A mathematical model of the bovine oestrous cycle: simulating outcomes of dietary and pharmacological interventions.

A mathematical model was constructed to simulate the bovine oestrous cycle by using nonlinear differential equations to describe the biological mechanisms which regulate the cycle. The model predicts circulating concentrations of gonadotrophin-releasing hormone, follicle-stimulating hormone, luteinizing hormone, oestradiol, inhibin and progesterone. These hormones collectively provide control and feedback mechanisms between the hypothalamus, pituitary gland and ovaries, which regulate ovarian follicular dynamics, corpus luteum function and ovulation.

Occurrence of a quadruplex motif in a unique insert within exon C of the bovine estrogen receptor alpha gene (ESR1).

The 5' end of exon C of the bovine estrogen receptor alpha gene (bov-ESR1) includes a unique G-rich insert, not found in other closely related mammalian genes, which lies close to both a double E-box transcription factor binding site and the site of a single nucleotide (G/A) polymorphism. Biophysical studies, using CD and UV absorbance measurements, show that this 22 base insert leads to the formation of a family of stable G-quadruplex structures which are unaffected by the G/A polymorphism. Multiplex PCR shows that the region including the G-quadruplex is transcribed into RNA, and studies with a synthetic RNA transcript sequence demonstrated formation of a highly stable parallel-folded quadruplex structure.

Repression of translation of human estrogen receptor alpha by G-quadruplex formation.

Tissue-specific expression of the human estrogen receptor alpha gene (ESR1) is achieved through multiple promoter sequences resulting in various mRNA transcripts encoding a common protein but differing in their 5'-untranslated region (5'-UTR). Many cancers are estrogen-sensitive with neoplastic growth stimulated through the estrogen receptor, a transcription factor that regulates developmental genes. We demonstrate that the human ESR1 gene is rich in potential quadruplex-forming sequences with 3 of 20 identified within exonic regions.

Rapid absorption of sumatriptan powder and effects on glyceryl trinitrate model of headache following intranasal delivery using a novel bi-directional device.

Objectives: The aim was to investigate the pharmacokinetics of intranasal sumatriptan (administered using a novel bi-directional powder delivery device) and study its effects on quantitative electroencephalography in patients with migraine. The safety profiles of the two formulations were also compared.

Methods: The pharmacokinetics of intranasal sumatriptan (10 mg and 20 mg) administered using a novel breath-actuated bi-directional powder delivery device were compared with subcutaneous sumatriptan (6 mg), along with an investigation of their effects on the electroencephalogram (EEG) following glyceryl trinitrate (GTN) challenge in 12 patients with migraine using a randomized, three-way cross-over design.

Modelling responses to nutritional, endocrine and genetic strategies to increase fertility in the UK dairy herd.

The United Kingdom, as in most countries using intensive dairy management programmes, is facing serious challenges in terms of dairy cow fertility, as highlighted by a rapidly increasing calving interval (CI). A mechanistic, mathematical model is described that predicts the size of the future national dairy herd required to supply domestic requirements and its inherent sustainability in terms of production of replacement female numbers. The results from the model suggest that continuing use of current management strategies may result in the national dairy herd being unsustainable due to increasing CI and reduced fertility in as few as 10years.

Peroxisome-proliferator-activated receptors and the control of levels of prostaglandin-endoperoxide synthase 2 by arachidonic acid in the bovine uterus.

Arachidonic acid is a potential paracrine agent released by the uterine endometrial epithelium to induce PTGS2 [PG (prostaglandin)-endoperoxide synthase 2] in the stroma. In the present study, bovine endometrial stromal cells were used to determine whether PTGS2 is induced by arachidonic acid in stromal cells, and to investigate the potential role of PPARs (peroxisome-proliferator-activated receptors) in this effect. Arachidonic acid increased PTGS2 levels up to 7.