Inhibition of Nb2 T-lymphoma cell growth by transforming growth factor-beta.

1. Mitochondria isolated from the gut-dwelling nematodes Nippostrongylus brasiliensis and Ascaridia galli (muscle and gut + reproductive tissue) were examined for cytochromes, and it was observed that N. brasiliensis and A. galli muscle tissue mitochondria contained a-, b- and c-type cytochromes, but their stoichiometries were quite different (1:2:1.9 and 1:11.4:13.6 respectively); A. galli gut + reproductive-tissue mitochondria, however, only contained b and c cytochromes, in a ratio of 1:0.8. 2. CO difference spectra showed the presence of CO-reacting b-type cytochrome(s) in all three types of mitochondria; the fast-reacting species comprised 30, 44 and 39% of the total in N. brasiliensis, A. galli muscle and A. galli gut + reproductive-tissue mitochondria respectively. 3. Cytochrome aa3 was observed in N. brasiliensis mitochondria and in those from A. galli muscle, but was below the level of detectability (less than 0.005 nmol/mg of protein) for A. galli gut + reproductive-tissue mitochondria. 4. Photochemical action spectra for the reversal of CO inhibition of the endogenous respiration of whole worms (at 24 microM- and 40 microM-O2 respectively for N. brasiliensis and A. galli) gave maxima at 598 and 542-543 nm, corresponding to the alpha- and beta-absorption maxima of cytochrome aa3, and at 567 nm (b-type cytochrome) for both worms. These results suggest that cytochrome aa3 is the major functional oxidase in N. brasiliensis, whereas the CO-reacting b-type cytochrome dominates in A. galli.     

Ataxia-telangiectasia fibroblasts have less fibronectin mRNA than control cells but have the same levels of integrin and β-actin mRNA

Summary The cytological behavior of the spindle apparatus was studied in cells prone to nondisjunction (ND), i.e., PHA-stimulated lymphocytes derived from children suffering from different types of neoplasia. These cells, which exhibited a high frequency of nonspecific aneuploidy, revealed an increased resistance of the spindle fibers to colchicine, podophyllotoxin, and cold, wich was several times that of lymphocytes derived from healthy children. The results are in accord with previous findings showing a high resistance of spindle microtubules to the antimicrotubular agents colchicine, podopyllotoxin, vinblastine, and cold in PHA-stimulated lymphocytes derived from individuals prone to meiotic ND. It is therefore assumed that high resistance of the spindle apparatus to antimicrotubule agents characterizes cells at high risk for aneuploidy, and possibly, the overstabilized spindle fibers are responsible for failure of chromosomal disjunction.     

Coronavirus and Paramyxovirus Shedding by Bats in a Cave and Buildings in Ethiopia

EcoHealth - Bats are important hosts of zoonotic viruses with pandemic potential, including filoviruses, MERS-Coronavirus (CoV), SARS-CoV -1, and likely SARS-CoV-2. Viral infection and transmission...     

<Emphasis Type="Italic">In vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis> antifungal activity of crude extracts and powdered dry material from Ethiopian wild plants against economically important plant pathogens

In Ethiopia extracts from specific plants are used traditionally as natural fungicides in small scale farming systems where synthetic chemicals are out of reach of the average subsistence farmer while no scientific base exists for this practice. Subsequently, methanolic crude extracts from Dolichos kilimandscharicus and Maerua subcordata roots as well as Phytolacca dodecandra berries were screened in vitro for antifungal activity against Botrytis cinerea Pers.:Fr., Fusarium oxysporum Schlechtend.:Fr., Sclerotium rolfsii Sacc., Rhizoctonia solani Kühn,, Botryosphaeria dothidea (Moug.:Fr.) Ces &; De Not. and Pythium ultimum Trow, using an agar diffusion method. Compared to the other plants as well as specific standard fungicides for each pathogen, the root extract of D. kilimandscharicus showed the highest broad-spectrum in vitro antifungal activity by inhibiting the mycelial growth of three of the six test organisms. Additionally, in vivo antifungal activity of dry powdered material from these plants against sorghum covered (Sporisorium sorghi) and loose kernel (Sporisorium cruentum) smuts was screened under field conditions by artificially inoculating separate sets of sorghum seed with smut spores before treating with plant material or two traditionally used fungicides, Thiram^® and Apron Plus^® that served as positive controls. Although the incidence of both loose and covered kernel smuts were significantly reduced by material from all plant species, the dry powdered berries of P. dodecandra were most effective. Compared to the untreated control, treatment with the plant material as well as standard fungicides resulted in significant yield increases. It was concluded that a rationale has been established for further investigation into the structured utilization of natural vegetation indigenous to Ethiopia in the agricultural industry.     

Exome Sequencing of Phenotypic Extremes Identifies CAV2 and TMC6 as Interacting Modifiers of Chronic Pseudomonas aeruginosa Infection in Cystic Fibrosis

Discovery of rare or low frequency variants in exome or genome data that are associated with complex traits often will require use of very large sample sizes to achieve adequate statistical power. For a fixed sample size, sequencing of individuals sampled from the tails of a phenotype distribution (i.e., extreme phenotypes design) maximizes power and this approach was recently validated empirically with the discovery of variants in DCTN4 that influence the natural history of P. aeruginosa airway infection in persons with cystic fibrosis (CF; MIM219700). The increasing availability of large exome/genome sequence datasets that serve as proxies for population-based controls affords the opportunity to test an alternative, potentially more powerful and generalizable strategy, in which the frequency of rare variants in a single extreme phenotypic group is compared to a control group (i.e., extreme phenotype vs. control population design). As proof-of-principle, we applied this approach to search for variants associated with risk for age-of-onset of chronic P. aeruginosa airway infection among individuals with CF and identified variants in CAV2 and TMC6 that were significantly associated with group status. These results were validated using a large, prospective, longitudinal CF cohort and confirmed a significant association of a variant in CAV2 with increased age-of-onset of P. aeruginosa airway infection (hazard ratio = 0.48, 95% CI=[0.32, 0.88]) and variants in TMC6 with diminished age-of-onset of P. aeruginosa airway infection (HR = 5.4, 95% CI=[2.2, 13.5]) A strong interaction between CAV2 and TMC6 variants was observed (HR=12.1, 95% CI=[3.8, 39]) for children with the deleterious TMC6 variant and without the CAV2 protective variant. Neither gene showed a significant association using an extreme phenotypes design, and conditions for which the power of an extreme phenotype vs. control population design was greater than that for the extreme phenotypes design were explored.     

Methylthioadenosine and polyamine biosynthesis in a Saccharomyces cerevisiae meu1delta mutant

As part of our studies on polyamine biosynthesis in yeast, the metabolism of methylthioadenosine was studied in a mutant that lacks methylthioadenosine phosphorylase (meu1delta). The nucleoside accumulates in this mutant and is mainly excreted into the culture medium. Intracellular accumulation of the nucleoside is enough to account for the inhibition of spermidine synthase and thus to indirectly regulate the polyamine content of the meu1delta cells. By comparing the results with this mutant with a meu1delta spe2delta mutant that cannot synthesize spermidine or spermine, we showed that >98% of methylthioadenosine is produced as a byproduct of polyamine synthesis (i.e., from decarboxylated S-adenosylmethionine). In contrast, in MEU1+ SPE2+ cells methylthioadenosine does not accumulate and is metabolized through the methionine salvage pathway. Using a met15delta mutant we show that this pathway (i.e., involving polyamine biosynthesis and methylthioadenosine metabolism) is a significant factor in the metabolism of methionine, accounting for 15% of the added methionine.