Analysis of gain-of-function mutations of the lin-12 gene of Caenorhabditis elegans

Certain cell fate decisions are specified by cell-cell interactions during the development of the nematode Caenorhabditis elegans. For example, in a wild-type hermaphrodite gonad, two cells, Z1.ppp and Z4.aaa, have the potential to become the anchor cell (AC). Intercellular communication establishes their fates and ensures that only one cell becomes the AC, while the other becomes a ventral uterine precursor cell (VU). One component of this intercellular communication seems to be the 'AC-to-VU' signal from the presumptive AC that causes the other cell to become a VU. Genetic and developmental studies indicated that the lin-12 gene specifies the fates of Z1.ppp and Z4.aaa. Molecular studies suggest that lin-12 directly participates in their communications, perhaps acting as the receptor for the 'AC-to-VU' signal. Here, we report the molecular lesions associated with lin-12 gain-of-function mutations, cell isolation experiments, and genetic studies of an unusual lin-12 allele. These data suggest that self-association of the putative lin-12-encoded receptor leads to its activation, and that certain gain-of-function mutations result in ligand-independent activation.     

Enzymatic processing of pheromones and pheromone analogs

Summary Pheromone perception requires rapid enzymatic degradation of the active chemical signal in the sensory hairs. Three insects are used to illustrate chemical approaches to studying the degradation of pheromones by antennal enzymes. First, hydrolysis of acetate and haloacetate esters is examined in the diamondback moth,Plutella xylostella. Second, aldehyde oxidation and the selective inhibition of the oxidase and dehydrogenase activities are described for the tobacco budworm moth,Heliothis virescens. Finally, a stereochemical analysis of the epoxide-hydrase catalyzed addition of a water molecule to the oxirane ring of disparlure is described for the gypsy moth,Lymantria dispar.     

Disruption of circadian rhythm of tissue respiration inChanna striatus by Metasystox®

Summary Oxygen consumption of gill, brain and muscle tissues ofChanna striatus exhibits a clearcut circadian rhythm with a maximum uptake at 18.00 h. Metasystox exposure decreased the oxygen consumption of all tissues. Maximum reduction is noted in gill followed by brain and muscle. The peak period of oxygen consumption is also eliminated in the pesticide-treated fish.Acknowledgments. Prof. G. Sundara Rajulu is thanked for suggestions and UGC for financial assistance.     

Growth inhibitory,insecticidal and antifeedant effects of some antileukemic and cytotoxic quassinoids on two species of agricultural pests

Summary Several quassinoids, obtained by isolation and derivatization fromSimaba multiflora andSoulamea soulameoides, were evaluated for growth inhibitory and insecticidal effects against the tobacco budworm (Heliothis virescens) and for antifeedant effects againstH. virescens and the fall armyworm (Spodoptera frugiperda). The relative activity of the quassinoids as insect growth inhibitors generally paralleled their known relative potency as antileukemic and cytotoxic agents.Phytochemical aspects of this work were supported by Contract CM-97295 with the Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, Md. Insects were kindly supplied by the agency of the United States Department of Agriculture at Brownsville, TX.     

Stimulated neutrophils from patients with autosomal recessive chronic granulomatous disease fail to phosphorylate a Mr-44,000 protein

Phagocytosing neutrophils, monocytes, macrophages and eosinophils produce a burst of non-mitochondrial respiration that is important for the killing and digestion of microbes. Much of the information about the oxidase system involved comes from studies on patients with chronic granulomatous disease (CGD), a syndrome in which an undue predisposition to infection results from complete absence of this burst of stimulated respiratory activity. The basis of the oxidase activity is an electron transport chain, the only established component of which is a very unusual b-type cytochrome (b-245) (ref. 2). The molecular defect in the X-linked subgroup of CGD is the absence of this cytochrome b-245, which, however, appears to be normal in those subjects with the autosomal recessive mode of inheritance. In an attempt to identify an abnormality of activation, or an absence or malfunction of a proximal component of the electron transport chain in this latter group, we examined protein phosphorylation in neutrophils after activation of the oxidase with phorbol myristate acetate. All four of the patients studied demonstrated a selective lack of the enhanced phosphorylation of a protein of relative molecular mass (Mr) 44,000 (44K) that was observed in normal subjects and in two CGD patients with an X-linked inheritance. This molecule, therefore, could be an important functional component of the oxidase.     

Thiarubrine A, a bioactive constituent of Aspilia (Asteraceae) consumed by wild chimpanzees

Two African species of Aspilia (Asteraceae), which are used medicinally by man and which are eaten by wild chimpanzees in an unusual manner, were found to contain the potent antibiotic thiarubrine A as a major leaf phytochemical. Its presence in leaf material strengthens the view that the feeding behavior of wild chimpanzees is related to special physiological or pharmacological effects on the animals.     

A comparison of the effects of the optical isomers of isoproterenol on energy metabolism in a mouse sarcoma

Summary Disturbance to energy production in the S180 sarcoma (CB) by optical isomers of isoproterenol was assessed from altered adenine nucleotide levels at 1 h. The L-isomer almost halved the ATP level and lowered the energy charge significantly; the D-isomer was inactive. Dependence of tumor injury on cytochrome P-450 activity appears unlikely.One of us (GRNJ) thanks the Department of Surgery, Medical School, Kings's College Hospital, London, England, for the provision of experimental facilities; the Institute of Biochemistry, German Cancer Research Centre, Heidelberg, FRG, for permitting the measurement of metabolites; the Cancer Research Campaign, London, UK, for a part-time grant; and Zyma GmbH, München, FRG, and the estate of the late Dr Lucie Polak for additional financial support.     

Consequences of acute ischemia for the electrical and mechanical function of the ventricular myocardium. A brief review

Reduction or interruption of the blood supply to the myocardium leads to marked disturbances of electrical and mechanical function within a few seconds. Electrical dysfunction is characterized by an initial depolarization of the resting membrane, and a decrease of the amplitude, the upstroke velocity and the duration of the action potential. Both depolarization and depression of the action potential are closely associated with intracellular metabolic acidosis. After this initial phase, electrical cell-to-cell uncoupling develops, probably as a consequence of increased cytosolic free [Ca++]. Mechanical dysfunction is characterized by a dissociation of the initial decrease of active force development from the subsequent ischemic contracture. Active force development in acute ischemia is inhibited by the accumulation of ischemic metabolic products (H+, inorganic phosphate (Pi), Mg++) but not by a marked decrease of [ATP]. The subsequent ischemic contracture is probably initiated by release of Ca++ from intracellular stores. This release causes rapid consumption of ATP and the development of rigor within 1-2 minutes.