Opting out from European Union legislation: the differentiation of secondary law

Differentiated integration in the European Union (EU) has been primarily discussed and analysed at the treaty level, whereas lack of systematic data has hampered the examination of secondary-law or legislative differentiation. We present a new data set of differentiation in EU legislation from 1958 to 2012, a descriptive analysis and a comparison of the patterns of primary- and secondary-law differentiation across time, member states and policies. We find that differentiation facilitating the accession of new members and constitutional differentiation accommodating the opposition against the integration of core state powers drive both primary- and secondary-law differentiation. In addition, we find complementarity between differentiation in treaty law and secondary legislation depending on the availability and salience of differentiation opportunities

Vitamin D receptor distribution in intestines of domesticated sheepOvis ammon f. aries

The biologically active form of vitamin D, i.e., 1,25-dihydroxycholecalciferol or calcitriol, plays an important role in bone metabolism and calcium homeostasis, which is often disturbed at the onset of lactation in high milk-yielding domestic ruminants. Gene transcription is modulated via vitamin D receptors, but nongenomic effects of vitamin D via membrane receptors have also been described. In the intestines, vitamin D promotes calcium absorption via vitamin D receptors. Vitamin D receptors are of clinical relevance, but have not been systematically assessed within all segments of the intestine in any species. Thus, we present for the first time an immunohistochemical study of the distribution patterns of the vitamin D receptor protein in sheep, which may be the basis for present and future investigations on mineral homeostasis in domestic ruminants. Tissue probes of the intestines were collected from five lambs and five nonlactating and nonpregnant dams, fixed in formalin, embedded in paraffin, and used for the assessment of vitamin D receptor protein. Nuclear vitamin D receptor immunoreaction was scored semiquantitatively and exhibited a segment-specific distribution pattern. Goblet cells always were devoid of any vitamin D receptor immunoreaction. Surface epithelial cells and enterocytes of the crypt openings generally demonstrated only a weak immunoreaction. Basally and/or intermediately located crypt epithelial cells exhibited stronger immunoreactions in duodenum, jejunum, and colon descendens. This basal/intermediate to superficial gradient was most pronounced in the duodenum and less evident in jejunum and colon descendens and not observed in ileum and cecum. There were no age-dependent variations in vitamin D receptor protein expression. Results demonstrate that intestinal vitamin D receptor distribution patterns are segment-specific and strongest immunoreactions correlate with highest intestinal calcium absorptive activities, as reported in literature. Strong expression of vitamin D receptors within the lower half of crypts also suggests a role for calcitriol in epithelial differentiation and cellular homeostasis