Alteichin: an unusual phytotoxin from Alternaria eichorniae, a fungal pathogen of water hyacinth

The phytopathogenic fungus Alternaria eichorniae attacks water hyacinth, an economically significant aquatic weed. The novel phytotoxin alteichin was isolated from liquid cultures of this fungus and its structure was deduced by X-ray crystallographic analysis. Altheichin is a doubly hydrated form of 4,9-dihydroxy perylene-3, 10-quinone. A single step dehydration of alteichin to anhydroalteichin is catalyzed both by acid and by a crude enzyme preparation from water hyacinth.     

Antihypertensive activity of some novel pyridinylidene arylurea derivatives in spontaneously hypertensive rats.

3 novel pyridinylidene arylurea derivatives were found to lower arterial pressure in spontaneously hypertensive rats. Their relative oral potency ranged from 6 to 32 times that of guanethidine. The onset of antihypertensive action following their oral administration was less than 1 h and the duration of action ranged from 8 to over 24 h. The antihypertensive activity of the pyridinylidene arylureas was found to be assoicated with depletion of tissue catecholamines. Compound C depleted cardiac norepinephrine with little or no effect on total brain norepinephrine levels. It is suggested that compound C may have useful antihypertensive properties without CNS depressant activity.     

Melanocyte biology and skin pigmentation

Melanocytes are phenotypically prominent but histologically inconspicuous skin cells. They are responsible for the pigmentation of skin and hair, and thereby contribute to the appearance of skin and provide protection from damage by ultraviolet radiation. Pigmentation mutants in various species are highly informative about basic genetic and developmental pathways, and provide important clues to the processes of photoprotection, cancer predisposition and even human evolution. Skin is the most common site of cancer in humans. Continued understanding of melanocyte contributions to skin biology will hopefully provide new opportunities for the prevention and treatment of skin diseases.     

Inhibition of RNA cleavage but not polyadenylation by a point mutation in mRNA 3' consensus sequence AAUAAA

A single U leads to G transversion in the 3' consensus sequence AAUAAA of the adenovirus early region 1A gene was constructed and the effect of this mutation on processing of the 3' end of the nuclear early region 1A RNAs was analysed. The results demonstrate that the intact AAUAAA is not required for RNA polyadenylation but is required for the cleavage step preceding polyadenylation to occur efficiently.     

Erythropoietic effects of PGE2 and 2 endoperoxide analogs

Summary The erythropoietic effects in exhypoxic polycythemic mice of two endoperoxide analogs were assessed and compared with PGE₂. The 9a, 11a epoxymethano analog (U-44069) was found to be a much more potent erythropoietic stimulus than the 11a,9a analog (U-46619) or PGE₂.This work was supported by a Senior Research Grant-in-Aid from the American Heart Association-Louisiana (DMG) and USPHS Grant No. AM 13211 (JWF).     

1-(Substituted)benzyl-5-aminoimidazole-4-carboxamides are potent orally active inhibitors ofTrypanosoma cruzi in mice

Summary 1-(Substituted)benzyl-5-aminoimidazole-4-carboxamides are potent orally active inhibitors ofTrypanosoma cruzi infections in mice. The most active compounds are the 1-(4-chlorobenzyl)- and 1-(3,4-dichlorobenzyl)-analogs (L-153,094 [2] and L-153,153 [4], resp.) which are approximately 7-fold more potent upon oral administration than nifurtimox (Lampit) in suppressing parasite levels in the blood of mice with acuteTrypanosoma cruzi infections.     

Electronic structure of the iron-based superconductor LaOFeP

The recent discovery of superconductivity in the iron oxypnictide family of compounds has generated intense interest. The layered crystal structure with transition-metal ions in planar square-lattice form and the discovery of spin-density-wave order near 130 K (refs 10, 11) seem to hint at a strong similarity with the copper oxide superconductors. An important current issue is the nature of the ground state of the parent compounds. Two distinct classes of theories, distinguished by the underlying band structure, have been put forward: a local-moment antiferromagnetic ground state in the strong-coupling approach, and an itinerant ground state in the weak-coupling approach. The first approach stresses on-site correlations, proximity to a Mott-insulating state and, thus, the resemblance to the high-transition-temperature copper oxides, whereas the second approach emphasizes the itinerant-electron physics and the interplay between the competing ferromagnetic and antiferromagnetic fluctuations. The debate over the two approaches is partly due to the lack of conclusive experimental information on the electronic structures. Here we report angle-resolved photoemission spectroscopy (ARPES) of LaOFeP (superconducting transition temperature, T(c) = 5.9 K), the first-reported iron-based superconductor. Our results favour the itinerant ground state, albeit with band renormalization. In addition, our data reveal important differences between these and copper-based superconductors.     

Dissection of epistasis in oligogenic Bardet-Biedl syndrome

Epistatic interactions have an important role in phenotypic variability, yet the genetic dissection of such phenomena remains challenging. Here we report the identification of a novel locus, MGC1203, that contributes epistatic alleles to Bardet-Biedl syndrome (BBS), a pleiotropic, oligogenic disorder. MGC1203 encodes a pericentriolar protein that interacts and colocalizes with the BBS proteins. Sequencing of two independent BBS cohorts revealed a significant enrichment of a heterozygous C430T mutation in patients, and a transmission disequilibrium test (TDT) showed strong over-transmission of this variant. Further analyses showed that the 430T allele enhances the use of a cryptic splice acceptor site, causing the introduction of a premature termination codon (PTC) and the reduction of steady-state MGC1203 messenger RNA levels. Finally, recapitulation of the human genotypes in zebrafish shows that modest suppression of mgc1203 exerts an epistatic effect on the developmental phenotype of BBS morphants. Our data demonstrate how the combined use of biochemical, genetic and in vivo tools can facilitate the dissection of epistatic phenomena, and enhance our appreciation of the genetic basis of phenotypic variability.