Defective calcium homeostasis in the cerebellum in a mouse model of Niemann-Pick A disease

We recently demonstrated that calcium homeostasis is altered in mouse models of two sphingolipid storage diseases, Gaucher and Sandhoff diseases, owing to modulation of the activities of a calcium-release channel (the ryanodine receptor) and of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) respectively, by the accumulating sphingolipids. We now demonstrate that calcium homeostasis is also altered in a mouse model of Niemann-Pick A disease, the acid sphingomyelinase (A-SMase)-deficient mouse (ASM-/-), with reduced rates of calcium uptake via SERCA in the cerebellum of 6-7-month-old mice. However, the mechanism responsible for defective calcium homeostasis is completely different from that observed in the other two disease models. Thus, levels of SERCA expression are significantly reduced in the ASM-/- cerebellum by 6-7 months of age, immediately before death of the mice, as are levels of the inositol 1,4,5-triphosphate receptor (IP3R), the major calcium-release channel in the cerebellum. Systematic analyses of the time course of loss of SERCA and IP3R expression revealed that loss of the IP3R preceeded that of SERCA, with essentially no IP3R remaining by 4 months of age, whereas SERCA was still present even after 6 months. Expression of zebrin II (aldolase C), a protein found in about half of the Purkinje cells in the adult mouse cerebellum, was essentially unchanged during development. We discuss possible pathological mechanisms related to calcium dysfunction that may cause Purkinje cell degeneration, and as a result, the onset of neuropathology in Niemann-Pick A disease.     

Dark CO(2) Fixation in Gladiolus Cormels and Its Regulation during the Break of Dormancy

The increase in dark CO₂ fixation during cold storage of Gladiolus x gandavensis van Houtte-type grandiflorus cormels is used to monitor changes in their state of dormancy. Dark fixation is also promoted by benzyladenine, which breaks cormel dormancy, and is inhibited by abscisic acid and gibberellin A₃, which inhibit cormel germination. The rate of dark fixation by nondormant cormels is five times higher than that in dormant ones. Dark fixation is not due to microorganisms. It is temperature-dependent and can be measured stoichiometrically in vivo. The apex and base of the cormels accumulate more label than the central part. Dark fixation of both dormant and nondormant cormels is also promoted by imbibition in water. The fate of the labeled assimilates was followed by ion exchange chromatography.     

Control of tubulin and actin gene expression in Tetrahymena pyriformis during the cell cycle

Poly(A)-containing mRNA was isolated from division synchronized populations of the ciliated protozoan, Tetrahymena pyriformis. The level of tubulin and actin mRNA at specific cell cycle stages was analyzed by hybridization to tubulin and actin cDNA probes and by gel analysis of their in vitro translation products. The pattern of fluctuation of tubulin mRNA levels was similar to that observed for the in vivo tubulin synthesis previously reported [1]. This suggests that as the cells progress through the cell cycle, tubulin synthesis is controlled at the mRNA level. There was little fluctuation of actin synthesis or actin mRNA levels during the cell cycle, which may be indicative of a different regulatory mechanism for actin than for tubulin.     

Respiratory muscle function during CO2 rebreathing with inspiratory flow-resistive loading

We investigated the respiratory muscle contribution to inspiratory load compensation by measuring diaphragmatic and intercostal electromyograms (EMGdi and EMGic), transdiaphragmatic pressure (Pdi), and thoracoabdominal motion during CO2 rebreathing with and without 15 cmH2O X l-1 X s inspiratory flow resistance (IRL) in normal sitting volunteers. During IRL compared with control, Pdi measured during airflow and during airway occlusion increased for a given change in CO2 partial pressure and EMGdi, and there was a greater decrease in abdominal (AB) end expiratory anteroposterior dimensions with increased expiratory gastric pressure (Pga), this leading to an inspiratory decline in Pga with outward AB movement, indicating a passive component to the descent of the abdomen-diaphragm. The response of EMGic to IRL was similar to that of EMGdi, though rib cage (RC)-Pga plots did infer intercostal muscle contribution. We conclude that during CO2 rebreathing with IRL there is improved diaphragmatic neuromuscular coupling, the prolongation of inspiration promoting a force-velocity advantage, and increased AB action serving to optimize diaphragm length and configuration, as well as to provide its own passive inspiratory action. Intercostal action provides increased assistance also. Therefore, compensation for inspiratory resistive loads results from the combined and integrated effort of all respiratory muscle groups.     

Ultrarapid endocytotic uptake of large molecules inDunaliella species

Summary This paper describes the uptake of Lucifer Yellow carbohydrazide and fluorescent dextrans labeled with fluorescein isothiocyanate or Sodium Green (molecular masses ranging from 522 to 2 × 10⁶ Da) byDunaliella spp. halotolerant unicellular green algae isolated from salt pools in the Sinai peninsula. The fluorescent dyes were taken up into a set of vesicles around the nucleus and just above the chloroplast. It proved impossible to inhibit uptake of the fluorescent compounds in cells treated with a large variety of metabolic and other inhibitors. Cell labeling was complete within half a minute of addition of fluorescent compounds to the outside medium; efflux was equally rapid. The results are interpreted in terms of an endocytotic process whereby the outside medium, together with any substance dissolved in it, remains within vesicles enclosed within the cell body but cycles rapidly between the plasma membrane and the interior of the cell. The outside medium does not pass across the vesicular membrane, nor enters the cytosol.Abbreviations LYCH Lucifer Yellow carbohydrazide - FITC fluorescein-5-isothiocyanate - TCA trichloroacetic acid - DMSO dimethylsulfoxide - NEM N-ethyl maleimide - DNP dinitrophenol - CCCP m-chlorocarbonyl-cyanide phenylhydrazone - APM amiprophos-methyl     

Multilocus population genetics: Relative importance of selection and recombination

Difficulties of the exact analysis of multilocus systems lead to a feeling that a radical change of point of view should be attempted. The questions one asks ãbout the behavior of a multilocus system should differ from the usual questions we ask when analyzing low-dimensional dynamical systems. We show in this paper that the likelihood for selection to prevail over recombination grows with the number of loci involved. In other words, the average fitness will in “most cases” behave as if the system were in complete linkage equilibrium.     

The theory of population dynamics—II. Physiological delays

Traditional population models describe changes in population size as a function of changes in the resources. Such first-order models cannot describe certain properties of population dynamics. General models with delays can account for all the observed dynamic complexities but are judged overgeneralized. It is proposed that the simplest model of intermediate complexity that explains such dynamic properties is a second-order model, which describes population dynamics as a function of a physiological variable, the dynamics of which in turn depends on resources. Data on accelerated decline of populations in the absence of food from experiments with brown and green hydra as well as literature data support the arguments.     

The determination of ectodermal derivatives in various species of amphibia

The process of labyrinth determination has been studied in amphibians (three Urodela and seven Anura species) using homoplastic transplantation of ear ectoderm, containing labyrinth material onto the abdominal wall of embryos of the same stage of development. The stage of appearance of organ-specific properties in ear ectoderm was determined and the increase of these properties in the course of development was observed. The frequency of ear vesicles formation, the level of their differentiation and their size served as criteria. These criteria allow to align the studied species into a row, where organ-specific properties appear earlier and most completely in representatives of Ranidae family and in Bufo viridis, and weakest, in smooth newt. A comparison of properties of labyrinth material and other areas of ectoderm allowed to conclude that specific differences in determination of different ectodermal primordia are based on specific peculiarities of the whole ectoderm. The appearance of these differences can be explained by the shift in the beginning of gastrulation towards later stages of cleavage during the evolution of amphibians.