Genomic,transcriptomic, and metabolomic analysis of Oldenlandia corymbosa reveals the biosynthesis and mode of action of anti-cancer metabolites

Plants accumulate a vast array of secondary metabolites,which constitute a natural resource for pharmaceuticals.Oldenlandia corymbosa belongs to the Rubiaceae family,and has been used in traditional medicine to treat different diseases,including cancer.However,the active metabolites of the plant,their biosynthetic pathway and mode of action in cancer are unknown.To fill these gaps,we exposed this plant to eight different stress conditions and combined different omics data capturing gene expressi...     

Use of Firefly Luciferase for ATP Measurement: Other Nucleotides Enhance Turnover

Firefly luciferase utilizes only ATP and a few closely related nucleotides as substrates for the formation of luciferyl adenylate which is an intermediate in the bioluminescent reaction sequence that oxidizes firefly luciferin. The enzyme shows two different time courses of light production depending on ATP concentration used: a flash with high concentrations of ATP (>8μM) or a fairly constant production of light with lower concentrations of ATP (< 1 μM). Many nucleotides, nucleotide-containing substances and other compounds, when added either prior to or 1 min after the addition of ATP, change the time course of light production. When added before ATP, these compounds yield a reaction mixture in which light production is fairly constant (at the level characteristic of the flash observed with that ATP concentration). When the compounds are added after ATP addition, light production is markedly stimulated and the higher rate of light production is maintained for several minutes. There is an increase in quanta of light produced per luciferase dimer from 1 to 5/min with the addition of any of several nucleotide analogues. These results are consistent with a stimulated release of the inhibitory product oxyluciferin, allowing turnover of the enzyme. This enzyme turnover permits more light output at high ATP concentrations, thus enhancing the sensitivity of enzyme determination.     

Minimum Effective Dose of Cattle and Sheep BSE for Oral Sheep Infection

The minimum dose required to cause infection of Romney and Suffolk sheep of the ARQ/ARQ or ARQ/ARR prion protein gene genotypes following oral inoculation with Romney or Suffolk a sheep Bovine spongiform encephalopathy (BSE)-derived or cattle BSE-derived agent was investigated using doses ranging from 0.0005g to 5g. ARQ/ARQ sheep which were methionine (M) / threonine (T) heterozygous or T/T homozygous at codon 112 of the Prnp gene, dosed ARQ/ARR sheep and undosed controls did not show any evidence of infection. Within groups of susceptible sheep, the minimum effective oral dose of BSE was found to be 0.05g, with higher attack rates following inoculation with the 5g dose. Surprisingly, this study found no effect of dose on survival time suggesting a possible lack of homogeneity within the inoculum. All clinical BSE cases showed PrP^d accumulation in brain; however, following cattle BSE inoculation, LRS involvement within Romney recipients was found to be significantly lower than within the Suffolk sheep inoculated group which is in agreement with previous reports.     

Synthesis and biological properties of novel glucocorticoid androstene C-17 furoate esters

A series of novel corticosteroid derivatives featuring C-17 furoate ester functionality have been synthesised. Profiling in vitro and in vivo has resulted in the identification of a compound with a longer duration of action and a lower oral side effect profile in rodents compared to budesonide.     

Determinants of plant U12-dependent intron splicing efficiency

Factors affecting splicing of plant U12-dependent introns have been examined by extensive mutational analyses in an in vivo tobacco (Nicotiana tabacum) protoplast system using introns from three different Arabidopsis thaliana genes: CBP20, GSH2, and LD. The results provide evidence that splicing efficiency of plant U12 introns depends on a combination of factors, including UA content, exon bridging interactions between the U12 intron and flanking U2-dependent introns, and exon splicing enhancer sequences (ESEs). Unexpectedly, all three plant U12 introns required an adenosine at the upstream purine position in the branchpoint consensus UCCUURAUY. The exon upstream of the LD U12 intron is a major determinant of its higher level of splicing efficiency and potentially contains two ESE regions. These results suggest that in plants, U12 introns represent a level at which expression of their host genes can be regulated.     

Grandmothering in Cambridgeshire, 1770–1861

The effects of grandparent survival on child survival and mean interbirth interval, both independent of and relative to parent survival, were investigated in a historical population. Families for the data set were reconstituted from the parish and census records of Cambridgeshire, 1770–1861. In a logistic regression analysis, only the mother’s and the maternal grandmother’s survival were found to be significant predictors of child survival. Maternal grandmother’s survival was found to influence child survival both via maternal survival and independent of maternal survival. Grandparent survival was not found to influence mean interbirth interval. These findings are reviewed with respect to other studies of grandmothering, the Grandmother Hypothesis, and the evolutionary significance of human female postreproductive lifespan. Gillian Ragsdale is a postgraduate student at the Leverhulme Centre for Human Evolution Studies (LCHES), Cambridge University, UK, currently investigating the evolution of human social cognition. She was originally a molecular geneticist, and subsisted through the intervening years in educational publishing.     

Removal of mandibular tooth follicles before distraction osteogenesis

Distraction osteogenesis is an innovative technique that has transformed the treatment of craniofacial malformations in young children. Bone generation obviates the need for graft material, which is in short supply in young patients, thus making possible surgical procedures on the craniofacial skeleton in young children. Sufficient mandibular volume is required for the osteotomy and placement of the device screws and/or pins. To have adequate bone stock and to facilitate distraction, the authors preoperatively examined all patients radiographically and selected those with tooth follicles that precluded successful osteotomy and pin placement for planned mandibular distraction. This report is of the first 13 children, aged 9 months to 6 years, who underwent predistraction enucleation. The osteotomy and device placement were performed successfully at least 4 months after enucleation. The described procedure has minimal morbidity and has resulted in successful subsequent distraction. The advantages, disadvantages, and cost-benefit issues are discussed.