Nf1;Trp53 mutant mice develop glioblastoma with evidence of strain-specific effects

Astrocytomas are the leading cause of brain cancer in humans. Because these tumours are highly infiltrative, current treatments that rely on targeting the tumour mass are often ineffective. A mouse model for astrocytoma would be a powerful tool for dissecting tumour progression and testing therapeutics. Mouse models of astrocytoma have been designed to express oncogenic proteins in astrocytes, but have had limited success due to low tumour penetrance or limited tumour progression. We present here a mouse model of astrocytomas involving mutation of two tumour-suppressor genes, Nf1 and Trp53. Humans with mutations in NF1 develop neurofibromatosis type I (NF1) and have increased risk of optic gliomas, astrocytomas and glioblastomas. The TP53 tumour suppressor is often mutated in a subset of astrocytomas that develop at a young age and progress slowly to glioblastoma (termed secondary glioblastomas, in contrast to primary glioblastomas that develop rapidly de novo). This mouse model shows a range of astrocytoma stages, from low-grade astrocytoma to glioblastoma multiforme, and may accurately model human secondary glioblastoma involving TP53 loss. This is the first reported mouse model of astrocytoma initiated by loss of tumour suppressors, rather than overexpression of transgenic oncogenes.     

Effect of Timing of Grazing on Soil-Surface Crytogamic Communities in a Great Basin Low-Shrub Desert: A Preliminary Report

Cover and species richness of vascular and cryptogamic components of the plant community were inventoried in experimental grazing paddocks at the USDA/FS Desert Range Experimental Station, Millard County, Utah. The grazing treatments considered have been applied continuously for over 50 years. The effects of heavy (ca 17 sheep days/acre) grazing treatment applied in two different seasons (early winter versus a split between early and late winter) differed significantly between seasons. Cryptogamic cover and cryptogamic species richness both showed larger decreases under early-late as opposed to early winter only grazing. Vascular plant cover (relative to controls) was also reduced by early-late winter grazing, but not to a significant degree. Late season grazing, likewise, had no significant effect on number of vascular species per transect.     

Radio harness system for bobcat kittens

Eight bobcat kittens were fitted with a specially designed harness system supporting a radio transmitter. These kittens were the youngest known to be radio-instrumented. This system was used successfully through two seasons, from June 1989 to January 1991. Litters of kittens were located soon after birth for weighing, marking, and aging (by tooth eruption). During the first year when kittens were at least eight weeks old and six weeks old the second year, attempts were made to radio-instrument kittens in each litter. This harness system allowed litters to be located periodically until their death or dispersal. We were able to collect important data during the most crucial and least known weeks of the lives of bobcat kittens.     

New insights into copper monooxygenases and peptide amidation: structure, mechanism and function

Many bioactive peptides must be amidated at their carboxy terminus to exhibit full activity. Surprisingly, the amides are not generated by a transamidation reaction. Instead, the hormones are synthesized from glycine-extended intermediates that are transformed into active amidated hormones by oxidative cleavage of the glycine N-C alpha bond. In higher organisms, this reaction is catalyzed by a single bifunctional enzyme, peptidylglycine alpha-amidating monooxygenase (PAM). The PAM gene encodes one polypeptide with two enzymes that catalyze the two sequential reactions required for amidation. Peptidylglycine alpha-hydroxylating monooxygenase (PHM; EC 1.14.17.3) catalyzes the stereospecific hydroxylation of the glycine alpha-carbon of all the peptidylglycine substrates. The second enzyme, peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL; EC 4.3.2.5), generates alpha-amidated peptide product and glyoxylate. PHM contains two redox-active copper atoms that, after reduction by ascorbate, catalyze the reduction of molecular oxygen for the hydroxylation of glycine-extended substrates. The structure of the catalytic core of rat PHM at atomic resolution provides a framework for understanding the broad substrate specificity of PHM, identifying residues critical for PHM activity, and proposing mechanisms for the chemical and electron-transfer steps in catalysis. Since PHM is homologous in sequence and mechanism to dopamine beta-monooxygenase (DBM; EC 1.14.17.1), the enzyme that converts dopamine to norepinephrine during catecholamine biosynthesis, these structural and mechanistic insights are extended to DBM.     

The significance of mycorrhizas for protective ecosystems

Summary On the basis of the reviews presented in this issue, the ecological significance of mycorrhizal symbioses is discussed. Mycorrhizas may have some importance in the acquisition of mineral nutrients during the productive phase of ecosystems in early stages of succession, but their main role is played during the protective phase of ecosystems in the final stages of succession when most resources are incorporated into biomass. In these successional stages, mycorrhizas short-circuit nutrient cycles by directly reacquiring nutrients in organic form from plant (and fungal) litter, and they may reallocate resources between different plant individuals, preventing loss of resources from the entire ecosystem.     

Oriential orchid (Cymbidium pumilum) attracts drones of the Japanese honeybee (Apis cerana japonica) as pollinators

The discovery that drones of the Japanese honeybee (Apis cerana japonica) pollinate the oriental orchid (Cymbidium pumilum) is reported. Drones are attracted to the orchid flower aroma mainly during their mating flights in April through May. Some drones cluster on the flower racemes and others insert their heads deep into the flowers. Drones with pollinia on their scutellum visit other orchids, which facilitates pollination. Individual workers and swarming colonies are also strongly attracted by the flower aroma, but the allopatric western honeybee (Apis mellifera) is not attracted.     

Suppression of immunization to tuberculosis and diphtheria by an extract of lymphoid tissue

Zusammenfassung Dank einer neuen Anwendung von Lymphknotenextrakten (statt Röntgenextrakten, Corticosteroiden, Antilymphozytenserum usw.) wird eine erhebliche Reduktion der immunologischen Reaktion erzielt, wenn die Tiere mit diesen Extrakten vorbehandelt und gleichzeitig mit Antigenen behandelt werden.

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This investigation was supported in part by U.S.P.H.S. Research Grant No. CA-02624 from National Cancer Institute; and in part by an institutional grant to Detroit Institute of Cancer Research from United Foundation of greater Detroit allocated through Michigan Cancer Foundation and the Detroit General Hospital Research Corporation, and Newaygo County Cancer Society.     

Defensive alkaloid in blood of Mexican bean beetle (Epilachna varivestis)

The blood of the Mexican bean beetle (Epilachna varivestis) contains a homotropane alkaloid, euphococcinine (1). The beetles 'reflex bleed' when disturbed, thereby deploying the alkaloid, which is provenly deterrent to spiders and ants. Newly emerged adults lack the alkaloid, but the compound builds up to deterrent levels in their blood within days. Eggs and larvae of Epilachna are devoid of the compound.     

Paternal allocation of sequestered plant pyrrolizidine alkaloid to eggs in the danaine butterfly,Danaus gilippus

Summary Pyrrolizidine alkaloid sequestered by adult maleDanaus gilippus from plants is transferred in large measure to the female at mating, and by the female to the eggs. The eggs, presumably, are protected as a result. The male's courtship pheromone, danaidone, derived from the sequestered alkaloid, may function to advertise the male's alkaloid-donating capacity.Acknowledgments. Paper Nr. 89 of the series Defense Mechanisms of Arthropods. Study supported by NIH (Grants AI-02908 and AI-12020; Predoctoral Traineeship to DED), Hatch funds (191-7416), the Bache Fund (National Academy of Sciences, to DED), and the Theodore Roosevelt Memorial Fund (American Museum of Natural History, to DED). We thank M. Weingarner and J. Miller forD. gilippus collection, J. Boggan for technical assistance, and the staff of the Archbold Biological Station, Lake Placid, Florida, for assistance and hospitality. One of us (DED) is indebted to M. D. Achey, who by demonstrating nuptial cardenolide transfer in the monarch butterfly [Honors Thesis, Amherst College, Amherst, Massachusetts (1979)] raised the possibility that other plant metabolites might be similarly transferred in danaines.Deceased July, 1985. This paper is affectionately dedicated to his memory.     

Effect of metabolic versus respiratory acid-base changes on isolated coronary artery and saphenous vein

Summary Experiments were performed on helically cut strips from coronary artery and saphenous vein to determine the relative influence of metabolic versus respiratory acid-base changes. Tensions were measured over a range of various HCO₃ ^– concentrations and pCO₂'s. The results suggest that tension is influenced by extracellular pH and is independent of pCO₂.Supported by USPHS grant No. HL24232.