An unexpectedly long history of sexual selection in birds-of-paradise

Background  

The birds-of-paradise (Paradisaeidae) form one of the most prominent avian examples of sexual selection and show a complex biogeographical distribution. The family has accordingly been used as a case-study in several significant evolutionary and biogeographical syntheses. As a robust phylogeny of the birds-of-paradise has been lacking, these hypotheses have been tentative and difficult to assess. Here we present a well supported species phylogeny with divergence time estimates of the birds-of-paradise. We use this to assess if the rates of the evolution of sexually selected traits and speciation have been excessively high within the birds-of-paradise, as well as to re-interpret biogeographical patterns in the group.     

Antimalarial benzo[c]phenanthridines

Analogues of the antimalarial alkaloid nitidine have been prepared with high potency against both chloroquine-sensitive and -resistant strains of Plasmodium falciparum in vitro. Simple modifications, using an established synthetic route, resulted in an analogue with IC(50) below 5ng/mL against a chloroquine-sensitive strain of P. falciparum. N-Ethylethoxidine had IC(50) below 30ng/mL against both chloroquine-sensitive and chloroquine-resistant strains of P. falciparum.     

The importance of amino acids as carbon sources for Micromonospora echinospora (ATCC 15837)

AIMS: This study set out to investigate the effect of amino acids on the uptake of glucose by Micromonospora eichinospora (ATCC 15837). METHODS AND RESULTS: The specific rate of glucose uptake was found to be reduced when organic nitrogen components were present in the medium. Radioactive uptake studies revealed that the Km for glucose in this organism was 53 mm, indicating a low affinity for uptake compared with other actinomycete sugar transport systems. Individual amino acids negatively influenced the rate of glucose transport, suggesting a relationship between amino acid metabolism and glucose uptake in this organism. The sugar transport system was found to be an active process being inhibited by ionophores and KCN. CONCLUSIONS: The data suggest a direct link between amino acid metabolism and glucose uptake at the level of sugar transport. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows that the uptake of glucose, a major carbon source for many antibiotic fermentations, is significantly reduced in the presence of amino acids. This fact should inform the medium design and feeding regimes of fermentations involving similar actinomycetes.     

Causes of fatal childhood accidents involving head injury in northern region, 1979-86.

OBJECTIVE--To examine the causes and circumstances surrounding fatal accidents involving head injuries in children in the Northern region. DESIGN--Retrospective review of the hospital case notes, necropsy reports, and records of the coroners'' inquests. SETTING--Northern Regional Health Authority. PATIENTS--All 255 children aged less than 16 years who died with a head injury during 1979-86. MAIN OUTCOME MEASURES--Cause of injury and circumstances of accident according to reports of inquests; injury severity score; number of fatal accidents and mortality per 100,000 children in 10 groups of local authority wards ranked according to their score on the overall deprivation index; and distance of site of accident from child''s home. RESULTS--Of the 255 children who died after a head injury, 136 (53%) children were playing at the time of the accident. 195 (76%) children sustained the head injury in road traffic accidents, 135 as pedestrians, 35 as cyclists, and 25 as passengers in a vehicle. In 120 accidents in child pedestrians the primary cause of accident was the unsafe behaviour of the child. 172 (67%) accidents occurred within one to two km of the child''s home and 153 (63%) between 3 pm and 9 pm. The mortality was significantly related to social deprivation; excluding eight children injured while on holiday in the region, 15-fold decrease in mortality was recorded between the local authority wards that ranked highest on the overall deprivation index and those that ranked lowest (14.0/100,000 children, group 10 v 0.9/100,000, group 1 respectively, p less than 0.00001). CONCLUSIONS--The finding that most accidents occurred in children living in deprived areas who were playing unsupervised near their home suggests that childhood mortality might be appreciably reduced if children at play were protected from traffic, particularly in socially deprived areas.     

Review of cytologic slides from the national women's hospital, New Zealand, cohort of women with cervical intraepithelial neoplasia 3 diagnosed in 1955-1976

OBJECTIVE: To review cytologic slides, mostly at least 25 years old, from women attending National Women's Hospital, Auckland, who had been diagnosed histologically with cervical carcinoma in situ in 1955-1976. STUDY DESIGN: Smears comprised all those from the 2 years following diagnosis as well as all subsequent smears for women who developed "microinvasive" or invasive lower genital tract cancer. The Victorian Cytology Service performed the review using the Australian Modified Bethesda System. was 0.97. RESULTS: Nine percent of 4,930 retrieved slides were technically unsatisfactory. Original (Papanicolaou) and review coding were available for 4,477 slides. Using categories of equivalence, smears coded as normal (original, 59.2%; review, 61.4%) or showing possible or definite high grade abnormalities (original, 25.9%; review, 29.6%) were found in similar proportions. The kappa statistic (0.79) indicated a high level of agreement between original and review coding. In comparison with the review, the sensitivity of the original coding in detecting high grade abnormalities was 0.80, while the ability of the original assessment to categorize smears as not high grade (specificity) CONCLUSION: This comprehensive review found nearly all archived cytology slides to be technically satisfactory and the broad diagnostic cytologic categories from earlier periods (apart from benign lesions) to be concordant with those currently used.     

Novel antibiotics: C-2 symmetrical macrocycles inhibiting Holliday junction DNA binding by E. coli RuvC

Holliday junctions (HJs) are formed as transient DNA intermediates during site-specific and homologous recombination. Both of these genetic exchange pathways are critical for normal DNA metabolism and repair. Trapping HJs leads to bacterial cell death by preventing proper segregation of the resulting interlinked chromosomes. Macrocyclic peptides designed to target this intermediate were synthesized with the goal of identifying compounds with specificity for this unique molecular target. We discovered ten macrocycles, both hexameric and octameric peptides, capable of trapping HJs in vitro. Those macrocycles containing tyrosine residues proved most effective. These data demonstrate that C-2 symmetrical macrocycles offer excellent synthetic targets for the development of novel antibiotic agents. Furthermore, the active compounds identified provide valuable tools for probing different pathways of recombinational exchange.     

Aspartyl protease inhibitor pepstatin binds to the presenilins of Alzheimer's disease.

Mutations in the presenilin genes PS1 and PS2 cause early-onset Alzheimer's disease by altering gamma-secretase cleavage of the amyloid precursor protein, the last step in the generation of Abeta peptide. Ablation of presenilin (PS) genes, or mutation of two critical aspartates, abolishes gamma-secretase cleavage, suggesting that PS may be the gamma-secretases. Independently, inhibition experiments indicate that gamma-secretase is an aspartyl protease. To characterize the putative gamma-secretase activity associated with presenilins, lysates from human neuroblastoma SH-SY5Y and human brain homogenates were incubated with biotin derivatives of pepstatin, followed by immunoprecipitation of PS and associated proteins, and biotin detection by Western blotting. Precipitation with PS1 antibodies, directed to either N-terminal or loop regions, yielded the same 43 kDa band, of apparent molecular mass consistent with that of full-length PS1, although it may represent an aspartyl protease complexed with PS1. Incubation of cell lysates with pepstatin-biotin, followed by streptavidin precipitation and PS1 Western blotting, revealed PS1 fragments and full-length protein, indicating that pepstatin-biotin bound to both cleaved and uncleaved PS1. Binding could be competed by gamma-secretase inhibitor L-685,458 and could not be achieved with a PS1 mutant lacking the two transmembrane aspartates. Pepstatin-biotin was also shown to bind to PS2. PS1 was specifically absorbed to pepstatin-agarose, with an optimal pH of 6. Binding of pepstatin-biotin to PS1 from lymphocytes of a heterozygous carrier of pathologic exon 9 deletion was markedly decreased as compared to control lymphocytes, suggesting that this PS1 mutation altered the pepstatin binding site.     

Location of a mutation in the aspartyl-tRNA synthetase gene of Escherichia coli K12

A mutation (tls-1) that confers a temperature-sensitive growth phenotype in Escherichia coli was shown by DNA cloning and sequencing to be an allele of aspS, the gene for aspartyl-tRNA synthetase. The mutation, which lies near minute 41 on the genetic map, was located some 2.3 kb from the 5' end of the ruvAB operon. A DNA fragment encoding the carboxy-terminus of AspRS was found to be sufficient to allow growth of a tls-1 strain at the non-permissive temperature.