In situ analysis of centromere segregation in C57BL/6 x Mus spretus interspecific backcrosses

The analysis of major satellite sequence differences between Mus spretus and laboratory mice provides a robust method for analyzing the centromere location for the genetic maps of each mouse chromosome. Fluorescence in situ hybridization (FISH) of a genomic probe, pMR196, for the laboratory mouse major satellite sequences was used to identify C57BL/6Ros (B6) pericentromeric heterochromatin in progeny of reciprocal backcross matings. These included 80 (B6xM. spretus)F₁xM. spretus progeny (BSS) and 70 (B6xM. spretus)F₁xB6 (BSB) progeny. FISH analysis of pericentromeric heterochromatin was conducted on the same metaphase spreads that were karyotypically analyzed for chromosomespecific banding patterns. Analysis of chromosomal segregation suggested that there was not primary deviation from random assortment during meiosis in the interspecific hybrid female, because nearly all of the 190 pair-wise comparisons did not deviate from expected and because there was no consistent pattern of deviation of the same chromosomes in the reciprocal backcross progeny from similar (C57BL/6xM. spretus)F₁ hybrid females. These results affirm the value of using the major satellite to genetically mark pericentromeric heterochromatin in the analysis of the segregation and assortment of centromeres in Mus interspecific crosses.     

Using real-world data to predict health outcomes—The prediction design: Application and sample size planning

The gold standard for investigating the efficacy of a new therapy is a (pragmatic) randomized controlled trial (RCT). This approach is costly, time-consuming, and not always practicable. At the same time, huge quantities of available patient-level control condition data in analyzable format of (former) RCTs or real-world data (RWD) are neglected. Therefore, alternative study designs are desirable. The design presented here consists of setting up a prediction model for determining treatment effects under the control condition for future patients. When a new treatment is intended to be tested against a control treatment, a single-arm trial for the new therapy is conducted. The treatment effect is then evaluated by comparing the outcomes of the single-arm trial against the predicted outcomes under the control condition. While there are obvious advantages of this design compared to classical RCTs (increased efficiency, lower cost, alleviating participants’ fear of being on control treatment), there are several sources of bias. Our aim is to investigate whether and how such a design—the prediction design—may be used to provide information on treatment effects by leveraging external data sources. For this purpose, we investigated under what assumptions linear prediction models could be used to predict the counterfactual of patients precisely enough to construct a test and an appropriate sample size formula for evaluating the average treatment effect in the population of a new study. A user-friendly R Shiny application (available at: https://web.imbi.uni-heidelberg.de/PredictionDesignR/ ) facilitates the application of the proposed methods, while a real-world application example illustrates them.     

Cytological Studies of the Nematocysts of Hydra : II. The Stenoteles

Entire hydras or tentacles were prepared for electron microscopy as described in the preceding paper. The stenotele capsule has been observed to be composed of an external membrane, a thick chitinous or keratin layer, and an inner membrane. A sac-like extension of the capsular wall into the capsule bears spines and stylets on its inner surface and evagination of this structure occurs on discharge. Profiles of tubular or membranous structures often are seen within the capsules of resting stenoteles. These structures are presumably related to the external filament. The spines often reveal a flattened aspect which suggests that at least some of them might more accurately be called "vanes." A cnidocil has been found to accompany each stenotele. This study revealed several aspects of the developmental stages of stenoteles: A vacuole is formed which is nearly surrounded by the nematocyte nucleus. The vacuole content changes in density and a capsular wall is formed at the periphery of the vacuole. Tubules differentiate from the capsular matrix, and spines and stylets develop somewhat later. An operculum is formed from the nematocyte cytoplasm.     

PRELIMINARY INFERENCES OF THE PHYLOGENY OF BRYOPHYTES FROM NUCLEAR-ENCODED RIBOSOMAL RNA SEQUENCES

Ribosomal RNA sequences and cladistic analysis were used to infer a phylogeny for eight bryophyte taxa. Portions of the cytoplasmic large (26S-like) and small (18S-like) subunit ribosomal RNA genes were sequenced for three marchantioid liverworts (Asterella, Conocephalum, and Riccia), three mosses (Atrichum, Fissidens, and Plagiomnium), and two hornworts (Phaeoceros and Notothylas). Cladistic analysis of these data suggests that the hornworts are the sister group to the mosses, the mosses and hornworts form a clade that is sister to the tracheophytes, and the liverworts form a clade sister to the other land plants. These results differ from previous cladistic analyses based on morphology, ultrastructure, and biochemistry, wherein the mosses alone are sister group to the tracheophytes. We conclude that cladistic analysis of molecular data can provide an independent data set for the study of bryophyte phylogeny, but the differences between the molecular and morphological results are a topic for further investigation.     

IDENTIFICATION OF CYTOKININS IN SARGASSUM MUTICUM (PHAEOPHYTA) AND PORPHYRA PERFORATA (RHODOPHYTA)1

Combined gas chromatography-mass spectrometry (GCMS) was used to identify and quantify specific cytokinins from Porphyra perforate J. Ag. and Sargassum muticum (Yendo) Fensh. The level of isopentenyladenosine was estimated to be 0.6 μ·kg^?1 fresh weight in Porphyra and 0.9 μ·kg^?1 fresh weight in Sargassum. The level of cis-zeatin riboside was estimated to be 0.2 μ·kg^?1 fresh weight in Sargassum. This is the first definitive identification of a cytokinin from a red alga, and the second report from a brown alga.     

PHYLOGENY OF THE ULVOPHYCEAE (CHLOROPHYTA): CLADISTIC ANALYSIS OF NUCLEAR-ENCODED rRNA SEQUENCE DATA1

Cladistic analysis of nuclear-encoded rRNA sequence data provided us with the basis for some new hypotheses of relationships within the green algal class Ulvophyceae. The orders Ulotrichales and Ulvales are separated from the clade formed by the remaining orders of siphonous and siphonocladous Ulvophyceae (Caulerpales, Siphonocladales /Cladophorales [S/C] complex, and the Dasycladales), by the Chlorophyceae and Pleurastrophyceae. Our results suggest that the Ulvophyceae is not a monophyletic group. Examination of inter- and intra-ordinal relationships within the siphonous and siphonocladous ulvophycean algae revealed that Cladophora, Chaetomorpha, Anadyomene, Microdictyon, Cladophoropsis and Dictyosphaeria form a clade. Thus the hypothesis, based on ultrastructural features, that the Siphonocladales and Cladophorales are closely related is supported. Also, the Caulerpales is a monophyletic group with two lineages; Caulerpa, Halimeda, and Udotea comprise one, and Bryopsis and Codium comprise the other. The Dasycladales (Cymopolia and Batophora) also forms a clade, but this clade is not inferred to be the sister group to the S/C complex as has been proposed. Instead, it is either the sister taxon to the Caulerpales or basal to the Caulerpales and S/C clade The Trentepohliales is also included at the base of the siphonous and siphonocladous ulvophycean clade. The Pleurastrophyceae, which, like the Ulvophyceae, posses a counter-clockwise arrangement of flagellar basal bodies, are more closely related to the Chlorophyceae than to the Ulvophyceae based on rRNA sequences. Thus, the arrangement of basal bodies does not diagnose a monophyletic group. Previously reported hypotheses of phylogenetic relationships of ulvophycean algae were tested. In each case, additional evolutionary steps were required to obtain the proposed relationships. Relationships of ulvophycean algae to other classes of green algae are discussed.     

Minocycline induced autoimmune hepatitis and systemic lupus erythematosus-like syndrome.

Monocycline is the most widely prescribed systemic antibiotic for acne largely because it needs to be given only once or twice a day and seems not to induce resistance. Up to April 1994 11 cases of minocycline induced systemic lupus erythematosus and 16 cases of hepatitis had been reported to the Committee on Safety of Medicines. An analysis of these cases together with seven other cases shows the severity of some of these reactions. Two patients died while taking the drug for acne and a further patient needed a liver transplant. Acne itself can induce arthritis and is often seen in association with autoimmine liver disease, but the clinical and biochemical resolution seen after withdrawal of the drug, despite deterioration of the acne, suggests a drug reaction. In five cases re-exposure led to recurrence. Because reactions may be severe early recognition is important to aid recovery and also to avoid invasive investigations and treatments such as corticosteroids and immunosuppresants. Safer alternatives should be considered for treating acne.     

Primate terminal complement inhibitor homologues of human CD59

The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession numbers L22862 (African green monkey CD59) and L22863 (baboon CD59)