Combining parametric and nonparametric models to estimate treatment effects in observational studies

Performing causal inference in observational studies requires we assume confounding variables are correctly adjusted for. In settings with few discrete-valued confounders, standard models can be employed. However, as the number of confounders increases these models become less feasible as there are fewer observations available for each unique combination of confounding variables. In this paper, we propose a new model for estimating treatment effects in observational studies that incorporates both parametric and nonparametric outcome models. By conceptually splitting the data, we can combine these models while maintaining a conjugate framework, allowing us to avoid the use of Markov chain Monte Carlo (MCMC) methods. Approximations using the central limit theorem and random sampling allow our method to be scaled to high-dimensional confounders. Through simulation studies we show our method can be competitive with benchmark models while maintaining efficient computation, and illustrate the method on a large epidemiological health survey.     

Mapping of the interleukin 5 receptor gene to human Chromosome 3 p25–p26 and to mouse Chromosome 6 close to the Raf-1 locus with polymorphic tandem repeat sequences

Simple-sequence tandem repeat sequences in the 3 UTR of interleukin 5 (IL5)-receptor gene of human and mouse are polymorphic in their length among humans and different strains of mice. In 20 different human Epstein-Barr virus (EBV)-transformed cell lines, six alleles of IL5R could be distinguished. In the mouse, three different alleles are found. With the human-specific IL5R tandem repeat marker in human-rodent somatic cell hybrids, the IL5R gene was mapped to human Chromosome (Chr) 3 p25–p26. With the mouse-specific IL5R tandem repeat sequence in recombinant inbred strains of mice, the Il5r gene was mapped to the distal part of mouse Chr 6 close to the Raf-1 locus.     

Rings, circles, and null-models for point pattern analysis in ecology

A large number of methods for the analysis of point pattern data have been developed in a wide range of scientific fields. First-order statistics describe large-scale variation in the intensity of points in a study region, whereas second-order characteristics are summary statistics of all point-to-point distances in a mapped area and offer the potential for detecting both different types and scales of patterns. Second-order analysis based on Ripley's K-function is increasingly used in ecology to characterize spatial patterns and to develop hypothesis on underlying processes; however, the full range of available methods has seldomly been applied by ecologists. The aim of this paper is to provide guidance to ecologists with limited experience in second-order analysis to help in the choice of appropriate methods and to point to practical difficulties and pitfalls. We review (1) methods for analytical and numerical implementation of two complementary second-order statistics, Ripley's K and the O-ring statistic, (2) methods for edge correction, (3) methods to account for first-order effects (i.e. heterogeneity) of univariate patterns, and (4) a variety of useful standard and non-standard null models for univariate and bivariate patterns. For illustrative purpose, we analyze examples that deal with non-homogeneous univariate point patterns. We demonstrate that large-scale heterogeneity of a point-pattern biases Ripley's K-function at smaller scales. This bias is difficult to detect without explicitly testing for homogeneity, but we show that it can be removed when applying methods that account for first-order effects. We synthesize our review in a number of step-by-step recommendations that guide the reader through the selection of appropriate methods and we provide a software program that implements most of the methods reviewed and developed here.     

MORPHOLOGY AND DEVELOPMENT OF HYPERPLASIA ON CYSTOSEIRA OSMUNDACEA (PHAEOPHYTA) ASSOCIATED WITH HALOGUIGNARDIA IRRITANS (ASCOMYCOTINA)

The tissue of Cystoseira osmundacea (Turn.) C. Ag. (Fucales, Phaeophyta) undergoes pronounced developmental changes when in association with the fungus Haloguignardia irritans (Setchell et Estee) Cribb et Cribb (Sphaeriales, Ascomycotina). Nonmeristematic cortical cells are induced to divide and ultimately form a structure composed of tightly packed club-shaped projections. Each projection contains a single fungal ascocarp or spermogonium. A protective multilayered algal tissue surrounds the fungal reproductive structures. This association significantly alters algal morphology to the apparent protective advantage of the fungus.     

Persistent Enhancement of Sustained Calcium-Dependent Glutamate Release by Phorbol Esters: Role of Calmodulin-Independent Serine/Threonine Phosphorylation and Actin Disassembly

Abstract: The phorbol ester 4β-phorbol 12,13-dibutyrate increases the final extent of Ca²⁺-dependent glutamate release during the continuous depolarization of the synaptosomal plasma membrane. Based on this finding, we suggested that the sustained activation of protein kinase C has a positive influence on the efficiency of synaptic vesicle recycling in the presence of saturating concentrations of Ca²⁺. Previous work from our laboratory demonstrated that this 4β-phorbol 12,13-dibutyrate-dependent enhancement of synaptic vesicle recycling persists following the removal of 4β-phorbol 12,13-dibutyrate, requires localized Ca²⁺ entry through voltage-regulated channels, and is insensitive to the protein kinase inhibitor staurosporine. In the present study, we examined the possibility that the facilitation of glutamate release may be propagated through interactions between the protein kinase C- and multifunctional Ca²⁺/calmodulin-dependent protein kinase pathways. However, our data argue strongly against the involvement of such a mechanism in the persistent enhancement of sustained glutamate release. We observed that 4β-phorbol 12,13-dibutyrate did not increase the availability of cytosolic free calmodulin or the level of autonomous Ca²⁺/calmodulin-dependent protein kinase activity. In addition, we determined the effects of various serine/threonine kinase and phosphatase inhibitors on the phorbol ester-dependent enhancement of sustained glutamate release and found that protein kinase C increased the extent, but not the duration, of Ca²⁺-dependent glutamate release through a kinase-independent mechanism. Given our finding that the actin-depolymerizing agent cytochalasin D totally occluded the effect of 4β-phorbol 12,13-dibutyrate on release, we postulate that protein kinase C signals may be transduced through direct interactions between protein kinase C isoforms and cytoskeletal protein kinase C binding proteins.     

Expression cloning of oncogenes by retroviral transfer of cDNA libraries.

a cDNA library transfer system based on retroviral vectors has been developed for expression cloning in mammalian cells. The use of retroviral vectors results in stable cDNA transfer efficiencies which are at least 100-fold higher than those achieved by transfection and therefore enables the transfer and functional screening of very large libraries. In our initial application of retroviral transfer of cDNA libraries, we have selected for cDNAs which induce oncogenic transformation of NIH 3T3 fibroblasts, as measured by loss of contact inhibition of proliferation. Nineteen different transforming cDNAs were isolated from a total of 300,000 transferred cDNA clones. Three of these cDNAs were derived from known oncogenes (raf-1, lck, and ect2), while nine others were derived from genes which had been cloned previously but were not known to have the ability to transform fibroblasts (beta-catenin, thrombin receptor, phospholipase C-gamma 2 and Spi-2 protease inhibitor genes). The Spi-2 cDNA was expressed in antisense orientation and therefore is likely to act as an inhibitor of an endogenous transformation suppressor. Seven novel cDNAs with transforming activities, including those for three new members of the CDC24 family of guanine nucleotide exchange factors, were also cloned from the retroviral cDNA libraries. Retroviral transfer of libraries should be generally useful for cloning cDNAs which confer selectable phenotypes on many different types of mammalian cells.     

Inositol lipid-mediated signalling in response to endothelin and ATP in the mammalian testis

Molecular and Cellular Biochemistry - The testis is a complex organ in which local control is achieved by signalling between its constituent cells. Herein we describe the responses of cultured rat...     

Determination of mitochondrial calcium content in hepatocytes by a rapid cellular-fractionation technique. Alpha-adrenergic agonists do not mobilize mitochondrial Ca2+.

A rapid cellular fractionation technique [the preceding paper, Shears & Kirk (1984) Biochem. J., 219, 375-382] was employed to separate a mitochondria-rich fraction from hepatocytes within seconds. Mitochondrial Ca was estimated to be no more than 41% of total cell Ca. At least half of the mitochondrial Ca was present in an energy-dependent pool; 20% of total cell Ca was accessible to EGTA within 10s. The alpha-adrenergic agonist phenylephrine stimulated glycogen phosphorylase activity by 100% within 0.5 min and induced a loss of 20% of total cell Ca after 10 min from the EGTA-inaccessible pool. However, between 0.5 and 10 min after the addition of phenylephrine to hepatocytes there was no significant change in the Ca content of the mitochondria-rich fraction. Hepatocytes that were preloaded with Ca2+ during 90 min incubation at 0-4 degrees C expelled this cation during 20 min incubation at 37 degrees C. After this time, phenylephrine failed to alter the Ca content of a mitochondria-rich fraction. It is concluded that alpha-adrenergic agonists do not mobilize Ca2+ from hepatocyte mitochondria.     

Seasonal variations in pituitary LH-gonadotropes of the hibernating bat Myotis lucifugus lucifugus: an immunohistochemical study

Pituitary gonadotropes were identified throughout the year in the seasonally breeding, hibernating bat Myotis lucifugus lucifugus by means of light microscopic immunohistochemistry. In both male and female bats, these cells were immunoreactive with an antiserum directed to the beta subunit of luteinizing hormone. Some gonadotropes were aggregated near a portion of the infundibular stalk which crosses the anterior lobe, while most were scattered singly in a uniform manner throughout the rest of the pars distalis. This cell population exhibited seasonal variations in both sexes. In males, the proportional volume of the pars distalis occupied by immunoreactive gonadotropes (volume fraction) was significantly reduced in late July, when plasma testosterone levels were approaching their seasonal peak. In females, the volume fraction declined in April, following ovulation, and remained low during pregnancy and lactation. The size and shape of gonadotropes appeared relatively constant throughout the annual reproductive cycle in male bats; the immunoreactive cells were irregular in shape, with cytoplasmic extensions insinuating between and often "cupping" other secretory cell types. In females, the gonadotropes resembled those of males throughout most of the year, except during pregnancy, when these cells became enlarged and ovoid. No evidence of involution was observed in these anterior pituitary cells in either males or females during hibernation.