in the adult milieu.
Chemical and morphological studies on inorganic phosphate deposits in Rana catesbeiana skin
Authors: Taylor R. E. , Taylor H. C. , Barker S. B.
Published: June 2005

Skin from Rana catesbeiana adults and tapoles was found to contain an unusually high concentration of inorganic phosphate which was chemically identified and histologically localized as dense granules of calcium phosphate deposited as a discrete layer at the junction between the stratum spongiosum and the stratum compactum of the dermis. Electron microscopic studies revealed that the granules were composed of fine needle‐like crystals and were not associated with cells which seemed obviously related to their genesis. Although no definite function was established for this apparently normal structure of bullfrog skin, its possible role as a reservoir of readily available calcium was suggested. As such, it would represent an important factor to be considered in studies of the biochemistry and physiology of frog skin, especially those which deal with the effects of calcium depletion.