Inhibition of RNA-directed DNA polymerase by aurintricarboxylic acid.

Commercial-grade aurintricarboxylic acid (ATA) inhibits poly(A), poly(C) and viral RNA-directed DNA synthesis by detergent-disrupted virions of Moloney murine leukemia virus. Paper chromatography of crude ATA yields two active components, which appear to behave identically, and at least two inactive components. The concentration of ATA needed to inhibit polymerase activity is proportional to the concentration of viral protein. The inhibition is neither attributable to contaminating heavy metal ions in the ATA preparation nor to chelation by ATA of Mn2+ or Zn2+, the necessary co-factors. Inhibition of the polymerase reaction by ATA greatly increases the Km for the primer [oligo(T)/oligo(dG)], while it only slightly lowers the Vmax and does not affect the Km's for the template [poly(A)/poly(C)] or the substrate (TTP/dGTP). Thus, ATA seems to reduce specifically the affinity of the polymerase for the DNA primer molecule.     

Reliability of statistical associations between genes and disease

Many statistical associations between a disease and alleles of specific genes have proven to be irreproducible. In part, this irreproducibility can be attributed to a lack of replication before publication and the fact that, until recently, the relationship between statistical significance and various measures of reproducibility was not widely understood. This review proposes a classification system, the Better Associations for Disease and GEnes (BADGE) system, for describing genetic associations. The BADGE classes, first class through fifth class, are based on the P value of the association. A first-class association, with P<2×10⁻⁷, is expected to be reproducible even in the absence of other evidence supporting the association. A fifth-class association corresponds to conventional statistical significance (P<5×10⁻²), which provides almost no assurance of reproducibility. Three intervening classes, described as second-, third-, and fourth-class associations, are defined by P values separated by factors of 20 or 25 from these extremes.     

A continuous-flow system for the growth of RNA tumor viruses.

By continuously pumping tissue culture medium into roller bottles containing infected cells and continuously harvesting the spent medium, RNA tumor virus can be harvested conveniently within 20 min of its release from the infected cells. An apparatus used to collect Moloney mouse leukemia virus in such a way yielded up to 390 μg protein in purified virus (about 1 mg virus) from each liter of tissue culture fluid.     

Effect of relative humidity and origin of isolates of Neozygites tanajoae (Zygomycetes: Entomophthorales) on production of conidia from cassava green mite, Mononychellus tanajoa (Acari: Tetranychidae), cadavers

Neozygites tanajoae is a very specialized fungus pathogenic to the cassava green mite (CGM), Mononychellus tanajoa, an important cassava pest introduced to Africa from the Neotropics. Conidial discharge from cadavers of CGM that died from infections with 14 isolates of N. tanajoae collected from diverse climates of Brazil was quantified to help select potential candidate strains for introduction to Africa. Studies aimed to identify isolates with lower requirements for relative humidity for sporulation and isolates that discharged more conidia during short periods of moisture. At 96 ± 0.5% RH, production of conidia was variable and even isolates from the Brazilian semi-arid region, e.g., Petrolina and Itaberaba, produced few conidia. Significant differences in the numbers of conidia produced by diverse Brazilian isolates were observed after 6, 9 and 12 h at 100% RH. At 100% RH, production of primary conidia increased considerably from an average of 57 ± 4 conidia at 6 h to 509 ± 37 conidia at 12 h. The isolate sporulating least (BIN21) discharged only 45.7% of the number of conidia produced by isolate BIN1, one of the isolates producing the most spores. Results from this study demonstrate that differences in production of conidia among isolates should be considered when selecting Neozygites isolates for new biological control introductions.     

Faster Cognitive and Functional Decline in Dysexecutive versus Amnestic Alzheimer's Subgroups: A Longitudinal Analysis of the National Alzheimer's Coordinating Center (NACC) Database

Objective

To compare the rate of cognitive and functional decline in dysexecutive, typical and amnestic subgroups of Alzheimer’s disease.

Methods

943 participants from the National Alzheimer’s Coordinating Center (NACC) database who had a diagnosis of probable AD were followed for a mean of 2.3 years. A dysexecutive subgroup (n = 165) was defined as having executive performance >1.5 SD worse than memory performance, an amnestic subgroup (n = 157) was defined as having memory performance >1.5 SD worse than executive performance and a typical subgroup (n = 621) was defined as having a difference in executive and memory performance of <1.5 SD. Generalized estimating equations (GEE) were used to model decline on the Folstein Mini Mental Status Exam (MMSE), rise on the Clinical Dementia Rating (CDR) sum of boxes and rise on the total Functional Assessment Questionnaire (FAQ).

Results

Compared with the amnestic subgroup, the dysexecutive subgroup declined 2.2X faster on the Folstein MMSE (p<.001), rose 42% faster on the CDR sum of boxes (p = .03) and rose 33% faster on the total FAQ (p = .01). Rate of change for the typical subgroup fell between that of the amnestic and dysexecutive subgroups for the MMSE, CDR sum of boxes and total FAQ. Among a subset of participants (n = 129) who underwent autopsy, the dysexecutive, amnestic and typical subgroups did not differ in odds of having an AD pathologic diagnosis, suggesting that variation in non-AD pathologies across subtypes did not lead to the observed differences.

Conclusions

A dysexecutive subgroup of AD has a unique disease course in addition to cognitive phenotype.     

A model for dispersion experiments

Summary A new model is proposed for the dispersion of animals and other organisms and its use is discussed for the analysis of the data from experiments on dispersion. The model is a generalisation of the random walk model, but because of its flexibility it should be much more widely applicable than the random walk model.The new model has been found to fit the results of many dispersion experiments and examples are given of its use with data for millipedes and Drosophila.